Endocrine Responses to Heated Resistance Exercise in Men and Women.

ABSTRACT: Pryor, JL, Sweet, DK, Rosbrook, P, Qiao, J, Looney, DP, Mahmood, S, and Rideout, T. Endocrine responses to heated resistance exercise in men and women. J Strength Cond Res 38(7): 1248-1255, 2024-We examined the endocrine responses of 16 (female = 8) resistance trained volunteers to a single bout of whole-body high-volume load resistance exercise in hot (HOT; 40° C) and temperate (TEMP; 20° C) environmental conditions. Thermoregulatory and heart rate (HR) data were recorded, and venous blood was acquired before and after resistance exercise to assess serum anabolic and catabolic hormones. In men, testosterone increased after resistance exercise in HOT and TEMP ( p < 0.01), but postexercise testosterone was not different between condition ( p = 0.51). In women, human growth hormone was different between condition at pre-exercise ( p = 0.02) and postexercise ( p = 0.03). After controlling for pre-exercise values, the between-condition postexercise difference was abolished ( p = 0.16). There were no differences in insulin-like growth factor-1 for either sex ( p ≥ 0.06). In women, cortisol increased from pre-exercise to postexercise in HOT ( p = 0.04) but not TEMP ( p = 0.19), generating a between-condition difference at postexercise ( p < 0.01). In men, cortisol increased from pre-exercise to postexercise in HOT only ( p < 0.01). Rectal temperature increased to a greater extent in HOT compared with TEMP in both men ( p = 0.01) and women ( p = 0.02). Heart rate increased after exercise under both conditions in men and women ( p = 0.01), but only women experience greater postexercise HR in HOT vs. TEMP ( p = 0.04). The addition of heat stress to resistance exercise session did not overtly shift the endocrine response toward an anabolic or catabolic response. When acute program variables are prescribed to increase postresistance exercise anabolic hormones, adding heat stress is not synergistic but does increase physiologic strain (i.e., elevated HR and rectal temperature).

Overview of Technologies Implemented During the First Wave of the COVID-19 Pandemic: Scoping Review.

BACKGROUND: Technologies have been extensively implemented to provide health care services for all types of clinical conditions during the COVID-19 pandemic. While several reviews have been conducted regarding technologies used during the COVID-19 pandemic, they were limited by focusing either on a specific technology (or features) or proposed rather than implemented technologies. OBJECTIVE: This review aims to provide an overview of technologies, as reported in the literature, implemented during the first wave of the COVID-19 pandemic. METHODS: We conducted a scoping review using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) Extension for Scoping Reviews. Studies were retrieved by searching 8 electronic databases, checking the reference lists of included studies and relevant reviews (backward reference list checking), and checking studies that cited included studies (forward reference list checking). The search terms were chosen based on the target intervention (ie, technologies) and the target disease (ie, COVID-19). We included English publications that focused on technologies or digital tools implemented during the COVID-19 pandemic to provide health-related services regardless of target health condition, user, or setting. Two reviewers independently assessed the eligibility of studies and extracted data from eligible papers. We used a narrative approach to synthesize extracted data. RESULTS: Of 7374 retrieved papers, 126 were deemed eligible. Telemedicine was the most common type of technology (107/126, 84.9%) implemented in the first wave of the COVID-19 pandemic, and the most common mode of telemedicine was synchronous (100/108, 92.6%). The most common purpose of the technologies was providing consultation (75/126, 59.5%), followed by following up with patients (45/126, 35.7%), and monitoring their health status (22/126, 17.4%). Zoom (22/126, 17.5%) and WhatsApp (12/126, 9.5%) were the most commonly used videoconferencing and social media platforms, respectively. Both health care professionals and health consumers were the most common target users (103/126, 81.7%). The health condition most frequently targeted was COVID-19 (38/126, 30.2%), followed by any physical health conditions (21/126, 16.7%), and mental health conditions (13/126, 10.3%). Technologies were web-based in 84.1% of the studies (106/126). Technologies could be used through 11 modes, and the most common were mobile apps (86/126, 68.3%), desktop apps (73/126, 57.9%), telephone calls (49/126, 38.9%), and websites (45/126, 35.7%). CONCLUSIONS: Technologies played a crucial role in mitigating the challenges faced during the COVID-19 pandemic. We did not find papers describing the implementation of other technologies (eg, contact-tracing apps, drones, blockchain) during the first wave. Furthermore, technologies in this review were used for other purposes (eg, drugs and vaccines discovery, social distancing, and immunity passport). Future research on studies on these technologies and purposes is recommended, and further reviews are required to investigate technologies implemented in subsequent waves of the pandemic.

Lack of mitochondria-generated acetyl-CoA by pyruvate dehydrogenase complex downregulates gene expression in the hepatic de novo lipogenic pathway.

During the absorptive state, the liver stores excess glucose as glycogen and synthesizes fatty acids for triglyceride synthesis for export as very low density lipoproteins. For de novo synthesis of fatty acids from glucose, the mitochondrial pyruvate dehydrogenase complex (PDC) is the gatekeeper for the generation of acetyl-CoA from glucose-derived pyruvate. Here, we tested the hypothesis that limiting the supply of PDC-generated acetyl-CoA from glucose would have an impact on expression of key genes in the lipogenic pathway. In the present study, although the postnatal growth of liver-specific PDC-deficient (L-PDCKO) male mice was largely unaltered, the mice developed hyperinsulinemia with lower blood glucose levels in the fed state. Serum and liver lipid triglyceride and cholesterol levels remained unaltered in L-PDCKO mice. Expression of several key genes (ACL, ACC1) in the lipogenic pathway and their upstream regulators (LXR, SREBP1, ChREBP) as well as several genes in glucose metabolism (Pklr, G6pd2, Pck1) and fatty acid oxidation (FAT, Cpt1a) was downregulated in livers from L-PDCKO mice. Interestingly, there was concomitant upregulation of lipogenic genes in adipose tissue from L-PDCKO mice. Although, the total hepatic acetyl-CoA content remained unaltered in L-PDCKO mice, modified acetylation profiles of proteins in the nuclear compartment suggested an important role for PDC-generated acetyl-CoA in gene expression in de novo fatty acid synthesis in the liver. This finding has important implications for the regulation of hepatic lipid synthesis in pathological states.

Postnatal Consumption of Black Bean Powder Protects against Obesity and Dyslipidemia in Male Adult Rat Offspring from Obese Pregnancies.

The adverse influence of maternal obesity on offspring metabolic health throughout the life-course is a significant public health challenge with few effective interventions. We examined if black bean powder (BBP) supplementation to a high-calorie maternal pregnancy diet or a postnatal offspring diet could offer protection against the metabolic programming of metabolic disease risk in adult offspring. Female Sprague Dawley rats were randomly assigned to one of three diets (n = 10/group) for a 3-week pre-pregnancy period and throughout gestation and lactation: (i) a low-caloric control diet (CON); (ii) a high-caloric obesity-inducing diet (HC); or (iii) the HC diet with 20% black bean powder (HC-BBP). At weaning [postnatal day (PND) 21], one male pup from each dam was weaned onto the CON diet throughout the postnatal period until adulthood (PND120). In addition, a second male from the HC group only was weaned onto the CON diet supplemented with BBP (CON-BBP). Thus, based on the maternal diet exposure and offspring postnatal diet, four experimental adult offspring groups were compared: CON/CON, HC/CON, HC-BPP/CON, and HC/CON-BBP. On PND120, blood was collected for biochemical analysis (e.g., lipids, glycemic control endpoints, etc.), and livers were excised for lipid analysis (triglycerides [TG] and cholesterol) and the mRNA/protein expression of lipid-regulatory targets. Compared with the CON/CON group, adult offspring from the HC/CON group exhibited a higher (p < 0.05) body weight (BW) (682.88 ± 10.67 vs. 628.02 ± 16.61 g) and hepatic TG (29.55 ± 1.31 vs. 22.86 ± 1.85 mmol/g). Although maternal BBP supplementation (HC-BBP/CON) had little influence on metabolic outcomes, the consumption of BBP in the postnatal period (HC/CON-BBP) lowered hepatic TG and cholesterol compared with the other treatment groups. Reduced hepatic TG in the HC/CON-BBP was likely associated with lower postnatal BW gain (vs. HC/CON), lower mRNA and protein expression of hepatic Fasn (vs. HC/CON), and lower serum leptin concentration (vs. CON/CON and HC groups). Our results suggest that the postnatal consumption of a black-bean-powder-supplemented diet may protect male rat offspring against the programming of obesity and dyslipidemia associated with maternal obesity. Future work should investigate the bioactive fraction of BBP responsible for the observed effect.

Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction.

Neonatal rats reared on high-carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity due to programming of islets and the hypothalamic energy circuitry. In this study, calorie restriction by pair-feeding was imposed on HC male rats (HC/PF) to normalize food intake similar to that of mother-fed (MF) rats from weaning until postnatal day 140. A group of HC/PF rats was switched over to ad libitum feeding (HC/PF/AL) from days 90 to 140. Pair-feeding reduced body weight gains and serum insulin and leptin levels in HC/PF rats compared with HC rats, but these parameters were restored to HC levels in the HC/PF/AL rats after ad libitum feeding. Interestingly, the heightened insulin secretory response of isolated islets from adult HC/PF and HC/PF/ AL rats to glucose, acetylcholine, and oxymetazoline were not significantly different from the responses of islets from HC rats. Similarly, the expression of neuropeptide Y and proopiomelanocortin in the hypothalamus was not significantly different among HC, HC/PF, and HC/PF/AL rats. Expression of the leptin receptor in the hypothalami from the HC, HC/PF, and HC/PF/AL rats mirrored that of serum leptin, whereas suppressor of cytokine signaling 3 (Socs3) expression remained high in these three groups. The results indicate that, although calorie restriction resulted in reduction in body weight gain and normalized the serum hormonal pattern, the programed predisposition for the hypersecretory capacity of islets and the hypothalamic hyperphagic response in the HC rats could not be permanently overcome by the pair-feeding imposed on HC rats.

Adult-onset obesity induced by early life overnutrition could be reversed by moderate caloric restriction.

Overnutrition during the suckling period (small litter, SL) results in the development of adult-onset obesity. Our aim was to investigate whether two levels of caloric restriction (CR) in the early postweaning period can reverse obese phenotype in SL rats. The normal litter (NL) had 12 pups/dam and SL had 3 male pups/dam from the postnatal day 3 until day 21. After weaning, rats consumed lab chow as indicated: 1) NL and SL groups were on ad libitum regimen up to day 140, 2) another SL group was pair-fed (SL/PF) to NL(∼14% reduction), 3) SL/PF/AL group was pair-fed up to day 94 and then switched to ad libitum feeding, 4) SL/CR group received 24% reduction (moderate CR) in food intake compared with SL, and 5) SL/CR/AL group was on 24% CR up to day 94 and then switched to ad libitum feeding. Pair-feeding reduced body weight gains and serum insulin and leptin levels compared with SL rats, but these parameters were restored to SL levels in the SL/PF/AL rats after switching to ad libitum feeding. Interestingly, the moderate CR normalized these parameters in SL/CR and SL/CR/AL rats compared with NL. The expression of neuropeptide Y, proopiomelanocortin, and leptin receptor returned to control levels in hypothalami from SL/CR and SL/CR/AL rats. These results indicate that appropriate manipulation of energy intake during the early postweaning period could lead to longer-lasting effects on the regulation of body weight homeostasis via reversal of the early preweaning programming effects on the hypothalamic appetite regulation mechanism.

Maternal pea fiber supplementation to a high calorie diet in obese pregnancies protects male offspring from metabolic dysfunction in adulthood.

