Relevant Blood Research Articles

Toxicological evaluation, postmortem case descriptions, and pharmacological activity of N,N-dimethylpentylone and related analogues.

Identification of N,N-dimethylpentylone (DMP) in counterfeit "Ecstasy" and "Molly" tablets poses risk to public health due to its adverse effects. Little information is available regarding the pharmacological activity or relevant blood or tissue concentrations of DMP, and even less is known about other structurally related beta-keto methylenedioxyamphetamine analogues on recreational drug markets, such as N-propyl butylone. Here, a novel toxicological assay utilizing liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS) was developed and validated for the quantitation of DMP and five related synthetic cathinones (eutylone, pentylone, N-ethyl pentylone (NEP), N-propyl butylone, and N-cyclohexyl butylone), with chromatographic resolution from isomeric variants and quantitation performed by standard addition. A forensic series of 125 cases is presented for DMP and related analogs, along with pharmacological activity assessments using monoamine transporter and mouse behavioral assays. The blood concentration range for DMP in postmortem forensic cases was 3.3-4,600 ng/mL (mean: 320±570 ng/mL, median: 150 ng/mL), whereas pentylone, the primary N-desmethyl metabolite of DMP, was identified in 98% of cases with a concentration range 1.3-710 ng/mL (mean±SD: 105±120 ng/mL, median: 71 ng/mL). N-Propyl butylone, a newly identified synthetic cathinone, was quantitated in seven cases (mean±SD: 82±75 ng/mL, median: 50 ng/mL, range: 1.7-200 ng/mL). DMP displayed potent uptake inhibition at the dopamine transporter (IC50=49 nM), with 100-fold weaker potency at the serotonin transporter (IC50=4990 nM). DMP was a locomotor stimulant in mice (ED50=3.5 mg/kg) exhibiting potency relatively similar to eutylone, N-ethyl pentylone, and pentylone. Our results show that DMP is a psychomotor stimulant associated with adverse clinical outcomes leading to death. Forensic laboratories must continue to update testing methods to capture emerging drugs, with specific emphasis on resolution and identification of isomeric species. Following the scheduling of DMP in early-2024, there could be an anticipated market shift towards a new unregulated synthetic stimulant to replace DMP.

Non-linear relationship between urinary creatinine and diabetic kidney disease: implications for clinical practice

ObjectiveThis study aims to investigate the relationship between urinary creatinine (UCr) and the risk and severity of Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM). The goal is to establish UCr as a potential biomarker for early DKD detection and severity assessment.MethodsA retrospective cross-sectional analysis was conducted using medical records of T2DM patients. Patients were classified into groups with and without DKD, and relevant clinical data, including demographic, blood, and urine parameters, were collected. Logistic regression and receiver operating characteristic (ROC) curve analysis evaluated the association between UCr levels and DKD. Curve fitting and threshold effect model were used to further evaluate the relationship between UCr and the incidence and severity of DKD.ResultsA total of 302 T2DM patients were analyzed, with 137 diagnosed with DKD. Significant differences in clinical parameters were observed between the DKD and non-DKD groups, particularly in UCr, urine albumin levels, and eGFR. UCr levels demonstrated a strong association with DKD. Moreover, a non-linear relationship was identified, with specific inflection points indicating different correlation patterns of UCr with DKD occurrence and progression.ConclusionThe findings of this study highlight the potential of UCr as a valuable biomarker for early detection and assessment of DKD in T2DM patients. Incorporating UCr measurements into routine clinical practice could enhance early identification of patients at risk for kidney complications, leading to timely intervention and improved patient outcomes.

Heart Attack Prediction

Cardiovascular diseases, including heart attacks, remain a leading cause of mortality globally. Early prediction and intervention play a critical role in preventing and managing such conditions. This project presents a comprehensive approach to heart attack prediction through the integration of machine learning techniques and a user-friendly graphical user interface (GUI) implemented in Python. The system leverages a dataset of relevant health parameters, including age, blood pressure, cholesterol levels, and other key factors. A machine learning model, trained on historical data, is employed to analyze and predict the likelihood of a heart attack based on these input features. The model's accuracy and efficiency are crucial to its effectiveness, and various algorithms are explored to identify the optimal solution. To enhance accessibility and usability, a GUI is developed using Python's Tkinter library. The GUI enables users to input their health parameters easily and receive an instant prediction regarding their potential risk of a heart attack. The visual representation of the prediction, along with additional informative features, aims to empower individuals to take proactive measures towards a healthier lifestyle. The project not only contributes to the field of cardiovascular health prediction but also serves as an educational tool for users to better understand the factors influencing their cardiovascular well-being. The integration of machine learning into a userfriendly GUI provides a practical and efficient solution for both healthcare professionals and individuals concerned about their heart health.

