Fusobacterium nucleatum: An Overview of Evidence, Demi-Decadal Trends, and Its Role in Adverse Pregnancy Outcomes and Various Gynecological Diseases, including Cancers.

Gynecological and obstetric infectious diseases are crucial to women's health. There is growing evidence that links the presence of Fusobacterium nucleatum (F. nucleatum), an anaerobic oral commensal and potential periodontal pathogen, to the development and progression of various human diseases, including cancers. While the role of this opportunistic oral pathogen has been extensively studied in colorectal cancer in recent years, research on its epidemiological evidence and mechanistic link to gynecological diseases (GDs) is still ongoing. Thus, the present review, which is the first of its kind, aims to undertake a comprehensive and critical reappraisal of F. nucleatum, including the genetics and mechanistic role in promoting adverse pregnancy outcomes (APOs) and various GDs, including cancers. Additionally, this review discusses new conceptual advances that link the immunomodulatory role of F. nucleatum to the development and progression of breast, ovarian, endometrial, and cervical carcinomas through the activation of various direct and indirect signaling pathways. However, further studies are needed to explore and elucidate the highly dynamic process of host-F. nucleatum interactions and discover new pathways, which will pave the way for the development of better preventive and therapeutic strategies against this pathobiont.

pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells and mouse model.

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.

Ambient heat exposure patterns and emergency department visits and hospitalizations among medicare beneficiaries 2008-2019.

OBJECTIVE: To assess the association between ambient heat and all-cause and cause-specific emergency department (ED) visits and acute hospitalizations among Medicare beneficiaries in the conterminous United States. DESIGN: Retrospective cohort study. SETTING: Conterminous US from 2008 and 2019. PARTICIPANTS: 2% random sample of all Medicare fee-for-service beneficiaries eligible for Parts A, B, and D. MAIN OUTCOME MEASURES: All-cause and cause-specific (cardiovascular, renal, and heat-related) ED visits and unplanned hospitalizations were identified using primary ICD-9 or ICD-10 diagnosis codes. We measured the association between ambient temperature - defined as daily mean temperature percentile of summer (June through September) - and the outcomes. Hazard ratios and their associated 95% confidence intervals were estimated using multivariable Cox proportional hazards regression, adjusting for individual level demographics, comorbidities, healthcare utilization factors and zip-code level social factors. RESULTS: Among 809,636 Medicare beneficiaries (58% female, 81% non-Hispanic White, 24% <65), older beneficiaries (aged ≥65) exposed to >95th percentile temperature had a 64% elevated adjusted risk of heat-related ED visits (HR [95% CI], 1.64 [1.46,1.85]) and a 4% higher risk of all-cause acute hospitalization (1.04 [1.01,1.06]) relative to <25th temperature percentile. Younger beneficiaries (aged <65) showed increased risk of heat-related ED visits (2.69 [2.23,3.23]) and all-cause ED visits (1.03 [1.01,1.05]). The associations with heat related events were stronger in males and individuals dually eligible for Medicare and Medicaid. No significant differences were observed by climatic region. We observed no significant relationship between temperature percentile and risk of CV-related ED visits or renal-related ED visits. CONCLUSIONS: Among Medicare beneficiaries from 2008 to 2019, exposure to daily mean temperature ≥ 95th percentile was associated with increased risk of heat-related ED visits, with stronger associations seen among beneficiaries <65, males, and patients with low socioeconomic position. Further longitudinal studies are needed to understand the impact of heat duration, intensity, and frequency on cause-specific hospitalization outcomes.

Clinicians Who Practice Primarily in Nursing Homes and the Quality of End-of-Life Care Among Residents.

Importance: Clinician specialization in the care of nursing home (NH) residents or patients in skilled nursing facilities (SNFs) has become increasingly common. It is not known whether clinicians focused on NH care, often referred to as SNFists (ie, physicians, nurse practitioners, and physician assistants concentrating their practice in the NH or SNF setting), are associated with a reduced likelihood of burdensome transitions in the last 90 days of life for residents, which are a marker of poor-quality end-of-life (EOL) care. Objective: To quantify the association between receipt of care from an SNFist and quality of EOL care for NH residents. Design, Setting, and Participants: This cohort study analyzed Medicare fee-for-service claims for a nationally representative 20% sample of beneficiaries to examine burdensome transitions among NH decedents at the EOL from January 1, 2013, through December 31, 2019. Statistical analyses were conducted from December 2022 to June 2023. Exposure: Receipt of care from an SNFist, defined as physicians and advanced practitioners who provided 80% or more of their evaluation and management visits in NHs annually. Main Outcomes and Measures: This study used augmented inverse probability weighting in analyses of Medicare fee-for-service claims for a nationally representative 20% sample of beneficiaries. Main outcomes included 4 measures of burdensome transitions: (1) hospital transfer in the last 3 days of life; (2) lack of continuity in NHs after hospitalization in the last 90 days of life; (3) multiple hospitalizations in the last 90 days of life for any reason or any hospitalization for pneumonia, urinary tract infection, dehydration, or sepsis; and (4) any hospitalization in the last 90 days of life for an ambulatory care-sensitive condition. Results: Of the 2 091 954 NH decedents studied (mean [SD] age, 85.4 [8.5] years; 1 470 724 women [70.3%]), 953 722 (45.6%) received care from SNFists and 1 138 232 (54.4%) received care from non-SNFists; 422 575 of all decedents (20.2%) experienced a burdensome transition at the EOL. Receipt of care by an SNFist was associated with a reduced risk of (1) hospital transfer in the last 3 days of life (-1.6% [95% CI, -2.5% to -0.8%]), (2) lack of continuity in NHs after hospitalization (-4.8% [95% CI, -6.7% to -3.0%]), and (3) decedents experiencing multiple hospitalizations for any reason or any hospitalization for pneumonia, urinary tract infection, dehydration, or sepsis (-5.8% [95% CI, -10.1% to -1.7%]). There was not a statistically significant association with the risk of hospitalization for an ambulatory care-sensitive condition in the last 90 days of life (0.0% [95% CI, -14.7% to 131.7%]). Conclusions and Relevance: This study suggests that SNFists may be an important resource to improve the quality of EOL care for NH residents.

Regional variations in allergen-induced airway inflammation correspond to changes in soluble guanylyl cyclase heme and expression of heme oxygenase-1.

Asthma is characterized by airway remodeling and hyperreactivity. Our earlier studies determined that the nitric oxide (NO)-soluble guanylyl cyclase (sGC)-cGMP pathway plays a significant role in human lung bronchodilation. However, this bronchodilation is dysfunctional in asthma due to high NO levels, which cause sGC to become heme-free and desensitized to its natural activator, NO. In order to determine how asthma impacts the various lung segments/lobes, we mapped the inflammatory regions of lungs to determine whether such regions coincided with molecular signatures of sGC dysfunction. We demonstrate using murine models of asthma (OVA and CFA/HDM) that the inflamed segments of these murine lungs can be tracked by upregulated expression of HO1 and these regions in turn overlap with regions of heme-free sGC as evidenced by a decreased sGC-α1ß1 heterodimer and an increased response to heme-independent sGC activator, BAY 60-2770, relative to naïve uninflamed regions. We also find that NO generated from iNOS upregulation in the inflamed segments has a higher impact on developing heme-free sGC as increasing iNOS activity correlates linearly with elevated heme-independent sGC activation. This excess NO works by affecting the epithelial lung hemoglobin (Hb) to become heme-free in asthma, thereby causing the Hb to lose its NO scavenging function and exposing the underlying smooth muscle sGC to excess NO, which in turn becomes heme-free. Recognition of these specific lung segments enhances our understanding of the inflamed lungs in asthma with the ultimate aim to evaluate potential therapies and suggest that regional and not global inflammation impacts lung function in asthma.

MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2.

