Genetic diversity, morphological traits, quality traits and antioxidants potentiality of Coccinia grandis germplasm under rainfed semi-arid region.

The present study was conducted to evaluate the genetic variability for morphological and qualitative traits of Coccinia for development of trait specific lines at ICAR-Central Horticultural Experiment Station (CIAH-RS), Panchmahals (Godhra), Gujarat during 2020-2022. In this study, we evaluated 26 gynoecious accessions to assess the genetic divergence through principal component and cluster analysis. The experiment was carried out in a randomized complete block design with three replications under rainfed semi-arid conditions. High values of PCV and GCV were observed for variables such as NFFP (25.13 and 22.20), PL (23.14 and 20.69), FD (24.01 and 21.46), AFW (22.98 and 20.13), NFPY (26.38 and 24.40), FYP (37.57 and 31.29), FY (35.55 and 33.20), AsC (28.65 and 27.73), Ac (24.32 and 21.06), TSS (37.23 and 35.94), DPPHL (20.71 and 20.38), FRAPL (21.08 and 20.92), TPF(20.81 and 20.45) respectively. High heritability coupled with high genetic advance as per cent of mean was observed for vine length (VL), internodal length (IL), number of female flowers per plant (NFFP), fruit length (FL), peduncle length (PL), fruit diameter (FD), average fruit weight (AFW), number of fruit per plant per year (NFPY), fruit yield per plant (FYP), fruit yield (FY), ascorbic acid (AsC), acidity (Ac), total soluble solids (TSS), total phenols in leaves TPL), total flavonoids in leaves TFL, CUPRAC in leaves (CUPRACL), DPPH in leaves (DPPHL), FRAP in leaves (FRAPL), Total phenols in fruits (TPF), Total flavonoids in fruits (TFF), CUPRAC in fruits (CUPRACF) and DPPH in fruits (DPPHF). The FYP exhibited a significant positive correlation with variables like VL (0.6833), IL (0.2991), NFFP (0.8107), FD (0.5245), AFW (0.6766), NFPY (0.7659), ASC (0.4611), TSS (0.5004) and TPF (0.4281). The estimates of genetic parameters revealed scope for further improvement of fruit yield by selection. Of the eight principal components, PC-I through PC-VIII had eigen values greater than 1 and it accounts 85.02% of the total variation for 26 gynoecious accessions of Ivy gourd. The eigen values of PC-I comprised 5.775% of total variation followed by PC-II (4.250%), PC-III (3.175%), PC-IV (2.588%), PC-V (1.828%), PC-VI (1.447%), PC-VII (1.179%) and PC-VIII (1.013%).The cluster VI and cluster I having highest mean values for most of traits under study. Thus, genotypes from the distinct cluster like cluster VI and I for should be used for selection of parents and varietal improvement for further breeding programme in ivy gourd.

Prescribing patterns and pharmacoeconomic analysis of antihypertensive drugs in South Indian population: A cross-sectional study.

Background: Global evidence-based recommendations for hypertension management are periodically updated, and ensuring adherence to the guidelines is imperative. Furthermore, the current high prevalence of hypertension effectuates a high health-care cost. Purpose: To evaluate the prescribing patterns of antihypertensive drugs and other factors affecting blood pressure (BP) with the objective of assessing the proportion of patients achieving the target BP and to perform a pharmacoeconomic analysis in a South Indian population. Materials and Methods: In a cross-sectional study, 650 patients previously diagnosed with hypertension and already on treatment with one or more drugs were included. A prospective interview of patients was done using a prevalidated questionnaire on various factors in BP control. Prescribing patterns and pharmacoeconomic analyses, namely, cost acquisition, cost of illness, and cost-effectiveness analyses were carried out. Results: Of 650 subjects, 257 (39.54%) achieved the target BP, while 393 (60.46%) did not. A significant association of age, occupational status, monthly family income, and area of residence in addition to physical activity and diet scores, with achieving target BP was noted. A significantly higher cost of anti-hypertensive drug treatment in achieving target BP (P = 0.02) was observed. Among patients who achieved target BP, 37.35% were on monotherapy and 48.25% on multiple drug therapy compared to 46.31% and 35.62%, respectively, in patients who did not. Average cost-effectiveness ratio were found to be Rs. 20.45 and Rs. 57.27, respectively, for single and multiple drug therapies, with incremental cost-effectiveness of Rs. 194.14 per additional patient treated with multiple free drug combinations. Conclusion: This study identified the anti-hypertensive prescribing pattern and provided insight into the various pharmacoeconomic factors that play a significant role in attaining target BP in the treated population.

A single institution pre-/post-comparison after introduction of an external urinary collection device for female medical patients.

Background: External urinary collection devices (EUCDs) may serve as an alternative to indwelling urinary catheters (IUCs) and decrease the rate of catheter associated urinary tract infections (CAUTIs). PureWick® is a novel female EUCD; however, no study has definitively proven benefit regarding reduction of CAUTIs. Aim: We sought to compare the CAUTI rate and IUC days before and after availability of the PureWick® EUCD at a single institution. We provide a descriptive analysis of female medical patients receiving an EUCD. Methods: A retrospective review of adult female patients admitted to a single institution on a medical service who received an IUC and/or an EUCD was performed. Patients who received an IUC in the 3 months before EUCD availability (PRE) were compared to patients who received an IUC and/or EUCD in the 12 months after (POST). Results: Out of 848 female patients, 292 received an EUCD in the POST cohort and overall, 656 received an IUC (259 (100%) PRE vs. 397 (67.4%) POST). Compared to the PRE cohort, the POST cohort had a higher number of IUC days (median, 3 vs 2 days, p = 0.001) and a higher rate of CAUTI (infections per 1000 catheter days, 9.3 vs 2.3, p = 0.001). The rate of UTI associated with EUCD use was 9.8 infections per 1000 device days. Discussion: While EUCDs might appear to be a promising alternative to IUCs for female patients, this single center pre-/post-analysis found that both the number of IUC days and the CAUTI rate increased after introduction of a female EUCD.

3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype.

Tumor immune response is shaped by the tumor microenvironment (TME), which often evolves to be immunosuppressive, promoting disease progression and metastasis. An important example is melanoma tumors, which display high numbers of tumor-associated macrophages (TAMs) that are immunosuppressive but also have the potential to restore anti-tumor activity. However, to therapeutically target TAMs, there is a need to understand the early events that shape their tumor-promoting profile. To address this, we built and optimized 3D in vitro co-culture systems, composed of a collagen-I matrix scaffolding murine bone-marrow-derived macrophages (BMDMs), YUMM1.7 melanoma cells, and fibroblasts to recreate the early melanoma TME and study how interactions with fibroblasts and tumor cells modulate macrophage immune activity. We monitored BMDM behavior and interactions through time-lapse imaging and characterized their activation and secretion. We found that stromal cells induced a rapid functional activation, with increased motility and response from BMDMs. Over the course of seven days, BMDMs acquired a phenotype and secretion profile that resembled melanoma TAMs in established tumors. Overall, the direct cell-cell interactions with the stromal components in a 3D environment shape BMDM transition to a TAM-like immunosuppressive state. Our systems will enable future studies of changes in macrophage-stromal cross-talk in the melanoma TME.

Cell shape, and not 2D migration, predicts extracellular matrix-driven 3D cell invasion in breast cancer.

Metastasis, the leading cause of death in cancer patients, requires the invasion of tumor cells through the stroma in response to migratory cues, in part provided by the extracellular matrix (ECM). Recent advances in proteomics have led to the identification of hundreds of ECM proteins, which are more abundant in tumors relative to healthy tissue. Our goal was to develop a pipeline to easily predict which ECM proteins are more likely to have an effect on cancer invasion and metastasis. We evaluated the effect of four ECM proteins upregulated in breast tumor tissue in multiple human breast cancer cell lines in three assays. There was no linear relationship between cell adhesion to ECM proteins and ECM-driven 2D cell migration speed, persistence, or 3D invasion. We then used classifiers and partial-least squares regression analysis to identify which metrics best predicted ECM-driven 2D migration and 3D invasion responses. We find that ECM-driven 2D cell migration speed or persistence did not predict 3D invasion in response to the same cue. However, cell adhesion, and in particular cell elongation and shape irregularity, accurately predicted the magnitude of ECM-driven 2D migration and 3D invasion. Our models successfully predicted the effect of novel ECM proteins in a cell-line specific manner. Overall, our studies identify the cell morphological features that determine 3D invasion responses to individual ECM proteins. This platform will help provide insight into the functional role of ECM proteins abundant in tumor tissue and help prioritize strategies for targeting tumor-ECM interactions to treat metastasis.

