Complex Population Research Articles

2551. Assessing Meropenem Concentrations in Children with Septic Shock: Population-Based Pharmacokinetic (PK) Modeling of Meropenem Demonstrates Variability from Acute Kidney (AKI) to Augmented Renal Clearance (ARC)

Abstract Background The primary objective of this study was to characterize meropenem (MERO) pharmacokinetics (PK) in critically ill infants and children with septic shock to develop dosing recommendations to achieve therapeutic drug exposure in this complex population with a spectrum of renal function from augmented renal clearance (ARC) to acute kidney injury (AKI). Methods Children ≥4 weeks old hospitalized with septic shock requiring fluid resuscitation and pressors, receiving MERO 20 mg/kg IV every 8 hr as standard-of-care, were enrolled and studied prospectively from 2019 to 2023. Population PK modeling was used to derive Bayesian post-hoc PK parameters (NONMEM 7.3). Renal biomarkers (serum creatinine [SCr], cystatin C [CYS], serum neutrophil gelatinase-associated lipocalin [NGAL]) were evaluated as covariates. Estimated glomerular filtration rate (e-GFR) was calculated by the modified Schwartz equation. Results A total of 304 MERO serum concentrations were included from 26 participants. Median age was 12.6 yr (range 1.2-19.6); weight 38.4 kg (10-98); SCr 0.36 mg/dL (0.09-2.57); CYS 448.9 mg/d (178.3-1824.1), and NGAL 176.05 ng/mL (29.3-1000). Median MERO serum concentration was 11 mcg/mL (range 0.033-217, interquartile range [IQR] 1.873-37.85). A two-compartment model with allometrically scaled weight on clearance (0.75) best described the data. Significant covariates (final model) were e-GFR, CYS, NGAL, age, diagnosis of appendicitis and albumin. Using the final model, the median CL was 0.15 (range 0.05-0.51, interquartile range [IQR] 0.06-0.25) L/hr/kg and V1 0.20 (0.07-0.57, IQR 0.12-0.31) L/kg, with GFR 139 (23-364, IQR 93-204) mL/min/1.73 m2 (Figure). The distribution of MERO concentrations, CL and GFR across quartiles documents wide variations in renal function observed in septic shock, from AKI to ARC (Figure). Meropenem Serum Concentration, Meropenem Renal Clearance, and Glomerular Filtration Rate, by Quartiles Conclusion Wide variation in MERO plasma exposure was documented in children with septic shock across the spectrum of renal function. GFR-based dosing recommendations may optimize MERO dosing and improve outcomes in this population. This work was supported by NICHD grant 1 R01 HD095547-01 Disclosures Edmund Capparelli, PharmD, Melinta: Advisor/Consultant

2206. Using Day-Level Registry Data on Patients in OPAT to Assess Heterogeneous Patterns of Time-Varying Antimicrobial Exposure and Unplanned Stopping across Multiple Infection Diagnoses, 2015-2022

Abstract Background Patients receiving outpatient parenteral antimicrobial therapy (OPAT) are often medically complex and require carefully tailored treatments to address severe and often concomitant infections. Methods We conducted a cohort study of patients enrolled in the University of North Carolina Medical Center OPAT program between March 2015 and December 2022 (2358 OPAT courses among 2072 unique patients). Patients were followed from OPAT regimen initiation (day 0) until observed treatment stop date, based on a grace period of 5 days to confirm discontinuation. Using hierarchical and mutually exclusive categorization schema, we classified patients into 1 of 10 infection diagnosis groups (Figure 1A), and classified all observed antibiotic cocktails (64 distinct antimicrobial medications comprising 520 distinct cocktails) into 18 treatments (Figure 1B). For each patient, we assessed their planned OPAT duration to classify their observed discontinuation as “planned,” “unanticipated early stop,” or “unanticipated prolonged treatment.” Stratified by infection diagnosis and treatment classifications, we used stacked bar charts to describe treatment heterogeneity, and Aalen-Johansen-based cumulative incidence curves to estimate occurrence of each type of discontinuation amid competing events. Results The cohort was 59.7% male with median age 56 years (IQR 45-66); the most common infection diagnosis was osteomyelitis +/- diabetic foot infection (28.1%, Figure 1A). Medication exposures were heterogeneous within and across infection diagnoses (Figure 1A and 1B). Median planned OPAT duration was 36 days (middle 90% 15-44). Overall cumulative incidence of unanticipated early discontinuation was 11.9%; overall incidence of unanticipated prolonged treatment was 22.9% (Figure 2). Conclusion Day-level data on medication use in this registry provided evidence of heterogeneity in medication exposure and unplanned discontinuation from OPAT, within and across infection diagnoses. These data highlight the need for multi-layered ascertainment of medication exposure, microorganisms, and infection diagnosis in this medically complex patient population to inform surveillance for adverse effects and comparative effectiveness research for post-discharge antibiotic treatment. Disclosures Asher J. Schranz, MD, MPH, WoltersKluwer: Honoraria Alan C. Kinlaw, PhD, MSPH, Genentech: Grant/Research Support

