Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell.

Hematopoietic stem cell transplantation is a potential curative therapy for malignant and nonmalignant diseases. Improving the efficiency of stem cell collection and the quality of the cells acquired can broaden the donor pool and improve patient outcomes. We developed a rapid stem cell mobilization regimen utilizing a unique CXCR2 agonist, GROß, and the CXCR4 antagonist AMD3100. A single injection of both agents resulted in stem cell mobilization peaking within 15 min that was equivalent in magnitude to a standard multi-day regimen of granulocyte colony-stimulating factor (G-CSF). Mechanistic studies determined that rapid mobilization results from synergistic signaling on neutrophils, resulting in enhanced MMP-9 release, and unexpectedly revealed genetic polymorphisms in MMP-9 that alter activity. This mobilization regimen results in preferential trafficking of stem cells that demonstrate a higher engraftment efficiency than those mobilized by G-CSF. Our studies suggest a potential new strategy for the rapid collection of an improved hematopoietic graft.

Prenatal vitamin D levels and infant cognitive, motor, language and social-emotional development at 6 and 9 months of age.

AIM: Vitamin D is involved in several processes related to the development of neuronal and non-neuronal cells. There is a possible link between maternal vitamin D status in pregnancy and delayed neurocognitive development in the offspring. The aim of the study was to explore the association of maternal and cord blood vitamin D levels with infants' neurodevelopment at 6 and 9 months of age. METHODOLOGY: A cohort study was conducted in western Rajasthan, India. Maternal and cord blood samples were collected at the time of delivery. Serum 25(OH)-vitamin D levels were measured in both. Infant neurodevelopment was assessed at 6 and 9 months of age in six domains namely cognitive, receptive language, expressive language, fine motor, gross motor and social-emotional using the Bayley Scale of Infant Development- III (BSID-III). RESULTS: A total of 175 mother-child pairs were enrolled. Among the mothers taking part in this study, 7.3% had deficient and 59.09% had insufficient levels of serum 25(OH) vitamin D during the third trimester of their pregnancy. Maternal and cord blood serum 25-OH vitamin D levels were 18.86 ± 8.53 ng/mL and 17.39 ± 8.87 ng/mL, respectively, and there was a significant correlation (r = 0.9778, p = 0.000) between levels of vitamin D. Based on the repeated measures ANOVA, post hoc Tukey's HSD test, maternal vitamin D levels had a significant relationship (p = 0.047) to the cognitive development of infants at 6 months of age. Furthermore, cord serum vitamin D levels showed a significant association (p = 0.023 and p = 0.010) with the social-emotional development of the infant at the age of 6 and 9 months. CONCLUSION: Maternal and cord serum 25-OH vitamin D deficiency was significantly associated with the cognitive and social-emotional development of infants.

Menstrual health and hygiene amongst adolescent girls and women of reproductive age: a study of practices and predictors, Odisha, India.

BACKGROUND: Menstruation is a major physiological change in a woman's life, but lack of knowledge, poor practices, socio-cultural barriers, poor access to products and their improper disposal have significant consequences on health, dignity and well-being of women and adolescent girls. OBJECTIVES: This study aimed to assess the knowledge and practices related to menstrual health and hygiene amongst females of 10-49 years of age; explore the experiences and challenges of women during menstruation; and identify the key predictors of healthy menstrual health and hygiene. METHODS: Using a cross-sectional study design, we adopted a mixed methods approach for data collection. For quantitative household survey, a total of 921 respondents were selected from three districts of Odisha. Qualitative findings through focus group discussions and in-depth interviews supplemented the survey findings and helped to identify the barriers affecting good menstrual practices. Epi data version 2.5 and R 4.2.2 was used for data entry and data analysis, respectively. Descriptive statistics was used to calculate proportion, mean and standard deviation; Chi square test was used to measure the association between categorical variables. Bivariate and multivariate logistics analyses were done to identify predictors of healthy menstrual health and hygiene. For qualitative data analysis, thematic analysis approach was adopted using software Atlas.ti 8. RESULTS: For 74.3% respondents, mothers were the primary source of information; about 61% respondents were using sanitary pad. The mean age at menarche was 12.9 years and almost 46% of respondents did not receive any information about menstruation before menarche. Lower age and education up to higher secondary level or above had statistically significant associations with the knowledge about menstruation. Age, caste, respondent's education, mother's education, sanitation facility, availability of water, accessibility and affordability for sanitary pads were found to be strongly associated with good menstrual hygiene practices. CONCLUSION: Traditional beliefs regarding menstruation still persists at the community level. Educating mothers, increasing awareness about safe menstrual hygiene, providing adequate water and sanitation facilities and ensuring proper disposal of menstruation products need priority attention.

Systematic review analyzing significance of endometrial cavity fluid during assisted reproductive techniques.

OBJECTIVE: The objective of our study is to estimate the prevalence of endometrial cavity fluid (ECF) in Assisted Reproductive Techniques (ART) cycles and analyze its effects on pregnancy outcome in such cycles. DATA SOURCES: PubMed, Cochrane Central, Scopus, and clinicaltrials.gov were searched for articles. The reference lists of relevant publications were explored for other studies. STUDY ELIGIBILITY CRITERIA: Studies that had assessed the pregnancy outcome in ART cycles and had commented on ECF accumulation were included. Pregnancy outcomes were assessed in all ART cycles where ECF was observed and were compared to the non-ECF cycles. RESULTS: A total of nine studies were included in the meta-analysis for a total of 28,210 cycles. Pooled analysis of the prevalence of ECF cycles out of total cycles in females undergoing ART using a fixed effect model showed that it was 14% (95% CI is 13% to 14%; I2 = 99%, p = < 0.01). The random effect model prevalence of ECF cycles was around 7% (95% CI: 4% to 10%). There was a statistically significant (25%) decrease in pregnancy rates per cycle transfer in the ECF cycle versus the non-ECF cycle group during ART [OR = 0.75, 95% CI = 0.67-0.84), p < 0.001; moderate quality evidence]. When ECF size was compared, there was a statistically significant increase in pregnancy rates if ECF size was less than 3.5 mm versus greater than or equal to 3.5 mm [OR = 13.67, 95% CI = 1.43-130.40), p = 0.02; high quality evidence]. Sub-group analysis revealed that the ECF present at the time of embryo transfer significantly decreased the pregnancy rates by 26% as compared to the group where the ECF was not present at the time of embryo transfer [OR = 0.74, 95% CI = 0.65-0.85), p < 0.001]. CONCLUSIONS: This meta-analysis proposes that the presence of ECF significantly decreases the implantation and pregnancy rates of ART cycles, and even more so if its size is greater than 3.5 mm. Interventions to decrease ECF formation or treat it have enhanced the pregnancy outcome in ART cycles. PROSPERO REGISTRATION: Date: 17th September 2020; Number: CRD42020182262.

Quality Assessment of Interactive Mobile Application - Maternal and Infant Care for Tribal Birth Attendants.

Digital health interventions can overcome geographical barriers and prepare health-care providers for better health outcomes in rural and remote tribal areas, however, it has not been explored among traditional birth attendants (TBAs). A mobile application, "maternal and infant care" (MAI) for capacity building of tribal birth attendants was developed and its quality was evaluated using the Mobile Application Rating Scale for user's interest in and satisfaction with the esthetics, information, and functionality. Thirteen Android user TBAs with the MAI application were piloted with the MARS checklist. Engagement, functionality, esthetics, and information quality; and one subjective quality scale having 29 items were used. The application was found to be entertaining excellent rating (mean score ± standard deviation) (4.00 ± 0.58), and scored high on performance (3.77 ± 0.93); layout design (3.85 ± 0.90); subjective quality (4.23 ± 0.93), however, scored minimum on interest; gestural design; visual appeal, etc. MAI is a user-friendly, culturally acceptable Android app that can be used for the capacity building of frontline workers.

WITHDRAWN: Tranexamic acid to reduce postpartum blood loss after a vaginal delivery: a double-blinded, randomized controlled trial.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.

AIMS: Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability. METHODS AND RESULTS: Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE-/- mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE-/-Irf5-/- mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts. CONCLUSION: Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture.

Does change in the shape of intrauterine contraceptive device Cu 375 and Cu T 380A affect the expulsion after post-partum insertion - a prospective randomized control trial.

PURPOSE: The objective of the study was to see the difference in expulsion rates of two types of Copper containing intrauterine contraceptive devices (IUCDs): Cu 375 & CuT 380 A, within or at 6 weeks after insertion. METHODS: It was a randomised control trial. A total of 396 pregnant women were recruited. Ultrasonography was done to look for the position of the IUCD at the time of discharge and at six weeks follow-up and the expulsion rate was calculated. RESULTS: Amongst 396 participants, 22 PPIUCDs were expelled completely at 6 weeks (modified intention to treat analysis [ITA]), 10 (5.3%) and 12 (6.7%) in the Cu 375 and CuT 380 A groups respectively. The expulsion rate was 6.02%. However, this difference was not statistically significant. When ultrasonologically assessed partial expulsions were also considered, the total expulsion rate in both groups (14.3% and 14.1% respectively) was also not significantly different. The expulsion rate was higher in the vaginal delivery group (10.7%) than in the caesarean section (3.6%) group (p = 0.007) and early postpartum insertion 12.3% than in the immediate post-placental insertion group, 3.7% (p = 0.002). CONCLUSIONS: The study concluded that the altered shape of Cu 375 has effectively no role in decreasing the expulsion rate. Placement of IUCD at or near the uterine fundus immediately after delivering the placenta (post-placental) decreases the expulsion rate, thereby increasing the contraceptive efficacy.SHORT CONDENSATIONThe altered shape of Cu 375 has effectively no role in decreasing the expulsion rate. Placement of IUCD at or near the uterine fundus immediately after delivering the placenta (post-placental) decreases the expulsion rate, thereby increasing the contraceptive efficacy.

Comparison of pain score between Foleys catheter and Leich-Wilkinson cannula in hysterosalpingography by numerical rating scale - A randomized control trial.

Hysterosalpingography (HSG) is the first-line investigation in infertility assessment to assess tubal patency. Clinicians use various instruments, including the Leich-Wilkinson cannula, Rubin cannula, Jorcho's cannula, Whitehead cannula, and foley's catheter, to instill the dye in the uterus. We randomly allocated 60 patients planned for hysterosalpingography to evaluate tubal patency as part of fertility workup to either Intra-uterine foley's catheter arm or Leich-Wilkinson cannula arm. The research team measured and compared immediate and delayed numerical pain scores in both arms. We observed significantly lower pain scores in Foley's catheter arm as compared to the Leich-Wilkinson arm for both early (5.7 ± 3.01 vs. 7.8 ± 1.95) and delayed (0.15 ± 0.37 vs. 0.40 ± 0.50) evaluation. We established that using a Foley catheter for the HSG procedure was associated with lesser pain to the patient, with no evident difference regarding imaging of the uterus and tubes.

Maternal and Newborn Blood Aluminum Levels and Neurodevelopment of Infants: Is there a Need for Concern?

Aluminum is a neurotoxic element that enters the human body due to its widespread usage in daily life. It has the potential to affect the neurological development of the fetus and infant adversely. This study aimed to evaluate the relationship between maternal and umbilical cord serum aluminum level and infant neurodevelopment. Over a period of March 2018 to September 2019, we conducted a prospective cohort study; 173 Mother-new-born pairs were enrolled. Aluminum levels were measured using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The correlation with Bayley Scales of Infant Development (BSID) -3rd edition score and maternal and cord serum aluminum were assessed via linear regression model. The mean concentration of maternal and cord serum aluminum was 2.58 ± 1.14 µg/dL and 1.44 ± 0.62 µg/dL, respectively. There was a significant correlation in aluminum level between maternal and umbilical cord serum (Pearson's r = 0.591, p < 0.000). There is no significant correlation between maternal and serum aluminum level, and BSID-3rd edition (cognitive, motor, language, and social-emotion) score at the average age of 6.5 months. In conclusion, maternal and cord serum aluminum levels were significantly correlated but did not correlate with infant neurodevelopment. Thus, low serum aluminum concentration and their association with child neurodevelopment deserve further investigation longitudinally in a large cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-021-01002-y.

