Social Media and the Allergist.

PURPOSE OF REVIEW: With this brief review, we summarize our findings of how allergists, professional organizations and patients within the allergy space are using social media to date. RECENT FINDINGS: Millions of Americans suffer from allergic conditions and it has been well established that there aren't enough allergists to help treat and reach each of these people. With a noticeable absence from social media platforms of board certified allergists with knowledge based in evidence and science, the vacuum has been filled by others - some of whom advocate for the exact things we discourage because they are not helpful, and can even be harmful, for our allergic patients. While there are drawbacks to using social media platforms, as a specialty we need to acknowledge and perhaps even embrace the idea that the use of social media can have a positive effect - as a means to not only introduce, engage and educate our patients and other HCPs, but also to reduce misinformation. Social media is a powerful tool that can be responsibly used by our allergy community to amplify our collective voice to share important health information with our patients and other healthcare professionals and we believe that more training and education needs to be done so that our speciality can join others in becoming a larger voice in the space.

A roadmap to artificial intelligence (AI): Methods for designing and building AI ready data to promote fairness.

OBJECTIVES: We evaluated methods for preparing electronic health record data to reduce bias before applying artificial intelligence (AI). METHODS: We created methods for transforming raw data into a data framework for applying machine learning and natural language processing techniques for predicting falls and fractures. Strategies such as inclusion and reporting for multiple races, mixed data sources such as outpatient, inpatient, structured codes, and unstructured notes, and addressing missingness were applied to raw data to promote a reduction in bias. The raw data was carefully curated using validated definitions to create data variables such as age, race, gender, and healthcare utilization. For the formation of these variables, clinical, statistical, and data expertise were used. The research team included a variety of experts with diverse professional and demographic backgrounds to include diverse perspectives. RESULTS: For the prediction of falls, information extracted from radiology reports was converted to a matrix for applying machine learning. The processing of the data resulted in an input of 5,377,673 reports to the machine learning algorithm, out of which 45,304 were flagged as positive and 5,332,369 as negative for falls. Processed data resulted in lower missingness and a better representation of race and diagnosis codes. For fractures, specialized algorithms extracted snippets of text around keywork "femoral" from dual x-ray absorptiometry (DXA) scans to identify femoral neck T-scores that are important for predicting fracture risk. The natural language processing algorithms yielded 98% accuracy and 2% error rate The methods to prepare data for input to artificial intelligence processes are reproducible and can be applied to other studies. CONCLUSION: The life cycle of data from raw to analytic form includes data governance, cleaning, management, and analysis. When applying artificial intelligence methods, input data must be prepared optimally to reduce algorithmic bias, as biased output is harmful. Building AI-ready data frameworks that improve efficiency can contribute to transparency and reproducibility. The roadmap for the application of AI involves applying specialized techniques to input data, some of which are suggested here. This study highlights data curation aspects to be considered when preparing data for the application of artificial intelligence to reduce bias.

Exploring Attitudes Toward "Sugar Relationships" Across 87 Countries: A Global Perspective on Exchanges of Resources for Sex and Companionship.

The current study investigates attitudes toward one form of sex for resources: the so-called sugar relationships, which often involve exchanges of resources for sex and/or companionship. The present study examined associations among attitudes toward sugar relationships and relevant variables (e.g., sex, sociosexuality, gender inequality, parasitic exposure) in 69,924 participants across 87 countries. Two self-report measures of Acceptance of Sugar Relationships (ASR) developed for younger companion providers (ASR-YWMS) and older resource providers (ASR-OMWS) were translated into 37 languages. We tested cross-sex and cross-linguistic construct equivalence, cross-cultural invariance in sex differences, and the importance of the hypothetical predictors of ASR. Both measures showed adequate psychometric properties in all languages (except the Persian version of ASR-YWMS). Results partially supported our hypotheses and were consistent with previous theoretical considerations and empirical evidence on human mating. For example, at the individual level, sociosexual orientation, traditional gender roles, and pathogen prevalence were significant predictors of both ASR-YWMS and ASR-OMWS. At the country level, gender inequality and parasite stress positively predicted the ASR-YWMS. However, being a woman negatively predicted the ASR-OMWS, but positively predicted the ASR-YWMS. At country-level, ingroup favoritism and parasite stress positively predicted the ASR-OMWS. Furthermore, significant cross-subregional differences were found in the openness to sugar relationships (both ASR-YWMS and ASR-OMWS scores) across subregions. Finally, significant differences were found between ASR-YWMS and ASR-OMWS when compared in each subregion. The ASR-YWMS was significantly higher than the ASR-OMWS in all subregions, except for Northern Africa and Western Asia.

Preoperative survey to evaluate the patients' allergy list and its relevance to perioperative care.

INTRODUCTION: Perioperative hypersensitivity and allergic reactions can result in significant morbidity and mortality. For routine anesthetic care, allergies are determined from a review of the electronic medical record supplemented by a detailed patient history. Although the electronic medical record is generally assumed to be accurate, it may be that allergies are erroneously listed or not based on sound medical practice. The purpose of the current study is to evaluate allergies listed in the electronic medical record of children presenting for surgery and determine their origin, authenticity, and impact on perioperative care. METHODS: Eligible patients included those presenting for a surgical procedure in the main operating room, who were ≤ 21 years of age, with a drug allergy listed on the EMR. Prior to intraoperative care, an electronic survey questionnaire containing questions related to medication allergies was provided to a guardian or parent. Two anesthesiology physicians reviewed the survey responses to determine the validity of any reported allergies. A second electronic survey was given postoperatively to the attending anesthesiologist to determine whether the documented allergy impacted anesthetic care. RESULTS: The study cohort included 250 patients, ranging in age from 5 to 14 years (median age 9 years). All of the patients had at least one allergy listed on the electronic medical record. Seventy of the 250 patients (28%) had more than one drug allergy listed for a total of 351 medication allergies. The majority of the listed allergies were related to antibiotics including 155 (44%) from the penicillin family, 26 (7%) cephalosporins, 16 (5%) sulfonamides, and 36 (10%) other antimicrobial agents. Other commonly listed allergies were 27 (8%) nonsteroidal anti-inflammatory agents and 15 (4%) opioids. The remaining 76 (22%) included a miscellaneous list of other medications. On further review of the allergies, the survey was completed for 301 medications. After physician review, 135 of 301 (45%) responses were considered consistent with IgE reactions "true allergy," 73 (24%) were deemed less relevant to IgE reactions "unlikely true allergy," and 93 (31%) were not related to IgE reactions "not an allergy." Care alterations during surgery were uncommon regardless of whether the issue was assessed as a true allergy (11%), unlikely to be a true allergy (3%), or not a true allergy (13%). CONCLUSION: A significant portion of the documented allergies in children are not true allergies, but rather recognized adverse effects (apnea from an opioid, renal failure from an NSAIDs) or other nonallergic concerns (gastrointestinal upset such as nausea). Erroneously listed allergies may lead to unnecessary alterations in patient care during perioperative care. A careful analysis of the allergy list on the EMR should be supplemented by a thorough patient history with specific questions related to the drug allergy. Once this is accomplished, the allergy listed should be updated to avoid its erroneous impact on perioperative care.

Engaging Participants Through Hybrid Community-Centered Approaches: Lessons Learned During the COVID CommUNITY Public Health Research Program.

