Phenylpropynones as Selective Disulfide Rebridging Bioconjugation Reagents.

Simple 1-phenylpropynones undergo a selective double thia-Michael addition with thiols in buffered media, yielding an interesting dithioacetal linkage joining two thiols. The reactivity of various Michael-alkyne reagents is compared in this chemoselective, atom economical, and non-oxidative cross-linking of two thiols. The stability and chemical reactivity of the dithioacetal links are studied, and the utility of the disulfide targeting bioconjugation methodology is shown by the selective rebridging of native cyclic peptides after the reductive cleavage of their disulfide bridge.

Determinants of Covid vaccine uptake and perinatal outcome in pregnant women at a tertiary care center.

OBJECTIVE: To determine the factors for hesitancy and uptake of coronavirus disease-2019 vaccine, and to compare perinatal outcomes in vaccinated and nonvaccinated pregnant women. METHODS: The cross-sectional study was conducted from November 2021 to February 2022 at the Ruth Pfau Civil Hospital, Karachi, and the Holy Family Hospital, Karachi, and comprised pregnant women admitted in delivery suite for operative or vaginal delivery. Data was collected using a self-designed questionnaire which also explored knowledge about vaccine, contextual factors and reasons for and against vaccination. Perinatal outcomes included stillbirth, preterm delivery, low birth weight and Appearance-Pulse-Grimace-Activity-Respiration score. Also, 3cc blood was collected from the umbilical cord at the time of delivery, and enzyme-linked immunosorbent assay technique was used for antibodies titre. Data was analysed using SPSS 24. RESULTS: Of the 186 women, 114(61.3%) with mean age 27.9±4.1 years were vaccinated, and 72(38.7%) with mean age 27.5±5.2 years were not vaccinated. Physician's advise 104 (91.2%), vaccine safety and its effect on foetus 52(72.2%) were main determinants for vaccine uptake and refusal, repectively. Family and peer pressure was also responsible in 19(26.4%) cases for vaccine refusal. Body mass index, parity, level of education, socioeconomic status, history of coronavirus disease-2019 infection, booking status and presence of gestational diabetes mellitus were significantly different between the vaccinated and unvaccinated groups (p<0.05). Antibody titers and Appearance-Pulse-Grimace-Activity-Respiration score at 1 minute were significantly higher in the group of vaccinated women (p<0.05). CONCLUSIONS: Vaccine uptake was found to be low. Safety concern against vaccine, and doctor's advice were the main determinants for hesitancy and uptake. Antibody titers in newborns were higher in the group of vaccinated women.

Prevalence of Lipohypertrophy and its Associations in Insulin-Treated Diabetic Patients.

Background and Objectives: Lipohypertrophy is a major complications of insulin therapy especially attributed to incorrect insulin technique. The objective was to determine the frequency of lipohypertrophy in diabetic population on insulin and its associations. Methods: This cross-sectional study was conducted at the Services Hospital Lahore from July 1st, 2020 to December 31st, 2020. Total of 363 diabetic patients, fulfilling the inclusion criteria were approached. The patients were examined and interviewed through a validated questionnaire. The data was stratified according to the age, gender, duration of diabetes, duration of insulin use, frequency of LH and duration since last instructions reviewed. The chi-square test was applied. Data was analyzed using SPSS 22. Results: Mean age of the study population was 49.71± 13.36 years. Majority were females (57.6%). LH was noted in 22.86% of participants (n=83). There was significant statistical difference noted (P <0.05) between different age groups as 29.7 % of patients in age group above 45 had LH as compared to 19.6% in the below 45 years age group. More females (28.2%) were having LH than the males (15.6%) with P<0.05. Also, significant difference was noted for needle reuse more than 10 times, more than two injections per day and longer duration since last instructions reviewed. No significant difference was noted between different devices for injection as well as for duration of diabetes. LH is strongly associated with hypoglycemia and hyperglycemia with P<0.05. Conclusion: A significant diabetic population on insulin has noted to have LH, and the risk is more with aged population, female gender, more injections per day and multiple time needle reuses. Risk of LH can be reduced by reinforcing education.

Bioinspired engineered nickel nanoparticles with multifunctional attributes for reproductive toxicity.

Nickel nanoparticles (Ni-NPs) have potential applications in high-tech sectors such as battery manufacturing, catalysis, nanotube printing and textile. Apart from their increasing utilisation in daily life, there are concerns about their hazardous nature as they are highly penetrable in biological systems. The carcinogenic and mutagenic ability of Ni-NPs is evident but the research gaps are still there concerning the safety evaluation of Ni-NPs regarding male reproductive ability. This controlled randomized research was planned to assess the male reproductive toxicity of Ni-NPs in Sprague Dawley rats. Ni-NPs of spherical shape and mean particle size of 56 nm were used in the study, characterized by SEM, EDS and XRD. The twenty-five healthy rats (200-220 g) were used for toxicity investigation of Ni-NPs and divided into five groups; negative control (0 Ni-NPs), placebo group (0.9% saline) and three Ni-NPs treated groups (@ 15, 30 and 45 mg/kg BW). The results of 14 days of intraperitoneal exposure to Ni-NPs revealed that a higher dose (45 mg/kg BW) of Ni-NPs caused a significant reduction in body weight, serum testosterone, daily sperm production while the testis index and Ni accumulation and histological changes (necrosis in basement membrane and seminiferous tubules, vacuole formation) in testicular tissues increased with increasing dose of Ni-NPs. It can be concluded from the study that Ni-NPs have potential reproductive toxicity. This study provided the baseline data of Ni-NPs toxicity for the male reproductive system and can be applied for risk assessment in Ni-NPs based products.

Deep eutectic solvent mediated synthesis of 3,4-dihydropyrimidin-2(1H)-ones and evaluation of biological activities targeting neurodegenerative disorders.

Substitution of hazardous and often harmful organic solvents with "green" and "sustainable" alternative reaction media is always desirous. Ionic liquids (IL) have emerged as valuable and versatile liquids that can replace most organic solvents in a variety of syntheses. However, recently new types of low melting mixtures termed as Deep Eutectic Solvents (DES) have been utilized in organic syntheses. DES are non-volatile in nature, have sufficient thermal stability, and also have the ability to be recycled and reused. Hence DES have been used as alternative reaction media to perform different organic reactions. The availability of green, inexpensive and easy to handle alternative solvents for organic synthesis is still scarce, hence our interest in DES mediated syntheses. Herein we have investigated Biginelli reaction in different DES for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Monoamine oxidases and cholinesterases are important drug targets for the treatment of various neurological disorders such as Alzheimer's disease, Parkinson's disease, depression and anxiety. The compounds synthesized herein were evaluated for their inhibitory potential against these enzymes. Some of the compounds were found to be highly potent and selective inhibitors. Compounds 1 h and 1c were the most active monoamine oxidase A (MAO A) (IC50 = 0.31 ± 0.11 µM) and monoamine oxidase B (MAO B) (IC50 = 0.34 ± 0.04 µM) inhibitors respectively. All compounds were selective AChE inhibitors and did not inhibit BChE (<29% inhibition). Compound 1 k (IC50 = 0.13 ± 0.09 µM) was the most active AChE inhibitor.

Chronic kidney disease diagnosis using decision tree algorithms.

BACKGROUND: Chronic Kidney Disease (CKD), i.e., gradual decrease in the renal function spanning over a duration of several months to years without any major symptoms, is a life-threatening disease. It progresses in six stages according to the severity level. It is categorized into various stages based on the Glomerular Filtration Rate (GFR), which in turn utilizes several attributes, like age, sex, race and Serum Creatinine. Among multiple available models for estimating GFR value, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), which is a linear model, has been found to be quite efficient because it allows detecting all CKD stages. METHODS: Early detection and cure of CKD is extremely desirable as it can lead to the prevention of unwanted consequences. Machine learning methods are being extensively advocated for early detection of symptoms and diagnosis of several diseases recently. With the same motivation, the aim of this study is to predict the various stages of CKD using machine learning classification algorithms on the dataset obtained from the medical records of affected people. Specifically, we have used the Random Forest and J48 algorithms to obtain a sustainable and practicable model to detect various stages of CKD with comprehensive medical accuracy. RESULTS: Comparative analysis of the results revealed that J48 predicted CKD in all stages better than random forest with an accuracy of 85.5%. The study also showed that J48 shows improved performance over Random Forest. CONCLUSIONS: The study concluded that it may be used to build an automated system for the detection of severity of CKD.

