Biological and social cascades of prenatal contextual risk and maternal psychological distress to early-childhood adjustment.

In the peripartum, putative mechanisms in the transmission of prenatal contextual risk and maternal psychological distress include biological and social processes. In this study, path analyses were used to test unique, cascading pathways of prenatal contextual risk and pre- and postnatal maternal psychological distress through social mediators (parenting) and biological mediators (infant stress physiology) on infant temperament and toddler adjustment. The sample is comprised of racially and ethnically diverse first-time mothers (N = 200) living in low-income contexts (< 200% poverty) who were followed from pregnancy to 18-36 months postpartum. In pregnancy, mothers reported contextual risk and psychological distress (anxiety, depression). In the postpartum, mothers reported their psychological distress. At 2-4 months postpartum, observed mother-infant interactions were coded for sensitive responsiveness. Infant cortisol baseline and reactivity to a lab stressor were collected when infants were 4-6 months old. Mothers reported on infant's temperament (negative affect, effortful control) at 10-12 months and on child adjustment (internalizing, externalizing symptoms) at 18-36 months. Prenatal contextual risk predicted infant cortisol reactivity. Prenatal psychological distress predicted postnatal distress but, when accounting for postnatal distress, did not predict putative mediators or indicators of child adjustment. In contrast, maternal postnatal depression predicted subsequent maternal sensitive responsiveness, which in turn predicted later infant baseline cortisol and cortisol reactivity. Baseline cortisol predicted infant negative affectivity, which predicted toddler internalizing and externalizing symptoms. There was no evidence of mediated effects of prenatal variables on child adjustment outcomes, whereas contextual risk, postnatal psychological distress, and parenting were more salient predictors of child adjustment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Whole-genome sequencing analysis of multidrug-resistant Serratia marcescens isolates in an intensive care unit in Brazil.

INTRODUCTION: Serratia marcescens is an opportunistic pathogen found ubiquitously in the environment and associated with a wide range of nosocomial infections. This multidrug-resistant bacterium has been a cause of concern for hospitals and healthcare facilities due to its ability to spread rapidly and cause outbreaks. Next generation sequencing genotyping of bacterial isolates has proven to be a valuable tool for tracking the spread and transmission of nosocomial infections. This has allowed for the identification of outbreaks and transmission chains, as well as determining whether cases are due to endogenous or exogenous sources. Evidence of nosocomial transmission has been gathered through genotyping methods. The aim of this study was to investigate the genetic diversity of carbapenemase-producing S. marcescens in an outbreak at a public hospital in Cuiaba, MT, Brazil. METHODOLOGY: Ten isolates of S. marcenses were sequenced and antibiotic resistance profiles analyzed over 12 days. RESULTS: The isolates were clonal and multidrug resistant. Gentamycin and tigecycline had sensitivity in 90% and 80% isolates, respectively. Genomic analysis identified several genes that encode ß-lactamases, aminoglycoside-modifying enzymes, efflux pumps, and other virulence factors. CONCLUSIONS: Systematic surveillance is crucial in monitoring the evolution of S. marcescens genotypes, as it can lead to early detection and prevention of outbreaks.

Cleavage of an engulfment peptidoglycan hydrolase by a sporulation signature protease in Clostridioides difficile.

In the model organism Bacillus subtilis, a signaling protease produced in the forespore, SpoIVB, is essential for the activation of the sigma factor σK, which is produced in the mother cell as an inactive pro-protein, pro-σK. SpoIVB has a second function essential to sporulation, most likely during cortex synthesis. The cortex is composed of peptidoglycan (PG) and is essential for the spore's heat resistance and dormancy. Surprisingly, the genome of the intestinal pathogen Clostridioides difficile, in which σK is produced without a pro-sequence, encodes two SpoIVB paralogs, SpoIVB1 and SpoIVB2. Here, we show that spoIVB1 is dispensable for sporulation, while a spoIVB2 in-frame deletion mutant fails to produce heat-resistant spores. The spoIVB2 mutant enters sporulation, undergoes asymmetric division, and completes engulfment of the forespore by the mother cell but fails to synthesize the spore cortex. We show that SpoIIP, a PG hydrolase and part of the engulfasome, the machinery essential for engulfment, is cleaved by SpoIVB2 into an inactive form. Within the engulfasome, the SpoIIP amidase activity generates the substrates for the SpoIID lytic transglycosylase. Thus, following engulfment completion, the cleavage and inactivation of SpoIIP by SpoIVB2 curtails the engulfasome hydrolytic activity, at a time when synthesis of the spore cortex peptidoglycan begins. SpoIVB2 is also required for normal late gene expression in the forespore by a currently unknown mechanism. Together, these observations suggest a role for SpoIVB2 in coordinating late morphological and gene expression events between the forespore and the mother cell.

