Optimization of Electrospinning Parameters for Lower Molecular Weight Polymers: A Case Study on Polyvinylpyrrolidone.

Polyvinylpyrrolidone (PVP) is a synthetic polymer that holds significance in various fields such as biomedical, medical, and electronics, due to its biocompatibility and exceptional dielectric properties. Electrospinning is the most commonly used tool to fabricate fibers because of its convenience and the wide choice of parameter optimization. Various parameters, including solution molarity, flow rate, voltage, needle gauge, and needle-to-collector distance, can be optimized to obtain the desired morphology of the fibers. Although PVP is commercially available in various molecular weights, PVP with a molecular weight of 130,000 g/mol is generally considered to be the easiest PVP to fabricate fibers with minimal challenges. However, the fiber diameter in this case is usually in the micron regime, which limits the utilization of PVP fibers in fields that require fiber diameters in the nano regime. Generally, PVP with a lower molecular weight, such as 10,000 g/mol and 55,000 g/mol, is known to present challenges in fiber preparation. In the current study, parameter optimization for PVP possessing molecular weights of 10,000 g/mol and 55,000 g/mol was carried out to obtain nanofibers. The electrospinning technique was utilized for fiber fabrication by optimizing the above-mentioned parameters. SEM analysis was performed to analyze the fiber morphology, and quantitative analysis was performed to correlate the effect of parameters on the fiber morphology. This research study will lead to various applications, such as drug encapsulation for sustained drug release and nanoparticles/nanotubes encapsulation for microwave absorption applications.

Acyl pyrazole sulfonamides as new antidiabetic agents: synthesis, glucosidase inhibition studies, and molecular docking analysis.

Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly α-glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles (5a-k) followed by their in vitro and in silico screening against α-glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against α-glucosidase than the standard drug, acarbose (IC50 = 35.1 ± 0.14 µM), with IC50 values ranging from 1.13 to 28.27 µM. However, compound 5a displayed the highest anti-diabetic activity (IC50 = 1.13 ± 0.06 µM). Furthermore, in silico studies revealed the intermolecular interactions of most potent compounds (5a and 5b), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure-activity relationships, while the docking results correspond to the IC50 values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM).

Synthesis of amantadine clubbed N-aryl amino thiazoles as potent urease, α-amylase & α-glucosidase inhibitors, kinetic and molecular docking studies.

A series of ten novel compounds were synthesized by incorporating a 1,3 thiazole core into amantadine and their structures were validated using different analytical and spectral methods such as FTIR, EI-MS, 1H NMR, and 13C NMR. The antibacterial and enzyme inhibitory properties of these newly synthesized compounds were evaluated. Remarkably, the compounds exhibited significant antibacterial activity against Escherichia coli and Bacillus subtilis. Additionally, the in vitro inhibitory activities of the synthesized compounds, against α-amylase, α-glucosidase, and urease were investigated. Among the tested compounds, compound 6d demonstrated potent and selective inhibition of α-amylase IC50 = 97.37 ± 1.52 µM, while acarbose was used as positive control and exhibited IC50 = 5.17 ± 0.25 µM. Compound 6d and 6e exhibited prominent inhibition against α-glucosidase IC50 = 38.73 ± 0.80 µM and 41.63 ± 0.26 µM respectively. Furthermore, compound 6d inhibited urease with exceptional efficacy IC50 = 32.76 µM, while positive control thiourea showed more prominent activity having IC50 = 1.334 µM. Molecular docking studies disclosed the binding mechanism and affinity of these new inhibitors within the binding sites of various amino acids. To investigate the association between molecular structural characteristics and inhibitory actions of synthesized derivatives, preliminary structure-activity relationship (SAR) studies were performed. These findings indicated that compounds 6a, 6c, 6d and 6e are potential candidates for hit-to-lead follow-up in the drug-discovery process for treating diabetes and hyperglycemia.

Tropylium Ion, an Intriguing Moiety in Organic Chemistry.

The tropylium ion is a non-benzenoid aromatic species that works as a catalyst. This chemical entity brings about a large number of organic transformations, such as hydroboration reactions, ring contraction, the trapping of enolates, oxidative functionalization, metathesis, insertion, acetalization, and trans-acetalization reactions. The tropylium ion also functions as a coupling reagent in synthetic reactions. This cation's versatility can be seen in its role in the synthesis of macrocyclic compounds and cage structures. Bearing a charge, the tropylium ion is more prone to nucleophilic/electrophilic reactions than neutral benzenoid equivalents. This ability enables it to assist in a variety of chemical reactions. The primary purpose of using tropylium ions in organic reactions is to replace transition metals in catalysis chemistry. It outperforms transition-metal catalysts in terms of its yield, moderate conditions, non-toxic byproducts, functional group tolerance, selectivity, and ease of handling. Furthermore, the tropylium ion is simple to synthesize in the laboratory. The current review incorporates the literature reported from 1950 to 2021; however, the last two decades have witnessed a phenomenal upsurge in the utilization of the tropylium ion in the facilitation of organic conversions. The importance of the tropylium ion as an environmentally safe catalyst in synthesis and a comprehensive summary of some important reactions catalyzed via tropylium cations are described.

