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Adrenal hypoplasia congenita is a relatively rare disorder characterized by atrophy or hypoplasia of the adrenal gland. It was first described by Sikl H in 1948 in 33‑day‑old infant. It is inherited as an autosomal recessive or X‑linked disorder. It presents usually with adrenal insufficiency. In this article, we are presenting a case of congenital adrenal hypoplasia which presented with hypoglycemia, adrenal insufficiency, hyperbilirubinemia, and acquired hyperpigmentation in the neonatal period. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Crigler–Najjar syndrome type 2 should be suspected in any young patient presenting with isolated indirect hyperbilirubinemia where all other common etiologies have been excluded. It is a relatively benign condition that responds to phenobarbitone. Crigler–Najjar syndrome (CNS) type 2 is an inborn cause of isolated indirect hyperbilirubinemia characterized by a partial deficiency of the enzyme uridine 5′‐diphosphate‐glucuronosyltransferase (UGT) responsible for bilirubin conjugation. Typically, this condition is diagnosed based on clinical manifestations, supplemented by enzyme analysis if feasible, and exhibits a significant response to phenobarbitone, known for its enzyme‐inducing properties. In this case, we present a young male patient who had experienced recurrent isolated indirect hyperbilirubinemia since early childhood, with negative results in the hemolytic workup. The patient exhibited a UGT1A1 gene defect and demonstrated a highly favorable response to phenobarbitone treatment. The purpose of this report is to raise awareness among physicians about this benign condition and underscore the importance of avoiding unnecessary investigations. [ABSTRACT FROM AUTHOR]

Transfusion-related acute lung injury (TRALI), a life-threatening condition, remains an under reported complication, especially among neonates postexchange transfusion for unconjugated hyperbilirubinemia. Appropriate recognition and prompt treatment change the prognosis for good. The present case emphasizes that TRALI must be kept as a differential diagnosis in previously well neonates presenting with sudden onset hypoxia within or during 6 h of transfusion with evidence of bilateral infiltrates on a frontal chest radiograph, and no evidence of circulatory overload, left atrial hypertension, or pre-existing respiratory distress before transfusion. We report the rare occurrence of TRALI and its successful management with supportive hemodynamic management and corrective ventilator strategies.

Key Clinical Message Crigler–Najjar syndrome type 2 should be suspected in any young patient presenting with isolated indirect hyperbilirubinemia where all other common etiologies have been excluded. It is a relatively benign condition that responds to phenobarbitone. Abstract Crigler–Najjar syndrome (CNS) type 2 is an inborn cause of isolated indirect hyperbilirubinemia characterized by a partial deficiency of the enzyme uridine 5′‐diphosphate‐glucuronosyltransferase (UGT) responsible for bilirubin conjugation. Typically, this condition is diagnosed based on clinical manifestations, supplemented by enzyme analysis if feasible, and exhibits a significant response to phenobarbitone, known for its enzyme‐inducing properties. In this case, we present a young male patient who had experienced recurrent isolated indirect hyperbilirubinemia since early childhood, with negative results in the hemolytic workup. The patient exhibited a UGT1A1 gene defect and demonstrated a highly favorable response to phenobarbitone treatment. The purpose of this report is to raise awareness among physicians about this benign condition and underscore the importance of avoiding unnecessary investigations.

Transfusion-related acute lung injury (TRALI), a life-threatening condition, remains an under reported complication, especially among neonates postexchange transfusion for unconjugated hyperbilirubinemia. Appropriate recognition and prompt treatment change the prognosis for good. The present case emphasizes that TRALI must be kept as a differential diagnosis in previously well neonates presenting with sudden onset hypoxia within or during 6 h of transfusion with evidence of bilateral infiltrates on a frontal chest radiograph, and no evidence of circulatory overload, left atrial hypertension, or pre-existing respiratory distress before transfusion. We report the rare occurrence of TRALI and its successful management with supportive hemodynamic management and corrective ventilator strategies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the difference in cerebral blood flow in neonates with and without extreme unconjugated hyperbilirubinemia. Methods: Transcranial Doppler parameters of 26 full term newborns with extreme unconjugated hyperbilirubinemia (UCH) were compared to 13 postnatal age and sex matched normal healthy neonates serving as controls. Resistance index (RI), pulsatility index (PI) and peak systolic velocity (PSV) were measured in the middle cerebral, internal carotid and posterior cerebral arteries on both sides by transcranial color Doppler ultrasound. Results: An increase in cerebral blood flow (decreased RI, PI and increased PSV) was observed in the extreme unconjugated hyperbilirubinemia (UCH) group. There was positive correlation between total serum bilirubin level and peak systolic velocity and vice versa with resistivity and pulsatility indices. Eight neonates developed clinical features of acute bilirubin encephalopathy and showed significantly increased peak systolic velocity in the right middle cerebral artery compared to those with normal outcome. Resistivity index and pulsatility index were lower in patients managed by exchange transfusion compared to those managed with phototherapy. Conclusion: An increase in cerebral blood flow was observed in neonates with UCH compared to those without hyperbilirubinemia. By assessing the cerebral blood flow velocity, resistivity index (RI), and pulsatility index (PI) of particular intracranial arteries, the transcranial Doppler can identify the at-risk neonates, for development of neurological affliction in extreme unconjugated hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Background: Phototherapy plays a significant role in the treatment of hyperbilirubinemia in neonates. However, this treatment may result in the development of some complications. There are limited studies with different results regarding the effect of phototherapy on platelet count. The aim of this research to detect the effect of phototherapy on platelet count in neonates with indirect hyperbilirubinemia. Methods: Across sectional study was conducted during the period from January 2018 to June 2018 at Neonatal Intensive Care Unit of Benha children hospital. The study included 54 term neonates with symptoms, signs and laboratory findings of neonatal indirect hyperbilirubinemia treated with phototherapy. Apart from jaundice, their physical examination was normal. Platelet count of jaundiced neonates was measured on admission and at discontinuation of phototherapy. Results: Total of 54 full term neonates were included in this study. The mean (+/-SD) platelet counts were 278.89 ± 60.63 before phototherapy and 319.67 ± 78.58 after phototherapy. There was an increase in the mean platelet count after phototherapy which was statistically significant (p=0.001). The study showed that mean platelet count increased with extended mean phototherapy time. Conclusion: Phototherapy leads to rise in platelet count in term icteric neonates exposed to phototherapy for more than two days. [ABSTRACT FROM AUTHOR]

Crigler Najjar syndrome(CNS); is a disease in which the diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme function, which plays a role in the glucuronidation of bilirubin, is deficient as a result of mutation in the uridine 5'-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) gene.1 As a result, non-hemolytic unconjugated hyperbilirubinemia is seen. Orthotopic liver transplantation (OLT) is seen as a curative treatment option in Crigler Najjar syndrome type 1 (CNS1). In this case report, we present our patients who were 11 months old and 8 years old with a diagnosis of CNS1, whose bilirubin levels were controlled by preoperative daily phototherapy and plasmapheresis, and who had OLT from their parents to two siblings. We wanted to show the importance of a close follow-up and multidisciplinary treatment approach in the early period before OLT in CNS1 patients and thus the benefit to the patient's prognosis in the postoperative period.

