Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease-causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1 Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease-causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management.

The family of polyhalogenated monoterpenes from Plocamium counts over a hundred known members. Using glyceraldehyde acetonide as a chiral-pool precursor, an enantioselective and divergent strategy was developed that provides a blueprint for the synthesis of many of the small yet complex acyclic members of this family. The broad applicability of this approach is demonstrated with the short, eight-step synthesis of four natural products and three analogues. These syntheses are the first of any members of the acyclic polyhalogenated Plocamium monoterpenes and permitted the evaluation of their selectivity against a range of tumor cell lines.

Fine-structure energy levels, oscillator strengths and transitions probabilities for transitions among the fine-structure levels of the terms belonging to the 1s22s22p63s2np (2P), 1s22s22p63s2nd (2D) (n= 3-5) and 1s22s22p63s2ns (2S), 1s22s22p63s2nf (2F) (n= 4, 5) configurations of the Al-like ions Ar VI, K VII, and Ca VIII have been calculated. The calculations are based upon the general configuration interaction code CIV3 of Hibbert. Calculated values are compared with experimental and other theoretical results where some unpublished energy values and oscillator strengths are reported.

The high abundance and advantages of polysaccharides make them among the most widely used chiral stationary phases in liquid chromatography. However, extended analysis time and consumption of toxic organic solvents, associated with traditional columns, remain the main stumbling blocks of such methods’ sustainability. A new green chiral HPLC-separation, with just 0.45 mL ethanol in mobile phase per run utilizing a 50-mm column as a stationary phase, achieves a significant determination of alfuzosin (ALF) enantiomers along with solifenacin (SOL) simultaneously. Enantioseparation of ALF was firstly evaluated in the reversed-phase mode using five polysaccharide-based Lux columns (Amylose 2 and Cellulose 1–4), highlighting Lux Cellulose 2 to reach the best enantioselectivity. Central composite design with Derringer's desirability function was then adopted to optimize the chromatographic conditions for an acceptable resolution. A mobile phase composed of ethanol and phosphate buffer, pH 4, (30:70, v/v) at a rate of 0.5 mL/min with UV-detection at 215 nm, exhibits good separation of ALF-enantiomers from SOL with resolution values of 1.45 and 2.64, respectively. The method’s greenness profile has been assessed and compared with that of mostly reported ones via the newest comprehensive analytical method greenness score (AMGS) calculator. The proposed method is considered a straightforward approach towards safer, more economic, eco-friendly and comparatively favorable for the cited drugs’ quantification in their formulation.

AIMS: Cardiac affection is common in diabetic patients. Although insulin exerts a cardioprotective role, it may not be enough to totally prevent this affection. The current study aimed to compare the cardioprotective effect of insulin alone or combined with sitagliptin in a rat model of type 1 diabetes mellitus.

MATERIALS AND METHODS: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Diabetic rats were treated with insulin (3 IU), insulin (6 IU), or insulin (3 IU) + sitagliptin (10 mg/kg) for 42 days.

KEY FINDINGS: Diabetic rats exhibited significant systolic and diastolic cardiac affection with significant elevation of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and brain natriuretic peptide (BNP) levels. Treatment with insulin prevented the deterioration of diabetes-induced cardiac condition, an effect that was significantly potentiated by the combined use of sitagliptin.

SIGNIFICANCE: The combined use of sitagliptin and insulin significantly improved the cardioprotective effect of insulin and prevented the early cardiac dysfunction in STZ diabetic rats.