Drozdowska et al.; Etherton et al.; Fabian et al.; Fandler et al.; McKinley et al.; Taylor-Rowanet al.; van de Graaf et al.; Wouters et al.; Zhou et al.) to evaluate the current state of knowledge about reperfusion therapy with the goal of educating our readership about the patient selection paradigms, challenges in clinical trial design, and identifying future directions.Endovascular thrombectomy to recanalize large vessel occlusions in ischemic stroke patients is now proven to improve clinical outcomes in randomized trials –6. This Wouters et al.; . McKinley et al. also acknowledge that deconvolution techniques are highly susceptible to noise and artifacts; they list measures to overcome these issues e.g., by adoption of a smoother residue function; and they report machine learning methodologies to identify the tissue-at-risk. The authors suggest that the best algorithms are those which are based on neural networks and random forests . Finally, Etherton et al. summarize the neuroimaging paradigms and the clinical trials that tested reperfusion therapy in stroke patients with unknown time of symptom onset. Perfusion mismatch, DWI-FLAIR mismatch, and other mismatch paradigms are discussed, and prognostic value of some of these measures discussed . The authors propose that more patients can be offered reperfusion therapy by refining the approach to identify additional populations of stroke patients with unknown onset who may benefit . The target of therapy—the tissue-at-risk (penumbra)—is better defined now and therefore there is greater opportunity to test preclinical research findings in the contemporary standard of care. To this end, we include Fabian et al. and Zhou et al. in this collection who report their data about methods to enhance ischemic preconditioning and to reduce oxidative stress respectively in acute stroke. Also, recanalization is not equivalent to reperfusion, and the goal should be to succeed with both .We now know that the benefit of endovascular recanalization in ischemic stroke patients with a target perfusion mismatch profile is independent of the time since symptom onset –16. Howe et al.; ]. Wouterith both . A largeFandler et al. present one example as a case report highlighting excellent outcomes from endovascular therapy in a patient with ischemic stroke who had a stroke recurrence within 9 days of the first thrombectomy. The subsequent stroke occurred in exactly the same vascular territory, was associated with significant mismatch, and continued to show irregular shaped ulcerated plaque. Fandler et al. offered endovascular treatment with TICI 3 recanalization with excellent outcomes on follow up. She also received carotid thrombo-endarterectomy for the ulcerated plaque Fandler et al.. Patients treated off label are a highly heterogeneous group and therefore difficult to assess in randomized clinical trials. There is a need to collate these data in a registry setting.Endovascular stroke trials showed benefit in patients with proven large vessel occlusion and/or presence of mismatch. The investigators selected a population of patients with homogeneous clinical profile because the goal was to have a trial success , 5. In tDrozdowska et al. and Taylor-Rowan et al. touch upon some of the relevant issues. Drozdowska et al. reviewed prognostic scales used in acute stroke and inform the readers about the validity of commonly used prognostic scores. Outcome prediction tools guide a stroke physician's discussion with patient's family in regard to possible outcomes. It also offers a clinical trialist a tool to stratify the patient population enrolled in studies to investigate a differential response to the treatment. Drozdowska et al., in their review, recommend the need for studies to investigate clinical usefulness in existing scales. Outcome measures used in complex trials like stroke trials should be valid, reliable, and responsive endpoint; and their analyses should be robust and acceptable to the regulatory bodies. In their review article, Taylor-Rowan et al. inform issues relevant to the selection of outcome measures and suggest robust analytics.Suboptimal trial design may well have been responsible for some of the neutral stroke trials reported in the last two decades. This Research Topic thus informs the current state of knowledge with respect to recanalization strategies and also stimulates readers to identify important research questions and tackle them through a robust research methodology.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. Opinions are personal and do not reflect that of the regulatory bodies or the authors' employers.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.


Smoking is a well-established risk factor for dementia, but the effects of passive smoking are unclear. We aimed to examine links between passive smoking and dementia or cognitive impairment.We searched seven medical research databases: MEDLINE, Web of Science (Core Collection), Cochrane, EMBASE, PsycINFO, Scopus, and CINAHL Plus. Studies were included if they examined measures of passive smoking and either cognitive impairment or dementia.Of 1,425 records found, nine papers of varying methodologies were included after screening against inclusion criteria. Eight papers reported weak associations between passive smoking and either cognitive impairment or dementia. One paper only found this association alongside carotid artery stenosis. The papers’ quality was variable, with only two deemed high quality.There is limited weak observational evidence linking passive smoking with an increased risk of cognitive impairment or dementia. However, the studies were methodologically diverse and of inconsistent quality, preventing firm conclusions. ConsequSome of the existing literature refers to “cognitive impairment,” a term which can encompass a variety of clinical syndromes including Mild Cognitive Impairment and static deficits.There have been no literature reviews to date on the links between passive smoking and dementia in adults. We, therefore, present the first systematic review on the association between passive smoking and both dementia and cognitive impairment.Two reviewers conducted a search of seven online databases: MEDLINE, Web of Science (Core Collection), Cochrane, EMBASE, PsycINFO, Scopus, and CINAHL Plus on 10th December 2014.et al., http:/journals.cambridge.org/ipg. Anticipating the field of research to be small, we intentionally kept our search terms broad and inclusive. We included studies with cognitive impairment or dementia as the outcome of interest and set no age limit in adults.“Passive” smoking is also referred to as “second-hand smoke,” “environmental tobacco exposure,” or “involuntary smoking.” Its definition normally includes both smoke exhaled by a nearby smoker and “side-stream” smoke released into the environment by lit cigarettes or other smoked tobacco  independently used a standardized data extraction form to collect key process and outcome data. We collated these summary data and resolved any disagreements.et al., We created a tailored quality assessment tool with the aim of detecting selection bias, confounding, and information bias . Ethical approval was not sought as we did not conduct any primary research.Our search identified a total of 1,425 records from the databases listed in http:/journals.cambridge.org/ipg. We have summarized each paper's methods, findings, and our overall quality ratings in The studies differed in their methodology, reported outcomes, and statistical methods. We considered the possibility of meta-analysis and found it would not be appropriate to pool data for this reason (The Cochrane Collaboration, et al., et al., et al., et al., et al., et al., Nine papers were included in the final analysis, four of which reported research conducted in China (Chen, et al., et al., et al., et al., et al., et al., et al., et al., et al., All studies included standard cognitive tests and justified their use. Three studies also included clinical interview to verify diagnoses of dementia or the presence of cognitive impairment (Barnes et al., et al., To quantify exposure to passive smoking, two studies measured levels of cotinine, a metabolite of nicotine, which is an accepted biological marker of exposure to cigarette smoke (Llewellyn et al., et al., et al., et al., et al., et al., Six papers reported an association between increased levels of passive smoking and a form of cognitive impairment (Llewellyn Most papers reported an association between passive smoking and either cognitive impairment or dementia. However, overall there was a paucity of evidence and the majority of studies were at moderate risk of bias. In particular, all of the studies specifically examining dementia were only of satisfactory quality, and the highest quality research was limited to cognitive impairment. The papers’ methodological heterogeneity prevented meta-analysis so we did not find convincing evidence of any associations.et al., et al., et al., Recent interest in this topic is reflected in the fact that all the papers identified were published since 2009, which complements contemporary research into the links between air pollution and dementia (Weuve et al., To our knowledge, there is only one other systematic review on the topic of passive smoking and cognitive impairment, presented in a 2013 paper alongside novel study data (Chen et al., Our review sought to be comprehensive by using broad search terms in multiple databases with no age limits in adults; this is reflected in the wide range of records returned by the search. The fact that no papers were found using citation tracking or bibliography searching provides further evidence suggesting that our search method was exhaustive. We included studies reporting both dementia and cognitive impairment, which is a term used inconsistently to describe a variety of clinical states. There is a lack of standardized quality assessment tools for systematic reviews of this type. We, therefore, created our own quality assessment tool structured around common causes of bias and based on existing guidelines for evaluating cohort studies (Hammer Our restriction to English-language publications may have led to the exclusion of potentially relevant research findings in other languages. Although the databases we searched were predominantly in English, some papers in other languages were excluded at the title screening stage.Overall, because outcome measures differed, it was impossible to directly compare the strengths of association between studies and to quantitatively meta-analyze the results. Therefore, conclusions from our review are limited to general observations on cognitive test results or diagnostic outcomes.et al., “most Chinese people are unaware of the health hazards of either active or passive smoking,” with only 32% of people understanding that exposure to passive smoking carries health risks. Furthermore, there was variation between the papers’ implied definitions of exposure to passive smoking. For example, one paper included structured questionnaires with more detail about exposure to cigarette smoke in different environments but this only applied to the last seven days (Orsitto et al., et al., A number of studies identified passive smoking through self-reporting which is open to criticism. In the studies based in China, high illiteracy rates (reported as 61% in one paper (Chen et al., Two papers used cotinine levels as a biomarker for passive smoking. Cotinine has a half-life of 15–19 hours (Benowitz, et al., et al., Four of the nine included papers were by the same first author and sampled different combinations of study participants from the same two cohorts. All of these papers identified cognitive impairment using the GMS-AGECAT algorithm. However, there were variations in how the categories were interpreted across the studies. For example, a score of 3 or more was defined as a “severe dementia syndrome” in one study (Chen et al., The outcome measures for cognitive function across the studies varied. In the papers exploring general cognitive impairment rather than dementia, outcomes included several different neuropsychological tests, with or without clinical assessment and participants’ subjective experience of memory loss. One study used a prospective memory test, which may be less relevant to clinical dementia assessment (Heffernan and O'Neill, None of the studies included or mentioned power calculations. Most of the studies were of relatively large cohorts and the analyses may have been adequately powered but this was not formally discussed in the papers. None of the papers mentioned whether raters were blinded when deciding outcomes. In cases where a clinical diagnosis was made, no papers included clarification of whether this was repeated by a second professional.et al., Publication bias suggests that studies finding positive associations are more likely to be published. This could have led to the disproportionate representation of positive results in the literature we found (Guyatt et al., A potential source of confounding is the smoking history of participants. All studies acknowledged this but accounted for it in different ways, either by excluding former smokers, analyzing them separately or adjusting for smoking history in their analyses. In addition, people exposed to passive smoking may share lifestyle factors with smokers, adding further potential confounding (Koo et al., et al., Four of the nine papers studied combinations of participants from two cohort studies. These did not meet our exclusion criteria because each paper studied a different subset with some variation in methods and were not strictly duplications. We included and discussed all of these for transparency. One of the papers (Chen et al., In the analysis of some studies’ results, ordinal data were used to make numerical calculations. This involved passive smoking being categorized as “no, none at all,” “yes, some,” or “yes, a lot” and each of these groups being allocated an “exposure level” number, 0, 1, or 2. The number of self-reported years of exposure to second-hand smoke was then multiplied by these “exposure levels” to give what the authors called a cumulative dose. The authors then performed calculations that inferred an increasing risk of dementia syndromes with increasing cumulative dose (Chen, “drinking in excess of UK Government guidelines for safe drinking” but the mean alcohol consumption across the groups studied was 30–34 units per week. At the time of the paper's publication, this level of intake exceeded UK Government recommendations on sensible drinking (Department of Health, Our broad search strategy led to the inclusion of a study assessing the association of passive smoke on changes in prospective memory in a sample of undergraduate students (Heffernan and O'Neill, et al., et al., et al., All the studies we included were observational and therefore, cannot be used to infer causality; the possibility of residual confounding remains. However, evidence from animal and human studies supports a mechanistic link between tobacco smoking and cognitive impairment and dementia, probably due to microglial activation and neuroinflammation (Ghosh et al., et al., There is some evidence to suggest a link between exposure to passive smoking and poorer cognitive outcomes in children and adolescents (Yolton Other possible explanations for the associations found could be confounding factors, which have not yet been identified as risk factors for dementia and were therefore not accounted for. Only two of the papers we reviewed were graded as high quality, defined as having little or no risk of bias. Therefore, this may also have contributed to the direction of overall findings.None.L Stirland designed data collection and quality assessment tools, screened for relevant articles, extracted data, assessed papers' quality, and wrote the paper. C O'Shea extracted data, assessed papers' quality, and wrote the paper. T Russ conceived of the research question, supervised data collection, and edited the paper.


