Effectiveness of scapula-focused approaches in patients with rotator cuff related shoulder pain: A systematic review and meta-analysis

Background: Rotator cuff related shoulder pain (RCSP) is common with a range of conservative treatments currently offered. Evidence supporting superiority of one approach over another is lacking. Scapula focused approaches (SFA) are frequently prescribed and warrant investigation. Objective: To evaluate the effectiveness of SFA in RCSP. Design: Systematic review of randomised controlled trials. Methods: An electronic search including MEDLINE, PEDro, ENFISPO to January 2016 was supplemented by hand searching. Randomised controlled trials were included; appraised using the PEDro scale and synthesised via meta-analysis or narratively, where appropriate. Results: Four studies (n = 190) reported on pain and three studies (n = 122) reported on disability. Regarding pain, there was statistical but not clinically significant benefit of SFA versus generalised approaches (mean difference (VAS) 0.714; 95% CI 0.402-1.026) in the short term (<6 weeks); regarding disability, there was significant benefit of SFA versus generalised approaches (mean difference 14.0; 95% CI 11.2-16.8) in the short term (<6 weeks). One study (n = 22) reported disability at 3 months, which was not statistically significant. Evidence is conflicting from four studies relating to the effect of SFA on scapula position/movement. Conclusion: SFA for RCSP confers benefit over generalised approaches up to six weeks but this benefit is not apparent by 3 months. Early changes in pain are not clinically significant. With regards to scapula position/movement, the evidence is conflicting. These preliminary conclusions should be treated with significant caution due to limitations of the evidence base

Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

BACKGROUND: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. METHODS AND FINDINGS: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. CONCLUSIONS: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The Self-Assessment Corner for Shoulder Strength: Reliability, Validity, and Correlations With Upper Extremity Physical Performance Tests.

Rotator cuff weakness and rotation ratio imbalances are possible risk factors for shoulder injury among overhead athletes. In consensus statements, organizations have highlighted the importance of a screening examination to identify athletes at risk of injury. The screening should be portable and designed to be feasible in many different environments and contexts.info:eu-repo/semantics/publishe

Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study

BACKGROUND: Hypospadias affects around 1/200 newborn males. Intrauterine testicular dysfunction may underlie a subset of cases. The long-term endocrine and reproductive outcomes in these men remain largely unknown. METHODS: Cross-sectional study in Ghent and Vienna University Hospitals to assess the endocrine and seminal parameters of young adult men (16–21 years) born with non-syndromic hypospadias (NSH) (n = 193) compared to healthy typical males (n = 50). Assessments included physical exam, semen analysis, hormone assays and exome-based gene panel analysis (474 genes). FINDINGS: All participants had experienced a spontaneous puberty, in spite of higher LH and INSL3 levels than typical males. Oligo- or azoospermia was observed in 32/172 (18·6%; 99%-CI: 12·2–27·4%) of NSH men; but in 5/16 (31·3%; 99%-CI: 11·1;62·4%) of complex NSH men and in 13/22 (59·1%; 99%-CI: 33·2–80·7%) of those born small for gestational age (SGA). No (likely) pathogenic coding variants were found in the investigated genes. Suboptimal statural growth affected 8/23 (34·8%; 99%-CI: 15·4–61·0%) of men born SGA with NSH. INTERPRETATION: Spermatogenesis is significantly compromised in NSH men, especially in those born SGA or those with complex NSH. Long-term andrological follow-up is recommended, including end-pubertal semen analysis. No clear monogenic causes could be demonstrated in our cohort even in proximal or complex NSH. Being born SGA with NSH is frequently associated with poor catch-up growth, requiring growth hormone therapy in some. FUNDING: Research grants from the European Society of Paediatric Endocrinology, the Belgian Society of Pediatrics, the Belgian Society of Pediatric Endocrinology and Diabetology and the Research Foundation Flanders (FWO)