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Background: A wide range of conditions, including mixed depressive symptoms, hyperactivity, cognitive impairment (CI) might be expressions of Bipolar Spectrum Disorder (BSD) according to the neo-Kraepelinian perspective, even in advanced age. CI, which has a high prevalence in the elderly population, when it occurs in comorbidity with depression further hinders therapy response and functional ability. The present study aims to explore risk factors associated with CI in elderly individuals experiencing a depressive episode during lockdown a period marked by significant stressors and rhythm disruption. Methods: A case-control study analyzed data from a previous RCT (secondary analyses) on elderly individuals living at home, assessing depressive symptoms, cognitive performance, hyperactivity, and hypertension before (T0) and during lockdown (T1). Results: Participants with lower pre-pandemic cognitive performance were more prone to lockdown depression compared to those with higher baseline function (F = 6.074; p = 0.016). Among those experiencing lockdown depression without prior depression, those with low cognitive performance were more prevalent than the control group without depression (OR = 11.8; p = 0.015). Conclusion: This study highlights a potentially vulnerable subgroup within the elderly population that requires targeted interventions and support during stressful events. Future research should explore the underlying mechanisms linking cognitive decline and depression in older adults, particularly those with a possible bipolar spectrum predisposition.

(1) Background: Herpes zoster (HZ) is a disease caused by the reactivation of the Varicella Zoster Virus (VZV). Clinical reactivation, herpes zoster, takes place in 10–20% of subjects who contracted the primary infection, with a higher risk of developing zoster increasing proportionally with age, especially after 50 years of age. HZ is a common clinical problem, particularly among patients aged over 50 years and immunocompromised patients. Immunocompromised patients and adults could present an atypical and more severe course. In addition, they are at greater risk of complications. For this reason, it is important to understand the real burden of the disease and to identify the subjects who are at higher risk of HZ and its complications, also to direct preventive strategies at the right targets. The aim of the present study is to analyze HZ-related hospitalization trends in Abruzzo in the period of 2015–2021. (2) Methods: Data related to hospital admissions were extracted from the hospital discharge records (HDRs) of the whole region, considering all admissions during the years of 2015–2021. The trends in hospital admissions and length of stay were evaluated and analyzed. (3) Results: A total of 768 hospital discharges with a diagnosis of herpes zoster were registered in Abruzzo during the 7-year study period. During the study period, an increasing trend was observed from the year 2015 to the year 2017, ranging from 8.19 cases/100,000 to 11.5 cases/100,000 (APC (Annual percentage change) +20.8%; 95%CI −2.3; 47.6). After the year 2017, a significantly decreasing trend was observed, reaching 5.46 cases/100,000 in the year 2021 (APC −18.4%; 95%CI −31.5; −12.0). Across the entire study period, an average annual percentage change (AAPC) of −7.0% (95%CI −13.0; −1.3) was observed. (4) Conclusions: Despite the trend of a reduction in hospitalizations, this study highlights that HZ continues to have a great impact on public health. So, it is important to update recommendations for the use of the already available HZ vaccine and to implement new strategies to increase awareness of the prevention of the disease.

(1) Background: Rotavirus is one of the leading causes of severe diarrhea and dehydration in infants and young children worldwide. The economic and social burden of rotavirus-related hospitalizations, particularly among children, remains a pressing concern for healthcare systems across the globe. Healthcare infrastructure and access to medical care can vary significantly within the region. Differences in the availability of healthcare facilities and the quality of care may influence the management and outcomes of rotavirus cases. (2) Methods: This was a retrospective study performed in the Abruzzo region, Italy. The study considered all hospitalization due to rotavirus gastroenteritis that occurred in the Abruzzo region from the year 2015 to 2021. Data were extracted from the hospital discharge records. The trend in hospital admissions, hospitalization costs and length of stay were evaluated and analyzed. (3) Results: A total of 664 admissions were reported during the study period. The incident rate grew till year 2019 with an annual percentage change of +13.9% (95%CI 12.6–15.2, p < 0.001). During the pandemic years, the incident rate showed a significant decrease with an annual percentage change of 12.5% (95%CI 15.5–9.3, p = 0.004). The length of stay of admissions was significantly higher among patients aged less than 1 year. (4) Conclusions: Rotavirus admission represents a heavy burden even in a high-income country such as Italy. These findings have the potential to inform targeted public health interventions, including vaccination strategies, and improve the overall well-being of children.

(1) Background: The human papillomavirus (HPV) is the most common agent related to sexually transmitted infections in the general population. Its genotypes are classified into two main classes, high-risk genotypes and low-risk genotypes, according to their capacity to induce cancers. The low-risk class (types 6 and 11) is associated with anogenital and genital lesions. The high-risk class is responsible for up to 4.5% of all new cancer cases yearly. The aim of this study was to evaluate the incidence of HPV-related hospitalizations and its trend in a southern Italian region for the years 2015–2021. (2) Methods: This was a retrospective study performed in the Abruzzo region, Italy. All admissions for the period 2015–2021 were extracted from the hospital discharge record (HDR). (3) Results: During the study period (2015–2021), a total of 5492 hospitalizations attributable to HPV infection occurred in the Abruzzo region, Italy. A significant number of admissions were related to cervical cancer (3386 cases) and genital warts (638 cases). The trend declined for all diagnoses except for penile cancer admissions. Considering the first year of the pandemic (year 2020), a decrease in the standardized incidence of the majority of the diseases considered was reported, particularly among cases of cervical cancer. (4) Conclusions: HPV-related hospitalizations decreased in Abruzzo during study period. These results could be useful to LHAs and policy-makers in improving vaccination coverage and screening adherence.

IntroductionItaly is one of the high-income countries hit hardest by Covid-19. During the first months of the pandemic, Italian healthcare workers were praised by media and the public for their efforts to face the emergency, although with limited knowledge and resources. However, healthcare workers soon had to face new challenges at a time when the national health system was working hard to recover. This study focuses on this difficult period to assess the impact of the COVID-19 pandemic on the mental health of Italian healthcare workers.Materials and MethodsHealthcare workers from all Italian regions [n = 5,502] completed an online questionnaire during the reopening phase after the first wave lockdown. We assessed a set of individual-level factors (e.g., stigma and violence against HCWs) and a set of workplace-level factors (e.g., trust in the workplace capacity to handle COVID-19) that were especially relevant in this context. The primary outcomes assessed were score ≥15 on the Patient Health Questionnaire-9 and score ≥4 on the General Health Questionnaire-12, indicators of clinically significant depressive symptoms and psychological distress, respectively. Logistic regression analyses were performed on depressive symptoms and psychological distress for each individual- and workplace-level factor adjusting for gender, age, and profession.ResultsClinically significant depressive symptoms were observed in 7.5% and psychological distress in 37.9% of HCWs. 30.5% of healthcare workers reported having felt stigmatized or discriminated, while 5.7% reported having experienced violence. Feeling stigmatized or discriminated and experiencing violence due to being a healthcare worker were strongly associated with clinically significant depressive symptoms [OR 2.98, 95%CI 2.36–3.77 and OR 4.72 95%CI 3.41–6.54] and psychological distress [OR 2.30, 95%CI 2.01–2.64 and OR 2.85 95%CI 2.16–3.75]. Numerous workplace-level factors, e.g., trust in the workplace capacity to handle COVID-19 [OR 2.43, 95%CI 1.92–3.07] and close contact with a co-worker who died of COVID-19 [OR 2.05, 95%CI 1.56–2.70] were also associated with clinically significant depressive symptoms. Similar results were found for psychological distress.ConclusionsOur study emphasizes the need to address discrimination and violence against healthcare professionals and improve healthcare work environments to strengthen the national health system's capacity to manage future emergencies.

Abstract Background Generalized anxiety disorder (GAD) is one of the most reported diagnoses in psychiatry, but there is some discrepancy between the cases identified in community studies and those identified in tertiary care. This study set out to evaluate whether the use of clinicians as interviewers may provide estimates in a community survey close to those observed in primary or specialized care. Methods This is a community survey on a randomly selected sample of 2338 adult subjects. The Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS) was administered by clinicians, providing lifetime diagnosis based on the DSM-IV-TR. Health-related quality of life (HR-QoL) was measured with the Short-Form Health Survey (SF-12). Results Overall, 55 (2.3%) subjects met the criteria for GAD, with greater prevalence in women (3.6%) than in men (0.9%): OR = 4.02; 95%CI: 1.96–8.26. Up to 40% of those with GAD had at least another diagnosis of mood, anxiety, or eating disorders. The mean score of SF-12 in people with GAD was 32.33 ± 6.8, with a higher attributable burden than in other conditions except for major depressive disorder. Conclusions We found a relatively lower lifetime prevalence of GAD than in community surveys based on lay interviewers and a structured interview. The identified cases of GAD showed a strong impact on the quality of life regardless of co-morbidity and high risk in women, suggesting a profile similar to the one identified from studies in primary and specialized care.

Abstract Objective This research note aimed to analyze the scientific productivity trends 2015–2019, focusing on the top 30 universities in Europe and United States and on the top 30 private companies—as classified in the SCImago Institutions Ranking. Our hypothesis is that private companies are gaining an increasingly prominent role in the research field, while academia is losing its predominance. Results From 2015 to 2019, all universities in Europe and the United States lost positions in the scientific production ranking, while private companies gained positions. These trends seem to be driven mainly by the scientific productivity sub-indicator “Innovation”. These data suggest that the role private companies will play in the future will not be limited to support research economically or influence it from “outside”. Private companies have taken a path that may lead them to directly control all stages of production/communication of knowledge, including research—a role once bestowed on universities. Our data, although preliminary, seem to suggest that, at present, academia risks losing its predominance in the research field. This scenario deserves attention because of the threats it may pose to the independence of research and its role in supporting human equity and sustainable health for all.

Background: The aim was to outline a methodology to monitor the impact of vaccinations in different countries comparing at two different times within countries and between countries the frequency of new cases and Covid-19 related deaths and the percentage of vaccinations conducted. Design and methods: The 25 countries with the largest increase in SARS-CoV-2 cases on 8 August 2021 were evaluated. In each nation was calculated the proportion of Covid-19 deaths divided per new cases x 100 and the proportion of new cases per 1.000 inhabitants on 10 January 2021 (before vaccinations’ distribution) and 8 August 2021 (when large percentage of the population had been vaccinated in many countries). Results: The study shows that in the countries with the highest number of cases as of 8 August 2021, the proportion of vaccinations carried out in the population correlates negatively with both the proportion between Covid-19 dead people x100 infected people and with the rate of new cases. However, the proportion of vaccinations does not correlate with the differences in the two same indicators considered in the weeks observed, thus additional factors seem to play an important role. Conclusions: This work indicates that mass vaccination is associated with a lower spread of the pandemic and, to greater extent, with a lowering of mortality in infected people.

Background: Functioning of Social Behavioral Rhythms (SBRs) may affect resilience toward stressful events across different age groups. However, the impact of SBRs on the coronavirus disease of 2019 (COVID-19) in elder people is yet to ascertain, representing the aim of the present report. Design and methods: Follow-up of a peer-reviewed randomized controlled trial on exercise on old adults (³65 years), concurrent to the onset of the pandemic-related lockdown. Post-RCT evaluations occurred after further 12 and 36 weeks since the beginning of the lockdown phase. People with Major Depressive Episode (MDE) at week-48 (follow-up endpoint) were deemed as cases, people without such condition were considered controls. MDE was ascertained using the Patient Health Questionnaire-9 (PHQ-9); SBRs functioning at week 12 onward, through the Brief Symptom Rating Scale (BSRS). Results: Seventy-nine individuals (53.2%, females) entered the RCT-follow-up phase. The frequency of MDE did not significantly change before versus during lockdown (OR 2.60, CI95%=0.87-9.13). People with BSRS>1 standard deviation of the whole sample score at week-12 had an inflated risk of DE during lockdown (OR=5.6, 95%CI: 1.5-21.4) compared to those with lower BSRS scores. Such odd hold after excluding individuals with MDD at week-12. The post-hoc analysis could be potentially affected by selection bias. Conclusions: Overall, older adults were resilient during the first phase of the pandemic when functioning of pre-lockdown was still preserved, in contrast to the subsequent evaluations when the impairment of daily rhythms was associated with impaired reliance.

Background: Changes in social and behavioral rhythms (SBR) in elderly are related to health status. Nevertheless, there is no data on factor analysis of the Brief Social Rhythm Scale (BSRS) an internationally well-known tool in this field. The aim was to analyze, in elderly, the factorial structure of the Italian version of BSRS. Design and Methods: Principal Component Analysis of the BSRS carried out in elderly living at home. Results: Sample of 141 participants (83 Females, 58,9%), aged 72.3±4.8. All the items of the questionnaire were related and could compose a single factor, explaining 56% of variance. A solution adopting two factors, the first (including items 1,2,3,4,9,10), the second (including items 5,6,7,8), covered cumulatively 78.8% of the variance. Conclusion: The study confirms that the BSRS is consistent with the idea for which it was built and can be useful for the study of regularity of SBR in old adults.

The study aimed to verify whether exercise training in older adults can improve social behavioral rhythms (SBR) and if any modification is maintained over time. Older adults (n=120) from a previous randomized controlled trial, were randomly allocated to either a moderate-intensity exercise group or a control group. SBR was evaluated at t0, t26, and t48 weeks (during the COVID-19 lockdown), using the brief social rhythms scale (BSRS). Seventy-nine participants completed the follow-up (age 72.3±4.7, women 55.3%). An improvement in the BSRS score was found in the exercise group at 26 weeks (p=0.035) when the exercise program was concluded, and it was maintained at 48 weeks (p=0.013). No improvements were observed in the control group. To conclude, SBR, previously found as a resilience factor in older adults during COVID-19, appear to improve after a moderate 12 weeks exercise program, and the improvement persisted even after stopping exercise during the COVID-19 lockdown.

Abstract Background Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib. We focused on Neuropilin 1 (NRP1), a transmembrane receptor expressed in OC and correlated with poor survival, which has been also proposed as a key molecule in OC multidrug resistance. Methods Using three OC cell lines (UWB, UWB-BRCA and SKOV3) as model systems, we evaluated the biological and molecular effects of Olaparib on OC cell growth, cell cycle, DNA damage and apoptosis/autophagy induction, through MTT and colony forming assays, flow cytometry, immunofluorescence and Western blot analyses. We evaluated NRP1 expression in OC specimens and cell lines by Western blot and qRT-PCR, and used RNA interference to selectively inhibit NRP1. To identify miR-200c as a regulator of NRP1, we used miRNA target prediction algorithms and Pearsons’ correlation analysis in biopsies from OC patients. Then, we used a stable transfection approach to overexpress miR-200c in Olaparib-resistant cells. Results We observed that NRP1 is expressed at high levels in resistant cells (SKOV3) and is upmodulated in partially sensitive cells (UWB-BRCA) upon prolonged Olaparib treatment, leading to poor drug response. Our results show that the selective inhibition of NRP1 is able to overcome Olaparib resistance in SKOV3 cells. Moreover, we demonstrated that miR-200c can target NRP1 in OC cells, causing its downmodulation, and that miR-200c overexpression is a valid approach to restore Olaparib sensitivity in OC resistant cells. Conclusions These data demonstrate that miR-200c significantly enhanced the anti-cancer efficacy of Olaparib in drug-resistant OC cells. Thus, the combination of Olaparib with miRNA-based therapy may represent a promising treatment for drug resistant OC, and our data may help in designing novel precision medicine trials for optimizing the clinical use of PARPi.

