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Background: Sepsis fluid resuscitation is controversial, especially for patients with volume overload risk. The Surviving Sepsis Campaign recommends a 30-mL/kg crystalloid fluid bolus for patients with sepsis-induced hypoperfusion. Criticism of this approach includes excessive fluid resuscitation in certain patients., Objective: The aim of this study was to assess the efficacy and safety of guideline-concordant fluid resuscitation in patients with sepsis and heart failure (HF) or end-stage kidney disease (ESKD)., Methods: A retrospective cohort study was conducted in patients with sepsis who qualified for guideline-directed fluid resuscitation and concomitant HF or ESKD. Those receiving crystalloid fluid boluses of at least 30 mL/kg within 3 h of sepsis diagnosis were placed in the concordant group and all others in the nonconcordant group. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS); vasoactive medications and net volume over 24 h; new mechanical ventilation, new or increased volume removal, and acute kidney injury within 48 h; and shock-free survival at 7 days., Results: One hundred twenty-five patients were included in each group. In-hospital mortality was 34.4% in the concordant group and 44.8% in the nonconcordant group (p = 0.1205). The concordant group had a shorter ICU LOS (7.6 vs. 10.5 days; p = 0.0214) and hospital LOS (12.9 vs. 18.3 days; p = 0.0163), but increased new mechanical ventilation (37.6 vs. 20.8%; p = 0.0052). No differences in other outcomes were observed., Conclusions: Receipt of a 30-mL/kg fluid bolus did not affect outcomes in a cohort of patients with mixed types of HF and sepsis-induced hypoperfusion., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study explored variations in food insecurity across sociodemographic groups and changes specific to the COVID-19 pandemic, including income loss, stimulus check receipt, and changes in household size., Design: A cross-sectional online survey was conducted using a 2-item food insecurity screener. COVID-19 related factors and sociodemographic data were collected., Setting: Data were collected in Arkansas, United States, during July and August 2020., Participants: A sample of 1205 adults was recruited using ARresearch, a volunteer research registry. Participants were over the age of 18 and living, working, or receiving health care in Arkansas., Results: The prevalence of food insecurity was 24.9% during the COVID-19 pandemic. Food insecurity was elevated even after the majority of respondents received a stimulus check. Chi-square and t -tests revealed that food insecurity was more prevalent among those who are younger, Black, Hispanic/Latinx, lower-income, less educated, and living in households with children. Multivariate logistic regression revealed that odds of food insecurity were greater for individuals who reported income loss due to the pandemic (OR = 3.29; p  < .001), Black respondents (OR = 2.06, p = .014), Hispanic respondents (OR = 3.34, p  = .001), those earning less than $25,000 annually (OR = 4.92; p < .001) or between $25,000 to $49,999 (OR = 2.04; p  = .023), respondents with a high school degree or less (OR = 4.21; p  < .001) or some college (OR = 2.55; p  < .001), and those living in households with children (OR = 1.62; p = .021). Odds of food insecurity were lower for those who had received a stimulus check (OR = 0.60; p = .026)., Conclusion: Food insecurity prevalence was high in Arkansas in July and August 2020. The risk of food insecurity was uneven across sociodemographic groups. Several factors related to the COVID-19 pandemic were indicators for increased risk of food insecurity. Interventions to address food insecurity that recognize social factors unique to the pandemic are needed to reduce levels of food insecurity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Certain clinical scenarios should alert a physician to take a deeper look into causative pathological processes. This was evident in the case of a 41-year-old man who presented for recurrent micro thromboembolic strokes, which is atypical for the patient's age. Our desire to explain the pathological process led to the rare finding of a plasminogen activator inhibitor-1 polymorphism, which has been associated with an increased risk of cerebrovascular thrombosis. A defect in this pathway leads to the inhibition of the tissue plasminogen activator protein. This genetic polymorphism has relatively been unexplored in recent medical literature, and we are hoping that our case may inspire future research that could help potential targets of risk factor stratifications as well as the development of novel pharmacological options., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Dayco et al.)

