Frequency Of Abnormalities Research Articles

Factors Associated With Survival Among Patients With Multiple Myeloma in Northeastern Tanzania.

This study sought to delineate the clinical, laboratory, and imaging characteristics during multiple myeloma (MM) diagnosis, outline the treatment modalities administered, and ascertain the survival rates among patients with MM over a comprehensive 5-year span in Tanzania. This retrospective cohort study investigated patients diagnosed with MM at the Cancer Care Clinic, Kilimanjaro Christian Medical Centre, between January 2017 and June 2022. Demographic data, clinical profiles, and survival outcomes were collected. The study employed the Kaplan-Meier method to determine overall survival (OS) and survival rates, supported by univariate analysis and a multivariate Cox regression model with significance of P < .05. In this study of 76 patients with MM, bone pain was the most common complaint (76.3%), and patients were age typically older than 50 years (82.5%). Laboratory tests showed frequent abnormalities, such as anemia (51.3%) and hypercalcemia (23.9%). Most patients were at stage III according to Durie Salmon Staging (82.7%), with imaging revealing various bone abnormalities. The median OS was 18.0 months, with 46.1% of patients passing away during the study period. Factors linked to shorter survival included anemia, renal failure, and bone involvement. Infection was the primary cause of death among these patients. The presenting complaint of bone pain significantly affected survival outcomes. This study provides a comprehensive understanding of MM within the Sub-Saharan African context, highlighting age-related disparities in diagnosis, predominant presenting symptoms like bone pain, factors contributing to delayed diagnoses, and the impact on survival rates. The findings underscore the critical need for early recognition, improved diagnostics, and tailored interventions to enhance outcomes for patients with MM in this region.

Small Fiber Neuropathy Associated with Post-COVID-19 and Post-COVID-19 Vaccination Arthritis: A Rare Post-Infective Syndrome or a New-Onset Disease?

Post-COVID-19 (PC) and post-COVID-19 vaccination (PCV) syndromes are considered emergent multidisciplinary disorders. PC/PCV small fiber neuropathy (SFN) was rarely described and its association with undifferentiated arthritis (UA) was never defined. We aimed to evaluate PC/PCV-UA associated with the recent onset of severe lower limb paresthesia, compare SFN positive (+) to negative (-) patients, and evaluate changes in biomarkers in SFN+ during treatments. Nineteen PC/PCV-UA-patients with possible SFN underwent skin biopsy at the Usl Tuscany Center (Florence) early arthritis outpatient clinic from September 2021 to March 2024. Eight selected SFN+ were compared to ten SFN- patients. In SFN+ patients, baseline joint ultrasound (US), electromyography (EMG), optical coherence tomography (OCT), and skin biopsy were repeated at six months. Moreover, SFN+ patients were clinically assessed by a 0-10 numeric rating scale for neurological symptoms and DAS28/ESR up to 12 months follow-up. SFN+ patients showed a lower intraepidermal nerve fiber density at histopathological examination of skin biopsies and a higher frequency of OCT and EMG abnormalities in comparison to SFN- patients. In SFN+ patients, US and DAS28/ESR significantly improved, while intraepidermal nerve fiber density did not significantly change at the six-month follow-up. Fatigue, motor impairment, burning pain, brain fog, and sensitivity disorders decreased at long-term follow-up (12 months).

Distinctive clinical traits of lupus-related myocarditis: a multicentre retrospective study.

Cardiovascular involvement in systemic lupus erythematosus (SLE) is frequent but little is known about possible distinctive traits of SLE-related myocarditis (myoSLE) in comparison to patients with SLE (onlySLE) or myocarditis alone (onlyMyo). A retrospective analysis was performed comparing patients with myoSLE (n = 25) from three centres with consecutive patients with onlySLE (n = 279) and onlyMyo (n = 88). SLE patients were dichotomised by disease duration ≤1 vs >1 year into recent onlySLE/early myoSLE vs longstanding onlySLE/late myoSLE. Further stratification into disease duration of 1-5, 5-10 and >10 years was also performed. SLE disease activity index 2000 (SLEDAI-2K) was used to estimate disease activity. Myocarditis was diagnosed through biopsy or magnetic resonance. Women were significantly more frequent among myoSLE than among onlyMyo (72% vs 43%; p= 0.013). Compared with onlyMyo, myoSLE patients had a higher frequency of conduction abnormalities (22% vs 5%; p= 0.046) and presented with numerically higher frequencies of left ventricular function compromise (48% vs 30%), along with higher pro-brain natriuretic peptide levels. Inflammation markers were higher in myoSLE compared with onlyMyo and to patients with onlySLE with >10 years of disease duration. SLEDAI-2K was significantly higher in late myoSLE than in longstanding onlySLE. Antiphospholipid syndrome was more frequent in myoSLE than in onlySLE. Multivariate analysis showed an association among myoSLE, anti-beta-2-glycoprotein I antibodies (aB2GPI, p= 0.014) and a higher number of involved British Isles Lupus Assessment Group domains in patient history (p= 0.003). myoSLE has unique clinical traits compared with other forms of myocarditis and is associated with aB2GPI and a more severe SLE course.

