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BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

This study explored the lived experiences of 21 graduate students in counselor education programs in talking about race, racism, oppression, and privilege in the classroom. We identified four themes from the data that will be shared in the study findings with implications for counselor education, counselor training, and research.

BACKGROUND: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution. METHODS: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan-Meier estimates and Cox proportional hazard regression method were used for survival analyses. RESULTS: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were

Abstract Gulf War Illness (GWI) is a chronic multisymptom disorder that affects approximately 25–32% of Gulf War veterans and is characterized by a number of symptoms such as cognitive impairment, psychiatric disturbances, chronic fatigue and gastrointestinal distress, among others. While the exact etiology of GWI is unknown, it is believed to have been caused by toxic exposures encountered during deployment in combination with other factors such as stress. In the present study we sought to evaluate the hypothesis that exposure to the toxin permethrin could prime neuroinflammatory stress response and elicit psychiatric symptoms associated with GWI. Specifically, we developed a mouse model of GWI, to evaluate the effects of chronic permethrin exposure followed by unpredictable stress. We found that subjecting mice to 14 days of chronic permethrin exposure followed by 7 days of unpredictable stress resulted in the development of depression-like behavior. This behavioral change coincided with distinct alterations in the microglia phenotype, indicating microglial activation in the hippocampus. We revealed that blocking microglial activation through Gi inhibitory DREADD receptors in microglia effectively prevented the behavioral change associated with permethrin and stress exposure. To elucidate the transcriptional networks impacted within distinct microglia populations linked to depression-like behavior in mice exposed to both permethrin and stress, we conducted a single-cell RNA sequencing analysis using 21,566 single nuclei collected from the hippocampus of mice. For bioinformatics, UniCell Deconvolve was a pre-trained, interpretable, deep learning model used to deconvolve cell type fractions and predict cell identity across spatial datasets. Our bioinformatics analysis identified significant alterations in permethrin exposure followed by stress-associated microglia population, notably pathways related to neuronal development, neuronal communication, and neuronal morphogenesis, all of which are associated with neural synaptic plasticity. Additionally, we observed permethrin exposure followed by stress-mediated changes in signal transduction, including modulation of chemical synaptic transmission, regulation of neurotransmitter receptors, and regulation of postsynaptic neurotransmitter receptor activity, a known contributor to the pathophysiology of depression in a subset of the hippocampal pyramidal neurons in CA3 subregions. Our findings tentatively suggest that permethrin may prime microglia towards a state of inflammatory activation that can be triggered by psychological stressors, resulting in depression-like behavior and alterations of neural plasticity. These findings underscore the significance of synergistic interactions between multi-causal factors associated with GWI.

A commonly accepted standard protocol for noninvasive techniques for the genetic evaluation of an embryo remains elusive due to inconclusiveness regarding the volume of spent media to be acquired and the possibility of acquiring the same for subsequent analysis. Single embryo culture is imperative for standardizing noninvasive preimplantation testing using cell-free DNA (cf-DNA) released by individual developing embryos. This study aims to compare the development dynamics of single-drop embryonic culture against with group embryonic culture to establish a standardized protocol for noninvasive Preimplantation Genetic Testing (PGT) in bovine. A total of 239 cumulus–oocyte complexes were aspirated and subjected to in vitro maturation and fertilization. Among these, 120 embryos of day 3 were transferred to single-drop culture until the blastocyst stage. The single-drop culture drops were prepared using microdrops of 30 μL. At the blastocyst stage, spent media from all single-drop embryos were utilized for extracting cell-free genomic DNA to standardize the protocol. The blastocyst rate indicates no significant difference between the two culture methods, suggesting that single-drop culture is suitable for the process. Additionally, the extracted spent media yielded sufficient quantities of cf-DNA, supporting its potential use for PGT (p

Introduction: Social Media (SM) has proven to be a valuable tool in various fields, including healthcare. However, its improper use can result in several ethical problems. Aim: To evaluate the knowledge, attitude, and practice of ethical SM usage for professional purposes. Materials and Methods: A cross-sectional study was conducted in the Department of Prosthodontics and Crown and Bridge at K.M. Shah Dental College and Hospital Vadodara, Gujarat, India between October 2022 and March 2023. A total of 319 respondents, including dental postgraduates, academicians, and dental practitioners, participated in the survey online through various SM groups. The questionnaire was created by analysing previous literature and reviewed by experts for accuracy. The survey comprised nine questions with three subsections to evaluate knowledge, attitude, and practice of ethical SM usage The survey was distributed through Google Forms, and the statistical analysis of the results was conducted using the Chi-square test (p

