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• Rare phenomenon : Study explores uncommon suicides—decapitation from hanging, sparsely documented despite frequent hanging suicides. • Case snapshot : A 35-year-old man decapitated in his garden, showcasing distinctive signs. • Literature review findings : Analysis of 22 cases reveals male victims, varied hanging methods, and specific decapitation patterns. • Forensic emphasis : Highlights importance of meticulous crime scene investigation and thorough post-mortem examination in reconstructing events. • Crucial comparisons : Stress on careful evidence collection and literature comparison to support forensic hypotheses in court. Suicidal hanging resulting in decapitation is rarely documented. This discussion involves a case of a 35-year-old man found decapitated in his residence's garden. A systematic literature review on hanging-induced decapitation was conducted to comprehensively investigate and compare the case to existing literature. The study aims to identify frequently described post-mortem findings in cases of suicidal hanging leading to decapitation. A 35-year-old man was found decapitated in his garden, with a jute strap and chimney debris nearby. The cervical region was completely severed along the dorsoventral and craniocaudal plane, exposing internal structures. A ligature mark was present, along with Amussat's sign and Simon's bleeding. The systematic review of the literature followed PRISMA standards, analyzing 3622 publications from Google Scholar, PubMed, and Scopus databases up to 2023. Inclusion criteria comprised cases of complete or incomplete decapitation resulting from hanging, available in full-text and written in English. 16 articles on hanging-induced decapitation met the selection criteria; 22 cases were analyzed. Studies, mostly from Europe, showed a mean victim age of 44.3, all male. Fall height ranged from 1 m to 18 m, with various suspension media. Most cases displayed complete decapitation, primarily between cervical vertebrae C1 and C3. Some cases noted collateral findings. Complete crime scene investigation and thorough post-mortem examination are crucial for reconstructing events, especially with confounding elements. Precise evidence collection and literature comparison are essential to understand the case and substantiate the forensic pathologist's hypothesis in court. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is caused by exposure to noxious particles and gases. Smoking is the main risk factor, but other factors are also associated with COPD. Occupational exposure to vapours, gases, dusts and fumes contributes to the development and progression of COPD, accounting for a population attributable fraction of 14%. Workplace pollutants, in particular inorganic dust, can initiate airway damage and inflammation, which are the hallmarks of COPD pathogenesis. Occupational COPD is still underdiagnosed, mainly due to the challenges of assessing the occupational component of the disease in clinical settings, especially if other risk factors are present. There is a need for specific education and training for clinicians, and research with a focus on evaluating the role of occupational exposure in causing COPD. Early diagnosis and identification of occupational causes is very important to prevent further decline in lung function and to reduce the health and socio‐economic burden of COPD. Establishing details of the occupational history by general practitioners or respiratory physicians could help to define the occupational burden of COPD for individual patients, providing the first useful interventions (smoking cessation, best therapeutic management, etc.). Once patients are diagnosed with occupational COPD, there is a wide international variation in access to specialist occupational medicine and public health services, along with limitations in workplace and income support. Therefore, a strong collaboration between primary care physicians, respiratory physicians and occupational medicine specialists is desirable to help manage COPD patients' health and social issues. [ABSTRACT FROM AUTHOR]

Background: Percutaneous, ultrasound-guided laser ablation is a proven management approach for the treatment of Benign Thyroid Nodules (BTN), but only sporadic cases of treatment of large-volume nodules with laser ablation have been reported. The aim of this study was to evaluate the efficacy and safety of laser ablation in the treatment of very large (> 100 mL) thyroid nodules. Methods: Between 2009 and 2016, 24 patients with very large, BTN received 2–3 sessions of laser ablation over the course of 12 months. Nodule volume was measured before treatment, and at 1 and 4 years. Results: Prior to treatment, median nodule volume was 138 mL (range: 102–289 mL). At 1 year, technique efficacy was achieved in 75% of patients, with median nodule volume significantly reduced to 26 mL (range: 15–31 mL, p < 0.001 vs pretreatment). Volume reduction ratio (VRR) at 1 year was 81%. At 4-year follow-up, median nodule volume was 27 mL (range: 15–33 mL, p < 0.001 vs pretreatment), with a VRR of 80%. Two patients had nodule regrowth > 50% and went to surgery – one patient after 1 year and the other after 3 years. Treatment was well tolerated; there were no major complications, although transient fever occurred in 12% (3/24) of patients and mild-to-moderate pain was experienced by 8% (2/24) of patients. Conclusions: In this patient series, percutaneous, ultrasound-guided laser ablation of very large thyroid modules provided long-term benefits and the treatment was well tolerated. [ABSTRACT FROM AUTHOR]

Purpose: To confirm the effectiveness of laser ablation on toxic nodules in a large population with three years of follow-up. Material and methods: Between 2009 and 2014, we treated 82 patients with hyperthyroidism related to the presence of a toxic nodular goitre. Patients were pre-treated pharmacologically with methimazole prior to single session of laser ablation (LA) and then followed up every 3 months with FT4 and TSH blood tests as well as ultrasound examination of the nodules treated. Results: All patients responded to the treatment. The median nodule volume decreased from 12 ml (range 5-118 ml) to 5 ml (range 1.2-40 ml) after three years (p < 0.001). The percentage of patients who discontinued methimazole therapy was reduced by increasing the initial volume of the toxic nodule. In nodules with a volume less than 5 ml, all patients were able to suspend methimazole; this percentage was reduced to 90.2% in nodules with a volume between 5 and 15 ml, 61.1% in those with volume 15-25 ml and only 28.5% in nodules larger than 25 ml. We had no major complications but only moderate pain and fever in the evening, a few hours after ablation therapy in 10% of treated patients. Conclusions: Single session of LA of toxic thyroid nodules is effective and safe, especially in nodules with a volume under 15 ml. [ABSTRACT FROM AUTHOR]

