Epoxygenase Cyp2c44 regulates hepatic lipid metabolism and insulin signaling by controlling FATP2 localization and activation of the DAG/PKCδ axis.

Cytochrome P450 epoxygenase Cyp2c44, a murine epoxyeicosatrienoic acid (EET) producing enzyme, promotes insulin sensitivity and Cyp2c44(-/-) mice show hepatic insulin resistance. Because insulin resistance leads to hepatic lipid accumulation and hyperlipidemia, we hypothesized that Cyp2c44 regulates hepatic lipid metabolism. Standard chow diet (SD) fed male Cyp2c44(-/-) mice had significantly decreased EET levels and increased hepatic and plasma lipid levels compared to wild-type mice. We showed increased hepatic plasma membrane localization of the FA transporter 2 (FATP2) and total unsaturated fatty acids and diacylglycerol levels. Cyp2c44(-/-) mice had impaired glucose tolerance and increased hepatic plasma membraneassociated PKCδ and phosphorylated IRS-1, two negative regulators of insulin signaling. Surprisingly, SD and high fat diet fed (HFD) Cyp2c44(-/-) mice had similar glucose tolerance and hepatic plasma membrane PKCδ levels, suggesting that SD-fed Cyp2c44(-/-) mice have reached their maximal glucose intolerance. Inhibition of PKCδ resulted in decreased IRS-1 serine phosphorylation and improved insulin-mediated signaling in Cyp2c44(-/-) hepatocytes. Finally, Cyp2c44(-/-) HFD-fed mice treated with the analog EET-A showed decreased hepatic plasma membrane FATP2 and PCKDδ levels with improved glucose tolerance and insulin signaling. In conclusion, loss of Cyp2c44 with concomitant decreased EET levels leads to increased hepatic FATP2 plasma membrane localization, diacylglycerol accumulation, and PKCδ-mediated attenuation of insulin signaling. Thus, Cyp2c44 acts as a regulator of lipid metabolism by linking it to insulin signaling.

Continuous Infusion of Ketamine in Mechanically Ventilated Patients with SARS-CoV-2.

Background: Widespread drug shortages led to higher utilization of ketamine in our intensive care unit, especially among patients with SARS-CoV-2. Objectives: To evaluate the impact of continuous infusion of ketamine on vasopressor requirements in patients with SARS-CoV-2. Method: This was a single-center, retrospective, cohort study comparing mechanically ventilated (MV), adult patients with SARS-CoV-2 receiving either propofol or ketamine for at least 72 hours. Results: 84 patients (mean age of 61-year-old, 68% male) were analyzed. 31 patients received ketamine, and 53 patients received propofol. Mean vasopressor doses were not significantly different between ketamine and propofol groups at prespecified timepoints. However, mean arterial pressures (MAP) were higher in the ketamine group at 24 h, 48 h, and 96 h postsedative initiation. The median opioid infusion requirements were 3 vs. 12.5 mg/hr (p < 0.0001) for ketamine and propofol groups, respectively. Comparing to propofol, C-reactive protein (CRP) values were significantly lower in the ketamine group at 24 h (7.53 vs. 15.9 mg/dL, p=0.03), 48 h (5.23 vs. 14.1 mg/dL, p=0.0083), and 72 h (6.4 vs. 12.1 mg/dL, p=0.0085). Conclusion: In patients with SARS-CoV-2 on MV, there was no difference in the vasopressor requirement in patients receiving ketamine compared to propofol. Nevertheless, the use of ketamine was associated with higher MAP, reductions in CRP in select timepoints, and overall lower opioid requirements.

Effects of Dronabinol on Dyspnea and Quality of Life in Patients With COPD.

