Age-stratified Assessment of Brain Volumetric Segmentation on the Indian Population Using Quantitative Magnetic Resonance Imaging.

BACKGROUND AND PURPOSE: Automated methods for quantifying brain tissue volumes have gained clinical interest for their objective assessment of neurological diseases. This study aimed to establish reference curves for brain volumes and fractions in the Indian population using Synthetic MRI (SyMRI), a quantitative imaging technique providing multiple contrast-weighted images through fast postprocessing. METHODS: The study included a cohort of 314 healthy individuals aged 15-65 years from multiple hospitals/centers across India. The SyMRI-quantified brain volumes and fractions, including brain parenchymal fraction (BPF), gray matter fraction (GMF), white matter fraction (WMF), and myelin. RESULTS: Normative age-stratified quantification curves were created based on the obtained data. The results showed significant differences in brain volumes between the sexes, but not after normalization by intracranial volume. CONCLUSION: The findings provide normative data for the Indian population and can be used for comparative analysis of brain structure values. Furthermore, our data indicate that the use of fractions rather than absolute volumes in normative curves, such as BPF, GMF, and WMF, can mitigate sex and population differences as they account for individual differences in head size or brain volume.

Changes in Natriuretic Peptide Levels and Subsequent Kidney Function Decline in SPRINT.

RATIONALE & OBJECTIVE: Novel approaches to the assessment of kidney disease risk during hypertension treatment are needed because of the uncertainty of how intensive blood pressure (BP) lowering impacts kidney outcomes. We determined whether longitudinal N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements during hypertension treatment are associated with kidney function decline. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 8,005 SPRINT (Systolic Blood Pressure Intervention Trial) participants with NT-proBNP measurements at baseline and 1 year. EXPOSURE: 1-year change in NT-proBNP categorized as a ≥25% decrease, ≥25% increase, or <25% change (stable). OUTCOME: Annualized change in estimated glomerular filtration rate (eGFR) and ≥30% decrease in eGFR. ANALYTICAL APPROACH: Linear mixed-effect and logistic regression models were used to evaluate the association of changes in NT-proBNP with subsequent annualized change in eGFR and ≥30% decrease in eGFR, respectively. Analyses were stratified by baseline chronic kidney disease (CKD) status. RESULTS: Compared with stable 1-year NT-proBNP levels, a ≥25% decrease in NT-proBNP was associated with a slower decrease in eGFR in participants with CKD (adjusted difference, 1.09%/y; 95% CI, 0.35-1.83) and without CKD (adjusted difference, 0.51%/y; 95% CI, 0.21-0.81; P = 0.4 for interaction). Meanwhile, a ≥25% increase in NT-proBNP in participants with CKD was associated with a faster decrease in eGFR (adjusted difference, -1.04%/y; 95% CI, -1.72 to -0.36) and risk of a ≥30% decrease in eGFR (adjusted odds ratio, 1.44; 95% CI, 1.06-1.96); associations were stronger in participants with CKD than in participants without CKD (P = 0.01 and P < 0.001 for interaction, respectively). Relationships were similar irrespective of the randomized BP arm in SPRINT (P > 0.2 for interactions). LIMITATIONS: Persons with diabetes and proteinuria >1 g/d were excluded. CONCLUSIONS: Changes in NT-proBNP during BP treatment are independently associated with subsequent kidney function decline, particularly in people with CKD. Future studies should assess whether routine NT-proBNP measurements may be useful in monitoring kidney risk during hypertension treatment. PLAIN-LANGUAGE SUMMARY: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker in the blood that reflects mechanical stress on the heart. Measuring NT-proBNP may be helpful in assessing the risk of long-term losses of kidney function. In this study, we investigated the association of changes in NT-proBNP with subsequent kidney function among individuals with and without chronic kidney disease. We found that increases in NT-proBNP are associated with a faster rate of decline of kidney function, independent of baseline kidney measures. The associations were more pronounced in individuals with chronic kidney disease. Our results advance the notion of considering NT-proBNP as a dynamic tool for assessing kidney disease risk.

Estimated Kidney Tubular Secretion and Kidney, Cardiovascular, and Mortality Outcomes in CKD: The Systolic Blood Pressure Intervention Trial.