Whether exposure to 50–60 Hz extremely low frequency magnetic fields (ELF-MF) exerts neurotoxic effects is a debated issue. Analogously, the potential role of Aluminum (Al) in neurodegeneration is a matter of controversial debate. As all living organisms are exposed to ELF-MF and/or Al daily, we found investigating the early effects of co-exposure to ELF-MF and Al in SH-SY5Y and SK-N-BE-2 human neuroblastoma (NB) cells intriguing. SH-SY5Y5 and SK-N-BE-2 cells underwent exposure to 50 Hz ELF-MF (0.01, 0.1 or 1 mT) or AlCl 3 (4 or 40 μM) or co-exposure to 50 Hz ELF-MF and AlCl 3 for 1 h continuously or 5 h intermittently. The effects of the treatment were evaluated in terms of DNA damage, redox status changes and Hsp70 expression. The DNA damage was assessed by Comet assay; the cellular redox status was investigated by measuring the amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) while the inducible Hsp70 expression was evaluated by western blot analysis and real-time RT-PCR. Neither exposure to ELF-MF or AlCl 3 alone induced DNA damage, changes in GSH/GSSG ratio or variations in Hsp70 expression with respect to the controls in both NB cell lines. Similarly, co-exposure to ELF-MF and AlCl 3 did not have any synergic toxic effects. The results of this in vitro study, which deals with the effects of co-exposure to 50 Hz MF and Aluminum, seem to exclude that short-term exposure to ELF-MF in combination with Al can have harmful effects on human SH-SY5Y and SK-N-BE-2 cells. [ABSTRACT FROM AUTHOR]

Background Environmental lead exposure is a possible causative factor for increased blood pressure and hypertension, but large studies at low-level exposure are scarce, and results inconsistent. Objective We aimed to examine the effects of environmental exposure to lead in a large population-based sample. Methods We assessed associations between blood lead and systolic/diastolic blood pressure and hypertension in 4452 individuals (46–67 years) living in Malmö, Sweden, in 1991–1994. Blood pressure was measured using a mercury sphygmomanometer after 10 min supine rest. Hypertension was defined as high systolic (≥140 mmHg) or diastolic (≥90 mmHg) blood pressure and/or current use of antihypertensive medication. Blood lead was calculated from lead in erythrocytes and haematocrit. Multivariable associations between blood lead and blood pressure or hypertension were assessed by linear and logistic regression. Two-thirds of the cohort was re-examined 16 years later. Results At baseline, mean blood pressure was 141/87 mmHg, 16% used antihypertensive medication, 63% had hypertension, and mean blood lead was 28 µg/L. Blood lead in the fourth quartile was associated with significantly higher systolic and diastolic blood pressure (point estimates: 1–2 mmHg) and increased prevalence of hypertension (odds ratio: 1.3, 95% confidence interval: 1.1–1.5) versus the other quartiles after adjustment for sex, age, smoking, alcohol, waist circumference, and education. Associations were also significant with blood lead as a continuous variable. Blood lead at baseline, having a half-life of about one month, was not associated with antihypertensive treatment at the 16-year follow-up. Conclusions Low-level lead exposure increases blood pressure and may increase the risk of hypertension. [ABSTRACT FROM AUTHOR]

Glyoxalase I (Glo1) is the main scavenging enzyme of methylglyoxal (MG), a potent precursor of advanced glycation end products (AGEs). AGEs are known to control multiple biological processes, including epithelial to mesenchymal transition (EMT), a multistep phenomenon associated with cell transformation, playing a major role in a variety of diseases, including cancer. Crystalline silica is a well-known occupational health hazard, responsible for a great number of human pulmonary diseases, such as silicosis. There is still much debate concerning the carcinogenic role of crystalline silica, mainly due to the lack of a causal demonstration between silica exposure and carcinogenesis. It has been suggested that EMT might play a role in crystalline silica-induced lung neoplastic transformation. The aim of this study was to investigate whether, and by means of which mechanism, the antiglycation defence Glo1 is involved in Min-U-Sil 5 (MS5) crystalline silica-induced EMT in BEAS-2B human bronchial epithelial cells chronically exposed, and whether this is associated with the beginning of a neoplastic-like transformation process. By using gene silencing/overexpression and scavenging/inhibitory agents, we demonstrated that MS5 induced hydrogen peroxide-mediated c-Jun-dependent Glo1 up-regulation which resulted in a decrease in the Argpyrimidine-modified Hsp70 protein level which triggered EMT in a novel mechanism involving miR-21 and SMAD signalling. The observed EMT was associated with a neoplastic-like phenotype. The results obtained provide a causal in vitro demonstration of the MS5 pro-carcinogenic transforming role and more importantly they provide new insights into the mechanisms involved in this process, thus opening new paths in research concerning the in vivo study of the carcinogenic potential of crystalline silica. [ABSTRACT FROM AUTHOR]

Glyoxalase I (Glo1) is a cellular defense enzyme involved in the detoxification of methylglyoxal (MG), a cytotoxic by-product of glycolysis, and MG-derived advanced glycation end products (AGEs). Argpyrimidine (AP), one of the major AGEs coming from MG modification of protein arginines, is a proapoptotic agent. Crystalline silica is a well-known occupational health hazard, responsible for a relevant number of pulmonary diseases. Exposure of cells to crystalline silica results in a number of complex biological responses, including apoptosis. The present study was aimed at investigating whether, and through which mechanism, Glo1 was involved in Min-U-Sil 5 crystalline silica-induced apoptosis. Apoptosis, by TdT-mediated dUTP nick-end labeling assay, and transcript and protein levels or enzymatic activity, by quantitative real-time PCR, Western blot, and spectrophotometric methods, respectively, were evaluated in human bronchial BEAS-2B cells exposed or not (control) to crystalline silica and also in experiments with appropriate inhibitors. Reactive oxygen species were evaluated by coumarin-7-boronic acid or Amplex red hydrogen peroxide/peroxidase methods for peroxynitrite (ONOO − ) or hydrogen peroxide (H 2 O 2 ) measurements, respectively. Our results showed that Min-U-Sil 5 crystalline silica induced a dramatic ONOO − -mediated inhibition of Glo1, leading to AP-modified Hsp70 protein accumulation that, in a mechanism involving JNK and NF-κB, triggered an apoptotic mitochondrial pathway. Inhibition of Glo1 occurred at both functional and transcriptional levels, the latter occurring via ERK1/2 MAPK and miRNA 101 involvement. Taken together, our data demonstrate that Glo1 is involved in the Min-U-Sil 5 crystalline silica-induced BEAS-2B cell mitochondrial apoptotic pathway via a novel mechanism involving Hsp70, JNK, and NF-κB. Because maintenance of an intact respiratory epithelium is a critically important determinant of normal respiratory function, the knowledge of the mechanisms underlying its disruption may provide insight into the genesis, and possibly the prevention, of a number of pathological conditions commonly occurring in silica dust occupational exposure. [ABSTRACT FROM AUTHOR]