Background: Dyspnea is frequently a debilitating symptom of chronic obstructive pulmonary disease (COPD). Cannabinoid receptor agonists have the potential to alter dyspnea in these patients. Objective: Our objective was to determine if dronabinol, a pure cannabinoid, improves dyspnea and exercise tolerance in COPD. Methods: In this double-blind randomized, crossover pilot study, COPD patients received up to 20mg of oral dronabinol or placebo daily for 6 weeks with an intervening washout period. Dyspnea and fatigue were assessed using the Borg scale at rest and after an incremental shuttle walk. Functional status, mood, and depression were measured using the St George's Respiratory Questionnaire (SGRQ), the Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ), and the Geriatric Depression Scale (GDS). Results: A total of 11 participants (with mean forced expiratory volume in 1 second 50.8 ± 24.8%) completed the study with no improvement in dyspnea at rest or postexercise taking dronabinol versus placebo (Borg scale 0.27, 95% confidence interval [CI] -0.59 to 1.14 versus 0.23 points, 95% CI -0.71 to 1.07 at rest and 0.82, 95% CI -0.59 to 2.22 versus 0.36 points, 95% CI 0.13 to 2.78 post exercise; p=0.94 and p=0.69 respectively). Dronabinol compared with placebo showed no significant change in PFSDQ dyspnea scores (0.64, 95% CI -3.92 to 5.20 versus 5.0, 95% CI -6.29 to 16.29; p=0.43) or shuttle walk distances (20.7m, 95% CI -21.5 to 62.8 versus 13.7m, 95% CI -24.8 to 52.2; p=0.69). There were no significant differences in fatigue at rest and postexercise, SGRQ scores, or GDS scores. Conclusion: In this pilot study, dronabinol did not significantly improve dyspnea or exercise capacity compared with placebo.

Effect of Succinamic Acid Derivative on the Growth Kinetics and Induction of Apoptosis in a Cancer Cell Line.

Introduction Head and neck cancers are heterogeneous malignancies associated with significant morbidity. Oral cancers are related to the use of tobacco products. Smokeless tobacco usage is a health problem worldwide, and its carcinogenic mechanism is largely unknown. Despite advances in conventional treatments, side effects and drug resistance remain unsolved. Therefore, novel therapeutic agents with minimal side effects using plant derivatives should be explored. An active antihyperglycemic and antioxidant compound known as FIIc was isolated from the fruit pulp of Eugenia jambolana (US Patent No.: 2,30,753). Although E. jambolana is reported to have anticancer activity, no study has been reported on its growth kinetics and apoptotic potential in the human head and neck cancer cell line (SCC4). The present study evaluated the effect of an herbal compound isolated from the fruit pulp of E. jambolana and chemically synthesized the same compound, α-hydroxy succinamic acid (α-HSA), on SCC4 proliferation and apoptotic gene expression. Methods The SCC4 cell line was cultured in Dulbecco's Modified Eagle Medium (DMEM). The dosages of smokeless tobacco extract (STE), herbal compound, and synthetic compound were determined by cell viability assay, and their effect on mRNA expression of apoptotic genes was measured by real-time polymerase chain reaction. Results The present study observed significant therapeutic effects of the natural and synthetic compounds from the fruit pulp of E. jambolana at the concentration range of 100-200 µg/mL on the SCC4 cell line. α-HSA had antiproliferative action; upregulated apoptotic genes like p53, p21, and Bax; and downregulated anti-apoptotic genes like survivin in the SCC4 cell line. Conclusion The therapeutic potential of α-HSA and the putative mechanisms involved may be explored to provide the basis for future therapeutic interventions in oral cancer mediated by smokeless tobacco.

DHEERA reaching the young, a novel approach addressing gender-based violence in India.

OBJECTIVE: To understand, build capacities, give guidance, and support school-going adolescent boys and girls on gender stereotypes and violence against women (VAW) and to assess the role of educational training in improving knowledge, attitudes, and practice to stop VAW. METHODS: An educational interventional study was conducted for a period of 18 months across schools in India, involving boys and girls studying in grades 9-12. Assessment of the program's effectiveness on influencing young minds in breaking the taboos surrounding gender stereotypes and stopping VAW was completed through a pre-test and post-test, consisting of 12 scenario-based questions. RESULTS: In all, 8931 participants (64% girls and 36% boys) from 26 states in India submitted their pre-test, post-test, and feedback forms. Participants showed improved clarity and comprehension on issues surrounding VAW/gender-based violence. There was a significant improvement in the knowledge on what actions can be taken and whom to approach for cases related to VAW/gender-based violence. The post-test survey showed a high level of commitment to overcoming gender stereotyping and stopping VAW. CONCLUSION: This unique nationwide study demonstrated the effectiveness of an educational intervention that led to improved knowledge, attitude, and commitment towards stopping VAW. A large-scale program can be self-sustaining when it is embedded in the schools responsible for shaping young minds.

