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Background: Epithelial tumors of lacrimal glands are rare and primary ductal adenocarcinoma of the lacrimal gland accounts for only 2% of all epithelial lacrimal gland tumors. Considering its rarity and lack of uniform diagnostic criteria, treatment protocols are not well defined. In this study, we describe a Her-2 positive case and review previously reported cases. Methods: In 2012, a 42-year-old woman affected by primary ductal adenocarcinoma of the lacrimal gland was treated with transpalpebral anterior orbitotomy and adjuvant radiotherapy. In July 2013, she presented local relapse and she underwent orbital exenteration. In November 2013, for neck nodal progression, seven cycles of chemotherapy (cisplatin and epirubicin) associated with a humanized monoclonal antibody-targeting HER 2 therapy (trastuzumab and pertuzumab) were performed, with a marked response rate. Then, she underwent total parotidectomy with right neck lymphadenectomy and adjuvant hadrontherapy. Results: Nine years later (113 months) after treatment completion, the patient was alive without disease and with acceptable toxicity. Conclusions: In primary ductal adenocarcinoma of the lacrimal gland, early diagnosis and multimodal treatments could be crucial, considering its often aggressive tendency. Considering the lack of treatment guidelines, case report recording can be useful in patient management., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 C. L. Deantoni et al.)

Background: Stereotactic ablative radiotherapy (SABR) is emerging as a potential local treatment option for oligometastatic RCC. This study aims to evaluate the efficacy of SABR in patients with oligorecurrent RCC., Methods: A total of 50 patients with histologically confirmed RCC underwent SABR for oligorecurrence between 2006 and 2022. Eligible patients had up to five extracranial metastases and were systemic treatment-naïve at the time of irradiation. The primary endpoints of the analysis were overall survival (OS), local control (LC), distant metastasis-free survival (DMFS), and time to systemic therapy initiation., Results: The median OS was not reached, with 1- and 3-year OS rates of 93.8% and 77.5%, respectively. LC rates at one and three years were 95.8% and 86.5%, respectively. The median time to systemic therapy initiation was 63.8 months, and the median DMFS was 17.9 months, with one- and three-year rates of 63.4% and 36.6%, respectively. Multiple metastases were a negative predictive factor for DMFS (HR 2.39, p = 0.023), whereas lung metastases were associated with a more favorable outcome (HR 0.38, p = 0.011)., Conclusions: SABR offers a valuable treatment option for oligometastatic RCC, demonstrating significant potential for achieving long-term disease control and delaying the need for systemic therapy.

Purpose: To assess late gastrointestinal (GI) and genitourinary (GU) side effects in patients with organ-confined unfavorable prostate cancer (PCa) treated with single-dose ablative radiation therapy (SDRT)., Methods and Materials: Thirty patients enrolled in a single-arm prospective trial received 24 Gy SDRT to the whole prostate with urethra-sparing and organ motion control delivered on a Linac platform with a 10 MV flattening filter-free single partial arc. Androgen deprivation therapy was prescribed as per standard of care. Treatment-related acute and late GU and GI toxicities (Common Terminology Criteria for Adverse Events_v5 scale) and quality of life (QoL) outcomes (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-PR25/C30, International Prostate Symptom Score [IPSS]) were assessed at different time points. Minimal important difference (MID) was established as a change of >0.5 pooled standard deviations from baseline. Statistical analysis included analysis of variance and logistic regression., Results: Median follow-up was 18 months (range, 6-31 months), with no ≥G3 late side effects observed. G2 late GI and G2 late GU toxicities occurred in 1 and 2 patients, respectively. GI toxicity of any grade correlated with maximum rectal dose (P = .021). Lower baseline QoL score (P = .025), higher baseline IPSS score (P = .049), acute GU toxicity (P = .029), and acute urinary domain MID (P = .045) predicted GU toxicity of any grade. In multivariate analysis (MVA), only baseline QoL score (odds ratio [OR], 0.95, P = .031) and acute GU toxicity (OR, 8.4, P = .041) remained significant. Significant QoL change was observed only in the urinary domain (P = .005), with a median increase from 8 to 17. Late urinary MID correlated with acute urinary MID (P = .003), acute QoL MID (P = .029), acute GU toxicity (P = .030), and lower baseline urinary score (P = .033). In MVA, only acute urinary MID predicted late urinary MID (OR, 9.7, P = .035)., Conclusions: Our findings provide promising data on the feasibility and safety of 24 Gy whole-gland SDRT with urethra-sparing and organ motion control, in association with androgen deprivation therapy and an adequate prophylactic medication, in organ-confined unfavorable PCa. Long-term follow-up is needed to confirm these results., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The assessment of heavy metals' effects on human health is frequently limited to investigating one metal or a group of related metals. The effect of heavy metals mixture on heart attack is unknown., Methods: This study applied the Bayesian kernel machine regression model (BKMR) to the 2011-2016 National Health and Nutrition Examination Survey (NHANES) data to investigate the association between heavy metal mixture exposure with heart attack. 2972 participants over the age of 20 were included in the study., Results: Results indicate that heart attack patients have higher levels of cadmium and lead in the blood and cadmium, cobalt, and tin in the urine, while having lower levels of mercury, manganese, and selenium in the blood and manganese, barium, tungsten, and strontium in the urine. The estimated risk of heart attack showed a negative association of 0.0030 units when all the metals were at their 25 th percentile compared to their 50 th percentile and a positive association of 0.0285 units when all the metals were at their 75 th percentile compared to their 50 th percentile. The results suggest that heavy metal exposure, especially cadmium and lead, may increase the risk of heart attacks., Conclusions: This study suggests a possible association between heavy metal mixture exposure and heart attack and, additionally, demonstrates how the BKMR model can be used to investigate new combinations of exposures in future studies., Competing Interests: Conflicts of Interest The authors declare no conflict of interest.

Introduction: The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging., Evidence Acquisition: A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations., Evidence Synthesis: Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident., Conclusions: PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.

Traditional products are particularly appreciated by consumers and among these products, cheese is a major contributor to the Italian mountainous area economics. In this study, shotgun metagenomics and volatilomics were used to understand the biotic and abiotic factors contributing to mountain Caciotta cheese typicity and diversity. Results showed that the origin of cheese played a significant role; however, curd cooking temperature, pH, salt concentration and water activity also had an impact. Viral communities exhibited higher biodiversity and discriminated cheese origins in terms of production farms. Among the most dominant bacteria, Streptococcus thermophilus showed higher intraspecific diversity and closer relationship to production farm when compared to Lactobacillus delbrueckii. However, despite a few cases in which the starter culture was phylogenetically separated from the most dominant strains sequenced in the cheese, starter cultures and dominant cheese strains clustered together suggesting substantial starter colonization in mountain Caciotta cheese. The Caciotta cheese volatilome contained prominent levels of alcohols and ketones, accompanied by lower proportions of terpenes. Volatile profile not only demonstrated a noticeable association with production farm but also significant differences in the relative abundances of enzymes connected to flavor development. Moreover, correlations of different non-homologous isofunctional enzymes highlighted specific contributions to the typical flavor of mountain Caciotta cheese. Overall, this study provides a deeper understanding of the factors shaping typical mountain Caciotta cheese, and the potential of metagenomics for characterizing and potentially authenticating food products., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Origin authentication methods are pivotal in counteracting frauds and provide evidence for certification systems. For these reasons, geographical origin authentication methods are used to ensure product origin. This study focused on the origin authentication (i.e. at the producer level) of a typical mountain cheese origin using various approaches, including shotgun metagenomics, volatilome, near infrared spectroscopy, stable isotopes, and elemental analyses. DNA-based analysis revealed that viral communities achieved a higher classification accuracy rate (97.4 ± 2.6 %) than bacterial communities (96.1 ± 4.0 %). Non-starter lactic acid bacteria and phages specific to each origin were identified. Volatile organic compounds exhibited potential clusters according to cheese origin, with a classification accuracy rate of 90.0 ± 11.1 %. Near-infrared spectroscopy showed lower discriminative power for cheese authentication, yielding only a 76.0 ± 31.6 % classification accuracy rate. Model performances were influenced by specific regions of the infrared spectrum, possibly associated with fat content, lipid profile and protein characteristics. Furthermore, we analyzed the elemental composition of mountain Caciotta cheese and identified significant differences in elements related to dairy equipment, macronutrients, and rare earth elements among different origins. The combination of elements and isotopes showed a decrease in authentication performance (97.0 ± 3.1 %) compared to the original element models, which were found to achieve the best classification accuracy rate (99.0 ± 0.01 %). Overall, our findings emphasize the potential of multi-omics techniques in cheese origin authentication and highlight the complexity of factors influencing cheese composition and hence typicity., Competing Interests: Declaration 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 paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: The definition of oligometastatic prostate cancer (OPCa) is currently based solely on the maximum number of detectable metastases, as there are no validated biomarkers available. The aim of this study was to identify novel predictive factors for OPCa patients who underwent metastases-directed therapy., Materials and Methods: This monocentre, retrospective study included consecutive OPCa patients with a maximum of five metastases in up to two organs, detected with choline- or PSMA-positron emission tomography, who were treated with metastases-directed stereotactic body radiation therapy. Endpoints were overall survival and progression-free survival, assessed with Kaplan-Meier analysis. Univariate and multivariable Cox regression was carried out to evaluate the association between clinical factors and survival outcomes., Results: Between 2009 and 2021, 163 patients and 320 metastases were treated with 226 stereotactic body radiation therapy courses. The median three-dimensional metastatic tumour volume was 4.1 cm 3 , with a range from 0.01 to 233.4 cm 3 . In total, 87 (53.4%), 21 (12.9%) and 55 (33.7%) metastases were classified as cN1, cM1a and cM1b, respectively. The median follow-up was 28.5 months. The rates of overall survival at 1, 3 and 5 years were 89.5% (95% confidence interval 83.4-93.4), 74.9% (95% confidence interval 66.1-81.7) and 57.2% (95% confidence interval 45.8-67.1), respectively. Multivariable analysis showed that overall survival reduced with the increase in three-dimensional total tumour volume (hazard ratio 1.93, 95% confidence interval 1.06-3.52; P = 0.030) and confirmed a significant difference between cN1 versus cM1a-b disease (hazard ratio 1.81, 95% confidence interval 1.01-3.25; P = 0.046). The cut-off value of total volume correlated with the highest risk of death was 20 cm 3 (hazard ratio 2.37, 95% confidence interval 1.34-4.18; P = 0.003). The median progression-free survival was 17.8 months, with 1-, 3- and 5-year rates of 63.7% (95% confidence interval 55.4-70.9), 31.5% (95% confidence interval 22.8-40.6) and 24.7% (95% confidence interval 16.0-34.3)., Conclusions: This study identified three-dimensional total tumour volume and the site of oligometastases as significant predictors of survival in OPCa patients treated with metastases-directed therapy. These parameters can potentially be used to personalised treatment and improve patient outcome., (Copyright © 2023. Published by Elsevier Ltd.)

Background: While SBRT to the prostate has become a valuable option as a radical treatment, limited data support its use in the postoperative setting. Here, we report the updated results of the multicentric Post-Prostatectomy Ablative Radiation Therapy (POPART) trial, investigating possible predictors of toxicities and patient-reported outcomes., Methods: Patients with PSA levels between 0.1-2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD2 1.5  = 74.3 Gy). Late toxicity was assessed using CTCAE v.5 scale, while EPIC-CP, ICIQ-SF, IIEF 5 questionnaires and PSA levels measured quality of life and biochemical control. Pre- and post-treatment scores were compared using a paired t -test, with MID established at > 0.5 pooled SD from the baseline. A logistic regression analysis was performed to evaluate potential associations between specific patient/tumor/treatment factors and outcome deterioration., Results: From April 2021 to April 2023 a total of 50 pts were enrolled and treated. Median follow-up was 12.2 (3-27) months. No late ≥ G2 GI or GU toxicity was registered. Late G1 urinary and rectal toxicities occurred in 46 % and 4 % of patients, respectively. Among 47 patients completing all EPIC-CP domains, four (9 %) showed worsened QoL, and eleven (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032). At Multivariate analysis bladder wall D10cc independently correlated with late G1 GU toxicity (P = 0.034). Median post-treatment PSA nadir was 0.04 ng/mL (0.00 - 0.84). At the last follow-up, six patients presented with biochemical failure, including two nodal relapses., Conclusions: Our findings show that post-prostatectomy SBRT did not result in increased toxicity nor a significant decline in QoL measures, thus showing that it can be safely extended to the postoperative setting. Long-term follow-up and randomized comparisons with different RT schedules are needed to validate this approach., Competing Interests: 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 paper., (© 2023 The Authors.)

Morbidities generally show patterns of concentration that vary by space and time. Disease mapping models are useful in estimating the spatiotemporal patterns of disease risks and are therefore pivotal for effective disease surveillance, resource allocation, and the development of prevention strategies. This study considers six spatiotemporal Bayesian hierarchical models based on two spatial conditional autoregressive priors. It could serve as a guideline on the development and application of Bayesian hierarchical models to assess the emerging risk trends, risk clustering, and spatial inequality trends, with estimation of covariables' effects on the interested disease risk. The method is applied to the Florida Birth Record data between 2006 and 2015 to study two cardiovascular risk factors: preeclampsia and gestational diabetes. High-risk clusters were detected in North Central Florida for preeclampsia and in Central Florida for gestational diabetes. While the adjusted disease trend was stable, spatial inequality peaked in 2011-2012 for both diseases. Exposure to PM2.5 at first or/and second trimester increased the risk of preeclampsia and gestational diabetes, but the magnitude is less severe compared to previous studies. In conclusion, this study underscores the significance of selecting appropriate disease mapping models in estimating the intricate spatiotemporal patterns of disease risk and suggests the importance of localized interventions to reduce health disparities. The result also identified an opportunity to study potential risk factors of preeclampsia, as the spike of risk in North Central Florida cannot be explained by current covariables., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Manganese (Mn) exposure has evolved from acute, high-level exposure causing manganism to low, chronic lifetime exposure. In this latter scenario, the target areas extend beyond the globus pallidus (as seen with manganism) to the entire basal ganglia, including the substantia nigra pars compacta. This change of exposure paradigm has prompted numerous epidemiological investigations of the occurrence of Parkinson's disease (PD), or parkinsonism, due to the long-term impact of Mn. In parallel, experimental research has focused on the underlying pathogenic mechanisms of Mn and its interactions with genetic susceptibility. In this review, we provide evidence from both types of studies, with the aim to link the epidemiological data with the potential mechanistic interpretation.

Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours., Methods: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186., Findings: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039)., Interpretation: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient's original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient's CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were -3.0% [-18.5-2.8] for CTV D99% and -2.6% [-17.8-1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments., Competing Interests: The authors declare no conflict of interest.

The presence of Listeria monocytogenes (Lm) in the food processing environment (facilities and products) is a challenging problem in food safety management. Lm is one of the main causes of mortality in foodborne infections, and the trend is continuously increasing. In this study, a collection of 323 Lm strain isolates recovered from food matrices and food industry environments (surfaces and equipment) over four years from 80 food processing facilities was screened using a restriction site-associated tag sequencing (2b-RAD) typing approach developed for Lm. Thirty-six different restriction site-associated DNA (RAD) types (RTs) were identified, most of which correspond to lineage II. RT1, the most represented genotype in our collection and already reported as one of the most prevalent genotypes in the food environment, was significantly associated with meat processing facilities. The sequencing of the genomes of strains belonging to the same RT and isolated in the same facility in different years revealed several clusters of persistence. The definition of the persistent strains (PSs) allowed the identification of the potential source of contamination in the incoming raw meat that is introduced in the facility to be processed. The slaughterhouses, which, according to the European Union (EU) regulation, are not inspected for the presence of Lm could be hotspots for the persistence of Lm PSs., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Modern industrial agricultural processes expose human beings to multifactorial environmental pollution including heightened levels of heavy metals. The effects of acute heavy metal exposures at toxic levels are usually known; they are tested for and treated promptly. The effects of low/moderate-level chronic heavy metal exposures are less known as they may be subclinical, and pathogenic effects may only manifest clinically over time under the disguise of a diagnosable disease or miscellaneous symptoms attributed to aging. Consequently, the health impact of low-moderate heavy metal exposure is unlikely to be identified. Furthermore, established heavy metal safety levels often fail to recognize the potential toxic effects on humans. We report in this review what is known about the sub-chronic and chronic effects of exposure to heavy metals, particularly lead, mercury, cadmium, arsenic, and nickel, and we highlight their possible effects in the brain, cardiovascular and endocrine-metabolic systems, and on reproduction.

Purpose of Review: At elevated levels, the essential element manganese (Mn) is neurotoxic and increasing evidence indicates that environmental Mn exposure early in life negatively affects neurodevelopment. In this review, we describe how underlying genetics may confer susceptibility to elevated Mn concentrations and how the epigenetic effects of Mn may explain the association between Mn exposure early in life and its toxic effects later in life., Recent Findings: Common polymorphisms in the Mn transporter genes SLC30A10 and SLC39A8 seem to have a large impact on intracellular Mn levels and, in turn, neurotoxicity. Genetic variation in iron regulatory genes may to lesser extent also influence Mn levels and toxicity. Recent studies on Mn and epigenetic mechanisms indicate that Mn-related changes in DNA methylation occur early in life. One human and two animal studies found persistent changes from in utero exposure to Mn but whether these changes have functional effects remains unknown. Genetics seems to play a major role in susceptibility to Mn toxicity and should therefore be considered in risk assessment. Mn appears to interfere with epigenetic processes, potentially leading to persistent changes in developmental programming, which warrants further study., (© 2022. The Author(s).)

Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970)., Methods: Patients with post-radical prostatectomy PSA levels of ≥0.1-2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD2 1.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up., Results: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55-82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18-1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0-0.48 ng/mL)., Conclusions: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

The 2030 United Nations Goal 8 for sustainable development focuses on decent work. There is utility in identifying the occupational safety and health aspects of Goal 8, as they pertain to the four pillars of decent work: job creation, social protection, rights of workers, and social dialogue. A workgroup of the International Commission on Occupational Health and collaborators addressed the issue of decent work and occupational safety and health (OSH) with the objective of elaborating a framework for guidance for practitioners, researchers, employers, workers, and authorities. This article presents that framework, which is based on an examination of the literature and the perspectives of the workgroup. The framework encompasses the intersection of the pillars of decent (employment creation, social protection, rights of workers, and social dialogue) work with new and emerging hazards and risks related to various selected determinants: new technologies and new forms of work; demographics (aging and gender); globalization; informal work; migration; pandemics; and OSH policies and climate change. The OSH field will need an expanded focus to address the future of decent work. This focus should incorporate the needs of workers and workforces in terms of their well-being. The framework identifies a starting point for the OSH community to begin to promote decent work.

