Plant secondary metabolites (PSMs) are produced by plants to overcome environmental challenges, both biotic and abiotic. We were interested in characterizing how non-growing seasonality in temperate climates affects overall PSM production in comparison to herbivory. Typically, herbivory is measured from spring to summer when plants have high resource availability and are prioritizing growth and reproduction. However, autumn seasonality also challenges plants as they cope with limited resources and prepare survival for winter. Using meta-analysis, we recorded overall PSM concentrations across 22 different PSM classes from 58 published papers, as well as compared concentrations of five phenolics PSM classes – hydroxybenzoic acid, flavan-3-ol, flavonol, hydrolysable tannin, and condensed tannin. We then calculated effect sizes for herbivory (absence to presence) and seasonality (growing to non-growing), while considering other variables (e.g., plant type, time after herbivory, temperature, and precipitation). We found that neither herbivory nor seasonality affect overall PSM production. However, we discovered different trends among the individual phenolics classes, including herbivory having a positive effect on flavonol production and non-growing seasonality having a positive effect on flavan-3-ol and condensed tannin production. We discuss how these responses stem from three factors: 1. some PSMs are constitutively produced by plants whereas others are induced only during herbivory or non-growing seasonality, 2. plants produce metabolites with higher costs only during seasons when other resources for growth and reproduction are less available, and 3. some PSM classes serve more than one function for plants and such functions can be season-dependent. The final outcome of our meta-analysis is that non-growing seasonality does affect PSM production differently from herbivory, and we therefore see value in further investigating how non-growing seasonality impacts interactions between PSM production and herbivory.

Alicia Domínguez Estirado, Inmaculada Sánchez-Machín, Paloma Poza-Guedes and Ruperto González-Pérez

Hoffa fractures are rare fractures of the femoral condyle that occur in the coronal plane. In most cases, high-energy trauma leads to isolated coronal fractures of one of the femoral condyles, medial or lateral. The fracture was approached from both the medial and lateral sides of the distal femur

While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of food allergy is evolving towards less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, co-administration of biologicals, adjuvants, and tolerance-inducing formulations. The ultimate goal is to improve immunotherapy and develop precision-based medicine via risk phenotyping allowing optimal treatment for each food-allergic patient.

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis. Its success as a pathogen is dependent on an arsenal of secreted virulence factors which target host cell organelles. In this report, we have characterized the effects of two proteins known to be secreted by Mtb on eukaryotic mitochondria: ESAT-6 and a member of the poorly-described PE/PPE protein family, PE17. Intracellular expression of ESAT-6 in A549 cells did not induce mitochondrial fragmentation. In contrast, expression of PE17 caused extensive mitochondrial fragmentation and an overall reduction in mass. Further characterization of the effects of PE17 within host cells revealed a dramatic decrease in the mass of the trans-Golgi network and the Golgi stack with lesser but significant decreases in late endosomes and lysosomes. The endoplasmic reticulum and organelles of the early endocytic pathway were not significantly affected. PE17 specifically colocalized with large, cytoplasmic lipid droplets via a C-terminal domain, suggesting a significant role for PE17 in the disruption of multiple host cell organelles and a novel interaction with host lipid droplets.

Studies exploring the effect of microclimatic changes on host-parasite relationships are scarce, however, many models predict changes in the distribution and incidence of diseases associated with climate change. In this study, we increased both temperature and relative humidity in blue tit nest-boxes during the breeding season, trying to discern between the effect of both variables on the abundance of ectoparasites reported in previous studies and, also, on the body condition of the nestlings and adults. Temperature and relative humidity were experimentally increased an average of about 2ºC and 15 units respectively. The abundance of blowfly Protocalliphora azurea pupae was significantly reduced in nests with increased temperature as compared to control nests and nests with increased relative humidity, and was also significantly reduced in nests with increased relative humidity as compared to control nests. The abundance of Dermanyssus spp. mites and Ceratophyllus gallinae flea larvae was significantly reduced in nests with increased relative humidity. However, there was no significant effect of the experiment on flying insect vectors abundance (Blackflies and biting midges.). On the other hand, body condition and mass of nestlings were lower in nests with increased relative humidity and nestlings’ mass was also lower in heated nests. However, the body condition and mass of the adults was not significantly affected by the experiment. In addition, blowfly Protocalliphora azurea pupae and biting midges Culicoides spp. had a significant negative effect on body condition and mass of nestlings and adults. In conclusion, an increase in temperature, on the one hand, and relative humidity, on the other, reduces the abundance of ectoparasites, which suggests that these parasites are sensitive to sudden changes in the microclimate in which they develop. In addition, these fluctuations negatively affect the body condition and mass of blue tit nestlings despite the concurrent decrease of parasites in nests.

A document by Jun Lu . Click on the document to view its contents.

