Listening to a lecture on “itching—what's behind it?” can induce observable scratching behavior and self-reported itchiness in the audience . That is, both the quality of itchiness (self-reported) and the action of scratching (as observed) is vicariously shared—as already noted by Holle et al. . Similarly, we coded the part of the body that was scratched. Although the visual stimuli depicted scratching only to the arms and chest (and with cropping at the neck), the vast majority of the participants' own scratches were directed toward their face and hair  vs. conceptually induced itch . A more recent behavioral study by Lloyd et al.  used sta


A biological and socio-cognitive framework may enhance our understanding of the security process, as the two perspectives collectively acknowledge that (i) competition for resources is/was an important factor in human social behavior and evolution  based on uncertain outcomes. Error management theory proposes that cognition has evolved so that when faced with two alternate strategies, we pick the strategy that would result in the least-costly errors  given their own personality or immediate environment? These issues are clearly very current, as commentators debate the “trade off” between security and civil liberties. Indeed, the extent to which human error accounts for the false conviction of suspects  and losers are more likely to withdraw from future confrontation [reviewed in Hsu et al. ]. Recentintent on causing harm to others (their perceived trustworthiness) and the extent to which an individual appears capable of causing harm to others [their perceived dominance; (Oosterhof and Todorov, Information provided by the face plays an important role in social interaction (Bruce and Young, Perceptions of dominance and trust appear to have an underlying biological basis and are of obvious relevance to security scientists. Although the relationship between hormones and facial appearance is complex (see Pound et al., Other aspects of facial appearance may predict trusting behavior in the exchange of resources. While attractive individuals are more likely to be trusted in economic exchanges (Solnick and Schweitzer, immediate costs on others during face-to-face competition. Future research could explore the relationship between personality and hacking behavior using a behavioral measure of “persistence” in “code-cracking” tasks.If visible cues play an important role in trusting behavior and the exchange of resources, the context in which we interact with others may be important for security-related outcomes. For example, while direct face-to-face combat could be described as the “traditional method” of resource competition, online theft presents an evolutionary-novel challenge that strategists might only just be coming to terms with (see Anderson et al., Understanding how individual and environmental differences predict security outcomes could generate practical solutions to problems. The extent to which personality and appearance influence social judgments and behavior at key “barriers” to entry may enhance the overall quality of professional recruitment and training. For example, work has already demonstrated that self-rated attention to detail is predictive of security screening performance (Rusconi et al., Competition for resources could be investigated at the neural level by exploring the neural basis of individual differences in morality and risk-taking in contexts related to resource acquisition and defence. Testosterone is associated with both financial risk-taking (Apicella et al., Biology provides a unifying framework with which to understand human behavior in light of differences between individuals and their surrounding environment. An understanding of the biological basis of strategic “biases” in social judgments can potentially increase the quality of security decision-making in light of greater awareness of the contexts and environments that might mitigate or exacerbate the risk of lost resources.


In a recent article in Frontiers in Evolutionary Psychology, Krupp et al.  propose Krupp et al.  state, “nepotistic assistance to highly psychopathic individuals by less psychopathic kin. Psychopathy may persist in human populations in part because of kin support to (not from) psychopathic individuals.We applaud these authors for raising the issue of the treatment of relatives by psychopathic individuals as it is commonly asserted that offenders do better when they have supportive family ties .integrated emotions systems (IES) model .” We disagree, as there is significant co-morbidity between paranoid personality disorder and psychopathy  (Johnson et al., Rather than being “an adaptation” psychopathy may represent a spandrel—a syndrome that arises as a consequence of other features (Buss et al., We strongly dispute the assertion that psychopathy is not a disorder. Psychopathy is a mental disorder according to both the Wakefield definition cited in this study and American Psychiatric Association criteria (American Psychiatric Association,


This thematic series presents theoretical and empirical papers focused on understanding autism from the perspective of reward processing deficits. Although the core symptoms of autism have not traditionally been conceptualized with respect to altered reward-based processes, it is clear that brain reward circuitry plays a critical role in guiding social and nonsocial learning and behavior throughout development. Additionally, brain reward circuitry may respond to social sources of information in ways that are similar to responses to primary rewards, and recent clinical data consistently suggest abnormal behavioral and neurobiologic responses to rewards in autism. This thematic series presents empirical data and review papers that highlight the utility of considering autism from the perspective of reward processing deficits. Our hope is that this novel framework may further elucidate autism pathophysiology, with the ultimate goal of yielding novel insights with potential therapeutic implications. This thematic series presents theoretical and empirical papers focused on understanding autism from the perspective of reward processing deficits. This framework suggests that the well-known deficits in social functioning that characterize individuals with autism may reflect or may even be caused by decreased motivation to interact with the social world and decreased feelings of pleasures during social exchanges . Likehttp://www.nimh.nih.gov/research-funding/rdoc.shtml), we feel that understanding autism through the lens of reward systems has the potential to both improve etiologic understanding of autism and to suggest novel approaches for diagnosis and intervention.Although the core symptoms of autism have not traditionally been conceptualized with respect to altered reward-based processes, it is clear that brain reward circuitry plays a critical role in guiding social and nonsocial learning and behavior throughout development . Additioet al.[Research on reward processing in autism is in a nascent stage, and there is a pressing need for empirical studies to define the boundary conditions of reward processing deficits in this disorder. This thematic series contains six empirical papers spanning a number of measurement methods. Cascio et al. extend tet al.,9). Thiset al.,11. By eet al.-16.et al.[McPartland et al. used eveet al.,19 by foet al.[Lin et al. examinedet al.[Damiano et al. used an et al.. These aet al.[This thematic series also includes a pupilometry study by Sepeta et al. that addet al.[This thematic series is complemented by a number of review papers as well. Kohls et al. evaluateDawson et al. ) review et al.[Dichter et al. take a bet al.[Kishida et al. describeet al.[Finally, Watson et al. provide This thematic series suggests a novel framework for understanding the core features of autism, and, perhaps most critically, includes reviews that suggest the utility of considering this framework for understanding variability in treatment response in autism. Articles contained within this thematic series introduce a new theoretical perspective, review vast literature across several disciplines, and suggest ways to leverage an established neurobiological framework and associated behavioral and neuroimaging tasks for understanding the core features of autism. Our hope with this thematic series is to encourage other researchers to consider this framework, and to complement existing research programs addressing social-communicative deficits and restricted and repetitive behaviors in autism.GD is an Assistant Professor of Psychiatry and Psychology and an investigator at the Carolina Institute for Developmental Disabilities at the University of North Carolina at Chapel Hill. RA is the Bren Professor of Psychology and Neuroscience and a Professor of Biology at the California Institute of Technology.


Sir,et al.[et al.[With reference to the article on honey treatment for burns by Baghel et al. and commet al. the folll.[et al. in theirl.[et al. about thHoney may contain botulinum, and hence it is necessary to sterilize honey by gamma irradiation, but majority of the clinical studies used raw honey and no adverse effects have been reported so far.


Sir,et al. with great interest. We applaud the authors for conducting such a study in Indian setup. However, the high cost of therapy with interferon and even glatiramer acetate is a matter of concern in treatment of patients with multiple sclerosis in Indian setup. A study by Singhal et al. has concluded that mitoxantrone, which is a cheap alternative to interferon, has shown promising results in Indian setup when given as an initial therapy for the patients with multiple sclerosis[et al.[We read the article “Beta-interferons in multiple sclerosis: A single center experience in India” by Guptasclerosis and coulsclerosis Mitoxantis[et al. Althoughis[et al.et al. reported reduced disability in patients treated with alemtuzumab.[et al. showed significant improvement in disability score with use of natalizumab.[The new emerging therapies for the treatment of multiple sclerosis include alemtuzumab, natalizumab, and autologous stem cell transplantation which have also shown promising results in trials with respect to disability improvement. A study done by Cole mtuzumab. A multicalizumab. Another alizumab. However,Nonetheless, the authors have done a commendable job in view of the patients who seriously impaired by multiple sclerosis and we appreciate their efforts.


Dear Editor,Attention should be drawn to the study by colleagues Saito O et al. published in the International journal of Endocrinology and Metabolism . The stu


The role of these processes in recovery may be due to the multi-componential character of neglect syndrome (Milner and McIntosh, Remapping of space (Berti and Frassinetti, In such view, however, it is necessary to consider that the well-known dissociation far and near space is not exhaustive to explain treatment success. One may speculate further that the multisensory integration facilitated by the immediate feedback provided by seeing one owns upper limb reflected in the far space while reaching objects, might facilitate the spatial remapping between far and near space through the updating of the body schema, which is strongly dependent on multisensory integration (Aglioti et al., ad hoc to allow within group contrasts, aimed at verifying the suitability of paradigms across different neglect subtypes.As a final remark, effectiveness of VG based treatments on diverse subtypes of neglect should be explored. For instance, these techniques might not be suitable for all neglect patients, considering that additional impairments such as somatoparaphrenia or perseverations might be present (Bottini et al., wider and enriched scenario including meaningful actions, rather than abstract geometric targets as stimuli and movements that do not resemble reality, is more motivating, encouraging, and finally ecological for patients engaged in recovery programs (Laver et al., Appropriate rehabilitation techniques may influence cognitive functions even in the chronic phase (Teasell et al.,


Elevated levels of stress and anxiety often accompany vestibular dysfunction, while conversely complaints of dizziness and loss of balance are common in patients with panic and other anxiety disorders. The interactions between stress and vestibular function have been investigated both in animal models and in clinical studies. Evidence from animal studies indicates that vestibular symptoms are effective in activating the stress axis, and that the acute stress response is important in promoting compensatory synaptic and neuronal plasticity in the vestibular system and cerebellum. The role of stress in human vestibular disorders is complex, and definitive evidence is lacking. This article reviews the evidence from animal and clinical studies with a focus on the effects of stress on the central vestibular pathways and their role in the pathogenesis and management of human vestibular disorders. Stress may influence central vestibular function in health and disease either directly through the actions of glucocorticoids (cortisol and corticosterone) on ion channels and neurotransmission in the brain, or indirectly through the effects of stress-related neuroactive substances  on these structures. In the periphery stress hormones also regulate the function of ion transporters and ionic homeostasis in the inner ear, while in some conditions the anti-inflammatory actions of glucocorticoids may also come into play  have been shown to activate the stress axis. Gliddon et al.  measuredTighilet et al.  quantifiBy contrast, Lindsay et al.  and ZhanIn contrast to the effects of UVD, following bilateral vestibular deafferentation (BVD) in rats serum corticosterone was not found to be elevated when compared with sham surgery at 3 weeks , into the middle ear to induce a functional inactivation of the injected ear Figure . FollowiIn the frog, hypophysectomy delays compensation after UVL while ACTH (4–10) administered post-UVL restores it  and the cerebellum , Meniere’s disease, or migrainous vertigo. If the process of vestibular compensation is inadequate, the underlying dysfunction may persist and eventually present as chronic dizziness (Bronstein et al., While animal studies (e.g., in Figure Human imaging and behavioral studies, particularly with reference to spatial memory in patients with loss of vestibular function, suggest the hippocampus may be an important center for vestibular compensation (Brandt et al., In addition, of particular relevance is that stress responsiveness is importantly influenced by various developmental and environmental factors including genetic and fetal programming and early life stressful events, as well as varying with age and gender (de Kloet et al., A number of clinical studies have suggested a beneficial role for steroids in the treatment of acute vestibular dysfunction. Ariyasu et al.  studied Kitahara et al.  comparedA systematic study on 141 patients with acute onset vestibular neuritis was conducted by Strupp et al. . PatientThe effects of prednisolone treatment in vestibular neuritis were investigated by Shupak et al.  in 30 paKarlberg and Magnusson  reportedTwo recent meta-analyses have reviewed the role of steroids in the treatment of acute vestibular dysfunction (Goudakos et al., Horii et al.  reportedIn patients with chronic bilateral vestibular loss, testing with virtual navigation tasks without self motion revealed significantly impaired spatial memory that was accompanied by a reduction in hippocampal volume on MRI imaging (Brandt et al., Eagger et al.  reportedArousal with aversion and a lack of control are behavioral hallmarks of the stress response (Kim and Diamond, In a cross-sectional study Eckhardt-Henn et al.  found thHowever, not all patients perceive or handle stress in the same way. Patients’ ability to habituate or cope with repeated stress may be factors that determine outcomes. Tschan et al.  assessedThe causal relationships between balance dysfunction, anxiety, and stress need to be explored experimentally especially within the context of vestibular compensation. An acute stress response is known to be essential for learning and memory formation (Joels et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In Response: We thank Davies et al. for their letter (S. aureus (MRSA) registry data were derived from swab specimens and clinical isolates; the distribution of anatomic sites differed between the cases and controls in our study. However, all study participants were proven MRSA carriers. As per their comment in their letter (Davies et al. correctly note that the original methicillin-resistant Davies et al. apparently pooled data from 3 studies and stated that there is negligible risk for livestock-associated–MRSA among persons who do not have livestock or farm contact. Each of these studies was designed differently and had different comparison groups, and each report conceded that factors such as indirect human or environmental transmission could have exposed study participants who lacked known farm risk factors.In addition, Davies et al. state that our observed association of increased odds of livestock-associated–MRSA compared with a typeable strain of MRSA in regions with higher livestock densities should be limited to hypothesis generation. We agree, as stated in the final sentence of our report (To clarify our statement comparing pig densities in the United States and the Netherlands (


We thank Tsuda et al. for sharing their views. Along with their previous publications on Minamata disease, we find their comments useful as a complement to our brief historical review of the mass poisonings in Japan and associated events . However


Research in oral and maxillofacial pathology has unlimited potential. We use every technology available to us for better and faster reliable diagnosis. But in most institutions, private laboratories and multispecialty hospitals, tissue processing takes considerable time, and therefore delays the diagnosis, which is required in urgent cases. We, in this institution, conducted a study to hasten the processing by using a simple kitchen microwave.To analyze tissue sections processed by microwave as compared to the gold standard of conventional processing.et al., in 2008. This is the second such study that used a sample size of 50 cases.Studies published from 1970 till 2008, used body tissues such as brain, liver, kidney, heart, and lungs, for microwave processing. Oral tissues were not processed in microwave till now, except one study by Dr Shivaparthasundaram A kitchen microwave was used for irradiation of the tissues. Conventional processing was carried out as per departmental protocol. A total of 50 microwave-coded slides were mixed with 50 conventional slides. All 100 slides were evaluated by four different pathologists.The result was subjected to statistical analysis using Chi-square test.It was found that to make a diagnosis, microwave-processed tissue were at par with the conventional technique. Thus, it is time to move on from conventional processing to microwave processing to yield faster and reliable results. Conventional tissue processing is as old as 100 years and still remains the gold standard against which all new technologies and methods need to be assessed. A laborious and tedious manual sequence, tissue processing is of paramount importance for having good thin sections without artifacts.Microwaves, which were invented by Percy Spencer in 1945, created a small buzz and soon became an integral part of our daily lives.[This study uses microwaves for the processing of oral tissues and Analysis the cellular and nuclear morphology as well as staining characteristics. Comparison is done with the conventional technique with the same parameters.To evaluate the quality of stained sections by both techniques.Microwave ovens can generate heat from within, and thereby warm tissues and reagents uniformly in a short time. The objective of this study is to process the tissues in a microwave oven and then compare the sections with the gold standard of conventional processing.National microwave oven ; Model no.: NN – 5208; Serial no.: N 09130085; Input- 1180 W, 5.2 A, 240 V, 50 Hz; Output- 600 W, 2450 MHz.Jar- 600 ml; two jars of 200 ml each; seven glass vessels of 200 ml each10% Formalin; acetone; absolute alcohol; xylene; chloroform and paraffin waxSpecimens for this study were selected randomly from those received in the department of Oral and Maxillofacial Pathology, Bharati Vidyapeeth Dental College and Hospital, Pune, and from private hospitals and clinics in and around Pune.Only soft tissue was preferred for this studyThe sample size was 1 cm × 1 cm or greaterThe thickness of 5-8 mm was taken for microwave processingThe tissue was then divided into equal halves; one was processed in a microwave and the other was processed conventionally.10% formalin was used as a fixative.The processing was started at 8.30 am; the cassette was kept in water for 1 hour to remove formalin. Dehydration in acetone was done in four steps of 1 hour each, using graded acetone  from 9.30 to 1.30 pm. Tissue was cleared in xylene in three steps of 1 hour each , using 100% concentration of the solution. At the end of the college hours, the cassette was kept in paraffin wax bath I for impregnation, which had a preset temperature of 40°C. The subsequent morning at 9.00 am, the tissues were removed from paraffin wax bath I and placed in wax bath II for 1 hour (preset temperature of 40°C). This was done to allow proper impregnation of the wax into the tissues. At 10.00 am, tissue was removed from the wax bath II and embedded. This procedure was followed routinely.All processing was done at room temperature, except for impregnation and embedding.Xylene has a high boiling point and low microwavability, ie, it will take double the time for the same amount of reagent to get heated. Therefore, in this study, chloroform was used as a clearing agent for microwave tissue processing.A pilot study was done in which each reagent was microwaved for 5 and 10 minutes. The tissues microwaved for 5 minutes showed improper dehydration, clearing, and impregnation, while those microwaved for 10 minutes showed improper clearing and tissue breakage while cutting. The tissues and reagents were microwaved for 15 minutes. The dehydration, clearing, and impregnation of tissues were found to be satisfactory. Hence, this method was taken as a standard protocol for all tissues.et al., where the following steps were used:The time taken for dehydration, clearing, and impregnation was same as that of Klump et al., Absolute alcohol: 15 minutes (one step)Chloroform: 15 minutes (“)Paraffin impregnation: 15 minutes (“)The solutions are not covered with the lid because we had two jars: the first jar contained a 200 ml solution  along with the tissue inside, and the second one contained a water load of 500 ml and placed next to the first jar. In this way, We were able to control the excess heat, which was absorbed by the water.Due to very small size of the oral tissues, the temperature of the tissue cannot be measured. Thus, it was assumed to be similar to that reached in the solution, which was in the range of 45°C-58°C.The power of the microwave available for this model was warm, low, medium low, high. In this study, the power modes used were as follows:Power mode for each solution:First 5 min- low mode and next 10 min - warm modePower mode for paraffin wax:First 5 min- medium low mode and next 10 min - low modeThis was done to allow chloroform to effectively boil out of the tissue and replace it with paraffin.A total of 50 pairs of slides were obtained; one each for microwave and conventional tissue processing. All 100 slides were coded by an independent observer, in which 50 slides were coded with an alphabet (A) and the other 50 slides were coded (B). Four observers evaluated all 100 slides without the knowledge of the type of processing used.For cellular morphology evaluation, greater eosinophilia of cytoplasm producing enhancement of the nuclear-cytoplasmic contrast, good stroma, whether secretory products are appreciable, red cell lysis absent, whether differentiation can be made between inflammatory cells. If most Evaluation of slides for nuclear morphology was done on the basis of chromatin condensation, prominent nuclear membrane, and crisp staining of the nucleus and mitotic activity, if appreciable. It was dStaining of tissues was evaluated as poor, satisfactory, and good. Poor indicates that the tissue failed to take up stain adequately, stained unevenly or had artifacts in processing or staining. Satisfactory indicates that details were not visualized up to the mark, but slide was suitable to give diagnosis. Good means good contrast between the nucleus and cytoplasm, and visibility of details along with brilliance of staining.67 The ov6After evaluation by all four observers, the processing code was broken and results were subjected to statistical analysis.The reliability test was done to evaluate the interobserver variations. Similarly, The histological assessment was done by three independent observers and myself. The observers were as follows: observer no 1- Oral pathologist with 15 years of teaching experience; observer no 2- a General pathologist with a teaching experience of 7 years; and observer no 3- an Oral pathologist with a teaching experience of 2 years.et al.[The microscopic quality of the sections was comparable to, or slightly better than, conventionally processed tissue having the same formalin fixation time. The architecture in the sections was well preserved as in concordance with Kok et al.From these results, we believe that rapid microwave-assisted tissue processing is the optimal method for producing quality sections. Also, excellent microscopic sections obtained by this technique revealed no differences in the cellular and nuclear morphology in several types of tissues.The formula for diffusion states that: the average squared distance covered by a particle in solution is proportional to the diffusion time. This shows that the thickness of biopsies should be small: three times as thick means nine times as long for comparable effects. It should be noted that the length and breadth does not matter here.Proteins in the tissue are denatured by absolute alcohol to such a degree that subsequent heating does not have any additional influence on the light microscopic results. Alcohol is also used as a coagulant fixative that hardens the tissue, and this is needed for cutting of sections. This hardening effect is caused by coagulation of proteins.The literature on microwaves for histoprocessing comprises several papers that advocate the use of domestic microwave ovens. In the book by Kok and Boon, the total processing time was 111 minutes when 500-ml containers were used and 30 blocks were prepared. In all steps, the working temperature of 75°C was maintained.et al.,[et al.[In this study, the microwave processed tissue sections had better cytoplasmic  and nuclet al.,12 Mathai.,[et al.et al.,[et al.,[et al.,[et al.[Boon et al., Chaudhar,[et al., and Mora,[et al.,12 found ,[et al.,. No cris.,[et al.et al.[In this study, the effect of microwaves on the different types of tissue such as epithelium, fibrous, and glandular, showed no statistically significant variation, as also seen in studies by Panja et al.et al.[Boon et al. found thet al. and 5, aet al.et al.,[et al.[Red cells were not lysed  by microet al., Mayers,[et al., Leong,[4et al., the red et al.,, and thi.,[et al.et al.,[The microwave processed slides of malignancy cases such as angiosarcoma , verrucoet al., who acceThere was excellent staining of tumor cells as compared to similar sections processed with conventional technique Figures –9. Irreget al.,[Foci of dystrophic calcification were preserved as seen in cases of Hopewood et al., and exceThere was no significant difference between nuclear size and shapes, as seen in Figures  and 15 aet al.,[et al.,[et al.,[et al.,[et al.,[et al.,[et al.,[et al.,[et al.,[et al.[The staining of tissues in the microwave and conventionally processed slides did not show significant variation . This waet al., Chaudhar,[et al., Morales ,[et al.,12 Panja ,[et al., Zenobia ,[et al., Galvez e,[et al., Suri et ,[et al., Leong et,[et al.,21 Kok et,[et al., and Rohr.,[et al. Microwav.,[et al. and 17, et al., where cytoplasm stained moderately eosinophilic, with no deeper eosinophilia observed.[et al.[Similar findings were observed in the study carried out by Sivdas observed. Also, Hod.[et al. and Leond.[et al. noted eod.[et al.et al.[As the tissue that can be processed is very small, often the sample may not be representative of the site, and hence proper diagnosis could not be reached in few cases, which were in consonance with Suri et al. This disFew sections seen in conventional technique showed artifacts, such as uneven staining. This was due to inadequate dehydration and also due to faulty clearing techniques during the staining process.Moreover, residual paraffin in the tissue would have resulted in uneven staining.–25 CelluRight from pre-cancerous conditions and lesions to malignancy, reactive lesions to benign tumors, microwave technique has shown a remarkable difference without losing the architecture and morphology of the cells.The slides obtained by microwave processing did not in any way alter the cellular morphology, nuclear morphology, or staining characteristics. A comparison of the microwave processed slides with the conventionally processed slides shows that the results are statistically insignificant.In addition, the profitability of any diagnostic laboratory would be increased by using this technique, as this will enable handling a large batch of samples in a single day. Moreover, this will be a boon for the technical personnel whose work practices and lifestyles would change for the better, and this is something which defies statistical analysis.