Rational & Objective: Many drugs, metabolites, and toxins are cleared by the kidneys via tubular secretion. Whether novel endogenous measures of tubular secretion provide information about kidney, cardiovascular, and mortality risk is uncertain. Study Design: Longitudinal subgroup analysis of clinical trial participants. Setting & Participants: 2,089 Systolic Blood Pressure Intervention Trial participants with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline. Exposure: Summary score incorporating urine-to-plasma ratios of 10 endogenous secretion markers measured in paired urine and plasma samples at baseline. Outcome: The primary outcome was longitudinal change in eGFR. Secondary outcomes included chronic kidney disease (CKD) progression (≥50% eGFR decline or incident kidney failure requiring dialysis or kidney transplantation), a cardiovascular disease (CVD) composite (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes), and mortality. Analytical Approach: Linear mixed-effect models were used to evaluate the association between the secretion score and change in eGFR, and Cox proportional hazards models were used to evaluate associations with CKD progression, CVD, and mortality. Results: At baseline, mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.3 years, mean change in eGFR was -1.44% per year, and 72 CKD progression events, 272 CVD events, and 144 deaths occurred. In multivariable analyses, lower secretion score was associated with faster eGFR decline and greater risk of CKD progression, CVD, and mortality. After further adjustment for baseline eGFR and albuminuria, each 1-standard deviation lower secretion score was associated with faster eGFR decline (-0.65% per year; 95% CI, -0.84% to -0.46%), but not CKD progression (HR, 1.23; 95% CI, 0.96-1.58), CVD (HR, 1.02; 95% CI, 0.89-1.18), or mortality (HR, 0.90; 95% CI, 0.74-1.09). The secretion score association with eGFR decline appeared stronger in participants with baseline eGFR <45 mL/min/1.73 m2 (P for interaction < 0.001). Limitations: Persons with diabetes and proteinuria >1 g/d were excluded. Conclusions: Among SPRINT participants with CKD, lower estimated tubular secretion was associated with faster eGFR decline, independent of baseline eGFR and albuminuria, but not with CKD progression, CVD, or mortality.

Markers of Kidney Tubular Secretion and Risk of Adverse Events in SPRINT Participants with CKD.

BACKGROUND: Kidney tubular secretion is an essential mechanism for clearing many common antihypertensive drugs and other metabolites and toxins. It is unknown whether novel measures of tubular secretion are associated with adverse events (AEs) during hypertension treatment. METHODS: Among 2089 SPRINT (Systolic Blood Pressure Intervention Trial) participants with baseline eGFR <60 ml/min per 1.73 m2, we created a summary secretion score by averaging across the standardized spot urine-to-plasma ratios of ten novel endogenous tubular secretion measures, with lower urine-to-plasma ratios reflecting worse tubular secretion. Multivariable Cox proportional hazards models were used to evaluate associations between the secretion score and risk of a composite of prespecified serious AEs (hypotension, syncope, bradycardia, AKI, electrolyte abnormalities, and injurious falls). The follow-up protocol for SPRINT routinely assessed two laboratory monitoring AEs (hyperkalemia and hypokalemia). RESULTS: Overall, 30% of participants experienced at least one AE during a median follow-up of 3.0 years. In multivariable models adjusted for eGFR and albuminuria, lower (worse) secretion scores at baseline were associated with greater risk of the composite AE outcome (hazard ratio per 1-SD lower secretion score, 1.16; 95% confidence interval, 1.04 to 1.27). In analyses of the individual AEs, lower secretion score was associated with significantly greater risk of AKI, serious electrolyte abnormalities, and ambulatory hyperkalemia. Associations were similar across randomized treatment assignment groups. CONCLUSION: Among SPRINT participants with CKD, worse tubular secretion was associated with greater risk of AEs, independent of eGFR and albuminuria.

Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Serious Adverse Events in SPRINT.