We investigated the influence of maternal yellow-pea fiber supplementation in obese pregnancies on offspring metabolic health in adulthood. Sixty newly-weaned female Sprague-Dawley rats were randomized to either a low-calorie control diet (CON) or high calorie obesogenic diet (HC) for 6-weeks. Obese animals were then fed either the HC diet alone or the HC diet supplemented with yellow-pea fiber (HC + FBR) for an additional 4-weeks prior to breeding and throughout gestation and lactation. On postnatal day (PND) 21, 1 male and 1 female offspring from each dam were weaned onto the CON diet until adulthood (PND 120) for metabolic phenotyping. Adult male, but not female, HC offspring demonstrated increased body weight and feed intake vs CON offspring, however no protection was offered by maternal FBR supplementation. HC male and female adult offspring demonstrated increased serum glucose and insulin resistance (HOMA-IR) compared with CON offspring. Maternal FBR supplementation improved glycemic control in male, but not female offspring. Compared with CON offspring, male offspring from HC dams demonstrated marked dyslipidemia (higher serum cholesterol, increased number of TG-rich lipoproteins, and smaller LDL particles) which was largely normalized in offspring from HC + FBR mothers. Male offspring born to obese mothers (HC) had higher hepatic TG, which tended to be lowered (p = 0.07) by maternal FBR supplementation.Supplementation of a maternal high calorie diet with yellow-pea fiber in prepregnancy and throughout gestation and lactation protects male offspring from metabolic dysfunction in the absence of any change in body weight status in adulthood.

Maternal Pea Protein Intake Provides Sex-Specific Protection against Dyslipidemia in Offspring from Obese Pregnancies.

Increased consumption of dietary pulse protein has been shown to assist in body weight regulation and improve a range of metabolic health outcomes. We investigated if the exchange of casein for yellow pea protein (YPPN) in an obese-inducing maternal diet throughout pregnancy and lactation offered protection against obesity and dyslipidemia in offspring. Sixty female Sprague Dawley rats were fed a low-calorie control diet (CON), a high-caloric obesity-inducing diet (with casein protein (CP), HC-CP), or an isocaloric/macronutrient-matched HC diet supplemented with YPPN isolate (HC-PPN) in pre-pregnancy, gestation, and lactation. Body weight (BW) and metabolic outcomes were assessed in male and female offspring at weaning and in adulthood after consuming the CON diet in the postnatal period. Consumption of the HC-PPN diet did not protect against maternal obesity but did improve reproductive success compared with the HC-CP group (72.7% versus 43.7%) and reduced total energy, fat, and protein in maternal milk. Male, but not female, offspring from mothers fed the HC-CP diet demonstrated hyperphagia, obesity, dyslipidemia, and hepatic triglyceride (TG) accumulation as adults compared with CON offspring. Isocaloric exchange of CP for YPPN in a high-calorie obese-inducing diet did not protect against obesity but did improve several aspects of lipid metabolism in adult male offspring including serum total cholesterol, LDL/VLDL cholesterol, triglycerides (TGs), and hepatic TG concentration. Our results suggest that the exchange of CP for YPPN in a maternal obese-inducing diet selectively protects male offspring from the malprogramming of lipid metabolism in adulthood.

Trace elements-based Auroshell gold@hematite nanostructure: Green synthesis and their hyperthermia therapy.

Hyperthermia is an additional treatment method to radiation therapy/chemotherapy, which increases the survival rate of patients without side effects. Nowadays, Auroshell nanoparticles have attracted much attention due to their precise control over heat use for medical purposes. In this research, iron/gold Auroshell nanoparticles were synthesised using green nanotechnology approach. Auroshell gold@hematite nanoparticles were synthesised and characterised with rosemary extract in one step and the green synthesised nanoparticles were characterised by X-ray powder diffraction, SEM, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy analysis. Cytotoxicity of Auroshell iron@gold nanoparticles against normal HUVEC cells and glioblastoma cancer cells was evaluated by 2,5-diphenyl-2H-tetrazolium bromide method, water bath hyperthermia, and combined method of water bath hyperthermia and nano-therapy. Auroshell gold@hematite nanoparticles with minimal toxicity are safe against normal cells. The gold shell around the magnetic core of magnetite caused the environmental and cellular biocompatibility of these Auroshell nanoparticles. These magnetic nanoparticles with targeted control and transfer to the tumour tissue led to uniform heating of malignant tumours as the most efficient therapeutic agent.

Evaluation of Phosphorus Storage and Performance of Broilers Using Phytase Synthetic Enzyme.

