Search

BackgroundDespite recommendations, many middle-age adults neglect to check their blood cholesterol levels. Short message service (SMS, also known as texting) has been seldom studied for preventive education. We estimated how SMS can be a cost-effective method in encouraging people to check their blood cholesterol levels.MethodsIn a field trial, 3600 cell phone users (age > 30) were randomly assigned to the intervention (N: 1200) and the control groups (N: 2400). An SMS was sent to the intervention group for five rounds every two weeks, which targeted the cognitive and affective learning and finally advised the blood cholesterol level to be checked, if not checked during the past twelve months. Two weeks after the last round, both groups were asked for the time/level of their latest blood cholesterol, family history of early cardiac death and having a family member with coronary heart disease (CHD), and to report their attitude about whether annual blood sampling is worth the cost and time to prevent CHD. Moreover, the intervention group was asked if they remembered the SMS content. The cost-effectiveness was evaluated by estimating the "number needed to treat" (NNT) and calculating the cost of sending SMS to that number of people.ResultsIn the intervention group, 629 individuals (72.0%) recalled the SMS content. The factors associated with cholesterol screening during the past two years were older age, diabetes, family history of coronary disease, higher education, female gender and being non-smoker. In both groups, women were significantly more aware of their blood cholesterol level (68.7% vs. 53.6%). The relative frequency of respondents who believed it was not worth checking their cholesterol annually was significantly lower in the intervention group (P

Acesulfame potassium (ACE-K) is an artificial sweetener widely used in many foods. This investigation assessed the cytotoxic effect of ACE-K using MTT assay in human hepatocellular carcinoma (HepG2) cell line and the genotoxic effect using chromosomal aberrations (CAs), micronucleus (MN), and comet assays in human lymphocytes. 7.5-240 μg/mL concentrations of ACE-K were applied to cells. ACE-K notably decreased the cell viability on HepG2 cells, especially at 120 and 240 μg/mL at 24 and 48 h. It also significantly reduced the mitotic index (MI) at 60, 120, and 240 μg/mL at both treatments (24 and 48 h) in human lymphocytes. The frequency of the CAs significantly increased at 60, 120, and 240 μg/mL for 48 h treatment compared to control. However, no difference was observed in the frequency of MN and nuclear division index (NDI) at all the treatments. ACE-K also induced comet tail length, tail intensity, and moment at 15 μg/mL in isolated human lymphocytes. Therefore, ACE-K showed a cytotoxic effect in HepG2 cells as well as human lymphocytes at higher concentrations. It also exhibits a mild genotoxic effect by increasing the frequency of CAs at long-term treatment and DNA damaging effect only at 15 μg/mL. [ABSTRACT FROM AUTHOR]

Background: Finger-stick point-of-care and dried blood spot (DBS) hepatitis C virus (HCV) RNA testing increases testing uptake and linkage to care. This systematic review evaluated the diagnostic accuracy of point-of-care testing and DBS to detect HCV RNA.Methods: Bibliographic databases and conference presentations were searched for eligible studies. Meta-analysis was used to pool estimates.Results: Of 359 articles identified, 43 studies were eligible and included. When comparing the Xpert HCV Viral Load Fingerstick assay to venous blood samples (7 studies with 987 samples), the sensitivity and specificity for HCV RNA detection was 99% (95% confidence interval [CI], 97%-99%) and 99% (95% CI, 94%-100%) and for HCV RNA quantification was 100% (95% CI, 93%-100%) and 100% (95% CI, 94%-100%). The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing was 6% (95% CI, 3%-11%). When comparing DBS to venous blood samples (28 studies with 3988 samples) the sensitivity and specificity for HCV RNA detection was 97% (95% CI, 95%-98%) and 100% (95% CI, 98%-100%) and for HCV RNA quantification was 98% (95% CI, 96%-99%) and 100% (95% CI, 95%-100%).Conclusions: Excellent diagnostic accuracy was observed across assays for detection of HCV RNA from finger-stick and DBS samples. The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing highlights the importance of operator training and quality assurance programs. [ABSTRACT FROM AUTHOR]

Summary: Background: The early detection and management of children with metabolic associated fatty liver disease (MAFLD) is challenging. Objective: To develop a non‐invasive and accurate prediction protocol for the identification of MAFLD among children with overweight/obesity candidates to confirmatory diagnosis. Methods: A total of 115 children aged 8–12 years with overweight/obesity, recruited at a primary care, were enrolled in this cross‐sectional study. The external validation was performed using a cohort of children with overweight/obesity (N = 46) aged 8.5–14.0 years. MAFLD (≥5.5% hepatic fat) was diagnosed by magnetic resonance imaging (MRI). Fasting blood biochemical parameters were measured, and 25 candidates' single nucleotide polymorphisms (SNPs) were determined. Variables potentially associated with the presence of MAFLD were included in a multivariate logistic regression. Results: Children with MAFLD (36%) showed higher plasma triglycerides (TG), insulin, homeostasis model assessment of insulin resistance (HOMA‐IR), alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyl‐transferase (GGT) and ferritin (p < 0.05). The distribution of the risk‐alleles of PPARGrs13081389, PPARGrs1801282, HFErs1800562 and PNLPLA3rs4823173 was significantly different between children with and without MAFLD (p < 0.05). Three biochemical‐ and/or SNPs‐based predictive models were developed, showing strong discriminatory capacity (AUC‐ROC: 0.708–0.888) but limited diagnostic performance (sensitivity 67%–82% and specificity 63%–69%). A prediction protocol with elevated sensitivity (72%) and specificity (84%) based on two consecutive steps was developed. The external validation showed similar results: sensitivity of 70% and specificity of 85%. Conclusions: The HEPAKID prediction protocol is an accurate, easy to implant, minimally invasive and low economic cost tool useful for the early identification and management of paediatric MAFLD in primary care. [ABSTRACT FROM AUTHOR]

Background: The anion gap (AG) is often used to evaluate acid–base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non‐gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation. Aims: To determine the reference interval for AG based on current laboratory techniques. Methods: During a health‐screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally accredited clinical laboratory. AG was calculated by [Na+] − [Cl−] − [HCO3−] and AGK by [Na+] + [K+] − [Cl−] − [HCO3−]. The reference interval was determined at 2.5th–97.5th percentiles. Analysis was further undertaken for a subcohort of 156 individuals with no suboptimal health indicators. Results: Median age was 35 years, body mass index 23.4 kg/m2 and the glomerular filtration rate was 106 mL/min/1.73 m2. Median AG was 13 mmol/L and the reference interval for normal AG is 10–18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin, but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub‐cohort of 156 individuals. Median AGK was 17.7 mmol/L and reference interval was 14.6–22.5 mmol/L. Conclusions: The AG reference interval of 10–18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non‐gap acidosis or mixed acid–base disorders. [ABSTRACT FROM AUTHOR]

Background There are few data on the utility of tenofovir diphosphate (TFV-DP) in dried blood spots (DBSs) to predict future viral load (VL) in postpartum women with HIV on antiretroviral therapy (ART). Methods We conducted a nested case-control study within a trial of postpartum ART delivery strategies. Participants started ART containing tenofovir disoproxil fumarate (TDF) in pregnancy, were <10 weeks postpartum, and had a VL <400 copies/mL. VL and TFV-DP samples were taken every 3–6 months over 24 months. Cases had ≥1 VL ≥20 copies/mL; controls were randomly sampled from women with persistent viral suppression (VS; VL <20 copies/mL). Generalized estimating equations were used to calculate likelihood odds ratios (LORs) for future VL ≥20 copies/mL by TFV-DP concentration at the preceding visit. Results 61 cases and 20 controls contributed 365 DBS-VL pairs (median ART duration, 16 months). Sensitivity and specificity of TFV-DP <700 fmol/punch to detect future viremia were 62.9% (95% CI, 54.7–70.6%) and 89.7% (84.9–93.4%), respectively. Adjusting for age, ART duration, previous VL, and duration between the TFV-DP and VL measures, LORs of viremia for TFV-DP concentrations 350–699 and <350 fmol/punch versus TFV-DP ≥1850 fmol/punch were 3.5 (95% CI, 1.1–10.8; P  = .033) and 12.9 (3.6–46.6; P  < .0001), respectively. Including only samples taken during VS, the LOR of future viremia for TFV-DP concentration <350 fmol/punch versus TFV-DP ≥1850 fmol/punch was 9.5 (1.9–47.0). Conclusions TFV-DP concentrations in DBSs were strongly associated with future viremia and appear useful to identify nonadherence and predict future elevated VL. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the diagnostic accuracy of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin for pediatric Cushing's disease (CD). Methods: We reviewed studies performed in children that evaluated the accuracy of BIPSS with desmopressin. Results: All included studies were case series of children with adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome. The overall accuracy of BIPSS before stimulation was 84.1% (37/44), and after stimulation it was 92.3% (36/39). The overall lateralizing accuracy of BIPSS was 50.0%. Conclusion: Considering that available evidence is limited, it appears that BIPSS with desmopressin stimulation is accurate for the diagnosis of pediatric CD, but its lateralizing accuracy is probably not suitable for pediatric clinical practice. [ABSTRACT FROM AUTHOR]

Hyperspectral imaging (HSI) has become a crucial innovation in forensic science, particularly for analysing bodily fluids. This advanced technology captures both spectral and spatial data across a wide spectrum of wavelengths, offering comprehensive insights into the composition and distribution of bodily fluids found at crime scenes. In this review, we delve into the forensic applications of HSI, emphasizing its role in detecting, identifying, and distinguishing various bodily fluids such as blood, saliva, urine, vaginal fluid, semen, and menstrual blood. We examine the benefits of HSI compared to traditional methods, noting its non-destructive approach, high sensitivity, and capability to differentiate fluids even in complex mixtures. Additionally, we discuss recent advancements in HSI technology and their potential to enhance forensic investigations. This review highlights the importance of HSI as a valuable tool in forensic science, opening new pathways for improving the accuracy and efficiency of crime scene analyses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Symphysodon discus is known in the world of aquariums for its market value, beauty, and behavior. However, more substantial information about its physiology and biology must be available, which can hinder its development and maintenance in breeding systems. The study evaluated the blood biochemistry and erythrogram of 20 specimens of S. discus captured in the municipality of Barcelos, Amazonas, with an average weight of 89.80 ± 7.13 g and an average length of 13.48 ± 0.55 cm. The erythrogram evaluated variables such as hematocrit (Ht), hemoglobin (Hb), red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Blood biochemistry was analyzed, including cholesterol levels, total proteins, triglycerides, glucose, urea, and chlorides. Intra-specific variations were observed between the surveyed individuals about the Hb, MCV, and MCH values. The values of triglycerides, cholesterol, and chlorides were elevated compared to other cichlids. This study may be useful to serve as a parameter to indicate the normal health conditions of this Amazonian cichlid. It can be applied in studies for ornamental fish farming and actions for managing and conserving the species.

Objectives: To compare the hematologic, blood chemistry, and coagulation test results between two blood sampling methods via central venous access devices (CVADs) and venipuncture., Method: The authors searched PubMed, Embase, Cochrane, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for controlled studies that compared the differences in hematologic, blood chemistry, and coagulation test results between venipuncture and CVADs from the date of database establishment to July 2022. Two researchers independently performed the literature screening, data extraction, and quality assessment. The standardized mean difference was used as the effect size for continuous variables and a 95% confidence interval was provided. The random-effects model was used for an I 2  > 50%, otherwise the fixed-effects model was used. Sources of heterogeneity were determined by subgroup analysis or sensitivity analysis, as indicated., Results: This review ultimately identified 17 studies for systematic review, of which 12 were selected for meta-analysis. A total of 541 adult participants were included in the meta-analysis. With the exception of the activated partial thromboplastin time, there were no significant differences in hematologic, blood chemistry, and coagulation test results between blood sampling via venipuncture and CVADs., Conclusions: The results of this study provide substantial evidence that blood sampling via venipuncture and CVADs had equal reliability in most laboratory tests. Serial blood sampling via CVADs will reduce the risk of bleeding episodes and pain at the blood collection site, and safety for healthcare professionals., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and aimsEarly child interventions focused on the family prevented neurodevelopmental and behavioral delays and can provide more knowledge regarding responsive feeding, thus creating learning opportunities to promote better quality nutrition and preventing failure to thrive. The aim is to verify the impact of a continuous program of early home-based intervention on the body composition of preschool infants who were born preterm with very low birth weight (VLBW).MethodsThis is a longitudinal analysis from a randomized controlled trial, including VLBW preterm children, born in a tertiary hospital in Southern Brazil and followed up at the high-risk institutional ambulatory clinic. Participants were divided into the intervention group (IG): skin-to-skin care with the mother (kangaroo care), breastfeeding policy, and tactile-kinesthetic stimulation by mothers until hospital discharge. Subsequently, they received a program of early intervention with orientation and a total of 10 home visits, independently from the standard evaluation and care that was performed following the 18 months after birth; conventional group (CG): standard care according to the routine of the newborn intensive care unit (NICU), which includes kangaroo care, and attending to their needs in the follow-up program. Body composition estimation was performed using bioelectrical impedance analyses (BIA), and physical activity and feeding practices questionnaires were evaluated at preschool age, as well as anthropometric measurements and biochemical analysis.ResultsData of 41 children at 4.6 ± 0.5 years old were evaluated (CG n = 21 and IG n = 20). Body weight, height, body mass index, waist and arm circumferences, and triceps and subscapular skinfold did not differ between groups. The IG presented higher segmented fat-free mass (FFM) when compared to the CG (right arm FFM: 0.74 vs. 0.65 kg, p = 0.040; trunk FFM: 6.86 vs. 6.09 kg, p = 0.04; right leg FFM: 1.91 vs. 1.73 kg, p = 0.063). Interaction analyses showed that segmented FFM and FFM Index were associated with higher iron content in the IG. In the CG, interaction analyses showed that increased visceral fat area was associated with higher insulin resistance index.ConclusionAn early intervention protocol from NICU to a home-based program performed by the mothers of VLBW preterm children of low-income families presents a small effect on FFM.

Background: Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear. To address this, we conducted a meta-analysis comparing viral load results from paired dried blood spot and plasma specimens analyzed with commonly used viral load testing technologies.Methods and Findings: Standard databases, conferences, and gray literature were searched in 2013 and 2018. Nearly all studies identified (60) were conducted between 2007 and 2018. Data from 40 of the 60 studies were included in the meta-analysis, which accounted for a total of 10,871 paired dried blood spot:plasma data points. We used random effects models to determine the bias, accuracy, precision, and misclassification for each viral load technology and to account for between-study variation. Dried blood spot specimens produced consistently higher mean viral loads across all technologies when compared to plasma specimens. However, when used to identify treatment failure, each technology compared best to plasma at a threshold of 1,000 copies/ml, the present World Health Organization recommended treatment failure threshold. Some heterogeneity existed between technologies; however, 5 technologies had a sensitivity greater than 95%. Furthermore, 5 technologies had a specificity greater than 85% yet 2 technologies had a specificity less than 60% using a treatment failure threshold of 1,000 copies/ml. The study's main limitation was the direct applicability of findings as nearly all studies to date used dried blood spot samples prepared in laboratories using precision pipetting that resulted in consistent input volumes.Conclusions: This analysis provides evidence to support the implementation and scale-up of dried blood spot specimens for viral load testing using the same 1,000 copies/ml treatment failure threshold as used with plasma specimens. This may support improved access to viral load testing in resource-limited settings lacking the required infrastructure and cold chain storage for testing with plasma specimens. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is a common virus worldwide that is an etiologic agent in the development of many diseases, including cancer. Recent reports have shown the association of EBV with tumorigenesis in head and neck squamous cell carcinoma (HNSCC). Moreover, EBV has been reported to be present in tonsillar tissues, which suggests a close relationship between viral infections and tonsillar diseases, including chronic tonsillitis. The aim of the study was to analyze the prevalence of EBV DNA in 86 patients with HNSCC, in 70 patients with chronic tonsillitis, and in 144 healthy individuals (control group) and the associations between EBV infection and clinicopathological and demographic characteristics and the use of stimulants in all study groups. The objective of this study was also to analyze the prevalence of coinfection with human papillomavirus (HPV). After prior DNA isolation, EBV detection was performed using an EBV kit by real-time polymerase chain reaction. The prevalence of EBV infection in patients with HNSCC, patients with chronic tonsillitis, and the control group was 47.7%, 60%, and 24.3%, respectively. Compared to controls, a significantly higher prevalence of EBV in patients with chronic tonsillitis and HNSCC may suggest that EBV is a potential risk factor. No association was found between EBV infection and demographic or clinical data. Further studies are warranted due to inconclusive reports that were mainly related to geographic distribution, sample type, and detection technique. Considering the prevalence of the virus and the risk of serious diseases, attention should be paid to screening diagnosis and prevention of the infection. [ABSTRACT FROM AUTHOR]

