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Introduction: Appropriate perinatal care provision and utilization is crucial to improve maternal and newborn survival and potentially meet Sustainable Development Goal 3. Ensuring availability of healthcare infrastructure as well as skilled personnel can potentially help improve maternal and neonatal outcomes globally as well as in resource-limited settings. Methods: A systematic review on effectiveness of perinatal care regionalization was updated, and a new review on facility-based interventions to improve postnatal care coverage and outcomes was conducted. The interventions were identified through literature reviews and included transport, mHealth, telemedicine, maternal education, capacity building, and incentive packages. Search was conducted in relevant databases and meta-analysis conducted on Review Manager 5.4. We conducted subgroup analysis for evidence from low- and middle-income countries (LMICs). Results: Implementation of regionalization programs significantly decreased maternal mortality in LMICs (OR: 0.43; 95% CI: 0.34–0.55, 2 studies), stillbirth overall (OR: 0.70; 95% CI: 0.54–0.89, 5 studies), perinatal mortality overall (OR: 0.54; 95% CI: 0.5–0.58, 2 studies), and LMICs (OR: 0.54; 95% CI: 0.50–0.58, 1 study). Transport-related interventions significantly decreased maternal mortality overall (OR: 0.55; 95% CI: 0.40–0.74, 1 study), neonatal mortality (RR: 0.76; 95% CI: 0.66–0.88, 1 study), perinatal mortality (RR: 0.86; 95% CI: 0.77–0.95, 1 study), and improved postnatal care coverage (OR: 6.89; 95% CI: 5.15–9.21, 1 study) in LMICs. Adding maternity homes/units significantly decreased stillbirth (OR: 0.75; 95% CI: 0.61–0.93, 1 study) in LMICs. Incentives for postnatal care significantly improved infant mortality (RR: 0.79; 95% CI: 0.65–0.96, 1 study), stillbirth (OR: 0.60; 95% CI: 0.44–0.83, 1 study), and postnatal care coverage (RR: 1.13; 95% CI: 1.03–1.25, 1 study) in LMICs. Telemedicine improved postnatal care coverage significantly in LMICs (RR: 2.54; 95% CI: 1.22–5.28, 3 studies) and decreased maternal mortality (OR: 0.46; 95% CI: 0.21–0.98, 1 study) and infant mortality (OR: 0.65; 95% CI: 0.45–0.95) in LMICs. Maternal education significantly decreased neonatal mortality (RR: 0.75; 95% CI: 0.66–0.84, 2 studies), perinatal mortality (RR: 0.86; 95% CI: 0.77–0.95, 1 study), infant mortality (RR: 0.79; 95% CI: 0.65–0.96, 1 study), and stillbirth (RR: 0.61; 95% CI: 0.45–0.82, 1 study). Capacity-building interventions significantly decreased maternal mortality in LMICs (OR: 0.37; 95% CI: 0.29–0.46, 5 studies), neonatal mortality overall (OR: 0.72; 95% CI: 0.53–0.98, 4 studies) and in LMICs (OR: 0.63; 95% CI: 0.54–0.74, 3 studies, and RR: 0.61; 95% CI: 0.48–0.79, 3 studies), perinatal mortality (OR: 0.53; 95% CI: 0.45–0.62, 2 studies, and RR: 0.86; 95% CI: 0.77–0.95, 1 study), infant mortality (OR: 0.50; 95% CI: 0.43–0.59, 1 study, and RR: 0.79; 95% CI: 0.65–0.96, 1 study), under-5 mortality (RR: 0.79; 95% CI: 0.66–0.94, 1 study), and stillbirth in LMICs (OR: 0.71; 95% CI: 0.62–0.82, 4 studies), and preterm birth overall (OR: 0.39; 95% CI: 0.19–0.81, 1 study). Conclusion: Perinatal regionalization and facility-based interventions have a positive impact on maternal and neonatal outcomes and calls for implementation in high burden settings but a better understanding of optimal interventions is needed through comprehensive trials in diverse settings. [ABSTRACT FROM AUTHOR]

The current study was designed to assess the safety and quality status of street‐vended barbecue chicken samples. The samples were collected from four regions of Faisalabad city: Ghulam Mohammad Abad (R1), Jhang Road (R2), Sargodha Road (R3), and Satiana Road (R4); and compared with the self‐prepared barbecue chicken sample (R0). Purposely, all the collected samples were subjected to assess the quality aspects by physicochemical analyses. The results of the physicochemical analysis showed that moisture content varied from 54% to 60%, crude protein 26.97% to 32.87%, crude fat 7.25% to 9.00%, crude ash 1.61% to 1.72%, pH 5.60 to 6.30, free fatty acid value 1.00% to 1.39%, and peroxide value 0.63 to 0.84 meq/Kg. Results pertaining to the enumeration of total microbial load and total coliform count exhibit 2.39–5.17 and 1.20–3.20 log cfu/g, respectively. The samples were assessed for heavy metals (Pb, Zn, Cd, and Fe) by atomic absorption spectrophotometer (AAS). The concentration of highly toxic metals Pb and Cd was found to be much higher than recommended value as they ranged from 1.90 to 3.70 mg/kg for Pb and 0.10 to 0.90 mg/kg for Cd. However, the level of essential metals (Fe and Zn) in barbecue chicken samples ranged from 67.10 to 180 and 8.30 to 35.80 mg/kg which was much higher than their safe limits for Fe (15 ppm) and Zn (5 ppm), respectively. The study concludes that the consumption of street‐vended barbecue chicken possesses to be a serious public health risk for consumers. [ABSTRACT FROM AUTHOR]

This research work aims at providing power quality improvement for the nonlinear load to improve the system performance indices by eliminating maximum total harmonic distortion (THD) and reducing neutral wire current. The idea is to integrate a shunt hybrid active power filter (SHAPF) with the system using machine learning control techniques. The system proposed has been evaluated under an artificial neural network (ANN), gated recurrent unit, and long short-term memory for the optimization of the SHAPF. The method is based on the detection of harmonic presence in the power system by testing and comparison of traditional pq0 theory and deep learning neural networks. The results obtained through the proposed methodology meet all the suggested international standards of THD. The results also satisfy the current removal from the neutral wire and deal efficiently with minor DC voltage variations occurring in the voltage-regulating current. The proposed algorithms have been evaluated on the performance indices of accuracy and computational complexities, which show effective results in terms of 99% accuracy and computational complexities. deep learning-based findings are compared based on their root-mean-square error (RMSE) and loss function. The proposed system can be applied for domestic and industrial load conditions in a four-wire three-phase power distribution system for harmonic mitigation. [ABSTRACT FROM AUTHOR]

Background: The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) trial proved that tranexamic acid (TXA) is a time-dependent drug, having a better outcome if given within 1-hour of injury. In order to test this theory, studies have been conducted to examine the effect of TXA in the pre-hospital setting. We conducted a systematic search and meta-analysis to evaluate the role of TXA administration in the civilian pre-hospital setting on patient outcomes. Methods: Embase, Medline, CINAHL and Cochrane were searched for randomized control trials (RCTs), retrospective, and prospective studies that examined the effect of TXA on patients in the pre-hospital setting versus a control group. Outcome measures were overall mortality rate and thromboembolic events. Two authors extracted the data independently. To appraise the included studies, we used the NIH quality assessment tool for cohort and cross-sectional studies. Results are presented as Risk Ratio (RR), a random-effect model was implemented, and the I2 test was used to assess heterogeneity. Results: The search identified 1886 papers, but only five retrospective studies met the inclusion/exclusion criteria and were selected for further analysis. A meta-analysis confirmed that TXA reduced the overall mortality rate (pooled risk ratio of 0.74 (95% CI 0.45, 1.25)) and thromboembolic events (risk ratio of 0.71 (95% CI 0.35, 1.44)). Conclusion: The pooled effects for both outcome measures favour the administration of TXA in the pre-hospital setting, although none of the findings reported a significant effect. Our study highlights the need for additional high-quality evidence to validate the significance of these findings. Level of evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Technology enabled learning: Policy, pedagogy and practice: edited by Sanjaya Mishra and Santosh Panda, Vancouver, Commonwealth of Learning, 2020, open access, 264pp. ICTs must be included as a part of policy implementation, as institutional infrastructure, as teaching and learning tools and in the form of open educational resources, massive open online courses and blended courses. The key areas highlighted in the book are technology-enabled learning, Open Education Resources, online and blended education, application of information and communication technologies and Information and Communication Technologies policy intervention. [Extracted from the article]

Background: Intrauterine contraceptive devices (IUCDs) are considered as one of the safest and effective form of contraception. There are 128 million women users worldwide. We fall in those countries where unmet need of contraception is still high. Motivating women for intra caesarean copper T insertion can reduce the incidence of unplanned pregnancies. Postpartum intrauterine contraceptive device (PPIUCD) insertion is an effective, long-term, reversible, non-hormonal contraceptive and best suited for most women. This study was conducted to evaluate the long term complications like bleeding, pain, expulsion rate, perforation, infection and missing strings amongst the users. Objective: To determine the frequency of complications of intra - caesarean IUCD insertion. Methodology: This study was conducted in Lady Willingdon hospital, Lahore after approval of ethical committee. The non-probability purposive sampling technique was used. Informed consent was taken from all the patients. IUCD insertion was done under aseptic technique by the researcher. Women were advised to attend for follow-up after 6 weeks. Information was obtained about the complications of IUCD through a proforma that was same for all cases and the variables are listed under heading of operational definitions. Setting: Lady Willingdon Hospital Lahore, a Leading Tertiary Care Hospital Results: Total no of insertions in our study were 250 and they were followed for a period of 6 months. Mean age of the patients was 27.16 years. The patients who received PPIUCD with no previous baby was 14.8%, para one 18.4%, para two were 24.4% and 42.4% were with higher parity. Continuation rate was higher with 85.2% at the end of 6 months as compared to the expulsion rate of 14.8%. Bleeding was reported in 14 %, pain in 10% and infection in 18 % of cases. Missing strings were observed in 12% of cases. Removal rate after 6 months was 10%. Majority of the removal were due to infection 5% followed by planning a pregnancy in 3%. Pain was the cause for removal in only 0.5% and bleeding in 0.5% cases. Conclusion: Intra caesarean IUCD insertion was concluded to be a safe and effective method of contraception for spacing with high continuance rate, low expulsion and complication rates. [ABSTRACT FROM AUTHOR]

Background: Maternal nutrition is critically important for the well-being of both the mother and the developing fetus. Multiple micronutrient (MMN) supplements have the added advantage of addressing nutritional deficiencies. This study aimed to review the effects of MMN supplementation trials to prevent maternal and fetal complications from the preconception period to the post-natal phase by incorporating adequate micronutrients into the daily diet. Methodology: A comprehensive review of online literature was conducted following PRISMA guidelines. Three databases--PubMed, ScienceDirect, and Google Scholar--were searched for clinical trials from 2019 to 2023. MeSH terms such as "maternal," "micronutrient supplementation," "Pakistan," "trials," "clinical trials," and "micro-element supplementation" were used with Boolean operators "AND" and "OR." Titles and abstracts of the articles were screened initially, followed by full-text reviews in the second round. A total of seven articles meeting the inclusion criteria and diagnostic accuracy (STARD) were selected. Results: Risk of bias and quality assessment of clinical trials were evaluated using a 23-item questionnaire, with scores ranging from 0 to 2. Conclusion: Nutritional supplements were found to be most effective when taken daily for three months before conception and continued throughout the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

The use of plant protection products (PPPs) has become fundamental to guarantee excellent field productivity. Nevertheless, their usage presents critical issues, such as the quantity of substances used, the relative toxicity, and the contamination of nearby fields caused by atmospheric drift. This study focuses on the characterization of aerosol droplets of PPPs produced by spraying a chemical marker, fluorescein, with an orchard airblast sprayer equipped with conventional hollow cone (HC) and anti-drift air inclusion (AI) nozzles, using a wind tunnel as a controlled environment. A particle/droplet image analysis was employed to study the droplet production of the nozzles, while a liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analysis allowed us to evaluate samples collected using a cascade impactor located at 5 m, 10 m, and 20 m from the emission point. Overall, HC nozzles are very accurate at producing specific drop size distributions (DSDs), while AI nozzles produce a much wider DSD, concentrating the largest part of the distributed volume into droplets of a larger size. The marker concentration was much lower for the AI nozzles compared to the HC nozzles; moreover, the two nozzles show a similar trend in the coarse droplet range, while significantly differing in the fine droplet spectrum. [ABSTRACT FROM AUTHOR]

