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Background and Purpose: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infections worldwide, with hypervirulent strains linked to severe disease and higher mortality. This study aims to analyze the epidemiology of CDI at a tertiary-care hospital in Italy and compare clinical outcomes between patients infected with hypervirulent and non-hypervirulent strains. Methods: A retrospective comparative study was conducted on patients diagnosed with CDI at ASST Spedali Civili di Brescia, Italy, from January 2015 to June 2023. Hypervirulent strains were identified using the GeneXpert assay as positive for cytotoxin gene (tcdB), binary toxin genes (tcdA and tcdB) and a single nucleotide deletion at position 117 in the tcdC gene and compared to a randomized matched control group with non-hypervirulent CDI. Clinical data were collected and analyzed, with multivariate logistic regression employed to identify risk factors for hypervirulent CDI. Results: Of 1,059 positive C. difficile specimens, a statistically significant trend between January 2015 to June 2023 was found in the increasing incidence of CDI cases per 1,000 hospital admissions and 10,000 bed-days. Notably, a remarkable increase of hypervirulent strains was recorded in 2021 and 2022 when compared to previous years. A total of 130 patients were analyzed: 62 (47.7%) with hypervirulent CDI and 68 (52.3%) controls. Hypervirulent CDI was associated with higher 30-day mortality (18% vs. 5.8%, p = 0.03). Multivariate analysis showed that hypervirulent CDI significantly increased 30-day mortality risk (OR = 9.915, CI = 2.37–61.05, p = 0.005) and that prior antibiotic therapy was a significant risk factor (OR = 5.49, CI = 1.19–39.96, p = 0.047). Discussion: Our epidemiological data, while suggesting a potential resurgence in CDI transmission during COVID-19 pandemic, are derived from a single-center experience with limited generalizability to the broader population. Nonetheless, they highlight the need for strengthened antimicrobial stewardship and national surveillance systems to effectively monitor and manage these strains. [ABSTRACT FROM AUTHOR]

High-Dependency care Units (HDUs) have been introduced worldwide as intermediate wards between Intensive Care Units (ICUs) and general wards. Performing a comparative assessment of the quality of care in HDU is challenging because there are no uniform standards and heterogeneity among centers is wide. The Fenice network promoted a prospective cohort study to assess the quality of care provided by HDUs in Italy. This work aims at describing the structural characteristics and admitted patients of Italian HDUs. All Italian HDUs affiliated to emergency departments were eligible to participate in the study. Participating centers reported detailed structural information and prospectively collected data on all admitted adult patients. Patients' data are presented overall and analyzed to evaluate the heterogeneity across the participating centers. A total of 12 HDUs participated in the study and enrolled 3670 patients. Patients were aged 68 years on average, had multiple comorbidities and were on major chronic therapies. Several admitted patients had at least one organ failure (39%). Mortality in HDU was 8.4%, raising to 16.6% in hospital. While most patients were transferred to general wards, a small proportion required ICU transfer (3.9%) and a large group was discharged directly home from the HDU (31%). The expertise of HDUs in managing complex and fragile patients is supported by both the available equipment and the characteristics of admitted patients. The limited proportion of patients transferred to ICUs supports the hypothesis of preventing of ICU admissions. The heterogeneity of HDU admissions requires further research to define meaningful patients' outcomes to be used by quality-of-care assessment programs. [ABSTRACT FROM AUTHOR]

