Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. RESULTS: We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. CONCLUSION: Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.

Converging findings from linkage between periodontal pathogen with atopic and allergic immune response.

This study aims to explore a relationship between exposures of whole-cell Porphyromonas gingivalis in various doses with atopic inflammatory responses at experimental mice. A pretest-posttest controlled group design, with 16 Wistar rats (Rattus novergicus) randomized into four groups. Group 1 was the control group. Group 2 was given low-dose (9 × 107 colony-forming unit) of P. gingivalis. Group 3 was given medium-dose (9 × 109 colony-forming unit) of P. gingivalis. Group 4 was given high-dose (9 × 1011 colony-forming unit) of P. gingivalis. Interleukin-4, Interleukin-5, Interleukin-17F, Interleukin-21, Immunoglobulin-E, Immunoglobulin-G4, and γ-Interferon were measured by direct-sandwich ELISA just before the treatments began, day-4, and day-11 after treatments. There is a sudden increase of Interleukin-4 in the group 4 (23.79 ±â€¯0.91 pg/ml to 54.17 ±â€¯0.79 pg/ml; p = 0.01) and slight increase of Interleukin-5 in the group 4 (207.60 ±â€¯11.15 pg/ml to 243.40 ±â€¯9.33 pg/ml; p = 0.03). No change was observed for Interleukin-17F in all groups. Serum concentration of Immunoglobulin-E was decreased in group 2 (-10.44 ±â€¯8.13 pg/ml), but increased in group 4 (+1.03 ±â€¯4.57 pg/ml). Taken together, some cytokines are up-regulated and others are down-regulated after exposure to whole-cell P. gingivalis. Moreover, study of host responses during periodontal infection may offer critical key insight that contribute to the development of atopy. CLINICAL IMPLICATIONS: We introduced and explained the potential role of periodontal pathogen Porphyromonas gingivalis in systemic immune responses, along with its virulence factor inside the oral cavity. Our results consider several changes and differences of cytokines and immunoglobulins following whole-cell Porphyromonas gingivalis exposure. However, results of the study need to be interpreted with caution due to its limitations. CAPSULE SUMMARY: Interleukin (IL)-4 and IL-5 had been found increase after exposure to the periodontal pathogens Porphyromonas gingivalis, whereas no or minimal change had been found in the level of IL-17F, Ig-G4, and IFN-γ. The various cytokines and immunoglobulins shown in this study do not prove a causal relationship, and the precise role of Porphyromonas gingivalis in the regulation of atopic immune response warrants further investigation. Nevertheless, these findings may provide some critical key insight into the host responses following Porphyromonas gingivalis infection.

The Roles of Renal Oxygen Saturation in Septic Shock Children.

Introduction: Septic shock, the most severe form of sepsis, has high morbidity and mortality rates among children. In patients with septic shock, impaired microcirculatory perfusion is associated with the severity of organ failure and the likelihood of death. Because near-infrared spectroscopy (NIRS) can assess microcirculation status and peripheral tissue oxygenation directly and noninvasively, provides real-time results, and can be performed at the patient's bedside. This study aimed to determine the prognostic value of renal oxygen saturation (rRSO2) measured by NIRS in septic shock among children. Methods: This prospective observational study enrolled children aged 1 month to 18 years with septic shock who were treated in a pediatric intensive care unit from August 2020 to January 2021. NIRS was used to measure rRSO2 in patients diagnosed with septic shock according to the Third International Consensus Definition of Sepsis and Septic Shock. The baseline rRSO2 value (%) formed a receiver operating characteristic curve and was used to calculate the optimal cutoff value, sensitivity, specificity, and odds ratio (OR). Results: We enrolled 24 patients, 13 nonsurvivors and 11 survivors, whose mean baseline rRSO2 values were 67.27 ± 12.95 versus 48.69 ± 16.17, respectively (P = 0.006). The optimal cutoff value for baseline rRSO2 was <60.5%, with a sensitivity of 76.9%, a specificity of 81.8%, and an area under curve 0.804 (95% confidence interval [CI]: 59.2%-98.1%, P = 0.012; OR = 15; 95 CI: 2.04-111.74). Conclusion: Measured by NIRS, rRSO2 values are a good predictor of mortality among children with septic shock.