Cannabis sativa is a plant containing over 70 active compounds called cannabinoids  in the left parahippocampal gyrus and decreased rCBF in the amygdala-hippocampus complex, including the posterior cingulate cortex (Crippa et al., Accordingly, it would be worthwhile to examine how the impact of CBD on ACC activity may extend to the domain of cognitive performance. Since modulation of ACC activity is assumed to be the mechanism through which CBD affects brain connectivity during emotional processing (Fusar-Poli et al., Taken together, research regarding the impact of CBD on ACC activity appears to be contradictory (see Table It is also interesting to consider the ACC-mediated impact of CBD on emotional processing. Animal research indicates that the anxiolytic effect of CBD depends on action of the compound on specific brain areas and that the effect could also, in some cases, be anxiogenic (Marco et al., In sum, existing research seems to undermine Schier's et al.  suggesti


Dear Editor,I read with interest the article by Kashani et al, on the use of hydroxyurea (HU) in the treatment of chronic hepatitis B published in Hepatitis Monthly . In thei


Traditional theories of motor skill learning . To illustrate, in a naturalistic investigation of the attentional foci adopted by elite golfers during competition, Bernier et al. (r et al.  found thr et al. . In anotr et al.  discoverr et al. , is “selvice versa. This may happen, for example, when they relinquish spontaneity and use knowledge of facts to alter “attenuated” movement patterns in the practice context or when they are strategizing during competitive performance. Although Stanley and Krakauer (knowledge of what to do to initiate an action, the current paper provides evidence of how skill may be continually improved by proprioceptive knowledge of how to change/alter an action and how performance proficiency may be maintained by propositional knowledge of how best to plan an action during competition.The research literature on the cognitive psychology and neuroscience of skill has tended to present a dichotomized view of the role knowledge plays in guiding skilled performance. According to this body of work, skilled performers engage in intuitive or absorbed coping (see Dreyfus and Dreyfus, Krakauer  use an e


Dear Editor,et al. Vocal cord position Vocal cord movement Coughing Movement of the limbs Intubating conditions are regarded as excellent , good , and poor   for tracheal intubation without neuromuscular blocking agents (NMBAs) with regard to the incidence of coughing.I read with keen interest the article by Imani et al.  in which  or not required to facilitate surgical access .


Cataract is one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Mechanisms related to glucose toxicity, namely oxidative stress, processes of non-enzymatic glycation and enhanced polyol pathway significantly contribute to the development of eye lens opacity under conditions of diabetes. There is an urgent need for inexpensive, non-surgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in the prevention of cataract since flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of diabetic cataract. In the present paper, natural flavonoids are reviewed as potential agents that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification. In addition, the bioavailability of flavonoids for the lens is considered. Cataract, eye lens opacification, is one of the earliest secondary complications of diabetes mellitus , pyridazines  and carboxymethylated pyridoindoles , isolated as a bioactive flavonoid from the leaves of et al., 1997).The flavonoid venoruton, a mixture of mono-, di-, tri- and tetrahydroxyethylrutosides, significantly reduced the degree of opacification and the leakage of lactate dehydrogenase in rat lens organ culture simulating diabetic conditions . Analogically, in the same galactosemic rat model, Mohan et al.  recorded et al., . The reset al., et al., 2009; Kyselova, et al.  did not affect cataract formation. The flavonoid fraction from Emilia sonchifolia was reported  was reported . Grape seed extract rich in flavonoids reduced hydrogen-peroxide-induced apoptosis of human lens epithelial cells and depressed H2O2-induced activation and translocation of NF-kB . Flavonoid chelating activity for transition metal ions has been well documented . Flavonoids inhibit xanthine oxidase, the enzyme responsible for superoxide anion production . Interestingly, isorhamnetin (3-methylquercetin) was found to inhibit xanthine oxidase, even more efficiently than the aglycone form of quercetin  and spirohydantoins, with epalrestat and sorbinil being the most representative members of each respective family catechin>kaempferol  is not a substrate of lactase phlorizin hydrolase. The quercetin aglycone is released hydrolytically by bacterial α-rhamnosidases and β-glucosidases in the lower gastrointestinal tract. Thus absorption of quercetin from rutin is delayed, and quercetin bioavailability is much smaller in comparison with that of quercetin-glucosides. This example stresses the role of sugar type for bioavalability of natural flavonoid glycosides (Hollman et al., et al., et al., et al., et al., et al., et al., et al., Flavonoids occur in plants mainly in the form of O-glycoside conjugates linked to sugars like glucose, galactose, arabinose or rhamnose (Bravo, et al., et al., et al., et al., Excellent reviews covering broadly the topic of bioavalability of flavonoids were published (Scalbert & Williamson, ex vivo experiments reported by Cornish et al. (et al., et al., et al., To date, only a few studies have investigated delivery of flavonoids to the eye. Drug delivery to the ocular tissues depends on the physicochemical and biopharmaceutical characteristics of the selected flavonoids and very importantly on the route of administration. Topical application is the most favored mode for ocular conditions. The topical route is mainly used to deliver drugs to the anterior segment of the eye. Local administration may yield much higher and effective concentrations of the parent flavonoids in the ocular tissues and at much lower doses, than the oral route. In the anterior chamber of the eye, the aqueous humor bathes the anterior surface of the lens, providing all oxygen and nutrient requirements. It is therefore this route through which dietary flavonoids would reach the lens. For example, in the h et al. , quercet et al., , it was et al., et al., Presently, surgical extraction remains the only cataract cure. Cataract surgery has become the most frequent surgical procedure in people aged 65 years or older in the Western world, causing a considerable financial burden to the health care system (Head, In diabetic patients, tight control of hyperglycemia is the first prerequisite to attenuate the risk of cataract. In addition, adjunct therapy is needed to help preserve vision in diabetic patients, aimed at correcting biochemical and metabolic abnormalities in the hyperglycemic milieu of the diabetic individual.The current data on natural polyphenols in relation to cataract, along with epidemiological knowledge on diet and lens opacity, demonstrate that flavonoids may play a role in cataract prevention. Yet future clinical trials are needed to assess the benefits of flavonoids in lowering the risk of both age-related and diabetic eye complications.


An improved algorithm for the piecewise-smooth Mumford and Shah functional is presented. Compared to the previous work of Chan and Vese, and Choi et al., extensions of the key functions


The role of the neuropeptide oxytocin in social cognition and prosocial behavior continues to fascinate the scientific community  of 18–90 year old African Americans with low-incomes: they found that individuals with the GG genotype on rs53576 who experienced severe childhood maltreatment were more likely to have disorganized attachment styles and higher levels of emotional dysregulation.In a study recently published in this journal, McQuaid et al.  examinedThus, in contrast to the majority of published studies focusing on rs53576, Bradley et al.  and McQuFindings from Bradley et al.  and McQu


The integration of different stimulus properties as an object is the process of feature binding. The research topic “Inhibition in the process of feature binding” aimed to debate which features bind together, why, and how; and what happens to features which are not integrated.The authors of the review articles took up the debate in earnest. Wyatte et al.  emphasizThe relevance of features is the key factor in the process of binding for Jaswal . She attHerzog et al.  also addMeier and Rey-Mermet  discuss Moving from features to objects, Dent et al.  review bThe four articles contributing original research extend the study of binding to novel avenues. As merits empirical investigations, all studies not only document details of current work in these new areas, they also indicate hypotheses for future investigations.Delogu et al.  enter thGiersch et al.  scale upThe two original research articles based on computational models conceptualize binding as part of other processes. Schrobsdorff et al.  propose The aim of this research topic was to consider the process of binding from various perspectives such that an integrated view emerged to guide future research and theory. Challenging the assumption that feature binding is an automatic “event” driven by bottom up processes dependent on conjunctively coding neurons or synchrony, the collection of these articles yield the conclusion that the emergence of a bound object capable of further processing, is itself a sub-process, which is heavily contingent on re-entrant mechanisms and is probably resource demanding. Future investigations may explore feature binding as a basic process in myriad behavioral sequences of diverse populations.


Rice is a staple food for at least 50% of the world's population. Therefore, it is one of the most important crop plants on Earth  were identified, as transport proteins which only internalize Fe during germination, chelating molecules such as nicotianamine and deoximugineic acid, low levels of ferritin protein in the endosperm tissue and mostly high levels of phytic acid (Paul et al.,


Different views have been expressed on the topic of ‘combination therapy of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB): rational or irrational?’ in the form of correspondences published in the Indian Journal of Pharmacology.–4et al.,[The discussion on this topic started with the editorial by Gautam and Aditya in which they had suggested that the combination of enalapril and losartan is irrational. Tandon, Sharma eet al., and Petret al., have arget al., categoriThe results of the ONTARGET study have been published in a recent issue of the New England Journal of Medicine; the study found that the combination of telmisartan (an ARB) and ramipril (an ACE inhibitor) was associated with more adverse events, without offering any increase in benefits. This particular combination showed higher rates of hypotensive symptoms, syncope, renal dysfunction, and hyperkalemia, with a trend toward an increased risk of renal dysfunction requiring dialysis. The VALI9To sum up, available evidence-based information indicates that the combination of an ARB and an ACE inhibitor is irrational.


Dear Sir,et al.,[We read the article “MRI in T staging of rectal cancer: How effective is it?" by Mulla et al., publisheet al.[However, it would be interesting to know the criterion used by the authors for predicting the involvement of the CRM. Beets et al. have shoet al. have als


The suicide rate in India is 10.3. In the last three decades, the suicide rate has increased by 43% but the male female ratio has been stable at 1.4 : 1. Majority (71%) of suicide in India are by persons below the age of 44 years which imposes a huge social, emotional and economic burden. Fifty four articles on suicides have been published in IJP. Several studies reveal that suicidal behaviours are much more prevalent than what is officially reported. Poisoning, hanging and self immolation (particularly women) were the methods to commit suicide. Physical and mental illness, disturbed interpersonal relationships and economic difficulties were the major reasons for suicide. The vulnerable population was found to be women, students, farmers etc. A social and public health response in addition to a mental health response is crucial to prevent suicidal behaviour in India. More than one lakh lives are lost every year due to suicide in India. In the last three decades (from 1975 to 2005), the suicide rate increased by 43%. The rates were approximately the same in 1975 and 1985; from 1985 to 1995 there was an increase of 35% and from 1995 to 2005, the increase was 5%. However, the male-female ratio has been stable at around 1.4 to 1. There is a wide variation in suicide rates within the country. The southern states of Kerala, Karnataka, Andhra Pradesh and Tamil Nadu have a suicide rate of >15 while in the Northern States of Punjab, Uttar Pradesh, Bihar and Jammu and Kashmir, the suicide rate is <3. This variable pattern has been stable for the last 20 years. Higher literacy, a better reporting system, lower external aggression, higher socioeconomic status and higher expectations are the possible explanations for the higher suicide rates in the southern states .[Majority of the suicides (37.8%) in India are by those below the age of 30 years. The fact that 71% of suicides in India are by persons below the age of 44 years imposes a huge social, emotional and economic burden on society.The near equal suicide rates of young men and women and consistently narrow male:female ratio denotes that more Indian women die by suicide than their Western counterparts. Poisoning (34.8%), hanging (31.7%) and self-immolation (8.5%) were the common methods used to commit suicide .[Fifty four articles on “Suicide” have been published in the IJP from 1958 to 2009. The relative paucity in publications can be attributed to several factors but chiefly to the fact that it is an extremely difficult area to take up for research considering its sensitive nature, associated stigma and legal implications. It is interesting to note that the first article on attempted suicide appeared only in 1965. The articles ranged from references to suicide in ancient literature to psychobiological variables in suicide, epidemiological studies to prevention strategies.The publications have been categorized under (1) Incidence and prevalence studies (2) Profiling and identification of risk factors (3) Suicide and suicidal behavior in specific communities (4)Studies on Non Fatal Deliberate Self Harm (DSH) (5) Suicide prevention strategies (6) and other, suicide related publications. The segregation is for the sake of convenience alone and should not be seen as being exclusive to its allocated category.There have been four studies from abroad published in the IJP that have not been covered in the present review, these comprise of a study on women from Trinidad and Tobago, a study from US on adolescence, on teenage suicide attempters from UK and a Japanese study on pesticide suicides.There have been several studies reporting the incidence of suicide in India. Over the years the studies have reported incidence rates ranging from 2.36 to 42 per 100,000 populations. The majority of these have been hospital based studies along with a few community based samples.In one of the first article on attempted suicide published by the IJP, Venkoba Rao reportedet al.[Nandi et al. studied Hedge in his set al.[In contrast to these reports Shukla et al. in theiret al.[These findings were supported by Banarjee et al. who studMajority of the published studies on suicide have dealt with identifying the socio-demographic and psychosocial aspects of suicide attempters and those who have completed suicide. Some of these have also attempted to identify the characteristic differences between the two groups. Most of these were hospital based studies. The study methods used varied, from use of psychological autopsies to interviews to perusal of records.Venkoba Rao in his hIn another hospital based study Lal and Sethi reportedet al.[Nandi et al. investiget al.[et al.[Bagadia et al. attemptel.[et al. (2004) iet al.[In their study from Ludhiana, Narang et al. reportedet al.[Bagadia et al. conducteet al.[et al.[et al.[These findings were also confirmed by Gupta and Singh who repoet al. investigl.[et al. also foul.[et al. identifiBadrinarayana found a et al.[et al.[Anand, et al. in theirl.[et al. revealedIn his comparison study between suicide attempters and completers, Suresh Kumar, reportedVery few studies pertaining to the biology of suicides have been published in the IJP. The earliest article published was by Devi and Rao, who studet al.[Palaniappan, et al. exploredet al. in theirThere have been several studies which focus on vulnerable populations and high risk populations including students, the aged, women, armed forces, farmers, migrant populations and those with chronic physical and mental illness.Venkoba Rao, in his aet al.[et al.[In an another study on the psychosocial and clinical factors associated with adolescent suicidal attempts Kumar, Sudhir et al. comparedl.[et al. in theirRao Venkoba, studied et al.[In a study on 100 female burns cases admitted at the Madurai Medical college Venkoba Rao, et al. reportedet al.[Jacob, et al. in theirIn a study on terminally ill cancer patients Latha and Bhat examinedet al.[Satyavati investiget al. in theirSrivastava and Kumar in theirIn a study on the armed forces Goel argued tet al.[The need to focus on migrants as a specifically vulnerable group was brought out by the study of Chavan, et al. who usedOn a study on farmer suicides in the Vidarbha region, Behere and Behere employedet al.[Sethi, et al. studied et al.[Sarkar et al. attempteet al.[et al.[Das, et al. in theirl.[et al. who founet al.[In their study on non fatal deliberate self harm attempters, Chowdhury et al. identifiThere have been very few articles that have dealt exclusively with suicide preventive strategies or with a scientific and systematic evaluation of a strategy.Singh in his aVenkoba Rao in his aJena and Siddharta reviewedVijayakumar in an edet al.[Gupta, et al. publisheet al.[Somasundaram et al. in theirA social and public health response to suicide is crucial in India, and should complement a mental health response. Mental illness is a risk factor for suicide, in India, as it is in developed countries. However, additional risk factors are prominent in India. These tend to relate to societal structures and specific stressors. A social and public health approach acknowledges that suicide is preventable, and promotes a framework in integrated system of interventions across multiple levels within society including the individual, the family, the community, and the health care system. A key step in such an approach involves modifying attitudes toward suicide via educational efforts and legal levers .