Background Assessing the risk of serious adverse events (SAEs) during hypertension treatment is important for understanding the benefit-harm trade-offs of lower blood pressure goals. It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) provide information about SAEs. Methods and Results In SPRINT (Systolic Blood Pressure Intervention Trial), hs-cTnT and NT-proBNP were measured at baseline in 8828 (94.3%) and 8836 (94.4%) participants, respectively. Multivariable Cox proportional hazards models were used to evaluate hs-cTnT and NT-proBNP associations with a composite of SPRINT's SAEs of interest: hypotension, syncope, bradycardia, acute kidney injury, electrolyte abnormalities, and injurious falls. Elevations in hs-cTnT and NT-proBNP were associated with increased composite SAE risk (hazard ratio [HR] per 2-fold higher hs-cTnT: 1.15; 95% CI, 1.06‒1.25; HR per 2-fold higher NT-proBNP: 1.09; 95% CI, 1.05‒1.14). Compared with both hs-cTnT and NT-proBNP in the lower tertiles, both biomarkers in the highest tertile was associated with increased composite SAE risk (HR, 1.56; 95% CI, 1.32‒1.84). Composite SAE risk was higher in the intensive-treatment group than in the standard-treatment group for participants with both biomarkers in the lower tertiles, but similar between treatment groups for participants with both biomarkers in the highest tertile (P for interaction=0.008). Conclusions Elevations in hs-cTnT and NT-proBNP individually and in combination are associated with higher composite SAE risk in SPRINT. The differential impact of blood pressure treatment on SAE risk across combined biomarker categories may have implications for identifying individuals with more favorable benefit-harm profiles for intensive blood pressure lowering.

Kidney tubule health, mineral metabolism and adverse events in persons with CKD in SPRINT.

BACKGROUND: Measures of kidney tubule health are risk markers for acute kidney injury (AKI) in persons with chronic kidney disease (CKD) during hypertension treatment, but their associations with other adverse events (AEs) are unknown. METHODS: Among 2377 Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD, we measured at baseline eight urine biomarkers of kidney tubule health and two serum biomarkers of mineral metabolism pathways that act on the kidney tubules. Cox proportional hazards models were used to evaluate biomarker associations with risk of a composite of pre-specified serious AEs (hypotension, syncope, electrolyte abnormalities, AKI, bradycardia and injurious falls) and outpatient AEs (hyperkalemia and hypokalemia). RESULTS: At baseline, the mean age was 73 ± 9 years and mean estimated glomerular filtration rate (eGFR) was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.8 years, 716 (30%) participants experienced the composite AE. Higher urine interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1), lower urine uromodulin (UMOD) and higher serum fibroblast growth factor-23 were individually associated with higher risk of the composite AE outcome in multivariable-adjusted models including eGFR and albuminuria. When modeling biomarkers in combination, higher NGAL [hazard ratio (HR) = 1.08 per 2-fold higher biomarker level, 95% confidence interval (CI) 1.03-1.13], higher MCP-1 (HR = 1.11, 95% CI 1.03-1.19) and lower UMOD (HR = 0.91, 95% CI 0.85-0.97) were each associated with higher composite AE risk. Biomarker associations did not vary by intervention arm (P > 0.10 for all interactions). CONCLUSIONS: Among persons with CKD, several kidney tubule biomarkers are associated with higher risk of AEs during hypertension treatment, independent of eGFR and albuminuria.

Device for Assessing Knee Joint Dynamics During Magnetic Resonance Imaging.

BACKGROUND: Knee assessment with and without load using magnetic resonance imaging (MRI) can provide information on knee joint dynamics and improve the diagnosis of knee joint diseases. Performing such studies on a routine MRI-scanner require a load-exerting device during scanning. There is a need for more studies on developing loading devices and evaluating their clinical potential. PURPOSE: Design and develop a portable and easy-to-use axial loading device to evaluate the knee joint dynamics during the MRI study. STUDY TYPE: Prospective study. SUBJECTS: Nine healthy subjects. FIELD STRENGTH/SEQUENCE: A 0.25 T standing-open MRI and 3.0 T MRI. PD-T2 -weighted FSE, 3D-fast-spoiled-gradient-echo, FS-PD, and CartiGram sequences. ASSESSMENT: Design and development of loading device, calibration of loads, MR safety assessment (using projectile angular displacement, torque, and temperature tests). Scoring system for ease of doing. Qualitative (by radiologist) and quantitative (using structural similarity index measure [SSIM]) image-artifact assessment. Evaluation of repeatability, comparison with various standing stances load, and loading effect on knee MR parameters (tibiofemoral bone gap [TFBG], femoral cartilage thickness [FCT], tibial cartilage thickness [TCT], femoral cartilage T2 -value [FCT2], and tibia cartilage T2 -value [TCT2]). The relative percentage change (RPC) in parameters due to the device load was computed. STATISTICAL TEST: Pearson's correlation coefficient (r). RESULTS: The developed device is conditional-MR safe (details in the manuscript and supplementary materials), 15 × 15 × 45 cm3 dimension, and <3 kg. The ease of using the device was 4.9/5. The device introduced no visible image artifacts, and SSIM of 0.9889 ± 0.0153 was observed. The TFBG intraobserver variability (absolute difference) was <0.1 mm. Interobserver variability of all regions of interest was <0.1 mm. The load exerted by the device was close to the load during standing on both legs in 0.25 T scanner with r > 0.9. Loading resulted in RPC of 1.5%-11.0%, 7.9%-8.5%, and -1.5% to 13.0% in the TFBG, FCT, and TCT, respectively. FCT2 and TCT2 were reduced in range of 1.5-2.7 msec and 0.5-2.3 msec due to load. DATA CONCLUSION: The proposed device is conditionally MR safe, low cost (material cost < INR 6000), portable, and effective in loading the knee joint with up to 50% of body weight. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Urine Biomarkers of Kidney Tubule Health and Incident CKD Stage 3 in Women Living With HIV: A Repeated Measures Study.