Objective: To determine the sensitivity of axillary ultrasound in detecting axillary nodal metastasis in clinically and radiologically uninvolved axillary nodes in early carcinoma breast by comparing with sentinel node biopsy histopathology on frozen section. Study Design: Comparative cross-sectional study Place and Duration of Study: Breast Clinic, CMH, Rawalpindi Pakistan, from Aug 2020 to May 2021. Methodology: Patients included in the study presented with breast cancer lesions with clinically impalpable axillary lymph nodes aged 18-75. Patients with clinically impalpable nodes underwent an ultrasound of the axilla; if suspicious nodes were found, the patient had subsequent axillary node dissection. Sentinel node biopsy (SLNB) was performed on axillary ultrasound in all patients with no suspicious or benign-looking nodes. Histopathological reporting was taken as standard. Lymph nodal status on axillary ultrasound, SLN biopsy and axillary lymph node clearance were documented and analyzed. Results: Twenty-nine patients were included who had benign-looking lymph nodes on axillary ultrasound and underwent sentinel lymph node biopsy. The mean age of the patients was 54.03 ± 7.94. Out of 29 patients, 24(82.8%) patients had negative Sentinel lymph node biopsy, and 5(17.2%) had positive Sentinel lymph node biopsy, who then underwent axillary lymph node dissection. Conclusion: Sentinel lymph node biopsy is the gold standard to determine axillary lymph nodes involved in early carcinoma breast, which seem benign on pre-operative axillary ultrasound. [ABSTRACT FROM AUTHOR]

A novel mobile cone-beam computed tomography (CBCT) imaging device (Elekta Inc.) aims to improve efficiency with on-demand imaging in the HDR vault during and after applicator insertion. We evaluated whether inter-observer contour variability of standard organs-at-risk (OARs) was similar using this novel CBCT (Ring-CBCT) as compared to diagnostic-quality simulation CT (CT-Sim) for cervical cancer HDR brachytherapy. A patient with stage IIB cervical cancer was implanted with the CT/MR Venezia Tandem (6-cm, 30-deg) with 26-mm dia. Lunar Ovoids. Images were acquired with Ring-CBCT (Elekta ImagingRing v 2.5.2) using 120 kVp, 8 mA, and 0.6x0.6x1.2 mm voxel size, and CT-Sim (Siemens SOMATOM go.Open Pro) using department standard pelvis imaging protocol (120 kVp, 1.17x1.17x1 mm voxel size, 0.8 pitch). Zypher transfer system (Orfit Inc.) was used to move patient to reduce applicator motion. Bladder, rectum, sigmoid, and lower bowel were independently contoured by 11 brachytherapists on Ring-CBCT and CT-Sim in Oncentra TPS. After each session, the physician answered a survey with a score from 1-10 for a qualitative evaluation of their comfort level for each contour. Inter-observer contour variability was quantitatively evaluated using Average Surface Distance, 95% Housdorff Distance, 100% Housdorff Distance, Surface Overlap, Surface Dice, and Volumetric Dice comparisons between a reference contour (RA) and each physician's contour. Wilcoxon signed-rank test was applied to test the statistical difference between the metrics on CT-sim and Ring-CBCT. Eleven physicians completed all four OAR contours on both imaging modalities and completed all surveys. The questionnaire results revealed there was greater confidence in the CT contours when compared to the Ring-CBCT contours. Comfort levels were a median of 10 (9-10) vs. 8 (6-10 (p<0.01) for bladder, 9 (8-10) vs. 8 (4-10) (p<0.01) for rectum, 8.5 (8-10) vs. 6.5 (2-10) (p<0.001) for sigmoid and 8 (7-10) vs. 5 (1-10) (p<0.001) for bowel, respectively. Inter-observer variations in OAR delineation on CT-sim and Ring CBCT are shown in Table 1. Overall, CT-sim showed lower interobserver variation when compared to the Ring-CBCT. There were no statistically significant differences between contour variability with Ring-CBCT when compared to contour variability assessed with CT-sim for most OARs and metrics evaluated. Bladder showed the most prevalent statistically significant variability differences between CT-Sim and Ring-CBCT as evaluated by surface metrics (Average Surface Distance and Hausdorff Distance). Using a multi-center approach and a comprehensive suite of comparison metrics, this study provides the first report of image quality assessment of a novel Ring CBCT for HDR applications. Our data show that for the presented patient, the contours generated using the Ring-CBCT show similar variability when compared to contours generated using standard of care CT-Sim imaging. Based on the physician survey however, OARs contouring confidence with CT-Sim is higher than Ring-CBCT. This study provides a framework for future studies of CBCT imaging for OARs delineation and treatment planning for gynecological cancer brachytherapy. [ABSTRACT FROM AUTHOR]

Context: To provide a systematic review and cost-effectiveness analysis on smoking interventions targeting smokers not ready to quit, a population that makes up approximately 32% of current smokers.Evidence Acquisition: Twenty-two studies on pharmacological, behavioral, and combination smoking-cessation interventions targeting smokers not ready to quit (defined as those who reported they were not ready to quit at the time of the study) published between 2000 and 2017 were analyzed. The effectiveness (measured by the number needed to treat) and cost effectiveness (measured by costs per quit) of interventions were calculated. All data collection and analyses were performed in 2017.Evidence Synthesis: Smoking interventions targeting smokers not ready to quit can be as effective as similar interventions for smokers ready to quit; however, costs of intervening on this group may be higher for some intervention types. The most cost-effective interventions identified for this group were those using varenicline and those using behavioral interventions.Conclusions: Updating clinical recommendations to provide cessation interventions for this group is recommended. Further research on development of cost-effective treatments and effective strategies for recruitment and outreach for this group are needed. Additional studies may allow for more nuanced comparisons of treatment types among this group. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To calculate the frequencies of various histopathological types of prostatic diseases and to assess the grade of the prostate cancer. STUDY DESIGN: A cross sectional study. PLACE AND DURATION: The study was conducted from 1st January 2014 to 31st August 2015 at pathology laboratory of Al Nafees Medical College & Hospital, Islamabad. METHODOLOGY: 170 Prostate specimen including, Transurethral resection of prostate (TURP), transvesical prostatectomy (TVP) and Needle biopsies were included in the study. Cases of carcinoma were graded according to Modified Gleason score for diagnostic purpose and to assess the frequency. Data was analyzed by SPSS version 17. Frequencies were calculated in terms of percentages. RESULTS: Out of 170 prostate samples, there were 78.8% Benign and 21.2% malignant cases. All Benign cases were diagnosed as Benign Prostatic Hyperplasia (BPH) i-e 78.8%. The additional findings noted in the benign cases along with BPH were prostatitis in 5.2% cases. There was Acute/chronic prostatitis in 3% cases, Granulomatous prostatitis in 1.5% cases and Eosinophilic prostatitis in 0.7% case. Among the Malignant 21.2% cases, Prostatic acinar adenocarcinoma was seen in 11.1%. Among the malignant cases there were 5.8% cases of Transitional cell carcinoma. All cases of adenocarcinoma were graded by Modified Gleason scoring. Grade 8 (38.2%) was most frequently diagnosed. CONCLUSION: Benign prostatic hyperplasia (BPH) was the most common pathology followed by prostatic acinar adenocarcinoma. [ABSTRACT FROM AUTHOR]