Conformational changes and binding property of the periplasmic binding protein BtuF during vitamin B12 transport revealed by collision-induced unfolding, hydrogen-deuterium exchange mass spectrometry and molecular dynamic simulation.

The periplasmic binding protein (PBP) BtuF plays a key role in transporting vitamin B12 from periplasm to the ATP-binding cassette (ABC) transporter BtuCD. Conformational changes of BtuF during transport can hardly be captured by traditional biophysical methods and the exact mechanism regarding B12 and BtuF recognition is still under debate. In the present work, conformational changes of BtuF upon B12 binding and release were investigated using hybrid approaches including collision-induced unfolding (CIU), hydrogen deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics (MD) simulation. It was found that B12 binding increased the stability of BtuF. In addition, fast exchange regions of BtuF were localized. Most importantly, midpoint of hinge helix in BtuF was found highly flexible, and binding of B12 proceed in a manner similar to the Venus flytrap mechanism. Our study therefore delineates a clear view of BtuF delivering B12, and demonstrated a hybrid approach encompassing MS and computer based methods that holds great potential to the probing of conformational dynamics of proteins in action.

An overview of therapeutic potential of N-alkylated 1-deoxynojirimycin congeners.

Polyhydroxylated alkaloids display a wide range of biological activities, suggesting their use in the treatment of various diseases. Their most famous representative, 1-deoxynojirimycin (DNJ), is a natural product that shows α- and ß-glucosidase inhibition. This molecule has been since converted into two clinically approved drugs i.e., Zavesca® and Glyset®, targeting type I Gaucher's disease and type II diabetes mellitus, respectively. This review examines the therapeutic potential of important DNJ congeners reported in last decade and presents concise mechanism of glycosidase inhibition. A brief overview of substituents conjugation's impact on DNJ scaffold (including N-alkylated DNJ derivatives, mono-valent, di-valent and multivalent DNJ congeners, N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin (AMP-DNM) look alike DNJ based lipophilic derivatives, AMP-DNM based neoglycoconjugates, DNJ click derivatives with varying carboxylic acids and aromatic moieties, conjugates of DNJ and glucose, and N-bridged DNJ analogues) towards various enzymes such as α/ß glucosidase, porcine trehalase, as F508del-CFTR correctors, α-mannosidase, human placental ß-glucocerebrosidase, N370S ß-GCase, α-amylase and insect trehalase as potent and selective inhibitors have been discussed with potential bioactivities, which can provide inspiration for future studies.

Impact of Multifaceted Workplace Bullying on the Relationships between Technology Usage, Organisational Climate and Employee Physical and Emotional Health.

This research article investigates the effect of organisational climate and technology usage on employees' physiological and emotional health damage resulting from face-to-face bullying and cyberbullying at the workplace. Furthermore, we investigated emotional intelligence as a coping strategy to moderate employee physiological and emotional health damage. The research used a quantitative research design. A five-point Likert-scale questionnaire was used to collect data from a multistage sample of 500 officials from Pakistan's four service sectors. Results revealed that organisational climate and technology usage are negatively related to face-to-face bullying and cyberbullying at the workplace. At the same time, workplace bullying adversely affects an employee's emotional and physiological health. However, emotional intelligence can reduce an employee's emotional health damage due to workplace bullying. Thus, we suggest incorporating emotional intelligence training at the workplace to minimise the devastating effects of face-to-face bullying and cyberbullying on employees' physical and emotional health.

Perspectives of Nanoparticles in Male Infertility: Evidence for Induced Abnormalities in Sperm Production.

Advancement in the field of nanotechnology has prompted the need to elucidate the deleterious effects of nanoparticles (NPs) on reproductive health. Many studies have reported on the health safety issues related to NPs by investigating their exposure routes, deposition and toxic effects on different primary and secondary organs but few studies have focused on NPs' deposition in reproductive organs. Noteworthy, even fewer studies have dealt with the toxic effects of NPs on reproductive indices and sperm parameters (such as sperm number, motility and morphology) by evaluating, for instance, the histopathology of seminiferous tubules and testosterone levels. To date, the research suggests that NPs can easily cross the blood testes barrier and, after accumulation in the testis, induce adverse effects on spermatogenesis. This review aims to summarize the available literature on the risks induced by NPs on the male reproductive system.

Investigation of oxidative stress enzymes and histological alterations in tilapia exposed to chlorpyrifos.

Chlorpyrifos (ChF) is an organophosphate pesticide that is widely used in agricultural fields and indoor for controlling pests. Aquatic ecosystems are the recipients of various pesticide residues due to leaching spray drift and agricultural runoff and pose toxicity for aquatic organisms. Therefore, the current study was designed to investigate the oxidative stress enzymes and histological alterations in the vital organs of tilapia due to ChF exposure. LC50 (24 h) was calculated as 52.78 µg/l by exposing tilapia with different acute concentrations of ChF. For assessment of sub-lethal toxicity of ChF, the fish were divided into four groups (ChF1, ChF2, ChF3, and control group). ChF1 group was treated with 1/15th of LC50, whereas ChF2 and ChF3 groups were treated with 1/10th and 1/5th of LC50, respectively for 14 days. After that, ChF induced changes in oxidative stress enzymes and histological alterations were evaluated. It was found that the level of glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) increased significantly in the liver of ChF-treated tilapia. Histological study of liver tissues showed an increased number of Kupffer cells, hydropic degeneration, necrosis, and hemorrhage. In the spleen of treated fish, increased melanomacrophage centers, necrosis, and congestion were detected. Disorganized muscle fibers, cardiac muscle fiber degeneration, and coagulative necrosis were observed in the heart of ChF-treated fish. It is concluded that sub-lethal concentrations of ChF can induce oxidative stress and histological alterations in the tissues of tilapia.

Stunting diagnostic and awareness: impact assessment study of sociodemographic factors of stunting among school-going children of Pakistan.

BACKGROUND: Stunting is a major public health issue in most of developing countries. Although, its worldwide prevalence is decreasing slowly but the number of stunted children is still rising in Pakistan. Stunting is highly associated with several long-term consequences, including higher rate of mortality and morbidity, deficient cognitive growth, school performance, learning capacity, work capacity and work productivity. To prevent stunting, we proposed Stunting Diagnostic and Education app. This app includes detailed knowledge of stunting and it's all forms, symptoms, causes, video tutorials and guidelines by the Pediatricians and Nutritionists. METHODS: A cross-sectional study has been conducted in schools of Multan District, Pakistan for the period of January 2019 to June 2019. Sample data of 1420 children, aged 4 to 18 years using three age groups, were analyzed by using SPSS version 21.0 to assess the prevalence of stunting and to analyze the risk factors associated with it in children under and over 5 age. Chi square test was applied in comparison with rural and urban participants and p-value < 0.05 was considered as significant. This study includes distribution of sociodemographic characteristics, parental education, working status of mothers, dietary patterns of school going children and prevalence of stunting in school going children. After getting study results, Stunting Diagnostic and Education app was developed according to the instructions of child experts and nutritionists. RESULTS: 354 (24.93%) participants were stunted out of 1420, 11.9% children were obese and 63.17% children were normal. Out of 354 stunted children, higher ratio of stunting was found in the age group of 8-11 years children with 51.98 percentage. 37.85% stunted children were found in the age group of 4-7 years and 10.17% stunting was found in the age group of 12-18 years children. It was observed in the study that male children were highly stunted than female with 57.91 and 42.09% respectively. Children living in rural areas were more stunted affected as compared to the children living in urban society with percentage 58.76 and 41.24 respectively. CONCLUSIONS: Our study concluded that 24.93% children were stunted, out of which, age group of 8-11 years children were highly stunted. The study showed that the literacy of mother or caregiver had high impact on children's health. Therefore, Stunting Diagnostic and Education app was developed to educate mothers to diagnose stunting and to teach about the prevention of stunting.

AI- modelling of molecular identification and feminization of wolbachia infected Aedes aegypti.

BACKGROUND: The genetic control strategies of vector borne diseases includes the replacement of a vector population by "disease-refractory" mosquitoes and the release of mosquitoes with a gene to control the vector's reproduction rates. Wolbachia are common intracellular bacteria that are found in arthropods and nematodes. Wolbachia infected male mosquitos have been used in different experimental trials around the world to suppress the target population of Aedes aegypti and this genetic control strategy has proved to be a promising alternative to other treatment strategies. Due to certain limitations, the successful application of this strategy is still awaited. METHODS: Mathematical frame work for Wolbachia induced genetic control strategy has been developed in this article. With the aid of Artificial Intelligence (AI) tools, accurate parametric values are depicted. For the first time, the model is well synchronized with the experimental findings. The model is comprised of the generalized varying coefficient and multiple mating rates between infected and uninfected compartments of Aedes aegypti dengue to forecast the disease control. RESULTS: Two mathematical models are developed in this article to demonstrate different mating rates of the genetic control strategy. The important parameters and time varying coefficients are well demonstrated with the aid of numerical computations. The resulting thresholds and forecasting may prove to be a useful tool for future experimental studies. CONCLUSIONS: From our analysis, we have concluded that the genetic control strategy is a promising technique and the role of Wolbachia infected male mosquitos, in genetic control strategies, can be better interpreted in an inexpensive manner with the aid of a theoretical model.

Selective Protection/Deprotection in 1-Deoxynojirimycin Scaffold: Regioselective Mono-Benzoylation and Alkylation using TBAB-NaOH Catalytic System.

Protecting groups play an important role in the carbohydrate chemistry and considerably influence the reactivity of substrate. A study of the substitution of various protecting groups in 1-deoxynojirimycin was carried out. Substrate N-benzyloxycarbonyl- 1,5-dideoxy-1,5-imino-4,6-O-isopropylidene-D-glucitol was subjected to alkylation at positions 2- and 3- to obtain di-substituted products and N-Cbz group was selectively removed by using NaOH in EtOH/H2O. Regioselective benzoylation and alkylation of N-benzyloxycarbonyl-1,5-dideoxy-1,5-imino-4,6-O-isopropylidene-D-glucitol were conducted under the action of TBAB-NaOH catalytic system. It was found that all protected and mono-protected analogs form simultaneously and their structures were confirmed by spectroscopic means. The results showed that electrophiles play an important role in determining the product distribution.

Frequency of peripheral neuropathy in patients with diabetes mellitus.

BACKGROUND: The main purpose of this study was to ascertain the frequency of peripheral diabetic neuropathy in diabetic patients and to stratify the different variants of peripheral neuropathy in patients. METHODS: Two hundred and fifty diabetic patients presenting to diabetic management centre, were included in this cross sectional study. Effect modifier (duration of diabetes) were studied through stratification. Eleven point neuropathic pain scale was used to access the extent of neuropathy. RESULTS: The frequency of neuropathy in diabetic patients was 187 (74.8%). Out of 250 patients 116 (46.4 %) patients were found to have burning type of pain and 114 (45.6%) were found' to have numbness while 61 (24.4%) had tingling. Out of 250 patients 17 (6.8%) were found to have sharp pain and 55 (22%) had dullness. Out of 250 patients 44 (17.6%) had coldness. Ten patients (4%) out of 250 had sensitive type of pain. frequency of itchy type of pain was 6.4%. CONCLUSION: The study showed that painful diabetic.neuropathy is present in majority of controlled diabetics and most of them belong to old age. It further showed that majority of sufferer were females. The most common variety of pain encountered was burning type of pain.

Critical elements in implementations of just-in-time management: empirical study of cement industry in Pakistan.

In recent years, inventory management is continuous challenge for all organizations not only due to heavy cost associated with inventory holding, but also it has a great deal to do with the organizations production process. Cement industry is a growing sector of Pakistan's economy which is now facing problems in capacity utilization of their plants. This study attempts to identify the key strategies for successful implementation of just-in-time (JIT) management philosophy on the cement industry of Pakistan. The study uses survey responses from four hundred operations' managers of cement industry in order to know about the advantages and benefits that cement industry have experienced by Just in time (JIT) adoption. The results show that implementing the quality, product design, inventory management, supply chain and production plans embodied through the JIT philosophy which infect enhances cement industry competitiveness in Pakistan. JIT implementation increases performance by lower level of inventory, reduced operations & inventory costs was reduced eliminates wastage from the processes and reduced unnecessary production which is a big challenge for the manufacturer who are trying to maintain the continuous flow processes. JIT implementation is a vital manufacturing strategy that reaches capacity utilization and minimizes the rate of defect in continuous flow processes. The study emphasize the need for top management commitment in order to incorporate the necessary changes that need to take place in cement industry so that JIT implementation can take place in an effective manner.