Background/Aim: Inflammatory processes are often implicated in oncology, and inflammatory markers and indices have been much studied in this context. In gynecological surgery, frozen sections have proven valuable in decision-making. Here we aim to identify laboratory parameters that correlate with frozen section results and thus develop new indices in neoplastic decision-making. Methods: In this retrospective cross-sectional study at Bursa Yüksek İhtisas Training and Research Hospital, we evaluated 139 patients diagnosed with adnexal mass and endometrial intraepithelial neoplasia. We divided the patients whose frozen sections were reported as malignant, borderline, or benign into three groups and compared the pre-operative complete blood parameters. Results: The mean age of our patients was 57.3 (11.5) years, and frozen section reports were benign in 33 (23.7%), borderline in 43 (30.9%), and malignant in 63 (45.3%) patients. The mean corpuscular volume and mean platelet volume values were different, and this difference was significant between borderline and malignant groups in post-hoc analyses (P = 0.04 and P = 0.03, respectively). While the percentage of lymphocytes was lower in malignant groups, the percentage of neutrophils was higher (P = 0.01 and P = 0.03, respectively). According to post-hoc analysis, the percentage of neutrophils differs between benign and malignant groups (P = 0.05). The difference in lymphocyte percentage was significant between benign-borderline and benign-malignant groups (P = 0.02, P = 0.05; respectively). The blood neutrophil/lymphocyte ratio was higher in the malignant groups compared to the other two groups (P = 0.02). We used the Multi Linear Regression Analysis method to analyze the factors that play a role in predicting the frozen outcome as malignant. Accordingly, the model with the best performance used lymphocyte percentage, neutrophil/lymphocyte ratio, and Ca-125 parameters (P = 0.03). Conclusion: This study indicates that inflammatory markers may give a clue about the character of the neoplastic mass before oncology surgery. Thus, we can make new contributions to the surgical and clinical approach in the literature by developing new malignancy indices. [ABSTRACT FROM AUTHOR]

Background: Strategies to support adherence are constrained by the lack of tools to objectively monitor medication intake in low-resource settings. Pharmacologic measures are objective, but pharmacy refill data is more accessible and cost-efficient. This study compared short-term and long-term efavirenz (EFV) drug levels with pharmacy refill adherence data (PRA) and evaluated their ability to predict viral suppression among people living with HIV in Nigeria. Methods: Paired hair and dried blood spot (DBS) samples were obtained from 91 adults living with HIV receiving 600 mg EFV-based antiretroviral therapy (ART) and EFV concentrations were measured via validated methods using liquid-chromatography-mass-spectrometry. PRA was estimated from pharmacy records, based on the number of days a patient collected medication before or after the scheduled pick-up date. PRA was categorized into ≤ 74%, 75–94% and ≥ 95%, defined as poor, medium and high adherence, respectively. HIV viral loads closest to the hair sampling time (within 6 months) were also abstracted. Receiver Operating Characteristics (ROC) curve analyses compared the ability of adherence metrics to predict viral suppression. Results: Based on PRA, 81% of participants had high adherence while 11% and 8% had medium and poor adherence, respectively. The median (IQR) EFV concentrations were 6.85 ng/mg (4.56–10.93) for hair and 1495.6 ng/ml (1050.7–2365.8) for DBS. Of the three measures of adherence, hair EFV concentration had the highest Area Under Curve (AUC) to predict viral suppression. Correlations between EFV concentrations in DBS and hair with PRA were positive (r = 0.12, P = 0.27 and r = 0.21, P = 0.05, respectively) but not strong. Conclusions: EFV concentrations in hair were the strongest predictor of viral suppression and only weakly correlated with pharmacy refill adherence data in Nigeria. This study suggests that resource-limited settings may benefit from objective adherence metrics to monitor and support adherence. [ABSTRACT FROM AUTHOR]

BACKGROUND: An important aspect of ensuring blood safety is the performance of mandatory serological testing for transfusion transmissible infections. The practice of internal quality control (IQC) in blood banks in India is nonuniform, especially the use of third-party materials. Cited reasons are cost, lack of access to control materials, and need for deep-freezers for storage, if prepared in-house. OBJECTIVE: Validation of dried tube specimen (DTS) from HIV-positive plasma as a low-cost, stable material for use as IQC material in blood banks. METHODS: Fresh-frozen plasma (FFP) prepared from four HIV-positive blood-donors were pooled. Equal numbers of seronegative FFPs were pooled. Twenty microlitre aliquots of plasma were made in micro-centrifuge tubes and air-dried overnight at room-temperature. These were stored in 2–8°C refrigerators and tested once weekly for 6 months on multiple platforms with different detection principles: Rapid tests, second-generation enzyme-linked immunosorbent assay (ELISA), fourth-generation ELISA, and fourth-generation Chemiluminescence immunoassay. The protocol was sustained over the next 6 months with decreased testing frequency to study the extended stability of DTS. RESULTS: A total of 139 positive-DTS and 139 negative-DTS were tested with 100% samples showing consistent results on all platforms over 1 year. There was mild deterioration in reaction strengths, which did not interfere in result interpretations. CONCLUSION: Plasma in form of DTS maintained stability when stored at 2–8°C for 1 year. This provides evidence that DTS can be a modality for the production of cost-effective, stable, in-house control material for resource-restricted countries. [ABSTRACT FROM AUTHOR]

Introduction: Prolactin (PRL) measurement during inferior petrosal sinus sampling (IPSS) can be helpful to improve the accuracy. We aimed to evaluate the effect of measuring PRL levels as a predictor for the accuracy of IPSS and evaluate its impact on the lateralization of adenomas. Methods: In this retrospective cohort study, we reviewed 51 patients who had undergone IPSS for the investigation of ACTH-dependent hypercortisolism. Results: Forty-nine patients had proven Cushing's disease (CD), one had EAS, and the remaining one patient had adrenal adenoma. Forty-seven patients had an above 2 ACTH IPS/P ratio at baseline, and all the post-corticotropin-releasing hormone (CRH) ACTH IPS/P ratios of patients with proven CD were above 3. In these two patients whose ACTH IPS/P ratio at baseline was below 2, PRL IPS/P ratios were above 1.8 in only the dominant side, which was considered secondary to a prolactin intersinus gradient due to the biological effects of the tumor. PRL-adjusted ACTH IPS/P ratios were > 1.3 in all patients with proven CD; it was 0.7 in the patient with EAS. Surgically confirmed positive lateralization was observed in 55.1% of patients with the ACTH gradient, but when PRL-adjusted ACTH IPS/IPS ratios were used in addition to the ACTH gradient, the ratio increased to 67.3%. Conclusion: Although PRL-adjusted ACTH IPS/P ratios can be helpful to improve the accuracy of results during IPSS procedures, a prolactin intersinus gradient towards the ACTH-dominant side in patients with CD may invalidate PRL as an indicator of pituitary venous outflow. [ABSTRACT FROM AUTHOR]

Objective Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM. Methods Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. Results A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM. Conclusion The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients' metabolomics patterns compared to those of patients with only NAFLD or T2DM. [ABSTRACT FROM AUTHOR]

Background: Cushing's disease (CD) is among the most common etiologies of hypercortisolism. Magnetic resonance imaging (MRI) is often utilized in the diagnosis of CD, however, up to 64% of adrenocorticotropic hormone (ACTH)-producing pituitary microadenomas are undetectable on MRI. We report 15 cases of MRI negative CD who underwent surgical resection utilizing a purely endoscopic endonasal approach. Methods: Endoscopic endonasal transsphenoidal surgery (EETS) was performed on 134 CD cases by a single surgeon. Fifteen cases met inclusion criteria: no conclusive MRI studies and no previous surgical treatment. Data collected included signs/symptoms, pre- and post-operative hormone levels, and complications resulting from surgical or medical management. Data regarding tumor diameter, location, and tumor residue/recurrence was obtained from both pre- and post-operative MRI. Immunohistochemistry was performed to assess for tumor hormone secretion. Results: Aside from a statistically significant difference (P = 0.001) in histopathological results between patients with negative and positive MRI, there were no statistically significant difference between these two groups in any other demographic or clinical data point. Inferior petrosal sinus sampling (IPSS) with desmopressin (DDAVP®) administration was performed on the 15 patients with inconclusive MRIs to identify the origin of ACTH hypersecretion via a central/peripheral (C/P) ratio. IPSS in seven, five and three patients showed right, left, and central side lateralization, respectively. With a mean follow-up of 5.5 years, among MRI-negative patients, 14 (93%) and 12 patients (80%) achieved early and long-term remission, respectively. In the MRI-positive cohort, over a mean follow-up of 4.8 years, 113 patients (94.9%) and 102 patients (85.7%) achieved initial and long-term remission, respectively. Conclusions: Surgical management of MRI-negative/inconclusive Cushing's disease is challenging scenario requiring a multidisciplinary approach. An experienced neurosurgeon, in collaboration with a dedicated endocrinologist, should identify the most likely location of the adenoma utilizing IPSS findings, followed by careful surgical exploration of the pituitary to identify the adenoma. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type I (MPS I), a lysosomal storage disease caused by a deficiency of α-L-iduronidase, leads to storage of the glycosaminoglycans, dermatan sulfate and heparan sulfate. Available therapies include enzyme replacement and hematopoietic stem cell transplantation. In the last two decades, newborn screening (NBS) has focused on early identification of the disorder, allowing early intervention and avoiding irreversible manifestations. Techniques developed and optimized for MPS I NBS include tandem mass-spectrometry, digital microfluidics, and glycosaminoglycan quantification. Several pilot studies have been conducted and screening programs have been implemented worldwide. NBS for MPS I has been established in Taiwan, the United States, Brazil, Mexico, and several European countries. All these programs measure α-L-iduronidase enzyme activity in dried blood spots, although there are differences in the analytical strategies employed. Screening algorithms based on published studies are discussed. However, some limitations remain: one is the high rate of false-positive results due to frequent pseudodeficiency alleles, which has been partially solved using post-analytical tools and second-tier tests; another involves the management of infants with late-onset forms or variants of uncertain significance. Nonetheless, the risk-benefit ratio is favorable. Furthermore, long-term follow-up of patients detected by neonatal screening will improve our knowledge of the natural history of the disease and inform better management. [ABSTRACT FROM AUTHOR]

Background: Caregivers in healthcare settings are exposed to a risk of antineoplastic drug contamination which can lead to adverse health effects. Biological monitoring is necessary to estimate the actual level of exposure of these workers. This study was conducted with the aim of assessing blood contamination levels by irinotecan and its metabolites of pharmaceutical staff operating inside and outside a compounding unit. Methods: The study took place within the pharmaceutical unit of a French comprehensive cancer centre. Blood samples were collected from the pharmacy workers operating inside and outside the compounding unit, and analysed by UHPLC-MS/MS. Plasma and red blood cell irinotecan and its metabolites (SN-38; APC) were determined with a validated analytical method detection test. Results: A total of 17/78 (21.8%) plasma and red blood cell-based assays were found to be contaminated among staff. Overall, the total number of positive assays was significantly higher for staff members working outside the compounding unit than for workers working inside it (P = 0.022), with respectively 5/42 (11.9%) and 12/36 (33.3%) positive assays. For plasma dosages, the "outside" group had a significantly higher number of positive assays (P = 0.014). For red blood cell-based assays, no significant difference was found (P = 0.309). Conclusions: This study reveals that pharmaceutical staff serving in health care settings are exposed to a risk of antineoplastic drug contamination, not only inside the compounding room but also in adjacent rooms. The results would help to raise awareness and potentially establish protective measures for caregivers working in areas close to the compounding room as well. [ABSTRACT FROM AUTHOR]

Introduction: Real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR) assays were established to detect severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). However, due to the high rate of false negative results, additional tests as computed tomography (CT) scans of the chest and blood chemistry are required to properly diagnose COVID‐19 infection. Abnormal morphological changes of peripheral blood cells as granulocytic dysmorphism and abnormal reactive lymphocytes have been described in some cases. The aim of the present study was to investigate the morphological changes affecting all peripheral blood cells of COVID‐19 patients, in order to find any specific abnormalities that could help in the early diagnosis and/or prognosis. Methods: Peripheral blood smears of 113 COVID‐19 patients and 50 non‐COVID‐19 controls were examined for morphological changes in the period between October 2020 and January 2021 (second wave). We set a score value in which every morphological abnormality was given one point in each examined blood smear. Score, neurophil/lymphocyte (N/L) ratio, and blood chemistry were compared to the severity and outcome of the disease. Results: Significant morphological changes were found when compared to control blood smears. Various abnormalities as pyknotic cells, broken cells, pseudo Pelger‐Huët, abnormal lymphocytes, abnormal monocytes, and leukoerythroblastic reaction were found. Cases with higher scores had unfavorable outcomes (p =.005). High interleukin‐6 (IL‐6) levels were correlated to pyknotic cells (p =.003). Conclusion: The blood picture of COVID‐19 patients revealed various morphological changes that are not detected with the same frequency and variability in other viral infections. The prominent morphological changes can be predictive of an undesirable outcome of the disease. [ABSTRACT FROM AUTHOR]

Background: Dried blood spot samples are suitable for diagnosing some congenital errors of metabolism; however, they provide limited benefit in the regular monitoring of amino acids. Objectives: The present study aimed to evaluate alanine (Ala), arginine (Arg), citrulline (Cit), glutamic acid (Glu), glycine (Gly), isoleucine (Ileu), leucine (Leu), methionine (Met), ornithine (Orn), phenylalanine (Phe), tyrosine (Tyr), and valine (Val) amino acid concentrations in dried blood and plasma samples obtained simultaneously. Methods: Amino acid concentrations were determined in the plasma, and dried blood spot samples obtained simultaneously from 145 patients (50 females and 95 males). Amino acid concentrations in the plasma and dried blood spot samples were studied by LC-MS/MS using original kits. Results: There were significant differences between dried blood spots and plasma in all amino acid concentrations, except for Met and Val. Bland-Altman analysis revealed the highest mean differences in Glu (-148.1), Gly (-70.1), and Ala (-58.1). Deming regression analysis showed that plasma and dried blood spot samples were consistent concerning Cit, Met, Phe, and Tyr concentrations. Conclusions: Differences in methodology and sample can influence amino acid concentrations. Dried blood spot samples might cause errors in amino acid screening programs. [ABSTRACT FROM AUTHOR]

The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small molecules commonly reach concentrations similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates aromatic amino acid metabolites. Our results reveal that this pathway produces twelve compounds, nine of which are known to accumulate in host serum. All three aromatic amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the molecular output of the gut bacterial community.

ObjectiveThe US preexposure prophylaxis (PrEP) Demonstration Project (U.S. Demo) evaluated MSM on PrEP postmarketing and found low seroconversion rates. The objective of this study is to examine hair levels as an adherence measure to PrEP.DesignUsing an 'opt-in' design, participants of PrEP Demo were invited to enroll into a substudy where hair was collected quarterly.MethodsTenofovir concentrations were measured in hair by liquid chromatography/tandem mass spectrometry. Hair levels consistent with ≥4 doses/week (protective in other studies) defined adequate adherence. Mixed effects multivariate logistic regression models examined factors associated with ≥4 doses/week. Separate mixed effects models evaluated the relationship between hair PrEP levels and changes in creatinine clearance (CrCl) over time.ResultsOverall, 58% of U.S. Demo participants enrolled into this opt-in study; reasons for nonparticipation included insufficient hair (61%) and concerns about hairstyle (27%). Hair and dried blood spots levels consistent with ≥4 doses/week were highly concordant (84%). Hair levels showed adequate adherence in 87% of 875 person-visits (among 280 participants). Factors associated with adequate adherence in multivariate models were amphetamine use [adjusted odds ratio (aOR) 2.59 (0.97-6.9, P 0.06)], condomless receptive anal sex [aOR 2.28 (1.19-4.40, P 0.01)], and stable housing [aOR 2.63 (1.03-6.67), P 0.04]. Hair levels of tenofovir showed a monotonic relationship with decline in CrCl (P 0.01 for trend).ConclusionIn this substudy of the U.S. PrEP demonstration project, hair and dried blood spots levels were highly concordant and hair concentrations demonstrated adequate adherence 87% of the time, with stable housing and high-risk behavior associated with higher adherence. Daily PrEP drug taking is associated with modest declines in CrCl.

ObjectiveThe California heat illness prevention study (CHIPS) devised methodology and collected physiological data to assess heat related illness (HRI) risk in Latino farmworkers.MethodsBilingual researchers monitored HRI across a workshift, recording core temperature, work rate (metabolic equivalents [METs]), and heart rate at minute intervals. Hydration status was assessed by changes in weight and blood osmolality. Personal data loggers and a weather station measured exposure to heat. Interviewer administered questionnaires were used to collect demographic and occupational information.ResultsCalifornia farmworkers (n = 588) were assessed. Acceptable quality data was obtained from 80% of participants (core temperature) to 100% of participants (weight change). Workers (8.3%) experienced a core body temperature more than or equal to 38.5 °C and 11.8% experienced dehydration (lost more than 1.5% of body weight).ConclusionsMethodology is presented for the first comprehensive physiological assessment of HRI risk in California farmworkers.

The article comments on a study which presented computational approach to estimate concentrations of chemicals in human blood and calculated toxic or bioanalytical equivalencies to prioritize toxicity testing. It suggests the potential use of the computational model to screen alternatives that may have been introduced without adequate toxicity testing and stresses the importance of chemical prioritization for toxicity testing to protecting low-income communities and communities of color.

The real-time monitoring of specific analytes in situ in the living body would greatly advance our understanding of physiology and the development of personalized medicine. Because they are continuous (wash-free and reagentless) and are able to work in complex media (e.g., undiluted serum), electrochemical aptamer-based (E-AB) sensors are promising candidates to fill this role. E-AB sensors suffer, however, from often-severe baseline drift when deployed in undiluted whole blood either in vitro or in vivo. We demonstrate that cell-membrane-mimicking phosphatidylcholine (PC)-terminated monolayers improve the performance of E-AB sensors, reducing the baseline drift from around 70 % to just a few percent after several hours in flowing whole blood in vitro. With this improvement comes the ability to deploy E-AB sensors directly in situ in the veins of live animals, achieving micromolar precision over many hours without the use of physical barriers or active drift-correction algorithms.

To analyze the characters of Down syndrome (DS) who failed to be diagnosed after prenatal screening and hope to be able to improve the programs of prenatal screening and reduce the missed diagnosis of DS. In this multicenter study, we collected the missed cases from 3 prenatal diagnosis centers and analyzed their characters. A total of 126 DS babies failed to be diagnosed after prenatal screening. Their mothers accepted the prenatal screening in second trimester. We collected the mothers' blood and detected the levels of alpha-fetoprotein (AFP) and the free beta subunit of human chorionic gonadotropin (fβhCG) by time-resolved fluoroimmunoassay. The values were also presented as multiples of the median (MoM) and determined the risk of carrying a fetus with DS by Wallace LifeCycle Elipse analysis software. Compared with normal control group, the level of fβhCG and hCG MoM were dramatically increased, while AFP and AFP MoM were decreased. The area under the receiver-operating-characteristic curve of trisomy 21 was 0.8387 for hCG-MoM and AFP-MoM testing. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.6%, 74.8%, 75.4%, and 83.6%, respectively. Meanwhile, the prediction mode was "0.39957 + 1.90897HCG-MOM -3.32713AFP-MOM". It was worthwhile noting that the risk of 65.9% DS missed diagnosis group were higher than 1/1000, 92.9% higher than 1/3000. However, 72.5% cases in normal control group were lower than 1/3000. Only 9.2% mothers would be higher than the value of risk in 1/1000. The prediction mode of hCG MoM and AFP MoM might be able to help us reduce the missed diagnosis. It is also necessary to adjust more reasonable range of noninvasive prenatal testing with further clinical researches.

BackgroundPhysiologic factors in dogs that might contribute to enhanced platelet yield in platelet concentrates (PCs) are largely unknown.ObjectiveTo determine whether individual differences in weight, age, preprocessing blood chemistry, and CBC variables predict the final platelet concentrations in PCs. Our hypotheses were (1) increased lipemic indices would be positively associated with increased platelet concentrations in PCs and (2) increased preprocessing platelet concentrations would be associated with higher platelet concentrations in the PCs.AnimalsAll blood donation records of dogs from February 2, 2009 through April 1, 2015 at the University of California-Davis Veterinary Blood Bank were examined with 104 cases included in this study.MethodsIn this retrospective study, data were collected from medical records of canine blood donors. Records were reviewed for internal consistency and accuracy and subjects were included in the study if donor screening and donation occurred on the same day and a viable PC was obtained. Univariate and multivariable regressions were used to test the impact that each variable had on the final platelet concentration in PCs.ResultsFinal platelet concentration in PCs was positively associated with the predonation CBC platelet values (P < .001), lipemic index (P = .01), and phosphorous levels (P = .001). Collectively these 3 variables explained 29% of the variance in platelet concentrations in PCs.Conclusions and clinical importanceFuture prospective studies are required to determine if canine blood donations from dogs with lipemia yield PCs with higher platelet concentrations without negatively affecting other blood components.

Associations between temperature and cardiovascular (CVD) mortality have been reported, but the underlying biological mechanisms remain uncertain. We explored the association between apparent temperature and serum biomarkers for CVD. Using linear mixed effects models, we examined the relationships between residence-proximate apparent temperature (same day and 1, 7, and 30 days prior) and several inflammatory, hemostatic, and lipid biomarkers for midlife women from 1999 through 2004. Our study population consisted of 2,306 women with mean age of 51 years (± 3 years) enrolled in Study of Women's Health Across the Nation (SWAN) in Chicago, Illinois; Detroit, Michigan; Los Angeles and Oakland, California; Newark, New Jersey; and Pittsburgh, Pennsylvania. Mean daily apparent temperature was calculated using temperature and relative humidity data provided by the National Climatic Data Center and the US Environmental Protection Agency, while daily data for fine particles, ozone, carbon monoxide, and nitrogen dioxide from the US Environmental Protection Agency Air Quality Data Mart were considered as confounders. All analyses were stratified by warm and cold seasons. More significant (p

BackgroundThe widespread adoption of electronic health records provides new opportunities to better predict which patients are likely to suffer a stroke. Using electronic health records, we assessed the correlation of different laboratory tests to future occurrences of a stroke.MethodsWe examined the electronic health records of 2.4 million people over a two year time span. These records contained 26,964 diagnoses of stroke. Using Cox regression analysis, we measured whether any one of 1796 different laboratory tests were effectively correlated with a future diagnosis of stroke.ResultsWe identified 38 different laboratory tests that had significant short-term (two year) prognostic value for a future diagnosis of stroke. For each of the 38 laboratory tests we also compiled the Kaplan-Meier survival curve, and relative risk ratio that the test confers.ConclusionSeveral dozen laboratory tests are effective short-term correlates of stroke.

