Insulin Dependant Diabetes Mellitus: Implications for Male Reproductive Function.

BACKGROUND Diabetes mellitus (DM) is increasing in men of reproductive age. Despite this, the prevalence of diabetes in men attending fertility clinics is largely unknown. Furthermore, studies examining the effects of DM on sperm fertility potential have been limited to conventional semen analysis. METHODS Conventional semen analysis (semen volume, sperm count, motility and morphology) was performed for 27 diabetic (mean age 34 +/- 2 years) and 29 non-diabetic subjects (control group, men undergoing routine infertility investigations, mean age 33 +/- 1 years). Nuclear DNA (nDNA) fragmentation was assessed using the alkaline Comet assay and mitochondrial DNA (mtDNA) deletions by Long-PCR. RESULTS Other than a small, but significant, reduction in semen volume in diabetic men (2.6 versus 3.3 ml; P <0.05), conventional semen parameters did not differ significantly from control subjects. Diabetic subjects had significantly higher mean nDNA fragmentation (53 versus 32%; P <0.0001) and median number of mtDNA deletions (4 versus 3; P <0.05) compared with control subjects. CONCLUSIONS Diabetes is associated with increased sperm nuclear and mtDNA damage that may impair the reproductive capability of these men.

Nutrient regulation of pancreatic beta-cell function in diabetes: problems and potential solutions

increasing prevalence of obesity combined with longevity will produce an epidemic of Type 2 (non-insulin-dependent) diabetes in the next 20 years. This. disease is associated with defects in insulin secretion, specifically abnormalities of insulin secretory kinetics and pancreatic beta-cell glucose responsiveness. Mechanisms underlying beta-cell dysfunction include glucose toxicity, lipotoxicity and beta-cell hyperactivity. Defects at various sites in beta-cell signal transduction pathways contribute, but no single lesion can account for the common form of Type 2 diabetes. Recent studies highlight diverse beta-cell actions of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). These intestinal hormones target the beta-cell to stimulate glucose-dependent insulin secretion through activation of protein kinase A and associated pathways. Both increase gene expression and proinsulin biosynthesis, protect against apoptosis and stimulate replication/neogenesis of beta-cells. Incretin hormones therefore represent an exciting future multi-action solution to correct beta-cell defect in Type 2 diabetes.

The prevalence of nonadherence in difficult asthma

Rationale: With the advent of new and expensive therapies for severe refractory asthma, targeting the appropriate patients is important. An important issue is identifying nonadherence with current therapies. The extent of nonadherence in a population with difficult asthma has not been previously reported.

Objectives: To examine the prevalence of nonadherence to corticosteroid medication in a population with difficult asthma referred to a Specialist Clinic and to examine the relationship of poor adherence to asthma outcome.

Methods: General practitioner prescription refill records for the previous 6 months for inhaled combination therapy and short-acting ß-agonists were compared with initial prescriptions and expressed as a percentage. Blood plasma prednisolone and cortisol assay levels were used to examine the utility of these measures in assessing adherence to oral prednisolone. Patient demographics, hospital admissions, lung function, oral prednisolone courses, and quality of life data were analyzed to indentify the variables associated with reduced medication adherence.

Measurements and Main Results: A total of 182 patients were assessed. Sixty-three patients (35%) filled 50% or fewer inhaled medication prescriptions; 88% admitted poor adherence with inhaled therapy after initial denial. Twenty-one percent of patients filled more than 100% of presciptions, and 45% of subjects filled between 51 and 100% of prescriptions. Twenty-three of 51 patients (45%) prescribed oral steroids were found to be nonadherent.

Conclusions: A significant proportion of patients with difficult-to-control asthma remained nonadherent to corticosteroid therapy. Objective surrogate and direct measures of adherence should be performed as part of a difficult asthma assessment and are important before prescibing expensive novel biological therapies.

Community-living nonagenarians in northern ireland have lower plasma homocysteine but similar methylenetetrahydrofolate reductase thermolabile genotype prevalence compared to 70-89-year-old subjects

This cross-sectional study assessed relationships between plasma homocysteine, 'thermolabile' methylenetetrahydrofolatereductase (MTHFR) genotype, B vitamin status and measures of renal function in elderly (70-89 years) and nonagenarian (90+ years) subjects, with the hypothesis that octo/nonagenarian subjects who remain healthy into old age as defined by 'Senieur' status might show reduced genetic or environmental risk factors usually associated with hyperhomocysteinaemia. Plasma homocysteine was 9.1 micromol/l (geometric mean [GM]) for all elderly subjects. Intriguingly, homocysteine was significantly lower in 90+ (GM; 8.2 micromol/l) compared to 70-89-year-old subjects (GM; 9.8 micromol/l) despite significantly lower glomerular filtration rate (GFR) and serum B12 in nonagenarian subjects and comparable MTHFR thermolabile (TT) genotype frequency, folate and B6 status to 70-89-year-olds. For all elderly subjects, the odds ratio and 95% confidence intervals for plasma homocysteine being in the highest versus lowest quartile was 4.27 (2.04-8.92) for age 90 years, 3.4 (1.5-7.8) for serum folate 10.7nmol/l, 3.0 (0.9-10.2) for creatinine >140 compared

Visual disability, visual function, and myopia among rural chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES)--report 1.

