Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis.

BACKGROUND: Given that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset. METHODS: Data from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that. RESULTS: A total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively). CONCLUSIONS: We identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis.

Occupational exposure to electromagnetic fields in magnetic resonance environment: an update on regulation, exposure assessment techniques, health risk evaluation, and surveillance.

Magnetic resonance imaging (MRI) is one of the most-used diagnostic imaging methods worldwide. There are ∼50,000 MRI scanners worldwide each of which involves a minimum of five workers from different disciplines who spend their working days around MRI scanners. This review analyzes the state of the art of literature about the several aspects of the occupational exposure to electromagnetic fields (EMF) in MRI: regulations, literature studies on biological effects, and health surveillance are addressed here in detail, along with a summary of the main approaches for exposure assessment. The original research papers published from 2013 to 2021 in international peer-reviewed journals, in the English language, are analyzed, together with documents published by legislative bodies. The key points for each topic are identified and described together with useful tips for precise safeguarding of MRI operators, in terms of exposure assessment, studies on biological effects, and health surveillance.

Accelerating the experimental responses on cell behaviors: a long-term prediction of cell trajectories using Social Generative Adversarial Network.

The incremented uptake provided by time-lapse microscopy in Organ-on-a-Chip (OoC) devices allowed increased attention to the dynamics of the co-cultured systems. However, the amount of information stored in long-time experiments may constitute a serious bottleneck of the experimental pipeline. Forward long-term prediction of cell trajectories may reduce the spatial-temporal burden of video sequences storage. Cell trajectory prediction becomes crucial especially to increase the trustworthiness in software tools designed to conduct a massive analysis of cell behavior under chemical stimuli. To address this task, we transpose here the exploitation of the presence of "social forces" from the human to the cellular level for motion prediction at microscale by adapting the potential of Social Generative Adversarial Network predictors to cell motility. To demonstrate the effectiveness of the approach, we consider here two case studies: one related to PC-3 prostate cancer cells cultured in 2D Petri dishes under control and treated conditions and one related to an OoC experiment of tumor-immune interaction in fibrosarcoma cells. The goodness of the proposed strategy has been verified by successfully comparing the distributions of common descriptors (kinematic descriptors and mean interaction time for the two scenarios respectively) from the trajectories obtained by video analysis and the predicted counterparts.

Rummaging through the bin: Modelling marine litter distribution using Artificial Neural Networks.

Marine litter has significant ecological, social and economic impacts, ultimately raising welfare and conservation concerns. Assessing marine litter hotspots or inferring potential areas of accumulation are challenging topics of marine research. Nevertheless, models able to predict the distribution of marine litter on the seabed are still limited. In this work, a set of Artificial Neural Networks were trained to both model the effect of environmental descriptors on litter distribution and estimate the amount of marine litter in the Central Mediterranean Sea. The first goal involved the use of self-organizing maps in order to highlight the importance of environmental descriptors in affecting marine litter density. The second goal was achieved by developing a multilayer perceptron model, which proved to be an efficient method to estimate the regional quantity of seabed marine litter. Results demonstrated that machine learning could be a suitable approach in the assessment of the marine litter issues.

Elastofibroma dorsi: clinicopathological analysis of 71 cases.

