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Background: This study aimed to evaluate the safety and efficacy of minimally invasive sacrospinous ligament (SSL) fixation of apical pelvic organ prolapse (POP) in older patients compared to younger patients. Methods: A cohort of 271 older (≥65 years) patients (mean age 71.8 ± 5.2 years) and 60 younger patients (mean age 47.6 ± 7.1 years) with stage III or IV apical POP who underwent SSL fixation by the EnPlace® device was retrospectively analyzed. The age range of older patients was further divided into early old (65–74 y, N = 209), old (75–84 y, N = 58), and late old (>85 y, N = 4). Patient characteristics, surgical safety, and 6-month postoperative outcomes were compared between the four age groups. Results: Duration of surgery and blood loss were similar among all age groups. Most patients (99.4%) were discharged on the day of surgery or the day after. Subjective patient satisfaction rates were high among all patients. Point C measurements at six months postoperatively were less favorable among the younger patients. Furthermore, four (6.7%) younger patients versus six (2.2%) older patients required surgical repair of recurrent apical POP within the follow-up period. Conclusions: The short-term outcomes of minimally invasive SSL fixation suggest that it is a safe and effective procedure for significant apical POP repair among older patients. [ABSTRACT FROM AUTHOR]

Objective: The EnPlace® device is a novel minimally invasive tool allowing transvaginal sacrospinous ligament (SSL) fixation of apical pelvic organ prolapse (POP). The study aimed to investigate the safety and short–term efficacy of the EnPlace® SSL fixation for significant apical POP repair. Methods: A retrospective cohort study of 123 consecutive patients (mean age 64.4 ± 11.1 years) with stage III or IV apical POP who underwent SSL fixation by the EnPlace® device. Safety and 6‐month outcome results were analyzed and compared between 91 (74%) patients with uterine prolapse versus 32 (26%) patients with vaginal vault prolapse. Results: There were no intraoperative or early postoperative complications. The mean (± standard deviation) duration of surgery was 30 ± 6.9 min and mean blood loss was 30.5 ± 18.5 mL. The average position of point C by POP‐Quantification measurements before surgery and at 6 months postoperatively was 4.5 ± 2.8 cm and −3.1 ± 3.3 cm, respectively. Of 91 patients with preoperative uterine prolapse, eight (8.8%) patients developed a recurrent uterine prolapse within 6 months postoperatively. Of 32 patients with preoperative vault prolapse, two patients (6.3%) had recurrent vault prolapse. Conclusion: Short‐term outcome results of EnPlace® SSL fixation suggest that it is a safe and effective minimally invasive transvaginal procedure for significant apical POP repair. Synopsis: Short‐term outcome results of EnPlace® sacrospinous ligament fixation suggest that it is a safe and effective minimally invasive transvaginal procedure for significant apical POP repair. [ABSTRACT FROM AUTHOR]

Abstract Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of childhood chronic kidney disease. Congenital nephrotic syndrome of the Finnish type (CNF) (MIM# 256300) is caused by biallelic variants in the gene NPHS1, encoding nephrin, an integral component of the kidney filtration barrier. No causal treatments exist, and children inevitably require kidney replacement therapy. In preparation for gene replacement therapy (GRT) in CNF, we established a quantifiable and reproducible phenotypic assessment of the nephrin-deficient CNF mouse model: 129/Sv-Nphs1 tm1Rkl /J. We assessed the phenotypic spectrum of homozygous mice (Nphs1 tm1Rkl /Nphs1 tm1Rkl ) compared to heterozygous controls (Nphs1 tm1Rkl /Nphs1 WT ) by the following parameters: 1. cohort survival, 2. podocyte foot process (FP) density per glomerular basement membrane (GBM) using transmission electron microscopy, 3. tubular microcysts in brightfield microscopy, and 4. urinary albumin/creatinine ratios. Nphs1 tm1Rkl /Nphs1 tm1Rkl mice exhibited: 1. perinatal lethality with median survival of 1 day, 2. FP effacement with median FP density of 1.00 FP/µm GBM (2.12 FP/µm in controls), 3. tubular dilation with 65 microcysts per section (6.5 in controls), and 4. increased albumin/creatinine ratio of 238 g/g (4.1 g/g in controls). We here established four quantifiable phenotyping features of a CNF mouse model to facilitate future GRT studies by enabling sensitive detection of phenotypic improvements.

Objective Determine whether data collected from a smartphone camera can be used to detect anemia in a pediatric population. Methods HEMO-AI (Hemoglobin Easy Measurement by Optical Artificial Intelligence), a clinical study carried out from December 2020 to February 2023, recruited patients from the Pediatric Emergency Department, Pediatric Inpatient Department and Pediatric Hematology Unit of the Haemek Medical Center, Afula, Israel. A population-based sample of 823 patients aged 6 months to 18 years who had undergone a venous blood draw for a complete blood count since being admitted to the hospital were enrolled. Patients with total leukonychia, nailbed darkening or discoloration due to medication, nail clubbing, clinically indicated jaundice, subungual hematoma, nailbed lacerations, avulsion injuries, or nail polish applied on fingernails were not eligible for study recruitment. Video and images of the patients’ hand placed in a collection chamber were collected using a smartphone camera. Results About 823 samples, 531 from a 12.2 megapixel camera and 256 from a 12.2 megapixel camera, were collected. About 26 samples were excluded by the study coordinator for irregularities. About 97% of fingernails and 68% of skin samples were successfully identified by a post-trained machine learning model. Separate models built to detect anemia using images taken from the Pixel 3 had an average precision of 0.64 and an average recall of 0.4, whereas models built using the Pixel 6 had an average precision of 0.8 and an average recall of 0.84. Further supplementation of training data with synthetic data boosted the precision of the latter to 0.84 and the average recall to 0.87. Conclusions This study lays the groundwork for the future evolution of non-invasive, pain-free, and accessible anemia screening tools tailored specifically for pediatric patients. It identifies important sample collection parameters and design, provides critical algorithms for the pre-processing of fingernail data, and reports an initial capability to detect anemia with 87% sensitivity and 84% specificity. Trial Registration Prospectively registered on www.clinicaltrials.gov (Identifier: NCT04573244) on 15 September 2020, prior to subject recruitment.

Abstract Background Congenital disorders of the mitochondrial respiratory chain are a heterogeneous group of inborn errors of metabolism. Among them, NADH:ubiquinone oxidoreductase (complex I, CI) deficiency is the most common. Biallelic pathogenic variants in NDUFAF2, encoding the nuclear assembly CI factor NDUFAF2, were initially reported to cause progressive encephalopathy beginning in infancy. Since the initial report in 2005, less than a dozen patients with NDUFAF2-related disease have been reported. Methods Clinical, biochemical, and neuroradiological features of four new patients residing in Northern Israel were collected during 2016–2022 at Emek Medical Center. Enzymatic activities of the five respiratory-chain complexes were determined in isolated fibroblast mitochondria by spectrophotometric methods. Western blot analyses were conducted with anti-human NDUFAF2 antibody; antibody against the mitochondrial marker VDAC1 was used as a loading control. Genetic studies were performed by chromosome microarray analysis using Affymetrix CytoScan 750 K arrays. Results All four patients presented with infantile-onset growth retardation, ophthalmological impairments with nystagmus, strabismus (starting between 5 and 9 months), and further progressed to life-threatening episodes of apnea usually triggered by trivial febrile illnesses (between 10 and 18 months) with gradual loss of acquired developmental milestones (3 of 4 patients). Serial magnetic-resonance imaging studies in two of the four patients showed a progressive pattern of abnormal T2-weighted hyperintense signals involving primarily the brainstem, the upper cervical cord, and later, the basal ganglia and thalami. Magnetic-resonance spectroscopy in one patient showed an increased lactate peak. Disease progression was marked by ventilatory dependency and early lethality. 3 of the 4 patients tested, harbored a homozygous 142-kb partial interstitial deletion that omits exons 2–4 of NDUFAF2. Mitochondrial CI activity was significantly decreased in the only patient tested. Western blot analysis disclosed the absence of NDUFAF2 protein compared to normal controls. In addition, we reviewed all 10 previously reported NDUFAF2-deficient cases to better characterize the disease. Conclusions Biallelic loss-of-function mutations in NDUFAF2 result in a distinctive phenotype in the spectrum of Leigh syndrome with clinical and neuroradiological features that are primarily attributed to progressive brainstem damage.

