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1.
Sci Adv ; 5(10): eaat9480, 2019 10.
Article in English | MEDLINE | ID: mdl-31692957

ABSTRACT

Recent progress in passive radiative cooling technologies has substantially improved cooling performance under direct sunlight. Yet, experimental demonstrations of daytime radiative cooling still severely underperform in comparison with the theoretical potential due to considerable solar absorption and poor thermal insulation at the emitter. In this work, we developed polyethylene aerogel (PEA)-a solar-reflecting (92.2% solar weighted reflectance at 6 mm thick), infrared-transparent (79.9% transmittance between 8 and 13 µm at 6 mm thick), and low-thermal-conductivity (k PEA = 28 mW/mK) material that can be integrated with existing emitters to address these challenges. Using an experimental setup that includes the custom-fabricated PEA, we demonstrate a daytime ambient temperature cooling power of 96 W/m2 and passive cooling up to 13°C below ambient temperature around solar noon. This work could greatly improve the performance of existing passive radiative coolers for air conditioning and portable refrigeration applications.

3.
Br J Dermatol ; 180(3): 574-579, 2019 03.
Article in English | MEDLINE | ID: mdl-30030843

ABSTRACT

BACKGROUND: There is no cure or firm clinical recommendations for the treatment of vitiligo. One of the main issues is the heterogeneity of outcome measures used in randomized controlled trials for vitiligo. OBJECTIVES: To define successful repigmentation from the patients' point of view and to propose how and when repigmentation should be evaluated in clinical trials in vitiligo. METHODS: We conducted three workshops with patients with vitiligo and their parents or caregivers. Workshop 1 was held at World Vitiligo Day (Detroit, MI), workshop 2 at the University of Texas Southwestern Medical Center and workshop 3 at the Vitiligo and Pigmentation Institute of Southern California, University of California. RESULTS: Seventy-three participants were recruited. Consensus on the following questions was achieved unanimously: (i) the definition of 'successful repigmentation' was 80-100% of repigmentation of a target lesion and (ii) both an objective and a subjective scale to measure repigmentation should be used. CONCLUSIONS: This was the largest patients' outcomes workshop. We followed the guidance from the CSG-COUSIN and the Vitiligo Global Issues Consensus Group. Our recommendations to use percentage of repigmentation quartiles (0-25%, 26-50%, 51-79%, 80-100%) and the Vitiligo Noticeability Scale are based on the best available current evidence. A limitation of the research is that the workshops were conducted only in the U.S.A., due to pre-existing organisational support and the availability of funding.


Subject(s)
Consensus Development Conferences as Topic , Consensus , Patient Satisfaction , Skin Pigmentation , Vitiligo/therapy , Adolescent , Adult , Clinical Trials as Topic , Color , Delphi Technique , Female , Humans , Male , Skin/diagnostic imaging , Treatment Outcome , United States , Vitiligo/diagnosis
4.
J Perinatol ; 38(2): 137-141, 2018 02.
Article in English | MEDLINE | ID: mdl-29095429

ABSTRACT

OBJECTIVE: Meconium aspiration syndrome (MAS) is a common cause of neonatal morbidity and mortality. Incomplete understanding of the pathogenesis of MAS has hindered the development of specific therapies. We hypothesized that activation of Toll-like receptors (TLRs) might play a role in the pathogenesis of MAS. The present study evaluated the expression of TLR 1, 4, 7, 8 and 9 in neonates with MAS. STUDY DESIGN: The study included 39 neonates with MAS and 17 healthy gestational age-matched neonates as controls. Neonates with maternal chorioamnionitis, perinatal asphyxia, sepsis and congenital malformations were excluded. Good-quality total RNA from umbilical cord blood was reverse transcribed to prepare cDNA using Bio-Rad reverse transcription kit. This cDNA was used to study the expression status of TLR 1, 4, 7, 8 and 9 by real-time quantitative polymerase chain reaction. RESULTS: Compared with controls, TLR1 and TLR4 were highly expressed, TLR9 was moderately expressed, TLR7 was weakly expressed and TLR8 expression was neutral in neonates with MAS. Within the MAS group, no difference in TLR expression was observed with respect to consistency of meconium, severity of the disease, oxygenation index and outcome. CONCLUSION: There is activation of TLRs in neonates with MAS. We speculate that these TLRs probably act as endogenous ligands for various components of meconium that initiate the inflammatory cascade of MAS and contribute to its pathogenesis.