Data about relapse of type 2 diabetes mellitus (T2D) after bariatric surgery remains scarce. In addition, most of the reports referring to this issue stand on gastric bypass (GBP) and very little information can be collected about T2D relapse after laparoscopic sleeve gastrectomy (LSG) which is one of the most popular bariatric procedures nowadays. To determine the incidence of durable remission of T2D after sleeve gastrectomy and factors associated with T2D relapse. A case series analysis of all patients with T2D who had undergone primary LSG from the year 2008 where both the hospital records and data on follow-up visit has been studied and carefully included was performed in the present study. At baseline (T1), preoperative characteristics were assessed by descriptive statistics. Outcomes were evaluated in the first year postoperative (T2) and at the most recent control (T3). Between June 2006 and December 2010, 47 patients underwent LSG at our Institution. After the operation (T2), all patients showed rapid improvement in their T2D; 79% achieved complete remission and 21% registered an improvement in their metabolic control. At T3, the average follow-up time was 8.8 years (7.7–12 years) and 54% of the patients with initial T2D control after surgery experienced relapse. T2D results were compared between patients with adequate weight loss maintenance (n = 25) versus those with inadequate weight loss maintenance at T3 (n = 22). Remission or improvement was significantly greater within the first group (p ˂ 0.02). Sleeve gastrectomy significantly improved diabetes control and appeared to improve the trajectory of the disease even after 8 years. [ABSTRACT FROM AUTHOR]

Purpose: COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021. Methods: The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded. Results: We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p < 0.001). One subject discontinued posaconazole due to an adverse reaction. Among the 46 patients who received it, only one patient reached an effective plasma concentration of posaconazole. Conclusion: AFP was associated with reduced incidence and mortality from CAPA and was well tolerated in patients with severe COVID-19. Posaconazole concentrations below the efficacy threshold in almost all patients may be attributable to drug interactions and prompt further studies to define its clinical significance. [ABSTRACT FROM AUTHOR]

In recent years, the viral outbreak named COVID-19 showed that infectious diseases have a huge impact on both global health and the financial and economic sectors. The lack of efficacious antiviral drugs worsened the health problem. Based on our previous experience, we investigated in vitro and in silico a series of quinoline-3-carboxylate derivatives against a SARS-CoV-2 isolate. In the present study, the in-vitro antiviral activity of a series of quinoline-3-carboxylate compounds and the in silico target-based molecular dynamics (MD) and metabolic studies are reported. The compounds' activity against SARS-CoV-2 was evaluated using plaque assay and RT-qPCR. Moreover, from the docking scores, it appears that the most active compounds (1j and 1o) exhibit stronger binding affinity to the primary viral protease (NSP5) and the exoribonuclease domain of non structural protein 14 (NSP14). Additionally, the in-silico metabolic analysis of 1j and 1o defines CYP2C9 and CYP3A4 as the major P450 enzymes involved in their metabolism. [ABSTRACT FROM AUTHOR]

The pandemic of coronavirus disease 19 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), had severe repercussions for breast cancer patients. Increasing evidence indicates that SARS-CoV-2 infection may directly impact breast cancer biology, but the effects of SARS-CoV-2 on breast tumor cells are still unknown. Here, we analyzed the molecular events occurring in the MCF7, MDA-MB-231 and HCC1937 breast cancer cell lines, representative of the luminal A, basal B/claudin-low and basal A subtypes, respectively, upon SARS-CoV-2 infection. Viral replication was monitored over time, and gene expression profiling was conducted. We found that MCF7 cells were the most permissive to viral replication. Treatment of MCF7 cells with Tamoxifen reduced the SARS-CoV-2 replication rate, suggesting an involvement of the estrogen receptor in sustaining virus replication in malignant cells. Interestingly, a metagene signature based on genes upregulated by SARS-CoV-2 infection in all three cell lines distinguished a subgroup of premenopausal luminal A breast cancer patients with a poor prognosis. As SARS-CoV-2 still spreads among the population, it is essential to understand the impact of SARS-CoV-2 infection on breast cancer, particularly in premenopausal patients diagnosed with the luminal A subtype, and to assess the long-term impact of COVID-19 on breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have detected mitochondrial alterations in tissues of individuals with obesity and type 2 diabetes mellitus (T2DM). Metabolic surgery could be an effective treatment to improve mitochondrial morphology and reduce oxidative stress (OS). Methods: An experimental study was carried out using 48 male Wistar rats, divided into 6 groups (n = 8): control (C), induced Metabolic Syndrome (MS); intervention with sleeve gastrectomy (SG), MS + SG with 6 weeks postoperatively (MS + SG6), MS + SG with 12 weeks postoperatively (MS + SG12), and MS + SG with 24 weeks postoperatively (MS + SG24). Biochemical markers indicative of MS (glycemia, cholesterol, and triglyceride levels) and oxidative stress markers (nitric oxide levels, Superoxide dismutase and Myeloperoxidase activity) were determined. To study mitochondrial morphology, tissue sections of the thoracic aorta, stomach, liver, heart, and kidney were observed by electron microscopy. Results: MS group exhibited elevated glycemic values and dyslipidemia. SG and MS + SG groups showed improvements in glycemia and lipid profiles compared to MS. OS biomarkers indicated reduced oxidative stress in SG and MS + SG groups compared to MS. Electron microscopy revealed mitochondrial alterations in MS. SG group showed no changes compared to the control. MS + SG6 and MS + SG12 groups showed a recovery of mitochondrial morphology until reaching images similar to the control in MS + SG24. Conclusion: Metabolic surgery could improve mitochondrial function by restoring mitochondrial morphology and architecture and, consequently, reducing systemic oxidative stress and remitting associated metabolic alterations. [ABSTRACT FROM AUTHOR]

This work evaluated if strategic control based on no more than three or four annual treatments is useful to control Rhipicephalus microplus infestations on cattle when it is applied to intensive rotational grazing and silvopastoral systems with high stocking rates in subtropical areas. In the intensive rotational grazing system, three annual treatments with chemical acaricides were applied on cattle in two different schemes: between spring and early summer and from late winter and late spring. Strategic control based on three treatments with chemical acaricides from late winter to late spring plus an additional fourth treatment in summer was tested in the silvopastoral system. In the intensive rotational grazing systems, the control schemes allow to reach a significant reduction in the tick load on cattle considering a time interval from spring to autumn. However, the efficacy levels were not high enough in some specific moments, namely, the tick counts of summer and autumn (there were not significant differences between treated and control groups). The scheme evaluated in the silvopastoral grazing system yielded better results than those tested for the intensive rotational system, because significant differences in tick load between treated and control groups were observed in all post-treatment counts and when the analysis was performed for the whole study period. However, values of efficacy in the count-by-count comparison were disparate, ranging from 64.1 to 99.7. Although the efficacy values obtained in the silvopastoral system were better than those of the rotational grazing systems, the total tick load on treated cattle in autumn was not low enough (mean abundance values 25.14 and 38.14). Ticks were more evenly distributed among hosts in late summer and autumn than in spring or early summer, where few hosts carry most of the ticks. Some management strategies as intensive rotational systems or silvopastoral structures can lead to a more efficient forage use, but they imply greater tick challenge than in extensive grazing systems. In these situations, the schemes of strategic control bases on three or four annual treatments should be complemented with additional tactical treatments in late summer or autumn. [ABSTRACT FROM AUTHOR]

We prove that the Ring Learning With Errors (RLWE) and the Polynomial Learning With Errors (PLWE) problems over the cyclotomic field Q (ζ n) are not equivalent. Precisely, we show that reducing one problem to the other increases the noise by a factor that is more than polynomial in n. We do so by providing a lower bound, holding for infinitely many positive integers n, for the condition number of the Vandermonde matrix of the nth cyclotomic polynomial. [ABSTRACT FROM AUTHOR]

High-throughput phenotyping (HTP) approaches are potentially useful for designing indirect selection strategies, which consists in the selection of a primary target trait X based on secondary trait Y. Usually, the secondary trait Y is correlated to the target trait X and is easier, faster and cheaper to measure. In this context, the use of secondary traits (such as vegetation indices derived from HTP platforms) could potentially lead to a fast, non-invasive, accurate and efficient selection of superior genotypes. Considering the lack of information in the literature regarding high-throughput phenotyping approaches in tropical wheat breeding, this study aimed to (i) determine the best stages to carry out image acquisition for applying multi-spectral vegetation indices for genotype evaluation and selection; (ii) evaluate the heritability and accuracy of multi-spectral vegetation indices; (iii) understand the relationships between vegetation indices and target agronomic traits; and (iv) evaluate the efficiency of indirect selection via UAV-based high-throughput phenotyping. A diversity panel of 49 tropical wheat cultivars was evaluated during the 2022 winter season. Weekly flight campaigns were performed to further build the dataset with multi-spectral vegetation indices, which were then analyzed together with four target agronomic traits. Statistical analysis based on Mixed Effect Model was performed to estimate genetic parameters and predict genetic values, which were subjected to correlation analysis. Additionally, factor analysis was applied, and the factorial scores were used in an indirect selection strategy (indirect via HTP). This strategy was compared to three alternative strategies: direct via grain yield, direct via days to heading, and the multi-trait genotype-ideotype distance index. The results indicate that vegetation indices are suitable for indirect selection strategies and highly efficient for the indirect selection of grain yield and cycle. These findings will help in the decision making regarding the adoption of remote or proximal sensing-based approaches in Brazilian public wheat breeding programs. [ABSTRACT FROM AUTHOR]

Early identification of sepsis is particularly important in the emergency department (ED). However, data on the diagnosis of sepsis in the ED are scanty, especially within the Italian context. To quantify sepsis incidence and recognition in the ED from Lombardy, Italy, we used EUOL data from the Regional Emergency Agency for the years 2017–2022. Sepsis was identified based on the ED discharge diagnosis; recognized sepsis cases were those assigned to a high-priority code at triage, while unrecognized ones were those assigned to a low priority code. Odds ratios (ORs) for sepsis recognition according to various patient characteristics were estimated using multivariable mixed-effects logistic regression models. The rate of sepsis diagnosis in ED was 1.9 per 1000 (6626 patients) in 2017 and increased to 3.4 per 1000 in 2022 (11,508 patients). In 2022, 67% of sepsis cases were correctly identified. Death in the ED was more frequent in patients with recognized sepsis (10.4%) than in those with unrecognized sepsis (2.3%). The probability of sepsis being recognized at ED admission was higher in men (multivariable OR: 1.06), in individuals with advanced age (OR: 1.71 for age ≥ 90 years vs < 60), and in those with access to the second (OR: 1.48) and third ED level (OR: 1.87). Conversely, it was lower in patients arriving at the ED through autonomous transportation (OR: 0.36). This large real-world analysis indicates an increase in sepsis cases referred to the ED in recent years. About one-third of sepsis cases are not correctly identified at triage, although more severe cases appear to be promptly recognized. [ABSTRACT FROM AUTHOR]

Background: Drugs used for sedation/analgesia may affect the basic cardiac electrophysiologic properties or even supraventricular tachycardia (SVT) inducibility. Dexmedetomidine (DEX) is a selective alpha-2 adrenergic agonist with sedative and analgesic properties. A comprehensive evaluation on use of DEX for reentrant SVT ablation in adults is lacking. The present study aims to systematically assess the impact of DEX on cardiac electrophysiology and SVT inducibility. Methods: Hemodynamic, electrocardiographic, and electrophysiological parameters and SVT inducibility were assessed before and after DEX infusion in patients scheduled for ablation of reentrant SVT. Results: The population of this prospective observational study included 55 patients (mean age of 58.7 ± 14 years, 29 males [52.7%]). A decrease in systolic and diastolic blood pressure and in heart rate was observed after DEX infusion (p = 0.001 for all). DEX increased corrected sinus node refractory time, atrial effective refractory period, AH interval, AV Wenckebach cycle length, and AV node effective refractory period without affecting the His-Purkinje conduction or ventricular myocardium refractoriness. No AV blocks or sinus arrests occurred during DEX infusion. Globally, there was no difference in SVT inducibility in basal condition or after DEX infusion (46/55 [83.6%] vs. 43/55 [78.1%] patients; p = 0.55), without a difference in isoprenaline use (p = 1.0). In 4 (7.3%) cases, the SVT was inducible only after DEX infusion. In 34.5% of cases, DEX infusion unmasked the presence of an obstructive sleeping respiratory pattern, represented mainly by snoring. Conclusions: DEX depresses sinus node function and prolongs atrioventricular refractoriness without significantly affecting the rate of SVT inducibility in patients scheduled for reentrant SVT ablation [ABSTRACT FROM AUTHOR]

