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Cureus Jun 2024Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in...
Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in psychomotor development and epilepsy in children. Lissencephaly (smooth brain) forms a major group of brain malformations. Microtubules help in the migration of neuronal cells. Defect in tubulin gene alpha-tubulin (TUBA), beta-tubulin (TUBB), and gamma-tubulin (TUBG) leads to defective neuronal migration. This group of disorders is termed as "tubulinopathies." The important genes implicated in causing lissencephaly are LIS1, XLIS, and TUBA1A gene. Recently, a mutation in the TUBG1 gene is associated with it. Here, we report a one-and-a-half-year-old girl with global developmental delay, microcephaly, infantile-onset epilepsy, epileptic spasms, dysmorphism, and motor signs. There was no significant birth history. Neuroimaging (MRI) showed a broad thick gyri and a decreased number of sulci suggestive of lissencephaly/pachygyria spectrum. There was dilatation of the ventricles, and no grey matter heterotopia was noted. Sleep EEG showed multifocal epileptiform discharges. The child was treated with multiple anti-seizure medicines (ASMs). A genetic test, whole exome sequencing, was done to determine the etiology of MCD. A heterozygous missense variation in exon 6 of the TUBG1 gene was identified and reported as a "variant of unknown significance." Still, because the genotype matched with the clinical phenotype of the patient, it was considered clinically significant. Therefore, a complete diagnosis of TUBG1 mutation-associated cortical malformation (lissencephaly/pachygyria) with microcephaly and early-onset epilepsy was established. TUBG1 mutation is de novo in most cases, but parental testing is recommended. The parents of such patients need to be counseled about the need for prenatal testing and the risk of the disease to siblings. The overall prognosis in such cases is poor because of refractory seizures, physical limitations, and intellectual disability.
PubMed: 38912084
DOI: 10.7759/cureus.62749 -
Journal of Indian Association of... 2024Pediatric upper gastrointestinal (UGI) endoscopy is an important procedure in the management of gastrointestinal pathologies. Conventionally, it has been the forte of...
INTRODUCTION
Pediatric upper gastrointestinal (UGI) endoscopy is an important procedure in the management of gastrointestinal pathologies. Conventionally, it has been the forte of medical gastroenterologists. However, unlike adults, the availability of pediatric gastroenterologists is limited, especially during emergency hours. We present our early experience of UGI endoscopy done by the department of pediatric surgery.
AIMS
The aim of this study was to study the feasibility and benefits of UGI endoscopy by pediatric surgeons.
MATERIALS AND METHODS
A retrospective descriptive study was carried out by the department of pediatric surgery of a tertiary-level medical college, from January 2017 to January 2022. Data were collected from electronic and physical medical records. Parameters included age, gender, indication for endoscopy, and procedures done endoscopically or based on endoscopic findings and complications.
RESULTS
One hundred and thirty endoscopies were done in 95 patients aged 1-16 years, from January 2017 to January 2022. The most common indication for UGI endoscopy was esophageal stricture (71 procedures in 41 patients), followed by UGI foreign body (18 cases). All other indications were mostly diagnostic, other than four patients with achalasia. Thirty of these patients underwent UGI endoscopy as an emergency procedure. Seventeen patients were followed through or had added procedures, with UGI endoscopy. There was one perforation when dilating an esophageal stricture who responded to conservative management.
CONCLUSION
UGI endoscopy is a valuable diagnostic and therapeutic procedure, which can be performed by pediatric surgeons after necessary training. It supplements decision-making in management, avoids waste of time in referring, avoids additional anesthesia, and is valuable in emergencies.
PubMed: 38912033
DOI: 10.4103/jiaps.jiaps_246_23 -
ACS Omega Jun 2024Spalling failure is a typical failure phenomenon after excavation and unloading of a deep, hard brittle rock mass, which seriously threatens the safe construction of...
Spalling failure is a typical failure phenomenon after excavation and unloading of a deep, hard brittle rock mass, which seriously threatens the safe construction of deep roadways (tunnels) and other projects. From the engineering viewpoint, it is essential to accurately evaluate the range and depth of surrounding rock spalling failure. From the perspective of the laboratory and engineering site, the strength and formation mechanism of hard rock spalling failure were statistically summarized and analyzed. Under uniaxial and low confining pressure conditions, when the load reached the rock damage stress, cracks in the rock penetrated to form a failure plane approximately parallel to the axial loading direction, and the strength of rock mass spalling was much smaller than that of intact rock spalling. A triaxial compression test was conducted to analyze the dilatation axial strain and dilatation lateral strain characteristics of gneiss. The results showed that dilatation axial strain gradually increased with the increase of confining pressure, whereas dilatation lateral strain was almost unchanged. Therefore, a safety factor (FS) based on dilatation lateral strain was developed. Through comparison with other strain-based spalling criteria, the establishment and physical meaning of the method were described in detail. In addition, FS was applied to analyze the deep roadway of the Hongtoushan Copper Mine in China and the Rm415 test tunnel in Canada. The results showed that the spalling criterion could accurately indicate the range and depth of the surrounding rock spalling failure, which verified the rationality and applicability of the new spalling criterion. Thus, FS can be utilized as a new theory and analysis tool for the assessment and prevention of spalling failure in deep hard rock roadways.
