Many neurological diseases may cause acute respiratory failure (ARF) due to involvement of bulbar respiratory center, spinal cord, motoneurons, peripheral nerves, neuromuscular junction, or skeletal ...muscles. In this context, respiratory emergencies are often a challenge at home, in a neurology ward, or even in an intensive care unit, influencing morbidity and mortality. More commonly, patients develop primarily ventilatory impairment causing hypercapnia. Moreover, inadequate bulbar and expiratory muscle function may cause retained secretions, frequently complicated by pneumonia, atelectasis, and, ultimately, hypoxemic ARF. On the basis of the clinical onset, two main categories of ARF can be identified: (i) acute exacerbation of chronic respiratory failure, which is common in slowly progressive neurological diseases, such as movement disorders and most neuromuscular diseases, and (ii) sudden-onset respiratory failure which may develop in rapidly progressive neurological disorders including stroke, convulsive status epilepticus, traumatic brain injury, spinal cord injury, phrenic neuropathy, myasthenia gravis, and Guillain–Barré syndrome. A tailored assistance may include manual and mechanical cough assistance, noninvasive ventilation, endotracheal intubation, invasive mechanical ventilation, or tracheotomy. This review provides practical recommendations for prevention, recognition, management, and treatment of respiratory emergencies in neurological diseases, mostly in teenagers and adults, according to type and severity of baseline disease.
Newborn screening (NBS) is an essential, preventive public health programme for early identification of disorders whose early treatment can lead to significant reduction in morbidity and mortality. ...NBS for Duchenne muscular dystrophy (DMD) has been a controversial matter for many years, because of false positives, the lack of effective drugs and the need of more data about screening efficacy. The still high diagnostic delay of DMD and the current availability of drugs such as steroid, ataluren, eteplirsen, golodirsen and forthcoming new drugs, improving the clinical conditions if early started, make appropriate to begin a concrete discussion between stakeholders to identify best practice for DMD screening. A two-step system CK/DNA screening programme is presented to be performed in male infants aged between 6 months and 42 months involving more than 30,000 male infants. Five to eight DMD subjects are believed to be diagnosed. The pilot project would give the opportunity to test in a small population the feasibility of an infant screening programme, which in the near future could be applicable to an entire country.
•Political corruption and legislative complexity.•Economic impact of legislative complexity on economic growth.•The effects of legislative complexity on welfare and per capita income ...distribution.•Fiscal policies and legislative measures of economic policy.
This paper investigates the macroeconomic impact of legislative complexity in relation to political corruption on growth rate, welfare level and income distribution. After reviewing economic literature on corruption and legislative complexity, an endogenous model is provided. The main theoretical findings of the analysis are that a high level of legislative complexity, like political corruption, constitutes a constraint to growth, reduces the welfare and determines a redistribution of income in favor of the politicians.
Muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG) is a rare, frequently more severe, subtype of MG with different pathogenesis, and peculiar clinical features. The prevalence varies among ...countries and ethnic groups, affecting 5–8% of all MG patients. MuSK-MG usually has an acute onset affecting mainly the facial-bulbar muscles. The symptoms usually progress rapidly, within a few weeks. Early respiratory crises are frequent. The disease may lead to generalized muscle weakness up to muscle atrophy. The main bulbar involvement, the absence of significant thymus alterations, and the association with HLA class II DR14, DR16, and DQ5 alleles have been confirmed. Atypical onset, such as ocular involvement, lack of symptom fluctuations, acetylcholinesterase inhibitors failure, and negative results of electrophysiologic testing, if not specifically performed in the mainly involved muscle groups, makes MuSK-MG diagnosis challenging. In most cases, steroids are effective. Conventional immunosuppressants are not commonly able to replace steroids in maintaining a satisfactory long-term control of symptoms. However, the majority of MuSK-MG patients are refractory to treatment. In these cases, the use of rituximab showed promising results, resulting in sustained symptom control.
