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

A Probabilistic Assessment of Soil Erosion Susceptibility in a Head Catchment of the Jemma Basin, Ethiopian Highlands

Soil erosion represents one of the most important global issues with serious effects on agriculture and water quality, especially in developing countries, such as Ethiopia, where rapid population growth and climatic changes affect widely mountainous areas. The Meskay catchment is a head catchment of the Jemma Basin draining into the Blue Nile (Central Ethiopia) and is characterized by high relief energy. Thus, it is exposed to high degradation dynamics, especially in the lower parts of the catchment. In this study, we aim at the geomorphological assessment of soil erosion susceptibilities. First, a geomorphological map was generated based on remote sensing observations. In particular, we mapped three categories of landforms related to (i) sheet erosion, (ii) gully erosion, and (iii) badlands using a high-resolution digital elevation model (DEM). The map was validated by a detailed field survey. Subsequently, we used the three categories as dependent variables in a probabilistic modelling approach to derive the spatial distribution of the specific process susceptibilities. In this study we applied the maximum entropy model (MaxEnt). The independent variables were derived from a set of spatial attributes describing the lithology, terrain, and land cover based on remote sensing data and DEMs. As a result, we produced three separate susceptibility maps for sheet and gully erosion as well as badlands. The resulting susceptibility maps showed good to excellent prediction performance. Moreover, to explore the mutual overlap of the three susceptibility maps, we generated a combined map as a color composite where each color represents one component of water erosion. The latter map yields useful information for land-use managers and planning purposes

Endoscopic approach for paranasal sinuses osteomas: Our experience and review of literature

Osteomas are common benign bone tumors of the skull and facial structures involving primarily the cranial vault, mandible, external auditory canal, paranasal sinuses, nasal cavity, and orbit.1,2 These neoplasms are usually asymptomatic and account for 0.43% of tumor in population with an incidental finding on 1% of radiographs and on 3% of computed tomography (CT) scans. [1] These solid nodular sclerotic lesions usually arise from the outer table and are usually < 10 mm; lesions larger than 30 mm in diameter are considered giant tumors.3,4,7 Most of patients with such a diagnosis have few or no symptoms, in general only 10% is symptomatic, in the second to fifth decades of life 5,6. In literature, endoscopic endonasal approaches are mainly indicated for small ethmoidal osteomas without significant orbital or frontal extension7, while large osteomas require Caldwell-Luc surgery8 or other more aggressive approaches25. We report our experience about the treatment of paranasal sinuses osteomas treated endoscopically or by endoscope-assisted Caldwell-Luc approach, achieving total removal of the neoplasms with all the advantages deriving by endoscopic technique such as closer visualization of the anatomy, no damage to the surrounding structures, better cosmetic results, less morbidity and shorter hospitalization17

Visceral leishmaniasis, hypertriglyceridemia and secondary hemophagocytic lymphohistiocytosis

Visceral leishmaniasis (VL), a protozoan disease, is 100 % fatal if left untreated. Anemia is common in VL which plays a role in expression of clinically overt VL disease. Laboratory clues are scarce for strengthening clinical suspicion for severity in VL. Hypertriglyceridemia has emerged as a new concept for the diagnosis and prognosis in VL. The present study is aimed at correlating the magnitude of hypertriglyceridemia with the severity in VL. Materials and methods: A retrospective case–control study was conducted between January 2012 to December 2013 among 124 patients coming for treatment from VL endemic areas, who had fever of more than 15 days and did not respond to antimalarials and antibiotics. The parasitologically confirmed VL cases (n = 87) were categorized as mild/moderate (n = 60) and severe (n = 27) groups according to WHO classification for anemia and parasite burden. Serum triglycerides were assayed in VL groups along with controls (n = 37). Results: Serum triglyceride level was significantly higher in VL than controls [mean values were 173.50 ± 47.67 versus 127.1 ± 53.79 mg/dl, respectively (p 161.7 mg/dl) was noted in all severe VL patients, compared to 31.66 % of mild or moderate group (p < 0.0001). There was no significant difference between mild/moderate VL and controls. Conclusions: It is hypothesized that hypertriglyceridemia could be of additional diagnostic benefit to assess the probability and severity of VL in endemic areas. © 2015, Springer-Verlag Berlin Heidelberg

Analysis of the iron coatings formed during marcasite and arsenopyrite oxidation at neutral-alkaline conditions

