Significant Abnormalities Research Articles

Assessment of Birth Weight Parameters in Sverdlovsk Region: Preliminary Results

Aim. To define median and large-for-gestational-age birth weight in Sverdlovsk Region and to compare them with the results of a population study conducted in Central Europe.Materials and Methods. We conducted a retrospective analysis of 41,745 women. Inclusion criteria were singleton, full-term pregnancy, absence of fetal malformations, and delivery in a licensed medical organization. Exclusion criteria were multiple pregnancy, signs of chromosomal abnormalities during the antenatal development, congenital malformations, and incomplete examination according to the standard used for normal pregnancy. The results were compared with a similar study carried out in Central Europe.Results. The median weight of newborns at 37, 38, 39, 40, and 41 weeks was 3010, 3180, 3350, 3490, and 3600 g, respectively. “Large for gestational age” (above the 90th percentile) weight at 37, 38, 39, 40, and 41 weeks was 3550, 3720, 3900, 4020, and 4150 g, respectively. These parameters were significantly lower than those in Central Europe. Reproductive age, parity, and metabolic disorders were significant population determinants of birth weight.Conclusion. Birth weight parameters in Sverdlovsk Region differ from those in Central Europe, requiring further research. These data might be used for the correct assessment of the newborns and for development of a territorial strategy for the prevention of fetal growth disorders.

Clinical Analysis and Red Flag Signs in Pediatric Headache According to Age

Purpose: The clinical characteristics of headaches vary by age among pediatric patients. Red flag signs are key factors in differentiating secondary headaches and should be considered in the context of the patient’s age.Methods: This study involved a retrospective chart review of pediatric patients presenting with headaches. Patients were categorized by age into three groups: pre-school age (under 6 years), school-age (6 to 12 years), and adolescence (over 12 years). Demographic data, headache characteristics, laboratory findings, and neuroimaging results were evaluated. Overall, 17 potential red flags were assessed.Results: A total of 687 patients were included, of whom 102 were of pre-school age, 314 were school-aged, and 271 were adolescents. The frequency of overweight/obesity was found to increase with age. The pre-school age group experienced a shorter period from symptom onset to presentation and a briefer duration of pain. In contrast, adolescents displayed a longer period from symptom onset, a greater frequency of headaches occurring at least three times per week, and a higher rate of headache episodes lasting over 3 days. Children under 6 years old were more commonly diagnosed with secondary headaches than older children. Across age groups, secondary headaches were suspected when systemic symptoms such as fever were present, when the headache had a sudden onset, when the patient responded poorly to medication, or when abnormal neurological signs and symptoms were observed.Conclusion: The clinical features of pediatric patients vary by age group. Clinicians should consider red flag signs in the context of patient age and individual characteristics.

Abstract 6719: TriTCE Co-Stim: A next generation trispecific T cell engager platform with integrated CD28 costimulation, engineered to improve responses in the treatment of solid tumors

