Navigating Viral Gastroenteritis: Epidemiological Trends, Pathogen Analysis, and Histopathological Findings.

BACKGROUND: Gastroenteritis is a common cause of morbidity and mortality globally. Its cause encompasses a spectrum of agents, including viruses, bacteria, parasites, toxins, and drugs. Viruses account for a considerable portion of gastroenteritis cases across all age groups, typically presenting with symptoms like nausea, vomiting, diarrhea, dehydration, anorexia, and weight loss. While sporadic cases occur, viral gastroenteritis is more frequently observed in outbreaks within closely knit communities such as daycare facilities, nursing homes, and cruise ships. Therefore, it becomes necessary to determine when healthcare providers should consider this condition in their differential diagnosis and to develop the most effective strategy to confirm the diagnosis. METHODS: De-identified data of patients with gastroenteritis were collected over a five-year period utilizing the Patient Cohort Explorer, an electronic health record at the University of Mississippi Medical Center. Confirmatory laboratory tests employed the BioFire® FilmArray® multiplex polymerase chain reaction for gastrointestinal pathogens. Out of the 22 most common agents associated with gastroenteritis, only viral pathogens, specifically adenovirus, astrovirus, norovirus, rotavirus, and sapovirus, were included in the analysis. When available, histopathology was reviewed. RESULTS: Among the various causes of gastroenteritis, both infectious and non-infectious, our findings revealed that 25.46% of the cases were linked to viral pathogens. This included a significantly higher percentage of pediatric patients (72.73%) when compared to adults (27.07%), with a p-value of 0.015. Norovirus genogroups I and II emerged as the most frequently detected viruses across all age groups, with a significant prevalence among adults. No discernible gender-based differences were observed. The histopathological findings included inflammation, ulceration, erosion, architectural distortion, and the pathognomonic viral inclusion bodies associated with adenovirus. CONCLUSION: Our comprehensive analysis of viral gastroenteritis cases highlights the substantial burden of this condition, particularly among pediatric patients. Norovirus emerges as a prevalent culprit which emphasizes the importance of vigilant surveillance and timely diagnosis, especially in settings where outbreaks are common.

Evaluation of the ARK Diagnostics immunoassay for qualitative detection of xylazine in urine.

Xylazine exposure is common in some US cities, but a commercial assay for routine laboratory testing for xylazine is not currently available. We evaluated a pre-release version of the ARK Diagnostics immunoassay for qualitative detection of xylazine/4-hydroxyxylazine in urine. Studies were conducted using either the semi-quantitative assay application (A. Roche Cobas 503 analyzer) or the qualitative assay application (B. Beckman Coulter AU480 analyzer). Study specimens consisted of deidentified patient urine samples submitted for routine drugs-of-abuse testing. Measurements of xylazine (X) were performed by LC-MS-MS to obtain X-NEGATIVE (X <10 ng/mL) and X-POSITIVE (X ≥10 ng/mL). The semi-quantitative ARK assay was calibrated with a 10 ng/mL cutoff for ARK-POSITVE. For (A): among 74 X-POSITIVE samples, there was 1 ARK-NEGATIVE result (false-negative rate = 1.4%); among 78 X-NEGATIVE samples by LC-MS-MS, there were 0% ARK-POSITIVE results (false-positive rate = 0%). For (B), among 74 X-POSITIVE samples, there were 0 ARK-NEGATIVE results (false-negative rate = 0%); among 78 X-NEGATIVE samples there was 1 ARK-POSITIVE sample (false-positive rate = 1.3%). Common sources of interferences were investigated without evidence of interference. The ARK xylazine/4-OH-xylazine immunoassay was found to be suitable for routine use in screening patient urine samples for presence of xylazine >10 ng/mL.

Using the Sustainable Development Goals in undergraduate leadership programs.

Undergraduate leadership education prepares students for meaningful roles in various aspects of civic and professional life. In this article, the authors explore the contextual facets of undergraduate academic leadership programs and courses utilizing the Sustainable Development Goals (SDGs) as a framework for addressing local and global challenges through leadership education and development at two higher education institutions. Each example is described contextually followed by promising classroom practices embedded through the use of the SDG framework.