Introduction: Immunosuppression after kidney transplantation (KTx) exposes recipients to Human Polyomaviruses (HPyVs) infections, whose natural history is still misunderstood. Methods: Allograft biopsies, and urine from 58 donor-recipient pairs were collected before KTx (T0) and 1 (T1), 15 (T2), 30 (T3), 60 (T4), 90 (T5), 180 (T6), 270 (T7), 360 (T8), and 540 (T9) days after transplant. Specimens were tested for JC (JCPyV) and BK (BKPyV), by quantitative Real-Time PCR. The course of post-KTx HPyVs viruria, and the association between JCPyV viruria in recipients and donors, were evaluated. Results: HPyVs were detected in 3/58 (5.2%) allograft biopsies. HPyVs viruria was present in 29/58 (50%) donors and 41/58 (70.7%) recipients. JCPyV DNA was detected in 26/58 (44.8%) donors and 25/58 recipients (43.1%), 19 of whom received kidney from JCPyV positive donor, whereas BKPyV genome was detected in 3 (5.2%) donors and 22 (37.9%) recipients. The median time of JCPyV, and BKPyV first episode of replication was 1, and 171 days post KTx, respectively. At T0, JCPyV viruria of donors was associated with increased risk of JCPyV replication post-KTx; recipients with JCPyV positive donors showed lower risk of BKPyV replication post-KTx. Conclusions: The results suggested that JCPyV may be transmitted by allograft, and that its replication post KTx might prevent BKPyV reactivation. Future investigation regarding correlation between chronic exposure to immunosuppressive agents and HPyVs urinary replication are warranted. [ABSTRACT FROM AUTHOR]

Cardiotocography (CTG) is the most common technique for electronic fetal monitoring and consists of the simultaneous recording of fetal heart rate (FHR) and uterine contractions. In analogy with the adult case, spectral analysis of the FHR signal can be used to assess the functionality of the autonomic nervous system. To do so, several methods can be employed, each of which has its strengths and limitations. This paper aims at performing a methodological investigation on FHR spectral analysis adopting 4 different spectrum estimators and a novel PRSA-based spectral method. The performances have been evaluated in terms of the ability of the various methods to detect changes in the FHR in two common pregnancy complications: intrauterine growth restriction (IUGR) and gestational diabetes. A balanced dataset containing 2178 recordings distributed between the 32nd and 38th week of gestation was used. The results show that the spectral method derived from the PRSA better differentiates high-risk pregnancies vs. controls compared to the others. Specifically, it more robustly detects an increase in power percentage within the movement frequency band and a decrease in high frequency between pregnancies at high risk in comparison to those at low risk. [ABSTRACT FROM AUTHOR]