Background and Objectives: The improved life expectancy was associated to the increased in the incidence of hip fractures among elderly people. Subjects suffering hip fractures frequently show concomitant conditions causing prolonged lengths of stay and higher in-hospital mortality. The knowledge of factors associated to in-hospital mortality or adverse events can help healthcare providers improve patients’ outcomes and management. The aim of this study was to develop a score to predict in-hospital mortality among hip fractured patients. Materials and Methods: Cases were selected from hospital admissions that occurred during the period 2006–2015 in Abruzzo region, Italy. The study population was split into two random samples in order to evaluate the accuracy of prediction models. A multivariate logistic regression was performed in order to identify factors associated to in-hospital mortality. All diagnoses significantly associated to in-hospital mortality were included in the final model. Results: The PRIMOF ranged between 0 and 27 and was divided into four risk categories to allow the score interpretation. An increase in odds ratio values with the increase in PRIMOF score was reported in both study groups. Conclusions: This study showed that a simple score based on the patient’ clinical comorbidities was able to stratify the risk of hip-fractured patients in terms of in-hospital mortality.

Background: The aim was to verify whether the density of particulate matter (PM10), the climate, and the mobility of people can influence the pandemic in the 19 regions and in the two autonomous Italian provinces as incidence rate and lethality. Design and Methods: The incidence rates per 100,000 inhabitants and the case fatality ratio (CFR) (dependent variables) in all Italian regions were calculated in January 2021 at John Hopkins University Coronavirus Center. The independent variables were: -Minimum average temperatures in the same month (January) of 2020, -Average pollution of PM10 in the air in each region in the last year available reported on a 0-10 scale to 0 = total absence of PM10 to 10 maximum pollutions. -Number of places in hotels occupied per inhabitants in 2020. Linear regression and Multiple Regression Analysis were carried out. Results: The spread of the COVID-19 in the Italian regions seems to be related to pollution of PM10, the number of beds occupied in hotels (as an index of mobility and temperature (indirect correlation). On the contrary, the CFR correlates inversely with temperature but not with pollution. Measuring the concomitant effect of two independent variables by means of Multiple Regression Analysis, temperature and pollution show a synergistic effect on COVID-19 incidence. Conclusions: The study seems to confirm the literature on the influence of temperature on the lethality of COVID-19 but adds the new results of an inverse relationship between the spread of the virus and low temperature in regions between the Mediterranean area (which includes southern Italy and Sicily and Sardinia islands) and the cold European temperate zone which includes the northern regions under the Alps. A new date also concerns the summation effect of the risk between cold weather and PM10 air pollution was found. Due to several methodic weakness the study has an exploratory than conclusive relevance.

Several studies evaluated the presence of SARS-CoV-2 in the environment. Saliva and nasopharyngeal droplets can land on objects and surfaces, creating fomites.

