Abnormal Function Research Articles

Early menopause is associated with abnormal diastolic function and poor clinical outcomes in women with suspected angina

Early identification of women at high risk for cardiovascular diseases (CVD), with subsequent monitoring, will allow for improved clinical outcomes and generally better quality of life. This study aimed to identify the associations between early menopause, abnormal diastolic function, and clinical outcomes. This retrospective study included 795 menopausal women from is a nationwide, multicenter, registry of patients with suspected angina visiting outpatient clinic. The patients into two groups: early and normal menopause (menopausal age ≤ 45 and > 45 years, respectively). If participants met > 50% of the diastolic function criteria, they were classified as having normal diastolic function. Multivariable-adjusted Cox models were used to test associations between menopausal age and clinical outcomes including the incidence of major adverse cardiovascular events (MACE), over a median follow-up period of 771 days. Early menopause was associated with increased waist circumference (p = 0.001), diabetes prevalence (p = 0.003), obstructive coronary artery disease (p = 0.005), abnormal diastolic function (p = 0.003) and greater incidences of MACE, acute coronary syndrome, and hospitalization for heart failure. In patients with abnormal diastolic function, early menopause increased MACE risk significantly, with no significant difference in normal diastolic function. These findings highlight early menopause and abnormal diastolic function as being potential risk markers in women for midlife CVD events.

A cross-sectional study on the correlation of pulmonary function with duration of Rheumatoid arthritis

Rheumatoid arthritis (R.A.) is characterized by chronic inflammatory symmetrical peripheral polyarthritis associated with systemic involvement. Pulmonary involvement is one of them. Therefore, early assessment of pulmonary function may help identify the type of respiratory involvement and hence can contribute to properly managing pulmonary complications.The study aims to evaluate the type and extent of pulmonary function abnormality in relation to the duration of Rheumatoid Arthritis. Settings and Design: tertiary care treating hospital- a cross-sectional observational study A cross-sectional study was conducted at Department of General Medicine in forty R.A. cases in whom spirometry was performed and values of spirometry results were statistically compared with the duration of R.A. using S.P.S.S. software. Cases were grouped into three categories based on the duration of the disease. Category A –less than 5 yrs, category B– 5 to 9 yrs and category C – more than 9 yrs duration. In category A, abnormal pulmonary function test (PFT) was observed in 43.5% of cases in the form of obstructive 17.4%, restrictive 17.4% and mixed pattern in 8.7% of cases. In category B, the restrictive pattern was found in 63.6% and a mixed pattern in 9.1% of cases. However, abnormal pulmonary function test (PFT) was observed in all cases in category C, with obstructive pattern in 16.7%, restrictive 66.7% and mixed 16.7% cases. From the study, it was found that early pulmonary involvement occurs in R.A. With an increase in the duration of R.A., pulmonary involvement becomes a more severe and restrictive pattern. Most cases with a duration of more than 9yrs had significant pulmonary involvement either in the form of restrictive or obstructive pattern. Hence PFT should be done at the earliest as a routine and repeated periodically in R.A. cases.

Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.

Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. Recent years altered this perception, as a growing number of leukodystrophies was described to have an onset at adult ages. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16 patients from eight families carrying one of four different stop-gain or frameshift dominant variants in the CST3 gene. Clinical and radiological features differ markedly from the previously described Icelandic Cerebral Amyloid Angiopathy that was found in patients carrying p.Leu68Asn substitution in CST3. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. In addition, in some cases acute onset clinical deterioration led to a prolonged episode with reduced consciousness and even early death. Radiologically, pathognomonic changes are found at typical predilection sites involving the deep cerebral white matter sparing a periventricular and directly subcortical rim, the middle blade of corpus callosum, posterior limb of the internal capsule, middle cerebellar peduncles, cerebral peduncles, and specifically the globus pallidus. Histopathologic characterization in two autopsy cases did not reveal angiopathy, but instead micro- to macrocystic degeneration of the white matter. Astrocytes were activated at early stages and later on displayed severe degeneration and loss. In addition, despite loss of myelin, elevated numbers of partly apoptotic oligodendrocytes were observed. A structural comparison of the variants in CST3 suggests that specific truncations of Cystatin C result in an abnormal function, possibly by rendering the protein more prone to aggregation. Future studies are required to confirm the assumed effect on the protein and to determine pathophysiologic downstream events at the cellular level.

Diet-induced hyperhomocysteinemia causes sex-dependent deficiencies in offspring musculature and brain function.

Hyperhomocysteinemia (HHcy), characterized by elevated homocysteine (Hcy) levels, is a known risk factor for cardiovascular, renal, and neurological diseases, as well as pregnancy complications. Our study aimed to investigate whether HHcy induced by a high-methionine (high-Met) diet exacerbates cognitive and behavioral deficits in offspring and leads to other breeding problems. Dietary HHcy was induced four weeks before mating and continued throughout gestation and post-delivery. A battery of behavioral tests was conducted on offspring between postnatal days (PNDs) 5 and 30 to assess motor function/activity and cognition. The results were correlated with brain morphometric measurements and quantitative analysis of mammalian target of rapamycin (mTOR)/autophagy markers. The high-Met diet significantly increased parental and offspring urinary tHcy levels and influenced offspring behavior in a sex-dependent manner. Female offspring exhibited impaired cognition, potentially related to morphometric changes observed exclusively in HHcy females. Male HHcy pups demonstrated muscle weakness, evidenced by slower surface righting, reduced hind limb suspension (HLS) hanging time, weaker grip strength, and decreased activity in the beaker test. Western blot analyses indicated the downregulation of autophagy and the upregulation of mTOR activity in HHcy cortexes. HHcy also led to breeding impairments, including reduced breeding rate, in-utero fetal death, lower pups' body weight, and increased mortality, likely attributed to placental dysfunction associated with HHcy. In conclusion, a high-Met diet impairs memory and cognition in female juveniles and weakens muscle strength in male pups. These effects may stem from abnormal placental function affecting early neurogenesis, the dysregulation of autophagy-related pathways in the cortex, or epigenetic mechanisms of gene regulation triggered by HHcy during embryonic development.

Suppression head impulse test in children-experiences in a tertiary paediatric vestibular centre.

The suppression head impulse paradigm (SHIMP) involves suppression of the vestibulo-ocular reflex (VOR) and anticompensatory saccades generated thereof. SHIMP is gaining importance to understand vestibular compensation with its different parameters (VOR gain/peak saccadic velocity PSV/latency of saccades). SHIMP studies are emerging in adults, but pediatric studies have hardly been performed. This study is a retrospective case note audit over a period of 2 months in a tertiary pediatric vestibular center in the United Kingdom to investigate whether SHIMP is safe/robust to be used in children conforming to existing standards/norms in normal children and whether it yields any meaningful inferences in pediatric vestibular hypofunction. This is the largest pediatric SHIMP study to date. A total of 44 referred children (6-18 years, female children>male children) with a range of complaints from dizziness, imbalance, motor incoordination, postural instability, and hearing loss were included, and their SHIMP parameters were measured. All children underwent comprehensive functional/objective audiovestibular assessments. Two groups were defined-Group A with normal vestibular function and Group B with abnormal vestibular function. The normal population showed an average SHIMP VOR gain of 0.98+/-0.08 and latency of overt saccades at 215.68+/-46.16 milliseconds agreeing with published evidence. The PSV of overt saccades was 315.39+/-56.30/s, and there was a gain asymmetry of 7.42+/-4.68 between the sides. Statistically significant differences with moderate/large effect sizes were observed between the groups in terms of VOR gain and PSV but not in saccade latencies. Covert saccades were rare in SHIMP, while overt saccades were observed in 100% of children. VOR gain difference between the head impulse paradigm (HIMP) and the SHIMP was significant as well. We observed statistically significant differences in side asymmetry of VOR gain between the groups. Furthermore, we identified a group of children with cerebellar lesions where overt saccades in SHIMP were rather low in number. Further research is recommended to investigate pediatric PSV, asymmetry, and inability to generate overt saccades that may suggest useful means to assess compensation and central function. We conclude that SHIMP yields valuable information and is a safe, easy to perform, and a reliable test that should be used in children to supplement HIMP.