Subject(s)
Inflammation/metabolism , Meconium Aspiration Syndrome/metabolism , Toll-Like Receptors/metabolism , Biomarkers/blood , Case-Control Studies , Female , Fetal Blood , Gestational Age , Humans , Infant, Newborn , Male , Meconium Aspiration Syndrome/blood , Prospective Studies , Signal Transduction , Toll-Like Receptors/blood
5.
Neurol Res Int ; 2017: 1524548, 2017.
Article in English | MEDLINE | ID: mdl-28713592

ABSTRACT

Seizures are one of the common causes for hospital admissions in children with significant mortality and morbidity. This study was conducted to study the prevalence and clinicodemographic profile of children with seizures in a tertiary care hospital of western Nepal. This prospective cross-sectional study conducted over a period of 2 years included all admitted children (2 months-16 years) with seizures. Among 4962 admitted children, seizures were present in 3.4% (n = 168) of children, with male preponderance. 138 (82.1%) children had generalized tonic-clonic seizures (GTCS) and 30 (17.9%) children had partial seizures. GTCS were more common than partial seizures in both sexes (male = 82.7%; female = 81.2%) and age groups. There was no statistical significance in the distribution of seizures (GTCS and partial seizures) with sexes (P = 0.813) and age groups (P = 0.955). Mean ages of children having GTCS and partial seizures were 8.2 ± 4.6 years and 8.2 ± 4.2 years, respectively. Loss of consciousness (55.4%), fever (39.9%), vomiting (35.1%), and headache (16.1%) were common complaints in seizure patients. Significant number of GTCS cases had fever (P = 0.041) and neurocysticercosis (n = 72; 43%) was the most common etiology in seizure patients. Idiopathic epilepsy (38 (22.6%)), meningoencephalitis (26 (15.5%)), and febrile convulsions (14 (8.33%)) were other leading disorders in children with seizures.

6.
Eur J Pediatr ; 176(3): 317-325, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28062958

ABSTRACT

To estimate the levels of malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in cord blood plasma of newborns born through meconium-stained amniotic fluid (MSAF) and also to find out the correlation between their levels with birth weight and gestation, we measured the cord blood plasma levels of MDA and 8-OH-dG in 59 newborns born through MSAF and 50 newborns born through clear liquor. The levels of cord blood plasma MDA and 8-OH-dG were significantly higher in full-term and late-preterm newborns born through MSAF. On further comparison, it was found that both full-term and late-preterm intrauterine growth restricted (IUGR) neonates had higher levels of these markers as compared to babies born as appropriate for gestational age (AGA) through MSAF. Plasma levels of MDA and 8-OH-dG were significantly correlated with birth weight even after controlling the relationship with gestational age for all cases as well as all full-term cases. These markers are also significantly correlated to each other. CONCLUSIONS: The present study suggest that the neonates born through MSAF experience higher degrees of oxidative stress, as evidenced by increased levels of cord blood plasma MDA and 8-OH-dG. What is known: • Aspirated meconium has been found to induce free radical generation and cellular damage in animal studies. • Its role in free radical generation and oxidative damage in human neonates is scarce. What is new: • Neonates born through meconium-stained amniotic fluid experience significant oxidative stress.


Subject(s)
Amniotic Fluid , Delivery, Obstetric/adverse effects , Fetal Blood/chemistry , Meconium , Oxidative Stress/physiology , 8-Hydroxy-2'-Deoxyguanosine , Biomarkers/blood , Birth Weight , Chi-Square Distribution , Cross-Sectional Studies , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Enzyme-Linked Immunosorbent Assay , Female , Fetal Growth Retardation/etiology , Gestational Age , Humans , Infant, Newborn , Malondialdehyde/blood , Pregnancy
8.
J Clin Diagn Res ; 9(2): SD01-3, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25859496

ABSTRACT

Neurocysticercosis (NCC) is one of the most common parasitic infestations (Taenia solium) of central nervous system (CNS) in children. Seizures are the common presenting symptoms. Hydrocephalus and optic atrophy are rare complications which may require neurosurgical interventions. We report a case of NCC with hydrocephalus and bilateral optic atrophy associated with vision loss in a Nepalese patient who improved with anti-parasitic therapy followed by ventriculo-peritoneal (VP) shunting.