Evaluating the regulation of transporter proteins and P-glycoprotein in rats with cholestasis and its implication for digoxin clearance.

BACKGROUND: Cardiac and hepatic functionality are intertwined in a multifaceted relationship. Pathologic processes involving one may affect the other through a variety of mechanisms, including hemodynamic and membrane transport effects. AIM: To better understand the effect of extrahepatic cholestasis on regulations of membrane transporters involving digoxin and its implication for digoxin clearance. METHODS: Twelve adult rats were included in this study; baseline hepatic and renal laboratory values and digoxin pharmacokinetic (PK) studies were established before evenly dividing them into two groups to undergo bile duct ligation (BDL) or a sham procedure. After 7 d repeat digoxin PK studies were completed and tissue samples were taken to determine the expressions of cell membrane transport proteins by quantitative western blot and real-time polymerase chain reaction. Data were analyzed using SigmaStat 3.5. Means between pre-surgery and post-surgery in the same experimental group were compared by paired t-test, while independent t-test was employed to compare the means between sham and BDL groups. RESULTS: Digoxin clearance was decreased and liver function, but not renal function, was impaired in BDL rats. BDL resulted in significant up-regulation of multidrug resistance 1 expression in the liver and kidney and its down-regulation in the small intestine. Organic anion transporting polypeptides (OATP)1A4 was up-regulated in the liver but down-regulated in intestine after BDL. OATP4C1 expression was markedly increased in the kidney following BDL. CONCLUSION: The results suggest that cell membrane transporters of digoxin are regulated during extrahepatic cholestasis. These regulations are favorable for increasing digoxin excretion in the kidney and decreasing its absorption from the intestine to compensate for reduced digoxin clearance due to cholestasis.

Postoperative consequences of cancer cachexia after head and neck free flap reconstruction.

BACKGROUND: Cachexia is detrimental for patients with head and neck cancer (HNC). However, postoperative consequences of HNC cachexia remain unknown. METHODS: A 2014-2019 retrospective review was performed of adults undergoing aerodigestive HNC resection with free tissue reconstruction. Propensity score matching using inverse probability of treatment weighting (IPTW) of cachectic and control groups was employed to adjust for covariate imbalances followed by binary logistic regression on postoperative outcomes. RESULTS: Out of 252 total patients, 135 (53.6%) had cancer cachexia. The cohort was predominantly white (94.4%) males (65.1%) aged 61.5 ± 11.5 years with stage III-IV (84.1%) malignancy of the oral cavity (66.3%). After matching cohort pre- and intra-operative covariates using IPTW, cancer cachexia remained a strong, significant predictor of serious National Surgical Quality Improvement Program (NSQIP) complications (OR [95%CI] = 3.84 [1.80-8.21]) and major Clavien-Dindo complications (OR [95%CI] = 3.00 [1.18-7.60]). CONCLUSIONS: Cancer cachexia is associated with worse HNC free flap reconstruction outcomes.

Efficacy of POC Antibody Assays after COVID-19 Infection and Potential Utility for "Immunity Passports".

OBJECTIVE: Numerous manufacturers market lateral flow assays for the detection of SARS-CoV-2 antibodies, but there are many questions about the reliability and efficacy of these tests. MATERIALS AND METHODS: Serum specimens from 60 individuals were analyzed using 2 lateral flow antibody assays, an in-house enzyme-linked immunosorbent assay (ELISA), and the Abbott SARS-CoV-2 IgG chemiluminescent immunoassay. RESULTS: The BioMedomics and Premier Biotech lateral flow assays were positive for IgM in 73.3% and 70% and for IgG in 80% and 73.3% of specimens, respectively. The ELISA assay was positive for IgM and IgG in 73.3% and 86.7% of specimens from infected individuals, whereas the Abbott assay was positive in 80%. The specificities of the 4 assays ranged from 96.7% to 100% for IgM and from 93.3% to 100% for IgG. CONCLUSION: Results of the 2 lateral flow assays were comparable to those of the ELISA and Abbott assays. Assay efficacy depended on length of time after SARS-CoV-2 infection.