INTRODUCTION: Elastofibroma dorsi (ELD) is a rare soft tissue benign tumor of the chest wall. So far, only a few large series have been reported in the English literature and, to the best of our knowledge, radiological assessment and clinical management remain without consensus. The aim of this study is to provide, on the basis of a single-institutional, homogeneous and large experience, ample evidences to support etiological and "clinical-usefulness-grade" classification hypotheses. MATERIALS AND METHODS: We report observational information on 71 ELD cases and, on the basis of these, we discuss the clinical onset features, radiological and surgical characteristics, as well as pathological and immunohistochemical evidences. RESULTS: In the period between January 1994 and September 2009, 71 consecutive patients (23 male and 48 female; mean age: 60.2 years; standard deviation [SD] ± 8.3 years) with ELD diagnosis were surgically treated at our institution. ELD was right sided in 34 patients (47.9%), left in 25 (35.2%), and bilateral in 12 (16.9%). In nine patients, ELD were diagnosed synchronously and three metachronously. Thirty-eight patients (53.5%) had no significant symptoms; 33 (46.5%) reported a clunking sensation or a localized scapular swelling during the shoulder movements. Sixty-six (93%) patients underwent surgical excision with radical intent while in five patients, a biopsy-only procedure was undertaken. Mean hospital stay was 3.0 days (SD ± 1.2 days) with a morbidity of 10.6% (one case of major postoperative bleeding requested a surgical revision of the hemostasis). At the univariate analysis, the probability of occurrence of morbidity increases with tumor size. All operated patients are alive and well at follow-up with no sign of recurrence and complete resolution of the symptomatology. CONCLUSIONS: ELD is relatively uncommon, benign, and well controlled by radical surgery.

IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation.

Cytokines that are induced by infection may contribute to the initiation of immune responses through their ability to stimulate dendritic cells (DCs). In this paper, we have addressed the role of IL-15 in DC activation, investigating its expression by DCs in response to three different signals of infection and examining its ability to stimulate DCs. We report that the expression of both IL-15 and the IL-15 receptor alpha-chain are increased in splenic DCs from mice inoculated with dsRNA (poly(I:C)), LPS, or IFN-alphabeta, and in purified murine splenic DCs treated with IFN-alphabeta in vitro. Furthermore, IL-15 itself was able to activate DCs, as in vivo or in vitro exposure of splenic DCs to IL-15 resulted in an up-regulation of costimulatory molecules, markedly increased production of IFN-gamma by DC and an enhanced ability of DCs to stimulate Ag-specific CD8(+) T cell proliferation. The magnitude of all of the IL-15-induced changes in DCs was reduced in mice deficient for the IFN-alphabeta receptor, suggesting a role for IFN-alphabeta in the stimulation of DCs by IL-15. These results identify IL-15 as a stimulatory cytokine for DCs with the potential for autocrine activity and link its effects to expression of IFN-alphabeta.

Cyclophosphamide induces type I interferon and augments the number of CD44(hi) T lymphocytes in mice: implications for strategies of chemoimmunotherapy of cancer.

In a previous study, we reported that a single injection of cyclophosphamide (CTX) in tumor-bearing mice resulted in tumor eradication when the animals were subsequently injected with tumor-sensitized lymphocytes. Notably, CTX acted by inducing bystander effects on T cells, and the response to the combined CTX/adoptive immunotherapy regimen was inhibited in mice treated with antibodies to mouse interferon (IFN)-alpha/beta. In the present study, we have investigated whether CTX induced the expression of type I IFN, and we have characterized the CTX effects on the phenotype of T cells in normal mice. CTX injection resulted in an accumulation of type I IFN messenger RNA in the spleen of inoculated mice, at 24 to 48 hours, that was associated with IFN detection in the majority of the animals. CTX also enhanced the expression of the Ly-6C on spleen lymphocytes. This enhancement was inhibited in mice treated with anti-type I IFN antibodies. Moreover, CTX induced a long-lasting increase in in vivo lymphocyte proliferation and in the percentage of CD44(hi)CD4(+) and CD44(hi)CD8(+ )T lymphocytes. These results demonstrate that CTX is an inducer of type I IFN in vivo and enhances the number of T cells exhibiting the CD44(hi) memory phenotype. Since type I IFN has been recently recognized as the important cytokine for the in vivo expansion and long-term survival of memory T cells, we suggest that induction of this cytokine may explain at least part of the immunomodulatory effects observed after CTX treatment. Finally, these findings provide a new rationale for combined treatments with CTX and adoptive immunotherapy in cancer patients. (Blood. 2000;95:2024-2030)

Congenital fibroepithelial polyp of prostatic urethra in an adult.

OBJECTIVE: To describe an unusual case of congenital fibroepithelial polyp of the prostatic urethra in an adult, presented with acute urinary retention. METHODS: Cystouretrographic, endoscopical and pathological investigations are discussed. RESULTS: The definitive diagnosis of the tenth case of this benign lesion was made only after endoscopic resection and pathological examination. The complete resolution of the symptoms has been quick. CONCLUSIONS: We stress this unusual pathology in order to focus its peculiarity in aetiopathogenesis, diagnosis and treatment.

[Granulomatous prostatitis as collateral effect of intravesical immunotherapy with BCG]. / Prostatite granulomatosa come effetto collaterale dell'immunoterapia endovescicale con BCG.

Twenty-five male patients with superficial bladder cancer underwent intravesical Bacillus Calmette Guerin immunotherapy. A high incidence of side effects has occurred using three different substrains of BCG. Our interest has been focused on BCG related granulomatous prostatitis: we have found four asymptomatic patients with histologically diagnosed disease. We suppose therefore that its incidence is underestimated.

[Qualitative and quantitative parameters for prognosis in renal carcinoma in early and advanced stages]. / Parametri qualitativi e quantitativi per la prognosi del carcinoma renale in stadio precoce ed avanzato.

AIM OF THE STUDY: A minority of stage I renal cell cancers have a bad prognosis, a minority of those in stage II-IV may behave favorably. Are there parameters which characterize such cases? In this study, a number of qualitative and quantitative parameters are used to detect differences between cases with at least 9 years of survival and those with a survival of less than 9 years. MATERIAL AND METHODS: 133 cases of renal cell cancer were subdivided into stage subgroups: Robson's I; Robson's II-IV. The following data and parameters were registered and/or measured: sex, stage, tumor size, histological type, mean nuclear profile area (mA) and pleomorphism (standard deviation of mean nuclear profile area--SDA) nuclear grade (NG) and combined nuclear grade (CNG), DNA index, cell proliferation, as determined by mitotic index (MI), per cent of PCNA positive cells (PCNA + cells %), per cent of S-phase cells (SP cells %), p53 and EGFR expression, intratumoral T lymphocytes. RESULTS: Older patients have a worse prognosis independently of the stage. Stage is the most discriminant qualitative parameter; tumor dimensions and both nuclear and combined nuclear grade are important too. Mean nuclear profile area and pleomorphism are also discriminant, while no prognostic value of histological type is shown and histology is not related to other parameters. Higher DNA index characterizes cases with worse prognosis, as well as MI, SP cells %, PCNA + cells %, and EGFR expression. No significant differences are detected for p53 expression and lymphoid infiltrates. A minority of patients with stage I tumors die within 9 years of diagnosis. They are older than survivors with the same stage, their tumors have larger nuclear area and greater pleomorphism, and are more frequently aneuploid with higher DNA index. A minority of patients with stage II-IV tumors survive at least 9 years from the time of diagnosis. They are younger than non-survivors in the same stages and have lower MI and PCNA positivity in the tumors, while other parameters are not discriminant.

[Oral therapy with ciprofloxacin in the prophylaxis of urinary infections in surgical patients with permanent bladder catheter]. / Terapia orale con ciprofloxacina nella profilassi della infezione urinaria in pazienti chirurgici con catetere vescicale a permanenza.

Urinary infections represent about 30% of all infections observed within a hospital environment in surgical patients with indwelling catheter. The aim of the research was to assess the effectiveness of ciprofloxacin the prophylaxis of bacteriuria in vesical catheter-bearing patients, during the post-operative period. A comparative investigation was carried out in 33 patients submitted to surgery and carries of vesical catheters during the post-operative period. The patients were divided into 2 group: one group of 23 patients received ciprofloxacin, and a group of 10 patients represented the control group. A urine culture was carried out in every patient before positioning the catheter, and urine cultures were taken every 72 hours; the urethero-vesical portion of the catheter was always submitted to cultural examination after its removal. Patients treated with ciprofloxacin received good protection against Gram- urinary infections, and catheter cultures also demonstrated inhibiting activity with respect to urethral colonisation on the part of Gram- infections. Confirmation of this results in larger series would be an indication for the use of ciprofloxacin in the prophylaxis of urinary infections caused by indwelling vesical catheters in the postoperative period.