A Positively Selected fur-R88H Mutation Enhances Helicobacter pylori Fitness in a High-Salt Environment and Alters Fur-Dependent Regulation of Gene Expression.

Both Helicobacter pylori infection and a high-salt diet are risk factors for gastric cancer. We previously showed that a mutation in fur (encoding the ferric uptake regulator variant Fur-R88H) was positively selected in H. pylori strains isolated from experimentally infected Mongolian gerbils receiving a high-salt diet. In the present study, we report that continuous H. pylori growth in high-salt conditions in vitro also leads to positive selection of the fur-R88H mutation. Competition experiments with strains containing wild-type fur or fur-R88H, each labeled with unique nucleotide barcodes, showed that the fur-R88H mutation enhances H. pylori fitness under high-salt conditions but reduces H. pylori fitness under routine culture conditions. The fitness advantage of the fur-R88H mutant under high-salt conditions was abrogated by the addition of supplemental iron. To test the hypothesis that the fur-R88H mutation alters the regulatory properties of Fur, we compared the transcriptional profiles of strains containing wild-type fur or fur-R88H. Increased transcript levels of fecA2, which encodes a predicted TonB-dependent outer membrane transporter, were detected in the fur-R88H variant compared to those in the strain containing wild-type fur under both high-salt and routine conditions. Competition experiments showed that fecA2 contributes to H. pylori fitness under both high-salt and routine conditions. These results provide new insights into mechanisms by which the fur-R88H mutation confers a selective advantage to H. pylori in high-salt environments.

Mucosal Gene Expression in Response to SARS-CoV-2 Is Associated with Viral Load.

Little is known about the relationships between symptomatic early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate coronavirus disease 19 (COVID-19). We measured SARS-CoV-2 viral load using reverse transcription-quantitative PCR (RT-qPCR). We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 95% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited codetection of other respiratory viruses, with the human Rhinovirus C being identified in 4 (6%) samples. This limited codetection of other respiratory viral pathogens may be due to the implementation of public health measures, like social distancing and masking practices. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusting for age, sex, and race. Interestingly, the expression levels of most of these genes plateaued at a cycle threshold (CT) value of ~25. Overall, our data show that the early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, potentially modifying COVID-19 outcomes. IMPORTANCE Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load, airway mucosal gene expression, and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load, interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load dependent and may modify COVID-19 outcomes.

Ligation-based assay for variant typing without sequencing: Application to SARS-CoV-2 variants of concern.

BACKGROUND: COVID-19 prevalence has remained high throughout the pandemic with intermittent surges, due largely to the emergence of genetic variants, demonstrating the need for more accessible sequencing technologies for strain typing. METHODS: A ligation-based typing assay was developed to detect known variants of severe acute respiratory syndrome virus 2 (SARS-CoV-2) by identifying the presence of characteristic single-nucleotide polymorphisms (SNPs). General principles for extending the strategy to new variants and alternate diseases with SNPs of interest are described. Of note, this strategy leverages commercially available reagents for assay preparation, as well as standard real-time polymerase chain reaction (PCR) instrumentation for assay performance. RESULTS: The assay demonstrated a combined sensitivity and specificity of 96.6% and 99.5%, respectively, for the classification of 88 clinical samples of the Alpha, Delta, and Omicron variants relative to the gold standard of viral genome sequencing. It achieved an average limit of detection of 7.4 × 104 genome copies/mL in contrived nasopharyngeal samples. The ligation-based strategy performed robustly in the presence of additional polymorphisms in the targeted regions of interest as shown by the sequence alignment of clinical samples. CONCLUSIONS: The assay demonstrates the potential for robust variant typing with performance comparable with next-generation sequencing without the need for the time delays and resources required for sequencing. The reduced resource dependency and generalizability could expand access to variant classification information for pandemic surveillance.

MaHPIC malaria systems biology data from Plasmodium cynomolgi sporozoite longitudinal infections in macaques.

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades.

Species-specific transcriptomic changes upon respiratory syncytial virus infection in cotton rats.