9.
JNMA J Nepal Med Assoc ; 53(199): 184-7, 2015.
Article in English | MEDLINE | ID: mdl-27549502

ABSTRACT

INTRODUCTION: Hypoxemia is the major cause of neonatal morbidity and mortality. The study aims to determine the influence of birth weight, Apgar score, gestation age, body mass index and hemoglobin of mother on levels of SpO2 in healthy newborns born vaginally and through cesarean section. METHODS: A hospital Based, observational study conducted in Department of Pediatrics, Universal College of Medical Sciences-Teaching Hospital, Bhairahawa, Lumbini, Nepal; on 49 vaginal and 49 cesarean deliveries with Apgar Score ≥ 6. SpO2 was estimated by pulse oximeter post-ductally between 1 to 30 minutes of birth. The observed SpO2 values were correlated with neonatal and maternal factors. RESULTS: Vaginal and Cesarean deliveries SpO2 were comparable for birth weight, gestational age, Apgar score of neonates, body mass index and hemoglobin of the mother. Birth weight in vaginally delivered babies and Apgar score in cesarean births showed significant change in SpO2 (P<0.05). At all points of time the SpO2 values were higher in neonates, born by cesarean than those born out of spontaneous vaginal deliveries (P<0.001). CONCLUSIONS: SpO2 levels in neonates born through cesarean section were higher in comparison to thoseborn by vaginal route. Birth weight and Apgar score had correlation with SpO2 in vaginal and cesarean births, respectively.


Subject(s)
Apgar Score , Birth Weight , Gestational Age , Hemoglobins/metabolism , Hypoxia/epidemiology , Infant, Newborn, Diseases/epidemiology , Adult , Body Mass Index , Cesarean Section , Delivery, Obstetric , Female , Humans , Infant, Newborn , Male , Nepal , Oximetry , Pregnancy , Risk Factors , Young Adult
10.
Phys Med ; 31(1): 98-103, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25440940

ABSTRACT

Existing protocols for assessing the performance characteristics of large field-of-view (LFOV) gamma cameras can be inappropriate and require modification for use with small field-of-view (SFOV) gamma camera systems. This communication proposes a generic scheme suitable for evaluating the performance characteristics of SFOV gamma cameras, based on modifications to the standard procedures of NEMA NU1-2007. Key differences in methodology between tests for LFOV and SFOV gamma cameras are highlighted along with the rationale for these changes. It is envisaged that this scheme will provide more appropriate methods for equipment characterisation, ensuring quality and consistency for all SFOV cameras.


Subject(s)
Gamma Cameras , Equipment Design
12.
Phys Med ; 30(3): 331-9, 2014 May.
Article in English | MEDLINE | ID: mdl-24225012

ABSTRACT

A handheld, high-resolution small field of view (SFOV) pinhole gamma camera has been characterised using a new set of protocols adapted from standards previously developed for large field of view (LFOV) systems. Parameters investigated include intrinsic and extrinsic spatial resolution, spatial linearity, uniformity, sensitivity, count rate capability and energy resolution. Camera characteristics are compared to some clinical LFOV gamma cameras and also to other SFOV cameras in development.


Subject(s)
Gamma Cameras , Algorithms , Equipment Design , Linear Models
13.
Oncogene ; 30(4): 410-22, 2011 Jan 27.
Article in English | MEDLINE | ID: mdl-20890301

ABSTRACT

Deregulation of the Rb/E2F tumor suppressor complex and aberrantion of Sonic hedgehog (Shh) signaling are documented across the spectrum of human malignancies. Exaggerated de novo lipid synthesis is also found in certain highly proliferative, aggressive tumors. Here, we show that in Shh-driven medulloblastomas, Rb is inactivated and E2F1 is upregulated, promoting lipogenesis. Extensive lipid accumulation and elevated levels of the lipogenic enzyme fatty acid synthase (FASN) mark those tumors. In primary cerebellar granule neuron precursors (CGNPs), proposed Shh-associated medulloblastoma cells-of-origin, Shh signaling triggers E2F1 and FASN expression, whereas suppressing fatty acid oxidation (FAO), in a smoothened-dependent manner. In the developing cerebellum, E2F1 and FASN co-localize in proliferating CGNPs. in vivo and in vitro, E2F1 is required for FASN expression and CGNP proliferation, and E2F1 knockdown impairs Shh-mediated FAO inhibition. Pharmacological blockade of Rb inactivation and/or lipogenesis inhibits CGNP proliferation, drives medulloblastoma cell death and extends survival of medulloblastoma-bearing animals In vivo. These findings identify a novel mechanism through which Shh signaling links cell cycle progression to lipid synthesis, through E2F1-dependent regulation of lipogenic enzymes. These findings pertinent to the etiology of tumor metabolism also underscore the key role of the Shh→E2F1→FASN axis in regulating de novo lipid synthesis in cancers, and as such its value as a global therapeutic target in hedgehog-dependent and/or Rb-inactivated tumors.


