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Bluetongue (BT) and Epizootic Hemorrhagic Disease (EHD) are two notifiable animal diseases transmitted to ruminants by small hematophagous midges belonging to the Culicoides genus. The etiological agents, Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV), are both members of the Sedoreoviridae family and Orbivirus genus, which include double-stranded (ds) RNA segmented genomes (10 segments). By the end of the summer 2023, first's outbreaks of EHD were reported from the south west of France, concurrently with unexpectedly severe BT cases in Central France and Corsica. Within a few weeks, numerous BT and EHD outbreaks were recorded with significant sanitary and economic impact on cattle and sheep farms (no sanitary impact of EHD for sheep). Using a customized SISPA approach and the nanopore sequencing technology we successfully recovered genomic sequences from viral isolates and blood samples from infected animals from EHD and BT outbreaks. Three different viruses were responsible for these outbreaks: EHDV-8, BTV-8 and BTV-4. The EHDV-8 strain detected in France corresponded to the strain circulating in Tunisia, Sardinia and Spain since 2021 and 2022. A new BTV-8 strain of unknown origin, clearly different from the enzootic strain circulating in France since 2015, was responsible of the BT outbreaks in domestic ruminants in 2023 on both mainland France and Corsica. A second BTV, BTV-4, also involved in BT outbreaks in Corsica, corresponded to a BTV-4 strain occasionally detected on Corsica island since 2016, suggesting either a new introduction of this strain or a silent circulation on the field. The exceptional nature of orbivirus epizootics in France in 2023, including new introduction, emergence or incursions, raises numerous questions regarding BTV and EHDV dynamics and epidemiology and stresses out the need to identify factors involved in these emergences.

In response to the uncertainty and volatility arising from renewable sources, there is a growing need for enhanced flexibility within the energy system to maintain a continuous balance between power generation and demand. In this context, interest is growing around the so-called Multi-Energy Systems (MES) where different energy vectors coexist and optimally interact through conversion technologies and energy networks, creating additional flexibility opportunities. Nevertheless, there exists a gap in research regarding the impact of the network on flexibility availability. Typically, these complex systems are treated as power nodes or energy hubs without comprehensive network considerations. For this reason, the paper aims to propose a methodology and a tool to evaluate flexibility in a Multi-Energy System, considering not only the individual devices in place and the users' demands but also their interactions with the physical energy network. In detail, a simulation-based methodology is developed and described, and finally tested on a Case Study. As a result, both the physical and operational flexibilities (UP-flex and DOWN-flex) of the system regarding the electrical vector were obtained analytically and graphically. Particular attention was given to the evolution of key temperatures within the district heating network and the thermal power produced by the central unit in various flexibility scenarios. The outcomes demonstrate the utility of this tool for defining flexibility boundaries and profiles, as well as for assessing whether the flexibility demanded by grid operators aligns with the physical constraints of the network.

Epizootic haemorrhagic disease (EHD), caused by the EHD virus (EHDV), is a vector-borne viral disease transmitted through Culicoides biting midges. EHDV comprises seven serotypes (1, 2, and 4–8), with EHDV-8 having recently emerged and spread in Europe over the last two years. Such event has raised concerns about the significant threat posed by EHDV-8 to livestock industry. In this study, an inactivated vaccine against EHDV-8 (vEHDV8-IZSAM) was developed. Safety and efficacy of the vaccine were evaluated in calves through clinical, serological, and virological monitoring following experimental challenge.The vaccine was proven safe, with only transient fever and localized reactions observed in a few animals, consistent with adjuvanted vaccine side effects. vEHDV8-IZSAM elicited a robust humoral response, as evidenced by the presence of neutralizing antibodies. After challenge with a virulent isolate, viraemia and clinical signs were evidenced in control animals but in none of the vaccinated animals.This study highlights the potential of vEHDV8-IZSAM as a safe and highly effective vaccine against EHDV-8 in cattle. It offers protection from clinical disease and effectively prevents viraemia. With the recent spread of EHDV-8 in European livestock, the use of an inactivated vaccine could be key in protecting animals from clinical disease and thus to mitigate the economic impact of the disease. Further investigations are warranted to assess the duration of the induced immunity and the applicability of this vaccine in real-world settings. Accordingly, joint efforts between public veterinary institutions and pharmaceutical companies are recommended to scale up vaccine production.

In this paper we describe the validation of a focus reduction neutralization test (FRNT) to quantitate human SARS-CoV-2 neutralizing antibodies by using the CTL Immunospot S6 Universal Analyzer. We employed a previously published protocol and compared its performances to a well-established and traditional serum-neutralization assay (SN). To assess diagnostic sensitivity, a total number of 201 human sera positive by SN for SARS-CoV-2 NAbs were processed: 196/201 tested positive by FRNT50 (97.51 %). A diagnostic specificity of 100 % was obtained by evaluating 206 negative serum samples. Repeatability of the test was evaluated by determining the intra and inter-assay coefficient of variation (CV). A standard deviation of 0.83 and a CV of 13 % were evidenced demonstrating an acceptable reproducibility of the assay. Moreover, a Cohen's Kappa of 0.975 was obtained proving an extremely high level of agreement between the FRNT protocol and the SN. Despite an acceptable correlation between methods (p

The present study gathers mineralogical and isotopic geochemical data of 45 soil samples collected from the La Guardiense and Cantina di Solopaca wineries (Southern Italy) in order to provide useful information for the geotraceability of Falanghina white wine terroir. Mineralogical analyses show the ubiquitous presence of quartz, frequent and moderate contents of feldspars and phyllosilicates (i.e., illite/mica, kaolinite, and smectite). Rhizosphere soils from La Guardiense vineyards show a strontium isotope signature (87Sr/86Sr) ranging from 0.708604 to 0.711234 (average 0.710334; 1σ = 0.000943; n = 7) for the total fraction and a narrower range (from 0.706907 to 0.708807; average 0.708120; 1σ = 0.000641; n = 7) for the bioavailable one. For the rhizosphere soils collected from the vineyards of Cantina di Solopaca winery, 87Sr/86Sr ratios range from 0.708268 to 0.712413 (average 0.710145; 1σ = 0.001622; n = 8) and from 0.707968 to 0.709157 (average 0.708384; 1σ = 0.000409; n = 8) for the total and the bioavailable fraction, respectively. Actually, the bioavailable Sr fraction shows a narrower range of 87Sr/86Sr ratios compared to that of the total fraction, making the former more suitable for any study of wine traceability.

Objective: Canine distemper virus (CDV) is a highly infectious virus that represents a threat for domestic dogs and several wild species. Despite recognized in several African countries, current knowledge of its molecular epidemiology is scarce and poorly updated. Design: Twenty-two hemagglutinin sequences, obtained from symptomatic Namibian dogs from 2020 to 2023, were analysed through phylogenetic and phylodynamic analysis to characterize the local CDV epidemiology and contextualize it in the international scenario. Results: Two unrelated clades were identified, including strains sampled in different Namibian towns, in the absence of a strong geographical clustering. The ancestors of the two clades were estimated to have originated from South America, likely Brazil, and South Africa, approximately in 2000 and 2006, respectively. While the introduction from South Africa was predictable, the introduction from Brazil was unexpected. The mediation of other African countries, particularly Angola, appears to be the most likely importation pathway. Conclusions: The occurrence of multiple introduction events, likely originating from cross-border illegal animal trade between African countries, and the absence of any geographical clustering within Namibian regions, suggest a need for further investigation into its spreading pattern, as well as improved biosecurity measures to limit foreign viral introduction into the country.