PURPOSE: To evaluate visual acuity, visual function, and prevalence of refractive error among Chinese secondary-school children in a cross-sectional school-based study. METHODS: Uncorrected, presenting, and best corrected visual acuity, cycloplegic autorefraction with refinement, and self-reported visual function were assessed in a random, cluster sample of rural secondary school students in Xichang, China. RESULTS: Among the 1892 subjects (97.3% of the consenting children, 84.7% of the total sample), mean age was 14.7 +/- 0.8 years, 51.2% were female, and 26.4% were wearing glasses. The proportion of children with uncorrected, presenting, and corrected visual disability (< or = 6/12 in the better eye) was 41.2%, 19.3%, and 0.5%, respectively. Myopia < -0.5, < -2.0, and < -6.0 D in both eyes was present in 62.3%, 31.1%, and 1.9% of the subjects, respectively. Among the children with visual disability when tested without correction, 98.7% was due to refractive error, while only 53.8% (414/770) of these children had appropriate correction. The girls had significantly (P < 0.001) more presenting visual disability and myopia < -2.0 D than did the boys. More myopic refractive error was associated with worse self-reported visual function (ANOVA trend test, P < 0.001). CONCLUSIONS: Visual disability in this population was common, highly correctable, and frequently uncorrected. The impact of refractive error on self-reported visual function was significant. Strategies and studies to understand and remove barriers to spectacle wear are needed.

Impact of posterior subcapsular opacification on vision and visual function among subjects undergoing cataract surgery in rural China: Study of Cataract Outcomes and Up-Take of Services (SCOUTS) in the Caring is Hip Project, report 5.

AIM: To study the effect of posterior capsular opacification (PCO) on vision and visual function in patients undergoing cataract surgery in rural China, and to compare this with the effect of refractive error. METHODS: Patients undergoing cataract surgery in at least one eye by local surgeons in a rural setting between 8 August and 31 December 2005 were examined with slit lamp grading of PCO 10-14 months after surgery. Subjects with any PCO associated with best-corrected visual acuity of 6/7.5 or worse, or with grade 2+ or worse PCO without visual decrement, were offered YAG laser capsulotomy. Vision and self-reported visual function were assessed, and various demographic and clinical factors potentially associated with PCO were recorded. RESULTS: Of 313 patients operated on within the study window, 239 (76%) could be contacted by telephone; study examinations were performed on 176 (74%). Examined subjects had a mean (SD) age of 69.4 (10.5) years, 116 (67%) were female, and 149 (86%) had been blind (presenting visual acuity < or = 6/60) in the operated eye before surgery. PCO of grade 1 or above was present in 34 of 204 operated eyes (16.7%). Those with PCO had significantly worse presenting vision (p = 0.007) but not visual function (p>0.3) than those without PCO. Women had a significantly higher prevalence of PCO (20.9%) than did men (8.6%, p<0.05). Of 19 eyes undergoing capsulotomy with best-corrected visual acuity measured the next day, 13 (68%) improved by one or more lines, and seven (37%) improved by two or more lines. Despite a higher uptake of capsulotomy (95%) as opposed to refraction (35%) in this cohort, the yield in terms of eyes with poor presenting visual acuity (< 6/18) that could be improved was higher for refraction (26% = 9/35) than for capsulotomy (9% = 3/35). CONCLUSION: The prevalence of PCO and impact on vision and visual function in this cohort was modest 1 year after surgery. However, PCO prevalence increases with time. Follow-up of this cohort is underway to determine the effectiveness of this early intervention in identifying and treating subjects who will eventually experience clinically significant PCO.

Prevalence and determinants of spectacle nonwear among rural Chinese secondary schoolchildren: the Xichang Pediatric Refractive Error Study Report 3.

OBJECTIVE: To study spectacle wear among rural Chinese children. METHODS: Visual acuity, refraction, spectacle wear, and visual function were measured. RESULTS: Among 1892 subjects (84.7% of the sample), the mean (SD) age was 14.7 (0.8) years. Among 948 children (50.1%) potentially benefiting from spectacle wear, 368 (38.8%) did not own them. Among 580 children owning spectacles, 17.9% did not wear them at school. Among 476 children wearing spectacles, 25.0% had prescriptions that could not improve their visual acuity to better than 6/12. Therefore, 62.3% (591 of 948) of children needing spectacles did not benefit from appropriate correction. Children not owning and not wearing spectacles had better self-reported visual function but worse visual acuity at initial examination than children wearing spectacles and had a mean (SD) refractive error of -2.06 (1.15) diopter (D) and -2.78 (1.32) D, respectively. Girls (P < .001) and older children (P = .03) were more likely to be wearing their spectacles. A common reason for nonwear (17.0%) was the belief that spectacles weaken the eyes. Among children without spectacles, 79.3% said their families would pay for them (mean, US $15). CONCLUSIONS: Although half of the children could benefit from spectacle wear, 62.3% were not wearing appropriate correction. These children have significant uncorrected refractive errors. There is potential to support programs through spectacle sales.

Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia

Background
Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function.
Methods and setting
159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at >104 colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed.

Results
Mycoplasmataceaewerefoundin49%(95%CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was M. salivarium. Blood monocytes from healthy volunteers incubated with M. salivarium displayed an impaired TNF-α response to lipopolysaccharide ( p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to M. salivarium demonstrated impaired phagocytosis ( p=0.005).

Discussion and conclusions
This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, M. salivarium, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.