The charcot foot in diabetes.

The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity

Evaluation of a new, rapid, simple test for the detection of influenza virus

BACKGROUND: Influenza virus infections are responsible for significant morbidity and mortality in both pediatric and adult populations worldwide. Rapid and accurate diagnosis of influenza is necessary for appropriate patient management during the influenza season and for optimal utilization of anti-influenza therapy. We prospectively tested the accuracy of a simple and rapid diagnostic method. METHODS: Ninety-eight samples (nasal and pharyngeal swabs) from patients with upper respiratory tract infection symptoms who presented to primary healthcare centres in Barcelona (Spain) were prospectively analyzed. The samples were collected as part of influenza surveillance program. Samples that had enough volume to make the new test after aliquoting the amount needed to perform routine tests were included. None of the samples were pre-selected as a result of their status in relation to influenza virus. Samples were analyzed by in-house real-time PCR and Alere™ i Influenza A & B (Alere™ i), which uses isothermal amplification of nucleic acids for the qualitative detection of influenza A and B in nasal swabs transported in viral transport media. The two techniques were compared by positive percent agreement (PPA) and negative percent agreement (NPA). Statistical analysis was performed with Stata. RESULTS: Of the 98 samples analysed 90 were concordant; 46 (46.9%) were positive and 44 (44.9%) were negative. Five samples showed invalid results with the Alere™ i test and could be not re-tested due to insufficient sample volume and were not included in the final statistical analysis. In the 93 remaining samples, the Alere™ i test showed 97% of accuracy having correctly classified 90 samples. We obtained discordant results in 3 samples (3%). The PPA was 93.8% for influenza A and 94.1% for influenza B, and NPA was 100% for influenza A and influenza B virus. In addition, the Alere™ i was very rapid (15 minutes or less) and extremely easy to use. CONCLUSIONS: The Alere™ i test provided a good correlation compared to the real-time PCR test for the diagnosis of influenza. Since this method can be performed in minutes, it allows immediate, accurate clinical decisions to prescribe appropriate antiviral treatment or isolation of patients

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Unusual Dengue Virus 3 Epidemic in Nicaragua, 2009

The four dengue virus serotypes (DENV1–4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009–January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009–10, compared to 13–65 cases in 2004–9. In both studies, significantly more patients experienced “compensated shock” (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009–10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1–2 days) in 2009–10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years – similar to the cohort study. DENV-3 predominated in 2008–9, 2009–10, and 2010–11, and full-length sequencing revealed no major genetic changes from 2008–9 to 2010–11. In 2008–9 and 2010–11, typical dengue was observed; only in 2009–10 was unusual presentation noted. Multivariate analysis revealed only “2009–10” as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral genomic sequence, immune status, and sequence of serotypes can play a role in modulating dengue disease outcome

Livelihood and vulnerability in the wake of Typhoon Yolanda: lessons of community and resilience

Livelihood strategies that are crafted in ‘extra-ordinary’ post-disaster conditions should also be able to function once some semblance of normalcy has resumed. This article aims to show that the vulnerability experienced in relation to Typhoon Yolanda was, and continues to be, directly linked to inadequate livelihood assets and opportunities. We examine the extent to which various livelihood strategies lessened vulnerability post-Typhoon Yolanda and argue that creating conditions under which disaster survivors have the freedom to pursue sustainable livelihood is essential in order to foster resilience and reduce vulnerability against future disasters. We offer suggestions to improve future relief efforts, including suggestions made by the survivors themselves. We caution against rehabilitation strategies that knowingly or unknowingly, resurrect pre-disaster vulnerability. Strategies that foster dependency, fail to appreciate local political or ecological conditions or undermine cooperation and cohesion in already vulnerable communities will be bound to fail. Some of the livelihood strategies that we observed post-Typhoon Yolanda failed on some or all of these points. It is important for future policy that these failings are addressed

Functional Characterization of MODY2 Mutations Highlights the Importance of the Fine-Tuning of Glucokinase and Its Role in Glucose Sensing

Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and regulates insulin secretion. Heterozygous mutations in the human GK-encoding GCK gene that reduce the activity index increase the glucose-stimulated insulin secretion threshold and cause familial, mild fasting hyperglycaemia, also known as Maturity Onset Diabetes of the Young type 2 (MODY2). Here we describe the biochemical characterization of five missense GK mutations: p.Ile130Thr, p.Asp205His, p.Gly223Ser, p.His416Arg and p.Ala449Thr. The enzymatic analysis of the corresponding bacterially expressed GST-GK mutant proteins show that all of them impair the kinetic characteristics of the enzyme. In keeping with their position within the protein, mutations p.Ile130Thr, p.Asp205His, p.Gly223Ser, and p.His416Arg strongly decrease the activity index of GK, affecting to one or more kinetic parameters. In contrast, the p.Ala449Thr mutation, which is located in the allosteric activator site, does not affect significantly the activity index of GK, but dramatically modifies the main kinetic parameters responsible for the function of this enzyme as a glucose sensor. The reduced Kcat of the mutant (3.21±0.28 s−1 vs 47.86±2.78 s−1) is balanced by an increased glucose affinity (S0.5 = 1.33±0.08 mM vs 7.86±0.09 mM) and loss of cooperativity for this substrate. We further studied the mechanism by which this mutation impaired GK kinetics by measuring the differential effects of several competitive inhibitors and one allosteric activator on the mutant protein. Our results suggest that this mutation alters the equilibrium between the conformational states of glucokinase and highlights the importance of the fine-tuning of GK and its role in glucose sensing

Knowledge and perceptions of diabetes in a semi-urban Omani population

<p>Abstract</p> <p>Background</p> <p>Diabetes mellitus is a major public health problem in the Sultanate of Oman. This study aimed to evaluate the knowledge and perception of diabetes in a sample of the Omani general population, and the associations between the elements of knowledge and perception, and socio-demographic factors.</p> <p>Methods</p> <p>The study was carried out in two semi-urban localities. A total of 563 adult residents were interviewed, using a questionnaire specifically designed for the present study. In addition to demographic information, the questionnaire contained questions on knowledge related to diabetes definition, symptoms, risk factors, complications and preventative measures, as well as risk perception for diabetes.</p> <p>Results</p> <p>Knowledge of diabetes was suboptimal. The percentages of correct responses to questions on diabetes definition, classical symptoms, and complications were 46.5%, 57.0%, and 55.1%, respectively. Only 29.5%, 20.8% and 16.9% identified obesity, physical inactivity and a positive family history, respectively, as risk factors for diabetes. A higher level of education, a higher household income, and the presence of a family history of diabetes were found to be positively associated with more knowledge.</p> <p>Conclusion</p> <p>This study demonstrated that there is lack of awareness of major risk factors for diabetes mellitus. Level of education is the most significant predictor of knowledge regarding risk factors, complications and the prevention of diabetes. Given that the prevalence of diabetes has increased drastically in Oman over the last decade, health promotion seems essential, along with other means to prevent and control this emerging health problem.</p

Dissecting the Transcriptional Regulatory Properties of Human Chromosome 16 Highly Conserved Non-Coding Regions

Non-coding DNA conservation across species has been often used as a predictor for transcriptional enhancer activity. However, only a few systematic analyses of the function of these highly conserved non-coding regions (HCNRs) have been performed. Here we use zebrafish transgenic assays to perform a systematic study of 113 HCNRs from human chromosome 16. By comparing transient and stable transgenesis, we show that the first method is highly inefficient, leading to 40% of false positives and 20% of false negatives. When analyzed in stable transgenic lines, a great majority of HCNRs were active in the central nervous system, although some of them drove expression in other organs such as the eye and the excretory system. Finally, by testing a fraction of the HCNRs lacking enhancer activity for in vivo insulator activity, we find that 20% of them may contain enhancer-blocking function. Altogether our data indicate that HCNRs may contain different types of cis-regulatory activity, including enhancer, insulators as well as other not yet discovered functions