In vitro exposure to PM2.5 of olfactory Ensheathing cells and SH-SY5Y cells and possible association with neurodegenerative processes.

PM2.5 exposure represents a risk factor for the public health. PM2.5 is able to cross the blood-alveolar and blood-brain barriers and reach the brain through three routes: nasal olfactory pathway, nose-brain pathway, blood-brain barrier pathway. We evaluated the effect of PM2.5 to induce cytotoxicity and reduced viability on in vitro cultures of OECs (Olfactory Ensheathing Cells) and SH-SY5Y cells. PM2.5 samples were collected in the metropolitan area of Catania, and the gravimetric determination of PM2.5, characterization of 10 trace elements and 16 polycyclic aromatic hydrocarbons (PAHs) were carried out for each sample. PM2.5 extracts were exposed to cultures of OECs and SH-SY5Y cells for 24-48-72 h, and the cell viability assay (MTT) was evaluated. Assessment of mitochondrial and cytoskeleton damage, and the assessment of apoptotic process were performed in the samples that showed lower cell viability. We have found an annual average value of PM2.5 = 16.9 µg/m3 and a maximum value of PM2.5 = 27.6 µg/m3 during the winter season. PM2.5 samples collected during the winter season also showed higher concentrations of PAHs and trace elements. The MTT assay showed a reduction in cell viability for both OECs (44%, 62%, 64%) and SH-SY5Y cells (16%, 17%, 28%) after 24-48-72 h of PM2.5 exposure. Furthermore, samples with lower cell viability showed a decrease in mitochondrial membrane potential, increased cytotoxicity, and also impaired cellular integrity and induction of the apoptotic process after increased expression of vimentin and caspase-3 activity, respectively. These events are involved in neurodegenerative processes and could be triggered not only by the concentration and time of exposure to PM2.5, but also by the presence of trace elements and PAHs on the PM2.5 substrate. The identification of more sensitive cell lines could be the key to understanding how exposure to PM2.5 can contribute to the onset of neurodegenerative processes.

Polystyrene microplastics impair the functions of cultured mouse Leydig (TM3) and Sertoli (TM4) cells by inducing mitochondrial-endoplasmic reticulum damage.

Many laboratory studies demonstrated that the exposure to microplastics causes testosterone deficiency and spermatogenic impairment in mammals; however, the mechanism underlying this process remains still unclear. In this study, we investigated the effects of polystyrene microplastics (PS-MP) on the proliferation and functionality of cultured Leydig (TM3) and Sertoli (TM4) cells, focusing on the mitochondrial compartment and its association with the endoplasmic reticulum (ER). The in vitro exposure to PS-MP caused a substantial reduction in cellular viability in TM3 and TM4 cells. In TM3 cells PS-MP inhibited the protein levels of StAR and of steroidogenic enzymes 3ß-HSD and 17ß-HSD, and in TM4 cells PS-MP inhibited the protein levels of the androgen receptors other than the activity of lactate dehydrogenase (LDH). PS-MP inhibited the functions of TM3 and TM4, as evidenced by the decrease of the phosphorylation of ERK1/2 and Akt in both cell lines. The oxidative stress caused by PS-MP decreased antioxidant defense in TM3 and TM4 cells, promoting autophagic and apoptotic processes. Furthermore, we found mitochondrial dysfunction and activation of ER stress. It is known that mitochondria are closely associated with ER to form the Mitochondrial-Associated Endoplasmic Reticulum Membranes (MAM), the site of calcium ions transfer as well as of lipid biosynthesis-involved enzymes and cholesterol transport from ER to the mitochondria. For the first time, we studied this aspect in PS-MP-treated TM3 and TM4 cells and MAMs dysregulation was observed. This study is the first to elucidate the intracellular mechanism underlying the effects of PS-MPs in somatic testicular cells, corroborating that PS-MP might be one of the causes of an increase in male infertility through the impairment of steroidogenesis in Leydig cells and of the nurse function of Sertoli cells. Thus, our findings contributed with new information to the mechanism underlying the effects of PS-MP on the male reproductive system.

Association between air pollution and sudden sensorineural hearing loss (SSHL): A systematic review and meta-analysis.

Recent studies have indicated that air pollution (AP) has harmful effects on hearing and ear diseases such as Sudden Sensorineural Hearing Loss (SSHL). The purpose of this study was to evaluate the impact of exposure to AP on SSHL incidence. Valid electronic databases were searched to retrieve studies published until December 1, 2022, using appropriate keywords. The result of the search was 1146 studies, and after screening according to the defined criteria, in total 8 studies were obtained. The risk of bias (ROB) in the studies and their quality were assessed. Finally, the meta-analysis with a significance level of 5% was performed. The findings revealed that the mean level of SO2, CO, NO2, and PM10 in the patient group was more than that of the control group, and p-values were 0.879, 0.144, 0.077, and 0.138, respectively. There was an indirect relation between air pollutants and SSHL, and PM2.5 showed a significant effect (p < 0.05). Given the limited research and the use of different statistical methods, more research is suggested to confirm this association and to determine the mechanisms by which AP exposure may cause SSHL.

Evidence of the protective role of D-Aspartate in counteracting/preventing cadmium-induced oxidative stress in the rat testis.

Cadmium (Cd), by producing oxidative stress and acting as an endocrine disruptor, is known to cause severe testicular injury, documented by histological and biomolecular alterations, such as decreased serum testosterone (T) level and impairment of spermatogenesis. This is the first report on the potential counteractive/preventive action of D-Aspartate (D-Asp), a well-known stimulator of T biosynthesis and spermatogenesis progression by affecting hypothalamic-pituitary-gonadal axis, in alleviating Cd effects in the rat testis. Our results confirmed that Cd affects testicular activity, as documented by the reduction of serum T concentration and of the protein levels of steroidogenesis (StAR, 3ß-HSD, and 17ß-HSD) and spermatogenesis (PCNA, p-H3, and SYCP3) markers. Moreover, higher protein levels of cytochrome C and caspase 3, together with the number of cells positive to TUNEL assay, indicated the intensification of the apoptotic process. D-Asp administered either simultaneously to Cd, or for 15 days before the Cd-treatment, reduced the oxidative stress induced by the metal, alleviating the consequent harmful effects. Interestingly, the preventive action of D-Asp was more effective than its counteractive effect. A possible explanation is that giving D-Asp for 15 days induces its significant uptake in the testes, reaching the concentrations necessary for optimum function. In summary, this report highlights, for the first time, the beneficial role played by D-Asp in both counteracting/preventing the adverse Cd effects in the rat testis, strongly encouraging further investigations to consider the potential value of D-Asp also in improving human testicular health and male fertility.

A randomized controlled phase III study comparing hadrontherapy with carbon ions versus conventional radiotherapy - including photon and proton therapy - for the treatment of radioresistant tumors: the ETOILE trial.

BACKGROUND: Some cancers such as sarcomas (bone and soft tissue sarcomas) and adenoid cystic carcinomas are considered as radioresistant to low linear energy transfer radiation (including photons and protons) and may therefore beneficiate from a carbon ion therapy. Despite encouraging results obtained in phase I/II trials compared to historical data with photons, the spread of carbon ions has been limited mainly because of the absence of randomized medical data. The French health authorities stressed the importance of having randomized data for carbon ion therapy. METHODS: The ETOILE study is a multicenter prospective randomized phase III trial comparing carbon ion therapy to either advanced photon or proton radiotherapy for inoperable or macroscopically incompletely resected (R2) radioresistant cancers including sarcomas and adenoid cystic carcinomas. In the experimental arm, carbon ion therapy will be performed at the National Center for Oncological Hadrontherapy (CNAO) in Pavia, Italy. In the control arm, photon or proton radiotherapy will be carried out in referent centers in France. The primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival and local control, toxicity profile, and quality of life. In addition, a prospective health-economic study and a radiobiological analysis will be conducted. To demonstrate an absolute improvement in the 5-year PFS rate of 20% in favor of carbon ion therapy, 250 patients have to be included in the study. DISCUSSION: So far, no clinical study of phase III has demonstrated the superiority of carbon ion therapy compared to conventional radiotherapy, including proton therapy, for the treatment of radioresistant tumors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02838602 . Date of registration: July 20, 2016. The posted information will be updated as needed to reflect protocol amendments and study progress.

Role of diffusion-weighted MRI in recurrent rectal cancer treated with carbon ion radiotherapy.

