The association of right ventricular-pulmonary arterial coupling and pulmonary vascular resistance in adult patients with uncorrected atrial septal defect.

BACKGROUND: Atrial septal defects (ASD) are the most common type of adult congenital heart disease (ACHD) associated with a high risk developing of pulmonary arterial hypertension (PAH). ASD closure is not recommended in patients with PAH and Pulmonary Vascular Resistance (PVR) ≥ 5 Wood Unit (WU). Noninvasive methods have been proposed to measure PVR; however, their accuracy remains low. Right Ventricle (RV) - Pulmonary Artery (PA) coupling is defined as the ability of the RV to adapt to high-resistance conditions. Tricuspid Annular Plane Systolic Excursion (TAPSE)/estimated pulmonary artery systolic pressure (ePASP) calculation using echocardiography is a noninvasive technique that has been proposed as a surrogate equation to evaluate RV-PA coupling. Currently, no research has demonstrated a relationship between RV-PA coupling and PVR in patients with ASD. METHODS: The study participants were consecutive eligible patients with ASD who underwent right heart catheterization (RHC) and echocardiography at Hasan Sadikin General Hospital, Bandung. Both the procedures were performed on the same day. RV-PA Coupling, defined as TAPSE/ePASP > 0.31, was assessed using echocardiography. The PVR was calculated during RHC using the indirect Fick method. RESULTS: There were 58 patients with ASD underwent RHC and echocardiography. Among them, 18 had RV/PA Coupling and 40 had RV/PA Uncoupling. The PVR values were significantly different between the two groups (p = 0.000). Correlation test between TAPSE/ePASP with PVR showed moderate negative correlation (r= -0.502, p = 0.001). TAPSE/ePASP ≤ 0.34 is the cutoff point to predict PVR > 5 WU with sensitivity of 91.7% and specificity 63.6%. CONCLUSION: This study showed a moderate negative correlation between TAPSE/ePASP and PVR. TAPSE/ePASP ≤ 0.34 could predict PVR > 5 WU with good sensitivity.

Comparison of clinical presentation and outcome of childhood-onset and adulthood-onset of systemic lupus erythematosus among Indonesian patients.

INTRODUCTION: The clinical presentation of childhood-onset systemic lupus erythematosus (SLE) is generally perceived to differ from that of adult-onset SLE. OBJECTIVE: We aimed to compare the demographic and clinical manifestation between childhood-onset vs. adult-onset SLE in a cohort of Indonesian patients at tertiary care centers. METHODS: This retrospective study included patients in the Hasan Sadikin Lupus Registry from 2008 until December 2017. The demographics, clinical presentations, and outcomes were compared between childhood-onset SLE (<18 years old) (Group 1) and adult-onset SLE (≥18 years old) (Group 2). RESULTS: Eight hundred seventy patients were involved into this study. The proportion of childhood-onset SLE was 20% (174 patients). The mean age of group 1 versus group 2 was 13.56 ± 3.04 vs 30.41 ± 8.54 years. The following clinical manifestations at SLE diagnosis were significantly more common in childhood-onset than in adult-onset SLE patients: hematological disorder (p = 0.033) and arthritis (p = 0.006). While discoid rash (p = 0.036) and photosensitivity (p < 0.001) were significantly found higher in adult-onset SLE. Cyclophosphamide therapy was significantly more common to be used in childhood-onset (38.5% vs 21.0%, p = <0.001). However, frequency of mortality on follow-up tended to be higher in childhood-onset group (11.5% vs 7.0%, p = 0.208). CONCLUSION: Arthritis and hematologic involvements at SLE diagnosis were more prominent in childhood-onset compared to adult-onset patients, and mortality in childhood-onset SLE during follow-up relatively higher. This data may suggest the need for more aggressive management approach to childhood-onset patients with SLE.

Low serum 25-hydroxyvitamin D (vitamin D) level among children with ventricular septal defect: how big is the risk for pulmonary hypertension?

INTRODUCTION: Ventricular septal defect is the most common CHD, leading to pulmonary hypertension. Significantly lower 25-hydroxyvitamin D level was reported in children with CHD compared with healthy controls. The current study aimed to investigate the correlation between 25-hydroxyvitamin D level and pulmonary hypertension in children with ventricular septal defect. METHODS: A cross-sectional study was conducted on ventricular septal defect paediatric patients from January to June, 2019. Serum 25-hydroxyvitamin D was measured using electrochemiluminescence. Pulmonary hypertension was defined as mean pulmonary artery systolic pressure > 20 mmHg for children >3 months of age at sea level, measured by Doppler echocardiography. RESULTS: From forty-four subjects, the majority of the subjects were female (56.8%) with normal nutritional status and perimembranous ventricular septal defect. Bivariate analysis showed that 25-hydroxyvitamin D level was associated with pulmonary hypertension (p < 0.01), type and size of ventricular septal defect (p = 0.02), and heart failure (p < 0.01). Higher 25-hydroxyvitamin D level was correlated with better nutritional status (p = 0.04, r = 0.26), and lower 25-hydroxyvitamin D level was correlated with the occurence of perimembranous ventricular septal defect (p = 0.01, r = -0.39), larger defect size (p < 0.01, r = -0.70), history of pneumonia (p = 0.02, r = -0.31), and heart failure (p < 0.01, r = -0.64). Subjects with 25-hydroxyvitamin D deficiency had prevalence ratio of 24.0 times for pulmonary hypertension. Higher pulmonary artery pressure was correlated to the occurence perimembranous ventricular septal defect (p = 0.01, r = 0.47), larger defect size (p < 0.01, r = 0.78), history of pneumonia (p = 0.01, r = 0.38), and heart failure (p < 0.01, r = 0.75). CONCLUSION: Children with ventricular septal defect who had low 25-hydroxyvitamin D level posed a higher risk of having pulmonary hypertension.

Stunting as a Risk Factor for Asthma: The Role of Vitamin D, Leptin, IL-4, and CD23.

Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1-Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.

Association of maternal vitamin D deficiency and infants' neurodevelopmental status: A cohort study on vitamin D and its impact during pregnancy and childhood in Indonesia.

AIM: Vitamin D deficiency in early pregnancy may cause the disruption of fetal brain development and neurodevelopmental function. This study aimed to explore the extent of neurodevelopment disruption could be associated with maternal vitamin D deficiency. METHODS: A cohort study was conducted in Sukabumi and Waled, West Java, Indonesia, beginning in July 2016. Maternal serum 25(OH)-vitamin D was measured between 10 and 14 weeks of gestational age. Child development was measured using the Ages and Stages Questionnaire-3 (ASQ-3) at age 3, 6 and 12 months. RESULTS: A total of 141 mother-infant pairs participated. One pair was excluded due to anencephaly of the infant. Vitamin D deficiency was found in 27 (19%) mothers, but delays occurred in gross motor function among 104 (76.1%) infants and in problem-solving functions among 61 (43.7%) infants at 3 months old. In general, the mean ASQ score at ages 3 and 6 months were lower among infants whose mothers had a vitamin D deficiency. The mean ASQ score for gross motor function at age 3 months was found to be significantly lower among these infants (31.5 vs. 37.9; P = 0.02), with increased risk for delayed motor function at age 3 months (relative risk (95% confidence interval) = 1.22 (1.09-1.49); P = 0.03). CONCLUSION: Neurodevelopmental function disruptions among infants whose mothers had vitamin D deficiency during pregnancy were reflected in lower ASQ scores, in which gross motor function was significantly impaired at 3 months of age.

Association of first trimester maternal vitamin D, ferritin and hemoglobin level with third trimester fetal biometry: result from cohort study on vitamin D status and its impact during pregnancy and childhood in Indonesia.

INTRODUCTION: The role of vitamin D in placental functions and fetal growth had been addressed in many reports with conflicting results. However, such report is limited for Indonesian population. The aim of this study was to explore the association between maternal vitamin D level in the first trimester and fetal biometry in the later stage of pregnancy with adjusted OR for other determinants like hemoglobin and ferritin level. METHODS: From July 2016 a prospective cohort study of pregnant women had begun in four cities in West Java, Indonesia. Data on maternal vitamin D, ferritin, hemoglobin level, maternal demography and fetal biometry were analyzed with linear regression. RESULTS: Among 203 recruited women, 195 (96.06%) had hypovitaminosis D. One hundred fifty two (75%) were in deficient state and 43 women (21%) were in insufficient state. Women with insufficient vitamin D had the highest proportion of anemia, while women with normal vitamin D level had the highest proportion of low ferritin level. Maternal serum vitamin D showed significant associations with biparietal diameter (ß = 0.141, p = 0.042) and abdominal circumference (ß = 0.819, p = 0.001) after adjustment with maternal age, pre-pregnancy body mass index, parity, serum ferritin level, and hemoglobin level. CONCLUSION: Our study suggested that sufficient maternal vitamin D level was an important factor to improve fetal growth and development.

Optimizing ultraviolet B radiation exposure to prevent vitamin D deficiency among pregnant women in the tropical zone: report from cohort study on vitamin D status and its impact during pregnancy in Indonesia.

BACKGROUND: Vitamin D deficiency during pregnancy carries potential threat to fetal well being. Natural conversion of vitamin D in the skin can be facilitated by direct ultra violet B (UVB) radiation, but the effect is reduced by wearing umbrellas, clothes, or sunblock cream. Muslim women wear hijab that allows only face and hands to be seen. With increasing proportion of muslim women wearing hijab and the lack of vitamin D fortification and fish consumption in Indonesia, it poses a problem for vitamin D deficiency among pregnant women. This study aimed at finding the best timing of UVB exposure and the duration of exposure which can be suggested to prevent vitamin D deficiency among pregnant women, for those wearing hijab or not. METHODS: This study recruited 304 pregnant women in the first trimester, 75-76 women from 4 cities of the most populated province, West Java, Indonesia which represented 70-80% percent of pregnancy per year. A 3-day notes on duration, time and type of outdoor activity and the clothing wore by the women were collected. UVB intensity radiation were obtained. Calculation on body surface area exposed to direct UVB radiation and UVB radiation intensity were done. Measurement of vitamin D level in sera were done on the same week. RESULTS: The median of maternal sera vitamin D level was 13.6 ng/mL and the mean exposed area was around 0.48 m2 or 18.59% of total body surface area. Radiation intensity reached its peak around 10.00 and 13.00, but the mean duration of exposure to UVB during this window was lower than expected. Significant correlation was found between maternal sera vitamin D level and exposed body surface area (r = 0.36, p < 0.002) or percentage of exposed body surface (r = 0.39, p < 0.001) and radiation intensity (r = 0.15, p = 0.029). Further analysis showed that duration of exposure to UVB should be longer for pregnant women wearing hijab as compared to women without hijab. CONCLUSION: This study suggested that the best timing to get UVB exposure was between 10.00-13.00, with longer duration for women wearing hijab (64.5 vs 37.5 min) of continuous exposure per day.

Risk Factors for Poor Pregnancy Outcome in Systemic Lupus Erythematosus Patients.

BACKGROUND: systemic lupus erythematosus (SLE) is still a challenging autoimmune disease, especially in pregnancy setting. An early risk factors awareness of poor pregnancy outcome is important to optimize the outcome of pregnancy in SLE patients. This study was conducted to describe pregnancy outcome and determine the risk factors associated with poor pregnancy outcome in SLE patients. METHODS: a retrospective case-control study of SLE patients with poor and normal pregnancy outcome was performed. Pregnancy histories were reviewed from Dr. Hasan Sadikin General Hospital lupus registry study. The case group was pregnancy with poor outcome, defined as abortion, premature birth, stillbirth, intrauterine growth restriction (IUGR) and neonatal death. The control group was pregnancy with good outcome, defined as live birth and full term. RESULTS: a total of 84 SLE patients were enrolled in this study with 109 pregnancies after SLE diagnosis. The median age of subjects at the time of pregnancy was 28 (25-32) years old. Poor pregnancy outcome comprising 22.9% abortion, 14.7% premature birth, 5.5% stillbirth, 1.8% IUGR and 4.6% neonatal death. There was a significant difference in the number of planned pregnancy (P=0.011) between groups with poor and good outcome. Clinical variables significantly associated with poor pregnancy outcome were lupus nephritis (OR = 4.813, 95% CI 1.709 - 13.557, P = 0.003) and neuropsychiatric SLE (OR = 5.045, 95% CI 1.278 - 19.920, P = 0.021). CONCLUSION: the pregnancy in SLE patient should be planned to have better outcome. Lupus nephritis and neuropsychiatric (NP) SLE were risk factors for poor pregnancy outcome in SLE patient.

Fcγ receptor III expression and morphological maturity on neutrophil are associated with higher iron level of major beta-thalassemia.

Lifetime blood transfusion experienced by major ß-thalassemia patients complicated with iron overload, therefore, may lead to their tissue injury. Ultimately, free toxic iron may alter immune response via dysregulation of immune cell activity producing prolonged effector reaction. Neutrophil as one of the vital innate immune cell despite serves as the first line of defense resulting acute inflammation has a pivotal role in chronic inflammation while releasing the toxic substance that interferes biological processes. This process is initiated by one of them by activation of Fcγ Receptor III (CD16), a neutrophil membrane-bound protein. A cross-sectional laboratory study involving lysed-erythrocyte heparinized whole blood of fifty pediatric major ß-thalassemia patients treated with monoclonal antibodies i.e. CD16, CD14, and HLA-DR, dissected into CD16+ and CD16++ population using flow cytometry. Expression of Fcγ Receptor III was measured as Median Fluorescent Intensity (MFI). Hematology and iron status were measured. A correlation analysis was done. MFI of CD16 neutrophil [509.5 (371 - 796.5)] and ferritin level [(3209 µg/L, 1862 - 4564)] was positively correlated (r = 0.4, P = 0.007). Respectively, ferritin and serum iron were found negatively correlated with segmented neutrophils (r = -0.3, P = 0.02; r = -0.3, P = 0.02). Change in CD16 expression may implicate preliminarily neutrophil activation as a response of iron-overloaded tissue and result in chronic inflammation in ß-thalassemia patients. However, the maturity of this cell may be altered.  Future study in the understanding of neutrophil-mediated inflammation, particularly related to immune complexes and functionality, is imperative to be explored.

The association of 25(OH)D, interleukin-4, interleukin-5, and interleukin-13 levels with the burden of soil-transmitted helminth infection in stunted children aged 24-59 months.

Soil-transmitted helminth (STH) among children aged 24-59 months is one cause of chronic infection that could lead to stunting. The association of 25(OH)D and immune responses during chronic infection in stunted populations has not yet been well established. An association study of case-control data was conducted in Bandung district from October 2019 to January 2023. Sociodemographic factors, stool samples, and serum levels of 25(OH)D, interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) were assessed. Statistical analysis was performed to evaluate the prevalence and association of 25(OH)D, IL-4, IL-5, and IL-13 with the burden of STH infection in stunted children. In total, 401 stunted children were recruited. A higher burden of STH infection was found for lower levels of IL-5 (r = -0.477; p = 0.004) and IL-13 (r = -0.433; p = 0.028). Thus, 25(OH)D, IL-4, IL-5, and IL-13 play a role in the burden of STH infection.

Factors influencing stunted growth in children: A study in Bandung regency focusing on a deworming program.

The prevalence of neglected tropical diseases, specifically those caused by soil-transmitted helminths (STHs) and other parasites that infest the intestine as part of their life cycle, remains a problem in Indonesia. We assessed the effects of deworming programs and socioeconomic and ecological factors on the incidence rate of infections with STHs and other parasites in an urban area of the Bandung Regency. We recruited 361 children with stunted growth who met the inclusion criteria, and 48 of those children were at high risk of STH infection. The study was conducted between September 2020 and September 2021. We collected possible socioeconomic factors influencing the incidence rate of infections. We found the incidence rate of STH infections among the children with stunted growth to be 3.6%. We confirmed infections with Cyclospora and Cryptosporidium after a Ziehl-Nieelsen stool smear examination in two of the 48 children at risk of infection. We found 43.75% of the children had short stature and weight below the normal limits, while stunting and severe stunting were associated with Ascaris lumbricoides infection (44.70%, p = 0.035). Parents of children with stunted and severely stunted growth were more likely to have a low education level, lack knowledge about deworming program, and to be earning a low income. The mother's occupation had a particularly strong influence on the severity of the stunting (89.58%, p = 0.012). Our results show that deworming programs can affect the growth and development of children and that socioeconomic and ecological factors also play a role.

Surveillance of Soil-Transmitted Helminth Infection in Preschool Child Population: Do Changes in Behavior and Immunological Responses Affect Prevalence?

Soil-transmitted helminths (STHs) persist as a significant global public health issue among neglected tropical diseases (NTDs), particularly in children. STH infection can induce immune responses that affect the course of the disease; if treatment fails, chronic infection can lead to stunting, especially among children aged 24-59 months, which is a vulnerable period for growth and development. We conducted a correlational, cross-sectional data collection study to evaluate the characteristics and association of 25(OH)D, interleukin-5 (IL-5), and interleukin-13 (IL-13) with the prevalence of STH infection in children aged 24-59 months in Bandung District, Indonesia, in October 2019-January 2023. We recruited 694 subjects (401 stunted and 293 normal-height children). The prevalence of STH infection among the stunted and normal-height groups was 5.7% (95% CI: 3.85-8.46%) and 3.4% (95% CI; 1.86-6.17%) (p = 0.156), respectively. The probability of the prevalence of STH infection in children with levels of 25(OH)D, IL-5, and IL-13 below the cut-off point was 6,93 to 16.71 times higher. We found a relationship between IL-5, IL-13, and environmental factors and the prevalence of STH infection in stunted children.

A Meta-Analysis of Atrial Septal Defect Closure in Patients With Severe Pulmonary Hypertension: Is There a Room for Poking Holes Amid Debate?

Severe pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) poses a challenge to a closure of ASD, particularly severe PAH that persists even after pharmacological therapeutic strategy. Our study was aimed to evaluate this matter. A systematic literature search from several databases was conducted up until August 1st, 2023. A meta-analysis was undertaken on studies that reported hemodynamic measurements in ASD patients with severe PAH before and after closure. The primary objectives were the extent of improvement in all hemodynamic parameters following closure, and the secondary outcomes were major adverse cardiac events (MACEs) during follow-up. Our study comprised 10 studies with a total of 207 participants. Patients were divided into treat-and-repair and straight-to-repair groups based on the therapeutic strategy. Meta-analysis of all studies demonstrated significant improvement in mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), pulmonary vascular resistance index (PVRI), 6-minutes walking distance (6MWD), and lower prevalence of World Health Organization functional classes (WHO fc), particularly in the treat-and-repair strategy subgroup. Additionally, merely 4 of the 156 individuals died from cardiac causes, and only 1 required rehospitalization, indicating a low likelihood of MACEs arising. Our new findings support the notion that effective shunt closure can improve various hemodynamic parameters in carefully chosen patients with noncorrectable ASD-PAH. Further large and prospective observational studies are still warranted to validate these findings.

Correlation Between Vitamin D Status and HBsAg Antibody Levels in Indonesian Adolescents Immunised Against Hepatitis B.

Introduction: Hepatitis B virus (HBV) infection is a global health problem. Anti-hepatitis B surface antigen (HBsAg) levels increase along with vitamin D levels in adults. However, few studies have examined this relationship in adolescents. Few studies have examined the relationship between vitamin D and HBsAg antibody levels, especially in Indonesia. Methods: This cross-sectional study examined vitamin D and anti-HBsAg levels before and after hepatitis B immunisation. All subjects blood was taken to check for vitamin D level. This study was part of the Safety and Preliminary of Immunogenicity Following Recombinant Hepatitis B (Bio Farma) Vaccine in Adults and Children Phase I trial. Results: This study found that 25-hydroxyvitamin D [25(OH)D] status was primarily deficient based on endocrine criteria. The children's hepatitis B antibody response was mostly <10 mIU/mL before and ≥10 mIU/mL after vaccination. There was a relationship between sex and 25(OH)D status, with median 25(OH)D levels higher in females (18.2 ng/mL) than in males (9.8 ng/mL). However, the relationship between vitamin 25(OH)D status and anti-HBsAg levels pre- and post-vaccination was not significant. Discussion: However, some research found that vitamin D supplementation after immunisation did not impact vaccine response, several studies have reported that vitamin D can decrease HBV replication through various mechanisms, including reducing viral transcription and interfering with viral protein synthesis. Conclusion: There was no relationship between 25(OH)D status and anti-HBsAg levels. Further research is needed to elucidate the underlying mechanisms and establish optimal treatment strategies.

The Association between Vitamin D, Interleukin-4, and Interleukin-10 Levels and CD23+ Expression with Bronchial Asthma in Stunted Children.

Children with stunted growth have an increased risk of wheezing, and studies have shown that low levels of vitamin D and interleukin (IL)-10, along with increased IL-4 levels and CD23+ expression, are present in stunted and asthmatic children. To date, it is not known whether these factors are related to the incidence of asthma in stunted children. This case-control study investigated the association between vitamin D, IL-4, and IL-10 levels and CD23+ expression with bronchial asthma in stunted children. The study included 99 children aged 24-59 months, i.e., 37 stunted-sthmatic children (cases), 38 stunted children without asthma, and 24 non-stunted children with asthma. All children were tested for their 25(OH)D levels using chemiluminescent immunoassay (CLIA), IL-4 and IL-10 levels were measured through enzyme-linked immunosorbent assay (ELISA) testing, and CD23+ expression was measured through flow cytometry bead testing. The data were analyzed using chi-squared, Kruskal-Wallis, and Mann-Whitney tests. The results showed that stunted asthmatic children had a higher incidence of atopic family members than those without asthma. Additionally, stunted asthmatic children had a higher prevalence of vitamin D deficiency (48.6%) than the control group (44.7% and 20.8%). Furthermore, stunted asthmatic children had significantly lower levels of 25(OH)D [20.55 (16.18-25.55), p = 0.042] and higher levels of IL-4 [1.41 (0.95-2.40), p = 0.038], although there were no significant differences in IL-10 levels and CD23+ expression. The study concluded that low vitamin D and high IL-4 levels are associated with bronchial asthma in stunted children, while IL-10 and CD23+ do not show a significant association.

Epigenetic Regulation Interplays with Endometriosis Pathogenesis in Low-Birth-Weight Patients via the Progesterone Receptor B-VEGF-DNMT1 Axis.

BACKGROUND: Low birth weight (LBW) is a risk factor associated with endometriosis. Our study aimed to analyze the risk of endometriosis in women with a LBW history and the relationships of progesterone receptor B (PR-B) gene promoter methylation, DNA methyltransferase-1 (DNMT1) expression, PR-B expression, and vascular endothelial growth factors (VEGF) with endometriosis. METHODS: This study was conducted in two stages, a retrospective case-control design and a cross-sectional design, with 52 cases of endometriosis and 30 controls, which were further subdivided into LBW and non-LBW groups, at Hasan Sadikin General Hospital and its hospital networks from October 2017 to August 2021. Menstrual blood was taken from subjects and analyzed using pyrosequencing techniques to assess DNA methylation, while q-RT PCR was used to assess gene expression. RESULTS: There were significant differences in PR-B methylation, DNMT1 expression, PR-B expression, and VEGF expression (p < 0.001) between the case and control groups. There was a significant negative correlation between PR-B methylation and PR-B expression (r = -0.558; p = 0.047). Based on a multiple logistic analysis, the most dominant factor affecting endometriosis incidence is PR-B (OR 10.40, 95% CI 3.24-33.4, R2 = 45.8). We found that patients with a low birth weight history had a 1.41-times-higher risk of developing endometriosis (95% CI 0.57-3.49, p = 0.113), although the relationship was not statistically significant. CONCLUSION: Endometriosis is associated with PR-B gene promoter hypermethylation, decreased PR-B expression, and increased DNMT1 and VEGF expression. The methylation of PR-B is the most dominant factor affecting endometriosis incidence.

The Chemoprotective Role of Vitamin D in Skin Cancer: A Systematic Review.

Introduction: Research in mice showed that vitamin D receptor deficiency was correlated with an increased rate of non-melanoma skin cancer. Therapeutic supplemental vitamin D has also been reported to reduce cell growth in both melanoma and non-melanoma skin cancer. This paper aims to describe the existing research studies that discuss the potential and role of vitamin D in the management of skin cancer. Methods: Articles were searched from three databases (PubMed, ScienceDirect, Scopus) and manual search. 18 articles were included. These were further divided into in vivo and in vitro studies. The literature search was based on the following Patients, Intervention, Control, and Outcome (PICO) criteria: Patients with any types of skin cancer; Vitamin D and their derivates as the intervention; placebo or standard regimen as control, and survival rate or response rate as primary outcome. Results: From the three databases, we obtained 802 studies. Prior to screening of the literature obtained, several studies were excluded. In the eligibility assessment, seven studies were excluded due to their outcomes being not eligible for analysis, and two studies were excluded due to inaccessible full texts. The remaining 18 studies were included. Five studies had a clinical research design (randomized controlled trial or interventional study), which use vitamin D3 as vitamin D derivatives and the results showed that the administration of vitamin D3 reduces the proliferation of skin cancer cells. Similar results were also reported in studies with pre-clinical research designs, either in vivo or in vitro, where six were in vivo studies and nine studies were in vitro studies. Conclusion: Our literature review revealed that that vitamin D derivatives, such as 1,25(OH)2D3 or 20(OH)D3 can effectively reduce the proliferation of skin cancer cells by contributing in the inhibition of cell growth and development, highlighting vitamin D's role as good prognostic factor.

