Role of Endoscopic Assisted Microsurgery for Pituitary Tumors

Objective: To determine the outcome of endoscopic assisted microsurgery for pituitary tumors in terms of gross tumor removal and visual field improvement. Materials and Methods: This Descriptive case series conducted at Department of Neurosurgery, Lahore General Hospital Lahore over a period of six months from July 2012 to December 2012. Sixty five patients were included through non-probability purposive sampling technique. All cases of pituitary tumor diagnosed on MRI/CT scan of either gender having age 18 – 80 years and patients with recurrent cases, sellar and with suprasellar extension (assessed on CT and MRI findings). Informed consent was taken from the patients. All laboratory tests were done in hospital laboratory and reported by hospital pathologist Shaukat Khanum Memorial Hospital Lahore. Pre- and post-operative visual field status (at least 3 months after surgery) was analyzed. Surgery was performed by a single team of surgeons. Surgical procedure involves introduction of 4-mm to 2.7mm endoscope to visualize the sphenoethmoid recess. The bilateral sphenoid Ostia are entered. The posterior nasal septum was incised at middle turbinate and it was patients resected. All the data was entered and analyzed by using SPSS 20. Fre-quency and percentages were calculated for all qualitative variables like gross removal rate and visual filed improvement. Results: The mean age of the patients was 50.46 ± 17.80 years. There were 64.62% male patients and 35.38% female patients. Gross removal of tumor was observed in 56 (86.2%) and visual field improvement was found in 92.31% patients. 56 patients were those in which gross removal of tumor was observed in which 34 were males and 22 were females, similarly in 9 patients them was subtotal resection of tumor in which 8 were males and only 1 was female. Conclusion: In this study, gross removal of tumor as well as visual field improvement was found in maximum number of patients and it is concluded that endoscopic assisted microsurgery for pituitary tumors is a better technique for such surgeries.&nbsp

Anti-nociceptive and Anti-inflammatory Activities of Asparacosin A Involve Selective Cyclooxygenase 2 and Inflammatory Cytokines Inhibition: An in-vitro, in-vivo, and in-silico Approach

Triterpenes possess anti-inflammatory and anti-nociceptive effects. In this study anti-inflammatory activities of Asparacosin A were evaluated' using in-vitro cyclooxygenases 1 and 2 (COX-1/2) inhibition assays. Moreover, anti-nociceptive activities were assessed in-vivo by carrageenan-induced paw edema test, xylene-induced ear edema tests, and acetic acid-induced writhing and formalin tests. Additionally molecular docking was conducted to elucidate the binding mechanism of the compound and to correlate the in-vitro findings with the in-silico data. Oral administration of Asparacosin A at the doses of 10, 20, and 40 mg/kg induced significant anti-inflammatory effects (*p < 0.05, **p < 0.01, and ***p < 0.001) in a dose-dependent manner in both models. Asparacosin A also inhibited the human recombinant COX-2 enzyme and caused a dose-dependent decrease in the levels of TNF-α, IL-1β, and PGE2 in the carrageenan-induced paws. Moreover, Asparacosin A displayed significant anti-nociceptive effects (*p < 0.05, **p < 0.01, ***p < 0.001) at the doses of 10, 20, and 40 mg/kg in acetic-acid induced writhing test. However, in formalin test, Asparacosin A (10–40 mg/kg, p.o) produced anti-nociceptive effects only in the late phase, similar to the effect observed with the reference drug celecoxib (50 mg/kg, p.o). Molecular docking was carried out on both COX-1 and COX-2 structures which revealed that Asparacosin A targets allosteric binding site similar to the binding mode of the selective COX inhibitor. In conclusion, Asparacosin A exhibits anti-inflammatory and peripheral anti-nociceptive activities which are likely mediated via inhibition of COX-2 enzyme and inflammatory cytokines. Furthermore, Asparacosin A can serve as a model to obtain new and more selective potent anti-inflammatory and anti-nociceptive drugs

Identification of recurrent and novel mutations in TULP1 in Pakistani families with early-onset retinitis pigmentosa

