COUNTERING TERRORISM AND REDUCING STRATEGIC UNCERTAINTY: ANALYSING ‘SHAPING’ MULTINATIONAL MILITARY EXERCISES

The post-Cold War period has witnessed a significant increase in ‘shaping’ multinational military exercises, which are considered a valuable instrument of defence diplomacy. Shaping multinational military exercises aim to encourage the partner military's role and adapt relationship to reduce strategic uncertainty. Since 2014, Pakistan’s conduct and participation in multinational military exercises have increased significantly. Pakistan conducts four such exercises to reduce strategic uncertainty: recruitment, capacity-building, role-forming, and trust-developing. This article, therefore, argues that Pakistan pursues shaping multinational military exercises to mould the strategic thinking of both friends and potential adversaries to achieve foreign policy goals in a complex security environment.   Bibliography Entry Bashir, Sadaf, and Sumara Gul. 2021. "Countering Terrorism and Reducing Strategic Uncertainty: Analysing ‘Shaping’ Multinational Military Exercises." Margalla Papers 25 (2): 71-83

Expression and sequence characterization of growth hormone binding protein of Nili-Ravi buffaloes (Bubalus bubalis)

The growth hormone binding protein (GHBP) was isolated from the liver of Nili-Ravi buffaloes (Bubalus bubalis), reverse transcriptase-polymerase chain reaction (RT-PCR) amplified and sequence characterized. RT-PCR analysis demonstrated high degree sequence identities (97.3 to 99.6%) of BbGHBP cDNA with Bos taurus, Ovis aries and Capra hircus. An expression plasmid was constructed for the production of BbGHBP in Escherichia coli BL21 (RIPL) CodonPlus under the control of T7lac promoter. On induction with isopropyl β-D thiogalactopyranoside, the BbGHBP was expressed at levels >30% of the total E. coli proteins. The target protein expressed as inclusion bodies was solubilized in denaturing solution and refolded by step/pulsatile dilution method using cysteine and cystine redox potential. Purification to near homogeniety (>98%) was achieved by ion-exchange chromatography with a recovery yield of 64%. Mass spectrometric analysis of the purified BbGHBP showed a single peak of 30,756 Da. A radioprotein assay evaluated the binding affinity of recombinant BbGHBP with iodinated bovine growth hormone (bGH) which demonstrated active conformation of BbGHBP. These results demonstrate high expression and sequence characterization of BbGHBP in Nili-Ravi buffaloes and provide the basis for the assessment of BbGHBP in other breeds of buffalo.Keywords: Liver, Nili-Ravi buffalo, GHBP, MALDI-TOF mass spectrometry, radioprotein binding assay, refoldin

SERUM PROTEIN PROFILE OF MALARIA PATIENTS THROUGH SDS PAGE METHOD

Background: Malaria is a crucial disease that causes huge mortality and morbidity, along with economic losses in term of purchasing medicines in underdeveloped countries such as Pakistan. Materials and Methods: A total of 150 human blood samples were collected from the Districts of Karak and Kohat Khyber Pakhtunkhwa, in Pakistan, and were examined through microscopy and then all positive samples were analyzed by SDS-PAGE method for the detection of antibodies against plasmodium. Result: The overall prevalence of malaria was found to be 18% (27/150). The prevalence of plasmodium species was “21.3% (16/75) and 14.6% (11/75) in the Districts of Karak and Kohat respectively. The prevalence of plasmodium species i.e. P. vivax and P. falciparum, in the Districts of Karak and Kohat, was found to be 14.6% (22/150) and 3.33% (5/150) respectively. Among these, P. vivax 10.6% (8/75) and P.falciparum 4% (3/75) were noted in the District of Kohat; while P. vivax 18.6% (14/75) and P. falciparum 2.6% (2/75) were found in the District of Karak Khyber Pakhtunkhwa, Pakistan respectively”. The serum protein of malaria patients were 57KDA and 78KDA bands, which were determined by Sodium Dodecyl Sulfate Poly-Acrylamide Gel Electrophoresis (SDS-PAGE) technique. Conclusion: The SDS page method is the most accurate diagnostic assay and was recognized as a most reliable method in the diagnosis of antibodies produced against Plasmodium spps. The proteins bands of Serum protein of malaria patients may be undertaken for study to develop possible future vaccine

Wood-derived biochar influences nutrient use efficiency of heavy metals in spinach (spinacia oleracea) under groundwater and wastewater irrigation

Present study analysed the influence of slow-pyrolyzed wood-derived biochar on growth performance and heavy metal accumulation in the leaves of spinach grown under groundwater and wastewater irrigation. Biochar was applied in soil as 5% (~30 t·ha−1) and 10% (~60 t·ha−1) amendment. According to results, plant biomass was significantly higher under wastewater than groundwater irrigation. Biochar amendment increased significantly the aboveground plant biomass and root biomass and promoted water use efficiency (WUE). Under groundwater irrigation, biochar amendment at 10% application rate, increased the leaf area index (P < 0.05), while amendment of biochar at all application rates significantly reduced leaf area index under wastewater irrigation (P < 0.05). Application of biochar also reduced accumulation of rhizosphere soil around roots under wastewater irrigation, indicating less exudate production in the rhizosphere of plants. Biochar significantly reduced the concentration of copper (Cu) in under wastewater irrigation. Biochar increased the nutrient use efficiency (NUE) of plants for zinc (Zn) and Cu under wastewater irrigation

Impact of Non-Surgical Periodontal Therapy on HbA1c Levels of Type 2 Diabetes at Khyber College of Dentistry, Peshawar: A Quasi-Experimental Study

