Wasted leg syndrome: An atypical slowly-progressive form of lower motor neuron disease.

We describe four male patients with wasted-leg syndrome, with predominant asymmetric thigh atrophy and weakness that stabilized after a period of slow progression (follow-up 7-18 years). Two patients had an Indian ethnic background and two were Portuguese, without known Indian ancestry. Other mimicking disorders were excluded, but one Indian patient was later diagnosed with CADASIL. Electromyography (EMG) revealed severe chronic neurogenic changes in proximal leg muscles, and mild changes in distal leg muscles, but EMG of the upper limbs was normal. Upper motor neuron signs were absent clinically and on transcranial magnetic stimulation. This seems to represent a variant of the common wasted-leg syndrome presentation.

Prevalence of Dirofilaria repens in dogs living in deltaic coastal plain of the Volturno River (Italy): a geographical risk model of infection.

The prevalence of vector-associated parasitic infections is high in central-southern Italy. The deltaic coastal plain of the Volturno River has been suspected, by veterinary practitioners, to have a high accidental incidence of Dirofilaria repens. Thus, the goal of this study was to evaluate the prevalence of dirofilariasis and other coinfections frequently described in dogs living in the Volturno area. Blood samples of 100 clinical asymptomatic dogs were examined using a Knott's technique and polymerase chain reaction in order to identify microfilariae. Other vector-borne coinfections were also investigated using ELISA kits. The results were analysed using statistical and Geographic Information System (GIS) software. Microfilariae of D. repens were detected in 10% of the dogs surveyed, with a presence of antibodies against Ehrlichia canis (4/10) and Dirofilaria immitis (1/10). Such high incidence should be considered in light of the zoonotic potential for D. repens and the support for more regular use of repellents to prevent the spread of this disease. The GIS analyses indicated that the study area provides suitable conditions to sustain populations of mosquito vectors and D. repens parasites throughout much of the year.

Muscular cramp: causes and management.

Muscular cramp is a common symptom in healthy people, especially among the elderly and in young people after vigorous or peak exercise. It is prominent in a number of benign neurological syndromes. It is a particular feature of chronic neurogenic disorders, especially amyotrophic lateral sclerosis. A literature review was undertaken to understand the diverse clinical associations of cramp and its neurophysiological basis, taking into account recent developments in membrane physiology and modulation of motor neuronal excitability. Many aspects of cramping remain incompletely understood and require further study. Current treatment options are correspondingly limited.

Epidemiological Data on Anaphylaxis in French Emergency Departments.

BACKGROUND: Although anaphylaxis has been considered a priority public health issue in the world allergy community, epidemiological data on morbidity and mortality remain suboptimal. We performed the first multicenter epidemiological study in French emergency departments (EDs). The study covered 7 EDs over a period of 1 year. The objectives were to identify areas that are amenable to change and to support ongoing national and international efforts for better diagnosis, management, and prevention of anaphylaxis. METHODS: Ours was a descriptive study based on data routinely reported to French institutional administrative databases from 7 French public health institutions in the Lorraine region between January and December 2015. Data were collected based on the anaphylaxisrelated codes of the International Classification of Diseases (ICD)-10, and cases were clinically validated as anaphylaxis. RESULTS: Of the 202 079 admissions to the EDs, 4817 had anaphylaxis-related codes; of these, 323 were clinically validated as anaphylaxis. Although 45.8% were severe, adrenaline was prescribed in only 32.4% of cases. Of the 323 cases, 57.9% were subsequently referred for an allergy work-up or evaluation (after or during hospitalization), and 17.3% were prescribed autoinjectable epinephrine. CONCLUSION: Our results highlight an urgent need for improved public health initiatives with respect to recognition and treatment of anaphylaxis. We flag key problems that should be managed in the coming years through implementation of national and international actions.

Hereditary amyloidosis related to transthyretin V30M: disease progression in treated and untreated patients.

