Phytochemical characterization of Typha domingensis and the assessment of therapeutic potential using in vitro and in vivo biological activities and in silico studies.

Typha domingensis, a medicinal plant with significant traditional importance for curing various human diseases, has potentially bioactive compounds but was less explored previously. Therefore, this study aims to investigate the therapeutic potential of T. domingensis by evaluating the phytochemical profile through high-performance liquid chromatography (HPLC) techniques and its biological activities (in vitro and in vivo) from the methanolic extract derived from the entire plant (TDME). The secondary metabolite profile of TDME regulated by reverse phase ultra-high-performance liquid chromatography-mass spectrometry (RP-UHPLC-MS) revealed some bioactive compounds by -ve and +ve modes of ionization. The HPLC quantification study showed the precise quantity of polyphenols (p-coumaric acid, 207.47; gallic acid, 96.25; and kaempferol, 95.78 µg/g extract). The enzyme inhibition assays revealed the IC50 of TDME as 44.75 ± 0.51, 52.71 ± 0.01, and 67.19 ± 0.68 µgmL-1, which were significant compared to their respective standards (indomethacin, 18.03 ± 0.12; quercetin, 4.11 ± 0.01; and thiourea, 8.97 ± 0.11) for lipoxygenase, α-glucosidase, and urease, respectively. Safety was assessed by in vitro hemolysis (4.25% ± 0.16% compared to triton × 100, 93.51% ± 0.36%), which was further confirmed (up to 10 g/kg) by an in vivo model of rats. TDME demonstrated significant (p < 0.05) potential in analgesic activity by hot plate and tail immersion tests and anti-inflammatory activity by the carrageenan-induced hind paw edema model. Pain latency decreased significantly, and the anti-inflammatory effect increased in a dose-dependent way. Additionally, in silico molecular docking revealed that 1,3,4,5-tetracaffeoylquinic acid and formononetin 7-O-glucoside-6″-O-malonate possibly contribute to enzyme inhibitory activities due to their higher binding affinities compared to standard inhibitors. An in silico absorption, distribution, metabolism, excretion, and toxicological study also predicted the pharmacokinetics and safety of the chosen compounds identified from TDME. To sum up, it was shown that TDME contains bioactive chemicals and has strong biological activities. The current investigations on T. domingensis could be extended to explore its potential applications in nutraceutical industries and encourage the isolation of novel molecules with anti-inflammatory and analgesic effects.

Intimate partner violence against women in Southern Punjab, Pakistan: A phenomenological study.

BACKGROUND: Intimate Partner Violence (IPV) refers to behavior by an intimate partner that can cause physical, sexual, or psychological harm; is a common global public health issue requiring immediate attention. IPV is the most common form of violence in rural areas of Punjab, Pakistan. METHODS: This qualitative phenomenological study collected 46 in-depth interviews from married women who experienced IPV in the rural areas of South Punjab. A semi-structured interview guide was used for data collection. These women were selected through a snowball sampling technique from October 2018 to March 2019. Researchers accessed the study setting with the help of gatekeepers (Lady Health Workers and Village Heads). The interviews were audio-recorded in the local language (Saraiki) and were translated into English. The data were analyzed using the thematic inductive analysis technique. RESULTS: The study has presented multifaceted factors of IPV by using the socio-ecological framework in rural areas of South Punjab, Pakistan. The current study introduced culturally contextualized terminologies of "protection," "physical submissiveness," "mental delicacy," and "social security". For married women, culturally embedded terms became the primary cause of IPV. In addition, the study also highlighted some of the cultural terminologies (such as run-mureed, watta-satta, beghairat, izzat, etc.) that are ubiquitous in the local context that sometimes intensifies IPV in the family and community sphere. Furthermore, the study discussed how gender-based inequalities trigger a status quo that ultimately creates power discrimination between spouses, which perpetuates violence in the domestic context. CONCLUSIONS: Gender-prejudiced roles and expectations imposed by orthodoxy, misinterpretations of Islamic teachings, and dominant patriarchy can be contested through awareness campaigns among the public, and gender sensitization drives among public institutions of police and judiciary. Education and employment-based can lead to women's empowerment and help to challenge the orthodox anti-feminist societal norms and the role of kinship-based networks in the family and community sphere.

Comprehensive Biological Potential, Phytochemical Profiling Using GC-MS and LC-ESI-MS, and In-Silico Assessment of Strobilanthes glutinosus Nees: An Important Medicinal Plant.

Plants of the genus Strobilanthes have notable use in folklore medicines as well as being used for pharmacological purposes. The present work explored the biological predispositions of Strobilanthes glutinosus and attempted to accomplish a comprehensive chemical profile through GC-MS of different fractions concerning polarity (chloroform and n-butanol) and LC-ESI-MS of methanolic extract by both positive and negative ionization modes. The biological characteristics such as antioxidant potential were assessed by applying six different methods. The potential for clinically relevant enzyme (α-amylase, α-glucosidase, and tyrosinase) inhibition was examined. The DPPH, ABTS, CUPRAC, and FRAP results revealed that the methanol fraction presented efficient results. The phosphomolybdenum assay revealed that the n-hexane fraction showed the most efficient results, while maximum metal chelation potential was observed for the chloroform fraction. The GC-MS profiling of n-butanol and chloroform fractions revealed the existence of several (110) important compounds presenting different classes (fatty acids, phenols, alkanes, monoterpenes, diterpenes, sesquiterpenoids, and sterols), while LC-ESI-MS tentatively identified the presence of 44 clinically important secondary metabolites. The n-hexane fraction exhibited the highest potential against α-amylase (497.98 mm ACAE/g extract) and α-glucosidase (605.85 mm ACAE/g extract). Significant inhibitory activity against tyrosinase enzyme was displayed by fraction. Six of the prevailing compounds from the GC-MS study (lupeol, beta-amyrin, stigmasterol, gamma sitosterol, 9,12-octadecadienoic acid, and n-hexadecanoic acid) were modelled against α-glucosidase and α-amylase enzymes along with a comparison of binding affinity to standard acarbose, while three compounds identified through LC-ESI-MS were docked to the mushroom tyrosinase enzyme and presented with significant biding affinities. Thus, it is assumed that S. glutinosus demonstrated effective antioxidant and enzyme inhibition prospects with effective bioactive molecules, potentially opening the door to a new application in the field of medicine.

Multifaced Assessment of Antioxidant Power, Phytochemical Metabolomics, In-Vitro Biological Potential and In-Silico Studies of Neurada procumbens L.: An Important Medicinal Plant.

This work was undertaken to explore the phytochemical composition, antioxidant, and enzyme-inhibiting properties of Neurada procumbens L. extracts/fractions of varying polarity (methanol extract and its fractions including n-hexane, chloroform, n-butanol, and aqueous fractions). A preliminary phytochemical study of all extracts/fractions, HPLC-PDA polyphenolic quantification, and GC-MS analysis of the n-hexane fraction were used to identify the phytochemical makeup. Antioxidant (DPPH), enzyme inhibition (against xanthine oxidase, carbonic anhydrase, and urease enzymes), and antibacterial activities against seven bacterial strains were performed for biological investigation. The GC-MS analysis revealed the tentative identification of 22 distinct phytochemicals in the n-hexane fraction, the majority of which belonged to the phenol, flavonoid, sesquiterpenoid, terpene, fatty acid, sterol, and triterpenoid classes of secondary metabolites. HPLC-PDA analysis quantified syringic acid, 3-OH benzoic acid, t-ferullic acid, naringin, and epicatechin in a significant amount. All of the studied extracts/fractions displayed significant antioxidant capability, with methanol extract exhibiting the highest radical-scavenging activity, as measured by an inhibitory percentage of 81.4 ± 0.7 and an IC50 value of 1.3 ± 0.3. For enzyme inhibition experiments, the n-hexane fraction was shown to be highly potent against xanthine oxidase and urease enzymes, with respective IC50 values of 2.3 ± 0.5 and 1.1 ± 0.4 mg/mL. Similarly, the methanol extract demonstrated the strongest activity against the carbonic anhydrase enzyme, with an IC50 value of 2.2 ± 0.4 mg/mL. Moreover, all the studied extracts/fractions presented moderate antibacterial potential against seven bacterial strains. Molecular docking of the five molecules ß-amyrin, campesterol, ergosta-4,6,22-trien-3ß-ol, stigmasterol, and caryophyllene revealed the interaction of these ligands with the investigated enzyme (xanthine oxidase). The results of the present study suggested that the N. procumbens plant may be evaluated as a possible source of bioactive compounds with multifunctional therapeutic applications.