Community-centered research studies can improve trust, cultural appropriateness, and accurate findings through meaningful, in-depth engagement with participants. During the COVID-19 pandemic, researchers shifted to implement pandemic-specific guidelines on top of already existing safety practices; these adjustments gave insight into bettering the structure of forthcoming research studies. At the Population Health Research Institute (PHRI)/McMaster University, the COVID CommUNITY study staff took field notes from their experience at the Ontario (ON) and British Columbia (BC) sites navigating an observational prospective cohort study during the pandemic. These field notes are outlined below to provide insight into culturally responsive, trust-centered, and communication-focused strategies used to improve hybrid research. A significant challenge the team overcame was obtaining blood sample collections by executing socially distanced sample collections outside of participants' homes, coined "Porch Pickups." Data collection was made more accessible through phone surveys and frequent virtual contact. To enhance recruitment strategies for sub-communities of the South Asian population, staff focused on cultural interests and "gift-exchange" incentives. Cultural awareness was prioritized through correct name pronunciation, conducting data collection in participant preferred languages, and using flexible approaches to data collection. These strategies were developed through weekly team meetings where improvement strategies were discussed, and concerns were addressed in real-time.

Microbes in gynecologic cancers: Causes or consequences and therapeutic potential.

Gynecologic cancers, starting in the reproductive organs of females, include cancer of cervix, endometrium, ovary commonly and vagina and vulva rarely. The changes in the composition of microbiome in gut and vagina affect immune and metabolic signaling of the host cells resulting in chronic inflammation, angiogenesis, cellular proliferation, genome instability, epithelial barrier breach and metabolic dysregulation that may lead to the onset or aggravated progression of gynecologic cancers. While microbiome in gynecologic cancers is just at horizon, certain significant microbiome signature associations have been found. Cervical cancer is accompanied with high loads of human papillomavirus, Fusobacteria and Sneathia species; endometrial cancer is reported to have presence of Atopobium vaginae and Porphyromonas species and significantly elevated levels of Proteobacteria and Firmicutes phylum bacteria, with Chlamydia trachomatis, Lactobacillus and Mycobacterium reported in ovarian cancer. Balancing microbiome composition in gynecologic cancers has the potential to be used as a therapeutic target. For example, the Lactobacillus species may play an important role in blocking adhesions of incursive pathogens to vaginal epithelium by lowering the pH, producing bacteriocins and employing competitive exclusions. The optimum or personalized balance of the microbiota can be maintained using pre- and probiotics, and fecal microbiota transplantations loaded with specific bacteria. Current evidence strongly suggest that a healthy microbiome can train and trigger the body's immune response to attack various gynecologic cancers. Furthermore, microbiome modulations can potentially contribute to improvements in immuno-oncology therapies.

Prescribing practices of Hormone Therapy for Menopausal females by OBGYN of Pakistan.

Objectives: To assess the prescribing practice of obstetricians and gynecologists (OBGYN) regarding Menopausal Hormone therapy (MHT) for menopausal females and assess the knowledge regarding indications for prescribing MHT and identify the barriers to HRT. Methods: This was a cross-sectional study conducted from May 2021 to December 2021. The participants were OBGYN experts (MCPS, FCPS, MRCOG) and senior experts. The tool was formulated after looking at contemporary literature and then validated by experts for face, content and construct validity. It was piloted and hence fourth given to study participants after approval by IRB of JSMU. Data was analyzed by SPSS version 22. Mean and Standard Deviation of categories in Likert scale were calculated. Results: Majority of the participant gynecologists prescribed HRT for Hot flushes and vaginal dryness having the highest mean scores nearing 4 on a Likert scale of (1-5). The prescription for other menopausal symptoms was observed to be less. The highest score for category of women in whom hormone therapy is specifically justified was "Premature ovarian failure" (4.37) followed by "Hysterectomy with bilateral oophorectomy before the age of 50" (4.23). Conclusion: Pakistani gynecologists are more cautious in their management strategies concerning MHT. Most of the gynecologists showed good and up to date information while prescribing MHT however knowledge for preventing fractures, alleviating anxiety/depression and weight gain was less among the gynecologist of Pakistan. We recommend refresher courses and online webinars for updated information on menopause and its management.

Synthesis, biological evaluation and docking studies of methylene bearing cyanopyrimidine derivatives possessing a hydrazone moiety as potent Lysine specific demethylase-1 (LSD1) inhibitors: A promising anticancer agents.

