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Rod photoreceptors in the retina adjust their responsiveness and sensitivity so that they can continue to provide meaningful information over a wide range of light intensities. By stimulating membrane guanylate cyclases in the outer segment to synthesize cGMP at a faster rate in a Ca2+-dependent fashion, bicarbonate increases the circulating “dark” current and accelerates flash response kinetics in amphibian rods. Compared to amphibian rods, mammalian rods are smaller in size, operate at a higher temperature, and express visual cascade proteins with somewhat different biochemical properties. Here, we evaluated the role of bicarbonate in rods of cpfl3 mice. These mice are deficient in their expression of functional cone transducin, Gnat2, making cones very insensitive to light, so the rod response to light could be observed in isolation in electroretinogram recordings. Bicarbonate increased the dark current and absolute sensitivity and quickened flash response recovery in mouse rods to a greater extent than in amphibian rods. In addition, bicarbonate enabled mouse rods to respond over a range that extended to dimmer flashes. Larger flash responses may have resulted in part from a bicarbonate-induced elevation in intracellular pH. However, high pH alone had little effect on flash response recovery kinetics and even suppressed the accelerating effect of bicarbonate, consistent with a direct, modulatory action of bicarbonate on Ca2+- dependent, membrane guanylate cyclase activity.

A phenotypic hallmark of cancer is aberrant transcriptional regulation. Transcriptional regulation is controlled by a complicated array of molecular factors, including the presence of transcription factors, the deposition of histone post-translational modifications, and long-range DNA interactions. Determining the molecular identity and function of these various factors is necessary to understand specific aspects of cancer biology and reveal potential therapeutic targets. Regulation of the genome by specific factors is typically studied using chromatin immunoprecipitation followed by sequencing (ChIP-Seq) that identifies genome-wide binding interactions through the use of factor-specific antibodies. A long-standing goal in many laboratories has been the development of a ‘reverse-ChIP’ approach to identify unknown binding partners at loci of interest. A variety of strategies have been employed to enable the selective biochemical purification of sequence-defined chromatin regions, including single-copy loci, and the subsequent analytical detection of associated proteins. This review covers mass spectrometry techniques that enable quantitative proteomics before providing a survey of approaches toward the development of strategies for the purification of sequence-specific chromatin as a ‘reverse-ChIP’ technique. A fully realized reverse-ChIP technique holds great potential for identifying cancer-specific targets and the development of personalized therapeutic regimens.

Deepa Rajan,1 Vinod G Pillai,2 Patsy Varghese1 1Department of Obstetrics and Gynecology, Believers Church Medical College Hospital, Thiruvalla, Kerala, India; 2Department of Surgery, Believers Church Medical College Hospital, Thiruvalla, Kerala, IndiaCorrespondence: Vinod G PillaiDepartment of Surgery, Believers Church Medical College Hospital, Thiruvalla, Kerala, 689103, IndiaTel/Fax +91 469 3503100Email drvinodpillai@gmail.comIntroduction: The Covid pandemic and social distancing has adversely impacted the conventional apprenticeship method of postgraduate training in laparoscopic surgery. Social media may be a useful adjunct for laparoscopic training, but its utility in developing countries like India has not been studied carefully. This paper describes an observational, cross-sectional study on the educational utility of Facebook groups based in India and which focus on laparoscopic gynecologic surgery.Methods: The most popular Facebook groups involving Indians and focusing on laparoscopic gynecology were identified using appropriate search terms as well as inclusion and exclusion criteria. Demographic data related to the groups, the authors of posts as well as descriptive statistics of all the posts during the study period were collected and appropriate statistical analysis was performed.Results: All the groups in this study were large and growing steadily. Posts related to laparoscopy were more likely to be videos, dealing with operative techniques and having educational value for postgraduate residents (p value < 0.001) compared to posts unrelated to laparoscopic surgery. The majority of posts (88.2%) presented original content created by group members rather than material shared from other sources. Members preferred to share laparoscopic content using links to their personal YouTube channels rather than using institutional YouTube channels, dedicated websites for laparoscopic surgery or direct posts on Facebook. Group members liked educational content and laparoscopic surgery-related content significantly more than other content. Only 16.7% of the laparoscopic surgeons could be identified to be working in academic institutes.Conclusion: Social media for medical education has inherent advantages and disadvantages. This article provides objective data regarding its utilisation in a developing country in the midst of the Covid pandemic, and provides a guide for further research and development of innovative teaching methods.Keywords: online learning, distance learning, surgical education, laparoscopic gynecology, Covid pandemic, social media