BACKGROUND AND PURPOSE: Hereditary amyloidosis related to transthyretin V30M (hATTR V30M) is a progressive length-dependent sensorimotor axonal neuropathy. We aimed to compare the disease progression of treated [liver transplantation (LT) or tafamidis] versus untreated patients with hATTR V30M. METHODS: A total of 81 patients with hATTR V30M were included: 27 untreated, 25 treated with LT and 29 undergoing tafamidis treatment. Neuropathy was assessed at baseline, 12, 24 and 36 months after study entry. We evaluated disease stage, modified polyneuropathy disability (mPND) score and a composite neurophysiological score comprised of sensory and motor conduction parameters. The effect of treatment on disease progression was analysed using linear mixed-effects modelling. RESULTS: At baseline, patients from the untreated group were older (P < 0.01) and those in the LT group had longer disease duration than those in the tafamidis group (P < 0.05). Gender, mPND and motor scores at study entry were equal in the three groups; however, the untreated group had lower sensory scores compared with the tafamidis group (P < 0.01). During the 3-year follow-up period, progression to stage II of the disease was seen only in the untreated group. The progression on mPND, sensory and motor scores was significantly higher in the untreated patients. When treated groups were compared, the LT group had lower rates of composite neurophysiological score progression. However, the sensory score outcome was similar between tafamidis responders and LT patients. CONCLUSION: Both LT and tafamidis therapy modified the natural history of hATTR V30M by reducing neuropathy progression.

Plasma level of club-cell (CC-16) predicts outcome in amyotrophic lateral sclerosis.

OBJECTIVES: The club cell protein (CC-16) is a biomarker associated with respiratory distress and pulmonary inflammation. We evaluated CC-16 as a candidate biomarker for respiratory failure in amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: We studied 81 ALS patients and 30 matched controls. We used an ALS-related measure of functional capacity, and tested forced vital capacity (FVC) and the amplitude of the diaphragmatic response by phrenic nerve stimulation (PhrenAmpl). Plasma CC-16 levels were measured in venous blood. Kaplan-Meier survival curves were plotted to evaluate risk to non-invasive ventilation and death in patients with abnormal CC-16 levels. RESULTS: CC-16 levels were significantly raised in ALS patients (10.56 ng/mL ± 6.84 vs 8.34 ng/mL ± 3.10, P = .02), and in 17% of them, CC-16 level was above the upper cutoff value (mean + 2.5SD). CC-16 levels did not correlate with age, onset region, disease duration, functional status, FVC, and PhrenAmpl. In patients with increased CC-16 level, the risk of non-invasive was greater in the following 6 months (P = .01) and tended to have higher mortality in the following 30 months (P = .07). CONCLUSIONS: We propose that increased CC-16 levels is a marker of lung inflammatory response that associated with ventilatory insufficiency are related to impending respiratory failure, not fully predicted by conventional respiratory tests. The latter are limited by the moment of testing.

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. PATIENTS AND METHODS: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. RESULTS: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.

The recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slow-releasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR) were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.) injected with C48/80 (3µg/site) or histamine (1µmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3-100nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected 125I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis increased both Tyrode and C48/80-induced responses in the skin, whereas the blockade of KATP channels by glibenclamide did not. H2S-releasing donors significantly attenuate C48/80-induced mast cell degranulation either in vivo or in vitro. We provide first evidences that H2S donors confer protective effect against histamine-mediated acute pruritus and cutaneous inflammation. These effects can be mediated, at least in part, by stabilizing mast cells, known to contain multiple mediators and to be primary initiators of allergic processes, thus making of H2S donors a potential alternative/complementary therapy for treating inflammatory allergic skin diseases and related pruritus.

Phenotypic and genotypic characterization of clinically relevant bacteria isolated from dental waste and waste workers' hands, mucosas and coats.

Infectious wastes are potential sources of pathogenic micro-organisms, which may represent a risk to the professionals who manage them. In this study, we aimed to characterize the infectious bacteria present in dental waste and waste workers. The dental waste produced over 24 h was collected and waste workers were sampled by swabbing. Isolate resistance profiles were characterized by Vitek® and PCR and biofilm formation by Congo Red agar, string test and microtitre assay. To assess similarity between the waste and the workers' samples, a random amplified polymorphic DNA test was used. Twenty-eight bacteria were identified as clinically relevant. The most frequent gene was blaTEM present in five Gram-negative micro-organisms, and one blaSHV in Klebsiella pneumoniae. All Pseudomonas aeruginosa were positive to extracellular polymeric substances formation, except one isolated from a worker. Klebsiella pneumoniae had negative results for the string test. Pseudomonas aeruginosa showed better adherence at 25°C after 48 h of incubation and K. pneumonia had the best biofilm formation at the same temperature, after 24 h. The similarity between P. aeruginosa recovered from dental waste and from workers was low, however, it is important to note that a pathogen was found on a worker's hands and that improvements in biosafety are required. SIGNIFICANCE AND IMPACT OF THE STUDY: Infectious dental waste can contain clinically relevant bacteria with important resistance and biofilm profiles. These micro-organisms could be transmitted to waste workers, other professionals and patients if the principles of biosafety measures are neglected. To our knowledge, no study has ever evaluated the microbial characterization and the potential contamination risk of dental infectious waste and waste handlers. The presence of clinically relevant bacteria in the hands and nasal mucosa of waste workers highlights the need for studies in this field to clarify the risk of these pathogens in dental healthcare services, and to stress the need for an efficient waste management.

Squalus bassi sp. nov., a new long-snouted spurdog (Chondrichthyes: Squaliformes: Squalidae) from the Agulhas Bank.

The long-snouted African spurdog Squalus bassi sp. nov. is described based on material collected from the outer shelf and upper continental slope off South Africa and Mozambique. Squalus bassi shares with S. mitsukurii, S. montalbani, S. chloroculus, S. grahami, S. griffini, S. edmundsi, S. quasimodo and S. lobularis a large snout with prenarial length greater than distance between nostrils and upper labial furrows, dermal denticles tricuspidate and rhomboid and elevated number of vertebrae. Squalus bassi can be distinguished from all its congeners by a combination of body and fin colouration, external morphometrics, vertebral counts and shape of dermal denticles. Similar long-snouted congeners from the Indo-Pacific region, including S. montalbani, S. edmundsi and S. lalannei are compared in detail with the new species. This new species has been misidentified as the Japanese S. mitsukurii and the Mediterranean S. blainvillei due to the lack of comparative morphological analyses. The validity of the nominal species S. mitsukurii in the south-eastern Atlantic Ocean and western Indian Ocean is also clarified herein, indicating it has a more restricted geographical distribution in the North Pacific Ocean.

Synergism of thymol, carvacrol and eugenol in larvae of the cattle tick, Rhipicephalus microplus, and brown dog tick, Rhipicephalus sanguineus.

The effects of combinations of the monoterpenes thymol and carvacrol and the phenylpropanoid eugenol in larvae of Rhipicephalus microplus (Canestrini, 1888) (Acari: Ixodidae) and Rhipicephalus sanguineus sensu lato (s.l.) (Acari: Ixodidae) were assessed by the larval packet test. The CompuSyn program was used to make qualitative assessments of the effects (synergistic, additive and antagonistic) of the associations. The effects of all combinations tested against R. microplus larvae were synergistic, with combination indices (CIs) <0.70. When tested against R. sanguineus, eight of the mixtures showed a synergistic effect (CI < 0.70); only the carvacrol + thymol mixture at LC50 presented a moderate synergistic effect, with CIs between 0.70-0.90. This study is the first to determine the effects of the interactions of these substances in the control of these two tick species. The combinations of carvacrol + thymol, carvacrol + eugenol and thymol + eugenol have synergistic effects in R. microplus and R. sanguineus s.l. larvae.

Occurrence of microsporidians Glugea hertwigi and Pleistophora ladogensis, in smelt Osmerus eperlanus from two German rivers, North Sea coast.