PubMed: 38911813
DOI: 10.1021/acsomega.4c02572 -
Experimental and Therapeutic Medicine Aug 2024Acute kidney injury (AKI) caused by ischemia and, exogenous or endogenous nephrotoxic agents poses a serious health issue. AKI is seen in 1% of all hospital admissions,...
Acute kidney injury (AKI) caused by ischemia and, exogenous or endogenous nephrotoxic agents poses a serious health issue. AKI is seen in 1% of all hospital admissions, 2-5% of hospitalizations and 67% of intensive care unit (ICU) patients. The in-hospital mortality rates for AKI is 40-50, and >50% for ICU patients. Ischemia-reperfusion (I/R) injury in the kidney can activate inflammatory responses and oxidative stress, resulting in AKI. The common endpoint in acute tubular necrosis is a cellular insult secondary to ischemia or direct toxins, which results in effacement of brush border, cell death and decreased function of tubular cells. The aim of the present study was to assess if the reported antioxidant and anti-inflammatory agent lupeol can exert any effects against renal I/R damage. In total, 24 Wistar Albino rats were randomly assigned into four groups of 6, namely Sham, lupeol, ischemia and therapy groups. In the lupeol group, intraperitoneal administration of 100 mg/kg lupeol was given 1 h before laparotomy, whilst only laparotomy was conducted in the sham group. The renal arteries of both kidneys were clamped for 45 min, 1 h after either intraperitoneal saline injection (in the ischemia group) or 100 mg/kg lupeol application (in the therapy group). The blood samples and renal tissues of all rats were collected after 24 h. In blood samples, blood urea nitrogen (BUN) was measured by the urease enzymatic method, and creatinine was measured by the kinetic Jaffe method. Using ELISA method, TNF-α and IL-6 levels were measured in the blood samples, whereas malondialdehyde (MDA), glutathione (GSH), caspase-3 levels were measured in kidney tissues. In addition, kidney histopathological analysis was performed by evaluating the degree of degeneration, tubular dilatation, interstitial lymphocyte infiltration, protein cylinders, necrosis and loss of brush borders. It was determined that renal damage occurred due to higher BUN, creatinine, MDA, TNF-α and caspase-3 values observed in the kidney tissues and blood samples of rats in ischemia group compared with the Sham group. Compared with those in the ischemia group, rats in the therapy group exhibited increased levels of GSH and reduced levels of BUN, TNF-α, MDA. Furthermore, the ischemia group also had reduced histopathological damage scores. Although differences in creatinine, IL-6 and caspase-3 levels were not statistically significant, they were markedly reduced in the treatment group. Taken together, these findings suggest that lupeol can prevent kidney damage as mainly evidenced by the reduced histopathological damage scores, decreased levels of oxidative stress and reduced levels of inflammatory markers. These properties may allow lupeol to be used in the treatment of AKI.
PubMed: 38911048
DOI: 10.3892/etm.2024.12602 -
Cureus May 2024Cyclin-dependent kinase 13 (CDK13)-related disorder is a rare autosomal dominant disease caused by pathogenic variants in the gene. This disorder was found to be...