Acetaminophen and Xenobiotic Metabolites in Human Milk and the Development of Bronchopulmonary Dysplasia and Retinopathy of Prematurity in a Cohort of Extremely Preterm Infants.

This retrospective cohort study sought to identify the association between certain xenobiotic metabolites in maternal breast milk and the diagnoses of bronchopulmonary dysplasia and retinopathy of prematurity in extremely preterm infants. Several acetaminophen metabolites were associated with a 3- to 6-fold increased odds of these disorders, and metabolites of certain food products, benzoate, and caffeine were associated with decreased odds.

A Model of Care Optimized for Marginalized Remote Population Unravels Migration Pattern in India.

BACKGROUND AND AIMS: Access to basic health needs remains a challenge for most of world's population. In this study, we developed a care model for preventive and disease-specific health care for an extremely remote and marginalized population in Arunachal Pradesh, the northeasternmost state of India. APPROACH AND RESULTS: We performed patient screenings, performed interviews, and obtained blood samples in remote villages of Arunachal Pradesh through a tablet-based data collection application, which was later synced to a cloud database for storage. Positive cases of hepatitis B virus (HBV) were confirmed and genotyped in our central laboratory. The blood tests performed included liver function tests, HBV serologies, and HBV genotyping. HBV vaccination was provided as appropriate. A total of 11,818 participants were interviewed, 11,572 samples collected, and 5,176 participants vaccinated from the 5 westernmost districts in Arunachal Pradesh. The overall hepatitis B surface antigen (HBsAg) prevalence was found to be 3.6% (n = 419). In total, 34.6% were hepatitis B e antigen positive (n = 145) and 25.5% had HBV DNA levels greater than 20,000 IU/mL (n = 107). Genotypic analysis showed that many patients were infected with HBV C/D recombinants. Certain tribes showed high seroprevalence, with rates of 9.8% and 6.3% in the Miji and Nishi tribes, respectively. The prevalence of HBsAg in individuals who reported medical injections was 3.5%, lower than the overall prevalence of HBV. CONCLUSIONS: Our unique, simplistic model of care was able to link a highly resource-limited population to screening, preventive vaccination, follow-up therapeutic care, and molecular epidemiology to define the migratory nature of the population and disease using an electronic platform. This model of care can be applied to other similar settings globally.