The emergence of SARS-CoV-2 variants has led to several cases among children. However, limited information is available from North African countries. This study describes the SARS-CoV-2 strains circulating in Tunisian pediatric population during successive waves. A total of 447 complete sequences were obtained from individuals aged from 13 days to 18 years, between March 2020 and September 2022: 369 sequences generated during this study and 78 ones, available in GISAID, previously obtained from Tunisian pediatric patients. These sequences were compared with 354 and 274 ones obtained from Tunisian adults and a global dataset, respectively. The variant circulation dynamics of predominant variants were investigated during the study period using maximum-likelihood phylogenetic analysis. Among the studied population, adolescents were the predominant age group, comprising 55.26% of cases. Twenty-three lineages were identified; seven of which were not previously reported in Tunisia. Phylogenetic analysis showed a close relationship between the sequences from Tunisian adults and children. The connections of sequences from other countries were variable according to variants: close relationships were observed for Alpha, B1.160 and Omicron variants, while independent Tunisian clusters were observed for Delta and B.1.177 lineages. These findings highlight the pivotal role of children in virus transmission and underscore the impact of vaccination on virus spread. Vaccination of children, with booster doses, may be considered for better management of future emergences.

Open storage yards at industrial sites represent a significant fugitive dust emission source. Granular material subjected to wind erosion may emit significant dust into the atmosphere. Several windbreaks and fences with different shapes have been proposed to control and reduce those emissions. Solid fences are commonly erected around the open yard (i.e., open bays) to prevent and reduce those emissions, even though they have some limitations. The present study aims to enhance the effectiveness of solid fences by coupling them with dynamic wind deflectors. Computational fluid dynamics was employed to simulate the flow and shear stresses on storage pile surfaces using the numerical Reynolds-averaged Navier–Stokes equations and the k-ω SST turbulence model. At the same time, dust emission was estimated using an Environmental Protection Agency (EPA) method, which estimates the emission potential of a material based on the wind friction velocity and the material's threshold friction velocity. The numerical model was validated against experimental data from an EPA study. In addition, this study investigated the efficiency of various dynamic wind deflectors with different heights and inclination angles. The results showed that most of the investigated dynamic fence-deflector models reduced the velocity magnitude, vortices, and turbulence intensity, lessening the impact of shear stresses compared to single solid fences and consequently reducing the emission of dust from the exposed surfaces (i.e., a primary measure of impact reduction). More specifically, the deflector of width (Ydef) 2 m with an inclination of (∅def) 65° was the most effective, where the shear stress on the pile surface and the emission factor were reduced by 29.16% and 21.79%, respectively, compared to the single fence of the same height. Finally, adding dynamic wind deflectors enhances the performance of solid fences, and it is a more effective and less expensive solution than replacing single fences with other windbreak models.

Within public health control strategies for SARS-CoV-2, whole genome sequencing (WGS) is essential for tracking viral spread and monitoring the emergence of variants which may impair the effectiveness of vaccines, diagnostic methods, and therapeutics. In this manuscript different strategies for SARS-CoV-2 WGS including metagenomic shotgun (SG), library enrichment by myBaits® Expert Virus-SARS-CoV-2 (Arbor Biosciences), nCoV-2019 sequencing protocol, ampliseq approach by Swift Amplicon® SARS-CoV-2 Panel kit (Swift Biosciences), and Illumina COVIDSeq Test (Illumina Inc.), were evaluated in order to identify the best approach in terms of results, labour, and costs. The analysis revealed that Illumina COVIDSeq Test (Illumina Inc.) is the best choice for a cost-effective, time-consuming production of consensus sequences.

The primary goal of this project is to create a framework to extract Real-World Evidence to support Health Technology Assessment, Health Technology Management, Evidence-Based Maintenance, and Post Market Surveillance (as outlined in the EU Medical Device Regulation 2017/745) of medical devices using Natural Language Processing (NLP) and Artificial Intelligence. An initial literature review on Spontaneous Reporting System databases, Health Information Technologies (HIT) fault classification, and Natural Language Processing has been conducted, from which it clearly emerges that adverse events related to HIT are increasing over time. The proposed framework uses NLP techniques and Explainable Artificial Intelligence models to automatically identify HIT-related adverse event reports. The designed model employs a pre-trained version of ClinicalBERT that has been fine-tuned and tested on 3,075 adverse event reports extracted from the FDA MAUDE database and manually labelled by experts.

From 24 December 2020 to 8 February 2021, 163 cases of SARS-CoV-2 Alpha variant of concern (VOC) were identified in Chieti province, Abruzzo region. Epidemiological data allowed the identification of 14 epi-clusters. With one exception, all the epi-clusters were linked to the town of Guardiagrele: 149 contacts formed the network, two-thirds of which were referred to the family/friends context. Real data were then used to estimate transmission parameters. According to our method, the calculated Re(t) was higher than 2 before the 12 December 2020. Similar values were obtained from other studies considering Alpha VOC. Italian sequence data were combined with a random subset of sequences obtained from the GISAID database. Genomic analysis showed close identity between the sequences from Guardiagrele, forming one distinct clade. This would suggest one or limited unspecified viral introductions from outside to Abruzzo region in early December 2020, which led to the diffusion of Alpha VOC in Guardiagrele and in neighbouring municipalities, with very limited inter-regional mixing.

Objective: The TackSHS project aims to comprehensively elucidate the impact that exposure to second-hand smoke (SHS) from cigarettes and second-hand aerosols (SHA) from electronic cigarettes have on the respiratory health of the European population according to socioeconomic characteristics and other determinants. Method: The TackSHS project involves a series of coordinated studies carried out by 11 academic and public health organisations from six European countries. The project will investigate: a) the determinants of SHS and SHA exposure assessed at the individual level (surveys on representative general population samples) and in common environments (environmental sampling in specific settings); b) the overall disease burden, mortality and morbidity attributable to such exposure; and c) its economic impact in terms of direct health care costs. The project will also examine specific acute respiratory health changes in healthy individuals and patients with respiratory diseases exposed to SHS and SHA. In addition, the project will examine the effectiveness of a novel intervention to reduce SHS exposure in households where smoking is permitted. All these studies are inter-related and involve collaborative coordination among the participant organisations. Conclusion: The comprehensive, integrated approach of the TackSHS project will enable a significant step forward from the current status quo in the understanding of the impact of SHS and SHA exposure on health and provide the basis for health policy recommendations to help European countries to further reduce the harm caused by SHS and SHA exposure. Resumen: Objetivo: El proyecto TackSHS pretende caracterizar el impacto global de la exposición al humo ambiental de tabaco (HAT) y al aerosol de los cigarrillos electrónicos (ACE) en la salud respiratoria de la población europea según variables socioeconómicas y otros determinantes. Método: El proyecto TackSHS consiste en una serie de estudios coordinados y gestionados por 11 organizaciones académicas y de salud pública de seis países europeos. El proyecto estudiará: a) los determinantes de la exposición al HAT y al ACE a nivel individual (encuestas en muestras representativas de la población general) y en espacios comunes (muestras ambientales en lugares específicos); b) su carga general de enfermedad y la morbimortalidad atribuible a tal exposición; y c) su impacto económico en términos de costes sanitarios directos e indirectos. Además, el proyecto investigará cambios específicos a corto plazo en la salud respiratoria en personas sanas y en pacientes con enfermedades respiratorias expuestos al HAT y al ACE. También examinará la efectividad de una intervención novedosa para reducir la exposición al HAT en hogares donde se permite fumar. Todos estos estudios están interrelacionados y conllevan una coordinación colaborativa entre las instituciones participantes. Conclusión: El enfoque integral del proyecto TackSHS permitirá un avance significativo en la evidencia sobre la comprensión del impacto de la exposición al HAT y al ACE en la salud, y proporcionará una base para desarrollar recomendaciones políticas sanitarias para ayudar a los países europeos a reducir los daños causados por la exposición al HAT y al ACE. Keywords: Second-hand smoke, Passive smoking, Electronic cigarette, Electronic nicotine delivery systems, Aerosols, Second-hand aerosols, Respiratory health, Burden of disease, Economic impact, Palabras clave: Humo ambiental del tabaco, Tabaquismo pasivo, Cigarrillos electrónicos, Sistemas electrónicos de administración de nicotina, Exposición al aerosol, Salud respiratoria, Carga de enfermedad, Impacto económico

Introduction: A precise knowledge of the possible Adverse Events (AEs) related to spinal surgical procedures is crucial in clinical practice. Research Question: Purposes of this study are: to determine the prevalence and severity of perioperative AEs associated with pediatric and adult spine surgery in a high volume center; to estimate the impact of perioperative AEs on length of hospital stay (LOS). Material and Methods: This is a prospective, observational, monocenter study, including 346 consecutive patients (294 adults and 52 pediatrics). The SAVES-V2 questionnaire was used to record AEs. The form was updated by the medical staff every time an adverse event was recorded during hospitalization. Results: 21,2% of pediatric patients and 20,7% of adults had at least 1 perioperative AEs. In adults, dural tear (3.1%) and neuropathic pain (4,8%), were the most frequent intraoperative and postoperative AE, respectively. In pediatric patients, neurologic deterioration was the most frequent postoperative AE. A diagnosis of deformity (p=0.01), an ASA grade equal or superior to 3 (p=0.023) and the procedure ‘Posterior Spinal Fusion’ (p=0.001) were associated with a higher frequency of AEs. AEs required prolonged LOS in 40 cases, 7 (70%) pediatric patients and 33 (65%) adults. Discussion and Conclusion: The overall prevalence of AEs is 20.8%, and, although the distribution is almost equal between adult and pediatric patients, their severity is related to age, being higher in pediatric patients. Deformities, deformity correction, revision surgery and AP surgery are the most impactful factors. AEs seriously affect hospitalization, with prolonged LOS (mean 6 days).

• Following the announcement on December 2020 about the emergence of a new variant (VOC 202012/01, B.1.1.7 lineage) in the United Kingdom, a targeted surveillance was put in place in the Abruzzo region (Italy), which allowed detection of 313 persons affected by lineage B.1.1.7, up to the 20th of February 2021. We investigated the results of RT-PCR on nasopharyngeal swabs tested from December 2020 to February 2021 to verify any difference on the viral load and persistence between people infected by lineage B.1.1.7 and others. Statistically significant lower values of CT associated with the detection of the N protein encoding gene (CT N) were observed in persons with lineage B.1.1.7 infection (median CT N = 15.8) in comparison to those infected by other lineages (median CT N = 16.9). A significantly longer duration of the persistence of SARS-CoV-2 RNA in nasopharyngeal swabs was observed in persons with lineage B.1.1.7 infection (16 days) in comparison to those infected by other lineages (14 days).

The present article provides chemical, paleontological and mineralogical data obtained during an archaeometric characterization of 40 samples (33 pottery sherds, 5 clay samples, 1 sand sample and 1 red earth pigment) collected in the Via dei Sepolcri ceramic workshop in Pompeii, Italy. The workshop was still active during the 79 CE eruption of Mt. Vesuvius and the archaeometric data obtained in our investigation reveal distinct differences between pottery and geological raw materials belonging to an early 'Phase 1′ production (from the beginning of the 1st century CE to the 62 CE earthquake) and a subsequent 'Phase 2′ production (from the 62 CE earthquake to the 79 CE eruption). These data inform the discussions and interpretations presented in the article entitled “A pottery workshop in Pompeii unveils new insights on the Roman ceramics crafting tradition and raw materials trade”, edited by Grifa et al. [1].

The current pandemic is caused by a novel coronavirus (CoV) called SARS-CoV-2 (species Severe acute respiratory syndrome-related coronavirus, subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae). In Italy, up to the 2nd of April 2020, overall 139,422 confirmed cases and 17,669 deaths have been notified, while 26,491 people have recovered. Besides the overloading of hospitals, another issue to face was the capacity to perform thousands of tests per day. In this perspective, to support the National Health Care System and to minimize the impact of this rapidly spreading virus, the Italian Ministry of Health involved the Istituti Zooprofilattici Sperimentali (IZSs), Veterinary Public Health Institutes, in the diagnosis of SARS-CoV-2 by testing human samples. The Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise is currently testing more than 600 samples per day and performing whole genome sequencing from positive samples. Sequence analysis of these samples suggested that different viral variants may be circulating in Italy, and so in Abruzzo region. CoVs, and related diseases, are well known to veterinarians since decades. The experience that veterinarians operating within the Public Health system gained in the control and characterization of previous health issues of livestock and poultry including avian flu, bluetongue, foot and mouth disease, responsible for huge economic losses, is certainly of great help to minimize the impact of this global crisis.