Contains fulltext : 108208.pdf (publisher's version ) (Open Access)PURPOSE: To identify the genetic defects underlying retinitis pigmentosa (RP) in Pakistani families. METHODS: Genome-wide high-density single-nucleotide-polymorphism microarray analysis was performed using the DNA of nine affected individuals from two large families with multiple consanguineous marriages. Data were analyzed to identify homozygous regions that are shared by affected sibs in each family. Sanger sequencing was performed for genes previously implicated in autosomal recessive RP and allied retinal dystrophies that resided in the identified homozygous regions. Probands from both families underwent fundus examination and electroretinogram measurements. RESULTS: The tubby-like protein 1 gene (TULP1) was present in the largest homozygous region in both families. Sequence analysis identified a previously reported mutation (c.1138A>G; p.Thr380Ala) in one family and a novel pathogenic variant (c.1445G>A; p.Arg482Gln) in the other family. Both variants were found to be present in a homozygous state in all affected individuals, were heterozygous present in the unaffected parents, and heterozygous present or absent in normal individuals. Affected individuals of both families showed an early-onset form of RP. CONCLUSIONS: Homozygosity mapping, combined with candidate-gene analysis, successfully identified genetic defects in TULP1 in two large Pakistani families with early-onset retinitis pigmentosa

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Role of demographic diversity in online knowledge sharing

Knowledge sharing is not only the requirement of professional lives but it has proved its importance in daily lives as well. This study particularly addresses the behavior of knowledge sharing in online world. Therefore, this study explores the influence of demographic factors on the online knowledge sharing behavior in the sample of 319. In order to check the possible differences in the means of different demographic factor groups, this study applied independent sample t-test and one way analysis of variance (ANOVA). These findings are significant since they provide a better insight to the indifferent role of demographic diversity of students when it comes to online knowledge sharing as a result of online social interaction. This study can find many utilities regarding the course contents and online study plans in educational institutes and personnel screening of human resource in organizations

Trade Liberalisation Could Improve Producers Profitability in Agriculture: A Case of Basmati Rice.

This peace of research has been conducted, as part of PhD research of the first author, with the objectives to (i) identify various protection policies and interventions exercised in Basmati rice economy in Pakistan (ii) estimate welfare effects associated with existing protection policies and (iii) to estimate implications of WTO’s trade liberalisation in domestic economy and foreign markets. The quantitative analysis of data reveals that Basmati rice crop hanged about ‘price tax-cum-export tax’ regime during the study period. Welfare analysis of such policy interventions estimated higher losses to producers (Pak Rs 657.95 million per year) than gains to consumers (Rs 448.76 million per year) during pre-WTO period. The same trend continued during post-WTO period but producers’ losses were comparatively smaller i.e., 649.48 million per year. In case of free trade, simulation results demonstrate greater gains to producers than losses to consumers. If world market was liberalised, supplementary gains in the range of Rs 276.65 million to Rs 451.60 million per year during earlier and Rs 333.45 million to Rs 637.40 million per year during the later period would have occurred at domestic level. In light of analytical results, the following recommendations are made. (i) Government needs to curtail interventions in Basmati rice economy. (ii) Besides, improving the pace of trade liberalisation at domestic level, Pakistan should pursue with other members in WTO’s negotiations for early implementation of WTO’s trade liberalisation on international level. (iii) Government of Pakistan should gear up its efforts as facilitator of trade in accordance with WTO agreements and increase investment in areas of research, development, and out-reach. JEL classification: Q17, Q18, Q28 Keywords: Basmati Rice, Government Intervention, Welfare Effect, Trade Liberalisation, WTO

Enhancement of Cadmium Phytoremediation Potential of Helianthus annuus L. with Application of EDTA and IAA

The aim of the current study was to assess the cadmium (Cd) phytoremediation potential of Helianthus annuus L. that was exposed to 50, 100, and 150 mg/kg of cadmium for 15, 30, and 60 days with application of EDTA (Ethylenediaminetetraacetic acid) in the soil and IAA (indole acetic acid) as a foliar spray. The results indicated that the concentration, duration of exposure, and amount of Cd affect the phytoremediation potential. The maximum Cd was observed at 60 days (32.05, 16.86, and 10.63%) of Cd application, compared to 15 (2.04, 0.60, and 1.17%) or 30 days (8.41, 3.93, and 4.20%, respectively), in a dose-dependent manner. The application of EDTA in the soil and foliar IAA enhanced the Cd accumulation in the plants at 15, 30, and 60 days of exposure, with maximum accumulation at 60 days. Exposed plants with foliar IAA application showed 64.82%, 33.77%, and 25.84% absorption at 50, 100, and 150 mg/kg, respectively. Apart from higher absorption, the cadmium translocation to the edible part of the plants ceased, i.e., the seeds had 0% accumulation. The interesting fact was recorded that efficient phytoremediation was recorded at 15 days of exposure, whereas maximum phytoremediation was recorded at 60 days of exposure. To minimize the stress, the host also produced stress-related metabolites (i.e., flavonoids, phenolics, proline, and sugar) and antioxidants (i.e., catalases and ascorbate peroxidases). From the current evidence, it could be assumed that the use of EDTA and IAA, along with hyperaccumulating plants, could be a possible green method to remediate Cd-contaminated soil efficiently in a short period of time