Increased aortic pressures and pulsatile afterload components promote concentric left ventricular remodeling in adults with transposition of the great arteries and arterial switch operation

BackgroundFunctional abnormalities of the ascending aorta (AA) have been mainly reported in young patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA). ObjectivesTo compare systolic, diastolic brachial and central blood pressures (bSBP, bDBP, cSBP, cDBP), aortic biomechanical parameters, and left ventricular (LV) afterload criteria in adult ASO patients with healthy controls and to assess their relationships with LV remodeling and aortic size. Materials and methodsForty-one prospectively enrolled patients (16.8 to 35.8 years) and 41 age- and sex-matched healthy volunteers underwent cardiac MRI to assess LV remodeling with simultaneous brachial BP estimation. After MRI, carotid-femoral tonometry was performed to measure pulse wave velocity (cfPWV), cSBP and cDBP for further calculation of pulse pressure (cPP), AA distensibility (AAD), and AA and LV elastance (AAE, LVE). ResultsbSBP, bDBP, cSBP,cDBP and cPP were all significantly higher in ASO group than in controls: cSBP (116.5 ± 13.8 vs 106.1 ± 12.0, p < 0.001), cDBP (72.5 ± 6.9 vs 67.1 ± 9.4, p = 0.002), cPP (44.0 ± 12.1 vs 39.1 ± 8.9, p = 0.003) and not related to aortic size. AAD were decreased in ASO patients vs controls (4.70 ± 2.72 vs 6.69 ± 2.16, p < 0.001).LV mass was correlated with bSBP, cSBP, cPP (ρ = 0.48; p < 0.001), while concentric LV remodeling was correlated with AAE (ρ = 0.60, p < 0.001) and LVE (ρ = 0.32, p = 0.04), but not with distensibility. ConclusionEven without reaching arterial hypertension, aortic sBP and PP are increased in the adult TGA population after ASO, altering the pulsatile components of afterload and contributing to LV concentric remodeling.

Quantitative Proteomics Reveal Region-Specific Alterations in Neuroserpin-Deficient Mouse Brain and Retina: Insights into Serpini1 Function.

Neural regeneration and neuroprotection represent strategies for future management of neurodegenerative disorders such as Alzheimer's disease (AD) or glaucoma. However, the complex molecular mechanisms that are involved in neuroprotection are not clearly understood. A promising candidate that maintains neuroprotective signaling networks is neuroserpin (Serpini1), a serine protease inhibitor expressed in neurons which selectively inhibits extracellular tissue-type plasminogen activator (tPA)/plasmin and plays a neuroprotective role during ischemic brain injury. Abnormal function of this protein has been implicated in several conditions including stroke, glaucoma, AD, and familial encephalopathy with neuroserpin inclusion bodies (FENIB). Here, we explore the potential biochemical roles of Serpini1 by comparing proteome changes between neuroserpin-deficient (NS-/-) and control mice, in the retina (RE), optic nerve (ON), frontal cortex (FC), visual cortex (VC), and cerebellum (CB). To achieve this, a multiple-plex quantitative proteomics approach using isobaric tandem mass tag (TMT) technology was employed followed by functional enrichment and protein-protein interaction analysis. We detected around 5000 proteins in each tissue and a pool of 6432 quantified proteins across all regions, resulting in a pool of 1235 differentially expressed proteins (DEPs). Principal component analysis and hierarchical clustering highlighted similarities and differences in the retina compared to various brain regions, as well as differentiating NS-/- proteome signatures from control samples. The visual cortex revealed the highest number of DEPs, followed by cerebellar regions. Pathway analysis unveiled region-specific changes, including visual perception, focal adhesion, apoptosis, glutamate receptor activation, and supramolecular fiber organization in RE, ON, FC, VC, and CB, respectively. These novel findings provide comprehensive insights into the region-specific networking of Serpini1 in the central nervous system, further characterizing its potential role as a neuroprotective agent. Data are available via ProteomeXchange with identifier PXD046873.

NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia

NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.

Single microcystin exposure impairs the hypothalamic-pituitary-gonadal axis at different levels in female rats

Microcystin (MC) is most common cyanobacterial toxin. Few studies have evaluated the MC effects on the hypothalamic-pituitary-gonadal (HPG) axis and metabolic function. In this study, we assessed whether MC exposure results in HPG axis and metabolic changes. Female rats were exposed to a single dose of MC at environmentally relevant levels (5, 20 and 40 μg/kg). After 24 h, we evaluated reproductive and metabolic parameters for 15 days. MC reduced the hypothalamic GnRH protein expression, increased the pituitary protein expression of GnRHr and IL-6. MC reduced LH levels and increased FSH levels. MC reduced the primary follicles, increased the corpora lutea, elevated levels of anti-Müllerian hormone (AMH) and progesterone, and decreased estrogen levels. MC increased ovarian VEGFr, LHr, AMH, ED1, IL-6 and Gp91-phox protein expression. MC increased uterine area and reduced endometrial gland number. A blunted estrogen-negative feedback was observed in MC rats after ovariectomy, with no changes in LH levels compared to intact MC rats. Therefore, these data suggest that a MC leads to abnormal HPG axis function in female rats.

