A Novel Homozygous Variant in DYSF Gene Is Associated with Autosomal Recessive Limb Girdle Muscular Dystrophy R2/2B

Mutations in the DYSF gene, encoding dysferlin, are responsible for Limb Girdle Muscular Dystrophy type R2/2B (LGMDR2/2B), Miyoshi myopathy (MM), and Distal Myopathy with Anterior Tibialis onset (MDAT). The size of the gene and the reported inter and intra familial phenotypic variability make early diagnosis difficult. Genetic analysis was conducted using Next Gene Sequencing (NGS), with a panel of 40 Muscular Dystrophies associated genes we designed. In the present study, we report a new missense variant c.5033G>A, p.Cys1678Tyr ({"type":"entrez-nucleotide","attrs":{"text":"NM_003494","term_id":"1675063869"}}NM_003494) in the exon 45 of DYSF gene related to Limb Girdle Muscular Dystrophy type R2/2B in a 57-year-old patient affected with LGMD from a consanguineous family of south Italy. Both healthy parents carried this variant in heterozygosity. Genetic analysis extended to two moderately affected sisters of the proband, showed the presence of the variant c.5033G>A in both in homozygosity. These data indicate a probable pathological role of the variant c.5033G>A never reported before in the onset of LGMDR2/2B, pointing at the NGS as powerful tool for identifying LGMD subtypes. Moreover, the collection and the networking of genetic data will increase power of genetic-molecular investigation, the management of at-risk individuals, the development of new therapeutic targets and a personalized medicine.     

The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3

Proteins related to the ubiquitin-proteasome system play an important role during the differentiation and ciliogenesis of photoreceptor cells. Mutations in several genes involved in ubiquitination and proteostasis have been identified as causative of inherited retinal dystrophies (IRDs) and ciliopathies. USP48 is a deubiquitinating enzyme whose role in the retina is still unexplored although previous studies indicate its relevance for neurosensory organs. In this work, we describe that a pool of endogenous USP48 localises to the basal body in retinal cells and provide data that supports the function of USP48 in the photoreceptor cilium. We also demonstrate that USP48 interacts with the IRD-associated proteins ARL3 and UNC119a, and stabilise their protein levels using different mechanisms. Our results suggest that USP48 may act in the regulation/stabilisation of key ciliary proteins for photoreceptor function, in the modulation of intracellular protein transport, and in ciliary trafficking to the photoreceptor outer segment.     

The Mayo Clinic Florida Microdosimetric Kinetic Model of Clonogenic Survival: Application to Various Repair-Competent Rodent and Human Cell Lines

The relative biological effectiveness (RBE) calculations used during the planning of ion therapy treatments are generally based on the microdosimetric kinetic model (MKM) and the local effect model (LEM). The Mayo Clinic Florida MKM (MCF MKM) was recently developed to overcome the limitations of previous MKMs in reproducing the biological data and to eliminate the need for ion-exposed in vitro data as input for the model calculations. Since we are considering to implement the MCF MKM in clinic, this article presents (a) an extensive benchmark of the MCF MKM predictions against corresponding in vitro clonogenic survival data for 4 rodent and 10 cell lines exposed to ions from ¹H to ²³⁸U, and (b) a systematic comparison with published results of the latest version of the LEM (LEM IV). Additionally, we introduce a novel approach to derive an approximate value of the MCF MKM model parameters by knowing only the animal species and the mean number of chromosomes. The overall good agreement between MCF MKM predictions and in vitro data suggests the MCF MKM can be reliably used for the RBE calculations. In most cases, a reasonable agreement was found between the MCF MKM and the LEM IV.     

An early phase II trial combining cisplatin and carboplatin in advanced non-small cell lung cancer

We conducted an early phase II trial in advanced non-small cell lung cancer (NSCLC) to evaluate response efficacy of a combination of Cisplatin (CDDP) and Carboplatin (CBDCA). The twenty-six patients in the study had had no previous treatment. They received a sequential administration of 300 mg/m2 CBDCA and 80 mg/m2 CDDP with approximately 3,500 ml of hydration on day 1 every 4 weeks. All patients were evaluable for response and toxicity. Ten (38.5%) of all assessable patients achieved a partial response (95% confidence interval, 19.8-57.2%). Response rates for patients with stage III A, III B and IV- disease were 40.0 (2/5), 70.0 (7/10) and 9.1% (1/11), respectively. Response rates for patients with squamous cell carcinoma, adenocarcinoma and large cell carcinoma were 35.7 (5/14), 45.5 (5/11) and 0.0% (0/1), respectively. The median survival time (MST) of all patients was 11 months. The MST for patients with stage III disease was 14 months; for those with stage IV disease it was 7 months. The MST for responding patients was 15 months and for not responding patients 5 months. Major toxicities were hematologic and gastrointestinal, and the dose-limiting factor was thrombocytopenia. This combination chemotherapy was effective against NSCLC with tolerable toxicities. Further trials are warranted to determine the efficacy of the combination chemotherapy.     

