Particle size as a driver of dewatering performance and its relationship to stabilization in fecal sludge.

Poor and unpredictable dewatering performance of fecal sludge is a major barrier to sanitation provision in urban areas not served by sewers. Fecal sludge comprises everything that accumulates in onsite containments, and its characteristics are distinct from wastewater sludges and from feces. There is little fundamental understanding of what causes poor dewatering in fecal sludge. For the first time, we demonstrate that particle size distribution is a driver of dewatering performance in fecal sludge, and is associated with level of stabilization. Higher concentrations of small particles (<10 µm) and smaller median aggregate size (D50) corresponded to poor dewatering performance (measured by capillary suction time (CST) and supernatant turbidity) in field samples from Kenya and Uganda and in controlled laboratory anaerobic storage experiments. More stabilized fecal sludge (higher C/N, lower VSS/TSS) had better dewatering performance, corresponding to lower concentrations of small particles. Samples with the largest aggregates (D50 > 90 µm) had higher abundance of Gammaproteobacteria Pseudomonas, and samples with the smallest aggregates (D50 ≤ 50 µm) were characterized by higher abundance of Bacteroidetes Vadin HA17 and Rikenellaceae. Contrary to common perceptions, stabilization, particle size distribution, and dewatering performance were not dependent on time intervals between emptying of onsite containments or on time in controlled anaerobic storage experiments. Our results suggest that the stabilization process in onsite containments, and hence the dewaterability of sludge arriving at treatment facilities, is not dependent on time in containment but is more likely associated with specific microbial populations and the in-situ environmental conditions which promote or discourage their growth.

Genetic population structure of the Vietnamese ginseng (Panax vietnamensis Ha et Grushv.) detected by microsatellite analysis.

Panax vietnamensis Ha et Grushv. is a precious medicinal species native to the tropical forests of Vietnam. Due to habitat loss and over-harvesting, this species is endangered in Vietnam. To conserve the species, we investigated genetic variability and population structure using nine microsatellites for 148 individuals from seven populations across the current distribution range of P. vietnamensis in Vietnam. We determined a moderate genetic diversity within populations (HO = 0.367, HE = 0.437) and relatively low population differentiation (the Weir and Cockerham index of 0.172 and the Hedrick index of 0.254) and showed significant differentiation (P < 0.05), which suggested fragmented habitats, over-utilization and over-harvesting of P. vietnamensis. Different clustering methods revealed that individuals were grouped into two major clusters, which were associated with gene flow across the geographical range of P. vietnamensis. This study also detected that ginseng populations can have undergone a recent bottleneck. We recommend measures in future P. vietnamensis conservation and breeding programs.

Simultaneously Both Expression of LMP-1 and Methylation of E-cadherin: Molecular Biomarker in Stage IV of Nasopharyngeal Carcinoma Patients.

The phenome of E-cadherin gene methylation and the expression of latent membrane protein 1 (LMP-1) gene are associated with nasopharyngeal carcinoma (NPC). In order to determine whether cooperative LMP-1 expression or methylation of E-cadherin could serve as the potential molecule biomarker target for diagnosis and therapy of NPC, a case-control study including 93 NPC biopsy samples and 100 non cancerous nasopharyngeal swab samples were examined, as well as the strength of association among them by the quantitative polymerase chain reaction (qPCR) and nested-methylation-specific PCR methods. The significantly higher frequency of LMP-1 expression and E-cadherin methylation in NPC biopsy samples, accounting for 76.34 and 73.12%, respectively, compared to non cancerous samples, accounting for 0.00 and 30.00%, respectively, were observed. The significant correlation between the LMP-1 expression and E-cadherin methylation in NPC samples was reported. In detail, in the stage IV of NPC, in case of LMP-1-positive samples, 35 of 37 samples (accounting for 94.60%) were positive for methylation of E-cadherin. It was demonstrated that cooperative LMP-1 expression and E-cadherin gene methylation could serve as a molecular biomarker in NPC.

User preferences for a mobile application to report adverse events following vaccination.

The passive surveillance system is an important tool in pharmacovigilance of vaccines. However, reporting of adverse events following immunization (AEFI) post-marketing has limitations regarding under-reporting, biased reports and lack of exposure data resulting in imprecise estimates. New mobile application technology may provide an opportunity for an enhanced surveillance. A pre-requisite for the use of new app-based technology is to identify practical challenges and end users' preferences for design of app-features. The objectives were (i) to investigate the recruitment and feasibility of an app-based study in Germany, (ii) to assess individuals' motivation to participate in such a study and (iii) to identify app-features for reporting AEFI. We conducted a cross-sectional study among employees of a financial institution who attended the occupational health office during the seasonal influenza vaccination in November 2017. Participants tested feasibility and assessed an app prototype for AEFI reporting by using a case vignette and a questionnaire. Of the 153 attending employees, 65 (42%) agreed to participate and returned the questionnaire. Twenty-three (63%) rated the experience of reporting AEFI with the app prototype to be positive. Among three features offered for gamification, collecting points was most frequently chosen (n=22, 34%). The main reason for declining participation was the apprehension about data protection (n=28, 43%). Results suggest that the app-based technology was well accepted and is a suitable supplement for AEFI reporting and in our study. A convincing data protection concept is likely to enhance acceptability of such a system.

Inactivation of the bacterial pathogens Staphylococcus pseudintermedius and Acinetobacter baumannii by butanoic acid.

AIMS: This study was performed to evaluate the efficacy of butanoic acid against bacterial pathogens including Acinetobacter baumannii and Staphylococcus pseudintermedius. METHODS AND RESULTS: Vegetative bacteria were exposed to butanoic acid in vitro and log reduction was quantified using viable count assays. The maximum (8 and 9) log inactivation was determined by qualitatively assaying for growth/no-growth after a 48-h incubation (37°C). Membrane integrity after exposure to butanoic acid was determined by propidium iodide staining, scanning electron microscopy, membrane depolarization and inductively coupled plasma analysis. Cytosolic pH was measured by 5-(6-)carboxyfluorescein succinimidyl ester. CONCLUSIONS: Inhibitory concentrations of butanoic acid ranged between 11 and 21 mmol l-1 for Gram-positive and Gram-negative species tested. The maximum log reduction of A. baumannii was achieved with a 10-s exposure of 0·50 mol l-1 of butanoic acid. Staphylococcus pseudintermedius required 0·40 mol l-1 of butanoic acid to achieve the same level of reduction in the same time period. Inactivation was associated with membrane permeability and acidification of the cytosol. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibiotic resistance among bacterial pathogens necessitates the utilization of novel therapeutics for disinfection and biological control. These results may facilitate the development of butanoic acid as an effective agent against a broad-spectrum of antibiotic-resistant bacterial pathogens.

Autologous bilayered self-assembled skin substitutes (SASSs) as permanent grafts: a case series of 14 severely burned patients indicating clinical effectiveness.

Split-thickness skin autografts (AGs) are the standard surgical treatment for severe burn injuries. However, the treatment of patients with substantial skin loss is limited by the availability of donor sites for skin harvesting. As an alternative to skin autografts, our research group developed autologous self-assembled skin substitutes (SASSs), allowing the replacement of both dermis and epidermis in a single surgical procedure. The aim of the study was to assess the clinical outcome of the SASSs as a permanent coverage for full-thickness burn wounds. Patients were recruited through the Health Canada's Special Access Program. SASSs were grafted on debrided full-thickness wounds according to similar protocols used for AGs. The graft-take and the persistence of the SASS epithelium over time were evaluated. 14 patients received surgical care with SASSs. The mean percentage of the SASS graft-take was 98 % (standard deviation = 5) at 5 to 7 d after surgery. SASS integrity persisted over time (average follow-up time: 3.2 years), without noticeable deficiency in epidermal regeneration. Assessment of scar quality (skin elasticity, erythema, thickness) was performed on a subset of patients. Non-homogeneous pigmentation was noticed in several patients. These results indicated that the SASS allowed the successful coverage of full-thickness burns given its high graft-take, aesthetic outcome equivalent to autografting and the promotion of long-term tissue regeneration. When skin donor sites are in short supply, SASSs could be a valuable alternative to treat patients with full-thickness burns covering more than 50 % of their total body surface area.

Hepatitis B surface antigen loss and sustained viral suppression in Asian chronic hepatitis B patients: A community-based real-world study.

Community-based real-world outcomes on effectiveness of antiviral therapies for chronic hepatitis B virus (CHB) in Asians are limited. Whether hepatitis B surface antigen (HBsAg) loss correlates with undetectable virus and alanine aminotransferase (ALT) normalization on treatment or what predicts risk of seroreversion or detectable virus after stopping therapy is unclear. We aim to evaluate rates and predictors of HBsAg loss, seroconversion, ALT normalization and undetectable HBV DNA, including HBsAg seroreversion or re-emergence of HBV DNA among Asian CHB patients. We retrospectively evaluated 1072 CHB adults on antiviral therapy at two community gastroenterology clinics from 1997 to 2015. Rates of HBsAg loss, ALT normalization, achieving undetectable HBV DNA and developing surface antibody (anti-HBs) were stratified by HBeAg status. Following HBsAg loss, HBsAg seroreversion or re-emergence of detectable HBV DNA was analysed. With median treatment of 76.7 months, the overall rate of HBsAg loss was 4.58%, with similar HBsAg loss rates between HBeAg-positive and HBeAg-negative patients (4.44% vs 4.71%, P=.85) in a predominantly Asian population (98.1%). Among HBsAg loss patients, 33.3% developed anti-HBs, 95.8% achieved undetectable virus and 66.0% normalized ALT. No significant baseline or on-treatment predictors of HBsAg loss were observed. While six patients who achieved HBsAg loss had seroreversion with re-emergence of HBsAg positivity, viral load remained undetectable, demonstrating the sustainability of viral suppression. Among a large community-based real-world cohort of Asian CHB patients treated with antiviral therapy, rate of HBsAg loss was 4.58%. Despite only 33.3% of HBsAg loss patients achieving anti-HBs, nearly all patients achieved sustained undetectable virus.

Community-based real-world treatment outcomes of sofosbuvir/ledipasvir in Asians with chronic hepatitis C virus genotype 6 in the United States.

Sofosbuvir/ledipasvir (SOF/LDV) is the first all-oral ribavirin-free treatment approved for chronic hepatitis C virus (HCV) genotype 6, offering a safe and highly efficacious treatment option. Large studies evaluating real-world outcomes of this regimen are lacking. We aim to evaluate real-world treatment outcomes for HCV genotype 6. A retrospective cohort study evaluated 65 adults (age ≥18) with chronic HCV genotype 6 treated with SOF/LDV without ribavirin at a community gastroenterology clinic in the United States from November 2014 to May 2016. Rates of undetectable virus at week 4 on treatment, at end of treatment (EOT) and SVR12 were stratified by the presence of cirrhosis and prior treatment (treatment naïve vs treatment experienced). Among 65 patients with chronic HCV genotype 6 treated with SOF/LDV (52.3% male, mean age 66.3 years [SD 9.7], 41.5% cirrhosis and 15.4% treatment experienced), 97.3% had undetectable virus at week 4 on treatment, 96.9% had undetectable virus at EOT and 95.3% achieved SVR12. SVR12 was 100% in females vs 91.2% in males, P=.096, and 92.3% in patients with cirrhosis vs 97.4% in those without cirrhosis, P=.347. Resistance testing of treatment failures was attempted but unsuccessful due to lack of conforming primers to define the possible resistance mutations. Among the largest U.S. community-based real-world cohort of Asian chronic HCV genotype 6 patients treated with all-oral SOF/LDV without ribavirin, SVR12 was similar to SVR12 reported in clinical trials, confirming the safety and effectiveness of this regimen and validating current HCV genotype 6 treatment guideline recommendations.

Are Obese Individuals with no Feature of Metabolic Syndrome but Increased Waist Circumference Really Healthy? A Cross Sectional Study.

AIM: Patients displaying the metabolically healthy but obese phenotype have an intermediate cardiometabolic prognosis compared to normal weight healthy and metabolically unhealthy obese subjects. We aimed to evaluate the proportion of patients with a definite metabolically healthy obese phenotype and better characterize them. METHODS: Definite metabolically healthy obese phenotype was defined as having none of the International Diabetes Federation metabolic syndrome criteria, excluding waist circumference. We recruited 1 159 obese patients (body mass index 38.4±6.3 kg/m(2)) including 943 women, without known diabetes. Patients were characterized for cardiometabolic disorders. RESULTS: As the 202 (17.4%) metabolically healthy obese individuals were younger and had lower body mass indexes than the 957 metabolically unhealthy obese patients, they were matched for gender, age and body mass index with 404 metabolically unhealthy obese patients. In addition to the features of metabolic syndrome, when compared to unhealthy subjects, definite metabolically healthy obese patients were less frequently found with either homeostasis model assessment of insulin resistance index>3 (23.6 vs. 38.9%, p<0.001), or abnormal oral glucose tolerance test (13.9 vs. 33.9%, p<0.001), or HbA1c value≥5.7% (43.9 vs. 54.2%, p<0.05) or pulse pressure≥60 mmHg (11.7 vs. 64.9%, p<0.001). However, there were no significant differences in the prevalence of microalbuminuria (11.1 vs. 12.3%), cardiac autonomic dysfunction (45.5 vs. 35.3%) and fatty liver index ≥ 60 (5.6 vs. 10.2%). CONCLUSION: Our data do not support the characterization of metabolically healthy obesity, even definite, as really healthy, as many patients with this phenotype have abnormal cardiovascular markers and glucose or liver abnormalities. HbA1c measurement seems to be more sensitive than OGTT to detect dysglycemia in this population.

Pregnancy adverse outcomes related to pregravid body mass index and gestational weight gain, according to the presence or not of gestational diabetes mellitus: A retrospective observational study.

AIM: This study retrospectively evaluated the complications associated with prepregnancy overweight (OW) or obesity (OB) and gestational weight gain (GWG) in women with or without universally screened and treated gestational diabetes mellitus (GDM). METHODS: A total of 15,551 non-Asian women without pregravid diabetes or hypertension who delivered singleton babies (2002-2010) were classified according to GDM (13.5%), pregestational body mass index (BMI; normal range: 18.5-24.9kg/m(2)), OW (26.2%), OB (13.9%; BMI≥30kg/m(2)) and GWG (<7kg: 32%; 7-11.5kg: 37%; 11.6-16kg: 23%;>16kg: 8%). Main outcome measures were large/small for gestational age (LGA/SGA), caesarean section, preeclampsia, preterm delivery and shoulder dystocia. RESULTS: GDM was associated with more LGA babies [Odds Ratio (OR): 2.12, 95% confidence interval (CI): 1.85-2.43], caesarean section (OR: 1.49, 95% CI: 1.34-1.65) and preeclampsia (OR: 1.59, 95% CI: 1.21-2.09). OW/OB and GWG were associated with LGA infants whatever the GDM status, and with SGA babies only in women without GDM. LGA status was independently associated with GWG in women with GDM (11.6-16kg: OR: 1.74, 95% CI: 1.49-2.03 and>16kg OR: 3.42, 95% CI: 2.83-4.13 vs 7-11.5kg) and in women without GDM (OR: 2.14, 95% CI: 1.54-2.97 or OR: 2.65, 95% CI: 1.68-4.17, respectively), and with BMI only in women without GDM (OR: 1.12, 95% CI: 1.00-1.24, per 10kg/m(2)). SGA status was independently associated with OW (OR: 0.86, 95% CI: 0.77-0.98), OB (OR: 0.84, 95% CI: 0.72-0.98) and GWG<7kg (1.14, 95% CI: 1.01-1.29) only in women without GDM. CONCLUSION: In our European cohort and considering the triumvirate of GDM, BMI and GWG, GDM was the main contributor to caesarean section and preeclampsia. OW/OB and GWG contributed to LGA and SGA infants mainly in women without GDM.

Arterial stiffness is elevated in normotensive type 2 diabetic patients with peripheral neuropathy.

BACKGROUND AND AIMS: Arterial stiffness, a measure of macrovascular damage predictive of poor cardio-vascular outcomes, is strongly related to age and hypertension (HT). In diabetic patients peripheral neuropathy (PN) has been found to be associated with increased arterial stiffness, which might be due to the concomitant presence of HT. The aim of this study was to examine in type-2 diabetic patients, the relationship between arterial stiffness and presence or absence of PN and HT separately. METHODS AND RESULTS: Arterial stiffness was measured with the gold standard carotid-femoral pulse wave velocity (PWV) in 447 type-2 diabetic subjects of whom 66% were hypertensive, 53% had PN, and 40% had both. Patients with PN were older, more often hypertensive and had higher PWV than those free of PN. Patients were separated according to the presence or absence of PN and HT. PWV values above the 90th percentile age- and blood pressure-adjusted reference range (PWV+) were different across these groups (p < 0.005) with the following respective prevalences: 27.2%, 53.4%, 33.3% and 30.6%. Only PWV+ was significantly associated with PN and hypertension in the interaction analysis. CONCLUSION: Well controlled hypertensive patients did not have elevated arterial stiffness compared to normotensive patients. This might be due to anti-hypertensive treatment although our study design does not allow us to confirm it. A strong association between PN and arterial stiffness was only present in normotensive patients, suggesting that normotensive type 2 diabetic patients with PN and elevated arterial stiffness should be carefully managed to prevent future macrovascular complications.

[Relationship between blood pressure, heart rate and cardiac autonomic dysfunction in non-diabetic obese patients]. / Relation entre pression artérielle, fréquence cardiaque et dysfonction autonome cardiaque chez les obèses non diabétiques.

RATIONALE: Some studies suggest that a high heart rate (HR) would be predictive of the incidence of an elevated blood pressure (BP). Cardiac autonomic dysfunction (CAD) affects a high proportion of obese patients. CAD could be involved in BP increase. Our aim was to examine the relationship between CAD, HR and BP in obese patients without known diabetes. PATIENTS AND METHODS: We included 428 overweight or obese patients. CAD was assessed by analyzing HR variations during three standard tests (Valsalva, deep breathing, lying-to-standing), which are mostly dependent on vagal control. An oral load in glucose was performed and the Matsuda index was calculated. RESULTS: The population was separated in 4 groups according to the grade of CAD (no or only one abnormal test, 2 or 3 abnormal tests) and HR (< or ≥ 75 bpm). Age was similar in the four groups. Systolic (P=0.05), diastolic (P<0.005) and mean BP (P<0.001) differed significantly between the 4 groups, and was the highest in the group of patients who had 2 or 3 abnormal tests and HR ≥ 75 bpm. Matsuda index differed across the groups (P=0.018) and was the lowest in this group. CONCLUSION: These data indicate that among overweight or obese patients with a defect in cardiac vagal activity BP is elevated only in those with a high heart rate, which is indicative of a more marked insulin resistance and probably an excess in sympathetic activity.

Anthropometric markers for detection of the metabolic syndrome in adolescents.

OBJECTIVES: This study aimed to estimate, in a large group of Algerian adolescents, the prevalence of the metabolic syndrome (MetS), using four definitions (by Cook, De Ferranti, Viner and the IDF), and to test the validity of unique thresholds of waist circumference, waist/height ratio and BMI in screening for the MetS regardless of the definition used. SUBJECTS AND METHODS: A total of 1100 adolescent students, aged 12-18 y, were randomly selected from schools and classrooms in the city of Constantine; all had anthropometric measurements taken and 989 had blood tests. RESULTS: Prevalences of the MetS were: 2.6% for boys and 0.6% for girls by the Cook definition; 4.0% for boys and 2.0% for girls by the De Ferranti definition; 0.7% for boys and 0% for girls by the Viner definition; and 1.3% for boys and 0.5% for girls by the 2007 IDF definition. Prevalences ranged from 3.7% to 13.0% in obese adolescents. Unique thresholds, independent of gender, age and height, of 80cm for waist circumference, 0.50 for waist/height ratio and 25kg/m(2) for BMI had sensitivities of 72-100%, 67-100% and 72-100%, respectively, and specificities of 74-78%, 74-86% and 74-78%, respectively, depending on the MetS definition used. CONCLUSION: The MetS is present in Algerian adolescents and the prevalence is especially high in obese young people. Our thresholds for waist circumference, waist/height ratio and BMI for screening for the MetS should now be tested in other adolescent populations.

The clinical utility of whole-exome sequencing in the context of rare diseases - the changing tides of medical practice.

Whole-exome sequencing (WES) carries the potential to facilitate the identification of disease causing genes. This is particularly relevant concerning rare diseases, which proves particularly difficult for physicians to diagnose. However, the complexity of this technology renders its applicability onto the clinical setting uncertain. Our study thus aims to understand physicians' perspectives regarding the clinical utility of WES, particularly for providing a diagnosis for patients with rare diseases. Ten semi-structured interviews were conducted with physicians with experience and familiarity with WES, and the major themes that emerged from our interviews were (i) the relevance of WES in diagnosing patients with rare diseases (appropriateness); (ii) the cost-effectiveness of WES (accessibility), (iii) the practical issues related to the clinical implementation of WES (practicability); and (iv) ethical, legal and social issues (acceptability). Our study highlights how the clinical implementation of WES presents additional challenges where rare diseases are taken into consideration.

Hsp90 chaperones PPARγ and regulates differentiation and survival of 3T3-L1 adipocytes.

Adipose tissue dysregulation has a major role in various human diseases. The peroxisome proliferator-activated receptor-γ (PPARγ) is a key regulator of adipocyte differentiation and function, as well as a target of insulin-sensitizing drugs. The Hsp90 chaperone stabilizes a diverse set of signaling 'client' proteins, thereby regulates various biological processes. Here we report a novel role for Hsp90 in controlling PPARγ stability and cellular differentiation. Specifically, we show that the Hsp90 inhibitors geldanamycin and novobiocin efficiently impede the differentiation of murine 3T3-L1 preadipocytes. Geldanamycin at higher concentrations also inhibits the survival of both developing and mature adipocytes, respectively. Further, Hsp90 inhibition disrupts an Hsp90-PPARγ complex, leads to the destabilization and proteasomal degradation of PPARγ, and inhibits the expression of PPARγ target genes, identifying PPARγ as an Hsp90 client. A similar destabilization of PPARγ and a halt of adipogenesis also occur in response to protein denaturing stresses caused by a single transient heat-shock or proteasome inhibition. Recovery from stress restores PPARγ stability and adipocyte differentiation. Thus, our findings reveal Hsp90 as a critical stress-responsive regulator of adipocyte biology and offer a potential therapeutic target in obesity and the metabolic syndrome.

Yacon diet (Smallanthus sonchifolius, Asteraceae) improves hepatic insulin resistance via reducing Trb3 expression in Zucker fa/fa rats.

