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Human Genomics Jun 2024The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb...
BACKGROUND
The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb microdeletion, usually affecting the same ~ 106 genes. One of the genes affected by this deletion is DGCR8, which plays a crucial role in miRNA biogenesis. Therefore, the haploinsufficiency of DGCR8 due to this microdeletion can alter the modulation of the expression of several miRNAs involved in a range of biological processes.
RESULTS
In this study, we used next-generation sequencing to evaluate the miRNAs profiles in the peripheral blood of 12 individuals with typical 22q11DS compared to 12 healthy matched controls. We used the DESeq2 package for differential gene expression analysis and the DIANA-miTED dataset to verify the expression of differentially expressed miRNAs in other tissues. We used miRWalk to predict the target genes of differentially expressed miRNAs. Here, we described two differentially expressed miRNAs in patients compared to controls: hsa-miR-1304-3p, located outside the 22q11.2 region, upregulated in patients, and hsa-miR-185-5p, located in the 22q11.2 region, which showed downregulation. Expression of miR-185-5p is observed in tissues frequently affected in patients with 22q11DS, and previous studies have reported its downregulation in individuals with 22q11DS. hsa-miR-1304-3p has low expression in blood and, thus, needs more validation, though using a sensitive technology allowed us to identify differences in expression between patients and controls.
CONCLUSIONS
Thus, lower expression of miR-185-5p can be related to the 22q11.2 deletion and DGCR8 haploinsufficiency, leading to phenotypic consequences in 22q11.2DS patients, while higher expression of hsa-miR-1304-3p might be related to individual genomic variances due to the heterogeneous background of the Brazilian population.
Topics: Humans; MicroRNAs; Male; High-Throughput Nucleotide Sequencing; Female; DiGeorge Syndrome; Child; Gene Expression Profiling; Adolescent; Adult; Case-Control Studies; RNA-Binding Proteins; Gene Expression Regulation; Haploinsufficiency; Young Adult
PubMed: 38872198
DOI: 10.1186/s40246-024-00625-5 -
JBMR Plus Jul 2024Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults are relatively limited in Asian countries. This study aims to provide an overview...
Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults are relatively limited in Asian countries. This study aims to provide an overview of the secular trends in incidence, clinical characteristics, and treatment patterns of PHPT in South Korea. We used Korea's National Health Insurance Claim database (2005-2020) to identify newly diagnosed PHPT cases. Individuals with age below 19, fewer than 2 E21.0 diagnoses, fewer than 2 PTH measurements, secondary hyperparathyroidism, undergoing dialysis or kidney transplantation within a year of diagnosis, parathyroidectomy (PTX) within a year prior to the diagnosis code, and diagnosis of multiple endocrine neoplasm or parathyroid carcinoma were excluded from the analysis. A total of 6837 patients with PHPT (PTX, = 2989; non-surgery, = 3848) were compared with 1:10 age- and sex-matched controls ( = 68 370). The mean age of patients with PHPT was 56.0 years, with 77.4% being women. The annual incidence of PHPT increased from 0.23/100 000 persons in 2005 to 1.75 in 2020, with higher rate in women than in men. Compared with 2005-2010 ( = 675), the number of newly diagnosed PHPT cases increased up to 3.1-fold ( = 2119) in 2011-2015 and 6.0-fold ( = 4043) in 2016-2020 periods. Among all patients with PHPT, 43.7% of patients underwent PTX, with decrement of proportion of bilateral surgery among PTX group across time (11.9% in 2005-2010 to 8.9% in 2016-2020, for trend .033). Among all patients with PHPT, non-surgery group increased from 41.6% in 2005-2010 to 58.0% in 2016-2020 ( for trend <.001). Patients with PHPT had higher odds of osteoporosis (odds ratio [OR] 7.03), renal stones (OR 10.55), chronic kidney diseases (OR 7.42), and cardiovascular, metabolic, and neurological conditions after adjustment for comorbidity index. In summary, the incidence of PHPT increased from 2005 to 2020 with predominance of non-surgical treatment, which calls for research focus on improving non-surgical management.
PubMed: 38868595
DOI: 10.1093/jbmrpl/ziae065 -
BMC Endocrine Disorders Jun 2024Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of...
Identification of novel risk factors for postoperative severe hypocalcemia in patients with primary hyperparathyroidism undergoing parathyroidectomy: a case control study.
BACKGROUND
Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters.
METHODS
A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH.
RESULTS
Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity.
CONCLUSION
Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX.
Topics: Humans; Hyperparathyroidism, Primary; Female; Male; Parathyroidectomy; Middle Aged; Risk Factors; Retrospective Studies; Case-Control Studies; Hypocalcemia; Postoperative Complications; Aged; Calcium; Prognosis; Biomarkers; Adult; Follow-Up Studies; Parathyroid Hormone
PubMed: 38867205
DOI: 10.1186/s12902-024-01620-6 -
Revista Da Associacao Medica Brasileira... 2024
Topics: Humans; Hyperparathyroidism; Osteitis Fibrosa Cystica
PubMed: 38865551
DOI: 10.1590/1806-9282.2024S132 -
Bioconjugate Chemistry Jun 2024Peptide fibrillization is crucial in biological processes such as amyloid-related diseases and hormone storage, involving complex transitions between folded, unfolded,...