Purpose: The literature reports a wide range of percentages of ablation in the treatment of thyroid nodules. The aim of this nested case-control study was to evaluate whether the different morphological (well-defined vs. agglomerate) characteristics of nodules affect the success rate. Materials and methods: We selected 20 patients with a single and /or dominant well-defined nodule (group 1) and 20 with a nodular formation resulting from the fusion of multiple nodules (group 2). All the nodules were treated by the laser method receiving the same energy. Results: At 6 months, patients in group 1 showed a greater decrease in volume than those in group 2. These differences were more evident after 12 months. Conclusions: Our study demonstrates that the efficacy of laser treatment can be predicted by nodule morphology and contributes to explaining the wide differences in the percentages of ablation reported in literature. [ABSTRACT FROM AUTHOR]

Recently, there has been an enormous increase in the number of people seeking treatment for cocaine addiction. Fifteen male cocaine users aged 20-30 years who requested hair analysis from our forensic toxicology laboratory (Perugia, Italy) from March to June 2012, reported using scopolamine without medical supervision to reduce the anxiety associated with cocaine withdrawal. Self-reports were verified with the results obtained from the hair analysis. We discuss whether the use of scopolamine in cocaine abusers could be supported by a neurobiological and pharmacological point of view. [ABSTRACT FROM AUTHOR]

Highlights: [•] PS metabolism modification in MnCl2-treated PC12 cells. [•] PS metabolism modification precedes PS exposure. [•] MnCl2 exposure affects activity and expression of PS-synthesizing enzymes in PC12 cells. [ABSTRACT FROM AUTHOR]

Peyote, a cactus containing the hallucinogen mescaline, is used to induce altered states of consciousness in religious ceremonies or for recreational purpose. This study reports a case of an underage boy suspected of mescaline abuse. For this purpose, we analyzed a dark green liquid sample found in the bedroom of the boy whose urine and hair samples were collected shortly after the drink was found. A method by gas chromatography-mass spectrometry tandem mass spectrometry (GC-MS/MS) in positive chemical ionization mode was developed and validated in terms of linearity, specificity, accuracy, and sensitivity for mescaline determination at the low concentrations present in hair. GC- MS analysis of the liquid identified mescaline, while urine was negative; GC- MS/ MS segmental hair analysis identified mescaline in the proximal segment (root to 2 cm), while the distal segments were negative. Although peyote was uncommonly encountered, its use was confirmed by segmental hair analysis that can provide long-term information about drugs use. [ABSTRACT FROM AUTHOR]

Crystalline silica (Min-U-Sil-5) induces oxidative stress in human bronchial epithelial cells (BEAS-2B), through the intracellular accumulation of ROS that cause oxidative damage leading to the degradation of extracellular matrix (ECM) proteins and to the loss of cell adhesion molecules inducing apoptosis and genotoxic damage. This paper briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which the cronic and cumulative exposure to crystalline silica can induce cellular damage that promotes changes in extracellular matrix and in apoptosis gene expression. [ABSTRACT FROM AUTHOR]

Abstract: Reactive oxygen species (ROS) play an important role as mediators of pulmonary damage in mineral dust-induced diseases. Studies carried out to date have largely focused on silica-induced production of ROS by lung phagocytes. In this study we investigated the hypothesis that crystalline silica Min-U-Sil 5 can induce elevations in intracellular ROS in human bronchial epithelial cells BEAS-2B, via an indirect mechanism that involves ROS-inducing intracellular factors, through a reduction of antiglycation (glyoxalase enzymes) and antioxidant (paraoxonase 1 and glutathione-S-transferases) enzymatic defenses. The results show that crystalline silica Min-U-Sil 5 causes a significant reduction in the efficiency of antiglycation and antioxidant enzymatic defenses, paralleled by an early and extensive ROS generation, thus preventing the cells from an efficient scavenging action, and eliciting oxidative damage. These results confirm the importance of ROS in development of crystalline silica-induced oxidative stress and emphasize the pivotal role of antiglycation/antioxidant and detoxifying systems in determining the level of protection from free radicals-induced injury for cells exposed to crystalline silica Min-U-Sil 5. [Copyright &y& Elsevier]

Type 1 diabetes mellitus (T1DM) is a typical autoimmune disease and results from the destruction of insulin-producing β cells of the pancreas. It develops in the presence of genetic susceptibility, even though more than 85% of patients with T1DM do not have a close relative with the disorder. The etiology of T1DM is complex, and both genetic and environmental factors play important roles. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association idengified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) and DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of the subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. Major histocompatibility complex (MHC) class I chain–related A (MICA) is located in a candidate susceptibility region and activates natural killer (NK) cells, T cells and γδ CD8 T cells by its receptor NKG2D. The polymorphism of the MICA gene is associated with T1DM in different populations as demonstrated in several papers published in the last 7 years. [ABSTRACT FROM AUTHOR]

Hexavalent chromium compounds are well-documented human carcinogens. In vitro experiments show Cr (VI) induces cell death by apoptosis by activating p53 protein. The aim of this study was to evaluate Cr (VI)-induced apoptosis in a human bronchial epithelial cell line (BEAS-2B) and in a lymphoblastic leukemia cell line (MOLT-4). Cr (VI) caused a dose- and time-dependent increase in the apoptosis rate in both cell lines. Western blotting showed increased p53 protein expression in MOLT-4 cells, but not in BEAS-2B cells, after exposure to 0.5 and 3 muM hexavalent chromium for 12 hours and 4 hours, respectively. Apoptotic cell death induced by Cr (VI) was not decreased by pretreatment with caspase-3, -8, and -9 inhibitors. These preliminary results provide evidence of Cr (VI)-induced apoptosis, which deserves further investigation in occupationally exposed workers. [ABSTRACT FROM AUTHOR]

Hexavalent chromium compounds are well-documented human carcinogens. In vitro experiments show Cr (VI) induces cell death by apoptosis by activating p53 protein. The aim of this study was to evaluate Cr (VJ)-induced apoptosis in a human bronchial epithelial cell line (BEAS-2B) and in a lymphoblastic leukemia cell line (MOLT-4). Cr (VI) caused a dose- and time-dependent increase in the apoptosis rate in both cell lines. Western blotting showed increased p53 protein expression in MOLT-4 cells, but not in BEAS-2B cells, after exposure to 0.5 and 3 µM hexavalent chromium for 12 hours and 4 hours, respectively. Apoptotic cell death induced by Cr (VI) was not decreased by pretreatment with caspase-3, -8, and -9 inhibitors. These preliminary results provide evidence of Cr (VI)-induced apoptosis, which deserves further investigation in occupationally exposed workers. [ABSTRACT FROM AUTHOR]

The effects of physical activity on sleep were evaluated in 12-month-old rats. The animals (n = 18) were induced to walk or run for 45 min in a rota-rod treadmill while control mates remained in their home cages. Immediately after the trial, they were left free to sleep for four hours, during which their electroencephalographic activity was recorded. Baseline electroencephalogram showed no differences among groups in sleep parameters and spike wave discharges during wakefulness in all rats. Sleep variables and spike wave discharges remained constant in the controls over times. On the contrary, Student's t-test for paired data indicated a decrease in spike wave discharges in both walking and running rats while paradoxical sleep rose parallel with slow wave sleep in walking animals but declined in running rats, in spite of an increment in slow wave sleep. The results seem to indicate that: i) light exercise improves sleep quality in middle aged rats, provided it is not stressful and ii) physical activity supplies important benefits to waking brain by reducing spike wave discharges. [ABSTRACT FROM AUTHOR]

Controversial data are available on the association between the retrovirus-like long-terminal repeat (LTR) DQ-LTR13 and genetic susceptibility to type 1 diabetes and other autoimmune diseases. We analyzed DNA samples from 315 type 1 diabetic patients, 166 autoimmune Addison's disease (AAD) patients, 1,054 healthy subjects, and 144 families of type 1 diabetic offspring. DQ-LTR13 was more frequent among patients than healthy subjects (P(c) < 0.0006), and a preferential transmission of DQB1*0302-LTR13(+) from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB1*0302 but not DQB1*0201. The presence of DQ-LTR13 increased the odds ratio of DQB1*0302 2.9- to 3.2-fold for type 1 diabetes and AAD. DRB1*0403 was absent in all of the 169 DRB1*04-positive patients but present in 27% (34 of 127) DRB1*04-positive healthy subjects (P(c) < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB1*0403-positive healthy subjects and 36 of 93 (39%) individuals carrying another DRB1*04 allele (P(c) = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13 is not independently associated with type 1 diabetes and AAD after correction for DQB1*0302 and DRB1*0403. Conversely, DQB1*0201, DQB1*0302, DRB1*0401, and DRB1*0403 were all significantly associated with disease risk also after correction for DQ-LTR13. We provide conclusive evidence that the genetic association of DQ-LTR13 with type 1 diabetes and AAD is primarily due to a LD with DQB1*0302 and DRB1*0403. [ABSTRACT FROM AUTHOR]

The attraction of leukocytes to tissues is essential for inflammation and the initiation of the autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytokines. We investigated whether human chemokine receptor gene polymorphisms, namely CCR5-Δ32 and CCR2-64I, are associated with susceptibility to autoimmune Addison's disease. Genotyping was performed in 56 patients and 127 healthy controls by a new method using pyrosequencing for CCR2-64I and by polymerase chain reaction and detecting gel for CCR5-Δ32. None of the CCR2 or CCR5 alleles was found to be associated, either positively or negatively, with disease risk. Our results indicate that the CCR2-64I and CCR5-Δ32 gene polymorphisms do not play a major role in conferring genetic risk for, and/or protection against, autoimmune Addison's disease. [ABSTRACT FROM AUTHOR]

In order to evaluate the primary DNA damage due to occupational exposure to chromium (VI), DNA strand-breaks and apoptosis in peripheral lymphocytes were measured in a group of 19 chrome-plating workers. DNA strand-breaks was assessed by alkaline (pH>13) single-cell microgel electrophoresis (‘comet’) assay, while apoptosis was measured by flow-cytometry after propidium iodide staining of the cells. Concentrations of chromium in urine, erythrocytes and lymphocytes were investigated as biological indicators of exposure. A group of 18 hospital workers (control group I) and another 20 university personnel (control group II) without exposure to chromium were also studied as controls. The results of the study show that chrome-plating workers have higher levels of chromium in urine, erythrocytes and lymphocytes than unexposed workers. Comet tail moment values, assumed as index of DNA damage, are increased in chromium-exposed workers and results are significantly correlated to chromium lymphocyte concentrations. No difference emerged in the percentage of apoptotic nuclei in exposed and unexposed workers. The study confirms that measurements of chromium in erythrocytes and lymphocytes may provide useful information about recent and past exposure to hexavalent chromium at the workplace. The increase in DNA strand-breaks measured by comet assay suggests this test is valid for the biological monitoring of workers exposed to genotoxic compounds such as chromium (VI). [Copyright &y& Elsevier]

It is well known that type 1 diabetes mellitus (T1DM) is a complex genetic disease resulting from the autoimmune destruction of pancreatic beta cells. Several genes have been associated with susceptibility and/or protection for T1DM, but the disease risk is mostly influenced by genes located in the class II region of the major histocompatibility complex. The attraction of leukocytes to tissues is essential for inflammation and the beginning of autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytolines. Some studies have shown that CCR2-64I and CCR5-&Delta;32 might be important for protection of susceptibility to some immunologically-mediated disorders. In the present study, we demonstrate the lack of association between CCR2-64I and CCR5-&Delta;32 gene polymorphism and TIDM and we desrcibe a new method for a simple and more precise genotyping of the CCR2 gene. [Copyright &y& Elsevier]

Absinthe, an alcoholic drink used in certain artistic circles and considered the inspiring muse of many famous artists because it was reputed to stimulate creativity and possess exciting, aphrodisiacal and healing properties, in the past enjoyed enormous popularity so much so that it led to a real collective abuse so causing its prohibition in many countries, is again enjoying a new period of popularity. Also in Italy there is increasing information about the use and abuse of this drink. We received a request to analyse and determine the nature of two samples of alcoholic drinks, obtained by macerating Artemisia absinthium leaves in ethanol. Analyses of extracts by gas chromatography/mass spectrometry (GC/MS) identified β-thujone, which is responsible for the activity and toxic effects on the CNS of absinthe, in both alcohol samples. [Copyright &y& Elsevier]