Subject(s)
Cerebellar Neoplasms/metabolism , E2F1 Transcription Factor/metabolism , Fatty Acid Synthases/metabolism , Hedgehog Proteins/metabolism , Lipogenesis/physiology , Medulloblastoma/metabolism , Neural Stem Cells/metabolism , Animals , Blotting, Western , Disease Models, Animal , Immunohistochemistry , Immunoprecipitation , Mice , Mice, Transgenic , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/physiology
14.
Neurosci Lett ; 488(2): 107-11, 2011 Jan 20.
Article in English | MEDLINE | ID: mdl-20816919

ABSTRACT

OBJECTIVE: The purpose of this work was to assess the effects of prematurity and intrauterine growth restriction on spinal cord synapses using H-reflex. METHODS: 33 babies were investigated at birth. 14 were full term appropriate for gestational age (FT AGA), 10 were full term intrauterine growth restricted (FT IUGR) and 9 were preterm appropriate for gestational age (PT AGA). The maximum amplitude of H-reflex (Hmax), H-reflex latency (HRL), H/M ratio, H-reflex conduction velocity (HRCV), and H-reflex response to double stimuli (conditioning and test) for H-reflex recovery cycle (HRRC) were recorded in right lower limb (soleus muscle) in all the three groups. RESULTS: Percentage recovery values of H-reflex were significantly higher in FT AGA and FT IUGR babies compared to PT AGA neonates for most of inter-stimulus intervals. No significant differences were observed in H-reflex parameters between FT AGA and FT IUGR groups, but HRL and HRCV were significantly affected in PT AGA group. CONCLUSIONS: Delayed H-reflex recovery in preterms may be due to a prolonged state of neurotransmitter delay in Ia terminals following initial activation by the conditioning stimuli. The cause of such prolonged depletion of neurotransmitters could be attributed to a poor neurotransmitter store in synaptic vesicles of spinal cord in preterm neonates.


Subject(s)
Fetal Growth Retardation/physiopathology , H-Reflex/physiology , Infant, Premature/physiology , Electric Stimulation , Electrophysiology , Humans , Infant, Newborn
15.
BMC Infect Dis ; 10: 298, 2010 Oct 15.
Article in English | MEDLINE | ID: mdl-20950457

ABSTRACT

BACKGROUND: Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age. METHODS: 299 healthy infants were randomised to receive either DTPw-HBV/Hib2.5 [Kft] DTPw-HBV/Hib2.5 or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age. RESULTS: One month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib2.5 [Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib2.5 vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ≥0.15 µg/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib2.5 [Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group. CONCLUSIONS: The DTPw-HBV/Hib2.5 [Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00473668.


Subject(s)
Diphtheria-Tetanus-Pertussis Vaccine/adverse effects , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Haemophilus Vaccines/adverse effects , Haemophilus Vaccines/immunology , Hepatitis B Vaccines/adverse effects , Hepatitis B Vaccines/immunology , Immunization Schedule , Vaccination/methods , Antibodies, Bacterial/blood , Antibodies, Viral/blood , Drug-Related Side Effects and Adverse Reactions , Female , Fever/chemically induced , Humans , Hyperemia/chemically induced , Infant , Male , Pain/chemically induced , Skin Diseases/chemically induced , Skin Diseases/pathology , Sleep Stages
17.
Trop Doct ; 38(4): 241-3, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18820199

ABSTRACT

We report on the clinico-haematological profile of pancytopenia in children from the Departments of Pediatrics and Pathology, Institute of Medical Sciences, Banaras Hindu University, India, over a period of 30 months. Pancytopenia was defined as: haemoglobin <10 g/dL, absolute neutrophil count 1.5 x 10(9)/L and platelet count <100 x 10(9)/L. A detailed history, clinical examination and haematological parameters were recorded. Bone marrow aspiration and trephine biopsy were carried out in all cases. One hundred and five cases aged 1.5-18 years, with a mean age of 8.6 years, were included in the study. Aplastic anaemia was the most common cause of pancytopenia (43%) followed by acute leukaemia (25%). Infections were the third most common cause of pancytopenia of which kala azar was the most common. Megaloblastic anaemia was seen in 6.7%.


