Culture, religion and gender: considerations in facing migration related health inequalities in Italy.

BACKGROUND: The presence in Italy of a significant foreign population (5-6 million including both formally residents and not officially registered ones) introduces significant transformations in the Italian demography with important challenges on ensuring fundamental rights including work, education and above all, health. Access to healthcare. Issues common to the entire migrant population concern the difficulty of accessing the health system of the host country due to the lack of knowledge of its rules and its functioning, the linguistic and cultural barriers and the distrust towards a system that is not recognized as his own, as well as the difficulties and misunderstandings encountered in the relationship with health professionals. Religion, culture and gender may even increase these difficulties. Conlusion and future perspective. Culture and religion should be taken into account when designing and implementing healthcare services and healthcare workers need to be trained in acknowledging these challenges. The National Health Service should become more sensitive to the increasing cultural and religious pluralism of patients starting with investing more in the training of health professionals.

The Role of Sex Differences in Bone Health and Healing.

Fracture healing is a long-term and complex process influenced by a huge variety of factors. Among these, there is a sex/gender disparity. Based on significant differences observed in the outcome of bone healing in males and females, in the present review, we report the main findings, hypotheses and pitfalls that could lead to these differences. In particular, the role of sex hormones and inflammation has been reported to have a role in the observed less efficient bone healing in females in comparison with that observed in males. In addition, estrogen-induced cellular processes such as autophagic cell cycle impairment and molecular signals suppressing cell cycle progression seem also to play a role in female fracture healing delay. In conclusion, it seems conceivable that a complex framework of events could contribute to the female bias in bone healing, and we suggest that a reappraisal of the compelling factors could contribute to the mitigation of sex/gender disparity and improve bone healing outcomes.

The Role of Religions in the COVID-19 Pandemic: A Narrative Review.

Culture, religion and health are closely intertwined, profoundly affecting people's attitudes and behaviors as well as their conception and experience of illness and disease. In order to analyze the impact of religion in the current COVID-19 pandemic, we performed a literature review investigating both the scientific and grey literature on the topic. COVID-19 outbreaks reported in pilgrimages and religious ceremonies around the world-especially in the first wave of the pandemic wave-and the role played by religion in conveying culturally sensitive information about COVID-19 are some of the evidence we reviewed. Our research highlights how religions have represented, on the one hand, a risk for the spread of the virus and, on the other, a precious opportunity to engage people, and in particular minorities, in fighting the pandemic. To overcome this pandemic and to be prepared for similar ones in the future, scientists, politicians and health professionals should acknowledge the role that culture and religion play in people's lives and how it can assist in tackling complex health challenges.

Gender differences in vitiligo: psychological symptoms and quality of life assessment description.

Objective: Assuming that the difference exist in the manifestation of psychological suffering among genders, the purpose of this review is to summarize the current knowledge on gender differences in vitiligo quality of life and psychological assessment. Methods: We searched in PubMed, Scopus, and Web of Science databases for original articles in English language. Results were screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA checklist). Results: The study yielded 107 results; 12 articles have been evaluated as eligible. Each eligible study has been screened and analyzed. The study's qualitative evaluation revealed that 8 papers were classifiable as satisfactory, 4 were classifiable as unsatisfactory. The agreement between the coders was high (% agreement = 84.6%; Cohen's kappa = 0.79). All considered researches (100%) were cross-sectional studies, based on self-report questionnaires. From our analysis, women with vitiligo had a higher risk to experience lower quality of life, and worse mental health in a wide range of psychopathology symptoms than men. A wide heterogeneity of tools is used to investigate the quality of life and psychological symptoms among these patients. Conclusion: Unfortunately, there are few explanatory models proposed in the literature to rationalize these findings. It will be important to investigate in further researches the specific influence of known risk factors for psychopathology in this population to better explore these phenomena.

Post-Acute COVID-19 Sequelae in a Working Population at One Year Follow-Up: A Wide Range of Impacts from an Italian Sample.

