Role of the Skin Immune System in Wound Healing.

Wound healing is a dynamic and complex process, characterized by the coordinated activities of multiple cell types, each with distinct roles in the stages of hemostasis, inflammation, proliferation, and remodeling. The cells of the immune system not only act as sentinels to monitor the skin and promote homeostasis, but they also play an important role in the process of skin wound repair. Skin-resident and recruited immune cells release cytokines and growth factors that promote the amplification of the inflammatory process. They also work with non-immune cells to remove invading pathogens and debris, as well as guide the regeneration of damaged host tissues. Dysregulation of the immune system at any stage of the process may lead to a prolongation of the inflammatory phase and the development of a pathological condition, such as a chronic wound. The present review aims to summarize the roles of different immune cells, with special emphasis on the different stages of the wound healing process.

Impact of the COVID-19 pandemic on Italian students' mental health and relationships: differences between adolescent males and females.

BACKGROUND: The negative effects of the COVID-19 pandemic on the mental health of young people have been reported, often with possible differences between the sexes. This study explores the impact of the COVID-19 pandemic on the differences in mental health status and healthy behaviors between adolescent males and females. METHODS: An online questionnaire exploring sociodemographic characteristics, living conditions, mental health, behaviors, and relationships during the implementation of the COVID-19 social restriction measures, was administered to 16-18 years old high school students living in the metropolitan area of Turin. The World Health Organization-5 Well-Being Index (WHO-5) questionnaire was used to evaluate self-perceived psychological health status. Descriptive analyses of the sample were carried out by sex. Chi-squared test and the associated P value were evaluated. The spatial sign method was used to assess multivariate differences by sex. RESULTS: Seventy-two Italian high school students completed the questionnaire. Sixty-eight percent of the students reported psychological problems, more often females (86% vs. 50%). Those living with multiple cohabitants and in dwellings with less personal space reported lower well-being. Females were also more likely to report stress when talking about COVID-19, difficulties in concentration and in falling asleep, daytime sleepiness, less physical activity, and concerns about losing control of eating. Finally, females spent more time with family members and, compared to males, found it harder to spend time and share experiences with friends and schoolmates. CONCLUSIONS: The pandemic has greatly impacted adolescents in terms of their mental well-being, routines, relationships with friends, and sleeping and eating patterns. Females reported more stress, boredom, bad mood, eating concerns, reduced relationships with friends, and possible difficulty in falling asleep than did males. These issues should be addressed when developing and promoting support programs, particularly at school.

Functional TRPA1 Channels Regulate CD56dimCD16+ NK Cell Cytotoxicity against Tumor Cells.

Transient receptor potential ankyrin 1 (TRPA1) channels are expressed on the surface of different cell types, including immune cells. However, TRPA1's role in the context of innate and adaptive immune responses has not been fully elucidated so far. In this study, we aimed at investigating the expression and function of TRPA1 channels on NK cells. Among NK cells, TRPA1 was highly expressed by the CD56dimCD16+ subpopulation, but not by CD56brightCD16- cells, as detected by FACS. TRPA1 activation with the potent ligand allyl isothiocyanate (AITC) induces intracellular calcium flux in CD56dimCD16+ cells, which was prevented by the TRPA1 antagonist HC-030031. AITC treatment increased the membrane around NKp44 and strongly decreased CD16 and CD8 expression, while CD158a, CD159a, NKG2d, NKp46 were substantially unaffected. Importantly, AITC increased the granzyme production and CD107 expression and increased NK cell-mediated cytotoxicity towards the K562 cell line and two different melanoma cell lines. In parallel, TRPA1 activation also plays regulatory roles by affecting the survival of NK cells to limit uncontrolled and prolonged NK cell-mediated cytotoxicity. Our results indicate that the activation of TRPA1 is an important regulatory signal for NK cells, and agonists of TRPA1 could be used to strengthen the tumor response of the immune system.

Newly arrived migrants did not represent an additional COVID-19 burden for Italy: data from the italian information flow.

BACKGROUND: During the COVID-19 pandemic, migrants arriving in host countries irregularly have not infrequently been perceived as increasing the COVID-19 burden. Italy is a transit and destination country for migrants who cross the Central Mediterranean route and, during the pandemic, all migrants who landed on Italian shores were COVID-19 tested and quarantined. Our study aimed to investigate the impact of the SARS-CoV-2 infection among migrants who landed on the Italian coasts by analyzing both incidence and health outcomes. METHODS: A retrospective observational study has been designed. The population of interest was represented by 70,512 migrants (91% male, 99% <60 years old) who landed in Italy between January 2021 and 2022. SARS-CoV-2 incidence rate per 1,000 (with 95%CI) in migrants and the resident population in Italy of the corresponding age group was computed. The incidence rate ratio (IRR) was used to compare the incidence rates in migrants and the resident population. RESULTS: 2,861 migrants out of those landed in Italy during the observation period tested positive, with an incidence rate of 40.6 (39.1-42.1) cases per 1,000. During the same period, 177.6 (177.5-177.8) cases per 1,000 were reported in the resident population, with an IRR of 0.23 (0.22-0.24). 89.7% of cases were male and 54.6% belonged to the 20-29 age group. 99% of cases reported no symptoms, no relevant comorbidities were reported and no cases were hospitalized. CONCLUSIONS: Our study found a low rate of SARS-CoV-2 infection in migrants reaching Italy by sea with an incidence rate that is roughly a quarter of that of the resident population. Thus, irregular migrants who arrived in Italy during the observation period did not increase the COVID-19 burden. Further studies are needed to investigate possible reasons for the low incidence observed in this population.

Two years of COVID-19. Impacts on accessibility of a mental health service for immigrants and individuals in socio-economic difficulties.

OBJECTIVES: Mental health services utilization decreased dramatically during the COVID-19 pandemic. For persons who are highly vulnerable and at risk of health and social care exclusion, restrictions negatively affected the accessibility to treatments and their mental conditions. METHODS: All psychiatric and psychological interviews carried out at National Institute for Health, Migration and Poverty (INMP) Italy from January 2018 to February 2022 were included in the study. To measure services use, an interrupted time-series analysis using March 2020 as the starting data of COVID-19 pandemic period was considered, and first visits vs follow-up session numbered. RESULTS: A significant decrease was observed in March 2020 due to the lockdown restrictive measures (p<0.001). Later on, the number of psychological interventions significantly increased (p<0.05), whereas the increment of the psychiatric interventions was not significant. By the end of February 2022 the number of visits returned to pre-COVID-19 levels, although recovery was slower than expected, especially for psychiatric visits. CONCLUSIONS: After a dramatic drop during the lockdown, access to mental health out-patient clinics slowly returned to pre-pandemic levels in the next two years. Considering that mental health needs have increased during the pandemic, mental health services should improve their efforts to reduce barriers of access and to implement outreach referral.

Platelet Derivatives and the Immunomodulation of Wound Healing.

Besides their primary role in hemostasis, platelets contain a plethora of immunomodulatory molecules that profoundly affect the entire process of wound repair. Therefore, platelet derivatives, such as platelet-rich plasma or platelet lysate, have been widely employed with promising results in the treatment of chronic wounds. Platelet derivatives provide growth factors, cytokines, and chemokines targeting resident and immigrated cells belonging to the innate and adaptive immune system. The recruitment and activation of neutrophils and macrophages is critical for pathogen clearance in the early phase of wound repair. The inflammatory response begins with the release of cytokines, such as TGF-ß, aimed at damping excessive inflammation and promoting the regenerative phase of wound healing. Dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wound. In this review, we summarize the role of the different immune cells involved in wound healing, particularly emphasizing the function of platelet and platelet derivatives in orchestrating the immunological response.

Anthropological Research Study of Migrants at the First Aid and Reception Center (CPSA) of Lampedusa.

A medical anthropology research study was conducted in 2015 at the First Aid and Reception Center (CPSA) on the island of Lampedusa (Italy) as part of a larger health project carried out by the National Institute for Health, Migration and Poverty (INMP) in Rome. The study investigated the health conditions of migrants at the moment of their departure and on arrival, their migration journey, and their life plans and expectations for the future. The ethnographic method adopted for the study was based on participant observation and on data collection by means of a semi-structured interview (51 items simultaneously translated by cultural mediators into Tigrinya, Arabic, English, and French). Interviewed were 112 adults (82 men and 30 women) from the Gulf of Guinea and the Horn of Africa. The cooccurrence of forced migration and economic concerns was confirmed; violence and torture were constants throughout the migration journey in 81% of cases. Ethnographic data detailed the timing, countries, settings, perpetrators, and types of violence endured. A combination of qualitative and quantitative findings can both facilitate the identification of fragile health conditions and support clinicians in the diagnostic, therapeutic, and rehabilitation pathways. These data illustrate the importance and feasibility of multidisciplinary collaboration even in emergency contexts.

The phosphoinositide-3-kinase (PI3K)-delta inhibitor seletalisib impairs monocyte-derived dendritic cells maturation, APC function, and promotes their migration to CCR7 and CXCR4 ligands.

PI3K pathway plays a crucial role in dendritic cells (DCs) functions, as it regulates different cellular processes, such as maturation and cytokines production. However, the specific role of PI3K p110δ isoform in human DCs has not been thoroughly addressed. In this study, we analyze the effects of seletalisib, a potent and specific inhibitor of PI3K p110δ, on phenotype and antigen-presenting functions of monocyte-derived DCs undergone maturation via LPS. Seletalisib treatment reduced membrane HLA-DR as well as CD83 and CD40 costimulatory molecules, whereas CD80 and CD86 expression was only partially affected. Additionally, DCs cultures showed reduced TNF-α, IL-10, and IL-12 and increased IL-23 secretion levels. This resulted in a reduced capacity of DCs to prime allogeneic T cells, with a strong decrease of Th1 differentiation. On the other hand, PI3K p110δ inhibitor seletalisib increased CXCR4 and CCR7 expression and augmented the DCs migration toward CCL19 and CXCL12 ligands. At molecular level, inhibition of PI3K p110δ isoform by seletalisib significantly down-regulated the phosphorylation of AKT and other downstream signaling molecules, such as ribosomal protein S6, 4E-BP1, and NF-κB p65. In contrast, seletalisib did not affect p38 MAP kinase phosphorylation or TLR-associated adapter molecule TIRAP in DCs. Our results indicate that PI3K p110δ can serve as an important regulatory signal for DCs, and selective inhibition of PI3K p110δ isoform by seletalisib could be used for the prevention of exaggerated and harmful immune responses occurring in pathologic conditions, such as autoimmune disorders.

Psychopathological effects of the Coronavirus (Sars-CoV-2) imposed lockdown on vulnerable patients in treatment in a mental health outpatient department for migrants and individuals in poor socioeconomic conditions.

BACKGROUND: The effects of Sars-Cov-2 pandemic may increase vulnerability of migrants. AIMS: To investigate the effects of the governmental lockdown on the mental health of vulnerable migrants in treatment at an outpatient department. METHOD: In a telephone survey post-migration living difficulties and psychopathological symptoms were investigated, particularly post-traumatic thoughts and nightmares, anxiety, depression, feelings of tension and irritability, other sleep problems, as well as COVID-19 related fears. Psychopathological changes during the lockdown were detected and rated by clinicians. Rates of treatment discontinuation and reasons why were also recorded. RESULTS: Of 103 eligible patients, 81 answered the phone call and were included in the study. Mental symptoms were frequent but not as severe as expected. About 32% of patients in psychopharmacological treatment and almost 52% of patients in psychotherapy had discontinued treatment. Patients who were globally considered to have worsened if compared to their pre-coronavirus mental health conditions had in fact higher scores on several mental symptoms but mild specific fears about coronavirus issues, similar to those of patients improved or stable. Worsening was significantly associated with unemployment, lack of VISA, and treatment discontinuation. Shifting the way of providing psychotherapy into a web-based modality was significantly more frequent in stable/improved patients. CONCLUSION: Findings suggest that concrete life problems and treatment discontinuation more than the coronavirus fear, have predominantly affected the mental health conditions of our patients.

Reduced Interleukin-17-Expressing Cells in Cutaneous Melanoma.

Characterization of tumor associated lymphocytes (TILs) in tumor lesions is important to obtain a clear definition of their prognostic value and address novel therapeutic opportunities. In this work, we examined the presence of T helper (Th)17 lymphocytes in cutaneous melanoma. We performed an immunohistochemical analysis of a small cohort of primary melanomas, retrospectively selected. Thereafter, we isolated TILs from seven freshly surgically removed melanomas and from three basal cell carcinomas (BCC), as a comparison with a non-melanoma skin cancer known to retain a high amount of Th17 cells. In both studies, we found that, differently from BCC, melanoma samples showed a lower percentage of Th17 lymphocytes. Additionally, TIL clones could not be induced to differentiate towards the Th17 phenotype in vitro. The presence or absence of Th17 cells did not correlate with any patient characteristics. We only observed a lower amount of Th17 cells in samples from woman donors. We found a tendency towards an association between expression by melanoma cells of placenta growth factor, angiogenic factors able to induce Th17 differentiation, and presence of Th17 lymphocytes. Taken together, our data indicate the necessity of a deeper analysis of Th17 lymphocytes in cutaneous melanoma before correlating them with prognosis or proposing Th17-cell based therapeutic approaches.