Cardiac involvement in systemic lupus erythematosus: Interest of 2D global longitudinal strain.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease of undetermined etiology. Cardiac involvement is common in SLE and constitutes one of the main causes of mortality. More recently, new ultrasound imaging techniques, such as transthoracic ultrasound (TTE) with strain evaluation, have appeared and seem promising for the detection of cardiac involvement. The objective of our work was to study the frequency and characteristics of ultrasound abnormalities found in lupus patients and to study the benefit of ultrasound with global longitudinal strain (GLS) for early management. It was an observational study of patients followed for SLE at the internal medicine and cardiology department of the HMPIT for 6months (May-November 2023). The definition of cardiac involvement was by ultrasound. All patients benefited from TTE coupled with 2D-strain. We divided the workforce into two groups: the first group (patients with heart disease) and the second group (patients without heart disease). In a series of 40 lupus patients including 33 women and seven men, cardiac manifestations were reported in 60% of patients. In the first group, 29% had palpitations, 25% had chest pain, 67% had dyspnea, 37% had pericarditis, 8% had pulmonary arterial hypertension (PAH) and 12% had myocarditis. The comparative study showed that patients in the first group presented significantly more frequently with dyspnea (p = 0.02), chest pain (p = 0.03) and serositis (p = 0.01) compared to those in the second group. The mean left ventricular ejection fraction (LVEF) did not show a significant difference between the two groups. On the other hand, the average Global Longitudinal Strain (GLS) was significantly altered in the first group (p = 0.01). Furthermore, the frequency of pathological GLS was significantly higher in patients with lupus heart disease (p < 0.01). Cardiac involvement during SLE is a frequent and most often asymptomatic complication. A systematic search for this impairment using a high-performance echocardiography examination, namely the 2D GLS, is essential for early treatment.

Contribution of chromosomal aberrations to the pathogenesis of primary and secondary amenorrhea: A study from Western Iran.

Amenorrhea is an abnormal condition characterized by the absence of menstruation in women of reproductive age. According to the World Health Organization, amenorrhea ranks as the sixth leading cause of female infertility. Approximately 2% to 5% of women of reproductive age experience amenorrhea, which can be classified as primary amenorrhea (PA) or secondary amenorrhea (SA). Several studies have named chromosomal abnormalities among the main causes of amenorrhea, though the prevalence of these abnormalities may differ across populations. The objective of this study was to ascertain the frequency and types of chromosomal abnormalities in women with amenorrhea in Kermanshah Province, Iran. This retrospective study included patients with PA and SA who underwent standard cytogenetic analysis. We also conducted a review of the literature on chromosomal abnormalities and their prevalence in SA. Among the 137 cases of PA in this study, 22% exhibited chromosomal abnormalities. Numerical changes were the most common finding (46.6%) in this group, including 45,X, mosaic, and 47,XXX karyotypes. These were followed by the 46,XY karyotype (40%). Of the 51 cases of SA that received chromosomal analysis, abnormalities were identified in only one case. Additionally, our review of the literature revealed that chromosomal aberrations are responsible for 7% of SA cases globally. In this study, we successfully characterized the cytogenetic causes of PA and SA in a substantial population from Kermanshah Province, Iran.

Intracranial vasculopathy: an important organ damage in young adult patients with late-onset Pompe disease

BackgroundLate-onset Pompe disease (LOPD) is mainly characterized by progressive limb-girdle muscle weakness and respiratory impairment, whereas stroke and cerebrovascular abnormalities have been insufficiently studied in LOPD. This study aimed to evaluate the frequency and pattern of intracranial artery and brain parenchyma abnormalities in LOPD patients.ResultsNeuroimaging data from 30 Chinese adult LOPD patients were collected from our center. Seven patients (7/30) had acute cerebral infarction or hemorrhage. Brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) revealed artery abnormalities in 23 patients (23/30). Dilative arteriopathy was found in 19 patients (19/30), with vertebrobasilar dolichoectasia found in 17 patients and dilatation of the anterior circulation arteries found in 8 patients. The maximum diameter of the basilar artery was correlated with disease duration (p < 0.05). In addition, aneurysms (7/30) and fenestrations (3/30) were discovered. There were 14 patients with arterial stenosis (14/30), and both anterior and posterior circulation involvement occurred in 9 patients (9/14). Stenosis and dilative arteriopathy simultaneously occurred in 10 patients (10/30). White matter hyperintensities were present in 13 patients (13/28). Microbleeds, predominantly located in the cerebellum and brainstem, were detected in 7 patients (7/22) via susceptibility-weighted imaging.ConclusionsIntracranial vasculopathy involving both large arteries and small vessels is an important organ damage in LOPD patients. LOPD should be considered a key differential diagnosis in young adults with cryptogenic stroke, and a series of imaging evaluations of the brain and intracranial blood vessels is recommended as a routine workup in adult LOPD patients.

