Diabetic Ketoacidosis in Children Before and During COVID-19 Pandemic: A Cross-sectional Study.

Background: Coronavirus disease 2019 (COVID-19) has spread quickly. Comorbidities, such as diabetes, have been determined as critical risk factors for COVID-19. Objectives: This study aimed to determine the frequency and severity of diabetic ketoacidosis (DKA) in children before and during the COVID-19 pandemic. Methods: This retrospective study examined children aged less than 18 years diagnosed with DKA hospitalized in Yazd Shahid Sadoughi Hospital from February 20, 2020, to November 21, 2021. The collected information was compared to those obtained during the same period in 2019 (pre-pandemic). According to the inclusion criteria, only children with suspected symptoms of COVID-19 or an infected family member underwent PCR. Results: The study included 70 children with confirmed DKA during the COVID-19 pandemic and 33 children hospitalized during the pre-pandemic period. The findings showed that the rate of DKA was higher during the pandemic than in the pre-pandemic period. In the DKA subgroups (during the COVID-19 pandemic vs. pre-pandemic), 35.7% vs. 21.2% were severe, 37.1% vs. 36.4% were moderate, and 27.1% vs. 42.4% were mild. Of 70 children, 30 underwent PCR tests for COVID-19, showing six positive cases. Among positive cases, five had mild symptoms, while one was hospitalized with signs of respiratory distress, polyuria, and polydipsia. All physical examinations of this patient were normal, except for the chest exam. Conclusions: A remarkable increase was observed in the frequency and severity of DKA in children during the pandemic.

Mutational and bioinformatics analysis of the NKX2.1 gene in a cohort of Iranian pediatric patients with congenital hypothyroidism (CH).

Congenital hypothyroidism (CH) occurs with a relatively alarming prevalence in infants, and if not diagnosed and treated in time, it can have devastating consequences for the development of the nervous system. CH is associated with genetic changes in several genes that encode transcription factors responsible for thyroid development, including mutations in the NK2 homeobox 1 (NKX2.1) gene, which encodes the thyroid transcription factor-1 (TTF-1). Although CH is frequently observed in pediatric populations, there is still a limited understanding of the genetic factors and molecular mechanisms contributing to this disease. The sequence of the NKX2.1 gene was investigated in 75 pediatric patients with CH by polymerase chain reaction (PCR), single-stranded conformation polymorphism (SSCP), and direct DNA sequencing. Four missense heterozygous variations were identified in exon 3 of the NKX2.1 gene, including three novel missense variations, namely c.708A>G, p.Gln202Arg; c.713T>G, p.Tyr204Asp; c.833T>G, p.Tyr244Asp, and a previously reported variant rs781133468 (c.772C>G, p.His223Gln). Importantly, these variations occur in highly conserved residues of the TTF-1 DNA-binding domain and were predicted by bioinformatics analysis to alter the protein structure, with a probable alteration in the protein function. These results indicate that nucleotide changes in the NKX2.1 gene may contribute to CH pathogenesis.

New onset of diabetes in a child infected with COVID-19: a case report.

BACKGROUND: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes. A few studies have reported that COVID-19 is associated with the development of new-onset diabetes. Here, we present an infected child with new onset diabetes leading to DKA. CASE PRESENTATION: A 10-year-old patient with respiratory distress admitted to the Emergency Department of our center. The patient's COVID-19 Polymerase Chain Reaction (PCR) test was positive and also biochemical analyses confirmed that he had DKA. Despite standard initial treatments, ketoacidosis remained resistant; hence we prescribed oral bicarbonate (40 cc every 8 h) to treat the patient's refractory acidosis. Due to the patient's improvement, he was discharged after 10 days (7 days in the PICU), receiving outpatient enoxaparin (for a week) and ongoing subcutaneous insulin. CONCLUSION: We report an interesting case of a child with COVID-19 infection precipitating presentation with new onset diabetes. Due to refractory acidosis, starting oral bicarbonate treatment after 2 days improved acidosis and tachypnea in the patient. The patient's medical team suggest close biochemical monitoring, prescribing enoxaparin for high level of D-dimer, and ordering oral bicarbonate acidosis persists.

Antimicrobial Peptides from Amphibian Innate Immune System as Potent Antidiabetic Agents: A Literature Review and Bioinformatics Analysis.