Recent evidence suggests that the development of skin lesions from arsenic exposure may be mediated by increases in the expression of various growth factors, including transforming growth factor-alpha (TGFα). To investigate this association in humans, levels of total urinary arsenic and urinary TGFα were determined in 41 individuals with and without arsenic-associated skin lesions from Bangladesh who have chronic exposure to arsenic in their drinking water. After adjusting for age and sex, total urinary arsenic was found to be correlated with urinary TGFα (R 2 = 0.37; p < 0.0001), particularly in those individuals with arsenic-associated skin lesions (R 2 = 0.70; p < 0.0001). Stratification of the cohort into quartiles based on urinary TGFα levels demonstrated a trend of increasing odds ratios for the presence of arsenic-associated skin lesions with increasing urinary TGFα, although this was not significant (p = 0.15). These results suggest that urinary TGFα may be a useful biomarker for the epidermal effects of arsenic exposure. [ABSTRACT FROM AUTHOR]

OBJECTIVE Glutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) in type 2 diabetic subjects with secondary failure to sulphonylurea treatment identify the so-called latent autoimmune diabetes of the adult (LADA). The aim of our study was to estimate the risk for endocrine autoimmunity in type 2 diabetic subjects with GAD65Ab. DESIGN AND PATIENTS We analysed serum samples from 600 adult subjects with a clinical diagnosis of type 2 diabetes mellitus for the presence and levels of GAD65Ab and antibodies directed against the islet autoantigen IA-2/ICA512 (IA-2/ICA512Ab). All the patients had been treated initially with hypoglycaemic agents and/or diet for at least 1 year. GAD65Ab+ subjects were studied for the presence of thyroid peroxidase autoantibodies (TPOAb), 21 hydroxylase autoantibodies (21OHAb) and frequency of HLA class II haplotypes. RESULTS GAD65Ab were found in 67/600 (11%) and IA-2/ICA512Ab in 12/600 (2%) subjects (P < 0.0001). The presence of GAD65Ab, but not that of IA-2/ICA512Ab, was significantly associated with insulin therapy, low BMI (P < 0.0001) and low basal C-peptide (P < 0.01). Islet-cell antibodies (ICA) were detected in 43/67 (64%) GAD65Ab+ and in 10/12 (83%) IA-2/ICA512Ab + subjects. TPOAb occurred more frequently in GAD65Ab+ (16/67, 24%) than in GAD65Ab-subjects (9/174, 5%) (P < 0.0001). 21OHAb were detected only in GAD65Ab+ subjects (3/67, 4.5%) (P = 0.03 vs. GAD65Ab-subjects). None of the 21OHAb+ subjects had metabolic or clinical signs of adrenal dysfunction. HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent in GAD65Ab+ subjects than in healthy controls (OR = 5.42, corrected P < 0.0026). The presence of TPOAb was significantly associated with DR3-DQ2 (P = 0.024). CONCLUSIONS Our study demonstrates that the presence of GAD65Ab identifies a subgroup of type 2 diabetic patients with high risk for thyroid and adrenal autoimmunity, and that both GAD65Ab and TPOAb are associated with the presence of... [ABSTRACT FROM AUTHOR]

Purpose: Hypothermia occurs when core body temperature drops below 35 °C. The purpose of this review was to identify and analyze studies on the topic of hypothermia from an immunohistochemical perspective to determine robust markers of fatal hypothermia.This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. It has been registered with Prospero (registration number: CRD42024572782).In total, 2618 publications met the search criteria. A total of 63 duplicate articles were excluded and a further 2489 publications were excluded for not meeting the inclusion criteria, leaving 29 full-text articles. Furthermore, from the bibliographies of the included articles, four more publications were selected, which also respected the established inclusion and exclusion criteria. Only six studies identified a statistically significant correlation between immunohistochemical patterns and hypothermia-related deaths.The existing literature examined appears fragmented and lacks robust statistical validation. Therefore, there is an evident need for more comprehensive and methodologically rigorous research to develop reliable diagnostic criteria.Methods: Hypothermia occurs when core body temperature drops below 35 °C. The purpose of this review was to identify and analyze studies on the topic of hypothermia from an immunohistochemical perspective to determine robust markers of fatal hypothermia.This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. It has been registered with Prospero (registration number: CRD42024572782).In total, 2618 publications met the search criteria. A total of 63 duplicate articles were excluded and a further 2489 publications were excluded for not meeting the inclusion criteria, leaving 29 full-text articles. Furthermore, from the bibliographies of the included articles, four more publications were selected, which also respected the established inclusion and exclusion criteria. Only six studies identified a statistically significant correlation between immunohistochemical patterns and hypothermia-related deaths.The existing literature examined appears fragmented and lacks robust statistical validation. Therefore, there is an evident need for more comprehensive and methodologically rigorous research to develop reliable diagnostic criteria.Results: Hypothermia occurs when core body temperature drops below 35 °C. The purpose of this review was to identify and analyze studies on the topic of hypothermia from an immunohistochemical perspective to determine robust markers of fatal hypothermia.This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. It has been registered with Prospero (registration number: CRD42024572782).In total, 2618 publications met the search criteria. A total of 63 duplicate articles were excluded and a further 2489 publications were excluded for not meeting the inclusion criteria, leaving 29 full-text articles. Furthermore, from the bibliographies of the included articles, four more publications were selected, which also respected the established inclusion and exclusion criteria. Only six studies identified a statistically significant correlation between immunohistochemical patterns and hypothermia-related deaths.The existing literature examined appears fragmented and lacks robust statistical validation. Therefore, there is an evident need for more comprehensive and methodologically rigorous research to develop reliable diagnostic criteria.Conclusion: Hypothermia occurs when core body temperature drops below 35 °C. The purpose of this review was to identify and analyze studies on the topic of hypothermia from an immunohistochemical perspective to determine robust markers of fatal hypothermia.This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. It has been registered with Prospero (registration number: CRD42024572782).In total, 2618 publications met the search criteria. A total of 63 duplicate articles were excluded and a further 2489 publications were excluded for not meeting the inclusion criteria, leaving 29 full-text articles. Furthermore, from the bibliographies of the included articles, four more publications were selected, which also respected the established inclusion and exclusion criteria. Only six studies identified a statistically significant correlation between immunohistochemical patterns and hypothermia-related deaths.The existing literature examined appears fragmented and lacks robust statistical validation. Therefore, there is an evident need for more comprehensive and methodologically rigorous research to develop reliable diagnostic criteria. [ABSTRACT FROM AUTHOR]