A Systematic Review of Relationship Between Empathy Deficits and Psychopathy

This systematic review undertook a comprehensive investigation into the intricate relationship between empathy deficits and individuals exhibiting psychopathic traits. Three primary objectives guided our analysis, each addressing a notable gap in the current research landscape: (1) To discern variations in empathy deficits among distinct psychopathic subtypes, (2) To rigorously analyze the predictive correlation between empathy deficits and the propensity to reoffend in individuals with psychopathy, and (3) To thoroughly examine the multifaceted factors influencing empathy within this complex population. This systematic review makes a significant contribution to existing research by addressing critical gaps in our understanding of psychopathy and empathy. By pinpointing the distinct empathy profiles of psychopathic subtypes, predicting the risk of reoffending based on empathy impairments, and offering insights into the contextual nature of empathy, this review bridges crucial knowledge gaps. These findings hold immense significance for the development of more empathetic approaches to both research and clinical practices, striving to improve interactions and rehabilitative efforts for individuals exhibiting psychopathic traits.

Progression of flood risk assessment in India at a decadal scale: a critical review

Abstract Floods are a recurrent natural phenomenon in India, including perennial occurrences in some parts of the country. Progressively, floods are transformed into flood hazards because of the anthropogenic activities in the flood plains and adjoining catchments, causing injuries, loss of lives, and property damage. Flood hazards, when considered in relation to vulnerability and exposure limits, describe the associated flood risk. This article aims to discuss the progression in flood risk assessment through several government policies and actions in India at a decadal scale from 1951 to 2020. While doing this, some important extreme flood events witnessed in those decades that shaped the perspectives, measures, action plans, and policies in the subsequent years are discussed. The review confirms that with the changing patterns of floods, associated hazards, and risks over the years, improvements in risk assessment approaches are noticeable on dual fronts. Technical advancements in flood risk assessment have corroborated the policy reforms. Albeit these developments, the issues related to the scale of study, data sources and resolutions, climatic variability, urban development, complex population dynamics, and their interrelationships in the context of flood risk need to be resolved with serious efforts. Addressing these issues through multidimensional strategies is imperative to aver robust flood risk assessment.

Imaging mass cytometry reveals tissue-specific cellular immune phenotypes in the mouse knee following ACL injury

ObjectiveTo develop an imaging mass cytometry method for identifying complex cell phenotypes, inter-cellular interactions, and population changes in the synovium and infrapatellar fat pad (IFP) of the mouse knee following a non-invasive compression injury. DesignFifteen male C57BL/6 mice were fed a high-fat diet for 8 weeks prior to random assignment to sham, 0.88 ​mm, or 1.7 ​mm knee compression displacement at 24 weeks of age. 2-weeks after loading, limbs were prepared for histologic and imaging mass cytometry analysis, focusing on myeloid immune cell populations in the synovium and IFP. Results1.7 ​mm compression caused anterior cruciate ligament (ACL) rupture, development of post-traumatic osteoarthritis, and a 2- to 3-fold increase in cellularity of synovium and IFP tissues compared to sham or 0.88 ​mm compression. Imaging mass cytometry identified 11 myeloid cell subpopulations in synovium and 7 in IFP, of which approximately half were elevated 2 weeks after ACL injury in association with the vasculature. Notably, two monocyte/macrophage subpopulations and an MHC IIhi population were elevated 2-weeks post-injury in the synovium but not IFP. Vascular and immune cell interactions were particularly diverse in the synovium, incorporating 8 unique combinations of 5 myeloid cell populations, including a monocyte/macrophage population, an MHC IIhi population, and 3 different undefined F4/80+ myeloid populations. ConclusionsDeveloping an imaging mass cytometry method for the mouse enabled us to identify a diverse array of synovial and IFP vascular-associated myeloid cell subpopulations. These subpopulations were differentially elevated in synovial and IFP tissues 2-weeks post injury, providing new details on tissue-specific immune regulation.