In this paper we study the impact of regulatory complexity, a measure of institutional quality, on the GDP, on per capita income and on the growth rate of the Italian regions. For comparative reasons ...we also use the duration of civil disputes as a further indicator of institutional quality used in the regressions as an alternative to the indicator of regulatory complexity. From the theoretical point of view, we use the approach of negative co‐ordination externalities, among the four sources of regulatory production that are at work at the same time. Our approach may be applied in all the countries with a multi‐level government system. Using the random effects and quantile regressions models we are able to quantify the effects of an improvement in institutional quality on the GDP and the growth rate, making a comparison between the results obtained using regulatory complexity or the duration of civil disputes as covariates. We also check for spatial dependence among variables. Econometric analysis supports the theoretical assumption that regulatory complexity is an impediment to the growth of regional GDP and per capita income. The main finding of our analysis is that a reduction in regulatory complexity would be more effective than a reduction in the duration of civil disputes in increasing the income and growth rate. This result could be useful for the policy‐maker because by reducing regulatory complexity we may obtain a considerable by‐product in the shorter duration of civil disputes.
Resumen
En este artículo se estudia el impacto de la complejidad regulatoria, que es una medida de la calidad institucional, en el PIB, en ingresos per cápita y en la tasa de crecimiento de las regiones italianas. Por razones comparativas, también se utilizó la duración de las disputas civiles como un indicador adicional de la calidad institucional empleada en las regresiones como una alternativa al indicador de complejidad regulatoria. Desde el punto de vista teórico, se utiliza el enfoque de las externalidades de coordinación negativas entre las cuatro fuentes de producción reguladora que funcionan al mismo tiempo. El enfoque de este artículo se puede aplicar en cualquier país con un sistema de gobierno multinivel. Mediante el uso de modelos de efectos aleatorios y regresiones cuantílicas se pudo cuantificar los efectos de una mejora en la calidad institucional sobre el PIB y la tasa de crecimiento, lo que permitió una comparación entre los resultados obtenidos utilizando la complejidad regulatoria o la duración de las disputas civiles como covariables. También se comprobó la dependencia espacial entre variables. El análisis econométrico apoya el supuesto teórico de que la complejidad regulatoria es un impedimento para el crecimiento del PIB regional y los ingresos per cápita. El principal hallazgo de este análisis es que una reducción en la complejidad regulatoria sería más efectiva que una reducción en la duración de las disputas civiles para aumentar los ingresos y la tasa de crecimiento. Este resultado podría ser útil para quienes formulan políticas, ya que al reducir la complejidad regulatoria se puede obtener un subproducto considerable en forma de una menor duración de las disputas civiles.
抄録
本稿では、制度の質の指標となるregulatory complexity(規制の複雑さ)が、GDP、一人当たり所得、イタリアの地方の経済成長率に及ぼす影響を検討する。また比較検討のために、民事紛争の期間をregulatory complexityの代替となる、制度の質のより詳細な指標として回帰分析に使用する。理論的観点から、同時に進行する規制立案の4つの情報源の中から、協調の負の外部効果のアプローチを使用する。このアプローチは、マルチレベルの行政システムのあるすべての国に応用できる可能性がある。変量効果モデルと分位点回帰モデルを使用することにより、制度の質の改善がGDPと経済成長率に与える影響の定量が可能となり、regulatory complexityまたは民事紛争の期間を共変量として用いて得られた結果を比較する。また、変数の中に空間依存性がないか確認を行う。計量経済学的分析から、regulatory complexityが地域のGDPと一人当たり国民所得の増加の障害となるという理論的仮説が裏付けられた。今回の分析の主な知見は、regulatory complexityの減少は、所得と経済成長率の増加に関する民事紛争の期間の減少よりも効果的であると考えられることである。regulatory complexityを減少させることにより、より短期間の民事紛争の間に、かなりの副次的結果が得られる可能性があるため、本結果は政策立案者にとって有用となる。
Multifocal motor neuropathy (MMN) is a rare disease with a prevalence of less than 1 per 100,000 people. Intravenous immunoglobulin (IVIG) therapy, performed for a long-term period, has been ...demonstrated able to improve the clinical picture of MMN patients, ameliorating motor symptoms and/or preventing disease progression. Treatment with subcutaneous immunoglobulin (SCIg) has been shown to be as effective as IVIG. However, previously published data showed that follow-up of MMN patients in treatment with SCIg lasted no more than 56 months. We report herein the results of a long-term SCIg treatment follow up (up to 96 months) in a group of 8 MMN patients (6 M; 2F), previously stabilized with IVIG therapy. Clinical follow-up included the administration of Medical Research Council (MRC) sum-score, the Overall Neuropathy Limitation Scale (ONLS) and the Life Quality Index questionnaire (LQI) at baseline and then every 6 months. Once converted to SCIg, patients' responsiveness was quite good. Strength and motor functions remained stable or even improved during this long-term follow-up with benefits on walking capability, resistance to physical efforts and ability in hand fine movements.
This article analyses the relationship between corruption and legislative complexity, their impact on growth rate, and per capita income distribution. An econometric analysis is performed using a new ...index of legislative complexity, built in a way that makes it internationally comparable. In the dataset, 67 countries are considered, for a period of 21 years from 1995 to 2015. The OLS and 2SLS regressions are provided. The results of the econometric analysis support the hypothesis that legislative complexity is a constraint to growth, and that in countries with a long history of liberal democracy legislative complexity determines an income redistribution to the detriment of the poorer social classes.
Hippo signaling pathway is considered a key regulator of tissue homeostasis, cell proliferation, apoptosis and it is involved in cancer development. In skeletal muscle, YAP, a downstream target of ...the Hippo pathway, is an important player in myoblast proliferation, atrophy/hypertrophy regulation, and in mechano-trasduction, transferring mechanical signals into transcriptional responses. We studied components of Hippo pathway in muscle specimens from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, limb-girdle muscular dystrophy type 2A and type 2B and healthy subjects. Only DMD muscles had decreased YAP1 protein expression, increased LATS1/2 kinase activity, low Survivin mRNA expression and high miR-21 expression. In light of our novel results, a schematic model is postulated: low levels of YOD1 caused by increased inhibition by miR-21 lead to an increase of LATS1/2 activity which in turn augments phosphorylation of YAP. Reduced amount of active YAP, which is also a target of increased miR-21, causes decreased nuclear expression of YAP-mediated target genes. Since it is known that YAP has beneficial roles in promoting tissue repair and regeneration after injury so that its activation may be therapeutically useful, our results suggest that some components of Hippo pathway could become novel therapeutic targets for DMD treatment.
In this paper the impact of legislation on the GDP growth rate is investigated, both before and after the great economic and financial crisis of 2007–2008. The analysis has been performed using data ...from the twenty Italian regions from 1995 to 2016. Using several econometric models, the most significant result shows that flows of legislation can push economic growth into a recovery phase of the business cycle, while they should be reduced during recession phases, as they constitute a constraint to economic growth.
In Duchenne muscular dystrophy (DMD), telomere shortening has been postulated to contribute to the failure of regenerative activity promoting the premature senescence of satellite cells. The aim of ...the present study was to investigate the telomere length and the expression of telomeric repeat-binding factor-1 (TRF1), poly (ADP-ribose) polymerase-1 (PARP1) and mouse telomerase reverse transcriptase (MTERT) in gastrocnemius, tibialis anterior and diaphragm muscles of the murine model of DMD, the
mdx
mouse and whether a chronic protocol of forced exercise impacts on them. Our results confirmed a telomere shortening in
mdx
muscles, more evident in the diaphragm, in which exercise induced a greater shortening than in wild-type mice. Moreover, we showed for the first time in
mdx
an increased TRF1 and PARP1 expression and an augmented activity of MTERT, further enhanced by exercise. These results reinforce the hypothesis that a deregulation of mechanisms involved in telomere length occurs and may pave the way for the test of compounds targeting proteins modulating telomere maintenance as a novel strategy to treat dystrophinopathies.
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