Noninvasive Evaluation of Liver Fibrosis in a Sample of Putative Inactive HBV Carriers in Rome, Italy.

BACKGROUND: Noninvasive methods are useful for investigating patients with chronic HBV infection. The severity of liver disease in inactive HBsAg carriers can be noninvasively assessed by transient elastography (TE) alone or in association with biochemical markers of fibrosis. OBJECTIVES: The study evaluates the effectiveness of the TE compared to common fibrosis scores (FSs), APRI, Forns Index, and FIB4, for identifying significant fibrosis in Italian and foreigner HBsAg carriers. To investigate the risk of progression of the liver disease, liver stiffness (LS) and HBV-DNA were monitored over time. METHODS: Viral load, biochemical parameters, and LS have been retrospectively evaluated in 125 putative inactive HBV carriers, who visited two outpatient departments (Colleferro Hospital and INMP) from 01/03/2014 to 31/12/2019. Differences in clinical, biochemical, and demographic variables between Italians and foreigners were analyzed. 66 of 125 patients were followed up for 24 months by monitoring liver stiffness and HBV-DNA. RESULTS: Mean overall LS was 5.55 ± 1.92 kPa; 18 (14.4%) patients had a LS ≥7.5 kPa. Mean of APRI, Forns, and FIB4 was 0.29 ± 0.11, 4.15 ± 1.63, and 1.16 ± 0.59, respectively. FS did not differ between the patients with LS <7.5 kPa and those with LS ≥7.5 kPa. Italians displayed a significant lower ALT (0.53 ± 0.18 vs. 0.67 ± 0.33, p < 0.05) and AST (0.59 ± 0.16 vs. 0.70 ± 0.21, p < 0.01) value than foreigners. No differences in LS and HBV-DNA levels were observed. In 66 patients followed up for 24 months, HBV-DNA increased by ≥2000 UI/ml after 12 months in 15 individuals and remained ≥2000 UI/ml after 24 months in 10/15 individuals. 7/10 patients showed LS ≥ 7.5 kPa after 24 months, and 4 of them underwent antiviral therapy for HBV. Patients with HBV-DNA <2000 IU/ml had a significantly lower LS than those with HBV-DNA ≥2000 IU/ml (5.30 ± 1.43 vs. 7.69 ± 1.07, p < 0.0001). CONCLUSIONS: Analysis shows lower effectiveness of FS vs. TE in the assessment of putative inactive HBV carriers. Furthermore, using FibroScan® and HBV-DNA can identify "false" inactive carriers.

Keratinocytes Regulate the Threshold of Inflammation by Inhibiting T Cell Effector Functions.

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production.

Outcomes of Culturally Tailored Dietary Intervention in the North African and Bangladeshi Diabetic Patients in Italy.

Immigrants show higher adjusted diabetes prevalence than Italians, especially among South-East Asians followed by North and Sub-Saharan Africans. Diabetes progression is influenced by food behaviors, and diet control is a critical aspect in disease management. Food habits have many cultural and symbolic implications. Guidelines recommend that every patient should receive appropriate self-management education according to cultural and socioeconomic characteristics. This study aims to test whether a customized diet and transcultural mediator's support can improve immigrants' food habits. A pre-post quali-quantitative study was conducted among 20-79-year-old Bangladeshi and North African diabetic immigrants. The INMP transcultural mediator, an expert in the social and health care field, actively participates in clinical activity by decoding linguistic and cultural needs expressed by the foreigner patient. Five culturally tailored dietary profiles were designed according to international diabetes guidelines and adjusted to traditional food habits. Data were collected with two different semi-structured questionnaires. Changes in food consumption were assessed through McNemar's test, while paired Wilcoxon Signed-Rank test was used to analyze pre and post intervention. Fifty-five patients were enrolled. At follow-up, cereals, meat, and potatoes intake significantly improved, and the number of adequate dietary habits for each patient increased significantly. Transcultural mediator support was 90% positively evaluated. Adherence to dietary control is favorably influenced by a transcultural intervention, which is based on clinical and socio-cultural criteria, in compliance with patient's lifestyles.