Background: Diabetes mellitus (DM) constitutes a spectrum of persistent metabolic disorders originating from irregular glucose metabolism due to insufficient insulin production, compromised insulin function, or a combination of the two, leading to elevated blood sugar levels. This study assessed the influence of non-surgical periodontal therapy on glycated hemoglobin (HbA1c) levels in individuals with Type 2 Diabetes. Methods: This quasi-experimental study was conducted at Khyber College of Dentistry, Peshawar, with 40 participants diagnosed with Type 2 diabetes for more than 3 years and suffering from chronic periodontitis. Patients with Type 1 diabetes, pregnant women, and those with other medical complications were excluded. HbA1c levels were assessed at baseline, and non-surgical periodontal therapy was administered. Patients were educated and scheduled for a follow-up after 3 months when HbA1c levels were reassessed. A paired t-test was employed to compare HbA1c levels pre-and post-intervention. Results: In this study, males were 29 (58%) whereas 21 (42%) females. The mean value of HbA1c was less post-treatment with non-surgical periodontal therapy (6.928±0.866%) than pretreatment (9.048±0.73%) and results were statistically significant (p<0.001). After receiving therapy, the HbA1c level was significantly reduced in both genders (p<0.001).  Irrespective of smoking status, the reduction of HbA1c level was statistically significant (p=0.01). Conclusion: Non-surgical periodontal treatment significantly reduces HbA1c levels, indicating a potentially positive impact on glycemic control in individuals with diabetes, which has enhanced the dentist’s role as a part of the health team, and timely interventions can significantly improve prognosis

Synthesis, characterization, lipoxygenase, and tyrosinase inhibitory activities of non- cytotoxic titanium(III) and (IV) hydrazide complexes

Ti(III) and (IV) hydrazide complexes were synthesized, characterized, and screened for their tyrosinase and lipoxygenase inhibitory and cytotoxic activities. The geometry of Ti(III) hydrazide complexes is tentatively assigned as octahedral. Magnetic moments were found around 1.7 B.M. and electronic spectral transition in the range of 495-518 nm. Evaluation of Ti(IV) and Ti(III) hydrazide complexes for tyrosinase and lipoxygenase inhibitory activities revealed varying inhibition potential. Hydrazide ligands were inactive against tyrosinase, while significant activity was observed against lipoxygenase (LOX). Good to moderate inhibition activity was observed by Ti(IV) and Ti(III) hydrazide complexes against both enzymes. At the same time, promising results were obtained for Ti(IV) hydrazide complexes against tyrosinase enzymes suggesting their broad application as tyrosinase inhibitors. Complex 4d possess negative inhibition, thus behaving as a tyrosinase activator. The docking results showed a good correlation between complex experimental activities and binding energies. Cytotoxic investigation revealed the non-toxicity of complexes against normal cells.Z. Shaikh is thankful to the Higher Education Commission for Indigenous Scholarship No. 213-65456-2PS2-101 under Ph.D. Fellowships for 5000 scholars, HEC (Phase-II). Furthermore, the authors thank the Higher Education Commission of Pakistan for financial support (‘The National Research Grants Program for Universities’, Grant No. 1862/R&D/10)

Discovery of novel 1,2,4-triazole tethered β-hydroxy sulfides as bacterial tyrosinase inhibitors: synthesis and biophysical evaluation through in vitro and in silico approaches

In this study, a series of 1,2,4-triazole-tethered β-hydroxy sulfide scaffolds 11a–h was synthesized in good to remarkable yields (69–90%) through the thiolysis of oxiranes by the thiols in aqueous basic catalytic conditions. The synthesized 1,2,4-triazole-tethered β-hydroxy sulfides were screened against bacterial tyrosinase enzyme, and Gram-positive and Gram-negative bacterial cultures i.e., (S. aureus) Staphylococcus aureus & (E. coli) Escherichia coli. Among the synthesized derivatives, the molecules 11a (IC50 = 7.67 ± 1.00 μM), 11c (IC50 = 4.52 ± 0.09 μM), 11d (IC50 = 6.60 ± 1.25 μM), and 11f (IC50 = 5.93 ± 0.50 μM) displayed the better tyrosinase inhibitory activity in comparison to reference drugs ascorbic acid (IC50 = 11.5 ± 1.00 μM) and kojic acid (IC50 = 30.34 ± 0.75 μM). The molecule benzofuran-triazol-propan-2-ol 11c proved to be the most potent bacterial tyrosinase inhibitory agent with a minimum IC50 of 4.52 ± 0.09 μM, as compared to other synthesized counterparts and both standards (kojic acid and ascorbic acid). The compound diphenyl-triazol-propan-2-ol 11a and benzofuran-triazole-propan-2-ol 11c showed comparable anti-bacterial chemotherapeutic efficacy with minimum inhibitory concentrations (MIC = 2.0 ± 2.25 mg mL−1 and 2.5 ± 0.00 mg mL−1, respectively) against S. aureus bacterial strain in comparison with standard antibiotic penicillin (MIC = 2.2 ± 1.15 mg mL−1). Furthermore, among the synthesized derivatives, only compound 11c demonstrated better anti-bacterial activity (MIC = 10 ± 0.40 mg mL−1) against E. coli, which was slightly less than the standard antibiotic i.e., penicillin (MIC = 2.4 ± 1.00 mg mL−1). The compound 11c demonstrated a better binding score (−7.08 kcal mol−1) than ascorbic acid (−5.59 kcal mol−1) and kojic acid (−5.78 kcal mol−1). Molecular docking studies also validate the in vitro anti-tyrosinase assay results; therefore, the molecule 11c can be the lead bacterial tyrosinase inhibitor as well as the antibacterial agent against both types of bacterial strains after suitable structural modifications

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit