Investigating vertical transmission and maternofoetal outcomes in pregnant women with COVID-19: a case-control study from Pakistan.

Objectives: To estimate the frequency of severe acute respiratory syndrome coronavirus-2 among pregnant women, the impact in terms of obstetrical and clinical outcomes and vertical transmission to the neonates. METHODS: The prospective, case-control study was conducted at Zainab Panjwani Memorial Hospital, Karachi, from March to December 2021, and comprised pregnant women regardless of gestational age who exhibited symptoms or had a suspicion of exposure to any confirmed coronavirus disease-2019 individual. They were screened for severe acute respiratory syndrome coronavirus-2 infection using polymerase chain reaction or serology. Those who tested negative were designated as control group A, while who had a positive serology result along with a negative polymerase chain reaction were taken as recovered case group B1, and those who tested positive for polymerase chain reaction were called the positive case group B2. Groups B1 and B2 were followed up till delivery. The clinical presentation of coronavirus disease-2019 infection in pregnancy and its obstetrical and neonatal outcomes was assessed. Products of conception were tested for the detection of the severe acute respiratory syndrome coronavirus-2 genome. The viral genome from group B2 cases was sequenced to confirm vertical transmission. Data was analysed using GraphPad Prism V8. RESULTS: Of the 139 pregnant women, 74(53.2%) were in group A with mean age 25.87±6.90 years, 49(35.3%) were in group B1 with mean age 25.53±7.02 years, and 16(11.5%) were in group B2 with mean age 27.12±5.03 years. The gestational age at which termination of pregnancy occurred was 38.3±1.26 weeks in group B1 and 38.3±1.85 weeks for group B2. There were 96 neonates across the 3 groups. Of the 11(11.45%) neonates in group B2, 1(9.09%) had postnatal transmission of severe acute respiratory syndrome coronavirus-2 and this mother-neonate case was taken as the Indexed case. The severe acute respiratory syndrome coronavirus-2 genome isolated from the neonate showed similar mutations as the viral strain infecting the mother. Conclusion: The risk of vertical transmission was found to be low. The severe acute respiratory syndrome coronavirus-2 genome was the same for both the mother and the neonate.

Synthesis, biological evaluation, and molecular docking study of xanthene-linked thiosemicarbazones as cholinesterase inhibitors.

This study delineates the design and synthesis of a series of xanthene-based thiosemicarbazones that show low µM inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), crucial enzymes associated with, among others, Alzheimer's Disease (AD) pathology. Despite FDA-approved AChE inhibitors being frontline treatments for AD, there remains a need for agents exhibiting improved efficacy and selectivity. Our synthesized series demonstrate meaningful inhibition against AChE (IC50 ranging from 4.2 to 62 µM). These compounds exhibit comparatively lower potency against BChE (IC50 values between 64 and 315 µM), showcasing a pronounced AChE selectivity compared to physostigmine. The selectivity index for the compounds between the two targets does vary between 0.02 and 0.75 highlighting that even minor structural differences can have drastic effects on protein interactions. Molecular docking insights further substantiated these observations, revealing the importance of the xanthene scaffold for AChE-binding and the aryl R2 moiety for BChE interactions. Notably, some compounds demonstrated dual enzyme targeting, emphasizing their interactions could be exploited for developing monotherapies against cholinesterase-associated neurodegenerative afflictions like AD. Collectively, these findings suggest that xanthene-based thiosemicarbazones are a promising and highly accessible scaffold that deserve further investigative exploration in the cholinesterase inhibitor therapeutic landscape.Communicated by Ramaswamy H. Sarma.

Current And Emerging Trends In The Management Of Pyoderma Gangrenosum: A Literature Review.

The first description of Pyoderma gangrenosum (PG) was made about a century ago. It is difficult to understand the aetiology, pathophysiology, and therapy of PG. This disease is believed to be caused by a systemic inflammatory response to neutrophil chemotaxis and faulty innate immune system control. Nearly fifty percent of the cases have underlying systemic symptoms. Significant improvements in PG management have been made over the years. The main goals of treatment are to reduce inflammation and speed up the healing of the PG wound. Even though the most recent medicines show promise, they are found on isolated case reports. The majority of patients are typically managed with topical treatment and local wound care, while resistant cases necessitate immunosuppressive medications. More progress can be made with improvements in technology in deciphering this complex disease and getting a greater understanding of the condition. The present standard therapies for refractory PG are not well supported by studies. In refractory PG, corticosteroids and cyclosporine have historically been administered. Tumour necrosis factor inhibitors are becoming a viable option; nonetheless, this requires careful research and upkeep. This review intended to describe the current trends in managing the PG. Several next-generation treatment options including the conventional therapies introduced to treat PG. We encompass the advantages and disadvantages of new treatments for PG.

Synthesis of indole-substituted thiosemicarbazones as an aldose reductase inhibitor: an in vitro, selectivity and in silico study.