[The lead concentration in the converted and special-formula milks used in infant feeding]. / Concentrazione del piombo nei latti adattati e speciali utilizzati nell'alimentazione del lattante.

In the last years a strict correlation between chronic exposure to low lead doses and neuropsychological impairment in first childhood is often reported in literature. The authors have measured and than compared the lead content of milk-based formulas, of special-formulas (hypoallergenic-protein formulas, lactose-free formulas, proteic-hydrolysate formulas) and soya formulas. 20 samples of milk-based formula, have been measured along with, 22 samples of special formula and 14 samples of soya formula. Lead mean concentration in milk-based formula was 73 +/- 139.11 microgr./l, whereas 23.95 +/- 13.76 microgr./l and 22.57 +/- 13.42 were measured in special formula and soya formula respectively. These results were compared with Student t-test and no significative difference was found. Lead mean concentration of milk-based formula was higher than that of special formula or soya formula. The authors hope milk-formula industry to have a more specific control on lead milk content for children feeding. In order to avoid possible toxic injuries in little infants, industry should certainly pay more attention both in supplying and in technological management of milk.

Detection of C-myb genetic alterations and mutant p53 serum protein in patients with benign and malignant colon lesions.

C-myb structural alterations were analysed by Southern blot hybridization in 55 adenomatous polyps and 21 adenocarcinomas of the colon. Gene amplification was observed in 8 cases (14.5%) and c-myb rearrangements in 3 cases (5.4%) of the preneoplastic lesions analysed. A higher percentage of c-myb abnormalities (23.8%) was shown by malignant tumors. As far as mutant p53 protein is concerned, it was detected both in sera of adenoma and adenocarcinoma patients, though at different levels. No statistically significant correlations were found between c-myb or p53 abnormalities and clinico-pathological variables.

Selection of patients with monoclonal gammopathy of undetermined significance is mandatory for a reliable use of interleukin-6 and other nonspecific multiple myeloma serum markers.

Serum levels of various immunochemical markers of clinical interest, as interleukin-6 (IL-6), C-reactive protein (CRP) and beta 2-microglobulin (beta 2M), were measured in sera from 98 subjects affected with monoclonal gammopathy of undetermined significance (MGUS; 80% of which bearing cancer too) and from 39 patients with multiple myeloma (MM). In addition, the ratio between serum IgG/IgA amounts (GAR) was also calculated in monoclonal gammopathies of IgG type. Consistent with our previous investigations, we found that tumor presence significantly influenced the serum levels of the various markers (except GAR) in MGUS patients; in fact, only when comparing MGUS without tumor and MM patients, was a clear difference observed for all markers considered. The data presented discourage the use of IL-6, CRP and beta 2M as discriminant indices between MGUS and MM patients, unless a careful selection of MGUS subjects is performed. Further investigations on these potential markers are therefore needed for a more rational clinical application.

[Osteochondrodysplasia: nosologic assessment and report of 6 clinical cases]. / Osteocondrodisplasie: inquadramento nosologico e descrizione di sei casi clinici.

Osteochondrodysplasias represent an important group of disease affecting cartilage and/or bone. The clinical evidence of disarmoniuous low stature, of a disproportion between trunk and limbs length, of a big skull can suggest this diagnosis and the necessity to carry out all the instrumental investigations. The diagnostic suspect can be placed, some time, already in the neonatal period. The complexity of problems regarding the osteochondrodysplasias bearer child and his family requires a multidisciplinary approach. The Authors present a personal experience of six cases of osteochondrodysplasias observed in a period of fifteen years.