Endometriosis is a common gynecologic problem. Malignant transformation of endometriosis, though a rare event, is well documented. Synchronous endometrial and ovarian carcinoma either primary or metastatic is also uncommon. Here we report a case of endometriosis with concurrent ovarian and uterine endometroid carcinoma. [ABSTRACT FROM AUTHOR]

Tyrosinase (EC1.14.18.1) was extracted from oyster mushroom, Pleurotus ostreatus, using 100 mM potassium phosphate buffer (pH 5.8) containing 1 mM of ethylenediaminetetra acetic acid. The enzyme was purified by ammonium sulfate precipitation, followed by Sephadex G-100 and diethylaminoethyl chromatography. The purified enzyme showed a specific activity of 46.4 U/mg with 20.3% yield. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed single peptide chain with a molecular weight of 75 kDa. The enzyme has optimum activity on pH 6.0 at 35? C. The kinetics parameter with L-DOPA (3,4-dihydroxy-L-phenylalanine), with a KM of 0.119 mM and Vmax of 2.97 mM. Thus, purified tyrosinase from P.ostreatus showed similarities with other tyrosinase sources. The results indicate that P.ostreatus can be a novel and better source of tyrosinase extraction due to its higher specific activity. The information offered here should help food industry in developing and using potential tyrosinase desirable efficacy and safety, and for improving food quality. [ABSTRACT FROM AUTHOR]

Melanogenesis is a biosynthetic pathway for the formation of the pigment melanin in human skin. A key enzyme, tyrosinase, catalyzes the first and only rate-limiting steps in melanogenesis. Since the discovery of its melanogenic properties, tyrosinase has been in prime focus and microbial sources of the enzyme are sought. Agaricus bisporus widely known as the common edible mushroom, it's taking place in high amounts of proteins, enzyme, carbohydrates, fibers, and low fat contents are frequently cited in the literature in relation to their nutritional value. In the present study tyrosinase fromAgaricus bisporus was purified by ammonium sulphate precipitation, dialysis followed by gel filtration chromatography on Sephadex G-100, and ion exchange chromatography on DEAE-Cellulose; the enzyme was purified, 16.36-fold to give 26.6% yield on total activity in the crude extract and final specific activity of 52.19U/mg. The SDS-PAGE electrophoresis showed a migrating protein band molecular weight of 95 kDa. The purified tyrosinase was optimized and the results revealed that the optimumvalues are pH7.0 and temperature 35°C. Thehighest activity was reported towards its natural substrate, L-DOPA, with an apparent Km value of 0.933 mM. This indicated that tyrosinase purified from Agaricus bisporus is a potential source for medical applications. [ABSTRACT FROM AUTHOR]

Tyrosinase is a natural enzyme and is often purified to only a low degree and it is involved in a variety of functions which mainly catalyse the o-hydroxylation of monophenols into their corresponding o-diphenols and the oxidation of o-diphenols to o-quinones using molecular oxygen, which then polymerizes to form brown or black pigments. The synthesis of o-diphenols is a potentially valuable catalytic ability and thus tyrosinase has attracted a lot of attention with respect to industrial applications. In environmental technology it is used for the detoxification of phenol-containing wastewaters and contaminated soils, as biosensors for phenol monitoring, and for the production of L-DOPA in pharmaceutical industries, and is also used in cosmetic and food industries as important catalytic enzyme. Melanin pigment synthesized by tyrosinase has found applications for protection against radiation cation exchangers, drug carriers, antioxidants, antiviral agents, or immunogen. The recombinant V spinosum tryosinase protein can be used to produce tailor-made melanin and other polyphenolic materials using various phenols and catechols as starting materials. This review compiles the recent data on biochemical and molecular properties of microbial tyrosinases, underlining their importance in the industrial use of these enzymes. After that, their most promising applications in pharmaceutical, food processing, and environmental fields are presented. [ABSTRACT FROM AUTHOR]

Abstract: The presence of distinct class of 5-HT receptors in the melanophores of tilapia (Oreochromis mossambicus) is reported. The cellular responses to 5-HT (5-hydroxytryptamine), 5-HT1, and 5-HT2, agonists on isolated scale melanophores were observed with regard to pigment translocation within the cells. It was found that 5-HT exerted rapid and strong concentration dependent pigment granule dispersion within the melanophores. The threshold pharmacological dose of 5-HT that could elicit a measurable response was as low as 4.7×10−12 M/L. Selective 5-HT1 and 5-HT2 agonists, sumatriptan and myristicin were investigated and resulted in dose-dependent pigment dispersion. The dispersing effects were effectively antagonized by receptor specific antagonists. It is suggested that 5-HT-induced physiological effects are mediated via distinct classes of receptors that possibly participate in modulation of pigmentary responses of the fish. [Copyright &y& Elsevier]

The article discusses the objective structured public health examination (OSPHE), a work-based learning developed by the Faculty of Public Health in England. It is stated that OSPHE is intended to measure healthcare professionals' clinical competence in an examination setting. It is concluded that the trainees will have to take responsibility to demonstrate public health competency and to ensure techniques to pass the examination.

