Secrets and lies of host-microbial interactions: MHC restriction and trans-regulation of T cell trafficking conceal the role of microbial agents on the edge between health and multifactorial/complex diseases.

Here we critically discuss data supporting the view that microbial agents (pathogens, pathobionts or commensals alike) play a relevant role in the pathogenesis of multifactorial diseases, but their role is concealed by the rules presiding over T cell antigen recognition and trafficking. These rules make it difficult to associate univocally infectious agents to diseases' pathogenesis using the paradigm developed for canonical infectious diseases. (Cross-)recognition of a variable repertoire of epitopes leads to the possibility that distinct infectious agents can determine the same disease(s). There can be the need for sequential infection/colonization by two or more microorganisms to develop a given disease. Altered spreading of infectious agents can determine an unwanted activation of T cells towards a pro-inflammatory and trafficking phenotype, due to differences in the local microenvironment. Finally, trans-regulation of T cell trafficking allows infectious agents unrelated to the specificity of T cell to modify their homing to target organs, thereby driving flares of disease. The relevant role of microbial agents in largely prevalent diseases provides a conceptual basis for the evaluation of more specific therapeutic approaches, targeted to prevent (vaccine) or cure (antibiotics and/or Biologic Response Modifiers) multifactorial diseases.

Transglutaminase type 2 plays a key role in the pathogenesis of Mycobacterium tuberculosis infection.

BACKGROUND: Mycobacterium tuberculosis (MTB), the aetiological agent of tuberculosis (TB), is capable of interfering with the phagosome maturation pathway, by inhibiting phagosome-lysosome fusion and the autophagic process to ensure survival and replication in macrophages. Thus, it has been proposed that the modulation of autophagy may represent a therapeutic approach to reduce MTB viability by enhancing its clearance. OBJECTIVE: The aim of this study was to investigate whether transglutaminase type 2 (TG2) is involved in the pathogenesis of MTB. RESULTS: We have shown that either genetic or pharmacological inhibition of TG2 leads to a marked reduction in MTB replicative capacity. Infection of TG2 knockout mice demonstrated that TG2 is required for MTB intracellular survival in macrophages and host tissues. The same inhibitory effect can be reproduced in vitro using Z-DON, a specific inhibitor of the transamidating activity of TG2. Massive cell death observed in macrophages that properly express TG2 is hampered by the absence of the enzyme and can be largely reduced by the treatment of wild-type macrophages with the TG2 inhibitor. Our data suggest that reduced MTB replication in cells lacking TG2 is due to the impairment of LC3/autophagy homeostasis. Finally, we have shown that treatment of MTB-infected murine and human primary macrophages with cystamine, a TG2 inhibitor already tested in clinical studies, causes a reduction in intracellular colony-forming units in human macrophages similar to that achieved by the anti-TB drug capreomycin. CONCLUSION: These results suggest that inhibition of TG2 activity is a potential novel approach for the treatment of TB.

Lack of Response to HBHA in HIV-Infected Patients with Latent Tuberculosis Infection.

Heparin-binding haemagglutinin (HBHA) has been proposed as an immunological biomarker for discriminating active tuberculosis (TB) from latent TB infection (LTBI) and to identify those at higher risk of progressing to active disease. Few data are available in immune-compromised patients, which are those with increased risk of TB reactivation. The aim of this stusy was to evaluate the immune response to HBHA in HIV-infected subjects with LTBI (HIV-LTBI) or active TB (HIV-TB) in comparison with the immune response to additional Mycobacterium tuberculosis (Mtb) or HIV and CMV antigens. The responses are evaluated in relation to TB status and in the LTBI subjects with the progression to active TB within 2 years. Forty-one HIV-infected antiretroviral-naïve subjects were prospectively enrolled: 18 were HIV-TB and 23 HIV-LTBI. Whole blood was in vitro stimulated overnight with several antigens and mitogen. Interferon-γ response in the harvested plasma was evaluated by ELISA. Despite that CD4 cell count was significantly different between HIV-LTBI and HIV-TB, no differences were observed in response to Mtb- or HIV-specific antigens. Differently, low responses to HBHA were observed in both HIV-LTBI and HIV-TB subjects. Importantly, none of the six HIV-LTBI responding to HBHA developed TB, while two of 17 non-HBHA responders developed active disease. HIV-TB-coinfected subjects, regardless of their TB status, showed low responses to HBHA despite maintaining detectable responses to other antigens; moreover, among the HIV-LTBI, the lack of HBHA responses indicated an increased risk to develop active TB. These results, although preliminary, suggest that a positive response to HBHA in HIV-LTBI correlates with Mtb containment.

