Steroid therapy in an alpha-dystroglycanopathy due to GMPPB gene mutations : A case report

Alpha-dystroglycanopathies are a group of progressive and untreatable neuromuscular disorders, due to aberrant alpha-dystroglycan glycosylation. We describe the effects of a short-term cycle of corticosteroid therapy in a 9-year-old boy, affected by an alpha-dystroglycanopathy due to GMPPB gene mutations. The patient was affected by a congenital progressive muscular dystrophy since the first month of life, associated with psychomotor delay, seizures, and congenital bilateral cataracts. Despite physical therapy he had a progressive motor impairment. At the age of 9 years, he was treated with 0.75 mg/kg/day of prednisone for 3 months and showed improvements in muscle strength and function scores and creatine kinase reduction. When steroid therapy was discontinued he showed again clinical and biochemical deterioration. These data suggest that corticosteroid may be considered as a treatment for patients with alpha-dystroglycanopathies due to GMPPB mutations. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Effect of feeding maltodextrins and dextrose on rearing and slaughtering performance of immunocastrated male pigs

This study aimed to verify previous research findings showing that feeding maltodextrins (M) and dextrose (D) leads to a reduction of voluntary feed intake in the Italian heavy pig. This may be interesting for immunocastrated pigs fed ad libitum (ad lib.), whose feed intake skyrockets after the 2nd vaccination, causing too fatty carcasses at slaughtering. Thirty-six male pigs (Italian Duroc x Italian Large White crossbred) received a double immunocastrating injection at 90 and 162 days of age. At 120 days, weighing 51.84+4.38 kg, the subjects were evenly housed in 9 boxes, fed ad lib. till the 2nd injection and then given, until slaughtering (197 days of age; 144.51±9.70 kg), one of the experimental diets: control diet, ad lib. (CL); control diet, restricted at 7.5% l.w.0.75 (CR); with MD (3.5 + 3.5%; adjusted for energy and protein), ad lib. (MD). The CR diet was introduced as the alternative choice to avoid too fatty carcasses. Compared to the restricted ones, pigs fed ad lib. (with or without MD) showed statistically higher (P<.01) ADG (1325 and 1325 vs 905 g/d), ADFI (4630 and 4637 vs 2760 g/d), feed:gain ratio (3.53 and 3.52 vs 3.11), and heavier carcasses (125.1 and 124.4 vs 113.2 kg; P<.01) with lower lean meat content (52.21 and 52.09 vs 55.83 %; P<.01). The results point out how immunocastrated pigs fed ad lib. showed similar rearing and slaughtering performance regardless of the inclusion of M and D in the diet

A methodological approach to assess nutrient requirements of heavy pigs in Italy

This paper reports the results of the work of the "Nutrient requirements of heavy pigs" ASPA Commission. The Commission work was mainly focused on the problem of identifying a good and flexible methodology for establishing nutrient requirements of heavy pigs in Italy, in a situation where the major part of the pigs are used for ham and other typical products. Nutrient allowance was considered to be a variable open to manipulation, since its optimal definition depends on the specific circumstances of each single production unit. It appeared that the most logical way to account for the many interactions involved was to integrate available information using computer simulation techniques. A methodology based on the following steps was proposed and analyzed: i) selection of a mathematical model to describe the chemical growth of pigs over time as result of the interactions of genotype, feed and climate; ii) developing suitable equations to predict the quality parameters of the carcass and, if possible, of the single cuts from the body's chemical status and implementation of these equations in the model; iii) identification of production targets and use of the model as a tool to simulate the effect of different genotypes, feed and climate on the productive and the economic results. A model strongly rooted in a theoretical framework, simple enough to be applied in practice and requiring a limited number inputs was selected from literature. From a preliminary evaluation, performed by using experimental calorimetric data, it was concluded that the model was potentially able to accurately predict the chemical growth of pigs under different conditions of feeding and climate. The major lack of knowledge regarded the values of genotypic descriptors of the national pig populations, the evaluation for which some simple experimental protocols are described in literature. Other lack of knowledge involved relationships to predict the anatomical growth and the evolution of quality parameters of carcass and cuts from the chemical composition of the body. If a correlation between the chemical composition of the pig's body and production targets is confirmed, then a link between the farmer and the industry can be established and the model could be used to identify more convenient feeding strategies. The conceptual basis and the way to assess nutrient requirements of heavy pigs have been clearly identified

A methodological approach to assess nutrient requirements of heavy pigs in Italy

This paper reports the results of the work of the "Nutrient requirements of heavy pigs" ASPA Commission. The Commissionwork was mainly focused on the problem of identifying a good and flexible methodology for establishing nutrient requirements of heavy pigs in Italy, in a situation where the major part of the pigs are used for ham and other typical products. Nutrient allowance was considered to be a variable open to manipulation, since its optimal definition depends on the specific circumstances of each single production unit. It appeared that the most logical way to account for the many interactions involved was to integrate available information using computer simulation techniques. A methodology based on the following steps was proposed and analyzed: i) selection of a mathematical model to describe the chemical growth of pigsover time as result of the interactions of genotype, feed and climate; ii) developing suitable equations to predict the qualityparameters of the carcass and, if possible, of the single cuts from the body's chemical status and implementation ofthese equations in the model; iii) identification of production targets and use of the model as a tool to simulate the effectof different genotypes, feed and climate on the productive and the economic results. A model strongly rooted in a theoreticalframework, simple enough to be applied in practice and requiring a limited number inputs was selected from literature.From a preliminary evaluation, performed by using experimental calorimetric data, it was concluded that the modelwas potentially able to accurately predict the chemical growth of pigs under different conditions of feeding and climate.The major lack of knowledge regarded the values of genotypic descriptors of the national pig populations, the evaluationfor which some simple experimental protocols are described in literature. Other lack of knowledge involved relationshipsto predict the anatomical growth and the evolution of quality parameters of carcass and cuts from the chemical compositionof the body. If a correlation between the chemical composition of the pig's body and production targets is confirmed,then a link between the farmer and the industry can be established and the model could be used to identify more convenientfeeding strategies. The conceptual basis and the way to assess nutrient requirements of heavy pigs have beenclearly identified

Acute effects of nicotine on visual search tasks in young adult smokers

Rationale Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. Objectives We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. Methods In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. Results In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and refixations on all letters in the display. Conclusions Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to refixate previously seen letters, suggesting an improvement in working memory

Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic.

Importance: Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. Objective: To examine the association of chilblain-like lesions with SARS-CoV-2 infection. Design, setting, and participants: This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. Main outcomes and measures: Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. Results: Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. Conclusions and relevance: This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: The InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device)

Background: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. Methods: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Results: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. Conclusions: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease