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ObjectiveTo determine the yield of genetic diagnoses using chromosomal microarray (CMA) and trio whole exome sequencing (WES), separately and combined, among patients with cryptogenic cerebral palsy (CP).MethodsTrio WES of patients with prior CMA analysis for cryptogenic CP, defined as disabling, non-progressive motor symptoms beginning before the age of 3 years without known cause.ResultsGiven both CMA analysis and trio WES, clinically significant genetic findings were identified for 58% of patients (26 of 45). Diagnoses were eight large CNVs detected by CMA and 18 point mutations detected by trio WES. None had more than one severe mutation. Approximately half of events (14 of 26) were de novo. Yield was significantly higher in patients with CP with comorbidities (69%, 22 of 32) than in those with pure motor CP (31%, 4 of 13; p=0.02). Among patients with genetic diagnoses, CNVs were more frequent than point mutations among patients with congenital anomalies (OR 7.8, 95% CI 1.2 to 52.4) or major dysmorphic features (OR 10.5, 95% CI 1.4 to 73.7). Clinically significant mutations were identified in 18 different genes: 14 with known involvement in CP-related disorders and 4 responsible for other neurodevelopmental conditions. Three possible new candidate genes for CP were ARGEF10, RTF1 and TAOK3.ConclusionsCryptogenic CP is genetically highly heterogeneous. Genomic analysis has a high yield and is warranted in all these patients. Trio WES has higher yield than CMA, except in patients with congenital anomalies or major dysmorphic features, but these methods are complementary. Patients with negative results with one approach should also be tested by the other.

Objectives Preterm birth clinics provide dedicated obstetric care to women at high risk of spontaneous preterm birth (SPTB). There remains a lack of conclusive evidence to support the overall utility of such clinics, attributable to a paucity and heterogeneity of primary data. This study audits Australia’s largest and oldest dedicated preterm birth clinic with the aim to add primary data to the area and offer opportunities for similar clinics to align practice. Methods A retrospective audit of referrals to the Preterm Labour Clinic at the Royal Women’s Hospital, Melbourne, Australia, between 2004 and 2018 was conducted. 1,405 singleton pregnancies met inclusion criteria. The clinic’s key outcomes, demographics, predictive tests and interventions were analysed. The primary outcomes were SPTB before 37, 34 and 30 weeks’ gestation. Results The overall incidence of SPTB in the clinic was 21.2% (n=294). Linear regression showed reductions in the adjusted rates of overall SPTB and pre-viable SPTB (delivery Conclusions Dedicated preterm birth clinics can reduce rates of SPTB, particularly deliveries before 24 weeks’ gestation, and improve short-term neonatal outcomes in pregnant women at risk of preterm birth.

Background Tinea capitis is a common fungal infection in Israel, most commonly caused by the dermatophyte Trichophyton tonsurans. Objectives To investigate the effectiveness of oral antifungal monotherapy in producing clinical or complete cure. We also evaluated the impact of topical therapy (bifonazole 1% shampoo and/or betamethasone valerate 0.1% solution), prior to oral treatment, on patients' likelihood of clinical or complete cure. Methods A retrospective chart review was conducted. Patients with mycologically confirmed tinea capitis were treated with one of four regimens: (1) terbinafine (greater than 40 kg: 250 mg/day, 20 to 40 kg: 125 mg/day, less than 20 kg: 62.5 mg/day), (2) itraconazole 5 mg/kg daily, (3) fluconazole 6 mg/kg daily, or (4) griseofulvin 20 mg/kg daily. We used generalized linear models (GLM) to determine whether there was a significant association between the odds of cure and choice of treatment. Results The causative species was Trichophyton tonsurans in all but 6 cases that grew T violaceum. For pediatric patients, the odds of having complete or clinical cure within 6 weeks was greater if they used terbinafine compared to itraconazole, fluconazole, or griseofulvin (odds ratio [OR] = 9.06, P = .047). The likelihood of complete or clinical cure within 8 weeks of oral therapy was lower if topical steroids were previously used compared to if topical antifungals were used prior to systemic treatment (OR = 0.29, P = .046). Conclusions Our findings substantiate prior literature demonstrating that terbinafine is non-inferior to griseofulvin, itraconazole, and fluconazole in the therapy of pediatric tinea capitis caused by T tonsurans.

Detection and imaging of subwavelength features in the subsurface using diffracted waves are rapidly gaining momentum in the oil and gas industry as well as in the fields of engineering, archeology, and homeland security. Most of the methods include coherent summation of the recorded wavefield along diffraction traveltime surfaces from point scatterers. The summation focuses energy onto point-like diffractors that appear at the resulting images as prominent anomalies. However, in cases in which the target is an elongated object such as a fault plane, fracture, tunnel, or elongated cave, a more efficient imaging method can be constructed. We have developed an algorithm for detecting and characterizing linear subsurface elements using a linear-diffractor operator. Our algorithm is based on the coherent summation of the edge diffraction generated by the entire lineament and on the analysis of the calculated coherence measure (semblance). The advantages and limitations of our method are discussed, and the results are compared to conventional point-diffractor-based techniques. Synthetic and real data examples demonstrate that using a linear-diffractor-based algorithm can dramatically improve the detection of linear objects.

This article deals with the identity of the figure of Maryam, who is mentioned numerous times in the Qur'an. Maryam is called in the holy book of Islam the ‘sister of Aaron’ and ‘the daughter of ʿI...

Objective Identify placental pathology-related complications, labor and neonatal outcomes in pregnancies complicated by pathological nuchal translucency (NT) with normal microarray analysis. Methods A retrospective study in which all women with singleton pregnancy who demonstrated NT above 3 mm and a normal microarray analysis were matched to women with normal NT and a normal microarray analysis (2013-2019) in a single tertiary academic center. The following placental pathology-related parameters were measured: preeclampsia, oligohydramnios, suspected intrauterine growth restriction, abnormal Doppler studies or small for gestational age (SGA) neonates. The primary outcome was defined as a composite of complications related to placental pathology including preeclampsia and SGA neonate. Secondary outcomes were labor complications and neonatal morbidity. Results A total of 185 women were included in the study: of them, 47 presented an abnormal NT (study group) and 138 presented normal NT (controls). Groups did not significantly differ in baseline characteristics. Regarding primary outcome, all placental-related complications frequencies were higher in the study group, with a composite rate of 17.02% versus 6.52% in controls (p = 0.042%). Secondary outcomes did not differ between groups. Conclusions Abnormal NT measurement presented in pregnancies with normal fetal microarray analysis is associated with higher rates of placental-related complications.

