Muscle-specific function of the centronuclear myopathy and Charcot-Marie-Tooth neuropathy-associated dynamin 2 is required for proper lipid metabolism, mitochondria, muscle fibers, neuromuscular junctions and peripheral nerves

The ubiquitously expressed large GTPase Dynamin 2 (DNM2) plays a critical role in the regulation of intracellular membrane trafficking through its crucial function in membrane fission, particularly in endocytosis. Autosomal-dominant mutations in DNM2 cause tissue-specific human disorders. Different sets of DNM2 mutations are linked to dominant intermediate Charcot-Marie-Tooth neuropathy type B, a motor and sensory neuropathy affecting primarily peripheral nerves, or autosomal-dominant centronuclear myopathy (CNM) presenting with primary damage in skeletal muscles. To understand the underlying disease mechanisms, it is imperative to determine to which degree the primary affected cell types require DNM2. Thus, we used cell type-specific gene ablation to examine the consequences of DNM2 loss in skeletal muscle cells, the major relevant cell type involved in CNM. We found that DNM2 function in skeletal muscle is required for proper mouse development. Skeletal muscle-specific loss of DNM2 causes a reduction in muscle mass and in the numbers of muscle fibers, altered muscle fiber size distributions, irregular neuromuscular junctions (NMJs) and isolated degenerating intramuscular peripheral nerve fibers. Intriguingly, a lack of muscle-expressed DNM2 triggers an increase of lipid droplets (LDs) and mitochondrial defects. We conclude that loss of DNM2 function in skeletal muscles initiates a chain of harmful parallel and serial events, involving dysregulation of LDs and mitochondrial defects within altered muscle fibers, defective NMJs and peripheral nerve degeneration. These findings provide the essential basis for further studies on DNM2 function and malfunction in skeletal muscles in health and disease, potentially including metabolic diseases such as diabete

Invertibility Conditions for Floating-Point Formulae

Automated reasoning procedures are essential for a number of applications that involve bit-exact floating-point computations. This paper presents conditions that characterize when a variable in a floating-point constraint has a solution, which we call invertibility conditions. We describe a novel workflow that combines human interaction and a syntax-guided synthesis (SyGuS) solver that was used for discovering these conditions. We verify our conditions for several floating-point formats. One implication of this result is that a fragment of floating-point arithmetic admits compact quantifier elimination. We implement our invertibility conditions in a prototype extension of our solver CVC4, showing their usefulness for solving quantified constraints over floating-points

Should the visceral peritoneum at the bladder flap closed at caesarean sections a post partum sonographic and clinical assessment?

Objective. To compare cesarean section (CS) using open or closed visceral peritoneum of the bladder flap (BF) in relation to fluid collection in vesico-uterine space (VUS) by ultrasound (US) and clinical outcome. Material and methods. A prospective cohort of repeat CS in 474 in advanced first and second stage of labor was studied. All women underwent a Misgav Ladach CS, in local combined anesthesia. These were divided into two groups by surgical management of the BF at the time of CS: Group I (n?262), with visceral peritoneum left open and Group II (n?212), with visceral peritoneum closed. An US check for the fluid collections in the VUS was done in the third post-operative day. The two groups were also clinically compared for: intra-operative estimated blood loss, the need for post-CS pain killers, febrile morbidity and duration of hospital stay. Results. Visceral peritoneum (VP) closure resulted in a significant increase blood collections in the VUS (p50.05). VP closure resulted in a significantly higher morbidity in all the following parameters. Rate of BFHs, post-operative fever, need for post-operative analgesia, require antibiotic administration and prolonged hospitalisation (p50.05). Conclusions. VP suturing of women requiring CS for dystocia is associated to increased rate of blood collection in the VUS, which could possibly explain the higher rate of puerperal complications in these patients. These data clearly indicate that suturing the VP of the BF in women undergoing CS for dystocia is contraindicated. This data could be probably extrapolated to all cesarean deliveries

Inversion of perceived direction of motion caused by spatial undersampling in two children with periventricular leukomalacia

We report here two cases of two young diplegic patients with cystic periventricular leukomalacia who systematically, and with high sensitivity, perceive translational motion of a random-dot display in the opposite direction. The apparent inversion was specific for translation motion: Rotation and expansion motion were perceived correctly, with normal sensitivity. It was also specific for random-dot patterns, not occurring with gratings. For the one patient that we were able to test extensively, contrast sensitivity for static stimuli was normal, but was very low for direction discrimination at high spatial frequencies and all temporal frequencies. His optokinetic nystagmus movements were normal but he was unable to track a single translating target, indicating a perceptual origin of the tracking deficit. The severe deficit for motion perception was also evident in the seminatural situation of a driving simulation video game. The perceptual deficit for translational motion was reinforced by functional magnetic resonance imaging studies. Translational motion elicited no response in the MT complex, although it did produce a strong response in many visual areas when contrasted with blank stimuli. However, radial and rotational motion produced a normal pattern of activation in a subregion of the MT complex. These data reinforce the existent evidence for independent cortical processing for translational, and circular or radial flow motion, and further suggest that the two systems have different vulnerability and plasticity to prenatal damage. They also highlight the complexity of visual motion perception, and how the delicate balance of neural activity can lead to paradoxical effects such as consistent misperception of the direction of motion. We advance a possible explanation of a reduced spatial sampling of the motion stimuli and report a simple model that simulates well the experimental results

Quantifier-Free Interpolation of a Theory of Arrays

The use of interpolants in model checking is becoming an enabling technology to allow fast and robust verification of hardware and software. The application of encodings based on the theory of arrays, however, is limited by the impossibility of deriving quantifier- free interpolants in general. In this paper, we show that it is possible to obtain quantifier-free interpolants for a Skolemized version of the extensional theory of arrays. We prove this in two ways: (1) non-constructively, by using the model theoretic notion of amalgamation, which is known to be equivalent to admit quantifier-free interpolation for universal theories; and (2) constructively, by designing an interpolating procedure, based on solving equations between array updates. (Interestingly, rewriting techniques are used in the key steps of the solver and its proof of correctness.) To the best of our knowledge, this is the first successful attempt of computing quantifier- free interpolants for a variant of the theory of arrays with extensionality

Trends in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections: effect of the MRSA "search and isolate" strategy in a hospital in Italy with hyperendemic MRSA

Abstract OBJECTIVE: To evaluate the secular trends in MRSA BSIs after the introduction of a nosocomial MRSA control intervention. DESIGN: Before-after study. SETTING: An 850-bed community hospital with an ICU and vascular surgery, neurosurgery, bone marrow transplantation, and AIDS units. MRSA is endemic at this hospital; the prevalence of methicillin resistance among patients with S. aureus infection is greater than 50%. PATIENTS: Among all inpatients, MRSA BSI was identified, its origin defined, and incidence rates calculated by ward and origin. INTERVENTION: A MRSA control program was implemented based on active surveillance cultures to identify MRSA-colonized patients, followed by isolation using contact precautions. Incidence rates of MRSA BSI during the intervention (i.e., July 1, 1997, to December 31, 2001) and preintervention (i.e., January 1, 1996, to June 30, 1997) periods were compared. RESULTS: Sixty-nine MRSA BSIs were identified. When compared with the preintervention period, the incidence rate of MRSA BSI was reduced from 0.64 to 0.30 per 1000 admissions (RR, 0.46; CI95, 0.25-0.87; P = .02) during the intervention period. The impact was greater in the ICU, with an 89% reduction (RR, 0.11; CI95, 0.01-0.98; P = .03), and for CVC-associated MRSA BSIs, with an 82% decrease (RR, 0.17; CI95, 0.05-0.55; P = .002). Methicillin resistance among S. aureus blood isolates decreased from 46% to 17% (RR, 0.36; CI95, 0.22-0.62; P = .0002). CONCLUSION: A reduction in MRSA bacteremia is achievable through use of the MRSA "search and isolate" intervention even in a hospital with high rates of endemic MRSA

New results on rewrite-based satisfiability procedures

Program analysis and verification require decision procedures to reason on theories of data structures. Many problems can be reduced to the satisfiability of sets of ground literals in theory T. If a sound and complete inference system for first-order logic is guaranteed to terminate on T-satisfiability problems, any theorem-proving strategy with that system and a fair search plan is a T-satisfiability procedure. We prove termination of a rewrite-based first-order engine on the theories of records, integer offsets, integer offsets modulo and lists. We give a modularity theorem stating sufficient conditions for termination on a combinations of theories, given termination on each. The above theories, as well as others, satisfy these conditions. We introduce several sets of benchmarks on these theories and their combinations, including both parametric synthetic benchmarks to test scalability, and real-world problems to test performances on huge sets of literals. We compare the rewrite-based theorem prover E with the validity checkers CVC and CVC Lite. Contrary to the folklore that a general-purpose prover cannot compete with reasoners with built-in theories, the experiments are overall favorable to the theorem prover, showing that not only the rewriting approach is elegant and conceptually simple, but has important practical implications.Comment: To appear in the ACM Transactions on Computational Logic, 49 page

Accidental Oleandrum (Nerium Oleander L.) Ingestion: Anatomo-Pathological consequences in livestock species

The oleander (Nerium oleander L.) is a flowering and evergreen shrub or small tree, belonging to the Dogbane family, cultivated as ornamental plants in gardens and public city areas. These plants, distributed originally in Asia and Mediterranean area, grow in many parts of the world, particularly in warm temperate and subtropical regions. Oleander is considered noxious weed and its toxicity has been known since ancient times. All parts of plants, including stems, leaves, young shoots, flowers, nectar, sap and products induced by combustion are toxic. The poisoning effects of plant induced sever negative changes especially in the heart, also in the lung, in the liver and in the kidney. Accidental and experimental cases of oleander poisonings have been described in several species. Several cases of accidental ingestion in human and animals have been reported from across the world. Therefore, this review summarizes the main anatomo-pathological effects found in livestock species after accidental oleandrum poisoning

Retraction Note: Cognitive deficits in multiple sclerosis: a review of functional MRI studies

n/

Creating a FACETS digital toolkit to promote quality of life of people with multiple sclerosis through Participatory Design

In this paper, we report on the first stages of creating a stand-alone digital toolkit focusing on the homework elements of FACETS (Fatigue: Applying Cognitive behavioural and Energy effectiveness Techniques to lifeStyle). FACETS is an evidence-based face-to-face fatigue management group programme for people with multiple sclerosis. This paper details the participatory design process from requirements elicitation to initial prototyping and how offline activities linked to each session have been mapped in the digitised solution (mobile app)