A century of BCG: Impact on tuberculosis control and beyond.

BCG turns 100 this year and while it might not be the perfect vaccine, it has certainly contributed significantly towards eradication and prevention of spread of tuberculosis (TB). The search for newer and better vaccines for TB is an ongoing endeavor and latest results from trials of candidate TB vaccines such as M72AS01 look promising. However, recent encouraging data from BCG revaccination trials in adults combined with studies on mucosal and intravenous routes of BCG vaccination in non-human primate models have renewed interest in BCG for TB prevention. In addition, several well-demonstrated non-specific effects of BCG, for example, prevention of viral and respiratory infections, give BCG an added advantage. Also, BCG vaccination is currently being widely tested in human clinical trials to determine whether it protects against SARS-CoV-2 infection and/or death with detailed analyses and outcomes from several ongoing trials across the world awaited. Through this review, we attempt to bring together information on various aspects of the BCG-induced immune response, its efficacy in TB control, comparison with other candidate TB vaccines and strategies to improve its efficiency including revaccination and alternate routes of administration. Finally, we discuss the future relevance of BCG use especially in light of its several heterologous benefits.

Immune profiling reveals umbilical cord blood mononuclear cells from South India display an IL-8 dominant, CXCL-10 deficient polyfunctional monocyte response to pathogen-associated molecular patterns (PAMPs) that is distinct from adult blood cells.

Neonate responses to pathogen-associated molecular patterns (PAMPS) differ from adults; such understanding is poor in Indian neonates, despite recognised significant infectious risk. Immune profiling analysis was undertaken of ten secreted mediators contextualised with cellular source induced by six PAMPs in umbilical cord (CB; n=21) and adult-blood (PBMC, n=14) from a tertiary care hospital in South India. Differential cytokine expression analysis (minimum log2-fold difference; adj p-value<0.05) identified bacterial PAMPs induced higher concentrations of IL-1ß, IL-10, TNF-α in adults versus IL-8, GM-CSF, IFN-γ and IL-2 in CB. CB responded to poly I:C and SARS-CoV-2 lysate with a dominant IL-8 response, whereas, in PBMC, CXCL-10 dominated poly I:C, but not SARS-CoV-2, responses, highlighting potential IL-8 importance, in absence of Type I Interferons, in antiviral CB immunity. Candida albicans was the only PAMP to uniformly induce higher secretion of effectors in CB. The predominant source of IL-8/IL-6/TNF-α/IL-1ß in both CB and PBMC was polyfunctional monocytes and IFN-γ /IL-2/IL-17 from innate lymphocytes. Correlation matrix analyses revealed IL-8 to be the most differentially regulated, correlating positively in CB versus negatively in PBMC with IL-6, GM-CSF, IFN-γ, IL-2, consistent with more negatively regulated cytokine modules in adults, potentially linked to higher anti-inflammatory IL-10. Cord and adult blood from India respond robustly to PAMPs with unique effector combinations. These data provide a strong foundation to monitor, explore, mechanisms that regulate such immunity during the life course, an area of significant global health importance given infection-related infant mortality incidence.

Variations in Site-Specific Costs for Infants Born Extremely Preterm in Canadian Neonatal Intensive Care Units.

OBJECTIVE: To quantify site-specific costs and their association with survival without major morbidity (SWMM) in Canada for neonates <28 weeks of gestation admitted to large tertiary neonatal intensive care units. METHODS: We conducted a retrospective analysis of infants born at <28 weeks of gestation and admitted to Canadian Neonatal Network sites from 2010 through 2021. Sites that cared for at least 50 eligible infants by gestational age in weeks over the study period were included. Using a validated costing algorithm that assessed physician, nursing, respiratory therapy, diagnostic imaging, transfusions, procedural, medication, and certain indirect costs, we calculated site and resource-specific costs in 2017 Canadian dollars (CAD) and evaluated their relationship with SWMM. RESULTS: Seven sites with 8180 (range 841-1605) eligible neonates with a mean (SD) gestation of 25.4 [1.3] weeks were included. Survival to discharge or transfer was 85.3% with a mean (SD) length of stay of 75 (46) days. The mean (SD) total and daily costs per neonate varied between $94 992 ($60 283) and $174 438 ($130 501) CAD and $1833 ($916) to $2307 ($1281) CAD, respectively. Between sites, there was no relationship between costs and SWMM. CONCLUSIONS: There was marked variation in costs and SWMM between sites in Canada with universal health care. The lack of concordance between both outcomes and costs among sites may provide possibilities for outcomes improvement and cost containment.

