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Journal of Cardiovascular Pharmacology May 2024Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus...
Hydroxychloroquine and Chloroquine-Induced Cardiac Arrhythmias and Sudden Cardiac Death in Patients with Systemic Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis.
Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Concerns regarding the risk of cardiac arrhythmia and death have been raised, yet the burden of HCQ and CQ-related cardiac toxicities remains unclear. A systematic literature search was conducted in the MEDLINE and Embase databases for articles published between the earliest date and April 2023 reporting cardiac conduction abnormalities in patients with systemic autoimmune rheumatic diseases taking HCQ or CQ. Meta-analysis was performed to calculate the difference in mean QTc and odds ratio of prolonged QTc in those taking HCQ or CQ versus not. Of 2673 unique records, 34 met the inclusion criteria, including 70,609 subjects. Thirty-three studies reported outcomes in HCQ and 9 in CQ. Five studies reported outcomes in RA, 11 in SLE, and 18 in populations with mixed rheumatic diseases. Eleven studies reported mean QTc and OR for prolonged QTc for meta-analysis, all reporting outcomes in HCQ. There was a significant increase in mean QTc among HCQ users in patients with RA (10.29 ms, p = 0.458). There was no difference in mean QTc between HCQ and non-HCQ users in other systemic autoimmune rheumatic diseases. When rheumatic diseases were pooled, HCQ users were more likely to have prolonged QTc (odds ratio 1.57, 95%CI: 1.19, 2.08). QTc prolongation was more likely in patients with systemic autoimmune rheumatic diseases. Clinicians should be aware of potential adverse cardiac events of HCQ and consider QTc monitoring.
PubMed: 38922589
DOI: 10.1097/FJC.0000000000001589 -
Musculoskeletal Surgery Jun 2024Hallux valgus (HV) is a frequent forefoot deformity affecting about 23% of adults and 35.7% of people over 65. The exact etiology is not fully understood. The first ray... (Review)
Review
Hallux valgus (HV) is a frequent forefoot deformity affecting about 23% of adults and 35.7% of people over 65. The exact etiology is not fully understood. The first ray plays a significant role in walking cause it bears the principal amount of weight and maintains the position of the medial arch. Several factors that deteriorate the integrality of the first ray, such as foot deformities, restrictive footwear, and pes planus, may be ascribed to the HV occurrence. Before any surgical correction, conservative treatment should always be initiated first. Currently, there is no consensus that conservative management by shoe modification and foot orthoses could correct the pathology or terminate the clinical worsening of the condition.From a careful analysis of the literature, proper footwear should be a shoe with an adequate length, wide toe box, cushioned sole, and a lowered heel to not increase the load on the metatarsal heads and cause pain. Personalized 3D printed customized toe spreaders may be applied in patients with HV, improving symptoms and bringing pain relief. Compensating the subtalar joint hyperpronation through foot orthoses plays a fundamental role in the HV development, preventing or at least controlling the condition's progress; this, along with weight reduction and regular physical activity.Data obtained suggest that dynamic foot orthoses prefer a biomechanical type with 3/4-length, which is less likely to negatively affect the dorsal or medial pressures, which instead were noted to increase with the sulcus- and full-length orthoses.Although some studies suggest that foot orthoses would favor the correction of HV deformity, results have been very variable and just in few studies appear to correct HV or reduce its progression, improving symptoms and bringing pain relief. In the case of HV surgical correction, orthoses seem to maintain the correct position acquired over time.
PubMed: 38922494
DOI: 10.1007/s12306-024-00839-9 -
Molecular Neurobiology Jun 2024Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of...
Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of NEAT1 in valproic acid (VPA)-induced autism spectrum disorder (ASD). A VPA-induced ASD rat model was constructed, and a series of behavioral tests were performed to examine motor coordination and learning-memory abilities. qRT-PCR and western blot assays were used to evaluate target gene expression levels. Loss-and-gain-of-function assays were conducted to explore the functional role of NEAT1 in ASD development. Furthermore, a combination of mechanistic experiments and bioinformatic tools was used to assess the relationship and regulatory role of the NEAT1-YY1-UBE3A axis in ASD cellular processes. Results showed that VPA exposure induced autism-like developmental delays and behavioral abnormalities in the VPA-induced ASD rat model. We found that NEAT1 was elevated in rat hippocampal tissues after VPA exposure. NEAT1 promoted VPA-induced autism-like behaviors and mitigated apoptosis, oxidative stress, and inflammation in VPA-induced ASD rats. Notably, NEAT1 knockdown improved autism-related behaviors and ameliorated hippocampal neuronal damage. Mechanistically, it was observed that NEAT1 recruited the transcription factor YY1 to regulate UBE3A expression. Additionally, in vitro experiments further confirmed that NEAT1 knockdown mitigated hippocampal neuronal damage, oxidative stress, and inflammation through the YY1/UBE3A axis. In conclusion, our study demonstrates that NEAT1 is highly expressed in ASD, and its inhibition prominently suppresses hippocampal neuronal injury and oxidative stress through the YY1/UBE3A axis, thereby alleviating ASD development. This provides a new direction for ASD-targeted therapy.
