Virulent and multidrug‐resistant Klebsiella pneumoniae from clinical samples in Balochistan

Klebsiella pneumoniae is an important pathogen causing hospital‐acquired infections in human beings. Samples from suspected patients of K pneumoniae associated with respiratory and urinary tract infections were collected at Bolan Medical Complex, Quetta, Balochistan. Clinical samples (n = 107) of urine and sputum were collected and processed for K pneumoniae isolation using selective culture media. Initially, 30 of 107 isolates resembling Klebsiella spp. were processed for biochemical profiling and molecular detection using gyrase A (gyrA) gene for conformation. The K pneumoniae isolates were analysed for the presence of drug resistance and virulence genes in their genomes. The 21 of 107 (19.6%) isolates were finally confirmed as K pneumoniae pathogens. An antibiogram study conducted against 17 different antibiotics showed that a majority of the isolates are multidrug resistant. All the isolates (100%) were resistant to amoxicillin, cefixime, amoxicillin‐clavulanic acid, cefotaxime, and ceftriaxone followed by tetracycline (95.2%), ciprofloxacin and gentamicin (76.2%), sulphamethoxazol (66.7%), nalidixic acid (61.9%), norfloxacine (42.9%), piperacillin‐tazobactam (23.8%), cefoperazone‐sulbactam (19%), and cefotaxime‐clavulanic acid (33.3%), whereas all the isolates showed sensitivity to amikacin, chloramphenicol, and imipenem. The presence of tetracycline, sulphamethoxazol‐resistant genes, and extended‐spectrum beta‐lactamase was reconfirmed using different specific genes. The presence of virulence genes fimH1 and EntB responsible for adherence and enterobactin production was confirmed in the isolates. The high virulence and drug resistance potential of these Klebsiella isolates are of high public health concern. Multidrug resistance and virulence potential in K. pneumoniae are converting these nosocomial pathogens into superbugs and making its management harder.     

Iris cerclage pupilloplasty and IOL implantation for traumatic mydriasis and aphakia after the blunt trauma of the eye

Four patients with traumatic mydriasis and aphakia following blunt injury of the eye globe were evaluated. Patients with severe glare and photophobia due to wide pupil diameter from 6.0 to 9.0 mm were managed by combined iris cerclage pupilloplasty and retropupillar iris-claw lens implantation. The postoperative anatomic results, visual acuity, subjective degree of glare, photophobia, as well as intraoperative and postoperative complications were evaluated. The mean follow-up time was 32.6 months. Best-corrected visual acuity improved in all patients from preoperative 20/60, 20/30, 20/25, 20/22 to postoperative 20/20, 20/22, 20/20, and 20/20 (Snellen charts). All eyes achieved satisfactory anatomic result with round pupil diameter 3.5–4.5 mm. Glare and photophobia disappeared in all patients. There were no intraoperative or postoperative complications. During the follow-up period, pupils remained round and iris-claw lenses well positioned, without tilting. Combined iris cerclage pupilloplasty with retropupillar iris claw lens implantation appears to be a safe and effective surgical technique in reducing pupil size and improving visual outcomes. It is also a cost- and time-effective procedure, providing great results with a single surgery.     

Health workers who ask about social determinants of health are more likely to report helping patients: Mixed-methods study

ObjectiveTo assess the feasibility of implementing a clinical decision aid called the CLEAR Toolkit that helps front-line health workers ask their patients about social determinants of health, refer to local support resources, and advocate for wider social change.DesignA mixed-methods study using quantitative (online self-completed questionnaires) and qualitative (in-depth interviews, focus groups, and key informant interviews) methods.SettingA large, university-affiliated family medicine teaching centre in Montreal, Que, serving one of the most ethnically diverse populations in Canada.ParticipantsFifty family doctors and allied health workers responded to the online survey (response rate of 50.0%), 15 completed in-depth interviews, 14 joined 1 of 2 focus groups, and 3 senior administrators participated in key informant interviews.MethodsOur multimethod approach included an online survey of front-line health workers to assess current practices and collect feedback on the tool kit; in-depth interviews to understand why they consider certain patients to be more vulnerable and how to help such patients; focus groups to explore barriers to asking about social determinants of health; and key informant interviews with high-level administrators to identify organizational levers for changing practice.Main findingsSenior administrators consider asking about social determinants to be part of the mandate of health workers. However, barriers perceived by front-line clinicians include insufficient training in social history taking, uncertainty about how to address these issues in clinical practice, and a lack of knowledge of local referral resources. Health workers with specific ways of asking patients about their social challenges were more likely to report having helped their patients as compared with those who did not know how to ask (93.8% vs 52.9%; P = .003).ConclusionWhile health workers recognize the importance of social determinants, many are unsure how to ask about these often sensitive issues or where to refer patients. The CLEAR Toolkit can be easily adapted to local contexts to help front-line health workers initiate dialogue around social challenges and better support patients in clinical practice.     