The association of prostatic lipids with progression, racial disparity and discovery of biomarkers in prostate cancer.

BACKGROUND: It remains under-investigated whether prostatic lipid profiles are associated with pathogenesis, progression, racial disparity, and discovery of biomarkers in prostate cancer (PCa). METHODS: The electrospray ionization-tandem mass spectrometry was applied to quantitate prostatic lipids in human and mouse PCa and non-cancer prostatic tissues. Biostatistics and bioinformatics were used to compare the concentrations of prostatic lipids at levels of total lipid, group, class and individual species between PCa and benign prostatic tissues, between races, and among pathological conditions of PCa. RESULTS: Prostatic concentrations of total lipids as well as neutral lipids were significantly higher in PCa than in benign prostatic tissues in all population and Caucasian American population, but not in African American population. The prostatic phospholipid were not statistically different between PCa and benign prostatic tissues in all study populations. Cholesteryl ester is the only lipid class significantly higher in PCa than in benign prostatic tissues in all study populations. A panel of prostatic lipid parameters in each study population was identified as diagnostic and prognostic biomarkers with >60% of sensitivity, specificity and accuracy simultaneously. Lipid profiling on mouse prostatic tissues further confirmed correlation of prostatic lipid profiles to the pathogenesis and progression of PCa. In addition, a few prostatic lipids in mouse can serve as prognostic biomarkers in differentiation of indolent from aggressive PCa. CONCLUSION: The prostatic lipids are widely associated with the pathogenesis, progression and racial disparity of PCa. A panel of prostatic lipids can serve as diagnostic, prognostic and race-specific biomarkers for PCa.

A systematic review and meta-analysis on the efficacy and safety of metformin as adjunctive therapy among women with metastatic breast cancer.

BACKGROUND: Breast cancer is the most common cancer among women worldwide and is one of the leading causes of cancer-related mortalities. Metformin has been found to have direct and indirect antitumor mechanisms, and because of its availability and good safety profile, it has been investigated to be useful in various malignancies including breast cancer. OBJECTIVE: This study aims to determine the efficacy and safety of metformin administration as adjunctive therapy on mortality among females with breast cancer. METHODS: This is a systematic review and meta-analysis of randomized clinical trials (RCTs) on the use of metformin as adjunctive therapy when combined with standard chemotherapy on the outcomes of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and clinical benefit rate (CBR). RESULTS: After a comprehensive literature search, only three phase 2 RCTs on the use of metformin as adjunctive therapy for locally advanced and metastatic breast cancer were included. Clinical trials on early breast cancer are still ongoing and none were included in the present review. This study, based on the systematic review, revealed that metformin added to standard chemotherapy does not improve the PFS and OS among women with metastatic breast cancer, and likewise, has no impact on the ORR with a relative risk of 1.42 95% CI 0.45-4.55 and CBR with an RR of 0.87, 95% CI 0.55-1.37. It appears to be safe and may even be protective for the development of neutropenia based on at least one study. CONCLUSION: This study clarifies that there is insufficient evidence on the benefits of metformin on survival among women with metastatic breast cancer.

Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model.