Abstract: Analysis of the MICA gene revealed a trinucleotide repeat (GCT) microsatellite polymorphism within the transmembrane region. So far, seven alleles of the exon 5 of the MICA gene, which consist of 4, 5, 6, 7, 9, and 10 repetitions of GCT or five repetitions of GCT with an additional nucleotide insertion (GGCT), have been identified. These alleles have been accordingly named A4, A5, A6, A7, A9, A10, and A5.1, and the sizes are, respectively, 179 bp, 182 bp, 186 bp, 189 bp, 194 bp, 197 bp, and 185 bp. We analyzed 1100 Italian subjects for MICA exon 5 microsatellite polymorphism. A new peak corresponding to 191-bp size was observed in one individual, and we confirmed the presence of new polymorphism in exon 5 by sequencing, which consisted of eight GCT repeats. We named this allele, as a current nomenclature, MICA8. [Copyright &y& Elsevier]

DNA quantification is a crucial step in the STR typing workflow for human identification purposes. Given the reaction's nature, qPCR assays may be subjected to the same stochastic effects of traditional PCR for low-input concentrations. The study aims to evaluate the precision of the PowerQuant® (Promega) kit assay measurements and the degree of variability for DNA templates falling below the optimal threshold of the PowerPlex® ESX-17 Fast STR typing kit (Promega). Five three-fold dilutions of the 2800 M control DNA (Promega) were set up. Each dilution (concentrations: 0.05, 0.0167, 0.0055, 0.00185, and 0.000617 ng/µL) was quantified and amplified in four replicates. Variability for qPCR results, STR profile completeness, and EPGs' peak height were evaluated. The qPCR-estimated concentration of casework samples was correlated with profile completeness and peak intensity, to assess the predictive value of qPCR results for the successful STR typing of scarce samples. qPCR was subjected to stochastic effects, of which the degree was inversely proportional to the initial input template. Quantitation results and the STR profile's characteristics were strongly correlated. Due to the intrinsic nature of real casework samples, a qPCR-derived DNA concentration threshold for correctly identifying probative STR profiles may be difficult to establish. Quantitation data may be useful in interpreting and corroborating STR typing results and for clearly illustrating them to the stakeholders. [ABSTRACT FROM AUTHOR]

Sudden unexpected deaths often remain unresolved despite forensic examination, posing challenges for pathologists. Molecular autopsy, through genetic testing, can reveal hidden causes undetectable by standard methods. This review assesses the role of molecular autopsy in clarifying SUD cases, examining its methodology, utility, and effectiveness in autopsy practice. This systematic review followed PRISMA guidelines and was registered with PROSPERO (registration number: CRD42024499832). Searches on PubMed, Scopus, and Web of Science identified English studies (2018–2023) on molecular autopsy in sudden death cases. Data from selected studies were recorded and filtered based on inclusion/exclusion criteria. Descriptive statistics analyzed the study scope, tissue usage, publication countries, and journals. A total of 1759 publications from the past 5 years were found, with 30 duplicates excluded. After detailed consideration, 1645 publications were also excluded, leaving 84 full-text articles for selection. Out of these, 37 full-text articles were chosen for analysis. Different study types were analyzed. Mutations were identified in 17 studies, totaling 47 mutations. Molecular investigations are essential when standard exams fall short in determining sudden death causes. Expertise in molecular biology is crucial due to diverse genetic conditions. Discrepancies in post-mortem protocols affect the validity of results, making standardization necessary. Multidisciplinary approaches and the analysis of different tissue types are vital. [ABSTRACT FROM AUTHOR]

Introduction. World Health Organization describes “long COVID” as a syndrome that occurs within 3 months from the beginning of SARS-CoV-2 infection. The symptoms, which last for at least 2 months, may be episodic, even recurrent, or lasting. The clinical manifestations of long COVID are heterogeneous (fatigue, difficulty breathing, myalgias, joint pain, etc). The purpose of this study is to evaluate the presence and intensity of psychological symptoms in a population of patients who have recovered from COVID. Methods and materials. In 2020, at the Respiratory Rehabilitation and Tisiopneumological Prevention Unit of ASL Umbria 1 Perugia, a clinical and functional evaluation pathway was activated for individuals who had recovered from COVID, at least one month after the molecular test turned negative, but continued to complain symptoms consistent with long COVID. The psychological assessment was conducted through clinical interviews, supplemented by the administering of three questionnaires: GAD-7, PHQ-9, IES-R. Results. Between June 2020 and December 2021, 152 people were evaluated, whom 73% had required hospitalization for COVID. Processing of the results of the questionnaires showed that: 53% of patients had anxious symptoms, 47% had depressive symptomatology, and 20% of patients had symptoms of post-traumatic stress disorder. Conclusions. The observed psychological symptoms encountered were correlated with SARS-CoV-2 infection, which is in line with the existing literature. In our study, hospitalization, as an expression of a more severe form of the disease, was not associated with an increased risk of developing psychological symptoms. Conversely, the most significant psychological discomfort emerged in subjects who had experienced a slighter form of the disease. [ABSTRACT FROM AUTHOR]

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24–0.65]) and need of further treatments (HR = 0.30 [CI 0.12–0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38–14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed. [ABSTRACT FROM AUTHOR]

Il presente studio ha avuto lo scopo di accertare le variazioni dell'abitudine al fumo tra gli operatori sanitari di un'Azienda Ospedaliera a distanza di oltre 10 anni da una prima rilevazione. I dati anagrafici, sull'attività lavorativa e sull'abitudine al fumo di tabacco sono stati raccolti nel corso delle visite mediche di sorveglianza sanitaria effettuate negli anni 1998-99 (n. 1727 infermieri, altri paramedici ed operatori socio-sanitari) e 2009-11 (n. 1461 lavoratori; raccolta dei dati in corso). Nel 1998-99 la prevalenza complessiva di fumatori è risultata pari al 40,0% mentre nel 2009-11 al 30,7%. La prevalenza di fumatori era inferiore in quest'ultimo studio in entrambi i sessi, nei diversi gruppi lavorativi e nelle diverse classi di età, ad eccezione di quella più giovane. Nonostante la percentuale di fumatori tra gli operatori sanitari si sia consistentemente ridotta nell'arco di oltre un decennio, essa resta elevata. I medici del lavoro che svolgono l'attività di Medico Competente possono svolgere un ruolo di rilievo nella lotta contro il fumo. In particolare essi potrebbero fornire a tutti i lavoratori che fumano il cosiddetto counseling breve, un intervento di provata efficacia per favorire la cessazione dell'abitudine al fumo, nel corso delle visite di sorveglianza sanitaria. [ABSTRACT FROM AUTHOR]