RATIONALE & OBJECTIVE: Single measurements of urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in HIV infection, but the prognostic value of repeat measurements over time is unknown. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 647 women living with HIV infection enrolled in the Women's Interagency Health Study. EXPOSURES: 14 urinary biomarkers of kidney tubule health measured at 2 visits over a 3-year period. OUTCOME: Incident CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at two 6-month visits and an average eGFR decline ≥ 3% per year. ANALYTICAL APPROACH: We used multivariable generalized estimating equations adjusting for CKD risk factors to evaluate baseline, time-updated, and change-over-time biomarker associations with incident CKD. We compared CKD discrimination between models with and without a parsimoniously selected set of biomarkers. RESULTS: During a median 7 years of follow-up, 9.7% (63/647) developed CKD. In multivariable-adjusted analyses, 3 of 14 baseline biomarkers associated with incident CKD. In contrast, 10 of 14 time-updated biomarkers and 9 of 14 biomarkers modeled as change over time associated with incident CKD. Urinary epidermal growth factor (EGF), α1-microglobulin (A1M), and albumin were selected using penalized regression methods. In the time-updated model, lower urinary EGF (risk ratio [RR] per 2-fold higher time-updated biomarker levels, 0.69; 95% CI, 0.58-0.81), higher urinary A1M (RR, 1.47; 95% CI, 1.25-1.73), and higher urinary albumin excretion (RR, 1.21; 95% CI, 1.03-1.42) were jointly associated with increased risk for CKD. Compared with a base model (C statistic, 0.75), CKD discrimination improved after adding urinary EGF, A1M, and albumin values across baseline (C = 0.81), time-updated (C = 0.83), and change-over-time (C = 0.83) models (P < 0.01 for all). LIMITATIONS: Observational design, incident CKD definition limited to eGFR. CONCLUSIONS: Repeat urinary biomarker measurements for kidney tubule health have stronger associations with incident CKD compared with baseline measurements and moderately improve CKD discrimination in women living with HIV infection.

A novel CRYGC E128* mutation underlying an autosomal dominant nuclear cataract in a south Indian kindred.

PURPOSE: To identify the mutation causing an autosomal dominant congenital nuclear cataract in a south Indian family by whole exome sequencing and to characterize further phenotypically the same in a zebra fish model. METHODS: A six-generation family (DKEC1) with several affected members registered at the Regional Institute of Ophthalmology (RIO), Chennai was documented to have congenital nuclear cataract. Detailed clinical history and blood samples were collected from all available family members. Genomic DNA of the proband was subjected to whole exome sequencing. Sequence variations suggestive of putative mutations were further confirmed by bidirectional sequencing and restriction site analysis. Functional analysis of the mutant CRYGC E128* in zebrafish embryos was done to dissect out the pathogenicity. RESULTS: A unique variation viz., c.382 G > T in the coding region of the CRYGC gene, resulting in a premature stop codon at position 128 (E128*) was documented in the affected family members. The same was absent in unaffected family members and in 120 unrelated population controls checked. Bioinformatic tools predicted that the mutation might cause a deleterious effect on protein structure and function. Molecular function analysis of this novel mutation (p. E128*, CRYGC) in the zebrafish indicated this mutation to impair lens transparency. CONCLUSION: This study identified a novel CRYGC mutation, E128* to cause autosomal dominant congenital nuclear cataract in a large south Indian family. Our study provides a new insight onto how the mutation might affect the γC-crystallin structure and function besides emphasizing the need for genetic diagnosis toward vision restoration.