Serum and urinary galectin-9 and C-X-C motif chemokine ligand 10.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by a type I interferon (IFN) signature, and traditional methods for its measurement like gene expression analysis are cumbersome for routine use. Thus, we aimed to study galectin-9 as a biomarker and compared it with a validated marker, C-X-C motifchemokine ligand 10(CXCL-10). METHODS: Ninety-seven patients with SLE (26 years; 89 females) were included and stratified based on renal involvement and activity into - active (SLEDAI > 4) renal (35), active non-renal (32) and inactive renal subgroups (30) along with 20 healthy controls (HC, 25 years; 15 females). The median disease duration was 24 months (6-48), and SLEDAI 2K was 9 (2-15). Serum and urine galectin-9 and CXCL-10 levels were measured by ELISA. Urine levels were normalized with spot urine creatinine values. Follow-up serum and urine galectin-9 levels were measured for those in the active renal group at 6 months. RESULTS: Patients with SLE had higher serum galectin-9 (5.6 vs 1.7 µg/mL, p = .0001) but not urine galectin-9 (0.52 vs 0.32 µg, p = .7) levels as compared to HC. Serum galectin-9 but not urine galectin-9 was higher in patients with active as compared to inactive lupus (12.9 - active renal, 16.7 - active non-renal vs 3.57 µg/mL, p = .04 and .005). Serum CXCL-10 (0.16 vs 0.05, p = .01) and urine CXCL-10 (0 vs 0, p = .01) were both significantly higher in the SLE group as compared with HC. Serum but not urine CXCL-10 was higher in the active as compared to inactive lupus (0.2 - active renal, 0.3 - active non-renal vs 0.08 µg/mL, p = .9 and .02). Serum galectin-9 showed a modest correlation with CXCL-10 0.4 (0.2-0.6), whereas none was found between their urine levels.Serum galectin-9 and CXCL-10 showed a moderate positive correlation with SLEDAI 2K. Serum galectin-9 showed a greater AUC than CXCL-10 (0.77 vs 0.67) in differentiating active from inactive SLE, and both tested together had the best AUC of 0.82. However, urinary levels had no association with SLEDAI 2K or renal SLEDAI. In a subset of patients with active renal disease, serum galectin-9 but not urine levels declined significantly after 6 months. CONCLUSION: Serum galectin-9 is a good marker of lupus activity; however, it does not differentiate between active renal and active non-renal disease. It performs slightly better than CXCL-10. Urinary galectin-9 does not reflect renal activity.

Impact of COVID-19 pandemic on obstetrics and gynecology residency training program in India: A national online survey.

OBJECTIVE: The goal of this study was to analyze how the COVID-19 pandemic affected the Obstetrics and Gynecology (OBG) residency program in India. STUDY DESIGN: This was a cross-sectional questionnaire-based online survey aimed to assess the impact of the pandemic on the residency training program in Obstetrics and Gynecology. The questionnaire consisted of five sections: demographic details, information regarding COVID-19 status, clinical work load, teaching and research, and psychological impact. RESULTS: The questionnaire was completed by 280 OBG trainees from different medical colleges from India. Training activity in general was reduced considerably during the pandemic, according to 79.6% (n = 223) respondents. According to 13.21% (n = 37) and 5% (n = 14) respondents, reduction in training activity were due to cancelation of elective operations and reduced patient foot fall respectively. In 74.3% (n = 208) of cases, trainees reported worry about meeting the goals of their specialty training. Logistic regression showed that the extent of training reduction was not significantly associated with residents' age (p = 0.806), gender (p = 0.982), marital status (p = 0.363), and status of their duty in COVID-19 dedicated hospitals (p = 0.110). However, year of residency was a significant predictor of the perception about degree of training reduction. CONCLUSION: The pandemic imposed a significant impact on OBG residency training in India. During the pandemic, exposure to learning opportunities, surgeries, and teaching were reduced, which may result in a decline in the quality of care offered to women in the future if training deficit is not overcome. At the same time, pandemic also gave birth to newer insights of learning and interaction by online mode.

Skin preparation for prevention of surgical site infection after obstetrics and gynecological abdominal surgery: A quality improvement project.

BACKGROUND: One of the most common causes of postoperative morbidity is postoperative surgical site infection (SSI). Healthcare-associated infection is a subject of great concern in healthcare services. The goal of the present study is to estimate the relative effectiveness of skin preparation solution chlorhexidine scrub followed by povidone-iodine painting in the prevention of SSIs after caesarean delivery and abdominal gynecological surgery. MATERIAL AND METHODS: This is a 1-year randomized prospective research done at a tertiary care institution in western Rajasthan. Women who underwent caesarean and gynecological operations were randomly assigned to one of two groups. Enrolled patients were randomly assigned to have the surgical site painted with 10% povidone-iodine or a chlorhexidine-alcohol preparatory scrub followed by povidone-iodine paint. According to the Centres for Disease Control and Prevention criteria, the outcomes were any SSI occurring within a week or during the 30-day follow-up period following the operation, including any superficial or deep SSI. RESULTS: A total of 251 patients were randomly assigned to two groups. Group A (povidone-iodine paint) received 121 patients, whereas Group B (chlorhexidine scrub + povidone-iodine paint) received 129 cases. The overall SSI rate in the present study was 8.76%. The SSI rate was lower in Group B (chlorhexidine scrub + povidone-iodine paint) as compared to Group A (povidone-iodine paint only) (5.4% vs. 12.4%; p = 0.04). CONCLUSION: This study highlighted that chlorhexidine-alcohol scrubbing followed by povidone-iodine painting provides superior skin antisepsis in comparison to povidone-iodine painting alone.

Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs.

Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood and distal ileum tissue were collected for fatty acid analysis. The distal ileum underwent histologic, proteomic, and metabolomic analyses. Eight pigs [3/14 SO (21%), 3/14 MO15 (21%), and 2/14 FO100 (14%)] developed NEC. No differences in NEC risk were evident between groups despite differences in induced fatty acid profiles in blood and ileal tissue. Metabolomic analysis of NEC versus no NEC tissue revealed differences in tryptophan metabolism and arachidonic acid-containing glycerophospholipids. Proteomic analysis demonstrated no differences by lipid group; however, 15 proteins differentiated NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling. Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC development. Metabolomic and proteomic analyses of NEC versus no NEC intestinal tissue provide mechanistic insights into the pathogenesis of NEC in preterm infants.NEW & NOTEWORTHY Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC risk in preterm pigs. Metabolomic and proteomic analyses provide mechanistic insights into NEC pathogenesis. Compared with healthy ileal tissue, metabolites in tryptophan metabolism and arachidonic acid-containing glycerophospholipids are increased in NEC tissue. Proteomic analysis differentiates NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling.

Hyperglycaemia-associated Caspase-3 predicts diabetes and coronary artery disease events.

BACKGROUND: Apoptosis is central in both diabetes and atherosclerosis, linked to pancreatic beta cell death and plaque progression. Circulating Caspase-3 has also been associated with diabetes and coronary calcium score. Here, we explored if soluble Caspase-3 (sCaspase-3) is associated with cardio-metabolic risk factors and predicts incidence of diabetes and coronary artery disease (CAD). METHODS: Clinical data and plasma from 4637 individuals from the Malmö Diet and Cancer cohort were studied. Plasma sCaspase-3 was measured by a Proximity Extension Assay. National registers were used to identify diabetes and CAD events during follow-up. Type 2 diabetes risk variants and expression quantitative trait loci (eQTL) for sCaspase-3 were retrieved from the DIAGRAM consortium and the Genotype-Tissue Expression project. RESULTS: HbA1c was the factor with the strongest association with sCaspase-3 (r = 0.18, P = 1.3x10-36 ). During follow-up 666 individuals developed diabetes and 648 individuals suffered from CAD. Increasing sCaspase-3 was associated with a higher risk of developing diabetes (hazard ratio (HR) 1.18 per 1unit; P = 7 × 10-5 ) and CAD (HR 1.2 per 1 unit, P = 1 × 10-4 ) during follow-up. A genetic variant rs60780116, located upstream of CASP3, showed strong association with type 2 diabetes (OR 1.06, 95%CI 1.04-1.07, P = 8.4 × 10-11 ). An eQTL was identified between this variant and gene expression of CASP3, where the allele positively correlated with type 2 diabetes was associated with increased CASP3 expression in blood. CONCLUSIONS: The present study provides evidence for plasma sCaspase-3 as a marker of cardio-metabolic risk factors and as a predictor of future diabetes and CAD in a cohort without cardiovascular disease or diabetes at baseline.

CXCR4 expression in the bone marrow microenvironment is required for hematopoietic stem and progenitor cell maintenance and early hematopoietic regeneration after myeloablation.