Studi sperimentali hanno dimostrato che l'alluminio, ad alte concentrazioni, è citotossico. Nelle cellule nervose produce stress ossidativo, rotture a carico del DNA e inibizione dei sistemi di riparo. Indagini epidemiologiche hanno evidenziato un'associazione tra l'esposizione cronica all'alluminio e alcune forme di tumori e malattie neurodegenerative. Questo studio ha avuto lo scopo di valutare, su cellule di neuroblastoma umano SK-N-BE(2), gli effetti genotossici e stressogeni di dosi non citotossiche di AlCl3, sale altamente solubile e una delle forme più comuni di esposizione umana all'alluminio. Le cellule sono state esposte a 5 dosi scalari di AlCl3 (0,1-1,6 μM) per 6 h e sono state raccolte al termine dell'esposizione o dopo 4 h di recupero. La genotossicità è stata determinata valutando il danno primario al DNA mediante il Comet assay effettuato alla fine dell'esposizione. Gli effetti stressogeni sono stati verificati misurando il livello di espressione della Heat Shock Protein 72kDa (Hsp70) mediante Western blotting. Questa proteina, che viene indotta da numerosi fattori di stress, è uno dei principali sistemi endogeni di citoprotezione. I risultati ottenuti hanno evidenziato che il AlCl3, nel range di concentrazioni saggiato, non causa danni primari ad DNA né induce espressione di Hsp70 nelle cellule SK-N-BE(2). Tuttavia, considerata l'ampia diffusione dell'alluminio nell'ambiente, sarà interessante verificare se queste dosi, in condizioni di co-esposizione, siano in grado di potenziare l'azione citotossica di altri fattori ambientali chimici o fisici. [ABSTRACT FROM AUTHOR]

The presence of background DNA (bgDNA) can hinder the evaluation of DNA evidence at the activity level, especially when the suspect is expected to be retrieved due to their habitual occupation of the investigated environment. Based on real-life casework circumstances, this study investigates the prevalence, composition, origin, and probable transfer routes of bgDNA found on personal items in situations where their owner and person of interest (POI) share the same workspace. Baseline values of bgDNA were evaluated on the participants' personal items. Secondary and higher degree transfer scenarios of non-self DNA deposition were also investigated. The DNA from co-workers and co-inhabiting partners can be recovered from an individual's personal belongings. Non-self DNA present on the hands and deposited on a sterile surface can generate uninformative profiles. The accumulation of foreign DNA on surfaces over time appears to be crucial for the recovery of comparable profiles, resulting in detectable further transfer onto other surfaces. For a thorough evaluation of touch DNA traces at the activity level, it is necessary to collect information not only about DNA transfer probabilities but also about the presence of the POI as part of the 'baseline' bgDNA of the substrates involved. [ABSTRACT FROM AUTHOR]

Wound age estimation is a significant issue in forensic pathology. Although various methods have been evaluated, no gold standard system or model has been proposed, and accurate injury time estimation is still challenging. The distinction between vital skin wounds—i.e., ante-mortem lesions—and skin alterations that occur after death is a crucial goal in forensic pathology. Once the vitality of the wound has been confirmed, the assessment of the post-trauma interval (PTI) is also fundamental in establishing the causal relationship between the traumatic event and death. The most frequently used techniques in research studies are biochemistry, molecular biology, and immunohistochemistry (IHC). Biochemical methods take advantage of the chemical and physical techniques. A systematic literature search of studies started on 18 February 2023. The search was conducted in the main databases for biomedical literature, i.e., PubMed and Scopus, for papers published between 1973 and 2022, focusing on different techniques of immunohistochemistry and immunofluorescence (IF) for estimating the PTI of skin wounds. The present study involves a comprehensive and structured analysis of the existing literature to provide a detailed and comprehensive overview of the different IHC techniques used to date skin lesions, synthesize the available evidence, critically evaluate the methodologies, and eventually draw meaningful conclusions about the reliability and effectiveness of the different markers that have been discovered and used in wound age estimation. [ABSTRACT FROM AUTHOR]

In a judiciary setting, questions regarding the mechanisms of transfer, persistence, and recovery of DNA are increasingly more common. The forensic expert is now asked to evaluate the strength of DNA trace evidence at activity level, thus assessing if a trace, given its qualitative and quantitative features, could be the result of an alleged activity. The present study is the reproduction of a real-life casework scenario of illicit credit card use by a co-worker (POI) of its owner (O). After assessing the shedding propensity of the participants, differences in DNA traces' qualitative and quantitative characteristics, given scenarios of primary and secondary transfer of touch DNA on a credit card, a non-porous plastic support, were investigated. A case-specific Bayesian Network to aid statistical evaluation was created and discrete observations, meaning the presence/absence of POI as a major contributor in both traces from direct and secondary transfer, were used to inform the probabilities of disputed activity events. Likelihood Ratios at activity level (LRα) were calculated for each possible outcome resulting from the DNA analysis. In instances where only POI and POI plus an unknown individual are retrieved, the values obtained show moderate to low support in favour of the prosecution proposition. [ABSTRACT FROM AUTHOR]

The road and rail transport sector, since the several work tipology and risk factors for workers safety and health, is an area where assessing exposure effects is very difficult. Muscoskeletal cardiovascular and neoplastic diseases are the disorders more frequently associated to professional drivers. The role of professional driving is rather well-defined in low back pain occurence, correlated to whole body vibration exposure. Professional drivers are at higher risk of ischemic cardiovascular diseases, but it is not clear whether the risk is attributable just to the occupational exposures or also to their life-style risk factors. Evidence of an excess of risk for lung, genito-urinary and hemolymphopoietic cancer is clear in the scientific literature for professional drivers. Anyway the lack in the control of confounding factors, in exposure assesment force to be very cautious in results interpretation. [ABSTRACT FROM AUTHOR]

Objectives: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. Methods: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. Results: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46–70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. Conclusions: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. Key Points: • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated. [ABSTRACT FROM AUTHOR]

Lysosomes play an important role in the immune system functioning and are involved in different aspects of inflammatory reaction, repair processes and tissue damage at various levels. Among various effects, it is known that physical exercise influences the release of different lysosomal components. The aim of this study was to evaluate enzyme activity and isoenzymatic profile of βN-acetylhexosaminidase both in kidney and urine of normal and trained rats. Enzyme activity was measured by fluorimetric assay while β-N-acetylhexosaminidase isoenzymes were separated using DEAE-cellulose chromatography. Hexosaminidase specific activity was significantly increased in urine of trained rats whereas there was no increase in the kidneys of trained rats. Indeed, no significant differences were observed in the isoenzyme profile of kidney and urine extracts from normal and trained rats. Our findings suggest the exerciseinduced release of lysosomal enzymes is a functional effect and not due to disruption of lysosomal membranes. [ABSTRACT FROM AUTHOR]

Objective: With the aim of standardizing and improving the use of ultrasound-guided PLA on PTMC, a panel of experts from China and Italy, jointly issued this expert consensus on the clinical use of PLA for low-risk PTMC. Methods: This expert consensus was developed by Chinese and Italian experts who have specific competence and expertise in this area. An evidence-based approach combining the knowledge and practical experience of the panelists was utilized. Results: Twenty-six expert consensus recommendations were developed, spanning topics including the indications and contraindications of PLA for PTMC, physician training, preoperative preparation of patients, intraoperative technical procedures, possible complications, efficacy assessment, follow-up strategy, the approach to new PTMC and metastatic lymph nodes after treatment, thyroid-stimulating hormone inhibition therapy, and quality control of the entire procedure. Conclusion: We summarized practical recommendations about standardized and improved PLA treatment for PTMC. [ABSTRACT FROM AUTHOR]

Background: The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy.Methods: The Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011-17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre.Results: Very few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10- 4. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL.Conclusions: Our findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is associated with high mortality in patients on oral anticoagulant treatment. The normalization of hemostatic balance usually requires slow-acting or risky treatments, such as vitamin K, fresh frozen plasma or prothrombin complex concentrates, which have narrow therapeutic windows particularly in cardiopathic patients like those with mechanical heart valves. Recombinant activated factor VII (rFVIIa) seems useful in patients with normal or pathologic coagulation who have an ICH. We report of a patient on acenocumarol for mitro-aortic valve replacement, referred for headache and found at computerized tomography scanning to have a parietal hemorrhage with ventricular invasion. International normalized ratio was 3.22. The patient was treated with vitamin K and with a bolus of 80 μg/kg of rFVIIa, with correction of the international normalized ratio within 15 min. Sequential computerized tomographies showed progressive reduction of the hematoma and normalization of ventricular spaces and the patient fully recovered. No valvular dysfunctions or cardiac thrombi were found at sequential echocardiograms. Neurological examination at 3 months follow-up visit was completely normal. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat ICH in a patient on oral anticoagulants for prosthetic heart valves. [ABSTRACT FROM AUTHOR]

Objective: To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mL-1 (Gla-300) and degludec 100 units ⋅ mL-1 (Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D).Research Design and Methods: Subjects with T1D (N = 22, 11 men, age 44.3 ± 12.4 years, disease duration 25.5 ± 11.7 years, A1C 7.07 ± 0.63% [53.7 ± 6.9 mmol ⋅ mL-1], BMI 22.5 ± 2.7 kg · m-2), naïve to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34 ± 0.08 units ⋅ kg-1) and Deg-100 (0.26 ± 0.06 units ⋅ kg-1), dosing at 2000 h, after 3 months of optimal titration of basal (and bolus) insulin.Results: At the end of 3 months, Gla-300 and Deg-100 reduced slightly and, similarly, A1C versus baseline. Clamp average plasma glucose (0-24 h) was euglycemic with both insulins. The area under curve of glucose infused (AUC-GIR[0-24 h]) was equivalent for the two insulins (ratio 1.04, 90% CI 0.91-1.18). Suppression of endogenous glucose production, free fatty acids, glycerol, and β-hydroxybutyrate was 9%, 14%, 14%, and 18% greater, respectively, with Gla-300 compared with Deg-100 during the first 12 h, while glucagon suppression was no different. Relative within-day PD variability was 23% lower with Gla-300 versus Deg-100 (ratio 0.77, 90% CI 0.63-0.92).Conclusions: In T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects. [ABSTRACT FROM AUTHOR]

Highlights • RT exposure increases lipid peroxidation and protein carbonyl levels in PC12 cells. • RT exposure induces impairment of energy metabolism in PC12 cells. • RT exposure induces impairment of neurotransmitter biosynthesis in PC12 cells. • RT exposure induces alterations in cytoskeletal homeostasis in PC12 cells. • RT exposure induces alterations in the proteostasis systems in PC12 cells. Abstract Rotenone is an environmental neurotoxin that induces degeneration of dopaminergic neurons and the most common features of Parkinson's disease in animal models. It acts as a mitochondrial complex I inhibitor that impairs cellular respiration, with consequent increase of reactive oxygen species and oxidative stress. This study evaluates the rotenone-induced oxidative damage in PC12 cells, focusing particularly on protein oxidation. The identification of specific carbonylated proteins highlighted putative alterations of important cellular processes possibly associated with Parkinson's disease. Carbonylation of ATP synthase and of enzymes acting in pyruvate and glucose metabolism suggested a failure of mechanisms ensuring cellular energy supply. Concomitant oxidation of cytoskeletal proteins and of enzymes involved in the synthesis of neuroactive molecules indicated alterations of the neurotransmission system. Carbonylation of chaperon proteins as well as of proteins acting in the autophagy-lysosome pathway and the ubiquitin-proteasome system suggested the possible formation of cytosolic unfolded protein inclusions as result of defective processes assisting recovery/degradation of damaged molecules. In conclusion, this study originally evidences specific protein targets of rotenone-induced oxidative damage, suggesting some possible molecular mechanisms involved in rotenone toxicity. [ABSTRACT FROM AUTHOR]

Purpose:To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. Materials and methods:Institutional review board approval was obtained, and patients’ consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. Results:No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was −67 ± 19% vs. −57 ± 21% (p < 0.001) − 70 ± 19% vs. −62 ± 22% (p= 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (−69 ± 19 vs. −50 ± 21,p = 0.001) and (−73 ± 18 vs. −54 ± 23 8,p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator’s skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions:LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator’s skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique. [ABSTRACT FROM PUBLISHER]