BACKGROUND: MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, by interacting with human papillomavirus (HPV)-encoded oncoproteins, and epigenetically regulating coding gene expression. Hence, we attempted to decipher the impact and underlying mechanisms of MAL downregulation in HPV16-related CaCx pathogenesis, by interrogating the interactive roles of MAL antisense lncRNA AC103563.8, E7 oncoprotein and PRC2 complex protein, EZH2. RESULTS: Employing strand-specific RNA-sequencing, we confirmed the downregulated expression of MAL in association with poor overall survival of CaCx patients bearing HPV16, along with its antisense long noncoding RNA (lncRNA) AC103563.8. The strength of positive correlation between MAL and AC103563.8 was significantly high among patients compared to normal individuals. While downregulated expression of MAL was significantly associated with poor overall survival of CaCx patients bearing HPV16, AC103563.8 did not reveal any such association. We confirmed the enrichment of chromatin suppressive mark, H3K27me3 at MAL promoter, using ChIP-qPCR in HPV16-positive SiHa cells. Subsequent E7 knockdown in such cells significantly increased MAL expression, concomitant with decreased EZH2 expression and H3K27me3 marks at MAL promoter. In silico analysis revealed that both E7 and EZH2 bear the potential of interacting with AC103563.8, at the same binding domain. RNA immunoprecipitation with anti-EZH2 and anti-E7 antibodies, respectively, and subsequent quantitative PCR analysis in E7-silenced and unperturbed SiHa cells confirmed the interaction of AC103563.8 with EZH2 and E7, respectively. Apparently, AC103563.8 seems to preclude EZH2 and bind with E7, failing to block EZH2 function in patients. Thereby, enhanced EZH2 expression in the presence of E7 could potentially inactivate the MAL promoter through H3K27me3 marks, corroborating our previous results of MAL expression downregulation in patients. CONCLUSION: AC103563.8-E7-EZH2 axis, therefore, appears to crucially regulate the expression of MAL, through chromatin inactivation in HPV16-CaCx pathogenesis, warranting therapeutic strategy development.

Unfurling the functional association between long intergenic noncoding RNAs (lincRNAs) and HPV16-related cervical cancer pathogenesis through weighted gene co-expression network analysis of differentially expressed lincRNAs and coding genes.

Long intergenic noncoding RNAs (lincRNAs) do not overlap annotated coding genes and are located in intergenic regions, as opposed to antisense and sense-intronic lncRNAs, located in genic regions. LincRNAs influence gene expression profiles and are thereby key to disease pathogenesis. In this study, we assessed the association between lincRNAs and HPV16-positive cervical cancer (CaCx) pathogenesis using weighted gene co-expression network analysis (WGCNA) with coding genes, comparing differentially expressed lincRNA and coding genes (DElincGs and DEcGs, respectively) in HPV16-positive patients with CaCx (n = 44) with those in HPV-negative healthy individuals (n = 34). Our analysis revealed five DElincG modules, co-expressing and correlating with DEcGs. We validated a substantial number of such module-specific correlations in the HPV16-positive cancer TCGA-CESC dataset. Four such modules, displayed significant correlations with patient traits, such as HPV16 physical status, lymph node involvement, and overall survival (OS), highlighting a collaborative effect of all genes within specific modules on traits. Using the DAVID bioinformatics knowledgebase, we identified the underlying biological processes associated with these modules as cancer development and progression-associated pathways. Next, we identified the top 10 DElincGs with the highest connectivity within each functional module. Focusing on the prognostic module hub genes, downregulated CTD-2619J13.13 expression was associated with poor patient OS. This lincRNA gene interacted with 25 coding genes of its module and was associated with such biological processes as keratinization loss and keratinocyte differentiation, reflecting severe disease phenotypes. This study has translational relevance in fighting various cancers with high mortality rates in underdeveloped countries.

Nocardia otitidiscaviarum causing pulmonary nocardiosis: a case report and its review of the literature.