Aim: To evaluate the association between pretreatment diffusion-weighted MRI (DW-MRI) and 12-month radiological response in locally recurrent rectal cancer treated with carbon ion radiotherapy. Methods: Histogram analysis was performed on pretreatment DW-MRI for patients re-irradiated with carbon ion radiotherapy for local recurrence of rectal cancer. Results: A total of 17 patients were enrolled in the study. Pretreatment DW-MRI b-value of 1000 s/mm2 (b1000) and apparent diffusion coefficient (ADC) lesion median values for 1-year nonresponders (six patients) and responders (11 patients) demonstrated a median (interquartile of median values) of 62.5 (23.9) and 34.0 (13.0) and 953.0 (277.0) and 942.5 (339.0) µm2/s, respectively. All b1000 histogram features (h-features) and ADC h-kurtosis showed statistically significant differences, whereas only b1000 h-median, b1000 h-interquartile range and ADC h-kurtosis demonstrated remarkable diagnostic accuracy. Conclusion: DW-MRI showed promising results in predicting carbon ion radiotherapy outcome in local recurrence of rectal cancer, particularly with regard to b1000 h-median, b1000 h-interquartile range and ADC h-kurtosis.

Carbon ion radiotherapy is a form of advanced radiotherapy that is especially suitable for radioresistant and/or difficult-to-irradiate tumors. In case of recurrence of rectal cancer after pelvic photon beam radiotherapy, carbon ion radiotherapy may be an option. In this study, the authors looked at the potential role of specific MRI sequences performed before treatment to predict response to carbon ion radiotherapy. If confirmed in a larger prospective cohort, the findings of this study may drive clinical decisions toward a more tumor- and patient-tailored therapeutic approach.

Possible association between PM2.5 and neurodegenerative diseases: A systematic review.

Air pollution is one of the most serious environmental problems that afflict our planet and one of the greatest risk factors for human health. In particular, PM2.5 is able to cross the blood-alveolar and blood-brain barriers, thus increasing the onset of respiratory, cardiovascular and neurodegenerative diseases. Neurodegenerative disease is a progressive neuronal dysfunction that leads to neuronal lesions in both structure and function, and includes several diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), vascular dementia (VaD), multiple sclerosis (MS), and others. We carried out a systematic review using PRISMA approach to investigate on the possible association between exposure to PM2.5 and neurodegenerative diseases. The international databases (PubMed, Science Direct, Web of Sciences) were used to find published studies on the topic. The search period was between January 2011 and June 2021. About 2000 full research articles were selected, and finally, we included 20 full-research articles. Selected studies have highlighted how PM2.5 exposure can be associated with the onset of neurodegenerative diseases (AD, PD, MS, VaD). This association depends not only on age, PM2.5 levels and exposure time, but also on exposure to other air pollutants, proximity to areas with high vehicular traffic, and the presence of comorbidities. Exposure to PM2.5 promotes neuroinflammation processes, because through breathing the particles can reach the nasal epithelial mucosa and transferred to the brain through the olfactory bulb. Furthermore, exposure to PM2.5 has been associated with an increased expression of markers of neurodegenerative diseases (e.g. alpha-synuclein or beta-amyloid), which can contribute to the etiopathogenesis of neurodegenerative diseases. Although many studies have revealed the pathological relationship between PM2.5 exposure and cognitive impairment, the potential cellular and molecular mechanisms of PM2.5 leading to neurodegenerative disease remain not entirely clear, and then, further studies need to be carried out on the topic.

Autophagy and mitochondrial damage in the testis of high-fat diet fed rats.

High-fat diet (HFD) affects the physiology of reproduction in males, and many studies have investigated its detrimental effects. In this study, we investigated the cellular response induced by an HFD in the rat testis, focusing on the mitochondrial compartment. After five weeks of HFD, an increase in the levels of malondialdehyde and of reduced form of glutathione in the rat testis indicated an increase in lipid peroxidation. The results showed an increase in autophagy, apoptosis, and mitochondrial damage in the testis of HFD rats. We found a decrease in the protein expression of mitochondrial antioxidant enzymes, such as catalase and SOD2. Immunohistochemical analysis revealed a decrease in the immunofluorescent signal of SOD2, mainly in the spermatogonia and spermatocytes of HFD rats. HFD-induced mitochondrial damage caused a reduction in mitochondria, as evidenced by a decrease in the protein expression of TOM20, a mitochondrial outer membrane receptor. Consistently, HFD enhanced the levels of the PINK1 protein, a mitophagy marker, suggesting the removal of damaged mitochondria under these conditions. Induction of mtDNA damage and repair was stronger in the HFD rat testis. Finally, we found a decrease in the mtDNA copy number and expression of the POLG enzyme, which is involved in mtDNA replication. In conclusion, our results showed that autophagy and apoptosis are activated in the testis of HFD rats as a survival strategy to cope with oxidative stress. Furthermore, HFD-induced oxidative stress affects the mitochondria, inducing mtDNA damage and mtDNA copy number reduction. Mitophagy and mtDNA repair mechanisms might represent a mitochondrial adaptive response.

