Diagnosis of Thyroid Nodules in Children and Adolescents with Subclinical Hypothyroidism and Their Outcomes after Early Thyroxine Treatment-A Longitudinal Study.

Pediatric thyroid nodules (TNs) present a higher malignancy rate compared to adults. We sought to diagnose the frequency and characteristics of TNs in children and adolescents with subclinical hypothyroidism (SH) and their outcomes after levothyroxine (LT4) therapy. A total of 256 children with TNs and SH were followed every semester from 2006 to 2018. All patients were treated with LT4. Clinical and radiologic findings, such as the size and texture of the nodules, were documented. Analysis included one-way ANOVA, Kruskal-Wallis, Chi-square, and Fisher's exact tests. After initial LT4 therapy, TNs disappeared in 85.5% and did not reappear throughout follow-up. In 14.5%, TNs remained the same or increased in size, but they decreased after subsequent LT4 administration with an increased dose. Thyroid disease family history (FHTD) was documented in 77.0%. In total, 64.5% developed a goiter, 46.0% exhibited thyroid heterogeneity on ultrasound, 23.4% had positive Anti-Tg, and 25.4% had positive anti-TPO autoantibodies. Our findings support the possible premise that early pharmacologic intervention with LT4 may be beneficial in children and adolescents with TNs and SH. The increased frequency of FHTD, goiter, thyroid heterogeneity, and Hashimoto in our patients emphasizes that thyroid ultrasounds may be warranted in children and adolescents with these characteristics in order to rule out the presence of TNs.

Vitamin B-related Gene Polymorphisms and Cardiovascular Disease.

Hyperhomocysteinemia is an independent risk factor for atherosclerosis, even in early childhood. A mutation in genes that code homocysteine metabolism enzymes or deficiency of specific vitamin cofactors may cause hyperhomocysteinemia. Vitamin B complex has been correlated with serum homocysteine levels. Any abnormality in its metabolism or nutritional deficiency may lead to hyperhomocysteinemia. Both vitamin B complex and homocysteine levels are partly genetically determined. Specifically, the most studied polymorphism is 677T-C in exon 5 of the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene, which plays an important role in folate's metabolism. This polymorphism has been shown to be correlated with hypertension and cardiovascular disease. Polymorphisms in methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L) gene have also been correlated with increased risk for coronary artery disease. Other common serious polymorphisms regard the area with high linkage disequilibrium, including the neuroblastoma breakpoint family, NBPF3 gene, and ~ 12-50 kb upstream of the tissue nonspecific alkaline phosphatase gene. Finally, the polymorphisms which have been mostly associated with vitamin B12 concentration are the rs11254363 polymorphism at intron 52 of the intrinsic factor vitamin B12 receptor of the CUBN and the rs526934 polymorphism at intron 8 of transcobalamin I. To sum up, several polymorphisms have already been associated with vitamin B complexes and therefore homocysteine level, highlighting the complex nature of vitamin B genetics.

Nursing staff fatigue and burnout during the COVID-19 pandemic in Greece.

