Differences in the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals using routine data.

OBJECTIVES: This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals. STUDY DESIGN: We retrospectively analysed data from the COVID-19 Italian integrated surveillance system (14 September 2020 to 17 October 2021). METHODS: We used multivariable Cox proportional hazards models to estimate the hazard ratio (HR) of infection and, among cases, the HRs of death, hospitalisation and subsequent admission to intensive care unit in non-Italian nationals relative to Italian nationals. Estimates were adjusted for differences in sociodemographic characteristics and in the week and region of diagnosis. RESULTS: Of 4,111,067 notified cases, 336,265 (8.2%) were non-Italian nationals. Compared with Italian nationals, non-Italians showed a lower incidence of SARS-CoV-2 infection (HR = 0.81, 95% confidence interval [CI]: 0.80-0.81). However, once diagnosed, they were more likely to be hospitalised (HR = 1.90, 95% CI: 1.87-1.92) and then admitted to intensive care unit (HR = 1.08, 95% CI: 1.04-1.13), with differences larger in those coming from countries with a lower human development index. Compared with Italian cases, an increased rate of death was observed in non-Italian cases from low-human development index countries (HR = 1.41, 95% CI: 1.23-1.62). The HRs of SARS-CoV-2 infection and severe outcomes slightly increased after the start of the vaccination campaign. CONCLUSIONS: Underdiagnosis and delayed diagnosis in non-Italian nationals could explain their lower incidence compared with Italians and, among cases, their higher probability to present clinical conditions leading to worse outcomes. Facilitating early access to vaccination, diagnosis and treatment would improve the control of SARS-CoV-2 transmission and health outcomes in this vulnerable group.

Strengthening preparedness against global health threats: A paradigm shift based on One Health approaches.

The implementation of preparedness strategies to prevent and mitigate the impact of global health threats poses several challenges. It should promptly identify cross-cutting drivers of pandemic threats, assess context-specific risks, engage multiple stakeholders, and translate complex data from multiple sources into accessible information for action. This requires a coordinated, multidisciplinary and multisectoral effort engaging systems that, most of the time, work in isolation. The One Health (OH) approach promotes the collaboration and communication among different disciplines and sectors, and could be applied across the preparedness phases at national and international level. We discuss here gaps and needs in preparedness strategies, which can benefit from the OH approach, and a set of actionable recommendations, as shared with the G20-2021 with a dedicated Policy Brief. The discussion adds to the current debate about OH operationalization and promotes a paradigm shift towards coordinated prevention and preparedness strategies for early assessment and management of global health threats.

Religiosity/Spirituality and Mental Health in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies.

Objectives: The present study investigated the association between religious and spiritual (RS) practices with the prevalence, severity, and incidence of mental health problems in older adults. Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated older adults aged 60+ years and assessed RS using valid scales and questions from valid scales, and mental health according to validated multidimensional or specific instruments. Studies were retrieved from MEDLINE, LILACS, SCOPUS, CINAHL, and AgeLine databases until July 31, 2021. The risk of bias was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). A pooled effect size was calculated based on the log odds ratio (OR) and Z-scores. This study is registered on PROSPERO. Results: One hundred and two studies that investigated 79.918 community-dwellers, hospitalized, and institutionalized older adults were included. Results indicated that high RS was negatively associated with anxiety and depressive symptoms, while a positive association was observed with life satisfaction, meaning in life, social relations, and psychological well-being. Specifically, people with high spirituality, intrinsic religiosity, and religious affiliation had a lower prevalence of depressive symptoms. In relation to longitudinal analysis, most studies supported that high RS levels were associated with a lower incidence of depressive symptoms and fear of death, as well as better mental health status. Conclusion: Findings of the present study suggest that RS are significantly associated with mental health in older adults. People with high RS levels had a lower prevalence of anxiety and depressive symptoms, as well as reported greater life satisfaction and psychological well-being, better social relations, and more definite meaning in life. Data provided by an increasing number of longitudinal studies have supported most of these findings.