Desalination of seawater, brackish water, and reclaimed water is becoming increasingly prevalent worldwide to supplement and diversify fresh water supplies. However, particularly for industrial wastewater, the need for environment-friendly and economically viable alternatives for concentrate management is the major impediment to deploying large-scale desalination. This review covers various strategies and technologies for managing reverse osmosis concentrate (ROC) and also includes their disposal, treatment, and potential applications. Developing energy-efficient, economical, and ecologically sound ROC management systems is essential if desalination and wastewater treatment are being implemented for a sustainable water future, particularly for industrial wastewater. The limitations and benefits of various concentrate management strategies are examined in this review. Moreover, it explores the potential of innovative technologies in reducing concentrate volume, enhancing water recovery, eliminating organic pollutants, and extracting valuable resources. This review critically discusses concentrate management approaches and technologies, including disposal, treatment, and reuse, including new technologies for reducing concentrate volume, boosting water recovery, eliminating organic contaminants, recovering valuable commodities, and minimizing energy consumption. HIGHLIGHT Developing energy-efficient, economical, and ecologically sound reverse osmosis concentrate management systems is essential. The limitations and benefits of various concentrate management strategies are examined in this review. Moreover, it explores the potential of innovative technologies in reducing concentrate volume, enhancing water recovery, eliminating organic pollutants, and extracting valuable resources.;

Introduction: Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the reciprocal translocation of chromosomes 9 and 22, which leads to a chimeric gene product known as BCR-ABL. Some studies have shown a higher incidence of secondary malignancies than the one seen in the general population in patients with CML. Hepatocellular carcinoma (HCC) is rarely reported in association with CML and/or CML-related treatment. Case Presentation: We describe a case of a patient with no history of liver disease and CML on imatinib for 10 years, who presented with worsening right upper quadrant abdominal pain. Imaging revealed a large hepatic mass highly suspicious of malignancy that later was confirmed to be HCC after biopsy. The patient was bracketed with advanced stage HCC (BCLC stage C) and given her advanced age and poor performance status; palliative care was offered. Conclusion: Patients with CML have a common association with secondary malignancies. This is the first case report based on our extensive review of available literature that HCC was diagnosed in a patient with CML on treatment with imatinib without any clear or usual underlying cause.

Purpose: To study the inner and outer retinal functions using a full-field electroretinogram (ERG) before and after intravenous chemotherapy (IVC) in children with retinoblastoma (RB). Methods: Of the 11 eyes, seven had RB and four were normal. All children were examined under anesthesia using a handheld ERG machine with a standard protocol – light-adapted single-flash ERG (fERG), photopic single-flash 3.0- and 30-Hz flickers, and photopic negative response (PhNR) amplitudes at 72 ms (P72). The amplitudes and peak times were compared before and after IVC. Results: Post-chemotherapy tumor regressed in all seven eyes. Of the seven eyes, the fERG peak time (a-wave) was delayed in two eyes (29%), whereas the b-wave was delayed in six eyes (86%). The fERG amplitude height for a- and b-waves decreased in five eyes (71%) and six eyes (86%), respectively. In addition, photopic flicker 30-Hz b-wave peak time delayed in five eyes (71%), whereas the b-wave amplitude height decreased in six eyes (86%). Simultaneously, the P72 amplitude height decreased in six eyes (86%), whereas the P-ratio increased in all seven eyes (100%). In comparison, the ERG responses improved in three of the four contralateral normal eyes. Overall, the cone function improved in two eyes (29%), whereas cone bipolar cell and retinal ganglion cell (RGC) function improved in one eye (14%) each. Conclusion: Comparison of light-adapted ERG changes before and after IVC showed reduced amplitudes and delayed peak times for both a and b waveforms, as well as reduced PhNR amplitude attributable to bipolar and RGC injury.

Abstract Breath analysis is an area of significant interest in medical research as it allows for non-invasive sampling with exceptional potential for disease monitoring and diagnosis. Volatile organic compounds (VOCs) found in breath can offer critical insight into a person’s lifestyle and/or disease/health state. To this end, the development of a rapid, sensitive, cost-effective and potentially portable method for the detection of key compounds in breath would mark a significant advancement. Herein, we have designed, built and tested a novel reagent-less atmospheric pressure photoionisation (APPI) source, coupled with mass spectrometry (MS), utilising a bespoke bias electrode within a custom 3D printed sampling chamber for direct analysis of VOCs. Optimal APPI-MS conditions were identified, including bias voltage, cone voltage and vaporisation temperature. Calibration curves were produced for ethanol, acetone, 2-butanone, ethyl acetate and eucalyptol, yielding R2 > 0.99 and limits of detection

Post-COVID conditions (PCCs) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about treatment, inflammation, and PCC. Among 882 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of COVID-19 convalescent plasma (CCP) vs control plasma with available biospecimens and symptom data, the association between early CCP treatment, cytokine levels, and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14, and day 90 using a multiplexed sandwich immunoassay (Meso Scale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between CCP treatment, cytokine levels, and PCC were examined using multivariate logistic regression models. One third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and anosmia (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis, female sex (adjusted odds ratio [AOR] = 2.69 [1.93-3.81]), older age (AOR = 1.32 [1.17-1.50]), and elevated baseline levels of IL-6 (AOR = 1.59 [1.02-2.47]) were independently associated with development of PCC. Those who received early CCP treatment (≤5 days after symptom onset) compared to late CCP treatment had statistically significant lower odds of PCC. IMPORTANCE Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC. In addition, among individuals treated early, within 5 days of symptom onset, with COVID-19 convalescent plasma, there was a trend for decreased odds of PCC after adjusting for other demographic and clinical characteristics. Future treatment studies should be considered to evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.