Modified radial-search algorithm for segmentation of tibiofemoral cartilage in MR images of patients with subchondral lesion.

PURPOSE: The quantitative analysis of weight-bearing articular cartilage superficial to subchondral abnormality is important in osteoarthritis (OA) progression studies. The current study aimed to address the challenges of a semi-automatic segmentation of tibiofemoral cartilage in MR images of OA patient with and without subchondral bone abnormalities (SBA). METHODS: In this study, knee MRI data [fat-suppressed proton density-weighted, multi-echo T2-weighted (CartiGram) images] of 29 OA patients, acquired at 3.0T MR scanner, were retrospectively collected. Out of 29 data, 9 had SBA in femur bone. Initially, a semi-automatic femur cartilage segmentation based on radial intensity search approach by Akhtar et al. was implemented in-house. This algorithm was considered as the radial-search method for further comparison. In this current study, the reported radial-search (RS)-based semi-automatic cartilage segmentation method was modified using thresholding, connected component labelling, convex-hull operation and spline-based curve fitting for the improved segmentation of tibiofemoral cartilage. Cartilage was manually segmented by two experienced radiologists, and inter-reader variability was estimated using coefficient of variation (CV). The segmentation results were validated using dice coefficient (DC), Jaccard coefficient (JC) and sensitivity index measurements. RESULTS: DC values for segmented femur cartilage in patients with SBA were 64.6 ± 7.8% and 81.4 ± 2.8% using reported RS method and modified radial-search method, respectively. DC values for segmented femur cartilage in patients without SBA were 82.5 ± 4.5% and 84.8 ± 2.0% using RS method and modified radial method, respectively. Similarly, DC values for tibial cartilage in all OA patients were 80.4 ± 1.6% and 81.9 ± 2.4% using RS method and modified radial method, respectively. Similar segmentation results were also obtained from the T2-weighted images. Inter-reader variability result based on CV in femur cartilage was 3.40 ± 2.12% (without SBA) and 4.18 ± 3.18% (with SBA). CONCLUSION: In the current study, a semi-automated segmentation of tibiofemoral cartilage was presented. Modified radial-search approach can successfully segment tibiofemoral cartilage, and the results were tested and validated on knee MRI data of OA patients with and without SBA.

The importance of using a right test method in diagnosing leptospirosis.

Leptospirosis is a common febrile illness in Malaysia. The disease is caused by pathogenic bacteria called leptospires that are transmitted directly or indirectly from animals to humans via contaminated water or soil. It is a potentially serious but treatable disease. Its symptoms may mimic those of other unrelated febrile illnesses such as dengue, influenza, meningitis, hepatitis or viral haemorrhagic fevers. The spectrum of the disease is extremely wide, ranging from subclinical infection to a severe syndrome of multiorgan infection with high mortality. The diagnosis requires high suspicion with history of exposure to water or environment possibly contaminated with infected animal urine. This is a case of a 13 year-oldgirl with no known medical illness, and a history of exposure to outdoor activities. However, paired sera for leptospirosis serology was not diagnostic. She then developed septic shock on day 14 of illness. But due to high suspicion of leptospirosis, antibiotic therapy was upgraded to ceftriaxone and samples were sent for further testing which revealed that leptospires were detected in the urine, using molecular technique. She improved after treated as leptospirosis.

The importance of using a right test method in diagnosing leptospirosis

@#Leptospirosis is a common febrile illness in Malaysia. The disease is caused by pathogenic bacteria called leptospires that are transmitted directly or indirectly from animals to humans via contaminated water or soil. It is a potentially serious but treatable disease. Its symptoms may mimic those of other unrelated febrile illnesses such as dengue, influenza, meningitis, hepatitis or viral haemorrhagic fevers. The spectrum of the disease is extremely wide, ranging from subclinical infection to a severe syndrome of multiorgan infection with high mortality. The diagnosis requires high suspicion with history of exposure to water or environment possibly contaminated with infected animal urine. This is a case of a 13 year-oldgirl with no known medical illness, and a history of exposure to outdoor activities. However, paired sera for leptospirosis serology was not diagnostic. She then developed septic shock on day 14 of illness. But due to high suspicion of leptospirosis, antibiotic therapy was upgraded to ceftriaxone and samples were sent for further testing which revealed that leptospires were detected in the urine, using molecular technique. She improved after treated as leptospirosis.