Graphene is a two-dimensional form of crystalline carbon, either a single layer of carbon atoms forming a hexagonal lattice or several coupled layers of this honeycomb structure. Graphene is a parent form of all graphitic structures of carbon. However, the field of graphene science and technology is relatively new. Progress depends not only on the basic science but also on the development of new ways to produce graphene on an industrial scale. The present study is focused primarily upon the thermal transport characteristics of graphene nanoribbons. The thermal transport characteristics of graphene nanoribbons are studied using molecular dynamics simulations and by experimental measurements. A specific heat flux is imposed through the graphene nanoribbon. The graphene nanoribbon is considered as a single layer of carbon atoms with each atom bound to three neighbors in a honeycomb structure. The thermal conductivity is determined from the temperature gradient obtained and the heat flux imposed. The present study aims to provide a fundamental understanding of the thermal transport properties of graphene nanoribbons. Particular emphasis is placed upon the effect of various factors on the thermal conductivity of graphene nanoribbons under different conditions. the results indicate that the mean free path of phonons depends on the nanoribbon structure and dimensions. The thermal conductivity increases with increasing nanoribbon length. Graphene nanoribbons offer tremendous promise for providing enhanced transport performance. Graphene undergoes a metallic-to-semiconducting transition as the nanoribbon width decreases. The properties of graphene nanoribbons are highly dependent on their width and edge structure. The graphene nanoribbons can be derived through the longitudinal splitting of carbon nanotubes.Keywords: Graphene nanoribbons; Graphitic structures; Carbon nanotubes; Carbon nanofibers; Thermal properties; Thermal conductivity

This study introduces a novel multi-objective optimization algorithm integrating Customized Mutated PSO (CM-PSO) and an innovative modified Genetic Algorithm (GA) using an unexplored merged chaotic map. The hybrid algorithm con- verges to desired results faster than CM-PSO and modified GA without trapping in local minima. Validation is conducted by designing a single-element and simple-structure dipole antenna so that its optimized S 11 is better than -30 dB at the resonance frequency and covers the 3.3 to 3.8 GHz fre- quency band with S 11 < − 1 0 dB. Certainly, the -30 dB and covering frequency band criteria can be modified in the pro- posed algorithm. In the algorithm, the isolation between el- ements of a quad-Multiple-Input/Multiple-Output antenna, constructed using optimized dipole antennas, is set to be less than -20 dB (changeable criteria) so that the smallest size can be achieved. CST carries out electromagnetic and high- frequency simulations, and the novel developed optimization algorithm in MATLAB determines what and how much pa- rameter values need to be changed by CM-PSO or an innova- tive modified GA in order to enhance the antenna’s S 11 result and its Impedance Bandwidth (IBW). The input parameters of the algorithm are the dimensions of the proposed antenna’s elements, which significantly influence its performance.

Developing analytical systems imposes several challenges related not only to the amount and heterogeneity of the involved data but also to the constant need to readapt and evolve to overcome new business challenges. Data is a determinant factor in the success of analytical and decision-making applications, being its nature, availability, and quality, crucial aspects for planning and structuring populating analytical systems. Today’s users are more demanding, requiring adaptable and flexible analytical applications, which impose serious challenges on ETL systems design and development for ensuring flexible and robust data populating services, operating 24/7, and managing and processing large volumes of data. Thus, we should design and implement ETL processes using innovative and up-to-date approaches, having real application evidence. In this paper, we present a service-oriented implementation for ETL design and development. We mapped and implemented some of the most conventional ETL processes in a service-oriented architecture, for demonstrating the application and benefits that this kind of approach will provide to ETL systems project development.

Anthropogenic global changes are impacting biodiversity, however, many previous meta-analyses investigating the impact of different global changes on biodiversity have omitted soil fauna, or are limited in the scope of the global changes studied. Threats to soil biodiversity by global changes need to be understood to mitigate effects on ecosystem services provided by soils. We conducted a meta-analysis using 3,173 effect sizes from 627 publications focused on six global changes (climate change, land-use intensification, pollution, nutrient enrichment, invasive species, and habitat fragmentation) and their associated environmental stressors on soil fauna. We classified stressors as either pulse (short-term, acute) or press (long-term, chronic) stressors, and expected pulse stressors to have less impact on soil biodiversity due to buffering effects of the soil. Unexpectedly, pollution caused the largest loss in soil fauna communities, which is worrying due to continually increasing levels of pollution, as well as the poor mechanistic understanding of pollution impacts. There was no clear pattern of pulse stressors having a smaller impact on soil biodiversity than press stressors. Overall, this work shows the importance of including soil biodiversity in large-scale global change analyses, as soil organisms often do not show the same responses as organisms above-ground.

Spatial patterns of human hunting and predation risk are mediated by the physical landscape, with human hunting risk often associated with habitat features contrasting those linked to risk from large carnivores. Risk patterns from hunters and large carnivores can also vary in time, which may allow prey species to adjust anti-predator strategies not only in risky places but also during risky times. We examined whether moose (Alces alces) in south-central Scandinavia adjusted diel habitat selection during and after the hunting season in response to contrasting human hunting and wolf (Canis lupus) predation risks. We found evidence for a diel and seasonal shift in habitat selection of moose consistent with a behavioural adaptation to no human hunting risk at night and after the hunting season. We found no evidence that moose responded to the spatiotemporal variation in wolf predation risk since moose selected habitats of high wolf predation risk both day and night during and after the hunting season. Human hunting risk was therefore the main driver of moose habitat selection during the hunting season while decreasing in importance during times when hunting did not occur. However, since we did not find evidence for a diel or seasonal shift in habitat selection consistent with an increase in the importance of wolf predation risk during the night and after the hunting season, our study is in line with the notion that moose in Scandinavia are currently naïve to wolves. Our findings show the importance of including the effects of humans in studies of predator-prey dynamics within anthropogenic landscapes. An increased understanding of the risk effects arising from humans and large carnivores and the responses of prey might be important for managing ungulate populations, since behaviours aimed at reducing exposure to risk may also affect crucial demographic traits like growth and reproduction.