Monthly samples of smelt Osmerus eperlanus (Linnaeus, 1758) were collected from July 1985 to May 1986, in the river Elbe (Germany), and examined for infections with microsporidians. Two microsporidians were found: Glugea hertwigi Weissenberg, 1911, infecting the digestive tract and Pleistophora ladogenis Voronin, 1978, infecting the skeletal musculature. G. hertwigi infection led to the formation of xenomas, whereas P. ladogensis was characterized by diffuse infections, with the production of macroscopic visible thread-like or oval-shaped infection foci. Development of G. hertwigi in the host cells showed characteristics typical of the genus Glugea. The ultrastructural development of P. ladogensis showed features typical of the genus Pleistophora, without evidence of the production of 2 types of spores. Host reaction consisted of inflammatory tissue surrounding some of the infection foci as well as phagocytosis of spores. G. hertwigi was only found in juvenile smelt (<10 cm in length), whereas P. ladogensis infected smelts from 6 to 26 cm in length. Prevalence increased with fish length to a maximum value of 9.6%. Seasonal fluctuations in prevalence of infection were also found, with the lowest value in the winter months (2.5% in January 1986) and the highest in summer (11.8% in July 1985). The differences in prevalence of infection with fish length and date of sampling were significant. Additionally, samples of smelt caught in April 1986 from the rivers Eider and Ems revealed infections with P. ladogensis in the first river system only.

Inducing autotetraploids in cassava using oryzalin and colchicine and their in vitro morphophysiological effects.

Polyploid induction has been used for plant breeding to produce bigger and more robust plants than diploid types. The present study aimed to develop a methodology for in vitro induction of polyploidy in cassava. Apical and lateral microcuttings from the BRS Formosa variety were treated with six oryzalin concentrations for 24 and 48 h. The same methodology was used for colchicine with different concentrations. After 45 days of cultivation and an additional 45 days of subculture, the viability of the explants was assessed and plant acclimatization was performed. Ploidy was determined using flow cytometry. Oryzalin dose and exposure negatively affected cassava explant growth and development compared to untreated explants. Furthermore, apical and lateral explants responded differently to the treatments, showing a diversity in antimitotic sensitivity and effect that is tissue-type specific. In contrast, the doses of 1.25 to 6.25 mM colchicine resulted in high mortality of cassava explants. Therefore, the type of antimitotic affects the morphophysiological behavior of cassava plants in vitro, although apical explants have higher viability and regenerative capacity compared to lateral explants. In addition, the lateral explants have lower mixoploid rates compared to apical explants. Of the 310 plants generated by oryzalin treatments, 277 were diploid, 31 were mixoploid, and 2 were tetraploid. Exposure to oryzalin led to low rate of tetraploids and colchicine caused phytotoxic reactions and death of the explants. The tetraploids were multiplied in vitro to evaluate their yield in the field as well as their behavior against abiotic and biotic stress.

Proximal tibia fracture in a patient with incomplete spinal cord injury associated with robotic treadmill training.

STUDY DESIGN: One case report of proximal tibia fracture in a patient with incomplete spinal cord injury (SCI) associated with robotic treadmill training. OBJECTIVE: To raise the awareness that bone densitometry may be recommended before starting the robotic treadmill therapy, as well as the active vigilance of symptoms after therapy. SETTING: Institute of Physical and Rehabilitation Medicine, Lucy Montoro Institute for Rehabilitation, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil. CASE REPORT: The patient, female gender, with a fracture of vertebra T12 and arthrodesis from T9 to L1 (American Spinal Injury Association Classification (ASIA-C)). Training on Lokomat consisted of five 30-min weekly sessions, under the supervision of a qualified professional. At the beginning of the 19th session, the patient complained of pain in the anterior region of the left knee. Lokomat and any other body support therapy were discontinued. Magnetic resonance imaging (MRI) evidenced a transverse, oblique, metaphyseal proximal anterior and medial tibial fracture. CONCLUSION: Fractures are among the chronic complications of a SCI, affecting 34% and many times arising from minimal traumas. Lokomat resembles physiological walking, and more studies show its benefits. Many studies encourage the use of robotic devices for the rehabilitation of lower limbs, but there are still several unanswered questions. However, there are not enough studies to show whether there is a higher risk of fracture incidence in patients with osteopenia or osteoporosis who trained on the Lokomat.

Verification and characterization of chromosome duplication in haploid maize.

Doubled haploid technology has been used by various private companies. However, information regarding chromosome duplication methodologies, particularly those concerning techniques used to identify duplication in cells, is limited. Thus, we analyzed and characterized artificially doubled haploids using microsatellites molecular markers, pollen viability, and flow cytometry techniques. Evaluated material was obtained using two different chromosome duplication protocols in maize seeds considered haploids, resulting from the cross between the haploid inducer line KEMS and 4 hybrids (GNS 3225, GNS 3032, GNS 3264, and DKB 393). Fourteen days after duplication, plant samples were collected and assessed by flow cytometry. Further, the plants were transplanted to a field, and samples were collected for DNA analyses using microsatellite markers. The tassels were collected during anthesis for pollen viability analyses. Haploid, diploid, and mixoploid individuals were detected using flow cytometry, demonstrating that this technique was efficient for identifying doubled haploids. The microsatellites markers were also efficient for confirming the ploidies preselected by flow cytometry and for identifying homozygous individuals. Pollen viability showed a significant difference between the evaluated ploidies when the Alexander and propionic-carmin stains were used. The viability rates between the plodies analyzed show potential for fertilization.

AM-879, a PPARy non-agonist and Ser273 phosphorylation blocker, promotes insulin sensitivity without adverse effects in mice.

Obesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the in vivo effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose. At lower doses, this ligand decreased BAT, increased leptin and Crh expression. However, at a higher dose, it promoted improvement on insulin sensitivity, ameliorates expression of metabolism-related genes, decreased the expression of genes related to liver toxicity, maintaining body weight and adipocyte size. These results present a new lead molecule to ameliorates insulin resistance and confirm AM-879 as a PPARγ non-agonist which blocks Ser273 phosphorylation as a good strategy to modulate insulin sensitivity without developing the adverse effects promoted by PPARγ full agonists.

Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres.

OBJECTIVE: To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. METHODS: Fifteen groups in 9 countries recorded CMAP scans twice, 1-2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. RESULTS: Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. CONCLUSIONS: It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SIGNIFICANCE: MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Proposal of a histopathological predictive rule for the differential diagnosis between American tegumentary leishmaniasis and sporotrichosis skin lesions.

BACKGROUND: American tegumentary leishmaniasis (ATL) and sporotrichosis exhibit similar histopathology and low frequencies of microorganism detection. OBJECTIVES: This study seeks to identify microscopic alterations that can distinguish between these diseases. METHODS: Haematoxylin and eosin stained slides of 171 ATL and 97 sporotrichosis samples from active cutaneous lesions were examined for histopathological alterations. The lesions were diagnosed by isolating the agent (which was not visible) in culture. An intuitive diagnosis was assigned to each slide. The strength of the association between the histopathological findings and the diagnosis was estimated by an odds ratio, and each finding was graded according to a regression model. A score was assigned to each sample based on the histopathological findings. A study of the interobserver reliability was performed by calculating kappa coefficients of the histopathological findings and intuitive diagnoses. RESULTS: The markers 'macrophage concentration', 'tuberculoid granuloma' and 'extracellular matrix degeneration' were associated with ATL. 'Suppurative granuloma', 'stellate granuloma', 'different types of giant cells', 'granulomas in granulation tissue' and 'abscess outside the granuloma' were associated with a diagnosis of sporotrichosis. 'Macrophage concentration' and 'suppurative granuloma' had the highest (substantial and almost perfect, respectively) reliability. The regression model score indicated 92.0% accuracy. The intuitive diagnosis had 82.5% diagnostic accuracy and substantial reliability. CONCLUSIONS: Taking into account the clinical and epidemiological context, some histopathological alterations might be useful for the differential diagnosis between ATL and sporotrichosis cutaneous lesions in cases in which the aetiological agent is not visible.