Objectives: We aimed to analyze the impact of a 3-week schedule of HypoFractionated (HF) radiotherapy (RT) after axillary dissection and breast surgery, in terms of safety and efficacy in patients with locally advanced breast cancer (BC)., Methods: Eligible patients were females with Stage IIA - IIIC BC who underwent axillary dissection and breast surgery, either quadrantectomy or mastectomy. HF RT was delivered in 15 or 16 fractions for a total dose of 40.05 Gy or 42.56 Gy, respectively, to the clavicular nodal region along with the whole breast (HF WBRT) or the chest wall (HF PMRT), according to the type of surgery. Locoregional recurrence (LRR), distant metastases-free survival (DMFS), overall survival (OS) and acute and late treatment-related toxicities were estimated., Results: 57 patients with a median age of 60 years (32-85) were retrospectively analyzed. 34 (60%) of patients underwent breast conservative surgery in the form of quadrantectomy and 23 (40%) were offered radical mastectomy. All patients underwent hypofractionated regional nodal irradiation (HF RNI). 34 (60%) of them underwent HF WBRT, while 23 (40%) received HF PMRT.At a median follow-up of 80 months (30-113), the 7-year LRR-free survival was 93% (95% CI, 74%-95%). The same features for DMFS and OS were 76% (95% CI, 52%-78%) and 67% (95% CI, 50%-80%), respectively. Only one (2%) patient experienced G3 acute skin toxicity. No grade ≥2 late toxicity was observed., Conclusion: Our study shows that HF RNI with HF RT to the whole breast or the chest wall after breast surgery is safe and effective in patients with locally advanced BC. Longer follow-up is needed to strengthen further analyses on late toxicity and clinical outcomes., Advances in Knowledge: This paper adds to the evidence that post-operative RNI with WBRT or PMRT can be safely and effectively delivered with 3-week HF regimen. Locally advanced BC patients can be offered HF RT to the regional nodes and the breast or the chest wall regardless the type of surgery.

Purpose: Our study investigated the association between treatment-related lymphopenia and overall survival (OS) in a series of glioblastoma (GBM) patients. We also explored clinical and dosimetric predictors of lymphocytes depletion., Methods: Between 2015 and 2019, 64 patients were treated at the same institution with postoperative chemoradiotherapy. Peripheral lymphocyte count (PLC) data and dose-volume histogram parameters were collected. Radiotherapy (RT) schedule consisted in standard total dose of 60 Gy in 30 daily fractions, with concomitant and adjuvant temozolomide (TMZ). Posttreatment acute absolute lymphopenia (nadir AAL) was calculated as a PLC lower than 1.0 × 10 3 /mm 3 . Acute relative lymphopenia (ARL) was expressed by the nadir-PLC/baseline-PLC ratio < 0.5. Nadir-PLC was the lowest PLC registered between the end of RT and the first month of follow-up. Survival rates were estimated with Kaplan-Meier curves. Clinical and dosimetric variables related to AAL/ARL and OS were identified by univariate and multivariate analyses., Results: A total of 57 patients were eligible and included in the analyses. The median PLC was significantly decreased following chemoradiotherapy (2180/mm 3 vs 900/mm 3 ). Median OS was 16 months (range 5-55 months), with no significant difference between patients who developed nadir AAL and those who did not (16 months vs 16.5 months; p = 0.304). When considering ARL vs non-ARL, median OS was 14 months vs 26 months (p = 0.013), respectively. In multivariate Cox regression only age, sex, extent of surgery, access to adjuvant chemotherapy and brain D98% were independently associated with OS., Conclusion: Although iatrogenic immunosuppression could be associated with inferior clinical outcomes, our data show that treatment-related lymphopenia does not adversely affect GBM survival. Prospective studies are required to confirm these findings., (© 2021. The Author(s).)

Manganese (Mn) is an essential metal with a biphasic relationship with health outcomes. High-level exposure to Mn is associated with manganism, but few data explore the effects of chronic, lower-level Mn on cognitive function in adults. We sought to determine the relationship between blood/urinary manganese levels and cognitive function in elderly individuals using 2011-2014 data from the National Health and Nutrition Examination Survey (NHANES). Weighted multivariate regression models were used to determine correlations, adjusting for several covariates. Blood Mn was inversely associated with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) immediate learning of new verbal information ( p -value = 0.04), but lost significance after adjusting for medical history ( p -value = 0.09). In addition, blood Mn was inversely associated with Animal Fluency scores after adjusting for all covariates. Urinary Mn was inversely associated with CERAD immediate learning after adjusting for all covariates ( p -value = 0.01) and inversely associated with the Digit Symbol Substitution Test scores ( p -value = 0.0002), but lost significance after adjusting for medical history ( p -value = 0.13). Upon stratifying by race/ethnicity, other Races and Non-Hispanic (NH)-Blacks had significantly higher blood Mn levels when compared to NH-Whites. Collectively, these findings suggest that increased blood and urinary Mn levels are associated with poorer cognitive function in an elderly US population.

Background: Extreme hypofractionation requires tight planning margins, high dose gradients, and strict adherence to planning criteria in terms of patient positioning and organ motion mitigation. This study reports the first clinical experience worldwide using a novel electromagnetic (EM) tracking device for intrafraction prostate motion management during dose-escalated linac-based stereotactic body radiation therapy (SBRT)., Methods: Thirteen patients with organ-confined prostate cancer underwent dose-escalated SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The EM tracking device consisted of an integrated Foley catheter with a transmitter. Patients were simulated and treated with a filled bladder and an empty rectum. Setup accuracy was achieved by ConeBeam-CT (CBCT) matching, and motion was tracked during all the procedure. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and, unless the offset was transient, target position was re-defined by repeating CBCT. Moreover, the displacements that would have occurred without any intrafraction organ motion management (i.e. no interruptions and repositionings) were simulated., Results: In 31 out of 56 monitored fractions (55%), no intervention was required to correct the target position. In 25 (45%) a correction was mandated, but only in 10 (18%), the beam delivery was interrupted. Total treatment time lasted on average 10.2 minutes, 6.7 minutes for setup, and 3.5 minutes for beam delivery. Without any intrafraction motion management, the overall mean treatment time and the mean delivery time would have been 6.9 minutes and 3.2 minutes, respectively. The prostate would have been found outside the tolerance in 8% of the total session time, in 4% of the time during the setup, and in 14% during the beam-on phase. Predominant motion pattern was posterior and its probability increased with time, with a mean motion ≤ 2 mm occurring within 10 minutes., Conclusions: EM real-time tracking was successfully implemented for intrafraction motion management during dose-escalated prostate SBRT. Results showed that most of the observed displacements were < 2 mm in any direction; however, there were a non-insignificant number of fractions with motion exceeding the predefined threshold, which would have otherwise gone undetected without intrafraction motion management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Panizza, Faccenda, Lucchini, Daniotti, Trivellato, Caricato, Pisoni, De Ponti and Arcangeli.)