Trend in the admissions of patients with non-COVID-19 respiratory symptoms during COVID-19 pandemic and its impact on hospital finances in Surabaya, Indonesia.

Background: COVID-19 cases surge, it has a crucial impact on healthcare systems, with rapidly increasing demand for healthcare resources in hospitals and intensive care units (ICUs) in Indonesia and worldwide. It is necessary to quantify the extent to which the effects of the COVID-19 pandemic on the hospital admissions, and clinical and financial outcomes of patients with non-COVID-19 respiratory symptoms. Objective: To determine whether the COVID-19 pandemic changed the hospitalisation of child and adult patients with non-COVID-19 respiratory conditions and whether these changes affected the patient's disease condition, clinical outcomes, and hospital finances. Methods: A retrospective cohort study was conducted from May 1, 2018 (before the COVID-19 pandemic) until December 31, 2021. Total sampling was done to compare hospital admission of patients with non-COVID-19 respiratory symptoms before versus during the COVID-19 pandemic. The results were analyzed using SPSS 26.0 and SmartPLS.v.3.2.9. Results: There was a reduction in hospitalisations for respiratory disorders unrelated to COVID-19 during the pandemic by 55.3% in children and 47.8% in adult patients. During the pandemic, the average hospital revenue per patient of child and adult patients increased significantly, but the profit per patient decreased. Pathway analysis showed that in children, the COVID-19 Pandemic changed disease severity and complexity (ß = 0.132, P < 0.001), as well as clinical outcomes (ß = 0.029, P < 0.05). In adults, the COVID-19 pandemic improves disease severity and complexity (ß = -0.020, P < 0.001), as well as clinical outcomes (ß = -0.013, P < 0.001). COVID-19 pandemic increases care charges (in children with ß = 0.135, P < 0.001; and in the adult patients with ß = 0.110, P < 0.001), worsens hospital financial outcomes relating to child (ß = -0.093, P < 0.001) and adult patient (ß = -0.073, P < 0.001). In adult patients, seasonal variations moderate the impact of the COVID-19 pandemic on improving disease conditions (ß = -0.032, P=<0.001). The child structural model effectively predicted clinical outcomes (Q2 = 0.215) and financial outcomes (Q2 = 0.462). The adult structural model effectively predicted clinical outcomes (Q2 = 0.06) and financial outcomes (Q2 = 0.472). Conclusion: The conclusions are that the number of non-COVID respiratory patients decreased during the COVID-19 pandemic (47.8% in adult patients, 55.3% in child patients). Disease severity and complexity increased in child patients but decreased in adult patient. Costs of care and insurance payments increased. Since the insurance payments did not increase as much as the cost of care, hospital profit decreased.

The Notorious Triumvirate in Pediatric Health: Air Pollution, Respiratory Allergy, and Infection.

A plausible association is suspected among air pollution, respiratory allergic disorder, and infection. These three factors could cause uncontrollable chronic inflammation in the airway tract, creating a negative impact on the physiology of the respiratory system. This review aims to understand the underlying pathophysiology in explaining the association among air pollution, respiratory allergy, and infection in the pediatric population and to capture the public's attention regarding the interaction among these three factors, as they synergistically reduce the health status of children living in polluted countries globally, including Indonesia.

Selenium level correlates negatively with antibodies but positively with thyroid function in children with down syndrome: an Indonesian study.

Background: Children with Down syndrome (DS) are prone to developing autoimmune thyroid disease (AITD). Previous studies found lower selenium (Se) levels in children with AITD. Glutathione peroxidase-3 (GPx3) and selenoprotein-P (SePP) are widely used to measure Se levels. DS children tend to have lower Se levels, the main contributor to hypothyroidism in this population. This study aimed to analyze the Se's role in AITD in Indonesian children with DS. Methods: This cross-sectional study was conducted between February 2021-June 2022 at the Pediatric Outpatient Clinic of Dr Soetomo Hospital. DS children aged 1 month to 18 years were enrolled using consecutive sampling. Thyroid-stimulating hormone, free thyroxine, thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) autoantibody, GPx3, and SePP levels were measured in plasma samples using enzyme-linked immunosorbent assays. Statistical analyses used Chi-square, Mann-Whitney, and Spearman's rank correlation (r s). All results with p<0.05 were considered statistically significant. Results: Among 62 children with DS, SePP and GPx3 levels were significantly lower in those with AITD than those without AITD (p=0.013 and p=0.018, respectively). SePP and GPx3 levels correlated significantly with lower TPO-Ab (r s=-0.439 with p=1×10-5 and r s=-0.396 with p=0.001, respectively) and Tg-Ab (r s=-0.474 with p=1×10-5 and r s=-0.410 with p=0.001, respectively) levels. SePP levels correlated significantly with lower thyroid dysfunction incidence (r s=-0.252, p=0.048) in the AITD group. Conclusion: Selenium deficiency contributes to autoimmune process in the thyroid and to thyroid dysfunction in children with Down syndrome. Our findings recommend increasing Se levels through Se-containing foods to reduce the risks of AITD and thyroid dysfunction in DS children with AITD.

Protein tyrosine phosphatase non-receptor type 22 C1858T gene polymorphism in children with down syndrome and autoimmune thyroid diseases.

Autoimmune Thyroid Disease (AIT) is a frequent comorbidity in Down Syndrome (DS). Protein Tyrosine Phosphatase Non- Receptor Type 22 C1858T (PTPN-22 C1858T) gene polymorphisms have a role in the progression of AIT. The study on PTPN- 22 C1858T gene polymorphism as the risk factor of AIT in DS children is still limited. This study aims to evaluate PTPN-22 C1858T polymorphism in Indonesian DS children. A cross-sectional study involving 31 DS children with hypothyroidism (19 boys/12 girls) was conducted for ten months from February to November 2020 at Dr. Soetomo General Hospital Surabaya. The PTPN-22 C1858T gene polymorphism was analyzed using Polymerase Chain Reaction-Restriction-Fragment-Length Polymorphism (PCR-RFLP). Anti-Thyroid Peroxidase (Anti- TPO) and Anti-Thyroglobulin (Anti-TG), FT4, T3, and TSH levels were analyzed using Enzyme-Linked-Immunosorbent-Assay (ELISA). The mean age of the subjects was 19.45±17.3 months. The CT variant of PTPN-22 C1858T was observed in all subjects. The mean level of T3, FT4, and TSH were 1.59±0.45 ng/mL, 0.81±0.57 ng/mL, 0.22±0.21 µU/mL, respectively. Around 83.9% of patients suffered from central hypothyroidism, 12.9% from primary hypothyroidism, and 3.2% from subclinical hypothyroidism. The positive anti-TG and anti-TPO were observed in 96.8% and 58.1%, respectively. CT variant was observed in Indonesian DS children who suffered from hypothyroidism.

Cytotoxic T-lymphocyte-associated protein 4 +49A/G polymorphism in Down syndrome children with Hashimoto's thyroiditis.

Thyroid dysfunction is the most common endocrine disorder in Down syndrome (DS) children. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is one of the immune regulatory genes that correlates with Hashimoto's thyroiditis (HT). However, studies on CTLA-4 +49A/G in DS children with HT are still limited. We aimed to evaluate CTLA-4 +49A/G gene polymorphism in DS children with HT. This case-control study, conducted from February 2020 to February 2022 at Dr. Soetomo General Hospital, Surabaya, enrolled 40 DS children with HT and 50 healthy children. The DNA sequencing was performed to identify the polymorphism (Sanger sequencing). Thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were analyzed by enzyme-linked immunosorbent assay (ELISA). The mean age of DS children with HT was 1.78 years. Males predominated in the study population. Subjects with GG genotype were diagnosed earliest with hypothyroidism (8 months) compared with other studies. The most common thyroid dysfunction was central hypothyroidism, with TgAb positivity present in all patients. The AA genotype (odds ratio [OR] 0.265, 95% confidence interval [CI] 0.094-0.746; P = 0.012) and A allele (OR 0.472, 95% CI 0.309-0.721; P = 0.0002) were significantly more frequent in the control group. The AG genotype (OR 2.65, 95% CI 0.094-0.746; P = 0.003) and G allele (OR 2.116, 95% CI 1.386-3.23; P = 0.003) were more frequent in the DS with HT group. The age of the subjects in this study was younger than in previous studies. The AG genotype and the G allele were more prevalent in the DS with HT group and may be a risk factor in HT development in DS children. Furthermore, the AA genotype may act as a protective factor against HT in DS children.

The efficacy of topical adipose mesenchymal stem cell-conditioned medium versus framycetin gauze dressing in chronic plantar ulcer of leprosy: A randomized controlled trial.

Background Wound healing shows a unique interaction of several cells, growth factors and cytokines. The healing of chronic plantar ulcer of leprosy is influenced by various factors, one of which is the concentration of growth factors and cytokines related to the pathogenesis of impaired wound healing. Growth factors and cytokines can be found in the secretome of adipose mesenchymal stem cells. Aim To compare the effectiveness of topical adipose mesenchymal stem cell-conditioned medium and framycetin gauze dressing only on the healing of chronic plantar ulcer of leprosy. Methods In this randomised controlled trial, 32 patients with chronic plantar ulcer of leprosy were recruited. After detailed clinical and initial debridement, patients were randomised to two groups to receive either topical adipose mesenchymal stem cell-conditioned medium (n = 16) or framycetin gauze dressing only (n = 16) applied every three days for up to eight weeks, following which the ulcer size, adverse reactions and complications if any were monitored weekly. Results Healing percentage increased each week in all groups. Statistical differences between groups (P < 0.05) were observed from week 2 onwards for ulcer mean size reduction and from week 3 onwards for ulcer mean depth reduction. There were no adverse reactions or complications. Limitations Off-loading on subjects were not performed. Conclusion Adipose mesenchymal stem cell-conditioned medium is a potential therapeutic agent in the management of chronic plantar ulcer of leprosy.

Incidence of SARS-CoV-2 infection in hospital workers before and after vaccination programme in East Java, Indonesia-A retrospective cohort study.

Background: The incidence of the Coronavirus Disease 2019 (COVID-19) among healthcare workers (HCWs) is widespread. It is important to understand COVID-19 characteristics among HCWs before and after vaccination. We evaluated the incidence of COVID-19 among HCWs in East Java, Indonesia comparing the characteristics of the disease between the pre- vs post-vaccination periods. Methods: A retrospective observational study was conducted among HCWs in two major hospitals in East Java, Indonesia, between April 01, 2020, and Oct 31, 2021. All HCWs were offered vaccination with inactivated viral vaccine (CoronaVac) from Jan 15, 2021. Therefore, we divided the time of the study into the pre-vaccination period (between April 01, 2020, and Jan 14, 2021) and post-vaccination period (between Jan 15 and Oct 31, 2021). We then compared the pattern of COVID-19 infections, and hospitalisations between these periods. Findings: A total of 434 (15.1%) and 649 (22.6%) SARS-CoV-2 infections were reported among study participants (n = 2878) during the pre-vaccination and post-vaccination periods, respectively. The vaccine effectiveness was 73.3% during the first 3-4 months after vaccination but this decreased to 17.6% at 6-7 months after vaccination, which coincided with the emergence of the delta variant. The overall hospitalisation rate was reduced from 23.5% in the pre-vaccination period to 14.3% in the post-vaccination period. Hypertension appeared to be the strongest risk factor affecting hospitalisation in the pre-vaccination period. However, the risk due to hypertension was reduced in the post-vaccination period. Interpretation: The risk to contract COVID-19 remains high among HCWs in East Java, Indonesia. Vaccination is important to reduce infection and hospitalisation. It is essentially important to evaluate the characteristics of COVID-19 infection, hospitalisation, the impact of co-morbidities and vaccine effectiveness in order to improve the measures applied in protecting HCWs during the pandemic. Funding: Mandate Research Grant No:1043/UN3.15/PT/2021, Universitas Airlangga, Indonesia.

Safety Profile and Issues of Subcutaneous Immunotherapy in the Treatment of Children with Allergic Rhinitis.

This study aims to evaluate safety issues of house dust mite subcutaneous immunotherapy (SCIT) among allergic rhinitis (AR) children. A retrospective cohort study was done between 2015 and 2020 to investigate the side effects of SCIT among AR children caused by a house dust mite allergy. Among 1098 patients who received house dust mite subcutaneous immunotherapy injections, 284 patients (25.87%) had side effects (SE). SE were found to be 699 times higher or in 2.27% of the 30,744 subcutaneous immunotherapy injections. A total of 17.9% of the patients had local SE during SCIT administration. Systemic side effects occurred in 8.38% of children receiving SCIT and in 0.53% of the total population who received SCIT injections. Only 2/92 (2.18%) of patients suffered an allergic reaction within 30 minutes of injection and these patients responded well to antiallergic medication. Severe anaphylaxis occurred in 0.091% of the 1098 patients in the SCIT group and in 0.0033% of the 30,774 SCIT injections. Systemic SE after SCIT occurred in 8.38% of patients receiving SCIT or 0.53% of the total number of SCIT injections. Anaphylactic episodes occurred in 16 patients (1.46%) and 15 patients (1.37%) who had first and second episodes. One severe attack was found and it was resolved with adrenaline. This study demonstrates that in pediatric patients with AR who received HDM SCIT for 18 months with high adherence, some experienced significant local SE and systemic SE caused by SCIT, but this did not interfere with the course of AR treatment or the effectiveness of SCIT.

HLA-DQA1 and HLA-DQB1 Gene Polymorphism in Indonesian Children with Type I Diabetes Mellitus.

BACKGROUND: More than 40 genes influence the progression of type 1 diabetes mellitus (T1DM), including human leukocyte antigen (HLA) alleles. Different HLA genotype patterns result in diverse rates of T1DM development. HLA class II DR, DQ, and DP vary among different populations and ethnicities. Data on HLA polymorphism in T1DM in Indonesia are lacking. Therefore, this study was designed to evaluate the gene polymorphism of HLA-DQA1 and HLA-DQB1 in Indonesian children with T1DM. PATIENTS AND METHODS: In this study, 31 patients with T1DM and 31 controls were enrolled from April 2020 to April 2021. This study was conducted at Dr. Soetomo Hospital, Indonesia. We evaluated the gene polymorphism of HLA-DQA1 and HLA-DQB1 using polymerase chain reaction-restriction fragment length polymorphism. The primers used were as follows: for HLA-DQA1, DQAS34: 5'-GGTGTAAACTTGTACCAG-3' (forward) and DQAA261: 5'-ATTGGTAGCAGCGGTAGA-3' (reverse); for HLA-DQB1, DQBS43: 5'-TGCTACT- TCACCAA(C/T)GGG-3' (forward) and DQBA249: 5'-GTAGTTGTGTCTGCA (C/T)AC-3' (reverse). RESULTS: The most common HLA-DQA1 subtype in the T1DM group was 0101/0102 accounting for 67.6%, and 01/03 and 02/03 were found in the T1DM group only. Meanwhile, the most common HLA-DQB1 subtype in the T1DM group was 0301, accounting for 54.8%. Most subjects in this study were Javanese. CONCLUSION: HLA-DQA1 0101/0102 and HLA-DQB1 0301 were commonly found in Indonesian children with T1DM.

Pediatric Residency Training amid the COVID-19 Pandemic: Exploring the Impact of Supervision and Clinical Practice Guidelines on Clinical and Financial Outcomes.

Objective: This study is aimed at calculating the magnitude of the effect of clinical practice guidelines (CPG) and supervision in inhibiting the negative impact of the COVID-19 pandemic on clinical and financial outcomes of non-COVID-19 inpatient care by pediatric residents in academic medical center (AMC) hospitals during the COVID-19 pandemic. Methods: The cohort retrospective study was conducted. This study collected patient data from pediatric residency programs. A research cohort consisted of non-COVID-19 pediatric patients at Dr. Soetomo General Academic Hospital. This study compared the subgroup of patients treated during the pandemic with those treated before the pandemic. The results were analyzed using SPSS 26.0 and Smart-PLS. Results: There was a 41.4% decrease in pediatric inpatients during the pandemic with an increased severity level and complexity level, a reduction of 7.46% availability of supervisors, an increase of 0.4% in readmission < 30 days, an increase of 0.31% in-hospital mortality, an increase the total costs of care, and a decrease of insurance claim profit. CPG did not moderate the effect of the COVID-19 pandemic on the clinical outcomes (ß = -0.006, P = 0.083) but moderated the financial outcomes (ß = -0.022, P = 0.000), by reducing the total cost of care and increasing insurance claim profit. Supervision moderated the effect of the COVID-19 pandemic on the clinical outcomes (ß = 0.040, P = 0.000) by increasing aLOS and on the financial outcomes (ß = -0.031, P = 0.000) by reducing the total cost of care and increasing insurance claim profit. This study model had a 24.0% variance of explanatory power for clinical outcomes and 49.0% for financial outcomes. This study's structural model effectively predicted clinical outcomes (Q 2 = 0.238) and financial outcomes (Q 2 = 0.413). Conclusion: Direct supervision inhibited the negative impact of the COVID-19 pandemic on both clinical and financial outcomes of non-COVID-19 inpatient care by pediatric residents, while CPG only inhibited the negative impact on financial outcomes. Implication of This Study. In a disaster, the availability of CPG and direct supervision makes AMC hospitals able to inhibit the negative impact of disasters on clinical and financial outcomes.

The Correlations of Human Atrial Natriuretic Peptide on Cardiac Function and Hemodynamics in Pediatric Septic Shock.

Purpose: We aimed to determine the correlations of human Atrial Natriuretic Peptide (ANP) on cardiac function and hemodynamics in pediatric septic shock. Patients and Methods: We conducted an observational and prospective study on 30 children with septic shock. Measurement of the level of human atrial natriuretic peptide was determined in the serum of patients. Cardiac power (CP) is a cardiac function parameter measured with cardiac output (cardiovascular flow) and mean arterial (intravascular) pressure. Cardiac output and mean arterial pressure were monitored using pressure recording analytical methods (PRAM). Hemodynamic status was represented by a vasoactive inotropic score. Results: Thirty pediatric septic shock patients fulfilled the eligibility criteria. The human ANP level was not significantly different in pediatric septic shock on three days of examination. Cardiac power was significantly different in pediatric septic shock on three days of examination. There was a correlation between human ANP and cardiac power on day 3 and human ANP and VIS on day 2. Conclusion: There was a significant correlation between human ANP level and cardiac power on day 3 and ANP level and VIS on day 2. The cardiac power on day 3 and VIS on 48 hours can be alternatives to evaluate the hemodynamic status and cardiac function concerning human ANP in pediatric septic shock.

Expression of cytokeratin-7 and cytokeratin-19 on newborn mice induced rhesus rotavirus as biliary atresia model.

Introduction: biliary atresia (BA) is a progressive inflammation that causes obstruction and fibro-obliteration of the bile ducts during the perinatal period. Biliary atresia occurs in about 1 in 5000 to 8000 live births, and 50% require liver transplantation. This study aims to iinvestigate the influence of induction and duration of illness after rhesus rotavirus (RRV) exposure to changes in the expression of cytokeratin-7 (CK-7) and cytokeratin-19 (CK-19) in mice models of AB. Methods: a total of 48 Balb/c less than a day after birth was included as model of BA. The overall sample was split randomly by using the randomization table into 4 control groups and 4 treatment groups. Groups 1,2,3, and 4 composed of 24 infant mice Balb/c (each group of 6 tails) with blue color code get a placebo (buffered saline) intraperitoneallyless than a day after birth. Groups 5, 6, 7, and 8 were composed of 24 mice Balb/c (eachgroup of 6 tails) with red color code get induction RRV 1.5 x 106 Plaque forming units (PFU) as treatment groups. Results: there are influence of the RRV induced changes in the expression of CK-7 murine model of BA day 3, 7, 14 and 21 after induction compared to the control (p<0.05). There was interaction between induction effects and duration of illness after RRV exposure to CK-7 expression in murine models of BA on days 3, 7, 14 and 21 (p<0.001). There was difference in the value of CK-19 expressions progressively between trial group and control group seen from day-3 and day 21. Conclusion: induction and duration of illness after rhesus rotavirus exposure effect on the expression of cytokeratin-7 and cytokeratin-19 mice models of biliary atresia.

Renal Oxygen Saturation as an Early Indicator of Shock in Children.

Background: Shock is a life-threatening syndrome in which tissue perfusion and oxygen delivery are inadequate. Near-infrared spectroscopy (NIRS) has been suggested as a noninvasive tool for monitoring and detecting the state of inadequate tissue perfusion. Renal and mesenteric oximetry show decreased cardiac output earlier than systemic or global parameters of tissue oxygenation or cerebral oximetry. However, until now there has been no study on the validity of regional renal oxygen saturation (rRSO2) by NIRS for diagnosing shock in children. Purpose: To analyze the validity of rRSO2 by NIRS to diagnose shock in children. Patients and Methods: This cross-sectional study was conducted in critically ill children (aged 1 month-18 years) who were admitted to the pediatric intensive care unit (PICU), from September to November 2020, consecutively. Patients were classified into two groups: shock and non-shock. The diagnosis of shock is based on clinical criteria (tachycardia, sign of hypoperfusion and decrease systolic blood pressure

The correlation between vitamin D and levels of IFN-γ, NF-κB, thyroid antibodies in down syndrome: study in Indonesian children.

BACKGROUND AND AIM: Vitamin D (VD) reduces interferon-gamma (IFN-γ) production and prevents nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, impacting the inhibition of the autoimmunity process such as autoimmune thyroiditis (AITD). Children with Down syndrome (DS) are reported to have a higher risk of autoimmunity and lower VD levels than non-DS. Therefore, this study aimed to evaluate VD levels in Indonesian DS children and their relationship with marker of AITD. METHODS: This study was conducted on DS children at Dr Soetomo Hospital between February 2021-June 2022. Socio-demographic status, amount of milk, fish and meat consumption, and duration of sun exposure were obtained using a self-report questionnaire. Thyroid hormone (TSH and FT4), thyroid antibody (TPO-Ab and Tg-Ab), 25 (OH)D, IFN-γ, and NF-κB levels were measured using ELISA. RESULTS: Of the 80 participants, 53.75% had sufficient (50.829±17.713 ng/ml) and 46.25% had non-sufficient (20.606±5.974 ng/ml) VD levels. Daily milk consumption, meat and fish consumption were risk factors contributing to VD levels in multivariate analysis [p=0.003, OR=1.007(1.003-1.012); p=0.004, OR=1.816(1.209- 2.728), respectively]. Participants with sufficient VD had significantly higher TPO-Ab (p=0.007) and Tg-Ab (p=0.016). Mean of VD levels were significantly negatively correlated with IFN-γ levels (r =-0.262, p=0.037) and positively correlated with TPO-Ab (r= 0.432, p=1x10-5,) and Tg-Ab (r= 0.375, p=0.001). CONCLUSIONS: Majority of subjects had sufficient VD levels. VD suppresses IFN-g, but is unable to affect NF-κB levels, presumably causing high levels of TPO-Ab and Tg-Ab in sufficient VD patient.

CTLA-4 CT-60 A/G and CTLA-4 1822 C/T Gene Polymorphisms in Indonesians with Type 1 Diabetes Mellitus.

Introduction: CTLA-4 gene polymorphism plays an important role in children with type 1 diabetes mellitus (T1DM). However, data on this subject vary among different races and ethnics. Purpose: To analyze CTLA-4 CT-60 A/G and CTLA-4 1822 C/T gene polymorphism among children with T1DM compared to control. Patients and Methods: The CTLA-4 CT-60 A/G and CTLA-4 1822 C/T gene polymorphism in children with T1DM using polymerase chain reaction-restriction fragment length polymorphism in 25 T1DM and 25 controls. The inclusion criteria were patients regularly controlled at the Pediatric Endocrine Outpatient Clinic of Dr. Soetomo Hospital, aged 4-18 years and willing to join this study and the exclusion criteria were T1DM patients hospitalized in the pediatric intensive care unit. In the control group, the inclusion criteria were healthy children, aged 4-18 years and willing to join this study. The exclusion criteria included children with ongoing infection, history of other autoimmune diseases, allergies, or malignancy. Results: The mean age was 12.48 years old, and the mean of T1DM onset was 9.28 years old. The CTLA-4 1822 T allele observed in 62% T1DM and 56% in control (p = 0.388, OR = 0.78, 95% CI = 0.44-1.37) and CTLA-4 CT-60 G allele observed in 52% T1DM and 58% in control (p = 0.393, OR = 1.27, 95% CI = 0.73-2.22). The C/T genotypes was significantly higher in control group (p = 0.045, OR = 3.27, 95% CI = 1.00-10.62). The A/G genotypes was commonly found in control group (p = 0.765, OR = 1.20, 95% CI = 0.37-3.86). The Javanese was the dominant ethnic group in our study. Conclusion: The frequency of CTLA-4 CT-60 A/G polymorphism almost equivalent in T1DM and control group. However, CTLA-4 1822 C/T polymorphism was more prevalent in the control group; thus, this genotype may have a protective effect against T1DM.

