Correlation between FIX genotype and pharmacokinetics of Nonacog alpha according to a multicentre Italian study

Pharmacokinetic (PK) studies on recombinant FIX concentrate, Nonacog alpha, were conducted with different sampling time designs which gave rise to not complete and homogenous outcomes. In addition, patient's FIX genotype/PK relationship has never been investigated

The relationship of the knowledge of letter names and reading achievement in grade one.

Thesis (Ed.M.)--Boston Universit

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Effects of early rehabilitation on motor function, dyspnoea intensity, respiratory muscle performance and handgrip strength in patients with COVID-19: an observational study

Background/aims Although an increasing volume of research is emerging, rehabilitative treatment of patients with COVID-19 still continues to be a matter of great importance that must be explored further. The purpose of the present study was to describe the effects of inpatient rehabilitation in acute patients treated in a sub-intensive hospital setting during the COVID-19 pandemic.Methods A retrospective analysis was conducted based on the prospectively collected data of 192 patients with COVID-19 undergoing a physiotherapeutic regimen during their hospitalisation. Patients were admitted because of COVID-19-related pneumonia from the periods of 25 March-12 June 2020 and 2 November 2020-9 June 2021. This study investigated dyspnoea intensity using the modified Borg scale, motor function through the 1-minute sit-to-stand test, and daily walked distance. In a subset of 57 patients, handgrip strength and respiratory muscle function was also evaluated. Measurements were taken at baseline and discharge.Results Patients were classified according to the severity of their ratio of arterial oxygen partial pressure to fractional inspired oxygen (mean 225 +/- 82 mmHg). At discharge to home or to another hospital facility, patients performed a mean of 12 repetitions (1-minute sit-to-stand test); dyspnoea intensity was 1.4 (modified Borg scale), and they were able to walk a mean distance of 266.7 metres. The mean handgrip strength of the dominant hand was 29.3 kg, the maximal inspiratory pressure was 43.5 cmH(2)O, and the maximal expiratory pressure was 59.1 cmH(2)O. Overall, significant differences before and after treatment were detected for all clinical variables. Dyspnoea improved by 0.7 points; walked distance by 200 metres; the number of repetitions at the 1-minute sit-to-stand test by 5.6; the handgrip strength by 1.2 kg (right hand) and 1.7 kg (left hand); maximal inspiratory pressure by 7.7 cmH(2)O; and maximal expiratory pressure by 9.5 cmH(2)O.Conclusions Patients obtained significant improvements in functional capacity, dyspnoea perception, handgrip strength and respiratory muscle function. In addition, the treatment was feasible and well tolerated by patients, and no adverse related events were observed in a sub-intensive care setting

A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study)

BACKGROUND: Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients' well-being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well- of children with hemophilia. OBJECTIVE: This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image-proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10-year time period. METHODS: Forty-five children with severe hemophilia A, aged 1-7 years (median 4), with negative clinical-radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU kg(-1) 3 × week) or episodic therapy with ≥25 IU kg(-1) every 12-24 h until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated. RESULTS: Twenty-one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events per patient per month (P < 0.02). Plain-film radiology showed signs of arthropathy in six patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (P < 0.05). Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds (0.12 joint bleeds per patient per month) and no radiologic signs of arthropathy. CONCLUSION: This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life

Disruption of ST5 is associated with mental-retardation and multiple congenital anomalies

We observed a patient with a cryptic subtelomeric de novo balanced translocation 46,XY.ish t(11;20)(p15.4;q13.2) presenting with severe mental retardation, muscular hypotonia, seizures, bilateral sensorineural hearing loss, submucous cleft palate, persistent ductus Botalli, unilateral cystic kidney dysplasia and frequent infections. Fluorescence in situ hybridization mapping and sequencing of the translocation breakpoints showed that no known genes are disrupted at 20q13.2 and that ST5 (suppression of tumorigenicity 5; MIM 140750) is disrupted on 11p15.4. By quantitative PCR from different human tissues we found ST5 relatively evenly expressed in fetal tissues. ST5 expression was more pronounced in adult brain, kidney and muscle than in the corresponding fetal tissues, whereas expression in other tissues was generally lower than in the fetal tissue. Using RNA in situ hybridization in mouse we found that St5 is expressed in the frontal cortex during embryonic development. In adult mouse brain expression of St5 was especially high in the hippocampal area and cerebellum. Hence we suppose that ST5 plays an important role in central nervous system development probably due to disturbance of DENN-domain mediated vesicle formation and neurotransmitter trafficking. Thus, our findings implicate ST5 in the etiology of mental retardation, seizures and multiple congenital anomalies

il paziente con deficit di ormone della crescita

Il capitolo rivolge l'attenzione alle patologie del distretto oro-cefalico del paziente pediatrico affetto da deficit di GH, offrendo indicazioni di diagnosi e terapia sulla base dell'esperienza clinica e delle evidenze presenti in letteratura