Physiological and proteomic analysis of Stenotrophomonas maltophilia grown under the iron-limited condition.

Aims: To study physiological and proteomic analysis of Stenotrophomonas maltophilia grown under iron-limited condition. Methods: One clinical and environmental S. maltophilia isolates grown under iron-depleted conditions were studied for siderophore production, ability to kill nematodes and alteration in protein expression using isobaric tags for relative and absolute quantification (ITRAQ). Results & conclusions: Siderophore production was observed in both clinical and environmental strains under iron-depleted conditions. Caenorhabditis elegans assay showed higher killing rate under iron-depleted (96%) compared with normal condition (76%). The proteins identified revealed, 96 proteins upregulated and 26 proteins downregulated for the two isolates under iron depletion. The upregulated proteins included several iron acquisition proteins, metabolic proteins and putative virulence proteins.

Molecular epidemiology of Clostridium difficile isolated from piglets.

Information on the epidemiology of C. difficile infection (CDI) in South-East Asian countries is limited, as is data on possible animal reservoirs of C. difficile in the region. We investigated the prevalence and molecular epidemiology of C. difficile in piglets and the piggery environment in Thailand and Malaysia. Piglet rectal swabs (n = 224) and piggery environmental specimens (n = 23) were collected between 2015 and 2016 from 11 farms located in Thailand and Malaysia. All specimens were tested for the presence of C. difficile with toxigenic culture. PCR assays were performed on isolates to determine the ribotype (RT), and the presence of toxin genes. Whole genome sequencing was used on a subset of isolates to determine the evolutionary relatedness of RT038 (the most prevalent RT identified) common to pigs and humans from Thailand and Indonesia. C. difficile was recovered from 35% (58/165) and 92% (54/59) of the piglets, and 89% (8/9) and 93% (13/14) of the environmental specimens from Thailand and Malaysia, respectively. All strains from Thailand, and 30 strains from Malaysia (23 piglet and 7 environmental isolates) were non-toxigenic. To our knowledge, this is the first and only report with a complete lack of toxigenic C. difficile among piglets, a feature which could have a protective effect on the host. The most common strain belonged to RT038 (ST48), accounting for 88% (51/58) of piglet and 78% (7/9) of environmental isolates from Thailand, and all 30 isolates tested from Malaysia. Piglet RT038 isolates from Thailand and Malaysia differed by only 18 core-genome single nucleotide variants (cgSNVs) and both were, on average, 30 cgSNVs different from the human strains from Thailand and Indonesia, indicating a common ancestor in the last two decades.

Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease.

BACKGROUND: Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. METHODS: We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. RESULTS: At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m2. Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01-1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02-1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. CONCLUSIONS: Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.

Diagnostic accuracy of rapid diagnostic tests for the early detection of leptospirosis.

BACKGROUND: Leptospirosis is often misdiagnosed with several other tropical febrile illnesses in Malaysia due to similarities in clinical manifestations. Although treatment regimens could be started based on clinical judgments, early diagnosis has become paramount as a guide to chemotherapeutic interventions. Confirmed laboratory diagnosis through MAT or PCR is time consuming and usually available only in reference laboratories and not practical in healthcare settings. Rapid and easy to perform diagnostic tests are widely used in these settings as the point of care diagnosis. The present study was undertaken to compare the diagnostic performance of two IgM based immunodiagnostic assay kits for acute leptospirosis. METHODS: A total of 50 serum samples were collected from patients clinically suspected for acute leptospirosis on admission in the Hospital Serdang, from June 2016 to June 2017. All the samples were subjected to MAT, lipL32 PCR and the two rapid tests (Leptocheck-WB and ImmuneMed Leptospira IgM Duo Rapid test). RESULTS: Out of the 50 clinically suspected patients sampled, 19 were confirmed positive for leptospirosis. Six (12%) were confirmed by MAT and 13 (26%) by PCR. Similarly, of the 50 clinically suspected cases, 17 (34%) showed positivity for Leptocheck-WB and 7 (14%) for ImmuneMed Leptospira IgM Duo Rapid test. The overall sensitivity and specificity was 47.37% and 80.65% for Leptocheck-WB, and 21.05% and 90.32% for ImmuneMed Leptospira IgM Duo Rapid test. In another set of previously confirmed MAT positive samples (1:400-1:3600) obtained from a reference laboratory, Leptocheck-WB showed higher sensitivity (90.72%) than ImmuneMed Leptospira IgM Duo Rapid test (40.21%), and comparable specificity for ImmuneMed Leptospira IgM Duo Rapid test (88.89%) and Leptocheck-WB (82.86%). CONCLUSION: The sensitivity was higher for Leptocheck-WB and had a comparable specificity with ImmuneMed Leptospira IgM Duo Rapid test. Therefore, based on the present study, Leptocheck-WB is found to be a more sensitive rapid immunodiagnostic test for acute leptospirosis screening in hospital settings.