Environmental chemical exposure has been linked to numerous diseases in humans. These diseases include cancers; neurological and neurodegenerative diseases; metabolic disorders including type 2 diabetes, metabolic syndrome and obesity; reproductive and developmental disorders; and endocrine disorders. Many studies have associated the link between exposures to environmental chemicals and cardiovascular disease (CVD). These chemicals include persistent organic pollutants (POPs); the plastic exudates bisphenol A and phthalates; low molecular weight hydrocarbons (LMWHCs); and poly nuclear aromatic hydrocarbons (PAHs). Here it is reported that though the chemicals reported on differ widely in chemical properties and known points of attack in humans, a common link exists between them. All are lipophilic species that are found in serum. Environmentally induced CVD is related to total lipophilic chemical load in the blood. Lipophiles serve to promote the absorption of otherwise not absorbed toxic hydrophilic species that promote CVD. Lipophilic chemicals are routinely used to promote the permeation of hydrophilic species and are used in pharmaceutical delivery systems since most hydrophilic drugs do not penetrate epithelial barriers at rates necessary for clinical usefulness without lipophilic permeability enhancers . Kow is indicative of the relative lipophilic character of a given chemical. It is defined as the logarithm of the ratio of that quantity of chemical dissolved in the n-octanol phase to that dissolved in the water phase of an octanol-water mixture. Species with Kow of 2.00 or higher are considered lipophilic and those with Kow values of less than 2.00 are labeled as hydrophilic Zeliger, .As a general rule, hydrophilic chemicals are more acutely toxic than lipophilic chemicals as can be seen from their permissible exposure levels , permissible exposure levels (PEL), or maximum contamination level (MCL).It has been previously shown that mixtures of toxic chemicals containing at least one lipophile and one hydrophile produce effects that are not predicted from the known toxicology of the individual species. These effects include attack on organs and systems not known to be impacted by the individual species and low-level toxicity induced by exposures to concentrations far below those known to be toxic by the single chemicals in the mixtures Zeliger, . The corIn all the published studies, the levels of lipophiles in the blood are far lower than those known to be acutely toxic for the individual species.Total lipophilic load in serum is postulated as responsible for the induction of CVD. As used here, total lipophilic load refers to the total concentration of all exogenous lipophilic chemicals found in serum, without specification of individual chemical species.et al., et al., et al., et al., et al., Mechanisms by which environmental chemicals trigger cardiovascular diseases have been proposed. These include: include oxidative stress  have been found to be associated with CVDs. The POPs include PCBs, OCs, dioxins and furans, PBDEs and PFOEs. Plastic exudates include BPA and phthatlates. LMWHCs include benzene, toluene, ethyl benzene, xylenes, C3–C8 aliphatics, gasoline, chlorinated methanes and ethanes and chlorinated ethylenes. PAHs include the following 17 compounds:Though most studies on PAHs have been carried out on benzo[a]pyrene, all 17 of these compounds have been associated with cardiovascular disease and all are environmental pollutant products of the combustion of fuel and tobacco smoke ATSDR, .Diethylhexyl phthalateDibutyl phthalateDi-n-pentyl phthalateDicyclohexylphthalateDiallyl phthalateDiethyl phthalateDiisodecyl phthalateDi-n-hexyl phthatateDiisobutyl phthalateDi-n-octyl phthalateDiisononyl phthalateDiheptyl phthalateMany different phthalates are used in the manufacturing of phthalates. These include the following 12 compounds ; triclosan, an antibacterial compound widely used in tooth paste, cleaners and other consumer products , phthalates, BPA and hydrocarbons. These chemicals come from a variety of chemical classes that include chlorinated and brominated hydrocarbons, esters, ethers, polynuclear aromatic hydrocarbons, mononuclear aromatic hydrocarbons and straight chain aliphatic hydrocarbons. These chemicals differ widely in chemical properties, reactivities and rates of metabolism and elimination from the body.et al., et al., et al., et al., POPs are long-lived and accumulate in white adipose tissue (WAT) from which they can transfer to the blood and be transported around the body , endocrine disruption , periodontal disease (Lee et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Support for this proposal comes from a consideration of other environmental diseases that have been attributed to exposures to these chemicals. POPs exposures have been associated with type 2 diabetes (Zeliger, et al., et al., As previously discussed, PAHs, emanating from the combustion of fossil fuels and tobacco, are considered to induce cardiovascular disease. Several of the studies cited have made the association with inhalation of fine particulates rather than with the PAHs (Costello, et. al., et al., et al., et al., et al., et al., et al., It is to be noted that although the literature relating CVD to other exogenous lipophilic chemicals is scanty, both triclosan (Cherednichenko Cardiovascular disease is rising rapidly throughout the world. It is proposed here that this increase is due in large part to increased exposure to exogenous lipophilic chemicals which, though varying widely in structure, toxicology and chemical reactivity, render the body susceptible to attack via subsequent exposure to low levels of hydrophilic toxins that would otherwise not be absorbed. The lipophilic chemicals can be POPs that are metabolized and eliminated slowly, or BPA, phthalates, PAHs, LMWHCs and other lipophilic species that are eliminated from the body more rapidly, but are constantly replenished in the body from polluted air and water and contaminated food. The accumulation of lipophilic chemicals in the body proceeds until a critical level is reached, at which point the body is vulnerable to attack by low levels of toxic hydrophilic chemicals that would otherwise not be toxic. Sequential absorption of lipophiles followed by hydrophiles provides a unified explanation of how low levels of far different environmental pollutants are responsible for the growing pandemic of cardiovascular disease and other environmental diseases. These findings suggest that allowable levels of exposure need to be dramatically lowered and that research be carried out to find ways to help the body eliminate even low levels of serum exogenous lipophilic chemicals.


Complete surgical resection is associated with improved outcomes in gallbladder cancer. Whether the extra-hepatic bile duct (EHBD) should be routinely excised for gallbladder cancer is unclear. Objective: To analyze literature concerning EHBD excision to determine if it is associated with survival advantage and hence can be routinely recommended.A systematic search using Medline, Embase, and Cochrane Central Register of Controlled Trials for the years 1988-2008.EHBD excision was reported to be performed routinely for T1-4 in some studies, while others reported resection to facilitate lymph node clearance or if the EHBD was grossly involved by disease that remained otherwise resectable. While one study demonstrated 100% survival in T1 disease, other reports do not demonstrate any survival benefit of EHBD excision in T1 disease. Four studies (level IV-V) demonstrated 60% to 90% five-year survival for routine excision in T2 disease, while three other studies demonstrated no survival advantage but increased morbidity due to the procedure. In T3/4 disease, one study (level IV-V) demonstrated a benefit in T4 disease only, and another study (level IV-V) reported a survival advantage in patients in whom the bile duct was not involved; five other studies showed no impact of routine EHBD excision on survival but reported morbidity following anastomotic leaks.Available evidence does not support routine resection of EHBD in gallbladder cancer. EHBD excision should be performed in the presence of specific indications, viz., to achieve an R0 resection of the primary tumor and/ or to aid complete lymph node dissection that would compromise the EHBD by devascularization. It is widely accepted that complete surgical resection offers the best chance of long-term survival in gallbladder cancer.–18 HowevWhile some surgeons routinely recommend the resection of the extra-hepatic bile duct (EHBD) for gallbladder cancer, the possibility of post-EHBD-resection complications and the lack of a survival advantage lead us to the question, “Does the EHBD need to be routinely resected in gallbladder cancer?”While the patterns of spread of gallbladder cancer have been presented by various authors,1920 the 19How is the EHBD involved in gallbladder cancer?What is the justification of an EHBD resection?Should the bile duct be resected in all stages of gallbladder cancer?An extensive and systematic Medline and Embase search was performed to identify the existing literature on resection of the EHBD in gallbladder cancer. The search terms used included ‘gallbladder cancer,’ ‘extra-hepatic bile duct,’ ‘resection,’ ‘hepatoduodenal ligament,’ ‘radical,’ ‘aggressive,’ ‘surgery,’ ‘anastomotic leak.’ Using the above search terms yielded a total of 981 publications published in the last 30 years. These publications were then analyzed specifically looking at those papers which addressed the resection of the extra-hepatic bile duct in gallbladder cancer. Of the 51 papers thus retrieved and referenced in the current review, only 15 that actually looked at the impact of extra-hepatic bile duct resection on outcomes of gallbladder cancer were analyzed.While considering the development of gallbladder cancer, it is important to realize that there are differences in the pathophysiology of gallbladder cancer in different parts of the world. The basiet al.,29]et al.[et al.[et al.[et al.[et al.[et al.,[Suzuki et al. suggestel.[et al. supportel.[et al. found thl.[et al. were impl.[et al. They alsl.[et al. Shirai el.[et al.35 recomml.[et al. while thl.[et al. suggeste.[et al., too, advet al.[et al.[et al.[et al.[Todoroki et al. recommenl.[et al. Kosuge el.[et al. recommenl.[et al. This stul.[et al. did recoet al.[Kaneoka et al. routinelConsiderable data has accumulated over the last few years to substantiate the argument that routine excision of the EHBD is not warranted in gallbladder cancer . The two11311131Literature on the role of EHBD resection for gallbladder cancer is confusing and at times contradictory. This probably stems from a number of factors: the most likely being the low number of cases of gallbladder carcinoma and their uneven distribution around the world, the often delayed presentation by patients who attribute the early symptoms to other common benign diseases including gallstones, a possible difference in aggressiveness amongst surgeons while managing such patients, and the possibility of a varied pathogenesis (as highlighted above). Also, the management strategies employed in the treatment of gallbladder cancer center around the T stage. However, the inability to accurately predict this T stage preoperatively leads to further confusion, with some surgeons preferring to do more, rather than less, given the dismal prognosis associated with a non-curative resection. So, is there sufficient evidence to support the routine resection of the bile duct irrespective of the T stage of the disease?A closer analysis of the studies supporting the routine resection of EHBD for early stages seems to indicate that there have been instances where some groups have chosen to be conservative with regard to the EHBD, and it has not affected survival.et al.[et al.[et al.[et al.,[In the case of patients with T1 disease, Shimada et al. found thl.[et al. found nol.[et al. The auth.[et al., who founet al.[et al.[et al.,[Suzuki et al. noted thl.[et al. compared.[et al., the outcet al.[et al.[et al.[Further, the data supporting the role of routine EHBD resection in stages II-IV seems to be contradictory based on the conclusions of Chijiiwa et al. and Kosul.[et al. Studies l.[et al. that in Thus, for T2 cancers and even some T3 tumors, in the absence of gross nodal disease, a resection that includes a cholecystectomy with a wedge resection of the gallbladder bed/ segment IVB and V resection, along with a regional lymph nodal dissection, has been shown to constitute a curative surgery.4246–4942et al.[et al.,[39The role of EHBD resection in the presence of bile duct involvement is also very confounding. However, what seems to emerge is that the involvement of the bile duct in gallbladder cancer is itself a poor prognostic indicator of survival. Sikora et al. had prev.[et al., the over.[et al.,3940 BesiThe studies highlighted in Indications for the resection of the EHBD in all stages of disease include —Tumors involving the EHBD - PreopeTumors/gross lymph nodal enlargement close to or involving the common hepatic duct or hilumInflamed or a fatty hepatoduodenal ligament rendering nodal dissection difficultPatients undergoing re-resection (since postoperative inflammation makes differentiation of tumor and scar difficult).50 This iPositive cystic duct margin on intraoperative frozen sectionCystic duct cancers43Patients with associated APBDJ /choledoIn case of need for associated vascular resection/ reconstructionWhile theoretically there is the possibility of involvement of the EHBD in gallbladder cancers, the synchronous existence of a malignancy in the EHBD and the gallbladder is uncommon. In the absence of convincing data to demonstrate a survival advantage for the routine excision of the EHBD in gallbladder cancer, the morbidity of the procedure needs to be taken into consideration. This is because the most important complication following bile duct resection and reconstruction, is the development of an anastomotic leak with its attendant short-term sequelae of sepsis and peri-operative mortality; also, there are long-term effects like stricture formation and repeated attacks of cholangitis, rendering the patient a “biliary cripple.” Given the biases in different parts of the world with regard to the excision of the EHBD, it seems unlikely that a randomized controlled trial would be undertaken. In the absence of level 1 evidence to support the routine resection of the EHBD in gallbladder cancer, such a resection should be performed only in the presence of the specific indications, viz., to achieve an R0 resection of the primary tumor and/ or to aid the performance of a complete lymph node dissection that would compromise the EHBD due to devascularization.


A case of a female child born at full term after normal vaginal delivery with bilateral secondary complete cleft palate and vomerine hamartoma mimicking intra-oral midline encephalocoele. Radiologically the tumour was confined to the vomer without intra-cranial extension. The lesion was occupying the oral cavity causing feeding problem. Surgical excision of the tumour at the age of six months and two flaps palatoplasty at the age of twelve months were performed. On histopathology the lesion turned out to be a lipomatous hamartoma of a benign nature. The child was followed for 9 years with no evidence of recurrence and a satisfactory speech. To our knowledge this is the first report of cleft palate with vomerine hamartoma in the English literature. Congenital malformations may be the product of errors in embryogenesis or the result of intrauterine events disturbing embryonic and foetal growth. Hamartomas and teratomas presenting at birth are tumour-like malformations of anatomical developmental error.–4 Hamart12A female child, a product of a full term spontaneous normal vaginal delivery, with a birth weight of 3.500 kg and the Apgar at birth, 5, and 15 minutes was 9, 11, and 14, respectively had a positive parental consanguinity and positive family history of cleft palate. She presented to our clinic at the age of four days. Clinical examination revealed bilateral complete cleft palate and a midline palatal mass extending to the palatal shelves laterally and alveolar arch anteriorly measuring about 4cm × 3cm × 0.5cm . The lipAt the age of 6 months, under general anaesthesia and endotracheal intubation the tumour mass was excised leaving a sleeve of mucosal tissues on either side for closure . Histopaet al.[et al.,[et al.,[et al.,[et al.,[et al.,[et al.[Hamartoma of the oral cavity is a rare tumour.–10 The l.[et al., Piattell,[et al., De Biase,[et al., Liang et,[et al., and Zait.,[et al. made theet al.[et al.[et al.[Takeyama et al. describel.[et al. has repol.[et al. reportedHaving a cleft palate and a vomerine or palatal tumour would be preferably managed by starting with tumour excision at the age of 3–6 months. This would solve the problem of dysphagia or dyspnoea if present, give more time to study the lesion histologically, and to evaluate the risk of recurrence or the need for re-excision. Consequently, definitive treatment of the cleft can take place later at the age of 9–12 months. More reports of these rare tumours are needed to understand their nature and behaviour.