PREPARATION OF B-CYCLODEXTRIN-THIABENDAZOLE-PIPERONYL BUTOXIDE SUPRAMOLECULAR COMPLEX AND ITS ACTIVITY AGAINST BLUE AND GREEN MOULD DECAY ON INOCULATED SATSUMA FRUIT.

The supramolecular complex of ß-cyclodextrin-thiabendazole-piperony butoxide (ßCD-TBZ/PBO) was prepared and its structure was characterized by 1H NMR. Additionally, the antifungal activity of ßCD-TBZ/PBO was investigated in comparison with the commercially available thiabendazole (TBZ) fungicide by in vitro tests and on artificially inoculated 'Okitsu' satsuma fruit dipped in water at 20 degrees C or at 50 degrees C to control postharvest blue (Penicillium italicum) and green mould (P. digitatum). ß-CD-TBZ/PBO is stable for several months when stored as powder in a dark bottle. At pH 7.0 the water solubility of the ßCD-TBZ/PBO complex was consistently higher than free TBZ. Water dip at 20 degrees C did not affect decay incidence caused by blue mould but favoured the development of green mould during 4-8 days of storage at 20 degrees C with respect to untreated (control) fruit. Water at 50 degrees C effectively reduced the incidence of blue mould and totally suppressed green mould during the first 4 days but lost its efficacy afterwards. By contrast, both TBZ and ßCD-TBZ/PBO had a lasting effect and were equally effective in controlling green and blue mould decay when applied at 20 degrees C and 60 mg L(-1) active ingredient (a.i.). When applied at 50 degrees C and 20 mg L(-1) a.i. the activity of the complex against blue mould was inferior than the corresponding treatment with TBZ. In vitro assays revealed a significant effectiveness of ßCD-TBZ/PBO complex at low concentration compared to commercial formulation of TBZ.

Consensual end-of-life for depressed patients: a right or a danger?

Abstract: Recent events have brought the debate on end-of-life issues to the forefront, particularly regarding the principle of self-determination for depressed patients. Belgian legislation, in fact, allows for requesting euthanasia when patients, capable of expressing their own will consciously, suffer in an unbearable manner and find no meaning in continuing their existence, even in the absence of incurable and/or severely debilitating conditions. The state of the art is an increasing number of people who die from euthanasia. An open question is when a situation can be defined as unbearable. Moreover, does such an assessment necessarily lead to death, or are there other solutions? In our opinion, such a practice should be limited to prevent inappropriate applications that could lead to infringing depressed patients' rights.

The obligation of the physician to save the life of the detainee on a hunger strike: the opinion of the Italian National Bioethics Committee.

Abstract: The Cospito case has highlighted a widely debated bioethical issue regarding the need to choose between safeguarding the life of a detainee and their right to self-determination through the practice of a hunger strike. Recently, the Italian National Bioethics Committee has been called upon to give an opinion on this matter. On the other hand, the media resonance of this case has shed light on the need to pose an ethical and social question regarding such situations: does the physician have an obligation to protect the detainee's health at the expense of their free choice? To be able to answer, it is necessary to understand whether law no. 219/17 is applicable to this context.

First Case of Medically Assisted Suicide in Italy Set New Legal Perspectives.