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic multi-systemic disease characterized by extreme fatigue that is not improved by rest, and worsens after exertion, whether physical or mental. Previous studies have shown ME/CFS-associated alterations in the immune system and mitochondria. We used transmission electron microscopy (TEM) to investigate the morphology and ultrastructure of unstimulated and stimulated ME/CFS immune cells and their intracellular organelles, including mitochondria. PBMCs from four participants were studied: a pair of identical twins discordant for moderate ME/CFS, as well as two age- and gender- matched unrelated subjects-one with an extremely severe form of ME/CFS and the other healthy. TEM analysis of CD3/CD28-stimulated T cells suggested a significant increase in the levels of apoptotic and necrotic cell death in T cells from ME/CFS patients (over 2-fold). Stimulated Tcells of ME/CFS patients also had higher numbers of swollen mitochondria. We also found a large increase in intracellular giant lipid droplet-like organelles in the stimulated PBMCs from the extremely severe ME/CFS patient potentially indicative of a lipid storage disorder. Lastly, we observed a slight increase in platelet aggregation in stimulated cells, suggestive of a possible role of platelet activity in ME/CFS pathophysiology and disease severity. These results indicate extensive morphological alterations in the cellular and mitochondrial phenotypes of ME/CFS patients' immune cells and suggest new insights into ME/CFS biology.

Sutlej basin, a mountainous river basin is located in N-W Himalayan region. This basin has highest potential for hydropower generation as compared to other basins of Indus River system. Recent studies have revealed rise in mean annual surface temperature which will modify pattern of Sutlej River flow in this basin. The present paper has aimed for studying annual and seasonal patterns of river discharge at different gauging sites of Sutlej River basin (middle catchment), India. The study has been performed over three gauging sites, namely, Kasol, Sunni and Rampur located under different physiographic and climatic conditions. The daily historical records (1970-2010) of 41 years river discharge data have been employed for statistical analysis. The annual and seasonal Standardized Discharge Indices (SDI) has been derived in order to preserve uniformity and facilitate comparison between flows of Sutlej River at different sites. Mann-Kendall (MK) test, a non-parametric test method, has been applied to detect trend in annual and seasonal SDI for periods 1970-2010. Decadal (annual and seasonal) patterns in SDI have also been discussed. The results of annual and seasonal trend analysis have revealed decreasing trends in SDI at all the gauging sites. The trend in annual SDI is statistically significant (95% confidence level) at Rampur (0,04 cumec/year) and insignificant at Kasol (0,02 cumec/year) and Sunni (0,01 cumec/year) respectively. The study of annual decadal change in SDI at all the sites shows that reduction in river discharge has occurred in the decade of 2001-2010. Before this, continuous rise in annual discharge has been reported at all the sites from decades 1970-1980 to the last decade of 20th century (1991-2000). The decline in river flow may affect agriculture and electricity production as well as there may be problems related with drinking water. The present study is expected to be useful for planning water resources related projects that can be undertaken in the Sutlej basin.

The problem of finding the optimal shape of an aluminum plate to mitigate air blast loading is considered. The goal is to minimize the dynamic displacement of the plate relative to the test fixture, while monitoring plastic strain values, mass, and envelope constraints. This is a computationally challenging problem owing to (a) difficulty with finding optimal shapes with higher dimensional shape variations, (b) non-differentiable, non-convex and computationally expensive objective and constraint functions, and (c) difficulties in controlling mesh distortion that occur during explicit finite element analysis. An approach based on coupling LS-DYNA finite element software and a differential evolution (DE) optimizer is presented. Since DE involves a population of designs which are then crossed-over and mutated to yield an improved generation, it is possible to use coarse parallelization wherein a computing cluster is used to evaluate fitness of the entire population simultaneously. However, owing to highly dissimilar computing time per analysis, a result of mesh distortion and minimum time step in explicit finite element analysis, implementation of the parallelization scheme is challenging. Sinusoidal basis shapes are used to obtain an optimized 'double-bulge' shape.

Background: Neonatal birth/perinatal asphyxia is a critical condition that can adversely affect many different bodily tissues, particularly the brain; depending on duration and severity of asphyxia, leading to difficulties and lifelong disabilities. These can be avoided by early detection of the biochemical derangements and prompt intervention. Serum alpha-ketoglutarate (α-KG) and cord blood lactate have been found to be associated with birth asphyxia and may have potential to act as biomarkers for birth asphyxia. Methods: Serum levels of α-KG and cord blood lactate were estimated in 34 birth asphyxiated neonates with clinical evidence of asphyxia. The levels were also analyzed in 46 apparently healthy controls, and data was compared among different groups by using appropriate statistical analysis. Serum α-KG was estimated by enzyme-linked immunosorbent assay (ELISA) and cord blood lactate by blood gas autoanalyzer (BGA) in the serum samples. Results: Serum α-KG levels were found to be increased in birth asphyxiated neonates as compared to healthy controls (p-value = 0.06). Correlation of serum α-ketoglutarate (ng/mL) levels with outcome (discharged/expired) in birth asphyxiated neonates was not found to be statistically significant (r value = 0.156, p-value = 0.384). A statistically significant correlation was not found between severity of birth asphyxia and levels of serum α-ketoglutarate (ng/mL) (r value = 0.029, p-value = 0.86). Also, correlation of cord blood lactate levels (mmol/L) with severity in birth asphyxiated neonates was not found to be statistically significant (r value = 0.326, p-value = 0.10). Correlation between cord blood lactate levels (mmol/L) and outcome in birth asphyxiated neonates (discharged/ expired) was not found to be statistically significant (r value = 0.03, p-value = 0.87), while correlation of cord pH levels and severity of birth asphyxia in cases was found to be highly statistically significant (r value = -0.60, p-value < 0.01) Conclusions: Serum α-KG and cord blood lactate bear the potential to act as biomarkers in neonates with birth asphyxia. [ABSTRACT FROM AUTHOR]

A repeat kidney transplant is the preferred treatment for graft failure due to its enhanced survival benefits and improved quality of life, despite facing greater medical, immunological, and surgical challenges compared to the first transplant. Immunosuppressive medications are indispensable for organ recipients to prevent rejection and prolong the viability of transplanted organs. At present, triple-drug therapy comprising calcineurin inhibitors, corticosteroids, and antiproliferative medications is the prevailing protocol for immunosuppressive treatment in renal transplant recipients. In conjunction with the intended therapeutic outcomes, the administration of immunosuppressive agents entails the potential for specific adverse reactions. This patient developed chronic diarrhea due to mycophenolate mofetil, severe bone marrow suppression with azathioprine due to thiopurine methyltransferase enzyme deficiency, and developed thrombotic microangiopathy with tacrolimus, despite maintaining recommended therapeutic drug levels, leading to the withdrawal of all three drugs. The case highlights the need for newer immunosuppressive drugs and protocols that are more effective and less toxic.

Neurolymphomatosis (NL) is the direct infiltration of the peripheral nervous system (PNS) by lymphoma cells and represents the least common form of PNS involvement by lymphoma. Clinical presentation is varied, and early diagnosis remains challenging. Nerve biopsy remains the diagnostic gold standard, use of magnetic resonance imaging (MRI) and fluorodeoxyglucose–positron emission tomography (FDG-PET) may help in diagnosis and selecting targets for biopsy. We report an account of an older male patient who presented with subacute onset multifocal neuropathy involving bilateral lower limbs and left foot drop. The patient was initially misdiagnosed as chronic inflammatory demyelinating polyneuropathy; however radiological assessment revealed fusiform thickening of the L5 nerve root and biopsy from the site revealed extensive infiltration by diffuse large B cell type non-Hodgkin lymphoma (NHL). High index of suspicion is vital to ensure correct diagnosis, timely treatment, and to improve patient survival.

A phenotypic hallmark of cancer is aberrant transcriptional regulation. Transcriptional regulation is controlled by a complicated array of molecular factors, including the presence of transcription factors, the deposition of histone post-translational modifications, and long-range DNA interactions. Determining the molecular identity and function of these various factors is necessary to understand specific aspects of cancer biology and reveal potential therapeutic targets. Regulation of the genome by specific factors is typically studied using chromatin immunoprecipitation followed by sequencing (ChIP-Seq) that identifies genome-wide binding interactions through the use of factor-specific antibodies. A long-standing goal in many laboratories has been the development of a 'reverse-ChIP' approach to identify unknown binding partners at loci of interest. A variety of strategies have been employed to enable the selective biochemical purification of sequence-defined chromatin regions, including single-copy loci, and the subsequent analytical detection of associated proteins. This review covers mass spectrometry techniques that enable quantitative proteomics before providing a survey of approaches toward the development of strategies for the purification of sequence-specific chromatin as a 'reverse-ChIP' technique. A fully realized reverse-ChIP technique holds great potential for identifying cancer-specific targets and the development of personalized therapeutic regimens. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the color changes (ΔE) of two different composite resins after staining and bleaching. Material and Methods: A total of 100 specimens were prepared from microhybrid and nanohybrid composites. The samples were divided into five groups and stained for 30 days with tea, coffee, cola, red wine, or distilled water (control). Each group was further divided into two subgroups to receive a 14-day application of Opalescence PF or VivaStyle® Paint On Plus bleaching materials. The color of all samples was determined at baseline, after staining, and after bleaching. Data were analyzed using ANOVA and independent sample t-test. Results: The highest ΔE values were observed in the red wine groups for both composites. Bleaching agents decreased ΔE values; however, they were unable to return the values to baseline values. Conclusion: Staining and bleaching may affect color, depending on the type, filler, and matrix content of the composite resin.

Rod photoreceptors in the retina adjust their responsiveness and sensitivity so that they can continue to provide meaningful information over a wide range of light intensities. By stimulating membrane guanylate cyclases in the outer segment to synthesize cGMP at a faster rate in a Ca2+-dependent fashion, bicarbonate increases the circulating "dark" current and accelerates flash response kinetics in amphibian rods. Compared to amphibian rods, mammalian rods are smaller in size, operate at a higher temperature, and express visual cascade proteins with somewhat different biochemical properties. Here, we evaluated the role of bicarbonate in rods of cpfl3 mice. These mice are deficient in their expression of functional cone transducin, Gnat2, making cones very insensitive to light, so the rod response to light could be observed in isolation in electroretinogram recordings. Bicarbonate increased the dark current and absolute sensitivity and quickened flash response recovery in mouse rods to a greater extent than in amphibian rods. In addition, bicarbonate enabled mouse rods to respond over a range that extended to dimmer flashes. Larger flash responses may have resulted in part from a bicarbonate-induced elevation in intracellular pH. However, high pH alone had little effect on flash response recovery kinetics and even suppressed the accelerating effect of bicarbonate, consistent with a direct, modulatory action of bicarbonate on Ca2+- dependent, membrane guanylate cyclase activity. [ABSTRACT FROM AUTHOR]

