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Data from the large, prospective, multinational, phase 3b JUMP study were analyzed to identify factors predictive of spleen and symptom responses in myelofibrosis patients receiving ruxolitinib. Factors associated with higher spleen response rates included International Prognostic Scoring System (IPSS) low/intermediate-1 risk vs intermediate-2/high risk (43.1% vs 30.6%; adjusted OR [aOR] 0.65 [95% CI 0.44-0.95]), ruxolitinib as first- vs second- or later-line therapy (40.2% vs 31.5%; aOR 0.53 [95% CI 0.38-0.75]), and a ruxolitinib total daily dose at Week 12 of >20 mg/day vs ≤20 mg/day (41.3% vs 30.4%; aOR 0.47 [95% CI 0.33-0.68]). No association was seen between baseline characteristics or total daily dose at Week 12 and symptom response. Ruxolitinib led to higher spleen response rates in patients with lower IPSS risk, and when used earlier in treatment. Higher doses of ruxolitinib were associated with higher spleen response rates, but not with symptom improvement.Trial registrationINC424 for patients with primary myelofibrosis, post polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis (JUMP).2010-024473-39; NCT01493414Date of registration 16 December 2011https//www.clinicaltrialsregister.eu/ctr-search/search?query=2010-024473-39https//clinicaltrials.gov/ct2/show/NCT01493414.

The number of female athletes has grown exponentially since Title IX. However, little data exists on the proportion of women and girls who play each sport.

To quantify changes in female sports participation in high school sports from 1973 to 2018.

Retrospective analysis of data from the National Federation of State High School Associations Participation Survey.

US high schools.

US high school athletes from 1973 to 2018.

Percentage of female participation for each high school sport in 5-year intervals; and changes in rates of participation by player gender and sport at designated intervals.

From 1973 to 2018, the percentage of high school sports played by girls increased from 24.2% to 42.9% ([95%CI, 18.6,18.8], p <0.0001). In the 14 sports included in our study, all had an increase in the percentage of female participation between 1973 and 2018. >80% of the increases occurred between 1973 and 1998 for all sports except lacrosse, ice hockey, football, and wrestling. Between 1998 and 2018, the percentage of girls playing each sport increased by less than 5% in all sports, except for ice hockey (11.5%, 95% CI 11.0, 12.0, p <0.001) and wrestling (7.1%, 95% CI 6.9, 7.1, p <0.001).

Girls' participation in high school sports continues to grow not only in numbers but in the types of sports played. Between 1998 and 2018, the greatest increases were noted in ice hockey and wrestling, which had fewer than 1% female participation before 1998. Physicians providing care for female athletes should be aware of these changes and understand the potential injuries associated with these sports.

Girls' participation in high school sports continues to grow not only in numbers but in the types of sports played. Between 1998 and 2018, the greatest increases were noted in ice hockey and wrestling, which had fewer than 1% female participation before 1998. Physicians providing care for female athletes should be aware of these changes and understand the potential injuries associated with these sports.The host defense peptides or antimicrobial peptides (AMPs) often contain short sequence of amino acids, either positive or negatively charged and express broad-spectrum antibacterial, antiviral and antifungal activity. Many researchers had reported that tryptophan, arginine and proline rich AMPs have a promising source of next-generation antibiotics. Nowadays, AMPs are used as a possible therapeutic source for future antibiotics. In the present study, the amino acid sequences of 2924 AMPs belonging to various sources rich in Tryptophan, Proline and Arginine was chosen for investigation. The AMPs were further categorized according to their source, structure and antimicrobial activities. The AMPs with tryptophan, arginine, proline residues in abundance with maximum sequence length of 20 amino acids alone was obtained. Homology modeling was performed with PEP-FOLD and the modeled structures were evaluated using RAMPAGE to identify the structural information. Further, the stability of peptide in aqueous condition was probed using molecular dynamics simulations. Communicated by Ramaswamy H. Sarma.

Evaluation of airway inflammation and dysfunction is important in management of allergic rhinitis (AR) since AR is a risk factor for developing asthma. Theoretical nonlinear modeling of exhaled nitric oxide (NO) has revealed extended flow-independent NO parameters that could explain where or how NO metabolism was altered. We aimed to evaluate the association between extended NO parameters and bronchial hyperresponsiveness (BHR) in children with AR.

Exhaled NO was measured in 74 children with AR on the same day they underwent the provocholine challenge test (PCT). Extended NO was measured in three different exhaled flow rates (30, 100, 200 mL/s) and calculated using the Högman-Meriläinen model. We compared the extended NO parameters including bronchial NO (JawNO), airway tissue NO (CawNO), alveolar tissue NO (CaNO), and diffusing capacity of NO (DawNO) between AR with and without BHR groups, and analyzed the correlation between extended NO parameters and the response-dose ratio (RDR) of the PCT. We additionally evaluated 49 respiratory healthy controls.

Among the 74 children with AR, nine showed BHR. check details JawNO increased more in children with AR than the control group. In children with AR, JawNO was higher in the AR with BHR than without BHR group, and was correlated positively with log RDR (

 = 0.373,

 = .001).

Extended NO analysis including JawNO can be a useful tool for assessing BHR in AR.

Extended NO analysis including JawNO can be a useful tool for assessing BHR in AR.Receptor-interacting protein kinase-1 (RIPK1) is a master regulator of cell death and inflammation, and mediates programmed necrosis (necroptosis) via mixed-lineage kinase like (MLKL) protein. Prior studies in experimental intracerebral hemorrhage (ICH) implicated RIPK1 in the pathogenesis of neuronal death and cognitive outcome, but the relevant cell types involved and potential role of necroptosis remain unexplored. In mice subjected to autologous blood ICH, early RIPK1 activation was observed in neurons, endothelium and pericytes, but not in astrocytes. MLKL activation was detected in astrocytes and neurons but not endothelium or pericytes. Compared with WT controls, RIPK1 kinase-dead (RIPK1D138N/D138N) mice had reduced brain edema (24 h) and blood-brain barrier (BBB) permeability (24 h, 30 d), and improved postinjury rotarod performance. Mice deficient in MLKL (Mlkl-/-) had reduced neuronal death (24 h) and BBB permeability at 24 h but not 30d, and improved post-injury rotarod performance vs. WT. The data support a central role for RIPK1 in the pathogenesis of ICH, including cell death, edema, BBB permeability, and motor deficits.