Background Systemic-lupus-nephritis is a chronic autoimmune disease characterized by immune complex deposition and a flare of autoantibodies and leading to renal injury. Objectives To expose anti-Dense-Fine-Speckled-70 (DFS70)-antibodies to genetically-prone-lupus-mice. Methods NZBXW/F1 female mice were monitored for the onset of glomerulonephritis by proteinuria upon infusion of anti-DFS70 (40 μg/mouse), commercial-human-IgG (cIgG) or phosphate-buffered-saline (PBS) as controls. The survival time was detected by mice death. Circulating anti-dsDNA were tested by ELISA. Proteinuria, was defined by a standard semi-quantitative-Bayer-Multistix-dipstick. Kidney histology was analyzed by periodic-acid–Schiff-PAS staining. Results A significantly higher percentage of anti-DFS70-infused mice exhibited prolonged survival time as compared with cIgG and PBS-subjected mice (p Conclusions anti-DFS70 attenuated the progression of glomerulonephritis and prolonged the survival time. Circulating anti-DFS70-autoantibodies may confer a protective role against renal injury in murine-lupus-nephritis. Our data may propose a novel therapy approach for lupus patients.

INTRODUCTION Inflammatory myopathies are treated with glucocorticoids and other immunosuppressive medications. Intravenous immunoglobulin (IVIG) is increasingly used for refractory or severe cases; however, the evidence for their effectiveness is limited. We assessed effectiveness and safety of IVIG when used with other immunomodulatory agents in the treatment of inflammatory myopathies. METHODS This study reviewed records of patients diagnosed with dermatomyositis or polymyositis and treated with IVIG, from 2009 through 2016 in 1 tertiary medical center. Mixed-effects general linear regression models were applied to determine effectiveness of treatment on muscle strength, creatinine phosphokinase levels, and steroid dosage. RESULTS Twenty-three patients with dermatomyositis/polymyositis treated with IVIG were followed up for a mean of 31 (SD, ±25) months. During this period, a significant improvement in muscle strength was demonstrated, with a mean increase of 0.92 Medical Research Council scale points (β = 0.14; confidence interval [CI], 0.136-0.149; p < 0.0001), a significant reduction of creatinine phosphokinase levels and steroid dosage with a mean decrease of 1140 IU/L (β = -0.274; CI, -0.354 to -0.195; p < 0.0001), and 36 mg/d (β = -0.008; CI, -0.011 to -0.006; p < 0.0001), respectively. Overall, remission was observed in 10 patients (43.5%), and partial remission in 6 patients (26%), whereas 1 patient (17%) remained refractory to treatment, and 6 patients (27%) were lost to follow-up. CONCLUSIONS The majority of patients with inflammatory myopathies experienced a clinical and laboratory improvement during IVIG treatment. In addition, a steroid-sparing effect was noticed in most patients. These results encourage the use of IVIG as an alternative treatment option for patients with limited responsiveness to conventional methods.

Background Immunomodulators and anti tumor-necrosis-α antibodies (anti-TNFs) have been implicated in increased risk of Epstein–Barr virus (EBV)–driven B-cell lymphoproliferative disorders in inflammatory bowel disease (IBD) patients. However, the underlying mechanisms are poorly understood. Methods An in-vitro model of lymphoblastoid cell line (LCL) was established by co-incubation of EBV-infected human peripheral blood mononuclear cells (PBMC) with Cyclosporin-A (CSA). After 4 weeks, the resultant LCLs were analyzed by flow cytometry, telomerase activity assay, and next generation sequencing. Subsequently, LCLs were explored in the presence of therapeutic agents for IBD (anti-TNFs, vedolizumab, 6-Mercaptopurine [6MP], methotrexate). Epstein–Barr virus titers were quantitated by real-time polymerase chain reaction. Results In cultures of PBMC with EBV and CSA, LCLs were characterized as an expanded, long lived population of CD58+CD23hi B-cells with high telomerase activity and clonal expansion. Upon addition to the cell cultures, LCL percentages were higher with infliximab (median 19.21%, P = 0.011), adalimumab (median 19.85%, P = 0.003), and early washed-out 6MP (median 30.57%, P = 0.043) compared with PBMC with EBV alone (median 9.61%). However, vedolizumab had no such effect (median 8.97%; P = 0.435). Additionally, LCL expansion was accompanied by increase in intracellular, rather than extracellular, EBV viral copies. Compared with PBMC with EBV alone, high levels of LCL were subsequently observed after triple depletion of NK cells, CD4+ T cells, and CD8+ T cells (median 52.8% vs 16.4%; P = 0.046) but also in cultures depleted solely of CD4+ T cells (median 30.7%, P = 0.046). Conclusions These results suggest that both anti-TNFs and 6MP, but not vedolizumab, propagate EBV-driven lymphoblastoid transformation in an in vitro model of lymphoma. This model may prove useful for studying mechanisms underlying proneoplastic viral immune interactions of novel drugs in IBD therapy.

To determine whether meconium-stained amniotic fluid (MSAF) encountered in pregnancies complicated by preterm premature rupture of membranes (PPROM) is associated with adverse maternal and perinatal outcome. A retrospective cohort study of all singleton pregnancies with PPROM and MSAF who delivered in a tertiary hospital at 24 + 0–36 + 6 weeks of gestation between 2007 and 2017. Women with PPROM–MSAF (study group) were compared to women with PPROM and clear amniotic fluid (control group). Controls were matched to cases according to age, gravidity, parity and gestational age at delivery in a 3:1 ratio. Primary outcome was defined as neonatal intensive care unit admission. Secondary outcomes were neonatal adverse outcomes, chorioamnionitis and placental abruption diagnosed clinically or by placental cultures and histology. Seventy-five women comprised the study group and were matched to 225 women representing the control group. A significantly higher rate of neonatal intensive care unit admissions was noted in the study group compared to controls (61.3% vs. 45.7%, p = 0.03). Multivariate analysis demonstrated that MSAF is an independent risk factor for neonatal intensive care unit admission (adjusted OR = 2.82, 95% CI 1.39–5.75, p = 0.004). MSAF was found to be associated to higher rates of cesarean and operative vaginal deliveries (30.7% vs. 24.4% and 5.3% vs. 2.7%, p = 0.057, respectively) as well as to chorioamnionitis and placental abruption (33.3% vs. 19.3%, p = 0.034 and 16.0% vs. 7.7%, p = 0.021, respectively). MSAF is associated with higher frequencies of adverse perinatal outcome when compared to clear amniotic fluid in pregnancies complicated by PPROM.

Background: Cell-free DNA (cfDNA) molecules circulating in blood are emerging as important non-invasive biomarkers for monitoring physiological and pathological processes. Tumor-derived circulating cell-free DNA (cfDNA) is present in the plasma of individuals with cancer. Assays aimed at detecting common cancer mutations in cfDNA are being developed for the detection of multiple cancer types. In breast cancer, however, such assays have failed to detect the disease at a sensitivity relevant for clinical use, in part due to the absence of multiple common mutations that can be co-detected in plasma. Unlike individual mutations that exist in only a subset of tumors, unique DNA methylation patterns are universally present in cells of a common type and therefore may be ideal biomarkers. Here we describe the detection and quantification of breast derived cfDNA, using a breast-specific DNA methylation signature. Methods: In order to identify regions of the genome with unique methylation patterns in breast epithelium, we compared genome-wide methylation profiles of normal breast tissue and breast cancer to genome-wide methylation profiles of other normal and cancerous tissues and aimed to identify CpG sites that are uniquely hypermethylated or hypomethylated in the breast. By quantifying the proportion of molecules in a sample that harbored 3 chosen breast-specific methylation sites, we could obtain an estimate of the proportion of the sample derived from breast epithelial cells. We have collected plasma prospectively from healthy women, metastatic breast cancer patients and patients with localized (stage II-III) breast cancer who were assigned to preoperative chemotherapy at our cancer institute. In the latter cohort, samples were collected before and throughout treatment until surgery. The trial was approved by the Institutional Ethics Committee and all patients gave written informed consent. Results: All three markers clearly distinguished between the plasma of healthy donors (n=64) and patients with metastatic disease (n=14, p-value Conclusion: A breast-unique epigenetic signature in circulating cell-free DNA can be used as a universal biomarker for breast cancer, to allow sensitive detection and monitoring of localized breast cancer treatment outcomes. Further research will aid to evaluate this promising and affordable method in additional clinical scenarios. Citation Format: Albert Grinshpun, Aviad Zick, Joshua Moss, Einat Carmon, Myriam Maoz, Bracha Ohana, Ofri Abraham, Lili Germansky, Benjamin Glaser, Ruth Shemer, Yuval Dor, Beatrice Uziely. Non-personalized detection of circulating breast-derived DNA for monitoring of preoperative breast cancer treatment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-10.

Context There is an unmet need for biomarkers of pancreatic beta-cell death to improve early diagnosis of type 1 diabetes, enroll subjects into clinical trials, and assess treatment response. To address this need, several groups developed assays measuring insulin deoxyribonucleic acid (DNA) with unmethylated CpG sites in cell-free DNA. Unmethylated insulin DNA should be derived predominantly from beta-cells and indicate ongoing beta-cell death. Objective To assess the performance of three unmethylated insulin DNA assays. Design and Participants Plasma or serum samples from 13 subjects undergoing total pancreatectomy and islet autotransplantation were coded and provided to investigators to measure unmethylated insulin DNA. Samples included a negative control taken post-pancreatectomy but pretransplant, and a positive control taken immediately following islet infusion. We assessed technical reproducibility, linearity, and persistence of detection of unmethylated insulin DNA for each assay. Results All assays discriminated between the negative sample and samples taken directly from the islet transplant bag; 2 of 3 discriminated negative samples from those taken immediately after islet infusion. When high levels of unmethylated insulin DNA were present, technical reproducibility was generally good for all assays. Conclusions The measurement of beta cell cell-free DNA, including insulin, is a promising approach, warranting further testing and development in those with or at-risk for type 1 diabetes, as well as in other settings where understanding the frequency or kinetics of beta cell death could be useful.

Background/Objective: Alpha-thalassemia is one of the most prevalent genetic diseases, with the –α3.7 deletion being the most common mutation. Molecular studies have suggested mechanisms to explain the mild phenotype of “silent carrier” heterozygotes. However, the correlation between the clinical laboratory picture and the –α3.7 heterozygous state remains unclear, thus we chose to investigate. Methods: We analyzed the medical files of 192 children evaluated for microcytosis at our tertiary center between 2007 and 2017 and diagnosed as heterozygotes for the –α3.7 deletion. Additional α-thalassemia mutations, iron deficiency anemia, and β-thalassemia were ruled out. Laboratory parameters were compared to age- and sex-matched reference values. Results: The –α3.7 carriers had significantly lower Hb and mean corpuscular volume (MCV) than the reference population, and significantly higher red blood cell counts across all age groups. The greatest reduction in Hb level appeared among male adolescents, while MCV was consistently 2 SDs lower than normal in most patients older than 2 years. Conclusion: Heterozygosity for the –α3.7 deletion was associated with clinically significant microcytosis and mild anemia in our pediatric population. In the absence of iron deficiency and β-thalassemia, this finding provides a diagnosis for mild microcytic anemia, making additional investigations of microcytosis unnecessary.

BackgroundMethodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate real-world VE in a closely monitored population.MethodsWe conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples – at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher’s exact test.FindingsOf the 1,567 HCP enrolled between December 27, 2020 and February 15, 2021, 1,250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR- confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.InterpretationOur prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 during a period of predominant alpha variant circulation.FundingClalit Health Services

BackgroundInvasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from non-pharmacological interventions. We used multiple ongoing cohort surveillance projects in children MethodsThe first SARS-CoV-2 cases were detected in February-2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), non-alveolar lower respiratory infections necessitating chest X-rays (NA-LRI), nasopharyngeal pneumococcal carriage in non-respiratory visits, nasopharyngeal respiratory virus detection (by PCR), and nationwide invasive pneumococcal disease (IPD). Monthly rates (January-2020 through February-2021 vs. mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity, were compared.FindingsCAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios, [IRRs] 0η07 and 0η19, respectively); NA-LRI and non-pneumonia IPD were also reduced, with a lesser magnitude (IRRs, 0η46 and 0η42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced and density of colonization and pneumococcal serotype distributions were similar to previous years. The pneumococcus-associated disease decline was temporally associated with a full suppression of RSV, influenza viruses, and hMPV, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels.InterpretationReductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic were not predominantly related to reduced pneumococcal transmission and carriage but were strongly associated with the complete disappearance of specific respiratory viruses.FundingPartially funded by Pfizer, Inc.

