Effects of short-term continuous and pulse cadmium exposure on gut histology and microbiota of adult male frogs (Pelophylax nigromaculatus) during pre-hibernation

Cadmium (Cd) is an environmental endocrine-disrupting pollutant which mainly occurs in pulsed manner in natural waters, while traditional toxicology experiments have less examined the effects of pulsed exposure. Here, we studied the effects of short-term (7 days) continuous and pulse exposure to 100 μg/L Cd on gut morphology and microbiota of frogs (Pelophylax nigromaculatus) during pre-hibernation. Compared to continuous exposure, Cd pulse exposure significantly increased individual mortality and decreased the villi height and the ratio of villi height to crypt depth of the gut. Cd continuous and pulse exposure both changed the community structure and relative abundance of intestinal microbiota. Compared to continuous exposure, Cd pulse exposure significantly decreased the relative abundance of beneficial bacteria (e.g., Cetobacterium and Aeromonas genus), and significantly increased the relative abundance of harmful bacteria (e.g., Parabacteroides, Odoribacter, and Acinetobacter genus). This study shows that the gut histology and microbiota of amphibians during pre-hibernation are more susceptible to Cd pulse exposure than continuous exposure.     

Occurrence,detection and ecotoxicity studies of selected pharmaceuticals in aqueous ecosystems- a systematic appraisal

Pharmaceutical compounds (PCs) have globally emerged as a significant group of environmental contaminants due to the constant detection of their residues in the environment. The main scope of this review is to fill the void of information on the knowledge on the African occurrence of selected PCs in environmental matrices in comparison with those outside Africa and their respective toxic actions on both aquatic and non-aquatic biota through ecotoxicity bioassays. To achieve this objective, the study focused on commonly used and detected pharmaceutical drugs (residues). Based on the conducted literature survey, Africa has the highest levels of ciprofloxacin, sulfamethoxazole, lamivudine, acetaminophen, and diclofenac while Europe has the lowest of all these PC residues in her physical environments. For ecotoxicity bioassays, the few data available are mostly on individual groups of pharmaceuticals whereas there is sparsely available data on their combined forms.     

The use of isotretinoin for acne – an update on optimal dosing,surveillance, and adverse effects

ABSTRACT

Introduction

Acne is a chronic, inflammatory, and immune mediated disease of pilosebaceous unit, highly prevalent in adolescents. It involves face, trunk, and back; may leave scars and affect quality of life. Early, effective, and safe treatment is the key for disease resolution. Oral isotretinoin is the unique treatment for cure or prolonged remission for moderate and severe acne, preventing psychosocial impact and scars. It inhibits sebaceous glands activity and has anti-inflammatory and immunoregulatory properties.     

Neuropeptides Profile and Increased Innervation in Becker's Nevus

BackgroundMelanocytes are derived from neural crest, and various pigmentary disorders may accompany abnormalities in nerve system or develop following dermatome, suggesting that melanocyte and pigmentation may be closely related to neural factors. There are reports of Becker''s nevus (BN) showing linear and segmental configuration, suggesting the association of BN with nerve system. However, there are no studies regarding the expression of neuropeptides in BN.ObjectiveWe investigated the expression of neuropeptides and innervation in BN.MethodsPolymerase chain reaction (PCR) array of 84 genes related to neuronal process was done. Among the genes with 10-fold or more increase in lesional, real-time PCR was performed for neuropeptide Y (NPY), galanin, neurotensin (NTS) and their receptors skin compared to normal skin. IHC stain was done to look for the expression of NPY, galanin, NTS and their receptors and the distribution of protein gene products (PGP) 9.5 immunoreactive nerve fibers.ResultsPCR array revealed that 16 out of 84 genes related to neuronal process were increased by 10-fold or more in lesional skin. In real-time PCR of NPY, galanin, NTS and their receptors, statistically significant increase of NPY1R (p<0.05) and marginally significant increase of NPY2R, GAL2R, and NTS2R (p<0.1) was verified in lesional skin. In immunohistochemistry, NPY, NPY1R NPY2R, and NTS2R were highly expressed in lesional skin and increased PGP 9.5 immunoreactive linear nerve fibers were found in the epidermis of BN.ConclusionNPY, galanin, NTS and their receptors and increased innervation may play a role in the pathogenesis of BN.     

