Associations between post-traumatic stress symptoms and sleep/circadian parameters: Exploring the effect of chronotype as a moderator variable.

The present study aimed at evaluating how post-traumatic stress symptoms (PTSS) are associated with rest-activity circadian and sleep-related parameters, assessed both subjectively (via questionnaires) and objectively (via actigraphy). Specifically, we explored whether chronotype could moderate the association between sleep/circadian parameters and PTSS. Participants (n = 120 adults; mean age 35.6 ± 14; 48 male) were assessed through the Trauma and Loss Spectrum Self Report (TALS-SR) for lifetime PTSS, the reduced version of the Morningness-Eveningness Questionnaire (rMEQ) for chronotype, the Pittsburgh Sleep Quality Index (PSQI) for self-reported sleep quality, and wrist actigraphy for sleep and circadian parameters. Eveningness, poor self-reported sleep quality, lower sleep efficiency (SE), lower interdaily stability (IS), and higher intradaily variability (IV) were correlated with higher TALS-SR scores. Regression analyses showed that IV, SE, and PSQI remained associated with TALS symptomatic domains after adjusting for potentially confounding factors (age and gender). Moderation analysis showed that only the PSQI remained significantly associated with TALS symptomatic domains; however, the interaction with chronotype was not significant. Targeting self-reported sleep disturbances and rest-activity rhythms fragmentation could mitigate PTSS. Although the effect of chronotype as a moderator of the associations between sleep/circadian parameters and PTSS was not significant, eveningness was associated with higher TALS scores, thus confirming the vulnerability of evening types to worse stress reactions.

Poor sleep quality and unhealthy lifestyle during the lockdown: an Italian study.

BACKGROUND: The lockdown measure implemented to face the 2019 Coronavirus Disease (COVID-19) first wave deeply modified the lifestyle of the Italian population. Despite its efficacy in limiting the number of infections, forced home confinement was paralleled by sleep/wake cycle disruptions, psychological distress and maladaptive coping strategies (i.e., unhealthy behaviours, such as tobacco and alcohol consumption). Under these unprecedented stress conditions, we explored a possible association between poor sleep quality and increased likelihood of engaging in an unhealthy lifestyle. METHODS: A cross-sectional study was conducted by disseminating an online survey via social networks and e-mail. We collected information on demographics, COVID-19-related data, sleep quality, chronotype, circadian misalignment, and lifestyle before and during the lockdown (i.e., consumption of cigarettes, alcoholic beverages, coffee, hypnotics, comfort food and fresh food; practice of physical activity). A global healthiness score was computed to assess participants' modifications in lifestyle since the beginning of the lockdown. RESULTS: 1297 respondents were included in the study: 414 (31.9%) from Northern Italy, 723 (55.8%) from Central Italy, 160 (12.3%) from Southern Italy. The following variables were found to be significant predictors of the adoption of an unhealthy lifestyle since the beginning of the lockdown: poor sleep quality, high BMI and considering the measures adopted by the government to fight the pandemic as excessive. Living in Northern Italy, instead, was associated with healthier habits compared to living in Central Italy. CONCLUSIONS: Poor sleepers may represent the share of the general population who paid the highest price for social isolation. Further investigations are required to explore the role of sleep quality assessment in the identification of individuals vulnerable to unhealthy behaviours under stressful conditions.

Sleep quality mediates the effect of chronotype on resilience in the time of COVID-19.

This study aimed to explore the relationship between chronotype and resilience, sleep quality, and post-traumatic stress reactions during the first COVID-19 lockdown in Italy. An online survey was distributed through social networks during forced home confinement, collecting data from1298 participants of 19 different Italian regions. Chronotype was evaluated using the reduced version of the Morningness/Eveningness Questionnaire (rMEQ); sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI); resilience levels were measured by the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC10); post-traumatic stress reactions were assessed by the 6-item version of the Impact of Event Scale (IES6). Resilience and sleep quality were significantly lower in the evening compared to non-evening types, as well as in females as compared to males. Moreover, resilience was negatively correlated with post-traumatic stress reactions and positively correlated with sleep quality. A negative correlation was also reported between sleep quality and post-traumatic stress reactions. Sleep quality was identified as a possible mediator between chronotype and resilience, and between resilience and post-traumatic stress reactions, after controlling for age and sex. These findings provide new insights into the role of chronotype in adapting to continuous stressful situations. Sleep quality seems to mediate the causal path between the antecedents of resilience and the development of trauma. Further research is needed to explore the suitability of primary interventions based on chronobiology and sleep hygiene to mitigate the impact of pandemic-related home confinement measures on mental health among the general population.

Circulating fatty acids in relation to alcohol consumption: Cross-sectional results from a cohort of 60-year-old men and women.

BACKGROUND & AIMS: Alcohol consumption is considered to affect circulating fatty acids (FAs) but knowledge about specific associations is limited. We aimed to assess the relation between alcohol consumption and serum FAs in 60-year-old Swedish men and women. METHODS: In a random sample of 1917 men and 2058 women residing in Stockholm county, cross-sectional associations between different categories of alcohol consumption and FAs were assessed using linear regression; ß1 coefficients with 95% confidence interval (CI) were calculated. Self-reported alcohol consumption was categorized as none, low (≤9.9 g/day) (reference), moderate (10-29.9 g/day) and high (≥30 g/day). Moderate alcohol consumption was further subdivided into consumption of beer, wine, liquor and their combinations. Thirteen serum cholesterol ester FAs were measured by gas chromatography and individual FAs were expressed as percentage of total FAs. RESULTS: Increasing alcohol consumption was associated to linear increase of saturated myristic acid, monounsaturated FAs and n-6 polyunsaturated (PUFA) arachidonic acid, whereas linear decrease was noted for saturated pentadecanoic acid and for n-6 PUFA linoleic acid. With non-linear associations, increasing alcohol consumption also associated to decreased saturated stearic acid, n-6 PUFA dihomo-gamma-linolenic acid, and n-3 PUFA docosahexaenoic acid and increased saturated palmitic acid, n-6 PUFA gamma-linolenic acid and n-3 PUFA eicosapentaenoic acid. Among types of beverages, wine consumption was associated with n-6 PUFA arachidonic acid (ß1 0.59; 95% CI: 0.30;0.88) and the n-3 PUFAs eicosapentaenoic acid (ß1 0.54; 95% CI: 0.30;0.78), and docosahexaenoic acid (ß1 0.06; 95% CI: 0.00;0.12). CONCLUSIONS: These findings may give important basis for further investigations to better understand biological mechanisms behind the dose-dependent associations between alcohol consumption and health outcomes observed in many previous studies.

Childhood onset inflammatory bowel disease and risk of cancer: a Swedish nationwide cohort study 1964-2014.

Objective To assess risk of cancer in patients with childhood onset inflammatory bowel disease in childhood and adulthood.Design Cohort study with matched general population reference individuals using multivariable Cox regression to estimate hazard ratios.Setting Swedish national patient register (both inpatient and non-primary outpatient care) 1964-2014.Participants Incident cases of childhood onset (<18 years) inflammatory bowel disease (n=9405: ulcerative colitis, n=4648; Crohn's disease, n=3768; unclassified, n=989) compared with 92 870 comparators from the general population matched for sex, age, birth year, and county.Main outcome measures Any cancer and cancer types according to the Swedish Cancer Register.Results During follow-up through adulthood (median age at end of follow-up 27 years), 497 (3.3 per 1000 person years) people with childhood onset inflammatory bowel disease had first cancers, compared with 2256 (1.5 per 1000 person years) in the general population comparators (hazard ratio 2.2, 95% confidence interval 2.0 to 2.5). Hazard ratios for any cancer were 2.6 in ulcerative colitis (2.3 to 3.0) and 1.7 in Crohn's disease (1.5 to 2.1). Patients also had an increased risk of cancer before their 18th birthday (2.7, 1.6 to 4.4; 20 cancers in 9405 patients, 0.6 per1000 person years). Gastrointestinal cancers had the highest relative risks, with a hazard ratio of 18.0 (14.4 to 22.7) corresponding to 202 cancers in patients with inflammatory bowel disease. The increased risk of cancer (before 25th birthday) was similar over time (1964-1989: 1.6, 1.0 to 2.4; 1990-2001: 2.3, 1.5 to 3.3); 2002-06: 2.9, 1.9 to 4.2; 2007-14: 2.2, 1.1 to 4.2).Conclusion Childhood onset inflammatory bowel disease is associated with an increased risk of any cancer, especially gastrointestinal cancers, both in childhood and later in life. The higher risk of cancer has not fallen over time.

Mutational analysis of Polycomb genes in solid tumours identifies PHC3 amplification as a possible cancer-driving genetic alteration.

BACKGROUND: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. METHODS: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. RESULTS: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8-35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (P<0.01). Gene amplification correlates with mRNA overexpression (P<0.01), suggesting a functional role of this aberration. CONCLUSION: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours.

An EZH2 polymorphism is associated with clinical outcome in metastatic colorectal cancer patients.

BACKGROUND: Despite therapeutic innovations, metastatic colorectal cancer (mCRC) is still characterized by poor prognosis and few molecular markers predict the risk of progression. Polycomb group genes (PcGs) are epigenetic modifiers involved in tumor suppressor gene silencing. PcG member EZH2 mediates gene silencing through histone-H3 lysine-27 methylation. In colorectal cancer (CRC), EZH2 overexpression predicts shorter survival. Recently, four EZH2 single-nucleotide polymorphisms (SNPs) have been described. The present study was aimed at evaluating the correlation between EZH2 SNPs and outcome parameters in mCRC patients. PATIENTS AND METHODS: DNA was extracted from blood samples of 110 mCRC patients treated with first-line 5-fluorouracil, folinic acid, irinotecan (FOLFIRI) and bevacizumab. Genotyping was carried out by real-time PCR. Genotype was used to predict objective response, progression-free survival (PFS) and overall survival (OS). EZH2 messenger RNA levels were evaluated on lymphocytes of a parallel cohort of 50 CRC patients. RESULTS: One allelic variant (rs3757441 C/C versus C/T or T/T) was significantly associated with shorter PFS and OS (P < 0.01 and P < 0.05, respectively). At multivariate analysis, the same variant resulted an independent predictor of PFS and OS (P < 0.05). The C/C variant was associated with significantly higher EZH2 expression (P < 0.05). CONCLUSION: An EZH2 SNP may be useful to predict clinical outcome in mCRC patients.

Thyroid-stimulating hormone levels in the first days of life and perinatal factors associated with sub-optimal neuromotor outcome in pre-term infants.

AIM: To identify perinatal factors associated with sub-optimal neuromotor outcome in infants without evident central nervous system lesions (intraventricular hemorrhage/ periventricular leukomalacia), with gestational age ≤30 (group I) and of 31-32 weeks (group II). PATIENTS AND METHODS: A total of 102 premature infants admitted to the Neonatal Intensive Care Unit of Pisa, at 26-32 weeks of gestation, were studied. Data about perinatal factors and TSH values at 3-4 days of life were collected. The assessment of neuromotor development was performed at 18 months of corrected age, using the locomotor subscale of the Griffiths Scales of Mental Development. RESULTS: Risk factors supposed to be predictive of sub-optimal neuromotor outcome (odds ratio >1) were at ≤30 weeks: male sex, small for gestational age, patent duct arterious, respiratory distress syndrome, and at 31-32 weeks: Apgar at 5 min <7, respiratory distress syndrome, patent duct arterious and birth weight <1500 g. A strong correlation was also found between TSH screening values >4,3 mU/l and suboptimal neuromotor outcome in both groups. CONCLUSIONS: Several perinatal factors, acting on an immature and more vulnerable nervous system, such as the pre-term one, different for different gestational ages, are associated with a sub-optimal neuromotor outcome. Higher, but within the normal range, TSH values at screening seem to be a strong risk factor for neuromotor outcome in preterm infants without intraventricular hemorrhage or periventricular leukomalacia.

Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer.

BACKGROUND: The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC). METHODS: Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF: -2578A/C, -1498C/T, -1154A/G, -634C/G and 936C/T; and VEGFR-2: -604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients. RESULTS: Treatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found. CONCLUSION: Our study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies.

Videourodynamics in patients with neurogenic bladder due to multiple sclerosis: our experience.

PURPOSE: The aims of this study were to: (a) analyse the most frequent morphofunctional features of the lower urinary tract observed during videourodynamic examination in patients with neurogenic bladder due to multiple sclerosis; (b) investigate the role of the videourodynamic examination in the clinical management of these patients; and (c) demonstrate the relationship between morphological and functional variables. MATERIALS AND METHODS: We performed videourodynamic examinations in 75 patients affected by neurogenic bladder secondary to multiple sclerosis. RESULTS: The introduction of pharmacological therapy, based on clinical and functional evaluation of the lower urinary tract, is correlated with satisfactory morphofunctional outcomes, reducing moderate-to-severe postvoid residual (PVR; p < 0.1) and compliance (p < 0.05) at the price of reduced bladder sensation. Clinical management of these patients based on morphological evaluation of the lower urinary tract decreased the occurrence of detrusor-sphincter dyssynergy (DSD) and detrusor overactivity incontinence at the following examination. CONCLUSIONS: Our study confirmed a relationship between detrusor overactivity and hypertonic bladder, bladder diverticula, vesicoureteral reflux, between detrusor underactivity and PVR and between DSD and bladder diverticula. Our data show how the videourodynamic examination may improve evaluation and urological management of these patients.