Dapaglifozin in adults with a systemic right ventricle:initial results from the DAPA-SERVE trial

Abstract Background Sodium-glucose Cotransporter-2(SGLT2) inhibitors are currently recommended as first line therapy for all patients with heart failure with reduced ejection fraction (HFrEF).Adults with a systemic right ventricle (sRV) may develop progressive systolic dysfunction during follow-up. Optimal medical therapy for HFrEF remains still to be determined in this complex population. Purpose We aimed to assess safety and evaluate potential clinical benefit of dapagliflozin in patients with a sRV compared to standard medical treatment for HF. Methods Inclusion criteria were:age ≥ 18 years; transposition of the great arteries (TGA) following Senning/Mustard repair or congenitally corrected TGA, sRV EF ≤ 40%, already on optimized medical therapy including sacubitril/valsartan for at least 3 months. Exclusion criteria were: systolic blood pressure (SBP) <90 mmHg, glomerular filtration rate (GFR)<30ml/min and univentricular physiology. All eligible patients attending our tertiary center for adult congenital heart disease were randomly assigned to the treatment or control group. Patients in the treatment arm were prescribed 10 mg dapagliflozin o.d. on top of their medical therapy, while control group continued standard therapy. Patients were scheduled for a structured follow-up including clinical evaluation, blood test, echocardiography, and 6 minute-walking at 6 months from study inclusion for both groups. Results Fifty patients (41±11 years, 54% male, 64% TGA) met the inclusion criteria: 25(50%) were started on 10 mg dapagliflozin. There was no significant difference in terms of age (p=0.4), sex(p=0.1), anatomy(p=0.2) and baseline sRV EF (p=0.2). Up to February 2023, 14 patients in the treatment group and 13 controls completed the 6-month follow-up. Clinical and echocardiographic findings at baseline and at 6-month in the treatment group are summarized in Table1: dapagliflozin was well tolerated and no major adverse events were reported. Treatment did not impact on the systolic blood pressure and renal function. However a significant improvement in the sRV freewall global longitudinal strain(GLS) was found (-15.8±3 Vs -18.3±3; p=0.03). Differences in main echocardiographic indices of sRV systolic function between baseline and follow-up in the two arms are shown in Table2: treatment resulted in significant positive changes of sRV FAC, GLS, and free wall GLS compared to the group on standard therapy. Conclusions Initial results from the ongoing single-centre DAPA-SERVE trial provided reassuring data on the safety profile of dapagliflozin in patients with a sRV. Furthermore, significant improvement of echocardiographic indices of sRV function in patients on dapagliflozin compared to those on standard medical therapy was demonstrated at 6-month. Longer follow-up is warranted to determine the clinical impact of those positive changes and to shed light on the potential benefit of SGLT2 inhibitors use on top of standard therapy in this complex population.

Is staging for cardiac damage in aortic stenosis associated with MACE in cancer patients with prior radiotherapy or chemotherapy that underwent transcatheter aortic valve replacement?