With the advent of new antiepileptic drugs comes the potential for significant advances in the emergent management of status epilepticus. Traditional antiepileptic drugs possess side effect profiles that may limit their clinical utility or lead to increased patient morbidity or mortality. The relatively recent development of levetiracetam shows promise for effective control of acute status epilepticus in adults, but current objective data of its use as a first-line agent for control of status is quite limited. This paper serves to examine existing literature while considering levetiracetam as a first-line therapy in status in the adult patient population. Although existing studies are narrow in their scope, the present data lay a substantial foundation for further investigation of levetiracetam as a primary therapy in acute status epilepticus. The emergent management of status epilepticus has been restricted to a small subset of antiepileptic drugs suitable for acute intravenous infusion. Of the three major traditional drugs used in first-line therapy for status, each carries a side effect profile that may ultimately lend to limited clinical utility in the critical patient. Lorazepam, phenytoin, and phenobarbital individually convey specific risks to the patient, among them respiratory depression, medication interaction due to cyp450 induction, and teratogenicity . Each ofGiven its minimal known side effect profile, limited drug interactions, and availability as a rapid delivery IV formulation, levetiracetam, a relatively new AED by comparison, may be a viable, and practical option in the first-line management of status epilepticus , 3. StatThe traditional approach taken in the emergent management of status was described by Riviello et al.  in theirThe reasoning behind the traditional management of status is perhaps most apparent in Brophy et al.’s  discussiWhile levetiracetam is approved as an adjuvant agent for the management of status, data on its use as a first-line therapy is quite limited, as noted in the Neurocritical Care Society’s Guidelines discussed previously. Review of available literature via PubMed search reveals fewer than 10 reports of levetiracetam used as a first-line agent in status, with only a single randomized pilot study and a limited number of case and retrospective reports available in current publication. Despite this, evaluating existing data as a whole opens the discussion for levetiracetam administration as a first-line approach in status epilepticus.A clinical pilot performed by Misra et al.  providesIn a review written by Zelano and Kumlien , levetirLevetiracetam’s limited side effect profile makes it particularly appealing in older patient populations, where drug interaction and the potential for intubation leading to significant mortality is of great concern. Fattouch et al. explored this in a limited retrospective of nine patients, older than 65 years old with video EEG confirmed status epilepticus who received loading doses of 1500 mg IV levetiracetam as a first-line agent . Eight oAdditionally, Farooq et al.  reportedBerning et al.  addresseIt is the potential for limited increase in mortality that makes levetiracetam particularly appealing for first-line use in critically ill patients, which was explored by Rüegg et al. . In theiSpencer et al.  pointed Nau et al.  served tLiu et al.  served tAiguabella et al.  set out While clinical studies of the use of levetiracetam are undoubtedly not yet sufficient to dictate large-scale changes to clinical practice, a substantial foundation for future clinical trials has been laid. Given multiple case reports of successful use of levetiracetam as an initial agent in the emergent treatment of status, there is certainly basis for the development of larger scale randomized controlled trials allowing for a direct, standardized comparison between traditional first-line agents and levetiracetam for emergent management of status epilepticus. The clinical utility of levetiracetam is most suggested by Misra et al.’s  pilot stSuch a hypothesis exists that levetiracetam may well fit the description of an ideal agent as outlined by Reugg et al. . Lyseng Certainly no pharmacotherapy is without fault, and it remains both possible and likely that levetiracetam carries administration concerns not yet apparent to clinical practitioners. Just as our understanding of its clinical benefits are restricted by limited data, so too is our comprehension of its potential pitfalls. With the growing establishment of levetiracetam’s clinical pedigree, as well as ever-increasing desire for an efficacious, accessible, and comparatively benign agent for the emergent treatment of status, levetiracetam may prove a worthy contender in the future of acute treatment of status epilepticus.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Maternity care providers, particularly midwives, have a window of opportunity to influence pregnant women about positive health choices. This aim of this paper is to identify evidence of effective public health interventions from good quality systematic reviews that could be conducted by midwives.Relevant databases including MEDLINE, Pubmed, EBSCO, CRD, MIDIRS, Web of Science, The Cochrane Library and Econlit were searched to identify systematic reviews in October 2010. Quality assessment of all reviews was conducted.Thirty-six good quality systematic reviews were identified which reported on effective interventions. The reviews were conducted on a diverse range of interventions across the reproductive continuum and were categorised under: screening; supplementation; support; education; mental health; birthing environment; clinical care in labour and breast feeding. The scope and strength of the review findings are discussed in relation to current practice. A logic model was developed to provide an overarching framework of midwifery public health roles to inform research policy and practice.This review provides a broad scope of high quality systematic review evidence and definitively highlights the challenge of knowledge transfer from research into practice. The review also identified gaps in knowledge around the impact of core midwifery practice on public health outcomes and the value of this contribution. This review provides evidence for researchers and funders as to the gaps in current knowledge and should be used to inform the strategic direction of the role of midwifery in public health in policy and practice. The reproductive period offers maternity care providers the opportunity to maximise the health and well-being of women and their families potentially impacting on public health outcomes, both short and long term. Although all maternity care providers who engage with pregnant women are presented with such opportunities, it is the midwife that could have the most significant impact from regular contact and building of relationships through continuity of care. There are interventions that could be implemented by midwives, which potentially would have a public health impact but it is important such interventions are evidence based. Recognition of the importance of the relationship between public health and midwifery was highlighted when a general review of midwifery in the UK, named phttp://www.midwifery2020.org. A systematic review of systematic reviews was selected as the methodology, given the breadth of this topic area and the timescale of the project. This paper outlines the review methodology and builds on the original review findings by providing new and updated information about effective high quality public health interventions which could be implemented by midwives or other health care providers for women during pregnancy and the postnatal period who have a similar role, for example, public health nurses, obstetric nurses, labour and delivery nurses or health visitors.This paper presents an update of a systematic review of systematic reviews conducted in 2009. The aim of the 2009 review was to evaluate the effectiveness of interventions relevant to the public health role of the midwife. The 2009 review was commissioned and conducted within the context of the Midwifery 2020 initiative. The final report of the Midwifery 2020 initiative (Delivering Expectations) and full report of the systematic review of reviews are avaiet al.[The Preferred Reporting Items of Systematic reviews Meta-Analyses (PRISMA) guidelines was adhered to when conducting this review. A systeet al..Databases searched included: MEDLINE, PubMed, EBSCO (CINAHL/British Nursing Index), MIDIRS Online Database, Web of Science, The Cochrane Library, CRD (NHS EED/DARE/HTA) and EconLit. Eligibility criterion included reviews published from 1999 onwards; English language publications and reviews originating from economically developed countries as indicated by membership of the Organisation for Economic Co-operation and Development (OECD). An additional search was conducted of the National Institute for Health and Clinical Excellence, UK (NICE) website to identify key publications or findings from systematic reviews within guidelines. Reference lists of identified reviews were manually searched for additional relevant reviews. The searches were initially conducted in November 2009 and updated in October 2010. The titles and abstracts were obtained and the decision process for eligibility was conducted by all members of the project team in collaboration . Full text was obtained of all eligible reviews and those whose eligibility could not be discerned from reading the abstract. Eligible systematic reviews also had to publish a clearly identified search strategy or detail the reference databases used.Data were extracted on: number of papers included in the review; methodological details; midwifery intervention; outcome measures and results. Data were systematically extracted using a data extraction form by individual project team members and verified by one other project team member. The project team subsequently met to discuss and achieve consensus regarding any contentious issues. A parallel process of developing a logic model to act as an overarching framework to inform forward planning was also conducted. Logic models are essentially a conceptual framework, which can be used for evidence‐based decision making and planning. The modet al.[et al.[any public health intervention relevant to midwifery. However for the purpose of this paper the focus was to report on public health interventions relating to midwifery that demonstrated a statistically significant effect in favour of the intervention (referred to subsequently as effective interventions for the sake of brevity). Reviews graded 1- or above and of high methodological quality which reported evidence of no effect, are not discussed in this paper. However, they have been summarised in TableIt is important to consider both the type of evidence included in reviews i.e. was the review restricted to randomised trials only or were other types of studies included and also assess how well the review was conducted methodologically. As such, a two stage process was employed: initially the level of evidence was graded and secondly, the methodological quality was assessed. Recognised frameworks were used to support this process,14. In tet al.. Reviewsl.[et al.. A diffeA narrative review is provided for each of the systematic reviews and in table format the number and date range of papers included, intervention(s), primary outcome or other public health outcomes of interest, results  are described and whether the review included a meta analysis or not. It was not expected that a quantitative analyses would be conducted given the diversity of interventions across the broad subject of public health.In total 214 systematic reviews were eligible of which 91 reported on effective interventions and 117 found no effect or were inconclusive. This paper only reports on high quality reviews with a level of evidence grading above 1-. Of the 91 systematic reviews which reported on effective interventions, 36 were identified which were graded as evidence level 1- or above and rated as high quality. The flow chart in FigureThere were no high quality reviews that reported on effective interventions in the pre conceptual period.The majority of reviews reporting effective interventions were relevant to the antenatal period (n=20). Included reviews have been grouped into screening, supplementation, support, education and mental health.et al.[et al.[et al.[et al.[et al.[et al.[Reviews (n=4) related to screening reported on interventions relating to ultrasound,27, loweet al. conductel.[et al. however,l.[et al. indicate.[et al.. The rev.[et al. conducteet al.[Eight reviews-37 consiet al. reviewedet al.[et al.[et al.[et al.[Calcium supplementation was the focus of three reviews-36. Hofmet al. reportedl.[et al. reportedl.[et al. on calcil.[et al. reviewedet al.[Three reviews-40 consiet al. reviewedet al. assessedet al.[et al.,[et al.[et al.[et al.[et al.[Educational interventions in the antenatal period were the focus of four systematic reviews-44 that et al. reviewed[et al., reviewed,[et al. and Lemol.[et al. reportedl.[et al..One review by Dennis & Creedy considerEligible systematic reviews relevant to the intranatal period yielded the smallest number in comparison to either the antenatal or postnatal periods. Five reviews-50 were et al.[Cluett & Burns reviewedet al. reviewedet al.. Althouget al.[et al.[et al.[The birth setting was the subject of four reviews although all were on different aspects. Hodnett et al. reviewedl.[et al.. The intl.[et al. concludeOne review considered interventions aimed at reducing caesarean section rates. ChailleEleven reviews-61 reporet al.[et al.[et al.[et al.[et al.[et al.[2 =55%; p= 0.006). The authors also highlighted an increased rate (22%) of any  and exclusive  short term breastfeeding with interventions that included a component of lay support. Sikorski et al.[et al.[2=53.4%). Early skin to skin contact was reviewed by Moore et al.[Reviews on this topic generally related to either support or promotion of breastfeeding. Britton et al. reviewedl.[et al. and Sikol.[et al.. Breastfl.[et al. and Chunl.[et al. involvedl.[et al. from a mki et al. reviewedl.[et al. focused re et al. reviewedOne review focused on improving maternal mental health and considered postnatal psychological and psychosocial interventions. Dennis et al.[One review considered support for women in relation to weight reduction in the post partum period focusinget al. demonstrThe parallel development of the logic model resulted in a summary model Figure providesThe focus of this paper is the development of the public health role of the midwife based on effective interventions and highlighting the short, medium and long term effects that these interventions could bring about. Any intervention must be considered within the context in which it is to be delivered as inequalities, resources, culture and vulnerable groups can influence the choice of intervention to best suit the population of women being served. The second column represents the inputs or activities; these are the interventions which are intended to bring about the change in outcomes. In relation to public health and midwifery these are interventions that may impact on public health primarily through education, screening and support. The outputs are the products or the targets of the service delivered and can been seen in the boxes entitled organisation of care under short and medium term outcomes. While the logic model provides a visual outline of midwifery public health roles, using this approach facilitates understanding of how public health programs can be planned and subsequently evaluated. Conducting the data synthesis in tandem with developing the logic model has also highlighted where the gaps in knowledge are and identified areas where midwives could potentially have a much greater role and subsequent impact on public health.This paper sought to report on systematic reviews providing high quality evidence of effective interventions, in essence the ‘cream of the crop’. Reviews reporting on effective interventions were those which presented a statistically significant meta analysis or where the intervention was supported by a generally positive trend of results when a meta analysis was not possible to ensure the recommendations of the paper are based on strong evidence of good quality. There were a number of reviews included which presented statistically significant positive findings. However, in some cases these were limited by small numbers of participants or small numbers of trials included in the review. As a result of conducting the review and analyzing eligible systematic review evidence, three key areas for future consideration were identified including: recommendation and implementation of effective evidence; gaps in knowledge and developing the role of the midwife in public health which are discussed further in the following sections.It is clear from this review of effective interventions, there are areas where evidence has been incorporated into guidelines and thus recommended for implementation into routine practice. However, it has also highlighted many areas where it has not. There has been extensive debate and commentary in the literature about knowledge transfer and translation of knowledge into practice, however, this paper confirms that despite the existence of good quality evidence, the gap remains. From this review, several effective interventions were identified, which are already recommended as routine practice, for example education about folic acid supplementation and pelvic floor muscle training to prevent or reduce the risk of urinary incontinence are advocated by current practice guidelines in the UK and furtThe review identified many gaps in systematic review literature relating to core midwifery practice, which potentially could impact on public health population goals. The UK Department of Health, Public Health Strategy emphasizIn order for midwives to utilise their potential in relation to public health it is important not only to consider the interventions that could be implemented but also take cognisance of wider strategies and policy relating to public health. The logic model Figure, which wet al.[There are a number of methodological challenges in using systematic review evidence which must be taken into account. It is difficult to summarise the evidence from systematic reviews as often there is significant diversity between interventions included in individual reviews or outcome measures used. In addition the results presented may be inconsistent between reviews or inconclusive, however, Smith et al. suggest et al. highlighet al.. HoweverThis paper has reported on high quality effective interventions identified from a larger systematic review on public health interventions that could be delivered primarily by midwives or maternity care providers. From the effective interventions identified it is clear that while some have been recommended for implementation into routine practice, others have not. This highlights the continuing gap between evidence and practice and the need for professionals and researchers to work better together to ensure specific interventions that are effective, are translated into practice and subsequently audited to provide evidence of knowledge translation. The public health role of the midwives has not been well researched or reviewed and the impact of everyday midwifery practice on longer term, holistic maternal and family well-being outcomes is poorly articulated in review literature. A shift in research, policy and practice is needed to fully articulate the public health role of the midwife. This systematic review of systematic reviews identifies a number of effective interventions that provide a useful starting point on which to build future practice. The logic model demonstrates the need to fill in major gaps in our knowledge on effective interventions to achieve both short and long term public health benefits for women and their families. Such benefits will remain elusive without investment in a collaborative, strategic approach to the role of public health in midwifery.The authors declare that they have no competing interest.Ms Liz Bannon, Senior Midwife, & Co Director of Maternity Services, Social Services, Family & Child Care Belfast Health and Social Care Trust, Belfast, Northern Ireland; Professor Debra Bick, Professor of Evidence Based Midwifery Practice, Kings College London, England; Dr Helen Cheyne, Nursing, Midwifery & Allied Professions Research Unit, University of Stirling, Scotland; Professor Mike Clarke, then Professor of Clinical Epidemiology & Director of UK Cochrane Centre, now Professor/Director of MRC Methodology Hub, Queen’s University Belfast; Ms Joanne Gluck, Consumer Representative; Professor Billie Hunter, Professor of Midwifery, Swansea University, Wales; Dr Dermot O’Riley, Centre of Excellence for Public Health Northern Ireland, Queen’s University Belfast, Northern Ireland.JM extracted and interpreted data and wrote the first draft of the manuscript. FL conducted the searches of the literature, extracted and interpreted data and assisted with the manuscript. FA extracted and interpreted data and assisted with the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/955/prepub