Nigella sativa L. as immunomodulator and preventive effect on renal tissue damage of lupus mice induced by pristane.

Introduction: Nigella sativa L. is an herbal plant with Thimoquinone as the main therapeutic properties. This plants has been shown to cure for various diseases and affected the immune system by modulating cytokines and T regulatory cell (Treg) sot that able to prevent renal injury in several diseases, but studies on Systemic Lupus Erythematous are still rare. Objective: This study aimed to investigate immunomodulation and preventive effects of Nigella sativa L. on renal tissue damage in Pristane induced Lupus (PIL)-mice model. Methods: This true experimental study included 48 female Balb/C mice, 38 mice were injected pristane intraperitoneally and waited 16 weeks to become lupus model. Only 30 mice met the Systemic Lupus International Collaborating Clinics criteria. Ten healthy mice were used as control, 30 PIL mice model divided into 3 groups (placebo, steroid, Nigella sativa L.). At the end of 28 days of treatment, the mice were sacrificed to take a blood sample and kidney organ to evaluate the injury histopathologically. Results: The results showed that the cytokine expression Interleukin (IL) (IL-17, IL-6, IL-23) in the Nigella sativa L. group was the lowest. The highest absolute number of Tregs was the steroid group followed Nigella sativa L. group. Renal injury assessed histopathologically showed the Nigella sativa L. group was the lowest and almost close to normal. Conclusion: This study indicate that Nigella sativa L. has an immunomodulatory effect and can prevent kidney injury PIL-treated mice. We suggest that Nigella sativa L. may need to be considered for further research on its use as a complementary supplement in lupus patients.

The role of probiotics in the treatment of adult atopic dermatitis: a meta-analysis of randomized controlled trials.

BACKGROUND: Atopic dermatitis (AD) is chronic inflammatory skin disease that is relapsing and a serious condition that disrupts the quality of life of affected individuals. Probiotics are an immunomodulator that can enhance the immune control of atopic dermatitis. METHODS: All randomized controlled trials of probiotics for the treatment of adult AD published before December 2020 were included in this study from the PubMed databases and manual searching. RESULTS: Six randomized controlled trials (n = 241) were selected for this meta-analysis study. Probiotics were effective in treating adult patients with AD, indicated by the decrease in Scoring Atopic Dermatitis/SCORAD (Mean Difference (MD) - 7.90, 95% CI - 7.25 to - 6.92; p < 0.00001; I2 = 96%) and improved quality of life (MD - 7.68, 95% CI - 14.08 to - 1.29; p = 0.02; I2 = 47%) which were statistically significant. However, skin severity, itch severity, Dermatology Life Quality Index (DLQI), IL-4, TFN-γ, and IgE showed no significant difference in this meta-analysis study (p > 0.05). LIMITATIONS: The study found no available data for side effects of probiotics. STRENGTH: This meta-analysis analyzed a total of 241 AD patients of Asian and European origin. CONCLUSION: The use of probiotics decreased SCORAD significantly in adult patients with AD. Probiotics can improve the quality of life of patients with AD. The use of probiotics in atopic dermatitis has been widely studied, with controversial results. This meta-analysis suggests that the use of probiotics can improve SCORAD and the quality of life of patients with atopic dermatitis.