The Role of Mitophagy in Various Neurological Diseases as a Therapeutic Approach.

Mitochondria are critical to multiple cellular processes, from the production of adenosine triphosphate (ATP), maintenance of calcium homeostasis, synthesis of key metabolites, and production of reactive oxygen species (ROS) to maintain necrosis, apoptosis, and autophagy. Therefore, proper clearance and regulation are essential to maintain various physiological processes carried out by the cellular mechanism, including mitophagy and autophagy, by breaking down the damaged intracellular connections under the influence of various genes and proteins and protecting against various neurodegenerative diseases such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), and Huntington disease (HD). In this review, we will discuss the role of autophagy, selective macroautophagy, or mitophagy, and its role in neurodegenerative diseases along with normal physiology. In addition, this review will provide a better understanding of the pathways involved in neuron autophagy and mitophagy and how mutations affect these pathways in the various genes involved in neurodegenerative diseases. Various new findings indicate that the pathways that remove dysfunctional mitochondria are impaired in these diseases, leading to the deposition of damaged mitochondria. Apart from that, we have also discussed the therapeutic strategies targeting autophagy and mitophagy in neurodegenerative diseases. The mitophagy cycle results in the degradation of damaged mitochondria and the biogenesis of new healthy mitochondria, also highlighting different stages at which a particular neurodegenerative disease could occur.

Blood-Brain Barrier Dysfunction in Hypertensive Disorders of Pregnancy.

PURPOSE OF REVIEW: The incidence of hypertensive disorders of pregnancy (HDP), especially preeclampsia has increased significantly over the last two decades. Patients with these disorders often report cerebral and visual symptoms, which are listed as potential diagnosis criteria for preeclampsia, if accompanied by new-onset hypertension. Recent studies indicate that cerebral complications in HDP patients are associated with a compromised blood-brain barrier (BBB). The purpose of this review is to highlight the recent literature focused on the BBB in HDP, identify gaps in knowledge, and discuss future directions in this research area. RECENT FINDINGS: Majority of the studies addressing BBB changes in HDP are focused on preeclampsia. Recent studies show that hypertension induces increased association of perivascular macrophages/microglia to the cerebral vessels, increased circulating extracellular vesicles, and decreased autoregulation of cerebral blood flow. There is a critical need for more animal studies targeted to protecting the BBB and preventing cerebrovascular complications in the context of HDP. More clinical studies are needed that investigate both the short- and long-term interplay between each HDP subtype and BBB and cognitive function.

Online Interest for Electronic Cigarettes Using Google Trends in the UK: A Correlation Analysis.

BACKGROUND: Google Trends provides an easily accessible and cost-effective method of providing real-time insight into user interest. OBJECTIVE: to address the gap in UK prevalence data for e-cigarettes by analyzing Google Trends to identify correlations with official data from Action on Smoking and Health. The study further evaluates Google Trend's sensitivity to real-time events and the ability for predictive models to forecast future data based on Google Trends. METHODS: UK Google Trends data from 2012 to 2021 was analyzed to assess (a) the most popular electronic nicotine device terminology; (b) statistically significant points in time; (c) correlations between Relative Search Volumes and official reports on electronic cigarette use and (d) whether Google Trends could predict future patterns in data. These were achieved using Locally Weighted Scatterplot Smoothing regression, Pruned Exact Linear Time Method, cross correlation, and Autoregressive Integrated Moving Average algorithms respectively. RESULTS: "Vape" was revealed to be the most popular electronic nicotine device terminology with a correlation coefficient greater than +0.9 when compared to official electronic cigarette consumption data within a one-year timescale (lag 0). Results from ARIMA modeling were varied with the algorithms forecasted trends line occasionally lying outside of a 95% prediction interval. CONCLUSION: Google Trends may correspond to population-based prevalence of electronic cigarette use. The changing trends coincide with changing policy decisions. Google Trends based prediction for online interest in electronic cigarettes requires further validation so should currently be used in conjunction with other traditional methods of data collections.

Response of the plant core microbiome to Fusarium oxysporum infection and identification of the pathobiome.

