Exome sequencing in four families with neurodevelopmental disorders: genotype-phenotype correlation and identification of novel disease-causing variants in VPS13B and RELN.

Neurodevelopmental disorders (NDDs) are a clinically and genetically heterogeneous group of early-onset pediatric disorders that affect the structure and/or function of the central or peripheral nervous system. Achieving a precise molecular diagnosis for NDDs may be challenging due to the diverse genetic underpinnings and clinical variability. In the current study, we investigated the underlying genetic cause(s) of NDDs in four unrelated Pakistani families. Using exome sequencing (ES) as a diagnostic approach, we identified disease-causing variants in established NDD-associated genes in all families, including one hitherto unreported variant in RELN and three recurrent variants in VPS13B, DEGS1, and SPG11. Overall, our study highlights the potential of ES as a tool for clinical diagnosis.

Synthesis, Characterization, Biological Activities and Ab-initio Study of Transition Metal Complexes of [Methyl 2-((4-chlorophenyl)(hydroxy)methyle) Acrylate].

Taking cognizance of the medicinal significance and diverse functions of synthetic Morita-Baylis-Hillman adducts (MBHA), the title ligand was synthesized and purified through column chromatography. Cr+3, Mn+2, Co+3, Ni+2, Cu+2 complexes of the ligand were synthesized under basic conditions, subjected to characterization through spectral analyses and verified with the IR spectrum that was generated computationally by the DFT B3LYP method, with 6-311++ G (d,p) basis set and Hartree Fock (HF) B3LYP method in conjunction with 3-21G(d,p) basis set. Powder XRD helped to testify crystals of the complexes. Moreover, the antibacterial, and antioxidant characteristics of MBHA and its complexes were also established. All of them were found to be active antioxidants. The antibacterial activities, examined against S. aureus, E. coli, B. pumilis and S. typhi have revealed that its Cobalt complex has an excellent potential to act against all of them. Hence, these compounds maybe having potentialities for the discovery of new, cheaper and efficient drugs against various infectious diseases. The study also uncovers the first example of utilization of MBHA towards metal complex formation.

Dynamic Magnetic Resonance Imaging: An Aid To Preoperative-Planning Of Pelvic Organ Prolapse.

BACKGROUND: Magnetic resonance imaging (MRI) has been commonly used in the assessment of preoperative pelvic organ prolapse to evaluate anatomical defects prior to surgery. This study aimed at evaluating the dynamic MRI reliability in the determination of pelvic organ prolapse and to assess its compliance with the physical examination for preoperative planning of women. METHODS: A prospective cross-sectional study was performed at the radiology department of the Jinnah Postgraduate Medical Centre Karachi from April-October 2019. All women irrespective of age and parity status having obstructed defecation, constipation, organ prolapse, pelvic pain, or stress urinary incontinence undergoing dynamic pelvic MRI were consecutively enrolled. A brief history was obtained followed by a physical examination for pelvic organ prolapse followed by MRI examination. Kappa coefficient was applied to see the agreement of physical examination with MRI finding. RESULTS: A total 38 women were included. A significantly moderate agreement was observed between MRI and physical exam findings with respect to the presence or absence of cystocele (K=0.554, p<0.001), rectocele (K=0.632, p<0.001), and enterocele (K=0.587, p<0.001). However, agreement with respect to the MRI and physical examination findings on uterine descent was non-significant (K=0.130, p 0.421). CONCLUSIONS: MRI examination is an effective diagnostic modality in determination of the pelvic organ prolapse in suspected symptomatic patients. MRI could add value primarily in research areas, taking into account its ability to examine the entire pelvis.

Simultaneous determination of anti-diabetic drugs

A novel reverse phase, isocratic HPLC method is described to separate five anti-diabetic drugs i.e., glimepiride, metformin, sitagliptin, rosiglitazone and pioglitazone. Nucleosil C18 analytical column was used as stationary phase, while mobile phase consisted of acetonitrile:phosphate buffer: methanol (40/40/20, v/v) pH 2.0. Effluent was monitored at a flow rate 1 mL/min and detected at wavelength of 240 nm. This research produced excellent chromatography over a wide concentration range of 25-10000 ng/mL. Sepprated and well resolved quantifiable peaks were obtained and test results were linear in this range. Correlation coefficient of more than 0.9990 was witnessed as well as Low %RSD values i.e., maximum 2.0% documented excellent precision of the method. Good recoveries from pharmaecutical (99-101%), urine and plasma samples (>96%) in a range of concentrtion granted very good linearity, accuracy and precision. The projected method has satisfactory applications in quality control of these molecules as well as quantification of these molecules in urine and plasma samples.

Structural mass irregularities and fiber volume influence on morphology and mechanical properties of unsaturated polyester resin in matrix composites.

This paper presents the comparative results of a current study on unsaturated polyester resin (UPR) matrix composites processed by filament winding method, with cotton spun yarn of different mass irregularities and two different volume fractions. Physical and mechanical properties were measured, namely ultimate stress, stiffness, elongation%. The mechanical properties of the composites increased significantly with the increase in the fiber volume fraction in agreement with the Counto model. Mass irregularities in the yarn structure were quantitatively measured and visualized by scanning electron microscopy (SEM). Mass irregularities cause marked decrease in relative strength about 25% and 33% which increases with fiber volume fraction. Ultimate stress and stiffness increases with fiber volume fraction and is always higher for yarn with less mass irregularities.

Pregabalin and tranexamic Acid evaluation by two simple and sensitive spectrophotometric methods.

This paper demonstrates colorimetric visible spectrophotometric quantification methods for amino acid, namely, tranexamic acid and pregabalin. Both drugs contain the amino group, and when they are reacted with 2,4-dinitrophenol and 2,4,6-trinitrophenol, they give rise to yellow colored complexes showing absorption maximum at 418 nm and 425 nm, respectively, based on the Lewis acid base reaction. Detailed optimization process and stoichiometric studies were conducted along with investigation of thermodynamic features, that is, association constant and standard free energy changes. The method was linear over the concentration range of 0.02-200 µgmL(-1) with correlation coefficient of more than 0.9990 in all of the cases. Limit of detection was in range from 0.0041 to 0.0094 µgmL(-1) and limit of quantification was in the range from 0.0137 to 0.0302 µgmL(-1). Excellent recovery in Placebo spiked samples indicated that there is no interference from common excipients. The analytical methods under proposal were successfully applied to determine tranexamic acid and pregabalin in commercial products. t-test and F ratio were evaluated without noticeable difference between the proposed and reference methods.