Ultrasound-Assisted Synthesis of Piperidinyl-Quinoline Acylhydrazones as New Anti-Alzheimer's Agents: Assessment of Cholinesterase Inhibitory Profile, Molecular Docking Analysis, and Drug-like Properties.

Alzheimer's disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer's disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4-6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer's disease (AD).

Leiomyosarcoma of the Penis: A Case Report and Re-Appraisal.

Background: Penile leiomyosarcoma arises from smooth muscles, which can be from dartos fascia, erector pili in the skin covering the shaft, or from tunica media of the superficial vessels and cavernosa. We describe presentation, treatment options, and recurrence pattern of this rare malignancy. Case Presentation: We present a case of penile leiomyosarcoma in a 70-year-old patient who presented to the urology clinic with 1-year history of a slowly enlarging penile mass associated with phimosis. Conclusions: Prognosis of penile LMS is difficult to ascertain because reported cases are rare. Penile leiomyosarcoma can be classified as superficial or deep based on tumor relation to tunica albuginea. Deep tumors (> 3 cm), high-grade lesions, and tumors with involvement of corpora cavernosa, tend to spread locally and metastasize to distant areas and require more radical surgery with or without postoperative radiation therapy. In contrast, superficial lesions can be treated with local excision only.

Population genetic portrait of Pakistani Lahore-Christians based on 32 STR loci.

Phylogenetic relationship and the population structure of 500 individuals from the Christian community of Lahore, Pakistan, were examined based on 15 autosomal short tandem repeats (STRs) using the AmpFℓSTR Identifiler Plus PCR Amplification Kit and our previously published Y-filer kit data (17 Y-STRs) of same samples. A total of 147 alleles were observed in 15 loci and allele 11 at the TPOX locus was the most frequent with frequency value (0.464). The data revealed that the Christian population has unique genetic characteristics with respect to a few unusual alleles and their frequencies relative to the other Pakistani population. Significant deviations from Hardy-Weinberg equilibrium were found at two loci (D13S317, D18S51) after Boneferroni's correction (p ≤ 0.003). The combined power of discrimination, combined power of exclusion and cumulative probability of matching were 0.999999999999999978430815060354, 0.999995039393942 and 2.15692 × 10-17, respectively. On the bases of genetic distances, PCA, phylogenetic and structure analysis Lahore-Christians appeared genetically more associated to south Asian particularly Indian populations like Tamil, Karnataka, Kerala and Andhra Pradesh than rest of global populations.

Applications and impact of computer technologies in management of multimorbidity.

OBJECTIVE: To highlight clinical scenarios and healthcare practitioners' difficulties where computer applications can help in multimorbidity management. METHODS: The cross-sectional study was conducted from December 2017 to January 2019 in the twin cities of Rawalpindi and Islamabad, Pakistan, and comprised local physicians/practitioners. Data was collected using a self-generated questionnaire which was distributed among the subjects. It identified four problems as most commonly faced: treatment/dose management, time management, forgetting to ask necessary questions about disease, and 'others', such as bad handwriting errors and ethical issues. Data was analysed using SPSS 17. RESULTS: Of the 53 subjects, 33(62%) marked problems related to treatment management, 35(66%) marked problems related to shortage of time, 34(64%) marked those related to difficulty in asking relevant questions about disease, 15(28%) marked the 'other' option. CONCLUSIONS: Computer technologies are significantly helpful in managing the problems of treating multimorbidity by adopting standard database.

A Comparative Analysis of Data Augmentation Approaches for Magnetic Resonance Imaging (MRI) Scan Images of Brain Tumor.

INTRODUCTION: Machine Learning (ML) is a rapidly growing subfield of Artificial Intelligence (AI). It is used for different purposes in our daily life such as face recognition, speech recognition, text translation in different languages, weather prediction, and business prediction. In parallel, ML also plays an important role in the medical domain such as in medical imaging. ML has various algorithms that need to be trained with large volumes of data to produce a well-trained model for prediction. AIM: The aim of this study is to highlight the most suitable Data Augmentation (DA) technique(s) for medical imaging based on their results. METHODS: DA refers to different approaches that are used to increase the size of datasets. In this study, eight DA approaches were used on publicly available low-grade glioma tumor datasets obtained from the Tumor Cancer Imaging Archive (TCIA) repository. The dataset included 1961 MRI brain scan images of low-grade glioma patients. You Only Look Once (YOLO) version 3 model was trained on the original dataset and the augmented datasets separately. A neural network training/testing ecosystem named as supervisely with Tesla K80 GPU was used for YOLO v3 model training on all datasets. RESULTS: The results showed that the DA techniques rotate at 180o and rotate at 90o performed the best as data enhancement techniques for medical imaging. CONCLUSION: Rotation techniques are found significant to enhance the low volume of medical imaging datasets.