Cost of Goods Analysis Facilitates an Integrated Approach to Identifying Alternative Synthesis Methodologies for Lower Cost Manufacturing of the COVID-19 Antiviral Molnupiravir.

Orally delivered drugs offer significant benefits in the fight against viral infections, and cost-effective production is critical to their impact on pandemic response in low- and middle-income countries. One example, molnupiravir, a COVID-19 therapy developed by Emory, Ridgeback, and Merck & Co., had potential to benefit from significant cost of goods (COGs) reductions for its active pharmaceutical ingredient (API), including starting materials. A holistic approach to identifying, developing, and evaluating optimized synthetic routes, which includes detailed COGs modeling, provides a rapid means to increase the availability, uptake and application of molnupiravir and other antivirals in global markets. Identification and development of alternate processes for the synthesis of molnupiravir has been conducted by the Medicines for All Institute at Virginia Commonwealth University (M4ALL) and the Green and Turner Labs at the University of Manchester. Both groups developed innovative processes based on synthetic route design and biocatalysis aimed at lowering costs and improving global access. The authors then performed COGs modeling to assess cost saving opportunities. This included a focus on manufacturing environments and facilities amenable to global public health and the identification of key parameters using sensitivity analyses. While all of the evaluated routes provide efficiency benefits, the best options yielded 3-6 fold API COGs reductions leading to treatment COGs as low as <$3/regimen. Additionally, key starting materials and cost drivers were quantified to evaluate the robustness of the savings. Finally, COGs models can continue to inform the focus of future development efforts on the most promising routes for additional cost savings. While the full price of a treatment course includes other factors, these alternative API synthetic approaches have significant potential to help facilitate broader access in low- and middle-income countries. As other promising therapeutics are developed, a similar process could enable rapid cost reductions while enhancing global access.

Can a quantitative assessment of SARS-CoV-2 PCR predict degree of severity and outcomes in critical care patients with COVID-19?

Real-Time polymerase chain reaction (qPCR) is the gold standard diagnostic method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold (Ct) is defined as the number of heating and cooling cycles required during the PCR process. Ct-values are inversely proportional to the amount of target nucleic acid in a sample. Our aim, in this retrospective study, was to determine the impact of serial SARS-CoV-2 qPCR Ct-values on: mortality, need for mechanical ventilation (MV) and development of acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU) with COVID-19. Ct values were evaluated during the time points from pre-ICU admission to week 1, week 2 and week 3 during ICU stay; impact on mortality, need for MV and AKI was determined. There was a continuous increment in Ct-values over the ICU stay from 1st week through to 3rd week. Although not significant, lower ICU 1st week Ct-values were associated with Black ethnicity, increased need for MV and mortality. However, patients who had developed AKI at any stage of their illness had significantly lower Ct-values compared to those with normal renal function. When ICU 1st-week Ct-values are subcategorised as <20, 20-30 and >30 the 28-day survival probability was less for patients with Ct-values of <20. This report shows that the impact of Ct-values and outcomes, especially AKI, among patients at different time points prior to and during ICU stay, larger studies are required to confirm out findings.

An Economical Route to Lamivudine Featuring a Novel Strategy for Stereospecific Assembly.

An economical synthesis of lamivudine was developed by employing a new method to establish the stereochemistry about the heterocyclic oxathiolane ring. Toward this end, an inexpensive and readily accessible lactic acid derivative served the dual purpose of activating the carbohydrate's anomeric center for N-glycosylation and transferring stereochemical information to the substrate simultaneously. Both enantiomers of the lactic acid derivative are available, and either ß-enantiomer in this challenging class of 2'-deoxynucleoside active pharmaceutical ingredients can be formed.

TargetCPP: accurate prediction of cell-penetrating peptides from optimized multi-scale features using gradient boost decision tree.

Cell-penetrating peptides (CPPs) are short length permeable proteins have emerged as drugs delivery tool of therapeutic agents including genetic materials and macromolecules into cells. Recently, CPP has become a hotspot avenue for life science research and paved a new way of disease treatment without harmful impact on cell viability due to nontoxic characteristic. Therefore, the correct identification of CPPs will provide hints for medical applications. Considering the shortcomings of traditional experimental CPPs identification, it is urgently needed to design intelligent predictor for accurate identification of CPPs for the large scale uncharacterized sequences. We develop a novel computational method, called TargetCPP, to discriminate CPPs from Non-CPPs with improved accuracy. In TargetCPP, first the peptide sequences are formulated with four distinct encoding methods i.e., composite protein sequence representation, composition transition and distribution, split amino acid composition, and information theory features. These dominant feature vectors were fused and applied intelligent minimum redundancy and maximum relevancy feature selection method to choose an optimal subset of features. Finally, the predictive model is learned through different classification algorithms on the optimized features. Among these classifiers, gradient boost decision tree algorithm achieved excellent performance throughout the experiments. Notably, the TargetCPP tool attained high prediction Accuracy of 93.54% and 88.28% using jackknife and independent test, respectively. Empirical outcomes prove the superiority and potency of proposed bioinformatics method over state-of-the-art methods. It is highly anticipated that the outcomes of this study will provide a strong background for large scale prediction of CPPs and instructive guidance in clinical therapy and medical applications.

The Role of Socio-demographics in Adoption of Religious-Spiritual and Other Coping Strategies Among Muslim Chronic Patients with Hepatitis C in Pakistan.

Coping has emerged as a vital indicator among patients in the chronic conditions. The current study examined the role of demographic characteristics (such as age, education, gender, marital status, residential background, family type and number of children) in adoption of coping (emotion-focused, problem-solving, religious-spiritual) strategies for nursing among hepatitis patients. A sample of 500 patients (of hepatitis C) was drawn from five most populous districts (Lahore, Faisalabad, Rawalpindi, Gujranwala and Multan) of Punjab, Pakistan, by using Epi Info software with an alpha level of 0.03. The data were collected using a well-structured multi-sectional interview schedule through multistage proportionate sampling technique. Descriptive analysis, regression analysis and reliability analysis were computed using SPSS (version 21.0). In the overall adoption of coping strategies, lower monthly household income, lower education, rural residences, nuclear family setting and married status were contributing to the adoption of higher coping strategies among Muslim chronic patients with hepatitis C. The results of socio-demographics are also discussed with other coping strategies (such as religious-spiritual coping strategies, problem-solving coping strategies, emotion-focused coping strategies and constructive coping strategies). It was the first quantitative study of adoption of coping strategies among Muslim hepatitis patients in Pakistan. The study highlighted the importance of socio-demographic resources to cope with chronic illness. The empirical findings would start a new discussion from hepatic, counseling and nursing perspective. For terminal patients, these socio-demographic characteristics can serve as a guideline to provide community sources of social support. Medical social workers and healthcare experts need to facilitate the efforts of patients to cope with chronic illness through revision of nursing policy according to the socio-demographic and spiritual-religious needs of the patients.

The Role of Socio-Economic Status in Adoption of Coping Strategies Among Adolescents Against Domestic Violence.

In the current study, researchers explored different types of coping strategies such as problem-focused coping, emotion-focused coping, and non-constructive coping of adolescents witnessing and experiencing domestic violence. Furthermore, they tried to find out the association of socio-economic status with coping strategies against domestic violence in family sphere. A cross-sectional survey was conducted with 210 adolescents of both sexes, aged 13 to 18 years in Hafizabad city using multistage sampling technique. Multivariate analysis was used to find out the association between adolescents' resistance and resilience strategies against domestic violence. The information was collected through a structured interview schedule. This study revealed that age, gender, parents' education, and family income were major factors that influenced the adoption of coping strategy among adolescents. Overall, the study suggested that adolescents were being victimized of various forms of domestic violence frequently in Pakistan, which needs to be addressed on immediate basis through policies and programs by integrating the social institutions of family and education. Findings of the study can enable parents to nurture and support the developmental needs of children in their care. It can help youth in defending themselves from extreme violent behavior adopters and preventing them from becoming the perpetrators of the domestic violence.

DEDICATED BREAST CANCER MANAGEMENT CENTRES WITH. FACILITIES FOR FULL IMAGE-GUIDED ASSESSMENT AND IMAGE-GUIDED SURGERY IN THE DEVELOPING AREAS OF PAKISTAN--A LONG OVERDUE NECESSITY.

BACKGROUND: Dedicated centres to manage breast cancers are important to combat this menace. An example of practice in the U.K. Hospitals is given with an attempt to explain reasons for an urgent need of dedicated breast cancer centres in developing areas of Pakistan. METHODS: The rates of breast conservation, mastectomy, and immediate breast reconstruction are compared between a centre in the U.K. and a secondary radiotherapy facility in developing areas in Pakistan for 2011. RESULTS: At Kettering General Hospital, 152 patients (71%) had breast conservation therapy including image-guided surgery, 45 (29%) had mastectomy and 15 (33.3%) had immediate breast reconstruction. All the 263 patients who had adjuvant therapy with surgery, has had mastectomy at the institute of radiotherapy and nuclear medicine (IRNUM) in Peshawar, and no patient had immediate reconstruction. CONCLUSION: The availability of mammogram in individual clinics in Peshawar, without the back up of dedicated breast cancer centre fails to materialize the dream of provision of whole spectrum of breast cancer care. Government and international donor organisations may need to be approached for. investment in technology and training of personnel.

The impact of PCR in the management of prosthetic joint infections.

An accurate diagnosis of prosthetic joint infection (PJI) remains a challenging clinical problem and is essential for the success of treatment regardless of the treatment option chosen by patients and surgeons. In recent years, PCR for the diagnosis of PJI has received much attention. Here, we review the impact of common PCR-based techniques on identifying causative organisms, antibiotic management and economics of PJI.

Assessment of odour problem in sewage-treated effluent in a closed loop irrigation system.

Uses of wastewater drives significant economic activity, supports countless livelihoods particularly those for developing countries. While using wastewater, the challenge is to identify practical, affordable safeguards that do not threaten the health of users. In Yanbu Al-Sinaiyah, treated sewage effluent (TSE) is used for landscape purposes. In the present study, the odour problem caused by TSE in community area has been addressed. Samples were collected and analysed for total coliform, odour, trihalomethanes (THMs), total organic carbon (TOC) and other physicochemical parameters. Results show that in distribution network, residual chlorine was below the detection limit, turbidity, THMs, TOC and total coliform concentration was much higher than point source, and concentration of these parameters was further increased in problematic areas. It was also observed that areas with odourous problem were at the tail of irrigation network. This indicates that odour problem was due to less residual chlorine high turbidity, high rate of coliform and TOC. In odourous water samples, carbon disulphide and dimethyl sulphide were also identified by GC/MS, while in other areas where there was no odour, both these compounds were not detected. Odour problem was successfully resolved by improving sand filtration system to minimise turbidity the main cause of odour, increasing the residual chlorine at the treatment plant and regularly flushing the distribution network.