Background: Tuberculosis (TB) remains a Global Health challenge, with diagnostic delays contributing significantly to its spread. This study investigates the differences in diagnostic delays between native and migrant TB patients in Italy, examining patient-related diagnostic delay (PDD), health system-related diagnostic delay (HDD), and total diagnostic delay (TDD)., Methods: We conducted a retrospective, multicenter, cross-sectional study of TB cases in 10 Italian hospitals from 2018 to 2023. We compared PDD, HDD, and TDD between native and migrant populations. Socio-demographic data and clinical histories were analyzed to identify factors contributing to diagnostic delays., Results: We included 669 TB patients (390 migrants and 279 natives). Migrants experienced significantly longer PDD (median 90 vs 10 days, P < 0.0001) but shorter HDD (median 5 vs 40 days, P < 0.0001) compared to natives, resulting in a longer TDD (median 96 vs 65 days, P < 0.0001). Furthermore, migrants had higher Timika scores, longer sputum conversion times, and were more frequently lost to follow-up., Conclusion: Migrants face longer PDD, emphasizing substantial barriers to healthcare access. Natives experience longer HDD, reflecting neglect of TB in low-endemic regions. Future research should focus on the impact of social determinants and training for healthcare providers on TB diagnosis and develop strategies to reduce diagnostic delays., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: We investigated perceived invalidating environment during childhood and stress-coping strategies in patients with; functional dissociative seizures (FDS, n=26), drug-resistant epilepsy patients with no psychiatric comorbidity (DREnc, n=23), and drug-resistant epilepsy patients with psychiatric comorbidity (DREpc, n=34)., Design/methods: We performed a cross-sectional study. Patients underwent Video Electroencephalography to confirm the diagnosis and completed a psychiatric assessment supported by clinical instruments. Invalidating environment and stress coping were studied through the ICES and CAE questionaries, respectively. A series of multinomial logistic regression analyses were performed with the explored variables., Results: The maternal negative response model predicted a higher probability of FDS condition. A chaotic family type increased the likelihood of DREpc instead of FDS. DREpc and FDS patients displayed many different behaviors to cope with stress other than trying to solve the problem, the most used strategy in the DREnc group. Parental invalidation was higher in DREpc than in FDS., Conclusions: Our results deepen the data provided by previous studies indicating that multiple variables of biosocial origin have significant effects on these groups of patients. The presence of an invalidating environment may predict FDS but also the presence of psychiatric disorders among DRE. Psychotherapeutic strategies to enhance these variables might be necessary for this population., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Relevant ethical guidelines regulating research involving human participants were followed throughout the project. All data collection, storage, and processing were done in compliance with the Helsinki Declaration. The authors have no disclosures that could be interpreted as conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Depression and anxiety are psychiatric disorders related to chronic stress, commonly found in patients with drug-resistant epilepsy (DRE) and functional dissociative seizures (FDS). The present study compares the levels of perceived stress, resilience, and the styles of stress coping among patients with DRE (n=60), FDS (n=28), and controls (n=31)., Methods: We performed a cross-sectional study. All patients underwent Video Electroencephalography to confirm the diagnosis and completed the psychiatric assessment (SCID I and II of DSM IV) supported by several instruments validated in Spanish., Results: FDS scored higher in perceived stress (p = 0.004) with lower levels of resilience compared to controls (p = 0.01). Stress coping subscales show higher scores in negative self-focus and hostility in patients with FDS compared to controls (p=0.003). Similarly, DRE patients scored higher in perceived stress (p = 0.001), and presented lower levels of resilience (p = 0.004) with higher levels of hostility compared to controls (p=0.02). However, no significant differences were found between FDS and DRE on stress coping variables. Anxiety scores and depression rates were higher in the FDS group compared to DRE (p=0.008) and higher in DRE compared to controls (p<0.05). A positive correlation between depression and perceived stress was found (r = 0.6, p=0.0001)., Conclusions: Our results delineate a more detailed picture of the psychological profile of this population, emphasizing the importance of stress factors in patients with FDS and DRE. Combined intervention strategies which enhance stress coping may be appropriate to direct treatment and psychotherapy., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Relevant ethical guidelines regulating research involving human participants were followed throughout the project. All data collection, storage, and processing were done in compliance with the Helsinki Declaration. The authors have no disclosures that could be interpreted as conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: In the present study we evaluated the efficacy of an innovative model of HCV micro-elimination in a hospital setting in an area of high HCV prevalence., Patients and Metods: Between January and December 2019, a prospective, interventional study for a program of HCV case-finding and linkage-to-care was performed in S. Anna and S. Sebastiano hospital of Caserta, in Campania, a region in southern Italy. All adult patients who were admitted to the Caserta hospital in the study period and resulted positive for anti-HCV were included in the study. The outcomes evaluated were the number of subjects resulting HCV-RNA-positive, those linked-to-care and treated with a DAA and the subjects whose anti-HCV-status was unknown., Results: In the study period, 14,396 subjects, admitted to the hospital for different reasons, were tested for anti-HCV: 529 (3.7%) subjects resulted positive for anti-HCV. Of the 529 anti-HCV-positive subjects, 10 died during hospitalization and 243 were already treated with a DAA. The remaining 276 subjects were contacted and agreed to be evaluated. Of these 276 subjects, 68 patients resulted HCV- RNA-negative and 194 HCV-RNA-positive and 180 of these were treated with a DAA according to the international guidelines., Discussion: A simple, rapid, inexpensive model of HCV micro-elimination in the hospital setting allowed us to find anti-HCV-positive subjects with unknown anti-HCV status or not linked to a clinical center., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Psychiatric disorders are frequently found in both patients with PNES and DRE, making the differential diagnosis even more complex. The aim of this study was to analyze and compare psychiatric aspects and the quality of life in patients with psychogenic non-epileptic seizures (PNES) and drug resistant epilepsy (DRE)., Methods: Patients admitted to video-electroencephalograpy (VEEG) unit with confirmed PNES and DRE were included. Demographical characteristics, psychiatric diagnosis according to SCID I and II of DSM IV, pharmacological treatment, general functioning measured with GAF (Global assessment of functionality), quality of life (QoL) using QlesQSF (Quality of Life Enjoyment and Satisfaction Questionnaire Short Form) and depression severity using BDI II (Beck depression inventory), were compared between the groups. Non-parametric tests, chi square test, and logistic regression were used for statistical analysis., Results: 148 patients consecutively admitted to VEEG were included (DRE n = 97; PNES n = 51). Somatization disorder (RR: 13.02, 95% CI: 1.23-137.39, p = 0.03) and a history of trauma (RR: 8.66, 95% CI: 3.21-23.31, p = 0.001) were associated with PNES. The QlesQ score and the GAF score were lower with a higher prevalence of suicide attempts in the PNES group (p < 0.01). A negative correlation was observed between the severity of depression and the quality of life (DRE r = - 0.28, p = 0.013; PNES r = - 0.59, p = 0.001)., Conclusions: Higher psychiatric comorbidity with poorer QoL were found in PNES patients compared to DRE. However, depression comorbidity negatively affected the QoL in both groups. Future studies based on illness perception will be orientated to complete this analysis., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: The aim of this study is to explore explanatory models (EM) about epilepsy in patients with drug-resistant epilepsy (DRE) in Buenos Aires, Argentina., Design: A qualitative approach gathered data through semi-structured interviews, oriented to gain an in-depth and contextual understanding of EM about epilepsy of patients with DRE. Data collection and analysis were followed by an inductive and interpretive approach informed by the principles of thematic analysis., Results: 75 patients from two public hospitals participated. Emerging codes were grouped into three categories: Biomedical EM, Psychosocial EM, and Traditional EM. Also, factors that trigger or increase the frequency of seizures were reported., Conclusions: Patients' EM regarding epilepsy are complex, as biological, psychological, and supernatural aspects intertwine. EM represent a method of understanding the way people explain, recognize, and act in relation to a medical condition. Since patients' beliefs regarding their illness are related to mental disorders, and quality of life, EM could shed light on the real impact of illness in the life of people, and, in turn, guide those intervention strategies to the patients' subjectivity, in order to improve the treatment compliance, reduce distress, and improve health-related quality of life, among other aspects., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: A growing amount of evidence suggests that the rifampicin dosing currently recommended for tuberculosis treatment could be associated with inadequate exposure and unfavourable outcomes. We aimed to compare clinical and microbiological efficacy and safety outcomes of standard and higher rifampicin dosing., Methods: Data sources were MEDLINE, Google Scholar and the Cochrane Library. This was a systematic review and meta-analysis that included experimental or observational studies comparing 8-week sputum culture conversion, treatment failure, or safety outcomes in naïve patients with pulmonary tuberculosis treated with standard (10 mg/kg) or higher doses of rifampicin., Results: Of a total of 9683 citations screened, eight randomized controlled trials were included, accounting for 1897 subjects; the risk of bias was low in three studies, high in two and