Plant core microbiomes consist of persistent key members that provide critical host functions, but their assemblages can be interrupted by biotic and abiotic stresses. The pathobiome is comprised of dynamic microbial interactions in response to disease status of the host. Hence, identifying variation in the core microbiome and pathobiome can significantly advance our understanding of microbial-microbial interactions and consequences for disease progression and host functions. In this study, we combined glasshouse and field studies to analyse the soil and plant rhizosphere microbiome of cotton plants (Gossypium hirsutum) in the presence of a cotton-specific fungal pathogen, Fusarium oxysporum f. sp. vasinfectum (FOV). We found that FOV directly and consistently altered the rhizosphere microbiome, but the biocontrol agents enabled microbial assemblages to resist pathogenic stress. Using co-occurrence network analysis of the core microbiome, we identified the pathobiome comprised of the pathogen and key associate phylotypes in the cotton microbiome. Isolation and application of some negatively correlated pathobiome members provided protection against plant infection. Importantly, our field survey from multiple cotton fields validated the pattern and responses of core microbiomes under FOV infection. This study advances key understanding of core microbiome responses and existence of plant pathobiomes, which provides a novel framework to better manage plant diseases in agriculture and natural settings.

Google Trends Data: A Potential New Tool for Monitoring the Opioid Crisis.

INTRODUCTION: There is a need to strengthen the standard surveillance of the opioid overdose crisis in the USA. The role of Google Trends (GT) was explored in this context. METHODS: In this study, a systemic GT search was done for a period from January 2004 to December 2018. "Naloxone" and "drug overdose" were chosen as search inputs. By using locally weighted scatterplot smoothing, we locally regressed and smoothed the relative search data generated by the GT search. We conducted a changepoint analysis (CPA) to detect significant statistical changes in the "naloxone" trend from 2004 to 2018. Cross-correlation function analyses were done to examine the correlation between 2 time series: year-wise relative search volume (RSV) for "naloxone" and "drug overdose" with the age-adjusted drug overdose mortality rate. Pearson's correlation was performed for the state-wise age-adjusted mortality rate due to drug overdose and RSV for "naloxone" and "drug overdose." RESULTS: Smoothed and regressed GT of "naloxone" were similar to the "opioid overdose" trend published by the National Center for Health Statistics. The CPA showed 2 statistically significant points in 2011 and 2015. CPA of year-wise RSV for "naloxone" and "drug overdose" showed significantly positive correlation with the age-adjusted drug overdose mortality at lag zero. State-wise RSV for "naloxone" and "drug overdose" too showed a strong and significant positive correlation with the state-wise mortality data. DISCUSSION/CONCLUSION: Inexpensive, publicly accessible, real-time GT data could supplement and strengthen the monitoring of opioid overdose epidemic if used in conjunction with the existing official data sources.

Characterization of oleosin genes from forage sorghum in Arabidopsis and yeast reveals their role in storage lipid stability.

MAIN CONCLUSION: Overexpression of forage sorghum oleosin genes in Arabidopsis oleosin-deficient mutant and yeast showed increased germination rate, triacylglycerol content, and protection against lipase-mediated TAG degradation. Plant lipids are an important source of ration for cattle or other livestock animals to fulfil their energy needs. Poor energy containing green forages are still one of the major sources of food for livestock animals, leaving the animals undernourished. This lowers the milk and meat production efficiency, thereby affecting human consumption. Oleosin, an essential oil body surface protein, is capable of enhancing and stabilizing the lipid content in plants. We identified and functionally characterized three forage sorghum oleosin genes (SbOle1, SbOle2, and SbOle3) in Arabidopsis and yeast. Phylogenetic analysis of SbOle proteins showed a close relationship with rice and maize oleosins. Expression analysis of SbOle genes determined a higher expression pattern in embryo followed by endosperm, while its expression in the non-seed tissues remained negligible. Overexpression of SbOle genes in Arabidopsis ole1-deficient mutants showed restoration of normal germination whereas control mutant seeds showed lower germination rates. Heterologous overexpression of SbOle in yeast cells resulted in increased TAG accumulation. Additionally, the TAG turnover assay showed the effectiveness of SbOle genes in reducing the yeast endogenous and rumen bacterial lipase-mediated TAG degradation. Taken together, our findings not only provide insights into forage sorghum oleosin for increasing the energy content in non-seed organs but also opened up the direction towards implication of oleosin in rumen protection of fodders.

Use and interest of electronic nicotine delivery systems (ENDS): Assessing the validity of Google Trends.

Background: Initial evidence suggests a role for Google Trends (GT) in monitoring use and interest in Electronic Nicotine Delivery Systems (ENDS).Objective: To examine the validity of GT data for assessing population behavior and interest in ENDS.Methods: GT search, done from the US and India to assess: (a) whether descriptive and statistical trends of specific search words depicting online interest in ENDS were similar to the published reports on actual use of these products in the US; (b) correlations between state-wise relative search volumes (RSV) of these words and prevalence of ENDS use; (c) the change in the online interest of ENDS after change in its regulatory policy.Results: Locally weighted scatter plot analysis showed "electronic cigarette," "vaping," and "cigarette" trends mirrored the use trend reported by the US-based National Youth Tobacco Survey (2019). Online interest in "Juul pods" followed the trends of its use. Geo-spatial RSVs of "electronic cigarette" (r=0.74, p<0.0001) and "vaping" (r=0.55, p<0.0001) correlated positively with state-wise prevalence of switch to ENDS in adults. Complete ENDS use prohibition in India was associated with a decrease in the online interest in "electronic cigarettes" (t=3.18, p=0.01) and "vaping" (t=2.3, p=0.04). Regulation of use in New Mexico (USA) was associated with a reduction in "electronic cigarettes" (t=4.09, p=0.0005) but not in "vaping."Conclusion: GT may be used to validate existing information and assess the potential effect of ENDS regulations. Its role can also be extended for monitoring interest and use of other drugs and alcohol.

Informing Environmental Water Management Decisions: Using Conditional Probability Networks to Address the Information Needs of Planning and Implementation Cycles.

One important aspect of adaptive management is the clear and transparent documentation of hypotheses, together with the use of predictive models (complete with any assumptions) to test those hypotheses. Documentation of such models can improve the ability to learn from management decisions and supports dialog between stakeholders. A key challenge is how best to represent the existing scientific knowledge to support decision-making. Such challenges are currently emerging in the field of environmental water management in Australia, where managers are required to prioritize the delivery of environmental water on an annual basis, using a transparent and evidence-based decision framework. We argue that the development of models of ecological responses to environmental water use needs to support both the planning and implementation cycles of adaptive management. Here we demonstrate an approach based on the use of Conditional Probability Networks to translate existing ecological knowledge into quantitative models that include temporal dynamics to support adaptive environmental flow management. It equally extends to other applications where knowledge is incomplete, but decisions must still be made.

Role of Autophagy and Mitophagy in Neurodegenerative Disorders.

Autophagy is a self-destructive cellular process that removes essential metabolites and waste from inside the cell to maintain cellular health. Mitophagy is the process by which autophagy causes disruption inside mitochondria and the total removal of damaged or stressed mitochondria, hence enhancing cellular health. The mitochondria are the powerhouses of the cell, performing essential functions such as ATP (adenosine triphosphate) generation, metabolism, Ca2+ buffering, and signal transduction. Many different mechanisms, including endosomal and autophagosomal transport, bring these substrates to lysosomes for processing. Autophagy and endocytic processes each have distinct compartments, and they interact dynamically with one another to complete digestion. Since mitophagy is essential for maintaining cellular health and using genetics, cell biology, and proteomics techniques, it is necessary to understand its beginning, particularly in ubiquitin and receptor-dependent signalling in injured mitochondria. Despite their similar symptoms and emerging genetic foundations, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) have all been linked to abnormalities in autophagy and endolysosomal pathways associated with neuronal dysfunction. Mitophagy is responsible for normal mitochondrial turnover and, under certain physiological or pathological situations, may drive the elimination of faulty mitochondria. Due to their high energy requirements and post-mitotic origin, neurons are especially susceptible to autophagic and mitochondrial malfunction. This article focused on the importance of autophagy and mitophagy in neurodegenerative illnesses and how they might be used to create novel therapeutic approaches for treating a wide range of neurological disorders.

Enhanced antichemobrain activity of amino acid assisted ferulic acid solid dispersion in adult zebrafish (Danio rerio).