Risk of hospitalization and death for healthcare workers with COVID-19 in nine European countries, January 2020-January 2021.

This article presents and compares coronavirus disease 2019 attack rates for infection, hospitalization, intensive care unit (ICU) admission and death in healthcare workers (HCWs) and non-HCWs in nine European countries from 31st January 2020 to 13th January 2021. Adjusted attack rate ratios in HCWs (compared with non-HCWs) were 3.0 [95% confidence interval (CI) 2.2-4.0] for infection, 1.8 (95% CI 1.2-2.7) for hospitalization, 1.9 (95% CI 1.1-3.2) for ICU admission and 0.9 (95% CI 0.4-2.0) for death. Among hospitalized cases, the case-fatality ratio was 1.8% in HCWs and 8.2% in non-HCWs. Differences may be due to better/earlier access to treatment, differential underascertainment and the healthy worker effect.

The Bicentenary of Bell's Description of the Neuroanatomical Basis of Facial Paralysis: Historical Remarks.

Charles Bell was a talented and versatile Scottish anatomist, neurophysiologist, artist, and surgeon. On July 12, 1821, he reported his studies regarding facial innervation in the essay "On the Nerves," read before the Royal Society in London. Since then, idiopathic peripheral facial paralysis has been named "Bell's palsy." He was the first author to describe the neuroanatomical basis of facial paralysis, in an essay enriched by beautifully self-made illustrations. The aim of this article is to trace the history of Bell's description of the neuroanatomy of the facial nerve, reexamining his 1821 article, in which he stated that the lower facial expression muscles were dually innervated by both the fifth and seventh cranial nerves. In 1829, he rectified this conclusion, recognizing the exclusive role of the facial nerve, which he defined as the "respiratory nerve." We offer a tribute to this polymath scientist on the bicentenary of his 1821 publication.

Xenobiotic metabolism and transport in Caenorhabditis elegans.

Caenorhabditis elegans has emerged as a major model in biomedical and environmental toxicology. Numerous papers on toxicology and pharmacology in C. elegans have been published, and this species has now been adopted by investigators in academic toxicology, pharmacology, and drug discovery labs. C. elegans has also attracted the interest of governmental regulatory agencies charged with evaluating the safety of chemicals. However, a major, fundamental aspect of toxicological science remains underdeveloped in C. elegans: xenobiotic metabolism and transport processes that are critical to understanding toxicokinetics and toxicodynamics, and extrapolation to other species. The aim of this review was to initially briefly describe the history and trajectory of the use of C. elegans in toxicological and pharmacological studies. Subsequently, physical barriers to chemical uptake and the role of the worm microbiome in xenobiotic transformation were described. Then a review of what is and is not known regarding the classic Phase I, Phase II, and Phase III processes was performed. In addition, the following were discussed (1) regulation of xenobiotic metabolism; (2) review of published toxicokinetics for specific chemicals; and (3) genetic diversity of these processes in C. elegans. Finally, worm xenobiotic transport and metabolism was placed in an evolutionary context; key areas for future research highlighted; and implications for extrapolating C. elegans toxicity results to other species discussed.

Interactions of Environmental Chemicals and Natural Products With ABC and SLC Transporters in the Digestive System of Aquatic Organisms.

An organism's diet is a major route of exposure to both beneficial nutrients and toxic environmental chemicals and natural products. The uptake of dietary xenobiotics in the intestine is prevented by transporters of the Solute Carrier (SLC) and ATP Binding Cassette (ABC) family. Several environmental chemicals and natural toxins have been identified to induce expression of these defense transporters in fish and aquatic invertebrates, indicating that they are substrates and can be eliminated. However, certain environmental chemicals, termed Transporter-Interfering Chemicals or TICs, have recently been shown to bind to and inhibit fish and mammalian P-glycoprotein (ABCB1), thereby sensitizing cells to toxic chemical accumulation. If and to what extent other xenobiotic defense or nutrient uptake transporters can also be inhibited by dietary TICs is still unknown. To date, most chemical-transporter interaction studies in aquatic organisms have focused on ABC-type transporters, while molecular interactions of xenobiotics with SLC-type transporters are poorly understood. In this perspective, we summarize current advances in the identification, localization, and functional analysis of protective MXR transporters and nutrient uptake systems in the digestive system of fish and aquatic invertebrates. We collate the existing literature data on chemically induced transporter gene expression and summarize the molecular interactions of xenobiotics with these transport systems. Our review emphasizes the need for standardized assays in a broader panel of commercially important fish and seafood species to better evaluate the effects of TIC and other xenobiotic interactions with physiological substrates and MXR transporters across the aquatic ecosystem and predict possible transfer to humans through consumption.