Background: Infections caused by Nocardia spp. can occur in immunocompromised as well as immunocompetent individuals. Although nocardiosis is rare, it is being increasingly recognized owing to the rise in occurrence rate over the years. The documentation of pleural involvement in nocardiosis is rare in India. Case: We report a case of pulmonary nocardiosis in an immunocompromised individual caused by Nocardia otitidiscaviarum. Discussion: Pulmonary nocardiosis caused by Nocardia otitidiscaviarum may go unnoticed without clinical suspicion. Correct and timely identification is the key to proper patient management. Conclusion: Coordination between clinicians and microbiologists is necessary for early diagnosis and appropriate management of nocardiosis.

Building Climate Change into Medical Education: A Society of General Internal Medicine Position Statement.

Building expertise in climate and planetary health among healthcare professionals cannot come with greater urgency as the threats from climate change become increasingly apparent. Current and future healthcare professionals-particularly internists-will increasingly need to understand the interconnectedness of natural systems and human health to better serve their patients longitudinally. Despite this, few national medical societies and accreditation bodies espouse frameworks for climate change and planetary health-related education at the undergraduate (UME), graduate (GME), and continuing (CME) medical education level. As a community of medical educators with an enduring interest in climate change and planetary health, the Society of General Internal Medicine (SGIM) recognizes the need to explicitly define structured educational opportunities and core competencies in both UME and GME as well as pathways for faculty development. In this position statement, we build from the related SGIM Climate and Health position statement, and review and synthesize existing position statements made by US-based medical societies and accreditation bodies that focus on climate change and planetary health-related medical education, identify gaps using Bloom's Hierarchy, and provide recommendations on behalf of SGIM regarding the development of climate and planetary health curricula development. Identified gaps include (1) limited systematic approach to climate and planetary health medical education at all levels; (2) minimal emphasis on learner-driven approaches; (3) limited focus on physician and learner well-being; and (4) limited role for health equity and climate justice. Recommendations include a call to relevant accreditation bodies to explicitly include climate change and planetary health as a competency, extend the structural competency framework to climate change and planetary health to build climate justice, proactively include learners in curricular development and teaching, and ensure resources and support to design and implement climate and planetary health-focused education that includes well-being and resiliency.

Rapid Decline of SARS-CoV-2 Viral Load in Single vs. Double-Dose (Short-Interval <6 Weeks) ChAdOx nCoV-19 Vaccinated Health-Care Workers.

The present work was carried out during the emergence of Delta Variant of Concern (VoC) and aimed to study the change in SARS CoV-2 viral load in Covishield vaccinated asymptomatic/mildly symptomatic health-care workers (HCWs) to find out the optimum isolation period. The SARS CoV-2 viral load was carried out in sequential samples of 55 eligible HCWs which included unvaccinated (UnV; n = 11), single-dose vaccinated (SDV, n = 20) and double-dose vaccinated [DDV, n = 24; short-interval (<6 weeks)] subjects. The mean load of envelope (E) gene on day 5 in SDV [0.42 × 105 copies/reaction] was significantly lower as compared to DDV [6.3 × 105 copies/reaction, P = 0.005] and UnV [6.6 × 105 copies/reaction, P = 0.001] groups. The rate of decline of SARS CoV-2 viral load in the initial 5 days of PCR positivity was significantly higher in SDV as compared to that in DDV (Mean log decline 0.39 vs. 0.19; P < 0.001). This was possibly due to interference of adenoviral immunity of first dose of adenovirus-vectored vaccine in double-dose vaccinated HCWs who had received vaccines within a shorter interval (<6 weeks).

Greener Approach for Synthesis of δ-MnO2 Nanoparticles: Access to Pharmaceutically Important Pyrimidines and their Antimicrobial Activity Studies.