Haplotype diversity of 17 Y-STRs in Sheikh population of Punjab.

Y chromosomal short tandem repeat (Y-STR) haplotype diversity of 180 genetically unrelated male individuals from Sheikh population of Punjab Pakistan was studied by amplifying 17 Y-STR markers through the AmpFISTR®Yfiler™ PCR amplification kit. The analysis of data revealed mean discrimination capacity of 0.6438 and matching probability of 0.3561. Sheikh population was also compared with 11 other populations in order to determine its population relationships which indicated that Punjabi Sheikhs have low genetic resemblance with Indian-Balmiki, UAE [Arab], Yousafzai Pathan from Pakistan, and Pathans from Afghanistan. The data of this study could have valuable application in forensic cases, in population genetics studies, and in strengthening the Y-STR database.

Genetic polymorphism of Y-chromosomal STRs in Gujjar population of Punjab.

Y-STR polymorphism of Gujjar population was determined by using AmpFISTR®YfilerTM PCR amplification kit. A total 176 haplotypes were obtained after the analysis of 17 Y-STR loci in 176 genetically unrelated individuals. Haplotype diversity and discrimination capacity attained was 0.99730 and 0.652201325, respectively. The comparison of Gujjar population with 16 other populations revealed that Gujjars have low genetic distance from Punjabi, Sindhi, and Pakhtun population of Pakistan; Azad Kashmir, Saraswat Brahmin from India; Bangladeshi population; north and south of Afghanistan; and Uttar Pradesh India which hints toward the migrational route Gujjars took over the centuries. This data is of significant value for population studies and forensic applications.

Comparative Study of Efficacy of Topical Mometasone with Calcipotriol versus Mometasone Alone in the Treatment of Alopecia Areata.

BACKGROUND: Alopecia areata is one of the common causes of nonscarring hair loss with autoimmune etiology. This study was designed to evaluate any added benefit of topical calcipotriol when combined with topical mometasone in the treatment of alopecia areata. To the best of our knowledge, no such study has been conducted in the past. MATERIALS AND METHODS: It was a comparative analytical study done over 100 patients of clinically diagnosed alopecia areata. Group A patients (n = 50) were advised to apply topical mometasone 0.1% cream along with topical calcipotriol 0.005% ointment each once daily, whereas patients of Group B (n = 50) were advised to apply only topical mometasone 0.1% cream in the same amount, once a day. Follow-up of all patients was done at 6, 12, and 24 weeks, and the outcome was assessed according to the Severity of Alopecia Tool (SALT) score at every visit. RESULTS: Both the groups were statistically comparable in terms of age (P = 0.694) and sex (P = 0.683) distribution. Baseline mean SALT score of Group A and Group B patients was 7.22 and 6.05, respectively (P = 0.145). At the end of 24 weeks, mean SALT score of Group A and Group B patients decreased by 4.24 and 3.39, respectively (P < 0.001). We also found that there was a significant decrease (P < 0.001) in mean SALT score at 24 weeks in patients of both groups when compared with baseline values. CONCLUSION: We found that adding topical calcipotriol 0.005% ointment with topical mometasone 0.1% cream has higher efficacy than topical mometasone alone, in the treatment of alopecia areata.

Potential biomarkers for the diagnosis of respiratory tract infection and lungs cancer.

Major hurdle faced by many physicians in treating various respiratory tract infections and lung carcinomas is their late or mis-diagnosis. In most respiratory tract infections the manner of infection is not completely understood. Similarly, various lung carcinomas are diagnosed at advance stages at which not only the treatment possibilities are narrowed but the chances of survival are also reduced. So, for the sake of better treatment, the quick and improved diagnostic strategies are suggested. Protein biomarkers fully fit the description in this regard as they have shown great potential in specific diagnosis of many respiratory diseases and also have shown capability in timely pin pointing different stages of lung carcinomas. Many serum biomarkers are presently being used for diagnosis but the efficiency for diagnosis of these biomarkers is lower when used alone. So, physicians are suggested to use the combination of different biomarkers. Moreover, genetic biomarkers are also currently studied to indicate the exact stage of disease, the possible damage occurred, the severity of disease and also for the analysis of the possible body response to the therapeutics.