Panax ginseng C.A. Meyer., a famous and valuable traditional Chinese medicine with thousand years of history for its healthcare and therapeutic effects. It is necessary and meaningful to study the pharmacokinetic behavior of ginsenosides in vivo as they are the most active components. Dried blood spots (DBS) are a mature and advanced blood collection method with meet the needs for the measurement of numerous analytes. This study aimed to explore the feasibility on DBS in the metabolic profile analysis of complex herbal products. An ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ginsenosides. The preparation of DBS samples was conducted by spiking the whole blood with analytes to obtain 20 μL of blood spots on Whatman 903 collection card. A punched dish of 10 mm in diameter was extracted with 70 % methanol aqueous solution, digoxin was used as an internal standard. Target compounds were separated on a Waters T3 column (2.1 × 100 mm, 1.8 μm) with acetonitrile and water (0.1 % formic acid) at a flow rate of 0.4 mL/min. The various ginsenosides showed good linearity in the range of 1–2000 ng/mL. The extraction recoveries and matrix effects of the target analytes were above 82.2%. The intra- and inter-batch accuracy and precision were within the limits of ≤15% for all tested concentrations. Moreover, the collected dried blood spot samples could be stably stored at room temperature for 14 days and 4 °C for 1 month without being affected. And it is delightful that the DBS-based analysis is compatible or even superior to the conventional protein precipitation in terms of sensitivity, linearity, and stability. In particular, the target analytes are stable in the DBS sampling under normal storing condition and the sensitivity for some trace metabolites of ginsenosides, such as 20(S)-Rg3, 20(R)-Rg3, F1, Rk1, Rg5, etc. increases 3–4 folds as evaluated by LLOQ. The established method was successfully applied to pharmacokinetic studies of ginseng extract in mice, this suggests a more feasible strategy for pharmacokinetic study of traditional and natural medicines both in animal tests and clinical trials. [Display omitted] • A new strategy using DBS with 20 μL of blood for pharmacokinetics of ginseng extract. • Ginsenosides were quantified with comprehensive advantages by DBS treatment. • Four pairs of epimeric rare ginsenosides metabolites were monitored at the same time. [ABSTRACT FROM AUTHOR]

Background: In 2018, the Community-Based Research Centre (CBRC) invited gay, bisexual, trans, queer men and Two-Spirit and non-binary people (GBT2Q) at Pride Festivals across Canada to complete in-person Sex Now surveys and provide optional dried blood spot (DBS) samples screening for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). As there is a lack of research evaluating the implementation of DBS sampling for GBT2Q in community settings, we aimed to evaluate this intervention, identifying key facilitators and ongoing challenges to implementing community-based DBS screening for HIV/HCV among GBT2Q.Methods: We conducted sixteen one-on-one interviews with individuals involved with the community-based DBS collection protocol, including research staff, site coordinators, and volunteer DBS collectors. Most individuals involved with DBS collection were "peers" (GBT2Q-identified). The Consolidated Framework for Implementation Research (CFIR) guided our data collection and analysis.Results: Interviewees felt that DBS collection was a low-barrier, cost-effective, and simple way for peers to quickly screen a large number of Sex Now respondents. Interviewees also noted that the community and peer-based aspects of the research helped drive recruitment of Sex Now respondents. Most interviewees felt that the provision of results took too long, and that some Sex Now respondents would have preferred to receive their test results immediately (e.g., rapid or point-of-care testing).Conclusion: Peer-based DBS sampling can be an effective and relatively simple way to screen GBT2Q at Pride Festivals for more than one sexually transmitted and blood borne infection. [ABSTRACT FROM AUTHOR]

Background: Sofosbuvir is converted to its active form, 007 triphosphate (007-TP), within cells. To date, the association between treatment adherence and 007-TP in dried blood spots (DBS) and factors that influence this relationship remain unknown.Objectives: To examine relationships between adherence and 007-TP concentrations in DBS and identify factors that influence 007-TP in DBS.Methods: Persons with HCV or HIV/HCV coinfection and self-reported drug and/or alcohol use were randomized to one of two technology-based approaches for monitoring 12 week adherence to once-daily ledipasvir/sofosbuvir. Convenience blood samples were collected every 2 weeks during treatment. 007-TP in DBS was quantified using LC/MS and analysed using mixed-effects models.Results: A total of 337 observations were available from 58 participants (78% male; 21% black; 22% Hispanic/Latino; 26% cirrhotic; 78% HIV-coinfected). The mean half-life of 007-TP in DBS was 142 h (95% CI 127-156) and concentrations increased by 7.3% (95% CI 2.2-12.6) for every 10% increase in between-visit adherence. Geometric mean (95% CI) 007-TP concentrations in DBS were 301 (247-368), 544 (462-639) and 647 (571-723) fmol/punch by adherence categories of ≤50%, >50 to ≤80%, and >80%. Adherence, time on therapy, increasing age and decreased estimated glomerular filtration rate were associated with higher 007-TP, whereas increased time since last dose, male sex, black race and higher BMI were associated with lower 007-TP.Conclusions: 007-TP has an extended half-life in DBS and concentrations increased with adherence. Further research is needed to examine additional factors that affect 007-TP and the clinical utility of this measure. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to profile the cytokine/chemokine response from day 0 to 7 in infants (≥36 weeks of gestational age) with neonatal encephalopathy (NE) and to explore the association with long-term outcomes. Study Design  This was a secondary study of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network randomized controlled trial of whole body hypothermia for NE. Eligible infants with moderate–severe NE were randomized to cooling or normothermia. Blood spots were collected on days 0 to 1, 2 to 4, and 6 to 7. Twenty-four cytokines/chemokines were measured using a multiplex platform. Surviving infants underwent neurodevelopmental assessment at 6 to 7 years. Primary outcome was death or moderate–severe impairment defined by any of the following: intelligence quotient <70, moderate–severe cerebral palsy (CP), blindness, hearing impairment, or epilepsy. Results  Cytokine blood spots were collected from 109 participants. In total 99 of 109 (91%) were assessed at 6 to 7 years; 54 of 99 (55%) developed death/impairment. Neonates who died or were impaired had lower early regulated upon activation normal T cell expressed and secreted (RANTES) and higher day 7 monocyte chemotactic protein (MCP)-1 levels than neonates who survived without impairment. Though TNF-α levels had no association with death/impairment, higher day 0 to 1 levels were observed among neonates who died/developed CP. On multiple regression analysis adjusted for center, treatment group, sex, race, and level of hypoxic ischemic encephalopathy, higher RANTES was inversely associated with death/impairment (odds ratio (OR): 0.31, 95% confidence interval [CI]: 0.13–0.74), while day seven MCP-1 level was directly associated with death/impairment (OR: 3.70, 95% CI: 1.42–9.61). Targeted cytokine/chemokine levels demonstrated little variation with hypothermia treatment. Conclusion  RANTES and MCP-1 levels in the first week of life may provide potential targets for future therapies among neonates with encephalopathy. Key Points Elevation of specific cytokines and chemokines in neonates with encephalopathy has been noted along with increased risk of neurodevelopmental impairment in infancy. Cytokine/chemokines at <7 days were assessed among neonates in a trial of hypothermia for HIE. Neonates who died or were impaired at 6 to 7 years following hypoxic-ischemic encephalopathy had lower RANTES and higher MCP-1 levels than those who survived without impairment. [ABSTRACT FROM AUTHOR]

Background: Early recognition of severe COVID‐19 is essential for timely patient triage. Aims: To report clinical and laboratory findings and patient outcomes at a tertiary hospital in Melbourne, Australia. Methods: This is a retrospective study of adult inpatients with COVID‐19 admitted to Northern Health from March to September 2020. Data were extracted from electronic medical records. Results: Key admission data were available for 182 patients (median age 67.0 years (interquartile range, 47.9–83.1); 51.1% female). Fifty‐six (30.8%) were from residential care. One hundred and seventeen (64.3%) patients were assigned Goals of Patient Care (GOPC) A or B and 65 (35.7%) GOPC C or D. Comorbidities were present in 135 patients (74.2%). 63.2% of patients received antibiotics, 6.6% had antivirals, 45.6% received systemic glucocorticoid and 3.3% had tocilizumab. Fifty‐six (30.8%) developed clinical deterioration (24 requiring ventilation, 21 receiving critical care, 34 died). Overall, inhospital clinical deterioration was significantly associated with older age (P < 0.001), history of diabetes (P = 0.038), lower lymphocyte count (P = 0.002) and platelet count (P = 0.004), higher neutrophil‐to‐lymphocyte ratio (P = 0.002), elevated fibrinogen (P = 0.004), higher serum ferritin (P = 0.027) and C‐reactive protein (CRP; P = 0.002). The accuracy of the 4C Deterioration model was moderate, with an area under the curve (AUC) of 0.79 (95% confidence interval (CI), 0.68–0.90) compared with an AUC of 0.77 (95% CI, 0.76–0.78) in the original validation cohort. Conclusions: In the present study, high neutrophil‐to‐lymphocyte ratio, abnormal d‐dimer, high serum CRP and ferritin appear to be useful prognostic markers. [ABSTRACT FROM AUTHOR]

Objectives: To summarize and assess the literature on the performances of methods beyond the Friedewald formula (FF) used in routine practice to determine low-density lipoprotein cholesterol (LDL-C).Methods: A literature review was performed by searching the PubMed database. Many peer-reviewed articles were assessed.Results: The examined methods included direct homogeneous LDL-C assays, the FF, mathematical equations derived from the FF, the Martin-Hopkins equation (MHE), and the Sampson equation. Direct homogeneous assays perform inconsistently across manufacturers and disease status, whereas most FF-derived methods exhibit variable levels of performance across populations. The MHE consistently outperforms the FF but cannot be applied in the setting of severe hypertriglyceridemia. The Sampson equation shows promise against both the FF and MHE, especially in severe hypertriglyceridemia, but data are still limited on its validation in various settings, including disease and therapeutic states.Conclusions: There is still no consensus on a universal best method to estimate LDL-C in routine practice. Further studies are needed to assess the performance of the Sampson equation. [ABSTRACT FROM AUTHOR]

Menopausal symptoms severely reduce the quality of life of post-menopausal women worldwide. Nutraceuticals are widely prescribed as a viable and safer alternative and complementary approach to standard therapies. The aim of this study was to evaluate the clinical efficacy and safety of a nutraceutical in post-menopausal women. The study was designed as a randomized, double-blinded, placebo-controlled clinical trial. Post-menopausal women aged 45–60 years old were enrolled and randomly assigned to either treatment (n = 50) or placebo group (n = 51). The intervention, a proprietary combination of soy isoflavone, black cohosh, chasteberry and evening primrose oil extracts, and the placebo, were administered to each group for total of 12 weeks. Menopausal symptoms, endocrine profiles, and blood chemistry were evaluated at baseline, 6 weeks, and 12 weeks of the study. Nutraceutical supplementation demonstrated a statistically significant reduction in hot flushes and sweating (p < 0.0001), sleep problems (p < 0.0005), depressed mood (p = 0.0004) and irritability symptoms (p < 0.0003) compared with the placebo group. There were no significant differences in hormonal levels between the test and placebo groups, however levels of C-reactive protein were significantly decreased. Moreover, serum LDL-C and triglyceride levels were significantly lower than baseline levels in the treatment group at 6- and 12-week timepoints. No adverse effects were reported during the treatment. These data indicate that a nutraceutical containing a combination of four medicinal herbs effectively and safely improved menopausal symptoms, as well as general health indicators, in post-menopausal women. [ABSTRACT FROM AUTHOR]

Objective: Although the sensitivity and specificity of bilateral inferior petrosal sinus sampling (BIPSS) were shown to be quite high in adult patients, pediatric studies are limited in number and have conflicting results, since BIPSS is much less commonly performed in children. The aim of this study was to assess the role of BIPSS in the detection and accuracy of lateralization of pituitary adenomas in pediatric patients with Cushing disease (CD) and its possible advantage over other diagnostic methods. Methods: This was a multicenter, nationwide, web-based study. The diagnostic value of BIPSS in 16 patients, aged between four and 16.5 years with a confirmed diagnosis of CD, was evaluated retrospectively. The sensitivity and specificity of BIPSS and magnetic resonance imaging (MRI) were calculated, and compared statistically. Results: Standard tests, except for morning cortisol level, were effective in proving the presence of Cushing syndrome. While MRI findings were consistent with microadenoma in eight cases (50%), CD presence and lateralization was successfully predicted in 14 of 16 patients using BIPSS. BIPSS compared with MRI examination was significantly more accurate, both in pre-stimulation and poststimulation results (p=0.047 and p=0.041, respectively). BIPSS showed a significantly higher sensitivity (92.8%) than MRI in detecting the pituitary source of adrenocorticotropic hormone secretion. Conclusion: These results suggest that BIPSS is superior to MRI for diagnostic work-up to confirm the diagnosis of CD. Moreover, in line with previous studies, BIPSS was shown to provide better information about adenoma location, which is vital for possible surgical intervention. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate microRNA let7i in ischemic stroke and its regulation of leukocytes.MethodsA total of 212 patients were studied: 106 with acute ischemic stroke and 106 controls matched for risk factors. RNA from circulating leukocytes was isolated from blood collected in PAXgene tubes. Let7i microRNA expression was assessed using TaqMan quantitative reverse transcription PCR. To assess let7i regulation of gene expression in stroke, messenger RNA (mRNA) from leukocytes was measured by whole-genome Human Transcriptome Array Affymetrix microarray. Given microRNAs act to destabilize and degrade their target mRNA, mRNAs that inversely correlated with let7i were identified. To demonstrate let7i posttranscriptional regulation of target genes, a 3' untranslated region luciferase assay was performed. Target protein expression was assessed using ELISA.ResultsLet7i was decreased in patients with acute ischemic stroke (fold change -1.70, p < 0.00001). A modest inverse correlation between let7i and NIH Stroke Scale score at admission (r = -0.32, p = 0.02), infarct volume (r = -0.21, p = 0.04), and plasma MMP9 (r = -0.46, p = 0.01) was identified. The decrease in let7i was associated with increased expression of several of its mRNA targets, including CD86, CXCL8, and HMGB1. In vitro studies confirm let7i posttranscriptional regulation of target genes CD86, CXCL8, and HMGB1. Functional analysis predicted let7i regulates pathways involved in leukocyte activation, recruitment, and proliferation including canonical pathways of CD86 signaling in T helper cells, HMGB1 signaling, and CXCL8 signaling.ConclusionsLet7i is decreased in circulating leukocytes of patients with acute ischemic stroke. Mechanisms by which let7i regulates inflammatory response post stroke include targeting CD86, CXCL8, and HMGB1.

BackgroundTranscranial Doppler (TCD) with agitated saline has been shown to be an alternative for the detection of right-to-left shunts (RLS) with similar diagnostic accuracies as transesophageal echocardiography (TEE). It is hypothesized that the addition of blood to agitated saline increases the sensitivity of TCD for the detection of RLS. The aim of this meta-analysis was to determine whether agitated saline with blood increases the sensitivity of TCD for the detection of RLS compared to agitated saline alone and other contrast agents.MethodA systematic review of Medline, Cochrane, and Embase was performed to look for all prospective studies assessing intracardiac RLS using TCD compared with TEE as the reference; both tests were performed with a contrast agent and a maneuver to provoke RLS in all studies.ResultsA total of 27 studies (29 comparisons) with 1,968 patients met the inclusion criteria. Of 29 comparisons, 10 (35%) used echovist contrast during TCD, 4 (14%) used a gelatin-based solution, 12 (41%) used agitated saline, and 3 (10%) utilized 2 different contrast agents. The addition of blood to agitated saline improved the sensitivity of TCD to 100% compared to agitated saline alone (96% sensitivity, P = 0.161), echovist (94% sensitivity, P = 0.044), and gelatin-based solutions (93% sensitivity, P = 0.041).ConclusionThe addition of blood to agitated saline improves the sensitivity of TCD for the detection of RLS to 100% when compared to other conventional contrast agents; these findings support the addition of blood to agitated saline during TCD bubble studies.