Health impact assessment and evaluation of economic costs attributed to PM2.5 air pollution using BenMAP-CE.

Air pollution is considered the most prominent public health. Economically, air pollution imposes additional costs on governments. This study aimed to quantify health effects and associated economic values of reducing PM2.5 air pollution using BenMAP-CE in Qom in 2019. The air quality data were acquired from Qom Province Environmental Protection Agency, and the population data were collected from Qom Province Management and Planning Organization website. The number of deaths due to Stroke, Chronic Obstructive Pulmonary Disease, Lung Cancer, and Ischemic Heart Disease attributable to PM2.5 were estimated using BenMAP-CE based on two control scenarios, 2.4 and 10 µg/m3, known as scenarios I and II, respectively. The associated economic effect of premature deaths was assessed by value of a statistical life (VSL) approach. The annual average of PM2.5 concentration was found to be 16.32 µg/m3 (SD: 9.93). A total of 4694.5 and 2475.94 premature deaths in scenarios I and II were found to be attributable to PM2.5 in overall, respectively. The total associated cost was calculated to be 855.91 and 451.40 million USD in scenarios I and II, respectively. The total years of life lost due to PM2.5 exposure in 2019 was 158,657.06 and 78,351.51 in scenarios I and II, respectively. The results of both health and economic assessment indicate the importance of solving the air pollution problem in Qom, as well as other big cities in Iran. The elimination of limitations, such as insufficient local data, should be regarded in future studies.

Liposomal ferric pyrophosphate and ascorbic acid supplementation in pregnant women with iron deficiency anaemia: haematochemical, obstetric, neonatal and psychological outcomes in a prospective observational study.

This study aimed to determine the effects of liposomal iron pyrophosphate/ascorbic acid on clinical and psychological outcomes in pregnant women. Women at the 11th-13th weeks of gestation with iron deficiency anaemia assuming Sideremil™ from April 2018 to May 2019 were recruited. Haematochemical, obstetric, neonatal and psychological outcomes were investigated at the enrolment, 21-23 weeks of gestation, 30-32 weeks of gestation and after 6 weeks from childbirth. Results showed significant positive effects on haemoglobin, ferritin, sideremia and transferrin levels, compared to baseline data. A significant improvement of anxiety and depression levels was also observed. Regarding the quality of life, all the domains significantly improved, especially the Physical Role domain. Our results indicate that Sideremil™ may be a valid treatment for iron deficiency anaemia in pregnant women, since it significantly improves haematological and mental health outcomes. However, further studies are needed to confirm these results.

Elucidating the Genetic Relationships on the Original Old Sicilian Triticum Spp. Collection by SNP Genotyping.

Several Triticum species spread in cultivation in Sicily and neighboring regions over the centuries, which led to the establishment of a large genetic diversity. Many ancient varieties were widely cultivated until the beginning of the last century before being replaced by modern varieties. Recently, they have been reintroduced in cultivation in Sicily. Here, the genetic diversity of 115 and 11 accessions from Sicily and Calabria, respectively, belonging to Triticum species was evaluated using a high-density SNP array. Einkorn, emmer, and spelta wheat genotypes were used as outgroups for species and subspecies; five modern varieties of durum and bread wheat were used as references. A principal coordinates analysis (PCoA) and an unweighted pair group method with arithmetic mean (UPGMA) showed four distinct groups among Triticum species and T. turgidum subspecies. The population structure analysis distinguished five gene pools, among which three appeared private to the T. aestivum, T. turgidum subsp. Turgidum, and 'Timilia' group. The principal component analysis (PCA) displayed a bio-morphological trait relationship of a subset (110) of ancient wheat varieties and their wide variability within the T. turgidum subsp. durum subgroups. A discriminant analysis of principal components (DAPC) and phylogenetic analyses applied to the four durum wheat subgroups revealed that the improved varieties harbored a different gene pool compared to the most ancient varieties. The 'Russello' and 'Russello Ibleo' groups were distinguished; both displayed higher genetic variability compared to the 'Timilia' group accessions. This research represents a comprehensive approach to fingerprinting the old wheat Sicilian germplasm, which is useful in avoiding commercial fraud and sustaining the cultivation of landraces and ancient varieties.