Statistical segmentation and structural recognition for floor plan interpretation

A generic method for floor plan analysis and interpretation is presented in this article. The method, which is mainly inspired by the way engineers draw and interpret floor plans, applies two recognition steps in a bottom-up manner. First, basic building blocks, i.e., walls, doors, and windows are detected using a statistical patch-based segmentation approach. Second, a graph is generated, and structural pattern recognition techniques are applied to further locate the main entities, i.e., rooms of the building. The proposed approach is able to analyze any type of floor plan regardless of the notation used. We have evaluated our method on different publicly available datasets of real architectural floor plans with different notations. The overall detection and recognition accuracy is about 95 %, which is significantly better than any other state-of-the-art method. Our approach is generic enough such that it could be easily adopted to the recognition and interpretation of any other printed machine-generated structured documents.     

The use of packaging techniques to maintain freshness in fresh-cut fruits and vegetables: a review

Browning and other discolourations, softening, surface dehydration, water loss, translucency, off-flavour and off-odour development, as well as microbial spoilage are some of the most frequent causes of quality loss in fresh-cut products. Nowadays, the use of innovative modified atmospheres and edible coatings stands out among other techniques in the struggle for maintaining freshness and safety of fresh-cut fruits and vegetables. A few studies have demonstrated the effectiveness of these techniques when applied to different fresh-cut commodities. However, treatment and storage conditions for fresh-cut fruits are still being largely explored to better keep their fresh-like quality attributes. This review discusses the recent advances in the use of innovative modified atmosphere packaging (MAP) systems to maintain freshness of fresh-cut fruits and vegetables. Furthermore, special attention is devoted to the development of coatings that can be used as a complement or alternative to MAP.     

Hydrous oxide formation on gold in base under potential cycling conditions

The formation of hydrous oxide films on gold in base under potential cycling conditions was investigated and found to be less inhibited than the same type of reaction observed when gold is strongly anodized at high potentials under d.c. conditions at high pH. The overall behaviour on cycling is quite similar to that observed with other metals, e.g. platinum. The importance of the lower limit, for instance, again appears to be related to the need under film thickening conditions to significantly reduce the compact oxide layer formed on the metal surface during the anodic sweep. It was noted that the earlier duplex model for this type of system, i.e. an inner compact and an outer dispersed oxide layer, is not always valid. Under certain conditions about six distinct peaks (suggesting six different states of gold oxide hydration, dispersion or polymerization) were observed in cathodic sweeps recorded for the reduction of thick films grown on gold under potential cycling conditions in base.     

An outbreak of needlestick injuries in hospital employees due to needles piercing infectious waste containers

OBJECTIVES: To investigate the cause of an outbreak of needlestick injuries (NSIs) in hospital employees. SETTING: A 700-bed university hospital. DESIGN: Outbreak investigation, laboratory evaluation of a medical waste disposal device, cost analysis. METHODS: Employee health department records were reviewed of workers suffering sticks from needles piercing fiberboard-contaminated material containers (CMCs). A laboratory evaluation of needle-puncture resistance properties of the CMCs was performed using a testing apparatus. The cost of a hospital waste disposal program using fiberboard CMCs was compared with the cost of a program using rigid plastic (polypropylene) boxes. RESULTS: During 40 months of surveillance in 1986 and from 1989 to 1991, only one NSI had occurred from a needle piercing a CMC. During 9 months in 1993, 13 NSIs occurred due to needles piercing CMCs (P < .001). No clinical illness resulted from the NSIs. The outbreak was halted by a temporary change to plastic (polypropylene) boxes for sharps disposal ($4.92 to $23.33/cu ft) until receipt of a box with a newly designed solid fiberboard liner ($1.25/cu ft). CMC liners used during the epidemic had a mean needle puncture resistance of 527 g, as compared with 660 g for liners used before the outbreak (P < .001). The new solid fiberboard liner has a mean puncture resistance of 1,765 g. A program of waste disposal using fiberboard CMCs was found to cost approximately one-seventh the cost of a program using plastic boxes for disposal of infectious waste. CONCLUSION: A program for infectious waste disposal using fiberboard CMCs can be safe and cost-effective if appropriate standards for puncture resistance are met.     

The High Temperature Properties of Mar-M Alloy 509

Mar-M alloy 509 is a contemporary Co-base alloy intended for constructional use in a corrosive environment at high temperature. This paper is the result of a continuing investigation to evaluate mechanical, process and physical parameters of this alloy system. The alloy exhibits low room-temperature ductility; heat treatments can improve ductility but will reduce rupture life at moderate stress and temperature (25ksi, 1600°F.) Mar-M alloy 509 exhibits good oxidation resistance to 1900°F and excellent hot-corrosion resistance at 1600°F. The flat negative slope of the Mar-M alloy 509 stress-rupture curve also indicates a high degree of phase stability.