The archerfish is unique in its ability to hunt by shooting a jet of water from its mouth that hits insects situated above the water’s surface. To aim accurately, the fish needs to overcome physical factors including changes in light refraction at the air-water interface. Nevertheless, archerfish can still hit the target with a high success rate under changing conditions. One possible explanation for this extraordinary ability is that it is learned by trial and error through a motor adaptation process. We tested this possibility by characterizing the ability of the archerfish to adapt to perturbations in the environment to make appropriate adjustments to its shots. We introduced a perturbing airflow above the water tank of the archerfish trained to shoot at a target. For each trial shot, we measured the error, i.e., the distance between the center of the target and the center of the water jet produced by the fish. Immediately after the airflow perturbation, there was an increase in shot error. Then, over the course of several trials, the error was reduced and eventually plateaued. After the removal of the perturbation, there was an aftereffect, where the error was in the opposite direction but washed out after several trials. These results indicate that archerfish can adapt to the airflow perturbation. Testing the fish with two opposite airflow directions indicated that adaptation took place within an egocentric frame of reference. These results thus suggest that the archerfish is capable of motor adaptation, as indicated by data showing that the fish produced motor commands that anticipated the perturbation.

Background: Chronic Spontaneous Urticaria (CSU) is an immune-mediated skin disease that may require prolonged treatments. Currently, there are no recommendations for treatment discontinuation once CSU symptoms are controlled, particularly among patients primarily diagnosed with severe CSU. Objective: In this real-life study we aimed to describe our experience of omalizumab (Oma) treatment withdrawal in CSU and define biomarkers related to these outcomes. Methods: CSU patients followed at our allergy clinic from January 2016 to December 2022 were included. Response to Oma therapy, and Oma-withdrawal outcomes among patients who reached complete remission for >6 months were analyzed. Results: During the study period 192/335(%) CSU patients were categorized as severe-CSU and entitled to receive Oma according to our country's regulations. Of them, 131/192(68%) were considered “Oma-responders”, and 95/131(72.5%) patients underwent gradual treatment withdrawal. Successful Oma-withdrawal was documented in 47/95(49.5%) whereas 48/95(50.5%) patients experienced flare and were defined as unsuccessful OMA-withdrawal. The first was associated with shorter disease duration 7.1 ± 7.4 years vs. 10.7 ± 9.4 (P = 0.042), lower baseline-IgE 81.6 ± 84.1IU/ml vs. 324.7 ± 555.9 (P = 0.005), and lower baseline-eosinophils count 131.4 ± 110.5 vs. 195.6 ± 98.4 (P = 0.043) in comparison to failure of Oma-withdrawal group. Conclusion: OMA may be successfully withdrawn in up to 50% of severe CSU patients following complete remission of disease symptoms, utilizing a gradual withdrawal protocol. Oma-withdrawal failure was linked with longer duration of disease as well as high IgE and eosinophil counts prior to initiation of Oma therapy. These parameters may enable the design of a treatment withdrawal algorithm.

Objective: Azathioprine, a prodrug of 6-mercaptopurine (6-MP), is used in the treatment of inflammatory bowel disease and may be continued during pregnancy. Acute cholestatic liver injury has been reported to occur with azathioprine. We aimed to examine azathioprine related cholestasis effect on pregnancy complications and outcome. Case report: We present a unique case of 6-MP-induced severe intrahepatic cholestasis of pregnancy (ICP) that required meticulous combined therapy including plasma exchange. The symptoms resolved following 6-MP withdrawal. A literature review revealed 11 pregnancies complicated by early-induced severe ICP among women treated with azathioprine or 6-MP. Conclusion: We recommend weekly bile acid level tests for pregnant women treated with azathioprine or 6-MP, beginning early in the second trimester of pregnancy, and the prompt discontinuation of treatment upon establishment of an ICP diagnosis.

Abstract Autism Spectrum Disorder (ASD) is characterized mainly by social and sensory-motor abnormal and repetitive behavior patterns. Over hundreds of genes and thousands of genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region and compared them to neurons derived from a first-degree relative without the mutation. Using a whole-cell patch-clamp, we observed that the mutant cortical neurons demonstrated hyperexcitability and early maturation compared to control lines. These changes were characterized by increased sodium currents, increased amplitude and rate of excitatory postsynaptic currents (EPSCs), and more evoked action potentials in response to current stimulation in early-stage cell development (3–5 weeks post differentiation). These changes that appeared in all the different mutant lines, together with previously reported data, indicate that an early maturation and hyperexcitability may be a convergent phenotype of ASD cortical neurons.