Background and Objective Methods Results Conclusion Severe asthma is a heterogeneous disease with subtype classification according to dominant airway infiltrates, including eosinophilic (Type 2 high), or non‐eosinophilic asthma. Non‐eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non‐eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies. The cystic fibrosis transmembrane conductance regulator (CFTR) is dysregulated in multiple respiratory diseases including cystic fibrosis and chronic obstructive pulmonary disease and has proven a valuable therapeutic target. We hypothesized that the CFTR may also play a role in non‐eosinophilic asthma.Patient‐derived human bronchial epithelial cells (hBECs) were isolated and differentiated at the air‐liquid interface. Single cell RNA‐sequencing (scRNAseq) was used to identify epithelial cell subtypes and transcriptional activity. Ion transport was investigated with Ussing chambers and immunofluorescent quantification of ionocyte abundance in human airway epithelial cells and murine models of asthma.We identified that hBECs from patients with non‐eosinophilic asthma had reduced CFTR function, and did not differentiate into CFTR‐expressing ionocytes compared to those from eosinophilic asthma or healthy donors. Similarly, ionocytes were also diminished in the airways of a murine model of neutrophilic‐dominant but not eosinophilic asthma. Treatment of hBECs from healthy donors with a neutrophilic asthma‐like inflammatory cytokine mixture led to a reduction in ionocytes.Inflammation‐induced loss of CFTR‐expressing ionocytes in airway cells from non‐eosinophilic asthma may represent a key feature of disease pathogenesis and a novel drug target. [ABSTRACT FROM AUTHOR]

Shallow foundations are uses for safe transmission of structural load to the ground considering soil bearing capacity and allowable settlement. In this research, an empirical analysis is present by using Terzaghi and Meyerhof model. Which is compared with numerical analysis using PLAXIS 3D Foundation. Bearing capacity determined by both cases matched well. The purpose of the study is to predict the maximum allowable stress capacity of shallow foundation in different conditions and establish relationships between stress and settlements for different footing dimensions under various circumstances, as well as the impact of pressure bulb overlapping of two adjacent footing. There are some notable findings are found in this study such as Ultimate stress bearing capacity of soil under allowable settlement varies if two adjacent footings are placed 1.5 m apart. Similar results have been found by varying spacing 2 m & 2.5 m. Sizes of footing may have insignificant effect on spacing between two adjacent footings. And footing may act as an isolated footing in 3 m away from another footing on sandy soil and 2 m away from another footing on clayey soil. [ABSTRACT FROM AUTHOR]

Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in adults with craniopharyngioma undergoing GTR versus STR-RT. This retrospective study enrolled 115 patients with craniopharyngioma in 5 institutions. Patients with STR received postoperative RT with stereotactic radiosurgery or fractionated radiation therapy per institutional preference and ability to spare optic structures. Median age was 44 years (range, 19–79 years). GTR was performed in 34 patients and STR-RT was performed in 81 patients with median follow-up of 78.9 months (range, 1–268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT, local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection, there was no difference in local control (P = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT groups. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in patients receiving STR-RT who were underdosed with fractionated radiation therapy (P = 0.03) or stereotactic radiosurgery (P = 0.04). Good long-term control was achieved in adults with craniopharyngioma who underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long-term morbidity. [ABSTRACT FROM AUTHOR]

Our objective is to investigate dosimetric differences between clinically deliverable Gamma Knife® (GK) Icon™ and linac-based FSRT plans on the basis of normal brain dose sparing for large (>14 cm³) recurrent glioblastomas (GBM). Sixteen patients with large, recurrent GBM were treated using re-irradiation via linac-based FSRT, 35 Gy in 10 fractions. For each patient, a new GK FSRT plan was created in Leksell GammaPlan® V11 (LGP). To maintain clinical deliverability, the LGP optimization included a planning goal of treatment time <20 minutes per fraction. Dosimetric comparison of coverage and normal brain dose between the linac and GK treatment plans was performed in MIM. The GK FSRT plans had significantly (p < 0.05) lower mean normal brain dose values (-8.85%), mean values of normal brain V20 (-32.4%) and V12 (-25.9%), and a lower mean V4 (-10.0%). GK FSRT plans have the potential to reduce the risk of radiation-related toxicities. [ABSTRACT FROM AUTHOR]

Objective: This study explored the effect of simvastatin on the histomorphology of islets of Langerhans, glucose and insulin levels in rats. Study Design: The study was a one-year laboratory-based experimental control trial. Place and duration of study: It was conducted at Army Medical College Rawalpindi, in collaboration with the National Institute of Health Islamabad and Armed Force Institute of Pathology Rawalpindi. Methods: A one-year, laboratory-based, two-group experimental control trial was conducted. Thirty rats were assigned to each group: a control group receiving saline injections, and a simvastatin group receiving a simvastatin 60 mg/kg/day. Histological analysis of pancreatic islets, and measurements of blood glucose and insulin levels were performed. Statistical analysis was conducted using independent sample t-tests, with significance set at p < 0.005. Results: While simvastatin treatment did not affect the number of islets of Langerhans, The area of pancreatic islets of Langerhans was significantly higher in the simvastatin treatment group compared to control (52,664±38,871 μm² vs 24,643±16,256 μm², p=0.001). Serum insulin levels were also significantly elevated with simvastatin treatment (21.49±7.03 μIU/ml) compared to control (16.72±5.38 μIU/ml) (p=0.005). There were no significant differences in weekly fasting blood glucose levels at 4 or 12 weeks between groups (p>0.05). These findings suggest potential modulation of pancreatic islet function by simvastatin without affecting glycemic control in this model. Conclusions: These findings demonstrate that simvastatin treatment significantly impacts the morphology and function of pancreatic islets in rats, increasing insulin secretion without affecting blood glucose levels. Further research is necessary to elucidate the underlying mechanisms and clinical implications of these observations. [ABSTRACT FROM AUTHOR]

The world is moving toward renewable rich electricity generation systems. Pakistan being the sixth most populous country in the world and having median age of 21 years requires extensive resources for the next couple of decades to fulfill its energy requirements. Punjab is the largest province of Pakistan with 60% of total population and consumes about 80% of the electricity. The province does not have a lot of hydro and wind potential, but it has tremendous opportunity to utilize solar energy to fulfill its energy needs. In this paper, we explore the solar energy production possibilities in the province. Our objective in this paper is to find the best locations to install utility-scale solar power plants to fulfill 30% of energy needs by 2030. In addition to the technical feasibility of solar PV power plants, we also look at the economic aspects of such plants. To this end, we look at the complete life cycle of a solar PV power plant. Using data from an existing solar PV power plant we derive Profitability Index (PI) of various possible locations. According to our results, the transmission line losses range between 0.7% and 12.2% depending on the load and length of the transmission lines. Using data from transmission line losses the PI of potential utility-scale solar PV sites ranges between −9.11% and 69.65% based on various economic factors. These results provides detailed information on the best places to establish utility-scale power plants from technical as well as economic perspective. [ABSTRACT FROM AUTHOR]

Nutrition and other bioactive natural products present in specific foods within a balanced diet play an indispensable role in maintaining and promoting human health. Plants are rich sources of a balanced nutrition because of high content of bioactive products; hence, most of them recently have acquired the status of superfoods. It has been used since ancient times for the treatment of various ailments, and these traditional medicines still remain as one of the most affordable and easily accessible sources of treatment in the primary health-care system. The scientifically based use of these superfoods date back to the era of Prophet Muhammad along with other historical uses of plant products. Prescription of a large number of herbal foods such as dates, pomegranate, olives, figs, grapes, and black seeds was successfully proposed by him. These recently have become superfoods with their powerful healing properties and act as favorable dietary interventions for disease prevention as well as for the good maintenance of health. The use of these foods as ingredients of natural origin with fewer side effects seems to be more favorable than the chemical treatment, which is often complicated. The present review is an attempt to provide a brief survey of the literature on scientifically based significance of these superfoods carried out by various researchers and exploration of a wide spectrum of their pharmacological actions which include antidiabetic, anticancer, immune modulator, analgesic, anti-inflammatory, and hepatoprotective properties. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology. Background: Spontaneous abscesses are generally typical in patients with significant risk factors and have been linked to numerous muscle groups. The sternocleidomastoid muscle, however, piqued our interest as an unusual location, especially in this patient who, other than diabetes mellitus, had no associated risk factors or signs of trauma. Case Report: A 61-year-old man appeared with neck pain, erythema, and swelling that had been present for 9 days and for which he had previously been examined in the Emergency Department. He was discharged on oral doxycycline after initial computed tomography (CT) of the neck revealed infiltration without collection. He returned with worsening symptoms and new-onset fever and chills. Vital signs were normal on assessment, with no evidence of trauma. Swelling was observed near the right sternocleidomastoid muscle insertion. A repeat CT scan of the neck revealed an abscess 2.5 cm in diameter. He was originally treated with empiric antibiotics before being moved to targeted medications. Incision and drainage were completed without complication. The patient was given a 6-week course of oral antibiotics. Conclusions: Spontaneous intramuscular abscesses are uncommon in people who have had no previous trauma or other known risk factors, but could be encountered in diabetic patients with non-optimal blood glucose levels, due to bacteremia. As a result, these cases require a high level of suspicion to be recognized and treated early. The scarcity of literature on this illness makes determining the cause challenging. However, by highlighting this case, we intend to raise awareness and facilitate early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology. Background: Spontaneous abscesses are generally typical in patients with significant risk factors and have been linked to numerous muscle groups. The sternocleidomastoid muscle, however, piqued our interest as an unusual location, especially in this patient who, other than diabetes mellitus, had no associated risk factors or signs of trauma. Case Report: A 61-year-old man appeared with neck pain, erythema, and swelling that had been present for 9 days and for which he had previously been examined in the Emergency Department. He was discharged on oral doxycycline after initial computed tomography (CT) of the neck revealed infiltration without collection. He returned with worsening symptoms and new-onset fever and chills. Vital signs were normal on assessment, with no evidence of trauma. Swelling was observed near the right sternocleidomastoid muscle insertion. A repeat CT scan of the neck revealed an abscess 2.5 cm in diameter. He was originally treated with empiric antibiotics before being moved to targeted medications. Incision and drainage were completed without complication. The patient was given a 6-week course of oral antibiotics. Conclusions: Spontaneous intramuscular abscesses are uncommon in people who have had no previous trauma or other known risk factors, but could be encountered in diabetic patients with non-optimal blood glucose levels, due to bacteremia. As a result, these cases require a high level of suspicion to be recognized and treated early. The scarcity of literature on this illness makes determining the cause challenging. However, by highlighting this case, we intend to raise awareness and facilitate early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibody (aPL)-associated thrombophilia has been implicated in various adverse pregnancy outcomes, including preterm birth and impaired fetal development. This systematic review aimed to elucidate the relationship between aPL-associated thrombophilia and these outcomes, as well as to identify potential modifiers of this relationship such as maternal age, coexisting maternal medical conditions, type of aPL antibodies involved, and the timing of thrombophilia diagnosis during gestation. We conducted a comprehensive literature search in PubMed, Web of Science, Cochrane, and Scopus in May 2023, covering literature published within the last 10 years. Eight articles, involving 2935 patients, were eligible for inclusion in the review. Single aCL was the most common type of aPL found in patients, with rates up to 61.0% in some studies, followed by single LA and single ab2GPI. Multiple aPL antibody positivity was found to be associated with a higher risk of preterm birth, with odds ratios ranging from 1.29 to 9.61. Patient characteristics and previous pregnancy history varied significantly across the studies. Risk factors such as diabetes mellitus, thrombosis, and systemic lupus erythematosus were also variable across the studies, but presence of these risk factors did not consistently affect the risk of preterm birth. Furthermore, although a triple positive aPL test was the most important risk factor for preterm birth, it was observed that thrombophilia treatment during pregnancy significantly reduced the risk by 2.44 times (95% CI = 1.18–6.20). This review supports the evidence for aPL-associated thrombophilia being a significant contributor to preterm birth and fetal developmental abnormalities. Further research is required to investigate the exact mechanisms and to determine the best clinical management for patients with aPL-associated thrombophilia during pregnancy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on airway management for subglottic stenosis which was published in the previous issue.

Purpose: Anemia of chronic kidney disease (CKD) has traditionally been treated with recombinant human erythropoietin (rhEPO). Recently, daprodustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, has also been shown to increase hematocrit. It remains unclear whether daprodustat or rhEPO should be the treatment of choice for anemia of CKD. We aimed to assess the efficacy and cardiovascular safety of daprodustat versus rhEPO in CKD patients. Methods: Online databases were queried in April 2022 for articles comparing the efficacy and safety of daprodustat in DD-CKD and NDD-CKD subgroups. Results from trials were pooled using a random-effects model. Results: Data on 8245 CKD patients from eight clinical trials were included. Our results show that in comparison to rhEPO, daprodustat maintained the same efficacy in increasing hemoglobin levels in both the DD-CKD (MD: 0.10; 95% CI [− 0.13,0.34]; p = 0.50) and NDD-CKD (MD: − 0.01; 95% CI [− 0.38,0.35]; p = 0.95) subgroups. Daprodustat significantly lowered hepcidin levels and significantly increased TIBC in both subgroups. Additionally, daprodustat significantly reduced the incidence of major adverse cardiovascular events (MACE) (RR: 0.89; 95% CI: 0.89–0.98; p = 0.02) and its myocardial infarction (MI) component (RR: 0.74; 95% CI: 0.59–0.92; p = 0.006) in the DD-CKD subgroup. Conclusion: Daprodustat has similar efficacy compared to rhEPO for the treatment of anemia of CKD. On treatment, the reduced experience of MACE was reported in DD-CKD patients as compared to rhEPO. Furthermore, effects on iron metabolism varied by parameter, with daprodustat being superior to rhEPO in some cases and inferior in others. [ABSTRACT FROM AUTHOR]