Abstract Bispecific T cell engagers (TCEs) have exhibited clinical successes in the treatment of hematological cancers, while treatment of solid tumors remains a challenge. Treatment of solid tumors with conventional CD3-engaging TCEs can result in limited T cell proliferation and recruitment to the tumor site, and treatment related T cell anergy, thus restricting the ability of bispecific TCEs to inhibit growth of these poorly infiltrated tumors and rapidly growing tumors. Next generation tumor-targeting, trispecific T cell engagers with integrated costimulation (TriTCE Co-Stim) have the potential to provide more durable responses and re-invigorate T cell responses by mediating integrated signaling through CD3 (signal 1) and co-stimulation through CD28 (signal 2). Superagonist anti-CD28 antibodies activate T cells but resulted in clinical toxicities with severe cytokine release syndrome (CRS). Therefore, achieving a balance between signal 1 and 2 is critical for optimal T cell activation and proliferation. Using our AzymetricTM and EFECTTM platforms, we generated heterodimeric TriTCE Co-Stim antibody formats with various geometries and affinities to optimize T cell response and widen the therapeutic window for the treatment of solid tumors. We have previously described screening and interrogation of different TriTCE Co-stim formats and paratope affinities, and the selection of a lead format with optimized CD3 and CD28 T cell activation. Here, we have further expanded our validation of the TriTCE Co-stim platform with our lead CLDN18.2 TriTCE co-stim format, to include a tolerability assessment in nonhuman primates.Our lead TriTCE Co-Stim format exhibited a favorable safety profile in vitro and mediated target-dependent induction of T cell activity, with enhanced proliferation, survival, and T cell-mediated cytotoxic potency compared to bispecific TCEs. In a predictive in vivo model of CRS, our lead TriTCE Co-Stim did not exhibit systemic toxicity or peripheral cytokine release. TriTCE Co-Stim mediated enhanced tumor growth regression in vivo with an increase of T cells within the tumor and no increase of T cells within the periphery. Repeat doses of the lead TriTCE Co-Stim molecule at 3 mg/kg were well-tolerated in nonhuman primates with no abnormal clinical signs. Minor decreases in body weight and food consumption were observed. Clinical pathology changes were consistent with a mild systemic inflammatory response. In summary, our lead TriTCE co-stim molecule has enhanced target-dependent antitumor activity vs. bispecific benchmarks and is tolerated a murine CRS model and repeat dose non-human primate study. These data suggest TriTCE Co-stim may provide tolerable and more durable antitumor responses and contribute to improved clinical outcomes. Citation Format: Lisa Newhook, Purva Bhojane, Kurt Stahl, Nichole E. Escalante, Peter Repenning, Diego Perez Escanda, Polly Shao, Maya C. Poffenberger, Alec Robinson, Kesha Patel, Alexandra Livernois, Chayne L. Piscitelli, Nicole Afacan, Paul A. Moore, Nina E. Weisser, Thomas Spreter von Kreudenstein. TriTCE Co-Stim: A next generation trispecific T cell engager platform with integrated CD28 costimulation, engineered to improve responses in the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6719.

Burden and risk profile of acute kidney injury in severe COVID-19 pneumonia admissions: a Finding from Jimma University medical center, Ethiopia

Background Acute kidney injury (AKI) is a serious complication of the Corona Virus Disease of 2019 (COVID-19). However, data on its magnitude and risk factors among hospitalized patients in Ethiopia is limited. This study aimed to determine the magnitude of AKI and associated factors among patients admitted for severe COVID-19 pneumonia.Methods An institution-based retrospective cross-sectional study was conducted among 224 patients admitted to Jimma University Medical Center in Ethiopia for severe COVID-19 pneumonia from May 2020 to December 2021. Systematic random sampling was used to select study participants. Medical records were reviewed to extract sociodemographic, clinical, laboratory, therapeutic, and comorbidity data. Bivariable and multivariable logistic regressions were performed to examine factors associated with AKI. The magnitude of the association between the explanatory variables and AKI was estimated using an adjusted odds ratio (AOR) with a 95% confidence interval (CI), and significance was declared at a p-value of 0.05.ResultsThe magnitude of AKI was 42% (95% CI: 35.3–48.2%) in the study area. Mechanical ventilation, vasopressors, and antibiotics were required in 32.6, 3.7, and 97.7% of the patients, respectively. After adjusting for possible confounders, male sex (AOR 2.79, 95% CI: 1.3–6.5), fever (AOR 6.5, 95% CI: 2.7–15.6), hypoxemia (AOR 5.1, 95% CI: 1.4–18.9), comorbidities (AOR 2.8, 95% CI: 1.1–7.0), and severe anemia (AOR 10, 95% CI: 1.7–65.7) remained significantly associated with higher odds of AKI.ConclusionThe burden of AKI among patients with severe COVID-19 pneumonia is high in our setting. Male sex, abnormal vital signs, chronic conditions, and anemia can identify individuals at increased risk and require close monitoring and prevention efforts.

Integrative Assessment of Cardiopulmonary Fitness Using Cardiopulmonary Exercise Test With Supine Bicycle Echocardiography in Patients Presenting Dyspnea.

