T-cell help in the tumor microenvironment enhances rituximab-mediated NK-cell ADCC.

ABSTRACT: Rituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of NK cells activated by anti-CD20-coated target B cells. Here, we conducted studies using a novel mouse model and clinical correlative analysis to assess whether T-cell help contribute to RTX-mediated NK-cell ADCC in the tumor microenvironment (TME) in vivo. A humanized mouse model was developed using Raji lymphoma cells and normal donor peripheral blood mononuclear cells that allows for control of T-cell numbers in the lymphoma TME. In this model, NK-cell viability and CD16 and CD25 expression dropped after RTX in the absence of T cells but increased in the presence of T cells. RTX therapy was more effective when T cells were present and was ineffective when NK cells were depleted. In patients with indolent lymphoma, fine needle aspirates were obtained before and ∼1 week after treatment with a RTX-containing regimen. There was a strong correlation between CD4+ T cells as well as total T cells in the pretherapy TME and an increase in NK-cell CD16 and CD25 expression after RTX. We conclude that T-cell help in the TME enhances RTX-mediated NK-cell viability and ADCC.

A pilot randomized sham controlled trial of bilateral iTBS for depression and executive function in older adults.

INTRODUCTION: Executive function deficits (EFD) in late life depression (LLD) are associated with poor outcomes. Dysfunction of the cognitive control network (CCN) has been posited in the pathophysiology of LLD with EFD. METHODS: Seventeen older adults with depression and EFD were randomized to iTBS or sham for 6 weeks. Intervention was delivered bilaterally using a recognized connectivity target. RESULTS: A total of 89% (17/19) participants completed all study procedures. No serious adverse events occurred. Pre to post-intervention change in mean Montgomery-Asberg-depression scores was not different between iTBS or sham, p = 0.33. No significant group-by-time interaction for Montgomery-Asberg Depression rating scale scores (F 3, 44  = 0.51; p = 0.67) was found. No significant differences were seen in the effects of time between the two groups on executive measures: Flanker scores (F 1, 14  = 0.02, p = 0.88), Dimensional-change-card-sort scores F 1, 14  = 0.25, p = 0.63, and working memory scores (F 1, 14  = 0.98, p = 0.34). The Group-by-time interaction effect for functional connectivity (FC) within the Fronto-parietal-network was not significant (F 1, 14  = 0.36, p = 0.56). No significant difference in the effect-of-time between the two groups was found on FC within the Cingulo-opercular-network (F 1, 14  = 0, p = 0.98). CONCLUSION: Bilateral iTBS is feasible in LLD. Preliminary results are unsupportive of efficacy on depression, executive function or target engagement of the CCN. A future Randomized clinical trial requires a larger sample size with stratification of cognitive and executive variables and refinement in the target engagement.

Neonatal Intensive Care Unit Network Neurobehavioral Scale Profiles in Full-Term Infants: Associations with Maternal Adversity, Medical Risk, and Neonatal Outcomes.

OBJECTIVES: To examine healthy, full-term neonatal behavior using the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) in relation to measures of maternal adversity, maternal medical risk, and infant brain volumes. STUDY DESIGN: This was a prospective, longitudinal, observational cohort study of pregnant mothers followed from the first trimester and their healthy, full-term infants. Infants underwent an NNNS assessment and high-quality magnetic resonance imaging 2-5 weeks after birth. A latent profile analysis of NNNS scores categorized infants into neurobehavioral profiles. Univariate and multivariate analyses compared differences in maternal factors (social advantage, psychosocial stress, and medical risk) and neonatal characteristics between profiles. RESULTS: The latent profile analysis of NNNS summary scales of 296 infants generated 3 profiles: regulated (46.6%), hypotonic (16.6%), and fussy (36.8%). Infants with a hypotonic profile were more likely to be male (χ2 = 8.601; P = .014). Fussy infants had smaller head circumferences (F = 3.871; P = .022) and smaller total brain (F = 3.522; P = .031) and cerebral white matter (F = 3.986; P = .020) volumes compared with infants with a hypotonic profile. There were no differences between profiles in prenatal maternal health, social advantage, or psychosocial stress. CONCLUSIONS: Three distinct neurobehavioral profiles were identified in healthy, full-term infants with hypotonic and fussy neurobehavioral features related to neonatal brain volumes and head circumference, but not prenatal exposure to socioeconomic or psychosocial adversity. Follow-up beyond the neonatal period will determine if identified profiles at birth are associated with subsequent clinical or developmental outcomes.

