Search Results (97)

Purpose: The skeletal muscle has been proposed to contribute to the progressive loss of motor neurons typical of amyotrophic lateral sclerosis (ALS). However, this mechanism has not yet been clarified due to the lack of suitable imaging tools. Here, we aimed to verify whether PET imaging of the translocator protein 18 kDa (TSPO) can detect a muscular abnormality in an experimental model of ALS. Methods: In vivo biodistribution and kinetics of [¹⁸F]DPA-714 were analyzed in skeletal muscle and brain of SOD1^G93A transgenic mice and in wildtype (WT) littermates. Both cohorts were divided into three groups (n = 6 each) to be studied at 60, 90 and 120 days. After microPET imaging, animals were sacrificed to evaluate inflammatory infiltrates by hematoxylin/eosin staining and TSPO expression by immunohistochemistry and Western blot in both quadriceps and brain. Results: [¹⁸F]DPA-714 uptake was higher in the skeletal muscles of SOD1^G93A than in WT mice in the preclinical phase (60 and 90 days) and further increased up to the symptomatic late stage (120 days). Inflammatory cells were absent in the quadriceps of SOD1^G93A mice whose myocytes, instead, showed a progressive increase in TSPO expression with advancing age. By contrast, brain tracer uptake and TSPO expression were comparably low in both groups, regardless of age and genotype. Conclusion: Upregulation of TSPO expression is characteristic of skeletal muscle, but not the brain, in the experimental SOD1^G93A mouse model of ALS. Tracers targeting this pathway have been mostly proposed for the evaluation of inflammatory processes within the central nervous system. Nevertheless, the ubiquitous nature of TSPO expression and its responsiveness to various signals may broaden the diagnostic potential of these tracers to include disease conditions beyond inflammation. Full article

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumor syndrome caused by inactivating mutations of the MEN1 gene and characterized by the occurrence of multiple endocrine tumors within a single patient (i.e., parathyroid, pituitary, and pancreatic neuroendocrine tumors (NETs)). However, the lack of a genotype–phenotype correlation does not allow individual disease evolution to be foreseen. Epigenetic factors, such as microRNAs, are suspected to contribute to MEN1 tumorigenesis, presumably explaining the lack of genotype–phenotype association. Our previous studies indicated miR-24-3p, miR-1301-3p, miR-664a-3p, and miR-4258 as potentially involved in MEN1 parathyroid tumorigenesis. In this study, we examined the expression of two circulating microRNAs (c-miRNAs), miR-24-3p and miR-1301-3p, in the serum of MEN1 patients. c-miRNAs were evaluated by RT-qPCR in serum collected from 25 MEN1 patients and 25 age- and gender-matched healthy volunteers (HCs). Receiver operating characteristic (ROC) curves were constructed to determine miRNA sensitivity and specificity. RT-PCR analysis revealed that expression levels of circulating miR-1301-3p were significantly downregulated, while those of miR-24-3p were significantly upregulated in the serum of MEN1 patients compared to HCs. Additionally, ROC analysis exhibited a good diagnostic power for both miRNAs (area under the ROC curve (AUC) values: 0.7356 and 0.7928 for miR-1301-3p and miR-24-3p, respectively) in distinguishing MEN1 patients from matched HCs. These preliminary data suggest circulating miR-1301-3p and miR-24-3p as potential non-invasive diagnostic biomarkers for MEN1 syndrome, regardless of different clinical phenotypes and MEN1 mutation types. Full article

Although the broad-spectrum pesticide chlorpyrifos (CP) was banned in many developed countries, it is still widely used in developing countries. Its residues persist in the environment for unpredictable times. CP is toxic to various non-target organisms and humans and inhibits soil enzyme activity and bacterial and fungal abundance. This paper aimed to evaluate the effect of vermiremediation on soil chlorpyrifos content and soil fertility. The application of Eisenia fetida or vermicompost was studied in terms of soil chlorpyrifos concentration, microbial biomass content, and enzymatic activities in a 120-day trial. Pesticide application rates were 0, 25, and 50 ppm. The CP did not affect the earthworm survival rate at the tested doses. The earthworms markedly increased microbial biomass carbon and the activity of β-glucosamminidase, while the vermicompost had a noticeably positive effect mainly on alkaline phosphatase activity. Finally, although the vermiremediation techniques studied did not perform a bioremediation activity, they proved effective in improving the biological fertility of the soil in the presence of high concentrations of chlorpyrifos. Full article

Bagrada hilaris is an invasive stink bug causing important yield losses in Brassica crops. It originates from India, Southeast Asia, the Middle East and South Africa and is reported as invasive in several southwestern US states, Hawaii, Mexico, Chile and in the Mediterranean islands of Malta and Pantelleria (Italy). In this study, we tested the effects of gamma rays on the longevity, fecundity and fertility of bagrada bugs. We irradiated them at two different stages of their life cycle (fifth-instar nymphs and two-week-old adults). Irradiation at the nymphal stage had a strong impact on female fecundity, with egg numbers approaching zero at a dose of 80 Gy. Similarly, a full suppression of female fertility was achieved at 80 Gy when they were mated with males irradiated as nymphs or as mature adults. For longevity, gamma rays had only a slight impact on adult male and female life span. Due to the evidence of a gregarious phase during the autumn, these results suggest that small-scale SIT-localized applications by massive collections of bagrada bugs at various stages of development during autumn, followed by irradiation and reintroduction to the field, might be a safe and economically sound approach of control. Research is currently underway to evaluate the fitness of sterile males and mating patterns. Further studies in confined-field conditions will be needed. Full article

Bagrada hilaris (known as painted bug) is a pest native to India, Southeast Asia, and middle and central Africa and was reported as invasive in the southwestern USA, Hawaii, Mexico, South America, and two Mediterranean islands. The feeding activity results in extensive damage to economically important Brassicaceae crops. Among sustainable alternatives to synthetic pesticides, the Sterile Insect Technique (SIT) is considered a promising strategy because it relies on the release of competitive sterile males that can reduce the pest reproduction. In this study, the efficacy of different doses of gamma irradiation (60, 80, and 100 Gy) was evaluated to identify the treatment that would ensure high sterility without compromising the competitiveness of the treated males. Observational tests showed that the doses of 60 Gy and 80 Gy showed no difference in mating times compared to non-irradiated males, in contrast to 100 Gy. Thus, 80 Gy was identified as the most promising dose. For further investigation, tests were conducted under choice and no-choice conditions at 80 Gy for three days. The results showed that irradiated males had a comprehensive higher mating rate than non-irradiated males, and under choice conditions, they were often preferred by females, confirming that SIT has potential as an environment-friendly method for controlling B. hilaris. Full article

Background: The use of antibiotics in beekeeping has potential implications for honeybee health and environmental contamination. Recent research indicates that extensive antibiotic use in beekeeping, especially oxytetracycline, promotes antimicrobial resistance in bee-related bacteria. Honeybees can transport oxytetracycline-resistance genes during foraging, potentially establishing reservoirs of resistance in the colony and facilitating intergeneric gene transfer among various gut bacteria as well as in the microbiome of the flowers and the wider environment, where honeybees can spread antibiotic-resistance genes over a large distance. This study investigates the effects of oxytetracycline hydrochloride (OTC) treatment on honeybees from a One Health perspective, examining antibiotic residues in honey, environmental spread, and the presence of tetracycline-resistance genes (TET-RGs). Methods: In the spring of 2022, two groups of four honeybee hives were placed near an almond grove in Central Italy. One group was treated with 1.68 g of OTC, while the other remained untreated. Samples were collected from bees, honey, hive entrances, and flowers before treatment and at 3 as well as 9 days post-treatment. OTC residues and TET-RGs were analyzed to assess contamination and resistance gene dissemination. Results: OTC residues were detected in honey from both treated (day 3: 263,250.0 ± 100,854.3 µg/kg; day 9: 132,600 ± 146,753.9 µg/kg) and untreated hives (day 3: 20.5 ± 8.2 µg/kg; day 9: 135.8 ± 198.6 µg/kg), suggesting cross-contamination. Residues were also found in almond tree flowers (0.7 ± 0.1 µg/kg), with TET-RGs (tet(K), tet(L), tet(M), tet(B), tet(O), tet(D)) detected pre- and post-treatment. In honeybee gut bacteria, resistance genes (tet(M), tet(A), tet(D), tet(B)) appeared post-treatment in both groups. No significant correlation was observed between hive distance and resistance gene presence in flowers, although the presence of other farms located within the bees’ flight range, in which OTC might have been used in the past, could have influenced the results. Conclusions: These findings highlight the risk of OTC-induced antibiotic cross-contamination and the spread of TET-RG, raising concerns for bee health and environmental safety. Given honeybees’ social nature and the negative effects of antibiotics on their health, an antibiotic-free management approach is recommended for sustainable apiculture. Full article

Background/Objectives: Tumoral calcinosis (TC) is an extremely rare inherited disease characterized by multilobulated, dense ectopic calcified masses, usually in the periarticular soft tissue regions. In a previous study, we isolated a primary cell line from an ectopic lesion of a TC patient carrying a previously undescribed GALNT3 mutation. Here, we researched whether a stem cell (SC) subpopulation, which may play a critical role in TC progression, could be present within these lesions. Methods: A putative SC subpopulation was initially isolated by the sphere assay (marked as TC1-SC line) and characterized for its stem-like phenotype through several cellular and molecular assays, including colony forming unit assay, immunofluorescence staining for mesenchymal SC (MSC) markers, gene expression analyses for embryonic SC (ESC) marker genes, and multidifferentiation capacity. In addition, a preliminary expression pattern of osteogenesis-related pathways miRNAs and genes were assessed in the TC1-SC by quantitative Real-Time PCR (qPCR). Results: These cells were capable of differentiating into both the adipogenic and the osteogenic lineages. Moreover, they showed the presence of the MSC and ESC markers, confirmed respectively by using immunofluorescence and qualitative reverse transcriptase PCR (RT-PCR), and a good rate of clonogenic capacity. Finally, qPCR data revealed a signature of miRNAs (i.e., miR-21, miR-23a-3p, miR-26a, miR-27a-3p, miR-27b-3p, and miR-29b-3p) and osteogenic marker genes (i.e., ALP, RUNX2, COLIA1, OPG, OCN, and CCN2) characteristic for the established TC1-SC line. Conclusions: The establishment of this in vitro cell model system could advance the understanding of mechanisms underlying TC pathogenesis, thereby paving the way for the discovery of new diagnostic and novel gene-targeted therapeutic approaches for TC. Full article

Introduction: Dalbavancin (DAL) is a long-acting lipoglycopeptide active against Gram-positive bacteria, including multidrug-resistant isolates. A growing body of evidence supports its efficacy in various difficult-to-treat infections. DAL shows time-dependent bactericidal activity in vitro at free drug concentrations equal to 4×MIC values. However, the optimal dosing scheme for achieving the PK/PD target in multidose treatment has not been fully established. Methods: Pharmacokinetic analysis was based on a nonlinear mixed effects modelling approach performed in NONMEM v7.5/Pirana, while R was used for data management and graphical summaries. Final model parameters were used to simulate the plasma disposition of DAL by Monte Carlo simulations to determine the multidose DAL regimen associated with a 90% target attainment of 100% fT > 4×MIC. Results: A two-compartmental model with first-order elimination and allometric-scaled bodyweight best described DAL disposition in patients with CLcr > 30 mL/min. Monte Carlo simulations showed that two 1500 mg DAL doses 7 days apart granted an optimal PTA > 90% of 100% fT > 4×MIC up to 5, 4, and 3 weeks in patients weighting from 40–80 kg, 80–120 kg and 120–200 kg, respectively. An additional third 1500 mg dose at the above time points by weight bands may extend the optimal PTA up to 9, 7, and 6 weeks of total treatment. Conclusions: Two 1500 mg DAL doses administered 7 days apart could be a valuable starting strategy for patients of all weight classes with CLcr > 30 mL/min. In patients requiring long-term DAL treatment, the optimal timing of additional administrations should be guided by routine TDM or empirically through patients’ total body weight when TDM is unavailable. Full article

Background: Sepsis is a critical condition characterized by severe immune dysregulation, ranking among the leading causes of morbidity and mortality in intensive care and internal medicine units. Nutritional status plays a pivotal role in modulating these responses, as when inadequate it can compromise immune defenses, the body’s ability to handle stress and inflammation, and the clinical course. Malnutrition is frequently observed in septic patients and is strongly associated with worse clinical outcomes, including increased mortality, prolonged hospital stays, and greater complication rates. In this context, nutritional scoring systems have emerged as valuable tools to evaluate patients’ nutritional status and predict clinical trajectories. Objectives: Given the absence of a direct comparison of their performance in an internal medicine setting, this study aimed to assess the effectiveness of various nutritional scores as predictive tools for clinical outcomes in septic patients, emphasizing their application within the field of internal medicine. Methods and Results: A retrospective analysis was conducted on 143 patients diagnosed with sepsis or septic shock who were admitted to an internal medicine unit. Key variables included clinical and laboratory parameters, comorbidities, and nutritional scores at the time of diagnosis. The modified Glasgow Prognostic Score (mGPS), the Prognostic Nutritional Index (PNI), the Controlling Nutritional Status (CONUT) score, the modified Nutrition Risk in Critically Ill (mNUTRIC) score, and the blood urea nitrogen-to-albumin ratio (BAR) were evaluated in forecasting mortality and clinical outcomes in patients with sepsis. Among them, the mNUTRIC score emerged as the strongest independent predictor of in-hospital mortality, with a good performance and a reasonable threshold for risk stratification. Conclusions: The study highlights the mNUTRIC score’s practicality and reliability in assessing nutritional and inflammatory risks in septic patients, particularly in non-ICU settings. These findings suggest its potential utility in guiding nutritional interventions and improving clinical outcomes, emphasizing the importance of integrating nutritional assessment into sepsis management. Full article

Ghrelin (GhRL) is an orexigenic hormone influenced by nutritional state. It plays a role in skin repair and diseases, though little information exists regarding its function in this organ. GhRL and its receptor were investigated in the skin of sheep under different feeding conditions to explore GhRL system presence and possible modifications due to diet. Three-year-old female sheep were free to graze from June to the pasture maximum flowering (MxF group) and from this period to maximum dryness addicted (Exp group) or not (MxD group) with 600 gr/die/head of barley and corn. Skin samples were processed for immunohistochemistry and real-time PCR. The immunostaining showed the presence of the GhRL system in skin appendages. Indeed, the ligand was localized in the hair follicles whereas the receptor was also observed in sweat glands and smooth muscle cells. The expression of both genes was significantly higher in the Exp group (3.6 and 2.9 folds respectively, p < 0.05) compared with the MxF group. These results suggest that the GhRL system is involved in the regulation of hair follicles and sweat glands. In addition, diet supplementation may positively modulate the expression of GhRL and its receptor in the skin. Full article

Background and Objectives: Vision significantly contributes to postural control, balance, coordination, and body kinematics, thus deeply influencing everyday functionality. Sight-impaired subjects often show upper body anatomofunctional and kinetic chain alterations negatively impacting daily living efficiency and autonomy. The present study aimed to investigate and train, for the first time, upper body sensorimotor control in an Italian blind baseball team to boost global and segmental functionality while contemporarily prevent injuries. Materials and Methods: The whole team underwent a validated test battery using both quantitative traditional tools, such as goniometric active range of motion and muscular/functional tests, and an innovative biofeedback-based device, a Libra proprioceptive board. Consequently, a 6-week adapted training protocol was designed and leaded to improve sensorimotor control and, hence, counteract disability-related deficits and sport-specific overuse syndromes. Results: Statistically significant improvements were observed in all the investigated parameters. Noteworthy, an overall boost of global and segmental stability was detected through an orthostatic dynamic balance enhancement during the Y Balance test (p = 0.01) and trunk multiplanar control improvement on the Libra board (p = 0.01). Concurrently, the comparison of baseline vs. post-intervention outcomes revealed a consistent increase in upper body mobility (p < 0.05 for all the assessed districts), core recruitment (p = 0.01 for all the administered functional tests), and proprioceptive postural control (p = 0.01 for the Libra board validated test). Conclusions: Our findings suggest that a tailored sensorimotor training, conceived and led by an adapted physical activity kinesiologist, may effectively improve upper body functional prerequisites and global proprioceptive control, thus potentially promoting autonomy, quality of life, and physical activity/sport practice adherence in visually impaired individuals. Full article

Karstic sinkholes are peculiar structures hosting specific biological communities. Birds are still little studied in this regard. This note reports, for the first time, original data relating to the density of breeding species occurring within a sinkhole in central Italy obtained with a fine-grained and time-expensive sampling technique (mapping method). The results were compared with data sampled with the point counts method carried out in the same phenological period. We recorded 22 breeding species, all typical of meso-thermophilous forests and ecotonal habitats of hilly central Italy. Among them, two species (Turdus merula and Troglodytes troglodytes), typical of shady, undergrowth habitats, were recorded in the deepest part of the sinkhole (−70 m from the top). No significant differences emerged between the relative frequencies of the species obtained with the two methods, except for Luscinia megarhynchos (overestimated with the mapping method) and Aegithalos caudatus (underestimated). At the community level, the comparison of the two methods revealed similar values in univariate diversity metrics, Whittaker plots did not show a significant difference (ANCOVA test), and ordinary least squares regression between the frequencies showed a highly significant correlation. Therefore, in these peculiar habitats, data obtained from the two methods are comparable: since the point counts method needs lower sampling effort, it appeared to be more effective when compared to the mapping method to study these peculiar habitats. Full article

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome caused by inactivating mutations in the MEN1 tumor suppressor gene. The three main clinical manifestations of MEN1 are primary hyperparathyroidism (PHPT), duodenal–pancreatic neuroendocrine tumors (DP-NETs) and anterior pituitary tumors. Endocrine tumors in patients with MEN1 differ from sporadic tumors because of their younger age at onset, common multiple presentations and the different clinical course. MEN1 is characterized by a complex clinical phenotype; thus, patients should be followed by a multidisciplinary team of experts that includes an endocrinologist, a surgeon, a oncologist, a radiotherapist, and not least, a nutritionist. It is important to remember the fundamental role that diet plays as a primary prevention tool, together with a healthy and active lifestyle in preventing osteoporosis/osteopenia and reducing the risk of developing kidney stones due to hypercalciuria, two frequent clinical complications in MEN1 patients. Is very important for MEN1 patients to have an adequate intake of calcium, vitamin D, magnesium and phosphate to maintain good bone health. The intake of foods containing oxalates must also be kept under control because in combination with calcium they concur to form calcium oxalate crystals, increasing the risk of nephrolithiasis. Another aspect to consider is the management of patients with pancreatic neuroendocrine tumors undergoing major surgical resections of the pancreas that can lead to alterations in digestion and absorption mechanisms due to partial or total reduction in pancreatic enzymes such as amylase, lipase, and protease, resulting in malabsorption and malnutrition. Therefore, the nutritionist’s aim should be to devise a dietary plan that takes into consideration each single patient, educating them about a healthy and active lifestyle, and accompanying them through various life stages by implementing strategies that can enhance their quality of life. Full article

The outcome of liver transplantation (LT) for hepatocarcinoma (HCC) is strongly influenced by HCC staging, which is based on radiological examinations in a pre-LT setting; concordance between pre-LT radiological and definitive pathological staging remains controversial. To address this issue, we retrospectively analyzed our LT series to assess concordance between radiology and pathology and to explore the factors associated with poor concordance and outcomes. We included all LTs with an HCC diagnosis performed between 2013 and 2018. Concordance (Co group) was defined as a comparable tumor burden in preoperative imaging and post-transplant pathology; otherwise, non-concordance was diagnosed (nCo group). Concordance between radiology and pathology was observed in 32/134 patients (Co group, 24%). The number and diameter of the nodules were higher when nCo was diagnosed, as was the number of pre-LT treatments. Although concordance did not affect survival, more than three pre-LT treatments led to a lower disease-free survival. Patients who met the Milan Criteria (Milan-in patients) were more likely to receive ≥three prior treatments, leading to a lower survival in multi-treated Milan-in patients than in other Milan-in patients. In conclusion, the concordance rate between the pre-LT imaging and histopathological results was low in patients with a high number of nodules. Multiple bridging therapies reduce the accuracy of pre-LT imaging in predicting HCC stages and negatively affect outcomes after LT. Full article

Serum phosphate concentration is regulated by renal phosphate reabsorption and mediated by sodium–phosphate cotransporters. Germline mutations in genes encoding these cotransporters have been associated with clinical phenotypes, variably characterized by hyperphosphaturia, hypophosphatemia, recurrent kidney stones, skeletal demineralization, and early onset osteoporosis. We reported a 33-year-old male patient presenting a history of recurrent nephrolithiasis and early onset osteopenia in the lumbar spine and femur. He was tested, through next generation sequencing (NGS), by using a customized multigenic panel containing 33 genes, whose mutations are known to be responsible for the development of congenital parathyroid diseases. Two further genes, SLC34A1 and SLC34A3, encoding two sodium–phosphate cotransporters, were additionally tested. A novel germline heterozygous mutation was identified in the SLC34A1 gene, c.1627G>T (p.Gly543Cys), currently not reported in databases of human gene mutations and scientific literature. SLC34A1 germline heterozygous mutations have been associated with the autosomal dominant hypophosphatemic nephrolithiasis/osteoporosis type 1 (NPHLOP1). Consistently, alongside the clinical features of NPHLOP1, our patient experienced recurrent nephrolithiasis and lumbar and femoral osteopenia at a young age. Genetic screening for the p.Gly453Cys variant and the clinical characterization of his first-degree relatives associated the presence of the variant in one younger brother, presenting renal colic and microlithiasis, suggesting p.Gly453Cys is possibly associated with renal altered function in the NPHLOP1 phenotype. Full article