EFFICACY OF INTRAVENOUS IMMUNOGLOBULIN ALONE ON CORONARY ARTERY LESION REDUCTION IN KAWASAKI DISEASE.

Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin. This clinical trial was structured as a prospective, evaluator-blinded, multi-center randomized controlled trial with two parallel arms, aiming to assess the effectiveness of IVIG as a standalone primary therapy of KD in comparison to the combination of IVIG with high-dose aspirin therapy. KD patients were enrolled between September, 2016 and August, 2019. A final cohort of 134 patients were randomly assigned to the standard and test groups with 69 and 65 patients, respectively. The Standard group received IVIG (2 g/kg) along with aspirin (80-100 mg/kg/day) until fever subsided for 48 hours. The test group received IVIG (2 g/kg) alone. Following the initial treatment, both groups received a daily aspirin dose (3-5 mg/kg) for six weeks. The primary outcome measure was the occurrence of coronary artery lesions (CAL) at the 6-8 weeks mark. The secondary outcome is IVIG resistance. The overall rate of CAL in test group decreased from 10.8% at diagnosis to 1.5% and 3.1% at 6 weeks and 6 months, respectively. The CAL rate of standard group declined from 13.0% to 2.9% and 1.4%, with no statistically significant difference (P>0.1) in the frequency of CAL between the two groups. Furthermore, no statistically significant differences were found for treatment (P>0.1) and prevention (P>0.1) effect between the two groups. This marks the first prospective multi-center randomized controlled trial comparing the standard treatment of KD using IVIG plus high-dose aspirin against IVIG alone. Our analysis indicates that addition of high-dose aspirin during initial IVIG treatment is neither statistically significant nor clinically meaningful for CAL reduction. URL: http://www.clinicaltrials.gov ; identifier: NCT02951234. This study represents the first multi-center randomized controlled trial investigating the efficacy of high-dose aspirin or intravenous immunoglobulin (IVIG) during the acute stage of KD. This study assessed the impact of discontinuing high-dose aspirin (80-100 mg/kg/day) on the occurrence of CAL during the acute phase treatment of Kawasaki Disease.No significant differences were observed between high-dose aspirin plus IVIG treatment and IVIG alone treatment in terms of the frequency of abnormal coronary artery abnormalities. Additionally, our analysis revealed no statistically significant differences in either the treatment effect (the number of cases successfully treated) or prevention effect (the prevention of new cases) between these two treatments. Comparison analysis indicated the non-inferiority between two groups with or without high-dose aspirin.Administering the standard 2 g/kg/day IVIG without high-dose aspirin (80-100 mg/kg/day) during the acute phase therapy for KD does not increase the risk of coronary artery lesions, which are a primary cause of morbidity and mortality in KD patients.Addition of high-dose aspirin during initial IVIG treatment is not statistically significant or clinically meaningful.

Probiotics relieve growth retardation and stress by upgrading immunity in Nile tilapia (Oreochromis niloticus) during high temperature events

Global warming is disastrous to aquatic animals and supplementation of probiotics might mitigate its adverse effects. Therefore, to mitigate the effects of high temperature on growth retardation, stress and immunity, multi-species probiotics consisting of Bacillus subtilis (5×109 cfu/ml), B. thuringiencis (4×109 cfu/ml), Lactobacillus plantarum (5.8×109 cfu/ml), and L. buchneri (6.5×109 cfu/ml) were added in rearing water (1.0 ml/L) of Nile tilapia (Oreochromis niloticus). Fingerlings (1.08 ± 0.13 g) were reared at normal (31ºC) and elevated (34ºC and 37ºC) temperatures with or without probiotics for 6 weeks in triplicates. At the end of the experimental period, weight gain (WG) and specific growth rate (SGR) decreased significantly at 37ºC in fish supplemented with or without probiotics relative to normal temperature (31ºC). Importantly, at the high temperature (37ºC), WG and SGR were improved in fish supplemented with probiotics in contrast to fish reared without probiotics. The physiological status was improved by increasing the hemoglobin level and number of red blood cells and lowering white blood cells and glucose levels in the probiotics-treated high-temperature group. Frequencies of cellular and nuclear abnormalities of erythrocytes were significantly lowered in probiotics-supplemented fish. Histological observation demonstrated that multi-probiotics mitigated the high-temperature stress through increasing mucosal fold fattening, goblet cells, and the size of lamina propria and enterocytes in the intestine. Fish under higher temperatures (34 and 37ºC) showed up-regulated expression of the stress-related heat shock protein 70 (hsp70) gene, while its expression was decreased after probiotics addition. In contrast, two antioxidant-related genes (superoxide dismutase; SOD) and catalase; CAT) showed opposite expression patterns. The expression of three immune response-related genes (tumor necrosis factor alpha; TNF-α, interleukin 1 beta; IL-1β, and interferon gamma; IFN-γ) down-regulated with increase of temperature, while their expressions were increased after probiotics addition. Therefore, addition of probiotics in aquatic environment improved hemato-biochemical properties, blood cell structure, and immunity which ultimately relieve the growth retardation and stress in extreme temperatures in Nile tilapia.

O-262 Karyotyping of single sperm from non-obstructive azoospermia patients and obstructive azoospermia patients using a combination of micromanipulation and next-generation sequencing

Abstract Study question Is there a difference in the frequency of aberrant karyotype in sperm when the cause of infertility is non-obstructive azoospermia (NOA) versus obstructive azoospermia (OA)? Summary answer Aberrant karyotype was found in 7 of 46 sperm with NOA, none of 26 sperm with OA and none of 28 sperm with control. What is known already It is known that aberrant karyotype occurs more frequently in sperm from infertile men than sperm from general population, and that the severity of infertility is proportional to the frequency of sperm chromosomal abnormality. In fact, miscarriage rates are high in cases where TESE-ICSI is performed for azoospermia, and embryonic chromosomal aneuploidy derived from sperm is thought to be one of the causes of miscarriage. Azoospermia is classified into OA and NOA. However, it is unclear whether there is a difference in the frequency of sperm chromosomal abnormality between NOA and OA. Study design, size, duration Sperm were picked up individually by micromanipulation for the OA and NOA groups who underwent TESE in clinical practice. For comparison, ejaculated sperm from males who underwent IVF or ICSI for female infertility were picked up. As a quality control, ejaculated sperm from balanced reciprocal translocation (RcT) carriers were also picked up. Each sperm was karyotyped by next-generation sequencing (NGS) to compare the number of normal haploid sperm and aberrant sperm. Participants/materials, setting, methods Under the ethical review of Yokohama City University and informed consent with patients, we collected human sperm which were discarded after clinical use. Sperm samples were picked up individually by micromanipulation. Following whole-genome amplification (WGA), karyotyping was performed by NGS. For each sperm, if even one of all chromosomes had abnormality, that sperm was counted as aberrant sperm, and if all chromosomes were haploid, it was counted as haploid sperm. Main results and the role of chance We analyzed 10 sperm per patient. Karyotyping analysis was performed on sperm from 2 patients in the RcT group,4 patients in the control group, 4 patients in the OA group, and 5 patients in the NOA group. WGA was successful in 90% (18/20) of RcT carriers group, 95% (38/40) of the control group, 72.5% (29/40) of the OA group, and 92% (46/50) of the NOA group. Acquisition rate of karyotyping was 90% (18/20) of RcT carriers group, 70% (28/40) of the Control group, 65% (26/40) of the OA group, and 95% (46/50) of the NOA group. The results of karyotype analysis showed 28 haploid sperm and no aberrant sperm in the control group, 26 haploid sperm and no aberrant sperm in the OA group, and 39 haploid sperm and 7 aberrant sperm in the NOA group. Karyotyping of sperm from RcT carriers group showed sperm with unbalanced chromosomes derived from translocations of the carriers. The frequency of aberrant karyotype was significantly higher in NOA than control (P = 0.0297). It was also higher in NOA than OA(P = 0.0363). Limitations, reasons for caution In our research, micromanipulation was performed manually to isolate sperm, and the number of sperm that could be analyzed was small. Sperm with good morphology are selected using micromanipulation and analyzed by NGS, so the results do not reflect the results of all sperm actually collected by TESE. Wider implications of the findings In this study, sperm with good morphology were selected by micromanipulation and analyzed, so it is thought that the karyotype of sperm actually reflects the karyotype used in clinical practice. These results suggest that PGT-A is particularly effective in preventing miscarriages among patients whose azoospermia was caused by NOA. Trial registration number not applicable

P-560 Characterization of ploidy level and parental genome inheritance abnormalities in preimplantation human embryos

Abstract Study question Can preimplantation genetic testing (PGT) platforms with integrated genotyping aid the characterization of genome-wide chromosomal abnormalities in human embryos and factors contributing to their occurrence? Summary answer Signatures detected by genotype-criteria-based models in PGT pinpoint origin of haploidy, triploidy and genome-wide uniparental disomy (gwUPD), highlighting recombination deficiencies potentially underpinning these phenomena. What is known already While there is a growing body of knowledge on the frequency and origin of individual chromosome abnormalities, very little is known about genome-wide chromosomal abnormalities in human development. Indeed, genome-wide abnormalities are incompatible with normal human development, making the preimplantation stage the ideal time to characterize them. Novel PGT technologies provide the research and clinical opportunity to characterize both known ploidy-level abnormalities (triploid/haploid) and identify theoretical genome-wide abnormalities undetectable at later stages of development. Study design, size, duration PGT genotyping data from 96660 embryos were used to assess incidence of ploidy-level abnormalities and correlation with potential predisposing clinical factors. Parental origin of putative haploidy and triploidy was assessed on 14 and 41 embryos with parental genotypes available (trios), respectively. For the 41 triploid trios, meiotic origin and recombination rates were also evaluated. A novel genotype-criteria based model to detect theoretical gwUPD and meiotic origin was developed on a semi-contemporaneous 74009 female embryo dataset. Participants/materials, setting, methods PGT was performed with targeted next-generation sequencing, including 5000 genome-wide SNPs. Informative SNPs from trios were used to identify parental origin of haploidy/triploidy. Informative SNPs within 5cM of the centromere were used to evaluate meiotic origin and extended beyond 5cM to identify maternal recombination observing shifts between single (SPH) and biparental (BPH) homologs. gwUPD was predicted when low genome-wide heterozygosity, increased homozygosity in the centromeric region, and decreased similarity to sibling embryos were observed. Main results and the role of chance Genome wide ploidy abnormalities were detected in 1.1% (n = 1.063/96.660; CI 95%: 1-1,2%) of embryos. Haploidy was mainly of paternal origin (n = 12/14), whereas triploidy was exclusively maternal in origin (n = 41/41) and prominently due to meiosis II errors (n = 30/41; 73.2%; 95% CI:57.1-85.8%). Advanced maternal age was positively associated with an increased risk of triploid conceptions (OR = 1.059 per year; p &amp;lt; 0.001). Investigation of maternal recombination rates detected by three consecutive SNPs shifting between SPH and BPH (with a calculated genotyping error of 0.16%) in triploid embryos revealed an outlier group of 7 embryos with statistically lower (P &amp;lt; 0.001) identified crossover events (0-2 events genome-wide) compared to the average 23.7 detectable events genome-wide (SD:4.3). Recombinant gwUPD was predicted in 41 out of 74009 human embryos (0.05%; 95% CI:0.04-0.07%). These embryos showed a high homozygosity in pericentromeric regions, as a proof of each pair of chromosomes being the same parental homolog resulting from a faulty meiosis II, but with detectable heterozygosity regions throughout the rest of the genome, indicating that crossovers occurred between the two parental homologs during prophase I. Multifocal biopsies from the same embryos confirmed the reproducibility of identification of the number of recombination events in triploid embryos and the gwUPD prediction. Limitations, reasons for caution This assay genotypes only a portion of the genome and underestimation of recombination events is possible. Our current detection of gwUPD is limited to recombinant uniparental isodisomy of MII origin only. Therefore, the exact prevalence of these abnormal gwUPD configurations requires further understanding and analysis. Wider implications of the findings Genotyping in routine PGT can identify severe genome-wide abnormalities with associated gestational complications that would otherwise go undiagnosed. Comprehensive characterization of these abnormalities is not possible at later stages of development. Therefore, PGT offers a unique opportunity to delve into their biological origin and identify novel biomarkers for embryo competence. Trial registration number not applicable

Management of Cerebellopontine Angle Tumors

Abstract Background Cerebellopontine angle (CPA) tumors are the most common neoplasms in the posterior fossa. Most CPA tumors are benign, with 80-94% being vestibular schwannomas (acoustic neuromas), lipomas, vascular malformations, and hemangiomas. Treatment options include observation, radiosurgery, and microsurgery. Aim and Objectives Evaluation of the clinical presentation of various lesions in the Cerebellopontine Angle area and evaluate the different surgical approaches for management of these lesions. Subjects and Methods The study included cases of CPA tumors that were admitted and treated in the neurosurgical departments in Ain Shams University Hospital as well as Al Galaa Armed Forces Hospital and Al Maadi Armed ForcesHospital. Result Abnormal planter response were the most frequent neurological abnormality (72.0%). The most cranial nerve affected was the vestibulocochlear nerve (60.0%). Conclusion CPA tumors are challenging lesions to be treated surgically, which requires a high level of surgical experience. Retrosigmoid and middle fossa approaches accomplished significant outcome among patients with CPA tumors. Preoperative V-P shunt procedure improved noticeably the manifestations of increased intracranial tension.

Overview of the Use of Oralit and Zinc in Children with Diarrhea at the Community Health Center

Diarrhea is still one of the main problems can cause illness and death, especially in children. Diarrhea is an infectious disease caused by bacteria, virus or other microorganism which is characterized by abnormal frequency of defecation, 3 or more times in 24 hours with a soft feces consistency, the presence or absence of blood or foam in the feces. Giving oralit and zinc can reduce the incidence of diarrhea in children. The aim of this study was to determine the description of the use oralit and zinc in children suffering from diarrhea at the kawatuna Community Health Center during the peroid October 2022-March 2023. Method of this study is retrospective descriptive using secondary data, namely prescription sheets for pediatric patients with diarrhea who received oralit and zinc therapy. The research results showed that the population of diarrhea cases was 125 and the sample used was 96 cases. The highest use of oralit and zinc for treating casess of diarrhea is in October 2022 and the least in March 2023. The age of children most a affected by diarrhea is 1-6 months (50%) and the age least affected by diarrhea is 12-17 years (7,3%).

Acute exposure of zebrafish (Danio rerio) adults to psychotria carthagenensis leaf extracts: chemical profile, lack of genotoxicity and histological changes

Psychotria carthagenensis is a shrubby plant, often consumed by traditional populations in religious rituals. Previous studies have shown that this plant’s infusion can inhibit the activity of Acetylcholinesterase (AChE) in rats. Despite the therapeutic potential, there is a lack of research regarding its possible toxicological and genotoxic effects. Hence, this study aimed to analyze the chemical profile of the ethanol extract from P. carthagenensis leaves by LC-DAD-MS and assess its possible toxicity and genotoxicity in zebrafish (Danio rerio). Adult zebrafish (N = 9/group) were exposed at different concentrations and the LC50 was calculated. Frequencies of micronucleus (MN) and nuclear abnormalities (NA) were estimated for genotoxic effects, and degree of tissue changes (DTC) was used to assess the liver and gill histopathology. From the LC-DAD-MS analyses, the identified compounds included N-fructosyl valine, ethyl hexoside, 5-O-E-caffeoylquinic acid, N-feruloylagmatime, roseoside, di-O-deoxyhexoyl-hexosyl quercetin, loiolide, and oleamide. The calculated values of LC50 did not vary significantly during the time of exposure. At the concentrations of 1.25, 2.5, 3.75, 5, 7.5, 10 and 15 mg/L, there was no genotoxicity, and only low to moderate toxicity for the tissues was observed, despite mortality of 100% at doses of 20–100 mg/L of P. carthagenensis ethanolic leaf extract. There were changes in cytoplasm of hepatocytes at 1.25 mg/L, and karyorrhexis, karyolysis and megalocytosis at 10 mg/L. In the gills, the alterations were primary lamellar hyperplasia in all concentrations, and at 10 mg/L, secondary lamellar edema and vascular hyperemia were common. Additionally, the chemical composition of P. carthagenensis was expanded.

The Spectrum of Echocardiographic Findings Across Stages I-V of Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. This study aimed to assess the frequency of cardiac abnormalities across different stages of CKD, providing insights into the relationship between renal dysfunction and cardiac abnormalities. A cross-sectional observational study was conducted at Lahore General Hospital's Nephrology Department, enrolling 356 non-dialysis CKDpatients (stages I-V) over one year. Participants aged 18-65 years with CKD duration of three months or more were included. Exclusion criteria encompassed dialysis dependency, transplantation, acute kidney injury, and various cardiac conditions. Detailed echocardiographic evaluation of cardiac structure and function was noted. This study included 356 patients with CKDacross stages I-V, with the majority in stages III (44.7%) and IV (36.5%). Significant variations were observed in age (p<0.000), hypertension prevalence (p=0.004), and smoking status. Haemoglobin, calcium, and phosphate levels differed significantly across stages (p<0.001). Echocardiographic findings revealed significant differences: left ventricular hypertrophy frequency increased from 12.5% in stages I-II to 60.0% in stage V (p=0.001); diastolic dysfunction worsened, with grades 2-3 dysfunction increasing from 6.2% in stages I-II to 51.4% in stage V (p=0.000); systolic dysfunction increased with reduced ejection fraction (<45%) more common in advanced stages (p=0.000); global longitudinal strain worsened from -18.47% to -15.34% (p=0.000); left atrial volume index and pulmonary hypertension also increased significantly (p=0.049). This study demonstrates a significant correlation between the progression of CKDand the severity of echocardiographic abnormalities. As CKD advances, structural and functional cardiac abnormalities increase, underscoring the importance of early cardiac evaluation and intervention to improve cardiovascular outcomes in non-dialysis-dependent CKD patients.

Myomectomy: Choosing the Surgical Approach - A Systematic Review.

Myomectomy has evolved from open laparotomy to laparoscopy, hysteroscopy, VNOTES and robotic myomectomy. The surgical approach in doing myomectomy depends on the type and location of the myoma and the surgeon's expertise. Minimally invasive surgery has been the preferred approach due to the benefit of shorter hospital stay, lesser postoperative pain, earlier recovery, minimal blood loss and the cosmetic appearance of the scar. The success of this procedure depends on the incision technique, enucleation, and blood loss prevention by using hemostatic techniques and suturing techniques. Performing myomectomy for a large uterine myoma is a laparoscopic challenge; however, with the use of Lee-Huang point (midpoint between umbilicus and xiphoid) as the primary insertion and camera port, one can easily navigate thru the abdominal cavity in case the uterus is huge obscuring the umbilical port. Laparoscopic Myomectomy can be safely and efficiently performed by experienced laparoscopic surgeons regardless of myoma size, number and location. Removal of large myoma specimen from the abdominal cavity through the laparoscope became a challenge after the use of power morcellator was abandoned. To overcome this problem, the large myoma is placed inside an Endo bag and its edges brought extracorporeally through the port site. The myoma is incised in a C-manner using a scalpel to reduce the size. Myoma can also be removed using in-bag power morcellation. Fertility preservation is the long-term aim of doing myomectomy instead of hysterectomy in the management of leiomyoma aside from alleviating symptoms of abnormal uterine bleeding, urinary frequency and abdominal pain.

Prevalence of Fluorosis in Endemic Area of Sonebhadra, Uttar Pradesh: A Pilot Epidemiological Survey

Abstract Background: A long-term excess of fluoride ingestion from drinking water, food substances, and industrial pollution may result in fluorosis, a public health hazard. This survey aims to investigate the prevalence of dental and skeletal fluorosis, as well as the role of dietary variables. Materials and Methods: A cross-sectional survey was conducted in Sonebhadra district. The Dean’s Fluorosis Index and physical exercises demonstrated by the United Nations International Children’s Emergency Fund for diagnosing dental and skeletal fluorosis, respectively. The dietary habits of the participants were ascertained using a prevalidated questionnaire. Results: The participants’ socioeconomic status varied widely with heterogeneity. The frequent abnormalities found were genu varum (21.5%), genu valgum (6.8%), dental fluorosis (52.3%), and skeletal fluorosis (25.8%). Consequently, eight cases reported of multiple deformities. Conclusion: The findings showed the increased prevalence of moderate-to-severe fluorosis in fluoride endemic areas of Sonebhadra district. Dental fluorosis was more common in those aged 18–64 years, particularly in males, but skeletal fluorosis increased with age.

Selection based on the Breeding Soundness Evaluation is associated with the improvement of the reproductive quality of young Nellore bulls

Breeding soundness evaluation (BSE) is the best methodology to estimate the fertility potential of future bulls and performing indirect selection for their fertility. However, the outcome of the BSE is influenced by several factors, including genetics, environment, and BSE guidelines. Herein, in this retrospective study, our first aim was to characterize the reasons for failure in 46,566 BSE from 2-year-old beef Bos indicus bulls (Nellore) born from 1997 to 2018. Our second aim was to determine whether or not BSE was associated with reproductive potential improvement of the bulls over the years. Due to changes in the BSE criteria, we used the same dataset, but only bulls born from 2002 to 2018 were included resulting in 35,856 BSE. For the second aim, the effect of the year and farm were included in the model of the multivariate logistic regression. We also determined if the main reasons for BSE failure decreased over time. Bulls were classified as approved (satisfactory potential breeders and qualified for natural breeding service) and not approved (deferred and unsatisfactory potential breeders). The reasons for BSE failure in Nellore bulls were poor semen quality (53.1 %) and physical defects (46.9 %), with the main physical defect being testis abnormalities (19.7 %). The overall percentage of bulls approved each year was 87.1 %, with no improvement over the years of study. However, the percentage of approved bulls at the first BSE increased over the years (P < 0.05). This increase was evident by a reduction in the difference between the overall percentage of the bulls approved vs the percentage of bulls approved at the first BSE. Furthermore, there was an increase in the percentage of bulls classified as satisfactory potential breeders in the BSE and an evident decrease in the percentage of bulls qualified only for natural breeding service (P < 0.05). In addition, an increase of the scrotal circumference (SC) of the herd was found (P < 0.05). These results indicate the overall quality of the bulls improved over the years. To associate and identify the main sperm abnormalities, 3461 not approved bulls were clustered. The most frequent defects were strongly coiled tail spermatozoa, proximal droplets, and acrosomal defects. Overall, there was no change in the frequency of bulls not approved by the sperm morphology nor the frequency of the main sperm abnormalities over the years. Nevertheless, the frequency of the defects remained very low, implying they were controlled. Additionally, abnormalities in the testis decreased over the years and was associated with the increase in the SC of the herd and a decrease of culled bulls due to low SC. In conclusion, this study demonstrates that there is an association between implementation and use of BSE with improvements in the reproductive quality of future generation bulls.