Efficacy and Safety of Ketogenic Diet Treatment in Pediatric Patients with Mitochondrial Disease.

Mitochondrial diseases (MDs) are a heterogeneous group of disorders resulting from abnormal mitochondrial function. Currently, there is no causal treatment for MDs. The aim of the study was to assess the effectiveness and safety of the ketogenic diet (KD) in patients with MD and to analyse selected biochemical and clinical parameters evaluating the effectiveness of KD treatment in patients with MDs. A total of 42 paediatric patients were assigned to four groups: group 1-patients with MD in whom KD treatment was started (n = 11); group 2-patients with MD remaining on an ordinary diet (n = 10); group 3-patients without MD in whom KD treatment was initiated (n = 10), group 4-patients without MD on a regular diet (n = 11). Clinical improvement was observed in 9/11 patients with MD treated with KD. Among patients with MD without KD, the clinical condition deteriorated in 7/10 patients, improved in 2/10 patients, and remained unchanged in one patient. Adverse events of KD occurred with a comparable frequency in groups 1 and 3. There was no significant difference in changes in biomarker concentrations over the course of the study among patients treated and untreated with KD.

Renal function in pediatric urologic surgical patients: Insight from the National Surgical Quality Improvement Program—Pediatric cohort

Abstract Background Renal protection is a frequent indication for urological surgery in pediatric patients; however, preoperative assessment is not routinely performed. We assessed the rates of preoperative renal function testing and stratified outcomes after major pediatric urological surgery. Pediatric urology patients, specifically high-risk patients undergoing genitourinary surgeries, are likely to have an underdiagnosis of renal dysfunction after surgery. Materials and methods Cases were identified from the 2012 to 2019 National Surgical Quality Improvement Program—Pediatric database. Patients who underwent major urological surgery on an inpatient basis were included in this study. Abnormal renal function was defined as a creatinine (Cr) level of ≥0.5 mg/dL (younger than 2 years) and a glomerular filtration rate of &lt;90 mL/min (2 years or older). Glomerular filtration rate was calculated using the bedside Schwartz equation (2 years or older): estimated glomerular filtration rate = 0.413 × (height/Cr). Results A total of 17,315 patients were included, of whom 3792 (21.9%) had documented Cr values. Based on the defined criteria, abnormal renal function was found in 7.3% of infants (younger than 2 years), 33.6% of children (2–9 years), and 52.5% of adolescents (10–18 years). Patients with abnormal preoperative renal function values were significantly (p &lt; 0.001) more likely to experience readmission (10.2% vs. 5.8%), reoperation (3.7% vs. 1.6%), surgical organ/space infection (0.9% vs. 0.4%), transfusion (1.5% vs. 0.6%), renal insufficiency (1.6% vs. 0.4%), or urinary tract infection (5.1% vs. 3.6%). Conclusions In this pediatric population, 21.9% of the patients had documented preoperative Cr values before major urological surgery. Patients with documented abnormal preoperative renal function tests experienced higher complication rates. These patients have higher rates of progressive renal insufficiency and acute renal failure than those with normal renal function. The introduction of a standardized and unbiased risk assessment tool has the potential to offer patients benefits by pinpointing individuals with a heightened risk of complications. Further investigation is necessary to enhance the precise categorization of at-risk patients.

Hypoperfusion of Amygdala in Chronic Migraine: An Exploratory Quantitative Perfusion Imaging Using 3D Pseudo-Continuous Arterial Spin Labeling.

Although the amygdala has structural and functional abnormalities in Chronic Migraine (CM), less is known about the altered perfusion of the amygdala in CM. The current study aimed to assess amygdala perfusion in CM using a contrast agent-free and quantitative approach. 15 Normal Controls (NC) and 13 patients with CM during the migraine interval were assessed for brain structure and subjected to 3D Pseudo- Continuous Arterial Spin Labeling (3D-PCASL) MR imaging. The Cerebral Blood Flow (CBF) value of the amygdala was automatically extracted based on the individual amygdala mask for all participants. The independent sample t-test, Receiver Operating Characteristic (ROC) curve, and correlation analysis were used to evaluate the perfusion changes in CM. Bilateral amygdala cerebral perfusion was lower in CM (left amygdala, 42.21±4.49 ml/100mg/min; right amygdala, 42.38±4.41 ml/100mg/min) than in NC (left amygdala, 48.31±6.92 ml/100mg/min; right amygdala, 47.88±6.53 ml/100mg/min) (left, p = 0.01; right, p = 0.02). There was no significant correlation between the perfusion of bilateral amygdalas and the clinical variables. Also, there was no significant difference in the volume of bilateral amygdalas between the two groups. The Area Under the Curve (AUC) of the CBF values of the left and right amygdala was 0.78 (95%CI: 0.58-0.91) and 0.75 (95%CI: 0.55-0.89), respectively. The cut-off value was 44.24 ml/100mg/min (left amygdala, with sensitivity 76.90% and specificity 78.70%) and 46.75 ml/100mg/min (right amygdala, with sensitivity 92.3% and specificity 58.80%), respectively. CM presented bilateral hypoperfusion in the amygdala, offering potential diagnostic value in distinguishing CM from NC. The 3D-PCASL could be regarded as a simple and efficient neuroimaging tool to assess the perfusion status in CM patients.

Atrial Functional Substrates for the Prediction of Atrial Fibrillation Recurrence After Pulmonary Vein Isolation

Low-voltage areas have been used as atrial structural substrates in estimating fibrotic degeneration in patients with atrial fibrillation (AF). The high-resolution maps obtained by recently developed mapping catheters allow the visualization of several functional abnormalities. We investigated the association between left atrial (LA) functional abnormal findings on a high-resolution substrate map and AF recurrence in patients who underwent pulmonary vein isolation without any additional LA substrate ablation. This observational study included 100 consecutive patients who underwent second ablation for AF (paroxysmal, 48%; persistent, 52%). Patients with extra-pulmonary-vein LA substrate ablation during the initial and second ablation were excluded. LA mapping was performed using a 64-pole mini-basket catheter on the Rhythmia mapping system. Patients were followed for 2 years. AF recurrence developed in 39 (39%) patients. On the high-resolution substrate map, AF recurrence was associated with the presence of the following findings: low-voltage areas (<1.0 mV, >5cm2; hazard ratio [HR]=2.53; 95% confidence interval [CI]=1.30-4.93; p<0.006), fractionated-electrogram areas (≥5 peaks, >5cm2; HR=2.15, 95%CI=1.10-4.19; p=0.025), LA conduction time of >130 msec (HR=3.11, 95%CI=1.65-5.88, p<0.0001), deceleration zone (≥5 isochrones/cm2; HR=1.97, 95%CI=1.04-3.37, p=0.039), and multiple septal breakout points (HR=3.27, 95%CI=1.50-7.16, p=0.003). Accumulation of these risk factors increased AF recurrence in a stepwise manner, with an HR=1.90, 95%CI=1.44-2.52, p<0.00001 for each additional risk factor. In conclusion, high-resolution map revealed new LA functional substrates associated with AF recurrence. Implementation of functional substrates may improve the prediction of AF recurrence after ablation, and possibly aid the development of tailored AF ablation strategies.

Two-dimensional and Doppler Echocardiographic Findings in Healthy Non-sedated Captive European Pond Turtles (Emys orbicularis)

Abstract Two-dimensional (2D) and Doppler echocardiography is considered the most practical diagnostic tool for antemortem evaluation of reptilian heart disease but has only been described in a limited number of chelonian species. Cardiac morphology and function were evaluated by ultrasonography in 35 clinically healthy, captive non-sedated European pond turtles (Emys orbicularis) using 2D-mode, M-mode, and pulsed wave spectral Doppler. Turtles were placed in a temperature-controlled water tank (24-26°C, 75.2-78.8°F) for cardiac examination through the right cervicobrachial window using water as coupling agent. Each echocardiogram included the evaluation of 19 variables, including 6 in 2D-mode, 7 in M-mode, and 6 in Doppler mode, and was performed in 5.64 minutes on average. Morphological and functional abnormalities were identified in eight turtles, including atrioventricular insufficiencies (n = 5), pericardial effusions (n = 4), increased velocity of the ventricular outflow tract (n = 1) and bradyarrhythmia (n = 2). Reference intervals could be established for the 19 parameters in the remaining individuals after excluding outliers (n = 25). Statistically significant positive correlations between weight and diastolic (0.61, P = 0.001) and systolic (0.46, P = 0.018) ventricular volumes, and diastolic ventricular diameter (0.35, P = 0.03) were identified. This study establishes an initial database for the evaluation of captive European pond turtle cardiovascular system by a simple and clinically applicable echocardiographic technique.

