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2.
J Steroid Biochem Mol Biol ; 231: 106330, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37182754

RESUMO

Rapidly restoring vitamin D levels to normal might be desirable in certain clinical situations. Larger doses of supplementation, have been shown to increase bone loss and the risk of falls. The optimal way to perform vitamin D loading safely and effectively is still not well elucidated. Our study was aimed to assess the safety and efficacy of two oral vitamin D loading protocols. Sixty-nine subjects with vitamin D deficiency (25OH-vitamin D (25(OH)D) < 20 ng/ml) were included. Thirty-five participants received 30 000 IU of vitamin D3 per week for 10 weeks (group Slower Loading Dose (SLD)) and thirty-four received 30 000 IU twice weekly for 5 weeks (group Moderate Loading Dose (MLD)) resulting in a loading dose of 300 000 IU for all subjects. Following this initial loading phase, both groups received 30 000 IU biweekly for 4 weeks to test whether the recommended daily vitamin D supplementation in range of 2000 IU dose-equivalent could maintain the achieved levels. Seventy-nine percent of those subjects treated in group SLD and everyone in group MLD achieved a 25(OH)D level of 30 ng/ml, which is the lower limit of the recommended normal range in Hungary. The mean increase in 25(OH)D was significantly higher in group MLD than in group SLD (38.6 ± 1.80 ng/ml vs 46,6 ± 1.80 ng/ml). No significant decrease was observed with the administration of the maintenance dose. There were no clinically significant changes in serum or urine calcium, and bone biomarkers in either group. Both protocols were found to be safe and effective, but the five-week dosing caused a significantly greater increase in 25(OH)D. A maintenance dose applied for four weeks after the loading protocol did not raise 25(OH)D levels further but maintained the achieved increase. The administration of 30 000 IU of vitamin D3 twice weekly for five weeks is a rapid, effective and safe way to treat vitamin D deficiency in vitamin D deficient patients.


Assuntos
Doenças Ósseas Metabólicas , Deficiência de Vitamina D , Humanos , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D , Colecalciferol/efeitos adversos , Vitaminas/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Suplementos Nutricionais
3.
R Soc Open Sci ; 10(2): 191375, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36756055

RESUMO

The low reproducibility rate in social sciences has produced hesitation among researchers in accepting published findings at their face value. Despite the advent of initiatives to increase transparency in research reporting, the field is still lacking tools to verify the credibility of research reports. In the present paper, we describe methodologies that let researchers craft highly credible research and allow their peers to verify this credibility. We demonstrate the application of these methods in a multi-laboratory replication of Bem's Experiment 1 (Bem 2011 J. Pers. Soc. Psychol. 100, 407-425. (doi:10.1037/a0021524)) on extrasensory perception (ESP), which was co-designed by a consensus panel including both proponents and opponents of Bem's original hypothesis. In the study we applied direct data deposition in combination with born-open data and real-time research reports to extend transparency to protocol delivery and data collection. We also used piloting, checklists, laboratory logs and video-documented trial sessions to ascertain as-intended protocol delivery, and external research auditors to monitor research integrity. We found 49.89% successful guesses, while Bem reported 53.07% success rate, with the chance level being 50%. Thus, Bem's findings were not replicated in our study. In the paper, we discuss the implementation, feasibility and perceived usefulness of the credibility-enhancing methodologies used throughout the project.

4.
BMC Endocr Disord ; 23(1): 23, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703169

RESUMO

CONTEXT: Increasing diagnostic sensitivity in the detection of thyroid cancer has led to uncertainties in the optimal surgical approach of the smaller, low risk tumors. Current ATA guidelines consider lobectomy safe between 1 and 4 cm, while ETA advocates for primary total thyroidectomy to avoid reoperation, as final risk stratification is based on the histological results. OBJECTIVE: Our aim was to compare the differences in outcomes that are potentially achievable with adherence to the different guidelines, and also to examine the predictive value of clinical parameters on the incidence of postoperative risk factors. METHODS: We performed a retrospective cohort database analysis to identify the different surgical outcomes (based on postoperative risk factors) using ATA and ETA guidelines; the hypothetical rate of completion thyroidectomy when ATA or ETA recommends lobectomy; the accuracy of our preoperative evaluation; the utility of preoperative findings in predicting the optimal surgical strategy using binary logistic regression. RESULTS: Out of 248 patients, 152 (ATA) and 23 (ETA) cases would have been recommended for initial lobectomy. Following the guidelines, a postoperative risk factor would have been present in 61.8, and 65.2% of the cases, respectively. Except for angioinvasion, tumor size was not a significant predictor for the presence of postoperative risk factors. CONCLUSION: Current pre-operative criteria are inadequate to accurately determine the extent of initial surgery and our postoperative findings verify the frequent need for completion thyroidectomy using both guidelines. As a consequence, in the absence of effective pre-operative set of criteria, we advocate primary total thyroidectomy in most cases.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Fatores de Risco
5.
R Soc Open Sci ; 9(7): 211997, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35814910