The development of therapies to eliminate the latent HIV-1 reservoir is hampered by our incomplete understanding of the biomolecular mechanism governing HIV-1 latency. To further complicate matters, recent single-cell RNA sequencing (scRNA-seq) studies reported extensive heterogeneity between latently HIV-1-infected primary T cells, implying that latent HIV-1 infection can persist in greatly differing host cell environments. We show here that transcriptomic heterogeneity is also found between latently infected T cell lines, which allowed us to study the underlying mechanisms of intercell heterogeneity at high signal resolution. Latently infected T cells exhibited a dedifferentiated phenotype, characterized by the loss of T cell-specific markers and gene regulation profiles reminiscent of hematopoietic stem cells (HSC). These changes had functional consequences. As reported for stem cells, latently HIV-1-infected T cells efficiently forced lentiviral superinfections into a latent state and favored glycolysis. As a result, metabolic reprogramming or cell redifferentiation destabilized latent infection. Guided by these findings, data mining of single-cell RNA-seq data of latently HIV-1-infected primary T cells from patients revealed the presence of similar dedifferentiation motifs. More than 20% of the highly detectable genes that were differentially regulated in latently infected cells were associated with hematopoietic lineage development (e.g., HUWE1, IRF4, PRDM1, BATF3, TOX, ID2, IKZF3, and CDK6) or were hematopoietic markers (SRGN; hematopoietic proteoglycan core protein). The data add to evidence that the biomolecular phenotype of latently HIV-1-infected cells differs from that of normal T cells and strategies to address their differential phenotype need to be considered in the design of therapeutic cure interventions. IMPORTANCE HIV-1 persists in a latent reservoir in memory CD4 T cells for the lifetime of a patient. Understanding the biomolecular mechanisms used by the host cells to suppress viral expression will provide essential insights required to develop curative therapeutic interventions. Unfortunately, our current understanding of these control mechanisms is still limited. By studying gene expression profiles, we demonstrated that latently HIV-1-infected T cells have a dedifferentiated T cell phenotype. Software-based data integration allowed the identification of drug targets that would redifferentiate viral host cells and, by extension, destabilize latent HIV-1 infection events. The importance of the presented data lies within the clear demonstration that HIV-1 latency is a host cell phenomenon. As such, therapeutic strategies must first restore proper host cell functionality to accomplish efficient HIV-1 reactivation.

Introduction: Trauma training for front-line providers is a critical component of injury mitigation and trauma systems strengthening. Although the Advanced Trauma Life Support (ATLS) course is standard in much of the world, cost and administrative barriers are prohibitive to deploying the course in many low and middle income countries (LMICs). The purpose of this study was to identify alternative trauma training courses used in LMICs by scoping review and compare their effectiveness., Methods: Several peer-reviewed and grey literature databases were searched for relevant articles describing trauma training courses for front-line medical providers in LMICs. Studies were included if: performed in a LMIC; utilized a general trauma training course other than ATLS; trainees were hospital-based medical providers; study included some type of outcome measure., Results: A total of 34 manuscripts met inclusion criteria. The majority of courses were novel, hospital-initiated courses and ranged in length from 1 day to 1 week. Physicians were the most common target audience, followed by medical students and nurses. Courses were taught in 24 different countries throughout the Middle East, Asia, Latin America and Africa. Comparison of pre- and post-test knowledge was the most common metric used and nearly all courses demonstrated a statistically significant knowledge gain. One study demonstrated a reduction in mortality for injured patients after course implementation. The majority of courses were a collaboration between universities in a high income country and local faculty/practitioners in the LMIC where the course was taught. Reported cost per participant ranged from $10 to $232 USD., Conclusions: Several trauma courses are currently being utilized in LMICs effectively with increases in knowledge gained and at a lower reported cost than ATLS. More research is needed to link trauma training courses to patient outcomes., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Tetraspanins are a family of proteins with an array of functions that are well studied in cancer biology, but their importance in immunology is underappreciated. Here we establish the tetraspanin CD151 as a unique marker of T-cell activation and, in extension, an indicator of elevated, systemic T-cell activity. Baseline CD151 expression found on a subset of T-cells was indicative of increased activation of the MAPK pathway. Following TCR/CD3 activation, CD151 expression was upregulated on the overall T-cell population, a quintessential feature of an activation marker. CD151+ T-cell frequencies in the spleen, an organ with increased immune activity, were twice as high as in paired peripheral blood samples. This CD151+ T-cell frequency increase was not paralleled by an increase of CD25 or CD38, demonstrating that CD151 expression is regulated independently of other T-cell activation markers. CD151+ T-cells were also more likely to express preformed granzyme B, suggesting that CD151+ T cells are pro-inflammatory. To this end, HIV-1 patients on antiretroviral therapy who are reported to exhibit chronically elevated levels of immune activity, had significantly higher CD4+CD151+ T-cell frequencies than healthy controls, raising the possibility that proinflammatory CD151+ T cells could contribute to the premature immunological aging phenotype observed in these patients.