intermediate in three. At week 8 a higher proportion of patients in the high-dose group obtained a sputum culture conversion than those in the standard dose group (83.7% versus 80.6%, RR 1.06; 95%CI 1.01-1.12, p 0.028); this result was confirmed in the sub-analysis including patients treated with a rifampicin dose of ≥20 mg/kg, but not in those treated with 11-19 mg/kg. Events of treatment failure at end of treatment showed no significant difference between the two groups (RR 0.84; 95%CI 0.59-1.21, p 0.362). In the analysis evaluating safety outcome, the difference in the occurrence of a grade 3 or 4 liver toxicity or adverse drug reactions leading to discontinuation was not significant at the statistical analysis among the groups (7.2% versus 5.4%, RR 1.19; 95%CI 0.81-1.73, p 0.370, and 1.5% versus 0.6%, RR 2.31; 95%CI 0.65-8.21, p 0.195, respectively). No statistical heterogeneity among studies was observed for each outcome., Conclusions: High doses of rifampicin were associated with an increased rate of sputum culture conversion at 8 weeks of treatment, particularly in patients receiving ≥20 mg/kg., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To examine the effects of a three-session psychoeducational intervention on patients diagnosed with psychogenic non-epileptic seizures (PNES) in an Argentinian public hospital. It was hypothesized that patients would experience improvements in their understanding of PNES, illness perception and affective scores, but might not necessarily experience a significant change in post-traumatic and dissociative symptoms and in seizure frequency., Methods: This study included 12 patients (10 women, 2 men) who were invited to participate in a psychoeducational group after receiving a V-EEG confirmed diagnosis of PNES. The group consisted of 3 sessions lasting 2 h each. Pre and post measures included Psychoeducational Intervention Questionnaire, State-Trait Anxiety Inventory, Beck Depression Inventory-II, Brief Illness Perception Questionnaire, Posttraumatic Stress Disorder Diagnostic Scale 5, Dissociative Experiences Scale (DES-M)., Results: This psychoeducational intervention produced results that were similar to interventions reported in US and European studies with regard to changes on psychological measures. Moreover, many patients also reported (on the final day of the intervention) a decrease in seizure frequency. All patients reported that participating in the intervention was a positive experience. Also, all but one patient referred that the participation in the group would have a positive impact on their quality of life., Conclusions: Psychoeducational interventions appear to have had positive results in Argentinian patients with PNES. This is initial step in the design of empirically based psychoeducational/supportive initiatives for patients in South America., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: We compared various clinical characteristics of pediatric-onset psychogenic nonepileptic seizures (PNES) between patients from five countries. The purpose of this study was to advance our understanding of pediatric-onset PNES cross-culturally., Methods: In this retrospective study, we compared consecutive patients with PNES with an age at onset of 16 years and younger from epilepsy monitoring units in Iran, Brazil, the USA, Canada, and Venezuela. Age, gender, age at seizure onset, seizure semiology, predisposing factors, and video-EEG recordings of all patients were extracted. Pearson Chi-Square, one-way ANOVA and Bonferroni correction tests were used for statistical analyses., Results: Two hundred twenty-nine patients were studied (83 from Iran, 50 from Brazil, 39 from Canada, 30 from the USA, and 27 from Venezuela). Mean age at the onset of seizures was 12.1 ± 3.2 years (range: 4-16 years). The sex ratio of the patients was 1.83: 1 (148 females and 81 males). Clinical characteristics of pediatric-onset PNES showed some significant differences among the nations. However, factors associated with pediatric-onset PNES in these five nations were similar., Conclusion: This study underscores how international cross-cultural studies can make important contributions to our understanding of PNES. Patients with pediatric-onset PNES from different countries were similar on many risk factors associated with PNES. This suggests universality in many features of PNES. However, intriguing differences were also noted with regard to seizure semiology, which might be the result of cultural factors., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To understand the experience of drug-resistant epilepsy in patients from Argentina, a developing nation., Method: A qualitative approach using semi-structured interviews was used to gain an in-depth and contextual understanding of the perspectives of 20 patients with DRE. Data collection and analysis were followed by an inductive and interpretive approach informed by the principles of thematic analysis., Results: Six main themes emerged: 1) Characteristics of the illness, including seizure features -unpredictability, presence of auras, physical and cognitive consequences- and how patients relate with the use of antiepileptic drugs; 2) interactions with health system, regarding the features of the Argentine's health system, and patient's health-seeking behaviours; 3) beliefs about the illness, including psychosocial, biological and folk explanatory models; 4) beliefs about how other people perceive them, which included prejudice, responsibility and overprotection; 5) self-perception, and 6) impact of the illness on their activities., Conclusions: This information might be useful to help in the development of a conceptual model of the impact epilepsy on patients' lives. Many of the topics mentioned as relevant in Argentina coincide with those highlighted in studies that were carried out in first-world countries. However, additional topics were also reported including the role of traditional healing in health-seeking behaviour and explanatory models of illness. It is important to understand these perspectives to develop appropriate psychosocial interventions for this specific population., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Calcific aortic valve disease (CAVD) is the most common valvular disorder in the elderly, with the incidence of 3% in general population of Western countries. The initial phase of CAVD is characterized by leaflet thickening and possible spotty calcification (i.e. aortic valve sclerosis (AVSc)), while advanced stages have leaflets structure degeneration (i.e. aortic valve stenosis (AS)). The pathological cellular and molecular mechanisms, involved in CAVD, are extracellular matrix degradation, aberrant matrix deposition, fibrosis, mineralization, inflammation, lipid accumulation, and neo-angiogenesis. CAVD clinical risk shares considerable overlap with those of atherosclerosis and they include hypertension, smoking habits, and hyperlipidemia. Unfortunately, surgical aortic valve replacement and transcatheter aortic valve implantation are the only available treatments when the disease become severe and symptoms occur. Indeed, no approved pharmacological approach is available for CAVD patients. In this review, we describe the current literature evidence on possible future therapeutic targets for this debilitating and fatal disease such as PCSK9, P2Y2 receptor, cadherin 11, and DDP-4., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To analyse the methods of reasoning with regard to patients' experiences of living with psychogenic nonepileptic seizures (PNES) in Buenos Aires, Argentina., Method: A qualitative approach using semi-structured interviews was used to gain an in-depth and contextual understanding of the perspectives of five patients with PNES. Data collection and analysis were followed by an inductive and interpretive approach informed by the principles of thematic analysis., Results: Explanatory models and prototypes were identified from the patients' narratives. Four patients related their suffering regarding psychosocial causes -family conflicts, sexual harassment, and life changes, among others-. Hereditary and organic hypotheses appeared to be unspecific. Folk explanations were common to all participants (magic, witchcraft, energetic causes). Four patients used the term epilepsy as an illness prototype, focusing on seizures and the use of antiepileptic drugs. Three of them also compared their illness to other people's "attacks" (heart attacks, panic attacks, nervous breakdown). Only one of them referred to someone who was suspected of having epilepsy., Conclusion: Patients' psychosocial explanatory models are different from the results of previous studies because these studies indicate that most patients support somatic explanations. Patients also use folk explanations related to traditional medicine, which highlights the interpersonal aspects of the disease. Doctor-patient communication is essential for a correct understanding of PNES, resulting in better outcomes. It could also help to reduce the cultural distance between professionals and patients, leading to narrowing inequalities present in multicultural healthcare services., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Granule cells pathology in dentate gyrus, have received considerable attention in terms of understanding the pathophysiology of temporal lobe epilepsy with hippocampal sclerosis. The aim of this study was to determine the nestin (an intermediate filament protein expressed by newly formed cells), immunoreactivity (IR) in granular cells layers of hippocampal tissue extirpated during epilepsy surgical procedure, in patients with drug-resistant epilepsy., Methods: Hippocampal sections of 16 patients with hippocampal sclerosis and drug-resistant temporal lobe epilepsy were processed using immunoperoxidase with antibody to nestin. Archival material from 8 normal post-mortem hippocampus, were simultaneously processed. Reactive area for nestin-IR, the total number of positive nestin cells per field (20×), and the MGV (mean gray value) was determined by computerized image analysis (ImageJ), and compared between groups. Student's t test was used for statistical analysis., Results: Nestin-IR cells were found in granule cells layers of both controls and patients. Larger reactive somas (p < 0.01) were found in epileptic's sections but a significant reduction in the total number of nestin-IR cells per field and in the MGV was found in granular cells layers of patients with hippocampal sclerosis (p < 0.01)., Conclusion: Reduced expression of nestin-IR in granular cells layers of epileptic's dentate gyrus may reflect changes in dentate gyrus neuroplasticity associated to chronic temporal epilepsy with hippocampal sclerosis. Further studies are required to determine the clinical implications on memory an emotional alterations such as depression., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

To identify early predictors of a severe or fulminant course in patients with acute viral hepatitis B (AVH-B). One hundred and thirty-eight patients with symptomatic acute hepatitis B observed from 1999 to 2012 were enrolled. For each patient, the demographics, risk factors for the acquisition of hepatitis B virus (HBV) infection, clinical, biochemical and virological data (HBV DNA, HBV DNA sequences) were recorded and analysed. The HBV mutants in the polymerase region were sought in 110 (87%) patients by direct sequencing, and the rtM204V/I mutations also by an allele-specific PCR. AVH-B was severe in 13 (9.4%) of the 138 patients enrolled, fulminant in 6 (4.3%) and with a normal clinical course in 119. The 19 patients with severe or fulminant AVH-B more frequently than the 119 with a normal course stated intravenous drug use (63.2% versus 36.1%, p 0.04) and were HBV-DNA negative (31.6% versus 11.8%, p 0.03) and anti-hepatitis C virus (HCV) positive (57.9% versus 19.3%, p 0.0008); the prevalences of different HBV genotypes and of the rtM204V/I mutant were similar in these three forms of AVH-B. A multivariate logistic regression analysis identified a pre-existing HCV chronic infection as the only factor independently associated with a severe or fulminant clinical course of AVH-B (OR 4.89, 95% CI 1.5-15.94, p 0.01). A pre-existing HCV chronic infection was identified as the only factor independently associated with a severe clinical presentation of acute hepatitis B, an association most probably due to the combination of the liver lesions caused by acute hepatitis B and the pre-existing histological abnormalities related to HCV chronic infection., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Objective: To describe clinical features of epilepsy secondary to Malformation of Cortical Development (MCD) in a series of adult patients., Materials and Methods: We searched our database for all cases with confirmed epilepsy and MCD and included in the study only those with complete data. Mean age, sex, age at seizure onset (ASO), seizure types, abnormal neurological exam (ANE), mental retardation, family history, gestational or perinatal insults (G-PI), interictal EEG and response to treatment were analyzed. Cases were classified into the 3 main groups (G) according to the Barkovich classification (BC) and then compared: (G1) "malformations due to abnormal cell proliferation", (G2) "malformations due to abnormal migration" and (G3) "malformations due to abnormal cortical organization"., Results: We identified 152 (5.06%) patients with MCD from a total of 3000 with epilepsy. In total, 138 patients with complete medical data were included in this study. The mean age of patients was 36.2 years, 52.2% were female, the mean ASO was 12.3 years, 5.1% of cases had a positive family history and 21% had G-PI. An ANE was observed in 21% and mental retardation in 31.9%. Most of the patients (84.8%) had refractory epilepsy. The distribution of cases according to the BC was: 51.4% in G1, 28.9% in G2 and 19.6% in G3. Comparing the 3 groups, we found that an ANE was statistically more frequent in G3 and was present in 70.4% of cases., Conclusion: Our series of adult patients with epilepsy and MCD suggests that MCD are identified as commonly in a developing country as in previous "first world" series. Neurological deficits were more common in the subgroup of patients with polymicrogyria and schizencephaly (BC Group 3)., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Status epilepticus increases the production of new neurons (hippocampal neurogenesis) and promotes aberrant migration. However chronic experimental models of epilepsy and studies performed in human epilepsy showed controversial results suggesting a reduction in hippocampal neurogenesis in late stages of the disease. Doublecortin (DCX) has been validated to determine alterations in the production of new neurons in the human hippocampus., Objectives: Determine DCX expression in human hippocampal sclerosis (HS) from patients who underwent epilepsy surgery for refractory temporal lobe epilepsy (TLE)., Methods: Hippocampal sections of 9 patients with HS and TLE who underwent surgery, were processed using immunoperoxidase for DCX. Archival material from 5 normal post-mortem hippocampus were simultaneously processed., Results: Significantly lower staining intensity was observed in DCX-positive neurons localized in dentate gyrus (DG) and in CA1 of epileptic hippocampus; lower DCX reactive area was observed in pyramidal layers of CA1; and a reduced in the mean number of DCX-positive neurons were determined in DG compared to normal hippocampus (p<0.05)., Conclusions: This study found a decrease in DCX expression in hippocampus of patients with HS and chronic and refractory TLE suggesting alterations in NG and hippocampal synaptogenesis with potential cognitive and emotional repercussion., (Published by Elsevier Ltd.)

Purpose: The aim of this study is to describe similarities and differences in epidemiological, psychiatric and semiologic variables between patients with psychogenic none epileptic seizures (PNES) and comorbid epilepsy (mixed PNES), and patients with PNES without comorbid epilepsy (pure PNES)., Results: Forty-three patients with PNES diagnosed by Video-EEG were included. Twenty-four had pure PNES, and ninteen mixed PNES. Female population, age, duration of PNES, psychiatric institutionalization, psychopharmacotherapy, dissociative disorders and posttraumatic stress disorder (PTSD), were significantly higher in the pure PNES patients. Suicide attempts, antiepileptic therapy, conversive, affective and personality disorders were frequent in both groups. In the analysis of seizure semiology, the total lack of responsiveness was significantly higher in the mixed PNES group., Conclusions: Pure PNES patients showed similarities and differences in the psychiatric profile, with a greater prevalence of dissociative disorders and PTSD, factors related to psychiatric severity.

Objective: The purpose of this study is to identify specific clinical-electroencephalogram (EEG) patterns at seizure onset in patients with hippocampal sclerosis (HS)., Methods: Sixty-six ictal video-EEG recordings corresponding to 26 patients with HS have been reviewed, focusing on the EEG features found during the first 30 ictal s. The EEG activity has been classified into the following groups: (A) according to spatial distribution: type 1: temporal electrodes on one side; type 2: temporal and adjacent frontal electrodes on one side; and type 3: non-lateralizing electrographic activity; and (B) according to morphology; subtype (a): regular 5-9 Hz rhythmic activity (RA); subtype (b): low-voltage rapid activity, followed by a 5-9 Hz RA; and subtype (c): irregular EEG sharp waves. We analyzed the clinical symptoms sequence and established the relationship with the ictal EEG patterns., Results: Considering spatial distribution and morphology, the most frequent ictal EEG patterns were type 1 (57%), type 2 (37%), and subtype (a): 62%; subtype (b): 27%; and subtype (c): 11%. The sequence of clinical symptoms observed was: aura-->behavioral arrest-->oro-alimentary automatisms-->unilateral hand automatisms. All seizures with aura and including two or more symptoms of the clinical sequence (65%) were associated with a 1a, 1b, 2a or 2b EEG pattern., Conclusions: The identification of a specific clinical-EEG pattern provides a useful tool for the epileptogenic zone localization in non-invasive pre-surgical assessment of patients with hippocampal sclerosis., Significance: The identification of a specific clinical-EEG pattern associated to neuroimaging findings and neuropsychological testing allows indicating surgery for the treatment of epilepsy in patients with hippocampal sclerosis, without performing any further complementary studies.

Background: Human herpesvirus-6 (HHV-6) infection is widespread throughout the world. No data are available in Argentina about the loss of maternally derived HHV-6 immunity and natural infection in infants., Methods: A population of 100 pregnant women and 407 children between 1 and 15 months of age were assayed by indirect immunofluorescence to detect and quantify specific IgG anti-human herpesvirus-6 (anti-HHV-6) antibodies in Córdoba City, Argentina., Results: There was no significant difference in the positive rate between infants aged 1 to 9 months (range, 43.6 35.5%) and pregnant women (37%). Seropositive ratio dropped in the 10-month group (23.33% seropositive) and rose sharply in the 11-month group (38.89%), 12-month (60.61%), and 13- to 15-month group (63.46%). The geometric mean titer (GMT) for infants in the 12 to 15 months age group (23.4 41.64) was significantly higher than the GMT for infants 10 months of age (11.04) (P < 0.05 with the Tukey-HSD test)., Conclusions: This study shows a significant association between loss of passive HHV-6 antibody and age among infants. The results support evidence that HHV-6 enters the susceptible population at 11 months, leading to a high prevalence of antibodies in children between 13 and 15 months of age.

Behavioral toxicology is an emerging field which is becoming increasingly important in risk assessment of exposure to neurotoxic substances, due to the high sensitivity of behavior towards neurotoxic action and the integration in behavioral functions of several underlying processes and neurofunctions, such as motor, sensory, attention, motivational. Whenever it is difficult to isolate the relative contribution of sensory, motor, arousal, or cognitive factors that contribute to an observed behavioral change, possible mechanism of behavioral alteration may rely on the involvement of neurotransmitters, such as the dopaminergic system and catecholamines metabolism. Examples are given of different behavioral types of changes induced in humans by organic solvents (styrene), metals (manganese) and anaesthetic gases, based on a possible common underlying mechanism of toxicity.

Controlling occupational exposure to chemical substances in biomedical laboratories is very complex because of the high number of compounds involved, and the rapid changes in analytical techniques and methods. On the other hand, evidence of increased mortality for malignant lymphoma and leukemia has been observed in laboratory technicians. This calls for more precise procedures of risk assessment to identify the specific substances that may be responsible for these effects. A model of hazard identification is presented, which includes the following steps: identification, classification and periodical updating of the chemical substances used in each analytical technique; evaluation of the variables that can influence the exposure; quantification of exposure using environmental measurements. The availability of such a procedure can be useful for the organization of health and epidemiological surveillance programs for the laboratory workers.

The progressive improvement of hygienic conditions in the workplace has increased the importance of obtaining detailed information on extra-occupational factors that might influence the levels of the biological indicators. This information is indispensable both when subjects belonging to the general population are selected for establishing 'reference values' and when subjects occupationally exposed to specific chemical substances are studied. In non-occupationally exposed subjects the biological indicator levels may be influenced by circumstances which enhance absorption of the substance in question. Examples of interference factors considered for biological indicators of main metals are: gender, age, smoking habits, alcohol consumption and dietary habits. In occupationally exposed subjects the levels of the biological indicators can be influenced by factors that interfere with the metabolism of the substances absorbed in the workplace. In particular, factors such as alcohol, drugs and tobacco appear to play an important role in modifying the biological indicator levels in the occupationally exposed. Ethanol can inhibit as well as induce the metabolism of solvents. Inhibition occurs after excessive ingestion of ethanol, whereas induction occurs in subjects who regularly consume alcohol. There are several examples of inhibition of the metabolism of solvents by alcohol in man, occurring at levels of exposure frequently encountered in the workplace, also within the 'occupational exposure limits', (OEL). Conversely, there are very few studies on the effects of induction, which presumably occur only when the exposure levels greatly exceed OEL. Among drugs, analgesics seem to play a particular role in interfering with the metabolism of solvents. Since cigarette smoking is frequently associated with alcohol ingestion at present it is difficult to extrapolate the isolated effect of smoking on the metabolism of solvents. In order to facilitate interpretation of the results of biological monitoring, we propose to prepare informative sheets for the main substances which will contain information on factors that can influence the levels of the indicators.

Reference values for blood-cadmium levels (B-Cd) are available for only a limited number of geographical areas and for particular population strata (sex, age, smoking habits). This paper, in agreement with the TRACY guidelines, describes and discusses the criteria used to rank published papers on reference values for cadmium retrieved by Medline and Toxline between 1976 and 1991. The TRACY criteria deal with the grading of published papers in terms of their suitability for calculating provisional reference values. Only four out of 18 papers were considered suitable for the TRACY project. The four articles were finally used via meta-analysis to provide provisional reference values for smokers and non-smokers. The comparison of results obtained using published statistics and individual data is used to discuss the appropriateness of meta-analysis in the case of cadmium. Due to the availability of large enough studies and to the clear differences across countries, the suitability of a compound upper reference limit to B-Cd levels seems limited.

In order to evaluate the urinary excretion of cobalt, a study was carried out in two plants producing diamond segments and sintered wires for stone cutting. In both plants, the highest Co exposures were found during mixing and granulation of Co powders, generally performed 1-2 times per week for 1-2 h in the first plant and 3-4 h in the other. Environmental hygiene conditions were good in the first plant and poor in the other with environmental Co concentrations around the ACGIH TLV (50 micrograms/m3) in the first and many times higher (up to 8000 micrograms/m3) in the second. In two workers employed in the above mentioned jobs. Cobalt in urine (CoU) was determined in samples collected during the first day, before shift and about 2, 4, 7 and 10 h after the beginning of exposure; samples were also collected on the 2nd, 3rd and 4th day, before and at the end of the shift. The study showed that Co in urine rapidly increased in the hours following the cessation of exposure, with a peak of elimination about 2-4 h after exposure, and a subsequent decrease (more rapid for the first 24 h) in the following days. Such a pattern was apparently independent of the degree of exposure, since it was detected in both plants and confirmed also in an industrial hygienist with lower Co exposure. The data indicate that for a correct evaluation of Co exposure through CoU determination, variables such as type and characteristics of the job and most importantly, the times at which biological samples are collected should be carefully considered.

At present, the quantitative differences between environmental exposure and occupational exposure to toxic metals are steadily decreasing, it becomes important to establish reference values of the tests used for biological monitoring. However, the word 'reference values' is often used inappropriately and in particular its significance is often confused with that of 'limit values' or 'normal values'. The term reference values defines the levels of the biological indicators in the general population which are not occupationally exposed. It is necessary to refer to these values in order to compare the data obtained through biological monitoring programmes in workers and in groups of the general population which are presumed to be exposed. The most essential aspects for identifying reference values for toxic metals, using a rigorous methodology, are taken into consideration and in particular, the requisites needed for identifying the subjects which must be included in the reference groups are also examined. The modalities for using reference values for individual subjects as well as for groups are then discussed and the main points of research which must be faced in the near future regarding reference values are highlighted.

Beta-endorphin/beta-lipotropin immunoreactivity (BE/BLPH-IR) content was evaluated in the CSF of patients suffering by deafferentation pain syndromes. BE/BLPH-IR CSF concentrations of these patients were compared with those obtained in a group of patients affected by low back pain and in a control group without pain problems. No statistically significant variation in BE/BLPH-IR levels were found between controls and subjects with different types of chronic pain.

Neutron activation analysis-electrothermal atomic absorption spectroscopy (ETA-AAS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) have been used for the determination of 46 elements in urine, 35 in blood and 26 in serum of unexposed Italian subjects living in the same region (Lombardy). The results allowed the proposal of reference values for various elements determined in more than 350 healthy subjects, these being Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Se, Tl, V, Zn, in urine; Ag, As, Bi, Cd, Cr, Co, Cu, Hg, Pb, Se, Tl, Zn in blood; and Ag, Al, Be, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, Zn in serum (or plasma). For all other elements indicative values are suggested. In addition to the mean value and the "reference range", a "range of uncertainty" and an upper limit above which metabolic abnormalities could be expected have also been defined on the basis of simple statistical considerations.

The behaviour of blood (PbB) and two biological indicators of effect: erythrocyte protoporphyrin (EP) and urinary aminolaevulinic acid (ALAU), were studied in subjects who had ceased working with inorganic lead for at least one year. The relationships between these indices and chelatable lead (PbU-EDTA) were also analysed. As a comparison, a group of subjects currently exposed to inorganic lead was studied. At a given PbU-EDTA level, the PbB values were significantly lower in the workers with past exposure than those found in currently exposed subjects. The relationship between EP and PbU-EDTA illustrates that, for corresponding levels of chelatable lead, the values of the erythrocyte metabolite are identical in the two groups. Considering the EP-PbB relationship, however, at a given PbB level the protoporphyrin values appear distinctly more altered in the subjects with past exposure. The relationship between ALAU and PbU-EDTA shows that, at a given PbU-EDTA level the urinary metabolite in past exposed subjects is distinctly lower than in currently exposed workers, while the relationship between ALAU and PbB shows that, at similar blood lead values, the ALAU levels are identical in both groups. On the basis of these results, it is concluded that in subjects with past exposure, erythrocyte protoporphyrin can be used in establishing the persistence and extent of an "active deposit" of lead in the organism, while PbB and ALAU are of very limited value.

Methionine-enkephalin (ME-IR) and beta-endorphin (BE-IR) immunoreactive material CSF concentrations have been measured in subjects of different ages affected by lumbar or cervical disk hernia. The two peptides exhibited different age-related trends. ME-IR levels rose significantly with age while no changes were observed in the case of BE-IR.

The levels of cadmium in blood (CdB) and in urine (CdU) were measured in 40 women at delivery and in their offspring. The women were not occupationally exposed to cadmium. The CdB levels in the pregnant women were significantly lower than in a control group consisting of 40 subjects of the same sex and age living in the same area. The difference can probably be ascribed to the physiological hemodilution that takes place in pregnancy. The CdU levels in the two groups were identical, which suggests that no mobilization of the metal from tissue deposits occurs during pregnancy. The presence of cadmium in the blood and urine of the newborn demonstrates that cadmium crosses the placental barrier. There was a rather high correlation between the CdU levels of mothers and offspring. Since only traces of cadmium are present in tissues at birth, it is speculated that the CdU levels in the newborn are influenced by the tissue deposits of cadmium in the mother. Further research is required to ascertain whether, in the case of women occupationally exposed to cadmium or living in cadmium polluted areas, transfer of the metal across the placenta can produce toxic effects in the foetus.

Urinary mutagenic activity detected by the bacterial fluctuation assay, using Salmonella typhimurium TA98 and Escherichia coli WP2 uvrA with and without metabolic activation (S9 mix), was studied in a group of 21 workers exposed to inorganic lead and a control group of 22 non-occupationally exposed subjects. Occupational exposure to inorganic lead had no effect on urinary mutagenicity in the strains considered, with or without metabolic activation. In smokers (exposed and non-exposed), urinary mutagenic activity appeared to increase compared to non-smokers (exposed and non-exposed), only with Salmonella typhimurium TA98 in the presence of S9 mix.