Effect of Cadmium and Copper Exposure on Growth, Physio-Chemicals and Medicinal Properties of <i>Cajanus cajan</i> L. (Pigeon Pea)

Soil contamination with heavy metals is an emerging concern in the modern era, affecting all forms of life. Pigeon pea is a multi-use shrub with medicinal and nutritional values. On the basis of a randomized complete design, we investigated in the current project the combined cadmium (Cd) and copper (Cu) effect on plant growth and physio-chemical/medicinal properties of pigeon pea. Three-week-old seedlings were grown in combined Cd and Cu amended soil with increasing metal concentrations (control, 20 + 30 mg/kg, 40 + 60 mg/kg, and 60 + 90 mg/kg) for three months. At high-dose metal cumulative stress (60 + 90 mg/kg), plant shoot and root growth in terms of plant height as well as fresh and dry weight were significantly inhibited in association with decreased photosynthetic attributes (chlorophyll a and b contents, net photosynthesis, transpiration rate, stomatal conductance, intercellular CO2 concentrations) and diminished nutrient contents. Cd and Cu at high amounts inflicted oxidative stresses as assessed in elevated lipid peroxidation (MDA), hydrogen peroxide (H2O2), and electrolyte leakage contents. Antioxidant enzyme activities, namely, those of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione peroxidase (GPX), were enhanced, along with proline content with increasing metal quantity. Phenolics and flavonoids exhibited a diverse response regarding metal concentration, and their biosynthesis was significantly suppressed at high Cd and Cu cumulative stress. The reduction in secondary metabolites may account for declined medicinal properties of pigeon pea as appraised in reduced antibacterial, 2, 2-diphenyl-1-picrylhydrazyl (DPPH), and ferric-reducing antioxidant potential (FRAP) activities. Our results clearly demonstrate that the exposure of pigeon pea to Cd- and Cu-contaminated soil might affect consumers due to the presence of metals and the negligible efficacy of the herbal products

Identification of &alpha;-Glucosidase Inhibitors from Scutellaria edelbergii: ESI-LC-MS and Computational Approach

The recent study investigated the in vitro anti-diabetic impact of the crude extract (MeOH) and subfractions ethyl acetate (EtOAc); chloroform; n-butanol; n-hexane; and aqueous fraction of S. edelbergii and processed the active EtOAc fraction for the identification of chemical constituents for the first time via ESI-LC-MS analysis through positive ionization mode (PIM) and negative ionization mode (NIM); the identified compounds were further validated through computational analysis via standard approaches. The crude extract and subfractions presented appreciable activity against the &alpha;-glucosidase inhibitory assay. However, the EtOAc fraction with IC50 = 0.14 &plusmn; 0.06 &micro;g/mL revealed the maximum potential among the fractions used, followed by the MeOH and n-hexane extract with IC50 = 1.47 &plusmn; 0.14 and 2.18 &plusmn; 0.30 &micro;g/mL, respectively. Moreover, the acarbose showed an IC50 = 377.26 &plusmn; 1.20 &micro;g/ mL whereas the least inhibition was observed for the chloroform fraction, with an IC50 = 23.97 &plusmn; 0.14 &micro;g/mL. Due to the significance of the EtOAc fraction, when profiled for its chemical constituents, it presented 16 compounds among which the flavonoid class was dominant, and offered eight compounds, of which six were identified in NIM, and two compounds in PIM. Moreover, five terpenoids were identified&mdash;three and two in NIM and PIM, respectively&mdash;as well as two alkaloids, both of which were detected in PIM. The EtOAc fraction also contained one phenol that was noticed in PIM. The detected flavonoids, terpenoids, alkaloids, and phenols are well-known for their diverse biomedical applications. The potent EtOAc fraction was submitted to computational analysis for further validation of &alpha;-glucosidase significance to profile the responsible compounds. The pharmacokinetic estimations and protein-ligand molecular docking results with the support of molecular dynamic simulation trajectories at 100 ns suggested that two bioactive compounds&mdash;dihydrocatalpol and leucosceptoside A&mdash;from the EtOAc fraction presented excellent drug-like properties and stable conformations; hence, these bioactive compounds could be potential inhibitors of alpha-glucosidase enzyme based on intermolecular interactions with significant residues, docking score, and binding free energy estimation. The stated findings reflect that S. edelbergii is a rich source of bioactive compounds offering potential cures for diabetes mellitus; in particular, dihydrocatalpol and leucosceptoside A could be excellent therapeutic options for the progress of novel drugs to overcome diabetes mellitus