Peptide fibrillization is crucial in biological processes such as amyloid-related diseases and hormone storage, involving complex transitions between folded, unfolded, and aggregated states. We here employ light to induce reversible transitions between aggregated and nonaggregated states of a peptide, linked to the parathyroid hormone (PTH). The artificial light-switch 3-{[(4-aminomethyl)phenyl]diazenyl}benzoic acid (AMPB) is embedded into a segment of PTH, the peptide PTH, to control aggregation, revealing position-dependent effects. Through design, synthesis, and experimental validation of 11 novel PTH-derived peptides, we predict and confirm the amyloid-forming capabilities of the AMPB-containing peptides. Quantum-chemical studies shed light on the photoswitching mechanism. Solid-state NMR studies suggest that β-strands are aligned parallel in fibrils of PTH, while in one of the AMPB-containing peptides, β-strands are antiparallel. Simulations further highlight the significance of π-π interactions in the latter. This multifaceted approach enabled the identification of a peptide that can undergo repeated phototriggered transitions between fibrillated and defibrillated states, as demonstrated by different spectroscopic techniques. With this strategy, we unlock the potential to manipulate PTH to reversibly switch between active and inactive aggregated states, representing the first observation of a photostimulus-responsive hormone.
PubMed: 38865349
DOI: 10.1021/acs.bioconjchem.4c00188 -
Journal of the ASEAN Federation of... 2024Primary hyperparathyroidism (PHPT) is rare in pregnancy. This condition is challenging to diagnose and manage due to the limited diagnostic and therapeutic options that...
Primary hyperparathyroidism (PHPT) is rare in pregnancy. This condition is challenging to diagnose and manage due to the limited diagnostic and therapeutic options that are safe during pregnancy. If not diagnosed and managed in a timely manner, serious maternal and foetal complications may occur. We report two cases, one with surgical intervention and one without, to show the importance of timely surgical intervention and discuss the challenges in the management of PHPT in pregnancy.
Topics: Humans; Female; Pregnancy; Hyperparathyroidism, Primary; Adult; Pregnancy Complications; Parathyroid Neoplasms; Parathyroidectomy; Pregnancy Complications, Neoplastic; Adenoma; Treatment Outcome
PubMed: 38863924
DOI: 10.15605/jafes.039.01.17 -
Kidney Research and Clinical Practice May 2024With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of...
With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65-74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.
PubMed: 38863384
DOI: 10.23876/j.krcp.23.267 -
Doklady. Biochemistry and Biophysics Jun 2024The frequency and risk factors for the development of diastolic dysfunction (DD) in patients with CPPD and OA have not been studied. The objective of this study was to...
The frequency and risk factors for the development of diastolic dysfunction (DD) in patients with CPPD and OA have not been studied. The objective of this study was to determine the frequency and identify risk factors (RF) for the development of DD of the left and right ventricles (LV and RV) in patients with calcium pyrophosphate crystal deposition disease (CPPD) and osteoarthritis (OA). The study included 26 patients with CPPD and with knee OA 18-65 years old, matched in age and gender, without cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), and rheumatic diseases. Conventional risk factors (TRF) of CVD were assessed, and echocardiography was performed. The frequency of DD in patients with CPPD and OA was quite high and almost did not differ in both groups: it was detected in 19 patients, of which 11 (42%) had CPPD and 8 (31%) had OA (p = 0.39). Type 1 LV DD was detected in 10 (39%) patients with CPPD and in 8 (31%) with OA (p = 0.11); type 1RV DD was detected in 8 (31%) patients with CPPD and in 7 (27%) patients with OA (p = 0.17); and type 1 LV DD and RV DD was detected in 7 (27%) patients with both CPPD and with OA. DD types 2 and 3 were not detected in both groups. There were no differences in both groups in CV risk factors, except for the level of CRP (it was higher in CPPD) (p = 0.03). In the CPPD group, mean values of LV E/E' (p = 0.02), LVDT (p = 0.03), LVMI (p = 0.04) were significantly higher than in patients with OA. On the contrary, in patients with OA, indices EDV (p = 0.004) and TVC (p = 0.02) were higher. There were direct correlations between diastolic function indices and the following factors in CPPD: LVL, PWLV and PTH level (r = 0.7, p <0.005), LV E' and PTH level (r = 0.7, p < 0.005). Inverse correlations were found between the level of PTH and IS (r = -0.5, p < 0.005), LVMI (r = -0.5, p < 0.005), and the level of vitamin D and VDDT (r = -0.6, p < 0.005). Direct correlations in OA were found between the level of CRP and PVAdiast (r = 0.6, p < 0.005), and the level of sUA (r = 0.7, p < 0.005), and the level of vitamin D and E/E'LV (r = 0.6, p < 0.005). A high prevalence of LV and RV DD was found in patients with CPPD and OA. The presence of DD in CPPD was associated with lower vitamin D levels, and in OA with a higher level of sUA and a lower level of PTH.
PubMed: 38861149
DOI: 10.1134/S1607672924700881 -
JAMA Pediatrics Jun 2024Overweight and obesity in childhood and adolescence is a global health issue associated with adverse outcomes throughout the life course.
IMPORTANCE
Overweight and obesity in childhood and adolescence is a global health issue associated with adverse outcomes throughout the life course.
OBJECTIVE
To estimate worldwide prevalence of overweight and obesity in children and adolescents from 2000 to 2023 and to assess potential risk factors for and comorbidities of obesity.
DATA SOURCES
MEDLINE, Web of Science, Embase, and Cochrane.
STUDY SELECTION
The inclusion criteria were: (1) studies provided adequate information, (2) diagnosis based on body mass index cutoffs proposed by accepted references, (3) studies performed on general population between January 2000 and March 2023, (4) participants were younger than 18 years.
DATA EXTRACTION AND SYNTHESIS
The current study was performed in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. DerSimonian-Laird random-effects model with Free-Tukey double arcsine transformation was used for data analysis. Sensitivity analysis, meta-regression, and subgroup analysis of obesity among children and adolescents were conducted.
MAIN OUTCOMES AND MEASURES
Prevalence of overweight and obesity among children and adolescents assessed by World Health Organization, International Obesity Task Force, the US Centers for Disease Control and Prevention, or other national references.
RESULTS
A total of 2033 studies from 154 different countries or regions involving 45 890 555 individuals were included. The overall prevalence of obesity in children and adolescents was 8.5% (95% CI 8.2-8.8). We found that the prevalence varied across countries, ranging from 0.4% (Vanuatu) to 28.4% (Puerto Rico). Higher prevalence of obesity among children and adolescents was reported in countries with Human Development Index scores of 0.8 or greater and high-income countries or regions. Compared to 2000 to 2011, a 1.5-fold increase in the prevalence of obesity was observed in 2012 to 2023. Substantial differences in rates of obesity were noted when stratified by 11 risk factors. Children and adolescents with obesity had a high risk of depression and hypertension. The pooled estimates of overweight and excess weight in children and adolescents were 14.8% (95% CI 14.5-15.1) and 22.2% (95% CI 21.6-22.8), respectively.
CONCLUSIONS AND RELEVANCE
This study's findings indicated 1 of 5 children or adolescents experienced excess weight and that rates of excess weight varied by regional income and Human Development Index. Excess weight among children and adolescents was associated with a mix of inherent, behavioral, environmental, and sociocultural influences that need the attention and committed intervention of primary care professionals, clinicians, health authorities, and the general public.
PubMed: 38856986
DOI: 10.1001/jamapediatrics.2024.1576 -
Critical Reviews in Immunology 2024Thyroidectomy causes impaired blood supply to the parathyroid glands, which leads to hypoparathyroidism. Tanshinone IIA (Tan IIA) is helpful in blood activation and...
BACKGROUND
Thyroidectomy causes impaired blood supply to the parathyroid glands, which leads to hypoparathyroidism. Tanshinone IIA (Tan IIA) is helpful in blood activation and cardiovascular protection. Therefore, the efficacy of Tan IIA in improving hypoparathyroidism was explored in this study.
METHODS
New Zealand white rabbits were utilized to establish a unilateral parathyroid gland ischemia injury model. The model was created by selectively ligating the main blood supply vessel of one parathyroid gland, and the rabbits were then divided into three groups receiving 1, 5, and 10 mg/kg of Tan IIA. Serum calcium and parathyroid hormone (PTH) levels were measured using specialized assay kits. Immunohistochemistry was used to assess the microvessel density (MVD) in parathyroid glands. Western blotting (WB) was used to analyze protein expression related to the PI3K/AKT signaling pathway and the pathway-associated HIF-1α and VEGF. Moreover, MMP-2 and MMP-9 involved in angiogenesis were detected by WB.
RESULTS
Tan IIA treatment effectively restored serum calcium and PTH levels in a dose-dependent manner. Notably, MVD in the parathyroid glands increased significantly, especially at higher doses. The Tan IIA treatment also elevated the p-PI3K/PI3K and p-AKT/AKT ratios, indicating that the PI3K/AKT pathway was reactivated. Moreover, Tan IIA significantly restored the decreased expression levels of VEGF and HIF-1α caused by parathyroid surgery. Additionally, Tan IIA increased MMP-2 and MMP-9 levels.
CONCLUSION
Tan IIA activates the PI3K/AKT pathway, promotes angiogenesis by modulating VEGF, HIF-1α, MMP-2, and MMP-9, thereby further enhancing MVD within the parathyroid glands. This study demonstrates that Tan IIA improved post-thyroidectomy hypoparathyroidism.
Topics: Animals; Hypoparathyroidism; Abietanes; Thyroidectomy; Rabbits; Parathyroid Glands; Disease Models, Animal; Signal Transduction; Humans; Calcium; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Male; Parathyroid Hormone
PubMed: 38848291
DOI: 10.1615/CritRevImmunol.2024052462