A sustainable approach for pharmaceutically important pyrimidine derivatives is achieved by using biogenically produced single-phase δ-MnO2 NPs under external ligand-free conditions. The phytochemicals that comprise the extract of Areca Nut Husk (ANH) have been discovered to serve as reducing agents. The role of phytochemicals is not only to aid in the reduction of Mn(VII) into Mn(IV), but they also have an important role in stabilizing the catalyst. The establishment of δ-MnO2 NPs was confirmed inveterate by FE-SEM, p-XRD, ICP-OES (Mn content = 43.17% w/w), EDX, and with an active Mn content of 43.17% w/w. A series of pyrimidine derivatives were prepared in good yields using a one-pot multicomponent synthesis approach under atmospheric conditions. In addition, hot filtration tests, control experiments, gram-scale synthesis, and mechanistic investigations were demonstrated. Additionally, antimicrobial activity studies of δ-MnO2 NPs and pyrimidine derivatives against the Gram-negative bacteria E. coli, growth curve and minimum inhibitory concentration were studied.

Two-Dimensional Electronic Spectroscopy Reveals Dynamics within the Bright Fine Structure of CdSe Quantum Dots.

Semiconductor quantum dots are characterized by a discrete excitonic structure featuring coarse as well as fine structure. The lowest fine structure states have splittings into bright-dark states which are now well confirmed by single dot spectroscopy. In contrast, the splitting of the lowest coarse exciton into bright-bright fine structure states has not been observed nor the dynamics between these states. Here, we use the unique combination of time and energy resolution of two-dimensional electronic spectroscopy to directly observe the fine structure splittings into a bright-bright doublet. These splittings are strongly size dependent, with population relaxation on the <100 fs time scale.

Theranostic applications of peptide-based nanoformulations for growth factor defective cancers.

Growth factors play a pivotal role in orchestrating cellular growth and division by binding to specific cell surface receptors. Dysregulation of growth factor production or activity can contribute to the uncontrolled cell proliferation observed in cancer. Peptide-based nanoformulations (PNFs) have emerged as promising therapeutic strategies for growth factor-deficient cancers. PNFs offer multifaceted capabilities including targeted delivery, imaging modalities, combination therapies, resistance modulation, and personalized medicine approaches. Nevertheless, several challenges remain, including limited specificity, stability, pharmacokinetics, tissue penetration, toxicity, and immunogenicity. To address these challenges and optimize PNFs for clinical translation, in-depth investigations are warranted. Future research should focus on elucidating the intricate interplay between peptides and nanoparticles, developing robust spectroscopic and computational methodologies, and establishing a comprehensive understanding of the structure-activity relationship governing peptide-nanoparticle interactions. Bridging these knowledge gaps will propel the translation of peptide-nanoparticle therapies from bench to bedside. While a few peptide-nanoparticle drugs have obtained FDA approval for cancer treatment, the integration of nanostructured platforms with peptide-based medications holds tremendous potential to expedite the implementation of innovative anticancer interventions. Therefore, growth factor-deficient cancers present both challenges and opportunities for targeted therapeutic interventions, with peptide-based nanoformulations positioned as a promising avenue. Nonetheless, concerted research and development endeavors are essential to optimize the specificity, stability, and safety profiles of PNFs, thereby advancing the field of peptide-based nanotherapeutics in the realm of oncology research.

Ambient Heat and Risk of Serious Hypoglycemia in Older Adults With Diabetes Using Insulin in the U.S. and Taiwan: A Cross-National Case-Crossover Study.

OBJECTIVE: To measure the association between ambient heat and hypoglycemia-related emergency department visit or hospitalization in insulin users. RESEARCH DESIGN AND METHODS: We identified cases of serious hypoglycemia among adults using insulin aged ≥65 in the U.S. (via Medicare Part A/B/D-eligible beneficiaries) and Taiwan (via National Health Insurance Database) from June to September, 2016-2019. We then estimated odds of hypoglycemia by heat index (HI) percentile categories using conditional logistic regression with a time-stratified case-crossover design. RESULTS: Among ∼2 million insulin users in the U.S. (32,461 hypoglycemia case subjects), odds ratios of hypoglycemia for HI >99th, 95-98th, 85-94th, and 75-84th percentiles compared with the 25-74th percentile were 1.38 (95% CI, 1.28-1.48), 1.14 (1.08-1.20), 1.12 (1.08-1.17), and 1.09 (1.04-1.13) respectively. Overall patterns of associations were similar for insulin users in the Taiwan sample (∼283,000 insulin users, 10,162 hypoglycemia case subjects). CONCLUSIONS: In two national samples of older insulin users, higher ambient temperature was associated with increased hypoglycemia risk.