Sex-specific hippocampus volume changes in obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) patients show hippocampal-related autonomic and neurological symptoms, including impaired memory and depression, which differ by sex, and are mediated in distinct hippocampal subfields. Determining sites and extent of hippocampal sub-regional injury in OSA could reveal localized structural damage linked with OSA symptoms. Methods: High-resolution T1-weighted images were collected from 66 newly-diagnosed, untreated OSA (mean age ±â€¯SD: 46.3 ±â€¯8.8 years; mean AHI ±â€¯SD: 34.1 ±â€¯21.5 events/h;50 male) and 59 healthy age-matched control (46.8 ±â€¯9.0 years;38 male) participants. We added age-matched controls with T1-weighted scans from two datasets (IXI, OASIS-MRI), for 979 controls total (426 male/46.5 ±â€¯9.9 years). We segmented the hippocampus and analyzed surface structure with "FSL FIRST" software, scaling volumes for brain size, and evaluated group differences with ANCOVA (covariates: total-intracranial-volume, sex; P < .05, corrected). Results: In OSA relative to controls, the hippocampus showed small areas larger volume bilaterally in CA1 (surface displacement ≤0.56 mm), subiculum, and uncus, and smaller volume in right posterior CA3/dentate (≥ - 0.23 mm). OSA vs. control males showed higher bilateral volume (≤0.61 mm) throughout CA1 and subiculum, extending to head and tail, with greater right-sided increases; lower bilateral volumes (≥ - 0.45 mm) appeared in mid- and posterior-CA3/dentate. OSA vs control females showed only right-sided effects, with increased CA1 and subiculum/uncus volumes (≤0.67 mm), and decreased posterior CA3/dentate volumes (≥ - 0.52 mm). Unlike males, OSA females showed volume decreases in the right hippocampus head and tail. Conclusions: The hippocampus shows lateralized and sex-specific, OSA-related regional volume differences, which may contribute to sex-related expression of symptoms in the sleep disorder. Volume increases suggest inflammation and glial activation, whereas volume decreases suggest long-lasting neuronal injury; both processes may contribute to dysfunction in OSA.

Altered Regional Brain Cortical Thickness in Pediatric Obstructive Sleep Apnea.

RATIONALE: Obstructive sleep apnea (OSA) affects 2-5% of all children and is associated with cognitive and behavioral deficits, resulting in poor school performance. These psychological deficits may arise from brain injury, as seen in preliminary findings of lower gray matter volume among pediatric OSA patients. However, the psychological deficits in OSA are closely related to functions in the cortex, and such brain areas have not been specifically assessed. The objective was to determine whether cortical thickness, a marker of possible brain injury, is altered in children with OSA. METHODS: We examined regional brain cortical thicknesses using high-resolution T1-weighted magnetic resonance images in 16 pediatric OSA patients (8 males; mean age ± SD = 8.4 ± 1.2 years; mean apnea/hypopnea index ± SD = 11 ± 6 events/h) and 138 controls (8.3 ± 1.1 years; 62 male; 138 subjects from the NIH Pediatric MRI database) to identify cortical thickness differences in pediatric OSA subjects. RESULTS: Cortical thinning occurred in multiple regions including the superior frontal, ventral medial prefrontal, and superior parietal cortices. The left side showed greater thinning in the superior frontal cortex. Cortical thickening was observed in bilateral precentral gyrus, mid-to-posterior insular cortices, and left central gyrus, as well as right anterior insula cortex. CONCLUSION: Changes in cortical thickness are present in children with OSA and likely indicate disruption to neural developmental processes, including maturational patterns of cortical volume increases and synaptic pruning. Regions with thicker cortices may reflect inflammation or astrocyte activation. Both the thinning and thickening associated with OSA in children may contribute to the cognitive and behavioral dysfunction frequently found in the condition.

Obstructive sleep apnea is associated with altered midbrain chemical concentrations.

Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24±0.43, Control:1.47±0.41; p=0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23±0.57, Control:0.98±0.33; p=0.03), ascorbate (Asc; OSA:0.56±0.28, Control:0.42±0.20; (50.7±8.5years; p=0.03), and myo-inositol (mI; OSA:0.96±0.48, Control:0.72±0.35; p=0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.