Prevalence and temporal trends of epilepsy in children: A retrospective birth cohort study.

OBJECTIVE: Epilepsy is one of the most common chronic neurologic diseases in children, however, few recent studies examine the prevalence of epilepsy and its evolution over time according to birth or maternal characteristics. To examine the prevalence of epilepsy in children born between 2002 and 2020 and the temporal trends by year of birth, in Ontario, Canada, overall and according to maternal and birth characteristics. METHODS: We included all in-hospital deliveries between 2002 and 2020 (N=2 343 482) in Ontario, Canada, using linked administrative health dataset. We estimated the overall prevalence of epilepsy diagnosed before the age of 18 years, by birth and maternal characteristics. For temporal trend analyses, we restricted our population to children born up to 2012 (N=1 405 271) and examined the prevalence of epilepsy diagnosed by age 8 by their year of birth, using Poisson regression. RESULTS: The overall prevalence of epilepsy in our cohort was 8.1 per 1000 live births (95% CI 8.0-8.2). Prevalence was higher for boys, for children born preterm, with congenital malformations, from multiple pregnancies, from mothers born in Canada, and for children living in deprived areas. Epilepsy prevalence diagnosed by age 8 increased slightly between 2002 and 2012 cohorts (6.9 (95% CI 6.2-7.6) to 7.3 (95% CI 6.6-8.1) per 1000 live births, respectively). Differences by gestational age as gradient and socioeconomic characteristics were persistent and stable over time, while those by pregnancy plurality and sex decreased. SIGNIFICANCE: In a large population-based birth cohort in Canada, we observed a slight increase in epilepsy prevalence over time among children born in 2002 and those born in 2012 and persistent disparities by gestational age, socioeconomic position, and maternal immigration status. This study highlights the need for continued surveillance of rates to see if this increasing trend is persistent, to understand the potential causes behind it, and to understand the persistence of these disparities.

GRADE-ADOLOPMENT of hyperthyroidism treatment guidelines for a Pakistani context.

INTRODUCTION: The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. METHODS: We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. RESULTS: The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves' Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. CONCLUSION: Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients' finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.

Strength in silence: the journey of mothers raising children with hydrocephalus.

BACKGROUND: Raising a child with hydrocephalus can be very challenging, especially in low- and middle-income countries. In Pakistan, mothers being the primary caregivers for their hydrocephalic children are under tremendous stress. METHODS: This study explores the challenges faced by Pakistani mothers raising children with hydrocephalus, employing a qualitative methodology through focus group discussions comprising ten mothers of hydrocephalic babies at Tertiary Care Hospital in Pakistan. RESULTS: The findings highlight three main themes: emotional toll, social isolation, and financial strain. Mothers experience significant emotional stress due to societal stigma and a lack of support, particularly from their husbands and family. Social isolation is prevalent, as mothers fear sharing their burdens and face physical confinement due to their children's needs. Financial strain is another major issue, with high medical costs adding to their economic difficulties. CONCLUSION: The study emphasizes improved access to specialized care, awareness campaigns to reduce stigma, financial assistance, and stronger community support networks to support these mothers better. Addressing these unmet needs is crucial for empowering Pakistani mothers in their caregiving roles and improving the quality of life for their children with hydrocephalus.

In utero Exposure to Maternal Diabetes and the Risk of Cerebral Palsy: A Population-based Cohort Study.

BACKGROUND: Evidence on the effects of in utero exposure to maternal diabetes on cerebral palsy (CP) in offspring is limited. We aimed to examine the effects of pregestational (PGDM) and gestational diabetes (GDM) separately on CP risk and the mediating role of increased fetal size. METHODS: In a population-based study, we included all live births in Ontario, Canada, between 2002 and 2017 followed up through 2018 (n = 2,110,177). Using administrative health data, we estimated crude and adjusted associations between PGDM or GDM and CP using Cox proportional hazards models to account for unequal follow-up in children. For the mediation analysis, we used marginal structural models to estimate the controlled direct effect of PGDM (and GDM) on the risk of CP not mediated by large-for-gestational age (LGA). RESULTS: During the study period, 5,317 children were diagnosed with CP (187 exposed to PGDM and 171 exposed to GDM). Children of mothers with PGDM showed an increased risk (hazard ratio [HR]: 1.84 [95% confidence interval (CI): 1.59, 2.14]) after adjusting for maternal sociodemographic and clinical factors. We found no associations between GDM and CP (adjusted HR: 0.91 [0.77, 1.06]). Our mediation analysis estimated that LGA explained 14% of the PDGM-CP association. CONCLUSIONS: In this population-based birth cohort study, maternal pregestational diabetes was associated with increased risk of CP, and the increased risk was not substantially mediated by the increased fetal size.

Optimizing Ramadan fasting: A randomised controlled trial for people with type 2 diabetes during Ramadan applying the principles of the ADA/EASD consensus.

BACKGROUND: Fasting during the holy month of Ramadan is one of the five pillars of Islam. Fasting is not meant to create excessive hardship on the Muslim individual according to religious tenets. It is important that health professionals are aware of potential risks associated with fasting during the month of Ramadan (mainly hypoglycemia and hyperglycemia). AIMS: To explore the impact of applying the principles of our 2020 recommendations for the management of type 2 diabetes (T2D) during the month of Ramadan. METHODS: A multinational randomized controlled trial (RCT) was conducted in five Muslim majority countries. Six hundred and sixty participants were deemed eligible for the study; however, 23% declined to participate later for various reasons. In total, 506 participants were enroled and were equally randomized to the intervention or the control group. At the end of the study, data from 231 participants in the intervention group and 221 participants from the control group were collected after 12.6% and 8.7% were, respectively, lost to follow-up. Participants were randomized to receive a Ramadan-focussed education with treatment for diabetes adjusted as per our 2020 recommendation update compared with the local usual care (control group). Results are presented using mean, standard deviation, odds ratio (OR), and percentages. RESULTS: At the end of the study, the number of hypoglycemic episodes in the intervention group was less than in participants who received usual care. The intervention group had significantly lower severe hypoglycemia compared to the control group with an OR of 0.2 [0.1-0.8]. Compared to baseline, both groups had a significant reduction in glycated haemoglobin (HbA1c), but the improvements were significantly greater in the intervention group. Whilst body weight reduced and high-density lipoprotein cholesterol increased with the intervention, these changes were not significantly different from usual care. CONCLUSIONS: A pre-Ramadan assessment of people with T2D coupled with pre-Ramadan education and an adjustment of glucose-lowering treatment as per our updated 2020 recommendations can prevent acute complications and allow a safer fast for people with T2D. We have shown that such an approach reduces the risk of developing severe hypoglycemia and improves the metabolic outcomes in people with T2D.

Prevalence and temporal trends of cerebral palsy in children born from 2002 to 2017 in Ontario, Canada: Population-based cohort study.

AIM: To examine the prevalence and temporal trends of cerebral palsy (CP) overall and by population characteristics. METHOD: We identified 2 110 177 live births born in the province of Ontario, Canada, between 2002 and 2017 using administrative health data and estimated CP prevalence in children aged 0 to 16 years overall and by specific population characteristics. We also examined temporal trends in CP rates - overall and by characteristics - in young children (0-4 years) by their year of birth between 2002 and 2013 (n=1 587 087 live births) to allow for an equal follow-up time (4 years and 364 days) for all children. RESULTS: Overall CP prevalence among children aged 0 to 16 years was 2.52 (95% confidence interval 2.45-2.59) per 1000 live births. CP rates in ages 0 to 4 years peaked at 2.86 in 2007 births, but steadily declined afterwards to 1.94 per 1000 live births in 2013. CP rates were higher in children born preterm, small for gestational age, males, multiples, children with congenital malformations, and in children of young (<20 years), old (≥40 years), primiparous, or grand multiparous (≥4) mothers; differences by these characteristics decreased over time. We observed socioeconomic disparities in CP rates that persisted over time. INTERPRETATION: Despite the decreasing trend of CP rates overall, CP rates varied by the child and maternal characteristics over time. WHAT THIS PAPER ADDS: Overall cerebral palsy (CP) prevalence was 2.5 per 1000 live births among children born from 2002 to 2017. CP prevalence peaked in children born in 2007 then steadily decreased between 2007 and 2013. Changes in CP rates varied over time by child and maternal characteristics. Socioeconomic inequalities in CP persisted and remained stable over the study period.

Letter to the Editor: The Efficacy of Cell-Assisted Lipotransfer Versus Conventional Lipotransfer in Breast Augmentation: A Systematic Review and Meta-Analysis.

This is a letter to the editor about a meta-analysis titled "The efficacy of cell-assisted lipotransfer versus conventional lipotransfer in breast augmentation: a systematic review and meta-analysis" by Li and Chen published in the year 2021. The most frequently performed aesthetic procedure is breast augmentation surgery. In breast augmentation, cell-assisted lipotransfer (CAL) has received high recognition due to its positive outcomes. There are controversies in the medical literature on the use of CAL for breast augmentation. This meta-analysis by Li and Chen has concluded that CAL using ASC was superior to other methods as it improved fat survival rate in breast augmentation. We have written this letter to the editor of the Aesthetic Plastic Surgery journal about this meta-analysis because of its impactful information provided by this study to the medical literature for breast augmentation surgery using cell-assisted lipotransfer. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Biofilm-based simultaneous nitrification, denitrification, and phosphorous uptake in wastewater by Neurospora discreta.

Biological removal of nitrogen and phosphorous from wastewater conventionally involves multiple processing steps to satisfy the differing oxygen requirements of the microbial species involved. In this work, simultaneous nitrification, denitrification, and phosphorous removal from synthetic wastewater were achieved by the fungus Neurospora discreta in a single-step, biofilm-based, aerobic process. The concentrations of carbon, nitrogen, and phosphorous in the synthetic wastewater were systematically varied to investigate their effects on nutrient removal rates and biofilm properties. Biofilm growth was significantly (p < 0.05) affected by carbon and nitrogen, but not by phosphorous concentration. Scanning electron microscopy revealed the effects of nutrients on biofilm microstructure, which in turn correlated with nutrient removal efficiencies. The carbohydrate and protein content in the biofilm matrix decreased with increasing carbon and nitrogen concentrations but increased with increasing phosphorous concentration in the wastewater. High removal efficiencies of carbon (96%), ammonium (86%), nitrate (100%), and phosphorus (82%) were achieved under varying nutrient conditions. Interestingly, decreasing the phosphorus concentration increased the nitrification and denitrification rates, and decreasing the nitrogen concentration increased the phosphorus removal rates significantly (p < 0.05). Correlations between biofilm properties and nutrient removal rates were also evaluated in this study.

Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1 mediated suppression compromise regulatory T cell function in tuberculosis.

Chronic T cell activation is a hallmark of pulmonary tuberculosis (PTB). The mechanisms underpinning this important phenomenon are however, poorly elucidated, though known to rely on control of T effector cells (Teff) by regulatory T cells (Treg). Our studies show that circulating natural Treg cells in adults with PTB preserve their suppressive potential but Teff cells from such subjects are resistant to Treg-mediated suppression. We found this to be due to expansion of an activated Teff subset identified by Human Leukocyte Antigen (HLA)-DR expression. Sensitivity to suppression was restored to control levels by depletion of this subset. Comparative transcriptome analysis of Teff cells that contain HLA-DR+ cells versus the fraction depleted of this population identified putative resistance mechanisms linked to IFNG, IL17A, IL22, PD-L1 and ß-chemokines CCL3L3, CCL4 expression. Antibody blocking experiments confirmed HLA-DR+ Teff cells, but not the fraction depleted of HLA-DR+ effectors, to be resistant to Treg suppression mediated via CCR5 and PD-L1 associated pathways. In the presence of HLA-DR+ Teff cells, activation of NFκB downstream of CCR5 and PD-L1 was perturbed. In addition, HLA-DR+ Teff cells expressed significantly higher levels of Th1/Th17 cytokines that may regulate Treg function through a reciprocal counter-balancing relationship. Taken together, our study provides novel insight on how activated HLA-DR+CD4+ T cells may contribute to disease associated inflammation by compromising Treg-mediated suppression in PTB.

Detection of a novel mutation in a Tunisian child with polycystic kidney disease.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic disease that has an adverse impact on the patients' health and quality of life. ADPKD is usually known as "adult-type disease," but rare cases have been reported in pediatric patients. We present here a 2-year-old Tunisian girl with renal cyst formation and her mother with adult onset ADPKD. Disease-causing mutation has been searched in PKD1 and PKD2 using Long-Range and PCR followed by sequencing. Molecular sequencing displayed us to identify a novel likely pathogenic mutation (c.696 T > G; p.C232W, exon 5) in PKD1. The identified PKD1 mutation is inherited and unreported variant, which can alter the formation of intramolecular disulfide bonds essential for polycystin-1 function. We report here the first mutational study in pediatric patient with ADPKD in Tunisia.

Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis.

Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli-induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1ß, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis.

Characterization of Pseudomonas aeruginosa isolated from various environmental niches: New STs and occurrence of antibiotic susceptible "high-risk clones".

The aim of this study was to investigate the antimicrobial phenotypes, major virulence factors, and the molecular typing of 66 P. aeruginosa isolates collected from various sources: human patients and hospital environment, raw milk, poultry meat, chicken/sheep fecal samples, wastewater, thermal water, and seawater. All isolates, except one, were susceptible to all tested antibiotics. exoA, lasB, rhlR, and lasR genes were harbored by 60 isolates. Forty-six, 18, and 2 isolates amplified exoS, exoU, and exoS+exoU genes, respectively. Twenty-one isolates showed high elastase and pigment production. The PFGE typing identified 26 pulsotypes. Some pulsotypes included isolates from different environmental niches and areas. Twelve selected isolates were typed by MLST and eight different STs were found, three of them were new. Our results highlighted the dissemination of some clones amongst different settings and the occurrence of antibiotic susceptible 'high-risk clones' that might be very harmful when acquiring genes encoding antibiotic resistance.

Intestinal glucocorticoid synthesis enzymes in pediatric inflammatory bowel disease patients.

Inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis are devastating chronic immunopathologies of the intestinal mucosa, which are frequently treated by immunosuppressive glucocorticoids. Endogenous glucocorticoids are not only produced by the adrenal glands, but also by the intestinal epithelium. Local glucocorticoid synthesis critically contributes to the immune homeostasis of the intestinal mucosa. As defective intestinal glucocorticoid synthesis has been associated with the development of IBD, we investigated the expression of steroidogenic enzymes and the key transcriptional regulator Liver Receptor Homolog-1 (LRH-1/NR5A2) in ileal and colonic biopsies human pediatric IBD and control patients. Furthermore, the induction of steroidogenic enzymes and their transcriptional regulation by LRH-1 was investigated in a mouse model of experimental colitis. These analyses revealed that colitis-induced expression of steroidogenic enzymes in the murine colon is dependent on the presence of LRH-1, as intestinal deletion of LRH-1 strongly reduced their colitis-induced expression. Similarly, a strong correlation between the expression of LRH-1 and different steroidogenic enzymes was seen in intestinal biopsies of human pediatric patients. Importantly, reduced expression of hydroxysteroid dehydrogenase 11B1 (HSD11B1) was observed in IBD patients compared to control patients, suggesting that defective local reactivation of glucocorticoids could contribute to the pathogenesis of IBD.

Arrested fungal biofilms as low-modulus structural bio-composites: Water holds the key.

