Susceptible and Prognostic Genetic Factors Associated with Diabetic Peripheral Neuropathy: A Comprehensive Literature Review

Type 2 diabetes mellitus (T2D) is a disorder of glucose metabolism. It is a complex process involving the regulation of insulin secretion, insulin sensitivity, gluconeogenesis, and glucose uptake at the cellular level. Diabetic peripheral neuropathy (DPN) is one of the debilitating complications that is present in approximately 50% of diabetic patients. It is the primary cause of diabetes-related hospital admissions and nontraumatic foot amputations. The pathogenesis of diabetic neuropathy is a complex process that involves hyperglycemia-induced oxidative stress and altered polyol metabolism that changes the nerve microvasculature, altered growth factor support, and deregulated lipid metabolism. Recent literature has reported that there are several heterogeneous groups of susceptible genetic loci which clearly contribute to the development of DPN. Several studies have reported that some patients with prediabetes develop neuropathic complications, whereas others demonstrated little evidence of neuropathy even after long-standing diabetes. There is emerging evidence that genetic factors may contribute to the development of DPN. This paper aims to provide an up-to-date review of the susceptible and prognostic genetic factors associated with DPN. An extensive survey of the scientific literature published in PubMed using the search terms “Diabetic peripheral neuropathy/genetics” and “genome-wide association study” was carried out, and the most recent and relevant literature were included in this review

Development of broiler offal silage with molasses

Objective of the present study was to determine the feasibility of ensiling broiler offal (80) withmolasses. Forty two-days old broiler chicks were slaughtered and processed manually. Offal withoutfeathers were cut into small pieces and ensiled in airtight plastic containers for four weeks. Theexperiment followed a completely randomize design in 4*2 factorial arrangement. The treatmentcombinations were four molasses concentrations (5, 15,25 and 35% w/w) and two inoculation levels(0 and 10%). Yoghurt was used as the innoculum. Each treatment combination had five replicates.pH was measured at time 0, 12hrs, 24 hrs, day 3, day 7, day 14, day 21 and day 28 of the ensilingprocess. pH was 4.8 at the beginning of the ensiling process. After 12 hrs, in all treatments pHdropped slightly to around 4.6. The pH at 5% molasses level dropped quickly within a day of ensiling,and was significantly lower than the pH values of other molasses levels. However, pH at 5%molasses rose thereafter, and reached to an undesirable level by day 3. By one week of ensiling, thepH at 15,25 and 35% molasses levels were 4.1,4.2 and 4.2, respectively. Those were the lowest pHvalues observed for the respective molasses concentration. At all of the above three molasses levels,there was a slight pH increase by day 14 of the ensiling. Thereafter pH maintained at a constantlevels of 4.5,4.2 and 4.4 at 15,25 and 35% molasses levels, respectively. Except 5% molasses level,all other three levels of molasses gave typical odour of good silage. Liquefaction of the 80 was poorand thus grinding of the offal before ensiling may be useful. Inoculation had no effect on pH until day3 and, thereafter inoculation increased the pH and thus was detrimental for the ensiling process.. Itwas concluded that 80 could successfully be ensiled with 25% molasses. Inoculation with yoghurtculture had no beneficial effect on ensiling process.

Suitability of some agro-industrial by-products as litter material for poultry Physio-chemical properties

Paddy-husk (PH) based deep litter system is the most popular poultry management system in SriLanka. Physio-chemical properties of PH make it an ideal litter material for poultry keeping. SincePH is increasingly been demanded by other industries, availability of PH for poultry industry has beenrestricted from recent years. Objective of the present study was to screen the physio-chemicalproperties of some commonly available agro-industrial by-products, to be used as alternative littermaterials for poultry. Physio-chemical properties such as dry matter (OM), bulk density (BO), pH,water absorbability (WA) and water releasing capacity (WRC) of seven alternatives such as ricestraw (RS), coir dust (CD), wood shawing;WS, saw dust;SD, tree litter;TL, shredded paper;SP andrefused tea;RT)) were determined and, compared with the respective values of PH. The experimentfollowed a completely randomized design. The OM % of the alternatives tested ranged from 91 %(SO) to 92% (SP). OM contents ofWS and RT were statistically similar to that of PH. However,none ofthe material had either too low or too high OM levels to be disqualified as a litter material. pHvalues of the tested materials were statistically similar and were slightly acidic (mean 6.27; range6.1-6.5). PH had the highest BO (0.09g/cm'). The BOs of CD, SO and RT, though were lower thanPH, the values were not significantly different from that of PH. WA was also statistically differentbetween the materials. CD had the highest (ll 0 I%) WA while RT showed lowest (70%) WA. SO,SP and TL showed statistically similar WA as PH. Materials showed a great variability (from 7.7%for SO to 26.7% for RS) in relation to WRC. PH had 13.6% WRC within 241m. RT had the closestWRC capacity (17.9%) to PH. Materials such as RS, TS, WS and SP showed as high as 25%WRC. When materials were compared for the parameters tested against those of PH, RS and WSwere similar to PH only in relation to two parameters. Being comparable with PH for four parameters,SO was identified as the best alternative for PH. CD, TL, SP and RT were comparable with PH inrelation to three parameters. Since CD had excessive WA (I 10 I%) and very low WRC it can not berecommended further studies. This study concludes that physio-chemical properties of SO, TL, SPand RT are comparable with PH. Field studies involving live poultry are warranted to determine howbirds perform and behave when raised on these litter materials

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

A case series of five Sri Lankan patients with ovotesticular disorder of sex development

Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation in which the gonads of an individual are characterized by the presence of both mature ovarian and testicular tissues. The objective of this paper is to report the clinical, cytogenetic and histopathological findings in Sri Lankan patients diagnosed with OT-DSD who were referred to the Human Genetics Unit for cytogenetic evaluation during 2005 to 2011. Five patients had histopathologically confirmed OT-DSD. Their ages at presentation ranged from 2 mo to 47 yr. Clinical symptoms varied from ambiguous genitalia and inguinal hernias at birth to a lower abdominal mass presenting in adulthood. All 5 were reared as phenotypic males. An ovotestis was detected in all cases except one, and the predominant karyotype was 46,XY. The findings in this series of predominantly 46,XY karyotype are in contrast to previously published reports that have reported 46,XX as being the predominant karyotype. It is therefore recommended that individuals with ambiguous genitalia who have the 46,XY karyotype should be thoroughly investigated by ultrasonographic or laparoscopic assessment to determine the exact nature of their internal genital organs. OT-DSD should also be considered in the differential diagnosis of patients with cryptorchidism and inguinal hernia.Kalum T. Wettasinghe, Nirmala D. Sirisena, Prabha H. Andraweera, Rohan W. Jayasekara, Vajira H. W. Dissanayak