Current theories regarding accumulation of Alzheimer's disease-related deposits of abnormal intra- and extracellular proteins include reactions to inflammation and mitochondrial dysfunction. In this study, we explored whether age, genotype and inflammation via diet have a greater effect on dysregulatory protein accumulation in any particular subfield of the hippocampus. We stained for ferritin, ferroportin, hyperphosphorylated tau and β-amyloid proteins in the hippocampal region of Apolipoprotein E2 (ApoE2), ApoE3 or ApoE4 mice fed a control diet or a hypothesized inflammation-inducing methionine diet and euthanized at 3, 6, 9 or 12 months. We analysed stains based on hippocampal subfield and compared the protein accumulation levels within each group. We found significantly decreased ferritin expression in ApoE4 mice in the CA1 and Hi regions and decreased ferroportin expression in ApoE4 mice in the Hi region. There was also a significant effect on hyperphosphorylated tau protein levels based upon a given mouse genotype and diet interaction. Additionally, there were nonsignificant trends in each hippocampal subfield of increasing ferroportin and hyperphosphorylated tau after 6 months of age and decreasing β-amyloid and ferritin with age. This study identified that there are changes in iron regulatory molecules based on genotype in the Hi and CA1 regions. Our findings also suggest a diet-genotype interaction, which affects levels of specific Alzheimer's disease biomarkers in the hippocampus. Additionally, we identified a trend toward increased ability to clear β-amyloid and decreased ability to clear hyperphosphorylated tau with age in all subfields, in addition to evidence of increasing iron load with time. [ABSTRACT FROM AUTHOR]

The liquid drop model is an empirical hypothesis established on the idea that nuclei can be thought of as incompressible liquid droplets. The AME2020 dataset was used in this work to determine binding energy using a semi-empirical mass formula and compare it with binding energies predicted by a machine learning algorithm. Random forest regressor, MLPRegressor, and XGBoost models were employed. In terms of accuracy, root mean square error, and mean absolute error, machine learning models performed better than the semi-empirical mass formula. Compared to RFR, XGBoost, and SEMF, MLPRegressor performed better in predicting binding energies for lighter nuclei. Using estimated binding energies, nuclear masses were computed, and it was shown that all three models adequately predicted nuclear masses with minimal error. This finding highlights how machine learning can be applied to nuclear physics to predict various nuclei’s properties.

We present a case report of a 55-year-old woman who had a femoral vein intravascular papillary endothelial hyperplasia that required excision of the mass and subsequent repair of the right femoral vein using her right anterior accessory saphenous vein. She first presented with findings of a non-occlusive deep vein thrombus. However, after 6 months of persistent and enlarging mass with subsequent intravascular component on a follow-up duplex scan, a decision was made to bring her to the operating room for exploration and excision.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic multi-systemic disease characterized by extreme fatigue that is not improved by rest, and worsens after exertion, whether physical or mental. Previous studies have shown ME/CFS-associated alterations in the immune system and mitochondria. We used transmission electron microscopy (TEM) to investigate the morphology and ultrastructure of unstimulated and stimulated ME/CFS immune cells and their intracellular organelles, including mitochondria. PBMCs from four participants were studied: a pair of identical twins discordant for moderate ME/CFS, as well as two age- and gender- matched unrelated subjects—one with an extremely severe form of ME/CFS and the other healthy. TEM analysis of CD3/CD28-stimulated T cells suggested a significant increase in the levels of apoptotic and necrotic cell death in T cells from ME/CFS patients (over 2-fold). Stimulated Tcells of ME/CFS patients also had higher numbers of swollen mitochondria. We also found a large increase in intracellular giant lipid droplet-like organelles in the stimulated PBMCs from the extremely severe ME/CFS patient potentially indicative of a lipid storage disorder. Lastly, we observed a slight increase in platelet aggregation in stimulated cells, suggestive of a possible role of platelet activity in ME/CFS pathophysiology and disease severity. These results indicate extensive morphological alterations in the cellular and mitochondrial phenotypes of ME/CFS patients' immune cells and suggest new insights into ME/CFS biology. [ABSTRACT FROM AUTHOR]