Correlation between Cord Blood Vitamin D Levels and Problem-Solving Neurodevelopment in Early Childhood: A Cohort Study in Rural Indonesia.

Vitamin D influence on brain development and subsequent postnatal neurodevelopment remains controversial. We explored the correlation between cord blood vitamin D levels and longitudinal neurodevelopment in early childhood. A cohort study was conducted on term infants with no congenital abnormalities, born from pregnant women from a cohort study. Cord blood samples were collected to measure vitamin D. Neurodevelopment was examined three times in infants aged 6, 12 and 24 months using the Ages and Stages Questionnaire-3, which comprises 30 questions of five developmental domains: gross motor, fine motor, communication, problem-solving and social-personal. Statistical analysis was conducted with Spearman's rank correlation and multiple linear regression. Of the 141 babies born from previous cohort studies, only 116 participants were included. The mean level of cord blood vitamin D was 16.2 ng/mL. The percentage participants with vitamin D deficiency and insufficiency were 12.9 and 65.5, respectively. Cord blood vitamin D and the problem-solving domain for infant aged 12 and 24 months were correlated (r = 0.217 and 0.414, respectively). Multiple linear regression showed a decreased problem-solving domain score of 0.641 associated with decreased vitamin D levels. In conclusion, cord blood vitamin D levels correlated with infant neurodevelopmental status.

Exploring alternative cytokines as potential biomarkers for latent tuberculosis infection in pregnant women.

BACKGROUND: Interferon gamma release assays (IGRAs) are widely used to determine latent tuberculosis infection status. However, its pregnancy-affected performance and cost-expensive nature warrants for different alternatives for pregnant women. This study aims to evaluate the diagnostic performance of several alternative cytokines, including interleukin 2 (IL-2), interleukin 10 (IL-10), and interferon gamma-induced protein 10 (IP-10) to identify latent tuberculosis status in pregnant women. MATERIALS AND METHODS: 123 pregnant womens were recruited for this study. The IGRA status was determined by using QuantiFERON Gold In-Tube. Meanwhile, we measured the level IL-2, IL-10, and IP-10 by using sandwich-microELISA method. We performed normality and comparison test by SPSS. In addition, receiver-operator characteristic (ROC) analyses and the optimal cutoff scores were identified using the EasyROC webtool. RESULTS: We showed that IL-2, IL-10, and IP-10 were able to discriminate between IGRA-negative and IGRA-positive pregnant women. Moreover, IP-10 showed the highest discriminatory and diagnostic performance when compared to IL-2 and IL-10 with area under the curve (AUC) of 0.96 and cutoff point of 649.65 pg/mL. CONCLUSIONS: Our study showed that IP-10 can be considered as a promising alternative biomarker for IGRAs to diagnose LTBI in pregnant women.

Calcitriol potentially alters HeLa cell viability via inhibition of autophagy.

Objective: This study was conducted to evaluate the effect of Calcitriol on cellular death in HeLa cells via autophagy and turn over due to mitochondria homeostasis. Methods: HeLa cell lines were grown in 24-well plates and treated with Calcitriol at varying doses (0.013 µM-0.325 µM) for varying time periods (2, 6, 12, and 18 h). Cell proteins were extracted with scrapers and lysed using RIPA buffer. Western blots were performed for proteins involved with autophagy (Lc3, p62), signaling (mTOR, PI3K, HIF1α), mitochondria (PGC1α, COX4, and Tom 20), and apoptosis (Caspase 3, Caspase 9, and PARP). Protein carbonyl levels were determined by measuring the indirect ROS level. An inhibition study using L-mimosine was performed to analyze the significance of HIF1α. Results: Calcitriol treatment induced cytotoxicity in a dose- and time-dependent manner and caused growth arrest in HeLa cells. The PI3K-AKT-mTOR pathway was activated, leading to inhibition of autophagy and alterations in mitochondria biogenesis homeostasis. Treatment with Calcitriol produced protein carbonyl levels similar to those in the cisplatin-treated and control groups. Increased ROS levels may cause toxicity and induce cell death specifically in cancer cells but not in normal cells. The inhibition of HIF1α partially rescued the HeLa cells from the toxic effects of Calcitriol treatment. Conclusion: We suggest that Calcitriol may shut down mitochondrial homeostasis in HeLa cells by inducing the PI3K-AKT-mTOR pathway and inhibiting autophagy, which leads to cell death.