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trunk varices either wearing or not wearing compression stockings to assess the efficacy of this intervention. If compression stockings are found to be beneficial, further studies assessing which length and pressure is the most efficacious could then take place.

There is insufficient high-certainty evidence to determine whether or not compression stockings are effective as the sole and initial treatment of varicose veins in people without healed or active venous ulceration, or whether any type of stocking is superior to any other type. Future research should consist of large RCTs of participants with trunk varices either wearing or not wearing compression stockings to assess the efficacy of this intervention. If compression stockings are found to be beneficial, further studies assessing which length and pressure is the most efficacious could then take place.Injuries to the intra-articular anterior cruciate ligament (ACL) and the extra-articular medial collateral ligament (MCL) result in significant knee joint instability, pain, and immobility. Moderate endurance-type exercise can increase ligament strength but little is known on the effect of short-term regular bouts of high-intensity exercise on the extracellular matrix (ECM) structure of knee ligaments. Therefore, this study aimed to identify the effect of short-term regular bouts high exercise on the proteome of the rat ACL and MCL using mass spectrometry. Sprague-Dawley male rats (n = 6) were split into control and exercise groups, and subjected to high-intensity training for four 4 weeks followed by proteomic analyses of the ACL and MCL. Knee joint health status was assessed using OARSI and a validated histological scoring system. Histopathological analyses demonstrated no significant changes in either in cruciate, collateral ligaments, or cartilage between the control and exercised knee joints. However, significant proteins were found to be more abundant in the exercised ACL compared to ACL control group but not between the exercised MCL and control MCL groups. The significant abundant proteins in ACL exercise groups were mostly cytoskeletal, ribosomal and enzymes with several abundant matrisomal proteins such as collagen proteins and proteoglycans being found in this group. In conclusion, our results indicate that short-term regular bouts of high-intensity exercise have an impact on the intra-articular ACL but not extra-articular MCL ECM protein expression.

Ministries of health, donors, and other decision-makers are exploring how they can use mobile technologies to acquire accurate and timely statistics on births and deaths. These stakeholders have called for evidence-based guidance on this topic. This review was carried out to support World Health Organization (WHO) recommendations on digital interventions for health system strengthening.

Primary objective To assess the effects of birth notification and death notification via a mobile device, compared to standard practice. Secondary objectives To describe the range of strategies used to implement birth and death notification via mobile devices and identify factors influencing the implementation of birth and death notification via mobile devices.

We searched CENTRAL, MEDLINE, Embase, the Global Health Library, and POPLINE (August 2, 2019). We searched two trial registries (August 2, 2019). We also searched Epistemonikos for related systematic reviews and potentially eligible primary studies (August 27, 201 and timeliness of the birth and death data - Legal frameworks that allow births and deaths to be notified by mobile device and by different types of notifiers - Community awareness of the need to register births and deaths - Socio-cultural norms around birth and death - Government commitment - Cost to the system, to health workers and to families - Access to electricity and network connectivity, and compatibility with existing systems - Systems that protect data confidentiality We have low to moderate confidence in these findings. This was mainly because of concerns about methodological limitations and data adequacy.

We need more, well-designed studies of the effect of birth and death notification via mobile devices and on factors that may influence its implementation.

We need more, well-designed studies of the effect of birth and death notification via mobile devices and on factors that may influence its implementation.

β-thalassemia is a severe hereditary hemolytic anemia. Due to the diversity of mutations spectrum, β-thalassemia manifests a highly heterogeneous clinical severity. We noted that a previous report characterized HBBc.313delA, at the end of exon 2, as a β-thalassemia trait rather than dominant β-thalassemia, the classification given to similar mutations. We further explored the impact of this functional variant on globin structure through larger pedigree analysis and in vitro studies.

Hematological analysis and molecular genotyping were conducted on the proband and his family members. We evaluated functional effects of the variant on β-globin gene in the proband's nucleated erythrocytes and transfected HEK-293T cells. Three-dimensional construction of protein structure was carried out in silico to demonstrate amino acid changes.

The thalassemia major proband was identified as a compound heterozygote of HBBc.313delA and HBBc.126_129delCTTT. ALK inhibitor Three family members with heterozygotes of HBBc.313delA displayed microcytic hypochromic anemia. Molecular characterization demonstrated that the frameshift mutation could give rise to retro-positioning of the termination codon, resulting in an elongated β-globin chain with an extension of 10 amino acids. Clinical phenotype and functional experiments indicated that HBBc.313delA led to β

-thalassemia phenotype.

We concluded that the phenotype of HBBc.313delA was mainly related to the stability of mutant mRNA, the degradation of mutant proteins, and production of inclusion bodies according to a systematic description of clinical phenotype and a series of molecular experiments.

We concluded that the phenotype of HBBc.313delA was mainly related to the stability of mutant mRNA, the degradation of mutant proteins, and production of inclusion bodies according to a systematic description of clinical phenotype and a series of molecular experiments.The development of non-animal based New Approach Methodologies (NAMs) for chemical risk assessment and safety evaluation is urgently needed. The aim of the present study was to investigate the applicability of an in vitro in silico approach to predict human cardiotoxicity of the herbal alkaloid ibogaine and its metabolite noribogaine, being promising anti-addiction drugs. PBK models were developed using in silico-derived parameters and biokinetic data obtained from in vitro liver microsomal incubations and Caco-2 transport studies. Human induced pluripotent stem cell-derived cardiomyocytes combined with the multi-electrode array (MEA) assay were used to determine in vitro concentration-dependent cardiotoxicity reflected by prolongation of field potential duration, which was subsequently translated to in vivo dose-dependent QTc prolongation using PBK model based reverse dosimetry. Results showed that the predictions matched well with available in vivo kinetic data and QTc data for ibogaine and noribogaine available in literature, indicating a good performance of the NAM. Benchmark dose analysis of the predicted dose response curves adequately predicted the onset of in vivo cardiotoxicity detected by QTc prolongation upon oral exposure to ibogaine and noribogaine. The present study provides an additional proof of principle of using PBK modeling-based reverse dosimetry as a NAM to predict human cardiotoxicity.

The Nationwide Inpatient Sample Subarachnoid Hemorrhage (SAH) Severity Score (NIS-SSS) was developed as a measure of SAH severity for use in administrative databases. The NIS-SSS consists of International Classification of Diseases Ninth Revision (ICD-9) diagnostic and procedure codes derived from the SAH inpatient course and has been validated against the Hunt-Hess score (HH).

To externally validate both the NIS-SSS and a modified version of the NIS-SSS (m-NIS-SSS) consisting of codes present only on admission, against the HH in a Canadian province-wide registry and administrative database of SAH patients.

A total of 1467 SAH patients admitted to Ontario stroke centers between 2003 and 2013 with recorded HH were included. The NIS-SSS and m-NIS-SSS were validated against the HH by testing correlation between the NIS-SSS/m-NIS-SSS and HH, comparing discriminative ability of the NIS-SSS/m-NIS-SSS vs HH for poor outcome by calculating area under the curve (AUC), and comparing calibration of the NIS-SSS, m-NIS-SSS, and HH by plotting predicted vs observed outcome.

Correlation with HH was 0.417 (P≤.001) for NIS-SSS, and 0.403 (P≤.001) for m-NIS-SSS. AUC for prediction of poor outcome was 0.786 (0.764-0.808) for HH, 0.771 (0.748-0.793) for NIS-SSS, and 0.744 (0.721-0.767) for m-NIS-SSS. Calibration plots demonstrated that HH had the most accurate prediction of outcome, whereas the NIS-SSS and m-NIS-SSS did not accurately predict low risk of poor outcome.

The NIS-SSS and m-NIS-SSS have good external validity, and therefore, may be suitable to approximate traditional clinical scores of disease severity in SAH research using administrative data.

The NIS-SSS and m-NIS-SSS have good external validity, and therefore, may be suitable to approximate traditional clinical scores of disease severity in SAH research using administrative data.Extensive multifocal intradural lesions in children present a formidable challenge. This surgical video illustrates our management of a 14-yr=old boy with two intradural mass lesions on magnetic resonance imaging (MRI) one at T2-5 and the other from T12 through the sacral cul-de-sac. In a single procedure, we performed a T2-5 laminectomy and laminoplasty and T12-sacrum laminectomy for tumor resection. For reconstruction, we performed complete laminoplasty at all levels with supplementation at the thoracolumbar junction via T11-L2 posterior spinal fixation and allograft placement for fusion. In this video, we illustrate the microsurgical challenges of intradural tumor resection in both the thoracic cord and amidst the cauda equina. In young patients, prevention of postsurgical spinal deformity is of paramount concern. We discuss considerations for long-segment spinal stabilization in an adolescent and describe our decision-making to perform stabilization at the thoracolumbar junction to supplement laminoplasty while preserving function. The patient and their family consented to the procedure.  Image of the article at 051 is from McGirt et al, Short-term progressive spinal deformity following laminoplasty versus laminectomy for resection of intradural spinal tumors analysis of 239 patients, Neurosurgery, 2010, 66(5), 1005-1012, by permission of the Congress of Neurological Surgeons.A method involving silver-catalyzed aerobic oxidation/6-endo heterocyclization of ortho-alkynylbenzaldehydes to yield 3-substituted isocoumarins is described. The developed protocol allows convenient access to a range of synthetically useful 3-substituted isocoumarins and related fused heterocyclolactones in good to high yields, using silver tetrafluoroborate as the catalyst, and atmospheric oxygen as the terminal oxidant and the source of endocyclic oxygen. Mechanistic studies suggest the involvement of a free-radical pathway.