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects

PurposeFixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR.MethodsThis randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18–55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the pharmacokinetic (PK) parameters of saxagliptin, dapagliflozin, and metformin in both FCDPs and characterization of the PK parameters of the active metabolite of saxagliptin, 5-hydroxy saxagliptin, in healthy subjects. PK parameters (AUC_0–∞, AUC_0–t, and C_max) were used to assess the bioequivalence of the 2 FCDPs with their ICs. The C_max and AUC_0–t of the study drugs were compared between female and male subjects to assess sex differences in exposure. Safety and tolerability of both FCDPs and ICs were also assessed with adverse events, vital signs (systolic and diastolic blood pressures and pulse rate), 12-lead ECG, physical examinations, and laboratory assessments.FindingsBoth dapagliflozin/saxagliptin/metformin XR FCDPs were bioequivalent to their ICs. For the dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP, the 90% CI for the geometric mean ratio of dapagliflozin C_max was slightly above the 80%–125% bioequivalence limit, which is unlikely to be clinically relevant. Food delayed the absorption of the study drugs in both FCDPs, which is unlikely to have a clinically relevant impact on efficacy. In both cohorts, exposure was higher in female subjects compared with male subjects, potentially due to the lower body weight of the female subjects. The safety profile and tolerability of the FCDPs were similar to those of their ICs, and no deaths or serious adverse events were reported.ImplicationsThese data support the use of the dapagliflozin/saxagliptin/metformin XR FCDP in patients with T2DM. ClinicalTrials.gov identifier: NCT03169959.     

Standardized intraoperative application of an absorbable polysaccharide hemostatic powder to reduce the incidence of lymphocele after kidney transplantation – a prospective trial

We assessed whether standardized application of an absorbable polysaccharide hemostatic powder (HaemoCer?) has an effect on lymphocele rate after kidney transplantation. For this nonrandomized prospective trial, we first aimed to know our center‐specific lymphocele rate diagnosed by ultrasound imaging. We retrospectively assessed all patient records of the elapsed year resulting in a center‐specific rate of 20%, this was consistent with literature. The power analysis showed that 108 patients were required to detect a 50% reduction in lymphocele rate. During the prospective study period, 155 patients undergoing kidney transplantation were recruited to receive HaemoCer? intraoperatively. In two patients, the product accidentally was not used. Six patients were excluded from analysis because of failure to complete follow‐up (one early death and five early graft failures). Of the remaining 147 patients, 15 developed lymphoceles, which represents a rate of 10.2%; (95% CI: 6.3–16.2%). Compared to the expected occurrence, this was significantly lower (P = 0.003). Lymphoceles appeared to be associated with preoperative donor‐specific antibody, retransplantation and immunoadsorption in HLA or ABO incompatible donors. At our institution, the frequency of lymphoceles after kidney transplantation appeared to be significantly reduced when HaemoCer? was applied routinely. The magnitude of the effect warrants randomized evaluation.     

一种面向中医药数据的高效脱敏算法＊

目的 针对中医药大数据平台传统的加密方案效率不高的问题，提出一种高效的基于属性的内积加密的数据脱敏算法。方法 Hash（哈希）算法是应用广泛的高效的数据加密方法，但传统的哈希算法基于单一的控制策略，效率不高。本文提出一种基于属性的内积加密的数据脱敏算法，把批量的敏感数据分割为不同长度数据颗粒度，与特定密文的哈希进行内积处理。结果 在面对中医药大数据平台的海量数据加密的场景，与传统的哈希加密算法相比，本文提供的加密算法具有很好的性能。结论 为了保障个人隐私数据不被泄露，中医药大数据平台中的个人医疗数据需要加密脱敏后，才能进行分析处理或对外发布。本文提出的算法具备灵活的数据颗粒度、策略和高效的性能表现，适用于海量的中医药数据脱敏。     

Land- versus water-walking interventions in older adults: Effects on body composition

ObjectivesIncreasing physical activity is a priority worldwide, including for older adults who may have difficulty performing traditional forms of exercise, and for whom retention of muscle mass is an important consideration. Water-based exercise may provide an alternative if benefits are comparable. We compared the impact on body composition of 24-week water- versus land-walking interventions in healthy but inactive older adults.DesignRandomised, controlled trial.Methods72 participants (62.5 ± 6.8 yr) were randomised to a land-walking (LW), water-walking (WW) or control (C) group in a supervised centre-based program. The exercise groups trained 3 times/week at matched intensity (%HRR), increasing from 40–45% to 55–65% heart rate reserve (HRR). Height, weight, body mass index (BMI), waist and hip girths were recorded; dual X-ray absorptiometry (DXA) provided fat and lean tissue masses. Participants were re-assessed 24 weeks after completion of the intervention.ResultsThere were no significant changes in body mass or BMI following either exercise protocol, however central adiposity was reduced in both exercise groups, and the WW group increased lower limb lean mass. These benefits did not persist over the follow-up period.ConclusionsExercise can confer beneficial effects on body composition which are not evident when examining weight or BMI. Both WW and LW improved body composition. Water walking can be recommended as an exercise strategy for this age group due to its beneficial effects on body composition which are similar to, or exceed, those associated with land-walking. For benefits to persist, it appears that exercise needs to be maintained.