LMNA-related dilated cardiomyopathy is an inherited heart disease caused by mutations in the LMNA gene encoding for lamin A/C. The disease is characterized by left ventricular enlargement and impaired systolic function associated with conduction defects and ventricular arrhythmias. We hypothesized that LMNA-mutated patients’ induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) display electrophysiological abnormalities, thus constituting a suitable tool for deciphering the arrhythmogenic mechanisms of the disease, and possibly for developing novel therapeutic modalities. iPSC-CMs were generated from two related patients (father and son) carrying the same E342K mutation in the LMNA gene. Compared to control iPSC-CMs, LMNA-mutated iPSC-CMs exhibited the following electrophysiological abnormalities: (1) decreased spontaneous action potential beat rate and decreased pacemaker current (If) density, (2) prolonged action potential duration and increased L-type Ca2+ current (ICa,L) density, (3) delayed afterdepolarizations (DADs), arrhythmias and increased beat rate variability, (4) DADs, arrhythmias and cessation of spontaneous firing in response to β-adrenergic stimulation and rapid pacing. Additionally, compared to healthy control, LMNA-mutated iPSC-CMs displayed nuclear morphological irregularities and gene expression alterations. Notably, KB-R7943, a selective inhibitor of the reverse-mode of the Na+/Ca2+ exchanger, blocked the DADs in LMNA-mutated iPSC-CMs. Our findings demonstrate cellular electrophysiological mechanisms underlying the arrhythmias in LMNA-related dilated cardiomyopathy.

Importance Peripheral facial nerve (Bell) palsy has been reported and widely suggested as a possible adverse effect of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. Israel is currently the leading country in vaccination rates per capita, exclusively using the BNT162b2 vaccine, and all residents of Israel are obligatory members of a national digital health registry system. These factors enable early analysis of adverse events. Objective To examine whether the BNT162b2 vaccine is associated with an increased risk of acute-onset peripheral facial nerve palsy. Design, Setting, and Participants This case-control study was performed from January 1 to February 28, 2021, at the emergency department of a tertiary referral center in central Israel. Patients admitted for facial nerve palsy were matched by age, sex, and date of admission with control patients admitted for other reasons. Exposures Recent vaccination with the BNT162b2 vaccine. Main Outcomes and Measures Adjusted odds ratio for recent exposure to the BNT162b2 vaccine among patients with acute-onset peripheral facial nerve palsy. The proportion of patients with Bell palsy exposed to the BNT162b2 vaccine was compared between groups, and raw and adjusted odds ratios for exposure to the vaccine were calculated. A secondary comparison with the overall number of patients with facial nerve palsy in preceding years was performed. Results Thirty-seven patients were admitted for facial nerve palsy during the study period, 22 (59.5%) of whom were male, and their mean (SD) age was 50.9 (20.2) years. Among recently vaccinated patients (21 [56.7%]), the mean (SD) time from vaccination to occurrence of palsy was 9.3 (4.2 [range, 3-14]) days from the first dose and 14.0 (12.6 [range, 1-23]) days from the second dose. Among 74 matched controls (2:1 ratio) with identical age, sex, and admittance date, a similar proportion were vaccinated recently (44 [59.5%]). The adjusted odds ratio for exposure was 0.84 (95% CI, 0.37-1.90;P = .67). Furthermore, analysis of the number of admissions for facial nerve palsy during the same period in preceding years (2015-2020) revealed a relatively stable trend (mean [SD], 26.8 [5.8]; median, 27.5 [range, 17-35]). Conclusions and Relevance In this case-control analysis, no association was found between recent vaccination with the BNT162b2 vaccine and risk of facial nerve palsy.

Opto-mechanical interactions in guided wave media are drawing great interest in fundamental research and applications. Forward stimulated Brillouin scattering, in particular, is widely investigated in optical fibres and photonic integrated circuits. In this work, we report a comprehensive study of forward stimulated Brillouin scattering over standard, panda-type polarization maintaining fibres. We distinguish between intra-polarization scattering, in which two pump tones are co-polarized along one principal axis, and inter-polarization processes driven by orthogonally polarized pump waves. Both processes are quantified in analysis, calculations and experiment. Inter-modal scattering, in particular, introduces cross-polarization switching of probe waves that is non-reciprocal. Switching takes place in multiple wavelength windows. The results provide a first demonstration of opto-mechanical non-reciprocity of forward scatter in standard fibre. The inter-polarization process is applicable to distributed sensors of media outside the cladding and coating boundaries, where light cannot reach. The process may be scaled towards forward Brillouin lasers, optical isolators and circulators and narrowband microwave-photonic filters over longer sections of off-the-shelf polarization maintaining fibres.

Rosacea is a common inflammatory facial skin condition affecting the adult population. Its papulopustular subtype is mainly treated pharmacologically by topical and oral antibiotics. For severe or antibiotics-recalcitrant disease, daily low-dose isotretinoin has also been reported to be effective. However, no previous study has assessed the efficacy of once-weekly administered isotretinoin for papulopustular rosacea. For this purpose, a retrospective comparative study was conducted. For severe rosacea, 40mg/week isotretinoin (24 patients) was administered. For mild to moderate rosacea, once-weekly 20 mg/week isotretinoin (28 patients) was compared to 100 mg/day minocycline (24 patients). Treatment courses lasted 4 to 7 months. 40 mg/week isotretinoin was highly effective for severe rosacea, achieving complete response (over 90% improvement) in 62.5% of patients and partial response (50-90% improvement) in additional 29.2% of patients. 20 mg/week isotretinoin and 100 mg/day minocycline showed comparable efficacy for mild to moderate rosacea (complete response of 10.7% vs. 8.3% and partial response of 28.6% vs. 33.3%, respectively). This study demonstrates that that the use of a weekly low-dose isotretinoin is an effective treatment for papulopustular rosacea, including among patients with severe disease. This article is protected by copyright. All rights reserved.

BACKGROUND Inflammatory manifestations (IM) are well described in adult patients with myelodysplastic syndrome (MDS), but the presentation is highly variable and no standardized treatment exists. This phenomenon is rarely reported in children. As more pediatric patients are hematopoietic stem cell transplantation (HSCT) candidates, the role of anti-inflammatory treatment in relation to HSCT should be defined. PROCEDURE Here, we report a series of five children from a tertiary center. We describe the clinical presentation, molecular findings, and treatment options. RESULTS All patients presented with advanced MDS with blast percentages ranging 10-30%, all had severe IM. One patient had MDS secondary to severe congenital neutropenia, the other four patients had presumably primary MDS. All four were found to harbor a PTPN11 gene driver mutation, which is found in 35% of cases of juvenile myelomonocytic leukemia (JMML). The mutation was present in the myeloid lineage but not in T lymphocytes. Three had symptoms of Behcet's-like disease with trisomy 8 in their bone marrow. All patients were treated with anti-inflammatory medications (mainly systemic steroids) in an attempt to bring them to allogeneic HSCT in a better clinical condition. All demonstrated clinical improvement as well as regression in their MDS status post anti-inflammatory treatment. All have recovered from both MDS and their inflammatory symptoms post HSCT. CONCLUSION Primary pediatric MDS with IM is driven in some cases by PTPN11 mutations, and might be on the clinical spectrum of JMML. Anti-inflammatory treatment may reverse MDS progression and improve the outcome of subsequent HSCT.

SummaryThe SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. We performed a case-control study that examined the distribution of SARS-CoV-2 variants observed in infections of vaccinated individuals (“breakthrough cases”) and matched infections of unvaccinated individuals. We hypothesized that if there is lower vaccine effectiveness against one of the VOCs, its proportion among the breakthrough cases should be higher than among unvaccinated cases. Our results show that vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1). Those who tested positive between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs at particular time windows following vaccination. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high among those fully vaccinated. These results overall suggest that vaccine breakthrough infection may be more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.

Fanconi anemia (FA), an inherited bone marrow failure (BMF) syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with FA from the Israeli inherited BMF registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 years (range: 0.1-49); 63% were offspring of consanguineous parents. One-hundred patients (90%) had at least one congenital anomaly; over 80% of the patients developed bone marrow failure; 53% underwent hematopoietic stem-cell transplantation; 33% of the patients developed cancer; no significant association was found between hematopoietic stem-cell transplant and solid tumor development. Nearly 95% of the patients tested had confirmed mutations in the Fanconi genes FANCA (67%), FANCC (13%), FANCG (14%), FANCJ (3%) and FANCD1 (2%), including twenty novel mutations. Patients with FANCA mutations developed cancer at a significantly older age compared to patients with mutations in other Fanconi genes (mean 18.5 and 5.2 years, respectively, P=0.001); however, the overall survival did not depend on the causative gene. We hereby describe a large national cohort of patients with FA, the vast majority genetically diagnosed. Our results suggest an older age for cancer development in patients with FANCA mutations and no increased incidence of solid tumors following hematopoietic stem-cell transplant. Further studies are needed to guide individual treatment and follow-up programs.

Although dermatophytes are considered the predominant causative organisms in onychomycosis, non-dermatophyte mold (NDM) infections may be more prevalent than originally thought and may be more difficult to treat. There are limited data of oral antifungal efficacy in treating NDM onychomycosis.A retrospective chart review (2009-2016) was conducted in patients receiving continuous oral terbinafine or pulse itraconazole for toenail onychomycosis due to NDMs. Mycology results and percent nail affected were recorded with patient characteristics including demographics and concurrent diseases. Complete, clinical, and mycological cure were tabulated.Data from 176 patients were collected. Mycological and complete cure rates for terbinafine (69.8% and 17%) and itraconazole (67.5% and 22%) were not significantly different from each other. Regardless of oral treatment, age (Continuous terbinafine and pulse itraconazole were similar in efficacy for curing NDM onychomycosis. Age was the most consistent prognostic factor affecting likelihood of cure, with factors that may influence drug reaching the site of infection also decreasing likelihood of mycological cure.

Streptococcus is well associated with a myriad of inflammatory diseases. Among others, this bacterium is linked to the triggering of psoriasis and to post-streptococcal reactive arthritis (PSRA), an arthritis which is typically confined to peripheral joints. Three patients who developed acute psoriatic spondyloarthritis (SpA) following a recent streptococcal infection are described in this article. We searched the existing literature for cases of axial involvement in PSRA and reviewed the association between streptococcal infection and psoriasis or psoriatic arthritis )PsA). In all patients, psoriatic SpA occurred within 7-10 days of a confirmed streptococcal infection. The main presenting syndrome was inflammatory back pain with evidence of acute axial spondyloarthritis on magnetic resonance imaging. One patient had guttate psoriasis, the second patient developed pustular psoriasis, and the third patient had exacerbation of pustular palmoplantar psoriasis. Two patients required treatment with tumor necrosis factor alpha (TNF-α) blockers. Axial involvement in PSRA is very rare. A potential association of streptococcal infection and development of PsA has been explored in several articles. However, to the best of our knowledge, acute psoriatic SpA as a manifestation of PSRA has yet to be described. Acute psoriatic SpA should be considered in the differential diagnosis of new-onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection. KEY POINTS: • Our case series describes three cases of acute psoriatic spondyloarthritis that occurred within 7--10 days of a confirmed streptococcal infection and progressed to full blown chronic disease. • Acute psoriatic spondyloarthritis as a manifestation of post streptococcal reactive arthritis should be considered in the differential diagnosis of new onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.

Objective:To assess the impact of incorporating early rapid influenza diagnosis on antimicrobial usage, nosocomial influenza transmission, length of stay, and occupancy rates among hospitalized patients.Setting:A 1,100 bed tertiary-care hospital in southern Israel.Methods:We implemented early rapid detection of influenza with immediate communication of results. Using Orion methods, we compared the 2017–2018 influenza season to the prior season in our hospital and to the 2017–2018 occupancy rates at other Israeli hospitals.Results:During the intervention season, 5,006 patients were admitted; 1,824 were tested for influenza, of whom 437 (23.9%) were positive. In the previous season, 4,825 patients were admitted; 1,225 were tested and 288 (23.5%) were positive. Time from admission to test report decreased from 35.5 to 18.4 hours (P < .001). Early discharge rates significantly increased, from 21.5% to 41.6% at 36 hours, from 37.2% to 54.5% at 48 hours, and from 66% to 73.2% at 72 hours. No increase in repeat ER visits, readmission, or mortality rates was observed. Hospital occupancy decreased by 10% compared to the previous year and was 26% lower than the national rate. Hospital-acquired influenza cases were reduced from 37 (11.4%) to 12 (2.7%) (P < .001). Antibiotic usage was reduced both before and after notification of test results by 16% and 12%, respectively.Conclusions:Implementing this intervention led to earlier discharge of patients, lower occupancy in medical wards, reduced antibiotic administration, and fewer hospital-acquired influenza events. This strategy is useful for optimizing hospital resources, and its implementation should be considered for upcoming influenza seasons.