In mammalian melanocytes, melanosome is a highly specialized organelle where melanin is synthesized. Melanin synthesis is controlled by tyrosinase, the vital enzyme in melanogenic pathway. The present investigation is based on an effect of purified mushroom tyrosinase of Agaricus bisporus on B16F10 melanocytes for the melanin production via blocking pigment cell machinery. Using B16F10 melanocytes showed that the stimulation of melanogenesis by purified tyrosinase is due to increased tyrosinase absorption. Cellular tyrosinase activity and melanin content in B16F10 melanocytes were increased by purified tyrosinase in a dose-dependent manner. Western blot analysis revealed that cellular tyrosinase levels were enhanced after treatment with purified tyrosinase for 48 hours. Furthermore, tyrosinase induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner. The purified tyrosinase-mediated increase of tyrosinase activity was significantly attenuated by H89, LY294002, Ro-32-0432, and PD98059, cAMP-dependent protein kinase inhibitors. The results indicate that purified tyrosinase can be used as contestant for the treatment of vitiligous skin conditions. [ABSTRACT FROM AUTHOR]

Background: COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma. The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern. In this context, as the present study will exploit pooled diversified convalescent plasma collected from recovered COVID-19 patients, the proposed hyperimmune Anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy would be able to counter new infectious COVID-19 variants by neutralizing the virus particles. After the successful outcome of the phase I/II clinical trial of C-IVIG, the current study aims to further evaluate the safety and efficacy of single low dose C-IVIG in severe COVID-19 patients for its phase II/III clinical trial.Methods: This is a phase II/III, adaptive, multi-center, single-blinded, randomized controlled superiority trial of SARS-CoV-2 specific polyclonal IVIG (C-IVIG). Patients fulfilling the eligibility criteria will be block-randomized using a sealed envelope system to receive either 0.15 g/Kg C-IVIG with standard of care (SOC) or standard of care alone in 2:1 ratio. The patients will be followed-up for 28 days to assess the primary and secondary outcomes.Discussion: This is a phase II/III clinical trial evaluating safety and efficacy of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) in severe COVID-19 patients. This study will provide clinical evidence to use C-IVIG as one of the first-line therapeutic options for severe COVID-19 patients.Trial Registration: Registered at clinicaltrial.gov with NCT number NCT04891172 on May 18, 2021. [ABSTRACT FROM AUTHOR]

Organoid technology has provided unique insights into human organ development, function, and diseases. Patient-derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding disease pathogenesis. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined mixture of extracellular matrix proteins and growth factors extracted from the Engelbreth--Holm--Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and disease states of the same tissue. Therefore, we envisioned that the extracellular matrix derived from a native healthy tissue would be able to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than those cultured in Matrigel. Proteomic and Raman microspectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and, subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high-throughput, cell culture-based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies. [ABSTRACT FROM AUTHOR]

Anaemia increases with age and is common among older people. Due to its relationship with morbidity and mortality, accurate diagnosis is important. Thresholds defining the diagnosis of anaemia have been the subject of considerable scientific debate, with both higher and lower cut-offs proposed. High haemoglobin is also a health risk in some but not all studies. Using nationally representative data of 5,329 adults aged 65 + years (Health Survey for England 1998, 2005, 2006), linked to administrative mortality data, this paper describes the relationship between haemoglobin levels and mortality, adjusted for age and other confounders. Among men, a reverse J shaped relationship was observed: relative to the modal group (140-149 g/l), those with 'mild anaemia' of 120-129 g/l haemoglobin had a 56% (95% confidence interval 24-96%) greater mortality hazard, and those with 'severe anaemia', haemoglobin <120 g/l, had an 87% (39-153%) greater hazard. At the other end of the range, those with haemoglobin ≥160 g/l had 32% (2-70%) greater mortality hazard. Haemoglobin levels in women showed a similar but smaller, non-significant pattern: hazard ratio 1·32 (0·91-1·92) for severe anaemia (<110 g/l), and 1·30 (0·95-1·79) for high haemoglobin (≥150 g/l). This research supports the use of the World Health Organization thresholds (130 g/l for men, 120 g/l for women). [ABSTRACT FROM AUTHOR]

Bhopal 462 001, India Effects of histamine per se along with its specific agonists and antagonists were studied on the skin melanophores of Hemidactylus flaviviridis to study the role of histamine receptors in pigmentation. Histamine and 2-methyl histamine induced powerful melanin aggregation effects, leading to paling of the skin through stimulation of H1 receptors. On the other hand, 4-methyl histamine, a specific H2 receptor antagonist caused melanin dispersion via activation of H2 receptors, making the skin appear dark. It is concluded that histaminergic compounds have a considerable role in chromatic physiology of lower vertebrates, possibly as a neurotransmitter substance in melanin dysfunctions such as hyper and hypo pigmentation. [ABSTRACT FROM AUTHOR]

Background: the importance of vitamin D for bone health is well known, but emerging evidence also suggests that adequate vitamin D status may also be protective against non-communicable diseases. In the UK, government initiatives highlighting the importance of adequate vitamin D among older people have been in place since 1998. [ABSTRACT FROM PUBLISHER]

OBJECTIVE: To evaluate the frequency of benign and malignant breast diseases in females at Pathology Department, Al-Nafees Medical College & Hospital (ANMCH) Islamabad. STUDY DESIGN: A Cross sectional study. PLACE AND DURATION: From 10th January, 2015 to 20th October, 2015 at Department of Pathology, Al-Nafees Medical College & Hospital (ANMCH) Islamabad. METHODOLOGY: 120 breast specimens collected in a period of 9 months at pathology laboratory, Al-Nafees Medical College & Hospital (ANMCH) Islamabad were fixed in formalin, processed by automated tissue processor. Slides were stained with H&E stain and examined by consultant histopathologist under light microscope. All slides were divided into benign and malignant cases. Malignant cases were further graded according to Modified Bloom and Richardson system. RESULTS: Among total 120 breast specimens, commonest lesion is fibroadenoma (51%) followed by infiltrating duct carcinoma (12.5%), breast abscess (11.6%), fibrocystic change (10.8%), mastitis (3.3%) and medullary carcinoma (3.3%). CONCLUSION: Benign breast lesions were more common than malignant lesions in our study. Fibroadenoma was the commonest breast pathology. [ABSTRACT FROM AUTHOR]

The article discusses research which highlighted the differences in anaemia prevalence using various thresholds for anaemia in older people. According to the 2005 Health Survey for England (HSE), odds of having anaemia, defined using the World Health Organization (WHO) criteria, increase with age and with the presence of longstanding illness. In a multivariate model, older patients with serum ferritin level were twice as likely, while those with a raised soluble transferin receptor (sTfR) were three times as likely, to have anaemia.