A series of novel cyanopyrimidine-hydrazone hybrids were synthesized and characterized with various spectroscopic techniques. The synthesized compounds were tested at NCI, USA, on a 60-cell line panel and most of the compounds showed remarkable cytotoxic activity against different cancer cell lines. Compound 5a was found to be the most potent compound of the series and it was further selected for five dose assays wherein it exhibited GI50 value of 0.414 µM and 0.417 µM against HOP-62 and OVCAR-4 cell lines respectively. The in-silico mechanistic studies indicated that these compounds are acting through inhibition of lysine specific demethylase 1 (LSD1) as evident from in to vitro LSD1 inhibition activity of compounds. Among various synthesized derivatives, compound 5a was found to have IC50-value of 0.956 µM. In addition, absorption, distribution, metabolism, excretion and toxicity profile (ADMET) was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes which revealed that synthesized compounds showed acceptable metabolic stability in human liver microsomes with minimal inhibition of cytochrome P450s (CYPs). The results indicated that compound 5a could be a promising lead compound for further development as a therapeutic agent for anticancer activity.

In vitro & in vivo evaluations of PLGA nanoparticle based combinatorial drug therapy for baclofen and lamotrigine for neuropathic pain management.

AIM: Baclofen and Lamotrigine via PLGA nanoparticles were developed for nose-to-brain delivery for the treatment of Neuropathic pain. METHODS: Nanoparticles were prepared using the modified nano-precipitation method. The prepared NPs were characterised and further in vitro and in vivo studies were performed. RESULTS: The Bcf-Ltg-PLGA-NPs were ∼177.7 nm with >75%(w/w) drugs encapsulated. In vitro dissolution studies suggested zero-order release profiles following the Korsmeyer-Peppas model. In vitro cytotoxicity and staining studies on mammalian cells showed dose dependant cytotoxicity where nanoparticles were significantly less toxic (>95% cell-viability). ELISA studies on RAW-macrophages showed Bcf-Ltg-PLGA-NPs as a potential pro-inflammatory-cytokines inhibitor. In vivo gamma-scintigraphy studies on rats showed intra-nasal administration of 99mTc-Bcf-Ltg-PLGA-NPs showed Cmax 3.6%/g at Tmax = 1.5h with DTE% as 191.23% and DTP% = 38.61% in brain. Pharmacodynamics evaluations on C57BL/6J mice showed a significant reduction in licks/bites during inflammation-induced phase II pain. CONCLUSION: The findings concluded that the combination of these drugs into a single nanoparticle-based formulation has potential for pain management.

Baclofen and Lamotrigine loaded PLGA nanoparticles were prepared with a size of 177.7nm, PDI 0.057 and Zeta Potential −15.8 mVIn vitro cell lines based studies showed dose dependant cytotoxicity and Bcf-Ltg-PLGA-NPs were found to be pro-inflammatory cytokines inhibitorsIn vivo Pharmacokinetic studies showed C_max 3.6%/g at T_max = 1.5 h with Drug Targeting Efficiency 191.23% and Drug Target Organ Transport 38.61% in the brain for prepared nanoparticlesIn vivo pharmacodynamics studies showed a significant reduction in licks/bites during inflammation-induced phase II pain.

Community acquired versus hospital acquired acute kidney injury; causes and outcome.