Background & objectives: Clinical diagnosis of cutaneous leishmaniasis (CL) may bear a high rate of false diagnosis. This study assessed CL-suspected episodes, in an attempt to differentiate confirmed CL and non-CL diagnoses. Methods: In this retrospective, case-control study, medical files of CL-suspected episodes, tested by a biopsy for Leishmania-PCR, from 2013 to 2016, were collected and analysed statistically. Results: Of 324 suspected CL episodes, 48.8% were PCR-confirmed CL (96.2% Leishmania major) and 51.2% were non-CL (57.1% bacterial infections). Overall, 59.3% episodes were in males. Mean (± SD) duration until diagnosis was 3.7 ± 7.2 months. Lesions (mean 2.9 ± 3.8 per episode) were mostly (60.8%) sampled from September through February. Ulcer, pain, itching, purulent discharge and fever were recorded in 55.2, 47, 42.9, 18.2 and 4.7% of episodes, respectively. Univariate analysis showed that male gender, multiple lesions, ulcer, >1-month duration until diagnosis, and seasonality were associated with CL. Empiric CL treatment was recorded in 63.4 and 16% of CL-confirmed and non-CL episodes, respectively (p 1-month until diagnosis. In multivariate analysis, seasonality (odds ratio, OR = 2.144), empiric CL treatment (OR = 5.144) and ulcer (OR = 2.459) were associated with CL. Empiric CL treatment was associated with Jewish ethnicity (OR = 2.446) and duration of >1-month until diagnosis (OR = 3.304). Interpretation & conclusion: CL diagnosis should be laboratory confirmed, as clinical appearance is often misleading. Seasonality, ulcer appearance and gender may aid in correct identification and treatment of CL cases.

Background Sub-Saharan Africans exhibit a higher frequency of chronic kidney disease (CKD) than other populations. In this study, we sought to determine the frequency of apolipoprotein L1 (APOL1) genotypes in hypertension-attributed CKD in Kinshasa, Democratic Republic of the Congo. Methods We performed a case-control study identifying 162 subjects: 79 with hypertension-attributed CKD and 83 controls living in Kinshasa who were genotyped for APOL1 risk variants between July 2013 and November 2016. We selected control subjects from the general population and matched them with the cases according to age. Logistic regression analysis was used to examine the relationship between APOL1 high-risk genotypes and CKD. Results The frequencies of the APOL1 G1 and G2 alleles were 19.1 and 7.1%, respectively. The number of individuals with the G1 and G2 risk alleles was significantly higher in the CKD group (12.7%) than in the control group (2.4%), particularly in individuals with end-stage kidney disease (14.3%). Subjects carrying two risk alleles was strongly and independently associated with hypertension-attributed nephropathy, with an adjusted odds ratio of 7.7 (95% confidence interval 1.5-39.7; P = 0.014). The high-risk APOL1 genotypes were G1/G1 and G1/G2, whereas G2/G2 was not found in the study population. Conclusions The results of this study demonstrate the association of high-risk APOL1 genotypes with kidney disease in Kinshasa. The absence of G2/G2 may be consistent with powerful selective sweeps induced by Trypanosoma brucei gambiense infection. In contrast, the presence of APOL1 G2/G2 among individuals of African ancestry in the USA may indicate relaxation of natural selection in a trypanosome-free environment.

We analyzed the websites of 125 elementary and high school libraries in Israel for content that promotes reading. We found that the websites promote reading in many ways and to different degrees, and that there is no consensus regarding the websites’ role in promoting reading. The most common content found included: reports on a national project in which students ranked books, links to special websites that encourage reading, lists of new books purchased by the library, library forum on reading, book recommendations by librarians and students, and biographies of authors and poets.

We show that in order to guide waves, it is sufficient to periodically truncate their edges. The modes supported by this type of wave guide propagate freely between the slits, and the propagation pattern repeats itself. We experimentally demonstrate this general wave phenomenon for two types of waves: (i) plasmonic waves propagating on a metal-air interface that are periodically blocked by nanometric metallic walls, and (ii) surface gravity water waves whose evolution is recorded, the packet is truncated, and generated again to show repeated patterns. This guiding concept is applicable for a wide variety of waves., 5 pages, 4 figures

We describe a miniaturized field-deployable biosensor module, designed to function as an element in a sensor network for standoff monitoring and mapping of environmental hazards. The module harbors live bacterial sensor cells, genetically engineered to emit a bioluminescent signal in the presence of preselected target materials, which act as its core sensing elements. The module, which detects and processes the biological signal, composes a digital record that describes its findings, and can be transmitted to a remote receiver. The module is an autonomous self-contained unit that can function either as a standalone sensor, or as a node in a sensor network. The biosensor module can potentially be used for detecting any target material to which the sensor cells were engineered to respond. The module described herein was constructed to detect the presence of buried landmines underneath its footprint. The demonstrated detection sensitivity was 0.25 mg 2,4-dinitrotoluene per Kg soil.

In recent years, there has been an increasing interest in building video summarization tools, where the goal is to automatically create a short summary of an input video that properly represents the original content. We consider shot-based video summarization where the summary consists of a subset of the video shots which can be of various lengths. A straightforward approach to maximize the representativeness of a subset of shots is by minimizing the total distance between shots and their nearest selected shots. We formulate the task of video summarization as an optimization problem with a knapsack-like constraint on the total summary duration. Previous studies have proposed greedy algorithms to solve this problem approximately, but no experiments were presented to measure the ability of these methods to obtain solutions with low total distance. Indeed, our experiments on video summarization datasets show that the success of current methods in obtaining results with low total distance still has much room for improvement. In this paper, we develop ILS-SUMM, a novel video summarization algorithm to solve the subset selection problem under the knapsack constraint. Our algorithm is based on the well-known metaheuristic optimization framework -- Iterated Local Search (ILS), known for its ability to avoid weak local minima and obtain a good near-global minimum. Extensive experiments show that our method finds solutions with significantly better total distance than previous methods. Moreover, to indicate the high scalability of ILS-SUMM, we introduce a new dataset consisting of videos of various lengths.

Background There are limited data on influenza vaccine effectiveness (IVE) in preventing laboratory-confirmed influenza illness among healthcare personnel (HCP). Methods HCP with direct patient contact working full-time in hospitals were followed during three influenza seasons in Israel (2016–2017 to 2018–2019) and Peru (2016 to 2018). Trivalent influenza vaccines were available at all sites, except during 2018–2019 when Israel used quadrivalent vaccines; vaccination was documented by electronic medical records, vaccine registries, and/or self-report (for vaccinations outside the hospital). Twice-weekly active surveillance identified acute respiratory symptoms or febrile illness (ARFI); self-collected respiratory specimens were tested by real-time reverse transcription polymerase chain reaction (PCR) assay. IVE was 100 × 1-hazard ratio (adjusted for sex, age, occupation, and hospital). Results Among 5,489 HCP who contributed 10,041 person-seasons, influenza vaccination coverage was 47% in Israel and 32% in Peru. Of 3,056 ARFIs in Israel and 3,538 in Peru, A or B influenza virus infections were identified in 205 (7%) in Israel and 87 (2.5%) in Peru. IVE against all viruses across seasons was 1% (95% confidence interval [CI] = −30%, 25%) in Israel and 12% (95% CI = −61%, 52%) in Peru. Conclusion Estimates of IVE were null using person-time models during six study seasons in Israel and Peru.

Inter-polarization forward stimulated Brillouin scattering is studied in standard, polarization maintaining fibers. The process is driven by two orthogonally polarized pump tones. The stimulated acoustic waves induce non-reciprocal polarization switching of optical probe fields.

Introduction Universal vaccination of toddlers has led to very low hepatitis A (HAV) endemicity in Israel. However, sporadic outbreaks still occur, necessitating better surveillance. Aim To implement a comprehensive HAV surveillance programme. Methods In 2017 and 2018, sera from suspected HAV cases that tested positive for anti-HAV IgM antibodies were transferred to the Central Virology Laboratory (CVL) for molecular confirmation and genotyping. Sewage samples were collected in Israel and Palestine* and were molecularly analysed. All molecular (CVL), epidemiological (District Health Offices and Epidemiological Division) and clinical (treating physicians) data were combined and concordantly assessed. Results Overall, 146 cases (78 in 2017 and 68 in 2018, median age 34 years, 102 male) and 240 sewage samples were studied. Most cases (96%) were unvaccinated. In 2017, 89% of cases were male, 45% of whom were men who have sex with men (MSM). In 2018, 49% were male, but only 3% of them were MSM (p Conclusions Molecular confirmation of HAV infection in cases and analysis of environmental samples, combined with clinical and epidemiological investigation, may improve HAV surveillance. Sequence-based typing of both clinical and sewage-derived samples could assist in understanding viral circulation.

We study the evolution of linear and nonlinear Talbot carpets emerging in surface gravity water waves. In our measurements, we are able to record both amplitude and phase of the Temporal Talbot effect.

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs., At early time points after vaccination with a single dose or two doses of the BNT162b2 mRNA COVID-19 vaccine, breakthrough SARS-CoV-2 infections can be disproportionately caused by the B.1.1.7 or B.1.351 variants of concern, underlining the need to ensure rapid and complete vaccination.

The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. We aimed to prospectively (real-time) evaluate the feasibility of using a response-guided therapy approach, based on mathematical modeling of early viral kinetics, to reduce the duration of DAAs therapy. Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Twenty-nine patients (mean age 54 ± 16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Real-time mathematical modeling of early HCV kinetics can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy.Clinical trial registration: ClinicalTrials.gov Identifier: NCT03603327.

Over the years, numerous groups have employed human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as a superb human-compatible model for investigating the function and dysfunction of cardiomyocytes, drug screening and toxicity, disease modeling and for the development of novel drugs for heart diseases. In this review, we discuss the broad use of iPSC-CMs for drug development and disease modeling, in two related themes. In the first theme—drug development, adverse drug reactions, mechanisms of cardiotoxicity and the need for efficient drug screening protocols—we discuss the critical need to screen old and new drugs, the process of drug development, marketing and Adverse Drug reactions (ADRs), drug-induced cardiotoxicity, safety screening during drug development, drug development and patient-specific effect and different mechanisms of ADRs. In the second theme—using iPSC-CMs for disease modeling and developing novel drugs for heart diseases—we discuss the rationale for using iPSC-CMs and modeling acquired and inherited heart diseases with iPSC-CMs.

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophyte molds, and yeasts. This difficult-to-treat chronic infection has a tendency to relapse despite treatment. This paper aims to offer a global perspective on onychomycosis management from expert physicians from around the world. Overall, the majority of experts surveyed used systemic, topical, and combination treatments approved in their countries and monitored patients based on the product insert or government recommendations. Although the basics of treating onychomycosis were similar between countries, slight differences in onychomycosis management between countries were found. These differences were mainly due to different approaches to adjunctive therapy, rating the severity of disease and use of prophylaxis treatment. A global perspective on the treatment of onychomycosis provides a framework of success for the committed clinician with appreciation of how onychomycosis is managed worldwide.

Background An Israeli national taskforce performed a multi-center clinical and analytical validation of seven serology assays to determine their utility and limitations for SARS-CoV-2 diagnosis. Methods Serology assays from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, and Mt.-Sinai ELISA were included. Negative samples from 2391 individuals representative of the Israeli population, and 698 SARS-CoV-2 PCR positive patients, collected between March and May 2020, were analyzed Findings Immunoassays sensitivities between 81.5%-89.4% and specificities between 97.7%-100% resulted in a profound impact on the expected Positive Predictive Value (PPV) in low (

Detection of somatic mutations may help verify the diagnosis of myelodysplastic syndrome (MDS) in patients with persistent cytopenias or with MDS-predisposition syndromes, prior to the development of overt leukemia. However, the spectrum and consequences of acquired changes in paediatric patients have not been fully evaluated, and especially not in the context of an underlying syndrome. We incorporated a targeted next-generation-sequencing panel of 54 genes for the detection of somatic mutations in paediatric and young adult patients with inherited or acquired cytopenias. Sixty-five patients were included in this study, of whom 17 (26%) had somatic mutations. We detected somatic mutations in 20% of individuals with inherited MDS-predisposition syndromes, including in patients with severe congenital neutropenia and Fanconi anaemia, and with germline mutations in SAMD9L. Thirty-eight per cent of children with acquired cytopenias and suspected MDS had somatic changes, most commonly in genes related to signal transduction and transcription. Molecularly abnormal clones often preceded cytogenetic changes. Thus, routine performance of somatic panels can establish the diagnosis of MDS and determine the optimal timing of haematopoietic stem cell transplantation, prior to the development of leukaemia. In addition, performing somatic panels in patients with inherited MDS-predisposition syndromes may reveal their unique spectrum of acquired mutations.

Onychomycosis is estimated at a prevalence of 10% worldwide with the infecting organism most commonly Trichophyton rubrum (T. rubrum). Traditional culture identification of causative organisms has inherent risks of overestimating dermatophytes, like T. rubrum, by inhibiting the growth of possible nondermatophyte mould (NDM) environmental contaminants which could be causative agents. Recently, molecular methods have revealed that a proportion of onychomycosis cases in North America may be caused by mixed infections of T. rubrum as an agent co-infecting with one or more NDM. Determining the global burden of mixed infections is a necessary step to evaluating the best therapies for this difficult-to-treat disease. To determine the prevalence of mixed infections in a global population, nail samples from onychomycosis patients in Brazil, Canada, and Israel (n = 216) were analyzed by molecular methods for the presence of dermatophytes and five NDMs. If an NDM was detected, repeat sampling was performed to confirm the NDM. T. rubrum was detected in 98% (211/216) of infections with 39% mixed (84/216). The infection type was more likely to be mixed in samples from Brazil, but more likely to be a dermatophyte in samples from Canada and Israel (Χ2 = 16.92, df = 2, P

Single-stage group testing uses compressed sensing for efficient high-throughput SARS-CoV-2 testing., Recent reports suggest that 10 to 30% of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infected patients are asymptomatic and that viral shedding may occur before symptom onset. Therefore, there is an urgent need to increase diagnostic testing capabilities to prevent disease spread. We developed P-BEST, a method for Pooling-Based Efficient SARS-CoV-2 Testing, which identifies all positive subjects within a set of samples using a single round of testing. Each sample is assigned into multiple pools using a combinatorial pooling strategy based on compressed sensing. We pooled sets of 384 samples into 48 pools, providing both an eightfold increase in testing efficiency and an eightfold reduction in test costs, while identifying up to five positive carriers. We then used P-BEST to screen 1115 health care workers using 144 tests. P- BEST provides an efficient and easy-to-implement solution for increasing testing capacity that can be easily integrated into diagnostic laboratories.