Aim: Indole is an important component of many drug molecules, and its conjugation with thiosemicarbazone moiety would be advantageous in finding lead compounds for the development of diabetic complications. Methodology: We have designed, synthesized and evaluated a series of 17 indole-thiosemicarbazones (3a-q) as aldose reductase (ALR2) and aldehyde reductase (ALR1) inhibitors. Results: After in vitro evaluation, all indole-thiosemicarbazones showed significant inhibition against both enzyme ALR1 and ALR2 with IC50 in range of 0.42-20.7 and 1.02-19.1 µM, respectively. The docking study was also carried out to consider the putative binding of molecules with the target enzymes. Conclusion: Compound 3f was found to be most active and selective for ALR2. The indole-thiosemicarbazones series described here has selective hits for diabetes-mellitus-associated complications.

Exploring biologically active hybrid pharmacophore N-substituted hydrazine-carbothioamides for urease inhibition: In vitro and in silico approach.

Urease is potential target for various human's health complications, such as peptic ulcer, gastric cancer and kidney stone formation. The present study was based on synthesis of new hybrid pharmacophore N-substituted hydrazine-carbothioamides as potential urease inhibitors. Presented method gave excellent yield in range of 85-95% for hydrazine-carbothioamides derivatives (3a-s) after reaction of mono- and disubstituted hydrazides (1a-k) and substituted isothiocyanates (2a-d). All newly derivatives were characterized by advanced spectroscopic techniques (FTIR, 1HNMR, 13CNMR, EMS) and were assessed for their urease inhibition potential. All analogs except for 3k, 3l and 3m demonstrated strong inhibitory potential for urease with IC50 values of 8.45 ± 0.14 to 25.72 ± 0.23 µM as compared to standard thiourea (IC50 21.26 ± 0.35 µM). The structure-activity relationship and mode of interaction was established by molecular docking studies. It was revealed that the N-substituted hydrazine-carbothioamides interacted with nickel atoms present in the active site of urease and supported the correlations with the experimental findings. Therefore, the afforded hydrazine-carbothioamides derivatives are interesting hits for urease inhibition studies with future prospects of modification and optimization.

Routine Measurement of Thyroid Stimulating Hormone in Patients Presenting With Third-Degree Atrioventricular Block: Do We Really Need It?

Background Hypothyroidism can be a cause of sinus bradycardia. However, thyroid laboratory evaluation is often performed routinely in patients with complete heart block (CHB) though there is little data to support this practice. This study aimed to assess the frequency of thyroid dysfunction in patients presenting with CHB without clinical features of hypothyroidism. Methodology All patients referred for permanent pacemaker implantation for CHB were included in this cross-sectional study. Patients with known thyroid disorder or clinical features of thyroid disorder were excluded. Demographic, electrocardiography (EKG), and routine thyroid stimulating hormone (TSH) screening results were recorded. Results A total of 102 patients with complete atrioventricular (AV) block were enrolled in the study of which 50.0% (51) were male. The mean age was 61.09 ± 11.74. Co-morbidities included diabetes mellitus 44.1% (45), smoking 36.3% (37), and hypertension 55.9% (57). Mean EKG atrial rate was 82.97 ± 31.31 mmHg with a mean ventricular escape rate of 36.17 ± 5.93. Permanent pacemakers were implanted in all of the patients. Only one patient had an abnormal TSH. Conclusions We found a very low prevalence of thyroid dysfunction among patients without clinical features of thyroid dysfunction presenting with third-degree AV block. This calls for cautious prescription of thyroid testing in clinically euthyroid patients.

Probing 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones as multi-target directed ligands against cholinesterases, carbonic anhydrases and α-glycosidase enzymes.

With the fading of 'one drug-one target' approach, Multi-Target-Directed Ligands (MTDL) has become a central idea in modern Medicinal Chemistry. The present study aimed to design, develop and characterize a novel series of 4-(Diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) and evaluates their biological activity against cholinesterase, carbonic anhydrases and α-glycosidase enzymes. The hCA I isoform was inhibited by these novel 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones (3a-p) in low nanomolar levels, the Ki of which differed between 407.73 ± 43.71 and 1104.11 ± 80.66 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 323.04 ± 56.88 to 991.62 ± 77.26 nM. Also, these novel 4-(diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) effectively inhibited AChE, with Ki values in the range of 121.74 ± 23.52 to 548.63 ± 73.74 nM. For BChE, Ki values were obtained with in the range of 132.85 ± 12.53 to 618.53 ± 74.23 nM. For α-glycosidase, the most effective Ki values of 3b, 3k, and 3g were with Ki values of 77.85 ± 10.64, 96.15 ± 9.64, and 124.95 ± 11.44 nM, respectively. We have identified inhibition mechanism of 3b, 3g, 3k, and 3n on α-glycosidase AChE, hCA I, hCA II, and BChE enzyme activities. Hydrazine-1-carbothioamide and hydroxybenzylidene moieties of compounds play an important role in the inhibition of AChE, hCA I, and hCA II enzymes. Hydroxybenzylidene moieties are critical for inhibition of both BChE and α-glycosidase enzymes. The findings of in vitro and in silico evaluations indicate 4-(diethylamino)-salicylaldehyde-based thiosemicarbazone scaffold to be a promising hit for drug development for multifactorial diseases like Alzheimer's disease.