Several immunotherapeutic agents function against the T cell immune checkpoint inhibitor pathways thereby reestablishing immune response to elusive malignancies. Namely, the programmed death-1 co-receptor (PD-1) or ligand (PD-L1) and cytotoxic T lymphocyte- associated protein 4 (CTLA-4) are well known checkpoint targets of current FDA approved drugs. Among these drugs nivolumab, an IgG4 anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, are used to treat numerous malignancies but carry a large list of potential side effects termed immune-related adverse effects (irAEs). We describe the presentation, clinical course, and resolution of steroid-resistant immune checkpoint inhibitor-induced colitis secondary to administration of these two drugs in a 66-year-old female patient treated with infliximab., (Copyright© South Dakota State Medical Association.)

An anterior mediastinal mass has a broad differential. We report a case of a large anterior mediastinal malignancy in a pediatric patient presenting with left-sided supraclavicular pain without symptoms of cardiopulmonary compromise. The mass was revealed with CT imaging and diagnosis of T-cell lymphoblastic lymphoma was confirmed after supraclavicular lymph node biopsy. The patient was initially treated with methylprednisolone for cytoreduction and a combination of rasburicase and allopurinol for asymptomatic tumor lysis syndrome. There was then a 34-day induction phase of chemotherapy with vincristine, daunorubicin, PEG-asparaginase, and intrathecal methotrexate. CSF sampling and bone marrow biopsies were both negative at the end of induction. The patient is currently in the consolidation phase, taking cyclophosphamide, cytarabine, and 6-MP, and is tolerating the treatment well., (Copyright© South Dakota State Medical Association.)

The tetraspanin CD151 is a marker of aggressive cell proliferation and invasiveness for a variety of cancer types. Given reports of CD151 expression on T cells, we explored whether CD151 would mark T cells in a hyperactivated state. Consistent with the idea that CD151 could mark a phenotypically distinct T cell subset, it was not uniformly expressed on T cells. CD151 expression frequency was a function of the T cell lineage (CD8 > CD4) and a function of the memory differentiation state (naive T cells < central memory T cells < effector memory T cells < T effector memory RA + cells). CD151 and CD57, a senescence marker, defined the same CD28 - T cell populations. However, CD151 also marked a substantial CD28 + T cell population that was not marked by CD57. Kinome array analysis demonstrated that CD28 + CD151 + T cells form a subpopulation with a distinct molecular baseline and activation phenotype. Network analysis of these data revealed that cell cycle control and cell death were the most altered process motifs in CD28 + CD151 + T cells. We demonstrate that CD151 in T cells is not a passive marker, but actively changed the cell cycle control and cell death process motifs of T cells. Consistent with these data, long-term T cell culture experiments in the presence of only IL-2 demonstrated that independent of their CD28 expression status, CD151 + T cells, but not CD151 - T cells, would exhibit an Ag-independent, hyperresponsive proliferation phenotype. Not unlike its reported function as a tumor aggressiveness marker, CD151 in humans thus marks and enables hyperproliferative T cells., (Copyright © 2017 by The American Association of Immunologists, Inc.)