RESUMO

The preregistration of research protocols and analysis plans is a main reform innovation to counteract confirmation bias in the social and behavioural sciences. While theoretical reasons to preregister are frequently discussed in the literature, the individually experienced advantages and disadvantages of this method remain largely unexplored. The goal of this exploratory study was to identify the perceived benefits and challenges of preregistration from the researcher's perspective. To this end, we surveyed 355 researchers, 299 of whom had used preregistration in their own work. The researchers indicated the experienced or expected effects of preregistration on their workflow. The results show that experiences and expectations are mostly positive. Researchers in our sample believe that implementing preregistration improves or is likely to improve the quality of their projects. Criticism of preregistration is primarily related to the increase in work-related stress and the overall duration of the project. While the benefits outweighed the challenges for the majority of researchers with preregistration experience, this was not the case for the majority of researchers without preregistration experience. The experienced advantages and disadvantages identified in our survey could inform future efforts to improve preregistration and thus help the methodology gain greater acceptance in the scientific community.

6.
BMC Cancer ; 21(1): 706, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34130653

RESUMO

BACKGROUND: Epidemiological evidence suggests that synchronous or metachronous presentation of breast and thyroid cancers exceeds that predicted by chance alone. The following potential explanations have been hypothesized: common environmental or hormonal factors, oncogenic effect of the treatment for the first cancer, closer follow-up of cancer survivors, shared underlying genetic risk factors. While some cases were found to be related to monogenic disorders with autosomal inheritance, the genetic background of most cases of co-occurring breast and thyroid cancer is thought to be polygenic. METHODS: In this retrospective case-control study we compared the genetic profile of patients with a history of breast cancer (n = 15) to patients with co-occurring breast and thyroid cancer (n = 19) using next generation sequencing of 112 hereditary cancer risk genes. Identified variants were categorized based on their known association with breast cancer and oncogenesis in general. RESULTS: No difference between patients with breast and double cancers was observed in clinical and pathological characteristics or the number of neutral SNPs. The unweighted and weighted number of SNPs with an established or potential association with breast cancer was significantly lower in the group with breast cancer only (mean difference - 0.58, BCa 95% CI [- 1.09, - 0.06], p = 0.029, and mean difference - 0.36, BCa 95% CI [- 0.70, - 0.02], p = 0.039, respectively). The difference was also significant when we compared the number of SNPs with potential or known association with any malignancy (mean difference - 1.19, BCa 95% CI [- 2.27, - 0.11], p = 0.032 for unweighted, and mean difference - 0.73, BCa 95% CI [- 1.32, - 0.14], p = 0.017 for weighted scores). CONCLUSION: Our findings are compatible with the hypothesis of genetic predisposition in the co-occurrence of breast and thyroid cancer. Further exploration of the underlying genetic mechanisms may help in the identification of patients with an elevated risk for a second cancer at the diagnosis of the first cancer.


Assuntos
Neoplasias da Mama/genética , Oncogenes/genética , Polimorfismo de Nucleotídeo Único/imunologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia
7.
BMC Med Genet ; 21(1): 129, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534577

RESUMO

BACKGROUND: Vitamin D metabolism and obesity have been linked by several studies, however the reason for this association is unclear. Our objective was to investigate potential correlations between genetic variants in key enzymes of vitamin D metabolism and the body mass index on a representative and random sample of Hungarian adults. METHODS: Altogether 462 severely vitamin D deficient individuals were studied at the end of winter in order to decrease environmental and maximize any relevant genetic effect. Furthermore, participants with lifestyle factors known to affect vitamin D homeostasis were also excluded. We selected 23 target SNPs in five genes that encode key proteins of vitamin D metabolism (NADSYN1, GC, CYP24A1, CYP2R1, VDR). RESULTS: Variants in 2 genetic polymorphisms; rs2853564 (VDR) and rs11023374 (CYP2R1) showed a significant association with participants' BMI. These associations survived further adjustment for total-, free-, or bioactive-25(OH) vitamin D levels, although the variance explained by these 2 SNPS in BMI heterogeneity was only 3.2%. CONCLUSION: Our results show two novel examples of the relationship between genetics of vitamin D and BMI, highlighting the potential role of vitamin D hormone in the physiology of obesity.


Assuntos
Índice de Massa Corporal , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Variação Genética , Receptores de Calcitriol/genética , Vitamina D/sangue , Adulto , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição/genética
8.
Handb Exp Pharmacol ; 262: 93-120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32036458

RESUMO

Several endocrine systems have important effects on bone tissue. Thyroid hormones are essential for normal growth and development. Excess of these hormones will result in clinically significant changes that may require intervention. Glucocorticoids also have a marked effect on bone metabolism by several pathways. Their endogenous or exogenous excess will induce pathological processes that might elevate the risk of fractures. Insulin and the carbohydrate metabolism elicit a physiological effect on bone; however, the lack of insulin (type 1 diabetes) or insulin resistance (type 2 diabetes) have deleterious influence on bone tissue.