Cardiopulmonary exercise test (CPET) with supine bicycle echocardiography (SBE) enables comprehensive physiologic assessment during exercise. We characterized cardiopulmonary fitness by integrating CPET-SBE parameters and evaluated its prognostic value in patients presenting with dyspnea. We retrospectively reviewed 473 consecutive patients who underwent CPET-SBE for dyspnea evaluation. A dimensionality reduction process was applied, transforming 24 clinical and CPET-SBE parameters into a 2-dimensional feature map, followed by patient clustering based on the data distribution. Clinical and exercise features were compared among the clusters in addition to the 5-year risk of clinical outcome (a composite of cardiovascular death and heart failure hospitalization). Maximum exercise effort (R >1) was achieved in 95% of cases. Through dimensionality reduction, 3 patient clusters were derived: Group 1 (n=157), 2 (n=104), and 3 (n=212). Median age and female proportion increased from Group 1 to 2, and 3, although resting echocardiography parameters showed no significant abnormalities among the groups. There was a worsening trend in the exercise response from Group 1 to 2 and 3, including left ventricular diastolic function, oxygen consumption, and ventilatory efficiency. During follow-up (median 6.0 [1.6-10.4] years), clinical outcome increased from Group 1 to 2 and 3 (5-year rate 3.7% versus 7.0% versus 13.0%, respectively; log-rank P=0.02), with higher risk in Group 2 (hazard ratio, 1.94 [95% CI, 0.52-7.22]) and Group 3 (3.92 [1.34-11.42]) compared with Group 1. Comprehensive evaluation using CPET-SBE can reveal distinct characteristics of cardiopulmonary fitness in patients presenting with dyspnea, potentially enhancing outcome prediction.

Emergency Department Sepsis Triage Scoring Tool Elements Associated With Hypotension Within 24 Hours in Children With Fever and Tachycardia.

Pediatric sepsis screening is becoming the standard of care for children presenting to the emergency department (ED) and has been shown to improve recognition of severe sepsis, but it is unknown if these screening tools can predict progression of disease. The objective of this study was to determine if any elements of a sepsis triage trigger tool were predictive of progression to hypotensive shock in children presenting to the ED with fever and tachycardia. This study is a retrospective case-control study of children ≤18 years presenting to an ED with fever and tachycardia, comparing those who went on to develop hypotensive shock in the subsequent 24 hours (case) to those who did not (control). Primary outcome was the proportion of encounters where the patient had specific abnormal vital signs or clinical signs as components of the sepsis triage score. The secondary outcomes were the proportion of encounters where the patient had a sepsis risk factor. During the study period, there were 94 patients who met case criteria and 186 controls selected. In the adjusted multivariable model, the 2 components of the sepsis triage score that were more common in case patients were the presence of severe cerebral palsy (adjusted odds ratio, 9.4 [3.7, 23.9]) and abnormal capillary refill at triage (adjusted odds ratio, 3.1 [1.4, 6.9]). Among children who present to a pediatric ED with fever and tachycardia, those with prolonged capillary refill at triage or severe cerebral palsy were more likely to progress to decompensated septic shock, despite routine ED care.

Thirty-eight cases of paraovarian cysts in children and adolescents: a retrospective study.

Paraovarian cysts in children and adolescents can be challenging to accurately diagnose prior to surgery. Our objective is to outline the clinical characteristics of paraovarian cysts and enhance the precision of diagnosing paraovarian cysts in this age group. We retrospectively analyzed all patients with paraovarian cysts who underwent surgery in our department from 2013 to 2021. The review focused on demographic characteristics, clinical manifestations, intraoperative findings, and postoperative pathology of these patients. This cohort was composed of 38 children with paraovarian cysts. The average diameter of the cysts was 4.8cm (range 0.5-10cm). Among the cases, 25 (65.8%) had adnexal torsion. Postoperative pathology showed that all cases were simple cysts with serous fluid. After the procedure, the patients were monitored for a period ranging from 12 to 108 months. B-ultrasound and physical examination did not reveal any significant abnormalities. B-ultrasound can help diagnose paraovarian cysts by detecting slight deviation movement between the cyst and the uterus. The presence of adnexa torsion in children and adolescents with paraovarian cysts does not depend on BMI, but rather on the size of cysts. Laparoscopic cyst removal has proven to be an effective surgical approach with favorable outcomes.

Safety and performance of a novel subxiphoidal pacemaker system.

