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.

Effect of COVID-19 isolation measures on physical activity of children and their parents, and role of the family environment: a cross-sectional study.

Background: The rigorous isolation measures due to the COVID-19 pandemic seriously impacted children's lifestyles. A descriptive cross-sectional study was carried out to collect and analyze information about physical activity habits of children and their parents during the social distancing period resulting from the COVID-19 pandemic. Methods: An online questionnaire was administered to 363 families (507 children aged 5-13) recruited by convenience sampling, asking for physical activity type and frequency before, during, and after the lockdown period (9th March - May 3rd 2020), education, outdoor spaces, and children's weight gain perception. Results: Results show a remarkable decrease in children's physical activity during lockdown (88.9 vs 39.8% active children) associated with older age and low availability of outdoor spaces (p<0.001). Parents' physical activity was related to educational level, and a slight but significant correlation between parents' education and children's physical activity was found, especially with father's university degree (p<0.05). Active mothers significantly influenced children's physical activity during the lockdown, especially if not engaged in smart working. The return to an active lifestyle by children did not reach previous levels (75.9% active children) and was directly related to parent's physical activity. Finally, the risk of weight gain was lower in active children during the lockdown (OR = 0.46; p<0.001). Conclusions: This work highlights the importance of physical activity during a pandemic event to prevent the risk of gaining weight, and underlines the relevance of the entire family system as a source of promotion of healthy behaviors in children.

Sex-related differences of invasive therapy in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Sex-related differences in patients with aneurysmal subarachnoid hemorrhage (aSAH) exist. More females than males are affected. Aneurysm location is associated to sex. The relationship between sex and outcome, however, is unclear. Possible differences in management might influence the occurrence of primary and secondary brain injury and thus outcome. The study compares demographics, intensity of treatment, complications, and outcome among females and males with aSAH. METHODS: All consecutive patients with aSAH admitted to the neurocritical care unit, University Hospital Zurich over a 5-year period were eligible in this retrospective study. Patients' characteristics, comorbidities, aSAH severity, frequency of vasospasm/delayed cerebral ischemia, frequency of invasive interventions, and 3-month outcome were compared by sex. Univariate analysis was performed with the data dichotomized by sex, and outcome. Multivariate analysis for prediction of outcomes was performed. RESULTS: Three hundred forty-eight patients were enrolled (64% females). Women were older than men. Comorbidities, scores at admission, and treatment modality were comparable among males and females. Vasospasm and DCI occurred similarly among females and males. Interventions and frequency of intraarterial spasmolysis were comparable between sexes. In the multivariate analysis, increasing age, female sex, increasing comorbidities, WFNS and Fisher grade, and presence of delayed cerebral ischemia were predictors of unfavorable outcome when considering all patients. However, after excluding death as a possible outcome, sex did not remain a predictor of unfavorable outcome. CONCLUSIONS: In the study population, women with aSAH might have present a worse outcome at 3 months. However, no differences by sex that might explain this difference were found in intensity of treatment and management.

Physical activity, sedentary behaviour and screen time among youths with Down syndrome during the COVID-19 pandemic.

BACKGROUND: The COVID-19-related restrictions hampered habitual physical activity (PA), particularly affecting the more vulnerable, such as people with Down syndrome (DS). The study aimed to investigate changes in PA, sedentary behaviour (SB) and screen time (ST) of youths with DS, before, during and after the restrictions, also in relation to parental PA levels. METHODS: A cross-sectional design with a retrospective assessment of variables for the before and during restrictions periods was adopted. Parents of youths with DS completed an online questionnaire. Sociodemographic aspects, weekly PA levels and youths' daily SB and ST were investigated, referring to three time-points: before the pandemic, during the restrictions and the restrictions-easing phase. RESULTS: A total of 57 parents voluntarily participated in the study, proxy-reporting on their child (male = 41, female = 16, age = 21.4 ± 7.7 years). A repeated measures multivariate analysis of variance showed negative effects of restrictions (P < 0.05) on PA levels, SB and ST, independently from sociodemographic characteristics. In the restrictions-easing phase, PA levels did not return to before the pandemic values (P < 0.05). A positive correlation between parents and their child's PA was detected before the pandemic (r = 0.38; P < 0.01), no longer reported in the restrictions-easing phase. CONCLUSIONS: The findings showed the negative impact of restrictions on youths with DS lifestyle. Moreover, the importance of addressing the needs of the disabled community including the whole family is highlighted.

Hypothesis on the possible relevance of the immunogenic cell death in the treatment of gestational trophoblastic neoplasms.

The genetic background and the antigenic landscape of cancer cells play a critical role in the response to immunotherapies. A high tumor antigenicity, together with an increased adjuvanticity potentially induced by a peculiar type of cell death, namely immunogenic cell death (ICD), could foster the response to immunogenic therapies. The gestational trophoblastic neoplasm (GTN) is a one-of-a-kind cancer in the oncological landscape due to its exclusive genomic makeup. The prognosis of GTN is significantly better than non-gestational trophoblastic neoplasm (nGTN). Due to its peculiar genetic inheritance, GTN potentially constitutes a singular archetype in the immuno-oncological field.

The effects of human sera conditioned by high-intensity exercise sessions and training on the tumorigenic potential of cancer cells

Purpose There is growing evidence of an association between physical activity and a reduced risk of cancer and cancer recurrence. The aim of this study was to assess the effects of exercise-conditioned human serum (HS) effects on the proliferative and tumorigenic potential of triple-negative breast cancer (TNBC) and prostate cancer (PC) cells. Moreover, modulated mechanisms and several physiological factors that can predict exercise effects were investigated. Methods Thirty healthy sedentary subjects were recruited for the study. The subjects performed two high-intensity endurance cycling (HIEC) sessions before and after a nine-week period of high-intensity interval training (HIIT). Cell tumorigenic capacity affected by HS collected before (t0), immediately after (t1), 4 h (t2), and 24 h (t3) after the HIEC sessions was evaluated by in vitro three-dimensional colony formation. The modulation of molecular pathways was analyzed by western blotting and qPCR in TNBC and PC cells, and in TNBC xenografts in exercised mice. Results All of the HIEC-conditioned HS (t1, t2, and t3) markedly impacted the proliferative and the microtumor-forming capacity of both TNBC and PC cell lines, while the HS collected from the subjects at rest did not. Modulation of the Hippo and Wnt/β-catenin pathways by HIEC-conditioned HS before and after the period of HIIT was shown. Multiple linear regression analysis showed relationships between the effects of HIEC-conditioned HS in PC cells, lactate threshold and VO2max. Conclusions These results highlight the potential of HIEC bouts in tumor progression control and the importance of optimizing an approach to identify physiological predictors of the effects of acute exercise in tertiary cancer prevention (AU)

The effects of human sera conditioned by high-intensity exercise sessions and training on the tumorigenic potential of cancer cells.

PURPOSE: There is growing evidence of an association between physical activity and a reduced risk of cancer and cancer recurrence. The aim of this study was to assess the effects of exercise-conditioned human serum (HS) effects on the proliferative and tumorigenic potential of triple-negative breast cancer (TNBC) and prostate cancer (PC) cells. Moreover, modulated mechanisms and several physiological factors that can predict exercise effects were investigated. METHODS: Thirty healthy sedentary subjects were recruited for the study. The subjects performed two high-intensity endurance cycling (HIEC) sessions before and after a nine-week period of high-intensity interval training (HIIT). Cell tumorigenic capacity affected by HS collected before (t0), immediately after (t1), 4 h (t2), and 24 h (t3) after the HIEC sessions was evaluated by in vitro three-dimensional colony formation. The modulation of molecular pathways was analyzed by western blotting and qPCR in TNBC and PC cells, and in TNBC xenografts in exercised mice. RESULTS: All of the HIEC-conditioned HS (t1, t2, and t3) markedly impacted the proliferative and the microtumor-forming capacity of both TNBC and PC cell lines, while the HS collected from the subjects at rest did not. Modulation of the Hippo and Wnt/ß-catenin pathways by HIEC-conditioned HS before and after the period of HIIT was shown. Multiple linear regression analysis showed relationships between the effects of HIEC-conditioned HS in PC cells, lactate threshold and VO2max. CONCLUSIONS: These results highlight the potential of HIEC bouts in tumor progression control and the importance of optimizing an approach to identify physiological predictors of the effects of acute exercise in tertiary cancer prevention.

Transfer Factor as an Option for Managing the COVID-19 Pandemic.

Covid-19 or SARS-CoV-2, a new RNA virus with high infectivity, and seemingly low mutability, which appeared in 2019 in the Wuhan province of China, has created a pandemic with dire consequences. At the end of May 2020, it became the first cause of mortality. As no treatment or vaccine may become available before many months, and because occurrence of similar pandemics is only a matter of time, arguments are presented here for testing the effect of transfer factor (TF), an immunomodulator devoid of toxicity, which has been extensively studied in the past for the treatment and prevention of viral infections.

Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos.

BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations.

Influence of parental habits and drug use in adolescents' physical activity: a case study of an Italian high school.

