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Disseminated histoplasmosis is a life-threatening condition in immunocompromised patients. The majority of healthy persons have benign disease not requiring treatment. However, in persons living with HIV, mortality is high and accurate diagnosis is paramount. We present a case of a 48-year-old HIV-positive woman who presented with haematuria and flank pain. She had a history of recurrent urinary tract infection and nephrolithiasis with obstructive hydronephrosis. During cystoscopy, a bladder lesion was found. Pathological evaluation demonstrated abundant intracellular organisms with apparent budding. Subsequent urine histoplasma antigen was negative. Given the high index of suspicion for histoplasmosis based on the surgical pathology findings and epidemiological history, the patient was started immediately on antifungal therapy. One week later, PCR results of the bladder lesion confirmed the presence of Histoplasma capsulatum. This case highlights a rare presentation of genitourinary histoplasmosis and the utility of surgical pathology evaluation and PCR for diagnosis.

Background: This study aimed at understanding the trend in extracellular fluid (ECF) change and estimating the efficacy of the early complex decongestive therapy (CDT) program in terms of prevalence of lower limb lymphedema, as well as at identifying the quality of life (QoL) associated with response to CDT after gynecological cancer therapy. Methods and Results: Thirty-one patients undergoing gynecological cancer treatment were enrolled and randomly assigned to the CDT and control groups. In the CDT group, CDT was started within 2 weeks after surgery for 30 minutes a day, for 2 weeks (5 days per week). The patients' QoL was assessed through the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire; version 3. Inbody S10® (Biospace, Seoul, South Korea) was used to calculate the ECF. The assessment was performed at pre- and post-surgery and at 3, 6, and 12 months after surgery. Statistically significant differences, in favor of the CDT group, were encountered at the 3-month follow-up visit, especially with respect to the QoL score. Regarding the prevalence of lymphedema, no significant difference was observed between groups. The mean value of the impedance ratio was low in the CDT group during the entire 12 month follow-up. Conclusions: The results of the present study show that early CDT had a positive effect on the prevalence of lymphedema and body composition. Long-term follow-up studies with a larger sample size are needed to warrant the time-group effect of early rehabilitation.

Objective Cervical cancer (CC) is a major public health problem in women, and its early detection can help reduce morbidity and mortality. The objective of this study was to compare serum levels of soluble major histocompatibility complex class I-related chain A (sMICA) levels in various body fluids between women diagnosed with CC and healthy women.Methods A case-control study was conducted at a tertiary care hospital and a cancer center in Kolhapur, India. Overall, 150 individuals (100 CC patients and 50 healthy women) participated after providing informed written consent. Demographic data, histopathology history, parity, and tumor, node, and metastasis (TNM) staging data were collected. Pap smears, saliva, blood, and urine samples were collected. Pap smears were examined microscopically, and sMICA levels in all samples were determined by enzyme-linked immunoassay (ELISA).Results The mean age of women with cervical cancer was 49.86±8.18 years. Squamous cell carcinoma (70%) was the most common histological variant in CC patients. Serum soluble sMICA levels differed significantly with parity and TNM staging (P

Atrial natriuretic peptide (ANP) and its receptors natriuretic peptide receptor (NPR)-A and NPR-C are all highly expressed in alveolar epithelial type II cells (AEC2s) in the late-gestation ovine fetal lung and are dramatically decreased postnatally. However, of all the components, NPR-C stimulation inhibits ANP-mediated surfactant secretion. Since alveolar oxygen increases dramatically after birth, and steroids are administered to mothers antenatally to enhance surfactant lung maturity, we investigated the effects of O2 concentration and steroids on NPR-C-mediated surfactant secretion in AEC2s. NPR-C expression was highest at 5% O2 while being suppressed by 21% O2, in cultured mouse lung epithelial cells (MLE-15s) and/or human primary AEC2s. Surfactant protein-B (SP-B) was significantly elevated in media from both in vitro and ex vivo culture at 13% O2 versus 21% O2 in the presence of ANP or terbutaline (TER). Both ANP and C-ANP (an NPR-C agonist) attenuated TER-induced SP-B secretion; this effect was reversed by dexamethasone (DEX) pretreatment in AEC2s and by transfection with NPR-C siRNA in MLE-15 cells. DEX markedly reduced AEC2 NPR-C expression, and pregnant ewes treated with betamethasone showed reduced ANP in fetal sheep lung fluid. These data suggest that elevated O2 downregulates AEC2 NPR-C and that steroid-mediated NPR-C downregulation in neonatal lungs may provide a novel mechanism for their effect on perinatal surfactant production.