Biofilms are self-assembling structures consisting of rigid microbial cells embedded in a soft biopolymeric extracellular matrix (ECM), and have been commonly viewed as being detrimental to health and equipment. In this work, we show that biofilms formed by a non-pathogenic fungus Neurospora discreta, are fungal bio-composites (FBCs) that can be directed to self-organize through active stresses to achieve specific properties. We induced active stresses by systematically varying the agitation rate during the growth of FBCs. By growing FBCs that are strong enough to be conventionally tensile loaded, we find that as agitation rate increases, the elongation strain at which the FBCs break, increases linearly, and their elastic modulus correspondingly decreases. Using results from microstructural imaging and thermogravimetry, we rationalize that agitation increases the production of ECM, which concomitantly increases the water content of agitated FBCs up to 250% more than un-agitated FBCs. Water held in the nanopores of the ECM acts a plasticizer and controls the ductility of FBCs in close analogy with polyelectrolyte complexes. This paradigm shift in viewing biofilms as bio-composites opens up the possibility for their use as sustainable, biodegradable, low-modulus structural materials.

Trajectories of maternal depressive and anxiety symptoms from pregnancy to five years postpartum and their prenatal predictors.

BACKGROUND: Maternal depression and anxiety have distinct constellations of symptom trajectories, which are associated with factors that may vary between different groups of women. The aim of this study was to identify subgroups of women who exhibit unique longitudinal trajectory patterns of depressive and anxiety symptoms from pregnancy to 5 years postpartum and the antenatal predictors associated with these maternal groups. METHODS: The study used a longitudinal data collected from 615 women in Saskatchewan from pregnancy to 5 years postpartum. Semiparametric group-based models were used to identify latent maternal depressive and anxiety trajectory groups. Multinomial logit models were then used to assess the association between maternal characteristics and the identified latent trajectory groups. RESULTS: We identified four trajectory groups of maternal depressive symptoms: low-stable (35%); moderate-stable (54%); moderate-increasing (5%); and high-decreasing (6%), and three trajectory groups of maternal anxiety symptoms: very low-stable (13%); low-stable (58%); and moderate-stable (29%). We also identified several risk factors, most notably history of depression and stress, that were significantly associated with these trajectories. CONCLUSION: History of depression and increased stress are significant risk factors that can be identified during regular perinatal visits; therefore, clinicians should inquire about these risk factors to identify women at high risk of ongoing depression or anxiety.

Challenges in diagnosis of disease reported 100 years back: Cushing syndrome; recent advances.

Treatment of Cushing syndrome depends on diagnosis of etiology responsible for hypercortisolism in the body, which sometimes presents with a challenge. Inferior petrosal sinus sampling for ACTH levels, followed by peripheral venous sampling is a proven tool to be a gold standard for differentiating between peripheral and central cause of ACTH dependent Cushing syndrome. This case report is of an elderly female who presented as an outpatient in the endocrinology clinic of Aga Khan university hospital on 22/6/2017 with clinical features of hypercortisolism. After workup she was found to have cushing syndrome secondary to ACTH secreting bronchial carcinoid tumour.

Latent trajectory groups of perinatal depressive and anxiety symptoms from pregnancy to early postpartum and their antenatal risk factors.

The aim of this study is to identify subgroups of women who exhibit distinct trajectory patterns of depressive and anxiety disorders from pregnancy to early postpartum and the risk factors associated with the latent trajectory group memberships. Women (n = 615) from the Feelings in Pregnancy and Motherhood (FIP) longitudinal study were followed from early pregnancy to early postpartum for a 7-month period in 2006-2007. The semi-parametric group-based trajectory modeling approach was used to identify the latent trajectory groups. Multinomial logit models were then used to explore the association between latent trajectory group membership and antenatal characteristics. We identified four latent trajectory groups of perinatal depressive symptoms: "low-stable" (49.6%), "moderate-stable" (42.3%), "postpartum" (3.6%), and "antepartum" (4.6%). Significant risk factors associated with these trajectory group memberships were past depression, stress level, ethnicity, the mother's age, and relationship satisfaction. Three latent trajectory groups of perinatal anxiety symptoms were identified: "very low-stable" (8.9%); "low-stable" (60.7%); and "moderate-stable" (30.4%). Significant risk factor associated with these trajectories were past depression, stress level, and income level. Latent trajectory groups of perinatal depressive and anxiety symptoms were identified to uncover potential heterogeneity in populations. Our findings support the need for multiple assessments starting from early pregnancy to the postpartum, which can give some important insights on the characteristics of the women at high symptom burden trajectories for early interventions that may alter the progress of their mental symptoms.