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.

Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate.

Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) mediate the communication between the Endoplasmic Reticulum (ER) and the mitochondria, playing a fundamental role in steroidogenesis. This study aimed to understand how D-aspartate (D-Asp), a well-known stimulator of testosterone biosynthesis and spermatogenesis, affects the mechanism of steroidogenesis in rat testes. Our results suggested that D-Asp exerts this function through MAMs, affecting lipid trafficking, calcium signaling, ER stress, and mitochondrial dynamics. After 15 days of oral administration of D-Asp to rats, there was an increase in both antioxidant enzymes (SOD and Catalase) and in the protein expression levels of ATAD3A, FACL4, and SOAT1, which are markers of lipid transfer, as well as VDAC and GRP75, which are markers of calcium signaling. Additionally, there was a decrease in protein expression levels of GRP78, a marker of aging that counteracts ER stress. The effects of D-Asp on mitochondrial dynamics strongly suggested its active role as well. It induced the expression levels of proteins involved in fusion (MFN1, MFN2, and OPA1) and in biogenesis (NRF1 and TFAM), as well as in mitochondrial mass (TOMM20), and decreased the expression level of DRP1, a crucial mitochondrial fission marker. These findings suggested D-Asp involvement in the functional improvement of mitochondria during steroidogenesis. Immunofluorescent signals of ATAD3A, MFN1/2, TFAM, and TOMM20 confirmed their localization in Leydig cells showing an intensity upgrade in D-Asp-treated rat testes. Taken together, our results demonstrate the involvement of D-Asp in the steroidogenesis of rat testes, acting at multiple stages of both MAMs and mitochondrial dynamics, opening new opportunities for future investigation in other steroidogenic tissues.

Is motherhood still possible after pelvic carbon ion radiotherapy? A promising combined fertility-preservation approach.

INTRODUCTION: Preserving the endocrine and reproductive function in young female cancer patients undergoing pelvic radiation is a significant challenge. While the photon beam radiation's adverse effects on the uterus and ovaries are well established, the impact of pelvic carbon ion radiotherapy on women's reproductive function is largely unexplored. Strategies such as oocyte cryopreservation and ovarian transposition are commonly recommended for safeguarding future fertility. METHODS: This study presents a pioneering case of successful pregnancy after carbon ion radiotherapy for locally advanced sacral chondrosarcoma. RESULTS: A multidisciplinary approach facilitated the displacement of ovaries and uterus before carbon ion radiotherapy, resulting in the preservation of endocrine and reproductive function. CONCLUSION: The patient achieved optimal oncological response and delivered a healthy infant following the completion of cancer treatment.

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.

The Role of Carbon Ion Therapy in the Changing Oncology Landscape-A Narrative Review of the Literature and the Decade of Carbon Ion Experience at the Italian National Center for Oncological Hadrontherapy.

BACKGROUND: Currently, 13 Asian and European facilities deliver carbon ion radiotherapy (CIRT) for preclinical and clinical activity, and, to date, 55 clinical studies including CIRT for adult and paediatric solid neoplasms have been registered. The National Center for Oncological Hadrontherapy (CNAO) is the only Italian facility able to accelerate both protons and carbon ions for oncological treatment and research. METHODS: To summarise and critically evaluate state-of-the-art knowledge on the application of carbon ion radiotherapy in oncological settings, the authors conducted a literature search till December 2022 in the following electronic databases: PubMed, Web of Science, MEDLINE, Google Scholar, and Cochrane. The results of 68 studies are reported using a narrative approach, highlighting CNAO's clinical activity over the last 10 years of CIRT. RESULTS: The ballistic and radiobiological hallmarks of CIRT make it an effective option in several rare, radioresistant, and difficult-to-treat tumours. CNAO has made a significant contribution to the advancement of knowledge on CIRT delivery in selected tumour types. CONCLUSIONS: After an initial ramp-up period, CNAO has progressively honed its clinical, technical, and dosimetric skills. Growing engagement with national and international networks and research groups for complex cancers has led to increasingly targeted patient selection for CIRT and lowered barriers to facility access.

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.

Comparison of video-assisted pleurectomy/decortication surgery plus hyperthermic intrathoracic chemotherapy with VATS talc pleurodesis for the treatment of malignant pleural mesothelioma: A pilot study.

Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6-80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12-25) in Group A and 28 months (95% CI 0-56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0-34) in Group A and 45 months (95% CI 0-107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial.

Risk and Prognosis of Thyroid Cancer in Patients with Graves' Disease: An Umbrella Review.

Graves' disease (GD) is an autoimmune disease considered the most common cause of hyperthyroidism. Some studies have investigated its relationship with the risk and prognosis of developing thyroid cancer. Considering that there is no consensus on the relationship between GD and thyroid cancer risk, this umbrella review aimed to summarize the epidemiologic evidence and evaluate its strength and validity on the associations of GD with thyroid cancer risk and its prognosis. This umbrella review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched PubMed and Scopus from January 2012 to December 2022. The strength of the epidemiological evidence was graded as high, moderate, or weak by the Measurement Tool to Assess Systematic Reviews (AMSTAR-2). "Strong" evidence was found for the risk of thyroid cancer in GD patients with thyroid nodular disease (OR: 5.30; 95% CI 2.43-12) and for the risk of mortality from thyroid cancer in these patients (OR 2.93, 95% CI 1.17-7.37, p = 0.02), particularly in Europe (OR 4.89; 95% CI 1.52-16). The results of this umbrella review should be interpreted with caution; as the evidence comes mostly from retrospective studies, potential concerns are selection and recall bias, and whether the empirically observed association reflects a causal relationship remains an open question.

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.

D-Aspartate Depletion Perturbs Steroidogenesis and Spermatogenesis in Mice.

High levels of free D-aspartate (D-Asp) are present in vertebrate testis during post-natal development, coinciding with the onset of testosterone production, which suggests that this atypical amino acid might participate in the regulation of hormone biosynthesis. To elucidate the unknown role of D-Asp on testicular function, we investigated steroidogenesis and spermatogenesis in a one-month-old knockin mouse model with the constitutive depletion of D-Asp levels due to the targeted overexpression of D-aspartate oxidase (DDO), which catalyzes the deaminative oxidation of D-Asp to generate the corresponding α-keto acid, oxaloacetate, hydrogen peroxide, and ammonium ions. In the Ddo knockin mice, we found a dramatic reduction in testicular D-Asp levels, accompanied by a significant decrease in the serum testosterone levels and testicular 17ß-HSD, the enzyme involved in testosterone biosynthesis. Additionally, in the testes of these Ddo knockin mice, the expression of PCNA and SYCP3 proteins decreased, suggesting alterations in spermatogenesis-related processes, as well as an increase in the cytosolic cytochrome c protein levels and TUNEL-positive cell number, which indicate an increase in apoptosis. To further investigate the histological and morphometric testicular alterations in Ddo knockin mice, we analyzed the expression and localization of prolyl endopeptidase (PREP) and disheveled-associated activator of morphogenesis 1 (DAAM1), two proteins involved in cytoskeletal organization. Our results showed that the testicular levels of DAAM1 and PREP in Ddo knockin mice were different from those in wild-type animals, suggesting that the deficiency of D-Asp is associated with overall cytoskeletal disorganization. Our findings confirmed that physiological D-Asp influences testosterone biosynthesis and plays a crucial role in germ cell proliferation and differentiation, which are required for successful reproduction.

Effects of a high-fat diet on rat epididymis.

The epididymis plays an essential role in reproduction, promoting sperm cell maturation. In this study, we investigated the effects of a high-fat diet (HFD) in the three regions of the epididymis of rats, including caput, corpus, and cauda. Our results showed an increase in malondialdehyde and a decrease in superoxide dismutase, which indicated an increase in oxidative stress in all segments of the epididymis. The cellular response mechanisms were mostly detected in the corpus/cauda regions, which showed an increase in apoptosis, probably for eliminating dysfunctional cells arising from HFD-induced oxidative stress, and a decrease in mitophagy. Additionally, an increase in lipophagy to prevent lipid accumulation and a decrease in cell proliferation were recorded in the corpus.

Behaviour and fate of Ag-NPs, TiO2-NPs and ZnO-NPs in the human gastrointestinal tract: Biopersistence rate evaluation.

This study aims to provide information on the behaviour and biopersistence rate (BP) of metallic nanoparticles (Ag-NPs, TiO2-NPs, ZnO-NPs) naturally occurring in canned seafood and subjected to static in vitro digestion. Single particle ICP-MS analysis was performed to determine NPs distribution and concentrations in oral, gastric, and intestinal digests. Depending on the conditions of the digestive phase and the sample matrix, the phenomena of agglomeration and dispersion were highlighted and confirmed by Dynamic Light Scattering (DLS) technique. In standard suspensions, Ag-NPs had lower biopersistence (BP) than ZnO and TiO2-NPs (BP 34%, 89% and >100%, respectively). Among Ag-NPs and TiO2-NPs naturally present in the food matrix, those in canned tuna were more degradable than those in canned clam (BP Ag-NPs 36% vs. > 100%; BP TiO2-NPs 96% vs. > 100%), while BP ZnO-NPs showed high biopersistence in both seafood matrix (>100%). The biopersistence rates were higher than the recommended limit set by European Food Safety Authority (EFSA) (12%), referred to nanotechnologies to be applied in the food and feed chain, thus the investigated naturally occurring NPs cannot be considered readily degradable.

Pragmatic, Prospective Comparative Effectiveness Trial of Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas (Soft Tissue/Bone) Involving the Bone: The PROSPER Study Rationale and Design.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

DNA Damage and Apoptosis as In-Vitro Effect Biomarkers of Titanium Dioxide Nanoparticles (TiO2-NPs) and the Food Additive E171 Toxicity in Colon Cancer Cells: HCT-116 and Caco-2.

This study investigated the DNA damage and apoptosis in colon cancer cells HCT-116 and Caco-2 induced by engineered titanium dioxide nanoparticles (TiO2-NPs) (60 nm) and titanium dioxide food additive E171. MTT assays showed that both chemical forms significantly reduced cancer cell viability in a dose-dependent manner. In particular the food additive E171 induced a pronounced inhibitory effect on the growth of HCT-116 and Caco-2 cell lines (E171 IC50: 3.45 mg/L for HTC-116 and 1.88 mg/L Caco-2; TiO2-NPs 60 nm IC50: 41.1 mg/L for HTC-116 and 14.3 mg/L for Caco-2). A low level of genotoxicity was observed in Caco-2 cells, especially when treated with TiO2 60 nm. Western blot analysis showed that HCT116 and Caco-2 treated cells did not overexpress apoptotic markers such as cleaved Caspase 3 and cleaved Parp. Moreover, further analysis by quantitative real-time PCR (qRT-PCR) showed that TiO2-NPs and E171 did not promote the expression of Bax or downregulation of Bcl-2, nor did they increase the Bax/Bcl-2 ratio. The assay data provide clear evidence that TiO2 can cause DNA damage but does not induce apoptosis or decrease long-term cell proliferation. In addition, the results show that E171 has a slightly higher level of cytotoxicity and genotoxicity. This suggests that exposure to E171 may be hazardous to health and that further research on biological effects is needed to promote safer practices in the use of this compound.

Parenchymal liver metastasis in advanced ovarian cancer: Can bowel involvement influence the frequency and the related mortality rate?

OBJECTIVE: This retrospective study estimates the frequency of parenchymal liver metastasis (PLM) and the overall survival (OS) rate of patients with FIGO Stage IIIC-IV Advanced Epithelial Ovarian Cancer (EOC) with bowel involvement. STUDY DESIGN: Between November 2008 and July 2020, all consecutive patients with FIGO Stage IIIC-IV EOC who underwent Visceral Peritoneal Debulking and bowel resection(s) at the Gynaecological Oncology Unit of "Centro di Riferimento Oncologico (CRO)", Aviano, Italy, without evidence of PLM at pre-operative imaging assessment, were included in the study. The presence and the time of the onset of PLM during the follow-up period were detected by diagnostic imaging (CT-scan, Ultrasound and PET). The OS of patients with and without PLM was compared. Considering the bowel's layers, the association between depth of bowel involvement, number of PLM, and the relative OS rate was evaluated. RESULTS: The median follow-up period was 47.3 (12-138) months. PLM occurred in 24/72 (33.0%) cases; the average onset time of PLM was 13 months. PLM was associated with increased significant mortality risk and an average OS of 33.2 versus 56.8 months (p < 0.001). The risk of developing PLM correlated directly with the depth of bowel involvement. However, there was no statistical difference between the layers in terms of OS at the end of the observational period. CONCLUSIONS: PLM occurred more frequently among patients with EOC and bowel involvement. The PLM arose within 15 months of follow-up and the frequency increased according to the depth of involvement. Particularly, the difference is remarkably higher starting from muscular layer where the total number of PLM arose significantly (p = 0.02). Although there was no significant difference among the infiltrated bowel layers in terms of OS, patients with bowel involvement up to muscular had a dramatic reduction in the OS rate during the first 30 months of follow-up.

The links between microclimatic and particulate matter concentration in a multi-storey car parking: a case study iran.

Multi-storey cars increasing with population growth have excellent security and temporary parking for cars in big cities, which isn't suitable for parking in the streets. The goals of this study are (1) to determine PM concentrations in the ZGP and (2) to investigate the effect of temperature and humidity on PM concentration in ZGP. This study measured the levels of emitted PM1, PM2.5, and PM10 by GRIMM EDM 107 laser dust monitor in a busy multi-storey parking garage located in Qom. Moreover, the relationship between microclimatic parameters and the contaminants mentioned above was investigated. Samples were collected in two stages in different spatiotemporal conditions, namely, the summer and autumn of 2017. The results indicate that during the sampling period, the daily mean ± standard deviation of PM10, PM2.5, and PM1 were 120.9 ± 90.6, 28.5 ± 10.4, and 10.8 ± 3.8 µg/m3, respectively. A decrease in pollution level was observed during the measurement period. During rush hours, the levels of particulate matter increased. Also, a significant positive relationship between indoor humidity and particle level was observed, while there was a meaningful, inverse relationship between temperature and particle level. The high PM concentration in the parking garage indicates the necessity of proper management and planning.

Effects of Nano and Microplastics on the Inflammatory Process: In Vitro and In Vivo Studies Systematic Review.

BACKGROUND: Microplastics (MPs) and Nanoplastics (NPs) are plastic fragments that spread in the environment and accumulate in the human body, so they have been becoming a worldwide environmental concern because of their potential human health effects. The aim of this systematic review was to investigate the prospective impact of MPs and NPs on the inflammatory process. METHODS: Electronic article search was performed on PubMed, Scopus and Web of Science international databases from 1 Jan 2012 to 31 Dec 2021. Screenings of titles, abstracts and full texts were performed according to the Preferred Reporting Item for Systematic Review and Meta-analyses (PRISMA). The methodological quality of the studies was checked by the Toxicological data Reliability Assessment Tool. RESULTS: Electronic article search identified 125 records, from which 6 in vitro, 11 in vivo and 2 both in vivo and in vitro studies were included. Both in vivo and in vitro studies have showed an increase ofdifferent inflammatory outcomes (Interleukines, Tumor necrosis factor, Chemokines, Interferones, Transcription factors, Growth factors, Oxydoreductase, Proteins and others), thus it seems to confirm the association withthe exposure to microplastics of different types, sizes, exposure times and exposed species. CONCLUSIONS: This systematic review seems to support the relationship between the exposure to MPs and the inflammatory processboth in vivo and in vitro. Greater caution is needed about the role of NPs because ofa very small number of studies. Additional high-quality studies are warranted to confirm these results, especially the research should be focused on NPs being lacking literature.

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.

Custom-Made 3D-Printed Implants for Anterior Column Reconstruction in the Upper Cervical Spine after Intralesional Extracapsular Excision-Report of 2 Cases and Literature Review.

The use of three-dimensional (3D)-printed custom-made implants is spreading in the orthopedics field for the reconstruction of bone losses or for joint replacement, thanks to their unparalleled versatility. In particular, this novel technology opens new perspectives to formulate custom-made fixation strategies for the upper cervical region, sacrum and pelvis, where reconstruction is challenging. We report and analyze the literature concerning upper cervical reconstruction with 3D-printed personalized implants after tumor surgery, and discuss two cases of patients where this technology was used to reconstruct the anterior column after extracapsular debulking of C2 recurrent chordoma at our institution.

Benefits of Physical Activity during and after Thyroid Cancer Treatment on Fatigue and Quality of Life: A Systematic Review.

BACKGROUND: Several epidemiological studies have provided evidence of the usefulness of physical activity for cancer prevention, increased survival and quality of life (QoL), but no comprehensive review is available on the effects on thyroid cancer. The present systematic review provides an overview of the effects of physical activity on fatigue, QoL and health-related quality of life (HRQoL) in patients with thyroid cancer diagnosis both during and after treatment, with a focus on sex. METHODS: A literature search was conducted in the PubMed and Scopus databases. We included studies investigating the impact of physical activity during and after thyroid cancer treatment, including fatigue, QoL and/or HRQoL among the outcomes. Review articles, conference papers, short communications and articles written in a language other than English articles were excluded. Study selection followed the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA). Two reviewers independently selected the studies and assessed their eligibility. The same two reviewers independently screened studies, extracted data and assessed the risk of bias. Outcomes of interest were fatigue, QoL and HRQoL. The Newcastle-Ottawa Scale was used to assess the quality of the selected studies. We compared the outcomes between groups of patients with subclinical hyperthyroidism undergoing a physical activity program and a sedentary group, evaluating the possible presence of sex differences. RESULTS AND DISCUSSION: We found five studies eligible for inclusion in our review; only two were prospective studies including an exercise training program. One study was a quasi-experimental study with a non-equivalent control group. Three out of five studies comprised low-quality evidence with a high risk of bias. CONCLUSION: The level of confidence in the available evidence is very low. A close association between physical activity and fatigue, QoL and HRQoL in patients with thyroid cancer diagnosis with a focus on sex can neither be supported nor refuted. Future studies are needed to understand which training programs are optimal, both in terms of beneficial effects and to avoid potential adverse responses, in addition to focusing on gender differences. The protocol of this systematic review was registered with PROSPERO: CRD42022322519.