The bone marrow (BM) microenvironment/niche plays a key role in regulating hematopoietic stem and progenitor cell (HSPC) activities; however, mechanisms regulating niche cell function are not well understood. In this study, we show that niche intrinsic expression of the CXCR4 chemokine receptor critically regulates HSPC maintenance during steady state, and promotes early hematopoietic regeneration after myeloablative irradiation. At steady state, chimeric mice with wild-type (WT) HSPC and marrow stroma that lack CXCR4 show decreased HSPC quiescence, and their repopulation capacity was markedly reduced. Mesenchymal stromal cells (MSC) were significantly reduced in the BM of CXCR4 deficient mice, which was accompanied by decreased levels of the HSPC supporting factors stromal cell-derived factor-1 (SDF-1) and stem cell factor (SCF). CXCR4 also plays a crucial role in survival and restoration of BM stromal cells after myeloablative irradiation, where the loss of BM stromal cells was more severe in CXCR4-deficient mice compared to WT mice. In addition, transplantation of WT donor HSPC into CXCR4-deficient recipient mice demonstrated reduced HSPC homing and early hematopoietic reconstitution. We found that CXCR4 signaling attenuates irradiation-induced BM stromal cell loss by upregulating the expression of the antiapoptotic protein Survivin via the PI3K pathway. Our study suggests that SDF-1-CXCR4 signaling in the stromal microenvironment cells plays a crucial role in maintenance of HSPCs during homeostasis, and promotes niche regeneration and early hematopoietic reconstitution after transplantation. Modulation of CXCR4 signaling in the HSPC microenvironment could be a means to enhance hematopoietic recovery after clinical hematopoietic cell transplantation.

Elevated urinary IL-36γ in patients with active lupus nephritis and response to treatment.

INTRODUCTION: IL-36 is a new member of the IL-1 family with pro-inflammatory properties. Serum levels of IL-36 are elevated in patients with Systemic Lupus Erythematosus (SLE). However, no data is available on urinary levels of IL-36 in Lupus Nephritis (LN). In psoriasis expression of IL-36 is site specific and expressed in skin. Hence, we studied urinary levels of IL-36 cytokines in SLE patients. METHODS: A total of 196 patients with SLE [97 active LN patients (ALN), 42 inactive LN (ILN) and 57 active lupus patients with no renal involvement (ANR)] and 25 healthy subjects were recruited for the study after obtaining informed consent. Urinary and plasma IL-36α, IL-36γ and IL-36Ra levels were measured by ELISA. RESULTS: Out of 196 patients 178 were females. Urinary IL-36γ levels in SLE patients [0(14.3) pg/ml] were significantly higher than healthy controls [0(0) pg/ml, (P < 0.01)]. Patients with ALN [0(40.6) pg/ml] had significantly higher IL-36γ when compared to ANR [0(0) pg/ml] as well as ILN [0(0) pg/ml]. Urinary IL-36γ levels in ALN patients had a fair correlation with renal SLEDAI (r = 0.26, P = 0.004).The levels reduced significantly post 3 months in patients with ALN. No inverse relationship was noted between IL-36Ra and IL-36α/IL36γ levels. CONCLUSION: Urinary IL-36γ is produced locally in kidney, correlates with renal disease activity and reduces upon treatment, suggesting that it may have a role in pathogenesis of LN.

Alveolar Soft Part Sarcoma of Uterine Corpus in a Young Female: A Case Report With Review of Literature.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma, often occurs in adolescents and young adults with a particular predilection for the deep soft tissue of extremities. Occurrence of ASPS in the female genital tract is very uncommon and poses a significant diagnostic challenge. A case of ASPS of the uterine corpus is described in a young unmarried female, who presented to the out-patient clinic of our Institute with complaints of abnormal uterine bleeding for the past 9 mo. She was being treated with oral contraceptive pills, progesterone and tranexamic acid. Following radiological imaging and hysteroscopy, a therapeutic curettage of the lesion was done. The histopathologic features raised a differential diagnosis of a myriad of morphologic mimickers. The diagnosis was clinched by exclusion of mimickers by relevant immunohistochemical markers and strong nuclear expression of TFE3 on immunohistochemistry. The patient is on regular follow-up with oral contraceptives and antifibrinolytic medication. Despite being infrequent at this location, ASPS should be kept in differential diagnosis in young females presenting with abnormal uterine bleeding.