Chronic kidney disease (CKD), which can ultimately progress to kidney failure, is influenced by genetics and the environment. Genes identified in human genome wide association studies (GWAS) explain only a small proportion of the heritable variation and lack functional validation, indicating the need for additional model systems. Outbred heterogeneous stock (HS) rats have been used for genetic fine-mapping of complex traits, but have not previously been used for CKD traits. We performed GWAS for urinary protein excretion (UPE) and CKD related serum biochemistries in 245 male HS rats. Quantitative trait loci (QTL) were identified using a linear mixed effect model that tested for association with imputed genotypes. Candidate genes were identified using bioinformatics tools and targeted RNAseq followed by testing in a novel in vitro model of human tubule, hypoxia-induced damage. We identified two QTL for UPE and five for serum biochemistries. Protein modeling identified a missense variant within Septin 8 (Sept8) as a candidate for UPE. Sept8/SEPTIN8 expression increased in HS rats with elevated UPE and tubulointerstitial injury and in the in vitro hypoxia model. SEPTIN8 is detected within proximal tubule cells in human kidney samples and localizes with acetyl-alpha tubulin in the culture system. After hypoxia, SEPTIN8 staining becomes diffuse and appears to relocalize with actin. These data suggest a role of SEPTIN8 in cellular organization and structure in response to environmental stress. This study demonstrates that integration of a rat genetic model with an environmentally induced tubule damage system identifies Sept8/SEPTIN8 and informs novel aspects of the complex gene by environmental interactions contributing to CKD risk.

Tuberculosis case finding and case holding practices in selected Drug Abuse Treatment and Rehabilitation Centers (DATRCS) in Luzon, Philippines

@#<p style="text-align: justify;"><strong>Background and Objectives:</strong> Tuberculosis (TB) remains a public health problem in the Philippines despite trends indicating a decline in the burden of disease. Persons who use drugs who are confined in government-retained drug abuse treatment and rehabilitation centers (DATRCs) face an increased risk for TB because of the congestion in the facility coupled with the absence of guidelines on TB management specific to DATRCs. Thus, this study was conducted to document the current case finding and case holding practices as well as TB treatment pathway in six (6) Luzon-based, government-retained DATRCs.</p><p style="text-align: justify;"><strong>Methods:</strong> Key informant interviews were conducted with DATRC personnel involved in TB diagnosis and management in six selected DATRCs in Luzon, Philippines. Interviews were transcribed and coded for thematic analysis. We compared the DATRC practices with the provisions of the 2014 National TB Control Program (NTP) Manual of Procedures. Results were validated through a workshop with (a) a group of physicians and rehabilitation practitioners assigned in other DATRCs; and (b) a group of experts who have experience in managing or overseeing DATRCs in the country.</p><p style="text-align: justify;"><strong>Results:</strong> Two physicians and four nurses participated in the interviews. Variations in case finding and case holding practices in six DATRCs have been found. National guidelines exist for congregate settings but are more specific to jails/prisons, which are administratively and operationally different from DATRCs.</p><p style="text-align: justify;"><strong>Conclusion:</strong> Development of special guidelines for TB case finding and case holding in DATRCs as well as staff training on the latest NTP Manual of Procedures are recommended. However, gaps and inequities posed by the current set-up underscore the need to address health system-wide factors affecting the practice and performance of these facilities.</p><p style="text-align: justify;"><strong>Key Words:</strong> tuberculosis, case finding, case holding, drug abuse treatment and rehabilitation centers, Philippines</p>

Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome.

BACKGROUND: The incidence of acute kidney injury (AKI) during pregnancy precedes a high maternal mortality rate of 20-40%. AKI during pregnancy has multiple etiologies; however, the more common are maternal hypertensive disorders, which include preeclampsia and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. Therefore, we sought to assess the impact of AKI on blood pressure, kidney injury, and anti-angiogenic factors during pregnancies with and without HELLP syndrome. METHODS: On gestational day (GD) 12, mini-osmotic pumps were inserted into a subset of normal pregnant (NP) rats infusing 4.7 µg/kg soluble fms-like tyrosine kinase-1 (sFlt-1) and 7 µg/kg soluble endoglin (sEng) to induce HELLP syndrome. On GD18, the renal pedicles were occluded for 45 min to induce AKI via bilateral ischemia reperfusion in a subset of NP (n = 18) or HELLP (n = 20) rats. Control NP (n = 20) and HELLP (n = 20) rats underwent a SHAM surgery on GD18. Plasma, urine, and maternal organs were saved for further analysis. Renal injury was assessed via renal histopathology, glomerular filtration rate (GFR), T cell infiltration, and assessment of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Data was measured via two-way analysis of variance with Tukey's test for post hoc analysis. RESULTS: Blood pressures were increased in HELLP+AKI rats (p = 0.0001); both NP+AKI and HELLP+AKI rats had increased lactate dehydrogenase (p < 0.0001) and aspartate aminotransferase levels (p < 0.0001), and decreased platelet levels (p < 0.001) vs. NP rats. HELLP+AKI (p = 0.002) and HELLP rats (p = 0.0002) had evidence of renal fibrosis vs. NP rats. GFR was decreased in HELLP+AKI (p = 0.01) rats vs. NP rats. Urinary KIM-1 was increased in NP+AKI rats vs. NP (p = 0.003) and HELLP rats (p = 0.01). HELLP+AKI rats had increased urinary KIM-1 vs. NP (p = 0.0008) and HELLP rats (p = 0.004) and increased NGAL vs. HELLP rats (p = 0.002). HELLP+AKI rats had increased sFlt-1 (p = 0.009) vs. NP rats. NP+AKI (p = 0.02) and HELLP+AKI (p = 0.007) rats had increased sEng vs. NP rats. CD3+CD4+ T cells were significantly increased in HELLP+AKI rats vs. NP (p = 0.0002) and NP+AKI (p = 0.05) rats. T regulatory cells were significantly decreased in HELLP+AKI (p = 0.03) and NP+AKI (p = 0.02) rats vs. NP rats; there were no changes between groups in T helper 17 cells (p = 0.34). CONCLUSION: The findings in this study suggest that AKI during pregnancy contributes to increased blood pressure and biochemical markers for HELLP syndrome, creates an anti-angiogenic imbalance, and exacerbates kidney injury as shown on histopathology, GFR, and kidney injury markers.

Fas ligand neutralization attenuates hypertension, endothelin-1, and placental inflammation in an animal model of HELLP syndrome.

Neutralization of FasL is linked to suppression of hypertension, placental inflammation, and endothelin system activation in an animal model of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. During HELLP syndrome the placenta has been reported to serve as the primary source of Fas ligand (FasL), which has an impact on inflammation and hypertension during pregnancy and is dysregulated in women with severe preeclampsia and HELLP syndrome. We hypothesize that neutralization of FasL during pregnancy in an animal model of HELLP syndrome decreases inflammation and placental apoptosis, improves endothelial damage, and improves hypertension. On gestational day (GD) 12, rats were chronically infused with placental antiangiogenic factors sFlt-1 and sEng to induce HELLP syndrome. To neutralize FasL, MFL4 or FasL antibody was infused into a subset of HELLP or normal pregnant rats on GD13. IgG infusion into another group of NP and HELLP rats on GD13 was used as a control for FasL antibody, and all rats were euthanized on GD19 after blood pressure measurement. Plasma and placentas were collected to assess inflammation, apoptosis, and the degree of placental debris activation of endothelial cells. Administration of MFL4 to HELLP rats significantly decreased blood pressure compared with untreated HELLP rats and HELLP rats infused with IgG and improved the biochemistry of HELLP syndrome. Both circulating and placental FasL were significantly attenuated in response to MFL4 infusion, as were levels of placental and circulating TNFα when compared with untreated HELLP rats and HELLP rats infused with IgG. Endothelial cells exposed to placental debris and media from HP + MFL4 rats secreted significantly less endothelin-1 compared with stimulated endothelial cells from HELLP placentas. Neutralization of FasL is associated with decreased MAP and improvement in placental inflammation and endothelial damage in an animal model of HELLP syndrome.

AACC Guidance Document on Biotin Interference in Laboratory Tests.