A document by Mina Yamada. Click on the document to view its contents.

Abstract:Despite varying findings, TST has been used for a long time to treat hypogonadal males with type 2 diabetes mellitus (T2DM). The function of TST was evaluated in this meta-analysis in hypogonadal males with type 2 diabetes. Relevant randomised controlled trials and observational studies were identified by searching PubMed, Embase, and Google Scholar. The effects of TST were evaluated using pooled mean differences (MDs) and relative risks with 95% confidence intervals (CIs).Our meta-analysis includes 3,002 hypogonadal, type 2 diabetics from 13 randomised controlled trials and 2 observational studies. Total testosterone levels increase significantly with testosterone replacement, and TST significantly improves glycemic management compared to placebo by lowering homeostatic model assessment of insulin resistance (WMD = -1.47 [-3.14, 0.19]; p=0.08; I2=56.3%), fasting glucose (WMD = -0.30 [-0.75, 0.15]; p=0.19; I2= 84.4%), fasting insulin (WMD = -2.95 [-8. Overall, TST resulted in a greater increase in free testosterone levels compared to placebo (WMD = 81.21 [23.87, 138.54] p=0.07; I2= 70%) when comparing patients' individual measurements.We conclude that TST can help hypogonadal Type 2 Diabetes patients with better glycemic control and hormone levels, as well as lower total cholesterol, triglyceride, and LDL cholesterol while raising HDL cholesterol. Therefore, in addition to the usual care for diabetes, we advise TST for these individuals.Introduction:An abnormality in one or more of the testicular hormone concentrations along the hypothalamic-pituitary-testicular axis is the cause of the clinical syndrome known as hypogonadism. In men, hypogonadism is diagnosed when low levels of testosterone (both total and free) are found in the blood. [1] The annual incidence rate of hypogonadism is 12.3 per 1000 people, affecting between 5.1% and 12.3% of men between the ages of 30 and 79. When free testosterone levels fall below 225 pmol/l (65 pg/ml), a pathology is present and treatment is necessary. [2] Due to the devastating effects it can have on a patient's ability to perform basic bodily functions and their overall quality of life, hypogonadism is a global health problem. Recent studies have found strong evidence connecting hypogonadism and type 2 diabetes mellitus (T2DM). This is because low T levels cause an increase in fat storage, insulin resistance, and poor glycemic control, and a higher risk of obesity increases the likelihood of TD. [3] The use of testosterone in routine clinical care for type 2 diabetes is being questioned by a growing (and sometimes conflicting) body of research. Numerous studies have shown that testosterone treatment lowers the risk factors for cardiovascular disease and diabetes in men with type 2 diabetes, including systolic and diastolic blood pressure, lipid profiles, insulin sensitivity, inflammation, and levels of fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c). It has also been suggested that men with hypogonadism who undergo long-term testosterone therapy have a lower chance of developing type 2 diabetes and a higher quality of life, as measured by the Aging Male Symptoms (AMS) questionnaire. [5] There were, however, studies that found the opposite. Hypogonadal patients with type 2 diabetes have been shown in multiple studies to benefit greatly from testosterone replacement therapy (TRT), as measured by decreases in fasting serum glucose (FSG), fasting serum insulin (FSI), and haemoglobin A1C (HBA1C). [6] These indicators did not significantly decrease in TRT groups, according to other data. Total cholesterol, triglyceride, and serum low-density lipoprotein (LDL) levels have all been shown to be reduced in studies where TRT was used, while high-density lipoprotein (HDL) levels were found to be increased. [7,8] But no other studies found evidence of a statistically significant improvement in lipid metabolism.Only a small number of randomised control trials and observational studies have looked at the role of TRT in male hypogonadism caused by TDM, and the results have been inconsistent. To better understand the role of TRT in hypogonadal males with type 2 diabetes, we conducted a systematic review and meta-analysis. As far as we can tell, this meta-analysis provides the most recent look at how testosterone therapy stacks up against no treatment or placebo.Methods and MaterialsThis meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). [9]Search strategyMethods From the study's inception on September 5, 2022, to the present day, PubMed (Medline) and Cochrane were combed extensively. Searches on ClinicalTrials.gov, Google Scholar, and Medrxiv uncovered the grey literature and preprints. An indexing strategy was developed using both keywords and Medical Subject Headings (MESH terms). ['Testosterone' OR 'TST' OR Testosterone undecanoate] were among these. AND [[Diabetes Mellitus OR [Hypogonadism]]. Table S1 provides details on the search parameters and parameters. In conducting this search, we did not apply any filters or limitations. In the case of non-English text, Google Translate was used to produce an English version. The studies were located through manual searches of review articles. Two reviewers independently and anonymously evaluated the titles, abstracts, and full texts (MK and SK). The relevant studies were imported into Endnote X9 to avoid repetition (Clarivate Analytics, US).Criteria for EligibilityCriteria for inclusionThe studies were chosen based on their language, study design, patient population, intervention, comparison, outcomes of interest, and definition.Publications were limited to those written in English, and studies had to be either randomised clinical trials or observational studies that met certain criteria for inclusion before the meta-analysis could be performed.Hypogonadism patients are those who have type 2 diabetes and have been diagnosed with the condition.Patients who participated in the study's exposure group included those who had received testosterone therapy.The non-TST group served as a control and received either the gold standard of care or a placebo in this analysis.Implications on glucose homeostasis and hormonal levels after treatment constitute the Primary Outcomes.Measurements of cholesterol, body mass index, waist size, fat percentage, and systolic and diastolic blood pressure were recorded as secondary outcomes.Criteria for exclusionThe following significant exclusion criteria were established to ensure the quality of this meta-analysis:• There are no agreed-upon criteria for making a diagnosis of late-onset hypogonadism or type 2 diabetes, determining the appropriate population to study, dosage, or administration method for testosterone, or evaluating outcomes.There are no control or placebo groups• Duplicate publications • Inadequate data for estimating a mean difference (MD) with a 95% confidence intervalIn addition, the 25-item CONSORT checklists, which stress describing how trials were conceived, analysed, and interpreted, were used to assess all included RCTs (Table S2). The 25 reported items were used to evaluate the quality of the included RCTs. The strength of a randomised controlled trial (RCT) correlates with the number of outcomes that were reported. All 25 criteria should be present in high-quality research.Data ExtractionData ExtractionTwo researchers (HN and RI) independently read and evaluated each article to determine whether or not it should be included in the review. Questions were answered and doubts dispelled. We collected the following data from each trial: first author's name, publication year, country, ethnicity, testosterone cut-off point, diabetes duration, testosterone regimen, medications on comparators, mean age, Hba1c percentage, and total serum testosterone level. Table 1 summarises these facts. Parameters such as HOMA-IR, fasting plasma glucose, fasting serum insulin, haemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, body fat percentage, body mass index, systolic blood pressure, diastolic blood pressure, erectile function, and the ageing male score are listed in Table 2.Study quality assessmentPublished RCT quality was evaluated using a modified version of the Cochrane Collaboration risk of bias tool [10], while observational study quality was measured using the New Castle Ottawa scale. [11] Statistical analysis The aforementioned meta-analysis was conducted using the statistics software Review Manager 5.4 (Cochrane Collaboration). For a simple yes/no outcome, we found the relative risk (RR) and 95% CI. The average and standard deviation were used to illustrate continuous results. In this meta-analysis, we show the combined effect of relative risks (RRs) and weighted mean differences (WMDs) calculated with the generic-inverse variance and continuous outcome functions using a random-effects model. Results were considered to be statistically significant when the p-value was less than 0.05. In order to assess the possibility of publication bias, funnel plots were constructed for primary outcomes.Using I2 statistics, we were able to quantify the degree of disagreement between studies. Low heterogeneity was represented by an I2 value of 25%, moderate heterogeneity by a value between 25% and 50%, and high heterogeneity by a value of 50% or more. A sensitivity analysis on outcomes with a high degree of heterogeneity was performed to investigate the impact of individual studies on the overall pooled estimate.ResultsStudy selectionThe initial literature search yielded a total of 659 articles. Out of the initial 30 publications, only 15 met the inclusion criteria for this meta-analysis; 2 were observational [12,24] and 13 were randomised trials [5,8,13-23]. The distinguishing characteristics of the selected studies are outlined in (Supplementary table S2 and S3)Baseline characteristics Three thousand and two people met the criteria for hypogonadism across the 15 studies; 1484 received testosterone and 1518 received a placebo. Six studies [8,12,14,18,20,24] required the presence of at least three sexual symptoms and a total testosterone level of 12 nmol/L to diagnose hypogonadism, while the remaining studies [5,13,15,16,17,19,21,22] required the presence of a total testosterone level of 15 nmol/L or a free testosterone level of 225 pmol/L to make the diagnosis. The cutoff for hypogonadism in another study [13] was set at TT13 nmol/L. The primary testosterone regimens used in the included studies varied widely. Only one study () used oral testosterone, three (15,17,21) injected testosterone gel subcutaneously, and eleven (5,8,12-14,16,18-20,22,23,24) injected testosterone intramuscularly. Testosterone was administered in a wide variety of doses and at different intervals in these studies. Only two of the RCTs [17,19] lacked a control group entirely, while the other eleven [5,8,13-16,18,20-23] were double-blind placebo-controlled studies. Table 1 and Table 2 provide information about the participants' demographics, medical histories, hormone levels, and glycemic indices as appropriate for the study.Quality assessment and publication biasAccording to the New Castle-Ottawa scale, an instrument for assessing the quality of studies, there is a low risk of bias in observational studies (Supplementary Table 4). The Cochrane method for evaluating randomised controlled trials yielded results of moderate to high quality (Supplementary Table 5). Publication bias did not affect the findings, as demonstrated by the funnel plots (Supplementary Figure S1).Primary outcomes:The effects of testosterone on glucometabolism were assessed by measuring HOMA-IR, haemoglobin A1c, fasting serum glucose (FSG), and fasting serum insulin (FSI). Data from 9 of the 15 studies reporting on HOMA-IR ([5,8,13,14,16,17,21,22,24]) showed that testosterone therapy was superior to placebo at lowering HOMA-IR levels (WMD = -1.47 [-3.14, 0.19]; p = 0.08; I2 = 56.3%). Patients in the testosterone group showed a greater decrease in FSG after treatment compared to those in the placebo group (WMD = -0.30 [-0.75, 0.15]; p=0.19; I2= 84.4%). FSG was measured in 14 [5,8,12-19,21-24] of the 15 studies. WMD = -2.95 [-8.64,2.74]; p = 0.31; I2 = 49.3%]; 8 [8,13,15-18,22,24] of 15 studies found that patients treated with testosterone had greater reductions in FSI levels. Among the 15 studies, 13 reported HbA1c values, and pooled analysis showed that testosterone treatment was associated with a greater improvement in post-treatment HbA1c levels (WMD = -0.29 [-0.57, -0.02] p=0.04; I2= 89.8%). (Figure 3)Total testosterone, free testosterone, serum hormone binding protein (SHBG), and prostate specific antigen (PSA) were taken into account to determine testosterone's impact on hormone levels. The pooled analysis of 9 studies that measured total testosterone levels [5,12,13,18,19,21-24] found that testosterone therapy is associated with a significant increase in total testosterone levels (WMD = 4.51 [2.40, 6.61] p0.0001; I2= 96.3%). The in-study heterogeneity was unaffected by excluding individual studies from the pooled analysis.Combining data from three studies [13,14,21] found that patients on testosterone therapy experienced a greater increase in free testosterone levels compared to those on placebo (WMD = 81.21 [23.87, 138.54] p=0.07; I2= 70%). After pooling data from 5 studies [13,17,21,22,23], researchers found that SHBG level decreased more with testosterone therapy (WMD = -1.28 [-5.51, 2.96] p=0.55; I2 = 0%). There was no statistically significant difference in PSA levels between the two groups after therapy (WMD = -0.02 [-0.13, 0.08] p=0.65; I2 = 0%) across seven studies [8,13,14,15,17,21,23].Secondary outcomes: (Table 3)Treatment with testosterone has been shown in a pooled analysis of secondary outcomes to improve HDL cholesterol and IIEF, as well as reduce total cholesterol, LDL cholesterol, triglyceride, body fat, waist circumference, body mass index, systolic blood pressure, diastolic blood pressure, arterial mean stiffness, and mortality.Discussion:Recent studies have found that hypogonadism occurs in a high percentage of men with Type-2 diabetes. Despite growing knowledge of the correlation between T2D and hypogonadism, no universally accepted guidelines exist for dealing with the condition. The purpose of this meta-analysis was to develop clear, evidence-based recommendations for the treatment of hypogonadism in men with Type 2 diabetes mellitus who are taking testosterone replacement therapy. Evidence linking type 2 diabetes and low blood testosterone due to an amplified insulin signalling pathway has been established by multiple studies showing a significant incidence (30-80%) of hypogonadism in males with diabetes mellitus. [25] Hypogonadism is more common in males with diabetes than in non-diabetic men across the globe, including in the West, Asia, and Africa. The effects of testosterone replacement therapy in hypogonadal males with type 2 diabetes were compared to those in a control group in a systematic review and meta-analysis involving 15 studies and 3002 patients (T2DM). All men with Type 2 diabetes and all men with a body mass index (BMI) greater than 30 or a waist circumference greater than 104 cm were recommended for screening for hypogonadism by the American Academy of Clinical Endocrinologists in 2016. The 2018 Endocrine Society guidelines continue to discourage testosterone monitoring despite the high prevalence of hypogonadism in conditions like type 2 diabetes. [26] Screening for hypogonadism was advocated for in 2016 by the American Academy of Clinical Endocrinologists in all men with Type 2 diabetes and in all men with a body mass index (BMI) of 30 or higher, or a waist circumference of 104 centimetres or more. In spite of the high prevalence of hypogonadism in conditions such as type 2 diabetes, the Endocrine Society's 2018 guidelines still discourage testing for the hormone. [26] In men with hypogonadism, testosterone replacement therapy (TRT) has been shown to have a positive effect on a wide range of outcomes, including sexual desire and function, bone mineral density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life, and cardiovascular disease, but the indications for testosterone supplementation are still up for debate. Potential side effects of testosterone replacement therapy have been categorised by the guidelines into two groups: those with a strong association to testosterone therapy, such as acne and oily skin, an increase in hematocrit, decreased fertility, locally active prostatic carcinoma, and the development of metastatic prostatic carcinoma, and those with a weak association, such as gynecomastia, worsening sleep apnea, and the progression of breast cancer. [27] Our results confirm the findings of previous studies [5,8,12-19,21-24] showing that TRT can significantly enhance glucose control by