BACKGROUND: Physical activity is considered a fundamental element for health promotion, also during adolescence, contributing to the psycho-physical well-being of the individuals. Here we evaluate the relationship between risk behavior and physical activity habits of adolescents and their parents. METHODS: A total of 220 subjects (115 females, 105 males), aged between 14 and 18, were asked about their own and parents' physical activity habits and tobacco, alcohol, and light drug consumption. The chi-square test was used to detect differences between males and females. Categorical principal component analysis and Spearman's correlation were used to find associations between the variables analyzed. RESULTS: Our results show a prevalence of an active lifestyle of 52.3%, with no significant gender differences. The consumption of tobacco, alcohol, and light drugs was 28.2, 63.2, and 16.8%, respectively, with a higher prevalence in males and correlated with age. We found a positive correlation between physical activity practice and parents' physical activity, especially between mothers and daughters. Finally, male physical activity practice is inversely related to risk behaviors. CONCLUSIONS: Our findings underline the importance of family and parental involvement in promoting health behaviors, such as physical and sports activities, that can represent a powerful educational tool for the prevention of social dangers.

Swimming Pool safety and prevention at the time of Covid-19: a consensus document from GSMS-SItI.

Public health measures to cope with the Covid-19 pandemic, imposed also a shutdown of sports facilities and swimming pools. Safety issues related to recreational waters were emerging during the lockdown, rising concerns on how and when reopening pools and on how improve their management while SARS-CoV-2 is circulating in the population. The GSMS-SItI, Working Group on Movement Sciences for Health of the Italian Society of Hygiene Preventive Medicine and Public Health, discussed and summarized some indications for a suitable preventive approach. Several measures are highlighted, including social distancing, optimized water management, airflow and microclimatic parameters in the pool as well in the annexed rooms, verification of sanitation procedures. The GSMS-SItI underlines that prevention should be based on monitoring of the local epidemiological situation and on the constant collaboration with the local health authority and the national health service.

Searching for novel multimodal treatments in oligometastatic pancreatic cancer.

BACKGROUND: Metastatic pancreatic cancer has a median overall survival of less than 12 months, even if treated with chemotherapy. Selected patients with oligometastatic disease could benefit from multimodal treatments connecting chemotherapy and surgical treatment or radiofrequency ablation (RFA) of metastases. CASE PRESENTATION: We present a patient with oligometastatic pancreatic cancer recurrence who was successfully treated with a multimodal therapeutic approach. A 57-year-old male initially presenting with resectable pancreatic cancer underwent pancreatoduodenectomy. The histopathological diagnosis revealed ductal pancreatic adenocarcinoma with positive surgical resection margins and negative lymph nodes. He completed six cycles of adjuvant therapy with gemcitabine (1000 mg/mq 1,8,15q 28), followed by external radiotherapy (54 Gy in 25 fractions) associated with gemcitabine 50 mg/mq twice weekly. Three years later, the patient developed multiple liver metastases, and he started FOLFIRINOX (oxaliplatin 85 mg/mq, irinotecan 180 mg/mq, leucovorin 400 mg/mq and fluorouracil 400 mg/mq given as a bolus followed by 2400 mg/mq as a 46 h continuous infusion,1q 14) as a first-line treatment. The CT scan showed a partial response after 6 cycles. After multidisciplinary discussion, the patient underwent a laparotomic metastasectomy of the three hepatic lesions. After additional postsurgical chemotherapy with 4 cycles of the FOLFIRINOX schedule, the patient remained free of recurrence for 12 months. A CT scan showed a new single liver metastasis, which was treated with radiofrequency ablation (RFA). A second radiofrequency ablation was performed when the patient developed another single liver lesion 12 months after the first RFA; currently, the patient is free from recurrence with an overall survival of 6 years from the diagnosis. CONCLUSIONS: Our case has benefited from successful multimodal treatment, including surgical and local ablative techniques and systemic chemotherapy. A multimodal approach may be warranted in selected patients with oligometastatic pancreatic cancer and could improve overall survival. Further research is needed to investigate this approach.

Use of hormones in doping and cancer risk.

Hormones with anabolic properties such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are commonly abused among professional and recreational athletes to enhance physical ability. Despite their adverse effects are well-documented, the use of GH and IGF-1 has recently grown. This article highlights the anabolic activity related to mechanisms of cancer development and progression. GH/IGF-1 axis is able to activate cellular mechanisms that modulate every key stage of cancer formation and progression, such as inhibition of apoptosis, resistance to treatments, and induction of angiogenesis, metastatic process and cell proliferation. Results from pre-clinical studies and epidemiological observations in patients with an excess of GH and IGF-1 production or treated with these hormones showed a positive association with the risk to develop several types of cancer. In conclusion, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer, especially if associated with other licit or illicit drugs and/or high-protein diet.

Listeriolysin O antibodies detection in pregnant women: results from an Italian pilot study.

BACKGROUND: Listeriosis is a rare infection affecting primarily pregnant women, the elderly and individuals with a weakened immune system and is caused by the ubiquitous bacterium Listeria monocytogenes. Infection during pregnancy can cause severe consequences especially for the fetus, leading to sepsis, premature delivery, stillbirth and miscarriage. STUDY DESIGN: A pilot observational study has been conducted in order to establish the prevalence of seroconversion of specific antibodies against a peculiar toxin belonging to L. monocytogenes, listeriolysin O (LLO), in a population of pregnant women from Senigallia (Central Italy) and to find correlations between anti-LLO antibodies seropositivity and health and nutritional information. A total of 60 women were screened for anti-LLO antibody positivity and interviewed during their pregnancies. Statistical analyses were performed to evaluate antibody prevalence in serum samples and potential risk factors. RESULTS: The seroprevalence resulted 18% (95% CI, 8.2 - 27.7%), corresponding to 11 pregnant women. Categorical principal component analysis and hierarchical cluster analysis revealed a significant correlation between anti-LLO positivity and gastrointestinal pain events and vomit, fever and diarrhea episodes, and a possible association with consumption of pre-cooked meal. No significant correlation was observed in women with a previous miscarriage or with miscarriage cases in their families. CONCLUSIONS: Findings from this pilot study will be used to design a wider study focused on the prevalence of Listeria-specific antibodies in pregnant women and could allow to the identification of nutritional and behavioral habits related to Listeria infection which could lead to significant clinical implications.

Membrane human equilibrative nucleoside transporter 1 is associated with a high proliferation rate and worse survival in resected intrahepatic cholangiocarcinoma patients not receiving adjuvant treatments.

Human equilibrative nucleoside transporter 1 (hENT-1) is a membrane nucleoside transporter mediating the intracellular uptake of nucleosides and their analogues. hENT-1 was recently reported to have a predictive role in intrahepatic cholangiocarcinoma (iCC) patients receiving adjuvant gemcitabine-based chemotherapy, but its biological and clinical significance in iCC remains unsettled. This study investigated the role of hENT-1 in regulating tumour growth and predicting the survival of 40 resected iCC patients not receiving adjuvant treatments. hENT-1 expression was found to be significantly higher in iCC than in the matched non-tumoural liver. Patients harbouring hENT-1 localised on the tumour cell membrane had a worse overall survival than membrane hENT-1-negative patients (median 21.2 months vs 30.3 months, p = 0.031), with an adjusted hazard ratio of 2.8 (95% confidence interval 1.01-7.76). Moreover, membrane hENT-1-positive patients had a higher percentage of Ki67-positive cells in tumour tissue than membrane hENT-1-negative patients (median 23% vs 5%, p < 0.0001). Functional analyses in iCC cell lines revealed that hENT-1 silencing inhibited cell proliferation and induced apoptosis in HUH-28 cells expressing hENT-1 on the cell membrane, but not in SNU-1079 cells expressing the transporter only in the cytoplasm. Overall, these findings suggest that membrane hENT-1 is involved in iCC proliferation and associated with worse survival in resected iCC patients. Further prospective studies on larger cohorts are required to confirm these results and better define the potential prognostic role of membrane hENT-1 in this setting of patients.

Bone metastases in biliary cancers: A multicenter retrospective survey.

•Natural history of biliary cancers metastatic to bone•The role of skeletal events in patients with biliary cancer•Biliary cancer and bone metastases: role of bisphosphonates.

Radiotherapy in the management of gist: state of the art and new potential scenarios.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. The main treatment for localized gastrointestinal stromal tumors is surgical resection. Unresectable or advanced GIST are poorly responsive to conventional cytotoxic chemotherapy but the introduction of tyrosine kinase inhibitors (TKIs) marked a revolutionary step in the treatment of these patients, radically improving prognosis and clinical benefit. Historically GIST has been considered radiation-resistant, and the role of radiotherapy in the management of patients with GIST is currently restricted to symptomatic palliation in current treatment guidelines. CASE PRESENTATION: Here we report two patients affected by metastatic GIST, treated with radiotherapy and radiosurgery in combination with TKIs, achieving an unexpected objective response in the first case and a significant clinical benefit associated with a local tumor control of several months in the second case. CONCLUSIONS: These and other successful experiences that are progressively accumulating, open up new scenarios of use of radiation therapy in various settings of treatment. GIST is not universally radioresistant and radiotherapy, especially if combined with molecularly targeted therapy, can improve the outcomes for patients diagnosed with GIST.