Subject(s)
Pancytopenia/etiology , Adolescent , Anemia, Aplastic/complications , Child , Child, Preschool , Female , Humans , Infant , Leishmaniasis, Visceral/complications , Leukemia/complications , Male , Pancytopenia/blood
18.
Indian J Pediatr ; 75(7): 723-8, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18716743

ABSTRACT

Immune thrombocytopenic purpura (ITP) is the commonest cause of sudden onset thrombocytopenia in a healthy child. The condition is frequently preceded by a viral infection. The hematological parameters are essentially normal except a low platelet count. Bone marrow examination is not routinely indicated except in specific situations. The pros and cons of drug treatment have been discussed as the disease is benign with excellent prognosis in majority of the cases. The various treatment options including low and high dose steroids, intravenous immunoglobulins and anti D have been discussed at length with other modalities of treatment and role of splenectomy. Current therapeutic options with rituximab and other drugs for stimulating platelet production in chronic cases have also been included in discussion.


Subject(s)
Purpura, Thrombocytopenic/diagnosis , Purpura, Thrombocytopenic/drug therapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Child , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Methylprednisolone/therapeutic use , Platelet Transfusion , Prognosis , Purpura, Thrombocytopenic/surgery , Rho(D) Immune Globulin/therapeutic use , Rituximab , Splenectomy , Treatment Outcome
19.
Singapore Med J ; 49(7): 556-60, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18695864

ABSTRACT

INTRODUCTION: Very low birth weight (VLBW) neonates constitute approximately 4-7 percent of all live births and their mortality is very high. The objective of the present study was to determine the predictors of mortality in VLBW neonates. METHODS: A retrospective cohort of VLBW neonates admitted over three years was studied. Exclusion criteria were: (1) neonates weighing less than 500 g and with gestational age less than 26 weeks; (2) presence of lethal congenital malformations; and (3) death in the delivery room or within 12 hours of life. The outcome measure was in-hospital death. Medical records were reviewed and data was analysed. Univariate analysis and logistic regression analysis were done to determine the predictors of mortality. RESULTS: A total of 260 cases were enrolled, of which a total of 96 (36.9 percent) babies died. The survival rate was found to increase with the increase in birth weight and gestational age. Univariate analysis showed maternal per vaginal bleeding, failure to administer steroid antenatally, Apgar score less than or equal to 5 at one minute, apnoea, gestational age, neonatal septicaemia and shock are the factors directly responsible for neonatal mortality. Logistic regression equation showed maternal bleed (1.326), apnoea (3.159), birth weight (0.037), gestational age (0.063), hypothermia (1.132) and shock (3.49) predicted 65 percent of mortality in VLBW babies. CONCLUSION: Common antenatal and perinatal predictors of mortality in VLBW infants in India include maternal bleed, failure to administer antenatal steroids, low Apgar score, apnoea, extreme prematurity, neonatal septicaemia and shock.


Subject(s)
Infant, Premature, Diseases/epidemiology , Adolescent , Adult , Cohort Studies , Female , Humans , India , Infant, Newborn , Infant, Premature, Diseases/mortality , Infant, Very Low Birth Weight , Male , Morbidity , Prospective Studies , Regression Analysis , Retrospective Studies , Time Factors
20.
Indian J Pediatr ; 75(5): 451-4, 2008 May.
Article in English | MEDLINE | ID: mdl-18537006

ABSTRACT

OBJECTIVE: To study the clinico-hematological profile and treatment outcome in children suffering from auto immune hemolytic anemia (AIHA). METHODS: Twelve children were diagnosed with auto immune hemolytic anemia over a period of four years. Direct antiglobulin test was positive in all the cases. Other causes of hemolytic anemia like thalassemia syndromes, hereditary spherocytosis, G6PD deficiency were excluded by appropriate tests. The children were followed up for 6 months to 4 years. RESULTS: The age ranged from 7 mth to 9 yr with a mean age of 4.51 yr. All patients had pallor as the presenting complaint followed by splenomegaly (83.3%), jaundice (66.7%), fever (50%) and bleeding manifestations (16.7%). 9 patients had primary disease and 3 had secondary disease. Tubercular infection was seen in 2 patients with secondary disease. Jaundice was seen equally in both the groups. Oral prednisolone produced remission in 83.3% cases. 4 patients (3 in primary and one in secondary group) had relapse after initial response. All responded to a second course of steroids but had subsequent relapses and developed a chronic course. CONCLUSION: Autoimmune hemolytic anemia is an uncommon cause of hemolytic anemia in children. Tubercular infection is an underlying pathology in cases of secondary autoimmune hemolytic anemia. Although oral steroids induce remission in most of the cases, relapses are common.


Subject(s)
Anemia, Hemolytic, Autoimmune , Anemia, Hemolytic, Autoimmune/drug therapy , Child , Female , Humans , Male , Steroids/therapeutic use , Treatment Outcome
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