decreasing Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting serum glucose (FSG), fasting insulin (FSI), and glycated haemoglobin (HBA1C). Recent research has established a correlation between baseline HOMA-IR and body mass index, waist circumference, and C-peptide. Insulin sensitivity, as measured by changes in HOMA-IR, HOMA-%, and blood C-peptide and proinsulin levels, was also enhanced by testosterone supplementation, demonstrating the presence of metabolic syndrome. [28] Testosterone replacement therapy for hypogonadal males with diabetes has been linked to improvements in both body mass index and glucose control. The testosterone treatment group showed statistically significant improvements in body mass index, fasting glucose, A1C, blood pressure, lipid profiles, and liver enzymes, according to a study. [29] Twelve months of testosterone treatment (adjusted to mid-normal concentrations for healthy men) decreased insulin resistance modestly, HOMA-IR 0.6, p = 0.03, but had no effect on body weight or waist circumference in a large testosterone trial involving 788 men over the age of 65 (72% were obese and 37% had diabetes at baseline). [29] Testosterone therapy has been linked to long-term weight loss, a marked decrease in cardiometabolic risk factors, and in some cases, the complete reversal of diabetes, according to a number of case studies. Treatment with testosterone undecanoate depot injections was initiated for a 57-year-old man with benign prostatic hyperplasia, erectile dysfunction, apathy, and subpar physical fitness (intramuscular injections at 3-month intervals following a 6-week gap). Patients on testosterone therapy saw improvements in fasting blood glucose (to 6.0 mmol/L after 3 months, to below 5.7 mmol/L after 12 months, and then permanently below this value), insulin resistance (HOMA-IR: 3.9 at month 24), and serum lipid levels (LDL/HDL ratio: 3 and triglycerides: 2.5 mmol/L). [30] To fully understand the connection between circulating sex hormones and glucose metabolism, more interventional studies are required.In our meta-analysis, we looked at a lipid panel consisting of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride levels. Thirteen studies found that testosterone recipients had lower total cholesterol levels compared to placebo recipients. On the other hand, 14 studies showed that while HDL cholesterol increased, triglyceride levels decreased. However, there was less of a difference in LDL cholesterol levels between the two groups. Similarly, Si Hyun Kim et al2021 .'s meta-analysis found that TRT significantly lowered total cholesterol compared to placebo. There was also a reduction in triglycerides, though it was not statistically significant. HDL levels unexpectedly dropped after TRT compared to the placebo group. TRT's role in HDL was unclear due to a lack of evidence and conflicting results. It has been shown that high doses of TRT lower levels of HDL and lipoprotein A. TRT's effect on blood lipid and lipoprotein levels is controversial, however. [31] The 14 studies that made up our meta-analysis all showed a reduction in diastolic blood pressure (DBP) and a modest rise in systolic blood pressure (SBP). The effects of testosterone on lipid profiles in the blood are ambiguous. In men with and without type 2 diabetes, low testosterone has been linked to elevated levels of LDL and triglycerides and decreased HDL. In patients with high endogenous testosterone profiles, several cross-sectional studies found no association between elevated serum lipid levels or even elevated LDL. TRT has been shown to significantly reduce LDL-C and total cholesterol in men with eugonadism and hypogonadism in numerous systematic reviews and meta-analyses. [32] Measurements of the patient's waist and body mass index (BMI) can be used for screening for cardiometabolic risk. Testosterone supplementation is gaining popularity as an anti-obesity medication due to its ability to decrease visceral adipose tissue and increase muscle mass in males with hypogonadism. Thirteen additional studies, which contradict the aforementioned randomised controlled trials, have found that testosterone therapy results in a greater reduction in body mass index. [32]A significant correlation between total serum testosterone and AMS and IIEF scores was found in three studies. Treatment with testosterone significantly reduced AMS scores while increasing IIEF. Slight enhancements in sexual functioning, as measured by the AMS scale, the IIEF erectile dysfunction domain, and the IIEF-5 scale, have been associated with low testosterone in older men (testosterone threshold, 10.4 nmol/L [300 ng/dL]). Physical function, depressive symptoms, energy, vitality, and cognitive abilities do not significantly improve, however, according to the literature. Since the AMS scale was the only source of data on life satisfaction, we can assume that the slight improvement in quality of life was attributable to a rise in sexual satisfaction. [33] Different levels of testosterone were analysed including total, free, SHBG, and PSA. Both total and free testosterone levels increased significantly, while SHBG dropped significantly. However, PSA levels were not related to this therapy. The impact of TRT on PSA has been the subject of multiple meta-analyses. Despite this, the primary focus of the papers reviewed was not on PSA and testosterone but on TRT and the risk of prostate cancer. Risk factors for cardiovascular disease (CVD) such as obesity, hypertension, dyslipidemia, and diabetes are often co-occurring with androgen insufficiency. Androgens have a direct effect on PSA, and the protein's level has been suggested as a possible indicator of androgen deficiency in a number of studies. According to the research conducted by Do Kyung Kim et al., TRT significantly increased PSA levels compared to placebo. [34]Numerous benefits can be gained from our meta-analysis. If we add two more studies to our meta-analysis, we'll have about twice as large of a sample to work with. (2) A sensitivity analysis was run to determine the impact of various studies on the final tally. (3) Multiple plots and tests, such as the funnel plot, Egger's test, and Begg's test, were used to evaluate estimates of publication biases, and all of them concluded that the estimates were not statistically significant. Our meta-analysis also included an additional observational study, and we checked it for publication bias using the New Castle-Ottawa Scale. (4) We integrated mortality, total testosterone, free testosterone, SHBG, and PSA to account for new information in the literature that is rarely mentioned in individual studies.While we did collect a substantial amount of statistical data, it is important to note the caveats of our study. 1) Most studies had different follow-up times, with some indicating longer times. Because of the significance of homeostasis in the body, longitudinal follow-up studies are preferred when evaluating hormonal diseases like hypogonadism. Testosterone was used in a wide variety of doses and administration routes across a large number of studies spanning many weeks. This clinical heterogeneity may be attributable to (2) differences in study designs, interventions, and patient factors (including body mass index, age, sample size, ethnicity, and trial characteristics). (3) There have been few randomised controlled trials investigating the association between body fat, AMS and IIEF scores, free testosterone, and mortality rates. (4) All included RCTs displayed signs of selective reporting bias, except for Groti 2020. More research was needed to ascertain how testosterone therapy affected libido. (5) Also, most studies did not include information on doses for control groups, which may have added uncertainty.Conclusion Our results demonstrate that hypogonadal T2DM patients who underwent long-term testosterone replacement therapy experienced a sustained remission of their diabetes. 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PMID: 32329181.         Legends to figuresFigure 1: Prisma flow chartFigure 2: Effects on Glucometabolism; A= HOMA-IR (Homeostatic model assessment for insulin resistance), B= FSG (Fasting serum glucose), C= FSI (Fasting serum insulin), D= HbA1C (Glycated hemoglobin), WMD= weighted mean difference, CI= confidence intervalFigure 3:  Effects on Hormonal levels; A= TT (Total testosterone), B= FT (Free testosterone), C = SBHG (sex hormone binding globulin), D= PSA (Prostate specific antigen).   

Malaria and toxoplasmosis utilize similar known cellular and biochemical pathways to modulate immune responses. Co-infections with malaria and toxoplasmosis occur in malaria endemic regions but not much is known about immune response modulation in these co-infections. Cytokine profiles in response to malaria and toxoplasmosis co-infections were determined in Akinyele, southwest Nigeria. Blood from 192 volunteers were screened for Plasmodium falciparum, Toxoplasma gondii antibodies (IgG and IgM) and cytokine (IL2, IL6, IL10 and IL12) levels. PCV and epidemiological factors associated with toxoplasmosis and malaria were also determined. Prevalence of co-infection was 20.4%, Toxoplasma IgG and IgM was 27.5% and 8.98%, respectively, while 2.6% had high levels of both Toxoplasma IgG and IgM. Malaria prevalence was 72.9% and was highest in individuals below 20 years of age, while toxoplasmosis was most prevalent in 51-60year olds. Toxoplasma sero-positivity, malaria prevalence and Plasmodium intensity were significantly higher (P<0.05) in females. High Toxoplasma IgG was associated (P<0.05) with increased Plasmodium intensity and high IgM with decreased intensity (P>0.05). IL-2 was higher (59.02±0.19pg/ml) in malaria and Toxoplasma IgG co-infection. IL-10 was significantly (P<0.05) elevated with IgM positivity and malaria co-infection. IL-6 increased (P<0.05) with malaria severity while IL-2 was lowest in severe malaria infections. Anaemia was observed in 12.4% of participants, 13.6% of which were seropositive. Active Toxoplasma gondii co-infection with malaria may suppress malaria pathology while Plasmodium and chronic T. gondii co-infection may lead to increased production of IL-2 which may facilitate malaria parasite clearance. Malaria co-infection did not have any effect on anaemia severity.