In a recent paper published in this journal (Hendrickson and Poole, Gemmata obscuriglobus, and cited additional references, mostly from their own labs. G. obscuriglobus is relevant to our discussion of genetic compartmentation because it is the best-studied member of a phylum with members that have been reported as possessing a compartment with similarities to the eukaryote nucleus (Fuerst, G. obscuriglobus that are normally associated with eukaryotes, including endocytosis-like processes (Lonhienne et al., Gemmata and related bacteria is a “matter of ongoing debate” and respectfully disagree with Jogler and colleagues' conclusion (Jogler et al., G. obscuriglobus is neither compartmentalized or nucleated, a subsequent cryo-electron tomography study from an independent group (Sagulenko et al., Gemmata that resemble the eukaryote nuclear pore complex (Sagulenko et al., G. obscuriglobus cannot account for the observations that proteins associated with these pores are exclusive to inner membranes (Sagulenko et al., Gemmata so it is premature to refer to a paradigm shift as having taken place.Jogler et al.  recently Fuerst, . In addiGemmata.With characterization of the cellular architecture of this fascinating bacterium a subject of ongoing research, we are open to data that could show that Jogler and colleagues' interpretation is partially or even wholly correct. However, given the main focus of our paper, there seems to be limited value in weighing in on extensive debate on this topic when it was not germane to the primary point of our article. Indeed, the key point of our paper is wholly unaffected by Jogler and colleagues' concerns. It would have been utterly remiss of us to have discussed non-eukaryotic cases of genetic compartmentation and completely ignored the extensive literature on All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


Petroclival meningiomas (PCMs) have always been a challenge for surgeons because of their difficult anatomical location. The role of radiology in providing precise indications regarding the tumour site and aggressiveness plays a major part in guiding the subsequent therapeutic process. The purpose of this review is to provide a set of the main radiological features helpful in the management of PCMs towards the most correct therapeutic approach.We aim to offer a radiological overview to allow the patient to be directed to surgery with the least possible risk of complications. Meningiomas are meningothelial cell neoplasms, which typically attach to the inner surface of the dura matter. They are a very frequent intracranial neoplasia, routinely diagnosed in clinical practice, representing approximately between 16% and 20% of overall endocranial tumours [According to the WHO classification of central nervous system tumours published in 2016 [The most common histology is represented by meningothelial meningioma, followed by fibrous and transitional subtypes: as a whole, they account for 80% of meningiomas . MeningiThis kind of neoplasia arises generally from the upper two-thirds of the clivus, intimately associated with the brainstem, basilar artery, perforating arteries, and multiple cranial nerves and is partially obscured by the temporal bone. This particular anatomical site makes frequent surgical problems easy to understand , as showet al [Castellano and Ruggiero first understood that posterior fossa meningioma could have different prognostic evolution, thanks to extensive postmortem examinations. They considered five categories: convexity, tentorial, posterior surface of the petrous bone, clivus and foramen magnum . Howeveret al  suggesteet al , 10. Moret al , to suchet al .Surgery of PCM can nowadays be performed with excellent results after a presurgical safety assessment, including a detailed analysis of imaging characteristics of magnetic resonance imaging (MRI). The radicability of tumour resection is strongly associated with some anatomical features, easily evaluable with the imaging: tumour size, composition and aggressiveness, adherence to the brainstem, proximity to the neurovascular structures and tumour extension into the cavernous, petrosal sinus. Preoperative magnetic resonance is always necessary in order to predict the difficulties related to surgical resection: until now, the imaging features that might help to predict the complications and the feasibility of surgery of PCMs are not yet well characterised. The purpose of our study is to review the main works in the literature to establish the radiological characteristics that allow the patient to be directed to surgery with the least possible risk of complications .We searched on PubMed for the terms ‘meningioma’, ‘petroclival’, ‘surgery’ and ‘imaging’ in varying combinations. Our analysis included recent papers with the largest numbers of patients, trying to identify the principle features that can be related to a successful surgery. Studies not regarding meningiomas of the petroclival region were excluded.et al [.Mayberg and Symon were the first authors who approached neuroimaging focussing on PCMs: the use of pre-operative computed tomography (CT) scans and cerebral angiography has reduced the overall mortality to 9%. . Sekhar et al , especiaet al .The petroclival region is a surgical space circumscribed anteriorly by the clivus, laterally by the petrous apex, medially by the brainstem and posteriorly by the internal acoustic canal. It goes from the dorsum sellae to the foramen jugularis. It is intersected by cranial nerves IV to XI and by the basilar artery with its branches .et al [3. This evaluation plays an important role in planning anterior petrosectomy. Although the portion of bone resected is a pyramid  so as to prevent mistakes caused by the three-dimensional area, in that study, to obtain a good plan, the images were collected and worked out by Orsix for Mac (Pixmeo Sarl) [et al [The most important tips and tricks are represented by estimating the volume of the osseous area of the Kawase space, acquired by CT, reported by Altieri et al . This areo Sarl) . In an M) [et al  on 51 paIn the literature, there are some important analyses to estimate radiological features capable to give the chance of a satisfactory tumour removal: meningiomas usually appear as round-lobular shaped masses in the extra-axial space with thin and definite margins. Some of the most important features of PCMs are summarised in This kind of lesion usually shows isointensity to slight hypointensity relative to grey matter on the T1-weighted sequence; whilst they appear isointense to slightly hyperintense relative to grey matter on the T2 sequence. After contrast administration, meningiomas typically demonstrate rapid, rich and homogeneous enhancement . Calcification is a typical finding, best studied on CT. On MRI, calcification is best identified on susceptibility-weighted images as areas of low signal intensityContrast is of great help in ‘en plaque meningiomas’ evaluation since they typically appear as asymmetric thickened sheets of enhancing dura .et al [et al [et al [et al [et al [et al [et al [et al [et al [et al [et al [Several studies have been performed assessing the correlation between the MRI findings and the histology of meningiomas. Almost all studies have shown that the signal intensity on T1-weighted images does not correlate with tumour histology or histological subtype; in fact, most meningiomas are isointense to the brain cortex regardless of tumour histology –31. Dataet al  showed tl [et al  demonstrl [et al  showed tl [et al  report tl [et al  describel [et al  results l [et al  and Chenl [et al , supportl [et al  evaluatel [et al . All patl [et al . With rel [et al  demonstrl [et al . This, tl [et al  also deml [et al , 14. On et al [et al [Good correlation was also demonstrated between tumour resectability and certain preoperative findings such as the presence or absence of an arachnoidal cleavage plane; an arachnoidal cleavage plane was preoperatively shown in 80% of totally resected PCM whilst this was not demonstrated in 88% of the subtotally removed tumours. On the other hand, brainstem oedema did not correlate with incomplete tumour removal. Up till this date, no clear correlation has been demonstrated between tumour consistency and surgical outcome. Also, the values of apparent diffusion coefficient (ADC) in MRI diffusion images seem to have an excellent prognostic value in identifying the behaviour of meningiomas: Hakyemez et al  reportedet al . Tang etl [et al  describe2 s−1 seems to be helpful in differentiating aggressive meningiomas from low-grade tumours, whilst an ADC cut-off of greater than 0.85 × 10−3 mm2 s−1 in identifying low-grade meningiomas [An ADC cutoff of less than 0.70 × 10−3 mmingiomas .et al [et al [A study of Rempel et al  underlinet al . More sol [et al , by estil [et al et al. performed texture and shape analysis to quantitatively evaluate tumour heterogeneity and morphology on 131 pts by three texture features and three shape features and they have found significant differences between high-grade and low-grade meningiomas related to features of texture and shape; so it can be reliable in the preoperative determination of meningioma grade and seems to have potentially effective clinical application [Reagrding this, there are also novel methods to predict preoperative meningioma grade. Peng lication . In anotlication .In the new era of precision medicine, radiomics is an emerging translational field of research aiming to find associations between qualitative and quantitative information extracted from clinical images and clinical data, with or without associated gene expression to support evidence-based clinical decision-making. The concept underlying the process is that both morphological and functional clinical images contain qualitative and quantitative information, which may reflect the underlying pathophysiology of a tissue. Radiomics’ analyses can be performed in tumour regions, metastatic lesions, as well as in normal tissues. The radiomics quantitative features can be calculated by dedicated software, which accepts the medical images as an input. Despite many tools developed for this specific task being user-friendly in terms of use and well performing in terms of calculation time, it is still challenging to carefully check the quality of the input data and to select the optimal parameters to guarantee a reliable and robust output. The quality of features extracted, their association with clinical data, and also the model derived from them, can be affected by the type of image acquisition, postprocessing and segmentation. This article summarises the major issues regarding this multistep process, including radiomics, CT and MRI .The radiological features of PCMs are of great importance for clinicians in the choice of the most appropriate therapeutic approach.Where surgery is possible , radiological images play an important role in order to choose the best surgical approach.The profound knowledge of the radiological characteristics of the PCM is of great importance to assure the best management of patients with this type of lesion.Many new and innovative methods are being developed over recent years to analyse the radiological features of a meningioma, offering opportunities with great potential and interest.Nothing to declare.No funding was received for this article.All authors declare no conflict of interest.


Phantom limb pain (PLP) is a chronic pain disorder characterized by painful sensations that are perceived to arise from the missing limb, presumably due to structural and functional alterations in several regions of the brain (i.e., anterior midcingulate cortex, aMCC; Preißler et al., In Preißler et al. , particiIn addition to reporting a decrease in PLP among the participants after the training period, Preißler et al.  also repRecent advances in VR technology provide a promising avenue for the future of PLP treatment. Similar to the myoelectric prosthetic arm protocol utilized by Preißler et al. , immersiAlthough we discuss various beneficial approaches to reducing PLP, it is important to acknowledge that the benefits of the interventions discussed above vary among patients, with some patients who report no PLP reductions (see for example Ortiz-Catalan et al., In conclusion, PLP therapy has been extensively explored in the literature. In Preißler et al. , the autAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


The role of farm animals in the emergence and dissemination of both AMR bacteria and their resistance determinants to humans is poorly understood and controversial. Here, we systematically reviewed the current evidence that food animals are responsible for transfer of AMR to humans. We searched PubMed, Web of Science, and EMBASE for literature published between 1940 and 2016. Our results show that eight studies (18%) suggested evidence of transmission of AMR from food animals to humans, 25 studies (56%) suggested transmission between animals and humans with no direction specified and 12 studies (26%) did not support transmission. Quality of evidence was variable among the included studies; one study (2%) used high resolution typing tools, 36 (80%) used intermediate resolution typing tools, six (13%) relied on low resolution typing tools, and two (5%) based conclusions on co-occurrence of resistance. While some studies suggested to provide evidence that transmission of AMR from food animals to humans may occur, robust conclusions on the directionality of transmission cannot be drawn due to limitations in study methodologies. Our findings highlight the need to combine high resolution genomic data analysis with systematically collected epidemiological evidence to reconstruct patterns of AMR transmission between food animals and humans. E. coli is found in both human and food animal populations  explore the current evidence that food animals are of the source of resistant et al., E. coli, AMR terminologies, human, and food animal descriptors (www.liebertpub.com/fpd).A systematic literature search according to the PRISMA  guidelines  they reported only agents other than E. coli; (ii) they studied nonfood animals; (iii) they focused exclusively on food animals or humans without any overlap between the two populations and/or (iv) they focused exclusively on food of animal origin. Article searches and screening were performed by considering article titles and abstracts for inclusion according to the search criteria. Data extraction from studies was performed by one author (D.M.M.) and independently checked by another author (B.v.B.) using a customized checklist.Articles were included if they comprised an original research published in a peer reviewed journal, and investigated transmission of resistant For all included studies we categorized the direction of AMR transmission according to the authors' conclusions: (i) studies suggesting to provide evidence of transmission from food animals to humans with direction specified; (ii) studies suggesting to provide evidence of transmission from humans to food animals with direction specified; (iii) studies suggesting overlap indicating the possibility of between-host AMR transmission, with no direction specified; and (iv) studies suggesting no evidence of transmission in either direction.et al., The quality of evidence was assessed using a customized Grading of Recommendations Assessment, Development and Evaluation (GRADE) system  we did not perform a meta-analysis. However, we used Fisher's exact tests using R package “stats”  suggested to have data to support transfer of AMR bacteria and/or their AMR determinants from food animals to humans .Only one study (2%) based its conclusion regarding transmission on high resolution typing tools, 36 studies (80%) on intermediate resolution typing tools, six (13%) on low resolution typing tools, and two (5%) on co-occurrence of resistances . Overallet al., et al., et al., et al., Three studies suggested to find evidence for transfer of AMR bacteria from food animals to humans, two of which concluded there is transfer of resistant clones from poultry to humans (Al-Ghamdi et al., et al., et al., et al., et al., One study found identical ciprofloxacin-resistant isolates in chicken and humans, which they concluded was suggestive of food animal to human AMR transmission (Johnson E. coli isolates sourced from poultry and human patients (Leverstein-van Hall et al., et al., E. coli in humans in contact with tetracycline fed chicken and, therefore, suggested that chicken were a reservoir of AMR bacteria and plasmids for humans (Levy, Three studies suggested to support transmission of both AMR bacteria and their AMR determinants from food animals to humans. Two studies found similar sequence types, plasmid families and ESBL genes in ns Levy, .We found that studies suggesting to provide evidence of transmission of AMR from food animals to humans did not have distinct features compared to those suggesting overlap of resistance, with regard to study methodologies, food animal species, typing tools, or antibiotics tested. For most of these it is unclear why they suggested evidence of directional transmission when 25 broadly similar studies suggested only overlap of resistance.E. coli between humans and food animals. One of these studies found human and avian sequence types associated with multidrug resistance clustered together in a Bayesian phylogenetic tree (Ciccozzi et al., et al., E. coli phylogroups found that human, pig, and chicken isolates clustered together (Jakobsen et al., et al., Four studies suggested there was evidence of overlap of resistant et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Thirteen studies suggested there was evidence of overlap of AMR determinants in human and food animal isolates. Of the 13 studies, one study based on WGS and plasmid reconstruction found that clonally unrelated human and poultry isolates carried ESBL genes encoded on genetically identical plasmids (de Been E. coli and AMR determinants, with five of these finding that clonally related human and food animal isolates harbored similar ESBL gene types and plasmid types (Hu et al., et al., et al., et al., et al., et al., et al., E. coli pathotypes showed that human and food animal isolates clustered together (Jakobsen et al., Eight studies suggested there was evidence of overlap of resistant E. coli strains had distinct phylogenetic compositions (Graziani et al., E. coli isolates from sympatric children and chicken found that the isolates were source specific (Kariuki et al., Two studies found no evidence for transfer of resistant clones, with one of these studies finding that human and avian ciprofloxacin-resistant et al., et al., et al., Three studies reported no evidence for transfer of AMR determinants between food animals and humans with one of these studies reporting that human and porcine isolates had different distribution patterns of sulfonamide and tetracycline resistance genes (Schwaiger et al., et al., et al., et al., et al., et al., et al., Seven studies reported no evidence for transmission of bacterial clones together with AMR determinants between food animals and humans. These studies showed that human and food animal isolates belonged to different phylogenetic groups, and had different AMR genes and plasmid profiles (Maynard E. coli and their AMR determinants to humans. Some studies in our review suggested to provide evidence for the transfer of AMR from and between food animals and humans, while a larger number did not suggest to provide evidence of transmission in either direction. In addition to the differing nature of methods used to infer direction, studies in our review differed in sampling methodologies and antibiotics tested. These differences may have affected the conclusions made regarding the epidemiological connection between food animals and humans.We performed a systematic review to explore the evidence that food animals are responsible for the transfer of AMR E. coli clones and AMR determinants were indistinguishable in both food animal and human isolates. However, the demonstration of overlapping patterns should be interpreted with care as the direction of transmission is difficult to infer, and co-colonization from a shared source is also possible. Demonstrating the direction of transmission and thus the epidemiological history of pathogens and their determinants requires a quantitative description of relatedness, including phylogenetic analysis (Grad and Lipsitch, Much of the evidence regarding transfer of AMR was based on the demonstration that AMR et al., E. coli isolates were considered genetically indistinguishable based on MLST suggesting clonal transfer (Leverstein-van Hall et al., et al., et al., et al., Molecular techniques, such as MLST and PCR, used in most studies in our review, are limited in resolution (Didelot et al., et al., Just over half of the studies in our review did not consider spatiotemporal relationships between human and food animal isolates, a fundamental requirement for investigating transmission (Singer et al., None of the included studies provided a detailed overview of antibiotic usage in either human or food animal populations, or association between antibiotic usage and subsequent development of AMR. A recent systematic review has indicated that interventions that limit antibiotic use in food animals are associated with a reduction of AMR development in humans (Tang et al., et al., Although transfer of AMR from humans to food animals is likely Barber, , none ofet al., et al., Akin to the studies in our review, most AMR studies focus on a single bacterial type; however, rapid dissemination of AMR determinants frequently occurs between bacterial species, making it hard to track infection source (Sheppard et al., Our systematic review excluded studies focusing on transmission of resistant bacteria and/or their AMR determinants through food animal-sourced food products. However, we acknowledge the potentially significant role played by food products of food animal origin in dissemination of AMR as reported in a recent systematic review (Lazarus E. coli and their AMR determinants from food animals to humans. However, differences in study methodologies, such as lack of spatiotemporal overlap in sample collection, and the quality of typing tools used, suggest that transmission may occur, the evidence used to support the hypothesis is rarely compelling. The underlying problem is that demonstrating similarity or identity of AMR bacteria and/or AMR resistance determinants does not, by itself, provide information on directionality of transfer; this could be in either direction, or both, or neither but from a different source. Information on differential prevalence of resistance, and consumption of antibiotics, in the two populations may make stronger inference possible, but these data are rarely available.We have highlighted studies that suggest to provide evidence for transfer of resistant Taken together, by combining genomic data analysis and epidemiological approaches it may be possible to reconstruct the complex transmission dynamics of resistant bacteria and their AMR determinants between human and food animal populations. Although we still have some way to go before a truly comprehensive integration of data—differential antibiotic usage data, detailed denominator data, information about the origin of the samples, human-food animal contact data, and pathogen sequence data—is available, disentangling and quantifying transmission of resistant bacteria and their AMR determinants between humans and food animals may still be an attainable goal.


Cholestasis is defined as reduced bile flux, either caused by an obstruction of bile ducts or by compromised hepatocellular secretion (Pollheimer et al., 2014; FickertOne important discovery made by this method is that the most upstream domain of the biliary tract, bile canaliculi, responds differently to cholestasis than the more downstream interlobular ducts (Damle-Vartak et al., 2019[Recently, much effort has been invested to gain a better understanding of cholestasis (Ehrlich and Glaser, 2018; Sultan The author declares no conflict of interest.


Currently, just under six million people living in America are diagnosed with Alzheimer’s disease or related dementia. Most people with dementia live in a community setting and are cared for by a family member. Persons living with dementia almost universally experience behavioral and psychological symptoms (BPSD), such as agitation, aggression, and rejection of care as well as functional dependence. These symptoms are related to negative outcomes for both the person living with dementia and the family caregiver. Prior research shows that nonpharmacologic interventions such as meaningful activities, education, and multicomponent interventions have promise in managing behaviors. This symposium focuses on preliminary outcomes from the Dementia Behavior Study (DBS), a Randomized Control study that examined the effect of the Tailored Activity Program (TAP) in a community setting on BPSD and functional dependence in persons living with dementia, and caregiver wellbeing . Gitlin et al will present outcomes of the primary aim (BPSD) and secondary aims  of the DBS. Pizzi et al explore the cost analysis of the TAP intervention versus the active control group. Scerpella et al describe the alerts and adverse events that were associated with the DBS. Marx et al present the relationship between race and caregiver readiness to participate in TAP. Regier et al explore the BPSD Rejection of Care and the association to caregiver burden. Tailoring interventions, such as activities may improve quality of life for both the person with dementia and the family caregiver.


HOTAIR can play their important roles by changing the chromatin states of the genome  and Polycomb Repressive Complex2 (PRC2) in order to recruit them on specific target genes. This RNA interacts with Polycomb repressive Complex2 (PRC2) and has a lot of targets such as HOXD. By this way, PRC2 can repress the desired genes leading into increased growth, proliferation, survival, metastasis, invasion, and drug resistance in some cancer cells  are RNAs with more than 200 nucleotides and are mostly transcribed by RNA polymerase II from different regions across the genome. They are currently known as key regulators of cellular function through different mechanisms such as epigenetic regulation, miRNA sponging, and modulating of proteins and enzyme cofactors   patients. Also, The rs1899663 is associated with prostate cancer risk in co-dominant, dominant and recessive inheritance models. Researchers have reported that this SNP changes the affinity for binding of PAX-4, SPZ1, and ZFP281 transcription factors which can alter the HOTAIR gene expression level (Taheri et al., Another SNP located in the intronic region of HOTAIR gene, one named “rs7958904” is an exonic polymorphism. So, it seems that HOTAIR rs7958904 polymorphism can affect the secondary structure of HOTAIR.Among the SNPs in HOTAIR rs7958904 has been reported to be associated with decreased osteosarcoma (Zhou et al., HOTAIR rs7958904 can reduce osteosarcoma risk as well as HOTAIR expression level (Zhou et al., HOTAIR expression (Jin et al., HOTAIR in lung cancer (Jiang et al., HOTAIR function or expression (Xue et al., It is of noted that CC genotypes of HOTAIR have abnormal expression in the different human cancers. Different studies have revealed the cellular and molecular mechanisms in which HOTAIR is involved (Hajjari and Salavaty, HOTAIR in cancer susceptibility have been published. However, these studies are mostly derived from Asian population. Also, there are some controversial results on this field of study. With regard to the importance of HOTAIR regulation and function, more experiments on different populations, and ethnics are expected to reveal the importance of HOTAIR polymorphisms. Other polymorphisms in HOTAIR gene such Indel and CNV may be considered in future. However, the association between these SNPs and regulation/structure of HOTAIR has to be checked in various cancers. Also, we believe that whole genome sequencing projects can help to find the relation between the SNPs of this RNA with other SNPs in different cancers in future.MH designed and wrote the manuscript. SR worked on gathering the data and wrote the manuscript.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.


Although there are some commendable aspects regarding the methodology, some major shortcomings could preclude the conclusions drawn by Choukem et al. Nevertheless, independent assessments of the performance of blood glucose monitoring systems are an important issue.In their article, Choukem  Choukem et al. purchased the BGMS from pharmacies, thus using meters and test strips that are representative of those used by end-users. In the study, capillary blood was applied, which typically is the type of sample used by diabetes patients, because they do not readily have access to, for example, venous blood. Rotating the order in which the BGMS are used helps minimizing potential order effects. This shows that the authors were aware of several potential influencing factors and tried to minimize their impact. However, the methods used in the study by Choukem et al. had some flaws: Such comparative assessments should use the same sample type for the investigated systems as well as for reference measurements, because glucose concentrations can be different in venous and in capillary blood samples [et al. state that requirements of ISO 15197 are not met. However, this statement can only be made with limits because of relevant methodological deviations from the recommended procedure as outlined in ISO 15197 [et al., therefore, it is impossible to verify whether BGMS fulfill ISO 15197 accuracy criteria or not.In their recent publication, Choukem et al.  report o samples . Further samples , so that samples . In addiet al. at least in part. In addition, some of the requirements regarding methodology as outlined in ISO 15197 were not adhered to by Choukem et al. Therefore, it is our opinion that the conclusions drawn by Choukem et al. may possibly have been different if these methodological flaws had been avoided. Nevertheless, we want to encourage Choukem et al. to perform further testing, as we believe that independent assessment of BGMS performance is an important issue.These methodological flaws could likely lead to reference measurement results being systematically different than BGMS measurement results. Although their individual contribution to a systematic difference is hard to pinpoint, their combined effect would explain the positive bias values found by Choukem The authors declare no competing interest.


Drosophila, only starved animals are used and the length of the starvation period influences the results  that end with a jump, but with some degree of independence between each maneuver, allowing the fly to stop the sequence if it chooses to Card and Dickinson (Drosophila escape response—with either short or long take-offs—that can be biased toward short take-offs by increasing stimulus speed (von Reyn et al., Drosophila escape responses involve more neural control elements than a single command neuron, allowing a variety of computational and decision steps to take place before the evasive behavior occurs. Another common defensive strategy is freezing, where the animal remains still, reducing its chances of being noticed. A new study showed that Drosophila flies adopt a freezing strategy in a state-dependent manner (Zacarias et al., In ickinson ,b and Caickinson . Each stDrosophila, but upon encountering female wasps, female flies adopt different strategies that include choosing food containing toxic levels of alcohol to lay their eggs (promoting the death of wasps' eggs and larvae; Kacsoh et al., Perhaps even more interesting is how the presence of parasitoid wasps affects oviposition in adult flies, as a mechanism to protect their offspring from a possible future threat. Parasitoid wasps are not dangerous to adult Interestingly, flies form a nonassociative long-term memory of the exposure and will lay fewer eggs or choose alcohol-enriched food to lay their eggs for 24–48 h after wasp exposure (Kacsoh et al., Drosophila uncovered part of the neuronal network involved in the decision to expand the wings, and showed the connection with the decision to perch, which required an assessment of the external factors (Peabody et al., Curiously, these two biogenic amines differently modulate phototaxis, in what it seems to be a goal-directed or value-based decision-making process. Phototaxis seems to be a special case of photopreference and manipulating the ability of flies to fly can reversibly shift it from approach to avoidance in walking flies (Gorostiza et al., These examples serve to demonstrate how innate behaviors can in fact be the outcomes of complex modulatory processes, careful assessment of factors and decisions, and not mere stereotypic and automatic responses. Through these examples, we can see some aspects that resemble cognitive components (Menzel et al., The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Uncontrolled immune response in the brain contributes to the progression of all neurodegenerative disease, including Alzheimer’s disease (AD). Recent investigations have documented the prion-like features of tau protein and the involvement of microglial changes with tau pathology. While it is still unclear what sequence of events is causal, it is likely that tau seeding potential and microglial contribution to tau propagation act together, and are essential for the development and progression of degenerative changes. Based on available evidence, targeting tau seeds and controlling some signaling pathways in a complex inflammation process could represent a possible new therapeutic approach for treating neurodegenerative diseases. Recent findings propose novel diagnostic assays and markers that may be used together with standard methods to complete and improve the diagnosis and classification of these diseases. In conclusion, a novel perspective on microglia-tau relations reveals new issues to investigate and imposes different approaches for developing therapeutic strategies for AD. The most common cause of dementia is Alzheimer’s disease (AD), a progressive neurodegenerative disease that affects nearly 50 million people in the world. Histopathological features of AD are extracellular amyloid-β (Aβ) plaques and intracellular aggregation of hyperphosphorylated tau protein in a form of neurofibrillary tangles  during early embryonic development. Their appropriate response is crucial for maintaining homeostasis and to carry out the immune response in the CNS (Ginhoux et al., In the mature brain, microglia play an important role as the main immune agents. Under physiological conditions, microglial cells are in the resting state, but they actively survey the brain parenchyma with motile processes (Nimmerjahn et al., Neuroinflammation occurs in most neurodegenerative diseases (for review see Stephenson et al., MAPT gene and different RNA splicing can produce six tau isoforms in the human brain. Isoforms of tau have either three or four microtubule-binding repeats (Neve et al., in vitro findings, where we showed that exhaustive tau phosphorylation is either not essential for the stability of the putative tau oligomer once it is formed, or is necessary for initial oligomer formation (Boban et al., via non-cell-autonomous mechanisms, which leads to degeneration (Goedert et al., in vitro studies that describe the trans-synaptic spread of tau along anatomically connected brain regions. One study demonstrated this kind of propagation in transgenic mice that differentially express pathological human tau in the entorhinal cortex (Liu et al., In vitro studies also support the prion-like feature of tau (Kfoury et al., Tau protein is mainly expressed in neurons and is essential for microtubule assembly and stabilization of the cytoskeleton (Weingarten et al., via unconventional secretory pathways like other proteins lacking signal peptides (Rabouille et al., via exosomes. This mechanism was demonstrated in cell cultures in vitro such as M1C (Saman et al., via exosomes (Wang et al., 1–42 levels were detected up to 10 years prior to clinical diagnosis (Fiandaca et al., The prion-like hypothesis of tau transmission proposes that misfolded tau acts as a seed causing further misfolding of proteins inside healthy cells, implying that tau needs to be released outside of the cells. Tau released in the ISF can induce stronger microglial activation which in turn may promote the propagation of tau pathology. It is well known that the CSF levels of tau are elevated in AD patients (Zetterberg and Blennow, in vitro. Interestingly, microglia pretreated with NSAID attenuated tau overexpression (Lee et al., in vitro and in vivo. AT8 and PHF1 tau colocalized within hippocampal Iba1-expressing microglia, which convincingly demonstrate microglial uptake of tau (Asai et al., In vitro test supported this conclusion, showing more efficient phagocytic activity by microglia when compared to neurons and astroglia (Asai et al., in vitro and in vivo (Asai et al., It is well known that tau can mediate an inflammatory response in neurodegenerative disease. Many studies show microglial activation upon tau pathology (Bellucci et al., A recent study revealed one possible molecular mechanism that can explain noticed microglial changes in response to tau pathology and microglial contribution to tau propagation . AggregaThe harmful effect of tau protein oligomers and its potential to propagate through synaptically connected regions has been well established by recent evidence, along with microglial changes in close vicinity of tau pathology. Uncontrolled microglial response in the brain contributes to the progression of many neurodegenerative diseases and several lines of evidence suggest that inflammation may even precede the development of tau pathology in AD. Exosomes could be an important link between tau propagation and microglial activation. Reduction of microglial cells number and exosome synthesis inhibition reduces tau propagation (Asai et al., All animal experiments were conducted according to the Principles of Laboratory Animal Care and ARRIVE guidelinesGŠ conceived the manuscript. All authors edited the drafts of the manuscript.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.


We are proud to present 14 papers with focus on teenager health in this Special Issue entitled “Teenage Reproductive Health: Pregnancy, Contraception, Unsafe Abortion, Fertility”.Maternal mortality is still globally high and reducing it is a top priority. Teenage pregnancies have more complications and are also unwanted in many cases. This contributes to the high maternal mortality with both obstetric complications and burden of unsafe abortion. Additionally, many teenagers live in areas with heavy pollution that affects the mother and the unborn child. Global public health is a very important issue that aims to prevent disease, prolong life, and promote physical, mental and social well-being. Teenagers are the future, and maternal death is a disaster that should be prevented. Hence, research should aim to improve teenage reproductive health and influence policy makers. There are a variety of topics in this issue, with some conclusions and ways forward as described in different papers.Oppong-Darko et al.  describeGrossman et al.  have a vvon Rosen et al.  describeNinsiima et al.  went deePradhan et al.  publisheContributions to international health science from Russian authors are rapidly increasing. Usynina et al.  discuss Lafontan el al. state that it is very simple and easy to use electronic baby monitoring in Tanzania . They caScientific literature from Kazakhstan is increasing and improving. The paper from Dauletyarova et al.  discusseAbortion policies are very important in teenager health in all parts of the world. Frederico et al.  discuss Tsikouras et al.  describeBack in Africa, Odland et al.  discuss Kemigisha et al.  deliver Clarke et al.  have theFinally, Sharma and Nam  describeInternational Journal of Environmental Research and Public Health as a starting point in their career. All papers have been through a thorough review process, and many of them are now basis for the study towards academic degrees and introduction to further studies. Due to the age connection, young scientists are writing about health issues for young people. Let us hope for a new Special Issue soon, with contributions from other parts of the world. Teenagers have special health concerns in a very important transition period from child to adult. This is independent of geography, culture and religion. In total, this Special Issue provides very useful information for all parts of the world, even for those who are not presented in this nice collection of papers.There is a very important public health aspect in all the published papers in this Special Issue. Another good development is that young scientists are using the


The issue of how plants grow on saline soils is an interesting one in its own right, but commands added urgency in the context that irrigation and sea level rises are increasing the proportion of arable land that is salinized and that global demand for more food is leading to cultivation of marginal land.Terrestrial plants face formidable challenges when growing in saline conditions. High osmotic pressure around the roots can prevent efficient water absorption, yet the high concentrations of the sodium ion (NaNew Phytologist reminds us that these challenges are experienced by plants at cellular, tissue and whole organism levels. Major changes in energy metabolism are experienced by plants growing in saline conditions. Many of these changes relate to the decreased resource devoted to growth and the necessity for enhanced transport of ions that can be used to retain turgor, or to exclude those ions that leak into cells and tissues.‘Major changes in energy metabolism are experienced by plants growing in saline conditions.’A collection of research papers and review articles in this issue of et al. (The Tansley review by Munns et al. (Flexibility in plant metabolism can provide adaptation to saline environments. In a thoughtful analysis, Fricke (et al. (Plant salinity tolerance involves complex ‘decision‐making’ by a plant: for example, how is turgor maintained in an energetically‐effective way that does not compromise metabolic activity? Munns et al. (The process of cation absorption and compartmentation – intracellularly and through the plant – comprises a further challenge to plants in saline conditions. Rubio et al. (Coping with salinity stress involves not just selective exclusion and competition between Na and K: glycophytic plants possess inherent leaks in their membranes that facilitate futile cycles in transport, particularly in the case of Na. Shabala et al. (As multicellular organisms, the manner in which plants handle salinity stress cannot be considered at the cellular level alone. Arsova et al., et al., et al. (The articles briefly summarized here are invaluable in pointing to recent advances and discoveries in plant salinity tolerance. But more important, perhaps, are the questions relating to the big unknowns that the authors raise. There were hopes two decades ago that developing an understanding of signal transduction pathways would lead to rapid developments in generating salt‐tolerant plants Sanders, . These h, et al.  based onet al. (st century genomics is ever‐growing and this – alongside the machine‐learning approaches to understanding phenotypic diversity in an environmental context – will be key to developing the predictive breeding approaches that are needed for the realization of salinity‐tolerant crops.‘… salinity tolerance is multigenic and needs to be viewed in a wider context than just that of membrane transport of NaCl.’This collection of articles reminds us that salinity tolerance is multigenic and needs to be viewed in a wider context than just that of membrane transport of NaCl. Munns et al.  have proWider aspects of biodiversity should not be forgotten, either, as a way of devising strategies for crop improvement since there are many angiosperm species that are salt‐tolerant. There are clearly lessons to be learned from the physiological adaptations that enabled such species to live in saline soils and even in some cases to re‐colonize the sea.