BACKGROUND: Laboratory tests that use streptavidin-biotin binding mechanisms have the potential to be affected by high circulating biotin concentrations, which would produce positive and negative interference in biotinylated competitive and noncompetitive (sandwich) immunoassays, respectively. Consumption of high-dose biotin supplements for cosmetic or health-related reasons has drawn attention to biotin interference in clinical laboratory tests. Case reports and in vivo studies show that ingestion of supplemental biotin can cause clinically significant errors in select biotinylated immunoassays. CONTENT: This AACC Academy document is intended to provide guidance to laboratorians and clinicians for preventing, identifying, and dealing with biotin interference. In vivo and in vitro spiking studies have demonstrated that biotin concentrations required to cause interference vary by test and by manufacturer. This document includes discussion of biotin's mechanisms for interference in immunoassays, pharmacokinetics, and results of in vitro and in vivo studies and cites examples of assays known to be affected by high biotin concentrations. This document also provides guidance recommendations intended to assist laboratories and clinicians in identifying and addressing biotin interference in laboratory testing. SUMMARY: The recent increase in the use of high-dose biotin supplements requires laboratorians and clinicians to be mindful of the potential for biotin interference in biotinylated immunoassay-based laboratory tests. Laboratories, clinicians, regulators, and patients should work together to ensure accurate laboratory results. Laboratories have several options for identifying suspected biotin interference in specimens. Alternatively, the relatively fast elimination of biotin allows the potential for rapid follow-up specimen analysis if necessary.

Loss of Arhgef11 in the Dahl Salt-Sensitive Rat Protects Against Hypertension-Induced Renal Injury.

Arhgef11 is a Rho-guanine nucleotide exchange factor that was previously implicated in kidney injury in the Dahl salt-sensitive (SS) rat, a model of hypertension-related chronic kidney disease. Reduced Arhgef11 expression in an SS-Arhgef11SHR-minimal congenic strain (spontaneously hypertensive rat allele substituted for S allele) significantly decreased proteinuria, fibrosis, and improved renal hemodynamics, without impacting blood pressure compared with the control SS (SS-wild type). Here, SS-Arhgef11-/- and SS-wild type rats were placed on either low or elevated salt (0.3% or 2% NaCl) from 4 to 12 weeks of age. On low salt, starting at week 6 and through week 12, SS-Arhgef11-/- animals demonstrated a 3-fold decrease in proteinuria compared with SS-wild type. On high salt, beginning at week 6, SS-Arhgef11-/- animals demonstrated >2-fold lower proteinuria from weeks 8 to 12 and 30 mm Hg lower BP compared with SS-wild type. To better understand the molecular mechanisms of the renal protection from loss of Arhgef11, both RNA sequencing and discovery proteomics were performed on kidneys from week 4 (before onset of renal injury/proteinuria between groups) and at week 12 (low salt). The omics data sets revealed loss of Arhgef11 (SS-Arhgef11-/-) initiates early transcriptome/protein changes in the cytoskeleton starting as early as week 4 that impact a number of cellular functions, including actin cytoskeletal regulation, mitochondrial metabolism, and solute carrier transporters. In summary, in vivo phenotyping coupled with a multi-omics approach provides strong evidence that increased Arhgef11 expression in the Dahl SS rat leads to actin cytoskeleton-mediated changes in cell morphology and cell function that promote kidney injury, hypertension, and decline in kidney function.

Evaluating Novel Markers for Specimen Validity Testing.

CONTEXT.­: Synthetic urine products are commercially marketed for the purpose of specimen substitution for urine drug screens. These products are widely popular because they yield negative drug screen results, meet criteria for specimen validity testing, and are easily accessible and affordable. Current specimen validity criteria are ineffective for detecting these synthetic products, and new markers of specimen validity are required. OBJECTIVE.­: To develop and evaluate a multicomponent liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for urine specimen validity testing. DESIGN.­: A quantitative LC-MS/MS assay was developed for caffeine, cotinine, theobromine, and urobilin in urine. The assay was applied to known synthetic urine products (n = 10) as well as human specimens received for pre-employment testing (n = 500), for-cause workplace testing (n = 100), and medical pain management monitoring (n = 200). Specimens devoid of all 4 validity markers were subjected to follow-up testing that involved microscopic urinalysis and comprehensive gas chromatography mass spectrometry for drugs, pharmaceuticals, hormones, and lipids. RESULTS.­: Of the experimental groups, 10 of 10 synthetic urine products (100%), 12 of 500 pre-employment specimens (2.4%), and 4 of 200 pain management specimens (2.0%) failed the experimental LC-MS/MS assay. Follow-up testing indicated that each of the failed specimens was nonphysiologic in nature. CONCLUSIONS.­: Simultaneous application of the 4 experimental validity markers appeared to be a robust method for detecting nonphysiologic specimens. New markers of specimen validity must be developed in order to identify commercially available synthetic urine products.

Tuberculosis in Selected Drug Abuse Treatment and Rehabilitation Centers (DATRCs) in Luzon, Philippines

Background and Objectives@#Tuberculosis (TB) continues to be a public health concern in the Philippines. Vulnerable populations in congregate settings such as drug abuse treatment and rehabilitation centers (DATRCs) have higher risks of TB transmission and infection. With the Duterte administration’s intensified campaign against illegal drugs, government-retained DATRCs are filled to capacity. There is an identified need to profile drug users and dependents living in DATRCs. Furthermore, national guidelines for TB management specific to this population is absent. A study was conducted to determine the profile of admitted clients diagnosed with TB, TB prevalence, treatment outcomes and choice of TB diagnostic modalities in six (6) Luzon-based DATRCs from 2013-2015.@*Methods@#All medical records of drug users admitted in this period were reviewed. Information on the total patient census was sought from DATRC heads and used to compute for prevalence.@*Results@#A total of 347 records were obtained. Overall TB prevalence in the study sites was 7,216 per 100,000 population. The typical individual diagnosed with TB in a DATRC was male, with a mean age of 35 years, with at least high school education, and unemployed. Weight loss and fatigue were the most common symptoms reported. The majority (79.83%) completed TB treatment in the DATRCs. Sputum microscopy and chest x-ray were both used for TB diagnosis in 92.80% (322) of the cases.@*Conclusion@#The high burden of TB in Luzon-based, government-retained DATRCs is alarming and underscore the critical need for standards and guidelines in the National Tuberculosis Control Program addressing the unique context of these facilities.

Severe illness associated with reported use of synthetic cannabinoids: a public health investigation (Mississippi, 2015).

STUDY OBJECTIVES: In April 2015, a multistate outbreak of illness linked to synthetic cannabinoid (SC) use was unprecedented in magnitude and severity. We identified Mississippi cases in near-real time, collected information on cases to characterize the outbreak, and identified the causative SC. METHODS: A case was defined as any patient of a Mississippi healthcare facility who was suspected of SC use and presenting with ≥2 of the following symptoms: sweating, severe agitation, or psychosis during April 2-May 3, 2015. Clinicians reported cases to the Mississippi Poison Control Center (MPCC). We used MPCC data to identify cases at the University of Mississippi Medical Center (UMMC) to characterize in further detail, including demographics and clinical findings. Biologic samples were tested for known and unknown SCs by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). RESULTS: Clinicians reported 721 cases (11 deaths) statewide; 119 (17%) were UMMC patients with detailed data for further analysis. Twelve (10%) were admitted to an intensive care unit and 2 (2%) died. Aggression (32%), hypertension (33%), and tachycardia (42%) were common. SCs were identified in serum from 39/56 patients (70%); 33/39 patients (85%) tested positive for MAB-CHMINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide) or its metabolites. Compared to all patients tested for SCs, those positive for MAB-CHMINACA were more likely to have altered mental status on examination (OR = 3.3, p = .05). CONCLUSION: SC use can cause severe health effects. MAB-CHMINACA was the most commonly detected SC in this outbreak. As new SCs are created, new strategies to optimize surveillance and patient care are needed to address this evolving public health threat.

Hypertension, Anxiety, and Blood-Brain Barrier Permeability Are Increased in Postpartum Severe Preeclampsia/Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome Rats.