Venous thromboembolism in hospital emergency room. A retrospective study on climatic effect.

Several cardiovascular conditions exhibit seasonality in frequency and mortality, but little is known about the seasonality of Venous ThromboEmbolism (VTE), a very relevant medical condition, and seasonal influences are still conflicting. Patients having co-morbidities, individual suffered from dyspnea, swelling, edema of lower limb, pain (chest, lower limbs) are admitted frequently to the hospital emergency room (HER), particularly. Both mark a potential risk for VTE, that can be increased also by seasonality. A four years retrospective analysis (2016-2019) was carried out in individuals and patients admitted to the HER of the Hospital of Catania (a Mediterranean city of Sicily, Italy) to evaluate the VTE frequency and its seasonal differences, common symptoms, potential usage of some common laboratory tests. Dyspnea, swelling, edema of lower limb and pain (chest, lower limbs) were considered to suspect pulmonary embolism (PE) or for deep vein thrombosis of lower limb (DVT). Platelet count, platelet volume, fibrinogen, C-reactive protein, and D-dimer were considered. VTE frequency per year was 2.9/10,000 (2016), 4.9/10,000 (2017) 3.6/10,000 (2018), and 5.1/10,000 (2019) respectively. Dyspnea was highly frequent for PE, edema and lower limb pain were frequent in DVT patients. Fibrinogen, C reactive protein, and D-dimer values were found raised in all the VTE patients. Platelet volume was found higher in DVT than PE VTE events that occurred in warm periods were modestly greater (57 VTE: 38 DVT, 19 PE) compared to cold months (52 VTE: 34 DVT, 18 PE). Our results could be explained by the increased sweating due to the high temperatures, which in turn, can affect both on plasma concentration and on hematocrit value coupled to the reduction in atmospheric pressure determining both a hyper-coagulative condition. Climate seasonal characteristics, and environmental conditions in Catania city (Sicily) may be as reasonable items in expecting on different VTE rates in warm period compared to cold. This study highlights no specific symptoms, and confirms the common lab tests for individuals and patients admitted to HER as simple and helpful tools in initiating none or mini-invasive diagnostic strategy for the VTE. Finally, the climate/seasonality coupled with latitude can have a direct influence on the incidence of DVT.

Bidirectional association between COVID-19 and the environment: A systematic review.

The global crisis caused by SARS-CoV-2 (COVID-19) affected economics, social affairs, and the environment, not to mention public health. It is estimated that near 82% of the SARS-CoV-2 genome is similar to the severe acute respiratory syndrome. The purpose of the review is to highlight how the virus is impacted by the environment and how the virus has impacted the environment. This review was based on an electronic search of the literature in the Scopus, Science Direct, and PubMed database published from December 2019 to July 2020 using combinations of the following keywords: SARS-CoV-2 transmission, COVID-19 transmission, coronavirus transmission, waterborne, wastewater, airborne, solid waste, fomites, and fecal-oral transmission. Studies suggest the thermal properties of ambient air, as well as relative humidity, may affect the transmissibility and viability of the virus. Samples taken from the wastewater collection network were detected contaminated with the novel coronavirus; consequently, there is a concern of its transmission via an urban sewer system. There are concerns about the efficacy of the wastewater treatment plant disinfection process as the last chance to inactivate the virus. Handling solid waste also requires an utmost caution as it may contain infectious masks, etc. Following the PRISMA approach, among all reviewed studies, more than 36% of them were directly or indirectly related to the indoor and outdoor environment, 16% to meteorological factors, 11% to wastewater, 14% to fomites, 8% to water, 9% to solid waste, and 6% to the secondary environment. The still growing body of literature on COVID-19 and air, suggests the importance of SARS-CoV-2 transmission via air and indoor air quality, especially during lockdown interventions. Environmental conditions are found to be a factor in transmitting the virus beyond geographical borders. Accordingly, countries need to pay extra attention to sustainable development themes and goals.

Exposure to multiple metals/metalloids and human semen quality: A cross-sectional study.