Abstract Background Staging classification for severe aortic stenosis (AS) based on the extent of cardiac damage has been correlated with outcomes in the general population. This is categorized based on the following echocardiographic findings: stage 1 (increase in the left ventricular mass index; E/e’>14; and left ventricular ejection fraction <50%); stage 2 (left atrial volume index >34ml/m2; moderate to severe mitral regurgitation and atrial fibrillation), stage 3 (systolic pulmonary hypertension> 60mmHg and moderate to severe tricuspid regurgitation) and stage 4 (moderate to severe right ventricular dysfunction); its applicability in a cancer population exposed to chemo+/- radiotherapy and its correlation with MACE has not been explored. Purpose To evaluate if this staging system predicts MACE (cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure) at 18 months after TAVR in cancer patients who were previously exposed to cardiotoxic therapies. Methods We retrieved data of patients that underwent TAVR from 2013 to 2021. 544 patients were included in this study and divided in 3 groups: 187 patients with prior chest Radiotherapy and Chemotherapy (RT/CT), 155 with CT only, and 202 cancer patients not exposed to CT or RT control group. This was further subdivided in two groups based on the staging system in: stage ≤ 2 and ≥3. Fisher's exact test or chi-square was used to compare categorical variables and clinical outcomes among groups and ANOVA for continuous variables. Echocardiographic findings and correlation with the outcome were evaluated by a multivariable Cox model analysis and assessed by a proportional hazards model for time to event. Kaplan–Meier curves were performed to determine the event-free survival rate. Significance was considered as a p<0.05. Results RT/CT had a higher prevalence of moderate to severe mitral regurgitation (11.8%) p <0.001 and tricuspid regurgitation (13.9%) p=0.02. Stage ≥3 was (24.1%) in the RT/CT, (9.4%) in CT, and (16.1%) in controls p= 0.004. Additionally, stage ≥3 was a predictor of MACE at 18 months: RT/CT group HR 6.43 (3.06 – 13.1) p<0.001, CT HR 4.49 CI (2.27 – 8.89) p<0.001 and control HR 2.20 CI (1.13 – 4.26) p=0.02 (Table 1). MACE at 18 months for stage ≥3 was higher for all groups vs. stage ≤ 2. MACE at 18 months after TAVR was significantly higher in stage >3 for RT/CT (57.4%) and CT only (61.2%) vs. CL (27.2%) p<0.001 (Figure 1B). Conclusions In addition to predicting aortic stenosis risk in cancer patients before TAVR, cardiac damage staging is a strong predictor of MACE at 18 months in patients post-RT/CT and CT and suggests that these patients may benefit from earlier stratification for TAVR prior to reaching stage 3. Future studies with longer follow-up should be explored to evaluate its usefulness in this complex population.

Frailty prevalence among older decompensated heart failure patients

Abstract Background Frailty is a clinical syndrome characterized by diminished strenght, endurance and reduced physiologic function that increases an individual’s vulnerability. This syndrome often coexists in elderly patients with heart failure and can have a negative impact on their health and well-being. In the last few years four domains of frailty had been described: clinical, functional, psyco-cognitive and social. Purpose To determine the prevalence of frailty in each domain in patients 65 years of age and older with decompensated heart failure (DHF). Methods Prospective and observational study carried out in consecutive patients admitted to hospital due to DHF. Different validated scales were used. Clinical Domain: Charlson Comorbidity Index (CCI), MiniNutritional Assessment (MNA), Clinical Frailty scale CFS), New York Heart Association classification (NYHA); Functional Domain: Timed Up and Go (Up&Go), Short Physical Performance Battery, Fried phenotype (SPPB), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL); Psyco-cognitive Domain: Minimental State Examination (MMSE), Yesevage Geriatric Depression Scale (YGDS); Social Domain: Old American Resources and Services (OARS). All patients signed the informed consent and were evaluated when they were clinically stable. Results 200 consecutive patients were included, aged 81.1 (SD 7.7),108 (54%) were female. Diabetes was present in 89 (44.7%) patients, arterial hypertension in 182 (91.5%), dyslipidemia in 138 (69.3%), active smoking in 8 (4.1 %), chronic obstructive pulmonary disease in 66 (33.5%), apnea 44 (22.4%), neoplasms in 36 (18.3%), chronic renal failure in 48 (24.4%), previous myocardial infarction in 42 (21.3%), stroke in 245 (12.2%), previous heart failure in 145 (73.6%), atrial fibrillation in 132 (66.7%). 10 (5%) lived in a nursing home. The in-hospital all-cause mortality rate was 7 (3.5%). Clinical domain: 125 (65.1%) had high comorbidity (CCI). 60 (43.1%) were malnourished (MNA) and 129 (70.9 %) considered as frail (CFS). 151 (77%) were in NYHA Functional Class III-IV. Functional domain: 165 (99.4 %) (Up&Go) and 170 (97.1 %) (SPPB) were considered at fall risk. 147 (83.5%), frail by the Fried Phenotype. 188 (97.4 %) (ADL) and 173 (89.6 %) (IADL) had some degree of dependence. Psyco-cognitive: 82 (44.8%) had cognitive impairment (MMSE) and 70 (38%) some depression degree (YGDS). Social: 28 (15.4%) considered not to have a good social support (OARS). (See Table for details) Conclusions Patients with DHF are a complex and frail population that needs a holistic approach. The prevalence of frailty is high. In order to know how reversible frailty could be in older patients suffering DHF, clinical, functional, psyco-cognitive and social interventional trials are needed.

Kidney retransplantation outcomes in adults aged 70 and older: Analysis of risk factors and survival.