Long COVID-19 is a term used to describe the symptomatic sequelae that develop after suffering from COVID-19. Very few studies have investigated the impact of COVID-19 sequelae on employment status. The aim of this research was to characterise sequelae of COVID-19 in a population of workers who tested positive for COVID-19, with a follow-up within one year of the acute illness, and to analyse the possible association between this and changes in the workers' occupational status. In this retrospective cohort study, a questionnaire was administered to 155 workers; descriptive, univariate (chi-square tests), and multivariate (logistic regression model) analyses were carried out. The mean age was 46.48 years (SD ± 7.302); 76 participants were males (49.7%), and 33 participants reported being current smokers (21.3%). Overall, 19.0% of patients reported not feeling fully recovered at follow-up, and 13.7% reported a change in their job status after COVID-19. A change in occupational status was associated with being a smoker (OR 4.106, CI [1.406-11.990], p = 0.010); hospital stay was associated with age > 46 years in a statistically significant way (p = 0.025) and with not feeling fully recovered at follow-up (p = 0.003). A persistent worsening in anxiety was more common in women (p = 0.028). This study identifies smoking as a risk factor for workers not able to resume their job; furthermore, occupational physicians should monitor mental health more closely after COVID-19, particularly in female workers.

Sex and gender differences in migraines: a narrative review.

INTRODUCTION: Gender medicine is a new medical approach aimed at the study of the differences between women and men in terms of prevention, diagnosis, and the outcome of all diseases. Migraines are among these. They represent the most common neurological illness; they are most prevalent in adults between 20 and 50 years of age and are three to four times more frequent in woman than in men. Affecting people in working age, migraines are a problem that strongly impacts the psychophysical health and productivity of workers, regardless of the specific job task they have. METHODS: A narrative review was performed, searching for the most relevant articles describing gender differences in people suffering from migraines, and particularly in workers. RESULTS: Migraine global prevalence is 20.7% in women and 9.7% in men whereas prevalence in Italy is 32.9% for women and only 13.0% for men. This difference is partly explained by hormonal differences, as well as by differences in brain structure, genetic polymorphisms and neuronal pathways. Sex differences may also play a role in the progression from episodic to chronic migraine. In workers, migraines are mostly associated with strenuous physical work in men, whilst migraines triggered by night shifts, lack of sleep, or irregular sleep patterns are more common in women. CONCLUSIONS: To this day, the reasons of sex/gender disparity for migraine are still obscure. However, migraines, chronic migraine in particular, have a negative impact on the lives of all individuals affected by this disease, but particularly in women in which family cares and working activity are often superimposed. Migraine prevention strategies should be planned in workers through the occupational health physician.

Psychological Impact of the COVID-19 Pandemic on Pregnant Women.

Objective: The aim of this study is to assess the impact of the COVID-19 pandemic on mental health, type of delivery, and neonatal feeding of pregnant women with or without SARS-CoV-2 infection during gestation. Study Design: The study was conducted online, and anonymous survey was distributed to mothers that delivered during the COVID-19 pandemic. Results: The survey was completed by 286 women, and 64 women (22.4%) had COVID-19 during pregnancy. Women that had SARS-CoV-2 infection during pregnancy or at time of delivery had a significantly higher probability of being separated from the newborn (p < 0.0001) and a significantly lower probability of breastfeeding (p < 0.0001). The Edinburg Postnatal Depression Scale, to assess if mothers had symptoms of postnatal depression, showed that items suggestive of postnatal depression were relatively frequent in the whole cohort. However, women with SARS-CoV-2 infection during pregnancy reported higher probability of responses suggestive of postnatal depression in eight out of 10 items, with statistically significant differences in three items. Conclusion: The COVID-19 pandemic affected the type of delivery and breastfeeding of pregnant women, particularly when they had SARS-CoV-2 infection. This, in turn, had an impact on the psychological status of the interviewed mothers, aspects that could benefit of special support.

Hormones and Sex-Specific Medicine in Human Physiopathology.

A prodigious increment of scientific evidence in both preclinical and clinical studies is narrowing a major gap in knowledge regarding sex-specific biological responses observed in numerous branches of clinical practices. Some paradigmatic examples include neurodegenerative and mental disorders, immune-related disorders such as pathogenic infections and autoimmune diseases, oncologic conditions, and cardiovascular morbidities. The male-to-female proportion in a population is expressed as sex ratio and varies eminently with respect to the pathophysiology, natural history, incidence, prevalence, and mortality rates. The factors that determine this scenario incorporate both sex-associated biological differences and gender-dependent sociocultural issues. A broad narrative review focused on the current knowledge about the role of hormone regulation in gender medicine and gender peculiarities across key clinical areas is provided. Sex differences in immune response, cardiovascular diseases, neurological disorders, cancer, and COVID-19 are some of the hints reported. Moreover, gender implications in occupational health and health policy are offered to support the need for more personalized clinical medicine and public health approaches to achieve an ameliorated quality of life of patients and better outcomes in population health.

