Antimicrobial photodynamic therapy against Propionibacterium acnes biofilms using hypericin (Hypericum perforatum) photosensitizer: in vitro study

Lasers in Medical Science - Acne vulgaris is the most recurring skin condition in the world, causing great harm to the physical and psychological well-being of many patients. Antimicrobial...     

Clinical Phenotype and Relevance of LRP5 and LRP6 Variants in Patients With Early-Onset Osteoporosis (EOOP)

Reduced bone mineral density (BMD; ie, Z-score ≤−2.0) occurring at a young age (ie, premenopausal women and men <50 years) in the absence of secondary osteoporosis is considered early-onset osteoporosis (EOOP). Mutations affecting the WNT signaling pathway are of special interest because of their key role in bone mass regulation. Here, we analyzed the effects of relevant LRP5 and LRP6 variants on the clinical phenotype, bone turnover, BMD, and bone microarchitecture. After exclusion of secondary osteoporosis, EOOP patients (n = 372) were genotyped by gene panel sequencing, and segregation analysis of variants in LRP5/LRP6 was performed. The clinical assessment included the evaluation of bone turnover parameters, BMD by dual-energy X-ray absorptiometry, and microarchitecture via high-resolution peripheral quantitative computed tomography (HR-pQCT). In 50 individuals (31 EOOP index patients, 19 family members), relevant variants affecting LRP5 or LRP6 were detected (42 LRP5 and 8 LRP6 variants), including 10 novel variants. Seventeen variants were classified as disease causing, 14 were variants of unknown significance, and 19 were BMD-associated single-nucleotide polymorphisms (SNPs). One patient harbored compound heterozygous LRP5 mutations causing osteoporosis-pseudoglioma syndrome. Fractures were reported in 37 of 50 individuals, consisting of vertebral (18 of 50) and peripheral (29 of 50) fractures. Low bone formation was revealed in all individuals. A Z-score ≤−2.0 was detected in 31 of 50 individuals, and values at the spine were significantly lower than those at the hip (−2.1 ± 1.3 versus −1.6 ± 0.8; p = .003). HR-pQCT analysis (n = 34) showed impaired microarchitecture in trabecular and cortical compartments. Significant differences regarding the clinical phenotype were detectable between index patients and family members but not between different variant classes. Relevant variants in LRP5 and LRP6 contribute to EOOP in a substantial number of individuals, leading to a high number of fractures, low bone formation, reduced Z-scores, and impaired microarchitecture. This detailed skeletal characterization improves the interpretation of known and novel LRP5 and LRP6 variants. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Sources of regional and center-level variability in survival and cost of care for congenital diaphragmatic hernia (CDH)

PurposeEnormous variability in management and cost occurs in CDH care. The purpose of this study was to identify regional mortality and cost patterns underlying this variability.MethodsThis is a retrospective study of neonatal CDH patients at U.S. hospitals using data from the Pediatric Health Information System (PHIS) database (2015–2018). Patients were risk-stratified using CDH Study Group predicted survival (CDHSG-PS), and mortality and costs were assessed by region (East, West, Mid-West, and South) and center.ResultsHigher mortality and extracorporeal life support (ECLS) rates were found in the Mid-West and South (p < 0.0001). Higher mortality was seen with ECLS among low-volume centers in the South (p = 0.007). When broken down by CHDSG-PS, higher severity patients had higher mortality in the Mid-West and South (p = 0.038). Cost was significantly lower for high severity nonsurvivors than survivors ($244,005 vs $565,487, p = 0.0008). The East spent more on high-severity patients with lower mortality compared to other regions, but also spent 3.5 times more on low severity nonsurvivors than survivors. Costs were higher at high-volume centers for low- and medium-severity patients, but all centers spent the same on high-severity patients.ConclusionCenter volume, region, and patient severity all contribute to the complex survival and cost disparities that exist in CDH care. Standardization of care may improve survival and reduce cost variability.Type of studyRetrospective database study.Level of evidenceLevel II     

