The Erice 58 Charter on 'The health of migrants. An equity challenge for the public health system'.

Abstract: The Erice 58 Charter titled "The Health of Migrants: a Challenge of Equity for the Public Health System", was unanimously approved at the conclusion of the 58th Residential Course of the School of Epidemiology and Preventive Medicine 'Giuseppe D'Alessandro' entitled "The Health of Migrants: a Challenge of Equity for the Public Health System. Epidemiological, clinical-relational, regulatory, organisational, training and public communication aspects at international, national and local level', which took place from 28 March to 2 April 2022 in Erice (Sicily, Italy), at the 'Ettore Majorana' Foundation and Centre for Scientific Culture. The Course was promoted by the Italian Society of Migration Medicine (S.I.M.M.) and the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI), with the collaboration and patronage of the Istituto Superiore di Sanità (ISS). 72 learners participated (mainly resident doctors in 'Hygiene and Preventive Medicine' but also other health service professionals), whose average age was 37 years; on the basis of territorial origin, 13 of the 20 Italian regions were represented. During the intense learning experience, which consisted of 18 frontal lessons (with 20 lecturers from the bio-medical, socio-anthropological and journalistic fields) and 7 working group sessions (supported by 4 classroom tutors in addition to the lecturers) in 'blended learning' mode, the various dimensions and critical issues related to the possibility of guaranteeing truly inclusive health policies for foreigners/migrants, throughout the country, were identified and discussed from an 'Health Equity' perspective. This enabled a small editorial group to draw up the basic document that, in the last session of the Course, was discussed and modified by all participants into the version of the 'Erice 58 Charter' presented here.

First direct measurement of the 2H(α,γ)6Li cross section at big bang energies and the primordial lithium problem.

Recent observations of (6)Li in metal poor stars suggest a large production of this isotope during big bang nucleosynthesis (BBN). In standard BBN calculations, the (2)H(α,γ)(6)Li reaction dominates (6)Li production. This reaction has never been measured inside the BBN energy region because its cross section drops exponentially at low energy and because the electric dipole transition is strongly suppressed for the isoscalar particles (2)H and α at energies below the Coulomb barrier. Indirect measurements using the Coulomb dissociation of (6)Li only give upper limits owing to the dominance of nuclear breakup processes. Here, we report on the results of the first measurement of the (2)H(α,γ)(6)Li cross section at big bang energies. The experiment was performed deep underground at the LUNA 400 kV accelerator in Gran Sasso, Italy. The primordial (6)Li/(7)Li isotopic abundance ratio has been determined to be (1.5 ± 0.3) × 10(-5), from our experimental data and standard BBN theory. The much higher (6)Li/(7)Li values reported for halo stars will likely require a nonstandard physics explanation, as discussed in the literature.

Pharmacological Interventions versus Combined Treatment of Depression: A Prospective Study.

Introduction: Depression is a common disease worldwide but still, the role of combined treatment (pharmacological and psychological interventions) needs to be clarified. The study aims to compare the effectiveness of integrated treatment versus exclusive pharmacological intervention of depression. Materials and methods: The observational prospective study provided the collection of data relating to outpatients evaluated through the administration of the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impression Scale (CGI) both at T0 and at a 3-month follow up visit (T1). Results: A statically significant association between sex (female) and psychotherapy utilization emerged. A statistically significant association between education (graduated patients) and psychotherapy use was observed. The other qualitative variables showed no statistically significance associations. No significant association between drop out and type of treatment emerged. Discussion: Clinical research has not yet conclusively demonstrated the superiority of combined therapy over single treatments. As regards sex, the result is in line with the professional literature and provides support in describing how men have more stigmatizing beliefs about treatment of mental health. As regards education, graduated people present higher rates of adherence probably because they may have major introspective capacity and predisposition to communication. Conclusions: Limitations consist in small sample and short duration of the follow-up (3 months). The strengths, in the type of setting and the respect for routine clinical practice. Future perspective of the research could focus on application of rating instruments to highlight the variables involved in depressive disorder.

Inflammatory Biomarker and Response to Antidepressant in Major Depressive Disorder: a Systematic Review and Meta-Analysis.

Inadequate response to antidepressant treatment, in a significant proportion of patients diagnosed with Major Depressive Disorder, contributes to the large burden of disability associated with the disease; thus, predicting treatment response is one of the most important challenge for clinicians who deal with depressed patients. The cytokine hypothesis of depression suggests that altered pheripheral cytokine levels are involved in the pathophysiology of depressive disorder and in modulating response to treatment. Present meta-analysis aimed to investigate the association between cytokine levels at baseline and response to antidepressant therapies. Authors performed a systematic search of PubMed and Embase databases for studies published between 2010 and January 2021: of 3345 identified records, 31 studies met the inclusion criteria for the qualitative synthesis, whereas 19 studies were eligible for quantitative analysis. Patients who failed to respond to antidepressant had aberrant inflammatory process, namely higher baseline levels of C-Reactive Protein and Interleukine-8, which is associated with treatment outcome in Major Depressive Disorder. Despite these promising results, further investigations are needed in order to replicate the data and to examine the potential role of inflammatory marker as a novel predictive tool for pharmacological treatment of depressive disorder.

Differential phytotoxic effect of silver nitrate (AgNO3) and bifunctionalized silver nanoparticles (AgNPs-Cit-L-Cys) on Lemna plants (duckweeds).

Duckweeds are aquatic plants often used in phytotoxic studies for their small size, simple structure, rapid growth, high sensitivity to pollutants and facility of maintaining under laboratory conditions. In this paper, induced phytotoxic effects were investigated in Lemna minor and Lemna minuta after exposition to silver nitrate (AgNO3) and silver nanoparticles stabilized with sodium citrate and L-Cysteine (AgNPs-Cit-L-Cys) at different concentrations (0, 20 and 50 mg/L) and times (7 and 14 days). Lemna species responses were evaluated analyzing plant growth (mat thickness, fresh and dry biomass, relative growth rate - RGR) and physiological parameters (chlorophyll - Chl, malondialdehyde - MDA, ascorbate peroxidase - APX and catalase - CAT). Ag content was measured in the fronds of the two Lemna species by inductively coupled plasma optical emission spectrometry. AgNO3 and AgNPs-Cit-L-CYs produced phytotoxic effects on both duckweed species (plant growth and Chl reduction, MDA increase) that enhanced in response to increasing concentrations and exposure times. AgNPs-Cit-L-Cys caused much less alteration in the plants compared to AgNO3 suggesting that the presence of bifunctionalized AgNPs-Cit-L-Cys have a reduced phytotoxic effect as compared to Ag+ released in water. Based on the physiological performance, L. minuta plants showed a large growth reduction and higher levels of chlorosis and stress in respect to L. minor plants, probably due to greater Ag+ ions accumulation in the fronds. Albeit with some differences, both Lemna species were able to uptake Ag+ ions from the aqueous medium, especially over a period of 14 days, and could be considered adapt as phytoremediation agents for decontaminating silver ion-polluted water.

Analysis of variables predictive of severity in biliary peritonitis.

OBJECTIVE: To analyze clinical and laboratory findings in order to find variables predictive of severity of Biliary Peritonitis (BP). Patients and methods. Physical findings, course of illness, imaging and laboratory data were evaluated in 22 patients with BP, and statistically analysed to assess their prognostic significance. RESULTS: Serious illness and worse outcome were associated with: age > 60 years (P=0.034), long time between onset of symptoms and treatment (P=0.025), fever > 38°C (P=0.009), WBC count > 17.000 cell/mm³ (P=0.043), diffuse abdominal pain (P=0.034), and infected bile (P=0.048). CONCLUSIONS: Most patients become severely ill due to supervening infection, while early bile drainage avoids serious complications. In addition, abdominal pain, fever and WBC count are also predictive of severity of BP.

Natural history of SARS-CoV-2 infection in healthcare workers in Northern Italy.

At present, the time-frame used for the quarantine of individuals with coronavirus disease 2019 (COVID-19) is the entire duration of symptoms plus 14 days after symptom recovery; however, no data have been reported specifically for healthcare workers (HCWs). In the study population of 142 HCWs with COVID-19, the mean time for viral clearance was 31.8 days. Asymptomatic subjects cleared the virus more quickly than symptomatic subjects (22 vs 34.2 days; P<0.0001). The presence of fever at the time of diagnosis was associated with a longer time to viral clearance (relative risk 11.45, 95% confidence interval 8.66-14.25; P<0.0001). These findings may have a significant impact on healthcare strategies for the future management of the COVID-19 pandemic.

Population dynamics of Epicoccum nigrum, a biocontrol agent against brown rot in stone fruit.