Quantitative proteomic analysis of GnRH agonist treated GBM cell line LN229 revealed regulatory proteins inhibiting cancer cell proliferation.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) receptor, a rhodopsin-like G-protein coupled receptor (GPCR) family member involved in GnRH signaling, is reported to be expressed in several tumors including glioblastoma multiforme (GBM), one of the most malignant and aggressive forms of primary brain tumors. However, the molecular targets associated with GnRH receptor are not well studied in GBM or in other cancers. The present study aims at investigating the effect of GnRH agonist (Gosarelin acetate) on cell proliferation and associated signaling pathways in GBM cell line, LN229. METHODS: LN229 cells were treated with different concentrations of GnRH agonist (10-10 M to 10-5 M) and the effect on cell proliferation was analyzed by cell count method. Further, total protein was extracted from control and GnRH agonist treated cells (with maximum reduction in cell proliferation) followed by trypsin digestion, labeling with iTRAQ reagents and LC-MS/MS analysis to identify differentially expressed proteins. Bioinformatic analysis was performed for annotation of proteins for the associated molecular function, altered pathways and network analysis using STRING database. RESULTS: The treatment with different concentrations of GnRH agonist showed a reduction in cell proliferation with a maximum reduction of 48.2% observed at 10-6 M. Quantitative proteomic analysis after GnRH agonist treatment (10-6 M) led to the identification of a total of 29 differentially expressed proteins with 1.3-fold change (23 upregulated, such as, kininogen-1 (KNG1), alpha-2-HS-glycoprotein (AHSG), alpha-fetoprotein (AFP), and 6 downregulated, such as integrator complex subunit 11 (CPSF3L), protein FRG1 (FRG1). Some of them are known [KNG1, AHSG, AFP] while others such as inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), ITIH4, and LIM domain-containing protein 1 (LIMD1) are novel to GnRH signaling pathway. Protein-protein interaction analysis showed a direct interaction of KNG1, a hub molecule, with GnRH, GnRH receptor, EGFR and other interactors including ITIH2, ITIH4 and AHSG. Overexpression of KNG1 after GnRH agonist treatment was validated using Western blot analysis, while a significant inhibition of EGFR was observed after GnRH agonist treatment. CONCLUSIONS: The study suggests a possible link of GnRH signaling with EGFR signaling pathways likely via KNG1. KNG1 inhibitors may be investigated independently or in combination with GnRH agonist for therapeutic applications.

Liver iron quantification in children and young adults: comparison of a volumetric multi-echo 3-D Dixon sequence with conventional 2-D T2* relaxometry.

BACKGROUND: Magnetic resonance imaging (MRI)-based liver iron quantification is the standard of care to guide chelation therapy in children at risk of hemochromatosis. T2* relaxometry is the most widely used technique but requires third-party software for post-processing. Vendor-provided three-dimensional (3-D) multi-echo Dixon techniques are now available that allow inline/automated post-processing. OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of a volumetric multi-echo Dixon technique using conventional T2* relaxometry as the reference standard in a pediatric and young adult population. MATERIALS AND METHODS: In this retrospective study, we queried the radiology information system to identify all MRIs performed for liver iron quantification from July 2015 to January 2020. All patients had undergone T2* relaxometry on a 1.5-tesla (T) scanner for liver iron concentration (LIC) estimation. In addition, a 3-D multi-echo Dixon was performed using Siemens Healthineers LiverLab (Erlangen, Germany). Two readers independently estimated liver R2* and T2* on the multi-echo Dixon by drawing free-hand regions of interest on the scanner-generated R2* and T2* maps. Conventional T2*-relaxometry-based LIC was the reference standard. We estimated interobserver agreement by concordance correlation coefficient (CCC). We used Bland-Altman analysis and Pearson correlation coefficient (r) to compare LIC by the two methods. RESULTS: Fifty-four MRIs on 38 patients (22 females) were available for analysis. Mean patient age was 11.8 years (standard deviation [SD] 5.3 years). Reference standard LIC ranged 1.1-21.1 (median 6.8) mg/g dry weight of liver. The concordance between readers for T2* estimation using 3-D multi-echo Dixon was substantial (CCC 0.99, confidence interval 0.99-1.00). Bland-Altman plot showed that all observations were clustered around the zero bias line if the LIC average was ≤8 mg/g, and r was very strong (reader 1 r=0.93, reader 2 r=0.92, both P-values <0.001). With increasing LIC, there was a pattern of poor agreement on the Bland-Altman plot, with observations crossing the lower limits of agreement, and r was very weak (reader 1 r=0.05, P-value 0.84; reader 2 r=0.17, P-value 0.44). CONCLUSION: Vendor-based 3-D multi-echo Dixon allows for excellent interobserver correlation in liver T2* estimation. LIC estimated by this method has a very strong correlation with conventional T2* relaxometry if liver iron overload is mild-moderate (LIC ≤8 mg/g).

Evaluation of 2D FLAIR hyperintensity of the optic nerve and optic nerve head and visual parameters in idiopathic intracranial hypertension.

BACKGROUND AND PURPOSE: T2/FLAIR hyperintensity of the optic nerve/optic nerve head has been described as a sensitive finding in idiopathic intracranial hypertension using post-contrast 3D-T2/FLAIR imaging. The purpose of this study is to assess whether hyperintensity on non-enhanced 2D-T2/FLAIR imaging occurs more likely in diseased patients than controls and to evaluate the relationship between FLAIR signal and visual parameters MATERIALS AND METHODS: A retrospective case-control study was performed of patients with idiopathic intracranial hypertension and controls who underwent orbital MRI. Three neuroradiologists reviewed the FLAIR images, subjectively evaluating for hyperintense signal within the optic nerves/optic nerve heads using a 5-point Likert Scale. Quantitative assessment of optic nerve signal using regions of interests was performed. Clinical parameters were extracted. The diagnostic performance was evaluated, and Spearman correlation calculated to assess the relationship between FLAIR signal and visual outcomes. RESULTS: The sensitivity of abnormal FLAIR signal within the optic nerves and optic nerve heads in patients with idiopathic intracranial hypertension ranged from 25-54% and 4-29%, respectively, with specificities ranging from 67-92% and 83-100%. Quantitative assessment revealed a significant difference in CNR between cases and controls in the left posterior optic nerve (p=.002). A positive linear relationship existed between abnormal optic nerve head signal and papilledema grade (OD: p=.02, OS: p=.008) but not with other visual parameters. CONCLUSION: T2/FLAIR hyperintensity in the optic nerve/optic nerve head may support the diagnosis of idiopathic intracranial hypertension but its absence should not dissuade it. If present, abnormal signal in the optic nerve head correlates with papilledema.

Low Serum Hepcidin Is Associated With Reduced Short-Term Survival in Adults With Acute Liver Failure.

The liver has an important role in iron homeostasis through the synthesis of the serum transporter transferrin and the iron hormone hepcidin. The aim of this study was to analyze parameters of iron metabolism in a multicenter cohort of adult patients with acute liver failure (ALF) and in an acetaminophen (APAP)-induced ALF mouse model. A representative subset of 121 adults with ALF (including 66 APAP-related patients) had baseline serum samples tested for ferritin, transferrin, iron, and hepcidin. Outcomes at 3 weeks after enrollment were categorized as spontaneous survivor (SS) versus death/transplantation (NSS). Mice were assessed before (controls) and 4 and 18 hours after injection of 300 mg/kg APAP. Patients with ALF as well as APAP-treated mice displayed increased ferritin and diminished serum hepcidin and hepcidin/ferritin ratio. SS had lower iron (29.1% vs. 34.5 µmol/L; P < 0.05) and transferrin saturation (60.9% vs. 79.1%; P < 0.01), but higher hepcidin levels (8.2 vs. 2.7 ng/mL; P < 0.001) and hepcidin/ferritin ratio (0.0047 vs. 0.0009; P < 0.001) than NSS. In a multivariate analysis, a log-transformed hepcidin-containing model displayed similar prognostic power as the established Acute Liver Failure Study Group index (C-statistic 0.87 vs. 0.85) and was better than Model for End-Stage Liver Disease score (C-statistic 0.76). In mice, hepcidin levels inversely correlated with the surrogate of liver injury. Conclusion: Our findings demonstrate that several serum iron parameters significantly associate with 3-week outcomes in adults with ALF. Among them, hepcidin decreases early during experimental APAP-induced ALF, is an independent predictor and might be a useful component of future prognostic scores.

Gene integrated set profile analysis: a context-based approach for inferring biological endpoints.

The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an 'integrate by intersection' (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance.

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India.

Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in the gyrA and gyrB genes of Mycobacterium tuberculosis, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in the gyrA and gyrB genes of acid-fast bacillus (AFB) smear-positive sediments or of M. tuberculosis isolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of the gyrA and gyrB genes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in the gyrA genes of 25 strains, while no mutations were observed in the gyrB genes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. The gyrA mutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis.

Identification of mycobacterial species by PCR restriction enzyme analysis of the hsp65 gene­an Indian experience.

Nowadays, nontuberculous mycobacteria (NTM) often cause pulmonary and extrapulmonary disease. Species identification of NTM determines the line of treatment and management of the disease. The routine diagnostic methods, i.e., smear microscopy and biochemical identification, of nontuberculous mycobacteria are tedious and time consuming and not all laboratories can perform these tests on a routine basis. A PCR targeting the hsp65 gene was implemented using standard strains and was applied to 109 clinical isolates. The PCR-amplified product was subjected to restriction enzyme analysis using BstEII and HaeIII. The results obtained were compared with that of biochemical tests. Of 109 NTM, 107 were identified to species level. PCR plus restriction enzyme analysis (PRA) identified 12 types of NTM. Common species identified were Mycobacterium chelonae (32), a rapid growing NTM, and Mycobacterium avium complex (21), among the slow growing NTM. PRA and biochemical identification showed 95.32% (102/107) concordant results. PRA is fast, cheap, and accurate for identification of potentially pathogenic NTM.

Association of sociodemographic and nutritional factors with risk of neural tube defects in the North Indian population: a case-control study.

OBJECTIVE: To assess the role of sociodemographic and nutritional factors in the incidence of births affected by neural tube defects (NTD) in the North Indian population. DESIGN: Case-control study. SETTING: Government hospitals of Delhi, India. SUBJECTS: Subjects comprised 284 mothers of NTD children (cases) and 568 mothers of healthy children (controls). RESULTS: Significant differences were found between case and control mothers with respect to maternal age (P = 0·005), type of drinking water (P = 0·03) and consumption of milk (P = 0·01). Univariate and multivariate analysis suggested an association of unpasteurized milk use, low consumption of vegetables, low consumption of fruits and vegetarian dietary habits with NTD births. Further, variation in the risk factors for upper and lower NTD types was also observed, pointing towards phenotypic heterogeneity in the aetiology. CONCLUSIONS: The results of the present study suggest an increased risk of NTD infants in mothers with low consumption of vegetables, fruits and milk and having vegetarian dietary habits. So, in order to reduce these devastating birth defects in future offspring, better nutritional care should be provided to mothers by suggesting dietary modifications and augmenting additional micronutrient supplementation during the periconceptional period.