Distal rectus femoris surgery in children with cerebral palsy: results of a Delphi consensus project

PurposeThe purpose of this study was for an international panel of experts to establish consensus indications for distal rectus femoris surgery in children with cerebral palsy (CP) using a modified Delphi method.MethodsThe panel used a five-level Likert scale to record agreement or disagreement with 33 statements regarding distal rectus femoris surgery. The panel responded to statements regarding general characteristics, clinical indications, computerized gait data, intraoperative techniques and outcome measures. Consensus was defined as at least 80% of responses being in the highest or lowest two of the five Likert ratings, and general agreement as 60% to 79% falling into the highest or lowest two ratings. There was no agreement if neither threshold was reached.ResultsConsensus or general agreement was reached for 17 of 33 statements (52%). There was general consensus that distal rectus femoris surgery is better for stiff knee gait than is proximal rectus femoris release. There was no consensus about whether the results of distal rectus femoris release were comparable to those following distal rectus femoris transfer. Gross Motor Function Classification System (GMFCS) level was an important factor for the panel, with the best outcomes expected in children functioning at GMFCS levels I and II. The panel also reached consensus that they do distal rectus femoris surgery less frequently than earlier in their careers, in large part reflecting the narrowing of indications for this surgery over the last decade.ConclusionThis study can help paediatric orthopaedic surgeons optimize decision-making for, and outcomes of, distal rectus femoris surgery in children with CP.Level of evidenceV     

重组HBsAg免疫逃逸突变体的表达及其抗原性分析

为了深入研究乙型肝炎病毒S基因变异所致的包膜抗原抗原性的改变，从含ＨＢＶＤＮＡ双拷贝的质粒载体ｐＥｃｏｂ６，获得一个８３７ｂｐ的ＨＢＶ－Ｓ基因片段，将其插入至载体ｐＢｌｕｅｓｃｒｉｐｔ ＫＳ~＋的ＳｍａⅠ位点，通过体外寡核苷酸介导的人工定点突变分别获得第１４５位、１２６位和第１４５位＋１２６位氨基酸三种Ｓ基因变异型。然后将这些Ｓ基因变异片段克隆到真核表达载体ｐＭＥｐ４上，从而构建了含ＨＢＶ－Ｓ基因及其突变型的表达载体ＰＭＥｐ４ＨＢＶＳＭ。用其转染人肝癌细胞系ＨｅｐＧ２，获得稳定分泌ＨＢｓＡｇ及其变异体的抗性细胞系。经体外初步研究表明，ＨＢｓＡｇ １４５位氨基酸变异体可影响ＨＢｓＡｇ的“ａ”抗原决定簇的结构。     

Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1

OBJECTIVE: To determine nevirapine (NVP) plasma levels during the postpartum period after a single intrapartum NVP dose for the prevention of mother-to-child transmission. METHODS: Plasma samples at delivery and during days 8 to 45 postpartum were obtained from HIV-infected Thai women who received an intrapartum NVP dose in the Perinatal HIV Prevention Clinical Trial-2 (PHPT-2) for the prevention of perinatal HIV transmission. These data were combined with NVP concentration data from 2 phase 1 studies of NVP for a population analysis. RESULTS: The median NVP level fell to 68 ng/mL (range: <50-228, n = 43) 8 to 14 days after dosing and to 51 ng/mL (range: <50-166, n = 25) between 15 and 21 days. During the second and third weeks postpartum, NVP levels were below the limit of quantitation in 23% and 44% of samples, respectively. Between 21 and 45 days, no sample had a quantifiable NVP concentration. A simulation derived from the population analysis predicts that NVP concentration falls to less than 10 ng/mL in 5% of women by 11 days, in 50% of women by 17.5 days, and in 95% of women by 28 days. CONCLUSIONS: Significant NVP concentrations remained for up to 20 days in these Thai women. To ensure that coverage is maintained until NVP concentrations fall to nonsuppressive levels, 1 month of additional antiretroviral treatment after delivery should be considered to prevent the emergence of resistant viruses.