The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for respiratory syncytial virus (RSV). However, without a reference genome or a published transcriptome, studies requiring gene expression analysis in cotton rats are severely limited. The aims of this study were to generate a comprehensive transcriptome from multiple tissues of two species of cotton rats that are commonly used as animal models (Sigmodon fulviventer and Sigmodon hispidus), and to compare and contrast gene expression changes and immune responses to RSV infection between the two species. Transcriptomes were assembled from lung, spleen, kidney, heart, and intestines for each species with a contig N50 > 1600. Annotation of contigs generated nearly 120,000 gene annotations for each species. The transcriptomes of S. fulviventer and S. hispidus were then used to assess immune response to RSV infection. We identified 238 unique genes that are significantly differentially expressed, including several genes implicated in RSV infection (e.g., Mx2, I27L2, LY6E, Viperin, Keratin 6A, ISG15, CXCL10, CXCL11, IRF9) as well as novel genes that have not previously described in RSV research (LG3BP, SYWC, ABEC1, IIGP1, CREB1). This study presents two comprehensive transcriptome references as resources for future gene expression analysis studies in the cotton rat model, as well as provides gene sequences for mechanistic characterization of molecular pathways. Overall, our results provide generalizable insights into the effect of host genetics on host-virus interactions, as well as identify new host therapeutic targets for RSV treatment and prevention.

Mucosal gene expression in response to SARS-CoV-2 is associated with early viral load.

Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate COVID-19. We measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 85% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited co-detection of common respiratory viruses i.e., only the human Rhinovirus (HRV) being identified in 6% of the samples. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusted for age, sex and race. Interestingly, the expression levels of most of these genes plateaued at a CT value of ~25. Overall, our data shows that early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, which potentially could modify COVID-19 outcomes. AUTHOR SUMMARY: Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load and airway mucosal gene expression and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during Spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load with interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load-dependent and may modify COVID-19 outcomes.

Mucosal gene expression in response to SARS-CoV-2 is associated with early viral load.

Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate COVID-19. We measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 85% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited co-detection of common respiratory viruses i.e., only the human Rhinovirus (HRV) being identified in 6% of the samples. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusted for age, sex and race. Interestingly, the expression levels of most of these genes plateaued at a CT value of ~25. Overall, our data shows that early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, which potentially could modify COVID-19 outcomes. AUTHOR SUMMARYSeveral prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load and airway mucosal gene expression and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during Spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load with interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load-dependent and may modify COVID-19 outcomes.

COVID-19 severity from Omicron and Delta SARS-CoV-2 variants.

The Omicron variant of SARS-CoV-2 achieved worldwide dominance in late 2021. Early work suggests that infections caused by the Omicron variant may be less severe than those caused by the Delta variant. We sought to compare clinical outcomes of infections caused by these two strains, confirmed by whole genome sequencing, over a short period of time, from respiratory samples collected from SARS-CoV-2 positive patients at a large medical center. We found that infections caused by the Omicron variant caused significantly less morbidity, including admission to the hospital and requirement for oxygen supplementation, and significantly less mortality than those caused by the Delta variant.

Quantitative tumor depth determination using dual wavelength excitation fluorescence.

Quantifying solid tumor margins with fluorescence-guided surgery approaches is a challenge, particularly when using near infrared (NIR) wavelengths due to increased penetration depths. An NIR dual wavelength excitation fluorescence (DWEF) approach was developed that capitalizes on the wavelength-dependent attenuation of light in tissue to determine fluorophore depth. A portable dual wavelength excitation fluorescence imaging system was built and tested in parallel with an NIR tumor-targeting fluorophore in tissue mimicking phantoms, chicken tissue, and in vivo mouse models of breast cancer. The system showed high accuracy in all experiments. The low cost and simplicity of this approach make it ideal for clinical use.

Malaria disrupts the rhesus macaque gut microbiome.

