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Abstract Microglia, the resident immune cells of the brain, are increasingly implicated in the regulation of brain health and disease. Microglia perform multiple functions in the central nervous system, including surveillance, phagocytosis and release of a variety of soluble factors. Importantly, a majority of their functions are closely related to changes in their metabolism. This natural inter-dependency between core microglial properties and metabolism offers a unique opportunity to modulate microglial activities via nutritional or metabolic interventions. In this review, we examine the existing scientific literature to synthesize the hypothesis that microglial phagocytosis of amyloid beta (Aβ) aggregates in Alzheimer’s disease (AD) can be selectively enhanced via metabolic interventions. We first review the basics of microglial metabolism and the effects of common metabolites, such as glucose, lipids, ketone bodies, glutamine, pyruvate and lactate, on microglial inflammatory and phagocytic properties. Next, we examine the evidence for dysregulation of microglial metabolism in AD. This is followed by a review of in vivo studies on metabolic manipulation of microglial functions to ascertain their therapeutic potential in AD. Finally, we discuss the effects of metabolic factors on microglial phagocytosis of healthy synapses, a pathological process that also contributes to the progression of AD. We conclude by enlisting the current challenges that need to be addressed before strategies to harness microglial phagocytosis to clear pathological protein deposits in AD and other neurodegenerative disorders can be widely adopted.

There are numerous well-established parameters to judge and evaluate the standard of a medical journal like quality of its contents and geographic distribution of manuscripts, it attracts for publication, indexation and coverage in important indexes and databases like Medline, Web of Sciences by Clarivate known for its Impact Factor (IF), PubMed Central, Scopus etc., journal visibility and readership, timely regular publication. Impact Factor is one of the criteria and not the only criteria, which should be used to judge the standard of a journal. However, too much importance being given to the Impact Factor by the regulatory bodies in Pakistan as well as by medical institutions, asking those doing PhD to publish their research work in Impact Factor journals has created a crisis like situation not only for the researchers but also made the life of the IF journal editors miserable. They are under tremendous pressure to accommodate more and more papers by the authors anxious for early publication to meet certain deadlines for the completion of their research project and award of degrees while the editors on their part are faced with a dilemma due to human resource and financial resource constraints. In an environment where political stability remains in short supply most of the time, law and order situation is unpredictable, not to forget the frequent breakdown of electricity and inefficient internet service, it is not possible to either increase the frequency of publications or plan some other measures which all call for additional investment. Finding trained human resource and then retaining those remains a constant problem.

Abstract The development of high-precision large-area optical coatings and devices comprising low-dimensional materials hinges on scalable solution-based manufacturability with control over exfoliation procedure-dependent effects. As such, it is critical to understand the influence of technique-induced transition metal dichalcogenide (TMDC) optical properties that impact the design, performance, and integration of advanced optical coatings and devices. Here, we examine the optical properties of semiconducting MoS2 films from the exfoliation formulations of four prominent approaches: solvent-mediated exfoliation, chemical exfoliation with phase reconversion, redox exfoliation, and native redox exfoliation. The resulting MoS2 films exhibit distinct refractive indices (n), extinction coefficients (k), dielectric functions (ε1 and ε2), and absorption coefficients (α). For example, a large index contrast of Δn ≈ 2.3 is observed. These exfoliation procedures and related chemistries produce different exfoliated flake dimensions, chemical impurities, carrier doping, and lattice strain that influence the resulting optical properties. First-principles calculations further confirm the impact of lattice defects and doping characteristics on MoS2 optical properties. Overall, incomplete phase reconfiguration (from 1T to mixed crystalline 2H and amorphous phases), lattice vacancies, intraflake strain, and Mo oxidation largely contribute to the observed differences in the reported MoS2 optical properties. These findings highlight the need for controlled technique-induced effects as well as the opportunity for continued development of, and improvement to, liquid phase exfoliation methodologies. Such chemical and processing-induced effects present compelling routes to engineer exfoliated TMDC optical properties toward the development of next-generation high-performance mirrors, narrow bandpass filters, and wavelength-tailored absorbers.

The axial load-carrying capacity for a wide range of short concrete-filled steel tubular (CFST) members having different section profiles is evaluated in the presented work. A numerical study has been carried out through Finite-Element based demonstration and it has been accomplished in the ABAQUS package for relevancy of analytically predicted axial load carrying capacity by unified formula as suggested by Yu M. et al. (2010). To validate the results from the unified formula and the experimentally available literature, finite element-based models for hollow and solid sections of CFST columns with circular, octagonal, and square section profiles have been generated. A total of 31 hollow and 24 solid circular columns, 9 hollow, and 9 solid octagonal columns, and in the last 9 hollows and 38 solid square CFST columns are examined for the persistence of the results. After evaluation of obtained results from the modeling existing results are validated, and it is found that the proposed unified formula predicts satisfactory results when compared with the result of established models. Further, it is concluded that displacement in the direction of applied load is not uniform throughout the length of CFST columns thereby using the ring confinement technique for the region of applied force may be reasonable.

Studies done by the previous researchers in Concrete Filled Steel Tubes (CFST) have a significant focus on the bond performance of CFST. This paper includes studies on the evaluation of critical parameters such as interface condition, interface length, infilled concrete strength, and end friction and cross-section dimension in these members. It is found that the effect of interface length had very little impact on the bond stress as it shows a promising value when the interface length is in the range of 200-800 mm and after that, it gets shifted and reduced for larger interface length. But this decrease in the bond stress is affiliated with other parameters, like macro-locking, infilled concrete compressive strength distinctly affects the mean interface bond strength for the sample in the regular condition, the interface bond strength for the most part increases with infilled concrete strength. It is spotted that the friction coefficient of 0.15 is used at both column ends to provide the fixity and it becomes clear that the local buckling pattern of the stub column is independent of the end friction. In both categories of columns, the bond strength among the steel tube and infilled concrete reduced extraordinarily with increased cross-sectional dimension.

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BackgroundAccumulating evidence suggests that the COVID-19 pandemic has negatively impacted the mental health of individuals. However, the susceptibility of individuals to be impacted by the pandemic is variable, suggesting potential influences of specific factors related to participants’ demographics, attitudes, and practices. ObjectiveWe aimed to identify the factors associated with psychological symptoms related to the effects of the first wave of the pandemic in a multicountry cohort of internet users. MethodsThis study anonymously screened 13,332 internet users worldwide for acute psychological symptoms related to the COVID-19 pandemic from March 29 to April 14, 2020, during the first wave of the pandemic amidst strict lockdown conditions. A total of 12,817 responses were considered valid. Moreover, 1077 participants from Europe were screened a second time from May 15 to May 30, 2020, to ascertain the presence of psychological effects after the ease down of restrictions. ResultsFemale gender, pre-existing psychiatric conditions, and prior exposure to trauma were identified as notable factors associated with increased psychological symptoms during the first wave of COVID-19 (P

Objectives: To ascertain factors associated with worsening of psychiatric conditions during the coronavirus disease 2019 (COVID-19) pandemic.Methods: This study anonymously examined 2,734 psychiatric patients worldwide for worsening of their preexisting psychiatric conditions during the COVID-19 pandemic. An independent clinical investigation of 318 psychiatric patients from United States was used for verification.Results: Valid responses mainly from 12 featured countries indicated self-reported worsening of psychiatric conditions in two-thirds of the patients assessed that was through their significantly higher scores on scales for general psychological disturbance, posttraumatic stress disorder, and depression. Female gender, feeling no control of the situation, reporting dissatisfaction with the response of the state during the COVID-19 pandemic, and reduced interaction with family and friends increased the worsening of preexisting psychiatric conditions, whereas optimism, ability to share concerns with family and friends, and using social media like usual were associated with less worsening. An independent clinical investigation from the United States confirmed worsening of psychiatric conditions during the COVID-19 pandemic based on identification of new symptoms that necessitated clinical interventions such as dose adjustment or starting new medications in more than half of the patients.Conclusions: More than half of the patients are experiencing worsening of their psychiatric conditions during the COVID-19 pandemic.

Prolonged periods of social isolation can have detrimental effects on the physiology and behavior of exposed individuals in humans and animal models. This involves complex molecular mechanisms across tissues in the body which remain partly identified. This review discusses the biology of social isolation and describes the acute and lasting effects of prolonged periods of social isolation with a focus on the molecular events leading to behavioral alterations. We highlight the role of epigenetic mechanisms and non-coding RNA in the control of gene expression as a response to social isolation, and the consequences for behavior. Considering the use of strict quarantine during epidemics, like currently with COVID-19, we provide a cautionary tale on the indiscriminate implementation of such form of social isolation and its potential damaging and lasting effects in mental health.

BACKGROUND MD-PhD programmes throughout the world provide a platform for medical trainees to commit to a physician-scientist career, qualifying with both a medical degree (MD or equivalent) and Doctor of Philosophy (PhD). However, there are limited studies assessing the characteristics of MD-PhD programmes in Europe and the outcomes of MD-PhD students and graduates. PURPOSE This study aims at a first country-wise exploration of characteristics, opinions, and academic outcomes of MD-PhD students and graduates in Europe. METHODS Two questionnaires were developed to assess the demographics, MD-PhD programme characteristics, opinions, future career paths and academic outcomes of European MD-PhD students and graduates. An online survey of 278 MD-PhD students and 121 MD-PhD graduates from nine and six European countries, respectively, was completed between April 2016 and December 2017. The country-wise categorical responses were then compared through chi-square analysis followed by multiple logistic regression. RESULTS Responses from 266 MD-PhD students and 117 MD-PhD graduates were considered valid. Significant country-wise differences (p

Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two fatal neurodegenerative disorders with considerable clinical, pathological and genetic overlap. Both disorders are characterized by the accumulation of pathological protein aggregates that contain a number of proteins, most notably TAR DNA binding protein 43 kDa (TDP-43). Surprisingly, recent clinical studies suggest that dyslipidemia, high body mass index, and type 2 diabetes mellitus are associated with better clinical outcomes in ALS. Moreover, ALS and FTLD patients have a significantly lower incidence of cardiovascular disease, supporting the idea that an unfavorable metabolic profile may be beneficial in ALS and FTLD. The two most widely studied ALS/FTLD models, super-oxide dismutase 1 (SOD1) and TAR DNA binding protein of 43 kDA (TDP-43), reveal metabolic dysfunction and a positive effect of metabolic strategies on disease onset and/or progression. In addition, molecular studies reveal a role for ALS/FTLD-associated proteins in the regulation of cellular and whole-body metabolism. Here, we systematically evaluate these observations and discuss how changes in cellular glucose/lipid metabolism may result in abnormal protein aggregations in ALS and FTLD, which may have important implications for new treatment strategies for ALS/FTLD and possibly other neurodegenerative conditions.

Participation in the first ever course in Medical Editing conducted at the University of Health Sciences (UHS) in Lahore was highly inspirational, informative and historic. The course content covered a broad range of tremendously exciting learning developments in Medical editing that stimulated the learning process. The endeavors of the organiser of the course; Shaukat Ali Jawaid, Chief Editor, Pakistan Journal of Medical Sciences (PJMS) organized and facilitated this very first course in Medical Editing. It provided an opportunity of networking with many stalwarts in medical journalism in Pakistan as well as to learn from their experience that led to many ses-sions of enlightened peer to peer interaction.