Cholestasis is the impairment of normal bile flow causing accumulation of bile salts, lipids, and bilirubin in blood which presents as Jaundice. Jaundice beyond 2 weeks of age is rare in infancy with worldwide incidence of 1 in 2500 live births. Biliary atresia is the most common extra hepatic cause of cholestasis in late neonatal and infancy period. Cholestasis and hyperbilirubinemia cause irreversible brain and liver damage if not diagnosed and treated early. A 3-week-old neonate presenting with progressive yellowish discoloration of eyes and skin. Explorative laparotomy found anatomically normal liver and biliary tree, but a lymph node obstructing the common bile duct. This case was particularly unique as history of illness and initial investigations were suggestive of biliary atresia. However, the patient had lymph nodes with no history of any triggers to lymphadenopathy. It is a rare case of obstruction of biliary flow in this age group. Despite biliary atresia being the commonest cause of obstructive jaundice in infancy, it is important to rule out other causes like lymph nodes obstructing the biliary tree. • Cholestatic jaundice is rare in infancy and biliary atresia should be ruled out promptly as the most common cause. • It is important to do biopsy before exploratory laparotomy to minimize unnecessary surgical procedures. • Intrahepatic lymph node can mimic biliary atresia. [ABSTRACT FROM AUTHOR]

Background: Neonatal hyperbilirubinemia is observed in most newborns, and 5–15% of neonates require phototherapy. Phototherapy is effective but often prolongs hospitalization and has both short-term and potential long-term harms. The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid (UDCA) combined with phototherapy in neonatal hyperbilirubinemia. Methods: A literature search was conducted on September 1, 2021; 590 studies were screened, and 17 full texts were assessed by two authors. We included randomized controlled trials with or without placebo intervention. Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration. We calculated mean differences with 95% confidence intervals (CI). Results: Six studies with 880 neonates were included. Of these studies, only two used a placebo-controlled double-blinded design. The overall risk of bias was high in one and moderate in four of the included studies. The mean decrease in the total bilirubin level during the first 24 hours was 2.06 mg/dL (95% CI 0.82–3.30; six studies) greater in the UDCA treatment group. The phototherapy duration was 19.7 hours (95% CI 10.4–29.1; five studies) shorter in the UDCA treatment group. Conclusions: We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment. Further studies are needed to confirm the efficacy, acute and long-term outcomes, and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

We found in 31 patients with liver fibrosis evaluation (liver histology or Fibroscan) five patients (16%) with signs of advanced liver fibrosis. Keywords: encephalopathy; liver transplantation; phototherapy; UGT1A1; unconjugated hyperbilirubinemia EN encephalopathy liver transplantation phototherapy UGT1A1 unconjugated hyperbilirubinemia 1593 1604 12 06/27/22 20220701 NES 220701 Abbreviations ALT alanine aminotransferase AST aspartate aminotransferase CB conjugated bilirubin CNS Crigler-Najjar syndrome GGT gamma glutamyl transpeptidase PB phenobarbital PT phototherapy TB total bilirubin UCB unconjugated bilirubin UGT1A1 uridine 5'-diphosphate glucuronosyltransferase ULN upper limit of normal Abstract Background and Aims Crigler-Najjar syndrome (CNS) is a disorder of bilirubin conjugation leading to brain damage and death without treatment. That in our small subcohort of fibrosis evaluated patients only patient with PT showed fibrosis is most likely caused because of the more severe phenotype in these patients but an association between long-term PT use and development of fibrosis cannot be excluded based on our data. Better detection and characterizing of liver fibrosis in CNS patients is necessary to gain an understanding of aetiology, to identify patients at risk, to develop individual treatment plans (e.g. LT vs. gene therapy in the future) and to probably find a way to avoid the development of fibrosis. [Extracted from the article]

A clinical trial using adeno-associated virus serotype 8 (AAV8)-human uridine diphosphate glucuronosyltransferase 1A1 (hUGT1A1) to treat inherited severe unconjugated hyperbilirubinemia (Crigler-Najjar syndrome) is ongoing, but preclinical data suggest that long-term efficacy in children is impaired due to loss of transgene expression upon hepatocyte proliferation in a growing liver. This study aims to determine at what age long-term efficacy can be obtained in the relevant animal model and whether immune modulation allows re-treatment using the same AAV vector. Neonatal, suckling, and juvenile Ugt1a1-deficient rats received a clinically relevant dose of AAV8-hUGT1A1, and serum bilirubin levels and anti-AAV8 neutralizing antibodies (NAbs) in serum were monitored. The possibility of preventing the immune response toward the vector was investigated using a rapamycin-based regimen with daily intraperitoneal (i.p.) injections starting 2 days before and ending 21 days after vector administration. In rats treated at postnatal day 1 (P1) or P14, the correction was (partially) lost after 12 weeks, whereas the correction was stable in rats injected at P28. Combining initial vector administration with the immune-suppressive regimen prevented induction of NAbs in female rats, allowing at least partially effective re-administration. Induction of NAbs upon re-injection could not be prevented, suggesting that this strategy will be ineffective in patients with low levels of preexisting anti-AAV NAbs.

BACKGROUND AND OBJECTIVE: Jaundice (hyperbilirubinemia) is one of the most common clinical complaints during infancy among term and premature infants during the first week of life. Phototherapy is an effective and accepted treatment for neonatal hyperbilirubinemia, which may be associated with complications such as skin, eye and electrolyte disorders. This study was performed to compare the effect of phototherapy with oral calcium versus phototherapy alone in the treatment of unconjugated hyperbilirubinemia in healthy term infants. METHODS: This clinical trial study was performed on 50 healthy term infants with jaundice (serum bilirubin 6.9-21 mg/dL). Neonates were randomly divided into intervention (50 mg/kg body weight of oral calcium with phototherapy) and control (phototherapy) groups. Data related to age, gender, birth weight, gestational age, number of hospitalization days and bilirubin level at the beginning of hospitalization and at 24, 48 and 72 hours were collected and compared in a checklist. FINDINGS: Decrease in total bilirubin level was observed with a significant difference between the two groups (p=0.000). The mean unconjugated hyperbilirubinemia showed significant difference in the intervention group (2.1±0.5 mg/dl) and the control group (2.6±1.3 mg/dl) (p=0.03). The changes in unconjugated hyperbilirubinemia in repeated measures was also significant in the intervention group (p=0.01). CONCLUSION: The results of the study showed that oral calcium with phototherapy may be effective in reducing neonatal jaundice.