Background and objective: COVID‐19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS‐CoV‐2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. Methods: We obtained lower AEC from 145 people from two independent cohorts, aged 2–89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS‐CoV‐2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack‐years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM‐17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over‐represented in those with COVID‐19 complications. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular matrix (ECM) generating collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in pre-treatment serum with outcome in patients with PDAC. Matrix metalloprotease (MMP)-degraded type I collagen (C1M), type III collagen (C3M), type IV collagen (C4M) and a pro-peptide of type III collagen (PRO-C3) were measured by ELISA in pre-treatment serum from a randomized phase 3 clinical trial of patients with stage III/IV PDAC treated with 5-fluorouracil based therapy (n = 176). The collagen fragments were evaluated for their correlation (r, Spearman) with serum CA19-9 and for their association with overall survival (OS) based on Cox-regression analyses. In this phase 3 PDAC trial, pre-treatment serum collagen fragment levels were above the reference range for 67%-98% of patients, with median values in PDAC approximately two-fold higher than reference levels. Collagen fragment levels did not correlate with CA19-9 (r = 0.049–0.141, p = ns). On a continuous basis, higher levels of all collagen fragments were associated with significantly shorter OS. When evaluating degradation (C3M) and formation (PRO-C3) of type III collagen further, higher PRO-C3 was associated with poor OS (>25th percentile cut-point, HR = 2.01, 95%CI = 1.33–3.05) and higher C3M/PRO-C3 ratio was associated with improved OS (>25th percentile cut-point, HR = 0.53, 95%CI = 0.34–0.80). When adjusting for CA19–9 and clinical covariates, PRO-C3 remained significant (HR = 1.65, 95%CI = 1.09–2.48). In conclusion, collagen remodeling quantified in pre-treatment serum as a surrogate measure of desmoplasia was significantly associated with OS in a phase 3 clinical PDAC trial, supporting the link between desmoplasia, tumorigenesis, and response to treatment. If validated, these biomarkers may have prognostic and/or predictive potential in future PDAC trials. [ABSTRACT FROM AUTHOR]

Objectives: To study the effects of estrogen administration on histomorphology of avascular necrosis of the femoral head in male rats. Study Design: Lab-based experimental study. Place and Duration of Study: Department of Anatomy, Army Medical College, National University of Medical Sciences, Rawalpindi (NUMS), in collaboration with the National Institute of Health Islamabad, (NIH) Pakistan from Aug to Nov 2021. Methodology: Thirty male Sprague Dawley rats, three months of age, weighing 200-300 gm, were selected. Rats were equally divided into three groups. Group-A served as a control group in which no intervention was made, and the rats were fed on a standard lab diet. Groups B and C served as experimental groups. In Groups B and C, avascular necrosis was induced by steroids for the first week of the study. Group C along with steroids also received tab estrogen by oral gavage for eight weeks, starting from the fifth week of the study till the twelfth week of the study. All the rats were sacrificed after the completion of the experimental period. The microscopic parameters like cortical thickness and percentage of the empty lacunae were counted. Results: Histomorphological changes were observed when the comparison was made between Group B, Control Group A, and Experimental Groups B and C with statistically significant results (p-value 0.001). Conclusion: Estrogen helps in fracture healing and shows improvement in cortical and trabecular strength. It has shown improvement in the cortical thickness measurement after avascular necrosis causes a decrease in the thickness. [ABSTRACT FROM AUTHOR]

Social media presents a promising yet competitive communication landscape for health practitioners and organizations during the rapid spread of an emerging infectious disease. The current study examined the association between the level of fear-arousing sensationalism and user engagement in 800 Facebook posts regarding the 2016 Zika virus outbreak. Results revealed that the majority of nonnews posts completely lacked sensationalist elements, and that user engagement increased significantly as the level of fear-arousing sensationalism increased from low levels. We discuss the potential value of message design that can engender an appropriate level of public concern and increase user engagement on social media. [ABSTRACT FROM AUTHOR]

Sugarcane (Saccharum officinarum, L.) is the third major crop of Pakistan. It is not only an important sugar crop but also a source of raw material for various agro-based industries in Pakistan. Sugarcane yields have been severely reduced in many parts of Asia by some diseases which include white leaf and grassy shoot phytoplasma diseases. The current research was intended to identify the causative agent responsible for the disease in sugarcane crop. The samples were collected from the diseased ridden fields of Sindh, Pakistan with the symptoms closely related to phytoplasma infection. For the detection of phytoplasma, nested-PCR was aimed to perform. The reliable molecular tool for the detection of phytoplasma was found to be Nested PCR using P1/P7. Total DNA from different parts of plant such as; roots, stem, leaves and the leaves infected with white fly, were extracted by CTAB and phenol/chloroform extraction methods. Universal primer pair P1/P7 were used to amplify a portion of the 16S rRNA gene in phytoplasma. Negative results were obtained when symptom full plant host were subjected to PCR and then gel electrophoresis were carried out. Results of the current study indicated that the indication of phytoplasma disease symptoms such as chlorosis and stunted growth, can also be the result of low levels of minerals/nutrients (iron and others) in the field soil. Application of ferrous sulphate in soil or in parts of the affected crop might cure the symptoms and increase the yield of sugarcane. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19.Trial Design: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1).Participants: The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 <300, and lung infiltrates >50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study.Intervention and Comparator: The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only MAIN OUTCOMES: The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation.Randomisation: Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved.Blinding (masking): Single blinded study, with participants blinded to allocation.Numbers To Be Randomised (sample Size): Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients.Trial Status: Current version of the protocol is "Version 2" dated 29th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021.Trial Registration: This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). [ABSTRACT FROM AUTHOR]