All-terrain vehicle accidents that affect the spine can lead to complex injuries in adolescents. This requires that many subspecialties work together on a multidisciplinary team to improve patient outcomes. Our case presentation will examine the multidisciplinary approach to care required for an 11-year-old adolescent involved in an all-terrain vehicle accident that resulted in traumatic spinal cord injury.

A smooth response surface (SRS) algorithm is developed as an elaborate data mining technique for analyzing gene expression data and constructing a gene regulatory network. A three-dimensional SRS is generated to capture the biological relationship between the target and activator-repressor. This new technique is applied to functionally describe triplets of activators, repressors, and targets, and their regulations in gene expression data. A diagnostic strategy is built into the algorithm to evaluate the scores of the triplets so that those with low scores are kept and a regulatory network is constructed based on this information and existing biological knowledge. The predictions based on the identified triplets in two yeast gene expression data sets agree with some experimental data in the literature. It provides a novel model with attractive mathematical and statistical features that make the algorithm valuable for mining expression or concentration information, assist in determining the function of uncharacterized proteins, and can lead to a better understanding of coherent pathways.

A 30-year-old black woman was first seen at 34 weeks' gestation with pain in the right arm, which was already afflicted with neurofibroma. She was in hypovolemic shock on presentation, and after she was resuscitated, a live infant was delivered. The patient was diagnosed with a pseudoaneurysm of the right brachial artery with extravasation of blood in the interstitium of the arm. Although there have been other reported cases of arterial rupture in pregnancies with neurofibromatosis, the report of brachial artery rupture in this situation is believed to be the first documented case.

The glow discharge plasma deposition (GDPD) of tetraethylene glycol dimethyl ether is introduced as a novel method for obtaining surfaces that are resistant to protein adsorption and cellular attachment. Analysis of films by x-ray photoelectron spectroscopy and several biological assays indicate the formation of a fouling-resistant, PEO-like surface on several substrata (e.g., glass, polytetrafluoroethylene, polyethylene). Adsorption of 125I-radiolabelled proteins (fibrinogen, albumin and IgG) from buffer and plasma was very low (typically less than 20 ng/cm2) when compared to the untreated substrata, which exhibited much higher levels of protein adsorption. Not all coated substrata adsorbed equal amounts of protein (e.g., coated glass samples typically adsorbed more protein than coated polyethylene or coated polytetrafluoroethylene samples), suggesting that the substratum used may affect the amount of protein adsorbed. Measurement of dynamic platelet adhesion, using epifluorescent video microscopy, and endothelial cell attachment further demonstrates the short-term nonadhesiveness of these surfaces.

Symptoms commonly defined as the sick building syndrome were studied in a cross-sectional investigation of 147 office workers in five building areas using a linear-analog self-assessment scale questionnaire to define symptoms at a specific point in time. At the same time, the environment in the breathing zone was characterized by measuring thermal parameters (dry-bulb temperature, relative humidity, air speed, and radiant temperature), volatile organic compounds, respirable suspended particulates, noise and light intensity, and carbon dioxide and carbon monoxide levels. Demographic characteristics of the occupants and building characteristics were recorded. Up to 25% of the variance in regression models could be explained for mucous membrane irritation and central nervous system symptoms. These two symptom groups were related to the concentrations of volatile organic compounds, to crowding, to layers of clothing, and to measured levels of lighting intensity. Chest tightness was also related to lighting intensity. Skin complaints were related only to gender. Gender, age, and education failed to demonstrate a consistent relationship with symptom categories. This study suggests that the sick building syndrome may have specific environmental causes, including lighting and volatile organic compounds.