Abstract: The first act of assisted suicide in Italy was recently carried out. This event is an absolute novelty for the country, affected by recent legislative changes aimed only at introducing the right to interrupt health treatments and, therefore, carry out exclusively omissive end-of-life acts. These normative provisions lay their foundations in a cultural context centered on the protection of the right to life and health; however, the cases that have occurred over time, including the famous story of DJ Fabo, have led the Constitutional Court to re-evaluate these dictates, introducing in 2019 the right to resort to assisted suicide procedures within well-defined areas, including incurability of the condition, the serious suffering of the individual and the retained ability to stand trial. The case addressed concerns a quadriplegic subject who was the victim of a road accident. Following consultation with a specialized institution, the subject made the decision to undergo an assisted sui-cide procedure in Italy. Having obtained the authorization from the competent authorities, he started a fundraiser to finance the devices and drugs required and, finally, he died. The opening by Italy towards the assisted suicide procedure represents a great step towards a broad context, as well as a decisive act for the purpose of protecting the right to self-determination of the individual. However, the current legislative framework presents significant criticalities and shortcomings. In first place, the dissonance between the laws in force and the judicial sentences is likely to generate problems of uneven application of the rules in a country dominated by the principle of Civil Law. Furthermore, the need for the applicant to fully self-finance the procedure clearly clashes with the constitutional principle of free access to care. Then emerges the need for a guideline document regarding the completion of the procedure itself, the times, methods and drugs implied, in order to significantly reduce the decision-making process by the ethics committees that still weighs on each individual case. Finally, conside-ring what has been observed on the subject of voluntary termination of pregnancy, it is necessary to ask what will be the general orientation of the doctors called to perform the act and whether they will be given the opportunity to express their refusal. The case analyzed could represent the beginning of a new era for Italian culture, but the large-scale application of assisted suicide procedures requires the introduction of legislative provisions that definitively eliminate the critical issues that have emerged so far.

Obstetric Violence in Italy: From Theoretical Premises to Court Judgments.

Introduction: Historical mistreatment and violence directed toward women's bodies extend to the field of medicine, and obstetric and gynecological practices are not immune to such misconduct. Obstetric violence (OV) refers to actions involving disrespectful, abusive, or coercive treatment directed at pregnant and birthing women. This includes institutional and personal attitudes that lead to the violation of women's autonomy, human rights, and sexual and reproductive health. Despite various international legislative initiatives and recommendations from the World Health Organization (WHO) addressing disrespectful and abusive treatment, OV is still poorly known to Italian public opinion. This study aims to investigate whether the concept of OV has been conversely assimilated in judicial decisions. Materials and methods: A retrospective analysis was conducted to scrutinize judgments in Italy until June 2023 related to OV. The Italian legal database 'De Jure Giuffrè', which collects sentences by various Courts, and the terms 'obstetric' and 'violence' as keywords were used for the research. Results: The full-text revision of the results (n. 41 sentences) al-lowed the selection of 5 eligible contributions covering the following issues: Informed Consent, Kristeller maneuver, Vaginal Birth After Cesarean (VBAC), Acceleration of childbirth without indication, and Episiotomy. The analysis of individual judgments was complemented by an examination of the key issues involved. Conclusions: The reviewed judgments frequently seemed to be grounded in technical aspects and inclined towards a predominant evaluation of childbirth outcomes. However, some encouraging aspects emerged, particularly in terms of attention to the female body, acknowledgment of consequences within the intimate-relational dimension, and a commitment to the principle of self-determination through the provision of free and informed consent. Ensuring the psychophysical well-being of women and unborn children, fostering positive interactions between pregnant women and medical staff, and actively working to reduce the grounds for litigation are among actual emerging priorities in healthcare. In this sense, fundamental elements include the implementation of continuous staff training and education as well as a focus on promoting the self-determination of women, leveraging new technologies for this purpose, and ensuring legal protection of their rights.

Identification of new benzofuran derivatives as STING agonists with broad-spectrum antiviral activity.

The Stimulator of Interferon Genes (STING) is involved in cytosolic DNA sensing and type I Interferons (IFN-I) induction. Aiming to identify new STING agonists with antiviral activity and given the known biological activity of benzothiazole and benzimidazole derivatives, a series of benzofuran derivatives were tested for their ability to act as STING agonists, induce IFN-I and inhibit viral replication. Compounds were firstly evaluated in a gene reporter assay measuring luciferase activity driven by the human IFN-ß promoter in cells expressing exogenous STING (HEK293T). Seven of them were able to induce IFN-ß transcription while no induction of the IFN promoter was observed in the presence of a mutated and inactive STING, showing specific protein-ligand interaction. Docking studies were performed to predict their putative binding mode. The best hit compounds were then tested on human coronavirus 229E replication in BEAS-2B and MRC-5 cells and three derivatives showed EC50 values in the µM range. Such compounds were also tested on SARS-CoV-2 replication in BEAS-2B cells and in Calu-3 showing they can inhibit SARS-CoV-2 replication at nanomolar concentrations. To further confirm their IFN-dependent antiviral activity, compounds were tested to verify their effect on phospho-IRF3 nuclear localization, that was found to be induced by benzofuran derivatives, and SARS-CoV-2 replication in Vero E6 cells, lacking IFN production, founding them to be inactive. In conclusion, we identified benzofurans as STING-dependent immunostimulatory compounds and host-targeting inhibitors of coronaviruses representing a novel chemical scaffold for the development of broad-spectrum antivirals.

HPV infection in squamous cell carcinomas arising from different mucosal sites of the head and neck region. Is p16 immunohistochemistry a reliable surrogate marker?

BACKGROUND: Human papillomavirus 16 infection has been proven to be associated with oropharyngeal squamous cell carcinomas (SCCs) and is probably the main reason of the reported increase in the incidence. The role of high-risk (HR) HPV for carcinogenesis of other sites in the head and neck awaits confirmation. With the aim to evaluate the prevalence of HPV infection and the reliability of different diagnostic tools in SCCs of different sites, 109 consecutive untreated head and neck SCCs were enrolled, and fresh tumour samples collected. METHODS: Human papillomavirus DNA was detected by Digene Hybrid Capture 2 (HC2). Human papillomavirus E6 and E7 mRNA were detected by NucliSENS EasyQ HPVv1. P16 expression was evaluated by immunohistochemistry. RESULTS: In all, 12.84% of cases were infected by HR genotypes and 1.84% by low-risk genotypes. Human papillomavirus 16 accounted for 87% of HR infections. The overall agreement between DNA and RNA detection is 99.1%. Although p16 expression clearly correlates with HPV infection (P=0.0051), the inter-rater agreement is poor (k=0.27). The oropharynx showed the highest HR HPV infection rate (47.6%) and was also the only site in which p16 immunohistochemistry revealed to be a fair, but not excellent, diagnostic assay (κ=0.61). CONCLUSION: The prognostic role of HR HPV infection in oropharyngeal oncology, with its potential clinical applications, underscores the need for a consensus on the most appropriate detection methods. The present results suggest that viral mRNA detection could be the standard for fresh samples, whereas DNA detection could be routinely used in formalin-fixed, paraffin-embedded samples.

COVID-19 Risk Management: a Survey among Italian physicians.

Abstract: The COVID-19 pandemic had a significant global impact on public health. The increasing demand for intensive care and the closure of several health facilities has led to a reduction in the assistance of non-COVID patients. In our study, we investigated what changes health professionals have experienced in their professional activities and how they coped with them. A questionnaire was sent to 146 doctors, focused on three subjects: type of activity carried out during the pandemic; use of personal protective equipment (PPE) and recourse to vaccination; current medical liability profiles related to COVID-19. The questionnaire was completed by 111 doctors. The study showed no significant differences in the questionnaire response as regards the demographic and work variables of the participants (gender, age, area of specialties). Most of doctors assisted potentially positive patients, which also imposed derogations on their safety. Most of the complaints were about the low adequacy of PPE provision and about the compromission of specialist medical care. The interest in safety among participants was revealed by the high compliance to vaccination, with almost complete coverage. The questionnaires showed that most doctors (72,7%) believe that specialist medical care has been impaired during the COVID-19 pandemic. Secondly, a high percentage of participants (79.8%) expressed the need for both civil and criminal limitation of liability in connection with work in the management of SARS-Cov-2 patients. In conclusion, this survey tried to contribute to the identification of the main problems presented by healthcare professionals. Their versatility was a crucial element for the management of the pandemic, but also highlighted the need for health institutions to prepare pandemic plans in the future, with adequate and constant updating. Concerns were raised regarding financial deficits and legal protection. Political decisions must be entrusted to enhance medical assistance and to avoid the increasing phenomenon of defensive medicine.

Clinical applicability of Quantiferon-TB-Gold testing in psoriasis patients during long-term anti-TNF-alpha treatment: a prospective, observational study.

BACKGROUND: Psoriasis patients who are treated with tumour necrosis factor (TNF)-alpha antagonists are at increased risk of reactivation of latent tuberculosis infection (LTBI) and should be adequately screened and monitored during active treatment. OBJECTIVES: To evaluate in a prospective study, the performance of Quantiferon-TB-Gold in tube (QFT) in vitro assay compared to the conventional tuberculin skin test (TST) in detecting LTBI among a cohort of non-BCG-vaccinated patients with moderate-to-severe psoriasis during long-term treatment (12 months) with TNF-alpha antagonists. METHODS: A total of 50 patients underwent QFT and TST testing at baseline and after 6 and 12 months of continuous anti-TNF-alpha treatment. Diagnosis of LTBI was made on the basis of a positive QFT result and negative chest-radiographic and microbiological assays. Patients with LTBI were subjected to standard isoniazid chemoprophylaxis and after 1 month, they resumed anti-TNF-alpha treatment with subsequent QFT and TST testing after 6 months. In all the cases, a follow-up period of 12 months was observed. RESULTS: During the 12-month-study period, 14% of patients presented a QFT conversion. During active anti-TNF-alpha treatment, a QFT conversion was observed in 10% of patients (five cases). Agreement between QFT and TST was moderate (κ=0.408) at screening, good (κ=0.734) after 6 months and fair (κ=0.328) after 12 months of treatment. A total of 18% of patients presented a positive, discordant TST during the study period. CONCLUSIONS: A single-test QFT-based screening strategy for LTBI in psoriasis patients receiving long-term anti-TNF-alpha treatment could reduce the incidence of false-positive LTBI cases, preventing unnecessary TB chemoprophylaxis.

Microbiological and immunological diagnosis of tuberculous spondylodiscitis.

BACKGROUND: Tuberculous spondylodiscitis is one the many manifestations of active tuberculosis (TB) and can result following primary infection or, more frequently, from reactivation of active TB in subjects with latent TB. Definitive diagnosis of tuberculous spondylodiscitis requires the identification of Mycobacterium tuberculosis in the biological sample following microbiological analysis. AIM: To summarize the recent advancement in the diagnosis of TB, focusing on classical and molecular microbiological procedures, providing an overview on the recent advancements in the understanding of TB pathogenesis and their implications for the immunological diagnosis MATERIALS AND METHODS: Isolation in culture of the bacilli and detection using molecular tools are the gold standards, though sensitivity of these assays is significantly lower compared to what observed for pulmonary TB, making diagnosis of spinal TB challenging. RESULTS: The use of the interferon-gamma release assays (IGRAs) for the immunological diagnosis of TB infection could be of help and shall precede the invasive techniques, such as biopsy or surgery, required to obtain the biological sample. IGRAs measure the presence of effector T cells in the blood that can readily respond to an antigenic stimuli by secreting cytokines, and that are an indication of the presence of the bacilli in vivo. IGRAs are more sensitive and specific than the intradermic reaction of Mantoux, though both these immunological tests cannot distinguish between latent TB infection and active TB. CONCLUSIONS: A modern diagnosis of TB spondylodiscitis should rely on the use of microbiological and immunological assays and the latter could potentially be of great help in monitoring therapy effectiveness.

Voluntary interruption of pregnancy (VIP) in Italy: interpretation of the current situation according to the report 2019-2020 of the Italian Ministry of Health.