Although high sensitive imaging modalities such as MRI and PSMA PET/CT are becoming available for prostate cancer (PCa), the clinical benefit of an earlier detection of subclinical disease remains yet undetermined. Given these uncertainties, univocal recommendations are often lacking. The present survey was therefore developed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) to collect the opinion of expert radiation oncologists and delineate a representation of current clinical practice in our country. A nationwide cross-sectional survey was conducted in Italy by administering an anonymous questionnaire to experienced radiation oncologists, representative of the genitourinary (GU) tumor board at their Institution, using the cloud-based platform SurveyMonkey®. For each question, a consensus was achieved when ≥ 75% of the responders agreed on the same response. Thirty nine AIRO members from different Italian centers who were deemed experts in GU field accessed the proposed survey and completed all sections. Explored topics included staging of organ-confined disease, management of biochemical and local recurrence, imaging in the metastatic setting, imaging following metastasis-directed therapy (MDT), and future considerations. Response rate for single item of the questionnaire ranged between 51.2% and 100%. Expert GU AIRO members agree that advanced molecular and functional imaging are expanding their role in local and distant staging of PCa, as well as in the oncologic management and in the assessment of treatment response. However, many controversial issues still exist on the best timing for a diagnostic evaluation and the most appropriate imaging to aim at this purpose., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Lateral neck dissection (LND) leads to a significant morbidity involving accessory nerve injury. Modified radical neck dissection (MRND) aims at preservation of the accessory nerve, but patients often present with negative functional outcomes after surgery. The role of neuromonitoring (IONM) in the prevention of shoulder syndrome has not yet been defined in comparison to nerve visualization only. We retrospectively analyzed 56 thyroid cancer patients who underwent MRND over a period of six years (2015-2020) in a high-volume institution. Demographic variables, type of surgical procedure, removed lymph nodes and the metastatic node ratio, pathology, adoption of IONM and shoulder functional outcome were investigated. The mean number of lymph nodes removed was 15.61, with a metastatic node ratio of 0.2745. IONM was used in 41.07% of patients, with a prevalence of 68% in the period 2017-2020. IONM adoption showed an effect on post-operative shoulder function. There were no effects in 89.29% of cases, and temporary and permanent effects in 8.93% and 1.79%, respectively. Confidence intervals and two-sample tests for equality of proportions were used when applicable. Expertise in high-volume centres and IONM during MRND seem to be correlated with a reduced prevalence of accessory nerve lesions and limited functional impairments. These results need to be confirmed by larger prospective randomized controlled trials.

Purpose/objectives: To report preliminary data on treatment outcome and compliance to dose-intensified organ sparing SBRT for prostate cancer using a novel electromagnetic transmitter-based tracking system (RayPilotÒ System) to account for intra-fractional organ motion., Material/methods: Thirteen patients with intermediate unfavorable (9) and selected high-risk (4) prostate cancer underwent dose-escalated SBRT in 4 or 5 fractions (BED 1.5  = 279 Gy and 253 Gy, respectively). The VMAT treatment consisted in two 6FFF or 10FFF full arcs optimized to have the 95% isodose covering at least 95% of the PTV (2 mm isotropic expansion of the CTV). Whenever the real-time tracking registered a displacement that exceeded 2 mm during the setup and/or the beam delivery, the treatment was interrupted and the prostate motion was promptly corrected. The incidence of treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity, patient QoL and PSA outcomes were computed from the start of treatment to the last follow-up date., Results: All patients completed the treatment in the expected time (10.2 +/- 4.2 minutes) and their compliance to the procedure was excellent. No clinically significant acute Grade 2 or higher GI (rectal) and GU side effects were observed within 90 days from the treatment completion. The median IPSS increased from 8 at baseline to 12 one-month after treatment and settled to 6 at 3 months. EPIC-26 scores in the urinary domain decreased from a median baseline of 86 pre-treatment to 79 at one-month and returned to baseline at a later timepoint (median score of 85 at 3 months). EPIC-26 scores in the bowel domains did not show significant changes within 3 months following RT. The prostate was found within 1 mm from its initial position in 78% of the beam-on time, between 1 and 2 mm in 20%, and exceeded 2 mm only in 2%, after correction for motion which was performed in 45% of the fractions, either during setup or beam delivery., Conclusions: Our preliminary findings show that dose intensified SBRT for unfavorable prostate tumors does not come at the cost of an increased toxicity, provided that a reliable technique for real time prostate monitoring is ensured. Fast FFF beams contributed to reduce intra-fractional motion. These observations need to be confirmed on a larger scale and a longer follow up., (© 2021. The Author(s).)

This Special Issue of the International Journal of Environmental Research and Public Health is dedicated to increasing the scientific information available about the long-term effects of exposure to the 2001 World Trade Center disaster [...].

Introduction: Breast metastases although rare are challenging for diagnostic difficulties and management. Treatment differs according to morphological, immunophenotipycal and biologic features of the primary tumor and their general behaviour is extremely different compared to primary breast cancer. The most frequent primary tumors include melanoma, lymphomas, gynecological, pulmonary, head and neck, gastroenteric and urinary tract cancers. Patient's prognosis is poor being generally associated to disseminated systemic disease with limited survival despite the effects of systemic treatment., Patients and Methods: We report the analysis of the diagnostic and therapeutic approach on the institutional experience of four cases of breast metastases originating from melanoma, pulmonary adenocarcinoma and differentiated thyroid carcinomas., Conclusions: The management of breast secondarisms requires focused diagnosis and evaluation in order to provide an adequate treatment with a multidisciplinary approach especially when the primary tumor is unknown., Key Words: Breast metastases, Melanoma, Pulmonary, Thyroid.

Antibody drug conjugates represent an important class of anti-cancer drugs in both solid tumors and hematological cancers. Here, we report preclinical data on the anti-tumor activity of the first-in-class antibody drug conjugate MEN1309/OBT076 targeting CD205. The study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination and validation experiments on in vivo models. CD205 was first shown frequently expressed in lymphomas, leukemias and multiple myeloma by immunohistochemistry on tissue microarrays. Anti-tumor activity of MEN1309/OBT076 as single agent was then shown across 42 B-cell lymphoma cell lines with a median IC50 of 200 pM and induction of apoptosis in 25/42 (59.5%) of the cases. The activity appeared highly correlated with its target expression. After in vivo validation as the single agent, the antibody drug conjugate synergized with the BCL2 inhibitor venetoclax, and the anti-CD20 monoclonal antibody rituximab. The first-in-class antibody drug targeting CD205, MEN1309/OBT076, demonstrated strong pre-clinical anti-tumor activity in lymphoma, warranting further investigations as a single agent and in combination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels ( p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.

Exposure assessment traditionally relies on biomarkers that measure chemical concentrations in individual biological media (i.e., blood, urine, etc.). However, chemicals distribute unevenly among different biological media; thus, each medium provides incomplete information about body burden. We propose that machine learning and statistical approaches can create integrated exposure estimates from multiple biomarker matrices that better represent the overall body burden, which we term multi-media biomarkers (MMBs). We measured lead (Pb) in blood, urine, hair and nails from 251 Italian adolescents aged 11-14 years from the Public Health Impact of Metals Exposure (PHIME) cohort. We derived aggregated MMBs from the four biomarkers and then tested their association with Wechsler Intelligence Scale for Children (WISC) IQ scores. We used three approaches to derive the Pb MMB: one supervised learning technique, weighted quantile sum regression (WQS), and two unsupervised learning techniques, independent component analysis (ICA) and non-negative matrix factorization (NMF). Overall, the Pb MMB derived using WQS was most consistently associated with IQ scores and was the only method to be statistically significant for Verbal IQ, Performance IQ and Total IQ. A one standard deviation increase in the WQS MMB was associated with lower Verbal IQ (β [95% CI] = -2.2 points [-3.7, -0.6]), Performance IQ (-1.9 points [-3.5, -0.4]) and Total IQ (-2.1 points [-3.8, -0.5]). Blood Pb was negatively associated with only Verbal IQ, with a one standard deviation increase in blood Pb being associated with a -1.7 point (95% CI: [-3.3, -0.1]) decrease in Verbal IQ. Increases of one standard deviation in the ICA MMB were associated with lower Verbal IQ (-1.7 points [-3.3, -0.1]) and lower Total IQ (-1.7 points [-3.3, -0.1]). Similarly, an increase of one standard deviation in the NMF MMB was associated with lower Verbal IQ (-1.8 points [-3.4, -0.2]) and lower Total IQ (-1.8 points [-3.4, -0.2]). Weights highlighting the contributions of each medium to the MMB revealed that blood Pb was the largest contributor to most MMBs, although the weights varied from more than 80% for the ICA and NMF MMBs to between 30% and 54% for the WQS-derived MMBs. Our results suggest that MMBs better reflect the total body burden of a chemical that may be acting on target organs than individual biomarkers. Estimating MMBs improved our ability to estimate the full impact of Pb on IQ. Compared with individual Pb biomarkers, including blood, a Pb MMB derived using WQS was more strongly associated with IQ scores. MMBs may increase statistical power when the choice of exposure medium is unclear or when the sample size is small. Future work will need to validate these methods in other cohorts and for other chemicals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

[This retracts the article DOI: 10.3892/ol.2012.995.]., (Copyright: © Sanguinetti et al.)

Background: TIR3B thyroid nodules are considered to be at risk of malignancy (15-30%) but guidelines recommend conservative surgery with lobectomy with primary diagnostic porpoise. Risk stratification mainly based on ultrasound, elastography and genetic mutations usually may influences the surgical approach., Methods: We retrospectively analyzed 52 cases of TIR3B underwent between 2015 and 2017 total thyroidectomy (TT) and lobectomy (L), focusing mainly on the observed rate of malignancy. Chi-squared test and Fisher's exact probability test were used for analysis, considering a P values less than 0.05 as significant., Results: Out of 52 patients 49 underwent TT and 3 L. In TT group a multinodular goiter was associated in 67.3% of patients. Malignancy rate was 81.6 and 33.3% respectively after TT and L (P 0.003). Multicentric and contralateral tumors were detected respectively in 36.7% and in 32.6% of patients underwent TT. No main post-operative complications were registered., Conclusions: Ultrasound and elastography are useful to define within the TIR3B group those lesions at higher risk and therefore requiring a more radical approach. TT seems an appropriate approach to TIR3B lesions, especially in multinodular goiter, considering the incidence of malignancy with probably higher rate than previously reported.

An increased incidence of prostate cancer was reported in three cohorts of World Trade Center (WTC) respondents. It is uncertain whether this increase is because of WTC-related exposures or enhanced surveillance. Prostate cancer cases (2002-2013) were obtained from the WTC Health Program. Age, race, and Gleason score distribution were compared with New York State Cancer Registry cases from the same time period. Multivariate models were adjusted for age and race. Analyses of clinical characteristics of prostate cancer cases within the cohort were also carried out, adjusting for age, race, and WTC exposure categories. WTC respondents had a prostate cancer age-standardized rate ratio of 1.65 [95% confidence interval (CI): 1.37-1.93] compared with New York State; age-specific ratios were highest for ages 30-49 (2.28; 95% CI: 1.51-3.43), 70-74 (2.05; 95% CI: 1.03-4.10), and 80-84 years (5.65; 95% CI: 1.41-22.58). High WTC exposure was associated with advanced clinical stage (5.58; 95% CI: 1.05-29.76; Ptrend=0.03). WTC respondents continue to have a higher prostate cancer rate compared with New York State as a whole. Respondents with a higher WTC exposure level may have had more advanced clinical stage of prostate cancer.

Processing of alpine milk in malga farms is carried out under conditions that can favor contamination by coliforms, coagulase-positive staphylococci, or pathogens such as Listeria monocytogenes . With the aim to improve the hygienic characteristics and safety of cheese produced in four malga farms the use of lyophilized Natural Milk Culture prepared with selected strains was tested.. Two cheesemaking tests were carried out in the same day always starting from the same milk: in the first case following the malga recipe that uses either Natural Whey Culture or without the addition of a starter, in the second one using a Natural Milk Culture. Cheesemaking were carried out in four malga farms located in the west area of Trentino region within the same week. For hygienic and safety evaluation, aerobic colony count, coagulase-positive staphylococci, Escherichia coli , staphylococcal toxins, Listeria monocytogenes , and Salmonella spp, pH and a w were determined in raw milk from evening and morning milking, curd in vat, curd after extraction and two months-ripened cheese. Pathogens or toxins, high values of coagulase- positive staphylococci and E. coli were not found in cheese samples. However, in the curd coagulase-positive staphylococci reached values almost of 5 Log CFU/g in the two malga without starter cultures. The use of Natural Milk Culture reduced E. coli counts. In addition, DNA was extracted from cheese samples and from Natural Milk Culture and the composition of the microbial community determined by Next Generation Sequencing method. The determination of cheese microbial communities demonstrated that the use of Natural Milk Culture exerted different effects in the different malga , in any case preserving bacterial biodiversity., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.

The East Harlem (EH), Central Harlem (CH), and Upper East Side (UES) neighborhoods of New York City are geographically contiguous to tertiary medical care, but are characterized by cancer mortality rate disparities. This ecological study aims to disentangle the effects of race and neighborhood on cancer deaths. Mortality-to-incidence ratios were determined using neighborhood-specific data from the New York State Cancer Registry and Vital Records Office (2007-2011). Ecological data on modifiable cancer risk factors from the New York City Community Health Survey (2002-2006) were stratified by sex, age group, race/ethnicity, and neighborhood and modeled against stratified mortality rates to disentangle race/ethnicity and neighborhood using logistic regression. Significant gaps in mortality rates were observed between the UES and both CH and EH across all cancers, favoring UES. Mortality-to-incidence ratios of both CH and EH were similarly elevated in the range of 0.41-0.44 compared with UES (0.26-0.30). After covariate and multivariable adjustment, black race (odds ratio=1.68; 95% confidence interval: 1.46-1.93) and EH residence (odds ratio=1.20; 95% confidence interval: 1.07-1.35) remained significant risk factors in all cancers' combined mortality. Mortality disparities remain among EH, CH, and UES neighborhoods. Both neighborhood and race are significantly associated with cancer mortality, independent of each other. Multivariable adjusted models that include Community Health Survey risk factors show that this mortality gap may be avoidable through community-based public health interventions.

