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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.

Letter to the Editor

In this study, the authors show that the heritable behavioral and metabolic changes that are observed in rodents exposed to early life stress are mediated by changes in miRNA levels in the sperm of affected males. Injection of isolated RNA from the sperm of stressed males into donor fertilized oocytes is able to induce these phenotypic changes in the resulting offspring. Small non-coding RNAs (sncRNAs) are potential vectors at the interface between genes and environment. We found that traumatic stress in early life altered mouse microRNA (miRNA) expression, and behavioral and metabolic responses in the progeny. Injection of sperm RNAs from traumatized males into fertilized wild-type oocytes reproduced the behavioral and metabolic alterations in the resulting offspring.

The growing prevalence of human monkeypox infection has developed an alarming situation worldwide. Monkeypox virus was first time found in 1958 in monkeys and later spread to humans. The first case of human monkeypox was reported in September 1970 in the Democratic Republic of the Congo. Human monkeypox was found outside Africa in the year 2003 in United States. More recently, from May 7 2022 to June 29, 2022, the monkeypox cases are swiftly spread worldwide, involving over 50 countries, and affecting 5115 people in Europe, the United Kingdom, North America, and South America, Asia, Australia, and the Middle East. The confirmed monkeypox cases in the United Kingdom from May 7, 2022 to June 29, 2022, are 1076 (21.03%); Germany 874 (17.08%); Spain 800 (15.64%); France 440 (8.60%); Portugal 391 (7.62%); United States 350 (6.84); Canada 276 (5.39%); Netherlands 257 (5.02%); Italy 159 (3.10); Belgium 117 (1.59%); Switzerland 81 (1.58%); Israel 33 (0.64%), Ireland, and 31 (0.64%). However, in about 35 countries, the cases are less than 20 in each country. The epidemiological trends of the human monkeypox infection are swiftly shifting from endemic regions to non-endemic countries. The global health authorities must take priority-based preventive measures to stop the outbreaks of monkeypox disease across the globe. doi: https://doi.org/10.12669/pjms.38.6.6775 How to cite this:Meo SA, Jawaid SA. Human Monkeypox: Fifty-Two Years based analysis and Updates. Pak J Med Sci. 2022;38(6):---.  doi: https://doi.org/10.12669/pjms.38.6.6775 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

doi: https://doi.org/10.12669/pjms.40.9.10790 How to cite this: Jawaid SA. Growing demand for Bilateral Total Knee Arthroplasty (BTKA): How to balance patient outcome with healthcare system challenges. Pak J Med Sci. 2024;40(9):1895-1897. doi: https://doi.org/10.12669/pjms.40.9.10790 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT Objective: To investigate the efficacy of anti-vascular endothelial growth factor (VEGF) drugs in diabetic retinopathy (DR)-retinal microaneurysms, and its prognosis. Method: This was a retrospectively study in which total of 120 patients with DR in Baoding No.1 Central Hospital from June 2020 to June 2022 were retrospectively analyzed. According to different treatment methods based on macular edema, they were divided into an injection group and a control group. The control group was treated routinely, while the injection group was additionally intravitreally injected with an anti-VEGF drug. The patients were followed up for one year, and the changes in the number of retinal microaneurysms, best corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared between the two groups. The effect on retinal microaneurysms was analyzed. Result: After treatment for 12 months, the total efficacy of the injection group was 95.00%, which was higher than 80.00% of the control group (p< 0.05). After one, three, six and twelve months of treatment, both CRT and the number of retinal microaneurysms reduced in the injection group compared with those before treatment. After treatment for one, three, six and twelve months, BCVA showed increases in the injection group, but no obvious changes in the control group compared with that before treatment. Conclusion: For patients with DR complicated with macular edema, early use of anti-VEGF drugs can significantly improve the fundus lesions, reduce the CRT and number of retinal microaneurysms, and improve the BCVA of the patients, with high clinical efficacy.

doi: https://doi.org/10.12669/pjms.39.2.7398 How to cite this: Shah FA, Jawaid SA. The h-Index: An Indicator of Research and Publication Output. Pak J Med Sci. 2023;39(2):315-316.  doi: https://doi.org/10.12669/pjms.39.2.7398 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

doi: https://doi.org/10.12669/pjms.40.4.9408 How to cite this: Jawaid SA. Some essential pre-requisites and requirements to establish and run a successful Journal. Pak J Med Sci. 2024;40(4):555-556. doi: https://doi.org/10.12669/pjms.40.4.9408 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.