Previous studies have suggested that a relationship exists between severity and transmissibility of malaria and variations in the gut microbiome, yet only limited information exists on the temporal dynamics of the gut microbial community during a malarial infection. Here, using a rhesus macaque model of relapsing malaria, we investigate how malaria affects the gut microbiome. In this study, we performed 16S sequencing on DNA isolated from rectal swabs of rhesus macaques over the course of an experimental malarial infection with Plasmodium cynomolgi and analyzed gut bacterial taxa abundance across primary and relapsing infections. We also performed metabolomics on blood plasma from the animals at the same timepoints and investigated changes in metabolic pathways over time. Members of Proteobacteria (family Helicobacteraceae) increased dramatically in relative abundance in the animal's gut microbiome during peak infection while Firmicutes (family Lactobacillaceae and Ruminococcaceae), Bacteroidetes (family Prevotellaceae) and Spirochaetes amongst others decreased compared to baseline levels. Alpha diversity metrics indicated decreased microbiome diversity at the peak of parasitemia, followed by restoration of diversity post-treatment. Comparison with healthy subjects suggested that the rectal microbiome during acute malaria is enriched with commensal bacteria typically found in the healthy animal's mucosa. Significant changes in the tryptophan-kynurenine immunomodulatory pathway were detected at peak infection with P. cynomolgi, a finding that has been described previously in the context of P. vivax infections in humans. During relapses, which have been shown to be associated with less inflammation and clinical severity, we observed minimal disruption to the gut microbiome, despite parasites being present. Altogether, these data suggest that the metabolic shift occurring during acute infection is associated with a concomitant shift in the gut microbiome, which is reversed post-treatment.

Metatranscriptomics to characterize respiratory virome, microbiome, and host response directly from clinical samples.

We developed a metatranscriptomics method that can simultaneously capture the respiratory virome, microbiome, and host response directly from low biomass samples. Using nasal swab samples, we capture RNA virome with sufficient sequencing depth required to assemble complete genomes. We find a surprisingly high frequency of respiratory syncytial virus (RSV) and coronavirus (CoV) in healthy children, and a high frequency of RSV-A and RSV-B co-detections in children with symptomatic RSV. In addition, we have identified commensal and pathogenic bacteria and fungi at the species level. Functional analysis revealed that H. influenzae was highly active in symptomatic RSV subjects. The host nasal transcriptome reveled upregulation of the innate immune system, anti-viral response and inflammasome pathway, and downregulation of fatty acid pathways in children with symptomatic RSV. Overall, we demonstrate that our method is broadly applicable to infer the transcriptome landscape of an infected system, surveil respiratory infections, and to sequence RNA viruses directly from clinical samples.

Prevalence of abuse among the elderly population of Syangja, Nepal.

BACKGROUND: Elder abuse is recognized as a serious public health concern and top priority aging issues. World Health Organization reported that around 1 out of 6 old people in the world experienced some form of abuse. This study was carried out to find out the prevalence of different forms of abuse among elderly Nepalese people. METHODS: The cross-sectional, quantitative analytical study was carried out among 373 elders of the Syangja district of Nepal. The study population was selected through simple, proportionate, and systematic sampling methods. Data was collected through face-to-face interviews using a structured questionnaire. RESULTS: The majority of participants were female (54.5%). The prevalence of elderly abuse was found to be 54.5%. The most common form of abuse among the elderly population was neglect (23.1%), psychological abuse (20.6%), physical abuse (6.5%), financial abuse (2.4%), and sexual abuse (1.9%). Elderly females were significantly more likely to experience physical and psychological abuse. CONCLUSION: More than half of the elderly experienced at least one form of abuse. Neglect was found to be the most common form of abuse. The abuse was prevalent among elderly who were ill and with the habit of tobacco and alcohol consumption.

Impact of pulmonary rehabilitation in sleep in COPD patients measured by actigraphy.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) patients have poor sleep quality, longer time to sleep onset and frequent nocturnal awakenings. Poor sleep quality in COPD is associated with poor quality of life (QoL), increased exacerbations and increased mortality. Pulmonary rehabilitation (PR) improves functional status and QoL in COPD but effects on sleep are unclear. PR improves subjective sleep quality but there is paucity of objective actigraphy data. We hypothesized that actigraphy would demonstrate subjective and objective improvement in sleep following PR. Paired comparisons (t-test or Wilcoxon-signed-rank test) were performed before and after PR data on all variables. METHODS: This retrospective study of COPD patients undergoing PR utilized actigraphy watch recordings before and after 8-weeks of PR to assess changes in sleep variables including total time in bed (TBT), total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), wakefulness after sleep onset (WASO) and total nocturnal awakenings. A change in Pittsburg Sleep Quality Index (PSQI) was a secondary outcome. PSQI was performed before and after PR. RESULTS: Sixty-nine patients were included in the final analysis. Most participants were male (97%), non-obese (median BMI 27.5, IQR 24.3 to 32.4 kg/m2) with an average age of 69 ± 8 years and 71% had severe COPD (GOLD stage 3 or 4). Prevalence of poor sleep quality (PSQI ≥5) was 86%. Paired comparisons did not show improvement in actigraphic sleep parameters following 8-weeks PR despite improvements in 6-min-walk distance (6MWD, mean improvement 54 m, 95% CI 34 m to 74 m, p<0.0001) and St. George's Respiratory Questionnaire scores (SGRQ, mean improvement 7.7 points, 95% CI 5.2 to 10.2, p<0.0001). Stratified analysis of all sleep variables by severity of COPD, BMI, mood, mental status, 6-MWD and SGRQ did not show significant improvement after PR. In Veterans with poor sleep quality (PSQI ≥ 5), PR improved subjective sleep quality (PSQI, mean difference 0.79, 95% CI 0.07 to 1.40, p = 0.03). CONCLUSIONS: Pulmonary rehabilitation improved subjective sleep quality in Veterans who had poor sleep quality at the beginning of the PR but did not improve objective sleep parameters by actigraphy. Our findings highlight the complex interactions among COPD, sleep and exercise.

Relationship of Clinical Features with Candidal Carriage in Oral Submucous Fibrosis Patients: A Case-control Study.

BACKGROUND AND OBJECTIVES: Oral submucous fibrosis (OSF) is extensively prevalent in India and South-East Asia owing to the habit of arecanut (AN) use. Epithelial atrophy, hyposalivation, and immune alterations in OSF may predispose to increased Candidal carriage. Stomatopyrosis in OSF can result from multiple causes, which may also include Candidal infection. Hence, this study is aimed to assess Candidal carriage, species characterization, salivary flow rate (SFR) and its relationship with the clinical features (stomatopyrosis and mouth opening [MO]) in OSF patients alongwith the response to antifungal treatment in patients with higher Candidal carriage. METHODOLOGY: In this case-control study, 60 OSF patients and 30 age- and sex-matched control subjects were enrolled. SFR was assessed using modified Schirmer test. Samples for Candidal assessment were collected with the oral rinse technique and cultured. The isolated yeast species were counted and identified based on Gram staining, germ tube test, and CHROMagar. Data were analyzed with Chi-square test, Pearson's correlation test, and one-way ANOVA test. RESULTS: The distribution of mean visual analog scale (VAS) score, SFR and MO was significantly varied (P < 0.001) in the study and control groups. Candida was found to be present significantly (P = 0.048) in OSF group as compared to control group. Candida albicans was the predominant species. No statistically significant association was obtained regarding Candidal isolation and SFR, burning sensation and MO in OSF patients. Only 1 patient in the study group yielded a high Candidal carriage (>400 CFU/mL) and reported relief in burning sensation (VAS score) with antifungal therapy. CONCLUSIONS: OSF patients yielded a significant higher oral Candidal carriage. Although it was not found to be associated directly, its role as a "cause and effect" in SFR and clinical features (stomatopyrosis and MO) of OSF cannot be ignored.

Focal dynamic thermal imaging for label-free high-resolution characterization of materials and tissue heterogeneity.

Evolution from static to dynamic label-free thermal imaging has improved bulk tissue characterization, but fails to capture subtle thermal properties in heterogeneous systems. Here, we report a label-free, high speed, and high-resolution platform technology, focal dynamic thermal imaging (FDTI), for delineating material patterns and tissue heterogeneity. Stimulation of focal regions of thermally responsive systems with a narrow beam, low power, and low cost 405 nm laser perturbs the thermal equilibrium. Capturing the dynamic response of 3D printed phantoms, ex vivo biological tissue, and in vivo mouse and rat models of cancer with a thermal camera reveals material heterogeneity and delineates diseased from healthy tissue. The intuitive and non-contact FDTI method allows for rapid interrogation of suspicious lesions and longitudinal changes in tissue heterogeneity with high-resolution and large field of view. Portable FDTI holds promise as a clinical tool for capturing subtle differences in heterogeneity between malignant, benign, and inflamed tissue.