Redefining Clinically Significant Blood Loss in Complex Adult Spine Deformity Surgery.

Retrospective analysis of prospectively-collected data. This study aims to define clinically relevant blood loss in adult spinal deformity (ASD) surgery. Current definitions of excessive blood loss following spine surgery are highly variable and may be suboptimal in predicting adverse events (AE). Adults undergoing complex ASD surgery were included. Estimated blood loss (EBL) was extracted for investigation, and estimated blood volume loss (EBVL) was calculated by dividing EBL by the preoperative blood volume utilizing Nadler's formula. LASSO regression was performed to identify five variables from demographic and peri-operative parameters. Logistic regression was subsequently performed to generate a receiver operating characteristics (ROC) curve and estimate an optimal threshold for EBL and EBVL. Finally, the proportion of patients with AE plotted against EBL and EBVL to confirm the identified thresholds. In total 552 patients were included with a mean age of 60.7±15.1 years, 68% females, mean CCI was 1.0±1.6, and 22% experienced AEs. LASSO regression identified ASA score, baseline hypertension, preoperative albumin, and use of intra-operative crystalloids as the top predictors of an AE, in addition to EBL/EBVL. Logistic regression resulted in ROC curve which was used to identify a cut-off of 2.3 liters of EBL and 42% for EBVL. Patients exceeding these thresholds had AE rates of 36% (odds-ratio: 2.1, 95% CI [1.2-3.6]) and 31% (odds-ratio: 1.7, 95% CI [1.1-2.8]), compared to 21% for those below the thresholds of EBL and EBVL, respectively. In complex ASD surgery, intraoperative EBL of 2.3 liters and an EBVL of 42% are associated with clinically-significant AEs. These thresholds may be useful in guiding preoperative-patient-counseling, healthcare system quality initiatives, and clinical perioperative bloodloss management strategies in patients undergoing complex spine surgery. Additionally, similar methodology could be performed in other specialties to establish procedure-specific clinically-relevant bloodloss thresholds.

Lower Eyelid Surgical Anatomy and the Implications for Blepharoplasty Surgery: A Systematic Review of Anatomic Studies in the Literature.

Lower eyelid blepharoplasty is a procedure to address issues arising from age-related anatomic changes of the lower eyelid. These include excess skin, fat herniation, tear trough hollowing, and midface descent. Unlike the well-defined structures of the upper eyelid, the lower eyelid's anatomy, including the retractors and surrounding ligaments, is less distinct and understudied. In addition, lower eyelid blepharoplasty has an unfavorable complication profile compared with that of the upper eyelid. This review examines relevant studies on lower eyelid anatomy, focusing on age-related structural changes and the variability of key structures involved in blepharoplasty surgery to minimize the risk of complications and achieve desirable outcomes. A literature search for relevant publications on the topic was performed through Medline and PubMed, with the appropriate data extracted, identifying 54 relevant studies. These studies demonstrate how degenerative changes to the supporting structures of the lower eyelid contribute to prolapse of the orbital fat pads, and highlight the relevant ligamentous structures, blood supply, and innervation to avoid complications during transcutaneous or transconjunctival orbital fat repositioning. With detailed knowledge of the anatomy of the lower eyelid as outlined in our review, surgeons can improve and optimize outcomes whilst minimizing complications.