BACKGROUND: Exposure to metals/metalloids, including essential and nonessential elements, has been associated to male reproductive health in animals. However, findings from human studies are inconsistent. OBJECTIVES: To investigate the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters. MATERIALS AND METHODS: Men living in rural or industrial areas were recruited by personalized letters. No exclusion criteria were applied. Each man provided one semen sample and one blood sample. We analyzed the semen sample both to determine conventional sperm parameters (concentration, progressive motility and normal forms) and to quantify lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), vanadium (V) and selenium (Se) levels. The levels of these metals/metalloids were also quantified in venous blood and spermatozoa samples. Associations between the blood/seminal plasma metal/metalloid levels and semen quality parameters were assessed using confounder adjusted logistic regression models. Correlation and interactions between blood/seminal plasma and semen metal/metalloid levels were investigated using the Spearman's correlation. RESULTS: We found a positive association of seminal plasma cadmium level with lower Total count (OR = 4.48, 95%CI 0.25-80); whereas lead (OR = 4.51, 95%CI 0.86-23) and cadmium (OR = 3.45, 95%CI 0.77-16) seminal plasma levels had a positive association with progressive sperm motility. Overall, these associations remained suggestive after adjustment, though statistically unstable risks. Finally, we found weak interactions between beneficial effects of Se and detrimental ones only for Cd and Pb blood level on sperm concentration, total sperm count and progressive sperm motility. CONCLUSIONS: Our findings suggest that environmental exposure to Pb and Cd contributes to a decline in human semen quality, whereas Se can have beneficial effects. Measurements of metals/metalloids in the seminal fluid may be more predictable of semen quality than conventional blood measurements.

Convolutional Neural Networks Cascade for Automatic Pupil and Iris Detection in Ocular Proton Therapy.

Eye tracking techniques based on deep learning are rapidly spreading in a wide variety of application fields. With this study, we want to exploit the potentiality of eye tracking techniques in ocular proton therapy (OPT) applications. We implemented a fully automatic approach based on two-stage convolutional neural networks (CNNs): the first stage roughly identifies the eye position and the second one performs a fine iris and pupil detection. We selected 707 video frames recorded during clinical operations during OPT treatments performed at our institute. 650 frames were used for training and 57 for a blind test. The estimations of iris and pupil were evaluated against the manual labelled contours delineated by a clinical operator. For iris and pupil predictions, Dice coefficient (median = 0.94 and 0.97), Szymkiewicz-Simpson coefficient (median = 0.97 and 0.98), Intersection over Union coefficient (median = 0.88 and 0.94) and Hausdorff distance (median = 11.6 and 5.0 (pixels)) were quantified. Iris and pupil regions were found to be comparable to the manually labelled ground truths. Our proposed framework could provide an automatic approach to quantitatively evaluating pupil and iris misalignments, and it could be used as an additional support tool for clinical activity, without impacting in any way with the consolidated routine.

D-Amino acids in mammalian endocrine tissues.

D-Aspartate, D-serine and D-alanine are a regular occurrence in mammalian endocrine tissues, though in amounts varying with the type of gland. The pituitary gland, pineal gland, thyroid, adrenal glands and testis contain relatively large amounts of D-aspartate in all species examined. D-alanine is relatively abundant in the pituitary gland and pancreas. High levels of D-serine characterize the hypothalamus. D-leucine, D-proline and D-glutamate are generally low. The current knowledge of physiological roles of D-amino acids in endocrine tissues is far from exhaustive, yet the topic is attracting increasing interest because of its potential in pharmacological application. D-aspartate is known to act at all levels of the hypothalamus-pituitary-testis axis, playing a key role in reproductive biology in several vertebrate classes. An involvement of D-amino acids in the endocrine function of the pancreas is emerging. D-Aspartate has been immunolocalized in insulin-containing secretory granules in INS-1 E clonal ß cells and is co-secreted with insulin by exocytosis. Specific immunolocalization of D-alanine in pituitary ACTH-secreting cells and pancreatic ß-cells suggests that this amino acid participates in blood glucose regulation in mammals. By modulating insulin secretion, D-serine probably participates in the control of systemic glucose metabolism by modulating insulin secretion. We anticipate that future investigation will significantly increase the functional repertoire of D-amino acids in homeostatic control.

The role of air pollution (PM and NO2) in COVID-19 spread and lethality: A systematic review.