Adding Nanofat to Fat Grafting to Treat Velar Scarring in Velopharyngeal Incompetence.

Despite improved surgical techniques in palatoplasty a number of patients will present post-operatively with incomplete velopharyngeal closure due to several reasons including inherent shortness of the palate or midline scar contracture. This incomplete closure of the velopharynx during speech, known as velopharyngeal incompetence (VPI) causes hypernasality and nasal turbulence during speech. Treatment options in severe cases include revisions, pharyngeal flaps, and pharyngoplasties while in mild cases fat grafting has demonstrated its efficacy in improving velopharyngeal closure. Nevertheless, midline scarring can cause velar rigidity and inelasticity giving rise to inadequate velar elevation and retro position. Management of retracting velar scars is a real challenge. Despite an accurate surgical correction retracting scars tend to recur with negative effects on speech. Emulsified fat (nanofat) has proven to be a relevant source of stem cells and growth factors and has been successfully employed so far for the treatment of facial wrinkles and scars. The aim of this paper is to propose the application of the nanofat technique for the improvement of velar scar elasticity and pliability in addition to fat grafting to the posterior pharyngeal wall and the tonsillar pillars to further improve results when treating mild VPI. Studies with larger samples should follow to substantiate our findings but based on our preliminary experience, the authors feel that the nanofat could be a promising adjunct to the current repair procedures, due to its regenerative properties.

The First Pull-through Approach to a Tongue Tumor by Giorgio Regnoli in 1838.

The aim of this article is to describe the first report of a "pull-through" submental approach for excision of a tongue tumor, performed by Giorgio Regnoli in 1838 on a 14-year-old girl affected by a huge swelling of the tongue, which obstructed the upper airway and hindered swallowing and speech. Regnoli made a midline submental incision, divided the mylohyoid muscle and the oral mucosa, and entered the floor of the mouth. The tongue was pulled into the neck through the newly created opening, and the tumor was circumscribed by thread loops to prevent bleeding and was excised. Then the tongue stump was repositioned in the oral cavity. The skin margins were approximated by bandages. Despite limited armamentarium, the operation was successful. The described approach, subsequently named "pull-through," is still utilized nowadays for selected cases of tongue neoplasms when mandibular splitting is not required.

Strengths and limitations of morphological and behavioral analyses in detecting dopaminergic deficiency in Caenorhabditis elegans.

In order to develop a better understanding of the role environmental toxicants may play in the onset and progression of neurodegenerative diseases, it has become increasingly important to optimize sensitive methods for quickly screening toxicants to determine their ability to disrupt neuronal function. The nematode Caenorhabditis elegans can help with this effort. This species has an integrated nervous system producing behavioral function, provides easy access for molecular studies, has a rapid lifespan, and is an inexpensive model. This study focuses on methods of measuring neurodegeneration involving the dopaminergic system and the identification of compounds with actions that disrupt dopamine function in the model organism C. elegans. Several dopamine-mediated locomotory behaviors, Area Exploration, Body Bends, and Reversals, as well as Swimming-Induced Paralysis and Learned 2-Nonanone Avoidance, were compared to determine the best behavioral method for screening purposes. These behavioral endpoints were also compared to morphological scoring of neurodegeneration in the dopamine neurons. We found that in adult worms, Area Exploration is more advantageous than the other behavioral methods for identifying DA-deficient locomotion and is comparable to neuromorphological scoring outputs. For larval stage worms, locomotion was an unreliable endpoint, and neuronal scoring appeared to be the best method. We compared the wild-type N2 strain to the commonly used dat-1p::GFP reporter strains BY200 and BZ555, and we further characterized the dopamine-deficient strains, cat-2 e1112 and cat-2 n4547. In contrast to published results, we found that the cat-2 strains slowed on food almost as much as N2s. Both showed decreased levels of cat-2 mRNA and DA content, rather than none, with cat-2 e1112 having the greatest reduction in DA content in comparison to N2. Finally, we compared and contrasted strengths, limitations, cost, and equipment needs for all primary methods for analysis of the dopamine system in C. elegans.

Fat Grafting in the Management of War Injuries.

The healing potential of fat grafting was empirically noted by the surgeons who were confronted with the dramatic facial disfigurements resulting from World War 1. Fat was transplanted into the wounds either en bloc or in parcels to promote the healing capacity or to correct the uneven, depressed scars from gunshot wounds, enabling the poor soldiers to step back to society and families in a shorter period of time.The idea of transplanting fat into the wound of the facially disfigured started with Hippolyte Morestin (1869-1919), surgeon in chief at Val-de Grace Military Hospital in Paris and was widely adopted by HD Gillies (1882-1960), Erich Lexer (1867-1937), Gustavo Sanvenero Rosselli (1897-1974), and others, achieving amazing results. Successful treatment of facially injured individuals showed the importance of plastic surgical procedures, the social role of the discipline, basis for obtaining the official recognition as surgical specialty.

Management of Vocal Fold Scars by Concurrent Nanofat and Microfat Grafting.

Vocal fold scarring is the cause of severe dysphonia and represents a therapeutic challenge; dysphagia can also be present in case of soft tissue defect due to previous oncological surgery. The ideal surgical solution should concurrently provide vocal fold augmentation and re-establishment of tissue elasticity. Nanofat technique has given so far promising results in remodeling skin scars and improving tissue pliability. The present paper describes for the first time the use of nanofat injected into the vocal fold cover for pliability restoration, combined with traditional microfat for vocal fold augmentation. Seven patients (aged 23-77 years) affected by severe dysphonia, related to extensive vocal fold scarring (3 of them were also affected by dysphagia for liquid consistencies), underwent a single procedure of concurrent microfat and nanofat vocal fold injection under direct microlaryngoscopy in general anesthesia. Results were evaluated by objective outcome measures and auto evaluation performed by questionnaires concerning the phonatory and swallowing efficiency. The voice quality and the perceived swallowing capability of all patients improved after surgery and are stable at follow-up (4-8 months). The reported preliminary data show that nanofat, due to its regenerative potential related to adipose-derived stem cells and growth factors, can be a promising adjunct to traditional fat augmentation to improve elasticity of the delicate multilayered structure of the vocal fold and to enhance its vibratory capabilities. Further experience on a wider number of patients and long-term follow-up are necessary to confirm the validity of this technique.

An outbreak of severe invasive meningococcal disease due to a capsular switched Neisseria meningitidis hypervirulent strain B:cc11.

OBJECTIVES: The aim was to investigate an outbreak of invasive meningococcal disease (IMD) in Southern Sardinia. METHODS: Epidemiological and microbiological investigations were performed. The latter included antimicrobial susceptibility testing and whole-genome sequencing (WGS). RESULTS: Seven individuals with severe IMD were found to be infected with serogroup B (MenB) Neisseria meningitidis in the first quarter of 2018. Five of the seven cases (five males; mean age 19 years; range 18-21 years; CFR 40%) were due to a unique strain B:P1.5-1,10-8:F3-6:ST-11(cc11), probably switched from the hypervirulent C-cc11, as confirmed by WGS. All five patients had attended the same nightclub in the 2 weeks prior to symptom onset. Public health measures, including chemoprophylaxis of contacts and active immunization against MenB, were implemented. CONCLUSIONS: We observed five IMD cases due to the same switched MenB strain. The hypervirulent B:P1.5-1,10-8:F3-6:ST-11(cc11) strain, probably switched from C-cc11, is of concern due to the observed high virulence and case fatality rates. All the patients shared the same place of probable exposure. The molecular characterization of the invasive strain allowed the outbreak to be confirmed, which was then controlled through timely public health action.

Immunisation Registries at regional level in Italy and the roadmap for a future Italian National Registry.

BACKGROUND: Immunization Information Systems, or Immunisation registries (IRs), are essential to monitor and evaluate the accessibility, quality and outcomes of immunisation programmes both at local and national level. STUDY DESIGN: We conducted a cross-sectional survey in order to investigate and map the level of IRs implementation obtained by the 21 Italian Regional Health Authorities. On this basis we defined a roadmap towards implementing an Italian National IR. METHODS: We designed an online questionnaire. Data were collected from July to September 2016 from all the 21 Regional Health Authorities in charge of infectious diseases control and immunization management. RESULTS: 18/21 Italian Regions have fully implemented an IR, out of them, 11 use the same software for all Local Health Units. Two Regions have partially implemented their IRs and one Region is not yet computerised. CONCLUSION: The decentralization of the Italian Health System is reflected also on the IRs characteristics and functionalities in terms of fragmented implementation of IRs and diversity in the software systems and data flows in place. Future efforts should not only aim not only to clarify the functionalities of Regional IRs, but should also aim to define how aggregation of data at national level can be optimised.

Structural Fat Grafting to Improve Outcomes of Vocal Folds' Fat Augmentation: Long-term Results.

Objective Evaluating the long-term outcomes of vocal fold structural fat grafting. Study Design Case series with chart review. Setting University hospital. Subjects and Methods Seventy-nine dysphonic patients (16-82 years; 55 with unilateral laryngeal paralysis and 24 with vocal fold scarring) underwent vocal fold fat injection. Fat was harvested by low-pressure liposuction and then processed by centrifugation. Refined fat aliquots were placed in the vocal fold and paraglottic space in multiple tunnels to enhance graft neovascularization. All patients were followed for 12 months, 15 for 3 years, and 5 for 10 years with videolaryngostroboscopy, maximal phonation time (MPT) measurement, Voice Handicap Index (VHI) questionnaire, and GRBAS (grade, roughness, breathiness, asthenia, strain) perceptual evaluation. Laryngeal computed tomography (CT) and/or magnetic resonance imaging (MRI) studies were performed in 16 patients 3 to 28 months postoperatively; MRI was repeated in 5 cases 12 to 18 months after the first radiological study. Results The voice quality of all patients improved after surgery, and long-term stability was confirmed by MPT, GRBAS, and VHI ( P ranging between .004 and <.001). The results achieved 1 year postoperatively remained stable at 3 and 10 years. Videolaryn-gostroboscopy showed improved glottic closure in all patients despite a limited amount of fat resorption. CT and MRI demonstrated survival of the fat grafts in all of the 16 examined cases. Serial MRI scans showed no change in graft size over time. Conclusions The reported clinical and radiological data demonstrate that fat is an effective filler for permanent vocal fold augmentation if the refined micro-aliquots are placed in multiple tunnels.

Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences.

Cancer cells reprogram their metabolism to maintain both viability and uncontrolled proliferation. Although an interplay between the genetic, epigenetic and metabolic rewiring in cancer is beginning to emerge, it remains unclear how this metabolic plasticity occurs. Here, we report that in prostate cancer cells (PCCs) microRNAs (miRNAs) greatly contribute to deregulation of mitochondrial fatty acid (FA) oxidation via carnitine system modulation. We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. Moreover, the analysis of human prostate cancer and prostate control specimens confirmed the aberrant expression of miR-124-3p, miR-129-5p and miR-378 in primary tumors. Forced expression of the miRNAs mentioned above affected tumorigenic properties, such as proliferation, migration and invasion, in PC3 and LNCaP cells regardless of their hormone sensitivity. CPT1A, CACT and CrAT overexpression allow PCCs to be more prone on FA utilization than normal prostate cells, also in the presence of high pyruvate concentration. Finally, the simultaneous increase of CPT1A, CACT and CrAT is fundamental for PCCs to sustain FA oxidation in the presence of heavy lipid load on prostate cancer mitochondria. Indeed, the downregulation of only one of these proteins reduces PCCs metabolic flexibility with the accumulation of FA-intermediate metabolites in the mitochondria. Together, our data implicate carnitine cycle as a primary regulator of adaptive metabolic reprogramming in PCCs and suggest new potential druggable pathways for prevention and treatment of prostate cancer.