Chemotherapy-induced cognitive impairment (CICI), also known as "chemobrain," is a common side effect of breast cancer therapy which causes oxidative stress and generation of reactive oxygen species (ROS). Ferulic acid (FA), a natural polyphenol, belongs to BCS class II is confirmed to have nootropic, neuroprotective and antioxidant effects. Here, we have developed FA solid dispersion (SD) in order to enhance its therapeutic potential against chemobrain. An amorphous ferulic acid loaded leucin solid dispersion (FA-Leu SD) was prepared by utilizing amino acid through spray-drying technique. The solid-state characterization was carried out via Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). Additionally, in-vitro release studies and antioxidant assay were also performed along with in-vivo locomotor, biochemical and histopathological analysis. The physical properties showed that FA-Leu SD so formed exhibited spherical, irregular surface hollow cavity of along with broad melting endotherm as observed from FE-SEM and DSC results. The XRD spectra demonstrated absence of sharp and intense peaks in FA-Leu SD which evidenced for complete encapsulation of drug into carrier. Moreover, in-vitro drug release studies over a period of 5 h in PBS (pH 7.4) displayed a significant enhanced release in the first hr (68. 49 ± 5.39%) and in-vitro DPPH assay displayed greater antioxidant potential of FA in FA-Leu SD. Furthermore, the in-vivo behavioral findings of FA-Leu SD (equivalent to 150 mg/kg of free FA) exhibited positive results accompanied by in-vivo biochemical and molecular TNF-α showed a significant difference (p < 0.001) vis-à-vis DOX treated group upon DOX + FA-Leu SD. Additionally, histopathological analysis revealed neuroprotective effects of FA-Leu SD together with declined oxidative stress due to antioxidant potential of FA which was induced by anticancer drug doxorubicin (DOX). Overall, the above findings concluded that spray-dried FA-Leu SD could be useful for the treatment of chemotherapy induced cognitive impairment.

Risk factors and etiology of early-onset neonatal sepsis in Northeastern part of India: Case-control study.

Background: Sepsis, the second most common cause of neonatal mortality, causes more than one million deaths annually. India has the highest incidence of clinical sepsis (17000/100000 live birth). Objective: This study aimed to determine the risk factors and organisms of early-onset neonatal sepsis (EONS) in a tertiary care hospital in Northeast India. Materials and Methods: It was a case-control study conducted in the neonatal unit of MGM Medical College, Kishanganj, Bihar, from January 2022 to April 2023. All neonates admitted to the neonatal intensive care unit (NICU) within 72 hours of life constituted the study population. Neonates diagnosed as EONS by clinical and laboratory parameters were considered as cases and those not diagnosed for EONS as controls. Maternal and newborn information and laboratory parameters were collected and analyzed. For risk factor identification, the bivariate logistic regression was used. Result: An equal number of cases (78) and control (78) were enrolled in the study. Maternal age >30 years (adjusted odds ratio [aOR] = 3.017, confidence interval [CI]: 1.238 to 7.352; P < 0.015), maternal urinary tract infection (UTI) in the third trimester (aOR = 5.435, CI: 2.647 to 11.158; P < 0.0001), and premature rupture of membranes (PROM) (aOR = 2.918, CI: 4.61 to 33.73, P < 0.004) were significant predictors of EONS. Pseudomonas (41.02%), Klebsiella (16.66%), and coagulase-negative Staphylococcus aureus (20.51%) were commonly isolated organisms, which were highly resistant to cephalosporin, meropenem, aminoglycosides, and quinolones. Conclusion: Proper and adequate antenatal screening for diagnosis and treatment of maternal infection and high-risk pregnancies for perinatal management of newborn is recommended to prevent neonatal sepsis-related morbidity and mortality. Rational use of antibiotics may minimize the hazard of antibiotic resistance.

Trends of Buprenorphine Prescribing for Opioid Dependence Before, and During the Early and Later Part of the COVID-19: A Study from a Large Publicly-Funded Opioid Agonist Treatment Services in India.

BACKGROUND: The COVID-19 pandemic has affected the availability and access to medications for opioid dependence (OD). We examined the monthly trends in new buprenorphine/naloxone (BNX) treatment episodes, number of clinical visits for BNX, BNX dispensed per person, and BNX prescription over 56-month, which included pre-pandemic, during early, and later part of pandemic (Jan 2017 - Aug 2022). METHODS: Research data were collected from the pharmacy database of a large publicly funded treatment center in India. A flexible, low-threshold service was adopted in April 2020 in response to the lockdown implemented on 25 March 2020. Change Point analyses were performed to examine monthly trends visually and statistically. We used Autoregressive integrated moving averages to forecast trends from April to Aug 2020 and March to August 2022, using Jan 2017 to March 2020 and March 2020 to February 2022 as training datasets. RESULTS: 993 patients were started on BNX treatment, 40452 BNX clinic attendances were made, 1401393 BNX tablets were dispensed, and 6795 new patients with OD were registered. The observed data for clinic attendance for BNX was significantly lower than the projected estimates in April -Aug 2020; however, observed new treatment episodes and monthly BNX prescriptions were within the 95% projected estimates; BNX dispensed per person was significantly more than the projected estimate. In contrast, observed BNX prescription trends surpassed the upper limit of 95% CI in March-Aug 2022. CONCLUSION: A low-threshold and flexible treatment service could mitigate the unintended consequences of pandemic-induced restrictions.

Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Unearthing the power of microbes as plant microbiome for sustainable agriculture.

In recent years, research into the complex interactions and crosstalk between plants and their associated microbiota, collectively known as the plant microbiome has revealed the pivotal role of microbial communities for promoting plant growth and health. Plants have evolved intricate relationships with a diverse array of microorganisms inhabiting their roots, leaves, and other plant tissues. This microbiota mainly includes bacteria, archaea, fungi, protozoans, and viruses, forming a dynamic and interconnected network within and around the plant. Through mutualistic or cooperative interactions, these microbes contribute to various aspects of plant health and development. The direct mechanisms of the plant microbiome include the enhancement of plant growth and development through nutrient acquisition. Microbes have the ability to solubilize essential minerals, fix atmospheric nitrogen, and convert organic matter into accessible forms, thereby augmenting the nutrient pool available to the plant. Additionally, the microbiome helps plants to withstand biotic and abiotic stresses, such as pathogen attacks and adverse environmental conditions, by priming the plant's immune responses, antagonizing phytopathogens, and improving stress tolerance. Furthermore, the plant microbiome plays a vital role in phytohormone regulation, facilitating hormonal balance within the plant. This regulation influences various growth processes, including root development, flowering, and fruiting. Microbial communities can also produce secondary metabolites, which directly or indirectly promote plant growth, development, and health. Understanding the functional potential of the plant microbiome has led to innovative agricultural practices, such as microbiome-based biofertilizers and biopesticides, which harness the power of beneficial microorganisms to enhance crop yields while reducing the dependency on chemical inputs. In the present review, we discuss and highlight research gaps regarding the plant microbiome and how the plant microbiome can be used as a source of single and synthetic bioinoculants for plant growth and health.

Pelizaeus-Merzbacher Disease in a 4-Year-Old Female Child: "A Rare Case Report".

Pelizaeus-Merzbacher disease, a rare X-linked recessive disease occurring predominantly in males, is a disorder of proteolipid protein expression in myelin formation in the central nervous system. The disease is clinically manifested by neurodevelopmental delay, ataxia, hypotonia, and pendular eye movement. It is best confirmed by genetic study. A 4-year female child presented with ataxia, neuroregression, decreased scholastic performance, slurred speech, loss of bladder and bowel control, and hypotonia. MRI brain showed generalized hypomyelination and atrophy of the cerebrum and cerebellum. This case highlights that Pelizaeus-Merzbacher disease can be considered even in a female child who presented with neurodevelopmental delay and neuro regression, ataxia, and decreased scholastic performance and further confirmed by MRI showing diffuse demyelination along with cerebral and cerebellar atrophy.

Predictors of Treatment Completion in an Inpatient Substance Use Treatment Service in India.

INTRODUCTION: Treatment completion is associated with a better outcome in substance use disorders. We examined the rates of treatment completion and its predictors in patients admitted to specialized addiction treatment settings over a 13-year period. METHODS: Ours was a retrospective cohort study. We included consecutive 2850 patients admitted to the inpatient treatment between January 2007 and December 2019. We divided the patients into 2 groups: completed versus premature discontinuation of treatment. The predictor variables were based on previous research, clinical experience, and availability of the digital record. RESULTS: The number of patients who completed and discontinued treatments was 1873 (72.6%) and 707 (27.4%), respectively. The inpatient treatment discontinuation rate varied widely during the study period (18% in 2007 and 41% in 2012). The average rate of treatment discontinuation was 27%. The change-point analysis showed 5 statistically significant change points in the years 2008, 2010, 2012, 2014, and 2016. Patients who were prescribed medications for alcohol and opioid dependence and those who were on opioid agonist treatment had 4.7 and 6.3 higher odds of completing inpatient treatment than those who were not on medication. Patients with physical and psychiatric comorbidities had higher odds of treatment completion. Patients with a primary diagnosis of opioid dependence had lower odds of treatment completion than those with alcohol dependence. CONCLUSIONS: The rates of discontinuation may vary with concurrent changes in the treatment policies. Awareness of the risk factors and policy measures that may improve treatment completion must aid in informed decision making.