Background: The impact of the comorbidity between Obsessive-Compulsive Disorder (OCD) and Bipolar Disorder Spectrum (BDS) remains to be clarified. The objective of this study was to examine the lifetime prevalence of OCD, the strength of the association of OCD with comorbid BDS and the role of comorbidity of OCD with BDS in the impairment of health-related quality of life (HRQoL) in an Italian community survey.Methods: The study is a community survey. The sample (N = 2,267; women: 55.3%) was randomly selected after stratification by sex and four age groups from the municipal records of the adult population of one urban, one suburban, and at least one rural area in six Italian regions. Physicians using a semi-structured interview (Advanced Tools and Neuropsychiatric Assessment Schedule, ANTAS-SCID) made Diagnostic and Statistical Manual of Mental Disorders – 4th revision (DSM-IV) diagnoses of OCD, Major Depressive Disorder (MDD) and Bipolar Disorder (BD). HR-QoL was measured by the Health Survey Short Form (SF-12). Lifetime Hypomania and subthreshold hypomania were screened by the Mood Disorder Questionnaire (MDQ). BDS was defined as the sum of people shown to be positive for hypomania by the MDQ—with or without a mood disorder diagnosis—plus people with a BD-DSMIV diagnosis even if negative for hypomania at the MDQ.Results: Overall, 44 subjects were diagnosed with OCD, 6 with MDD and 1 with BD. The lifetime prevalence of OCD was 1.8% in men (n = 18) and 2.0% in women (n = 26). MDD with lifetime subthreshold hypomania (i.e., people screened positive at the MDQ, even without diagnosed mania or hypomania at the interview) was associated with OCD (OR = 18.15, CI 95% 2.45–103.67); MDD without subthreshold hypomania (and screened negative at the MDQ) was not (OR = 2.33, CI 95% 0.69–7.01). People with BDS were strongly associated with OCD (OR = 10.5, CI 95% 4.90–12.16,). People with OCD and BDS showed significantly poorer HR-QoL than people with OCD without BDS (F = 9.492; P < 0.003).Discussion: The study found a strong association between BDS and OCD. BDS comorbid with OCD was associated with more severe impairment of HR-QoL than OCD without comorbid BDS. Identification of symptoms of hypomania, including subthreshold symptoms, may therefore be important in people with OCD as they might predict a course with poorer HR-QoL.

Abstract Background Primary caesarean section (PCS) rate is one of the main indicators of quality of care suggested by the Italian Government. Hospital rankings are usually based on it, therefore lower rates reflect more appropriate clinical practice. The aim of this study is to describe a five-year trend of PCS rate in Abruzzo region from 2009 to 2013 and to examine the medical indications for this mode of delivery. Methods Forty-five thousand one hundred forty-nine deliveries occurring from 2009 to 2013 were collected from all hospital discharge records (HDR) and analyzed. Among them we found 12,542 PCS. Odds ratios (ORs) with 95% confidence interval (95% CI) were estimated using logistic regression methods to evaluate the relationship between maternal risk factors and PCS in hospital over 1000 delivery/yrs. Results The five-year PCS rate was 28.9%, with a decreasing trend from 31.4% in 2009 to 26.1% in 2013. Vasto Civil Hospital shows the lowest PCS rate (17.9% in 2013) among hospitals with a maximum of 1000 deliveries per year, while Pescara Civil Hospital shows the lowest PCS rate (25.4% in 2013) among hospitals with over 1000 deliveries per year. Women with major risk factors for cesarean section delivered more frequently in maternity units over 1000 delivery/yrs. Logistic regression analyses showed as diabetes, hypertension, twin pregnancy, fetal distress and preterm delivery were significant risk factors to deliver in unit over 1000 delivery/yrs. The most frequent (overall 66.6%) discharge diagnosis recorded in Hospital discharge records (HDR) is “Caesarean Delivery Without Indication”. 7.3% of PCS made in Abruzzo concerns women living in other Italian regions. 11.4% of PCS contains one of the indications to caesarean section (CS) that the Italian Guidelines consider appropriate. Conclusions During the analyzed period, Abruzzo showed a decreasing, but still too high, PCS rate, compared to the limits fixed by the Italian Ministry of Health. Considering the limitation of this study, based on administrative data that are poor in clinical information, it is not possible to define the appropriateness of all caesarean sections.

Background: The assessment of pain and its impact on quality of life is central to the evaluation of chronic pain syndromes. However, most available tools focus on the nociceptive experience of pain, and at best only consider the occurrence of anxious, depressive, or cognitive problems. Here is a new questionnaire aimed at measuring the multifaceted impact of pain in chronic pain syndromes, the Bodily and Emotional pErception of Pain (BEEP).Methods: All consecutive patients who accessed a center for the treatment of pain were invited to take part in the study. The sample included 222 participants (51 with fibromyalgia, 84 with low back pain; 87 with other chronic pain syndromes). Women were 77% of the sample, the mean age was 61 ± 15. Participants completed the BEEP, the Patient Health Questionnaire-9 (PHQ-9), and the Mood Disorder Questionnaire (MDQ).Results: Reliability was good for all questionnaires. The expected three dimensions of the BEEP were confirmed by confirmatory factor analysis, and a bifactor model with three orthogonal factors showed a good fit as well. Participants diagnosed with fibromyalgia showed higher scores on the BEEP than the participants who had been diagnosed with low back pain or other chronic pain syndromes. The prevalence of probable cases of major depression and bipolar disorder in the sample was higher than expected for non-clinical samples. Levels of depression, as measured by the PHQ-9, were associated with the three dimensions of the BEEP and with the intensity of pain.Conclusions: The BEEP is a promising measure of the impact of pain in daily life and differentiates fibromyalgia from other chronic pain syndromes. The BEEP may be helpful to evaluate the patient's response to the treatment over time and may favor the identification of unmet needs in patients' personal, social, and daily functioning.