Antimicrobial peptides, as an important member of the innate immune system, have various biological activities in addition to antimicrobial activity. There are some AMPs with antidiabetic activity, especially those isolated from amphibians. These peptides can induce insulin release via different mechanisms based on peptide type. In this review study, we collected all reported AMPs with antidiabetic activity. We also analyze the sequence and structure of these peptides for evaluation of sequence and structure effect on their antidiabetic activity. Based on this review, the biggest peptide family with antidiabetic activity is temporins with nine antidiabetic peptides. Frogs are the most abundant source of antidiabetic peptides. Bioinformatics analysis showed that an increase of positive net charge and a decrease of hydrophobicity can improve the insulinotropic effect of peptides. Peptides with higher positive net charge and Boman index showed higher activity. Based on this review article, AMPs with antidiabetic activity, especially those isolated from amphibians, can be used as novel antidiabetic drug for type 2 diabetes disease. So, amphibians are potential sources for active peptides which merit further evaluation as novel insulin secretagogues. However, strategy for the increase of stability and positive activity as well as the decrease of negative side effects must be considered.

The prevalence of zinc deficiency in morbidly obese patients before and after different types of bariatric surgery.

BACKGROUND: The prevalence of obesity is considered to be increased worldwide. Lack of mineral elements is one of the essential side effects of bariatric surgery as a trending treatment for obesity. We aimed to assess zinc deficiency among morbidly obese patients before and following different types of bariatric surgical procedures. METHODS: In the present retrospective cohort study, 413 morbidly obese patients (body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with a complication or risk factor, e.g., diabetes mellitus) were enrolled who received bariatric surgery, aged between 18 and 65 years old, and had a negative history of active consumption of alcohol and illicit drugs. Patients were assigned into three groups of bariatric surgeries: mini-gastric bypass, Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG). We recorded baseline clinical and demographic characteristics and zinc serum levels during the preoperative and postoperative follow-up periods at three, six, and 12 months after the operation. RESULTS: All patients with a mean age of 40.57 ± 10.63 years and a mean preoperative BMI of 45.78 ± 6.02 kg/m2 underwent bariatric surgery. 10.2% of the bariatric patients experienced zinc deficiency before the surgery, and 27.1% at 1 year after the surgery. The results showed that 27.7% of mini-gastric bypass patients, 29.8% of RYGB, and 13.3% of SG experienced zinc deficiency 12 months following surgery. We observed no statistical differences in the preoperative and postoperative zinc deficiency between different types of surgeries. CONCLUSION: A high prevalence of preoperative zinc deficiency among morbidly obese patients who underwent bariatric surgery was observed, which increased during the postoperative periods. We recommend assessing zinc serum levels and prescribing zinc supplements before the bariatric operation to alleviate the prevalence of zinc deficiency after the operation.

The Effect of Synbiotic Supplementation on Growth Parameters in Mild to Moderate FTT Children Aged 2-5 Years.

Synbiotic (probiotic bacteria and prebiotic) has beneficial effects on the gastrointestinal tract. This study was designed to investigate the effect of synbiotic supplementation on the growth of mild to moderate failure to thrive (FTT) children. A randomized, triple-blind, placebo-controlled trial was conducted involving 80 children aged 2-5 years with mild to moderate FTT, who were assigned at random to receive synbiotic supplementation (109 colony-forming units) or placebo for 30 days. The weights, height, and BMI were recorded in a structured diary, and the questionnaires were completed to monitor the numbers of infection episodes, gastrointestinal problems, admission to hospital, and appetite improvement during the study. Sixty-nine children completed the study. There were no differences in the demographic characteristic between the two groups. The mean weight was similar at baseline. After 30 days of intervention, the mean weight of the participants in the synbiotic group increased significantly than those in the placebo group (600 ± 37 vs. 74 ± 32 g/month P 0.000). BMI changes in synbiotic and placebo group were 0.44 and 0.07 kg/m2, and that the differences among the two groups were significant.(P 0.045) Furthermore, the height increment in synbiotic and placebo group was 0.41 and 0.37 cm respectively with no significant difference (P 0.761). Administration of 30-day synbiotic supplementation may significantly improve weight and BMI in Iranian children with mild to moderate FTT, but there is no effect on the height in this study. Further studies should be designed to found out the effect of synbiotic on growth parameters in undernourished and well-nourished children.

Mutation analysis of the NKX2.5 gene in Iranian pediatric patients with congenital hypothyroidism.

BACKGROUND: The embryonic development of the thyroid gland is regulated by the expression of several candidate genes which are related to congenital hypothyroidism. These genes include the numerous critical thyroid transcription factors such as NKX2.1, NKX2.5, FOXE1, and PAX8. The molecular analysis of these loci will be essential to the explanation of the participation of these transcription activators in the etiology of hypothyroidism. Among them, the role of NKX2.5 is important during the early thyroid morphogenesis and in controlling thyroidal cell differentiation and migration. Importantly, NKX2.5 change nucleotides are recognized to be central to the genesis of congenital hypothyroidism. METHODS: A case-control study was conducted in 65 unrelated patients, diagnosed with primary congenital hypothyroidism and all of them were diagnosed according to the clinical presentations of thyroid hypoplasia and without cardiovascular defects. Mutational screening of the entire NKX2-5 coding sequence was performed in a cohort of pediatric patients by PCR-SSCP and direct sequencing. RESULTS: We identified two known variations 73C>T (R25C) and 63A>G (E21E) in patients with thyroid hypothyroidism. Both of them are located in conserved region of the gene and previously reported in cases with thyroid dysgenesis and congenital heart defects. There was a significance association between 63A>G variation with primary hypothyroidism (p=0.003). CONCLUSIONS: These SNPs are probably related to thyroid hypoplasia because the allele frequency of the 63A>G polymorphism was significantly different in patients and controls and also R25C variation not observed in healthy cases.

Effect of vitamin D on HbA1c levels of children and adolescents with diabetes mellitus type 1.

BACKGROUND: Studies show the relationship between vitamin D deficiency and glucose metabolism disorders. The aim of this study was the evaluation of the effect of vitamin D administration in management of diabetes mellitus type 1 (T1D). METHODS: We evaluated the effect of supplementation with vitamin D on HbA1c levels of children and adolescents with T1D. In this before-after study, 70 subjects with T1D were enrolled. Fasting serum 25-hydroxyvitamin D, calcium, phosphate, alkaline phosphatase, glucose and HbA1c were measured at the initiation and after the administration of 50,000 IU of vitamin D3 biweekly for 3 months. The results were then compared using paired t-test. Between 70 patients, five patients were excluded from the study because they did not completed the study and finally 65 subjects finished the study. RESULTS: Sixty-five patients including 35 children and 30 adolescents were recruited. Forty-three (66.1%) subjects had vitamin D deficiency (<30 ng/mL). Vitamin D administration leads to decrease of fast blood sugar and HbA1c levels significantly in treated group without effect on calcium and alkaline phosphatase levels. So, no significant alterations occurred in calcium and alkaline phosphatase levels after supplementation with vitamin D. CONCLUSIONS: This study showed that HbA1c may be reduced by administration of vitamin D to children and adolescents with T1D without changing the dose of insulin.

Identification and biochemical characterization of a new antibacterial and antifungal peptide derived from the insect Sphodromantis viridis.

Antimicrobial peptides are members of the immune system that protect the host from infection. In this study, a potent and structurally novel antimicrobial peptide was isolated and characterized from praying mantis Sphodromantis viridis. This 14-amino acid peptide was purified by RP-HPLC. Tandem mass spectrometry was used for sequencing this peptide, and the results showed that the peptide belongs to the Mastoparan family. The peptide was named Mastoparan-S. Mastoparan-S demonstrated that it has antimicrobial activities against a broad spectrum of microorganisms (Gram-positive and Gram-negative bacteria and fungi), and it was found to be more potent than common antibiotics such as kanamycin. Mastoparan-S showed higher antimicrobial activity against Gram-negative bacteria compared to Gram-positive ones and fungi. The minimum inhibitory concentration (MIC) values of Mastoparan-S are 15.1-28.3 µg/ml for bacterial and 19.3-24.6 µg/ml for fungal pathogens. In addition, this newly described peptide showed low hemolytic activity against human red blood cells. The in vitro cytotoxicity of Mastoparan-S was also evaluated on monolayer of normal human cells (HeLa) by MTT assay, and the results illustrated that Mastoparan-S had significant cytotoxicity at concentrations higher than 40 µg/ml and had no any cytotoxicity at the MIC (≤30 µg/ml). The findings of the present study reveal that this newly described peptide can be introduced as an appropriate candidate for treatment of topical infection.