Phytic acid is a stored form of phosphorus in cereals, 65 to 70% of phosphorus in plant sources is phytate, and broilers are only able to use part of the phosphorus in plant sources. To meet the needs of chickens, it is necessary to use other artificial resources, which not only impose part of the cost of the breeding period because of its presence in the manure but is one of the factors polluting the environment. This study aimed to use different levels of phytase enzyme to reduce dietary phosphorus levels. 600 Ross 308 broilers were used in this experiment with five treatments and six replications, and in each replication, 20 chickens were used in a completely randomized design (CRD). Experimental treatments include 1) basal diet (control) 2) basal diet with 15% less phosphorus 3) basal diet with 15% less phosphorus + 1250 (FTU) phytase enzyme 4) basal diet with 15% less phosphorus + 2500 (FTU) phytase enzyme 5) basal diet with 15% less phosphorus + 5000 (FTU) phytase enzyme. The evaluated traits included weekly feed intake, weekly weight gain, feed conversion ratio, carcass characteristics, ash, calcium, and bone phosphorus. The use of phytase enzyme in different diets had no significant effect on food intake, weight gain, and feed conversion ratio (P>0.05). However, the use of phytase in different diets significantly affected the percentage of Gizzard, Heart, Liver, Proventriculus, and Spleen (P<0.05). The most changes were the increase in the ratio of feed intake and weight gain in the fourth week compared to the third week so that the changes in the ratio of feed intake ranged from 1.85 to 1.91, and this ratio for weight gain also ranged from 3.12 to 3.86 was recorded, and the lowest feed conversion ratio was obtained at the same age. The percentage of raw ash in broiler chickens was significantly increased by adding dietary phytase. The lowest amount of ash, calcium, and phosphorus belonged to the second group (diets with low phosphorus and no enzyme). The difference between the other groups and the control was not significant. Feed intake, weight gain, and feed conversion ratio with the addition of phytase enzyme were not affected by phosphorus reduction and had no significant effect on carcass characteristics. Environmental pollution can be prevented by reducing the level of dietary phosphorus and reducing excreted phosphorus.

Correlation of rs35753505 polymorphism in Neuregulin 1 gene with psychopathology and intelligence of people with schizophrenia.

BACKGROUND AND AIM: Schizophrenia is one of the most severe psychiatric disorders. About 0.5 to 1% of the world's population suffers from this non-Mendelian disorder. Environmental and genetic factors seem to be involved in this disorder. In this article, we investigate the alleles and genotypic correlation of mononucleotide rs35753505 polymorphism of Neuregulin 1 (NRG1), one of the selected genes of schizophrenia, with psychopathology and intelligence. MATERIALS AND METHODS: 102 independent and 98 healthy patients participated in this study. DNA was extracted by the salting out method and the polymorphism (rs35753505) were amplified by polymerase chain reaction (PCR). Sanger sequencing was performed on PCR products. Allele frequency analysis was performed using COCAPHASE software, and genotype analysis was performed using Clump22 software. RESULTS: According to our study's statistical findings, all case samples from the three categories of men, women, and overall participants significantly differed from the control group in terms of the prevalence of allele C and the CC risk genotype. The rs35753505 polymorphism significantly raised Positive and Negative Syndrome Scale (PANSS) test results, according to a correlation analysis between the two variables. However, this polymorphism led to a significant decrease in overall intelligence in case samples compared to control samples. CONCLUSION: In this study, it seems that the rs35753505 polymorphism of NRG1 gene has a significant role in the sample of patients with schizophrenia in Iran and also in psychopathology and intelligence disorders.

Recent Developments in Artificial Intelligence-Based Techniques for Prostate Cancer Detection: A Scoping Review.

Artificial intelligence (AI) techniques can contribute to the early diagnosis of prostate cancer. Recently, there has been a sharp increase in the literature on AI techniques for prostate cancer diagnosis. This review article presents a summary of the AI methods that detect and diagnose prostate cancer using different medical imaging modalities. Following the PRISMA-ScR principle, this review covers 69 studies selected from 1441 searched papers published in the last three years. The application of AI methods reported in these articles can be divided into three broad categories: diagnosis, grading, and segmentation of tissues that have prostate cancer. Most of the AI methods leveraged convolutional neural networks (CNNs) due to their ability to extract complex features. Some studies also reported traditional machine learning methods, such as support vector machines (SVM), decision trees for classification, LASSO, and Ridge regression methods for features extraction. We believe that the implementation of AI-based tools will support clinicians to provide better diagnosis plans for prostate cancer.

Aptasensor Based on Microfluidic for Foodborne Pathogenic Bacteria and Virus Detection: A Review.

In today's world, which is entangled with numerous foodborne pathogenic bacteria and viruses, it appears to be essential to rethink detection methods of these due to the importance of food safety in our lives. The vast majority of detection methods for foodborne pathogenic bacteria and viruses have suffered from sensitivity and selectivity due to the small size of these pathogens. Besides, these types of sensing approaches can improve on-site detection platforms in the fields of food safety. In recent, microfluidics systems as new emerging types of portable sensing approaches can introduce efficient and simple biodevice by integration with several analytical methods such as electrochemical, optical and colorimetric techniques. Additionally, taking advantage of aptamer as a selective bioreceptor in the sensing of microfluidics system has provided selective, sensitive, portable and affordable sensing approaches. Furthermore, some papers use increased data transferability ability and computational power of these sensing platforms by exploiting smartphones. In this review, we attempted to provide an overview of the current state of the recent aptasensor based on microfluidic for screening of foodborne pathogenic bacteria and viruses. Working strategies, benefits and disadvantages of these sensing approaches are briefly discussed.

PCSK9 pathway-noncoding RNAs crosstalk: Emerging opportunities for novel therapeutic approaches in inflammatory atherosclerosis.

A variety of mechanisms contribute to the occurrence and development of inflammatory atherosclerosis (IA), resulting in cardiovascular disease. PCSK9 (proprotein convertase subtilisin/ kexin type 9) has now been recognized as a key player in the pathophysiology of atherosclerosis. Following PCSK9 activation, LDL receptors (LDLR) are degraded and as a result, LDL cholesterol (LDLC) levels are increased. Increasing evidence reports that the PCSK9 axis mediates IA through different pathways, such as LDLR, LOX1, NF-kB, and TLR4. In recent years, PCSK9 pathway dysregulation has been identified as one of the fundamental mechanisms involved in IA. Recently, the importance of epigenetic factors, in particular, in non-coding RNAs, including miRNAs and long ncRNAs (lncRNAs) as well as circular RNAs (circRNAs) in the regulation of physiological and pathological events has received great attention. In this regard, an expanding body of research has revealed that different ncRNAs play important roles in the progression of inflammatory atherosclerosis through targeting genes related to the PCSK9 pathway at the post-transcriptional level. Of importance, the current study aimed to review the relationship between the various ncRNAs and PCSK9 pathway to identify the molecular mechanisms underlying IA pathogenesis as well as to introduce the novel PCSK9 pathway-related therapeutic interventions in combating IA.

Advances in Biosensing of Chemical Food Contaminants Based on the MOFs-Graphene Nanohybrids.

Food safety issue is becoming an international challenge for human health owing to the presence of contaminants. In this context, reliable, rapid, and sensitive detecting technology is extremely demanded to establish food safety assurance systems. MOFs (Metal-organic frameworks) are a new type of porous crystalline material with particular physical and chemical characteristics presented in food safety requirements. (Bio)sensors driven MOF materials have emerged as a promising alternative and complementary analytical techniques, owing to their great specific area, high porosity, and uniform and fine-tunable pore buildings. Nevertheless, the insufficient stability and electrical conductivity of classical MOFs limit their utilization. Employing graphene-derived nanomaterials with high functional elements as patterns for the MOF materials not only improves the structural instability and poor conductivity but also impedes the restacking and aggregation between graphene layers, thus significantly extending the MOFs application. A review of MOFs-graphene-based material used in food contamination detection is urgently needed for encouraging the advance of this field. Herein, this paper systematically outlines current breakthroughs in MOF-graphene-based nanoprobes, outlines their principles, and illustrates their employments in identifying mycotoxins, heavy metal ions, pathogens, antibiotics, and pesticides, referring to their multiplexing and sensitivity ability. The challenges and limitations of applying MOF-graphene composite for precise and efficient assessment of food were also debated. This paper would maybe offer some inspired concepts for an upcoming study on MOF-based composites in the food security context.

Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development.