An increasing number of older patients are undergoing kidney transplant. Because of a finite longevity, more patients will be faced with failing allografts. At present there is a limited understanding of the benefits and risks associated with kidney retransplantation in this challenging population. We performed a retrospective analysis of the Organ Procurement and Transplantation Network database of all adults ≥70 undergoing kidney retransplant from January 1, 2014 to December 31, 2022. We examined patient and graft survival of retransplanted patients compared to first time transplants. We also analyzed the risk factors that impacted the survival. During the study period there has been a significant rise in the number of retransplants performed, with 631 patients undergoing the procedure. Although clinically insignificant, overall graft, and patient survival rates were slightly lower in the retransplant group compared to the primary transplant group. With retransplant, patient survival was 91.3%, 75.6%, and 56.9% compared to 93.4%, 81.4%, and 64.4% with primary transplant at 1, 3, and 5 years, respectively. With retransplant, graft survival was 89.5%, 73.5%, 57.4% compared to 91.5%, 79.0%, and 63.6% in a primary transplant group at 1, 3, and 5 years, respectively. Multivariable analysis showed that factors predicting poor survival included longer time on dialysis before retransplantation and decreased functional capacity. No survival difference was noted between recipients of deceased versus living donor kidneys. Patients who underwent retransplantation before initiating dialysis had better patient and graft survival. Patients aged ≥70 achieve satisfactory outcomes following kidney retransplantation, highlighting that chronologic age should not preclude this medically complex population from this life-saving procedure. Improvement in functional status and timely retransplantation are the key factors to successful outcome.

Abstract 16276: Complex Corynebacterium Case: Management of Recurrent Corynebacterium Bacteremia in a Patient With Cardiac Implanted Electronic Device and Left Ventricular Assist Device

Background Cardiac implantable electronic device (CIED) infections are morbid and costly. Atypical organisms are increasingly recognized as a cause of CIED infections. We present a case of recurrent Corynebacterium striatum bacteremia requiring CIED and left ventricular assist device (LVAD) extraction. Case Presentation A 54-year-old female dialysis patient with diabetes, ischemic cardiomyopathy, primary prevention single chamber transvenous defibrillator (ICD) 8 years prior, and destination LVAD presented with chronic C. striatum driveline site infection and relapsing and remitting bacteremia. Over the prior two years, she suffered from chronic driveline infections requiring wound care, driveline washouts, and antibiotics, although not seen by the electrophysiology (EP) team. After a fourth episode of bacteremia, she underwent ICD extraction and LVAD pump exchange, followed by 6 weeks of vancomycin and 3 months of rifampin. She then remained free of bacteremia for 19 months, though continued to demonstrate evidence of driveline infection despite pump exchange. Ultimately, C. striatum bacteremia recurred. Given unrelenting soft tissue infection and recurrent bacteremia, redo LVAD exchange was deferred and she was treated with lifelong suppressive antibiotics. Discussion Corynebacterium species have historically been considered skin flora, but more recently have been identified as pathogens, both as a cause of endocarditis, and a common organism in LVAD associated soft tissue infections. There are few reports of CIED infection. Source control is difficult in bacteremia patients with both CIED and LVAD. In this case, recurrent bacteremia could be attributed to recurrent driveline-soft tissue infection. However, the prolonged freedom from bacteremia off antibiotics after CIED extraction, despite ongoing soft tissue and driveline infection, argues that her transvenous ICD may have been seeded. This case highlights the growing spectrum of bacteria implicated in CIED-related infection, that early extraction may be a critical intervention regardless of infectious source, and importance of multidisciplinary discussions including heart failure, surgery, infectious disease, and EP to improve outcomes in this complex population.

Genomic signals of local adaptation in Picea crassifolia

BackgroundGlobal climate change poses a grave threat to biodiversity and underscores the importance of identifying the genes and corresponding environmental factors involved in the adaptation of tree species for the purposes of conservation and forestry. This holds particularly true for spruce species, given their pivotal role as key constituents of the montane, boreal, and sub-alpine forests in the Northern Hemisphere.ResultsHere, we used transcriptomes, species occurrence records, and environmental data to investigate the spatial genetic distribution of and the climate-associated genetic variation in Picea crassifolia. Our comprehensive analysis employing ADMIXTURE, principal component analysis (PCA) and phylogenetic methodologies showed that the species has a complex population structure with obvious differentiation among populations in different regions. Concurrently, our investigations into isolation by distance (IBD), isolation by environment (IBE), and niche differentiation among populations collectively suggests that local adaptations are driven by environmental heterogeneity. By integrating population genomics and environmental data using redundancy analysis (RDA), we identified a set of climate-associated single-nucleotide polymorphisms (SNPs) and showed that environmental isolation had a more significant impact than geographic isolation in promoting genetic differentiation. We also found that the candidate genes associated with altitude, temperature seasonality (Bio4) and precipitation in the wettest month (Bio13) may be useful for forest tree breeding.ConclusionsOur findings deepen our understanding of how species respond to climate change and highlight the importance of integrating genomic and environmental data in untangling local adaptations.