Cognitive outcomes for congenital hypothyroid and healthy children: a comparative study.

OBJECTIVE: Early diagnosis and treatment of congenital hypothyroidism (CH) and the prevention of developmental retardation is the main goal of public health national screening programs. This study compares the cognitive ability of children with CH diagnosed by neonatal screening with a healthy control group (2007) in Yazd, Iran. MATERIALS & METHODS: In a case-controlled study, the intelligent quotient (IQ) of 40 five-year-old children with early treated CH and good compliance were evaluated by the Wechsler preschool and primary scale of intelligent test and compared to 40 healthy age and gender matched children as controls. RESULTS: 22 boys (55%) and 18 girls (45%) in both groups were evaluated. In children with CH, 19 (47.5%) and 21 (52.5%) persons had transient and permanent hypothyroidism, respectively. Range of TSH and T4 level at the onset of diagnosis were 11.41-81 mu/l and 1.50-14.20 µg/dl, respectively. The intelligence levels of all children with CH were within the average or normal range and IQs ranged from 91-108. Children with CH had lower full-scale IQs (107.25 ± 2. 9 versus 110.50 ± 2.66, p=0.001), verbal IQ (106.95 ± 3.5 versus 109.90 ± 3.44, P-value=0.001) and performance IQ (106.3 ± 3.68 versus 108.87 ± 3.70) than the control group. However, no statistically significant differences were observed for mean IQ scores in permanent and transient CH. CONCLUSION: Children with CH who had early treatment and good compliance had normal cognitive abilities, but may have a decreased IQ relative to the healthy control group.

Prevalence of Permanent Congenital Hypothyroidism in Children in Yazd, Central Iran.

BACKGROUND: Congenital hypothyroidism is a condition of thyroid hormone deficiency. Approximately 1 in 4000 newborn infants has a deficiency of thyroid function. The aim of this study is determination of the prevalence of permanent and transient congenital hypothyroidism (CH) in Yazd, Iran. METHODS: From May 2006 to June 2008, 35377 newborns were screened by measuring serum TSH obtained by heel prick. The neonates who had a TSH≥5mU/L were recalled for measurement of serum T4 and thyroid stimulating hormone (TSH) in venous samples. Based on the results of the secondary measurements (between days 7 and 28), neonates were considered hypothyroid if their T4 was <6.5 mg/dl and their TSH was ≥10mIU/L. In 22 primarily diagnosed as cases of CH, treatment was discontinued at age 3 years for 4 weeks and T4 and TSH were measured again. Permanent or transient CH was determined from the results of these tests; Patients with TSH levels ≥5 mIU/l were diagnosed with permanent CH. RESULTS: The incidence of congenital hypothyroidism was found to be 1:1608 with a female to male ratio of 0.69:1. In 22 patients with CH, 10 patients were diagnosed with permanent CH (45.5%) and 12 with transient hypothyroidism (54.5%). Permanent CH was associated with higher TSH levels at first measurement than transient hypothyroidism (P-value=0.041). CONCLUSION: The rate of transient CH in our study was higher than the comparable worldwide rate, so more and larger studies are needed to find clear information about the etiologic factors of this disease.

Efficacy of levothyroxine in migraine headaches in children with subclinical hypothyroidism.

OBJECTIVE: Hypothyroidism may be an exacerbating factor for primary headaches and migraine is one of the most common primary headaches in childhood. The purpose of this study was to evaluate the effect of treatment of subclinical hypothyroidism on children with migraine headache. MATERIALS & METHODS: In a quasi-experimental study, the severity and monthly frequency of headache of 25 migraineur children with subclinical hypothyroidism who were referred to the pediatric neurology clinic of Shahid Sadoughi University of Medical Sciences,Yazd, Iran between January 2010 and February 2011 and were treated with levothyroxine for two months were evaluated. RESULTS: Thirteen girls (52%) and 12 boys (48%) with the mean age of 10.2 ± 2.76 years were evaluated. In children with hypothyroidism, the monthly frequency of headache (mean ± SD: 17.64 ± 9.49 times vs. 1.2 ± 1.1 times) and the severity of headache (mean± SD: 6.24±1.8 scores vs. 1.33 ± 0.87 scores) were significantly decreased by treatment. CONCLUSION: Based on the results of this study, treatment of subclinical hypothyroidism was effective in reducing migraine headaches. Therefore, it is logical to check thyroid function tests in migraineur children.