Infestation with nonnative, "exotic" lice was first noted in Washington black-tailed deer (Odocoileus hemionus columbianus) in 1994 and has since then spread throughout the western United States. In California, infestation with the exotic louse Damalinia (Cervicola) sp. was first detected in black-tailed deer from northern California in 2004, and, in 2009, the exotic louse species Bovicola tibialis and Linognathus africanus were identified on mule deer (Odocoileus hemionus californicus) in central Sierra Nevada in association with a mortality event. Exotic lice have since been detected in various locations throughout the state. We describe the geographic distribution of these exotic lice within California, using data from 520 live-captured and 9 postmortem-sampled, free-ranging mule deer examined between 2009 and 2014. Data from live-captured deer were used to assess possible associations between louse infestation and host age, host sex, migratory behavior, season, and blood selenium and serum copper concentrations. Damalinia (Cervicola) sp. and B. tibialis lice were distinctively distributed geographically, with D. (Cervicola) sp. infesting herds in northern and central coastal California, B. tibialis occurring in the central coastal mountains and the Sierra Nevada, and L. africanus occurring only sporadically. Younger age classes and low selenium concentrations were significantly associated with exotic louse infestation, whereas no significant relationship was detected with serum copper levels. Our results show that exotic lice are widespread in California, and younger age classes with low blood selenium concentrations are more likely to be infested with lice than older deer.

Alternative specimens have been occasionally considered as substitutes for whole blood for postmortem toxicology testing. We studied the applicability of vitreous humor, and evaluated whether it would be suitable to replace (or augment) whole blood for routine drug screening. Results showed that from 51 autopsy cases, we were able to identify an aggregate of 209 findings in whole blood compared with 169 in vitreous. The total number of compounds identified was 71 for whole blood and 60 for vitreous humor. Quantitative analysis showed that whole-blood concentrations of trazodone were several fold higher than vitreous humor concentrations (1.42 ± 0.57 vs. 0.15 ± 0.05 mg/L, respectively) and similar results were also obtained for diazepam (0.37 ± 0.06 vs. 0.13 ± 0.01, respectively). For other drugs such as oxycodone, hydrocodone and doxylamine, a trend suggesting higher concentrations in vitreous humor vs. whole blood was observed; however, this was not significant. Our results are consistent with the limited work of other investigators, and suggest that vitreous humor could be an appropriate matrix for drug screening in postmortem toxicology.

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown compounds at m/z of 357 and 312 while decreased metabolites included creatinine, androgen derivatives and other unknown yet to be identified compounds. Furthermore, the creatine to creatinine ratio is significantly associated with disease progression in DMD patients. This ratio sharply increased with age in DMD patients while it decreased with age in healthy controls. Overall, this study yielded promising metabolic signatures that could prove useful to monitor DMD disease progression and response to therapies in the future.

ObjectiveThe cytokine/chemokine network is used by the innate and adaptive immune system to orchestrate effective immune responses. Here, we describe the cross-sectional association between cytokine levels and stage of HIV infection to gain novel insights into HIV-1 immunopathogenesis and identify novel therapeutic targets.DesignConcentrations of 31 cytokine/chemokines were retrospectively measured in blood and seminal plasma collected from 252 individuals enrolled in four well characterized cohorts: HIV-uninfected, untreated HIV-infected in early phase of infection, untreated HIV-infected in late phase of infection, and HIV-infected on antiretroviral therapy with undetectable HIV RNA levels in blood (

Background: Estimating rates of prenatal alcohol exposure (PAE) in a population is necessary to ensure that proper medical and social supports and interventions are in place. This study sought to estimate PAE in Ontario, Canada by quantifying phosphatidylethanol (PEth) homologues in over 2000 residual neonatal dried blood spots (DBS). Methods: A random selection of 2011 residual DBS collected over a 1‐week time period were anonymized and extracted. A targeted liquid chromatography–mass spectrometry method was used to quantify 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphoethanol (PEth (16:0/18:1) or POPEth), the clinically accepted biomarker, and six additional PEth homologues. A POPEth level above the United States Drug Testing Laboratories (USDTL) cutoff up to 4 weeks predelivery was indicative of PAE. All PEth homologues were correlated to one another and logistic regression was used to determine the association between PAE status and infant characteristics. Results: The estimated rate of PAE in Ontario, up to the last 4 weeks of gestation, was 15.5% (POPEth >28.5 nM). Most PEth homologues were moderately to strongly correlated to one another. A low birth weight and preterm birth were both associated with PAE, while being small for gestational age had lower odds of PAE. Conclusions: The results of this study suggest that PAE may be more prevalent in Ontario than previous estimates by self‐report or meconium testing. These findings support the need to consider the effectiveness of current interventions and the design of new interventions to address this significant public health issue. [ABSTRACT FROM AUTHOR]

The prevention effectiveness of oral preexposure prophylaxis (PrEP) is highly dependent on medication adherence but no validated longer term PrEP adherence measures are readily available for use by primary care clinicians caring for diverse populations. We compared two self-report measures (number of doses missed in past 7 days and day-by-day past week pill taking) to results of tenofovir concentrations in dried blood spot (DBS) samples at quarterly visits over the first 12 months of PrEP use. 1420 men and women in five US community health centers enrolled in a medication adherence substudy. For 3, 6, 9 and 12 months, the respective percentages of persons with self-report vs DBS levels consistent having taken all 7 doses in the week prior were 71% (51%), 70% (47%), 71% (46%) and 69% (44%). Conversely, the percentage of participants reporting taking 0–1 doses in the week prior by self-report vs DBS drug levels at 3, 6, 9 and 12 months consistent with this level of nonadherence of 6% (9%), 5% (10%), 8% (9%), and 9% (15%). The estimated risk of low adherence (estimated 0–1 doses in the week prior) was higher for participants of Black (RR 1.60, CI 1.09–2.34) or "Other" race (RR 1.62, CI 0.99–2.65) compared with participants of White race; being a transgender female (RR 2.31, CI 1.33–4.02) compared to men who have sex with men; or enrollment at a study site with less experience in the provision of PrEP. The estimated risk of low adherence by DBS was lower for participants with a higher number of sex partners in the past 3 months and those having a bachelor's degree or higher. More work is needed to provide clinicians with measures to assess medication adherence in diverse US populations being prescribed PrEP to support its effective use in reducing HIV acquisition in individuals and at the community level. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a prognostic biomarker in many disease states. The aim of this study was to evaluate the diagnostic utility of NLR to predict poor functional outcomes in patients with hemorrhagic stroke and to compare it with the intracranial hemorrhage (ICH) score. Materials and methods: Patients who presented to the emergency department with clinical features suggestive of stroke were evaluated with computed tomography (CT) brain to identify ICH. The ICH scores and NLR were estimated at the time of admission. Modified Rankin Scale (mRS) score equal to or greater than 3 at 90 days was used to define poor functional outcomes (major disability or death). Receiver operating characteristic (ROC) curve was plotted with NLR and the ICH score to analyze and compare their discriminative ability to predict poor functional outcomes. Results: A total of 158 patients were recruited for the study. One hundred and seven patients were found to have poor functional outcomes as per their mRS score at 90 days. The mean NLR and the ICH scores at presentation were significantly higher for the poor outcome group (6.57 and 2.83) compared to the good outcome group (2.75 and 1.49). The ROC analysis revealed that both NLR and the ICH scores were good predictors of functional outcomes at 90 days with area under the curve (AUC) of 0.814 and 0.819, respectively. The sensitivity and specificity of NLR were 84 and 66.3% and those of the ICH score were 66.7 and 78.3% to predict poor functional outcomes. Conclusion: In patients with hemorrhagic stroke, NLR at admission is a good predictor of functional outcomes at 90 days. When compared to the ICH score, NLR is more sensitive but less specific in predicting poor functional outcomes. [ABSTRACT FROM AUTHOR]