In order to study the nature of the precipitates formed on arsenopyrite and marcasite after reacting with neutral to alkaline solutions, a combination of techniques including Scanning Electron Microscope-Energy Dispersive Spectroscopy (SEM-EDS), X-ray Photoelectron Spectroscopy (XPS) and synchrotron-based techniques such as micro-X-Ray diffraction (µXRD) and Micro-X-ray Absorption Near Edge Structure (µXANES) have been used. The results showed that the oxidation of marcasite and arsenopyrite under neutral to alkaline conditions leads to the formation of an Fe rich coating which seems to prevent the oxidation of these sulphides. SEM observations confirmed the presence newly-formed phases after the sulphides reaction under the studied conditions. XPS analysis showed that iron, sulphur and arsenic in the case of the arsenopyrite are in oxidized states in the sulphide surfaces. The microscale analysis of the S and Fe speciation performed by µXANES suggested that due to the sulphide oxidation an increase in the oxidation state of those elements took place together with an increase of the sulphate content in the surface layer (grain boundary). Micro-X-ray diffraction results indicated that goethite (a-FeOOH) is the only crystalline newly-formed phase when the reaction occurs at pH 12 whereas at lower pH the products formed on the sulphide surfaces seem to be poorly crystalline and they do not contribute to the diffraction effects in the XRD diagrams

Noninvasive Assessment of Hemodynamic Stress Distribution after Indirect Revascularization for Pediatric Moyamoya Vasculopathy

n/

A multi-scale regional landslide susceptibility assessment approach: the SUFRA_SICILIA (SUscettibilit\ue0 da FRAna in Sicilia) project

The SUFRA project is based on a three level susceptibility mapping. According to the availability of more detailed data, the three scale for susceptibility mapping are increased respect to the ones suggested by the TIER group to 1:100,000, 1:50,000 and 1:25,000/1:10,000. The mapping levels exploit climatic, soil use (CORINE2009) and seismic informative layers, differentiating in the details of the core data (geology and topography), in the quality and resolution of the landslide inventory and in the modelling approach (Tab. 1). SUFRA_100 is based on a heuristic approach which is applied by processing a geologic layer (produced by ARTA integrating pre-CARG 1:100,000 geologic maps); the DEM exploited are IGMI 250m and the mapping units are 1km side square cells. Models are validated with respect to the PAI LIPs (Landslide Identification Points) which are reclassified adopting a simplified scheme. Output cuts of SUFRA100 will be referred to administrative boundaries (provinces). SUFRA50 is based on statistical analysis of new CARG geologic maps and 20m (ITA2000) - 2m (ATA2007) DEM. The mapping units are 500m and 50m cells, hydrographic and hydro-morphometric units. The landslide inventory is the IFFI2012_LIPs (first level) which is the result of the conversion in IFFI format of the PAI archive, which will be supported by remote landslide mapping (exploiting the ATA2007 aerial photos), according to the IFFI first level approach. Validation of the models will be performed exploiting both random spatial partition and temporal partition methods. Output cuts of SUFRA50 will be based on physiographic (basin) and administrative (municipalities) boundaries. SUFRA10/25 is based on statistical analysis of new CARG geologic maps (remotely and field adapted) and 2m (ATA2007) DEM. The mapping units are the slope units (SLUs) which are derived by further partitioning the hydro-morphometric units so to obtain closed morphodynamic units. The landslide inventories is the IFFI2012 which is the results of a field supported (on focus) landslide remote systematic mapping, according to the IFFI full level approach. Examples of SUFRA_100, SUFRA_50 and SUFRA_10 are presented for some representative key sector of Sicily. First results attest for the feasibility and goodness of the proposed protocol. The SUFRA program aims at enabling the regional governmental administration to cope with landslide prevision, which is the required operational concept in land management and planning. PAI has been a great advance with respect to the \u201cpre-SARNO\u201d conditions, but it is very exposed to fail: it is a blind approach for new activations; it is critically dependent on the quality of the landslide inventories; it cannot project the susceptibility outside the landslide area

High prevalence of BRCA1 deletions in BRCAPRO-positive patients with high carrier probability.

Mutation screening of the BRCA1 and BRCA2 genes in probands with familial breast/ovarian cancer has been greatly improved by the multiplex ligation-dependent probe amplification (MLPA) assay able to evidence gene rearrangements not detectable by standard screening methods. However, no criteria for selection of cases to be submitted to the MLPA test have been reported yet. We used the BRCAPro software for the selection of familial breast/ovarian cancer probands investigated with the MLPA approach after negative BRCA1/2 conventional mutation screening. One hundred and seventy-seven probands were investigated for germline BRCA1/2 mutations after assessment of genetic risk using BRCAPro. Probands were classified as BRCAPro positive (n = 67) when the carrier probability (CP) was >10% and as BRCAPro negative (n = 110), when the CP was <10%. Conventional mutational analyses of the BRCA1/2 genes and, in one case, of p53 identified 22 pathogenetic germline mutations, 12 in BRCA1, 9 in BRCA2 and 1 in p53, in 22/177 (12.4%) probands. All the mutations except one were detected in BRCAPro-positive patients. In the 46 BRCAPro-positive cases that resulted negative by BRCA1/2 mutation, screening analysis of rearrangements within BRCA1/2 by MLPA was carried out. Three patients with a very high CP showed BRCA1 deletions, consisting of deletions of exons 1–2 in two probands and of exon 24 in the third proband. In one case, the exons 1–2 deletion was shown to cosegregate with disease in the family. No BRCA2 rearrangements were detected, but one patient showed the 1100delC of the CHEK2 gene, whose probe is present in the BRCA2 kit. In our series, the highest carrier detection rate of mutation screening plus MLPA analysis (52.3%) was in patients with a BRCAPro CP >50%

To Push or To Pull? In a Post-COVID World, Supporting and Incentivizing Antimicrobial Drug Development Must Become a Governmental Priority

This is the final version. Available on open access from the American Chemical Society via the DOI in this recorddata availability: This study did not generate any new data. The data on COVID-19 deaths used in the publication are publicly available at https://www.worldometers.info/coronavirus/ (access date 15th December 2020).The COVID-19 pandemic has refocused attention worldwide on the dangers of infectious diseases, in terms of both global health and the effects on the world economy. Even in high income countries, health systems have been found wanting in dealing with the new infectious agent. However, the even greater long-term danger of antimicrobial resistance in pathogenic bacteria and fungi is still under-appreciated, especially among the general public. Although antimicrobial drug development faces significant scientific challenges, the gravest challenge at the moment appears to be economic, where the lack of a viable market has led to a collapse in drug development pipelines. There is therefore a critical need for governments across the world to further incentivize the development of antimicrobials. Most incentive strategies over the past decade have focused on so-called “push” incentives that bridge the costs of antimicrobial research and development, but these have been insufficient for reviving the pipeline. In this Perspective, we analyze the current incentive strategies in place for antimicrobial drug development, and focus on “pull” incentives, which instead aim to improve revenue generation and thereby resolve the antimicrobial market failure challenge. We further analyze these incentives in a broader “One Health” context and stress the importance of developing and enforcing strict protocols to ensure appropriate manufacturing practices and responsible use. Our analysis reiterates the importance of international cooperation, coordination across antimicrobial research, and sustained funding in tackling this significant global challenge. A failure to invest wisely and continuously to incentivize antimicrobial pipelines will have catastrophic consequences for global health and wellbeing in the years to come.Wellcome TrustGCRF One Health Poultry HubMedical Research Council (MRC

Aerosol-jet-printed, conformable microfluidic force sensors

This is the final version. Available on open access from Cell Press via the DOI in this recordData and code availability: The authors declare that data supporting the findings of this study are available within the article, the Supplemental information, and the DSpace@Cambridge data repository (https://doi.org/10.17863/CAM.63758).Force sensors that are thin, low-cost, flexible, and compatible with commercial microelectronic chips are of great interest for use in biomedical sensing, precision surgery, and robotics. By leveraging a combination of microfluidics and capacitive sensing, we develop a thin, flexible force sensor that is conformable and robust. The sensor consists of a partially filled microfluidic channel made from a deformable material, with the channel overlaying a series of interdigitated electrodes coated with a thin, insulating polymer layer. When a force is applied to the microfluidic channel reservoir, the fluid is displaced along the channel over the electrodes, thus inducing a capacitance change proportional to the applied force. The microfluidic molds themselves are made of low-cost sacrificial materials deposited via aerosol-jet printing, which is also used to print the electrode layer. We envisage a large range of industrial and biomedical applications for this force sensor.European Research Council (ERC)Engineering and Physical Sciences Research Council (EPSRC)Wellcome Trus