Acute sleep deprivation-induced hepatotoxicity and dyslipidemia in middle-aged female rats and its amelioration by butanol extract of Tinospora cordifolia.

BACKGROUND: Sleep deprivation (SD) due to an unhealthy lifestyle poses an oxidative challenge and is closely associated with an increased risk and prevalence of different metabolic disorders. Although the negative consequences of SD are well reported on mental health little is known about its detrimental effects on liver function and lipid metabolism. Tinospora cordifolia is reported for its hepatoprotective activity in different pre-clinical model systems. The current study was designed to elucidate the cumulative effects of aging and acute SD on liver functions, oxidative stress, and lipid metabolism, and their management by butanol extract of T. cordifolia (B-TCE) using middle-aged female acyclic rats as the model system. RESULTS: Rats were divided into 4 groups: (1) Vehicle-undisturbed (VUD) (2) Vehicle-sleep deprived (VSD) (3) B-TCE pre-treated sleep-deprived (TSD) (4) B-TCE pre-treated undisturbed sleep (TUD). TSD and TUD groups were given 35 mg/kg of B-TCE once daily for 15 days followed by 12 h of sleep deprivation (6 a.m.-6 p.m.) of VSD and TSD group animals using the gentle-handling method while VUD and TUD group animals were left undisturbed. SD of VSD group animals increased oxidative stress, liver function disruption, and dyslipidemia which were ameliorated by B-TCE pre-treatment. Further, B-TCE was observed to target AMPK and its downstream lipid metabolism pathways as well as the p-Akt/cyclinD1/p-bad pathway of cell survival as possible underlying mechanisms of its hepatoprotective activity. CONCLUSIONS: These findings suggest that B-TCE being a multi-component extract may be a potential agent in curtailing sleep-related problems and preventing SD-associated hepatotoxicity and dyslipidemia in postmenopausal women.

Gastrointestinal and Neuropsychological Symptoms Are Associated With Distinct Vomiting Profiles in Patients Receiving Chemotherapy.

OBJECTIVES: To identify subgroups of patients with distinct chemotherapy-induced vomiting (CIV) profiles; determine how these subgroups differ on several demographic, clinical, and symptom characteristics; and evaluate factors associated with chemotherapy-induced nausea and CIV profiles. SAMPLE & SETTING: Adult patients (N = 1,338) receiving cancer chemotherapy. METHODS & VARIABLES: Data were collected on demographic, clinical, and symptom characteristics. Differences among subgroups of patients with distinct CIV profiles were evaluated using parametric and nonparametric tests. RESULTS: Three CIV profiles (None, Decreasing, and Increasing) were identified. Compared with the None class, Decreasing and Increasing classes were more likely to have lower household income and a higher comorbidity burden, as well as to report higher rates of dry mouth, nausea, diarrhea, depression, anxiety, sleep disturbance, morning fatigue, and pain interference. IMPLICATIONS FOR NURSING: Clinicians need to assess common and distinct risk factors for CIV and chemotherapy-induced nausea.

Novel Magnetic Resonance Imaging Tools for Hypertrophic Cardiomyopathy Risk Stratification.

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder with a well described risk of sudden cardiac death; however, risk stratification has remained a challenge. Recently, novel parameters in cardiac magnetic resonance imaging (CMR) have shown promise in helping to improve upon current risk stratification paradigms. In this manuscript, we have reviewed novel CMR risk markers and their utility in HCM. The results of the review showed that T1, extracellular volume, CMR feature tracking, and other miscellaneous novel CMR variables have the potential to improve sudden death risk stratification and may have additional roles in diagnosis and prognosis. The strengths and weaknesses of these imaging techniques, and their potential utility and implementation in HCM risk stratification are discussed.

All Obstructive Sleep Apnea Events Are Not Created Equal: The Relationship between Event-related Hypoxemia and Physiologic Response.

Rationale: Obstructive sleep apnea (OSA) severity is typically assessed by the apnea-hypopnea index (AHI), a frequency-based metric that allocates equal weight to all respiratory events. However, more severe events may have a greater physiologic impact. Objectives: The purpose of this study was to determine whether the degree of event-related hypoxemia would be associated with the postevent physiologic response. Methods: Patients with OSA (AHI, ⩾5/h) from the multicenter Canadian Sleep and Circadian Network cohort were studied. Using mixed-effect linear regression, we examined associations between event-related hypoxic burden (HBev) assessed by the area under the event-related oxygen saturation recording with heart rate changes (ΔHRev), vasoconstriction (vasoconstriction burden [VCBev] assessed with photoplethysmography), and electroencephalographic responses (power ratio before and after events). Results: Polysomnographic recordings from 658 patients (median [interquartile range] age, 55.00 [45.00, 64.00] yr; AHI, 27.15 [14.90, 64.05] events/h; 42% female) were included in the analyses. HBev was associated with an increase in all physiologic responses after controlling for age, sex, body mass index, sleep stage, total sleep time, and study centers; for example, 1 standard deviation increase in HBev was associated with 0.21 [95% confidence interval, 0.2, 0.22], 0.08 [0.08, 0.09], and 0.22 [0.21, 0.23] standard deviation increases in ΔHRev, VCBev, and ß-power ratio, respectively. Conclusions: Increased event-related hypoxic burden was associated with greater responses across a broad range of physiologic signals. Future metrics that incorporate information about the variability of these physiologic responses may have promise in providing a more nuanced assessment of OSA severity.

Myelodysplasia cutis masquerading as granulomatous dermatitis.

Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic neoplasms resulting from mutations in stem cells. They carry a risk of transformation to acute myeloid leukemia. Cutaneous manifestations of MDS, including myelodysplasia cutis or infiltration by MDS tumor cells, are rare, but significantly associated with increased risk of progression to high-grade myeloid tumors. The clinical and histopathologic differential diagnosis for myelodysplasia cutis includes interstitial granulomatous dermatitis (IGD), a reactive granulomatous dermatitis (RGD) associated with systemic diseases including rheumatologic diseases, and hematologic malignancy like MDS. We report a patient with MDS who presented with myelodysplasia cutis masquerading as IGD both in a clinical and histopathological manner.

Nanotechnology-assisted treatment of pharmaceuticals contaminated water.

The presence of pharmaceutical compounds in wastewater due to an increase in industrialization and urbanization is a serious health concern. The demand for diverse types of pharmaceutical compounds is expected to grow as there is continuous improvement in the global human health standards. Discharge of domestic pharmaceutical personal care products and hospital waste has aggravated the burden on wastewater management. Further, the pharmaceutical water is toxic not only to the aquatic organism but also to terrestrial animals coming in contact directly or indirectly. The pharmaceutical wastes can be removed by adsorption and/or degradation approach. Nanoparticles (NPs), such as 2D layers materials, metal-organic frameworks (MOFs), and carbonaceous nanomaterials are proven to be more efficient for adsorption and/or degradation of pharmaceutical waste. In addition, inclusion of NPs to form various composites leads to improvement in the waste treatment efficacy to a greater extent. Overall, carbonaceous nanocomposites have advantage in the form of being produced from renewable resources and the nanocomposite material is biodegradable either completely or to a great extent. A comprehensive literature survey on the recent advancement of pharmaceutical wastewater is the focus of the present article.

Current studies on the degradation of microplastics in the terrestrial and aquatic ecosystem.

Soil and water are two important basic ecosystems for the survival of different organisms. The excessive microplastic pollutants in soil have been directly discharged into the terrestrial ecosystems. Microplastic pollutants (MPs) constitute a ubiquitous global menace due to their durability, flexibility, and tough nature. MPs posed threat to the sustainability of the ecosystem due to their small size and easy transportation via ecological series resulting in the accumulation of MPs in aquatic and terrestrial ecosystems. After being emitted into the terrestrial ecosystem, the MPs might be aged by oxidative degeneration (photo/thermal), reprecipitation (bioturbation), and hetero-accumulation. The mechanism of adsorption, degradation, and breakdown of MPs into unaffected plastic debris is accomplished by using several biological, physical, and chemical strategies. This review presents the importance of ecosystems, occurrence and sources of MPs, its toxicity, and the alteration in the ecology of the ecosystems. The inhibitory impact of MPs on the ecosystems also documents to unveil the ecological hazards of MPs. Further research is required to study the immobilization and recovery efficiency of MPs on a larger scale.

Advances in Monitoring and Prognostication for Lymphoma by Flow Cytometry.

Flow cytometry (FC) is a well-established method important in the diagnosis and subclassification of lymphoma. In this article, the role of FC in lymphoma prognostication will be explored, and the clinical role for FC minimal/measurable residual disease testing as a monitoring tool for mature lymphoma will be introduced. Potential pitfalls of monitoring for residual/recurrent disease following immunotherapy will be presented.