Assessment of the Activity of Nitroisoxazole Derivatives against Trypanosoma cruzi.

The development of new compounds to treat Chagas disease is imperative due to the adverse effects of current drugs and their low efficacy in the chronic phase. This study aims to investigate nitroisoxazole derivatives that produce oxidative stress while modifying the compounds' lipophilicity, affecting their ability to fight trypanosomes. The results indicate that these compounds are more effective against the epimastigote form of T. cruzi, with a 52 ± 4% trypanocidal effect for compound 9. However, they are less effective against the trypomastigote form, with a 15 ± 3% trypanocidal effect. Additionally, compound 11 interacts with a higher number of amino acid residues within the active site of the enzyme cruzipain. Furthermore, it was also found that the presence of a nitro group allows for the generation of free radicals; likewise, the large size of the compound enables increased interaction with aminoacidic residues in the active site of cruzipain, contributing to trypanocidal activity. This activity depends on the size and lipophilicity of the compounds. The study recommends exploring new compounds based on the nitroisoxazole skeleton, with larger substituents and lipophilicity to enhance their trypanocidal activity.

The cost of genetic diagnosis of suspected hereditary pediatric cataracts with whole-exome sequencing from a middle-income country perspective: a mixed costing analysis.

Up to 25% of pediatric cataract cases are inherited. There is sparse information in the literature regarding the cost of whole-exome sequencing (WES) for suspected hereditary pediatric cataracts. Molecular diagnosis of suspected hereditary pediatric cataracts is important for comprehensive genetic counseling. We performed a partial economic evaluation with a mixed costing analysis, using reimbursement data and microcosting approach with a bottom-up technique to estimate the cost of using WES for genetic diagnosis of suspected hereditary pediatric cataracts from the perspective of the Brazilian governmental health care system. One hundred and ten participants from twenty-nine families in Rio de Janeiro (RJ) were included. Costs of consumables, staff and equipment were calculated. Two scenarios were created: (1) The reference scenario included patients from RJ with suspected hereditary pediatric cataracts plus two family members. (2) The alternative scenario considered other genetic diseases, resulting in 5,280 exams per month. Sensitivity analysis was also performed. In the reference scenario, the total cost per exam was 700.09 United States dollars (USD), and in the alternative scenario, the total cost was 559.23 USD. The cost of WES alone was 527.85 USD in the reference scenario and 386.98 USD in the alternative scenario. Sensitivity analysis revealed that the largest costs were associated with consumables in both scenarios. Economic evaluations can help inform policy decisions, especially in middle-income countries such as Brazil.

Prophylactic use of standardized extract of propolis of Apis mellifera (EPP-AF®) reduces lung inflammation and improves survival in experimental lethal sepsis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.

Outcomes of atypical lobular hyperplasia managed by active surveillance or immediate surgery.

BACKGROUND: Atypical lobular hyperplasia (ALH) is typically diagnosed via needle core biopsy (NCB) and is commonly removed surgically in light of upgrade to malignancy rates of 1%-5%. As studies on radiographic outcomes of ALH managed by active surveillance (AS) are limited, we investigated the upgrade rates of surgically excised ALH as well as radiographic progression during AS. METHODS: In this retrospective study, 125 patients with 127 ALH lesions diagnosed via NCB at Weill Cornell Medicine from 2015 to 2021 were included. The upgrade rate to cancer was determined for patients who had surgical management ≤6 months after biopsy. Among patients with ALH managed by AS, we investigated radiographic progression on 6-month interval imaging. RESULTS: Of 127 ALH lesions, 75% (n = 95) were immediately excised and 25% (n = 32) were observed under AS. The upgrade rate of immediately excised ALH was 2.1% (n = 2; invasive ductal carcinoma [IDC], T1N0 and IDC, and T1Nx). In the AS cohort, no ALH lesions progressed radiographically during the follow-up period of 22.5 months (median), with all remaining stable (50%, n = 16), resolving (47%, n = 15), or decreasing in size (3%, n = 1). CONCLUSIONS: In this study, NCB-diagnosed ALH had a low upgrade to malignancy rate (2.1%), and no ALH lesions managed by AS progressed radiographically during the follow-up period of 22.5 months. These results support AS as the favorable option for patients with pure ALH on biopsy, with surgical excision for lesions that progress on surveillance.

Helicobacter pylori exposure among the Awajún of the Peruvian Amazon: Prevalence and environmental, social, and biological associations.

OBJECTIVES: Helicobacter pylori (H. pylori)-a gastric bacteria affecting almost 50% of the global population and leading to ulcers and cancer in severe cases-is a growing health concern among Indigenous populations who report a high burden of reported poor general health and gastrointestinal distress. We test hypothesized associations between H. pylori exposure patterns and environmental, social, and biological conditions among a sample of 212 Indigenous Awajún adults (112 males, 100 females, ages 18-65 years) living in the northern Peruvian Amazon. MATERIALS AND METHODS: Dried blood spots were analyzed for H. pylori-specific IgG using a recently developed enzyme-linked immunosorbent assay. Resulting seropositivity rates and antibody concentrations, proxying past exposures to H. pylori were analyzed in relation to relevant environmental (toilet type, floor material, reported water quality), social (household size and education level), and biological (age, sex, BMI, blood pressure, immune and metabolic biomarkers) factors using multivariable regression analyses. RESULTS: We found near ubiquitous seropositivity for H. pylori exposure in our sample (99.1% seropositive). In the regression analyses, elevations in H. pylori antibody concentrations were significantly higher among males compared to females (ß = 0.36, p = 0.01). No associations were found with any other factors. DISCUSSION: Anthropological research in the study communities suggests that the male bias in elevations of H. pylori antibody concentrations is related to cultural and biological factors. Future research is needed to further unravel these biocultural dynamics and determine whether elevations in H. pylori antibody concentrations have clinical relevance for gastrointestinal health outcomes in this population.

The impact of out-of-home care on brain development: a brief review of the neuroscientific evidence informing our understanding of children's attachment outcomes.

Researchers interested in the effects of early experiences of caregiving adversity have employed neuroscientific methods to illuminate whether and how such environmental input impacts on brain development, and whether and how such impacts underpin poor socioemotional outcomes in this population. Evidence is compelling in documenting negative effects on the individual's neurodevelopment following exposure to adverse or disadvantaged environments such as institutionalization or maltreatment. Neuroimaging research focused specifically on attachment-relevant processing of socioemotional stimuli and attachment outcomes among children looked-after is scarcer, but largely consistent. This review begins by summarizing the key general brain structural and functional alterations associated with caregiving deprivation. Then, neuroscientific evidence that is more directly relevant for understanding these children's attachment outcomes, both by employing social stimuli and by correlating children's neural markers with their attachment profiles, is reviewed. Brief interpretations of findings are suggested, and key limitations and gaps in the literature identified.

Acenaphthylene-Based Chromophores for Dye-Sensitized Solar Cells: Synthesis, Spectroscopic Properties, and Theoretical Calculations.

A set of acenaphthylene dyes with arylethynyl π-bridges was tested for dye-sensitized solar cells (DSSCs). Crucial steps for the extension of the conjugated system from the acenaphylene core involved Sonogashira coupling reactions. Phenyl, thiophene, benzotriazole, and thieno-[3,2-b]thiophene moieties were employed to extend the conjugation of the π-bridges. The systems were characterized by cyclic voltammetry and by UV-vis absorption and emission. The spectroscopic characterization showed that the last three bridges resulted in red-shifted absorption and emission spectra relative to the parent phenyl-bridged compound, in accordance with TD-DFT calculations. The phenylethynyl derivative 6a achieved a conversion efficiency of 2.51% with Voc, Jsc, and FF values of 0.365 V, 13.32 mA/cm2, and 0.52, respectively. The efficiency of this compound improved to 3.15% with the addition of CDCA (10 mM), representing the best efficiency result in this study. The overall conversion efficiency of the other aryl derivatives 6b-d proved to be significantly inferior (14-40%) to that of 6a due to a significant decrease of Jsc.

Micromechanical Indentation Platform for Rapid Analysis of Viscoelastic Biomolecular Hydrogels.

The advent of biomedical applications of soft bioinspired materials has entailed an increasing demand for streamlined and expedient characterization methods meant for both research and quality control objectives. Here, a novel measurement system for the characterization of biological hydrogels with volumes as low as 75 µL was developed. The system is based on an indentation platform equipped with micrometer drive actuators that allow the determination of both the fracture points and Young's moduli of relatively stiff polymers, including agarose, as well as the measurements of viscosity for exceptionally soft and viscous hydrogels, such as DNA hydrogels. The sensitivity of the method allows differentiation between DNA hydrogels produced by rolling circle amplification based on different template sequences and synthesis protocols. In addition, the polymerization kinetics of the hydrogels can be determined by time-resolved measurements, and the apparent viscosities of even more complex DNA-based nanocomposites can be measured. The platform presented here thus offers the possibility to characterize a broad variety of soft biomaterials in a targeted, fast, and cost-effective manner, holding promises for applications in fundamental materials science and ensuring reproducibility in the handling of complex materials.

Cultural applicability and desirability of 'Broodles': The first serious game intervention for siblings of children with disabilities.

Objective: Serious games can serve as easily accessible interventions to support siblings of children with disabilities, who are at risk of developing mental health problems. The Dutch serious game 'Broodles' was developed for siblings aged 6-9 years. The current study aims to assess the cultural applicability, desirability, feasibility, and acceptability of 'Broodles' in Norway. Methods: Norwegian siblings (N = 16) aged 6-13 years and parents (N = 12) of children with intellectual disabilities assessed the game. Their feedback data from interviews and questionnaires were sorted using a model of engagement factors in serious games. Results: At pre-use, participants showed interest in the game, and after initial use the participants were overall positive about the format, content and objectives, including validation of emotions and recognition. The participants had suggestions for improved engagement and feasibility. Conclusion: The game was found to be culturally applicable, desirable and acceptable, although Norwegian translation is necessary for further evaluation. Recommendations to enhance engagement were provided, including suggestions to play the game with parents or in a group. Innovation: This initial assessment of the serious game Broodles in a non-Dutch setting shows promise for an innovative way of supporting siblings of children with disabilities.

Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers.

Children with rare, relapsed or refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized treatment recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling with drug sensitivity testing (DST) of patient-derived tumor cells, has potential to identify treatment options when standard-of-care is exhausted. The goal of this prospective observational study was to generate FPM data for pediatric patients with relapsed or refractory cancer. The primary objective was to determine the feasibility of returning FPM-based treatment recommendations in real time to the FPM tumor board (FPMTB) within a clinically actionable timeframe (<4 weeks). The secondary objective was to assess clinical outcomes from patients enrolled in the study. Twenty-five patients with relapsed or refractory solid and hematological cancers were enrolled; 21 patients underwent DST and 20 also completed genomic profiling. Median turnaround times for DST and genomics were within 10 days and 27 days, respectively. Treatment recommendations were made for 19 patients (76%), of whom 14 received therapeutic interventions. Six patients received subsequent FPM-guided treatments. Among these patients, five (83%) experienced a greater than 1.3-fold improvement in progression-free survival associated with their FPM-guided therapy relative to their previous therapy, and demonstrated a significant increase in progression-free survival and objective response rate compared to those of eight non-guided patients. The findings from our proof-of-principle study illustrate the potential for FPM to positively impact clinical care for pediatric and adolescent patients with relapsed or refractory cancers and warrant further validation in large prospective studies. ClinicalTrials.gov registration: NCT03860376 .

Refractive Error Change and Overminus Lens Therapy for Childhood Intermittent Exotropia.

Importance: Increased myopic shift was found to be associated with 1 year of overminus spectacle treatment for children with intermittent exotropia (IXT). Persistence of myopic shift after discontinuing overminus spectacles is unknown. Objective: To compare refractive error change over 3 years in children with IXT originally treated with overminus vs nonoverminus spectacles. Design, Setting, and Participants: This study was an 18-month extension of the Trial of Overminus Spectacle Therapy for Intermittent Exotropia cohort, which previously randomized children aged 3 to 10 years with IXT and baseline spherical equivalent refractive error (SER) between -6.00 diopters (D) and 1.00 D to overminus spectacles (-2.50 D for 12 months, -1.25 D for 3 months, and nonoverminus for 3 months) or nonoverminus spectacles. Children were recruited from 56 sites from July 2010 to February 2022. Data were analyzed from February 2022 to January 2024. Interventions: After trial completion at 18 months, participants were followed up at 24 and 36 months. Treatment was at investigator discretion from 18 to 36 months. Main Outcomes and Measures: Change in SER (cycloplegic retinoscopy) from baseline to 36 months. Results: Of 386 children in the Trial of Overminus Spectacle Therapy for Intermittent Exotropia, 223 (57.8%) consented to 18 months of additional follow-up, including 124 of 196 (63.3%) in the overminus treatment group and 99 of 190 (52.1%) in the nonoverminus treatment group. Of 205 children who completed 36-month follow-up, 116 (56.6%) were female, and the mean (SD) age at randomization was 6.2 (2.1) years. Mean (SD) SER change from baseline to 36 months was greater in the overminus group (-0.74 [1.00] D) compared with the nonoverminus group (-0.44 [0.85] D; adjusted difference, -0.36 D; 95% CI, -0.59 to -0.12; P = .003), with 30 of 112 (26.8%) in the overminus group having more than 1 D of myopic shift compared with 14 of 91 (15%) in the nonoverminus group (risk ratio, 1.8; 95% CI, 1.0-3.0). From 12 to 36 months, mean (SD) myopic shift was -0.34 (0.67) D and -0.36 (0.66) D in the overminus and nonoverminus groups, respectively (adjusted difference, -0.001 D; 95% CI, -0.18 to 0.18; P = .99). Conclusions and Relevance: The greater myopic shift observed after 1 year of -2.50-D overminus lens treatment remained at 3 years. Both groups had similar myopic shift during the 2-year period after treatment weaning and cessation. The risk of myopic shift should be discussed with parents when considering overminus lens treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02807350.