Validating and Improving Adjusted Clinical Group's Future Hospitalization and High-Cost Prediction Models for Dutch Primary Care.

The rise in health care costs, caused by older and more complex patient populations, requires Population Health Management approaches including risk stratification. With risk stratification, patients are assigned individual risk scores based on medical records. These patient stratifications focus on future high costs and expensive care utilization such as hospitalization, for which different models exist. With this study, the research team validated the accuracy of risk prediction scores for future hospitalization and high health care costs, calculated by the Adjusted Clinical Group (ACG)'s risk stratification models, using Dutch primary health care data registries. In addition, they aimed to adjust the US-based predictive models for Dutch primary care. The statistical validity of the existing models was assessed. In addition, the underlying prediction models were trained on 95,262 patients' data from de Zoetermeer region and externally validated on data of 48,780 patients from Zeist, Nijkerk, and Urk. Information on age, sex, number of general practitioner visits, International Classification of Primary Care coded information on the diagnosis and Anatomical Therapeutic Chemical Classification coded information on the prescribed medications, were incorporated in the model. C-statistics were used to validate the discriminatory ability of the models. Calibrating ability was assessed by visual inspection of calibration plots. Adjustment of the hospitalization model based on Dutch data improved C-statistics from 0.69 to 0.75, whereas adjustment of the high-cost model improved C-statistics from 0.78 to 0.85, indicating good discrimination of the models. The models also showed good calibration. In conclusion, the local adjustments of the ACG prediction models show great potential for use in Dutch primary care.

Characteristics associated with blindness or visual impairment within the adolescent demographic: a national cohort analysis

BackgroundPsychosocial metrics associated with self-reported blindness or visual impairment for adolescents in the National Survey of Drug Use and Health (NSDUH) have not been fully characterized. This retrospective cohort analysis of the latest NSDUH aimed to determine novel characteristics associated with self-reported visual loss among adolescents in the United States. MethodsData from the NSDUH2020, a publicly available, federally validated database, were analyzed. Self-reported severe visual impairment or blindness was defined as being truly blind or having serious difficulty seeing even when wearing corrective lenses (s-rSVI). Inclusion criteria were all cases of s-rSVI in adolescents aged 12-17 years. NSDUH weights were used to accommodate complex survey design, nonresponse rates, and population variance. Weighted percentages, asymptotic two-sided Rao-Scott χ2 analyses, and multivariable binary logistic regression were performed. Statistical significance was considered reached at P < 0.05. ResultsA total of 5,667 adolescents aged 12-17 years were surveyed, and s-rSVI occurred in 236 cases (weighted percentage, 3.48%). Within our final risk model, characteristics associated with enhanced odds of s-rSVI based on multivariable logistic regression analysis were female sex, Asian and Latino race/ethnicity (relative to non-Hispanic White), and self-reported serious difficulty hearing and concentrating (all P < 0.05). ConclusionsThis national retrospective cohort analysis highlights risk factors associated with s-rSVI for adolescents within the 2020 NSDUH. Clinicians and policymakers should consider at-risk demographics for s-rSVI during development and enhancement of screening programs, population health initiatives, and healthcare policy issues.

Efficacy of Various Eco-Friendly Pesticides on Insect Pest Complex of Chilli (Capsicum annum L.)