Probing 2-acetylbenzofuran hydrazones and their metal complexes as α-glucosidase inhibitors.

Inhibition of α-glucosidase is one of the important approaches in designing antidiabetic drugs for its role in decrease of the carbohydrates digestion to avoid post-prandial increase in blood sugar levels in diabetic patients. In the present study we designed a novel series of 2-acetylbenzofuran hydrazones (L1-L7) and their metal (II) complexes Cu (II), Co (II), Zn (II) and Mn (II) (8-29) and screened for inhibitory activity against the yeast α-glucosidase. The synthesis of hydrazones incorporated the use of I2 as a catalyst which resulted in excellent yield of 94%. The ligand L3, showed good activity (IC50 = 47.51 ± 0.86 µM) while its metal complex (10) showed potent activity (IC50 = 1.15 ± 0.001 µM) compared to reference acarbose IC50 = 378.25 ± 0.12 µM. Similarly, the Cu (II) complexes with ligands L5 and L6 showed excellent α-glucosidase inhibition (IC50 = 0.15 ± 0.003 12 and 0.21 ± 0.002 µM for 13, respectively) whereas, the metal complexes of Co (II), Mn (II), and Zn (II) showed moderate to poor inhibitory activities against α-glucosidase. The The findings are supported by the ligands and enzyme interactions through molecular docking studies. In conclusion, it is indicated that metal complexes of 2-acetylbenzofuran hydrazones have good potential for research leading to antidiabetic therapies.

Development of sulfonamide-based Schiff bases targeting urease inhibition: Synthesis, characterization, inhibitory activity assessment, molecular docking and ADME studies.

A series of Sulfonamide-based Schiff bases (E)-4-(benzylideneamino)-N-(6-methoxypyridazin-3-yl) benzenesulfonamide (3a-r) targeting Urease Inhibition was synthesized from sulphamethoxy pyridazine and substituted aldehydes. The prepared compounds were characterized by various spectroscopic techniques including FTIR, 1HNMR, 13CNMR, and spectrometric HRMS analysis. The most active agent (3g) bearing halogens and OH groups gave IC50 value of 2.20 µM for urease inhibition against the standard Thiourea (IC50 = 20.03 ± 2.06) and the overall trend within the series was 3g > 3n > 3p > 3j > 3q > 3h, 3o > 3l, 3r > 3k, 3m > 3a > 3d > 3e > 3f. Structure-activity relationship study established that the nature as well as the position of varying groups attached to aryl group had crucial roles in defining the urease inhibition activity. Additionally, in silico investigation was carried out which demonstrated that the compounds exhibit polar and apolar contacts with the crucial residues in the binding site of urease. The ADME analysis suggested all the synthesized compounds to be non-toxic, and likely to undergo passive gastrointestinal absorption. Taken together, the study suggests that the synthesized Sulfonamide-based Schiff bases derivatives may serve as potential hits as urease inhibitors.

Synthesis, bioactivity and binding energy calculations of novel 3-ethoxysalicylaldehyde based thiosemicarbazone derivatives.

In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.

A Study of Magnitude and Psychological Correlates of Smartphone Use in Medical Students: A Pilot Study with A Novel Telemetric Approach.

CONTEXT: Smartphone use is being investigated as a potential behavioral addiction. Most of the studies opt for a subjective questionnaire-based method. This study evaluates the psychological correlates of excessive smartphone use. It uses a telemetric approach to quantitatively and objectively measure participants' smartphone use. METHODOLOGY: One hundred forty consenting undergraduate and postgraduate students using an Android smartphone at a tertiary care teaching hospital were recruited by serial sampling. They were pre-tested with the Smartphone Addiction Scale-Short Version, Big five inventory, Levenson's Locus of Control Scale, Ego Resiliency Scale, Perceived Stress Scale, and Materialism Values Scale. Participants' smartphones were installed with tracker apps, which kept track of total smartphone usage and time spent on individual apps, number of lock-unlock cycles, and total screen time. Data from tracker apps were recorded after 7 days. RESULTS: About 36 % of participants fulfilled smartphone addiction criteria. Smartphone Addiction Scale score significantly predicted time spent on a smartphone in the 7-day period (ß = 0.234, t = 2.086, P = 0.039). Predictors for time spent on social networking sites were ego resiliency (ß = 0.256, t = 2.278, P = 0.008), conscientiousness (ß = -0.220, t = -2.307, P = 0.023), neuroticism (ß = -0.196, t = -2.037, P = 0.044), and openness (ß = -0.225, t = -2.349, P = 0.020). Time spent gaming was predicted by success domain of materialism (ß =0.265, t = 2.723, P = 0.007) and shopping by ego resiliency and happiness domain of materialism. CONCLUSIONS: Telemetric approach is a sound, objective method for evaluating smartphone use. Psychological factors predict overall smartphone usage as well as usage of individual apps. Smartphone Addiction Scale scores correlate with and predict overall smartphone usage.