Association between human blood metabolome and risk of myocarditis: a mendelian randomization study

Myocarditis is a common disease of the cardiovascular and immune systems, but the relationship between relevant blood metabolites and the risk of myocarditis has not been well-established. To identify potential biometabolic markers associated with myocarditis, we conducted a two-sample Mendelian randomization (MR) study. We performed preliminary MR analysis using the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode methods to adjust for false discovery rate (FDR). Confounders were screened using the GWAS Catalog website. Sensitivity analyses included Cochrane Q-test, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), scatterplots, funnel plots, and forest plots. For genetic and directional analysis, we employed co-localization analysis and the Steiger test. MR analysis was performed using the FinnGen database and meta-analysis was performed using the IEU database. MR analysis identified significant correlations for five metabolic biomarkers after FDR correction. These included four known metabolites: kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, and 5-acetylamino-6-formylamino-3-methyluracil, as well as one unknown metabolite, X-25,422. Among these, kynurenine (OR = 1.441, 95%CI = 1.089–1.906, p-value = 0.018) and 1-stearoyl-GPE (18:0) (OR = 1.263, 95%CI = 1.029–1.550, p-value = 0.029) were identified as risk factors for myocarditis, while deoxycarnitine (OR = 0.813, 95%CI = 0.676–0.979, p-value = 0.029), 5-acetylamino-6-formylamino-3-methyluracil (OR = 0.864, 95% CI = 0.775–0.962, p-value = 0.018), and X-25,422 (OR = 0.721, 95%CI = 0.587–0.886, p-value = 0.009) were found to be protective factors. No evidence of heterogeneity, horizontal pleiotropy, or sensitivity issues was observed, and no shared genetic factors between exposure and outcome were detected. The causality was in the correct direction. Meta-analysis further confirmed the causal relationship between the five metabolites and myocarditis. This study identifies a causal relationship between five circulating metabolites and myocarditis. Kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, X-25,422, and 5-acetylamino-6-formylamino-3-methyluracil may serve as potential drug targets for myocarditis, providing a theoretical basis for the prevention, diagnosis, and treatment of the condition.

Is it useful to washing stored red blood cells in cardiopulmonary bypass priming fluid for neonatal cardiac surgery

Abstract Background The small blood volume and immature physiology of neonates necessitate careful consideration of the priming fluid composition during cardiopulmonary bypass (CPB) surgery, as it has a substantial impact on their physiologic stability. This study aimed to investigate the impact of allogeneic stored RBCs processed by an autotransfusion system into the CPB priming fluid for neonatal cardiac surgery. Methods This retrospective cohort study investigated the effects of incorporating unwashed (n=56) or washed (n=45) RBCs into the CPB priming fluid for elective neonatal cardiac surgery. We compared perioperative blood parameters, inflammatory mediators, coagulation indicators, vasoactive inotrope score (VIS), other relevant blood parameters and clinical outcomes between the two groups. The regression models were employed to evaluate the independent association between RBCs washing and prognostic outcomes. Results The autotransfusion system can effectively improve the quality of stored RBCs. During CPB, washed group exhibited higher peak hematocrit (P < 0.01), peak hemoglobin (P = 0.04), increased oxygen delivery index during rewarming (P < 0.05). The washed group exhibited significantly lower early postoperative lactate levels and VIS scores (P < 0.05). Despite demonstrating fluctuations in inflammatory (IL-6, IL-8, IL-10）and coagulation parameters(DD, FIB, FDP) compared to baseline, the two groups exhibited no significant divergence. Notably, the washed group experienced a lower incidence of hyperlactacidemia and delayed sternal closure at weaning from CPB. Conclusions The addition of washed allogeneic stored RBCs to neonatal CPB priming fluid significantly attenuated postoperative lactate elevation and lowered VIS without improving early alterations in the inflammatory and coagulation systems.

Differential effects of environmental exposures on clinically relevant endophenotypes between sexes

Sex and gender differences play a crucial role in health and disease outcomes. This study used data from the National Health and Nutrition Examination Survey to explore how environmental exposures affect health-related traits differently in males and females. We utilized a sex-stratified phenomic environment-wide association study (PheEWAS), which allowed the identification of associations across a wide range of phenotypes and environmental exposures. We examined associations between 272 environmental exposures, including smoking-related exposures such as cotinine levels and smoking habits, and 58 clinically relevant blood phenotypes, such as serum albumin and homocysteine levels. Our analysis identified 119 sex-specific associations. For example, smoking-related exposures had a stronger impact on increasing homocysteine, hemoglobin, and hematocrit levels in females while reducing serum albumin and bilirubin levels and increasing c-reactive protein levels more significantly in males. These findings suggest mechanisms by which smoking exposure may pose higher cardiovascular risks and greater induced hypoxia for women, and greater inflammatory and immune responses in men. The results highlight the importance of considering sex differences in biomedical research. Understanding these differences can help develop more personalized and effective health interventions and improve clinical outcomes for both men and women.

Blood inflammation relates to neuroinflammation and survival in frontotemporal lobar degeneration.

Neuroinflammation is an important pathogenic mechanism in many neurodegenerative diseases, including those caused by frontotemporal lobar degeneration (FTLD). Postmortem and in vivo imaging studies have shown brain inflammation early in these conditions, proportionate to symptom severity and rate of progression. However, evidence for corresponding blood markers of inflammation and their relationship with central inflammation and clinical outcome are limited. There is a pressing need for such scalable, accessible and mechanistically relevant blood markers as these will reduce the time, risk, and costs of experimental medicine trials. We therefore assessed inflammatory patterns of serum cytokines from 214 patients with clinical syndromes associated with FTLD as compared to healthy controls, including their correlation with brain regional microglial activation and disease progression. Serum assays used the MesoScale Discovery V-Plex-Human Cytokine 36 plex panel plus five additional cytokine assays. A sub-group of patients underwent 11C-PK11195 TSPO PET imaging, as an index of microglial activation. A Principal Component Analysis (PCA) was used to reduce the dimensionality of cytokine data, excluding cytokines that were undetectable in >50% of participants. Frequentist and Bayesian analyses were performed on the principal components, to compare each patient cohort to controls, and test for associations with central inflammation, neurodegeneration-related plasma markers and survival. The first component identified by the PCA (explaining 21.5% variance) was strongly loaded by pro-inflammatory cytokines, including TNF-α, TNF-R1, M-CSF, IL-17A, IL-12, IP-10 and IL-6. Individual scores of the component showed significant differences between each patient cohort and controls. The degree to which a patient expressed this peripheral inflammatory profile at baseline correlated negatively with survival (higher inflammation, shorter survival), even when correcting for baseline clinical severity. Higher pro-inflammatory profile scores were associated with higher microglial activation in frontal and brainstem regions, as quantified with 11C-PK11195 TSPO PET. A permutation-based Canonical Correlation Analysis confirmed the association between the same cytokine-derived pattern and central inflammation across brain regions in a fully data-based manner. This data-driven approach identified a pro-inflammatory profile across the FTLD clinical spectrum, which is associated with central neuroinflammation and worse clinical outcome. Blood-based markers of inflammation could increase the scalability and access to neuroinflammatory assessment of people with dementia, to facilitate clinical trials and experimental medicine studies.

Comparison of the Quantra QPlus and ROTEM Goal-Directed Transfusion Protocols in Cardiothoracic Surgery Patients: A Prospective Observational Study

To compare the designed treatment protocols for the Quantra QPlus and rotational thromboelastometry (ROTEM) with regard to transfusion advice. Prospective observational study. Maastricht University Medical Center, The Netherlands. Adults with elective cardiopulmonary bypass surgery with a ROTEM test. ROTEM tests were performed postoperatively for standard monitoring of coagulation status and clinical decision making. Simultaneously, a concurrent sample was analyzed for the Quantra QPlus. A total of 100 samples were analyzed using both the ROTEM and Quantra QPlus. Agreement between the transfusion advice for the ROTEM and Quantra QPlus protocols were compared using Cohen κ values for i.a. fibrinogen, platelet concentrates, and fresh frozen plasma (FFP). The agreement between ROTEM and Quantra QPlus was poor for overall transfusion (0.174) and fibrinogen transfusion (0.300). The agreement of cutoff values for fibrinogen clot stiffness for the Quantra QPlus and EXTEM A10 for the ROTEM was poor (0.160). The fibrinogen clot stiffness and FIBTEM A10 had a moderate agreement (0.731). A Cohen κ could not be calculated for the agreement of protamine, thrombocytes, FFP or cutoff values for these transfusions since frequencies included zero in these cases. The Quantra QPlus transfusion protocol advises transfusion in many non-bleeders, adjustments appear to be necessary. In a small group of cases in which clinically relevant blood loss was observed, the Quantra QPlus advised administration of transfusion products, whereas the ROTEM tests did not. ROTEM-guided and Quantra-guided transfusion did not correspond in this patient group, and agreement was moderate at best. Specificity and sensitivity for transfusion within protocols were heterogeneous between the methods. More clinical research in high-bleeding risk populations is needed to determine the clinical impact of the different protocols.