Risk Prediction for Atherosclerotic Cardiovascular Disease With and Without Race Stratification.

Importance: Use of race-specific risk prediction in clinical medicine is being questioned. Yet, the most commonly used prediction tool for atherosclerotic cardiovascular disease (ASCVD)-pooled cohort risk equations (PCEs)-uses race stratification. Objective: To quantify the incremental value of race-specific PCEs and determine whether adding social determinants of health (SDOH) instead of race improves model performance. Design, Setting, and Participants: Included in this analysis were participants from the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort study. Participants were aged 45 to 79 years, without ASCVD, and with low-density lipoprotein cholesterol level of 70 to 189 mg/dL or non-high-density lipoprotein cholesterol level of 100 to 219 mg/dL at baseline during the period of 2003 to 2007. Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke. Study data were analyzed from July 2022 to February 2023. Main outcome/measures: Discrimination (C statistic, Net Reclassification Index [NRI]), and calibration (plots, Nam D'Agostino test statistic comparing observed to predicted events) were assessed for the original PCE, then for a set of best-fit, race-stratified equations including the same variables as in the PCE (model C), best-fit equations without race stratification (model D), and best-fit equations without race stratification but including SDOH as covariates (model E). Results: This study included 11 638 participants (mean [SD] age, 61.8 [8.3] years; 6764 female [58.1%]) from the REGARDS cohort. Across all strata (Black female, Black male, White female, and White male participants), C statistics did not change substantively compared with model C (Black female, 0.71; 95% CI, 0.68-0.75; Black male, 0.68; 95% CI, 0.64-0.73; White female, 0.77; 95% CI, 0.74-0.81; White male, 0.68; 95% CI, 0.64-0.71), in model D (Black female, 0.71; 95% CI, 0.67-0.75; Black male, 0.68; 95% CI, 0.63-0.72; White female, 0.76; 95% CI, 0.73-0.80; White male, 0.68; 95% CI, 0.65-0.71), or in model E (Black female, 0.72; 95% CI, 0.68-0.76; Black male, 0.68; 95% CI, 0.64-0.72; White female, 0.77; 95% CI, 0.74-0.80; White male, 0.68; 95% CI, 0.65-0.71). Comparing model D with E using the NRI showed a net percentage decline in the correct assignment to higher risk for male but not female individuals. The Nam D'Agostino test was not significant for all race-sex strata in each model series, indicating good calibration in all groups. Conclusions: Results of this cohort study suggest that PCE performed well overall but had poorer performance in both BM and WM participants compared with female participants regardless of race in the REGARDS cohort. Removal of race or the addition of SDOH did not improve model performance in any subgroup.

Clinical Profile, Intensive Care Needs and Predictors of Outcome Among Children Admitted with Non-COVID Severe Acute Respiratory Illness (SARI) During the Pandemic.

OBJECTIVES: To study the epidemiology of non-coronavirus disease-2019 (non-COVID-19) respiratory viral infections with respect to their clinical profile, intensive care needs and predictors of outcome once the non-pharmacological interventions (NPI) during the coronavirus disease-2019 (COVID-19) pandemic were relaxed. METHODS: Retrospective analysis of children with Severe Acute Respiratory Illness (SARI) who were SARS-CoV-2 negative, admitted to the Pediatric Emergency/Intensive Care Unit (PICU) from July 2021 through October 2021 was conducted. RESULTS: One hundred and thirty nine children with median age of 11 (4-28.5) mo were included. Besides respiratory symptoms in all, diarrhea was reported in 90 (64.7%) children. Nearly half (n = 66; 47%) presented in hypoxemic respiratory failure (SpO2 <88%). Fifty-two (37.4%) children had co-morbidities, commonest being congenital heart disease in 12 (23.1%). Baseline parameters revealed leukopenia (specifically lymphopenia) 39 (28%), elevated aspartate transaminase [Serum glutamic-oxaloacetic transaminase (SGOT)] in 108 (77.6%), elevated N-acetyl-cysteine-activated creatinine kinase (CK-NAC) 23 (79%) and lactate dehydrogenase (LDH) 15 (88%). Intensive care needs included mechanical ventilation 51 (36.6%), vasoactive support 34 (24.5%), and renal replacement therapy 10 (7.1%). Forty-two (30.2%) children developed multi-organ dysfunction syndrome (MODS). One hundred and three (74.1%) children were discharged, 31 (22.3%) died, and 5 (3.6%) left against medical advice. On multivariate regression analysis, elevated liver enzymes (>5 times normal), hypoxemic respiratory failure at admission, hypotensive shock and MODS predicted mortality. CONCLUSIONS: A surge in non-COVID SARI was observed once lockdown measures were relaxed. Nearly 1/3rd progressed to multi-organ failure and died. Elevated liver enzymes, hypoxemic respiratory failure at admission, hypotensive shock and MODS predicted death.

Hot Excitons Cool in Metal Halide Perovskite Nanocrystals as Fast as CdSe Nanocrystals.

The idea of phonon bottlenecks has long been pursued in nanoscale materials for their application in hot exciton devices, such as photovoltaics. Decades ago, it was shown that there is no quantum phonon bottleneck in strongly confined quantum dots due to their physics of quantum confinement. More recently, it was proposed that there are hot phonon bottlenecks in metal halide perovskites due to their physics. Recent work has called into question these bottlenecks in metal halide perovskites. Here, we compare hot exciton cooling in a range of sizes of CsPbBr3 nanocrystals from weakly to strongly confined. These results are compared to strongly confined CdSe quantum dots of two sizes and degrees of quantum confinement. CdSe is a model system as a ruler for measuring hot exciton cooling being fast, by virtue of its efficient Auger-assisted processes. By virtue of 3 ps time resolution, the hot exciton photoluminescence can now be directly observed, which is the most direct measure of the presence of hot excitons and their lifetimes. The hot exciton photoluminescence decays on nearly the same 2 ps time scale on both the weakly confined perovskite and the larger CdSe quantum dots, much faster than the 10 ps cooling predicted by transient absorption experiments. The smaller CdSe quantum dot has still faster cooling, as expected from quantum size effects. The quantum dots of perovskites show extremely fast hot exciton cooling, decaying faster than detection limits of <1 ps, even faster than the CdSe system, suggesting the efficiency of Auger processes in these metal halide perovskite nanocrystals and especially in their quantum dot form. These results across a range of sizes of nanocrystals reveal extremely fast hot exciton cooling at high exciton density, independent of composition, but dependent upon size. Hence these metal halide perovskite nanocrystals seem to cool heavily following quantum dot physics.

Regions of Inflammation in mouse asthma correspond to regions of heme-free soluble guanylyl cyclase and can be tracked by marked expression of heme-oxygenase-1.

Asthma is characterized by airway remodeling and hyperreactivity. Our earlier studies determined that the Nitric Oxide (NO)-soluble Guanylyl Cyclase (sGC)-cGMP pathway plays a significant role in human lung bronchodilation. However this bronchodilation is dysfunctional in asthma due to high NO levels which cause sGC to become heme-free and desensitized to its natural activator, NO. In order to determine how asthma impacts the various lung segments/lobes we mapped the inflammatory regions of lungs to determine whether such regions coincided with molecular signatures of sGC dysfunction. We demonstrate using models of mouse asthma (OVA, CFA/HDM) that the inflammed segments of the mouse asthma lungs can be tracked by upregulated expression of HO1 and these regions in-turn overlap with regions of heme-free sGC as evidenced by a decreased sGC-α1ß1 heterodimer and an increased response to heme-independent sGC activator, BAY 60-2770 relative to naïve uninflamed regions. We also find that NO generated from iNOS upregulation in the inflamed segments has a higher impact in developing heme-free sGC as increasing iNOS activity correlates linearly with elevated heme-independent sGC activation. This excess NO works by affecting the epithelial lung hemoglobin (Hb) to become heme-free in asthma thereby causing the Hb to lose its NO scavenging function and exposing the underlying smooth muscle sGC to excess NO, which in-turn becomes heme-free. Recognition of these specific lung segments enhance our understanding of the inflammed lungs in asthma with the ultimate aim to evaluate potential therapies and suggests that regional and not global inflammation impacts lung function in asthma.