The Natural Estrogen Receptor Beta Agonist Silibinin as a Promising Therapeutic Tool in Diffuse Large B-cell Lymphoma.

BACKGROUND/AIM: About 40% of patients with diffuse large cell lymphoma (DLBCL) still have a poor prognosis. Additionally, DLBCL patients treated with doxorubicin are at risk of cardiac failure. Growing evidence suggests an antitumor and cardioprotective activity exerted by estrogen via its binding to estrogen receptor (ER) ß. The aim of this study was to evaluate the anticancer activity of the phytoestrogen silibinin, an ERß selective agonist, on DLBCL growth, and its potential cardioprotective effect. MATERIALS AND METHODS: DLBCL cell lines SUDHL-8, SUDHL-6, and RIVA were used. The anti-tumor activity of silibinin was also evaluated in vivo in NOD/SCID/IL2Rg-/- (NSG) xenografted mice. AC16 human ventricular cardiomyocytes were used to investigate the cardioprotective effects of silibinin. RESULTS: In vitro silibinin induced apoptosis and autophagy, and blocked tumor cell proliferation, also protecting AC16 cardiomyocytes from doxorubicin-induced toxicity. In vivo silibinin induced cell death and autophagy, and reduced tumor volume. CONCLUSION: Silibinin represents a promising therapeutic tool.

The Sex-Related Interplay between TME and Cancer: On the Critical Role of Estrogen, MicroRNAs and Autophagy.

The interplay between cancer cells and the tumor microenvironment (TME) has a fundamental role in tumor progression and response to therapy. The plethora of components constituting the TME, such as stroma, fibroblasts, endothelial and immune cells, as well as macromolecules, e.g., hormones and cytokines, and epigenetic factors, such as microRNAs, can modulate the survival or death of cancer cells. Actually, the TME can stimulate the genetically regulated programs that the cell puts in place under stress: apoptosis or, of interest here, autophagy. However, the implication of autophagy in tumor growth appears still undefined. Autophagy mainly represents a cyto-protective mechanism that allows cell survival but, in certain circumstances, also leads to the blocking of cell cycle progression, possibly leading to cell death. Since significant sex/gender differences in the incidence, progression and response to cancer therapy have been widely described in the literature, in this review, we analyzed the roles played by key components of the TME, e.g., estrogen and microRNAs, on autophagy regulation from a sex/gender-based perspective. We focused our attention on four paradigmatic and different forms of cancers-colon cancer, melanoma, lymphoma, and lung cancer-concluding that sex-specific differences may exert a significant impact on TME/cancer interaction and, thus, tumor growth.

Raft-like lipid microdomains drive autophagy initiation via AMBRA1-ERLIN1 molecular association within MAMs.

Mitochondria-associated membranes (MAMs) are essential communication subdomains of the endoplasmic reticulum (ER) that interact with mitochondria. We previously demonstrated that, upon macroautophagy/autophagy induction, AMBRA1 is recruited to the BECN1 complex and relocalizes to MAMs, where it regulates autophagy by interacting with raft-like components. ERLIN1 is an endoplasmic reticulum lipid raft protein of the prohibitin family. However, little is known about its association with the MAM interface and its involvement in autophagic initiation. In this study, we investigated ERLIN1 association with MAM raft-like microdomains and its interaction with AMBRA1 in the regulation of the autophagic process. We show that ERLIN1 interacts with AMBRA1 at MAM raft-like microdomains, which represents an essential condition for autophagosome formation upon nutrient starvation, as demonstrated by knocking down ERLIN1 gene expression. Moreover, this interaction depends on the "integrity" of key molecules, such as ganglioside GD3 and MFN2. Indeed, knocking down ST8SIA1/GD3-synthase or MFN2 expression impairs AMBRA1-ERLIN1 interaction at the MAM level and hinders autophagy. In conclusion, AMBRA1-ERLIN1 interaction within MAM raft-like microdomains appears to be pivotal in promoting the formation of autophagosomes.Abbreviations: ACSL4/ACS4: acyl-CoA synthetase long chain family member 4; ACTB/ß-actin: actin beta; AMBRA1: autophagy and beclin 1 regulator 1; ATG14: autophagy related 14; BECN1: beclin 1; CANX: calnexin; Cy5: cyanine 5; ECL: enhanced chemiluminescence; ER: endoplasmic reticulum; ERLIN1/KE04: ER lipid raft associated 1; FB1: fumonisin B1; FE: FRET efficiency; FRET: Förster/fluorescence resonance energy transfer; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GD3: aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)ceramide; HBSS: Hanks' balanced salt solution; HRP: horseradish peroxidase; LMNB1: lamin B1; mAb: monoclonal antibody; MAMs: mitochondria-associated membranes; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MFN2: mitofusin 2; MTOR: mechanistic target of rapamycin kinase; MYC/cMyc: proto-oncogene, bHLH transcription factor; P4HB: prolyl 4-hydroxylase subunit beta; pAb: polyclonal antibody; PE: phycoerythrin; SCAP/SREBP: SREBF chaperone; SD: standard deviation; ST8SIA1: ST8 alpha-N-acetyl-neuraminide alpha-2,8 sialyltransferase 1; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUBB/beta-tubulin: tubulin beta class I; ULK1: unc-51 like autophagy activating kinase 1; VDAC1/porin: voltage dependent anion channel 1.

On the role of sphingolipids in cell survival and death.

Sphingolipids, universal components of biological membranes of all eukaryotic organisms, from yeasts to mammals, in addition of playing a structural role, also play an important part of signal transduction pathways. They participate or, also, ignite several fundamental subcellular signaling processes but, more in general, they directly contribute to key biological activities such as cell motility, growth, senescence, differentiation as well as cell fate, i.e., survival or death. The sphingolipid metabolic pathway displays an intricate network of reactions that result in the formation of multiple sphingolipids, including ceramide, and sphingosine-1-phosphate. Different sphingolipids, that have key roles in determining cell fate, can induce opposite effects: as a general rule, sphingosine-1-phosphate promotes cell survival and differentiation, whereas ceramide is known to induce apoptosis. Furthermore, together with cholesterol, sphingolipids also represent the basic lipid component of lipid rafts, cholesterol- and sphingolipid-enriched membrane microdomains directly involved in cell death and survival processes. In this review, we briefly describe the characteristics of sphingolipids and lipid membrane microdomains. In particular, we will consider the involvement of various sphingolipids per se and of lipid rafts in apoptotic pathway, both intrinsic and extrinsic, in nonapoptotic cell death, in autophagy, and in cell differentiation. In addition, their roles in the most common physiological and pathological contexts either as pathogenetic elements or as biomarkers of diseases will be considered. We would also hint how the manipulation of sphingolipid metabolism could represent a potential therapeutic target to be investigated and functionally validated especially for those diseases for which therapeutic options are limited or ineffective.

The influence of patient sex on clinical approaches to malignant glioma.

Gliomas are tumors that originate from the glial tissue, thus involving the central nervous system with varying degrees of malignancy. The most aggressive and frequent form is glioblastoma multiforme, a disease characterized by resistance to therapies, frequent recurrences, and extremely poor median survival time. Data on overall glioma case studies demonstrate clear sex disparities regarding incidence, prognosis, drug toxicity, clinical outcome, and, recently, prediction of therapeutic response. In this study, we analyze data in the literature regarding malignant glioma, mainly glioblastoma multiforme, focusing on epidemiological and clinical evaluations. Less discussed issues, such as the role of viral infections, energy metabolism, and predictive aspects concerning the possible use of dedicated therapeutic approaches for male or female patients, will be reported together with different estimated pathogenetic mechanisms underlying astrocyte transformation and glioma chemosensitivity. In this era, where personalized/precision medicine is the most important driver for targeted cancer therapies, the lines of evidence discussed herein strongly suggest that clinical approaches to malignant glioma should consider the patient's sex. Furthermore, retrospectively revising previous clinical studies considering patient sex as a crucial variable is recommended.

Non-genomic Effects of Estrogen on Cell Homeostasis and Remodeling With Special Focus on Cardiac Ischemia/Reperfusion Injury.

This review takes into consideration the main mechanisms involved in cellular remodeling following an ischemic injury, with special focus on the possible role played by non-genomic estrogen effects. Sex differences have also been considered. In fact, cardiac ischemic events induce damage to different cellular components of the heart, such as cardiomyocytes, vascular cells, endothelial cells, and cardiac fibroblasts. The ability of the cardiovascular system to counteract an ischemic insult is orchestrated by these cell types and is carried out thanks to a number of complex molecular pathways, including genomic (slow) or non-genomic (fast) effects of estrogen. These pathways are probably responsible for differences observed between the two sexes. Literature suggests that male and female hearts, and, more in general, cardiovascular system cells, show significant differences in many parameters under both physiological and pathological conditions. In particular, many experimental studies dealing with sex differences in the cardiovascular system suggest a higher ability of females to respond to environmental insults in comparison with males. For instance, as cells from females are more effective in counteracting the ischemia/reperfusion injury if compared with males, a role for estrogen in this sex disparity has been hypothesized. However, the possible involvement of estrogen-dependent non-genomic effects on the cardiovascular system is still under debate. Further experimental studies, including sex-specific studies, are needed in order to shed further light on this matter.

Correction: X-chromosome-linked miR548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

X-chromosome-linked miR548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis.

Sex dimorphism in cell response to stress has previously been investigated by different research groups. This dimorphism could be at least in part accounted for by sex-biased expression of regulatory elements such as microRNAs (miRs). In order to spot previously unknown miR expression differences we took advantage of prior knowledge on specialized databases to identify X chromosome-encoded miRs potentially escaping X chromosome inactivation (XCI). MiR-548am-5p emerged as potentially XCI escaper and was experimentally verified to be significantly up-regulated in human XX primary dermal fibroblasts (DFs) compared to XY ones. Accordingly, miR-548am-5p target mRNAs, e.g. the transcript for Bax, was differently modulated in XX and XY DFs. Functional analyses indicated that XY DFs were more prone to mitochondria-mediated apoptosis than XX ones. Experimentally induced overexpression of miR548am-5p in XY cells by lentivirus vector transduction decreased apoptosis susceptibility, whereas its down-regulation in XX cells enhanced apoptosis susceptibility. These data indicate that this approach could be used to identify previously unreported sex-biased differences in miR expression and that a miR identified with this approach, miR548am-5p, can account for sex-dependent differences observed in the susceptibility to mitochondrial apoptosis of human DFs.

Functional Estrogen Receptors of Red Blood Cells. Do They Influence Intracellular Signaling?

BACKGROUND/AIMS: Estrogen could play a key role in the mechanisms underlying sex-related disparity in the incidence of thrombotic events. We investigated whether estrogen receptors (ERs) were expressed in human red blood cells (RBCs), and if they affected cell signaling of erythrocyte constitutive isoform of endothelial NO-synthase (eNOS) and nitric oxide (NO) release. METHODS: RBCs from 29 non-smoker volunteers (15 males and 14 females) aged between 20 and 40 years were analyzed by cytometry and western blot. In particular, content and distribution of ER-α and ER-ß, tyrosine kinases and eNOS phosphorylation and NO release were analyzed. RESULTS: We demonstrated that: i) both ER-α and ER-ß were expressed by RBCs; ii) they were both functionally active; and iii) ERs distribution and function were different in males and females. In particular, ERs modulated eNOS phosphorylation and NO release in RBCs from both sexes, but they induced the phosphorylation of specific tyrosine residues of kinases linked to eNOS activation and NO release in the RBCs from females only. CONCLUSION: Collectively, these data suggest that ERs could play a critical role in RBC intracellular signaling. The possible implication of this signaling in sex-linked risk disparity in human cardiovascular diseases, e.g. in thrombotic events, may not be ruled out.

Inflammatory cytokines associated with cancer growth induce mitochondria and cytoskeleton alterations in cardiomyocytes.

Cardiac dysfunction is often observed in patients with cancer also representing a serious problem limiting chemotherapeutic intervention and even patient survival. In view of the recently established role of the immune system in the control of cancer growth, the present work has been undertaken to investigate the effects of a panel of the most important inflammatory cytokines on the integrity and function of mitochondria, as well as of the cytoskeleton, two key elements in the functioning of cardiomyocytes. Either mitochondria features or actomyosin cytoskeleton organization of in vitro-cultured cardiomyocytes treated with different inflammatory cytokines were analyzed. In addition, to investigate the interplay between tumor growth and cardiac function in an in vivo system, immunocompetent female mice were inoculated with cancer cells and treated with the chemotherapeutic drug doxorubicin at a dosing schedule able to suppress tumor growth without inducing cardiac alterations. Analyses carried out in cardiomyocytes treated with the inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), interleukin 6 (IL-6), IL-8, and IL-1ß revealed severe phenotypic changes, for example, of contractile cytoskeletal elements, mitochondrial membrane potential, mitochondrial reactive oxygen species production and mitochondria network organization. Accordingly, in immunocompetent mice, the tumor growth was accompanied by increased levels of the inflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-8, either in serum or in the heart tissue, together with a significant reduction of ventricular systolic function. The alterations of mitochondria and of microfilament system of cardiomyocytes, due to the systemic inflammation associated with cancer growth, could be responsible for remote cardiac injury and impairment of systolic function observed in vivo.