INTRODUCTION: The coronavirus pandemic (COVID-19) is an unprecedented global health crisis with emotional and physical impact on health care workers. OBJECTIVE: The purpose of this study was to investigate the levels of fatigue and burnout in nursing staff during the pandemic. METHODS: The present study involved nursing staff from hospitals in Greece in February 2021, who completed the Fatigue (FAS) and Burnout (CBI) questionnaires. Gender, age, years of work experience, workplace (COVID-19 or non-COVID-19 wards) and SARS-CoV-2 infection status were recorded. RESULTS: The sample included 593 women and 108 men, with a mean age ± SD: 42.9 ± 9.9 years and 18.14 ± 10.8 years work experience. Slightly more than half, (367, 52.4%) worked in COVID-19 departments. Fifty-six (8%) tested positive for SARS-CoV-2 and 14 of them needed to be treated. The mean ± SD FAS and CBI scores were 25.6 ± 7.4 and 46.9 ± 18.8, respectively (67.9% and 42.9% had scores suggestive of fatigue and burnout, respectively). Women showed higher values in both scales (p < 0.01). Subjects working in COVID-19 wards scored significantly higher on both the FAS and CBI scales; they were also younger and with less work experience (p < 0.01). Staff treated for COVID-19 scored higher on the burnout scale (p < 0.01) than the uninfected staff. Fatigue showed a strong positive correlation with burnout (p < 0.01, r = 0.70). Stepwise multiple regression showed that the variation of fatigue was explained by 47.0% and 6.1% by the scores on the subscales of personal and work-related burnout, respectively. CONCLUSION: In conclusion, high rates of fatigue and burnout were found in the studied population. Nurses working with COVID-19 patients had higher rates of fatigue and burnout compared to those working elsewhere. There was a strong positive correlation (r = 0.70) between burnout and fatigue. Particular attention should be paid to staff who became ill and need to be treated.

Prevalence of Brucella antibodies on a previously acute brucellosis infected population: sensitivity, specificity and predictive values of Rose Bengal and Wright standard tube agglutination tests.

PURPOSE: Brucellosis is a zoonosis with worldwide distribution. The presence of antibodies after acute infection and the prevalence of positive serology in endemic area are not well documented. METHODS: Patients hospitalized with acute brucellosis were relocated 3-13 years after the initial infection. Hospital records of the initial infection were retrieved, and examination of Brucella antibodies using Rose Bengal test (RBT) and Wright standard tube agglutination (STA) test was performed. RESULTS: Eighty-three patients were hospitalized from 2000 to 2010; 50.6 % were farmers and 37.4 % livestock farmers. All had febrile illness and various focal complications. All had positive serology, and 82.2 % had positive blood cultures; 91.5 % were treated with streptomycin plus doxycycline. Seventy-two (86.7 %) were relocated on follow-up. Nine (12.5 %) had positive RBT and STA up to 1/320. Occupational history was associated with positive serology (p = 0.0172), and 8/9 of the positive individuals were livestock farmers (38.0 % of the livestock farmers checked). Residence, years after the infection, clinical presentation of brucellosis and treatment were not associated with serology results. Both tests had excellent sensitivity (nearly 100 %), specificity 87.5 % and excellent negative predictive value (nearly 100 %); however, positive predictive value was only 11.4 %. CONCLUSIONS: Rapid and low-cost tests as RBT and STA are still very useful in diagnosing acute brucellosis; however, every positive test must be examined together with clinical symptoms and occupational history. The tests can be used as screening tests in endemic populations to rule out acute brucellosis.

Protective mechanisms against oxidative stress and angiopathy in young patients with diabetes type 1 (DM1).

OBJECTIVE: Advanced glycation end-products (AGEs) via their receptor, RAGE, are involved in diabetic angiopathy. Soluble RAGE, an inhibitor of this axis, is formed by enzymatic catalysis (sRAGE) or alternative splicing (esRAGE). Malondialdehyde (MDA) is an oxidative stress marker, and ferric reducing ability of plasma (FRAP) is an anti-oxidant capacity marker. METHODS: In isolated mononuclear blood cells from 110 DM1-patients (P) and 124 controls (C) (4-29 years) RAGE mRNA (g) and protein expression (pe) were measured by RT-PCR and Western immunoblotting, respectively. Plasma levels of CML (AGEs) and sRAGE were measured by ELISA, MDA by flurometry and FRAP according to 'Benzie and Strain'. RESULTS: P showed: (i) higher g of RAGE, especially in p>13 years of age and >5 years DM1, (ii) increased pe of esRAGE in DM1>5 years and (iii) increased FRAP and MDA. CONCLUSIONS: The increased esRAGE and FRAP with increased levels of CML and MDA possibly reflects a protective response against the formation of diabetic complications in these young diabetic patients.