AIMS: To study the population dynamics of Epicoccum nigrum on peaches and nectarines and to enhance its colonization on fruit surfaces to improve its biocontrol efficacy against brown rot. METHODS AND RESULTS: Twelve surveys were performed to study E. nigrum populations and their effect on the number of the pathogenic Monilinia spp. conidia in peach orchards in Spain and Italy between 2002 and 2005. Fresh conidia and five different formulations of E. nigrum conidia were applied three to six times to peach and nectarine trees from full flowering to harvest. The size of the E. nigrum populations was determined from the number of colony-forming units and conidial numbers per flower or fruit. Treatment with all conidial formulations increased the size of the indigenous conidial population on peach surfaces. CONCLUSIONS: Formulations of E. nigrum having high viability are most effective against conidia of the pathogen when applied at pit hardening and during the month immediately before fruit harvest. SIGNIFICANCE AND IMPACT OF THE STUDY: Application of an E. nigrum conidial formulation decreased the number of conidia of Monilinia spp. on fruit surfaces during the growing season to the same extent as fungicides.

Chronic sub-lethal oxidative stress by spermine oxidase overactivity induces continuous DNA repair and hypersensitivity to radiation exposure.

In the aging process and in most degenerative diseases, the oxidant by-products of cellular metabolism lead to oxidative stress. Oxidative stress plays an important role in switching from cell proliferation to its opposite outcome, cell death. The metabolic pathways in charge of the interconversion and degradation of the polyamines are responsible for oxidant by-products. In the past few years, spermine metabolism has been found closely related to DNA oxidation and apoptosis. Moreover, that the ectopical expression of murine spermine oxidase induced DNA damage in the neuroblastoma cell line, and this was uncoupled with any increase in cell mortality, thus suggests an activation of DNA repair. In this work, we provide new evidence showing that only spermine oxidase overactivity can deliver sub-lethal chronic DNA damage and repair without affecting transcriptional and enzymatic levels of the PA key regulatory enzymes ODC and SSAT. Chronic sub-lethal DNA damage is below the cell cycle arrest induction threshold, but is able to activate apurinic/apyrimidinic endonuclease protein (APE1) and gamma H2AX. Of therapeutic interest, the chronic sub-lethal DNA damage and activation of the repair processes are in turn responsible for inducing hypersensitivity after exposure to radiation with no induction of adaptive response to damage.

Dosimetric analysis of Tomotherapy-based intracranial stereotactic radiosurgery of brain metastasis.

PURPOSE: This paper analyzes Tomotherapy-based intracranial stereotactic radiosurgery (HTSRS) of brain metastasis targeting two end-points: 1) evaluation of dose homogeneity, conformity and gradient scores for single and multiple lesions and 2) assay of dosimetric criticality of completion of HTSRS procedures. METHODS: 42 treatment plans of 33 patients (53 brain lesions) treated with HTSRS were analyzed. Dose to healthy brain, homogeneity, conformity and gradient indexes were evaluated for each lesion. Influence of Field Length and multiple lesions cross-talk effect were assessed. Treatment interruption and completion was investigated using radiochromic films in order to examine the delivered dose and its robustness to patient intrafraction movement. RESULTS: The average dose homogeneity index was 1.04 ±â€¯0.02 (SD). Average dose conformity and gradient score indexes were 1.4 ±â€¯0.2 and 50 ±â€¯14 respectively. We found a strong correlation of the dose to healthy brain and conformity and gradient indexes with target(s) volume for which analytical functions were obtained. Field Length and cross-talk effect were significantly correlated with poor gradient scores, but were found not to affect dose conformity. CONCLUSIONS: Homogeneity and conformity of HTSRS plans achieved excellent scores, while dose falloff and dose to healthy brain were slightly larger when compared with non-coplanar SRS techniques. Care should be given if treating large (>3 cc) or multiple near in-plane lesions in order to reduce dose to healthy brain. Analysis of interrupted treatments suggests splitting HTSRS treatments in two consecutive fractions in order to prevent target miss and overdosage due to patient intrafraction movement.

[Work efficiency and lighting conditions: an experimental study]. / Efficienza lavorativa e condizioni illuminotecniche: studio sperimentale.

Thirty-two voluntary subjects were selected, not suffering either from any degenerative ophthalmic diseases or refraction and ocular motility alterations. Each subject underwent close visual task experimental sessions (e.g. PC usage), under monitored experimental conditions. Aim of the study is the assessment of working efficiency effects caused by lighting conditions characterized by "according to law" illuminations, yet in presence of high or low luminance ratios in the occupational visual field". An analysis of the data showed that high luminance ratios conditions show a decrease of the performance (decrease overall efficiency, increase in the number of errors and time of execution), which where not detected with low luminance ratios conditions. Asthenopia did not show clear differences, possibly due to the effects of the intense near work which was present in both the experimental sessions.

Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells.

In mammals, the polyamines affect cell growth, differentiation, and apoptosis; their levels are increased in malignant and proliferating cells, thus justifying an interest in a chemotherapeutic approach to cancer. The flavoprotein SMO is the most recently characterized catabolic enzyme, preferentially oxidizing SPM to SPD, 3-aminopropanal and H(2)O(2). In this report, we describe a novel functional characterization of the recently cloned splice variant isoforms from mouse brain, encoding, among others, the nuclear co-localized spermine oxidase mSMOmu. The over-expression of the active isoforms mSMOalpha and mSMOmu, and the inactive mSMOdelta and mSMOgamma in mouse neuroblastoma cells, demonstrated the first evidence of the direct oxidative DNA damage by the SMO activities, either alone or, in a higher extent, when associated with radiation exposure, thus working as radio sensitizer. These effects were reverted by treatment with 50 muM and 100 muM doses of the inhibitor of SMO activity MDL 72,527. The over-expression of all SMO isoforms failed to influence the expression of the regulating enzymes of polyamines metabolism ODC and SSAT. Dealing with the unbalanced tissue specific SMO activities, these results could indicate a new direction to tailor chemotherapy-associated radiotherapy, improving dose-rate protocol and allowing the modulation of deleterious side effects on healthy tissues.

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

PURPOSE: The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS: One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS: Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION: This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

Helical Tomotherapy of the breast: can thermoplastic immobilization improve the reproducibility of the treatment setup and the accuracy of the delivered dose?

PURPOSE: To evaluate the impact of thermoplastic mask immobilization in the setup reproducibility and delivered dose for Helical Tomotherapy (HT) of the breast/chest wall. METHODS: 16 patients treated with Accuray Hi-Art HT for breast-cancer were considered. Patients were positioned supine with arms extended above the head using Civco Wing Board (WB) system. In 50% of patients an Orfit thermoplastic mask was added in order to improve immobilization. Before each treatment fraction a megavoltage CT (MVCT) scan was taken and registered to the planning CT by experienced medical staff. The impact of thermoplastic mask was investigated analysing MVCT shift-roll data and MVCT dose distribution using Planned Adaptive software. RESULTS: In the analysed cases, the addition of thermoplastic mask had minor impact on the lateral, longitudinal and roll data distribution. Variance of vertical shifts was significantly reduced in the WB + Orfit group. Van Herk's margins were not affected by addition of thermoplastic immobilization. In both groups, target coverage (V95) and maximum dose (D1) were almost identical to planned values. D1 of organs at risk were not significantly different in the two groups. CONCLUSIONS: Analysis of shift-roll data shows no improvement in the group of patients immobilized with the addition of thermoplastic mask. Van Herk's margin is quite large (7-10 mm) in both groups evidencing the need to perform daily setup correction. The adapted dose distribution complies well with the planned one, showing that if MVCT is used before each treatment fraction, a 3 mm margin (setup component) for CTVs expansion could be adequate.

Neural correlates of ankle movements during different motor tasks: A feasibility study.

This ongoing study investigates the neural correlates of ankle dorsi-plantar flexion in active, passive, and proprioceptive tasks. Specifically, we investigated two proprioceptive matching tasks that required a simple combination of active and passive ankle movements: (1) a memory-based ipsilateral matching task and (2) a contralateral concurrent matching task. As expected, during the passive tasks, subjects recruited the same brain areas involved in the correspondent active movements (primary motor cortex (M1), premotor cortex (PM) supplementary motor cortex (SMA) and primary somatosensory cortex (S1)), but the activations were lower. Instead, in both the proprioceptive matching tasks, subjects recruited more motor and sensory-motor areas of the brain and the activations were greater.

A rapid and versatile site-directed method of mutagenesis for double-stranded plasmid DNA.

This paper describes a new method for site-directed mutagenesis which allows mutations by deletion, insertion or substitution of large fragments of DNA with more than 50% efficiency and does not require subcloning in a single-stranded (ss) DNA vehicle. The site of mutagenesis is removed from a linearized plasmid DNA by BAL 31 digestion, ss DNA regions are generated by limited exonuclease treatment and the mutated target site is reconstituted by annealing of the plasmid DNA to a 35-70 nucleotide long mutated ss oligodeoxynucleotide containing the desired mutation. The circularized plasmid is finally used to transform directly Escherichia coli competent cells.