Relationship between adiponectin, glycemic control and blood lipids in diabetic type 2 postmenopausal women with and without complication of ischemic heart disease

BACKGROUND: Recently major adipocytokine, adiponectin, are thought to play important roles in the regulation of cardiovascular and metabolic homeostasis. We compared serum adiponectin concentrations and lipid profile in diabetic patients with and without complication of cardiovascular disease in postmenopausal women. METHODS: We included 120 female subjects between the age of 45 and 60 years. The subjects were divided into 3 groups and each group comprised of 40 subjects. First group comprised of normal healthy controls, second group diabetic type 2 patients with no history of ischemic heart disease (IHD) and the third group diabetic patients with IHD. Serum adiponectin concentrations, serum triglycerides, cholesterol, LDL cholesterol and HDL cholesterol concentrations were determined. RESULTS: Values of fasting and random blood glucose, serum triglycerides, cholesterol, LDL cholesterol were significantly increased (P<0.001) in diabetic patients with IHD as compared with normal control subjects except for serum adiponectin and HDL cholesterol concentrations, which were significantly decreased (P<0.001) in diabetic patients and diabetic patients with IHD group. When values of cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, fasting and random blood glucose and adiponectin were compared among diabetic and diabetic patients with IHD, it was observed that they were significantly increased (P<0.001) except for adiponectin, which was decreased significantly (P<0.001) and random blood glucose, LDL and HDL cholesterol in which no change was observed between the 2 groups. CONCLUSIONS: Serum adiponectin concentrations may be a predictor for development of cardiovascular disease in postmenopausal diabetic patients.     

Aortic pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease

Pulse pressure (PP), a marker of arterial stiffness, predicts cardiovascular risk. We aimed to determine whether augmentation pressure (AP) derived from the aortic pressure waveform predicts major adverse cardiovascular events (MACE) and death independently of PP in patients with established coronary artery disease (CAD). We prospectively followed-up 297 males undergoing coronary angiography for 1186+/-424 days. Ascending aortic pressure tracings obtained during catheterization were used to calculate AP (difference between the second and the first systolic peak). Augmentation index (AIx) was defined as AP as a percentage of PP. We evaluated whether AP and AIx can predict the risk of MACE (unstable angina, acute myocardial infarction, coronary revascularization, stroke, or death) and death using Cox regression. All models evaluating AP included PP to assess whether AP adds to the information already provided by PP. Both AP and AIx significantly predicted MACE. The hazard ratio (HR) per 10 mm Hg increase in AP was 1.20 (95% confidence interval [CI], 1.08 to 1.34; P<0.001); the HR for each 10% increase in AIx was 1.28 (95% CI, 1.11 to 1.48; P=0.004). After adjusting for other univariate predictors of MACE, age, and other potential confounders, AP remained a significant predictor of MACE (HR per 10 mm Hg increase=1.19; 95% CI, 1.06 to 1.34; P=0.002), as did AIx (adjusted HR, 1.28; 95% CI, 1.09 to 1.50; P=0.003). AP was a significant predictor of death (HR per 10 mm Hg increase=1.18; 95% CI, 1.02 to 1.39; P=0.03). Higher AIx was associated with a trend toward increased mortality (HR=1.22; 95% CI, 0.98 to 1.52; P=0.056). Aortic AP predicts adverse outcomes in patients with CAD independently of PP and other risk markers.     

Loss‐of‐function mutations in the melanocortin‐3 receptor gene confer risk for human obesity: A systematic review and meta‐analysis

The association between rare coding loss‐of‐function (LOF) mutations in the melanocortin receptor 3 (MC3R) gene and human obesity is controversial. To fill this gap of knowledge, we performed a systematic review and meta‐analysis of genetic association studies in all ages and ethnicities. Two reviewers independently performed risk of bias assessment and extracted data. We searched Medline, Embase, Web of Science Core Collection, BIOSIS Preview, CINAHL, ProQuest Dissertations & Theses, and reference lists of relevant studies. All case‐control, cross‐sectional, prospective, and retrospective studies that evaluated prevalence of rare (less than 1% frequency) coding partial/complete LOF mutations in MC3R among individuals with obesity and normal weight were included. Our systematic search identified 1925 references relevant to the present review. Six studies were deemed eligible. Meta‐analysis of 2969 individuals with obesity and 2572 with normal weight showed a positive association between rare heterozygous coding partial/complete LOF mutations in MC3R and obesity in children and adults of European, North African, and Asian ancestries (odds ratio = 3.07; 95% CI, 1.48‐7.00; P = 4.2 × 10^?3). Our data demonstrates that rare partial/complete LOF mutations in the coding region of MC3R confer three‐time increased risk of obesity in humans, and implies that rare genetic variants with intermediate effects contribute to the missing heritability of obesity.     

Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability

Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts by using induced pluripotent stem cells (iPSCs). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent-resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the PI3K pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening.