OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation.

Hearing impairment is the second most prevalent clinical feature after optic atrophy in Dominant Optic Atrophy associated with mutations in the OPA1 gene. In this study we characterized the hearing dysfunction in OPA1-linked disorders and provided effective rehabilitative options to improve speech perception. We studied two groups of OPA1 subjects, one comprising 11 patients (7 males; age range 13-79 years) carrying OPA1 mutations inducing haploinsufficiency, the other, 10 subjects (3 males; age range 5-58 years) carrying OPA1 missense mutations. Both groups underwent audiometric assessment with pure tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded through transtympanic electrocochleography from the group of patients harboring OPA1 missense mutations and were compared to recordings obtained from 20 normally-hearing controls and from 19 subjects with cochlear hearing loss. Eight patients carrying OPA1 missense mutations underwent cochlear implantation. Speech perception measures and electrically-evoked auditory nerve and brainstem responses were obtained after one year of cochlear implant use. Nine out of 11 patients carrying OPA1 mutations inducing haploinsufficiency had normal hearing function. In contrast, all but one subject harboring OPA1 missense mutations displayed impaired speech perception, abnormal brainstem responses and presence of otoacoustic emissions consistent with auditory neuropathy. In electrocochleography recordings, cochlear microphonic had enhanced amplitudes while summating potential showed normal latency and peak amplitude consistent with preservation of both outer and inner hair cell activities. After cancelling the cochlear microphonic, the synchronized neural response seen in both normally-hearing controls and subjects with cochlear hearing loss was replaced by a prolonged, low-amplitude negative potential that decreased in both amplitude and duration during rapid stimulation consistent with neural generation. The use of cochlear implant improved speech perception in all but one patient. Brainstem potentials were recorded in response to electrical stimulation in five subjects out of six, whereas no compound action potential was evoked from the auditory nerve through the cochlear implant. These findings indicate that underlying the hearing impairment in patients carrying OPA1 missense mutations is a disordered synchrony in auditory nerve fiber activity resulting from neural degeneration affecting the terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways by by-passing the site of lesion

ITA-MNGIE: an Italian regional and national survey for mitochondrial neuro-gastro-intestinal encephalomyopathy

Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly

ANALISIS INTERDEPENDENSI FOREIGN DIRECT INVESTMENT (FDI) DENGAN VARIABEL MAKRO EKONOMI

ABSTRAK Tujuan utama dari penelitian ini adalah untuk menganalisis interdependensi antara FDI dengan beberapa variabel yang lain, seperti PDB, Trade, Nilai Tukar, dan Tingkat bunga. Model VAR digunakan untuk menunjukkan pandangan yang komprehensif dari interdependensi ini. Hasil empiris menunjukkan bahwa melalui model VAR, interdependensi antara variabel FDI, PDB, Trade, Nilai Output Industri, Nilai Tukar dan Tingkat Suku Bunga telah diteliti dalam hubungan jangka panjang melalui kointegrasi vektor dan jangka pendek yang berdampak pada model VAR. Korelasi dinamis variabel telah diperoleh dengan analisis varian dan analisis respon impuls. Beberapa implikasi besar muncul dari hasil penelitian. Jika pemerintah Indonesia berkeinginan mendorong FDI dan pertumbuhan ekonomi, hal ini dapat dilakukan dengan output dan nilai tukar. Dalam jangka pendek maupun jangka panjang, keduanya sangat penting untuk stabilitas ekonomi. Kata Kunci : FDI, Pertumbuhan ekonomi, variabel makro dan model VARBanda Ace

EULAR Sjogren's syndrome disease activity index (ESSDAI):a user guide

The EULAR Sj\uf6gren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS

Relativistic Celestial Mechanics with PPN Parameters

Starting from the global parametrized post-Newtonian (PPN) reference system with two PPN parameters $\gamma$ and $\beta$ we consider a space-bounded subsystem of matter and construct a local reference system for that subsystem in which the influence of external masses reduces to tidal effects. Both the metric tensor of the local PPN reference system in the first post-Newtonian approximation as well as the coordinate transformations between the global PPN reference system and the local one are constructed in explicit form. The terms proportional to $\eta=4\beta-\gamma-3$ reflecting a violation of the equivalence principle are discussed in detail. We suggest an empirical definition of multipole moments which are intended to play the same role in PPN celestial mechanics as the Blanchet-Damour moments in General Relativity. Starting with the metric tensor in the local PPN reference system we derive translational equations of motion of a test particle in that system. The translational and rotational equations of motion for center of mass and spin of each of $N$ extended massive bodies possessing arbitrary multipole structure are derived. As an application of the general equations of motion a monopole-spin dipole model is considered and the known PPN equations of motion of mass monopoles with spins are rederived.Comment: 71 page

Post-Newtonian Gravitational Radiation

1 Introduction 2 Multipole Decomposition 3 Source Multipole Moments 4 Post-Minkowskian Approximation 5 Radiative Multipole Moments 6 Post-Newtonian Approximation 7 Point-Particles 8 ConclusionComment: 46 pages, in Einstein's Field Equations and Their Physical Implications, B. Schmidt (Ed.), Lecture Notes in Physics, Springe