Background: Despite an alarming rise in the global prevalence of dementia, the available modalities for improving cognition and mental wellbeing of dementia patients remain limited. Environmental enrichment is an experimental paradigm that has shown promising anti-depressive and memory-enhancing effects in pre-clinical studies. However, its clinical utility has remained limited due to the lack of effective implementation strategies. Objective: The primary objective of this study was to evaluate the usability (tolerability and interactivity) of a long-term virtual reality (VR)- based environmental enrichment training program in older adults with mild cognitive impairment (MCI) and mild dementia. A secondary objective was to assess the effect of VR-based environmental enrichment on stabilization of cognitive functioning and improvement of mental wellbeing in older adults with MCI and mild dementia. Methods: A total of seven participants (four patients with MCI and three with mild dementia) received biweekly VR-based environmental enrichment over a course of 6 months. The tolerability and interactivity of the participants in the VR training was serially assessed via virtual reality sickness questionnaire (VRSQ) and recording of input-error ratio. Cognitive functioning was assessed through Montreal cognitive assessment (MoCA) before and after the study. Mental wellbeing was assessed through Warwick-Edinburgh Mental Well Being Scale (WEMWBS). Results: VR-based environmental enrichment was well-tolerated by the patients with significant decrease in VRSQ scores (p < 0.01) and input-error ratio (p < 0.001) overtime. VR training was also effective in stabilization of MoCA scores over the course of therapy (non-significant difference in the MoCA scores before and after the therapy) and was associated with a trend (p < 0.1) towards improvement in WEMWBS scores between the first and the last assessments. Qualitative observations by the care-givers further corroborated a noticeable improvement in mental wellbeing of patients. Conclusions: This pilot study shows that VR can be a feasible, tolerable, and potentially effective tool in long-term support of older adults with MCI and mild dementia.

Protein phosphatase1 (PP1), a signalling and transcriptional regulator, and epigenetic modulator is known to be a memory suppressor. Here the authors show that memory control by PP1 involves the microRNA cluster miR-183/96/182, and that this cluster is selectively regulated during memory formation in mice.

Scientific writing has a proper format. The anatomical structure or important components of an original article consists of a structured abstract (usually in four sub-headings i.e. objective, methods, results and conclusions with appropriate key words), introduciton, methodology, results and discussion. It is summarized by the acronym IMRAD wherein: I stands for Introduction, M for Methods, R for Results, A for And, D for Discussion. This manuscript describes the information which has to be included in the Introduction and Discussion sections of an original article.

Objective:To ascertain cancer patients' views regarding disclosure of diagnosisin the Pakistani population, anxiety levels after disclosure of the diagnosis, interestin knowing all the treatment options and desire to inform their families. Patients and Methods:In this cross-sectional study, 147 cancer patients fromdifferent hospitals in Pakistan were asked questions to determine their opinionsregarding whether the diagnosis of cancer should be disclosed to patients and theirrelatives or not. Anxiety after diagnosis disclosure and who should disclose thisinformation were also asked. Patients were also asked about their views regardingwhether their families should be informed about the cancer diagnosis withoutpatient's prior consent.Results:Atotal of 147 cancer patients completed the questionnaire. Of these, 112(76.2%) wanted to know about their cancer diagnosis while only 28 (19.0%) patientsrefused. Anxiety levels were increased in 59 (40.1%) patients, remained the same in61 (41.5%) and decreased in 27 (18.4%). One hundred and twenty three patients(83.7%), wanted to know the diagnosis from their physicians. Eighty-four (57.1%)patients were interested in all treatment options, while 102 (69.4%) patients wantedto be actively involved in decision making about their treatment. Only 37 (25.2%)patients answered affirmatively to the question which asked if their families wereinformed about the patient's disease without patient's prior knowledge, while 82(55.8%) disagreed. Conclusion:The majority of cancer patients wanted disclosure of their diseaseby their doctor. The results of this study provide important implications for Pakistanidoctors concerning the practice of diagnostic cancer disclosure to the patients.

Background: Vascular dementia (VaD) is the second most common dementing illness. Multiple risk factors are associated with VaD, but the individual contribution of each to disease onset and progression is unclear. We examined the relationship between diabetes mellitus type 2 (DM) and the clinical variables of VaD.

Despite criticism and allegations of suppressing innovative ideas, Peer Review is widely cited as central in evaluation of manuscripts submitted to journals for publication. Peer Reviewers along with editors who are known as gatekeepers help improve the quality of the manuscripts. One of the primary responsibilities of the Editor is considered to create and maintain a high quality productive group of reviewers. In order to retain good reviewers, it is essential to give them due respect, recognize their services, refrain from over burdening the good reviewers, have some CME Credit for this activity, look at different ways of rewarding the reviewers i.e. providing good reading material, books, appreciation certificates, post review thanks letters besides elevating the good efficient reviewers to the Editorial Board. Publishing their name at the end of the year, concession in publication charges if they are authors or co-authors in manuscripts received for publication besides awarding distinguished reviewers are some of the measures that can prove fruitful.