Active breaks: a strategy to counteract sedentary behaviors for Health Promoting Schools. A discussion on their implementation in Italy.

Abstract: School Active Breaks are short bouts of physical activity (5-15 minutes) conducted by appropriately trained teachers and delivered during or between curricular lessons. They are a good strategy to counteract sedentary behaviors, and a growing body of evidence shows that they can represent also a tool to promote and improve health, school wellbeing and academic achievements. On 19 February 2022, the Working Group on Movement Sciences for Health of the Italian Society of Hygiene, Preventive Medicine and Public Health organized an Awareness Day on the effectiveness, usefulness and feasibility of School Active Breaks, opened to teachers, educators, school leaders, pediatricians, personnel from Departments of Prevention and Public Health and Health Policy-makers. During the event, the testimonies about the experiences already carried out in Italy showed that School Active Breaks are an effective intervention that each school can easily include in its educational offer and apply in any context.

Percutaneous cholecystostomy for severe (Tokyo 2013 stage III) acute cholecystitis.

PURPOSES: To evaluate the impact of percutaneous cholecystostomy (PC) on severe acute cholecystitis (AC). METHODS: According to the ICD-9 classification, we retrospectively retrieved medical records of patients discharged with a diagnosis of AC from January 2007 to December 2016 at our hospital. Patients were then stratified according to the Tokyo 2013 (TG 13) AC severity criteria. Grade III AC was diagnosed according to the TG 13 criteria. Indications for PC were failure of optimal medical treatment within 48 h, worsening of clinical condition within early medical treatment, patients unfit for upfront surgery and patient's preference. Ascites was considered a contraindication to PC while coagulopathy was considered a minor contraindication. Primary end points were: clinical improvement, morbidity and related mortality. Secondary endpoints were AC recurrences and elective laparoscopic cholecystectomies (LS). Response was evaluated by clinical and blood test improvement. Morbidity was evaluated according to the Dindo-Clavien scale. RESULTS: A total of 117 eligible patients were diagnosed as grade III AC. Of these, 29 (24.7%) underwent PC. The procedure was completed in all cases. Overall morbidity rate was 20.6%. Main complication was the drainage dislodgement due to involuntary patient's movement. Overall mortality was 17.2% but no causes of death were dependent upon the procedure. Clinical improvement was reported in 95.5% of surviving patients. CONCLUSION: This study confirms that PC is a valuable tool in the treatment of severe AC. Randomized trials are needed to clarify the criteria for patient selection and to optimize the timing for both cholecystostomy and cholecystectomy.

Marital status is a prognostic factor in amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVES: Several variables have been linked to a shorter survival in patients with amyotrophic lateral sclerosis (ALS), for example, female sex, older age, site of disease onset, rapid disease progression, and a relatively short diagnostic delay. With regard to marital status, previous studies suggested that living with a partner might be associated to a longer survival and a higher likelihood to proceed to tracheostomy. Therefore, to further strengthen this hypothesis, we investigated the role of marital status as a prognostic variable in a cohort of ALS patients. METHODS: We performed a retrospective analysis on 501 consecutive ALS patients for which a complete disease's natural history and clinical/demographic data were available. At diagnosis, 409 patients (81.6%) were married or lived with a stable partner, whereas 92 patients (18.4%) were single/widowed/divorced. RESULTS: In our ALS cohort, being married was associated with a median longer survival (married, 35 months [24-50] vs unmarried, 27 months [18-42]; P<.004). Moreover, married and unmarried patients were significantly different in many clinical and demographic variables, including age at disease onset, gender, body mass index, and number of children. Cox regression analysis showed that age at onset, diagnostic delay, and marital status were independent predictors of survival. In unmarried patients, female sex was also significantly associated with shorter survival. CONCLUSIONS: Marital status is a prognostic factor in ALS, and it significantly affects survival.

REM sleep behavior disorder and periodic leg movements during sleep in ALS.

OBJECTIVE: To assess sleep characteristics and the occurrence of abnormal muscle activity during sleep, such as REM sleep without atonia (RSWA), REM sleep behavior disorder (RBD), and periodic leg movements during sleep (PLMS), in patients with amyotrophic lateral sclerosis (ALS). METHODS: A total of 41 patients with ALS and 26 healthy subjects were submitted to clinical interview and overnight video-polysomnography. RESULTS: A total of 22 patients with ALS (53.6%) reported poor sleep quality. Polysomnographic studies showed that patients with ALS had reduced total sleep time, increased wakefulness after sleep onset, shortened REM and slow-wave sleep, and decreased sleep efficiency, compared to controls. Polysomnographic abnormalities were not different in patients reporting good or poor sleep and were not correlated to clinical and demographic variables. The PLMS index was significantly higher in patients with ALS than in healthy subjects, and 22 patients (53.6%) showed a PLMS index > 15/h, vs 4 (15.4%) controls (P < 0.001). Finally, two patients with ALS (4.9%) had RBD, and two more patients presented RSWA (4.9%), whereas no controls showed abnormalities of REM sleep. CONCLUSION: Patients with ALS frequently present abnormalities of sleep that can be documented both at the clinical interview and at the polysomnographic evaluation, including insomnia, fragmented sleep, and increased PLMS. Moreover, abnormalities of REM sleep can be found in some of these patients.