OBJECTIVE: To evaluate causes of community-acquired and hospital-acquired acute kidney injury and the factors associated with increased inpatient mortality. METHODS: The observational prospective study was conducted at the Aga Khan University Hospital, Karachi, from September 2018 to March 2019, and comprised patients having acute kidney injury either at the time of admission in group A or developed it after 48 hours of hospital stay in group B. The patients were followed up for 12 weeks and outcomes were categorised as recovered, developed chronic kidney disease, died or remained dialysis-dependent. Data was analysed using SPSS 19. RESULTS: Of the 400 patients, 347(86.8%) were in group A; 190(54.8%) males and 157(45.2%) females with an overall mean age of 57.2±17.0 years. The remaining 53(13.3%) were in group B; 31(58.5%) males and 22(41.5%) females with an overall mean age of 58.5±16.3 years. Urinary tract infection 105(30.3%) was the most frequent cause in group A, followed by volume depletion 73(21%). The causes in group B were multiple, with nephrotoxic antibiotics vancomycin 21(39.6%) and polymyxin 20(37.7%) being the most common. At 12 weeks, 224(56%) patients recovered, 55(13.8%) died, 82(20.5%) and 38(9.5%) developed new onset and progressive chronic kidney disease, respectively, and 1(0.25%) patient remained dialysis-dependent. Chronic liver disease, renin angiotensin system inhibitors, infection, shock, invasive ventilation and increasing length of stay were associated with increased inpatient mortality (p<0.05). CONCLUSIONS: Acute kidney injury was largely community-acquired, and infection was the leading cause with better outcome in contrast to hospital-acquired acute kidney injury which was mostly multifactorial.

Design and synthesis of pyrazole-pyrazoline hybrids as cancer-associated selective COX-2 inhibitors.

In continuation of our previous work on cancer and inflammation, 15 novel pyrazole-pyrazoline hybrids (WSPP1-15) were synthesized and fully characterized. The formation of the pyrazoline ring was confirmed by the appearance of three doublets of doublets in 1 H nuclear magnetic resonance spectra exhibiting an AMX pattern for three protons (HA , HM , and HX ) of the pyrazoline ring. All the synthesized compounds were screened for their in vitro anticancer activity against five cell lines, that is, MCF-7, A549, SiHa, COLO205, and HepG2 cells, using the MTT growth inhibition assay. 5-Fluorouracil was taken as the positive control in the study. It was observed that, among them, WSPP11 was found to be active against A549, SiHa, COLO205, and HepG2 cells, with IC50 values of 4.94, 4.54, 4.86, and 2.09 µM. All the derivatives were also evaluated for their cytotoxicity against HaCaT cells. WSPP11 was also found to be nontoxic against normal cells (cell line HaCaT), with an IC50 value of more than 50 µM. The derivatives were also evaluated for their in vitro anti-inflammatory activity by the protein (egg albumin) denaturation assay and the red blood cell membrane stabilizing assay, using diclofenac sodium and celecoxib as standard. Compounds that showed significant anticancer and anti-inflammatory activities were further studied for COX-2 inhibition. The manifestation of a higher COX-2 selectivity index of WSPP11 as compared with other derivatives and an in vitro anticancer activity against four cell lines further established that compounds that were more selective toward COX-2 also exhibited a better spectrum of activity against various cancer cell lines.

Assessment of the relationship between self-esteem and academic score of undergraduate medical students of Azad Kashmir, Pakistan.

A cross-sectional observational study was performed at the Poonch Medical College, Azad Kashmir, Pakistan, from June 2018 to June 2019 to assess the relationship between self-esteem and the academic score of undergraduate medical students. Rosenberg Self-Esteem (RSE) scale was used as data collection tool. The study questionnaire was electronically distributed to all 500 students enrolled in the Bachelor of Medicine and Surgery (M.B.B.S) programme out of which 253 submitted the questionnaire (response rate: 50.6%). The mean academic score of all students was 66.61± 5.42 and the mean RSE score was 28.66± 3.98). A statistically significant correlation was not found between age, academic score, and RSE score. Female students had slightly higher academic performance scores and RSE scores compared to the male students, but this difference was not statistically significant. Future studies are required to assess the contributing factors responsible for better academic performance.

Exploring Reproductive Health Impact of COVID 19 pandemic: In Depth Interviews with key stakeholders in Pakistan.

OBJECTIVE: To explore the effects of COVID 19 on reproductive and child health services and gender relations. METHODS: This is a Qualitative Exploratory Research. Due to lockdown, setting was online interviews on Zoom. Sampling was purposive. Five in-depth interviews were conducted in June 2020 followed by compilation of results and manuscript writing in July and August 2020. RESULTS: Maternal Neonatal morbidity and mortality will rise as part of collateral damage of C19. As all routine services of maternity care, family planning, post abortion care and vaccination were also in lockdown. Baby boom, unwanted pregnancies, unsafe abortions and violence against women will be the secondary consequences of C19. CONCLUSION: Some critical services should never stop which include maternal and neonatal essential services. MNCH service continuity has to be maintained to optimize maternal neonatal health, prevent unwanted pregnancy and abortion. With appropriate standard operating procedures, and protective equipments, health facilities need to open. LHWs and community mobilisers with PPEs should continue services.

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.

Restoration of PP2A levels in inflamed microglial cells: Important for neuroprotective M2 microglial viability.

PP2A, a trimeric Serine/Threonine Protein Phosphatase 2A highly expressed in brain, is a master regulator of cellular functions. Reduction in PP2A activity has been linked to progression of microglial mediated neuroinflammatory diseases. Inflammatory conditions are characterized by increased population of CD86+ve M1 cells and a therapeutic strategy to polarize microglial cells towards CD206+ve M2 cells is the need of hour. In this paper we analyzed A: whether the level of PP2A is altered in CD86+ve cells, B: whether FTY720, a known modulator of PP2A, is able to restore the level of PP2A in inflamed CD86+ve cells. Results revealed that PP2A activity was significantly diminished in inflamed cells but the surprising observation was the cell viability of only 35.99% upon FTY720 treatment in inflamed cells lacking basal PP2A activity. A sharp increase at mRNA level of CD95 and ASK-1 indicated that apoptosis occurred in these cells through CD95/ASK-1/JNK pathway. Importantly, flow cytometric analysis revealed apoptosis of not only CD86+ve cells but also CD206+ve cells. Previous studies have reported that FTY720 polarizes microglial cells towards M2 states; however apoptosis of M2 cells was not studied. As western blot analysis revealed that FTY720 failed to completely restore PP2A, another PP2A modulator, Memantine, was used for co-treatment. Upon co-treatment, the level of PP2A was completely restored and also viability of microglial cells was significantly improved with a significant reduction in apoptosis of M2 cells. These findings suggest that co-treatment strategy may prove beneficial to balance M1/M2 microglial population, thereby improving neuronal functions.

Synthesis, ADMET prediction and reverse screening study of 3,4,5-trimethoxy phenyl ring pendant sulfur-containing cyanopyrimidine derivatives as promising apoptosis inducing anticancer agents.

Cancer remains considered as one of the leading global health problems either due to meagre and suboptimal therapeutic response of chemotherapeutic agents or due to the emergence of spontaneous complex multidrug resistance in cancer cells. This created a persistent need for the development of new anticancer agents. Enthralled by the high success rate for natural product-based drug discovery and current research scenario, we synthesized a new series of 3,4,5-trimethoxy phenyl ring pendant sulfur-containingcyanopyrimidine derivatives clubbed with different amines intending to search an anticancer lead compound. To probe the anti-proliferative spectrum of the synthesized derivatives, an in-vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute (NCI) representing major types of cancer diseases. Most of the derivatives showed good to moderate anti-proliferative activity. The results revealed that compound 4e displayed the most promising broad-spectrum anticancer activity with high growth inhibition of various cell lines representing multiple cancers diseases. Mechanistic investigation of compound 4e in human breast cancer MDA-MB-231 cells showed that compound 4e triggers cell death through the induction of apoptosis. ADMET studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 3,4,5-trimethoxy phenyl ring pendant sulfur-containingcyanopyrimidine derivative 4e could act as a promising hit molecule for further development of novel anticancer therapeutics.

Clinical and social factors associated with excess weight in Hispanic and non-Hispanic White children.