Hypertension and inflammation during pregnancy are suggested to contribute to the development of postpartum depression and anxiety. Using a rat model of severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, which displays both hypertension and inflammation during pregnancy, we evaluated whether rats were prone to develop depression or anxiety in the postpartum period. On gestational day 12, miniosmotic pumps infusing sFlt-1 (soluble fms-like tyrosine kinase-1) and sEng (soluble endoglin) were placed into rats, a subset of these rats was infused with 2 mg/kg of Orencia (abatacept) the following day to determine whether immune suppression via T-cell depletion prevented any changes in maternal depression or anxiety-like behavior. All rats, including normal pregnant (NP) controls, delivered between gestational days 21 and 22. Postpartum severe preeclamptic rats buried significantly more marbles compared with NP rats ( P=0.002) and Orencia-treated rats ( P=0.05). Severe preeclamptic rats spent significantly more time in closed arms of the elevated plus maze compared with NP rats ( P=0.009) and Orencia-treated rats ( P=0.05). Severe preeclamptic rats were hypertensive compared with NP ( P=0.03) and Orencia-treated rats ( P=0.01). Finally, severe preeclamptic rats had increased blood-brain barrier permeability compared with NP rats ( P=0.03), which was reversed in Orencia-treated rats ( P=0.008). These results suggest that severe preeclampsia/hemolysis, elevated liver enzymes, and low platelet count syndrome during pregnancy contributes to an increase in anxiety-like behavior, blood-brain barrier permeability, and hypertension in the postpartum. The current results suggest that T-cell suppression during pregnancy can also help prevent chronic hypertension and increased anxiety in the postpartum period.

Attenuation of oxidative stress and hypertension in an animal model of HELLP syndrome.

HELLP (hemolysis elevated liver enzyme low platelet) syndrome is associated with hypertension, inflammation, oxidative stress and endothelial activation. The objective of this study was to determine if oxygen scavenging or endothelin A receptor antagonism improved hypertension and oxidative stress. sFlt-1 and sEndoglin were infused via mini-osmotic pump into normal pregnant rats (NP) on gestational day 12 to create HELLP syndrome. On gestational day 18 arterial catheters were inserted and on gestational day 19 mean arterial pressure was analyzed in rats; serum, urine and tissues were collected for molecular analysis. HELLP rats had significantly increased MAP compared to control normal pregnant rats (P < 0.0005). Endothelin A receptor antagonism via ABT-627 and Tempol, superoxide dismutase mimetic, were administered to a subset of normal pregnant and HELLP rats beginning on gestational day 13 and attenuated mean arterial pressure in HELLP rats (P < 0.05; P < 0.005). There were no statistically significant differences in mean arterial pressure between NP+ETA Receptor or NP+Tempol treated rats and NP rats (P = 0.22). Endothelin A receptor blockade significantly decreased HELLP induced isoprostane excretion (P < 0.0005), placental and hepatic reactive oxygen species (P < 0.05; P < 0.0005) and increased placental total antioxidant capacity (P < 0.005) compared to untreated HELLP rats. Similar results in isoprostane (P < 0.005), hepatic reactive oxygen species (P < 0.05) and placental total antioxidant capacity (P < 0.05) were seen in HELLP rats treated with Tempol or Endothelin A receptor antagonist vs. untreated HELLP rats. These data demonstrated a role for oxidative stress in contributing to the hypertension, placental and liver damage that is seen in HELLP syndrome.

Chromatin potentiates transcription.

Chromatin isolated from the chromosomal locus of the PHO5 gene of yeast in a transcriptionally repressed state was transcribed with 12 pure proteins (80 polypeptides): RNA polymerase II, six general transcription factors, TFIIS, the Pho4 gene activator protein, and the SAGA, SWI/SNF, and Mediator complexes. Contrary to expectation, a nucleosome occluding the TATA box and transcription start sites did not impede transcription but rather, enhanced it: the level of chromatin transcription was at least sevenfold greater than that of naked DNA, and chromatin gave patterns of transcription start sites closely similar to those occurring in vivo, whereas naked DNA gave many aberrant transcripts. Both histone acetylation and trimethylation of H3K4 (H3K4me3) were important for chromatin transcription. The nucleosome, long known to serve as a general gene repressor, thus also performs an important positive role in transcription.