The population of insect pest complex on chilli and its damage upon the plant was monitored upon treatment with formulated Beauveria bassiania (0.5 ml Lˉ¹), tobacco leaf extract (5 ml Lˉ¹), neem oil (5 ml Lˉ¹) and ginger garlic paste (50 g Lˉ¹) by giving two sprays. The experiment was conducted at the experimental farm, New Colony, Ward 7, Chumukedima, Nagaland beginning from February 2021 to May 2021. The experiment was laid out in Randomized Block Design with four treatments and one control. A total of nine insect pests under seven orders and ten families were observed. The incidence of aphids, whitefly, thrips and fruit borer were major pests while others were non-significant. The results revealed that all biopesticides under study were superior and there was significant reduction over control against the insect pest complex of chilli. The most effective control was recorded in neem oil against aphids, whitefly, thrips and fruit borer with mean per cent reduction of 56.08%, 61.76%, 53.09% and 57.37%, respectively while the least was recorded in the treatment done with tobacco leaf extract.

Small Non-Coding RNAs in Male Reproduction.

Male reproductive functions are strictly regulated in order to maintain sperm production and fertility. All processes are controlled by precise regulation of gene expression, which creates specific gene expression programs for different developmental stages and cell types, and forms the functional basis for the reproductive system. Small non-coding RNAs (sncRNAs) are involved in gene regulation by targeting mRNAs for translational repression and degradation through complementary base pairing to recognize their targets. This review article summarizes the current knowledge on the function of different classes of sncRNAs, in particular microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), during male germ cell differentiation, with the focus on sncRNAs expressed in the germline. Although transcriptionally inactive, mature spermatozoa contain a complex population of sncRNAs, and we also discuss the recently identified role of sperm sncRNAs in the intergenerational transmission of epigenetic information on father's environmental and lifestyle exposures to offspring. Finally, we summarize the current information on the utility of sncRNAs as potential biomarkers of infertility that may aid in the diagnosis and prediction of outcomes of medically assisted reproduction.

Trends in performance of hospital outpatient procedures and associated 30-day costs among Medicare beneficiaries from 2011 to 2018

BackgroundUnited States healthcare has increasingly transitioned to outpatient care delivery. The degree to which Academic Medical Centers (AMCs) have been able to shift surgical procedures from inpatient to outpatient settings despite higher patient complexity is unknown. MethodsThis observational study used a 20% sample of fee-for-service Medicare beneficiaries age 65 and older undergoing eight elective procedures from 2011 to 2018 to model trends in procedure site (hospital outpatient vs. inpatient) and 30-day standardized Medicare costs, overall and by hospital teaching status. ResultsOf the 1,222,845 procedures, 15.9% occurred at AMCs. There was a 2.42% per-year adjusted increase (95% CI 2.39%–2.45%; p < .001) in proportion of outpatient hospital procedures, from 68.9% in 2011 to 85.4% in 2018. Adjusted 30-day standardized costs declined from $18,122 to $14,353, (-$560/year, 95% CI -$573 to -$547; p < .001). Patients at AMCs had more chronic conditions and higher predicted annual mortality. AMCs had a lower proportion of outpatient procedures in all years compared to non-AMCs, a difference that was statistically significant but small in magnitude. AMCs had higher costs compared to non-AMCs and a lesser decline over time (p < .001 for the interaction). AMCs and non-AMCs saw a similar decline in 30-day mortality. ConclusionsThere has been a substantial shift toward outpatient procedures among Medicare beneficiaries with a decrease in total 30-day Medicare spending as well as 30-day mortality. Despite a higher complexity population, AMCs shifted procedures to the outpatient hospital setting at a similar rate as non-AMCs. ImplicationsThe trend toward outpatient procedural care and lower spending has been observed broadly across AMCs and non-AMCs, suggesting that Medicare beneficiaries have benefited from more efficient delivery of procedural care across academic and community hospitals.

Synaptic Involvement of the Human Amygdala in Parkinson’s Disease

α-Synuclein, a protein mostly present in presynaptic terminals, accumulates neuropathologically in Parkinson’s disease in a 6-stage sequence and propagates in the nervous system in a prion-like manner through neurons and glia. In stage 3, the substantia nigra are affected, provoking motor symptoms and the amygdaloid complex, leading to different nonmotor symptoms; from here, synucleinopathy spreads to the temporal cortex and beyond. The expected increase in Parkinson's disease incidence accelerates the need for detection biomarkers; however, the heterogeneity of this disease, including pathological aggregates and pathophysiological pathways, poses a challenge in the search for new therapeutic targets and biomarkers. Proteomic analyses are lacking, and the literature regarding synucleinopathy, neural and glial involvement, and volume of the human amygdaloid complex is controversial. Therefore, the present study combines both proteomic and stereological probes. Data-independent acquisition-parallel accumulation of serial fragmentation proteomic analysis revealed a remarkable proteomic impact, especially at the synaptic level in the human amygdaloid complex in Parkinson’s disease. Among the 199 differentially expressed proteins, guanine nucleotide-binding protein G(i) subunit alpha-1 (GNAI1), elongation factor 1-alpha 1 (EEF1A1), myelin proteolipid protein (PLP1), neuroplastin (NPTN), 14-3-3 protein eta (YWHAH), gene associated with retinoic and interferon-induced mortality 19 protein (GRIM19), and orosomucoid-2 (ORM2) stand out as potential biomarkers in Parkinson’s disease. Stereological analysis, however, did not reveal alterations regarding synucleinopathy, neural or glial populations, or volume changes. To our knowledge, this is the first proteomic study of the human amygdaloid complex in Parkinson’s disease, and it identified possible biomarkers of the disease. Lewy pathology could not be sufficient to cause neurodegeneration or alteration of microglial and astroglial populations in the human amygdaloid complex in Parkinson’s disease. Nevertheless, damage at the proteomic level is manifest, showing up significant synaptic involvement.

Parasites as indicators of habitat preferences by hybrids between estuarine and freshwater congeneric silversides (Atherinopsidae)

Silversides of the genus Odontesthes are characterized by their conserved morphology and vast phenotypic plasticity. They have developed complex population structures, promoting hybridization and speciation phenomena and often leading to intricate taxonomies. Within this genus, O. argentinensis, an originally marine species and O. bonariensis, a freshwater species, coexist in Mar Chiquita Coastal Lagoon (central Argentina). This lagoon has an inlet to the sea, creating a saline gradient that promotes highly variable conditions throughout the system. While O. argentinensis has established a resident population inside the lagoon, O. bonariensis is only sporadically found, inhabiting mainly tributary streams. Notably, hybrids between the two have been found in the lagoon. Parasites can significantly influence hybridization in host species, either promoting or hindering the process. From an evolutionary standpoint, parasites can impact hybridization by altering host immune responses, affecting host ecology and fitness. As a result, parasites can be valuable indicators of hybrid host ecology and their evolutionary trajectories. The present study analyzes the parasite communities of these sympatric Odontesthes and their hybrids, and determines their habitat preferences. While O. argentinensis showed evidence of marine parasites, O. bonariensis had a dominance of freshwater species as expected. And, although parasites of hybrids displayed similarities with both parental species, they indicated a preference of these hosts by freshwater habitats or longer periods of permanence in the oligohaline areas of Mar Chiquita. The presence of pure parental species, the differences in habitat use found between them and hybrids, and the conditioning effect of environmental heterogeneity over the hybridization event support a mosaic model for this hybrid zone. Finally, studies of parasitism in hybrid zones may contribute to understand the evolutionary history and stability of boundaries or possible biological barriers between host species, and they also provide insight on how natural selection and evolution drive speciation, colonization and habitat use in transitional environments.

Morpho-colorimetric characterization of the perigonium of the Alstroemeria pulchra complex (Alstroemeriaceae, Alstroemerieae) as an aid to delimit its infraspecific taxa

The main taxonomic characters of Alstroemeria derive from the perianth and have traditionally been used from qualitative perspectives, which difficult their interpretation, especially in species considered as infraspecific complexes. Through spectrophotometry and specialized image analysis approaches, a total of one hundred and sixty flowers from twenty populations of the Alstroemeria pulchra complex were quantified. Our results allowed us to recognize the infraspecific taxa A. pulchra subsp. lavandulacea, A. pulchra var. maxima, and A. pulchra var. pulchra through the color, shape, size, and ornamental patterns of their tepals. The colorimetric information subjected to discriminant analysis corroborate the taxonomic utility of flower color. Similar results were obtained from the analysis of ornamental patterns, sizes, and shapes of the tepals. The discriminant analysis of the combined matrix that included the shape and ornamental patterns allowed us to identify three non-overlapping groups within A. pulchra, with a high differentiation degree. These results significantly contribute to improving the understanding of the phenotypic variability of A. pulchra and its infraspecific taxa. This information will serve as a basis for systematic studies that will address the relationships between these and other related taxa from an integrative taxonomic perspective.

Sensitivity to tebuconazole and carbendazim in Fusarium graminearum species complex populations causing wheat head blight in southern Brazil

Sensitivity to tebuconazole and carbendazim in Fusarium graminearum species complex populations causing wheat head blight in southern Brazil