Comprehensive phylogeny of Pieridae butterflies reveals strong correlation between diversification and temperature.

Temperature is thought to be a key factor influencing global species richness patterns. We investigate the link between temperature and diversification in the butterfly family Pieridae by combining next generation DNA sequences and published molecular data with fine-grained distribution data. We sampled nearly 600 pierid butterfly species to infer the most comprehensive molecular phylogeny of the family and curated a distribution dataset of more than 800,000 occurrences. We found strong evidence that species in environments with more stable daily temperatures or cooler maximum temperatures in the warm seasons have higher speciation rates. Furthermore, speciation and extinction rates decreased in tandem with global temperatures through geological time, resulting in a constant net diversification.

Fasting reduces satiety and increases hunger but does not affect the performance in resistance training.

Intermittent fasting (IF) has been suggested to reduce body fat percentage and improve non-communicable chronic diseases. However, little is known about resistance training (RT) and the subjective perception of hunger under fasted conditions. This study aimed to examine the effects of overnight fasting (12 h or 16 h fasting) on the maximum voluntary isometric contraction (MVIC) and countermovement jump (CMJ) performance in resistance-trained young male adults. In RT sessions, the maximum number of repetitions (MNR) and the total volume load (TVL) were evaluated in the back squat and leg press 45°. The volunteers performed all tests and the RT session in 3 different conditions: fed state, 12 and 16 hours of IF. The subjective perception of hunger was applied through an adapted visual analogue scale (adVAS). The results showed that strength and power variables did not change significantly: MVIC (p = 0.960), CMJ (p = 0.986), MNR back squat (p = 0.856), MNR leg press 45° (p = 0.998), TVL (p = 0.954). However, hunger was significantly greater after the 16-hour fasting (p = 0.001) compared to 12 hours of fasting and the fed state. Also, the desire to eat was greater after 16 hours (p = 0.001) compared to 12 hours of fasting and the fed state. This study indicates that IF for 12 or 16 hours does not significantly impair strength and power, but the longer the fasting duration, the greater are the hunger and desire to eat.

Establishing an infrastructure to optimize the integration of genomics into research: Results from a precision health needs assessment.

Researchers across the translational research continuum have emphasized the importance of integrating genomics into their research program. To date capacity and resources for genomics research have been limited; however, a recent population-wide genomic screening initiative launched at the Medical University of South Carolina in partnership with Helix has rapidly advanced the need to develop appropriate infrastructure for genomics research at our institution. We conducted a survey with researchers from across our institution (n = 36) to assess current knowledge about genomics health, barriers, and facilitators to uptake, and next steps to support translational research using genomics. We also completed 30-minute qualitative interviews with providers and researchers from diverse specialties (n = 8). Quantitative data were analyzed using descriptive analyses. A rapid assessment process was used to develop a preliminary understanding of each interviewee's perspective. These interviews were transcribed and coded to extract themes. The codes included types of research, alignment with precision health, opportunities to incorporate precision health, examples of researchers in the field, barriers, and facilitators to uptake, educational activity suggestions, questions to be answered, and other observations. Themes from the surveys and interviews inform implementation strategies that are applicable not only to our institution, but also to other organizations interested in making genomic data available to researchers to support genomics-informed translational research.

Researchers have recognized the significance of integrating genomics into their studies across the translational research continuum. However, limited capacity and resources have hindered progress in genomics research. We conducted a survey and qualitative interviews with researchers and healthcare providers from our institution to assess their understanding of genomics in health, identify barriers, and facilitators to its adoption, and determine next steps for supporting translational research using genomics. Themes identified included different types of research, alignment with precision health, opportunities to incorporate precision health, examples of researchers in the field, barriers, and facilitators to adoption, educational recommendations, unanswered questions, and other valuable observations. The insights gathered from the surveys and interviews informed the development of implementation strategies. These strategies can benefit not only our institution but also other researchers who are interested in providing access to genomic data to support genomics-informed translational research.