Background: In Italy, the loss of confidence towards vaccination resulted in low vaccine coverage, also among healthcare workers (HCWs). Indeed, low vaccination coverage among HCWs can lead to dangerous outbreaks of disease, reduce productivity, and increase absenteeism. The aim of this study was to investigate the vaccine coverage and attitudes toward vaccination among HCWs. Methods: A multicenter cross-sectional study was conducted among HCWs referred to all hospitals of the Local Health Authority 02 of Abruzzo Region, Italy. The survey was based on the questionnaire proposed by the H-ProImmune Project. Results: A total of 347 HCWs were enrolled in the study. Of these, 57.3% reported missing diphtheritis-tetanus-pertussis (DTP) vaccination, 50.1% reported missing measles-mumps-rubella (MMR) vaccination, and 62.5% reported missing flu vaccination. Regarding attitudes, other healthcare professionals reported to believe more in natural immunization compared to vaccination (26.5%; p < 0.001), and they were worried about long-term effects of vaccination (10.2%; p = 0.044). Conclusions: This survey showed all vaccination coverage considered resulted below the 95% threshold. Training on vaccination and mandatory measures may be needed in order to achieve better coverage.

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a rare disease characterized by congenital aplasia of uterus and vagina. Although many studies have investigated several candidate genes, up to now none of them seem to be responsible for the aetiology of the syndrome. In our study, we identified differences in gene expression profile of in vitro cultured vaginal tissue of MRHKS patients using whole-genome microarray analysis. A group of eight out of sixteen MRKHS patients that underwent reconstruction of neovagina with an autologous in vitro cultured vaginal tissue were subjected to microarray analysis and compared with five healthy controls. Results obtained by array were confirmed by qRT-PCR and further extended to other eight MRKHS patients. Gene profiling of MRKHS patients delineated 275 differentially expressed genes, of which 133 downregulated and 142 upregulated. We selected six deregulated genes (MUC1, HOXC8, HOXB2, HOXB5, JAG1 and DLL1) on the basis of their fold change, their differential expression in most patients and their relevant role in embryological development. All patients showed upregulation of MUC1, while HOXB2 and HOXB5 were downregulated, as well as Notch ligands JAG1 and DLL1 in the majority of them. Interestingly, HOXC8 was significantly upregulated in 47% of patients, with a differential expression only in MRKHS type I patients. Taken together, our results highlighted the dysregulation of developmental genes, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract and providing a useful clue for understanding the pathophysiology of MRKHS.

The present study was designed to evaluate the clinical outcome of cell-based therapy with cultured adipose-derived stromal cells (ASCs) for the treatment of cutaneous manifestations in patients affected by systemic sclerosis (SSc). ASCs have an extraordinary developmental plasticity, including the ability to undergo multilineage differentiation and self-renewal. Moreover, ASCs can be easily harvested from small volumes of liposuction aspirate, showing great in vitro viability and proliferation rate. Here we isolated, characterized, and expanded ASCs, assessing both their mesenchymal origin and their capability to differentiate towards the adipogenic, osteogenic, and chondrogenic lineage. We developed an effective method for ASCs transplantation into sclerodermic patients by means of a hyaluronic acid (HA) solution, which allowed us to achieve precise structural modifications. ASCs were isolated from subcutaneous adipose tissue of six sclerodermic patients and cultured in a chemical-defined medium before autologous transplantation to restore skin sequelae. The results indicated that transplantation of a combination of ASCs in HA solution determined a significant improvement in tightening of the skin without complications such as anechoic areas, fat necrosis, or infections, thus suggesting that ASCs are a potentially valuable source of cells for skin therapy in rare diseases such as SSc and generally in skin disorders.