BACKGROUND: Changes in DNA methylation in the mammalian genome during development are frequent events and play major roles regulating gene expression and other developmental processes. It is necessary to identify these events so that we may understand how these changes affect normal development and how aberrant changes may impact disease. RESULTS: In this study Methylated DNA ImmunoPrecipitation (MeDIP) was used in conjunction with a NimbleGen promoter plus CpG island (CpGi) array to identify Tissue and Developmental Stage specific Differentially Methylated DNA Regions (T-DMRs and DS-DMRs) on a genome-wide basis. Four tissues (brain, heart, liver, and testis) from C57BL/6J mice were analyzed at three developmental stages (15 day embryo, E15; new born, NB; 12 week adult, AD). Almost 5,000 adult T-DMRs and 10,000 DS-DMRs were identified. Surprisingly, almost all DS-DMRs were tissue specific (i.e. methylated in at least one tissue and unmethylated in one or more tissues). In addition our results indicate that many DS-DMRs are methylated at early development stages (E15 and NB) but are unmethylated in adult. There is a very strong bias for testis specific methylation in non-CpGi promoter regions (94%). Although the majority of T-DMRs and DS-DMRs tended to be in non-CpGi promoter regions, a relatively large number were also located in CpGi in promoter, intragenic and intergenic regions (>15% of the 15,979 CpGi on the array). CONCLUSIONS: Our data suggests the vast majority of unique sequence DNA methylation has tissue specificity, that demethylation has a prominent role in tissue differentiation, and that DNA methylation has regulatory roles in alternative promoter selection and in non-promoter regions. Overall, our studies indicate changes in DNA methylation during development are a dynamic, widespread, and tissue-specific process involving both DNA methylation and demethylation.

Reprogramming of aerobic glycolysis in non-transformed mouse liver with pyruvate dehydrogenase complex deficiency.

The Pyruvate Dehydrogenase Complex (PDC), a key enzyme in glucose metabolism, catalyzes an irreversible oxidative decarboxylation reaction of pyruvate to acetyl-CoA, linking the cytosolic glycolytic pathway to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Earlier we reported a down-regulation of several key hepatic lipogenic enzymes and their upstream regulators in liver-specific PDC-deficient mouse (L-PDCKO model by deleting the Pdha1 gene). In this study we investigated gene expression profiles of key glycolytic enzymes and other proteins that respond to various metabolic stresses in liver from L-PDCKO mice. Transcripts of several, such as hexokinase 2, phosphoglycerate kinase 1, pyruvate kinase muscle-type 2, and lactate dehydrogenase B as well as those for the nonglycolysis-related proteins, CD-36, C/EBP homologous protein, and peroxisome proliferator-activated receptor γ, were up-regulated in L-PDCKO liver whereas hypoxia-induced factor-1α, pyruvate dehydrogenase kinase 1 and Sirtuin 1 transcripts were down-regulated. The protein levels of pyruvate kinase muscle-type 2 and lactate dehydrogenase B were increased whereas that of lactate dehydrogenase A was decreased in PDC-deficient mouse liver. Analysis of endoplasmic reticulum and oxidative stress indicators suggests that the L-PDCKO liver showed evidence of the former but not the latter. These findings indicate that (i) liver-specific PDC deficiency is sufficient to induce "aerobic glycolysis characteristic" in mouse liver, and (ii) the mechanism(s) responsible for these changes appears distinct from that which induces the Warburg effect in some cancer cells.

A Scoping Review to Find Out Worldwide COVID-19 Vaccine Hesitancy and Its Underlying Determinants.

BACKGROUND: The current crisis created by the coronavirus pandemic is impacting all facets of life. Coronavirus vaccines have been developed to prevent coronavirus infection and fight the pandemic. Since vaccines might be the only way to prevent and stop the spread of coronavirus. The World Health Organization (WHO) has already approved several vaccines, and many countries have started vaccinating people. Misperceptions about vaccines persist despite the evidence of vaccine safety and efficacy. OBJECTIVES: To explore the scientific literature and find the determinants for worldwide COVID-19 vaccine hesitancy as reported in the literature. METHODS: PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines were followed to conduct a scoping review of literature on COVID-19 vaccine hesitancy and willingness to vaccinate. Several databases (e.g., MEDLINE, EMBASE, and Google Scholar) were searched to find relevant articles. Intervention- (i.e., COVID-19 vaccine) and outcome- (i.e., hesitancy) related terms were used to search in these databases. The search was conducted on 22 February 2021. Both forward and backward reference lists were checked to find further studies. Three reviewers worked independently to select articles and extract data from selected literature. Studies that used a quantitative survey to measure COVID-19 vaccine hesitancy and acceptance were included in this review. The extracted data were synthesized following the narrative approach and results were represented graphically with appropriate figures and tables. RESULTS: 82 studies were included in this scoping review of 882 identified from our search. Sometimes, several studies had been performed in the same country, and it was observed that vaccine hesitancy was high earlier and decreased over time with the hope of vaccine efficacy. People in different countries had varying percentages of vaccine uptake (28-86.1%), vaccine hesitancy (10-57.8%), vaccine refusal (0-24%). The most common determinants affecting vaccination intention include vaccine efficacy, vaccine side effects, mistrust in healthcare, religious beliefs, and trust in information sources. Additionally, vaccination intentions are influenced by demographic factors such as age, gender, education, and region. CONCLUSIONS: The underlying factors of vaccine hesitancy are complex and context-specific, varying across time and socio-demographic variables. Vaccine hesitancy can also be influenced by other factors such as health inequalities, socioeconomic disadvantages, systemic racism, and level of exposure to misinformation online, with some factors being more dominant in certain countries than others. Therefore, strategies tailored to cultures and socio-psychological factors need to be developed to reduce vaccine hesitancy and aid informed decision-making.

The Role of Neural Network for the Detection of Parkinson's Disease: A Scoping Review.

Background: Parkinson's Disease (PD) is a chronic neurodegenerative disorder that has been ranked second after Alzheimer's disease worldwide. Early diagnosis of PD is crucial to combat against PD to allow patients to deal with it properly. However, there is no medical test(s) available to diagnose PD conclusively. Therefore, computer-aided diagnosis (CAD) systems offered a better solution to make the necessary data-driven decisions and assist the physician. Numerous studies were conducted to propose CAD to diagnose PD in the early stages. No comprehensive reviews have been conducted to summarize the role of AI tools to combat PD. Objective: The study aimed to explore and summarize the applications of neural networks to diagnose PD. Methods: PRISMA Extension for Scoping Reviews (PRISMA-ScR) was followed to conduct this scoping review. To identify the relevant studies, both medical databases (e.g., PubMed) and technical databases (IEEE) were searched. Three reviewers carried out the study selection and extracted the data from the included studies independently. Then, the narrative approach was adopted to synthesis the extracted data. Results: Out of 1061 studies, 91 studies satisfied the eligibility criteria in this review. About half of the included studies have implemented artificial neural networks to diagnose PD. Numerous studies included focused on the freezing of gait (FoG). Biomedical voice and signal datasets were the most commonly used data types to develop and validate these models. However, MRI- and CT-scan images were also utilized in the included studies. Conclusion: Neural networks play an integral and substantial role in combating PD. Many possible applications of neural networks were identified in this review, however, most of them are limited up to research purposes.

Tissue specific differentially methylated regions (TDMR): Changes in DNA methylation during development.

Tissue specific differentially methylated regions (TDMRs) were identified and localized in the mouse genome using second generation virtual RLGS (vRLGS). Sequenom MassARRAY quantitative methylation analysis was used to confirm and determine the fine structure of tissue specific differences in DNA methylation. TDMRs have a broad distribution of locations to intragenic and intergenic regions including both CpG islands, and non-CpG islands regions. Somewhat surprising, there is a strong bias for TDMR location in non-promoter intragenic regions. Although some TDMRs are within or close to repeat sequences, overall they are less frequently associated with repetitive elements than expected from a random distribution. Many TDMRs are methylated at early developmental stages, but unmethylated later, suggesting active or passive demethylation, or expansions of populations of cells with unmethylated TDMRs. This is notable during postnatal testis differentiation where many testis specific TDMRs become progressively "demethylated". These results suggest that methylation changes during development are dynamic, involve demethylation and methylation, and may occur at late stages of embryonic development or even postnatally.