Detection of multi-drug resistance & characterization of mutations in Mycobacterium tuberculosis isolates from North- Eastern States of India using GenoType MTBDRplus assay.

BACKGROUND & OBJECTIVES: Information on drug resistance tuberculosis is sparse from North-East (N-E) States of India. We undertook this study to detect multi-drug resistant tuberculosis (MDR-TB) among MDR-TB suspects, and common mutations among MDR-TB cases using GenoType MTBDRplus. METHODS: All MDR suspect patients deposited sputum samples to peripheral designated microscopy centres (DMC) in North-East States. The district TB officers (DTOs) facilitated the transport of samples collected during January 2012 to August 2012 to our laboratory. The line probe assay to detect common mutations in the rpoB gene for rifampicin (RIF) and katG and inhA genes for isoniazid (INH), respectively was performed on 339 samples or cultures. RESULTS: A total of 553 sputum samples from MDR suspects were received of which, 181 (32.7%) isolates were found to be multi-drug resistant. Missing WT8 along with mutation in codon S531L was commonest pattern for rifampicin resistant isolates (65.1%) and missing WT along with mutations in codon S315T1 of katG gene was commonest pattern for isoniazid resistant isolates (86.2%). Average turn-around time for dispatch of LPA result to these States from cultures and samples was 23.4 and 5.2 days, respectively. INTERPRETATIONS & CONCLUSIONS: The MDR-TB among MDR-TB suspects in North-Eastern States of India was found to be 32.7 per cent. The common mutations obtained for RIF and INH in the region were mostly similar to those reported earlier.

Evaluation of AAICare®-TB sequence analysis tool for accurate diagnosis of drug-resistant tuberculosis: A comparative study with TB-Profiler and Mykrobe.

A rapid and comprehensive drug susceptibility test is essential for eliminating drug resistant tuberculosis. Next generation sequencing (NGS) based susceptibility testing is being explored as a potential substitute for the conventional phenotypic and genotypic testing methods. However, the adoption of NGS based genotypic susceptibility testing depends on the availability of simple, accurate and efficient analysis tools. This preliminary study aimed to evaluate the performance of a Mycobacterium tuberculosis (Mtb) genome analysis pipeline, AAICare®-TB, for susceptibility prediction, in comparison to two widely used gDST prediction tools, TB-Profiler and Mykrobe. This study was performed in a National Reference Laboratory in India on presumptive drug-resistant tuberculosis (DR-TB) isolates. Whole genome sequences of the 120 cultured isolates were obtained through Illumina sequencing on a MiSeq platform. Raw sequences were simultaneously analysed using the three tools. Susceptibility prediction reports thus generated, were compared to estimate the total concordance and discordance. WHO mutation catalogue (1st edition, 2021) was used as the reference standard for categorizing the mutations. In this study, AAICare®-TB was able to predict drug resistance status for First Line (Streptomycin, Isoniazid, Rifampicin, Ethambutol and Pyrazinamide) and Second Line drugs (Fluoroquinolones, Second Line Injectables and Ethionamide) in 93 samples along with lineage and hetero-resistance as per the WHO guidelines.

Maternal prenatal social disadvantage and neonatal functional connectivity: Associations with psychopathology symptoms at age 12 months.

Recent research has reported effects of socioeconomic status on neurobehavioral development as early as infancy, including positive associations between income and brain structure, functional connectivity, and behavior later in childhood (Ramphal, Whalen, et al., 2020; Triplett et al., 2022). This study extends this literature by investigating the relation of maternal prenatal social disadvantage (PSD) to neonatal amygdala and hippocampus functional connectivity and whether socioeconomic-related alterations in functional connectivity subsequently predict behavior at age 12 months in a large, socioeconomically diverse sample (N = 261 mother-infant dyads). PSD was assessed across gestation; neonatal magnetic resonance imaging was completed within the first weeks of life; and infant internalizing and externalizing symptoms were evaluated using the Infant-Toddler Social and Emotional Assessment at age 12 months. The results showed that PSD was significantly related to neonatal right amygdala and left hippocampus functional connectivity with prefrontal and motor-related regions. Social disadvantage-related right amygdala and left hippocampus functional connectivity with these regions was subsequently related to infant externalizing and internalizing symptoms at age 12 months. Building off an emerging literature exploring prenatal impacts on neonatal functional connectivity, this study further emphasizes the important role of the maternal environment during gestation on infant brain function and its relationship with externalizing and internalizing behavior in the first years of life. The results suggest that the prenatal socioeconomic environment may be a promising target for interventions aimed at improving infant neurobehavioral outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Glycated serum proteins and albumin but not glycated albumin show negative correlation with BMI in an overweight/obese, diabetic population from the United States.

BACKGROUND AND AIMS: Multiple previously published studies have shown a weak to medium, negative correlation between BMI and glycated albumin (GA). However, many of these studies were in populations with a narrow range of BMI. It is unknown whether this trend exists if a wider BMI range is used. This is an important question for proper interpretation of GA levels in obese populations. MATERIALS AND METHODS: A retrospective analysis of clinical trial data (NCT02519309) was performed. After appropriate exclusions, 334 subjects remained. These included 73.7% with type 2 diabetes (T2D) diagnosis and 26.3% with prediabetes. BMI ranged from 24.8-86.9 kg/m2. Laboratory data were measured in a CLIA-certified laboratory using commercially available, automated methods. RESULTS: No significant, negative correlation was seen between GA and BMI. However, individual components (glycated serum proteins and albumin) as well as the GA/HbA1c ratio show a weak, negative correlation with BMI for all subjects and those with T2D. The strongest negative correlation was with albumin. Examination by traditional BMI subgroups also showed statistically significant differences for those with T2D, but not for the prediabetic cohort. Correlations between BMI and C-reactive protein were similar in those with diabetes and prediabetes; however, correlation between BMI and insulin was stronger in those with diabetes. CONCLUSION: Negative correlations between BMI and albumin or BMI and glycated serum proteins persist in diabetic populations that are obese and overweight, even when a statistically significant negative correlation is not observed between BMI and GA. Inflammation or insulin-mediated changes in protein synthesis could be contributors to these negative correlations, but BMI-related changes to the glomerulus could also affect clearance of albumin or glycated proteins and should be examined.

Bright Is Not Always Better: A Pictorial Review of Hyperechoic Malignant Breast Masses.

Hyperechogenic breast lesions are a relatively rare finding at breast ultrasonography and are traditionally thought to be benign. However, hyperechogenicity on the ultrasound alone does not provide enough evidence to rule out malignancy completely. We herein reported a short series of nine cases of echogenic malignant breast lesions, which include invasive ductal carcinoma, ductal carcinoma in situ, invasive lobular carcinoma, angiosarcoma, lymphoma, and metastasis to the breast. Echogenic breast lesions should be carefully evaluated and properly categorized based on any other suspicious sonographic characteristics and must be correlated with mammographic findings and clinical history to lower the threshold for biopsy and avoid delay in diagnosis. Hyperechogenicity should not be considered as a characteristically benign feature and should not supersede the less specifically benign features of the same lesion on the other examination.

MHD micro polar fluid flow over a stretching surface with melting and slip effect.

Objective of the present analysis is to represent the phenomenon of Heat-mass transfer on MHD micro polar fluids caused by permeable and continuously stretching sheet along with slip impacts fostered in a porous medium. Consequently, the equation of energy includes the term of non-uniform heat source/sink. The equation regarding species concentration in cooperates the terms indicating order of chemical reaction to characterize the chemically reactive species. The application software MATLAB with governing syntax of bvp4c technique are employed to reduce equations of momentum, micro-rations, heat, and concentration into suitable required simplifications to derive necessary arithmetic manipulations of available non-linear equations. Various dimensionless parameters are portrayed in the available graphs with essential consequences. Analysis discovered that micro-polar fluid improves velocity and temperature profile while it suppresses micro-rations profile also magnetic parameter ([Formula: see text]) and porosity parameter ([Formula: see text]) reduces the momentum boundary layer thickness. The acquired deductions verify remarkable correspondence with already reported in an open literature.

Social disadvantage during pregnancy: effects on gestational age and birthweight.

OBJECTIVE: Whether psychosocial adversity during pregnancy impacts fetal health outcomes at birth remains underexplored. This is a critical issue given significant social disadvantage and psychosocial stress faced by pregnant women worldwide. STUDY DESIGN: Measures of social disadvantage and psychological factors, and medical/reproductive and nutritional health status in pregnant women were obtained at each trimester. Using Structural Equation Modeling (SEM), we investigated the relationship of forms of adversity to each other and to infant gestational age, and birthweight. RESULTS: Among 399 singletons, Social Disadvantage significantly predicted gestational age (p = 0.003), and residual birthweight (p = 0.006). There was a 0.4 week decrease in gestational age and a 3% decrease in birthweight for each standard deviation increase in Social Disadvantage. CONCLUSION: Significant negative effects of social adversity on the developing fetus were found. Notably, these effects emerged despite good prenatal care and after accounting for maternal age and medical reproductive risk factors.

Oritavancin vs Standard of Care for Treatment of Nonendovascular Gram-Positive Bloodstream Infections.

Background: Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). Methods: This was a retrospective study of all patients in the Veteran's Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count 96-hours of treatment before the incident antimicrobial was started.The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Results: Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received >96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs 13.04% 9/69); P < .001). The pathogen most prevalent was methicillin susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (P = .34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs 3.7% (1/27); P = .01). Conclusions: ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs.

The Association Between Maternal Cortisol and Infant Amygdala Volume Is Moderated by Socioeconomic Status.

Background: It has been well established that socioeconomic status is associated with mental and physical health as well as brain development, with emerging data suggesting that these relationships begin in utero. However, less is known about how prenatal socioeconomic environments interact with the gestational environment to affect neonatal brain volume. Methods: Maternal cortisol output measured at each trimester of pregnancy and neonatal brain structure were assessed in 241 mother-infant dyads. We examined associations between the trajectory of maternal cortisol output across pregnancy and volumes of cortisol receptor-rich regions of the brain, including the amygdala, hippocampus, medial prefrontal cortex, and caudate. Given the known effects of poverty on infant brain structure, socioeconomic disadvantage was included as a moderating variable. Results: Neonatal amygdala volume was predicted by an interaction between maternal cortisol output across pregnancy and socioeconomic disadvantage (standardized ß = -0.31, p < .001), controlling for postmenstrual age at scan, infant sex, and total gray matter volume. Notably, amygdala volumes were positively associated with maternal cortisol for infants with maternal disadvantage scores 1 standard deviation below the mean (i.e., less disadvantage) (simple slope = 123.36, p < .01), while the association was negative in infants with maternal disadvantage 1 standard deviation above the mean (i.e., more disadvantage) (simple slope = -82.70, p = .02). Individuals with disadvantage scores at the mean showed no association, and there were no significant interactions in the other brain regions examined. Conclusions: These data suggest that fetal development of the amygdala is differentially affected by maternal cortisol production at varying levels of socioeconomic advantage.