Background: The effects of antenatal corticosteroids (ANS) in multiple pregnancies are disputed. In this article, we examined whether estimated effects differ in singletons and multiples and in small for gestational age (SGA) preterm infants., Methods: We studied 17 073 singletons (81% treated with ANS) and 8274 multiples (86% treated) born at 24-33 weeks from the Italian Neonatal Network (2005-2013). We used Poisson regression models with robust variance to estimate adjusted risk ratios (RR) of in-hospital death, severe intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), and the composite outcome of severe IVH and death., Results: Mortality was lower among ANS-treated vs. ANS-untreated infants, both in singletons (RR 0.63, 95% confidence interval (CI) 0.58, 0.68) and in multiples (RR 0.85, 95% CI 0.73, 0.98). IVH and the composite outcome of IVH and death, but not PVL, also occurred less frequently among ANS-treated infants. For these outcomes, the effect of ANS was stronger in singletons than in multiples (+35%, +32%, and +22% for death, IVH, and the composite outcome, respectively). Also among SGA infants, singletons, and multiples, ANS-treated infants had lower risk of death, IVH and of composite outcome than untreated ones., Conclusions: In this large cohort of preterm infants, both multiples and singletons treated with ANS had a lower risk of mortality, of severe IVH, and of composite outcome of IVH and death, both in the overall sample and in SGA infants. Although ANS effect was weaker in multiples, our results support current recommendations to administer ANS prophylaxis in multiple pregnancies at risk of preterm delivery., (© 2017 John Wiley & Sons Ltd.)

Manganese (Mn) is both essential and toxic for humans, mainly depending on the total levels and its species. Main sources of exposure include food and air pollution, particularly motorized traffic. We sought to determine the potential influence of these sources on serum total levels of Mn and Mn species. We selected a random sample of municipality residents from an Italian urban municipality, from whom we collected detailed personal information, dietary habits and a blood sample for serum Mn determination. We also assessed outdoor air Mn exposure, by modeling levels of particulate matter ≤10 µm (PM10) from motorized traffic at the residence of geocoded subjects. Serum Mn species generally showed higher levels in males and positive correlation with age, while no such differences were found according to smoking habits or use of dietary supplements. Among nutrients, only iron intake showed a relation with Mn [an inverse correlation with Mn‑ferritin (Mn‑Fer) and a direct one with inorganic‑Mn (Inorg‑Mn)]. Meat consumption directly correlated and fish and seafood inversely correlated with total Mn, Mn‑transferrin (Mn‑Tf) and Mn-citrate (Mn-Cit). Fruits and vegetables, including legumes and nuts, generally showed a positive correlation with all Mn species, especially Mn‑Cit, and an inverse one with Inorg‑Mn. Odds ratios (ORs) of having serum Mn levels above median value increased with increasing PM10 tertiles, with an OR for highest‑to‑lowest tertile of 7.40 (1.36‑40.25) in multivariate analysis. Analyses for Mn species did not highlight a clear comparable pattern. In conclusion, our results seem to demonstrate that PM10 exposure positively influences total Mn serum levels, while single Mn species show conflicting results.

Background: Medullary thyroid carcinoma is an aggressive tumor and presents with significant morbidity and mortality and a high rate of lymph node metastases. The combination of total thyroidectomy and cervical lymphadenectomy is the essential treatment for those patients presenting with cervical lymph node metastases., Materials and Methods: A retrospective analysis of 117 patients operated for medullary thyroid carcinoma over a period of 15 years at a single institution. Surgical complications and calcitonin levels were noted., Results: Nodal metastases were detected in the central compartment in 72.6% patients. Positive lymph nodes were detected in the lateral compartment of 34 patients who had undergone ipsilateral dissection and in all 10 patients of those with bilateral surgery. We found 3 cases of unilateral transient recurrent laryngeal nerve palsy, 15 cases of temporary hypoparathyroidism, a permanent accessory nerve lesion and a case of chylous fistula. Normalization of post-operative calcitonin was found in 82.6% and of patients who underwent total thyroidectomy and central neck dissection alone compared to 35.4% in those with ipsilateral and bilateral neck dissection., Conclusions: Total thyroidectomy and cervical lymphadenectomy planned on the ultrasound preoperative study and on the calcitonin level represent the standard of treatment for medullary thyroid carcinoma., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

A high prevalence of obesity has been observed among former World Trade Center (WTC) workers and volunteers. We hypothesized that unemployment and disability status would predict obesity. We surveyed 220 participants at the [INST] Mount Sinai WTC Clinical Center to assess their obesity and current employment and disability status, WTC occupational exposure level, medical comorbidities, and dietary and exercise habits. Bivariate and logistic regression multivariate analyses were used to explore associated risk factors. Obesity was associated with active employment status. Other significant covariates included non-Latino African American race, having a high number of comorbid chronic diseases, low exercise frequency, and not drinking any glass of juice daily. The association of obesity with active employment suggests that interventions that favor healthy habits among actively employed individuals are warranted.

This study presents the results of surgery in the elderly for primary hyperparathyroidism (PHPT) from a single institution's experience. We retrospectively analyzed 898 cases of surgically treated PHPT, divided into two groups: 135 elderly patients (A) and 763 patients younger than 65 years (B). PHPT was symptomatic in 68.8 per cent patients in group A and in 81.6 per cent in group B. Unilateral temporary recurrent laryngeal nerve palsy was observed in 0.9 per cent in group A and 0.1 per cent in group B (P > 0.05). No cervical hematomas, mortality or major cardiovascular, neurological, respiratory or metabolic postoperative complications were registered. All the patients evaluated at one year had improvement in the quality of life, with increase of bone mineral density (BMD) in 85.6 per cent and 79.8 per cent of patients in groups A and B, with no significant differences between symptomatic and asymptomatic patients. Parathyroidectomy in elderly PHPT patients is safe, with rate of morbidity similar to what observed in younger individuals. Further investigations are recommended to confirm the role of surgery as an effective approach in elderly PHPT patients.

Background: Secondary hyperparathyroidism in elderly fragile patients presents clinical difficulties due to severity of symptoms and related comorbidity. The optimal surgical approach for this group of patients is still debated., Aim: The aim of the study was to define the optimal technique of parathyroidectomy in elderly patients with secondary hyperparathyroidism., Methods: Retrospective analysis in a series of 253 patients including 35 elderly individuals at a single institution was carried out. Postoperative parathyroid hormone decrease, surgical complications and symptoms control were analyzed for all patients in relation to the types of parathyroidectomy performed., Results: In elderly patients, total parathyroidectomy was the most used approach. Subtotal parathyroidectomy was mostly reserved for younger patients suitable for kidney transplantation. No elderly patients treated with total parathyroidectomy were autotransplanted. No significant difference in surgical complications was observed between younger and elderly patients and considering the different procedures. Adequate symptom control after surgery was achieved in almost 90% of patients. A limited rate of recurrence requiring repeat surgery was observed only after subtotal parathyroidectomy., Discussion: Considering the features of all types of parathyroidectomy, very low recurrence rate, contained postoperative hypocalcemia and limited complications following total parathyroidectomy, might represent specific advantages for elderly patients., Conclusions: Total parathyroidectomy without parathyroid transplantation is safe for elderly patients with secondary hyperparathyroidism and a good alternative to the well-established total parathyroidectomy with autografting.

Manganese (Mn) is an essential metal that plays a fundamental role for brain development and functioning. Environmental exposure to Mn may lead to accumulation in the basal ganglia and development of Parkinson-like disorders. The most recent research is focusing on early-life overexposure to Mn and the potential vulnerability of younger individuals to Mn toxicity also in regard to cognitive and executive functions through the involvement of the frontal cortex.Neurodevelopmental disturbances are increasing in the society, and understanding the potential role of environmental determinants is a key for prevention. Therefore, assessing the environmental sources of Mn exposure and the mechanisms of developmental neurotoxicity and defining appropriate biomarkers of exposure and early functional alterations represent key issues to improve and address preventive strategies. These themes will be reviewed in this chapter.

Bacterial proteases are involved in food spoilage and shelf-life reduction. Among the bacterial proteases, a predominant role in spoilage of dairy products seems to be played by the thermostable metallo-protease AprX, which is produced by various strains of Pseudomonas fluorescens . Differences in AprX enzyme activity among different strains were highlighted, but the most proteolytic strains were not identified. In this study, the presence of the aprX gene was evaluated in 69 strains isolated from food matrices and 18 reference strains belonging to the P. fluorescens group, which had been previously typed by the multi locus sequence typing method. Subsequently, a subset of reference strains was inoculated in ultra-high temperature milk, and the expression of the aprX gene was evaluated at 22 and 6°C. On the same milk samples, the proteolytic activity was then evaluated through Azocasein and trinitrobenzenesulfonic acid solution assays. Finally, to assess the applicability of the former assay directly on dairy products the proteolityc activity was tested on industrial ricotta samples using the Azocasein assay. These results demonstrate the spread of aprX gene in most strains tested and the applicability of Azocasein assay to monitor the proteolytic activity in dairy products.

Over the past few years, the demand for the introduction of fish products in public canteens (schools, hospitals and nursing-homes) has grown due to their good nutritional proprieties. The particular health conditions and sensitivity of some groups of consumers exposes them to greater risks of food poisoning. It is therefore important to monitor the raw materials that end up in mass catering implementing strategies of mass catering control, both with self-monitoring strategies and with regular controls performed by the competent health authorities. The purpose of this study is to assess the overall quality of seafood dealt out from public catering services located in Northeast Italy. In this paper we illustrate the results of microbiological analysis performed on 135 fish samples (58% of samples were raw fishes, 27% cooked fishes, 6% raw fish products, 9% cooked fish products) and species identification performed on 102 fish samples. Additionally, 135 environmental swabs were collected to determine the effectiveness of cleaning and sanitation of food contact (cutting boards, cooking equipment and food processing surfaces) and non-contact (refrigerator wall and handle, tap lever) surfaces. Of raw seafood samples, 24% had total aerobic mesophilic bacteria count >10 5 CFU/g and for Enterobacteriaceae the faecal contamination was excluded since no Salmonella spp. and Escherichia coli were isolated. Just 3.8% of raw seafood samples resulted positive for Listeria monocytogenes . The results of swab samples of cooking utensils and surfaces showed that sanitation practices should be improved. Molecular analysis for fish species identification revealed a mislabelling for 25% of sampled fishes. The results of this survey can provide valuable information for monitoring and surveillance programmes for the control of quality of fish and fish products., Competing Interests: the authors declare no potential conflict of interest

In the past, milk whey was only a by-product of cheese production, but currently, it has a high commercial value for use in the food industries. However, the regulation of whey management (i.e., storage and hygienic properties) has not been updated, and as a consequence, its microbiological quality is very challenging for food safety. The Next Generation Sequencing (NGS) technique was applied to several whey samples used for Ricotta production to evaluate the microbial community composition in depth using both RNA and DNA as templates for NGS library construction. Whey samples demonstrating a high microbial and aerobic spore load contained mostly Firmicutes; although variable, some samples contained a relevant amount of Gammaproteobacteria. Several lots of whey acquired as raw material for Ricotta production presented defective organoleptic properties. To define the volatile compounds in normal and defective whey samples, a headspace gas chromatography/mass spectrometry (GC/MS) analysis was conducted. The statistical analysis demonstrated that different microbial communities resulted from DNA or cDNA library sequencing, and distinguishable microbiota composed the communities contained in the organoleptic-defective whey samples.

Background/aim: Hypoparathyroidism is the most significant morbidity after neck dissection for thyroid cancer. Addition of lateral neck dissection (ND) to central ND combined with total thyroidectomy (TT) increases the risk of postoperative hypoparathyroidism compared to TT plus central ND. The aim of this study was to verify if a modified procedure and different access to the neck for lateral ND may improve safety., Patients and Methods: In 62 patients with papillary thyroid cancer (PTC) undergoing TT plus central and lateral ND between 2010 and 2013, lateral ND was performed as first step approaching the neck via extrathyroideal space. Calcium in serum and parathormone (PTH) were determined preoperatively, intraoperatively and during the follow-up., Results: Twenty patients (32%) developed postoperative hypocalcemia. Calcium levels and PTH completely recovered for 58 out of 62 patients from 3 to 6 months after surgery. After a mean of 12 months' follow-up, only four patients (6.5%) had developed permanent hypoparathyroidism. The incidence of parathyroid complication after TT plus central ND and lateral ND did not differ from postoperative hypoparathyroidim after TT plus central ND., Conclusion: The presented surgical procedure may provide a better outcome in terms of parathyroid morbidity., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)