PubMed: 38922486
DOI: 10.1007/s12035-024-04309-y -
European Spine Journal : Official... Jun 2024Spinopelvic sagittal alignment is crucial for assessing balance and determining treatment efficacy in patients with adult spinal deformity (ASD). Only a limited number...
PURPOSE
Spinopelvic sagittal alignment is crucial for assessing balance and determining treatment efficacy in patients with adult spinal deformity (ASD). Only a limited number of reports have addressed spinopelvic parameters and lumbosacral transitional vertebrae (LSTV). Our primary objective was to study spinopelvic sagittal parameter changes in patients with LSTV. A secondary objective was to investigate clinical symptoms and quality of life (QOL) in patients with LSTV.
METHODS
In this study, we investigated 371 participants who had undergone medical check-ups for the spine. LSTV was evaluated using Castellvi's classification, and patients were divided into LSTV+ (type II-IV, L5 vertebra articulated or fused with the sacrum) and LSTV- groups. After propensity score matching for demographic data, we analyzed spinopelvic parameters, sacroiliac joint degeneration, clinical symptoms, and QOL for these two participant groups. Oswestry Disability Index (ODI) scores and EQ-5D (EuroQol 5 dimensions) indices were compared between the two groups.
RESULTS
Forty-four patients each were analyzed in the LSTV + and LSTV- groups. The LSTV + group had significantly greater pelvic incidence (52.1 ± 11.2 vs. 47.8 ± 10.0 degrees, P = 0.031) and shorter pelvic thickness (10.2 ± 0.9 vs. 10.7 ± 0.8 cm, P = 0.018) compared to the LSTV- group. The "Sitting" domain of ODI (1.1 ± 0.9 vs. 0.6 ± 0.7, P = 0.011) and "Pain/Discomfort" domain of EQ-5D (2.0 ± 0.8 vs. 1.6 ± 0.7, P = 0.005) were larger in the LSTV + group.
CONCLUSION
There was a robust association between LSTV and pelvic sagittal parameters. Clinical symptoms also differed between the two groups in some domains. Surgeons should be aware of the relationship between LSTV assessment, radiographic parameters and clinical symptoms.
PubMed: 38922415
DOI: 10.1007/s00586-024-08378-4 -
European Spine Journal : Official... Jun 2024This study aimed to clarify the relation between global spinal alignment and the necessity of walking aid use in patients with adult spinal deformity (ASD) and to...
PURPOSE
This study aimed to clarify the relation between global spinal alignment and the necessity of walking aid use in patients with adult spinal deformity (ASD) and to investigate the impact of spinal fixation on mobility status after surgery.
METHODS
In total, 456 older patients with ASD who had multi-segment spinal fixation surgery and were registered in a multi-center database were investigated. Patients under 60 years of age and those unable to walk preoperatively were excluded. Patients were classified by their mobility status into the independent, cane, and walker groups. Comparison analysis was conducted using radiographic spinopelvic parameters and the previously reported global spine balance (GSB) classification. In addition, preoperative and 2 years postoperative mobility statuses were investigated.
RESULTS
Of 261 patients analyzed, 66 used walking aids (canes, 46; walkers, 20). Analysis of preoperative radiographical parameters showed increased pelvic incidence and pelvic incidence-lumbar lordosis mismatch in the walker group and increased sagittal vertebral axis in the cane and walker groups versus the independent group. Analysis of GSB classification showed a higher percentage of walker use in those with severe imbalance (grade 3) in the sagittal classification but not in the coronal classification. While postoperative radiographical improvements were noted, there was no significant difference in the use of walking aids before and 2 years after surgery (P = 0.085).
CONCLUSION
A significant correlation was found between "sagittal" spinal imbalance and increased reliance on walking aids, particularly walkers. However, the limitation of improvement in postoperative mobility status suggested that multiple factors influence the mobility ability of elderly patients with ASD.
PubMed: 38922414
DOI: 10.1007/s00586-024-08380-w -
Archives of Gynecology and Obstetrics Jun 2024The aim of this study was to examine whether there is a correlation between different types of ventricular septal defects (VSD) and chromosomal abnormalities in the...
PURPOSE
The aim of this study was to examine whether there is a correlation between different types of ventricular septal defects (VSD) and chromosomal abnormalities in the low-risk setting of non-invasive prenatal testing (NIPT) and to evaluate the prognosis of fetuses with varying types of VSD.
METHODS
Cases of pregnant women who underwent amniocentesis due to fetal VSD were collected by Tianjin Central Hospital of Obstetrics and Gynecology from May 2017 to May 2022. Exclusions were made for those without NIPT, with high-risk NIPT results, genetic disorders, and those lost to follow-up. Data collected included ultrasound classification of VSD, prenatal NIPT results, copy-number variations (CNVs) results, and neonatal outcomes.
RESULTS
The prevalence of pathogenic CNVs was investigated in 74 cases of VSDs. Of these cases, 45 were isolated VSDs (9 muscular and 36 non-muscular) and 29 were non-isolated VSDs (10 with intracardiac and 19 with extra-cardiac structural anomalies). The results revealed that the incidence of pathogenic CNVs was lower in isolated VSDs compared to non-isolated VSDs in a low-risk NIPT condition (χ2 = 9.344, P = 0.002). There was no significant difference in the prevalence of pathogenic CNVs between VSDs with intracardiac and extra-cardiac structural anomalies (P = 0.541). Moreover, VSDs associated with intracardiac structural anomalies had the highest rate of surgical intervention.
CONCLUSION
When NIPT is low-risk and VSD is isolated, the likelihood of fetal chromosomal defects is not increased. However, if there are intra- or extra-cardiac structural abnormalities present alongside VSD, the possibility of pathogenic CNV is considerably greater, necessitating invasive prenatal diagnosis. Isolated muscular VSDs usually do not require surgery, which can be used as a basis for prenatal counseling regarding fetal VSD.
PubMed: 38922412
DOI: 10.1007/s00404-024-07566-3 -
Annals of Biomedical Engineering Jun 2024Evaluating Behind Armor Blunt Trauma (BABT) is a critical step in preventing non-penetrating injuries in military personnel, which can result from the transfer of...
Evaluating Behind Armor Blunt Trauma (BABT) is a critical step in preventing non-penetrating injuries in military personnel, which can result from the transfer of kinetic energy from projectiles impacting body armor. While the current NIJ Standard-0101.06 standard focuses on preventing excessive armor backface deformation, this standard does not account for the variability in impact location, thorax organ and tissue material properties, and injury thresholds in order to assess potential injury. To address this gap, Finite Element (FE) human body models (HBMs) have been employed to investigate variability in BABT impact conditions by recreating specific cases from survivor databases and generating injury risk curves. However, these deterministic analyses predominantly use models representing the 50th percentile male and do not investigate the uncertainty and variability inherent within the system, thus limiting the generalizability of investigating injury risk over a diverse military population. The DoD-funded I-PREDICT Future Naval Capability (FNC) introduces a probabilistic HBM, which considers uncertainty and variability in tissue material and failure properties, anthropometry, and external loading conditions. This study utilizes the I-PREDICT HBM for BABT simulations for three thoracic impact locations-liver, heart, and lower abdomen. A probabilistic analysis of tissue-level strains resulting from a BABT event is used to determine the probability of achieving a Military Combat Incapacitation Scale (MCIS) for organ-level injuries and the New Injury Severity Score (NISS) is employed for whole-body injury risk evaluations. Organ-level MCIS metrics show that impact at the heart can cause severe injuries to the heart and spleen, whereas impact to the liver can cause rib fractures and major lacerations in the liver. Impact at the lower abdomen can cause lacerations in the spleen. Simulation results indicate that, under current protection standards, the whole-body risk of injury varies between 6 and 98% based on impact location, with the impact at the heart being the most severe, followed by impact at the liver and the lower abdomen. These results suggest that the current body armor protection standards might result in severe injuries in specific locations, but no injuries in others.
PubMed: 38922366
DOI: 10.1007/s10439-024-03564-3 -
CoDAS 2024To analyze the influence of ankyloglossia on the prevalence and duration of exclusive breastfeeding of full-term infants up to the sixth month of life.
PURPOSE
To analyze the influence of ankyloglossia on the prevalence and duration of exclusive breastfeeding of full-term infants up to the sixth month of life.
METHODS
Prospective cohort study, carried out with 225 mother-infant dyads who were followed up in the first six months of life in a center specialized in breastfeeding in a tertiary hospital. Full-term infants with asymptomatic ankyloglossia (no need for surgery) were compared with infants without change at monthly follow-up. Ankyloglossia was diagnosed using the Bristol Tongue Assessment Tool, with a positive diagnosis being considered for those with a score less than or equal to 5 considering functional and anatomical aspects. Statistical analyzes were performed using descriptive statistics, logistic regression (weaning determinants), relative risk, and survival curves (to analyze breastfeeding duration between groups with and without ankyloglossia).
