Search Results (23)

Background: Varicocele is a common condition involving the dilation of veins in the scrotum, often linked to male infertility and testicular dysfunction. This study aimed to elucidate the molecular effects of successful varicocele treatment on sperm proteomes following percutaneous sclero-embolization. Methods: High-resolution tandem mass spectrometry was performed for proteomic profiling of pooled sperm lysates from five patients exhibiting improved semen parameters before and after (3 and 6 months) varicocele sclero-embolization. Data were validated by Western blot analysis. Results: Seven proteins were found exclusively in varicocele patients before surgery—such as stathmin, IFT20, selenide, and ADAM21—linked to inflammation and oxidative stress. After sclero-embolization, 55 new proteins emerged, including antioxidant enzymes like selenoprotein P and GPX3. Thioredoxin (TXN) and peroxiredoxin (PRDX3) were upregulated, indicating restoration of key antioxidant pathways. Additionally, the downregulation of some histones and the autophagy-related protein ATG9A suggests a shift toward an improved chromatin organization and a healthier cellular environment post-treatment. Conclusions: Varicocele treatment that improves sperm quality and fertility parameters leads to significant proteome modulation. These changes include reduced oxidative stress and broadly restored sperm maturation. Despite the limited patient cohort analyzed, these preliminary findings provide valuable insights into how varicocele treatment might enhance male fertility and suggest potential biomarkers for improved male infertility treatment strategies. Full article

Background/Objectives: Mental representation of spatial information relies on egocentric (body-based) and allocentric (environment-based) frames of reference. Research showed that spatial memory deteriorates as Alzheimer’s disease (AD) progresses and that allocentric spatial memory is among the earliest impaired areas. Most studies have been conducted in static situations despite the dynamic nature of real-world spatial processing. Thus, this raises the question: Does temporal order affect spatial memory? The present study, by adopting a dynamic spatial memory task, explored how the temporal order of item presentation influences egocentric and allocentric spatial judgments in individuals with early-stage Alzheimer’s disease (eAD) and healthy elderly individuals (normal controls—NC). Method: Participants were required to memorize dyads of simple 3D geometrical objects presented one at a time on a desk along with a bar. Afterwards, they had to choose what stimulus appeared either closest to them (egocentric judgment) or closest to the bar (allocentric judgment). Results: Results revealed that the temporal order significantly affected spatial judgments in eAD patients but not in NC participants. While eAD patients remain anchored to the item presented first, which is more accurate regardless of the frame used, NC are equally accurate with the item that appears first or second. This is presumably because eAD patients struggle to flexibly shift attention and update spatial representations in dynamic situations, which leads to reliance on initial information and difficulties with information presented later. Conclusions: This highlights the importance of further understanding the cognitive strategies employed by AD patients. Full article

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor characterized by a high infiltration capability and recurrence rate. Early diagnosis is crucial to improve the prognosis and to personalize the therapeutic approach. This research explored, by LC-MS proteomic analysis after proteolytic digestion, the molecular profile of pre- and post-operative saliva pools from newly diagnosed (ND) GBM patients by comparing different times of collection and tumor recurrence (R). CYCS, PRDX2, RAB1C, PSMB1, KLK6, TMOD3, PAI2, PLBD1, CAST, and AHNAK, all involved in processes of tumor invasiveness and chemo- and radio-resistance, were found to depict the pre-surgery saliva of both ND and R GBM. PADI4 and CRYAB proteins, identified among the most abundant proteins exclusive of ND GBM pre-surgery saliva and classified as proteins elevated in glioma, could have a potential role as disease biomarkers. Selected panels of S100 proteins were found to potentially differentiate ND from R GBM patient saliva. TPD52 and IGKV3, exclusively identified in R GBM saliva, could be additionally distinctive of tumor relapse. Among the proteins identified in all pools, label-free relative quantitation showed statistically significant different levels of TXN, SERPINB5, FABP5, and S100A11 proteins between the pools. All of these proteins showed higher levels in both ND_ and R_T0 pre-surgery saliva with respect to CTRL and different modulation after surgery or chemo-radiotherapy combined treatment, suggesting a role as a potential panel of GBM predictive and prognostic biomarkers. These results highlight and confirm that saliva, a biofluid featured for an easily accessible and low invasiveness collection, is a promising source of GBM biomarkers, showing new potential opportunities for the development of targeted therapies and diagnostic tools. Full article

Background: Endometrial cancer (EC) is, nowadays, the most frequent gynecological malignancy worldwide. The main treatment approach for EC is surgery, especially for early-stage tumors. For advanced EC, chemotherapy (CT) with carboplatin and paclitaxel is the standard treatment, especially for women with metastatic or recurrent disease. The present systematic review aimed to establish whether neoadjuvant treatment regimens with CT and/or radiotherapy (RT) lead to better survival outcomes compared to upfront surgery in advanced EC. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, through the string “((“Endometrial Neoplasms”[Mesh]) AND “Hysterectomy”[Mesh]) AND “Radiotherapy”[Mesh] AND Chemotherapy”, the selection of articles was made. A quality assessment was conducted using the Newcastle–Ottawa Scale (NOS). The studies included patients with EC with survival and recurrence outcomes—patients treated with upfront surgery or neoadjuvant CT ± External Beam Radiation Therapy (EBRT) or CT ± Brachytherapy (BT). Results: According to the selected evidence in the scientific literature, the 5-year DFS was 21.3% for upfront surgery and ranged from 42 to 73% for neoadjuvant chemotherapy. Also, the 5-year OS was 6.2 to 49.7% with upfront surgery and 15.5 to 100% for neoadjuvant schemes. None of the studies dedicated to surgery reported the 5-year Recurrence Rate (RR), while in the neoadjuvant treatments, it ranged from 27 to 64.7%. Conclusions: The literature’s paucity of data makes it difficult to compare neoadjuvant therapy regimens with upfront surgery in advanced endometrial carcinoma. Nevertheless, the current data show more encouraging results for the neoadjuvant treatment group. Full article

This study explores the interplay between executive functions and body weight, examining both the influence of biological factors, specifically sex, and methodological issues, such as the choice between Body Mass Index (BMI) and waist circumference (WC) as the primary anthropometric measure. A total of 386 participants (222 females, mean age = 45.98 years, SD = 17.70) were enrolled, from whom sociodemographic (sex, age, years of formal education) and anthropometric (BMI and WC) data were collected. Executive functions were evaluated using the Frontal Assessment Battery–15 (FAB15). The results showed the increased effectiveness of WC over BMI in examining the relationships between executive functions, sex differences, and body weight. In particular, this study revealed that there was a significant moderating effect of sex at comparable levels of executive functioning. Specifically, women with higher executive performance had lower WCs than their male counterparts, suggesting that executive function has a greater impact on WC in women than in men. Our findings highlight the importance of conducting more in-depth investigations of the complex relationship between cognitive deficits and weight gain, considering confounding variables of behavioral, psychobiological, and neurophysiological origin. Full article

Background and aims: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. Methods: A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the “Training Group” (215 patients) and the “Validation Group” (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. Results: Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named “SARCO-MELD” based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment. Full article

Purpose: to evaluate the clinical impact of a protocol for the image-guided percutaneous microwave ablation (MWA) of hepatocellular carcinoma (HCC) that includes cone-beam computed tomography (CBCT), fusion imaging and ablation volume prediction in patients with hepatocellular carcinoma unsuitable for standard ultrasound (US) guidance. Materials and Methods: this study included all patients with HCC treated with MWA between January 2021 and June 2022 in a tertiary institution. Patients were divided into two groups: Group A, treated following the protocol, and Group B, treated with standard ultrasound (US) guidance. Follow-up images were reviewed to assess residual disease (RD), local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Ablation response at 1 month was also evaluated according to mRECIST. Baseline variables and outcomes were compared between the groups. For 1-month RD, propensity score weighting (PSW) was performed. Results: 80 consecutive patients with 101 HCCs treated with MWA were divided into two groups. Group A had 41 HCCs in 37 patients, and Group B had 60 HCCs in 43 patients. Among all baseline variables, the groups differed regarding their age (mean of 72 years in Group A and 64 years in Group B, respectively), new vs. residual tumor rates (48% Group A vs. 25% Group B, p < 0.05) and number of subcapsular tumors (56.7% Group B vs. 31.7% Group A, p < 0.05) and perivascular tumors (51.7% Group B vs. 17.1% Group A, p < 0.05). The protocol led to repositioning the antenna in 49% of cases. There was a significant difference in 1-month local response between the groups measured as the RD rate and mRECIST outcomes. LTP rates at 3 and 6 months, and IDR rates at 1, 3 and 6 months, showed no significant differences. Among all variables, logistic regression after PSW demonstrated a protective effect of the protocol against 1-month RD. Conclusions: The use of CBCT, fusion imaging and ablation volume prediction during percutaneous MWA of HCCs provided a better 1-month tumor local control. Further studies with a larger population and longer follow-up are needed. Full article

Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 (MMP-2) and E-cadherin (CDH1). We wondered if specific interactors could affect its subcellular distribution. To this aim, we investigated the PTTG1 interactome in seminoma cell lines showing different PTTG1 nuclear levels correlated with invasive properties. A proteomic approach upon PTTG1 immunoprecipitation uncovered new specific securin interactors. Western blot, confocal microscopy, cytoplasmic/nuclear fractionation, sphere-forming assay, and Atlas database interrogation were performed to validate the proteomic results and to investigate the interplay between PTTG1 and newly uncovered partners. We observed that spectrin beta-chain (SPTBN1) and PTTG1 were cofactors, with SPTBN1 anchoring the securin in the cytoplasm. SPTBN1 downregulation determined PTTG1 nuclear translocation, promoting its invasive capability. Moreover, a PTTG1 deletion mutant lacking SPTBN1 binding was strongly localized in the nucleus. The Atlas database revealed that seminomas that contained higher nuclear PTTG1 levels showed significantly lower SPTBN1 levels in comparison to non-seminomas. In human seminoma specimens, we found a strong PTTG1/SPTBN1 colocalization that decreases in areas with nuclear PTTG1 distribution. Overall, these results suggest that SPTBN1, along with PTTG1, is a potential prognostic factor useful in the clinical management of seminoma. Full article

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs’ aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs. Full article

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used against cognitive impairment in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the neurobiological mechanisms underlying the rTMS therapeutic effects are still only partially investigated. Maladaptive plasticity, glial activation, and neuroinflammation, including metalloproteases (MMPs) activation, might represent new potential targets of the neurodegenerative process and progression from MCI to AD. In this study, we aimed to evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10; MMPs-related tissue inhibitors TIMP1 and TIMP2; and cognitive performances in MCI patients. Patients received high-frequency (10 Hz) rTMS (MCI-TMS, n = 9) or sham stimulation (MCI-C, n = 9) daily for four weeks, and they were monitored for six months after TMS. The plasmatic levels of MMPs and TIMPs and the cognitive and behavioral scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale, were assessed at baseline (T0) and after 1 month (T1) and 6 months (T2) since rTMS. In the MCI-TMS group, at T2, plasmatic levels of MMP1, -9, and -10 were reduced and paralleled by increased plasmatic levels of TIMP1 and TIMP2 and improvement of visuospatial performances. In conclusion, our findings suggest that targeting DLPFC by rTMS might result in the long-term modulation of the MMPs/TIMPs system in MCI patients and the neurobiological mechanisms associated with MCI progression to dementia. Full article

Background: The relationship binding body weight to psychological well-being is unclear. The present study aims at identifying the contribution, and specificity, of some dimensions (i.e., eating-related symptoms, body image disorders, eating habits, personality traits, and emotional difficulties) characterizing the psychological profile of obese adolescents (749 participants, 325 females; 58.3% normal-weight, 29.9% overweight, and 11.7% obese; mean age = 16.05, SD = 0.82). Methods: By introducing the scores obtained by standardized self-report tools into a generalized linear model, a factorial reduction design was used to detect the best fitting discriminant functions and the principal components explaining the higher proportion of the variance. Results: We found two discriminant functions correctly classifying 87.1% of normal-weight, 57.2% of overweight, and 68.2% of obese adolescents. Furthermore, two independent factors, explaining 69.68% of the total variance, emerged. Conclusions: The first factor, “Body Image Concerns”, included the drive for thinness, body dissatisfaction, and interpersonal distrust. The second factor, “Selective Depersonalization”, included a trend toward depersonalization and dissatisfaction with the torso. The neurophysiological implications of our findings will be discussed. Full article

In the last decades, it has been proposed that executive functions may be particularly vulnerable to weight-related issues. However, evidence on the matter is mixed, especially when the effects of sociodemographic variables are weighted. Thus, the current study aimed at further examining the relationship between executive functions and obesity. To this aim, we compared treatment-seeking overweight, obese, and morbidly obese patients with normal-weight control participants. We examined general executive functioning (Frontal Assessment Battery–15) and different executive subdomains (e.g., inhibitory control, verbal fluency, and psychomotor speed) in a clinical sample including 208 outpatients with different degrees of BMI (52 overweight, BMI 25–30, M age = 34.38; 76 obese, BMI 30–40, M age = 38.00; 80 morbidly obese, BMI > 40, M age = 36.20). Ninety-six normal-weight subjects served as controls. No difference on executive scores was detected when obese patients were compared with over- or normal-weight subjects. Morbidly obese patients reported lower performance on executive scores than obese, overweight, and normal-weight subjects. Between-group difference emerged also when relevant covariates were taken into account. Our results support the view that morbid obesity is associated with lower executive performance, also considering the critical role exerted by sociodemographic (i.e., sex, age, and education) variables. Our results support the view that executive functioning should be accounted into the management of the obese patient because of non-negligible clinical relevance in diagnostic, therapeutic, and prognostic terms. Full article

Background: Recent evidence suggests that a higher body weight may be linked to cognitive impairment in different domains involving executive/frontal functioning. However, challenging results are also available. Accordingly, our study was designed to verify whether (i) poor executive functions are related to a higher body weight and (ii) executive functioning could contribute to weight loss in treatment-seeking overweight and obese patients. Methods: We examined general executive functioning, inhibitory control, verbal fluency, and psychomotor speed in a sample including 104 overweight and obese patients. Forty-eight normal-weight subjects participated in the study as controls. Results: Univariate Analysis of Variance showed that obese patients obtained lower scores than overweight and normal-weight subjects in all executive measures, except for errors in the Stroop test. However, when sociodemographic variables entered the model as covariates, no between-group difference was detected. Furthermore, an adjusted multiple linear regression model highlighted no relationship between weight loss and executive scores at baseline. Conclusions: Our results provide further evidence for the lack of association between obesity and the executive domains investigated. Conflicting findings from previous literature may likely be due to the unchecked confounding effects exerted by sociodemographic variables and inclusion/exclusion criteria. Full article

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that is increasingly used as a nonpharmacological intervention against cognitive impairment in Alzheimer’s disease (AD) and other dementias. Although rTMS has been shown to modify cognitive performances and brain functional connectivity (FC) in many neurological and psychiatric diseases, there is still no evidence about the possible relationship between executive performances and resting-state brain FC following rTMS in patients with mild cognitive impairment (MCI). In this preliminary study, we aimed to evaluate the possible effects of rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC) in 27 MCI patients randomly assigned to two groups: one group received high-frequency (10 Hz) rTMS (HF-rTMS) for four weeks (n = 11), and the other received sham stimulation (n = 16). Cognitive and psycho-behavior scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status, Beck Depression Inventory-II, Beck Anxiety Inventory, Apathy Evaluation Scale, and brain FC, evaluated by independent component analysis of resting state functional MRI (RS-fMRI) networks, together with the assessment of regional atrophy measures, evaluated by whole-brain voxel-based morphometry (VBM), were measured at baseline, after five weeks, and six months after rTMS stimulation. Our results showed significantly increased semantic fluency (p = 0.026) and visuo-spatial (p = 0.014) performances and increased FC within the salience network (p ≤ 0.05, cluster-level corrected) at the short-term timepoint, and increased FC within the left fronto-parietal network (p ≤ 0.05, cluster-level corrected) at the long-term timepoint, in the treated group but not in the sham group. Conversely, regional atrophy measures did not show significant longitudinal changes between the two groups across six months. Our preliminary findings suggest that targeting DLPFC by rTMS application may lead to a significant long-term increase in FC in MCI patients in a RS network associated with executive functions, and this process might counteract the progressive cortical dysfunction affecting this domain. Full article

Caregivers of patients with early-onset Alzheimer’s disease (EOAD) experience higher level of burden, stress, and depression, due to premature role changes and social isolation. Moreover, the SARS-CoV-2 pandemic compelled restrictions regarding social interactions and mobility in Italy from March 2020, prompting telemedicine approaches for supporting patients and their families confined at home. We reported our experience regarding the effects of psychological phone-intervention (phone-I) on EOAD caregivers during pandemic. Twenty caregivers of EOAD patients were randomly assigned to treatment (TG) or control (CG) group. TG weekly underwent a phone-I for one month. All participants were assessed for caregiver burden and needs, anxiety and depression levels, and subjective impact of traumatic events at baseline (T0), at the fifth week (T1) and after 6 months (T2) from phone-I. We observed higher vulnerability to post-traumatic stress in TG compared to CG in all timepoints (p ≤ 0.05). Decreased stress effects and caregiver burden were revealed in TG at T1 compared to T0 (p ≤ 0.05), although showing an increase of these measures at T2 in the treated caregivers. Our findings suggest that although TG showed a peculiar vulnerability to post-traumatic stress, they showed increased wellbeing immediately after phone-I. However, this benefit disappeared six months later, along with the second infection wave, probably due to “exhaustion stage” achievement in “General Adaptation Syndrome”. This trend may suggest a beneficial but not solving role of a prompt phone-I on burden of caregivers of EOAD patients during the SARS-CoV-2 emergency. Full article