Predictors of whole exome sequencing in dystonic cerebral palsy and cerebral palsy-like disorders.

INTRODUCTION: Cerebral palsy (CP) is a group of permanent disorders attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. Cerebral palsy-like (CP-like) disorders may clinically resemble CP but do not fulfill CP criteria and have often a progressive course and/or neurodevelopmental regression. To assess which patients with dystonic CP and dystonic CP-like disorder should undergo Whole Exome Sequencing (WES), we compared the rate of likely causative variants in individuals regarding their clinical picture, co-morbidities, and environmental risk factors. METHOD: Individuals with early onset neurodevelopmental disorder (ND) manifesting with dystonia as a core feature were divided into CP or CP-like cohorts based on their clinical picture and disease course. Detailed clinical picture, co-morbidities, and environmental risk factors including prematurity, asphyxia, SIRS, IRDS, and cerebral bleeding were evaluated. RESULTS: A total of 122 patients were included and divided into the CP group with 70 subjects (30 males; mean age 18y5m±16y6m, mean GMFCS score 3.3 ± 1.4), and the CP-like group with 52 subjects (29 males; mean age 17y7m±1y,6 m, mean GMFCS score 2,6 ± 1,5). The WES-based diagnosis was present in 19 (27.1%) CP patients and 30 CP-like patients (57.7%) with genetic conditions overlap in both groups. We found significant differences in diagnostic rate in CP individuals with vs. without risk factors (13.9% vs. 43.3%); Fisher's exact p = 0.0065. We did not observe the same tendency in CP-like (45.5% vs 58.5%); Fisher's exact p = 0.5. CONCLUSION: WES is a useful diagnostic method for patients with dystonic ND, regardless of their presentation as a CP or CP-like phenotype.

Comparison of bone remodelling around short stem and conventional straight stem in total hip replacement: a prospective randomized radiographic and dual-energy X-ray absorptiometric study.

OBJECTIVE: The aim of study was to evaluate periprosthetic bone mineral density (BMD) changes of proximal femur, osseointegration and clinical outcomes after implantation of short-stemmed and conventional straight-stemmed prostheses. METHODS: This prospective, randomized study included 50 patients with unilateral total hip replacement. The patients were randomized into 2 cohorts: patients with a cementless short stem Metha (n=25) and patients with a cementless conventional straight stem Bicontact evaluated as the control (n=25). Periprosthetic BMD changes were measured using a DEXA performed at one-week, 3-monts, 6-months and 1-year follow up. Clinical evaluation with Harris hip score (HHS) and radiographic assessment were performed through a 1 year follow up. RESULTS: Compared to 1-week postoperative assessment, there were differences in BMD changes between the groups at the final follow-up in all ROIs, with statistical significances in ROI 1, 2, 3, 6 and 7. The loss of periprosthetic BMD in all ROIs around straight stems at each time-point was observed. There was a tendency towards a regain of BMD in all ROIs at 1-year follow-up compared to the 3-months postoperative assessment with the short stems. Less pronounced bone loss was observed around the short stems that the straight stems in ROI 1 (‒2.9 % % vs ‒16.2 %), 5 (‒4.7 % vs ‒8.9 %) and 7 (‒8.6 % vs ‒20 %). The periprosthetic BMD exceeded baseline values in the short stem cohort in ROI 2 (+4.4 % vs ‒5 %), 3 (+5.6 % vs ‒2.5 %) and 6 (+4.3 % vs ‒10 %). All stems had a radiographically stable fixation. Stress shielding-related bone resorption was markedly lower in the short stem cohort. The HHS score was comparable between the two cohorts. CONCLUSION: The implant-specific stress shielding altered the proximal loading condition for both stems; however, the results of this study suggest a more physiological strain distribution with the short stems versus the straight stems (Tab. 3, Fig. 3, Ref. 25).

[Epidemiology of the endocrine orbitopathy]. / Endokrinná orbitopatia-- epidemiologické súvislosti.

The goal of this paper was to evaluate epidemiological data of the endocrine orbitopathy in a group of 126 patients (250 eyes) during the 5-years period (1999-2004). The prevalence of endocrine orbitopathy was at the age 46.5 +/- 11.4 years, predominantly in females: 5.3 times more often than in males. In most cases (94%) and independently on the sex, hyperthyroidism accompanied the endocrine orbitopathy. Hyperthyroidism mostly (91%) preceded the appearance of the endocrine orbitopathy. Most patients with endocrine orbitopathy had eyelid signs (91% females and 85% males respectively), protrusion or exophtalmos (77% females, 75% males). 69% patients (68% females, 70% males) had elevated intraocular pressure (pseudoglaucoma, primary glaucoma). During the active stage of the endocrine orbitopathy with protrusion (52% patients), pseudoglaucoma was detected in 7% of patients. During the inactive stage of the endocrine orbitopathy with protrusion (34% patients), pseudoglaucoma was detected in 4% of patients. Primary glaucoma was found in 2% (active stage) and 1% (inactive astage).

Hypocrellin and hypericin-induced phototoxicity of HL-60 cells: apoptosis or necrosis?

Hypericin and hypocrellin are potential antiviral and antineoplastic agents with multiple modes of light-induced biological activity connected with a production of singlet oxygen and/or excited-state proton transfer and consequent pH drop formation in the drugs environment. In present work light-induced cytotoxicity of hypericin and hypocrellin and mechansim of cell death (apoptosis or necrosis) on human leukemic cell line HL-60 was studied. As a mean for apoptosis detection we used poly (ADP-ribose) polymerase (PARP) as a sensitive marker of early stages of apoptosis. Our results show that exposition of HL-60 cells to hypericin (1 x 10(-5) mol x l(-1)) for 4 hours has no effect on PARP cleavage. However, after 24 and 48 hours of illumination there is evident that hypericin in this concentration cleaved PARP (116 kDa) into two fragments (85 and 25 kDa). Contrary to hypericin, hypocrellin in concentration 1 x 10(-5) mol x l(-1) after 4 hours of illumination cleaved PARP into two fragments typical for apoptosis. In lower concentration (1 x 10(-6) mol x l(-1)) hypocrellin possess also significant cytotoxic activity. Because we detected no fragmentation of PARP in all observed time periods we suggest that cytotoxic effect of hypocrellin in this concentration is due to induction of necrosis. Our results support the hypotesis that the hypericin and hypocrellin has similar mechanism of action and illumination increases cytotoxic effect of both agents.