Background: Commonly used methods of comparison (e.g., network meta-analyses) require common comparator(s) across trials, such as placebo in placebo-controlled trials. Recent literature indicates that route of administration differences across placebo arms of clinical trials in pain disorders may contribute to differences in placebo effect. Methods: We conducted a meta-regression on placebo data from pivotal clinical trials of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies for migraine prevention to quantify the impact of route of administration, migraine type (episodic/chronic), and number of prior treatment failures on placebo reduction in monthly migraine days (MMDs) across weeks 1‒12 of treatment. A systematic literature review of Embase, MEDLINE, the Cochrane Library, and grey literature conducted in June 2021 identified relevant 14 randomised, placebo-controlled trials for analysis. Results: After testing models with different covariates, a meta-regression was fitted to the extracted placebo data with the covariates of route of administration, migraine type, and proportion of patients with ≥2 prior preventive treatment failures. An intravenous route of administration for the placebo arm was a predictor for higher MMD reduction. Predictors of lower MMD reduction were migraine type (episodic migraine) and a higher proportion of patients having ≥2 failed preventive treatments. Conclusions: The efficacy of intravenous anti-CGRP monoclonal antibodies are likely underestimated, and differences in the route of administration of placebo may necessitate use of alternative methods that do not assume the presence of a common comparator when comparing anti-CGRP monoclonal antibodies in migraine prevention. Further research into the contextual effects of the placebo effect is warranted.