Cyclin-dependent kinase 13 (CDK13)-related disorder is a rare autosomal dominant disease caused by pathogenic variants in the gene. This disorder was found to be related to several clinical features, including structural cardiac anomalies, developmental delay, anomalies of the corpus callosum, and a variety of facial dysmorphisms. In addition, feeding difficulties and neonatal hypotonia might also present. The diagnosis of this disorder is based on molecular genetic testing to detect the causative pathogenic variants. Here, we report a case of a one-year-old girl from Yemen, residing in Bahrain, with a CDK13-related disorder who was found to have an unusual association of abdominal situs inversus along with multiple structural cardiac anomalies, including atrial septal defect, ventricular septal defect, patent ductus arteriosus, interrupted inferior vena cava, bilateral superior vena cava, mild coarctation of the aorta, dilated coronary sinuses, and mild regurgitation in the tricuspid valve. Moreover, facial dysmorphism including medial epicanthal folds, posteriorly rotated ears, and a depressed nasal bridge was also noted. Further assessment showed a delay in reaching developmental milestones, including speech and motor delay. The patient also presented with recurrent episodes of upper respiratory tract infections, acute bronchiolitis, and lobar pneumonia which required admission to the intensive care unit and ventilation. The last infection episode was at the age of one year. Thereafter, the patient underwent cardiac repair of the ventricular septal defect followed by no more infection episodes until the age of one year and two months. The diagnosis of CDK13 was confirmed by a whole exome sequencing test which demonstrated a novel missense variant in exon 14 of the gene as a variant of uncertain significance in a heterozygous state.
PubMed: 38910624
DOI: 10.7759/cureus.60970 -
Cureus May 2024This case report presents a rare incidence of a persistent Eustachian valve (EV) causing notable venous dilation in the abdominal and pelvic regions of a 44-year-old...
This case report presents a rare incidence of a persistent Eustachian valve (EV) causing notable venous dilation in the abdominal and pelvic regions of a 44-year-old healthy male. Initially presenting with left flank pain, diagnostic evaluations identified a 4.8-mm calculus in the distal left ureterovesical junction. Incidentally, imaging also revealed unexplained venous distensions, subsequently attributed to a prominent EV obstructing the inferior vena cava (IVC). The EV, an embryological structure in fetal circulation that helps divert blood from the IVC to the left atrium via the foramen ovale, typically regresses postnatally. Its persistence into adulthood is uncommon and often does not necessitate intervention. However, a persistent EV is often associated with other cardiac findings, especially a patent foramen ovale (PFO) of an atrial septal defect (ASD). There were some reports demonstrating that persistent EV may play a role in an increased risk of paradoxical cerebral embolism in such cases. Therefore, the case underscores the importance of considering such embryological remnants in the differential diagnoses of unexplained venous distension and cryptogenic stroke. It also highlighted the need for a personalized approach to management, especially during the preparation phase before interventional procedures, such as an ASD closure, to minimize the risks during the operation. Furthermore, it also contributed to a broader understanding of the clinical implications of persistent embryological structures and emphasized the value of meticulous diagnostic processes in identifying the underlying causes of observed anomalies.
PubMed: 38910619
DOI: 10.7759/cureus.60994 -
Cureus May 2024Background Gender dysphoria is treated with gender affirmation surgery (GAS) for assigned male at birth (AMAB) individuals. This study aimed to evaluate the...
Background Gender dysphoria is treated with gender affirmation surgery (GAS) for assigned male at birth (AMAB) individuals. This study aimed to evaluate the postoperative anatomical changes in AMAB individuals who underwent GAS using magnetic resonance imaging (MRI) and to compare it with cis-females, thereby assessing the efficacy of the surgical technique in achieving pelvic anatomy similar to cis-females. Methodology This was a prospective observational study done in a tertiary care hospital. AMAB individuals who underwent gender affirmation genital surgery using single-stage solely penile skin inversion vaginoplasty were included after informed consent and approval by the Institutional Human Ethics Committee. Patients with complications such as deep space surgical site infection (SSI) and neo-vaginal prolapse were excluded. All the study participants were advised a vaginal self-dilatation regimen, reviewed three months after the surgery, and subjected to an MRI of the pelvis with a vaginal tutor. Parameters such as neo-vaginal depth, alpha (α) angle, rectovaginal thickness, and remnant of corpora cavernosa were measured and compared with cis-female parameters measured from images in the archives from the Department of Radiology. Result A total of 21 patients were included in the study, with a mean age of 27±4.7. Between the study group and cis-females, no significant difference was seen in vaginal depth, and cis-females had significantly higher values in other parameters. There was a significant difference between the subgroups, i.e., defaulters and non-defaulters in soft tissue parameters such as vaginal depth (p=0.001), α angle (p=0.002), and rectovaginal thickness (p=0.002) with the non-defaulter patients having higher values. Conclusion Single-stage penile skin inversion vaginoplasty is capable of producing anatomical parameters, importantly neo-vaginal depth, which is fairly comparable with cis-female, as evident in the non-defaulter subgroup patients. Proper compliance with the vaginal dilatation regimen plays a significant role in the maintenance of soft tissue pelvic anatomical parameters.
PubMed: 38910612
DOI: 10.7759/cureus.60823 -
Circulation. Heart Failure Jun 2024The mechanism of cardiac reverse remodeling (CRR) mediated by the left ventricular assist device remains unclear. This study aims to identify the specific cell type...
BACKGROUND
The mechanism of cardiac reverse remodeling (CRR) mediated by the left ventricular assist device remains unclear. This study aims to identify the specific cell type responsible for CRR and develop the therapeutic target that promotes CRR.
METHODS
The nuclei were extracted from the left ventricular tissue of 4 normal controls, 4 CRR patients, and 4 no cardiac reverse remodeling patients and then subjected to single-nucleus RNA sequencing for identifying key cell types responsible for CRR. Gene overexpression in transverse aortic constriction and dilated cardiomyopathy heart failure mouse model (C57BL/6J background) and pathological staining were performed to validate the results of single-nucleus RNA sequencing.
RESULTS
Ten cell types were identified among 126 156 nuclei. Cardiomyocytes in CRR patients expressed higher levels of than the other 2 groups. The macrophages in CRR patients expressed more anti-inflammatory genes and functioned in angiogenesis. Endothelial cells that elevated in no cardiac reverse remodeling patients were involved in the inflammatory response. Echocardiography showed that overexpressing through cardiomyocyte-specific adeno-associated virus 9 demonstrated an ability to improve heart function and morphology. Pathological staining showed that overexpressing could reduce fibrosis and cardiomyocyte size in the heart failure mouse model.
CONCLUSIONS
The present results of single-nucleus RNA sequencing and heart failure mouse model indicated that could mediate CRR and supported the development of therapeutics for overexpressing in promoting CRR.
PubMed: 38910562
DOI: 10.1161/CIRCHEARTFAILURE.123.011504 -
Circulation Journal : Official Journal... Jun 2024The incidence and prognostic predictors of heart failure (HF) without left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM), particularly...
BACKGROUND
The incidence and prognostic predictors of heart failure (HF) without left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM), particularly their differences in terms of developing LVSD (progression to end-stage) or sudden cardiac death (SCD), are not fully elucidated.Methods and Results: This study included 330 consecutive HCM patients with left ventricular ejection fraction (LVEF) ≥50%. HF hospitalization without LVSD and development of LVSD were evaluated as main outcomes. During a median follow-up of 7.3 years, the incidence of HF hospitalization without LVSD was 18.8%, which was higher than the incidence of developing LVSD (10.9%) or SCD (8.8%). Among patients who developed LVSD, only 19.4% experienced HF hospitalization without LVSD before developing LVSD. Multivariable analysis showed that predictors for HF hospitalization without LVSD (higher age, atrial fibrillation, history of HF hospitalization, and higher B-type natriuretic peptide concentrations) were different from those of developing LVSD (male sex, lower LVEF, lower left ventricular outflow tract gradient, and higher tricuspid regurgitation pressure gradient). Known risk factors for SCD did not predict either HF without LVSD or developing LVSD.
CONCLUSIONS
In HCM with LVEF ≥50%, HF hospitalization without LVSD was more frequently observed than development of LVSD or SCD during mid-term follow-up. The overlap between HF without LVSD and developing LVSD was small (19.4%), and these 2 HF events had different predictors.
PubMed: 38910134
DOI: 10.1253/circj.CJ-24-0049 -
Medical Ultrasonography Jun 2024Chronic venous disease is a common pathology characterized by valvular incompetence and venous hypertension. The venous network of the lymph nodes at the Scarpa triangle...
AIM
Chronic venous disease is a common pathology characterized by valvular incompetence and venous hypertension. The venous network of the lymph nodes at the Scarpa triangle connects the superficial and the deep venous systems. This study aimed to describe infrainguinal intranodal venous dilatations and to evaluate the connection with peripheral venous disease.
MATERIAL AND METHODS
The study included 183 subjects (116 women, 67 men) who underwent Doppler ultrasound examinations of the venous system of the inferior limb in the context of chronic venous disease. The diagnosis of lymph node varices was based on well-defined criteria and the severity of the lymph node varices was established using an original classification.
RESULTS
There was a statistically significant, moderately strong association, between the presence of intranodal varices and the great saphenous vein reflux (φ=0.341, p=0.000). There was a moderate-to-high positive correlation between intranodal varices and the chronic venous disease stage (rrb=0.457, p=0.000).
CONCLUSIONS
Patients with more advanced stages of chronic venous insufficiency have a higher probability of presenting intranodal varices. Lymph node venous network identification could considerably impact clinical decision-making and treatment choices.
PubMed: 38909378
DOI: 10.11152/mu-4390