Respiratory health and indoor air pollution at high elevation

In this research, the authors sought to provide experimental data on indoor air quality, and the resulting respiratory impact, for a high-elevation (4550 m), rural community in Ladakh, India. This community is of interest because the primarily nomadic residents burn biomass inside the home for heating and cooking. The concentrations of particulate matter (PM), endotoxin, and carbon monoxide were determined for 6 homes. Lung function data and induced sputum samples were collected for 9 female test-home subjects. In addition, lung function data were collected for 84 additional Ladakhi highlanders at this location. Sputum from 3 visiting scientists (sojourners) was collected and analyzed as well. The average PM concentration ranged from 2 mg/m3 to 7 mg/m3, with 85% of the sampled PM sized as respirable. The average endotoxin concentration ranged from 2.4 ng/m3 to 19 ng/m3, and average carbon monoxide levels ranged from 50 ppm to 120 ppm. Lung function values for the highlander population and the test-home subjects were equal to or greater than predicted, despite the highlanders' significant exposure to indoor pollutants. An induced sputum analysis revealed a significantly greater total inflammatory cell count (M +/- SD, 10(5) cell/mg) in the Ladakhi natives than in the sojourners (107.5 +/- 75.2 vs 7.1 +/- 8.1, p < .01). Although the high levels of indoor pollutants did not correlate with significant decrements in lung function, the induced sputum analysis revealed marked airway inflammation dominated by macrophages and neutrophils. It appears that augmented lung mechanics of this high-altitude population are adaptive to reduce the work of breathing; thus, decrements in lung function go undetected because the true predicted values are greater than expected.     

Mutations in betaB3-crystallin associated with autosomal recessive cataract in two Pakistani families

PURPOSE: To identify the disease locus for autosomal recessive congenital cataracts in consanguineous Pakistani families. METHODS: Two Pakistani families were ascertained, patients were examined, blood samples were collected, and DNA was isolated. A genome-wide scan was performed using >382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members. Two-point lod scores were calculated, haplotypes were formed by inspection, and candidate genes were sequenced. Real-time quantitative PCR techniques were used to determine the mRNA levels, and molecular modeling was performed to gain a better understanding of the significance of the disease-causing mutation. RESULTS: In the genome-wide scan, maximum lod scores of 2.67 and 2.77 for family 60004 and 2.02 and 2.04 for family 60006 were obtained for markers D22S539 and D22S315, respectively. The linked region, 22.7 cM (10 Mb) flanked by markers D22S420 and D22S1163, contains the beta-crystallin gene cluster including the genes CRYBA4, CRYBB1, CRYBB2, and CRYBB3. Sequencing of these genes showed a G-->C transition in exon 6 of CRYBB3 resulting in a p.G165R change in the betaB3-crystallin protein that cosegregates with the disease in both families. Real-time PCR analysis suggested that betaB3-crystallin mRNA levels approximate those of other betagamma-crystallins. Molecular modeling predicted changes in electrostatic potential that would be expected to reduce the stability of the fourth Greek-key motif, and hence the entire protein, dramatically. CONCLUSIONS: For the first time, a mutation in CRYBB3 is reported in two consanguineous Pakistani families with autosomal recessive congenital cataracts.     

A large unilocular mucinous cystadenoma in third trimester of pregnancy

Ovarian malignancy is the second most common gynaecological malignancy diagnosed during pregnancy. A grand multipara, aged 30 years presented with gestational amenorrhea with abdominal discomfort and breathlessness for last 15 days. Sonographic examination demonstrated a huge, unilocular ovarian cyst and an alive fetus of about 30 weeks gestation. Intraoperative findings were huge left ovarian cyst (42x40x20 cm) with straw coloured mucinous fluid. Left salpingo-oophorectomy was performed followed by peritoneal washings and omental biopsy. Histopathology revealed mucinous cystadenomas with inflammatory changes in omentum and no malignant cells in peritoneal washings. She delivered vaginally a female baby of 3.5 kg at 38 weeks with good Apgar score.     

Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuria

In two siblings of consanguineous parents with intermittent nephrotic-range proteinuria, we identified a homozygous deleterious frameshift mutation in the gene CUBN, which encodes cubulin, using exome capture and massively parallel re-sequencing. The mutation segregated with affected members of this family and was absent from 92 healthy individuals, thereby identifying a recessive mutation in CUBN as the single-gene cause of proteinuria in this sibship. Cubulin mutations cause a hereditary form of megaloblastic anemia secondary to vitamin B(12) deficiency, and proteinuria occurs in 50% of cases since cubilin is coreceptor for both the intestinal vitamin B(12)-intrinsic factor complex and the tubular reabsorption of protein in the proximal tubule. In summary, we report successful use of exome capture and massively parallel re-sequencing to identify a rare, single-gene cause of nephropathy.     

Meta-analysis of calcineurin-inhibitor-sparing regimens in kidney transplantation

Calcineurin-inhibitor-sparing strategies in kidney transplantation may spare patients the adverse effects of these drugs, but the efficacy of these strategies is unknown. Here, we conduct a meta-analysis to assess outcomes associated with reducing calcineurin inhibitor exposure from the time of transplantation. We search Medline, Embase, and Cochrane Register of Controlled Trials for randomized controlled trials published between 1966 and 2010 that compared de novo calcineurin-inhibitor-sparing regimens to calcineurin-inhibitor-based regimens. In this analysis, we include 56 studies comprising data from 11337 renal transplant recipients. Use of the contemporary agents belatacept or tofacitinib, in combination with mycophenolate, decreased the odds of overall graft failure (OR 0.61; 95% CI 0.39-0.96; P = 0.03). Similarly, minimization of calcineurin inhibitors in combination with various induction and adjunctive agents reduces the odds of graft failure (OR 0.73; 95% CI 0.58-0.92; P = 0.009). Conversely, the use of inhibitors of mammalian target of rapamycin (mTOR), in combination with mycophenolate, increases the odds of graft failure (OR 1.43; 95% CI 1.08-1.90; P = 0.01). Calcineurin-inhibitor-sparing strategies are associated with less delayed graft function (OR 0.89; 95% CI 0.80-0.98; P = 0.02), improved graft function, and less new-onset diabetes. The more contemporary protocols did not seem to increase rates of acute rejection. In conclusion, this meta-analysis suggests that reducing exposure to calcineurin inhibitors immediately after kidney transplantation may improve clinical outcomes.     

Concurrent validity of the Arabic version of General Medication Adherence Scale using two validated indirect adherences measures in Saudi patients with non-communicable diseases

PurposeThis study aimed to evaluate the concurrent validity of the Arabic version of the General Medication Adherence Scale (GMAS) using two validated scales namely Adherence to Refills and Medications Scale (ARMS) and Medication Adherence Rating Scale (MARS) in Saudi patients with non-communicable diseases.MethodsA cross sectional study was conducted for 2 months in out-patient departments at a tertiary care hospital in Khobar, Saudi Arabia. The study collected data from patients with chronic illnesses through convenience sampling. Pearson correlation (ρ) was conducted to report concurrent validity of GMAS. A correlation coefficient value ≥ 0.5 with p-value < 0.01 was considered threshold for establishing concurrent validity. The study was approved by an ethics committee (IRB-2019–05-002).ResultsA total of 406 patients responded to the study. The average age was 42.4 ± 5.94 years, and most patients were females (53.7%), married (70%), graduates (65.3%), employed (39.9%) and, had a monthly family income > SAR 10,000, i.e., USD 2666.2 (56.4%). The mean adherence scores obtained from MARS, ARMS and GMAS were 7.09, 19.9, and 27.4. The correlation (ρ) between GMAS and MARS scores was 0.65, and between GMAS and ARMS scores was −0.79, p < 0.01 for both comparisons.ConclusionThe concurrent validity of GMAS-AR was established in this study that would further substantiate psychometric properties of the scale in this population.