A new coronavirus (SARS-CoV-2) has determined a pneumonia outbreak in China (Wuhan, Hubei Province) in December 2019, called COVID-19 disease. In addition to the person-to person transmission dynamic of the novel respiratory virus, it has been recently studied the role of environmental factors in accelerate SARS-CoV-2 spread and its lethality. The time being, air pollution has been identified as the largest environmental cause of disease and premature death in the world. It affects body's immunity, making people more vulnerable to pathogens. The hypothesis that air pollution, resulting from a combination of factors such as meteorological data, level of industrialization as well as regional topography, can acts both as a carrier of the infection and as a worsening factor of the health impact of COVID-19 disease, has been raised recently. With this review, we want to provide an update state of art relating the role of air pollution, in particular PM2.5, PM10 and NO2, in COVID-19 spread and lethality. The Authors, who first investigated this association, often used different research methods or not all include confounding factors whenever possible. In addition, to date incidence data are underestimated in all countries and to a lesser extent also mortality data. For this reason, the cases included in the reviewed studies cannot be considered conclusive. Although it determines important limitations for direct comparison of results, and more studies are needed to strengthen scientific evidences and support firm conclusions, major findings are consistent, highlighting the important contribution of PM2.5 and NO2 as triggering of the COVID-19 spread and lethality, and with a less extent also PM10, although the potential effect of airborne virus exposure it has not been still demonstrated.

Micro- and nano-plastics in edible fruit and vegetables. The first diet risks assessment for the general population.

Microplastics (MPs) represent a current public health concern since toxicity has not yet fully investigated. They were found in several foods, but to the best of our knowledge, at this time no data was reported for the edible vegetables and fruits. We focused on diet exposure aiming to evaluate the number and the size (<10 µm) of MPs in the most commonly consumed vegetables and fruits, in relation to their recommended daily intake too. MPs extraction and analysis were carried out using an innovative Italian methodology and SEM-EDX, respectively. Finally, we calculated the Estimated Daily Intakes (EDIs) for adults and children for each type of vegetal and fruit. The higher median (IQR) level of MPs in fruit and vegetable samples was 223,000 (52,600-307,750) and 97,800 (72,175-130,500), respectively. In particular, apples were the most contaminated fruit samples, while carrot was the most contaminated vegetable. Conversely, the lower median (IQR) level was observed in lettuce samples 52,050 (26,375-75,425). Both vegetable and fruit samples MPs levels were characterized by wide variability. The smallest size of MPs was found in the carrot samples (1.51 µm), while the biggest ones were found in the lettuce (2.52 µm). Both vegetable and fruit samples had size of the MPs characterized by low variability. We found the highest median level of MPs in samples purchased from the "fruiter 3" (124,900 p/g) and the lowest in those purchased in "supermarket" (87,600 p/g). The median size of the MPs had overlapping dimensions in all the purchase sites, with the exception of the samples purchased at the "shop at km zero 2″ which had slightly smaller size (1.81 µm). The highest adults' (4.62 E+05) and children's (1.41 E+06) EDIs are due the ingestion of apples, instead the lowest are due to the ingestion of carrots (adults: 2.96 E+04; children: 1.15 E+05). We hypothesized that the mechanism of uptake and translocation of MPs can be the same described and reported for carbon-nanomaterials. This may be a possible translocation route of MPs by environment to vegetables permitting, so, the translocation or uptake inside of their biological systems. Based on the results obtained it is urgent important to perform toxicological and epidemiological studies to investigate for the possible effects of MPs on human health.

CSF neurotoxic metals/metalloids levels in amyotrophic lateral sclerosis patients: comparison between bulbar and spinal onset.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the central nervous system (CNS) that causes progressive and irreversible damage in motor neurons. Different causal hypotheses include genetic, viral, traumatic and environmental mechanisms, such as exposure to heavy metals. The aim of this study was to compare metal/metalloid levels in cerebro-spinal fluid of ALS subtypes (spinal vs bulbar clinical onset). MATERIAL AND METHODS: This observational study consecutively screened all ALS patients referring to the Neurology Clinic of the University of Catania (Italy). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify magnesium (Mg), cuprum (Cu), selenium (Se), iron (Fe), manganese (Mn), vanadium (V), zinc (Zn), alluminium (Al), arsenic (As), cobalt (Co), nickel (Ni), mercury (Hg), lead (Pb), cadmium (Cd) and palladium (Pd) levels. RESULTS: Thirty-seven patients were enrolled (62.2% females), median age of 65 years (IQR: 59-71 years). Thirty-one (83.8%) patients had a spinal onset and 6 (16.2%) a bulbar onset. Se and As levels were higher compared to the reference values (RV) both in spinal and bulbar onset, while Cu was higher than RV only in bulbar onset. Moreover, Cu (129.8 µg/L vs 29.8 µg/L), Fe (54.5 µg/L vs 33.3 µg/L), Mn (3.4 µg/L vs 1.8 µg/L), Zn (46.1 µg/L vs 35.7 µg/L), Al (12.2 µg/L vs 6.7 µg/L), Ni (2.80 µg/L vs 1.40 µg/L), and Pb (0.60 µg/L vs 0.30 µg/L) levels were higher in bulbar than in spinal onset, conversely As was slightly higher in spinal than in bulbar onset (1.40 µg/L vs 1.10 µg/L). Overall, Cu (129 µg/L vs 31 µg/L), Fe (92.2 µg/L vs 32.9 µg/L), Mn (3.35 µg/L vs 1.80 µg/L), Zn (56.5 µg/L vs 35.2 µg/L), Al (14.45 µg/L vs 6.70 µg/L), and Cd (0.40 µg/L vs 0.08 µg/L) levels were higher in patients with disease duration less than 19 months. CONCLUSION: Our results supported the hypothesis that metals/metalloids with neurotoxic effects could be involved in the etiology of ALS, showing higher levels of Cu, Se and As. Relevant differences in Cu and Mn levels were found between bulbar and spinal onset patients.

Phytoremediation potential of Arundo donax (Giant Reed) in contaminated soil by heavy metals.

Soil pollution from heavy metals poses a serious risk for environment and public health. Phytoremediation is an eco-friendly and cheaper alternative compared to chemical-physical techniques. We carried out in vitro tests where three microorganisms Trichoderma harzianum, Saccharomyces cerevisiae and Wickerhamomyces anomalus were exposed to eight different heavy metals (one metal at a time) in order to evaluate resistance, growth and bioaccumulation capability for each metal (Ni, Cd, Cu, V, Zn, As, Pb, Hg). Taking into account the natural characteristics of T. harzianum, (resistance to environmental stress, resistance to pathogenic fungi, ability to establish symbiotic relationships with superior green plants) and the good bioaccumulation capacity for V, As, Cd, Hg, Pb shown after in vitro tests, it was chosen as a microorganism to be used in greenhouse tests. Controlled exposure tests were performed in greenhouse, where Arundo donax and mycorrhized Arundo donax with T. harzianum were exposed for 7 months at two different doses (L1 and L2) of a heavy metal mix, so as to assess whether the symbiotic association could improve the bioaccumulation capability of the superior green plant A. donax. Heavy metals were determined with ICP-MS. The average bioaccumulation percentage values of A. donax for L1 and L2 were, respectively: Ni (31%, 26%); Cd (35%, 50%); Cu (30%, 35%); As (19%, 27%); Pb (18%, 14%); Hg (42%, 45%); V (39%, 26%); Zn (23%, 9%). The average bioaccumulation percentage values of mycorrhized A. donax with T. harzianum for L1 and L2 were, respectively: Ni (27%, 38%); Cd (44%, 42%); Cu (36%, 29%); As (17%, 23%); Pb (37%, 54%); Hg (44%, 60%); V (16%, 20%); Zn (14%, 7%). A. donax showed the highest BAF (bioaccumulation factor) for Cd (0.50), Cu (0.35), As (0.27) and Hg (0.45) after exposure to L2; mycorrhized A. donax with T. harzianum showed the highest BAF for Ni (0.38), Cd (0.42), Pb (0.54) and Hg (0.60) after exposure to L2. A. donax showed the highest TF (translocation factor) values for Cd (0.28) and Hg (0.26) after exposition at L1 and L2 respectively; A. donax mycorrhized with T. harzianum showed the highest TF values for Cd (0.70), As (0.56), V (0.24), Pb (0.18) after exposition at L2, and Zn (0.30) after exposition at L1. Our study showed a good growth capability in contaminated soils and a good bioaccumulation capability of heavy metals, both for A. donax and mycorrhized A. donax with T. harzianum. Furthermore, for three metals (Ni, Pb and Hg) the bioaccumulation capability was improved by the symbiosis of T. harzianum with A. donax. So, these results proved the suitability both for A. donax and mycorrhized A. donax with T. harzianum for phytoremediation processes.