Increased growth hormone receptor (GHR) degradation due to over-expression of cytokine inducible SH2 domain-containing protein (CIS) as a cause of GH transduction defect (GHTD).

OBJECTIVE: Children with growth hormone transduction defect (GHTD) have impaired growth and signal transducer and activator of transcription 3 (STAT3) activation. Here, we examine the etiology of GHTD. METHODS: Control (Cf) and GHTD (Pf) children's fibroblasts were induced with hGH, MG132, lactacystin or silence RNA/CIS (siCIS). Western immunoblotting (WI) examined protein expression. Immunofluorescent microscopy (IF) examined cellular localization. RESULTS: (i) Pf showed retarded activation of pJAK2 and pSTAT-5 and increased ubiquitinated CIS (UbCIS) by WI. (ii) After MG132, Pf showed normal activation of pJAK2, pSTAT5 and pSTAT3. (iii) IF showed membrane (ML) and cytoplasmic localization (CL) of the GHR in Cf while the Pf showed only CL. In Pf, induction with lactacystin or siCIS changed the localization of the GHR to ML. CONCLUSIONS: In GHTD, abnormal GH signalling may be caused by over-expression of CIS, which may increase degradation of GHR, thus reducing membrane GHR availability, delaying activation of pJAK2 and pSTAT5 and reducing activation of pSTAT3.

Association between serum levels of the soluble receptor (sRAGE) for advanced glycation endproducts (AGEs) and their receptor (RAGE) in peripheral blood mononuclear cells of children with type 1 diabetes mellitus.

AIM: The binding of AGEs to RAGE is involved in diabetic vascular complications. We studied sRAGE levels and RAGE protein expression (P) together with N-carboxymethyl lysine (CML), a major AGE, in 74 patients with type 1 diabetes mellitus (DM1) and 43 healthy (C) children. METHODS: sRAGE and CML levels were determined by ELISA and RAGE P was evaluated in mononuclear cells by Western immunoblotting. RESULTS: Serum sRAGE was higher in DM1 than in C (1430 +/- 759 vs 1158 +/- 595 pg/ml, p = 0.047), inversely correlated to diabetes duration (r = -0.265, p = 0.037) and directly correlated to LDL-cholesterol levels (r = 0.224, p = 0.039). Diabetes duration correlated independently with sRAGE (p = 0.034). Circulating CML levels were not significantly different between DM1 and C groups (3.51 +/- 1.49 vs 3.59 +/- 1.83 ng/ml, p > 0.05) and RAGE P was lower in DM1 than in C (61 +/- 46 vs 102 +/- 63%, p = 0.0001). CONCLUSIONS: Increased serum sRAGE in children with DM1 may provide temporary protection against cell damage and may be sufficient to eliminate excessive circulating CML.

The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells.

A primary goal of bone research is to understand the mechanism(s) by which mechanical forces dictate the cellular and metabolic activities of osteoblasts, the bone-forming cells. Several studies indicate that osteblastic cells respond to physical loading by transducing signals that alter gene expression patterns. Accumulated data have documented the fundamental role of the osteoblast-specific transcription factor Cbfa1 (core-binding factor) in osteoblast differentiation and function. Here, we demonstrate that low level mechanical deformation (stretching) of human osteoblastic cells directly up-regulates the expression and DNA binding activity of Cbfa1. This effect seems to be fine tuned by stretch-triggered induction of distinct mitogen-activated protein kinase cascades. Our novel finding that activated extracellular signal-regulated kinase mitogen-activated protein kinase physically interacts and phosphorylates endogenous Cbfa1 in vivo (ultimately potentiating this transcription factor) provides a molecular link between mechanostressing and stimulation of osteoblast differentiation. Elucidation of the specific modifiers and cofactors that operate in this mechanotranscription circuitry will contribute to a better understanding of mechanical load-induced bone formation which may set the basis for nonpharmacological intervention in bone loss pathologies.