Relevance of repeated analyses of albuminuria and glomerular filtration rate in African children with sickle cell anaemia.

Glomerular hyperfiltration and albuminuria are frequent kidney abnormalities in children with sickle cell anaemia (SCA). However, little is known about their persistence in African SCA children. This prospective study included 600 steady-state SCA children aged 2-18 years from the Democratic Republic of Congo. Participants were genotyped for apolipoprotein L1 (APOL1) risk variants (RVs) and haem oxygenase-1 (HMOX1) GT-dinucleotide repeats. Kidney abnormalities were defined as albuminuria, hyperfiltration or decreased estimated creatinine-based glomerular filtration rate (eGFRcr). At baseline, 247/600 (41.2%) participants presented with kidney abnormalities: 82/592 (13.8%) with albuminuria, 184/587 (31.3%) with hyperfiltration and 15/587 (2.6%) with decreased eGFRcr. After a median follow-up of 5 months, repeated testing was performed in 180/247 (72.9%) available participants. Persistent hyperfiltration and persistent albuminuria (PA) were present in 29.2% (38/130) and 39.7% (23/58) respectively. eGFR normalized in all participants with a baseline decreased eGFRcr. Haemoglobinuria (p = 0.017) and male gender (p = 0.047) were significantly associated with PA and persistent hyperfiltration respectively. APOL1 RVs (G1G1/G2G2/G1G2) were borderline associated with PA (p = 0.075), while HMOX1 long repeat was not associated with any persistent kidney abnormality. This study reveals that a single screening can overestimate the rate of kidney abnormalities in children with SCA and could lead to overtreatment.

Identifying significant structural factors associated with knee pain severity in patients with osteoarthritis using machine learning

Our main objective was to use machine learning methods to identify significant structural factors associated with pain severity in knee osteoarthritis patients. Additionally, we assessed the potential of various classes of imaging data using machine learning techniques to gauge knee pain severity. The data of semi-quantitative assessments of knee radiographs, semi-quantitative assessments of knee magnetic resonance imaging (MRI), and MRI images from 567 individuals in the Osteoarthritis Initiative (OAI) were utilized to train a series of machine learning models. Models were constructed using five machine learning methods: random forests (RF), support vector machines (SVM), logistic regression (LR), decision tree (DT), and Bayesian (Bayes). Employing tenfold cross-validation, we selected the best-performing models based on the area under the curve (AUC). The study results indicate no significant difference in performance among models using different imaging data. Subsequently, we employed a convolutional neural network (CNN) to extract features from magnetic resonance imaging (MRI), and class activation mapping (CAM) was utilized to generate saliency maps, highlighting regions associated with knee pain severity. A radiologist reviewed the images, identifying specific lesions colocalized with the CAM. The review of 421 knees revealed that effusion/synovitis (30.9%) and cartilage loss (30.6%) were the most frequent abnormalities associated with pain severity. Our study suggests cartilage loss and synovitis/effusion lesions as significant structural factors affecting pain severity in patients with knee osteoarthritis. Furthermore, our study highlights the potential of machine learning for assessing knee pain severity using radiographs.

A homozygous ARMC3 splicing variant causes asthenozoospermia and flagellar disorganization in a consanguineous family.

Male infertility due to asthenozoospermia is quite frequent, but its etiology is poorly understood. We recruited two infertile brothers, born to first-cousin parents from Pakistan, displaying idiopathic asthenozoospermia with mild stuttering disorder but no ciliary-related symptoms. Whole-exome sequencing identified a splicing variant (c.916+1G>A) in ARMC3, recessively co-segregating with asthenozoospermia in the family. The ARMC3 protein is evolutionarily highly conserved and is mostly expressed in the brain and testicular tissue of human. The ARMC3 splicing mutation leads to the exclusion of exon 8, resulting in a predicted truncated protein (p.Glu245_Asp305delfs*16). Quantitative real-time PCR revealed a significant decrease at mRNA level for ARMC3 and Western blot analysis did not detect ARMC3 protein in the patient's sperm. Individuals homozygous for the ARMC3 splicing variant displayed reduced sperm motility with frequent morphological abnormalities of sperm flagella. Transmission electron microscopy of the affected individual IV: 2 revealed vacuolation in sperm mitochondria at the midpiece and disrupted flagellar ultrastructure in the principal and end piece. Altogether, our results indicate that this novel homozygous ARMC3 splicing mutation destabilizes sperm flagella and leads to asthenozoospermia in our patients, providing a novel marker for genetic counseling and diagnosis of male infertility.