Effect of gluten-free diet on bone mineral content in growing patients with celiac disease.

Osteoporosis is a complication of celiac disease in adulthood, but little is known about the influence of the disease on bone mineralization in children. In the present study we evaluated radial bone mineral content (BMC) in celiac children and adolescents at diagnosis and after they consumed a gluten-free diet (GFD). The BMC values of 33 celiac patients at diagnosis were significantly lower than those of 255 control subjects (P < 0.001). There was no difference between diabetic and non-diabetic celiac patients. In 14 patients the BMC increased significantly (P < 0.05, ANCOVA) after 1.28 y of GFD. In these patients the mean annual BMC increment was 0.07 g/cm, significantly greater (P < 0.05) than the increment of normal growing children (0.05 g.cm-1.y-1). Our data indicate that although osteoporosis complicates celiac disease during childhood and adolescence, GFD alone is able to remarkably improve bone mineralization.

Bone density in young patients with congenital adrenal hyperplasia.

One of the major complications of glucocorticoid treatment is bone loss. 21-Hydroxylase deficiency is the most frequent inborn error of steroidogenesis, leading to congenital adrenal hyperplasia (CAH): synthesis of cortisol is impaired and replacement therapy is therefore mandatory. We studied the bone mineral density in a group of patients with congenital adrenal hyperplasia (CAH) on long-term glucocorticoid replacement therapy. We selected 30 Caucasian patients with CAH due to 21-hydroxylase deficiency (mean +/- SD age = 17.45 +/- 2.49 years). 22 patients had the classical CAH form and the remaining 8 had the nonclassical (late-onset) form. The mean duration of therapy was 15.20 +/- 4.04 years. Bone mineral density (BMD) was evaluated with a dual-energy X-ray absorptiometer. BMD was also measured in 73 healthy white volunteers of comparable age (17.35 +/- 2.99 years). BMD values of the spine (sBMD), total body (TBBMD), legs, and arms of CAH patients, adjusted for confounding variables (age, gender, body mass index), did not differ from those of control subjects (p = 0.86; p = 0.17; p = 0.06 and p = 0.26, respectively). sBMD and TBBMD values did not show relationships with the duration of treatment and the dose of corticosteroids. Patients with the classical form of CAH had bone density values comparable with those of patients with the nonclassical form (sBMD: p = 0.33; TBBMD: p = 0.97). Our data show that, despite long-term treatment with glucocorticoids, CAH patients have bone density values comparable with controls.

Bone turnover in neonates: changes of urinary excretion rate of collagen type I cross-linked peptides during the first days of life and influence of gestational age.

New markers have been used to monitor the changes of bone turnover occurring during growth. Data on bone turnover rate during the perinatal period are, however, very scarce. In the present study we evaluated bone turnover rate, assessed by the measurement of urinary N-terminal telopeptide of type I collagen (NTx) concentrations, at different gestational ages, and we documented the trend of bone turnover rate occurring in the first days after birth. Urine samples were obtained from 83 healthy full term newborn infants, 16 preterm, and 17 infants of diabetic mothers (IDMs). The first miction after birth was collected. Urine samples were also collected 24 and 48 h after birth. NTx was measured by an enzyme-linked immunosorbent assay (Osteomark, Ostex International, Inc. Seattle, WA). The relationship between NTx at birth and all the other variables has been evaluated using multiple regression analysis. The changes of NTx excretion over time and the effect of the groups were studied by multivariate analysis of variance (MANOVA) for repeated measures. We found a remarkable association between gestational age and NTx concentrations at birth (R = 0.56; p < 0.00001). NTx concentrations showed a progressive decrement, reaching a nadir between the 38th and the 42nd week of gestation. The NTx concentrations changed significantly during the first 48 h of life in the three groups. Moreover, preterm infants had NTx excretion values at birth significantly higher than full term infants (p < 0.001), whereas NTx excretion rates of IDMs were not different from those of the other two groups of subjects. In conclusion, gestational age seems to be the major determinant of bone turnover in neonates; NTx excretion rate is higher before term, it slows in proximity of delivery, and it increases significantly during the first 48 h of life. Preterm infants have higher bone turnover rate than full term infants. NTx excretion rate of IDMs was comparable with those of the control subjects.