In a recent issue of Current Biology, Ventura and Worobey  reviewedAmong the numerous factors discussed by the authors the genetic influence seems to cover a key role.The review addressed this aspect by discussing the growing research about the genetic factors which are responsible of the individual differences in perceiving flavors. For example, the authors reported that the TAS2R38 gene polymorphism is predictive of the level of bitterness  perceived when tasting some particular compound . The opioids have a role in the regulation of mechanisms of the hedonic impact (food “liking”), although they are able to modulate the “waiting” processes as well  and hyperphagia, which are characterized by two antithetic feeding behaviors, provide important evidence in support of the neuromodulator hypothesis.The core of the AN disorder is characterized by a marked disgust sensitivity for food and the human body (Troop et al., From a genetic point of view, there is evidence that the expression of the D2 dopamine receptor might play a role in the feeding behavior of AN. Bulik et al.  have shoSerotonin polymorphism has been also associated to AN. A recent meta-analysis (Calati et al., Hyperphagia is characterized by a strong desire to consume palatable, high calorie foods. Disgust seems to be reduced in these patients, which could, at least partly, explain their increased appetite (Houben and Havermans, 2 receptor in this region compared to lean individuals (Wang et al., It was already shown that a reduced serotonin 5-HT patter of neurotransmission may precipitate in compulsive eating behavior (Blundell, Even for this clinical condition, interesting insights are provided by the literature on the neuromodulators polymorphism. For example, a recent study (Dykens et al., There is also evidence of a relationship between dopaminergic polymorphism and hypherphagia. For example, a strong relationship was shown between a gene involved in the synthesis of dopamine, the A1 allele of the DRD2/ANKK1-TaqIA, and obesity (Felsted et al., Finally, it was shown (Davis et al., The evidence that the polymorphism of the above mentioned neuromodulators is able to affect the feeding behavior by influencing the hedonic experience and the motivational state of the individual, certainly provide intriguing elements of investigation for disclosing which factors might have an early influence on taste perception and preferences. In this framework of reference, it might be intriguing also to explore if the mentioned polymorphisms influence taste receptor function and the perceived palatability of food. This might be of particular relevance for serotonin, which is already known to participate within the bud (Kaya et al., However, we should keep in mind the study of de Araujo et al.  which reThis supports the suggestion that the inborn taste preference and avoidance might be founded on mechanisms of molecular polymorphism involving a central regulation; while the molecular polymorphism affecting the taste receptors might express its role by regulating the intensity of the hedonic/ disliking experience associated to a flavor.


Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo-vascular cross-talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla.Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle-like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and  An increase in net MBF would result in ‘washout’ of the cortico-medullary osmotic gradient Cowley  and impaet al. et al. et al. et al. It has been suggested previously that pericyte-mediated changes in DVR diameter can regulate MBF and alter its distribution in response to changes in active NaCl transport and the oxygen demands of renal tubular cells  velocity at two separate points on the same capillary], to determine blood flow, velocity and vasa recta diameter in the exposed rat papilla concluded that MBF is regulated within a limited arterial pressure range (125–130 mmHg) and that regulation of MBF is governed upstream by renal arterial pressure  techniques to measure regional red blood cell flux  have also failed to provide any clear answers  , endothelin-1 (ET-1), nitric oxide (NO), adenosine and prostaglandin E Pallone .2, NO, adenosine, adenosine triphosphate (ATP),] as are interstitial cells (PGE2) and sympathetic nerves  , hydrogen peroxide (H2O2) or hydroxyl free radical (OH)  are also known to be potent regulators of MBF methyl]-L-ornithine, methyl ester, monohydrochloride (L-NAME), a NO inhibitor, have demonstrated that inhibition of endogenous NO in live kidney slices shows pericyte-mediated vasoconstriction of vasa recta capillaries  and collecting duct epithelial cells (Pallone 2-mediated vasodilation is thought to increase NaCl excretion (Silldorff et al. 2 itself may modulate solute absorption along the nephron through its direct action at pericytes. Crawford et al. (in situ vasa recta, specifically at pericyte sites (Crawford et al. et al. et al. et al. in situ vasa recta, which is direct evidence for tubulo-vascular cross-talk in the medulla (Crawford et al. Similarly, the constrictive effects of both ET-1 and Ang-II are subject to attenuation by vasodilatory PGE Pallone . The ensd et al.  have demet al. et al. In support of this key role for pericytes in the kidney, there are similar studies describing pericyte communication or interactions with adjacent cell types in other systems. For example, retinal and cerebellar pericytes respond to changes in the metabolic demands of the surrounding neurones and alter capillary diameter accordingly; however, the exact mechanism by which this occurs is still unclear (Wu et al. et al. et al. et al. et al. In the retina, it is well established that loss of pericyte function is an instrumental factor in the development of pathological conditions such as diabetic retinopathy (Sakagami et al. et al. et al. et al. in vivo is still heavily debated (Wada et al. et al. et al. et al. et al. in vivo or ex vivo using cell markers because alpha-SMA, a commonly used myofibroblast marker, is also expressed by pericytes (Park et al. et al. In the kidney, a role for pericytes in the pathogenesis of renal fibrosis and progression of chronic kidney disease has been proposed (Lin in vitro cell culture approaches to isolated vessel preparations and LDF have been employed to further our understanding of MBF regulation. To make significant advances, the technical problem of renal medulla inaccessibility must first be overcome. As already discussed, early approaches to the investigation of MBF regulation based on the LDF technique or the dual-slit imaging method have been inconclusive. To date, the best-established technique for studying pericyte-mediated regulation of vasa recta is the isolated perfused DVR method (Pallone et al. in vivo, and it is at least consistent with our proposal that pericytes may be key mediators. The in vitro blood-perfused juxtamedullary technique (Casellas & Navar et al. A variety of experimental techniques from  Pallone . Althougin vivo and in vitro experiments (Layton & Layton Mathematical modelling has also been applied to investigate the regulation of MBF (Zhang & Edwards in vitro experimental model in which medullary structures can be investigated in situ. As with most techniques, this model is not without its limitations. For example, it is not possible to simulate the osmotic and oxygen gradients present in vivo, and DVR in the live slice model are not perfused (Crawford et al. in situ environment, and data collected using this model have confirmed that in vitro observations regarding pericyte activity are reproducible, and new insights into pericyte activity and regulation are being described (Crawford et al. et al. per se is a well-established model for investigating brain function and has previously been used to investigate the role of pericytes in regulating the cerebellar microcirculation (Peppiatt et al. A recent development of a live kidney slice model provides an alternative In summary, there appears to be significant experimental evidence, which favours regulated blood flow in the medulla, and this complements the need for maintained homoeostasis in this region. We propose pericytes are key players in the regulation of renal medullary function, a proposal that is supported not only by their physical location on the vasa recta, but also by evidence describing their ability to respond to endogenous vasoactive agents originating from neighbouring tubular and interstitial cells. There is still much to understand about renal pericyte activity, particularly about their ability to communicate with neighbouring structures and the way in which they transcribe changes in tubular function to changes in blood flow. However, technical advances coupled with increased interest, particularly because of the implication of pericytes in renal disease, should rapidly lead to increased understanding of pericyte activity in renal physiology and pathophysiology.