BackgroundApproaches are needed to better delineate the continuum of opioid misuse that occurs in hospitalized patients. A prognostic enrichment strategy with latent class analysis (LCA) may facilitate treatment strategies in subtypes of opioid misuse. We aim to identify subtypes of patients with opioid misuse and examine the distinctions between the subtypes by examining patient characteristics, topic models from clinical notes, and clinical outcomes.MethodsThis was an observational study of inpatient hospitalizations at a tertiary care center between 2007 and 2017. Patients with opioid misuse were identified using an operational definition applied to all inpatient encounters. LCA with eight class-defining variables from the electronic health record (EHR) was applied to identify subtypes in the cohort of patients with opioid misuse. Comparisons between subtypes were made using the following approaches: (1) descriptive statistics on patient characteristics and healthcare utilization using EHR data and census-level data; (2) topic models with natural language processing (NLP) from clinical notes; (3) association with hospital outcomes.FindingsThe analysis cohort was 6,224 (2.7% of all hospitalizations) patient encounters with opioid misuse with a data corpus of 422,147 clinical notes. LCA identified four subtypes with differing patient characteristics, topics from the clinical notes, and hospital outcomes. Class 1 was categorized by high hospital utilization with known opioid-related conditions (36.5%); Class 2 included patients with illicit use, low socioeconomic status, and psychoses (12.8%); Class 3 contained patients with alcohol use disorders with complications (39.2%); and class 4 consisted of those with low hospital utilization and incidental opioid misuse (11.5%). The following hospital outcomes were the highest for each subtype when compared against the other subtypes: readmission for class 1 (13.9% vs. 10.5%, pConclusionsA 4-class latent model was the most parsimonious model that defined clinically interpretable and relevant subtypes for opioid misuse. Distinct subtypes were delineated after examining multiple domains of EHR data and applying methods in artificial intelligence. The approach with LCA and readily available class-defining substance use variables from the EHR may be applied as a prognostic enrichment strategy for targeted interventions.

Glioma is a heterogeneous cellular environment in which immune cells play critical roles in tumor progression. Myeloid-derived suppressor cells (MDSCs) contribute to the formation of the immunosuppressive microenvironment of glioma; however, how glioma cells interact with MDSCs and how this interaction affects the function of other immune cells are unclear. Glioma cells can systemically communicate with immune cells via the secretion of exosomes, which contain microRNAs (miRNAs). Leveraging miRNA sequencing of exosomes, we identified enrichment of miR-1246 in glioma-derived exosomes and exosomes isolated from the cerebrospinal fluid (CSF) of glioma patients. We demonstrated that miR-1246 drives the differentiation and activation of MDSCs in a dual specificity phosphatase 3 (DUSP3)/extracellular signal‑regulated kinase (ERK)-dependent manner. In addition, postoperative CSF exosomal miR-1246 expression was found to be associated with the glioma recurrence rate. Hypoxia, a well-recognized feature of the glioblastoma microenvironment, increased miR-1246 levels in glioma-derived exosomes by enhancing miR-1246 transcription and selective packaging via upregulation of POU class 5 homeobox 1 (POU5F1) and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Importantly, we identified a mechanism of 2-methoxyestradiol, a microtubule inhibitor currently undergoing clinical trials for glioblastoma. 2-Methoxyestradiol suppresses MDSC activation by inhibiting hypoxia-driven exosomal miR-1246 expression in glioma cells and PD-L1 expression in MDSCs.

In the pertinent literature, standardized sonographic protocols have been widely described to evaluate the different compartments of the shoulder. However, the subcoracoid space is a complex anatomical region-usually not included/described in basic ultrasound approaches. Accordingly, starting from its anatomy, we describe a two-phase dynamic ultrasound protocol to scan the subcoracoid space. This way, we aim to optimize the diagnosis and management of patients with anterior shoulder pain and subcoracoid effusion.

The metabolic fate of a newly developed herbicide, epyrifenacil, (ethyl[(3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]phenoxy}pyridin-2-yl)oxy]acetate, S-3100), in rats was determined using 14C-labeled epyrifenacil. When it was administered orally to rats at 1 mg/kg, around 73-74% of the dose was absorbed, metabolized, and mainly excreted into feces within 48 h. The elimination of radioactivity in plasma and tissues was rapid, suggesting that exposure of epyrifenacil and metabolites is small. Metabolite analysis revealed that epyrifenacil was rapidly ester-cleaved to M1 and then mainly excreted into bile or further metabolized. No parent was detected in plasma, tissues, and urine. Remarkably, M1 was mainly distributed in the liver (at a concentration of 70-112 times higher than in plasma at a low dose). Furthermore, a significant sex-related difference was observed in urinary excretion of M1. Considering the above observations with those in the literature, the organic anion-transporting polypeptide (OATP) likely plays a role on the active transport of M1 in the liver and kidney.

Coronavirus with intact infectivity attached to PPE surfaces pose significant threat to the spread of COVID-19. We tested the hypothesis that an electroceutical fabric, generating weak potential difference of 0.5 V, disrupts the infectivity of coronavirus upon contact by destabilizing the electrokinetic properties of the virion. Porcine respiratory coronavirus AR310 particles (105) were placed in direct contact with the fabric for 1 or 5 min. Following one minute of contact, zeta potential of the porcine coronavirus was significantly lowered indicating destabilization of its electrokinetic properties. Size-distribution plot showed appearance of aggregation of the virus. Testing of the cytopathic effects of the virus showed eradication of infectivity as quantitatively assessed by PI-calcein and MTT cell viability tests. This work provides the rationale to consider the studied electroceutical fabric, or other materials with comparable property, as material of choice for the development of PPE in the fight against COVID-19.

The timely diagnosis and treatment of post-infectious glomerulonephritis (PIGN) is currently limited by the erased and low-symptom nature of the disease, which leads to the search for informative biological markers of the disease, which can be used as immunological indicators of blood and urine. The study was carried out in order to establish the characteristic changes in the immunological parameters of blood and urine in patients with PIGN. The study included 60 patients with PIGN from among the patients, hospitalized in the nephrology department of the Republican Clinical Hospital of Health Care Ministry of the Chuvash Republic in 2015-2018. In addition to the generally accepted research methods, the patients underwent: 1) the determination of indicators of innate and acquired immune response in the blood (CD3+ -, CD3+ CD4+-, CD3+CD8+-, CD4+CD25+-, CD95+-, CD20+-, CD14+CD282+-, CD14+CD284+- cells; levels of IgG, IgA, IgM, circulating immune complexes, C3, C4) and urine (levels of IgG, IgA, IgM, C3, C4); 2) the determination of the levels of cytokines - IL-1β, Ra-IL-1β, IL-2, IL-4, IL-8, IL-10, IL-17A in blood serum and urine. The data obtained were compared with those of the group of healthy individuals. The changes in blood immunological parameters, identified in the group of patients with PIGN, indicate the activation of innate immunity (the increase in the number of CD14+TLR2+- cells) and the humoral component of adaptive immunity (the increase in the number of B-lymphocytes, hyperimmunoglobulinemia - the increase in IgM and IgA levels) against the background of the decrease in the number of T (CD3+) - lymphocytes and regulatory (CD4+CD25high) - cells, hypocomplementemia (decreased levels of C3, C4). The increase in the content of C3, IgG and IgA was found in the urine. The cytokine profile of blood in patients with PIGN was characterized by the increase in the levels of pro- and anti-inflammatory cytokines IL-1β, Ra-IL-1β, IL-2, IL-8, IL-10, IL-17A, with the exception of IL-4, which remained on the levels of healthy individuals. The cytokine profile of urine in patients was characterized by the increase in the levels of pro-inflammatory cytokines IL-1β, IL-2, IL-8, IL-17A and anti-inflammatory cytokine - IL-10, with no changes in the content of Ra-IL-1β and IL-4. The revealed features of the immunological profile of blood and urine in patients with PIGN reflect the immunopathogenetic mechanisms of this disease.

Supplemental Digital Content is Available in the Text., Purpose: Innovative and sustainable sampling strategies for bioanalytical quantification of drugs and metabolites have gained considerable interest. Scavenging can be stratified as a sustainable sampling strategy using residual material because it aligns with the green principles of waste reduction and sampling optimization. Scavenged sampling includes all biological fluids' (eg, blood, liquor, and urine) leftover from standard clinical care. This review elaborates on the past and current landscape of sustainable sampling within therapeutic drug monitoring, with a focus on scavenged sampling. Methods: In February 2021, 4 databases were searched to assess the literature on the clinical use of innovative and sustainable sampling techniques without applying publication date restrictions. Studies reporting the clinical use of scavenged blood sampling and bridging studies of scavenged sampling and normal blood sampling were eligible for inclusion. Results: Overall, 19 eligible studies concerning scavenged sampling were identified from 1441 records. Scavenged sampling is mainly applied in the pediatric population, although other patient groups may benefit from this strategy. The infrastructure required for scavenged sampling encounters several challenges, including logistic hurdles, storage and handling conditions, and documentation errors. A workflow is proposed with identified opportunities that guide the implementation of scavenged sampling. Conclusions: This review presents current evidence on the clinical use of scavenged sampling strategies. Scavenged sampling can be a suitable approach for drug quantification to improve dosage regimens, perform pharmacokinetic studies, and explore the value of therapeutic drug monitoring without additional sample collection.

This study aimed to validate a modified QuEChERS method followed by ultra-high performance liquid chromatography–tandem mass spectrometry to determine 79 new psychoactive substances (NPS) and other drugs in blood and urine. Prescription drugs (n = 23), synthetic cathinones (n = 13), phenethylamines (n = 11); synthetic cannabinoids (n = 8), amphetamines (n = 7) and other psychoactive substances (n = 17) were included in the method. 500 µL of biological fluid was extracted with 2 mL of water/ACN (1:1), 500 mg of anhydrous MgSO4/NaOAc (4:1) added, followed by a supernatant cleanup with 25 mg of primary secondary amine and 75 mg of anhydrous MgSO4. Quantification was done using matrix-matched calibration curves and deuterated internal standards. The method was satisfactorily validated for blood and urine at limit of quantifications ranging from 0.4 to 16 ng/mL, and applied to the analysis of 54 blood (38 postmortem and 16 antemortem) and 16 antemortem urine samples from 68 forensic cases. All urine samples and 59.3% of the blood samples were positive for at least one analyte. Twenty-two analytes were detected in at least one biological sample, including the synthetic cathinones ethylone (222 ng/mL, antemortem blood), eutylone (246 and 446 ng/mL, urine), and N-ethylpentylone (597 and 7.3 ng/mL, postmortem and antemortem blood, respectively). The validated method was shown to be suitable for the analysis of blood and urine forensic samples and an important tool to collect information on emerging drug threats and understanding the impact of NPS and other drugs in poisoning cases.

Objectives Cellular analysis of body fluids (BFs) can assist clinicians for the diagnosis of many medical conditions. The aim of this work is the evaluation of the analytical performance of the UF-5000 body fluid mode (UF-BF) analyzer compared to the gold standard method (optical microscopy, OM) and to XN-1000 (XN-BF), another analyzer produced by the same manufacturer (Sysmex) and with a similar technology for BF analysis. Methods One hundred BF samples collected in K3EDTA tubes were analyzed by UF-BF, XN-BF and OM. The agreement was evaluated using Passing and Bablok regression and Bland–Altman plot analysis. The receiver operating characteristic (ROC) curves were selected for evaluating the diagnostic agreement between OM classification and UF-BF parameters. Results Comparison between UF-BF and OM, in all BF types, showed Passing and Bablok’s slope comprised between 0.99 (polymorphonuclear cells count, PMN-BF) and 1.39 (mononuclear cells count, MN-BF), the intercepts ranged between 26.47 (PMN-BF parameter) and 226.80 (white blood cell count). Bland–Altman bias was comprised between 7.3% (total cell count, TC-BF) and 52.9% (MN-BF). Comparison between UF-BF and XN-BF in all BF showed slopes ranged between 1.07 (TC-BF and PMN-BF) and 1.16 (MN-BF), intercepts ranged between 8.30 (PMN) and 64.78 (WBC-BF). Bland–Altman bias ranged between 5.8 (TC-BF) and 21.1% (MN-BF). The ROC curve analysis showed an area under the curve ranged between 0.9664 and 1.000. Conclusions UF-BF shows very good performance for the differential counts of cells in ascitic, pleural and synovial fluids and therefore it is useful to screen and count cells in this type of BF.

Renal cell carcinoma (RCC) is the second most common cancer of the urinary system, accounting for approximately 10–15% of kidney cancers in the world. Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with the highest mortality. Surgical resection or puncture of tumor tissue is still an important clinical treatment and diagnosis of ccRCC, but its high recurrence rate and poor prognosis often lead to the short survival period of patients. Hence, the development of novel molecular biomarkers is of great clinical importance. miRNAs are endogenous non-coding small RNAs with a length of 19–24 nt. A growing number of studies have reported that miRNAs, as proto-oncogenes or tumor suppressor genes, play a key role in the development of ccRCC and might be effective diagnostic and prognostic biomarkers. In addition, miRNAs can also predict the efficacy of treatment drug, thus improving the accuracy of clinical medication. Furthermore, non-invasive detection of miRNAs or extracellular vesicles (EV) in body fluids has better convenience and repeatability, which shows remarkable advantages compared with tissue detection. In this review, we summarized the typical miRNAs reported in recent years and place emphasis on evaluating miRNAs in different body fluids to provide reference for the clinical diagnosis and prognosis of ccRCC in the future.