Anthropological study on Chagas Disease: Sociocultural construction of illness and embodiment of health barriers in Bolivian migrants in Rome, Italy.

INTRODUCTION: Chagas Disease (CD) is endemic in many Latin-American countries, Bolivia in particular. It is now spreading in Italy as a host country for transcontinental migrants and becoming an emerging health problem. This anthropological action-research, as part of a wider medical project on Neglected Tropical Diseases, has the purpose of analyzing the sociocultural construction of CD and its representation in Bolivian people living in Rome as well as barriers, such as the stigma about the illness, to access the National Health Service for those potentially affected. METHODS: The ethnographic study was carried out from 2016 to 2018 by a medical anthropologist at the National Institute for Health, Migration and Poverty (INMP) on 72 Bolivian migrants (47 women and 25 men) living in Rome. The study was carried out through: a territorial mapping of Bolivian networks and communities aimed at recruiting people, participant observation, and application of semi-structured and unstructured interviews. The interviews were hold in Spanish and proposed to all participants before or during medical examination, or during events organized by the Bolivian community in Rome. The interview consisted of 16 items and covered four macro areas: personal and migration history, health status, access to the Italian National Health Service and knowledge about CD; plus 5 items for those who received a diagnosis of Chagas Disease in Italy. RESULTS: The sociocultural construction and the deep stigma about the illness built by participants and their families could hinder both diagnosis and treatment. Institutional barriers also contributed to reduce adherence to screening tests: often, opening hours of the outpatient clinic were incompatible with participants' precarious employments. To guarantee participant's access to public health services and their adherence to the diagnostic protocol, we implemented a profound revision of our cultural and institutional approach to them. CONCLUSIONS: The analysis evidenced the limitations of the conventional approach applied by the Italian National Health Service to this migrant community, such as the absence of socio-cultural and linguistics competences that can help understanding patients' perception and representation of the illness. The multidisciplinary approach instead-with clinicians using the ethnographic results to adjust their work to the participants' needs-was a successful attempt to ensure therapeutic alliance.

Prevalence of latent tuberculosis infection, hepatitis B, hepatitis C, and syphilis among newly arrived unaccompanied minors living in reception centers in Rome.

OBJECTIVE: This study aimed to address the prevalence of infectious diseases in a population of unaccompanied immigrant minors living in reception centres of Rome, Italy. METHODS: The study was carried out from January 2013 to January 2019. All unaccompanied immigrant minors were screened for hepatitis B, hepatitis C, syphilis and latent tuberculosis infection. RESULTS: A total of 879 unaccompanied immigrant minors, 858 males and 21 females, aged 13-18 years old were studied. Of these, 615 were from Africa, 179 from Asia and 84 from Eastern Europe. A low prevalence of HBsAg carriage (2.5%) was observed as was very low prevalence of hepatitis C (0.72%) and latent syphilis (0.4%); latent tuberculosis, defined as tuberculin skin test (TST)+ X-ray case, was diagnosed in 102 (12%) minors. CONCLUSIONS: Similar to previous studies, these data demonstrate that migrant minors are generally healthy. However, given the relatively high prevalence of hepatitis B and latent tuberculosis, systematic screening for these diseases among immigrant minors immigrants is highly recommended for early detection and treatment of potentially transmissible diseases.

Interleukin (IL)-17/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses.

In inflammatory skin conditions, such as psoriasis, vascular enlargement is associated with endothelial cell proliferation, release of cytokines and adhesion molecule expression. Interleukin (IL)-17A is a pro-inflammatory cytokine mainly secreted by T helper-17 cells that is critically involved in psoriasis pathogenesis. IL-36α, IL-36ß and IL-36γ are also inflammatory cytokines up-regulated in psoriasis and induced by various stimuli, including IL-17A. In this study, we found that human keratinocytes are the main source of IL-36, in particular of IL-36γ. This cytokine was strongly induced by IL-17A and, together with IL-17A, efficiently activated human dermal microvascular endothelial cells (HDMECs), which expressed both IL-17 and IL-36 receptors. Both IL-36γ and IL-17A induced cell proliferation through specific molecular cascades involving ERK1/2 only or ERK1/2, STAT3 and NF-κB, respectively. We highlighted the intense IL-17A- and IL-36γ -dependent interplay between keratinocytes and HDMECs, likely active in the psoriatic lesions and leading to the establishment of a cytokine network responsible for the development and maintenance of the inflamed state. IL-17A or IL-36γ showed in HDMECs a synergic activity with TNF-α by potently inducing inflammatory cytokine/chemokine release and ICAM-1 expression. We also investigated the involvement of IL-36γ and VEGF-A, substantially reduced in lesional skin of psoriatic patients pharmacologically treated with the anti-IL-17A antibody Secukinumab. Importantly, keratinocyte-derived IL-36γ represented an additional pro-angiogenic mediator of IL-17A. We observed that keratinocyte-derived VEGF-A influenced proliferation but did not act on expression of adhesion molecules in HDMECs. On the other hand, inhibition of IL-36γ released by IL-17A-treated keratinocytes impaired either proliferation or ICAM-1 expression both in HDMECs and in an in vivo murine model of psoriasis. Taken together, our data demonstrated that IL-17A and IL-36γ are highly involved in endothelial cells/keratinocytes crosstalk in inflammatory skin conditions.

Platelet lysate promotes the expansion of T regulatory cells that favours in vitro wound healing by increasing keratinocyte migration and fibroblast production of extracellular matrix components.

BACKGROUND: Platelet lysate (PL) contains a cocktail of growth factors and cytokines that promote tissue repair and regeneration. In vitro studies have shown that PL may affect the reparative function of keratinocytes and fibroblasts, but little is known about the effect of PL on immune cells involved in wound healing. OBJECTIVES: To analyse the effects of PL on T cells involved in the wound repair process. MATERIALS AND METHODS: The effect of PL on T cell proliferation, activation, and cytokine production was measured by ELISA and cytofluorometry and regulatory function based on cytofluorometry and Foxp3 RNA expression. Using an in vitro model of wound healing, we investigated the effect of PL-treated T cells on fibroblast proliferation and production of fibronectin and type-1 collagen as well as keratinocyte migration. RESULTS: PL induced T lymphocyte proliferation and CD69 expression, and promoted a transient upregulation of IFN-γ and TNF-α. However, later on, PL enhanced the number of CD25+ T cells releasing TGF-ß and expressing Foxp3 RNA, which was accompanied by a suppression in the level of type 1 cytokines. In the in vitro model, supernatants of PL-treated T cells positively affected the reparative capacity of human keratinocytes and induced fibroblast proliferation and production of fibronectin and type-1 collagen. CONCLUSION: These results indicate that PL temporally regulates T cells during the healing process, enhancing protective cytokines in the early phase, followed by a prominent expansion of TGF-ß+ T regulatory cells that promote tissue regeneration and dampen the inflammatory response to prevent excessive tissue damage.

Sociodemographic Characteristics Associated with Harmful Use of Alcohol Among Economically and Socially Disadvantaged Immigrant Patients in Italy.

In many contexts, individuals with lower socioeconomic status, especially immigrants, have a higher burden of negative alcohol-related consequences and a higher probability of receiving a psychiatric diagnosis. This study aimed at exploring sociodemographic and clinical characteristics associated with harmful use of alcohol (HUA) among immigrant patients. A cross-sectional study was conducted in Rome (Italy) on a sample of 330 immigrant patients admitted to the gastroenterology outpatient clinic of the INMP (March 2013-October 2014). HUA was evaluated through the Alcohol Use Disorders Identification Test (AUDIT) questionnaire. The presence of psychiatric disorders was diagnosed through SCID I-II interviews. The association between sociodemographic characteristics and psychiatric disorders and HUA was evaluated through a multivariate log-binomial regression model. HUA was associated with unemployment, longer stay in Italy, mood disorder and not being married, especially among African immigrants. We provide original findings about a selected, hard-to-investigate population, suggesting priorities in interventions on HUA among specific vulnerable subgroups.

Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development.

Immunomodulation with anti-TNF-α is highly effective in the treatment of various immune-mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti-TNF-α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as pDC, neutrophils, mast cells, macrophages, and monocytes. In addition, IFN-ß and IFN-α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)-α and LT-ß were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN-γ and TNF-α-releasing T lymphocytes. On the contrary, IL-22 immunoreactivity was significantly augmented together with the IL-36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA-C genomic region were found.