Langerhans Cell Histiocytosis (LCH) is a rare clinical condition of the mononuclear phagocyte system caused by abnormal clonal proliferation of aberrant histiocytes or Langerhans cells . We describe this by reporting a case of a 28-year-old male patient presenting multi-system LCH with pituitary and bone involvement.

Background: Omega-3 and omega-6 fatty acids are commonly used in pregnancy, lactation, and malnutrition. Paediatrics has been investigating whether omega-3/omega-6 supplementation affects human growth and neurodevelopment in recent decades.Aims: To assess the current state of knowledge regarding the use of omega-3/omega-6 type fatty acids in the diet in adolescent and adult populations.Materials and Methods: Through September 2022, Pubmed has chosen 72 original articles on the topic of human growth and nutrition in paediatrics.Results: According to the literature, the use of omega-3/omega-6 fatty acids, with a higher prevalence in the former group than the latter, appears to be most effective in hypertension, dyslipidemia, and high C- reactive protein values, cardiovascular risk, and neuropatic pain, while having less impact on neurodegenerative (except in multiple sclerosis) and mental disorders (except in depression). Combining omega-3 and omega-6 fatty acids with spirulina algae, chitosan, probiotics, vitamin D, fibre, and plant extracts yields intriguing results.Conclusions: Although significant evidence emerges on the importance of omega-3 and omega-6 fatty acid supplementation, significant structural flaws in research designs continue to emerge from published studies; additionally, many studies assume that fatty acid supplementation can have a curative effect on already active diseases, when in fact such prescriptions should be considered as adjuvant therapies to prevent or promote symptomatic regression, precisely because of their fatty acid content. Future research that can address the critical issues raised is hoped to promote a more comprehensive approach to the topic of omega-3/omega-6 supplementation in human health.Keywords: DHA. EPA. ALA. AA. Omega-3. Omega-6. Dietary Supplement.

Adaptation enables natural populations to survive in a changing environment. Understanding the mechanics of adaptation is therefore crucial for learning about the evolution and ecology of natural populations, and for better conservation and management of natural resources such as fish stocks. In this review we focus on the impact of random sweepstakes on selection in highly fecund populations. In random sweepstakes the distribution of individual recruitment success is highly skewed, resulting in a huge variance in the number of offspring contributed by the individuals present in any given generation. We also describe selective sweepstakes which are well approximated by recurrent selective sweeps of strongly beneficial allelic types arising by mutation. We demonstrate that both types of sweepstakes reproduction may facilitate rapid adaptation. Finally, we review an important case study in which a model of recurrent selective sweeps is shown to essentially explain population genomic data of the highly fecund Atlantic cod, with broad implications for studying the evolution and ecology of highly fecund populations across domains of life.

An angiomatoid fibrous histiocytoma is a rare soft tissue neoplasm of intermediate biologic potential, is often misdiagnosed because of its clinical and radiological similarity to other conditions. Surgery is the mainstay of management and can effectively control local recurrence and metastasis if properly evaluated preoperatively.

Bicuspid aortic valve is the most common congenital cause for the development of aortic valve calcification and stenosis. Calcification cause valvular stenosis or valvular insufficiency due to coaptation failure. We report a unique case of calcification of bicuspid valve was extending to left ventricular outflow tract and attached to interventricular septum which caused subvalvular stenosis.

The ability of Stemphylium lycopersici immobilized in MCM 48 zeolite structure as biocatalyst for ω-transamination reactions was evaluated. The conversion capacity for rac-1-methylbenzylamine, and also rac-1,2,3,4-tetrahydro-1-naphthylamine was verified in order to ascertain the potential of this biocatalyst in relation to the bioconversion of amines with different side chains when using immobilized crude enzyme extract in zeolite. In this first reaction (after 24 h), a conversion of 23% to acetophenone and 27% to tetralone was obtained. Observing the promising values obtained in the kinetic resolution reactions, an experimental design was carried considering the amount (mg) out of biocatalyst present in the support and the amount of ionic liquid used Central Compound Rotational Design (CCRD 2 complete). After optimization, values close to 36% conversion were achieved. In the present work, there were performed 25 cycles of 18 h with Zeolite MCM48 with the addition of ionic liquids (LI). The presence of LI’s helps with stability and still acts as structure drivers, which may have helped by providing a large number of recycles. In this analysis, 87% of the initial activity was maintained.

The domestic pig (Sus scrofa) and subfamilies have a long-term and extensive gene flow, especially in Southeast Asia. Demographically, as a gateway of southern China, Yunnan province with unique geographical location and complex climate system, but genomic, genetic introgression of Yunnan indigenous pigs is insufficient. Here, we analyzed population structure, differentiation, gene flow, adaptive introgression, signature selection and gene function of Yunnan indigenous pigs, European commercial and other Southeast Asia pigs using a pig genomics reference panel (PGRP v1) from pig Genotype-Tissue Expression project (PigGTEx). In this study, we clarified that the Diannan small-ear pig owned particular genetic information in the whole genome; we provided evidence of the introgression events from the Vietnam pig to the Diannan small-ear pig. We also outlined at least two conceptual routes of gene flow to Diannan small-ear in Southeast Asia. Three introgressed loci with similar chromosome positions and strong signature selection harbored the NAF1, NPY1R and NPY5R genes, which related to fat mass, immunity, and litter weight of pig complex trait using multiple bio-functionalization databases. Conclusively, these results laid the foundation for understanding introgression from Southeast Asia pigs to Yunnan indigenous pigs and provided a new insight into explaining the biological function of genes through multiple databases.

A supravesical hernia (SH) is a rare abdominal wall hernia that develops at the supravesical fossa. Their clinical manifestation is often an intestinal obstruction. Their diagnosis is difficult but computed tomography (CT) appearance and familiarity with the anatomy of the supravesical fossa may allow the preoperative diagnosis.