Interactions between epithelium and mesenchyme during wound healing are not fully understood, but Fibroblast Growth Factors (FGFs) and their receptors FGFRs are recognized as key elements. FGFR2 gene encodes for two splicing transcript variants, FGFR2-IIIb or Keratinocyte Growth Factor Receptor (KGFR) and FGFR2-IIIc, which differ for tissue localization and ligand specificity. Proinflammatory cytokines play an essential role in the regulation of epithelial-mesenchymal interactions, and have been indicated to stimulate FGFs production. Here we demonstrated that upregulation of FGFR2 mRNA and protein expression is induced by the proinflammatory cytokines Tumor Necrosis Factor-α, Interleukin-1β and Interleukin 2. Furthermore, we found that TNFα determines FGFR2 transcriptional induction through activation of pRb, mediated by Raf and/or p38 pathways, and subsequent release of the transcription factor E2F1. Experiments based on FGFR2 promoter serial deletions and site-directed mutagenesis allowed us to identify a minimal responsive element that retains the capacity to be activated by E2F1. Computational analysis indicated that this element is a non-canonical E2F responsive motif. Thus far, the molecular mechanisms of FGFR2 upregulation during wound healing or in pathological events are not known. Our data suggest that FGFR2 expression can be modulated by local recruitment of inflammatory cytokines. Furthermore, since alterations in FGFR2 expression have been linked to the pathogenesis of certain human cancers, these findings could also provide elements for diagnosis and potential targets for novel therapeutic approaches.

Keratinocyte growth factor receptor (KGFR) is a splice variant of the FGFR2 gene expressed in epithelial cells. Activation of KGFR is a key factor in the regulation of physiological processes in epithelial cells such as proliferation, differentiation and wound healing. Alterations of KGFR signaling have been linked to the pathogenesis of different epithelial tumors. It has been also hypothesized that its specific ligand, KGF, might contribute to the development of resistance to 5-fluorouracil (5-FU) in epithelial cancers and tamoxifen in estrogen-positive breast cancers.Small interfering RNA was transfected into a human keratinocyte cell line (HaCaT), a breast cancer derived cell line (MCF-7) and a keratinocyte primary culture (KCs) to induce selective downregulation of KGFR expression. A strong and highly specific reduction of KGFR expression was observed at both RNA (reduction = 75.7%, P = 0.009) and protein level. KGFR silenced cells showed a reduced responsiveness to KGF treatment as assessed by measuring proliferation rate (14.2% versus 39.0% of the control cells, P

Objective: To determine whether people with a Sardinian genetic background who live in the megacities of South America have a higher frequency of hypomania than residents of Sardinia. Methods: A community survey of Sardinian immigrants was carried out in four Brazilian metropoles (n=218) and Buenos Aires (n=306). The results were compared with those of a study involving a similar methodology (Mood Disorder Questionnaire [MDQ] as a screening tool) conducted in seven Italian regions, including a sub-sample from Sardinia. Results: There was a higher prevalence of lifetime hypomania among Sardinians living in the Brazilian metropoles than among those living in Sardinia. This result was also consistent with Sardinian immigrants in Buenos Aires. After stratification by sex and age, the lifetime prevalence of MDQ scores ≥ 8 among Sardinians in South-American megacities and Sardinia was 8.6% vs. 2.9%, respectively (p < 0.0001). Conclusions: The higher frequency of hypomania in migrant populations appears to favor an evolutionary view in which mood disorders may be a maladaptive aspect of a genetic background with adaptive characteristics.