RESULTS
Ankyloglossia was associated with weaning (considered even partial) before the sixth month of life. After adjusted analysis, a higher risk of weaning was detected in infants with this alteration, with a risk present from the second month of life. In the survival analysis, the duration of breastfeeding in infants with ankyloglossia was shorter when compared to children without alterations.
CONCLUSION
Compared to infants with normal lingual frenulum, babies with ankyloglossia had shorter exclusive breastfeeding time, but well above the average observed in the general population. The risk of weaning for this group was also higher.
Topics: Humans; Breast Feeding; Ankyloglossia; Prospective Studies; Infant, Newborn; Female; Male; Infant; Time Factors; Cohort Studies; Adult; Lingual Frenum; Weaning; Prevalence; Brazil; Risk Factors
PubMed: 38922259
DOI: 10.1590/2317-1782/20242023108pt -
Brazilian Dental Journal 2024This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes...
This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and parathyroid hormone (PTH). Orthodontic patients receiving treatment at a dental school were selected through convenience sampling. Intra-oral photographs were used to assess DDE, which were classified according to the criteria proposed by Ghanim et al. (2015) by a single calibrated examiner (Kappa>0.80). Enamel hypoplasia, molar-incisor hypomineralization (MIH), hypomimineralized second primary molar (HSPM), and non-MIH/HSPM demarcated opacities were considered for the analysis. Genomic DNA was extracted from buccal cells. The SNPs in VDR (rs7975232) and PHT (rs694, rs6256, and rs307247) were genotyped using real-time polymerase chain reactions (PCR). Statistical analyses were performed using the PLINK software (version 1.03, designed by Shaun Purcell, EUA). Chi-square or Fisher's exact tests were performed at a significance level of 5%. Ninety-one (n=91) patients (49 females and 42 males) (mean age of 14.1±5.8 years) were included. The frequency of DDE was 38.5% (35 patients). Genotype distributions were in Hardy-Weinberg equilibrium. No significant statistical association was found between DDE and the SNPs evaluated. A borderline association (p=0.09) was observed between DDE and the CC haplotype for SNP rs7975232 in VDR. In conclusion, the selected SNPs in VDR and PTH genes were not associated with DDE in the studied samples.
Topics: Humans; Receptors, Calcitriol; Polymorphism, Single Nucleotide; Female; Cross-Sectional Studies; Male; Parathyroid Hormone; Dental Enamel Hypoplasia; Child; Adolescent; Dental Enamel; Real-Time Polymerase Chain Reaction; Genotype
PubMed: 38922252
DOI: 10.1590/0103-6440202405900 -
Revista Paulista de Pediatria : Orgao... 2024To verify the prevalence and perform the clinical characterization of oral clefts in a sample of patients with trisomy of chromosome 18 in Southern Brazil.
OBJECTIVE
To verify the prevalence and perform the clinical characterization of oral clefts in a sample of patients with trisomy of chromosome 18 in Southern Brazil.
METHODS
This was a retrospective cross-sectional study, performed in a reference clinical genetic service in Southern Brazil. The initial sample consisted of 77 patients diagnosed in the neonatal period with trisomy 18 treated at the Clinical Genetics Service of a referral hospital at Federal University of Health Sciences of Porto Alegre (UFCSPA). The patients' diagnosis was confirmed by karyotype and care was provided during their stay in the intensive care unit (ICU) of the hospital that is a reference in Southern Brazil for care for malformed patients. The period covered was from 1975 to 2020.
RESULTS
During the study period, 77 patients diagnosed with trisomy 18 were treated, most of them in the ICU. Of these, 13 individuals were excluded due to incomplete data. The final sample consisted of 64 patients with an average age of 2.4 years of life, ranging from one day to 16 years old, the majority of whom were female. Regarding face dysmorphisms identified in the sample, three (4,68%) patients had cleft lip and two (3,11%) had cleft lip and palate.
CONCLUSIONS
This study contributed to the recognition of the characteristics and prevalence of oral clefts in individuals with trisomy 18 in a sample of patients from Southern Brazil. In addition, we described the clinical alterations found in patients with oral clefts, as well as other associated comorbidities, such as cardiac, neurological and pulmonary comorbidities, as well as cranial and facial dysmorphisms.
Topics: Humans; Cross-Sectional Studies; Female; Retrospective Studies; Male; Trisomy 18 Syndrome; Prevalence; Adolescent; Infant, Newborn; Brazil; Child; Infant; Child, Preschool; Cleft Palate; Cleft Lip
PubMed: 38922187
DOI: 10.1590/1984-0462/2024/42/2023169