Transient Receptor Potential (TRP) based polypharmacological combination stimulates energy expending phenotype to reverse HFD-induced obesity in mice.

BACKGROUND & AIM: Obesity is a worldwide epidemic leading to decreased quality of life, higher medical expenses and significant morbidity. Enhancing energy expenditure and substrate utilization in adipose tissues through dietary constituents and polypharmacological approaches is gaining importance for the prevention and therapeutics of obesity. An important factor in this regard is Transient Receptor Potential (TRP) channel modulation and resultant activation of "brite" phenotype. Various dietary TRP channel agonists like capsaicin (TRPV1), cinnamaldehyde (TRPA1), and menthol (TRPM8) have shown anti-obesity effects, individually and in combination. We aimed to determine the therapeutic potential of such combination of sub-effective doses of these agents against diet-induced obesity, and explore the involved cellular processes. KEY FINDINGS: The combination of sub-effective doses of capsaicin, cinnamaldehyde and menthol induced "brite" phenotype in differentiating 3T3-L1 cells and subcutaneous white adipose tissue of HFD-fed obese mice. The intervention prevented adipose tissue hypertrophy and weight gain, enhanced the thermogenic potential, mitochondrial biogenesis and overall activation of brown adipose tissue. These changes observed in vitro as well as in vivo, were linked to increased phosphorylation of kinases, AMPK and ERK. In the liver, the combination treatment enhanced insulin sensitivity, improved gluconeogenic potential and lipolysis, prevented fatty acid accumulation and enhanced glucose utilization. SIGNIFICANCE: We report on the discovery of therapeutic potential of TRP-based dietary triagonist combination against HFD-induced abnormalities in metabolic tissues. Our findings indicate that a common central mechanism may affect multiple peripheral tissues. This study opens up avenues of development of therapeutic functional foods for obesity.

Serum antibody levels to SARS-CoV-2 receptor-binding domain (RBD) in convalescent patients and vaccinated individuals of northern Nevada.

Antibodies reactive with the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein are associated with viral neutralization, however low antibody titers, specifically against SARS-CoV-2 variants, may result in reduced viral immunity post naturally acquired infection. A cohort study comprised of 121 convalescent individuals from northern Nevada was conducted looking at anti-RBD antibody levels by enzyme-linked immunosorbent assay. Serum was collected from volunteers by staff at the University of Nevada, Reno School of Medicine Clinical Research Center and assessed for antibodies reactive to various SARS-CoV-2 RBD domains relevant to the time of the study (2020-2021). A nonpaired group of vaccinated individuals were assessed in parallel. The goal of the study was to identify antibody levels against the RBD subunit in convalescent and vaccinated individuals from northern Nevada.

Corticotropin-releasing factor acting on corticotropin-releasing factor receptor type 1 is critical for binge alcohol drinking in mice.

BACKGROUND: The corticotropin-releasing factor (CRF) system has been implicated in the regulation of alcohol consumption. However, previous mouse knockout (KO) studies using continuous ethanol access have failed to conclusively confirm this. Recent studies have shown that CRF receptor type 1 (CRFR1) antagonists attenuate alcohol intake in the limited access "drinking in the dark" (DID) model of binge drinking. To avoid the potential nonspecific effects of antagonists, in this study, we tested alcohol drinking in CRFR1, CRFR2, CRF, and urocortin 1 (Ucn1) KO and corresponding wild-type (WT) littermates using the DID paradigm. METHODS: On days 1 to 3, the CRFR1, CRFR2, Ucn1, and CRF KO mice and their respective WT littermates were provided with 20% ethanol or 10% sucrose for 2 hours with water available at all other times. On day 4, access to ethanol or sucrose was increased to 4 hours. At the end of each drinking session, the volume of ethanol consumed was recorded, and at the conclusion of the last session, blood was also collected for blood ethanol concentration (BEC) analysis. RESULTS: CRFR1 KO mice had lower alcohol intakes and BECs and higher intakes of sucrose compared with WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had similar alcohol intakes on days 2 to 4 and similar BECs as the WTs. To determine the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1 KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced alcohol consumption and lower BECs compared with WTs. CONCLUSIONS: Our results confirm that CRFR1 plays a key role in binge drinking and identify CRF as the ligand critically involved in excessive alcohol consumption.