Behavioral and Brain Sciences about the ideas of Baumeister et al. (e.g., Budescu and Maciejovsky, Baumeister et al.  proposedWe hold that the ideas of Baumeister et al. do not generalize beyond individualistic cultures, and do not generalize to all kinds of tasks. We begin by describing important differences between individualistic and collectivist cultures. Later, we distinguish between survival and development tasks. Ultimately, we argue that the benefit of individuation in groups may only apply to a small portion of the space defined by individualistic vs. collectivist cultures, and survival vs. development tasks, as schematically depicted in Figure Baumeister et al.  ignore cWe agree with the view that for many types of tasks, the promotion of individual identity can facilitate group success, whereas promoting shared identity can reduce success. However, we argue that this result applies most strongly to individualistic cultures, and may not be observed at all when testing collectivist cultures (also pointed out by Brown, Baumeister et al.  also ignThe probability of survival is increased by shared identity because shared identity promotes helping (Penner et al., In short, Baumeister et al.  have proZZ drafted the manuscript. CW provided revisions and language editing. YL, QX, and HL provided revisions.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.


Indeed, FXS is considered a form of ASD (https://www.spectrumnews.org/news/fragile-x-syndromes-link-autism-explained/) and so are the murine models of this disease  in addition to a Nuclear Localization Signal (NLS) and a Nuclear Export Signal  is a neurodevelopmental disorder due to the silencing of Fragile X Mental Retardation 1  in the presence and in the absence of FMRP  motif, bound by FMRP in the GRK4 mRNA (G protein-coupled Receptor Kinase 4; Maurin et al., vivo. To do so, we computed an unpairing score for each base of each expressed transcript. We derived a score for each motif bound by FMRP and we compared the scores of motifs embedded in FMRP binding sites or present elsewhere in the transcript. Our analysis clearly shows that the CUGKA, GWRGA and UAY motifs present in regions bound by FMRP are more accessible to DMS modification in vivo than the unbound cognate motifs present in the same transcripts (Maurin et al., Importantly, we and others showed that the basis of FMRP/RNA interaction is the key to understand its function (Darnell et al., The second key point that should be considered to explain the double role of FMRP as repressor and enhancer of translation is represented by the interactors of FMRP, which can have different expression patterns (Bardoni et al., Another critical point is represented by the observation that, in the absence of FMRP, a set of its mRNA targets was shown to be less transported at the synapse (Dictenberg et al., Last but not least, the post-translational modification of FMRP can modify its function. For instance, sumoylation has been shown to have a strong impact on the ability of FMRP to interact with partners and generate complexes (Khayachi et al., are not modulated in the absence of FMRP, which in our opinion argues for a stronger implication of FMRP-containing mRNPs in storage/transport of mRNAs rather than in translational regulation. To date the role of FMRP was mainly studied in translational regulation probably due to its association to polyribosomes (Corbin et al., Fmr1-KO (Huber et al., In conclusion, it seems now the right time to renew the research on the mechanisms of action of FMRP. It is indeed remarkable that the study of Liu et al.  See Fig legend sFmr1-KO cells (Bechara et al., Fmr1-null mice (El Bekay et al., It is obvious that the function of this protein is intimately linked to the identification of a therapy for FXS, that, indeed, is still missing (Castagnola et al., The two authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


The study of coat protein assemblies on membranes by cryo-electron tomography and subtomogram averaging is discussed, outlining the methodological advancements that enabled the gain of crucial structural insight. in vitro reconstitutions or in situ is summarized. These studies have answered long-standing questions regarding the mechanisms of membrane binding, polymerization and assembly regulation of coat proteins.Coat proteins mediate vesicular transport between intracellular compartments, which is essential for the distribution of molecules within the eukaryotic cell. The global arrangement of coat proteins on the membrane is key to their function, and cryo-electron tomography and subtomogram averaging have been used to study membrane-bound coat proteins, providing crucial structural insight. This review outlines a workflow for the structural elucidation of coat proteins, incorporating recent developments in the collection and processing of cryo-electron tomography data. Recent work on coat protein I, coat protein II and retromer performed on  The large body of cryo-EM work carried out for protein structure characterization has utilized single-particle electron microscopy , coat protein I (COPI), clathrin and retromer Fig. 1. The cytQuestions that remain unanswered about coat proteins address the mechanism of their association with the membrane and their global assembly. Cryo-ET is well suited to address these questions as it can allow the high-resolution analysis of coat proteins in the process of modifying membranes.2.We describe our workflow for the investigation of coat protein membrane assemblies by cryo-ET in Fig. 32.1.et al., 2004et al., 2006et al., 2002et al., 2007et al., 2010et al., 2004et al., 2002in vitro reconstitution studies with purified components assembled on artificial membranes , which can affect tilt series alignment by cross-correlation. High-contrast gold fiducial markers are typically added to emClarity and IMOD  correction is essential for the recovery of higher resolution information. Appropriate CTF correction relies on accurate defocus determination. Modern CTF detection software such as i.e. the tilt series), the finely aligned and pre-processed tilt series are back-projected from their assigned orientation angles. To gain contrast for better visualization in the initial phases of processing, filters can be applied during the reconstruction process. For initial tomogram visualization, weighted back-projection (WBP) with iterations of simultaneous iterative reconstruction technique (SIRT)-like filtering can be performed using the Etomo IMOD interface  the result to obtain a featureless membrane density. This is used for initial alignment of the subtomograms, which helps to define particle centres and can often constitute a first cleaning step. The subtomogram dataset is typically split in half and processed separately during further alignment, following a ‘gold-standard’ approach . Firstly, it revealed the association of the coat and the Sar1 GTPase with the membrane. We observed for the first time how the N-terminal amphipathic helix of Sar1 is associated with the membrane: a helical hook is bent by 90° and inserts horizontally into the outer leaflet, running roughly parallel to the tube axis (Fig. 6et al., 2018Our recent cryo-ET and STA studies of ng Fig. 5a. Firstis Fig. 6. Also, tet al., 2001et al., 2007Moreover, our structure unveiled how the inner and outer coat are associated: through the binding of motifs embedded within the outer coat disordered C-terminal tails to two distinct sites on Sec23. Together with previous biochemical and X-ray crystallographic studies (Antonny 3.2.in vitro reconstituted assemblies and within the cell. Three consecutive studies have investigated the structure of COPI assembled in vitro from purified coatomer components on GUVs (Faini et al., 2012et al., 2015b; Dodonova et al., 2017in situ structural studies can reveal the interactions of coat proteins with cargo molecules. The power of in situ studies has been demonstrated in a recent study of COPI as a way of identifying protein–protein interactions that are relevant in an intracellular context (Bykov et al., 2017in vitro mimics that seen in physiological contexts. Moreover, they identified a novel density that is not present in in vitro reconstitutions, which was attributed to cargo or cargo receptors as informed by previous biochemical knowledge regarding the cargo-binding site of β-COPI.Two other coat protein assemblies, COPI and retromer, were analysed by cryo-ET and STA of in vitro from purified retromer Vps5 components on liposomes was recently determined to subnanometre resolution (Fig. 5c; Kovtun et al., 2018in situ validation of the structure of retromer obtained from in vitro reconstitutions confirmed that in vitro reconstituted assemblies mirrored native retromer arrangements within the cell (Kovtun et al., 2018The structure of retromer as assembled 4.et al., 2016et al., 2015et al., 2015et al., 2017et al., 2018et al., 2015et al., 2017et al., 2017et al., 2015et al., 2012et al., 2010et al., 2015et al., 2017et al., 2016et al., 2012Cryo-ET and STA have been applied to the study of units that do not form arrays, such as bacterial secretion systems (Chang et al., 2016et al., 2013et al., 2017et al., 2018et al., 2015et al., 2017et al., 2016et al., 2019While some studies have demonstrated that near-atomic resolution is possible with STA (Schur et al., 2017Data processing also requires significant user expertise and manual intervention. The ongoing developments in automatic tilt series alignment procedures and the establishment of user-friendly software for STA will greatly benefit the speed of processing (Mastronarde & Held, 2017In vitro reconstitutions provide control over sample composition and enable studies of the effect of varying the reaction environment in a controlled manner. Additionally, investigating the effect of mutations, which is central to the validation of structural information, is technically straightforward and is isolated from possible off-target effects. However, isolation from potential interacting partners, especially transient interactors that have not been biochemically established, limits discovery and the collection of exhaustive structural data. Information is also lost regarding the cellular context of the complex of interest. In situ studies can bridge the gap between in vitro analysis with purified proteins and the cell, allowing the identification of novel interacting surfaces, validating in vitro structural information, and providing global spatiotemporal insight (Kovtun et al., 2018et al., 2017et al., 2016et al., 2017in situ structural determination are beyond the scope of this review, we note that automated and sophisticated technologies for identifying assemblies of interest through template-matching may allow higher throughput and lower subjectivity (Lučič et al., 2013et al., 2015


Shen et al.  examinedFEE). Below we discuss four such implications with the goal of inspiring further research and insights into this important topic.The methods and findings from this study have novel implications concerning facial expressions of emotion  and had shown that they rarely occurred (Porter and ten Brinke, The findings from Shen et al.'s  study anShen et al.'s  findingsFinally, the findings by Shen et al.  and a grDM and HH authors contributed equally to the ideas presented. The DM wrote the first draft of the paper. Both authors contributed equally to editing the first draft to its final version.The authors declare that they are employees of Humintell, a for-profit company that sells microexpression related products.