Fatigue, sleep, and nocturnal complaints in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Fatigue is a common symptom in amyotrophic lateral sclerosis (ALS). Although sleep disturbances are a candidate factor that may interfere with fatigue in patients with ALS, the role of sleep-related abnormalities in determining fatigue in ALS is unknown. OBJECTIVE: To evaluate the frequency and determinants of fatigue in a group of 91 consecutive patients with ALS, with special attention to the relationship between fatigue and sleep problems. METHODS: Measures included the Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), ALS Functional Rating Scale-Revised (ALSFRS-R), and Beck Depression Inventory (BDI). RESULTS: The mean FSS score was 4.35 ± 1.1, and 48 patients with ALS (52.75%) reported clinical significant fatigue. FSS score correlated with ALSFRS-R score, forced vital capacity, ESS, BDI, and global PSQI score. Patients with fatigue were significantly more disabled and more frequently reported difficulties staying asleep and nocturnal complaints, such as nocturia and disturbing muscle cramps. After multivariate analysis, patients' disability and nocturnal complaints were significantly associated with fatigue. CONCLUSION: In this study, we demonstrated that fatigue, a troublesome and disabling symptom in ALS, is associated with physical impairment and night-time complaints (such as nocturia and muscle cramps), suggesting that treating sleep problems might be useful in alleviating fatigue in these patients.

Autosomal dominant hereditary spastic paraplegia: report of a large Italian family with R581X spastin mutation.

We describe a large kindred with a typical pure form of autosomal dominant hereditary spastic paraplegia (ADHSP). On the basis of maximum LOD score of 1.94 at theta (max)=0 with marker D2S367, we obtained suggestive evidence for linkage of ADHSP to SPG4 locus. Denaturing high-performance liquid chromatography (DHPLC) and direct sequence analysis allowed us to identify a nonsense mutation (1741* C>T) in exon 17 of the Spastin gene. This transition, carried by all the affected family members and two apparently healthy individuals, lead to truncation of the last 36 amino acids in the C-terminus of the protein. These results confirm the existence of mutation in the SPG4 gene with a reduced penetrance, indicating that other genetic or environmental factors are required to trigger full-blown disease.

Noninvasive positive-pressure ventilation in ALS: predictors of tolerance and survival.

OBJECTIVE: To identify factors associated with tolerance and survival after noninvasive positive-pressure ventilation (NIPPV) and to investigate the influence of NIPPV on lung function in patients with ALS. METHODS: NIPPV was offered to 71 patients with ALS in accordance with currently published guidelines. Effects of NIPPV on lung function and factors influencing tolerance and survival after NIPPV were studied. RESULTS: Forty-four patients (61.9%; 95% CI: 50.6 to 73.2) tolerated NIPPV (NIPPV use >or=4 h/day) and 27 (38.1%; 95% CI: 26.8 to 49.4) were intolerant (NIPPV use <4 h/day). Patients with mild or moderate bulbar symptoms were more likely to tolerate NIPPV than those with severe impairment (odds ratio = 6.09, 95% CI: 1.18 to 31.52, p = 0.031). After NIPPV introduction, a slower decline in forced vital capacity (FVC) was observed in tolerant vs intolerant patients (p = 0.002). The slope of FVC decline after NIPPV initiation (risk ratio [RR]: 0.78, 95% CI: 0.65 to 0.94, p = 0.01) together with NIPPV tolerance (RR: 0.32, 95% CI: 0.13 to 0.78, p = 0.013) were the only independent predictors of survival in the overall group of patients. In multivariate analysis, body mass index was the most powerful predictor of longer survival after NIPPV in tolerant patients (RR: 0.77, 95% CI: 0.61 to 0.96, p = 0.022). CONCLUSION: Survival after noninvasive ventilation was independently related to ventilatory use (>or=4 h/day) and to the modifications of forced vital capacity decline after treatment initiation. The severity of bulbar impairment and the nutritional status of the ALS patients at the introduction of ventilation may predict tolerance and survival.

Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.

Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both the TNFRs are overexpressed in these cells. No changes of the upstream p38MAPK cascade kinases or TNFRs occur in reactive astrocytes. These findings highlight the activation of a selective intracellular signaling pathway in the motor neurons of SOD1 mutant mice, which is likely implicated in their death.

Inter- and intracellular signaling in amyotrophic lateral sclerosis: role of p38 mitogen-activated protein kinase.

The pathogenetic processes underlying the selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) are complex and still not completely understood even in the cases of inherited disease caused by mutations in the Cu/Zn superoxide dismutase-dependent (SOD1) gene. Recent evidence supports the view that ALS is not a cell-autonomous disease and that glial-neuron cross-talk, throughout cytokines and other toxic factors like the nitric oxide and superoxide, is a crucial determinant for the induction of motor neuron death. This cell-cell interaction may determine the progression of the disease through processes that are likely independent of the initial trigger and that may converge on the activation of intracellular death pathways in the motor neurons. In this review we provide support to the hypothesis that aberrant expression and activity of p38 mitogen protein-activated kinases cascade (p38MAPK) in motor neurons and glial cells may play a role in the development and progression of ALS. Increased activation of p38MAPK may phosphorylate neuron-specific substrates altering their physiological properties and it may turn on responsive genes leading to neurotoxicity.

Bulbar-onset amyotrophic lateral sclerosis in a patient with Chiari I malformation.

We report on a patient with bulbar-onset, clinically defined, sporadic amyotrophic lateral sclerosis (ALS) who also showed a Chiari I malformation. This malformation, otherwise asymptomatic, was detected during the diagnostic work-up for ALS. To our knowledge this is the first report of an association between these two relatively uncommon disorders. Since our patient worked for many years as a bus-driver and because the ALS symptoms began in the brainstem region, we suggest that his hindbrain anomaly, along with the mechanical stress on the spine and cranio-vertebral junction due to the daily driving, might have played a role in the region-specific onset of ALS.