Biomarker responses in zebrafish (Danio rerio) larvae exposed to pristine low-density polyethylene fragments.

There are serious concerns over the adverse impacts of microplastics (MPs) on living organisms. The main objective of this study was to test the effects of MPs on the total length, weight, condition factor (CF), transcriptional level of antioxidant, anti and pro-apoptotic, and neurotransmitter genes, and the histopathology of the gill, liver, brain, kidney, and intestine in the larvae of zebrafish (Danio rerio). Fish were exposed to one of three levels of pristine low-density polyethylene (LDPE) fragments (5, 50, or 500 µg/L) for 10 or 20 days. No significant changes were observed in any of the selected biomarkers across MP concentrations at days 10 or 20. The expression of casp9 (caspase 9, apoptosis-related cysteine protease), casp3a (caspase 3, apoptosis-related cysteine protease a) and cat (catalase), however, were significantly lower in the larvae sampled at day 20 than day 10. We provide evidence that virgin short-term exposure to LDPE fragments has minimal impact on biomarker responses in D. rerio larvae.

Characterization of a Group B Streptococcus infection based on the demographics, serotypes, antimicrobial susceptibility and genotypes of selected isolates from sterile and non-sterile isolation sites in three major hospitals in Malaysia.

BACKGROUND/PURPOSE: The purpose of this study is to characterize GBS isolates that were collected from three major hospitals in a densely populated area of Klang Valley for their demographics, serotypes, antibiotic susceptibility patterns and genetic background. METHODS: Sixty GBS isolates from sterile and non-sterile samples in three major hospitals in the Klang Valley area of Malaysia were collected by convenience sampling from 2012 until March 2014. These isolates were studied for their antimicrobial susceptibilities, serotypes and genotypes. Patients' demographic data and clinical information were collected from lab request forms. RESULTS: Diabetes mellitus was the only underlying condition (7 patients, 23.3%); the remaining samples were from patients who were immunocompromised due to medications. Fifty-nine (98%) isolates were sensitive to penicillin, while 78.3% and 88.3% of the isolates were sensitive to erythromycin and clindamycin, respectively. Serotype Ia was the most common serotype (n=27, 45%), followed by serotype III (n=10, 16.7%), V (n=9, 15%), VI (n=8, 13.3%), VIII (n=2, 3.3%) and VII (n=1, 1.7%). Random Amplified Polymorphic DNA (RAPD) typing showed a diverse genetic pedigree for all isolates, including four major groups that clustered according to geographical location. CONCLUSION: This preliminary study determines the prevalence of limited common serotypes and antimicrobial resistance in distinct GBS isolates. Nonetheless, the RAPD clustering pattern suggests a close genetic lineage of the GBS isolates based on their isolation sites and location of hospitals.

Antigen negative red blood cell inventory of Indian blood donors.

BACKGROUND: Screening the donor population for clinically important antigens and creating a database of phenotyped donors will eliminate the tedious task of large scale screening for antigen negative units. The aim of the present study is to identify donors lacking common antigens and a combination of common antigens to establish an antigen negative inventory. MATERIALS AND METHODS: Blood samples of 1221 regular blood donors were phenotyped for the clinically important common antigens of the Rh, Duffy, Kell, Kidd and MNS blood group systems using standard tube technique. RESULTS: Out of 1221 total donors tested, we observed that 261 donors lacked a combination of clinically important common antigens (C, D, e, Fya, Jka, s). After excluding the RhD negative donors in this study 15.56% lacked a combination of two or three common antigens. Of all donors, 3.2% lacked Fya and Jka antigens, 1.96% Fya and s, 1.88% Jka and s antigens and 0.57% lacked three common antigens. DISCUSSION: An antigen negative inventory of donors who lack a single common antigen or a combination of common antigens was prepared from regular donors which will prove useful for efficient management of transfusion therapy in patients with multiple antibodies against common antigens.