Identification and verification of immune-related genes for diagnosing the progression of atherosclerosis and metabolic syndrome

BackgroundAtherosclerosis and metabolic syndrome are the main causes of cardiovascular events, but their underlying mechanisms are not clear. In this study, we focused on identifying genes associated with diagnostic biomarkers and effective therapeutic targets associated with these two diseases.MethodsTranscriptional data sets of atherosclerosis and metabolic syndrome were obtained from GEO database. The differentially expressed genes were analyzed by RStudio software, and the function-rich and protein-protein interactions of the common differentially expressed genes were analyzed.Furthermore, the hub gene was screened by Cytoscape software, and the immune infiltration of hub gens was analyzed. Finally, relevant clinical blood samples were collected for qRT-PCR verification of the three most important hub genes.ResultsA total of 1242 differential genes (778 up-regulated genes and 464 down-regulated genes) were screened from GSE28829 data set. A total of 1021 differential genes (492 up-regulated genes and 529 down-regulated genes) were screened from the data set GSE98895. Then 23 up-regulated genes and 11 down-regulated genes were screened by venn diagram. Functional enrichment analysis showed that cytokines and immune activation were involved in the occurrence and development of these two diseases. Through the construction of the Protein–Protein Interaction(PPI) network and Cytoscape software analysis, we finally screened 10 hub genes. The immune infiltration analysis was further improved. The results showed that the infiltration scores of 7 kinds of immune cells in GSE28829 were significantly different among groups (Wilcoxon Test < 0.05), while in GSE98895, the infiltration scores of 4 kinds of immune cells were significantly different between groups (Wilcoxon Test < 0.05). Spearman method was used to analyze the correlation between the expression of 10 key genes and 22 kinds of immune cell infiltration scores in two data sets. The results showed that there were 42 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE28829 (|Cor| > 0.3 & P < 0.05). There were 41 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE98895 (|Cor| > 0.3 & P < 0.05). Finally, our results identified 10 small molecules with the highest absolute enrichment value, and the three most significant key genes (CX3CR1, TLR5, IL32) were further verified in the data expression matrix and clinical blood samples.ConclusionWe have established a co-expression network between atherosclerotic progression and metabolic syndrome, and identified key genes between the two diseases. Through the method of bioinformatics, we finally obtained 10 hub genes in As and MS, and selected 3 of the most significant genes (CX3CR1, IL32, TLR5) for blood PCR verification. This may be helpful to provide new research ideas for the diagnosis and treatment of AS complicated with MS.

Emerging role of vitamin D deficiency as a risk factor for retinal venous occlusions and need for public health measures for its prevention.

To estimate levels of serum vitamin D in patients of retinal vein occlusion (RVO) and compare with age- and sex-matched controls. A prospective case-control study of 54 patients of RVO and 54 age- and sex-matched attendants of patients presenting to a tertiary care hospital in Delhi was performed. Patients on vitamin D supplementations and RVO due to infective or immunological causes or patients of glaucoma were excluded. Serum vitamin D levels of all the study participants along with relevant blood investigations with history and examination were documented. Vitamin D deficiency was defined as <20 ng/ml. The mean serum vitamin D levels seen in RVO patients and the control group were 14.19 ± 5.23 ng/ml and 19.42 ± 10.27 ng/ml, respectively (P value = 0.001) with an odds ratio of 10.558 (CI = 2.34-47.50), indicating vitamin D deficiency to be strongly correlated with RVO. Maximum patients of RVO (46.3%) were seen during the winter season. The study noted hypertension [odds ratio 20.22 (CI = 5.812-70.347)], dyslipidemia, and anemia [odds ratio 4.107 (CI = 0.62-26.90)] to be the risk factors for RVO as previously proved in the literature. Smoking, diabetes, alcohol intake, and body mass index did not emerge as risk factors for RVO. Vitamin D deficiency is associated with RVO; hence, estimation of serum vitamin D levels should be advised as a part of routine investigations while looking for the cause of RVOs. Public health measures like food fortification with vitamin D micronutrients and public awareness towards increased sunlight exposure in the community are simple, inexpensive measures that can decrease the burden of sight-threatening disease of RVO in the community.