Abstract: Voluntary interruption of pregnancy (VIP) in Italy is regulated by Law no. 194/1978. Its monitoring is carried out by the VIP Epidemio-logical Surveillance System, which periodically analyses the results of questionnaires compiled by the territorial healthcare structures and sent by each Region. The latest report, covering the years 2019 and 2020, highlights the adequacy of preventive and proactive strategies, an improvement in the quality and effectiveness of the service offered. Furthermore, considering the COVID-19 pandemic, the reorganization of the IVG application guidelines showed a considerable adaptation to the emergency context through measures such as the increase in pharmacological procedures compared to surgical procedures. The interpretation of the data shows that in Italy there is one of the lowest VIP rates in Europe, reflecting the effectiveness of campaigns that promote responsible procreation. Further implementations should be extended to the foreign population, which still shows a medium-high VIP rate. The efficiency of the service offered resulted to be high. The latter was assessed considering the waiting period required for the performance of the VIP procedure. Furthermore, the high percentage of conscientious objectors does not harm the healthcare service. The estimates show an adequate territorial coverage by the authorized structures compared to the female population of fertile age. In conclusion, the central action of planning, organization, and monitoring finds a valid ally in the territorial management entrusted to the Regions. The analyzed report reflects even more margins of efficiency and adequacy when considered within the particular historical context of the pandemic by COVID-19.

Molecular characterization of adenovirus from clinical samples through analysis of the hexon and fiber genes.

Human adenoviruses (HAdVs) are common pathogens associated with a variety of clinical manifestations. Although most infections are self-limiting, HAdVs can cause severe or lethal infections in immunocompromised as well as in healthy individuals. Several HAdVs have recently been characterized as emerging pathogens. In Italy, epidemiological, and especially molecular epidemiological, information on this pathogen is scarce. This study describes the characterization by cell culture, PCR and phylogenetic analysis of HAdV strains originating from a small collection of clinical samples gathered between 2008 and 2009. The distribution of different HAdV species was studied and the possible presence of newly emerging types was ascertained. A broad-range primer pair was used, targeting a portion of the hexon gene, in combination with species-specific primer pairs targeting a portion of the fiber gene. Human and animal reference AdV strains were included in the study. The broad-range assay identified all HAdV strains (study and reference samples), as well as three out of four animal AdV reference strains. Seven different types belonging to three HAdV species (B, C and F) were identified in the study samples. Species C was by far the most frequent. Two co-infections were detected, each with two serotypes within species C (types 1/2 and 2/6). The combined use of these two PCR assays--allowing not only the identification of known types but also, potentially, the discovery of newly emerging ones--can provide valuable epidemiological information on the spread of HAdVs.

Clinical presentation, microbiological features and correlates of disease severity of 2009 pandemic influenza A (H1N1) infection.

The purpose of this study was to describe epidemiological, clinical and microbiological characteristics of confirmed novel influenza A (H1N1) infection, investigating factors associated with disease severity. We retrospectively selected patients seeking care for respiratory symptoms in two periods (May-August and September-November 2009) with different epidemiological characteristics. Only patients with confirmed pandemic influenza A (H1N1) were enrolled in this study. A total of 104 patients with H1N1 infection were evaluated, mostly referring classic influenza symptoms; in addition, diarrhea and vomiting were often referred. Clinical signs, symptoms and respiratory complications were different in the two periods. Of all patients, 18 (17%) had pneumonia. Patients older than 50 years showed a lower probability of pneumonia diagnosis when compared to children aged 0-13 (p = 0.049); a longer duration of symptoms before medical care was associated with a higher probability of pneumonia (p = 0.026). Phylogenetic analysis showed a low variability both in hemagglutinin and neuraminidase genes. In addition, no neuraminidase mutation associated with antiviral resistance was detected. A detailed description of respiratory diseases associated with H1N1 infection was provided and factors associated with its severity were investigated, thus contributing to the insight into epidemiological, clinical and microbiological knowledge of the disease.

TLR2: a crossroads between infections and autoimmunity?