Deriving a Set of Privacy Specific Heuristics for the Assessment of PHRs (Personal Health Records).

With the emergence of personal health record (PHR) platforms becoming more widely available, this research focused on the development of privacy heuristics to assess PHRs regarding privacy. Existing sets of heuristics are typically not application specific and do not address patient-centric privacy as a main concern prior to undergoing PHR procurement. A set of privacy specific heuristics were developed based on a scoping review of the literature. An internet-based commercially available, vendor specific PHR application was evaluated using the derived set of privacy specific heuristics. The proposed set of privacy specific derived heuristics is explored in detail in relation to ISO 29100. The assessment of the internet-based commercially available, vendor specific PHR application indicated numerous violations. These violations were noted within the study. It is argued that the new derived privacy heuristics should be used in addition to Nielsen's well-established set of heuristics. Privacy specific heuristics could be used to assess PHR portal system-level privacy mechanisms in the procurement process of a PHR application and may prove to be a beneficial form of assessment to prevent the selection of a PHR platform with a poor privacy specific interface design.

Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4-antigen electrovaccination.

Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan-4 (hCSPG4)-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6-, 12-, 18- and 24-month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78-1694, 8 of 23 dogs alive] and 6-, 12-, 18- and 24-month disease-free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI 477 days, range 50-1694). Non-vaccinated dogs showed 6-, 12-, 18- and 24-month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST 200 days, range 75-1507, 1 of 19 dogs alive) and 6-, 12-, 18- and 24-month DFI rate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI 180 days, range 38-1250). Overall survival and DFI of vaccinated dogs was longer in those <20 kg. In vaccinated and non-vaccinated dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively.

Bergamo 3D Rhinoplasty Software: Select, Store, and Share Surgical Maneuvers in a Three-Dimensional Nasal Model.

BACKGROUND: Rhinoplasty is considered the most challenging chapter of plastic surgery due to its variability and the continuing evolution of surgical maneuvers. Worksheets became essential to unequivocally record surgical steps and to demonstrate their reciprocal effects/interactions during the follow-up period. After 1989, no other software was created to upgrade the Gunter Rhinoplasty Diagrams, the forefather and benchmark of the rhinoplasty "virtual" worksheet maker. METHODS: The authors built a new standard three-dimensional nasal framework model in STL format. All the basic components were modified to simulate the interaction among sutures, grafts, and the most common maneuvers performed during rhinoplasty. The authors created a total of 669 (99 built-in units and 285 unilateral units) three-dimensional figures which can be selected by the surgeon from among 230 options. The interface for the surgeon is Bergamo 3D Rhinoplasty Software. RESULTS: Bergamo 3D Rhinoplasty Software is made up of the database section, which gathers all the patient's personal information and documents, and the surgery section, which groups multiple selection lists in 10 surgical areas. Eighty percent of the options modify the original shape of the three-dimensional model. Several options help the surgeon to tailor the final result and to export it both in desktop software and in a real three-dimensional printed model. CONCLUSIONS: Bergamo Rhinoplasty Software revolutionizes the concept of patient and surgical data storage. Furthermore, the immediacy of three dimensions facilitates communication with patients, allows case sharing with colleagues, simplifies teaching, and encourages the surgeon's self-analysis and professional growth. Customization of the original model and of the maneuvers is the main limitation of the software, because of the currently existing technology in 2014.