Aim: In the process of opening a new Pelvic Floor Medicine Unit, we aimed to map the pelvic floor dysfunction and sexual issues using validated quality of life (QOL) questionnaires. Material and Methods: All the patients who attended the Pelvic Floor Medicine Unit clinic in Assuta University Medical Center in Ashdod, Israel, were given a validated Pelvic Floor Distress Inventory 20 (PFDI-20) and Prolapse Urinary Incontinence Sexual Questionnaire 12 (PISQ-12) questionnaires prior to meeting the physician. The patient’s age, parity, and route of delivery were collected from the medical record. All data has been statistically analyzed using Kruskal Wallis Test and Mann-Whitney U Test. Results: 647 patients were included in the study, of them 462 filled out the PFDI-20 questionnaires and 221 completed the PISQ-12 questionnaire filling. In the PFDI-20 results, POPDI-6 higher scores were found to be associated with higher parity (p=0.043) and with higher age (p=0.03). CARD-8 scores were found to be significantly associated with cesarean delivery only in patients’ history (p=0.023) and with higher age (p=0.05). UDI-6 scores were found significantly associated with older age (p Conclusions: Using validates questionnaires, we could demonstrate a correlation between parity and age, an association between aging and higher rates of bowel and sexual dysfunction, an association between higher parity and pelvic organ prolapse complaints, and an association between previous cesarean deliveries only and higher rates of bowel disfunction. The use of validated QoL questionnaires for describing the population suffering from PFDs presents an important tool in understanding the epidemiology of PFD in different communities.

Previous studies have suggested the applicability of cold atmospheric pressure plasma for the treatment of onychomycosis. Whether delivering cold plasma in sub-atmospheric pressure would be beneficial for this purpose is yet to be established. The current study aimed to evaluate efficacy of cold sub-atmospheric and atmospheric pressure plasma in Trichophyton rubrum growth inhibition. Bovine nails infected with T. rubrum were treated by a cold air plasma device, which enables utilizing plasma in sub-atmospheric pressures (Low = 100 millibar; High = 300 millibar) or atmospheric pressure. The infected foci were exposed to the plasma source directly or indirectly. Treatment with high sub-atmospheric pressure setting achieved T. rubrum growth reduction of 94.0% and 73.0%, for direct and indirect exposure to the plasma source, respectively (P < .001). Low sub-atmospheric pressure setting achieved similar T. rubrum growth reduction of 86.2% for direct exposure to the plasma source (P < .001), but only marginally significant 58.8% reduction rate for indirect exposure to the plasma source (P = .056). None statistically significant fungal growth reduction was attained with the use of atmospheric pressure setting. Cold plasma was shown to effectively inhibit T. rubrum nail growth, with sub-atmospheric pressure setting achieving better outcome than atmospheric pressure.

Background: The aims of this study were to evaluate the incidence of congenital cytomegalovirus (CMV) in term and near-term infants who fail hearing screen (target screening), the incidence of cong...

Congenital anemias are a wide spectrum of diseases including hypoproliferative anemia syndromes, dyserythropoietic anemias, sideroblastic anemias, red blood cell membrane and enzymatic defects, hemoglobinopathies, and thalassemia syndromes. The various congenital anemia syndromes may have similar clinical and laboratory presentations, making the diagnosis challenging. The traditional work-up, which includes a complete blood count, blood smears, bone marrow studies, flow cytometry, and the osmotic fragility test, does not always lead to the diagnosis. Specialized tests such as red blood cell enzyme activity and ektacytometry are not widely available. In addition, red blood cell transfusions may mask some of the laboratory characteristics. Therefore, genetic testing is crucial for accurate diagnosis of patients with congenital anemias. However, gene-by-gene testing is labor intensive because of the large number of genes involved. Thus, targeted next-generation sequencing using custom-made gene panels has been increasingly utilized, with a high success rate of diagnosis. Accurate genetic diagnosis is important for determining specific therapeutic modalities, as well as for avoiding splenectomy when contraindicated. In addition, molecular diagnosis can allow for genetic counseling and prenatal diagnosis in severe cases. We suggest a work-up scheme for patients with congenital anemias, including early incorporation of targeted next-generation sequencing panels.

Purpose Coronavirus disease 2019 (COVID-19) caused a global pandemic with millions infected worldwide. Little is known on the ocular involvement associated with the disease. The aim of this study was to assess the clinical and molecular ocular involvement among patients with confirmed COVID-19 admitted to a tertiary care facility. Methods Consecutive patients admitted to the COVID-19 Ward of the Shamir Medical Center in Israel during March and April, 2020 were included. The control group included patients negative for COVID-19 admitted during a similar period to a different ward. Patients were examined by trained Ophthalmologists. SARS-CoV-2 conjunctival swab samples were obtained. Results Included were 48 patients, 16 with confirmed COVID-19 and 32 controls. Median patient age was 68.5 (interquartile range: 31.5, mean: 63 ± 21) years and 48% were male. Active conjunctival injection was present in three patients (19%) with COVID-19, compared to none in the controls (p = 0.034). Patients with COVID-19 were more likely to complain of foreign body sensation (31.3% vs 3.1%, p = 0.005) and redness of the eye (25% vs 0%, p = 0.003). Conjunctival injection was associated with loss of smell and taste (75% vs 7.7%, p = 0.018). Viral conjunctival swab tests all showed negative results for all three viral genes tested (E, N, and RdRp). Conclusions Among patients admitted to a tertiary referral center with confirmed COVID-19, active conjunctival injection was noted in one out of five cases, and was associated with loss of smell and taste. Conjunctival swabs for viral RNA were negative in patients with and without ocular involvement. Electronic supplementary material The online version of this article (10.1007/s10792-020-01592-1) contains supplementary material, which is available to authorized users.