BACKGROUND: Hispanic children are disproportionately affected by obesity, with this disparity starting at a young age, and there is a paucity of data comparing factors associated with excess weight in the first year of life in Hispanic vs. non-Hispanic populations. METHODS: Excess weight was defined as weight-for-length ≥95th percentile. The associations of potential risk factors were compared by ethnicity stratification. RESULTS: Of the 1009 children, 302 (30.0%) were Hispanic and 707 (70.0%) were non-Hispanic White. The rate of excess weight was 30.1% and 13.6% among Hispanic and non-Hispanic White children, respectively. Factors associated with excess weight for non-Hispanic White children were higher than recommended weight gain during pregnancy (odds ratio (OR) 1.8 (1.2-3.1)), higher paternal body mass index (BMI) (OR 1.1 (1.02-1.15)), higher birth weight (OR 1.001 (1.001-1.002)), and lower breast milk feedings at 6 months (OR 0.98 (0.96-0.98)). Factors associated with excess weight for Hispanic children were lower maternal education (OR 2.37 (1.1-4.5)) and lower breast milk feedings at 6 months (OR 0.98 (0.96-0.99)). CONCLUSION: There are differential risk factors associated with excess weight at 12 months between Hispanic and non-Hispanic White children. Identification of differential factors in different ethnicities may allow for more targeted anticipatory guidance reduce obesity in at-risk populations.

Etiology and outcome of pulmonary renal syndrome: Retrospective study from a tertiary care hospitaln.

To determine the aetiology, clinical characteristics and outcome of patients admitted with pulmonary renal syndrome (PRS). This retrospective analysis was conducted at Aga Khan University Hospital from 2011 to 2015. A total of 17 adult patients admitted with PRS were included and followed up for a period of one year for the outcome of PRS as recovery, dialysis dependency or death. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) was found to be the single most frequent cause in 13 (76.4%) patients. The c o mm o n e s t c a u s e o f A AV w a s fo u n d t o b e Granulomatous polyangitis (GPA) in 10 (58.8%) followed by Microscopic angitis in 3 (17.6%) patients. Around 12 (70.5%) patients survived, 11 (64.7%) recovered while 1 patient remained dialysis dependent. Mortality rate was 29.4% and all these patients had severe alveolar haemorrhages. None of our patient died or relapsed during one year follow up.

In vitro antifungal activity of 9, 10-dihydrophenanthrene-2-carboxylic acid isolated from a marine bacterium: Pseudomonas putida.

An antifungal compound 9, 10-dihydrophenanthrene - 2 - carboxylic acid was isolated from a marine derived bacterium Pseudomonas putida isolated from surface water samples of Karachi fish harbor coast line. The structure was explored using extensive 1D- and 2D-NMR spectroscopic techniques. The compound was found to be active against fungal strains obtained from clinical samples whereas strong activity was noted against Candida albicans with a MIC value of 20µg/ml, as the purified compound showed promising anticandidal activity a multidisciplinary approach is needed to explore further this compound as potential pharmacological lead compound against Candida spp and will add in the global hunt for clinically functional antifungal agents.

Investigating reproducibility and tracking provenance - A genomic workflow case study.

BACKGROUND: Computational bioinformatics workflows are extensively used to analyse genomics data, with different approaches available to support implementation and execution of these workflows. Reproducibility is one of the core principles for any scientific workflow and remains a challenge, which is not fully addressed. This is due to incomplete understanding of reproducibility requirements and assumptions of workflow definition approaches. Provenance information should be tracked and used to capture all these requirements supporting reusability of existing workflows. RESULTS: We have implemented a complex but widely deployed bioinformatics workflow using three representative approaches to workflow definition and execution. Through implementation, we identified assumptions implicit in these approaches that ultimately produce insufficient documentation of workflow requirements resulting in failed execution of the workflow. This study proposes a set of recommendations that aims to mitigate these assumptions and guides the scientific community to accomplish reproducible science, hence addressing reproducibility crisis. CONCLUSIONS: Reproducing, adapting or even repeating a bioinformatics workflow in any environment requires substantial technical knowledge of the workflow execution environment, resolving analysis assumptions and rigorous compliance with reproducibility requirements. Towards these goals, we propose conclusive recommendations that along with an explicit declaration of workflow specification would result in enhanced reproducibility of computational genomic analyses.