A noncalcifying drug, aminodiphosphonate, was immobilized on pericardial collagen to inhibit calcification. The parameters of ADP binding were optimized by using labeled tracer. The effects of the detergents, Triton X-100 and sodium dodecyl sulfate, pH, and temperature on ADP binding to collagen in fresh pericardium, and stabilization of ADP-collagen bond by borohydride (BH) reduction, were optimized. These studies indicate that pretreatment of pericardium with SDS and TX-100 increases ADP binding three- to fivefold. Three-step cross-linking via Schiff-base reactions between collagen, ADP, and cross-linking via Schiff-base reactions between collage, ADP, and glutaraldehyde gives a high value of 30 to 35 molecules of ADP per collagen in pericardium. Twenty-five millimeter tissue valves were made with detergent (1% SDS, 1% TX-100) treated ADP-bound pericardium and implanted in the mitral annuli in calves, which were killed at 60 days post implantation. Regional calcium deposition was measured with atomic absorption spectrometry. The calcium level (micrograms/mg of tissue) in components of control and four processed valves were determined. Regional platelet deposition on zones of leaflets and components of tissue valves were quantified with 111In-labeled autologous platelets. The calcium levels in thrombus and flexion zones of treated valves are lower than that in the control valve. SEM studies of leaflet surfaces at 60 days indicate that these treatment processes reduce calcification and promote spontaneous cell coverage on leaflets around the smooth surface of the outflow tract.

With 111In-labeled platelets and 125I-labeled bovine fibrinogen, regional mapping of platelet and fibrinogen deposition on leaflets and sewing rings was obtained. Ten Holstein calves received 25-mm mitral valves (ISLM) and were killed 1, 14, and 30 days after implantation. Twenty-four hours before the calves were killed, 350 to 450 microCi of 111In-labeled platelets and 200 to 250 microCi of 125I-labeled bovine fibrinogen were administered intravenously. The components of the tissue valves, i.e., three leaflets and sewing rings, were separated. Each leaflet was cut into four sections: free edge, central zone, flexion zone, and attachment zone. From the radioactivity in blood, leaflet zones, sewing rings, area of leaflet zones, platelet count, and fibrinogen level in blood, the mean regional density of adherent platelets, fibrinogen-fibrin, and fibrinogen/platelet were calculated. The density of platelets and fibrinogen deposited on the components of the valves decreases with time postimplantation. The number of fibrinogen molecules per platelet is fivefold to 20-fold higher than that of the receptor concentration on platelets on leaflet zones, suggesting the heterogeneity of fibrinogen-fibrin in thrombus and components of the valve.

The metabolic effects of graded whole body hypothermia on complete global cerebral ischemia and recirculation was investigated in the cat. Hypothermia was induced to one of three levels prior to ischemia; T = 26.8 degrees +/- 0.5 degrees C (n = 4), T = 32.1 degrees +/- 0.2 degrees C (n = 5), and T = 34.6 degrees +/- 0.3 degrees C (n = 6), and maintained constant throughout 16 min of ischemia and 1.5-2 h of recirculation. Intracellular cerebral pH and relative concentrations of high-energy phosphate metabolites were continuously monitored, using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Except for the first 4 min of ischemia, no significant differences were detected in the response of adenylate intensities and intracellular pH to ischemia and recirculation between the hypothermic groups. The three hypothermic groups were then pooled into one group, and the data compared to previously published data from a normothermic group, T = 38.4 degrees +/- 0.6 degrees C (n = 14), and a hyperthermic group, T = 40.6 degrees +/- 0.2 degrees C (n = 9), subjected to the identical ischemic and NMR measurement protocols. The hypothermic animals exhibited a statistically significant reduction of cerebral intracellular acidosis, both during ischemia and recirculation, as well as a more rapid return of adenylate intensities during recirculation, compared to the normothermic or hyperthermic groups. The data thus suggest that mild hypothermia has an ameliorative affect on brain energy metabolism and intracellular pH under conditions of complete global cerebral ischemia and recirculation.