Environment has both pathogenic and protective roles in the determination of autoimmune disease development, possibly through infectious agents. TLR2 has the capability to recognize the widest range of PAMPs, and it is important for the recognition of mycobacteria and gram-positive bacteria. Here we review recent information showing that TLR2 ligands, its signaling machinery and the effects of its engagement on T cell polarization and differentiation, all play a decisive role in experimental models of autoimmunity. Thus, we propose that engagement of TLR2 is an important crossroad between encounter with bacteria and development of self-reactive diseases.

Effect of L-carnitine on oxidative stress and platelet activation after major surgery.

BACKGROUND: The surgical/anesthesia trauma is associated with an increased production of reactive oxygen species (ROS). This enhanced oxidative stress leads to cell damage resulting in various complications such as sepsis, myocardial injury and increased mortality. The aim of this study was to investigate the role of antioxidant treatment with l-carnitine in oxidative stress and platelet activation in patients undergoing major abdominal surgery. METHODS: Forty patients scheduled for abdominal surgery were randomly allocated to l-carnitine, administered with a rapid infusion (0.05 g/kg) diluted in 250 ml of saline solution, vs. placebo treatment just before the surgical intervention. At baseline and after treatment, oxidative stress was evaluated by detection of circulating levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of NADPH oxidase activation, and by analyzing platelet ROS formation. Platelet activation was studied by dosing sCD40L. RESULTS: We observed an increase of soluble sNOX2-dp, sCD40L and ROS production in the placebo group compared with the baseline after the surgical intervention. Conversely, in the l-carnitine-treated group, sNOX2-dp, sCD40L and ROS production did not significantly differ from the baseline. A linear correlation analysis showed that Δ of ROS correlated with Δ of sNOX2 (R(s) =0.817; P<0.001) and Δ of sCD40L (R(s) =0.780; P<0.001). Multiple linear regression analysis showed that the only independent predictive variable associated with Δ of ROS was Δ of serum NOX2 levels (SE=0.05; standardized coefficient ß=1.075; P<0.001). CONCLUSION: Our findings suggest that l-carnitine could be helpful in modulating oxidative stress and platelet activation during major abdominal surgery-dependent oxidative damage.

Suspected transmission of tuberculosis in a maternity ward from a smear-positive nurse: preliminary results of clinical evaluations and testing of neonates potentially exposed, Rome, Italy, 1 January to 28 July 2011.

We report preventive measures adopted after tuberculosis(TB) transmission from a nurse to a newborn assessed in late July 2011. All exposed neonates born between January and July 2011 were clinically evaluated and tested by QuantiFERON TB gold in-tube; newborns testing positive were referred for prophylaxis.Of 1,340 newborns, 118 (9%) tested positive and no other active cases of TB were found. Active surveillance for TB will be continued over the next three years for all those exposed.

Italian law no. 1/2021 on the subject of vaccination against Covid-19 in people with mental disabilities within the nursing homes.

ABSTRACT: The Coronavirus Disease-19 (Covid-19) pandemic, in the last year, has resulted in a significant number of infections and deaths among nursing homes' residents. This phenomenon has set up the necessity to subject these patients, often suffering from mental disabilities to a vaccination against Covid-19. However, vaccination has long been the subject of public atten-tion, being regulated differently in many European countries. In Italy, the Ministry of Health has given priority, vaccination-wise, to health facilities' patients. The government has regulated through-law no. 1 of January 5, 2021, art. 5, the manifestation of consent to be Covid-19 vac-cinated in incapacitated subjects admitted to assisted health facilities. This rule arose from the need to protect fragile individuals as well as providing real dispositions for the involved health professionals. Nursing homes' elderly guests could be divided into four catego-ries: a) subjects capable to express their will (affected by physical problems); b) subjects who, due to varying degrees of incapacitation, have their own legal guardian, curator or support administrator, ap-pointed in accordance with the law; c) incapacitated subjects without legal representatives d) subjects who, pursuant to law no. 219/2017, have appointed their own trustee. This paper provides for a clear exemplification of all the possible scenarios identified by the Italian law no.1/2021.