Executive function and decision-making in Colombian patients with paranoid schizophrenia

Background Schizophrenia (SCZD) is a mental disorder characterized by cognitive dysfunction, impaired decision-making abilities, abnormalities in brain functioning, and specific genetic markers. Ethnic and racial factors influence the development and presentation of schizophrenia, with different groups experiencing different levels of risk and exhibiting different patterns of mental disorders. Objective We sought to investigate the executive function and decision-making profile of Schizophrenia participants from Barranquilla, Colombia, which have a high genetic mixture and significant ethnic and racial diversity. Methods The sample consists of 40 individuals, 20 diagnosed with paranoid schizophrenia and 20 controls. We use the BANFE neuropsychological battery and the Iowa Gambling task to measure executive function and decision-making processes. Results The study found differences in cognitive performance, measured by the Neuropsychological Battery of Executive Functions and Frontal Lobes, in the medial orbit, anterior prefrontal, dorsolateral, and total executive function measures. In decision-making, as measured by the Iowa Gambling Test, there were also differences between the two groups, with those with schizophrenia performing worse and showing a preference for disadvantageous options. The study also found that there were no significant differences in socio-demographic characteristics between the two groups but that there were differences in terms of socio-economic status and educational level. Conclusion This study found that individuals with paranoid schizophrenia had significant differences in their prefrontal cortex compared to those without the condition, specifically in the dorsolateral and orbital-prefrontal cortex. These differences may be linked to difficulties adjusting to their environment and processing reinforcement, leading to impaired learning and arousal disturbances.

Dynamic Morphological Growth Trajectory of Crouzon Population: A Geometric Morphometric Analysis.

This study is to visualize the morphological growth trajectory of the Crouzon population and provide a more comprehensive and perceptual understanding of pathologic aggregation in terms of maxillofacial and soft tissue surfaces. Twenty-two patients with Crouzon syndrome were included in this retrospective surgery. Preoperative computed tomography was segmented into maxillofacial and soft tissue surface morphologies. Fifty-two anatomical landmarks and a standardized template were used to extract the morphological phenotypes and transform them into spatial coordinates. Geometric morphometrics (GM) were applied to visualize the growth trajectory and estimate the morphological variation of the Crouzon population. Cephalometric analysis was conducted to validate the growth trajectory in a clinical aspect. It was found that both maxillofacial and soft tissue surface morphologies were strongly covaried with age. Morphological development of the Crouzon population was characterized by (1) maxillary retrusion and clockwise rotation, (2) mandibular counterclockwise rotation, (3) facial width narrowing and aggregated concave face, and (4) sunken nasal bone. Pathologic maxillary retrusion continuously existed from infancy to adulthood, and rapid aggravation took place at 3 to 6 years old. In conclusion, this study is the first to visualize the dynamic growth trajectories on both maxillofacial and soft tissue surface morphologies. More attention and monitoring of breathing, snoring, intelligence, and global development should be cast on Crouzon patients between 3 and 6 years old in family care. If any functional abnormalities occur during this period, professional consultations and evaluations should be conducted timely to avoid pathologic aggravation. Consistency between GMs and cephalometry validates the reliability of GM potentials in the clinical field, allowing a promising and revolutionary methodology for dynamically and qualitatively analyzing pathologic changes in some rare congenital diseases.

Characteristics of adolescents referred for bariatric surgery in Abu Dhabi, United Arab Emirates.

About a third of children and adolescents are overweight or obese in the United Arab Emirates, and referrals for metabolic and bariatric surgery (MBS) are now common. Despite excellent evidence that MBS should be considered in adolescents with severe obesity, it remains a management approach of last resort in many cases. Baseline, real-world data on adolescent patients living with obesity referred for surgery, their characteristics, and how these relate to current and future referral policy are important to ensure best practice. Here we examined the demographic, anthropometric, and clinical characteristics of adolescents referred for MBS over a three-year period to Sheikh Shakhbout Medical City (SSMC), Abu Dhabi, UAE. Ninety-two adolescents living with obesity were recruited: 54.3% were female, the average age was 16.3 ± 2.4 years, and 88.0% of patients had a first-degree relative with a history of obesity and 62% a family history of bariatric surgery. The average BMI was 47.7 ± 10.5, and the average percentage of the 95th percentile BMI was 169.5 ± 38.8%. Complications of obesity (hypertension, type 2 diabetes and prediabetes, dyslipidemia, and liver function abnormalities) were common. Our analysis highlights that there exists a mismatch between the profiles of patients referred for MBS, local guidelines, and international best practice in decision-making for referral to MBS services. While many adolescents in the UAE seem to enjoy family support and experience in the surgical management of obesity, local guidelines need updating to reflect changes in the definitions of obesity, thresholds for referral, and to remove unnecessary developmental stage barriers to increase the window for personalized surgical management.

The establishment and evaluation of a swine model of deinagkistrodon acutus snakebite envenomation

ObjectiveTo establish a preclinical large-animal model of Deinagkistrodon acutus snakebite envenomation and evaluate its feasibility. MethodsThe venom of D. acutus (0 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, or 10 mg/kg) was injected into the left biceps femoris of 11 male pigs. Then, the circumferences of the limbs were regularly measured, and changes in muscle injury biomarkers, blood parameters, coagulation function, vital organ function and injury biomarkers were regularly detected. At 24 h after venom injection, the animals were euthanized, and the pathological damage to the vital organs mentioned above was evaluated. ResultsThe two pigs receiving 10 mg/kg and 5 mg/kg snake venom died at 8 h and 12 h after injection, respectively. The remaining pigs were equally divided into 0 mg/kg, 1 mg/kg, and 2 mg/kg snake venom groups, and all of them survived to 24 h after injection. Compared with the pigs receiving 0 mg/kg snake venom, the pigs receiving 1 mg/kg or 2 mg/kg snake venom exhibited significant abnormities, including limb swelling; increased muscle injury biomarker creatine kinase (CK) and coagulation function indicators prothrombin time and D-dimer; and decreased blood routine indicator platelet and coagulation function indicator fibrinogen. Moreover, significant abnormalities in myocardial and cerebral function and injury biomarkers in the heart, brain, liver, kidney and intestine were also observed. In particular, the abnormalities mentioned above were significantly obvious in those pigs receiving 2 mg/kg snake venom. Pathological evaluation revealed that the morphology of muscle, heart, brain, liver, kidney, and intestine in those pigs receiving 0 mg/kg snake venom was normal; however, pathological damage was observed in those pigs receiving 1 mg/kg and 2 mg/kg snake venom. Similarly, the pathological damage was more severe in those pigs receiving 2 mg/kg snake venom. ConclusionThe intramuscular injection of 2 mg/kg D. acutus venom seems to be an optimal dose for examining the preclinical efficacy of existing and novel therapeutics for treating D. acutus envenomation in pigs.

Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography. Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies.What is Known:• Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms.What is New:• Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.

A Community-Based Cross-Sectional Study on Respiratory Health and Spirometry-Assessed Pulmonary Function Among Textile Workers in Tamil Nadu, India.

Introduction The textile industry is one of the largest economic activities. Still, the laborers involved in it are exposed to various health-damaging air pollutants, putting them at risk of health issues including morbidities of the respiratory system. Therefore, this study aimed to assess the pulmonary function parameters of the workers involved in textile manufacturing-related jobs. Methodology A cross-sectional study was carried out among adult individuals who had been working in textile manufacturing-related jobs as their main work. The details such as sociodemographic, clinical, workplace conditions, and smoking habits were collected, as well as chest auscultation and lung spirometry using a hand-held spirometer. The participants who had normal and abnormal lung function patterns were statistically analyzed for potential influencing factors. Results The findings of the study conducted from 95 eligible participants identified that the pulmonary function parameters assessed by spirometry were in the abnormal range among 84 (88%) participants. Around 72 (82%) of them had a restrictive pattern, and six (6%) had both restrictive and obstructive (mixed) patterns of lung disease. Smokers and those who lacked cross-ventilation and/or fresh source of air in the workplace were more likely to have abnormal lung function. Participants who had their workplace and residence as same had significantly 6.44 (95% CI: 1.24, 33.36) times higher odds of having abnormal lung function in spirometry. Conclusion As workers involved in household-run textile manufacturing jobs are found to be at a higher risk of developing abnormal lung function, using personal protective equipment, following occupational safety measures, and improving the working environment to acceptable standards are essential to safeguard the respiratory health of laborers in such unorganized sectors.