Correlates and predictors of sarcopenia among men with metastatic castrate-resistant prostate cancer.

Sarcopenia is a predictor of clinical outcomes in men with metastatic castrate-resistant prostate cancer (mCRPC); however, correlates and predictors of sarcopenia are poorly understood in this population. The aim of this study was to examine correlates and predictors of sarcopenia in men with mCRPC prior to treatment. A secondary analysis of an observational study was performed. Participants were receiving care for mCRPC at the Princess Margaret Cancer Centre. Sarcopenia was assessed prior to treatment and was defined as the combination of low grip strength (<35.5 kg), low gait speed (<0.8 m/s), and computed tomography-derived low muscle mass or density. Participants' sociodemographic and clinical characteristics, comorbidity information, and clinically relevant blood markers were collected prior to treatment and were used to identify correlates and predictors of sarcopenia through Spearman correlations and multivariable logistic regression, respectively. In total, 110 men had complete data on sarcopenia measures and were included in the analysis. Sarcopenia was identified in 30 (27.3%) participants. Pre-treatment sarcopenia was moderately correlated with dependence in one or more instrumental activities of daily living (IADLs) (r=0.412), Vulnerable Elders Survey-13 (r=0.404), and a lower hemoglobin (r=0.407 per 10 g/L decrease). In adjusted logistic regression, dependence in one or more IADLs (odds ratio [OR] 4.37, 95% confidence interval [CI] 1.37-13.86, p=0.012), and a 10 g/L decrease in hemoglobin (OR 1.70, 95% CI 1.13-2.57, p=0.012) were significantly associated with sarcopenia. In settings where assessment of sarcopenia is not feasible, evaluation of IADLs and hemoglobin may be used to identify high-risk patients that can benefit from supportive care strategies aiming to improve muscle mass and function.

A Comparative Study of Novel Fibrosis Index and Other Non-invasive Serum Indices for Predicting Fibrosis in Patients of Chronic Liver Disease.

Introduction Chronic liver diseaseprogression leads to liver fibrosis/cirrhosis. Transient Elastography is used for staging liver fibrosis but ascites, obesity, and operator experience limit its applicability. In this study, we compared various non-invasive serum indices in predicting fibrosis in chronic liver disease patients. Materials and methods A total of 142 cases of confirmed Chronic Liver Disease were included. Quantitative determination of liver stiffness by Transient Elastography and relevant blood investigations was done. We compared the liver stiffness measurement by Transient Elastography and fibrosis indices, i.e., Aspartate Transaminase (AST) to Alanine Transaminase (ALT) Ratio (AAR), AST to Platelet Ratio Index (APRI), Fibrosis Index (FI), Fibrosis-4 (FIB-4) Index, Age-Platelet Index (API), Pohl score, and Fibrosis Cirrhosis Index (FCI) with Novel Fibrosis Index (NFI), to predict liver fibrosis stages. Results The optimum cutoff of NFI for the F4 stage was ≥ 6670 with a sensitivity of 75.8% and specificity of 81.8%, for the F3 stage was ≥ 2112 with a sensitivity of 63.6%and specificity of 72.7%, and for the F2 stage was ≥ 1334 with a sensitivity of 100% and specificity of 56.3%. The NFI had the maximum area under the curve compared to other indices in predicting fibrosis stages. Conclusion The Novel Fibrosis Index was the best in predicting fibrosis stages in Chronic Liver Disease patients, with good performance in predicting the F4 stage.

A Prognostic Model Incorporating Relevant Peripheral Blood Inflammation Indicator to Predict Postherpetic Neuralgia in Patients with Acute Herpes Zoster.

To determine the risk of postherpetic neuralgia (PHN) in patients with acute herpes zoster (HZ), this study developed and validated a novel clinical prediction model by incorporating a relevant peripheral blood inflammation indicator. Between January 2019 and June 2023, 209 patients with acute HZ were categorized into the PHN group (n = 62) and the non-PHN group (n = 147). Univariate and multivariate logistic regression analyses were conducted to identify risk factors serving as independent predictors of PHN development. Subsequently, a nomogram prediction model was established, and the discriminative ability and calibration were evaluated using the receiver operating characteristic curve, calibration plots, and decision curve analysis (DCA). The nomogram model was internally verified through the bootstrap test method. According to univariate logistic regression analyses, five variables, namely age, hypertension, acute phase Numeric Rating Scale (NRS-11) score, platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index, were significantly associated with PHN development. Multifactorial analysis further unveiled that age (odds ratio (OR) [95% confidence interval (CI)]: 2.309 [1.163-4.660]), acute phase NRS-11 score (OR [95% CI]: 2.837 [1.294-6.275]), and PLR (OR [95% CI]: 1.015 [1.010-1.022]) were independent risk factors for PHN. These three predictors were integrated to establish the prediction model and construct the nomogram. The area under the receiver operating characteristic curve (AUC) for predicting the PHN risk was 0.787, and the AUC of internal validation determined using the bootstrap method was 0.776. The DCA and calibration curve also indicated that the predictive performance of the nomogram model was commendable. In this study, a risk prediction model was developed and validated to accurately forecast the probability of PHN after HZ, thereby demonstrating favorable discrimination, calibration, and clinical applicability.

A cross-sectional pilot study to estimate the frequency of minor blood group alleles and phenotypes in RhD-negative North Indian blood donors by DNA microarray analysis.

There are scarce data on Indian blood donors with respect to blood group phenotypes using molecular diagnostic modalities. Hence, we planned to estimate frequencies of blood group alleles/phenotypes using DNA microarray analysis in the north Indian RhD-negative blood donor population. With this initial pilot study, we plan to expand it to our entire donor population. The cross-sectional prospective study was conducted on 50 Indian blood donors (O RhD negative), to study the blood group genotype frequency. Genotyping for the most relevant red blood cell antigens (Rh, Kell, Duffy, Kidd, MNS, Lutheran, and Dombrock) was done using Bioarray Precise TypeHM Human Erythrocyte Antigen BeadChip kit containing probes directed to polymorphic sites. In the Rh system, the most common alleles were RHCE*e/RHCE*e (98%) and RHCE*c/RHCE*c (80%). Phenotype K-k+ (genotype- KEL*02/KEL*02) was seen in 98% of samples, Js(a-b+) (KEL*02.07/KEL*02.07) was detected in 98% (49/50) of the samples tested. Jk(a + b+) (JK*01/JK*02) was the most common phenotype (48%) in the Kidd blood group system. In MNSs system, M+N+ (GYPA*01/GYPA*02) 44% and S+s+U+ (GYPB*03/GYPB*04) 34% were the most common phenotypes detected. This pilot study shows the feasibility of genotyping a Northern Indian donor population. To the best of our knowledge, it is the first study on molecular blood grouping in Indian blood donors using the Bioarray platform.

Prevalence of metabolic syndrome and its association with CT-based central adiposity measures: a cross-sectional study at a tertiary care hospital in Pakistan

ObjectivesTo assess the prevalence of metabolic syndrome (MS) and association of central obesity measures such as body mass index (BMI), visceral fat adiposity (VFA) and superficial fat adiposity (SFA) with...

Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.

The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation, including the importance of phosphorylation, remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals crucial for malaria parasite development.

MALDI-TOF direct identification of positive blood cultures: A four-year analytical evaluation of A Triton based workflow

Rapid and reliable identification of the causal organism in bloodstream infections and sepsis is crucial for both individual patient care and public health. We have implemented a rapid in-house identification protocol (with 10 % Triton) using MALDI-TOF MS for identifying the causative organism in positive blood cultures without prior culture. Our objective was to retrospectively analyze data collected over a four-year period while implementing this rapid in-house identification protocol and to develop a guide for evaluating and reporting the obtained results. Overall, our method utilizing MALDI-TOF MS for rapid in-house identification, demonstrated comparable results to other commercially available and in-house methods reported in the literature. Over the past four years, direct identification has facilitated the distinction between clinically relevant positive blood cultures and irrelevant ones, guiding rapid focus control and appropriate antibiotic treatment. The established guide can serve as a valuable tool in reporting positive blood cultures and associated antibiotic treatments.

Systemic Inflammation Differences in Brain-vs. Circulatory-Dead Donors: Impact on Lung Transplant Recipients.

Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor's plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.