Traditional cardiac pacemakers commonly have a range of complications related to the presence of intracardiac leads. A new class of extravascular and leadless pacemakers has recently emerged with the potential to mitigate these complications and expand access to cardiac pacing. The objective of this study is to evaluate the implantation, short-term chronic safety, and performance of a novel subxiphoidal extracardiac pacemaker. Normal Yorkshire Cross swine (n = 16) were implanted with the subxiphoidal pacemaker. The pacemaker was inserted through a midline chest incision and clipped to the underside of the sternum, with the stimulation electrode placed on the anterior pericardium. Animals were chronically paced and followed for 90days post-implant, with periodic measurement of pacing capture threshold (PCT) and electrode impedance. All 16 animals were successfully implanted with the study device. At implant, a consistent average PCT of 2.2 ± 0.4V at a pulse width of 1.0ms was observed in all animals, with an average implant impedance of 648 ± 44 Ω. Chronic pacing was programmed at a rate of 60bpm, an amplitude of 3.4 ± 0.7V, and a pulse width of 1.0ms. PCT rose to 4.6 ± 0.8V at 14days and stabilized; at 90days, PCT was 3.8 ± 1.2V and electrode impedance was 533 ± 105 Ω. All implanted animals completed the study with no clinically significant findings, no clinically significant abnormalities, and with no adverse events that affected animal welfare. This study demonstrated the safety and feasibility of a novel subxiphoidal extracardiac pacemaker to deliver short-term chronic extravascular therapy. Further studies are required to assess the safety, feasibility, and long-term chronic pacing performance in human subjects.

Dynamics of Right Ventricle Pressure During Stress Echocardiography in Patients with Heart Failure with Preserved Ejection Fraction

Shortness of breath during physical exertion is a non-specific symptom that can hide such potentially dangerous diseases as structural or functional bronchopulmonary, coronary heart disease, structural cardiac disease, but the frequent cause is left ventricle diastolic dysfunction due to its significant hypertrophy. Pathogenetic mechanisms leading to this symptom require detailed study for the possibility of a comprehensive approach in the treatment of such patients with the aim of maximally improving their prognosis and quality of life. Objective — evaluate changes in right ventricle systolic pressure during stress echocardiography in patients with LV myocardial hypertrophy and clinical manifestations of heart failure, search for other mechanisms leading to clinical symptoms. Materials and methods. The study included 49 patients with shortness of breath during physical exertion, who underwent further diagnostic examination after exclusion of coronary stenotic lesions by invasive coronary and ventricular angiography. Patients were excluded from bronchopulmonary pathology using spirometry and chest radiography, structural heart pathology using echocardiography, microvascular angina using echocardiography with intravenous dipyridamole infusion, and the change in systolic pressure in the right ventricle was investigated using echocardiography during a physical exercise test. Results and discussion. There were no cases of infiltrative lung changes, signs of emphysema, or other manifestations of significant pathology according to X-ray data. Spirometry also showed the absence of significant functional abnormalities. Echocardiography revealed significant hypertrophy of LV myocar­dium (thickness of IVS — on average (14.1 ± 0.5) mm, posterior wall thickness — on average (13.5 ± 0.3) mm) with the presence of LV diastolic dysfunction and echocardiographic signs of increased end-diastolic pressure in the LV, which was confirmed invasively during coronary and ventricular angiography. In 9 (18.4 %) cases, heart wall thickening was due to hypertrophic cardiomyopathy according to cardiac MRI, these patients had LV outflow tract obstruction and mild pulmonary hypertension at rest. Conducting strain imaging showed the presence of signs of myocardial ischemia (segmental contractility disorder) with varying degrees of severity (from 1 to 5 segments), which spread to the IVS, the apex of the heart and, less often, to the anterior wall of the LV. All patients experienced an increase in pulmonary artery systolic pressure during exercise, on average, from (37.4 ± 2.1) to (47.1 ± 1.6) mm Hg. Conclusions. The pathogenic mechanism underlying shortness of breath in patients with LV myocardial hypertrophy involves transient pulmonary hypertension occurring during exercise due to left ventricular diastolic dysfunction. Another contributing factor is the development of myocardial ischemia during physical exertion, which, in the absence of coronary stenosis and microvascular angina, is attributed to inadequate supply of coronary blood flow volume velocity relative to the significant left ventricular hypertrophy.

CD19-CAR-DNT cells (RJMty19) in patients with relapsed or refractory large B-cell lymphoma: a phase 1, first-in-human study

Current approved chimeric antigen receptor (CAR) T-cell products are autologous cell therapies that are costly and poorly accessible to patients. We aimed to evaluate the safety and antitumor activity of a novel off-the-shelf anti-CD19 CAR-engineered allogeneic double-negative T cells (RJMty19) in patients with relapsed/refractory large B-cell lymphoma. We report the results from a first-in-human, open-label, single-dose, phase 1 study of allogeneic CD19-specific CAR double-negative T (CAR-DNT) cells. Eligibility criteria included the presence of measurable lesions, at least 2 lines of prior immunochemotherapy, and an ECOG score of 0-1. We evaluated four dose levels (DL) of RJMty19 in a 3+3 dose-escalation scheme: 1×106, 3×106, 9×106 and 2×107 CAR-DNT cells per kilogram of body weight. All patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The primary endpoints were dose-limiting toxicities (DLTs), incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of standard cellular pharmacokinetic parameters, immunogenicity, objective response rates (ORR), and disease control rate (DCR) per Lugano 2014 criteria. A total of 12 patients were enrolled between 22 July 2022 and 27 July 2023. Among these patients, 66% were classified as stage IV, 75% had an IPI score of 3 or higher, representing an intermediate risk or worse. The maximum tolerated dose was not reached because no DLT was observed. Four patient experienced grade 1 or 2 cytokine release syndrome and dizziness. The most common AEs were hematologic toxicities, including neutropenia (N=12, 100%), leukopenia (N=12, 100%), lymphopenia (N=10, 83%), thrombocytopenia (N=6, 50%), febrile neutropenia (N=3, 25%), and anemia (N=3, 25%). Seven subjects died till the cut-off date, five of them died of disease progression and two of them died of COVID 19. In all patients (N=12), the ORR was 25% and CRR was 8.3%. DL1 and DL2 patients benefited less from the therapy (ORR: 17%, N=1; DCR: 33%, N=2). However, all DL3 patients achieved disease control (N=3, 100%), and all DL4 patients achieved objective response (N=3, 100%). Our results demonstrate that CD19-CAR-DNT cells appear to be well tolerated with promising antitumor activity in LBCL patients. Further study of this product with a larger sample size is warranted. This phase 1 study is registered on clinicaltrials.gov (NCT05453669). Wyze Biotech. Co., Ltd.

Antenatally detected urinary tract dilatation: a pediatric nephrologist's point of view

Antenatally diagnosed urinary tract dilatation (UTD), previously referred to as antenatal hydronephrosis, is the most commonly detected abnormality by prenatal ultrasonography. Several grading systems have been developed for the classification of antenatal UTD using prenatal and postnatal ultrasonography. UTD comprises a wide variety of congenital abnormalities of the kidney and urinary tract ranging from transient UTD to more significant abnormalities such as vesicoureteral reflux, ureteropelvic junction obstruction, ureterocele, ureterovesical junction obstruction, posterior urethral valves, and non-refluxing megaureter. Optimizing the evaluation of antenatally detected UTD is essential to recognize children with important disorders while avoiding excessive investigations. Conservative approach with close follow-up is increasingly accepted as an appropriate treatment option for patients with asymptomatic vesicoureteral reflux and ureteropelvic junction obstruction in recent years. However, predicting permanent kidney damage in an unselected group of children with antenatal UTD is still challenging. The management and follow-up of children with UTD should be individualized based on recommendations from a pediatric nephrologist, a pediatric urologist, or both. Future research directed at predicting long-term outcomes of children diagnosed with UTD from mild findings to severe disease is needed to refine management for those at higher risk of kidney disease progression.

Beyond numbers: integrating qualitative analysis into quantitative sensory testing for neuropathic pain.

This article investigates the benefits of adopting qualitative and quantitative sensory testing (QQST) in sensory assessment, with a focus on understanding neuropathic pain. The innovative QQST method combines participant qualitative experiences with quantitative psychophysical measurements, offering a more varied interpretation of sensory abnormalities and normal sensory function. This article also explores the steps for the optimization of the method by identifying qualitative signs of sensory abnormalities and standardizing data collection. By leveraging the inherent subjectivity in the test design and participant responses, the QQST method contributes to a more holistic exploration of both normal and abnormal sensory experiences. This article positions the QQST approach as a foundational element within the Sensory Evaluation Network, uniting international experts to harmonize qualitative and quantitative sensory evaluation methods.

Antagonistic Effect of Zinc Oxide Nanoparticles Dietary Supplementation Against Chronic Copper Waterborne Exposure on Growth, Behavioral, Biochemical, and Gene Expression Alterations of African Catfish, Clarias gariepinus (Burchell, 1822).

The harmful impact of waterborne copper (Cu) as a common abiotic stressor in aquatic environments has gained much more interest. The present study aimed to investigate the utilization of zinc oxide nanoparticles (ZnONPs) dietary supplementation to mitigate the chronic toxicity of Cu in African catfish (Clarias gariepinus). Two hundred and forty fish (92.94 ± 0.13 g) were assigned into six groups for 60 days. Control (C), ZnONPs20, and ZnONPs30 groups were fed on basal diets fortified with 0, 20, and 30 mg kg-1 ZnONPs without Cu exposure. Cu, Cu + ZnONPs20, and Cu + ZnONPs30 groups were exposed to Cu at a dose of 10mg L-1 and fed on basal diets fortified with 0, 20, and 30 mg kg-1 ZnONPs, respectively. The results revealed that the Cu-exposed fish experienced abnormal clinical signs and behavioral changes. The growth indices and acetylcholine esterase activity were significantly decreased (P < 0.05) in the Cu group. Meanwhile, hepatorenal and serum stress indices (P < 0.05) were significantly elevated with chronic Cu exposure. In addition, a higher expression of stress (P < 0.05) (heat shock protein 60 and hypoxia-inducible factor-1 alpha) and apoptotic-related genes (C/EBP homologous protein, caspase-3, and Bcl-2 Associated X-protein) with down-regulation (P < 0.05) of the anti-apoptotic-related genes (B-cell lymphoma 2 and proliferating cell nuclear antigen) was noticed in the Cu-exposed fish. Histopathological alterations in the gills, liver, kidney, and spleen were markedly reported in the Cu-exposed group. The dietary supplementation with ZnONPs significantly alleviated the negative impacts of chronic waterborne-Cu exposure on growth performance, physiological changes, gene expression, and tissue architecture, especially at 30 mg kg-1 diet level. In particular, the inclusion of ZnONPs at the 30 mg kg-1 diet level produced better outcomes than the 20 mg kg-1 diet. Overall, ZnONPs could be added as a feed supplement in the C. gariepinus diet to boost the fish's health and productivity and alleviate the stress condition brought on by Cu exposure.

Acute toxicity and genotoxicity evaluation of irradiated ophiopogonis radix at 25 kGy with electron beam

As concerned about the potential risks of irradiated Ophiopogonis Radix (IOR) at a high radiation level (25 kGy) by high-energy electron beam irradiation, this study evaluated oral acute toxicity and genotoxicity of IOR. Moisture, total ash, water-soluble extracts, and ruscogenin content in IOR meet the requirement of Ophiopogonis Radix described in the Chinese Pharmacopoeia. When the mice received by oral 21.5 g/kg BW administration of IOR in the acute toxicity test, neither mortality nor any other abnormal general clinical signs were found within 14 days, except that 10% of mice suffered from diarrhea on day 1, which disappeared and returned to normal on day 4. The acute toxicity test indicated the LD50 of IOR was higher than 21.5 g/kg BW. Ames test showed no dose-dependent increase in TA97a, TA98, TA100, TA102, and TA1535 strains with or without rat liver microsomal enzyme mixture (S9) metabolic activation, at a quantity range of 50–5000 μg IOR. Mouse micronucleus test of bone marrow cells demonstrated no significant increase in the frequencies of micronucleated polychromatic erythrocytes (MN PCEs) among each IOR dose. Mouse sperm abnormality test showed that there was no evidence of the potential to induce sperm malformation with oral administration at doses of 2.5, 5.0, and 10.0 g/kg BW. Overall, the acute toxicity or genotoxicity of IOR were not observed, indicating that IOR at 25 kGy with a high-energy electron beam is toxicologically safe.

Variants in CLCN1 and PDE4C Associated with Muscle Hypertrophy, Dysphagia, and Gait Abnormalities in Young French Bulldogs.

(1) Background: Muscle hypertrophy, swallowing disorders, and gait abnormalities are clinical signs common to many muscle diseases, including muscular dystrophies, non-dystrophic myotonias, genetic myopathies associated with deficiency of myostatin, and acquired inflammatory myopathies. Here, we investigated underlying causes of this triad of clinical signs in four young French bulldogs via muscle histopathology coupled with whole genome and Sanger sequencing. (2) Methods: Dogs were evaluated by veterinary clinical internists and neurologists, and biopsies were obtained for histopathological diagnosis. DNA was submitted for whole genome sequencing, followed by bioinformatics evaluation and confirmation of variants via Sanger sequencing in two cases. (3) Results: Two novel variants were identified. The first, found in two related French bulldogs, was a homozygous variant in the chloride channel gene CLCN1 known to cause non-dystrophic congenital myotonia, and the second, found in an unrelated French bulldog, was a heterozygous variant in the cAMP phosphodiesterase gene PDE4C, which is the major phosphodiesterase expressed in skeletal muscle and may play a role in decreasing muscle atrophy. An underlying molecular basis in one other case has not yet been identified. (4) Conclusions: Here, we identified two novel variants, one in the CLCN1 and one in the PDE4C gene, associated with clinical signs of muscle hypertrophy, dysphagia, and gait abnormalities, and we suggested other bases of these phenotypes in French bulldogs that are yet to be discovered. Identification of genes and deleterious variants associated with these clinical signs may assist breeders in improving the overall health of this very popular breed and may lead to the identification of new therapies to reverse muscle atrophy in people and animals with neuromuscular diseases.

Preoperative ECG Abnormalities Among Patients Who Underwent Elective Surgical Operations at the Kuwaiti Specialised Hospital, Khartoum, Sudan: A Cross-Sectional Study.

The presence of preoperative ECG abnormalities has shown wide variation, and its value has been argued; thus, this study aimed to determine preoperative ECG abnormalities among Sudanese patients and their correlates. An observational descriptive cross-sectional study was conducted at the Kuwaiti Specialised Hospital, Khartoum, Sudan, from October 2020 to March 2021, including all patients over 40 years of age who planned to undergo elective surgery. Demographic, clinical, and ECG findings were obtained during the pre-anaesthesia check-up. The data were analysed using IBM SPSS software version 28 (IBM Corp., Armonk, NY). The study included a total of 304 patients with a mean age of 60±14 years, a male predominance of 210 (69.1%) patients, the presence of hypertension (HTN) in 65 (21.4%), and diabetes mellitus (DM) in 58 (19.1%) patients. The study showed that 235 (77%) patients had at least one ECG abnormality. However, 62 (20.4%) were diagnosed as having normal ECG variations; the most commonly diagnosed abnormality was ischemic heart disease (IHD) (32.5%), followed by sinus tachycardia (39, 12.8%). The QRS complex abnormalities were the most common (100, 32.9%), with M-shaped QRS (RSR pattern) being the most common single ECG abnormal sign (65, 21.4%). The ECG abnormalities showed no significant association with age (p-value = 0.24), gender (p-value = 0.16), DM (p-value = 0.77), HTN (p-value = 0.35), asthma (p-value = 0.35), or the grade of surgery (p-value = 0.52). However, the diagnosis of IHD was associated with the presence of HTN (p-value = 0.001). Incidental preoperative ECG abnormalities are common among Sudanese patients undergoing elective surgery, affecting more than three-quarters of them and being of diagnostic value as they led to the diagnosis of ischemic heart disease in nearly one-third of patients. Hypertensive patients may benefit from routine preoperative ECG testing, as ECG signs of ischemic heart disease are more common among hypertensive patients.

Chemical composition and toxicity of commercial Mentha spicata and Eucalyptus citriodora essential oils on Culex quinquefasciatus and non-target insects.

Current vector control strategies based on synthetic chemicals are not eco-friendly against non-target organisms; hence, alternative approaches are highly required. Commercially purchased oil of Mentha spicata (Spearmint) and Eucalyptus citriodora (Citriodora) were examined against the medical pest Cx. quinquefasciatus (Say) and their non-toxicity on the aquatic species was evaluated. Chemical screening with gas chromatography coupled with mass spectrometry (GC-MS) analysis revealed a total of 14 and 11 compounds in Citriodora and Spearmint oils, respectively, with the highest peak (%) at carvone (70.44%) and isopulegol (30.4%). The larvicidal activity on the fourth instar larvae of Cx. quinquefasciatus showed dose-dependent mortality and significance at a 100ppm concentration 48h post-treatment with Citriodora (76.4%, P ≤ 0.001) and Spearmint (100%, P ≤ 0.001). Additionally, the photomicrograph of the fourth instar larvae revealed significant physical abnormalities in the head and midgut tissues post-exposure to Spearmint and Citriodora oils. Moreover, the histological assay revealed severe damage in the epithelial cells and gut lumen 2 to 24h post-treatment. The repellency percentage of adult Culex mosquitoes was prominent across both oils at 150ppm 210min post-exposure. Non-target toxicity on the aquatic predator showed both essential oils (Spearmint oil (17.2%) and Citriodora oil (15.2%)) are safer at the maximum treatment (200ppm) compared to temephos (75.4% at 1ppm). The in silico screening of phyto-compounds derived by both essential oils with BeeTox (online server) showed no contact toxicity to the honey bee Apis mellifera. Overall, the present research revealed that Spearmint and Citriodora essential oils and their active phyto-compounds were toxic to Cx. quinquefasciatus and harmless to the aquatic predator and honey bee.

Clinical Course, Laboratory Findings, and Prognosis of SARS-CoV-2 Infection in Infants up to 90 Days of Age: A Single-Center Experience and a Proposal for a Management Pathway.

To provide a comprehensive description of the clinical features, biochemical characteristics, and outcomes of infants up to 90 days old with COVID-19. Moreover, to assess the severity of the disease and propose an effective management pathway. Retrospective single-center study spanning three years. Patient data includes age, sex, symptoms, comorbidities, blood and urine test results, cultures, admission, length of stay, therapies, intensive care unit admission, and mortality. A total of 274 patients were enrolled in the study, comprising 55% males. Among them, 60 patients (22%) were under the age of 29 days, while 214 (78%) fell within the 29 to 90 days age range. The overall incidence of SARS-CoV-2 infections was 0.28 per 10,000 Pediatric Emergency Department admissions. Blood inflammatory markers showed no significant abnormalities, and there were no recorded instances of positive blood cultures. Less than 1% of infants showed urinary tract infections with positive urine cultures, and 1.5% of patients had a concurrent RSV infection. Hospitalization rates were 83% for neonates and 67% for infants, with a median length of stay (LOS) of 48 h for both age groups. None of the patients required admission to the Pediatric or Neonatal Intensive Care Unit, and only one required High Flow Nasal Cannula (HFNC). No secondary serious bacterial infections were observed, and all hospitalized patients were discharged without short-term sequelae. No deaths were reported. Infants with COVID-19 generally exhibit milder or asymptomatic forms of the disease, making home management a viable option in most cases. Blood tests, indicative of a mild inflammatory response, are recommended primarily for children showing symptoms of illness. Hospitalization precautions for infants without apparent illness or comorbidities are deemed unnecessary. Given the evolving nature of experiences with COVID-19 in infants, maintaining a high level of clinical suspicion remains imperative.

A severe case of cardiospondylocarpofacial syndrome with a novel MAP3K7 variant

Cardiospondylocarpofacial syndrome (CSCFS) is a congenital malformation characterized by growth retardation, facial features, short toes with carpal and tarsal fusion, extensive posterior neck vertebral fusion, congenital heart disease, and deafness. Here, we report a severe case of CSCFS with a novel variant, p.Thr187Ile, in MAP3K7. Thr187 is the main phosphorylation site for TGF-beta-activated kinase 1 encoded by MAP3K7, and this variant may cause significant abnormalities in downstream signaling.

Functionalized tin-loaded mesoporous silica nanoparticles for targeted therapy of triple-negative breast cancer: Evaluation of cytogenetic toxicity

In our previous study, we synthesized tin-conjugated mesoporous silica nanoparticles (MSN-SnPh3; S3) and reported their enhanced selective toxicity towards breast cancer cells in vitro. Hence, to validate our hypothesis on the inhibition of growth of breast tumor in mice, we conducted in vivo antitumor studies of S3 in Balb/C mice model. The results demonstrated a higher percentage of reactive oxygen species production, presence of more apoptotic cells along with reduced expression of the Ki-67 protein, indicating decreased cell proliferation and antitumor activity. The safety assessment of S3 as an anticancer agent was evaluated and revealed no significant abnormalities in the different organs and changes in serum biochemical parameters of tumor mice suggesting that S3 did not affect basic metabolism. Genotoxicity studies also confirmed that S3 did not exhibit clastogenic, aneugenic, or mitotoxic properties in the bone marrow cells of Swiss albino mice. Apart from this, S3 demonstrated high bio-compatibility and did not induce any histopathological changes in all the vital organs of mice. Therefore, these comprehensive investigations on the antitumor properties of tin-conjugated mesoporous silica nanoparticles (S3), particularly in reducing breast cancer tumors, warrant further exploration to uncover their potential as therapeutic agents for cancer treatment.