Original textP. patens mutant showed poorer recovery from salt and osmotic stress compared to the wild-type (WT), indicating that DHNs are indispensable for the alleviation of cell dehydration , indicating that DHNs are indispensable for the alleviation of cell dehydration (Saavedra et al., A DHN gene knockout Original textDHN genes are highly expressed under conditions of various types of stress, such as drought, cold, or high salinity (Yoon et al., Modified textDHN genes are highly expressed under conditions of various types of stress, such as drought, cold, or high salinity (Yoon et al., In the original article, we neglected to cite two previous studies. The authors apologize for this oversight. This error does not change the scientific conclusions of the article in any way.The original article has been updated.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.


They came to the conclusion that one component of the latter, mGPD, is responsible and a direct molecular target for metformin.+/NADH as co-factor [a Km value around 30 μM for glycerophosphate (GP)] and mGPD with FAD as co-factor. The mGPD has a high Km for GP (2 to 8 mM), is an important reactive oxygen species (ROS) producer  stimulation of succinate-driven OCR by metformin that has never been reported before. Third, high throughput screening for mGPD inhibitors with several thousands of chemicals yielded membrane permeable, high-affinity blockers such as iGP  but not metformin or related structures (Orr et al., Thus, the data by Calza et al.  and the After submission of the manuscript two publications came to our attention, which support the notion that mGPD must be removed from the list of direct molecular metformin targets. Alshawi and Agius  report tHG and OL discussed the topic and wrote the paper.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.


Liu et al. have recently published a paper highlighting blood-derived miRNAs as possible early diagnostic biomarkers in Pancreatic Cancer by conducting a narrative review and meta-analysis titled, “Blood-Derived microRNAs for Pancreatic Cancer Diagnosis: A Narrative Review and Meta-Analysis” (Li et al., Despite this, Liu et al.'s study stands out by the virtue of being the most updated study regarding this subject, and is therefore expected to have the largest pool of clinical data to support its meta-analysis. However, the study published by Sun et al. in May 2018 in the journal Disease Markers, titled, “Systematic Review and Meta-Analysis of Diagnostic Accuracy of miRNAs in Patients with Pancreatic Cancer,” includes a pool of 40 studies for its meta-analysis when compared to Liu et al.'s 17 studies (Sun et al., Though, it is worth highlighting, that the results of Liu et al.'s study conform to the results presented in aforementioned, previously published papers. All previous studies unanimously declare that the sensitivity and specificity of multiple miRNA profiles are superior to that of single miRNA profiles for pancreatic cancer diagnosis. However, a few single miRNA have been suggested to be more valuable as indicators of pancreatic cancer, compared to other miRNA. Li et al, Sun et al, Wan et al, and Pei et al.'s studies, all describe miR-21 as a promising marker for pancreatic cancer (Wan et al., Additionally, we would like to note that previous studies evaluating diagnostic test accuracy have shown that Chi-square and I-square values alone for analysis of pooled meta-analysis data may not be sufficiently informative as they do not consider threshold effect. In random effects model of meta-analysis, Tau-square value may also be included as the estimated variation or heterogeneity between the effects for test accuracy observed in different studies (Lee et al., Finally, considering the current evidence presented by Li et al., and previous studies, it is clear that miRNAs have potential clinical utility as diagnostic and prognostic markers in Pancreatic Cancer. Although Li et al., study presents potentially interesting data and results, the highlighted issues need to be resolved before it may be considered robust enough a study to be cited by and used for future research in this field.RJ conceived of this critical review and led the development of the letter to the editor. RJ and CK wrote the first draft of the letter, and coordinated and integrated comments from co-authors. SS, and SB critically revised and edited successive drafts of the manuscript. All authors read and approved the final version of the manuscript.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.


Nanotechnology plays an important role in advancing treatment and diagnosis of a variety of human diseases. The use of nanocarriers often leads to better pharmacokinetic and safety profiles as well as enhanced bioavailability of the entrapped molecules. Several nanoparticle formulations have already been approved by Food and Drug Administration  or have advanced into clinical trials (Andre et al., Certain types of exosomes have been demonstrated to have higher drug delivery efficiency when compared to commonly used nanocarriers (Kim et al., 2O density cushion to eliminate non-exosome proteins and to further reduce sample volume (Escudier et al., Lack of an efficient standardized isolation and purification method is a major challenge for bringing exosome technology into the clinic. It has been reported that exosomes can be isolated and purified by single or combinations of different methods, including immunoaffinity capture, size exclusion, polymeric precipitation, ultracentrifugation, microfluidics techniques, and commercially available kits (Kim et al., in vivo would be an exciting next set of challenges.In addition to developing reliable isolation and purification methods, researchers have recently developed new strategies to load cargos into exosomes. A decade ago, two independent research groups described exosomes as carriers of information and demonstrated their ability to transfer information from one cell type to another (Ratajczak et al., G12D siRNA to target undruggable oncogenic Kras in pancreatic tumor cells in vivo (Kamerkar et al., G12D expression, suppression of cancer cell proliferation, and an increase in overall survival in a mouse model of pancreatic cancer (Kamerkar et al., Another area of intense research is the development of better methods to enhance targeting ability of exosomal nanoparticles for cancer treatment. By utilizing normal human foreskin fibroblast-derived exosomes, Kamerkar and colleagues recently demonstrated the ability of exosomes to efficiently deliver KrasIn summary, recent research has made significant progress in overcoming major barriers for using exosomes as a delivery system. Exosomes are ideal systems for delivering cancer therapeutics, owing to their size, surface expression profiles, low immunogenicity, low cytotoxicity, and long-term safety. Their use has opened a new promising avenue for cancer treatment. Scaling up the production of highly targetable therapeutic exosomes that can be used off-the-shelf which does not require generation from autologous source will be the next critical challenge to bring this promising delivery technology into the clinic.SW initial conceptualization of the article. MY and SW wrote the manuscript.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.


Investigations into the relationship between bodily illusions and pain perception are representing a relatively modern trend in cognitive science. Recently, Bauer et al.  publisheThe analgesic effects linked to the vision of the own body  were initially described by Longo et al. . AlthougRHI alone did not change the MPT values significantly” and that this would be in contrast with Martini et al. (In their third control condition Bauer and colleagues asked their participants to close their eyes before the measurement of MPT, so they did not see any stimuli approaching the RH. During this condition a modulation of proprioceptive drift was reported and a high level of ownership was found, but no pain modulation was documented. The authors thus state that “the induction of the i et al. . Howeveri et al. , has notAnother point worth discussing might be the type of pain chosen to measure the participants' pain threshold: the majority of studies about visual analgesia during RHI/VHI paradigms made use of thermal or electrical stimuli. In Bauer's experiment mechanical stimuli were chosen. The authors explain their preference stating that “MPT is assumed to be closer to clinical pain than thresholds measured with thermal stimuli,” but unfortunately no explanations nor any references were provided to support their assertion. Mechanical, electrical and heat pain threshold have been shown to have some level of independence and can react differently to different modulators (for ex. Tong et al., qualitative data too. What is a praxis for clinical research with patients could be extended to healthy participants as well, to boost interpretability of data and comparability among studies.As a final point, given the high inter-subject variability and the complexity of the “embodiment” phenomenon (Longo et al., The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The publication titled “Vertebral Arteriovenous Fistula: An Unwelcome Thrill” by Edwards and his colleagues provided a review of the etiology, pathophysiology, and management of vertebral AV fistulae .Our primary concern centers on the discussion of the possible etiology of their patient's vertebral AV fistulae and its possible relationship to chiropractic manipulation. Edwards et al. claim that “numerous prior cases of vertebral AVFs report induction by chiropractic manipulation” which is the genesis of our communication. The patient in Edwards et al. case report had sought chiropractic care for chronic neck pain. Although their patient “did not associate onset of her symptoms with any known physical trauma” Edwards et al. stated that “it is therefore plausible that our patient's fistula was caused by unreported chiropractic manipulation, although this patient's fistula occurred in the distal cervical portion of her vertebral artery, where previous studies have determined that spontaneous vertebral AVFs form most commonly.” opposite. We observed that the patient in our case report suffered from an intracranial AVF, an anatomical location immune to any effects of spinal manipulation. Our case report also observed that “attending physicians initially believed the patient had experienced a rare complication from cervical manipulation, an impression that prevailed for several days, delaying proper intervention. The location and breadth of the patient's ischemia and the absence of similar cases in the literature, should have argued against chiropractic manipulation as the cause of the patient's ascending myelopathy. The admitting physician's prolonged focus on a possible complication from chiropractic manipulation may be characterized as an anchoring bias.”We believe Edwards et al. incorrectly cited our case report  as scienIn conclusion, we again thank Edwards et al. for providing an excellent overview of an uncommon vascular disorder. Edwards et al. held the role of an unreported chiropractic manipulation as “plausible” for the AVF in their case report. Contrary to the assertion of Edwards et al., our case report does not make an association between chiropractic manipulation and vertebral AVFs. Our case report demonstrated that the potential for attending clinicians to formulate inaccurate etiological opinions of causation is based solely on temporal association in patients with a history of receiving chiropractic manipulation.