Aggressive non-Hodgkin lymphoma in the pediatric and young adult population; diagnostic and molecular pearls of wisdom.

Mature non-Hodgkin lymphomas (NHLs) of the pediatric and young adults(PYA), including Burkitt lymphoma (BL), diffuse large B cell lymphoma (DLBCL), high-grade B cell lymphoma (HGBCL), primary mediastinal large B cell lymphoma (PMBL) and anaplastic large cell lymphoma (ALCL), generally have excellent prognosis compared to the adult population. BL, DLBCL and HGBCL are usually of germinal center (GCB) origin in the PYA population. PMBL neither belongs to the GCB nor the activated B cell subtype and is associated with a poorer outcome than BL or DLBCL of comparable stage. Anaplastic large cell lymphoma is the most frequent peripheral T cell lymphoma occurring in the PYA and accounts for 10-15% of childhood NHL. Most pediatric ALCL, unlike in the adult, demonstrate expression of anaplastic lymphoma kinase (ALK). In recent years, the understanding of the biology and molecular features of these aggressive lymphomas has increased tremendously. This has led to reclassification of newer PYA entities including Burkitt-like lymphoma with 11q aberration. In this review, we will discuss the current progress discovered in frequently encountered aggressive NHLs in the PYA, highlighting the clinical, pathologic and molecular features that aid in the diagnosis of these aggressive lymphomas. We will be updating the new concepts and terminologies used in the new classification systems.

Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.

Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe2+) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml-1), carotenoid accumulation (1.96-2.08 µg ml-1), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm-1) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.

Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration.

OBJECTIVE: The aim of this study was to evaluate baseline differences by HIV status and the impact of pomalidomide on lymphocyte counts and T-cell subsets in patients with Kaposi sarcoma. DESIGN: We prospectively evaluated CD4 + and CD8 + T-cell phenotypes in 19 participants with Kaposi sarcoma enrolled on a phase 1/2 study of pomalidomide (NCT01495598), seven without HIV and 12 with HIV on antiretroviral therapy. METHODS: Trial participants received pomalidomide 5 mg orally for 21 days of 28-day cycles for up to 1 year. Flow cytometry was performed on peripheral blood mononuclear cells at baseline, after three cycles, and at end-of-treatment. Lymphocyte count and T-cell subset comparisons were evaluated by Wilcoxon signed-rank and Mann--Whitney tests. RESULTS: At baseline, HIV + participants had lower CD4 + cell counts (median 416 vs. 742 CD4 + T cells/µl, P  = 0.006), and a decreased proportion of CD57 + (senescent) CD8 + T cells ( P  = 0.007) compared with HIV - participants. After three cycles, pomalidomide led to an increased proportion of CD45RO + CD27 + (central memory) CD4 + ( P  = 0.002) and CD8 + ( P  = 0.002) T cells, a decrease in CD45RO - CD27 - (effector) CD4 + cells ( P  = 0.0002), and expansion of CD38 + /HLADR + (activated) CD4 + ( P  = 0.002) and CD8 + ( P  ≤ 0.0001) T cells. Increased numbers of activated CD8 + T cells persisted at end-of-treatment ( P  = 0.002). After three cycles and at end-of-treatment, there was reduction in the proportion of CD57 + (senescent) CD4 + ( P  = 0.001, 0.0006), and CD8 + ( P  =  < 0.0001, 0.0004) T cells. CONCLUSION: Administration of pomalidomide decreased T-cell senescence and increased T-cell activation in patients with Kaposi sarcoma, suggesting pomalidomide activity in Kaposi sarcoma stems in part from its immunomodulatory effects.

Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats: possible involvement of PDE-1/TGF-ß/ Smad 2/3 signalling pathways.

OBJECTIVE: Diabetic cardiomyopathy (DC) is one of the severe secondary complications of diabetes mellitus in humans. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. The present study is designed to investigate the effect of vinpocetine in DC in rats. METHODS: Rats were fed a high-fat diet for nine weeks along with single dose of streptozotocin after the second week to induce DC. The haemodynamic evaluation was performed to assess the functional status of rats using the Biopac system. Cardiac echocardiography, biochemical, oxidative stress parameters and inflammatory cytokine level were analysed in addition to haematoxylin-eosin and Masson's trichome staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1), transforming growth factor-ß (TGF-ß) and p-Smad 2/3 expression in cardiac tissues were quantified using western blot/RT-PCR. KEY FINDING: Vinpocetine treatment and its combination with enalapril decreased the glucose levels compared to diabetic rats. Vinpocetine improved the echocardiographic parameters and cardiac functional status of rats. Vinpocetine decreased the cardiac biochemical parameters, oxidative stress, inflammatory cytokine levels, cardiomyocyte diameter and fibrosis in rats. Interestingly, expressions of PDE-1, TGF-ß and p-Smad 2/3 were ameliorated by vinpocetine alone and in combination with enalapril. CONCLUSIONS: Vinpocetine is a well-known inhibitor of PDE-1 and the protective effect of vinpocetine in DC is exerted by inhibition of PDE-1 and subsequent inhibition of the expression of TGF-ß/Smad 2/3.

Microbial dysbiosis and the host airway epithelial response: insights into HIV-associated COPD using multi'omics profiling.

BACKGROUND: People living with HIV (PLWH) are at increased risk of developing Chronic Obstructive Pulmonary Disease (COPD) independent of cigarette smoking. We hypothesized that dysbiosis in PLWH is associated with epigenetic and transcriptomic disruptions in the airway epithelium. METHODS: Airway epithelial brushings were collected from 18 COPD + HIV + , 16 COPD - HIV + , 22 COPD + HIV - and 20 COPD - HIV - subjects. The microbiome, methylome, and transcriptome were profiled using 16S sequencing, Illumina Infinium Methylation EPIC chip, and RNA sequencing, respectively. Multi 'omic integration was performed using Data Integration Analysis for Biomarker discovery using Latent cOmponents. A correlation > 0.7 was used to identify key interactions between the 'omes. RESULTS: The COPD + HIV -, COPD -HIV + , and COPD + HIV + groups had reduced Shannon Diversity (p = 0.004, p = 0.023, and p = 5.5e-06, respectively) compared to individuals with neither COPD nor HIV, with the COPD + HIV + group demonstrating the most reduced diversity. Microbial communities were significantly different between the four groups (p = 0.001). Multi 'omic integration identified correlations between Bacteroidetes Prevotella, genes FUZ, FASTKD3, and ACVR1B, and epigenetic features CpG-FUZ and CpG-PHLDB3. CONCLUSION: PLWH with COPD manifest decreased diversity and altered microbial communities in their airway epithelial microbiome. The reduction in Prevotella in this group was linked with epigenetic and transcriptomic disruptions in host genes including FUZ, FASTKD3, and ACVR1B.

METER (Mental health emergency response) program: Findings of psychological impact status and factors associated with depression, anxiety and stress among healthcare workers in public hospital in Malaysia during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has become the greatest challenge of the new millennium. Most healthcare workers (HCWs) experienced unprecedented levels of workload since the pandemic. This study aims to identify the prevalence and factors of depression, anxiety and stress among HCWs in Malaysian healthcare facilities in the midst of the pandemic due to the SARs-CoV-2. METHODS: An emergency response programme on mental health was conducted from June to September 2020. A standardized data collection form was distributed among the HCWs in the government hospital in Klang Valley. The form contained basic demographic information and the self-reported Malay version of the Depression, Anxiety and Stress scale (BM DASS-21). RESULTS: Of the1,300 staff who attended the Mental Health and Psychosocial Support in Covid-19 (MHPSS COVID-19) programme, 996 staff (21.6% male, 78.4% female) completed the online survey (response rate: 76.6%). Result showed that staff aged above 40 years old were almost two times more likely to have anxiety (AOR = 1.632; 95% CI = 1.141-2.334, p:0.007) and depression (AOR = 1.637; 95% CI = 1.1.06-2.423, p:0.014) as compared to staff who were less than 40 years old. Those who had direct involvement with COVID-19 patients were likely to suffer stress (AOR = 0.596; 95% CI = 0.418-0.849, p:0.004), anxiety (AOR = 0.706; 95% Ci = 0.503-0.990, p:0.044) and depression (AOR = 0.630; 95% Ci = 0.427-0.928, p:0.019). HCWs with stress (AOR = 0.638; 95% CI of 0.476-0.856, p = 0.003), anxiety (AOR = 0.720; 95% CI 0.542-0.958, p = 0.024) and depression (AOR = 0.657; 95% CI 0.480-0.901, p = 0.009) showed less confidence to treat critically ill patients and need psychological help during outbreak. CONCLUSION: This study showed the importance of psychosocial support to reduce psychological distress among HCWs when working or coping during the COVID-19 pandemic or outbreak.

Association of alternative polysomnographic features with patient outcomes in obstructive sleep apnea: a systematic review.

STUDY OBJECTIVES: Polysomnograms (PSGs) collect a plethora of physiologic signals across the night. However, few of these PSG data are incorporated into standard reports, and hence, ultimately, under-utilized in clinical decision making. Recently, there has been substantial interest regarding novel alternative PSG metrics that may help to predict obstructive sleep apnea (OSA)-related outcomes better than standard PSG metrics such as the apnea-hypopnea index. We systematically review the recent literature for studies that examined the use of alternative PSG metrics in the context of OSA and their association with health outcomes. METHODS: We systematically searched EMBASE, MEDLINE, and the Cochrane Database of Systematic Reviews for studies published between 2000 and 2022 for those that reported alternative metrics derived from PSG in adults and related them to OSA-related outcomes. RESULTS: Of the 186 initial studies identified by the original search, data from 31 studies were ultimately included in the final analysis. Numerous metrics were identified that were significantly related to a broad range of outcomes. We categorized the outcomes into 2 main subgroups: (1) cardiovascular/metabolic outcomes and mortality and (2) cognitive function- and vigilance-related outcomes. Four general categories of alternative metrics were identified based on signals analyzed: autonomic/hemodynamic metrics, electroencephalographic metrics, oximetric metrics, and respiratory event-related metrics. CONCLUSIONS: We have summarized the current landscape of literature for alternative PSG metrics relating to risk prediction in OSA. Although promising, further prospective observational studies are needed to verify findings from other cohorts, and to assess the clinical utility of these metrics. CITATION: Hajipour M, Baumann B, Azarbarzin A, et al. Association of alternative polysomnographic features with patient outcomes in obstructive sleep apnea: a systematic review. J Clin Sleep Med. 2023;19(2):225-242.

Essential oil nebulization in mild COVID-19(EONCO): Early phase exploratory clinical trial.

Background: Medications studied for therapeutic benefits in coronavirus disease 2019 (COVID-19) have produced inconclusive efficacy results except for steroids. Objective: A prospective randomized open-label, parallel-arm Phase I/II clinical trial was planned to compare essential oil (EO) blend versus placebo nebulization in mild COVID-19. Methods: A Phase I safety evaluation was carried out in a single ascending and multiple ascending dose study designs. We assessed Phase II therapeutic efficacy on COVID-19 and general respiratory symptoms on days 0, 3, 5, 7, 10, and 14 on the predesigned case record form. Viremia was evaluated on day 0, day 5, and day 10. Results: Dose-limiting toxicities were not reached with the doses, frequencies, and duration studied, thus confirming the formulation's preliminary safety. General respiratory symptoms (p < 0.001), anosmia (p < 0.05), and dysgeusia (p < 0.001) benefited significantly with the use of EO blend nebulization compared to placebo. Symptomatic COVID-19 participants with mild disease did not show treatment benefits in terms of symptomatic relief (p = 1.0) and viremia clearance (p = 0.74) compared to the placebo. EO blend was found to be associated with the reduced evolution of symptoms in previously asymptomatic reverse transcription polymerase chain reaction (RT-PCR)-positive study participants (p = 0.034). Conclusion: EO nebulization appears to be a safer add-on symptomatic relief approach for mild COVID-19. However, the direct antiviral action of the EO blend needs to be assessed with different concentrations of combinations of individual phytochemicals in the EO blend.

Water-to-Air Transfer of Nano/Microsized Particulates: Enrichment Effect in Bubble Bursting Jet Drops.

Bubbles dispersed in liquids are widely present in many natural and industrial processes and play a key role in mediating mass transfer during their lifetime from formation to rising to bursting. In particular, nano/microsized particulates and organisms present in the bulk water can be highly enriched in the jet drops ejected during bubble bursting, impacting global climate and public health. However, the detailed mechanism of this enrichment remains obscure with the enrichment factor being difficult to predict. Here, we experimentally investigate the enrichment of nano/microsized particles in bubble bursting jet drops and highlight the underlying hydrodynamic mechanism, combining the effects of bubble scavenge and bursting on the transport of particles. Scaling laws for the enrichment factor are subsequently proposed that describe both our and prior experimental results reasonably well. Our study may provide new insights for water-to-air transfer of bulk particulates such as microbes related to bubble bursting.