Apología del libre

És el poema del llibre 'Salmos al viento'

Toplum Gönüllüleri Vakfı' nın kuruluş süreci ve Türkiye' deki sivil toplum anlayışına etkisi

Ankara : İhsan Doğramacı Bilkent Üniversitesi İktisadi, İdari ve Sosyal Bilimler Fakültesi, Tarih Bölümü, 2015.This work is a student project of the The Department of History, Faculty of Economics, Administrative and Social Sciences, İhsan Doğramacı Bilkent University.by Aslan, Mustafa Çağatay

The effects of dietary changes on bone markers in postmenopausal vertebral osteopenia

Background & aims: Nutrition is one of the most important environmental factors affecting the formation of osteopenia. The purpose of this study was to investigate the effects of dietary changes on bone formation and bone resorption markers of postmenopausal women with vertebral osteopenia. Methods: In this study, 108 women with postmenopausal vertebral osteopenia were included. Patients were observed for a month to identify their regular nutritional status. Before intervention, blood and urine samples were taken from all patients. Then, 2-day food consumption records were taken and the patients were divided into 4 groups. Different types of diets (opposite of their regular diets) were prepared for these groups (1: control, 2: reduced-carbohydrate, 3: reduced-protein, 4: reduced-sodium) and followed for 3 months. At the end of follow-ups, blood and urine samples were taken again and changes in osteocalcin (OC) and N-terminal telopeptide (NTX) levels were examined. Results: According to biochemical analysis, there was a significant decrease (p 0,05) in reduced carbohydrate group. When NTX levels were assessed, a significant decrease (p < 0.001) in the reduced carbohydrate group and a significant increase in the reduced protein group (p < 0.05) were found. Conclusion: Our findings show that reduced carbohydrate diet protected whereas, reduced protein diet negatively affected bone health. Osteopenic individuals were thought to be able to improve bone health and their quality of life by early dietary intervention.Marmara Universit

Impaired gating of γ‐ and ε‐AChR respectively causes Escobar syndrome and fast‐channel myasthenia

Abstract Objective To dissect the kinetic defects of acetylcholine receptor (AChR) γ subunit variant in an incomplete form of the Escobar syndrome without pterygium and compare it with those of a variant of corresponding residue in the AChR ε subunit in a congenital myasthenic syndrome (CMS). Methods Whole exome sequencing, α‐bungarotoxin binding assay, single channel patch‐clamp recordings, and maximum likelihood analysis of channel kinetics. Results We identified compound heterozygous variants in AChR γ and ε subunits in three Escobar syndrome (1–3) and three CMS patients (4–6), respectively. Each Escobar syndrome patient carries γP121R along with γV221Afs*44 in patients 1 and 2, and γY63* in patient 3. Three CMS patients share εP121T along with εR20W, εG‐8R, and εY15H in patients 4, 5, and 6, respectively. Surface expressions of γP121R‐ and εP121T‐AChR were 80% and 138% of the corresponding wild‐type AChR, whereas εR20W, εG‐8R, and εY15H reduced receptor expression to 27%, 35%, and 30% of wild‐type εAChR, respectively. γV221Afs*44 and γY63* are null variants. Thus, γP121R and εP121T determine the phenotype. γP121R and εP121T shorten channel opening burst duration to 28% and 18% of corresponding wild‐type AChR by reducing the channel gating equilibrium constant 44‐ and 63‐fold, respectively. Interpretation Similar impairment of channel gating efficiency of a corresponding P121 residue in the acetylcholine‐binding site of the AChR γ and ε subunits causes Escobar syndrome without pterygium and fast‐channel CMS, respectively, suggesting that therapy for the fast‐channel CMS will benefit Escobar syndrome

PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome

OBJECTIVE: To investigate the genetic and physiologic basis of the neuromuscular symptoms of hypotonia-cystinuria syndrome (HCS) and isolated PREPL deficiency, and their response to therapy. METHODS: We performed molecular genetic, histochemical, immunoblot, and ultrastructural studies, investigated neuromuscular transmission in vitro in a patient with isolated PREPL deficiency, and evaluated the effect of pyridostigmine in this patient and in 3 patients with the HCS. RESULTS: HCS is caused by recessive deletions involving the SLC3A1 and PREPL genes. The major clinical features of HCS are type A cystinuria, growth hormone deficiency, muscle weakness, ptosis, and feeding problems. The proband with isolated PREPL deficiency had myasthenic symptoms since birth and a positive edrophonium test but no cystinuria. She and 1 of 3 patients with HCS responded transiently to pyridostigmine during infancy. The proband harbors a paternally inherited nonsense mutation in PREPL and a maternally inherited deletion involving both PREPL and SLC3A1; therefore, the PREPL deficiency determines the phenotype. We detected no PREPL expression in the patient's muscle and endplates. Electrophysiology studies revealed decreased quantal content of the endplate potential and reduced amplitude of the miniature endplate potential without endplate acetylcholine receptor deficiency or altered endplate geometry. CONCLUSION: Isolated PREPL deficiency is a novel monogenic disorder that causes a congenital myasthenic syndrome with pre- and postsynaptic features and growth hormone deficiency. The myasthenic symptoms in PREPL deficiency with or without cystinuria may respond to pyridostigmine in early life. We attribute the myasthenia to abrogated interaction of PREPL with adaptor protein 1.status: publishe

Znaczenie wskaźnika HATCH w prognozowaniu skutecznego powrotu do rytmu zatokowego po kardiowersji elektrycznej z powodu migotania przedsionków

Background: The HATCH score predicts the development of persistent and permanent atrial fibrillation (AF) one year after spontaneous or pharmacological conversion to sinus rhythm in patients with AF. However, it remains unknown whether HATCH score predicts short-term success of the procedure at early stages for patients who have undergone electrical cardioversion (EC) for AF. Aim: The present study evaluated whether HATCH score predicts short-term success of EC in patients with AF. Methods: The study included patients aged 18 years and over, who had undergone EC due to AF lasting less than 12 months, between December 2011 and October 2013. HATCH score was calculated for all patients. The acronym HATCH stands for Hypertension, Age (above 75 years), Transient ischaemic attack or stroke, Chronic obstructive pulmonary disease, and Heart failure. This scoring system awards two points for heart failure and transient ischaemic attack or stroke and one point for the remaining items. Results: The study included 227 patients and short-term EC was successful in 163 of the cases. The mean HATCH scores of the patients who had undergone successful or unsuccessful EC were 1.3 ± 1.4 and 2.9 ± 1.4, respectively (p &lt; 0.001). The area of the HATCH score under the curve in receiver operating characteristics analysis was (AUC) 0.792 (95% CI 0.727–0.857, p &lt; 0.001). A HATCH score of two and above yielded 77% sensitivity, 62% specificity, 56% positive predictive value, and 87% negative predictive value in predicting unsuccessful cardioversion. Conclusions: HATCH score is useful in predicting short-term success of EC at early stages for patients with AF, for whom the use of a rhythm-control strategy is planned.  Wstęp: Skala HATCH umożliwia prognozowanie rozwoju przetrwałego i utrwalonego migotania przedsionków (AF) w ciągu roku po samoistnym lub spowodowanym leczeniem powrocie do rytmu zatokowego u chorych z AF. Nie wiadomo jednak, czy wskaźnik HATCH jest przydatny w określaniu prawdopodobieństwa powodzenia zabiegu w perspektywie krótkoterminowej we wczesnym stadium u pacjentów, których poddano kardiowersji elektrycznej (EC) z powodu AF. Cel: Celem pracy była ocena, czy wskaźnik HATCH umożliwia prognozowanie wczesnego powodzenia EC u chorych z AF. Metody: Do badania włączono chorych w wieku 18 i starszych, których w okresie od grudnia 2011 r. do października 2013 r. poddano EC z powodu AF występującego krócej niż 12 miesięcy. U wszystkich chorych obliczono wskaźnik HATCH. Akronim HATCH oznacza Hypertension (nadciśnienie tętnicze), Age (wiek, powyżej 75 lat), Transient ischaemic attack or stroke (przemijające niedokrwienie mózgu lub udar mózgu), Chronic obstructive pulmonary disease (przewlekła obturacyjna choroba płuc) i Heart failure (niewydolność serca). W tej skali niewydolność serca i przemijające niedokrwienie mózgu lub udar oznaczają 2 punkty, natomiast obecność każdego z pozostałych elementów — 1 punkt. Wyniki: W badaniu uczestniczyło 227 chorych. W przypadku 163 z nich odnotowano powodzenie EC we wczesnym okresie po zabiegu. Średnie wartości w skali HATCH u chorych, u których przeprowadzono skuteczną i nieskuteczną EC, wynosiły odpowiednio 1,3 ± 1,4 i 2,9 ± 1,4 (p &lt; 0,001). Pole pod krzywą (AUC) wskaźnika HATCH w analizie krzywych ROC wynosiło 0,792 (95% CI 0,727–0,857; p &lt; 0,001). Wskaźnik HATCH ≥ 2 pozwalał na prognozowanie niepowodzenia kardiowersji, przy czym czułość tego parametru wynosiła 77%, swoistość — 62%, wartość predykcyjna dodatnia — 56%, a wartość predykcyjna ujemna — 87%. Wnioski: Skala HATCH jest przydatna w prognozowaniu szans powodzenia EC we wczesnym okresie po zabiegu u chorych z AF, u których planuje się zastosowanie strategii kontroli rytmu serca.

Rapsyn Mutations in Humans Cause Endplate Acetylcholine-Receptor Deficiency and Myasthenic Syndrome

Congenital myasthenic syndromes (CMSs) stem from genetic defects in endplate (EP)-specific presynaptic, synaptic, and postsynaptic proteins. The postsynaptic CMSs identified to date stem from a deficiency or kinetic abnormality of the acetylcholine receptor (AChR). All CMSs with a kinetic abnormality of AChR, as well as many CMSs with a deficiency of AChR, have been traced to mutations in AChR-subunit genes. However, in a subset of patients with EP AChR deficiency, the genetic defect has remained elusive. Rapsyn, a 43-kDa postsynaptic protein, plays an essential role in the clustering of AChR at the EP. Seven tetratricopeptide repeats (TPRs) of rapsyn subserve self-association, a coiled-coil domain binds to AChR, and a RING-H2 domain associates with β-dystroglycan and links rapsyn to the subsynaptic cytoskeleton. Rapsyn self-association precedes recruitment of AChR to rapsyn clusters. In four patients with EP AChR deficiency but with no mutations in AChR subunits, we identify three recessive rapsyn mutations: one patient carries L14P in TPR1 and N88K in TPR3; two are homozygous for N88K; and one carries N88K and 553ins5, which frameshifts in TPR5. EP studies in each case show decreased staining for rapsyn and AChR, as well as impaired postsynaptic morphological development. Expression studies in HEK cells indicate that none of the mutations hinders rapsyn self-association but that all three diminish coclustering of AChR with rapsyn