The neurocognitive approach points out how reduced self-awareness is related to cerebral disorders, particularly concerning focal lesions, emotional and motivational determinants, and concurrent neuropsychological impairments Palermo, . Given ia lack of self-awareness of deficits.” Indeed, executive-metacognitive dysfunctions have been formerly associated with loss of self-awareness across major neurocognitive disorders likely due to Alzheimer's Disease (AD) and frontotemporal dementia (Amanzio et al., In their brilliant mini-review, Bertrand and colleagues drew attention to the fact that neurological and neuropsychiatric patients can present severe—and often underestimated—impairments in metacognitive abilities that may result in “metacognition and perspective-taking as a key aspect for improving quality of life in AD patients. These authors specified that “metacognition refers to the monitoring and regulation of cognitive processes and its impairment can lead to a lack of self-awareness of deficits, or anosognosia” (Bertrand et al., Focusing on AD, Bertrand et al.  dwelt onAnosognosia and reduced self-awareness are frequently used as synonyms in the literature and an overlap between them has been highlighted. This is a delicate question because according to the interpretation given to those terms, the methods of detection and interpretation of the phenomenon could change. This topic was recently treated by Mograbi and Morris . In theithe ability to consciously process information about ourselves in a manner that reflects a relatively objective view while maintaining our unique phenomenological or subjective sense of self ” (Prigatano, where the processing in turn operates in a modular manner at any level of the hierarchy, so that damage in one functional domain may result in a different kind of reduced self-awareness” (Palermo et al., In our opinion, the notion of “self-awareness” is not entirely concerned with the concept of “anosognosia,” since the former is a complex neuropsychological notion, defined as “Bertrand et al.  suggesteThis model was applied by Amanzio et al. , who addirrefutable liaison between executive system dysfuntion, metacognitive disabilities and the occurrence of reduced self-awareness. The issues raised in this commentary have implications in considering executive-metacognitive disabilities as a neuropsychological marker for reduced self-awareness in AD.In conclusion, reduced self-awareness is often observed in AD patients who have suffered major damage to the central executive system. This could be due to the fact that the central executive system is a metacognitive facility of interest in controlling the flow of information in tasks requiring initiation, planning, set-shifting, strategy allocation, monitoring and inhibition (Amanzio et al., We would like to conclude by drawing attention to the fact that this phenomenon is worthy of clinical investigation. Indeed, distinct major neurocognitive disorders, brain pathologies and mood disturbances exhibit executive-metacognitive abnormalities as part of the anomalies of overlapping neural pathways. In this context, ACC hypofunctionality seems to represent one of the relevant underpinnings of a lack of self-awareness (Amanzio et al., The commentary is based on a concept developed by SP who performed the review and critique processes as PI. All the authors listed have contributed to writing the commentary. All authors have approved the submission of the manuscript.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.


The ongoing interest in organic and perovskite solar cells comes from the forecasted excellent potential for low-cost solar electricity generation that these technologies offer. Organic and perovskite solar cells can be fabricated from abundant materials with high-throughput compatible processes on flexible substrates and promise near future large-scale electricity production as well as novel and alternative applications in buildings, portable electronics or in tandem thin film devices.Research activities on perovskite solar cells have been exploding over the last years and a simple title search including ‘perovskite solar cell’ in the web of science delivers well over 1500 hits for the time January–October 2018 alone! Likewise, organic solar cells are still in the spotlight and recent advances with ternary blends and non-fullerene acceptors allow now for power conversion efficiencies exceeding 10% almost as a matter of routine.In this Focus Issue of Science and Technology of Advanced Materials, we present a collection of excellent research and review articles on recent milestones in materials development, device architectures and advanced characterization techniques that highlight the great progress that is being made in both photovoltaic technologies.The efficiency of ternary organic solar cells depends on the developing nanostructured network of donor and acceptor phases during film formation. In a typical ternary system for photovoltaic applications, a third sensitizing component is added to an underlying high-performing binary system. However, finding the ideal three-component composition by trial and error is a cumbersome process. The research paper of Makha and Heier et al.  demonstrNewman and Tsoi et al.  carried Two articles are dealing with ‘photon management’ in organic and perovskite solar cells. Zhang and Toudert  review rThe article of Pascual-San-José and Campoy-Quiles et al.  considerBeyond high efficiency, other critical factors are required for a photovoltaic concept to translate from the laboratory to a real-world technology. For perovskite specifically, there is a desire to replace lead, due to toxicology concerns. The review article by Zhang and Lin et al.  outlinesShen and Catchpole et al.  review tFinally, Neukom and Ruhstaller et al.  present We thank all authors that contributed to this Focus Issue.


The intent of this commentary is to constructively contribute to the recently published manuscript by Abbes et al.  by debatAbbes et al.  have selAnother relevant issue concerns the balance between PAP and fatigue, which was widely discussed by the authors (both in the introduction and in the discussion sections). Considering that the initial warm-up was a standard swimming workout (cf. Neiva et al., In swimming in particular, for potentiating performance, it is fundamental that muscular strength increments translate into increased ability to generate propulsive force in water, with technical aspects of swimming mechanics determining the extent to which increased force transfers into faster swimming velocity (Girold et al., The role of inter-individual variation in response to any training load should also be analyzed (Chen et al., Finally, we agree with Abbes et al.  in what JA, CB, and RF have fully reviewed and criticized the original article, drafted the commentary, reviewed, and approved the final manuscript.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.


Mycobacterium within five genera. In this paper Mycobacterium vulneris  and incompatible with M. vulneris. Therefore, we sequenced the type strain of M. vulneris, DSM 45247T. The genome sequence we obtained (NCXM01000000) found its expected phylogenomic position within the slowly growing species of the Mycobacterium avium complex (Tortoli et al., M. vulneris (van Ingen et al., Mycolicibacterium is inappropriate and recommend the reinstatement of the previous basonym Mycobacterium vulneris (van Ingen et al., We have published a study concerning the genus M. vulneris (EU834055; van Ingen et al., M. vulneris and likely belong to the species M. porcinum. An effect of the misleading power of genomes such as CCBG00000000 present in GenBank. Moreover, a check of all genomes retrieved from GenBank allowed us to detect six further cases of mislabeling (Tortoli et al., Notably, a check of the NCBI WGS sequence database with the 16S rRNA gene sequence of The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Stephen Maisto, Mark Galizio, Gerard J. Connors , 2017, 512 pages, ISBN: 978-1337408974Kids born in the 1990s were prone to a diagnosis of Attention-deficit/hyperactivity disorder, or ADHD (Maisto et al., A psychopharmacology book written by Stephen Maisto, Mark Galizio, and Gerard Connors describes a variety of drugs in great detail. Two main groups of drugs in the book include stimulants and depressants. The drugs classified as depressants consist of alcohol and opiates, such as morphine derivatives or other analgesic drugs (Maisto et al., Amphetamines, methylphenidate, and other stimulants share nearly the same pharmacokinetics (Maisto et al., Journal of the International Neuropsychological Society agrees that in the past 25 years, prevalence of ADHD diagnosis has increased (Mahone and Denckla, But in the book's discussion on stimulants, the medication Ritalin prominently stands out. Methylphenidate carries the brand name of Ritalin, Concerta, or Daytrana. The book by Maisto and associates emphasizes the controversy of prescribing methylphenidate to children with ADHD (Maisto et al., Stephen Maisto and his team of researchers argue that any child can be diagnosed with ADHD (Maisto et al., Journal of Attention Disorders agrees that ADHD negatively impacts focus in school, which was tested on over two hundred college students (Jones et al., However, methylphenidate does improve academic performance and reduces problem-behaviors (Maisto et al., American Journal of Health System Pharmacy (Sugrue et al., The effectiveness of methylphenidate is demonstrated in a research study by the But there are physical side effects of methylphenidate, such as loss of appetite and weight (Maisto et al., Another treatment for ADHD are the amphetamines, such as Adderall or Vyvanse, which are closely rated to methylphenidate (Maisto et al., A drug that is shockingly similar to methylphenidate is methamphetamine, which was created in the nineteenth century (Maisto et al., The pharmacology book authored by Stephen Maisto, Mark Galizio, and Gerard Connors dives into the controversy that methylphenidate is addictive (Maisto et al., Drug Use & Abuse book (Maisto et al., There is even a large market for the illegal sale of methylphenidate (Maisto et al., The author confirms being the sole contributor of this work and has approved it for publication.The author declares 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 her review paper, Dr. Ruth Itzhaki provides evidence that infection with herpes simplex virus type 1 (HSV1) makes a significant risk factor for Alzheimer's Disease (AD). She speculates that the use of antiviral drugs may decrease such a risk. In connection with this, it could be reminded that lithium is a drug, which anti-herpes properties have been documented both in experimental and clinical studies . This enzyme is important in the metabolism of amyloid precursor protein and the phosphorylation of the tau protein, the leading factors in the pathogenesis of the AD. Experimental studies on rats, using cortical and hippocampal neurons, showed that lithium treatment decreases the GSK3 mRNA (Mendes et al., The association between lithium treatment and a decreased risk of dementia was found in big cohorts and many case-control studies (Donix and Bauer, In patients with bipolar disorder, infection with herpes simplex virus type 1 was associated with impaired cognitive functioning (Dickerson et al., To conclude, let me mention two interesting recent papers where a connection between lithium level in drinking water and dementia was investigated. Kessing et al.  performeThe author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.