OBJECTIVE: Yacon is a perennial plant forming a clump of >20 big, edible underground tubers. Yacon, which originates from South America, has become increasingly popular in the Japanese diet for tubers have a lower caloric value and a high fiber content. Recent studies have suggested that yacon feeding ameliorates diabetes as indicated by reduced blood glucose. METHODS: We fed male Zucker fa/fa rats for 5 weeks with isocaloric normal chow diet containing from 6.5% control aroid or 6.5% yacon. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp study. RESULTS: Body weight was comparable between yacon- and aroid-fed rats. In the basal state, yacon feeding had an effect to lower fasting glucose levels from 184.1±4.1 to 167.8±2.7 mg dl(-1) (P<0.01), as well as basal hepatic glucose output (HGO) from 9.9±0.4 to 7.4 ± 0.2 mg kg(-1) per min (P<0.01). During the clamp studies, the glucose infusion rate required to maintain euglycemia was increased by 12.3% in yacon-fed rat. The insulin suppression of HGO was also increased in yacon-fed rats compared with control rats (85.3±2.4% vs 77.0±3.0%; P<0.05), whereas the glucose disposal rate was not different between the two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle. Furthermore, tribbles 3 (Trb3) expression, which is a negative regulator of Akt activity, was markedly reduced in the liver of yacon-fed rats compared with control rats. CONCLUSION: These results indicate that the effect of yacon feeding to reduce blood glucose is likely due to its beneficial effects on hepatic insulin sensitivity in the insulin resistant state.

Decreased stroke volume−brachial pulse pressure ratio in patients with type 2 diabetes over 50 years: the role of peripheral neuropathy.

BACKGROUND AND AIMS: To document the stroke volume to pulse pressure ratio (SV/PP, an index of total arterial compliance) and its correlates in patients with type 2 diabetes (T2DM) aged over 50 years whose peripheral neuropathy and silent myocardial ischemic (SMI) status were known. METHODS AND RESULTS: A total of 360 patients with T2DM aged ≥ 50 years, without cardiac history or symptom, left ventricular systolic dysfunction, dilatation and hypokinesia, were retrospectively enrolled. The SV/PP was calculated from echocardiographic left ventricular measurements and brachial blood pressure at rest. Peripheral neuropathy was defined as the presence of any two or more of the following: neuropathic symptoms, decreased distal sensation, or decreased or absent ankle reflexes. SMI was defined as an abnormal stress myocardial scintigraphy and/or stress echocardiography. A low SV/PP ratio (<0.53 ml/m²/mmHg, first tertile) was associated with age, creatinine clearance, 24 h urinary albumin excretion rate, peripheral neuropathy, hypertension, serum total cholesterol and triglycerides levels (p < 0.05-0.0001). In multivariate analysis, age (OR 1.1 [1.0-1.2], p < 0.01), triglycerides (OR 1.5 [1.2-2.0], p = 0.01) and peripheral neuropathy (OR 2.2 [1.2-3.9], p = 0.009) were independently associated with a low SV/PP. The patients with peripheral neuropathy had lower SV (p < 0.01) and higher PP (p < 0.05) than those without, and only lower SV after adjustment for age and nephropathy. Similar results were obtained in the patients with and without SMI. CONCLUSION: Peripheral neuropathy was independently associated with decreased SV/PP, mainly through decreased SV, in patients with T2DM over 50 years.

Do habitat shifts drive diversification in teleost fishes? An example from the pufferfishes (Tetraodontidae).

Habitat shifts are implicated as the cause of many vertebrate radiations, yet relatively few empirical studies quantify patterns of diversification following colonization of new habitats in fishes. The pufferfishes (family Tetraodon-tidae) occur in several habitats, including coral reefs and freshwater, which are thought to provide ecological opportunity for adaptive radiation, and thus provide a unique system for testing the hypothesis that shifts to new habitats alter diversification rates. To test this hypothesis, we sequenced eight genes for 96 species of pufferfishes and closely related porcupine fishes, and added 19 species from sequences available in GenBank. We time-calibrated the molecular phylogeny using three fossils, and performed several comparative analyses to test whether colonization of novel habitats led to shifts in the rate of speciation and body size evolution, central predictions of clades experiencing ecological adaptive radiation. Colonization of freshwater is associated with lower rates of cladogenesis in pufferfishes, although these lineages also exhibit accelerated rates of body size evolution. Increased rates of cladogenesis are associated with transitions to coral reefs, but reef lineages surprisingly exhibit significantly lower rates of body size evolution. These results suggest that ecological opportunity afforded by novel habitats may be limited for pufferfishes due to competition with other species, constraints relating to pufferfish life history and trophic ecology, and other factors.