Enhancing Multiexcitonic Emission in Metal-Halide Perovskites by Quantum Confinement.

Semiconductor metal halide perovskite nanocrystals have been under intense investigation for their promise in a variety of optoelectronic applications, which arises from their remarkable properties of defect tolerance and efficient light emission. Recently, quantum dot versions of perovskite nanocrystals have been available, enabling investigation of how quantum size effects control optical function and performance in these quantum dots (QD), past their well-known covalent II-VI analogues. We perform time-resolved photoluminescence (t-PL) experiments on CsPbBr3 perovskite nanocrystals spanning in diameter from 5.8 nm strongly confined quantum dots to 18 nm weakly confined quantum dots. Experiments are performed with sufficient time resolution of 3 ps to observe the interaction energies and recombination kinetics from excitons to multiexcitons. Comparing the same sized QD reveals that perovskite QD have a larger radiative rate constant for emission from X than CdSe QD due to a larger oscillator strength. The multiexciton (MX) regime reveals that perovskite QD emit brightly and with more focused bandwidth than equivalent sized CdSe QD enabling more spectrally pure brightness. The MX kinetics reveals that the perovskite QD maintain efficient radiative decay, effectively competing with Auger recombination. These experiments reveal that the strongly confined QD of perovskites can be efficient multiexcitonic emitters, such as in high brightness light emitting diodes, especially in the blue.

Role of line probe assay in detection of Mycobacterium tuberculosis in children with pulmonary tuberculosis.

BACKGROUND: India is the highest TB burden country in the world with almost 27 lakh cases reported in 2019. Pediatric tuberculosis in India accounts for almost 31% of global TB burden. Despite such high mortality and morbidity in children, diagnosis of pulmonary TB in children still remains very challenging. MATERIAL AND METHODS: This cross-sectional study was conducted in a tertiary care hospital in Delhi, India. Children between 1 and 12 months with clinical suspicion of pulmonary tuberculosis who had not previously taken ATT were included. Early morning gastric aspirate samples were collected after overnight fasting, on two days. Both days sputum sample were subjected to sputum smear microscopy and one of the two samples was subjected to line probe assay (LPA), cartridge based nucleic acid amplification (CBNAAT) and mycobacterium growth in tube (MGIT-960). RESULTS: 84 children with pulmonary tuberculosis were enrolled. The most common presenting complaint was fever seen in 83 patients (98.8%). Only 17 (20.24%) were sputum smear positive by Ziehl- Neelsen (ZN) staining. LPA was positive in 47 (55.95%) samples and among these positive samples both INH and RIF resistance was detected in 2 (4.26%) samples. CBNAAT was positive in 53 patients (63%). Growth in liquid culture media (MGIT 960) was observed in 44 (52.38%) samples. Among 17 smear positive samples, LPA was detected in 14 (82.35%) samples and among 67 smear negative sample LPA was detected in 33 (49.25%) samples. LPA had 63.46% sensitivity, 100% specificity in detecting mycobacterium tuberculosis. DISCUSSION: WHO's recommendation for using LPAs has been limited to culture isolates or smear-positive sputum specimens. New data has since been generated on the use of LPAs as newer versions of LPA have been developed over past few years. Previous studies conducted using LPA version 1.0 reported much lower detection rate of mycobacterium tuberculosis in smear negative specimens. With the availability of newer versions such as Hain GenoTypeMTBDRplusversion 2 and Nipro NTM + MDRTB detection kit 2, the diagnostic utility of LPA may be enhanced.