Assuntos
Diabetes Mellitus Tipo 2 , Glucocorticoides , Osso e Ossos , Humanos , Insulina/química , Insulina/metabolismo , Hormônios Tireóideos/química
9.
J Steroid Biochem Mol Biol ; 183: 62-67, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29792983

RESUMO

Serum 25-hydroxyvitamin D /25OHD/ levels in humans are determined primarily by environmental factors such as UV-B radiation and diet, including vitamin D intake. Although some genetic determinants of 25OHD levels have been shown, the magnitude of this association has not yet been clarified. The present study evaluates the genetic contribution to total- /t-25OHD/ and free-25OHD /f-25OHD/ in a representative sample of the Hungarian population (n = 462). The study was performed at the end of winter to minimize the effect of sunlight, which is a major determinant of serum vitamin D levels. Single nucleotide polymorphisms (SNPs) of five genes playing major roles in vitamin D metabolism were investigated (NADSYN1, DHCR7, GC, CYP2R1 and CYP24A1). The selected SNPs account for 13.1% of the variance of t-25OHD levels. More than half of the genetic effect on t-25OHD levels was explained by two polymorphisms (rs7935125 in NADSYN1 and rs2762941 in CYP24A1), which had not previously been investigated with respect to vitamin D metabolism. No SNPs exhibited association with f-25OHD levels. Unexpectedly, SNPs that showed univariate associations with vitamin D binding protein (DBP) levels were not associated with f-25OHD levels questioning the biological significance of these polymorphisms. The present study shows that t-25OHD levels are significantly influenced by genetic factors, however, the clinical significance of this observation remains to be defined, as variation in f-25OHD levels are marginally explained by genetic effects.


Assuntos
Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida/genética , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Polimorfismo de Nucleotídeo Único , Deficiência de Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética , Vitamina D3 24-Hidroxilase/genética , Vitamina D/análogos & derivados , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Vitamina D/sangue , Deficiência de Vitamina D/genética
10.
Endocrine ; 55(1): 60-65, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27718150

RESUMO

The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3-not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D3. The present study is a controlled, randomized, open-label, multicenter clinical trial, 3 months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D3 provide equal efficacy and safety profiles.


Assuntos
Colecalciferol/administração & dosagem , Suplementos Nutricionais , Deficiência de Vitamina D/dietoterapia , Adulto , Idoso , Calcifediol/sangue , Colecalciferol/efeitos adversos , Colecalciferol/uso terapêutico , Estudos de Coortes , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Comprimidos , Equivalência Terapêutica , Fatores de Tempo , Deficiência de Vitamina D/sangue
11.
J Bone Miner Metab ; 35(1): 83-90, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26661476

RESUMO

We sought the lowest serum total 25-hydroxyvitamin D (t-25OHD) values in geographic areas with four seasons and investigated whether the calculation of serum free 25-hydroxyvitamin D (f-25OHD) could provide additional information on vitamin D status. This is a representative, cross-sectional study restricted to a sampling period at the end of winter, using a non-probability, stratified sample of the adult community-dwelling Hungarian population (n = 882). We measured t-25OHD, vitamin D binding protein (DBP), parathyroid hormone (PTH), and albumin levels. f-25OHD concentrations were calculated. We assessed environmental factors that could affect vitamin D levels and diseases possibly related to vitamin D deficiency. Mean t-25OHD values of the total population were 41.3 ± 20.6 nmol/L. t-25OHD levels were below 75, 50, and 30 nmol/L in 97, 77, and 34 % of participants not receiving vitamin D supplementation, respectively. t-25OHD values weakly positively correlated with DBP (r = 0.174; p = 0.000), strongly with f-25OHD (r = 0.70; p = 0.000). The association between t-25OHD and f-25OHD and between t-25OHD and PTH were non-linear (p squared term = 0.0004 and 0.004, respectively). t-25OHD levels were not affected by gender, age, place of residence; however, they were related to body mass index, sunbed sessions, and tropical travel. In contrast, f-25OHD levels were different in males and females but were not related to obesity. t- and f-25OHD were lower among people with cardiovascular diseases (p = 0.012). Nearly the entire Hungarian population is vitamin D insufficient at the end of winter. The use of t-25OHD could show a spurious association with obesity; however, it does not reflect the obvious sex difference.


Assuntos
Doenças Cardiovasculares/sangue , Hormônio Paratireóideo/sangue , Estações do Ano , Vitamina D/análogos & derivados , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/prevenção & controle
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