Abstract Background Neonatal jaundice is one of the most common problems in neonates. Effective treatment of jaundice requires therapeutic intervention with high quality phototherapy. Over recent years, several studies reported fiberoptic phototherapy to be less effective than conventional phototherapy in term neonates. Our study aimed to compare the effectiveness of fiberoptic phototherapy with a larger illuminated area and higher irradiance to conventional phototherapy methods. Methods This was a randomized controlled trial conducted at the Kilimanjaro Christian Medical Centre (KCMC). A total of 41 term neonates, less than 7 days of age with unconjugated hyperbilirubinemia were randomized. Thirteen (13) neonates were allocated to receive fiberoptic phototherapy, 13 to blue light conventional phototherapy and 15 to white light conventional phototherapy. Effectiveness was assessed by comparing the duration of phototherapy, bilirubin reduction rate and side effects of treatment. The data was analyzed with the independent t-test. Results The mean overall bilirubin reduction rate was comparable in the fiberoptic phototherapy group (0.74%/h) and the blue light conventional phototherapy group (0.84%/h), with no statistically significant difference (p-value 0.124). However, white light conventional phototherapy had a significantly lower mean overall bilirubin reduction rate (0.29%/h) as compared to fiberoptic phototherapy (p-value

Background: Studies comparing serum bilirubin trend and hematological profile of neonates with hemolytic and nonhemolytic etiology are limited. Apart from high bilirubin load, they are at increased risk of developing anemia in early days of life. Methods: A prospective observational study was conducted in neonatal unit on late preterm and term neonates (>35 weeks) with unconjugated hyperbilirubinemia (UH) to compare serum bilirubin trend (initial and peak), hematological profile (hemoglobin [Hb] and hematocrit [PCV]) (initial and at 3 months), between hemolytic and non-hemolytic cases. Result: Among 240 enrolled neonates, initial serum bilirubin level was higher in haemolytic group than non-hemolytic (mg/dl) (16.9 ± 3.2 vs. 14.6 ± 4.1; p

The UGT1A1 enzyme is involved in the metabolism of bilirubin and numerous medications. Unconjugated hyperbilirubinemia, commonly presented as Gilbert syndrome (GS), is a result of decreased activity of the UGT1A1 enzyme, variable number of TA repeats in the promoter of the UGT1A1 gene affects enzyme activity. Seven and eight TA repeats cause a decrease of UGT1A1 activity and risk GS alleles, while six TA repeats contribute to normal UGT1A1 activity and non-risk GS allele. Also, the UGT1A1 (TA)n promoter genotype is recognized as a clinically relevant pharmacogenetic marker. The aim of this study was to assess diagnostic value of UGT1A1 (TA)n promoter genotyping in pediatric GS patients. Correlation of the UGT1A1 (TA)n genotypes and level of unconjugated bilirubin at diagnosis and after hypocaloric and phenobarbitone tests in these patients was analyzed. Another aim of the study was to assess pharmacogenetic potential of UGT1A1 (TA)n variants in Serbia. Fifty-one pediatric GS patients and 100 healthy individuals were genotyped using different methodologies, polymerase chain reaction (PCR) followed by acrylamide electrophoresis, fragment length analysis and/or DNA sequencing. Concordance of the UGT1A1 (TA)n promoter risk GS genotypes with GS was found in 80.0% of patients. Therefore, UGT1A1 (TA)n promoter genotyping is not a reliable genetic test for GS, but it is useful for differential diagnosis of diseases associated with hyperbilirubinemia. Level of bilirubin in pediatric GS patients at diagnosis was UGT1A1 (TA)n promoter genotype-dependent. We found that the frequency of pharmacogenetic relevant UGT1A1 (TA)n promoter genotypes was 63.0%, pointing out that UGT1A1 (TA)n promoter genotyping could be recommended for preemptive pharmacogenetic testing in Serbia.

There is limited literature on Gilbert's syndrome (GS) in children with persistent unconjugated hyperbilirubinemia from Indian subcontinent. All patients (< 18 y of age) with genetically confirmed GS were included, and their profile was analysed. A total of 170 subjects were confirmed as having GS as per genetic analysis (133 with homozygous and 37 with heterozygous status). Majority were diagnosed in the adolescent age group (mean age 13.6 y). The median serum total bilirubin (TB) levels were around 3.3 mg/dl with maximum levels reaching upto 18 mg/dl. Around 15% subjects had an associated condition including hematological or hepatobiliary disease amongst others. GS is an important but under-recognised cause of unexplained unconjugated hyperbilirubinemia in Indian pediatric subjects. It may co-exist with other hematological and hepatobiliary disorders, and complicate the clinical/laboratory picture. Extent of hyperbilirubinemia may fluctuate to levels much higher than what is usually described in current world literature. [ABSTRACT FROM AUTHOR]

Background: Neonatal jaundice is one of the most common problems in neonates. Effective treatment of jaundice requires therapeutic intervention with high quality phototherapy. Over recent years, several studies reported fiberoptic phototherapy to be less effective than conventional phototherapy in term neonates. Our study aimed to compare the effectiveness of fiberoptic phototherapy with a larger illuminated area and higher irradiance to conventional phototherapy methods.Methods: This was a randomized controlled trial conducted at the Kilimanjaro Christian Medical Centre (KCMC). A total of 41 term neonates, less than 7 days of age with unconjugated hyperbilirubinemia were randomized. Thirteen (13) neonates were allocated to receive fiberoptic phototherapy, 13 to blue light conventional phototherapy and 15 to white light conventional phototherapy. Effectiveness was assessed by comparing the duration of phototherapy, bilirubin reduction rate and side effects of treatment. The data was analyzed with the independent t-test.Results: The mean overall bilirubin reduction rate was comparable in the fiberoptic phototherapy group (0.74%/h) and the blue light conventional phototherapy group (0.84%/h), with no statistically significant difference (p-value 0.124). However, white light conventional phototherapy had a significantly lower mean overall bilirubin reduction rate (0.29%/h) as compared to fiberoptic phototherapy (p-value < 0.001). The mean treatment duration of phototherapy was 69 h, 68 h and 90 h in the fiberoptic, blue light conventional and white light conventional phototherapy groups respectively. Side effects such as loose stool and skin rash were noted in some participants who received conventional phototherapy. No side effects of treatment were noted in the fiberoptic phototherapy group.Conclusion: The effectiveness of fiberoptic PT and blue light conventional PT were comparable in terms of bilirubin reduction rate and treatment duration, whereas fiberoptic phototherapy was more effective than white light conventional PT, with a significantly higher bilirubin reduction rate and shorter treatment duration. Fiberoptic phototherapy may mitigate side effects caused by conventional phototherapy.Trial Registration: The Pan African Clinical Trial Registry, PACTR202004723570110 . Registered 22nd April 2020- Retrospectively registered. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Jaundice (hyperbilirubinemia) is one of the most common clinical complaints during infancy among term and premature infants during the first week of life. Phototherapy is an effective and accepted treatment for neonatal hyperbilirubinemia, which may be associated with complications such as skin, eye and electrolyte disorders. This study was performed to compare the effect of phototherapy with oral calcium versus phototherapy alone in the treatment of unconjugated hyperbilirubinemia in healthy term infants. METHODS: This clinical trial study was performed on 50 healthy term infants with jaundice (serum bilirubin 6.9-21 mg/dL). Neonates were randomly divided into intervention (50 mg/kg body weight of oral calcium with phototherapy) and control (phototherapy) groups. Data related to age, gender, birth weight, gestational age, number of hospitalization days and bilirubin level at the beginning of hospitalization and at 24, 48 and 72 hours were collected and compared in a checklist. FINDINGS: Decrease in total bilirubin level was observed with a significant difference between the two groups (p=0.000). The mean unconjugated hyperbilirubinemia showed significant difference in the intervention group (2.1±0.5 mg/dl) and the control group (2.6±1.3 mg/dl) (p=0.03). The changes in unconjugated hyperbilirubinemia in repeated measures was also significant in the intervention group (p=0.01). CONCLUSION: The results of the study showed that oral calcium with phototherapy may be effective in reducing neonatal jaundice. [ABSTRACT FROM AUTHOR]

Background: Neonatal jaundice is a common problem with a lot of faults that may happen during its management. Objective:To study the epidemiological features of the unconjugated hyperbilirubinemia(UHB)in Diyala Governorate and discuss the proper lines of therapy, as well as to discuss the daily practice adopted in our hospital, and its complications. Patients and Methods: A cross-sectional study included 100 neonates (term and preterm babies) with unconjugated hyperbilirubinemia aged 0-7 days who were admitted to the Al- Batool Teaching Hospital in Baqubah, Iraq, from 1st February 2018 to the 1st November 2018. Term infants with total serum bilirubin (TSB) = 22mg/dL were treated with exchange transfusion and phototherapy (Group A, 44 neonates). Those with total serum bilirubin levels from 13-<22mg/dL were treated with phototherapy only (Group B, 56 neonates). These decisions were made according to the TSB level and risk factors. Results: Forty-eight percent of neonates had hemolytic causes (Rh-isoimmunization 13%; ABO-incompatibility 10%; G6PD-deficiency 25%). Other include: sepsis 8%; prematurity 33%; congenital CMV infection 1%; and there were 10% had no evidence of hemolysis or other serious problems. The mortality rate was 3.8% of those who had an exchange transfusion. Conclusion: The decision of kind of treatment is dependent on the underlying etiology of unconjugated hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

A large fraction of DNA variants impairs pre-mRNA splicing in human hereditary disorders. Crigler-Najjar syndrome (CNS) is characterized by a severe unconjugated hyperbilirubinemia caused by variants in the UGT1A1 gene. We previously reported one CNS-type II patient with two splice-site variants in trans (c.864+5G>T and c.996+2_996+5del). According to MaxEntScan, both disrupt their corresponding donor sites (c.864+5G>T: 6.99 → 2.28; c.996+2_996+5del: 5.96 → −11.02), so they were selected for subsequent functional tests. Given the unavailability of patient RNA, we constructed an UGT1A1 splicing-reporter minigene with exons 1–4 to characterize the underlying splicing anomaly. The variant c.996+2_996+5del generated two aberrant transcripts, Δ(E2) (exon 2 skipping/64%) and ▼(E2q135) (intron retention of 135-nt/36%), which lead to the loss of 18 conserved amino-acids and the gain of 45 new ones of a critical functional domain, respectively. The c.864+5G>T variant mainly produced the aberrant transcript Δ(E1q141) (141-nt deletion/70.4%) and the full-length isoform (29.6%). Δ(E1q141) would provoke the loss of 47 amino-acids of the N-terminal domain that encodes for substrate specificity. Thus, the three anomalous transcripts are likely to inactivate UGT1A1. Moreover, this patient is also homozygous for the promoter variant A(TA)7TAA that decreases UGT1A1 expression by 70%, so the full-length transcript produced by c.864+5G>T would be even more reduced (

The potential for genetic variation to cause adult unconjugated hyperbilirubinemia is increasingly being recognized. However, the cumulative effects of genetic variants have not been fully illuminated. The current study aimed to investigate the effects of uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) and/or solute carrier organic anion transporter family member 1B (SLCO1B) polymorphic variants and their combined effects on mild unconjugated hyperbilirubinemia in Chinese adults. Fourteen genetic variants in the UGT1A1 or SLCO1B gene were genotyped through sequencing in 148 adults with unconjugated hyperbilirubinemia and 158 healthy controls. Variants c.-3275T > G, (TA)6>(TA)7, c.211G > A or c.1091C > T within the UGT1A1 gene as well as c.521T > C within the SLCO1B1 gene appear to be genetic risk factors for inherited unconjugated hyperbilirubinemia. After adjusting for covariates, the results of multivariate logistic regressions revealed that odds ratios (ORs) [(with 95% confidence interval (CI)] of these five variants were 2.35 (95% CI: 1.37–4.01, p = 0.002), 2.38 (95% CI: 1.35–4.20, p = 0.003), 2.99 (95% CI: 1.71–5.21, p < 0.001), 7.60 (95% CI: 1.99–28.96, p = 0.003), and 2.54 (95% CI: 1.27–5.11, p = 0.009), respectively. The OR for unconjugated hyperbilirubinemia is positively correlated with the cumulative number of these five variants in adults. And the greater the number of genetic variations, the higher the total bilirubin level. Adults carrying diplotype 3/4 (homozygous c.-3275T > G and heterozygous (TA)6>(TA)7) had higher bilirubin levels than those with diplotypes 1/3 (heterozygous c.-3275T > G and (TA)6>(TA)7)) or 1/4 (heterozygous c.-3275T > G) (P < 0.05). Similarly, bilirubin levels in individuals with diplotype 2/4 (heterozygous c.-3275T > G and c.211G > A) were higher than adults carrying diplotypes 1/2 (heterozygous c.211G > A) or 1/4 (P < 0.001). For subjects with heterozygous or homozygous variant c.211G> A, as the number of c.521T > C alleles variation increased, the incidence of unconjugated hyperbilirubinemia increased, but it was not statistically significant. Our results indicate that variants of UGT1A1 and/or SLCO1B1 have combined effects on Chinese adult mild unconjugated hyperbilirubinemia.

Background Neonatal jaundice remains a very common presentation in newborn babies, especially during the first week of life. Serious morbidities and long-term sequelae are seen in babies with delayed diagnosis and intervention. A timely and early decision-making workout would make the outcome better. First-hour-oflife presenting icterus is a worrisome sign, and hence, a swift intervention is much needed. Aim To compare the auditory brain stem response results between healthy newborns and newborns managed from pathological unconjugated hyperbilirubinemia started in the first day of life. Patients and methods A case-control study was conducted at the neonatal intensive care unit of Alexandria University Maternity Hospital on 55 full-term newborns; 30 were cases who had pathological unconjugated hyperbilirubinemia in the first day of life using Queensland Clinical Guideline: neonatal jaundice 2017, and 25 were controls who had no pathological jaundice and were healthy. The exclusion criteria were considered. Diagnostic auditory brain stem response tests were done at the Audiology Unit in Outpatient clinics at Alexandria Main University Hospital by an audiologist for each ear of the case group within 7 days of complete management and were made for each ear of the controls group from 7 to 15 days of age. Results The study found no significant difference between both studied groups regarding latency, amplitude of waves I, III, and V, V/I amplitude ratio, and interpeak interval betweenwaves I-III, III-V, and I-Vat intensity of 70 dBnHL on both right and left ears. Conclusions Early identification and management of newborns with early-onset pathological hyperbilirubinemia using Queensland Clinical Guidelines: Neonatal jaundice 2017 can protect them from the acute bilirubin encephalopathy and auditory neuropathy spectrum disorder. [ABSTRACT FROM AUTHOR]

A large fraction of DNA variants impairs pre-mRNA splicing in human hereditary disorders. Crigler-Najjar syndrome (CNS) is characterized by a severe unconjugated hyperbilirubinemia caused by variants in the UGT1A1 gene. We previously reported one CNS-type II patient with two splice-site variants in trans (c.864+5G>T and c.996+2_996+5del). According to MaxEntScan, both disrupt their corresponding donor sites (c.864+5G>T: 6.99 → 2.28; c.996+2_996+5del: 5.96 → −11.02), so they were selected for subsequent functional tests. Given the unavailability of patient RNA, we constructed an UGT1A1 splicing-reporter minigene with exons 1–4 to characterize the underlying splicing anomaly. The variant c.996+2_996+5del generated two aberrant transcripts, Δ(E2) (exon 2 skipping/64%) and ▼(E2q135) (intron retention of 135-nt/36%), which lead to the loss of 18 conserved amino-acids and the gain of 45 new ones of a critical functional domain, respectively. The c.864+5G>T variant mainly produced the aberrant transcript Δ(E1q141) (141-nt deletion/70.4%) and the full-length isoform (29.6%). Δ(E1q141) would provoke the loss of 47 amino-acids of the N-terminal domain that encodes for substrate specificity. Thus, the three anomalous transcripts are likely to inactivate UGT1A1. Moreover, this patient is also homozygous for the promoter variant A(TA)7TAA that decreases UGT1A1 expression by 70%, so the full-length transcript produced by c.864+5G>T would be even more reduced (<9%), thus supporting the diagnosis of CNS-type II. Therefore, minigenes represent valuable tools for the functional and clinical classifications of genetic variants. [ABSTRACT FROM AUTHOR]

Background: Prolonged jaundice is a type of neonatal jaundice, which occurs in infants with high bilirubin levels (>10 mg/dl) persisting beyond day 14 of life in term neonates, and beyond day 21 in preterm neonates. Prolonged jaundice may be caused by predominantly conjugated or unconjugated hyperbilirubinemia. Distinguishing between these types of jaundice helps to determine the risk for pathological causes of prolonged jaundice. Phenobarbital has been used to treat neonatal jaundice since the 1960s. Numerous clinical trials have shown that both administration of phenobarbital to pregnant mothers before delivery and phenobarbital administration to neonates after delivery limit the severity of unconjugated hyperbilirubinemia, reduce the peak serum total bilirubin concentrations caused by physiologic jaundice by 50%, and the need for exchange transfusion. Objective: The aim of this study was to evaluate the role of phenobarbital in reducing the total serum bilirubin(TSB) in neonates with prolonged unconjugated hyperbilirubinemia. Methods: This is a prospective clinical trial study that was performed in Karbala teaching hospital for children from 18th of December 2017 to the end of December 2018. A total of 101 neonate with prolonged unconjugated hyperbilirubinemia were included in this study. All neonates who included in this study received phenobarbital tablet (5 mg /kg/day) twice a day for 10 days and some of them need phototherapy according to American Academy Of Pediatrics Guidelines for phototherapy, Results: There was a highly statistically significant decrease in TSB for the patients who were treated with phenobarbital compared to the baseline level, mean baseline TSB 14.57± 2.31 mg/dl versus TSB after phenobarbital 6.79±1.62 mg/dl (P value <0.001). There was a highly statistically significant decrease in TSB for the patients who were treated with phototherapy in addition to phenobarbital compared to the baseline level, mean baseline TSB 19.94±1.36 mg/dl versus TSB after phototherapy and phenobarbital 6.33±1.37 mg/dl (P value <0.001). Conclusions: 1. Oral phenobarbital supplementation in the neonates with prolonged unconjugated hyperbilirubinemia can significantly accelerate reduction in serum bilirubin levels. 2. Phenobarbital was safe, tolerable and no obvious adverse effects had been reported. 3. No need for cessation of breast feeding in cases of presumed breast milk jaundice. [ABSTRACT FROM AUTHOR]

The potential for genetic variation to cause adult unconjugated hyperbilirubinemia is increasingly being recognized. However, the cumulative effects of genetic variants have not been fully illuminated. The current study aimed to investigate the effects of uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) and/or solute carrier organic anion transporter family member 1B (SLCO1B) polymorphic variants and their combined effects on mild unconjugated hyperbilirubinemia in Chinese adults. Fourteen genetic variants in the UGT1A1 or SLCO1B gene were genotyped through sequencing in 148 adults with unconjugated hyperbilirubinemia and 158 healthy controls. Variants c.-3275T > G, (TA)6>(TA)7, c.211G > A or c.1091C > T within the UGT1A1 gene as well as c.521T > C within the SLCO1B1 gene appear to be genetic risk factors for inherited unconjugated hyperbilirubinemia. After adjusting for covariates, the results of multivariate logistic regressions revealed that odds ratios (ORs) [(with 95% confidence interval (CI)] of these five variants were 2.35 (95% CI: 1.37–4.01, p = 0.002), 2.38 (95% CI: 1.35–4.20, p = 0.003), 2.99 (95% CI: 1.71–5.21, p < 0.001), 7.60 (95% CI: 1.99–28.96, p = 0.003), and 2.54 (95% CI: 1.27–5.11, p = 0.009), respectively. The OR for unconjugated hyperbilirubinemia is positively correlated with the cumulative number of these five variants in adults. And the greater the number of genetic variations, the higher the total bilirubin level. Adults carrying diplotype 3/4 (homozygous c.-3275T > G and heterozygous (TA)6>(TA)7) had higher bilirubin levels than those with diplotypes 1/3 (heterozygous c.-3275T > G and (TA)6>(TA)7)) or 1/4 (heterozygous c.-3275T > G) (P < 0.05). Similarly, bilirubin levels in individuals with diplotype 2/4 (heterozygous c.-3275T > G and c.211G > A) were higher than adults carrying diplotypes 1/2 (heterozygous c.211G > A) or 1/4 (P < 0.001). For subjects with heterozygous or homozygous variant c.211G> A, as the number of c.521T > C alleles variation increased, the incidence of unconjugated hyperbilirubinemia increased, but it was not statistically significant. Our results indicate that variants of UGT1A1 and/or SLCO1B1 have combined effects on Chinese adult mild unconjugated hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) vector-mediated gene therapy is currently evaluated as a potential treatment for Crigler–Najjar syndrome (CN) (NCT03466463). Pre-existing immunity to AAV is known to hinder gene transfer efficacy, restricting enrollment of seropositive subjects in ongoing clinical trials. We assessed the prevalence of anti-AAV serotype 8 (AAV8) neutralizing antibodies (NAbs) in subjects affected by CN and investigated the impact of low NAb titers (<1:5) on liver gene transfer efficacy in an in vivo passive immunization model. A total of 49 subjects with a confirmed molecular diagnosis of CN were included in an international multicenter study (NCT02302690). Pre-existing NAbs against AAV8 were detected in 30.6% (15/49) of screened patients and, in the majority of positive cases, cross-reactivity to AAV2 and AAV5 was detected. To investigate the impact of low NAbs on AAV vector-mediated liver transduction efficiency, adult wild-type C57BL/6 mice were passively immunized with pooled human donor-derived immunoglobulins to achieve titers of up to 1:3.16. After immunization, animals were injected with different AAV8 vector preparations. Hepatic vector gene copy number was unaffected by low anti-AAV8 NAb titers when column-purified AAV vector batches containing both full and empty capsids were used. In summary, although pre-existing anti-AAV8 immunity can be found in about a third of subjects affected by CN, low anti-AAV8 NAb titers are less likely to affect liver transduction efficiency when using AAV vector preparations manufactured to contain both full and empty capsids. These findings have implications for the design of liver gene transfer clinical trials and for the definition of inclusion criteria related to seropositivity of potential participants. [ABSTRACT FROM AUTHOR]

Background: Single nucleotide polymorphism (SNP) variants of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene have been studied as an important factor in neonatal hyperbilirubinemia (jaundice) severity. Specific ethnicities, including Asians, have certain SNPs that appear more frequently than others.Aim: To identify the most common SNPs in Indonesian neonates and their association with the severity of neonatal hyperbilirubinemia.Methods: Eighty-eight inborn and outborn jaundiced infants from three different hospitals (Bengkulu, Jakarta, Biak Papua) across Indonesia were enrolled in this cross-sectional study and their peak total serum bilirubin (TSB) levels assessed. SNP variant analyses of the TATAA box, promoter, and exon 1 regions of UGT1A1 gene from 78 of the 88 infants were carried out using the SNaPshotR Multiplex Polymerase Chain Reaction (PCR) System followed by DNA sequencing.Results: We detected SNP variants UGT1A1*28, UGT1A1*60, UGT1A1*93, and UGT1A1*6 in our population. Mean total serum bilirubin (TSB) was 14.59 ± 5.57 mg/dL. Bivariate analyses using delivery location, gestational age, birth weight, mother's age, and ethnicity were shown to be associated with moderate-to-severe hyperbilirubinemia (p < 0.05). None of the four SNPs appeared to be associated with moderate-to-severe hyperbilirubinemia. In multivariate analysis, however, only the “other ethnic group” (e.g., Chinese, Bengkulu, Papua, Bima) category showed an association with moderate-to-severe hyperbilirubinemia, with an odds ratio of 6.49 (95% CI 1.01–41.67; p < 0.05).Conclusions: We found that the UGT1A1*60 is the most common SNP detected in neonates with hyperbilirubinemia in the Indonesian population. Interestingly, in Indonesia, UGT1A1 polymorphisms do not appear to be associated with differences in the severity of hyperbilirubinemia.

Background: Ursodeoxycholic acid (UDCA) is a safe drug used in the treatment of cholestatic liver disorders in children. The aim of this study was to investigate the synergistic effect of UDCA in combination with phototherapy in treating indirect neonatal hyperbilirubinemia. Methods: Present double-blinded, randomized clinical trial was conducted among neonates with jaundice who were under treatment with phototherapy in the neonatal ward affiliated with the Zabol University of Medical Sciences in 2017. The patients (200 neonates) were randomly divided into intervention (phototherapy+ UDCA) and control (phototherapy alone) groups. The intervention group received 15 mg/kg UDCA daily. Results: Total bilirubin levels at birth, 24, 48, and 72 hours after therapy were 16.89± 2.49, 14.28± 2.05, 11.62± 2.46, and 10.26± 1.92 mg/dl in controls and 15.79± 2.18, 12.77± 1.86, 10.08± 1.66, and 8.94± 1.38 mg/dl in intervention group respectively (P< 0.001). The ratio of neonates with total bilirubin< 10 mg/dl were 28% and 55% after 48 hours, and 64% and 90% after 72 hours of therapy initiation in phototherapy alone and phototherapy+ UDCA groups respectively (P< 0.001). The mean reduction of direct bilirubin was not significantly different between the groups. Conclusion: UDCA was effective in accelerating reduction of total bilirubin level in neonates with unconjugated hyperbilirubinemia under phototherapy but had no effect on direct bilirubin levels.

Purpose: To evaluate the difference in cerebral blood flow velocity (CBFV) in neonates with and without hyperbilirubinemia. Methods: CBFV of 70 healthy late-preterm and term newborns with unconjugated hyperbilirubinemia (UCH) reaching the threshold of phototherapy requirement was compared with 70 gestational- and postnatal age-matched controls without hyperbilirubinemia. Resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV) and vascular diameter were measured in internal carotid, vertebral and middle cerebral arteries by transcranial color Doppler ultrasound at the beginning of phototherapy, after 48–72 h of starting phototherapy and at 5–7 days after its stoppage. In controls CBFV was assessed once at inclusion. Results: Both the groups were comparable. An increase in CBFV (decreased RI and PI, increased PSV and vasodilation) was observed in the UCH group. A further increase in CBFV was noticed after 48 h of phototherapy. After 5–7 days of stoppage of phototherapy, though there was a significant reduction in CBFV in mild-to-moderate UCH (serum bilirubin ⩽25 mg/dL), in severe UCH (serum bilirubin >25 mg/dL), CBFV remained increased. Four neonates developed features of acute bilirubin encephalopathy and had significantly higher CBFV compared to those with normal outcome. Conclusions: An increase in CBFV was observed in neonates with UCH compared to those without hyperbilirubinemia.

Inherited unconjugated hyperbilirubinemias are a group of disorders characterized by increased levels of serum unconjugated bilirubin and arise because of the imbalance between its production and elimination from the body. It includes Crigler-Najjar syndrome and Gilbert syndrome. Crigler-Najjar syndrome type 1 represents the extreme severe end of the spectrum with complete absence of hepatic bilirubin uridine diphosphoglucuronate glucuronosyltransferase (UGT1A1). Crigler-Najjar syndrome type 2 patients have intermediate levels of bilirubin owing to incomplete deficiency of UGT1A1, and Gilbert syndrome lies at the extreme mild end of the spectrum with only slightly raised bilirubin level. Here, we present spectrum of UGT1A1 genetic variants in 25 Pakistani children from 23 unrelated families affected with persistent unconjugated hyperbilirubinemias. The promoter region, coding exons and splice junctions of the UGT1A1 were PCR amplified and subjected to Sanger sequencing. Eleven sequence variants were identified underlying disease phenotype including a novel c.582delC variant. Overall, c.622_625dupCAGC was the most frequent variant followed by c.1021C>T found in Crigler-Najjar syndrome type 1 patients. The evaluation of promoter polymorphism A(TA) n TAA in the affected children and their families further supported the body of evidence that the A(TA) 7 TAA allele could enhance the effect of other structural variants in Crigler-Najjar syndrome patients. To our knowledge, this is the first comprehensive study on molecular genetics of persistent unconjugated hyperbilirubinemias from Pakistan. This study expands the spectrum of UGT1A1 variants and should help in improved clinical diagnosis, genetic counseling and prenatal diagnosis of the affected families. [ABSTRACT FROM AUTHOR]

Background: Serum bilirubin levels beyond the physiological limits, may lead to alterations in autonomic regulation in a newborn infant. Heart rate variability (HRV), is a noninvasive and quantitative marker of the activity of the autonomic nervous system (ANS). To date, few studies have demonstrated the undesirable effects of severe unconjugated hyperbilirubinemia (UHB) on autonomic functions, and only one study has used HRV as a marker of the autonomic activity. However, the relationship between altered cardiac autonomic functions and UHB by using the HRV derived from 24-hour Holter electrocardiography (ECG) recording has not been investigated previously.Objective: We aimed to assess whether a relationship exists between severe UHB and cardiac autonomic dysfunction by evaluating HRV via 24-hour Holter ECG recording.Methods: This single-center, prospective, case-control study was conducted on 50 full-term newborn infants with severe UHB requiring phototherapy and 50 healthy infants as controls. HRV assessment was performed by using 24-hour Holter ECG recording.Results: There was no significant difference in terms of mean average heart rate, mean maximum heart rate and mean RR duration between the groups. However, mean minimum heart rate was significantly lower in the study group. When 24-hour time and frequency domain parameters were compared, time and frequency domain parameters rMSDD as well as high frequency (HF), which represent parasymphathetic activity, were significantly higher in the study group. Furthermore, low frequency to high frequency (LF/HF) ratio, that serves as an indicator of sympathovagal balance, was significantly lower in the study group.Conclusion: Severe UHB may cause cardiac autonomic dysfunction in favor of parasympathetic predominance in jaundiced neonates. [ABSTRACT FROM AUTHOR]

ABSTRACT: BACKGROUND: neonatal jaundice is a commonly occurring cause of severe brain damage if not effectively treated and diagnosed. OBJECTIVE: To compare the effects of LED phototherapy with conventional phototherapy in treatment of unconjugated neonatal jaundice in terms of mean duration of phototherapy, drop in total serum bilirubin levels and side effects observed by the treatment modalities. METHODS: A randomized control trial was conducted in the department of Pediatrics, D.H.Q Hospital, Faisalabad. 140 neonates, aged between 2-28 days of both genders having unconjugated jaundice were included in the study. All the children were divided into two groups. Patients received LED phototherapy in group A and conventional phototherapy in group B. Data was subjected to percentages, chi square tests, frequency for qualitative and independent t tests for non-qualitative variables on the statistical package for social sciences (SPSS) software, version 22. RESULTS: Out of 140 patients, mean age of the patients in gestational weeks was 35.44±7.36. 77(55%) patients were male while 63(45%) patients were female. Mean duration of phototherapy in group A and B were 48.1±24.1 hours and 96.3±33.2 hours respectively (p-value=0.0001). The rates of fall of TSB were 0.45[SE = 0.03] and 0.10 [SE = 0.01] mg/dL/hour in the LED and fluorescent groups, respectively (P = 0.472)2(2.9%) patients had hyperthermia in group A while 10(14.3%) patients had hyperthermia in group B (p-value=0.016). CONCLUSION: LED phototherapy is more advantageous over the conventional method for the treatment of unconjugated neonatal jaundice, in terms of duration, safety profile and also it results in lesser degree of hyperthermia.

Some authors suggest a relation between Unconjugated Bilirubin (UCB) plasma high levels and schizophrenia, as schizophrenia patients have been showing higher UCB levels when compared with other psychiatric patients and general population. These higher UCB levels have been already correlated with acute psychotic states, positive symptoms, and poor outcome in patients with schizophrenia. Schizophrenia and schizoaffective disorders share common symptoms but there aren't yet accepted biomarkers for their distinction. In our study protocol we propose an observational longitudinal study on a sample composed of two subgroups: patients with schizophrenia and patients with schizoaffective disorder. We will compare the UCB levels between groups, and search for a possible correlation with patient's psychopathology. For that purpose we will use nosological, psychopathological, neuropsychological, and psychosocial instruments. Thus we will be testing two different hypotheses: (1) Is UCB serum level a diagnosis indicator, with categorical distinction potential, between groups of patients with different psychotic disorders? (2) Is UCB serum level a severity indicator, with dimensional distinction potential, among groups of patients with the same psychotic disorder? We believe that UCB mean levels may contribute to some clarification of this controversy, as a potential biological indicator, facilitating the distinction between these two diagnostic categories and\or discriminating the dimensional severity among each of these psychotic conditions. Thus we may be opening a new opportunities for innovative and exciting biological psychiatry research regarding organic aspects in the schizophrenia spectrum.

The UGT1A1 enzyme is involved in the metabolism of bilirubin and numerous medications. Unconjugated hyperbilirubinemia, commonly presented as Gilbert syndrome (GS), is a result of decreased activity of the UGT1A1 enzyme, variable number of TA repeats in the promoter of the UGT1A1 gene affects enzyme activity. Seven and eight TA repeats cause a decrease of UGT1A1 activity and risk GS alleles, while six TA repeats contribute to normal UGT1A1 activity and non-risk GS allele. Also, the UGT1A1 (TA)n promoter genotype is recognized as a clinically relevant pharmacogenetic marker. The aim of this study was to assess diagnostic value of UGT1A1 (TA)n promoter genotyping in pediatric GS patients. Correlation of the UGT1A1 (TA)n genotypes and level of unconjugated bilirubin at diagnosis and after hypocaloric and phenobarbitone tests in these patients was analyzed. Another aim of the study was to assess pharmacogenetic potential of UGT1A1 (TA)n variants in Serbia. Fifty-one pediatric GS patients and 100 healthy individuals were genotyped using different methodologies, polymerase chain reaction (PCR) followed by acrylamide electrophoresis, fragment length analysis and/or DNA sequencing. Concordance of the UGT1A1 (TA)n promoter risk GS genotypes with GS was found in 80.0% of patients. Therefore, UGT1A1 (TA)n promoter genotyping is not a reliable genetic test for GS, but it is useful for differential diagnosis of diseases associated with hyperbilirubinemia. Level of bilirubin in pediatric GS patients at diagnosis was UGT1A1 (TA)n promoter genotype-dependent. We found that the frequency of pharmacogenetic relevant UGT1A1 (TA)n promoter genotypes was 63.0%, pointing out that UGT1A1 (TA)n promoter genotyping could be recommended for preemptive pharmacogenetic testing in Serbia. [ABSTRACT FROM AUTHOR]

Some authors suggest a relation between Unconjugated Bilirubin (UCB) plasma high levels and schizophrenia, as schizophrenia patients have been showing higher UCB levels when compared with other psychiatric patients and general population. These higher UCB levels have been already correlated with acute psychotic states, positive symptoms, and poor outcome in patients with schizophrenia. Schizophrenia and schizoaffective disorders share common symptoms but there aren't yet accepted biomarkers for their distinction. In our study protocol we propose an observational longitudinal study on a sample composed of two subgroups: patients with schizophrenia and patients with schizoaffective disorder We will compare the UCB levels between groups, and search for a possible correlation with patient's psychopathology. For that purpose we will use nosological, psychopathological, neuropsychological, and psychosocial instruments. Thus we will be testing two different hypotheses: (1) Is UCB serum level a diagnosis indicator, with categorical distinction potential, between groups of patients with different psychotic disorders? (2) Is UCB serum level a severity indicator, with dimensional distinction potential, among groups of patients with the same psychotic disorder? We believe that UCB mean levels may contribute to some clarification of this controversy, as a potential biological indicator, facilitating the distinction between these two diagnostic categories and\or discriminating the dimensional severity among each of these psychotic conditions. Thus we may be opening a new opportunities for innovative and exciting biological psychiatry research regarding organic aspects in the schizophrenia spectrum. [ABSTRACT FROM AUTHOR]

BACKGROUND: neonatal jaundice is a commonly occurring cause of severe brain damage if not effectively treated and diagnosed. OBJECTIVE: To compare the effects of LED phototherapy with conventional phototherapy in treatment of unconjugated neonatal jaundice in terms of mean duration of phototherapy, drop in total serum bilirubin levels and side effects observed by the treatment modalities. METHODS: A randomized control trial was conducted in the department of Pediatrics, D.H.Q Hospital, Faisalabad. 140 neonates, aged between 2-28 days of both genders having unconjugated jaundice were included in the study. All the children were divided into two groups. Patients received LED phototherapy in group A and conventional phototherapy in group B. Data was subjected to percentages, chi square tests, frequency for qualitative and independent t tests for non-qualitative variables on the statistical package for social sciences (SPSS) software, version 22. RESULTS: Out of 140 patients, mean age of the patients in gestational weeks was 35.44±7.36. 77(55%) patients were male while 63(45%) patients were female. Mean duration of phototherapy in group A and B were 48.1±24.1 hours and 96.3±33.2 hours respectively (p-value=0.0001). The rates of fall of TSB were 0.45[SE = 0.03] and 0.10 [SE = 0.01] mg/dL/hour in the LED and fluorescent groups, respectively (P = 0.472)2(2.9%) patients had hyperthermia in group A while 10(14.3%) patients had hyperthermia in group B (p-value=0.016). CONCLUSION: LED phototherapy is more advantageous over the conventional method for the treatment of unconjugated neonatal jaundice, in terms of duration, safety profile and also it results in lesser degree of hyperthermia. [ABSTRACT FROM AUTHOR]