Campylobacter fetus spp. is a bacterium associated to reproductive losses in cattle worldwide. It is a venereal infectious disease known as bovine campilobacteriosis, with high impact mainly in countries with extensive production systems. Here, we show pathogenesis and diagnostic methods for Campylobacter fetus detection in cervico-vaginal mucus (CVM) samples from heifers experimentally infected and field cases from herds with low reproductive performance by campylobacteriosis infection. Bacterial culture, direct immunofluorescence test and qPCR were used as diagnostic methods to evaluate detection of C. fetus. In the experimental model 30 Aberdeen Angus and crossbred heifers and 4 Aberdeen Angus bulls for natural mating were assigned to 3 groups experimentally challenged with C. fetus subsp. fetus (Cff), C. fetus subsps venerealis (Cfv) and C. fetus subsp venerealis biovar intermedius (Cfvi), respectively, and a negative control group, all followed for 9 months. Also, field samples of CVM and aborted fetuses were recollected from seven beef cattle farms. Bacteriological culture had the higher C. fetus detection rate in CVM being the most appropriate, followed by qPCR (with commercial extraction DNA kit), direct immunofluorescence test and qPCR (with in-house extraction DNA method), in both, experimental model and field cases. From experimental model after natural mating, 62.5% and 25% heifers got pregnant from Cff and Cfvi groups, respectively, while from Cfv no pregnancy was detected. The strain more frequently detected was Cfvi, followed by Cff and Cfv. Colonization of Cff in female genital tract with high number of carriers and presence in aborted fetuses was evidenced, suggesting a high risk to bovine reproductive health. Bacteriemia was not detected after genital infection. Given the low detection rate of either test, we suggest the use of both, PCR based methods and bacterial culture could result in higher detection rate in farms with endemic campylobacteriosis. [ABSTRACT FROM AUTHOR]

Purpose: To assess the neurodevelopment outcomes of children younger than 42 months of age with intestinal failure (IF) using prolonged parenteral nutrition (PN) followed by a Pediatric Multidisciplinary Intestinal Rehabilitation Program from a public tertiary hospital in Brazil. Methods: Bayley III scale was administered in children aged 2 to 42 months with IF and receiving PN for more than 60 days. Composite scores in cognitive, motor, and language domains were analyzed. Developmental delay was defined as a performance 2 standard deviations (SD) below the average at the 3 domains. Association between Bayley III composite scores and clinical variables related to IF were tested. Results: Twenty-four children with median (IQR) age of 17.5 months (9–28.5) were studied, 58.3% were male. Developmental delay was found in 34%, 33% and 27% of the patients in cognitive, motor, and language domains, respectively. There was no significant association between the Bayley-III composite scores and length of hospitalization, prematurity, and number of surgical procedures with anesthesia. Conclusion: The study demonstrated impairments in the cognitive, motor and language domains in approximately one-third of young patients with IF on prolonged PN. [ABSTRACT FROM AUTHOR]

Breastmilk protects newborns from infections through specific and nonspecific compounds. This study investigated the neutralizing activity against SARS-CoV-2 of breastmilk from SARS-CoV-2 negative, unvaccinated mothers, and compared it to that from infected nursing mothers. We enrolled women after COVID-19 swab testing results upon maternity admission, and divided them into two groups: group A, COVID-19-positive mothers, and group B, negative mothers. Breastmilk was randomly sampled at 2, 7, and 20 days postpartum. We collected 19 samples for Group A and 41 for Group B. A microneutralization assay was used to determine the 50% neutralization (NT50) titre. The presence of neutralizing antibodies was also determined. Group A had 100% neutralizing samples at 2 days postpartum (T0), declining 7 days postpartum (T1) and 20 days postpartum (T2). Group B samples exhibited neutralizing activity mostly at 7 days postpartum (T1) (90%). Negative mothers' samples showed no correlation between NT50 titres and antibodies' presence, suggesting that non-specific breastmilk components may exert antiviral action against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Optogenetics relies on dynamic spatial and temporal control of light to address emerging fundamental and therapeutic questions in cardiac research. In this work, a compact micro-LED array, consisting of 16 × 16 pixels, is incorporated in a widefield fluorescence microscope for controlled light stimulation. We describe the optical design of the system that allows the micro-LED array to fully cover the field of view regardless of the imaging objective used. Various multicellular cardiac models are used in the experiments such as channelrhodopsin-2 expressing aggregates of cardiomyocytes, termed cardiac bodies, and bioartificial cardiac tissues derived from human induced pluripotent stem cells. The pacing efficiencies of the cardiac bodies and bioartificial cardiac tissues were characterized as a function of illumination time, number of switched-on pixels and frequency of stimulation. To demonstrate dynamic stimulation, steering of calcium waves in HL-1 cell monolayer expressing channelrhodopsin-2 was performed by applying different configurations of patterned light. This work shows that micro-LED arrays are powerful light sources for optogenetic control of contraction and calcium waves in cardiac monolayers, multicellular bodies as well as three-dimensional artificial cardiac tissues. [ABSTRACT FROM AUTHOR]

Background: Reliability of mismatch repair proteins and microsatellite instability assessment is essential in order to define treatment strategy and identify candidates to immune checkpoint inhibitors in locally advanced gastroesophageal carcinoma. We evaluated the concordance of deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status between endoscopic biopsies and surgical specimens. Methods: Consecutive patients with resectable gastric or gastroesophageal junction adenocarcinoma classified as MSI-H/dMMR by polymerase chain reaction (PCR) or immunohistochemistry (IHC) and operated at three referral Institutions were included. The primary endpoint was the rate of concordance between biopsy and surgical samples. If needed, central revision by IHC/PCR was performed by specialized pathologists from coordinating Institutions. Results: Thirteen (19.7%) out of 66 patients showed discordant MSI-H/dMMR results in the original pathology reports. In most cases (11, 16.7%) this was due to the diagnosis of proficient mismatch repair status on biopsies. Among the ten cases available for central review, four were due to sample issues, four were reclassified as dMMR, one case showed dMMR status but was classified as microsatellite stable by PCR, one was linked to misdiagnosis of endoscopic biopsy by the local pathologist. Heterogeneity of mismatch repair proteins staining was observed in two cases. Conclusions: Available methods can lead to conflicting results in MSI-H/dMMR evaluation between endoscopic biopsies and surgical samples of gastroesophageal adenocarcinoma. Strategies aiming to improve the reliability of assessment should be primarily focused on the optimization of tissue collection and management during endoscopy and adequate training of dedicated gastrointestinal pathologists within the multidisciplinary team. [ABSTRACT FROM AUTHOR]

Tele-neuropsychology, i.e., the application of remote audio-visual technologies to neuropsychological evaluation or rehabilitation, has become increasingly popular and widespread during and after the COVID-19 pandemic. New tools with updated normative data and appropriate methodological developments are necessary. We present Tele-GEMS, a telephone-based cognitive screening developed on N = 601 Italian participants. It yields a global score tapping on orientation, memory, spatial representation, language, and pragmatic abilities. Its administration lasts about 10 min. Clinical cut-offs are provided, accounting for demographic variables (age, education, and sex) and also for a comprehensive index taking into account cognitively stimulating life experiences that can build up a cognitive reserve. Tele-GEMS shows good internal consistency and a good inter-rater agreement. The test includes the thresholds for estimating a significant change after repeated measurements. Tele-GEMS has a good construct validity as assessed with MoCA and a suitable criterion validity assessed with its in-person version (GEMS). All the materials and the instructions, including scripts and an online Application for the automatic calculation of cut-offs, are accessible on OSF at https://osf.io/t3bma/ under a Creative Commons license. [ABSTRACT FROM AUTHOR]

Abstract Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non‐random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC‐positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of > 90% for successful molecular analysis of high‐quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre‐existing cells resistant to ERBB2‐targeted therapies suggesting ongoing microevolution at late‐stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance.

Heavy metal (HM) accumulation in soil affects plants and soil fauna, yet the effect on microbial alpha-diversity remains unclear, mainly due to the absence of dedicated research synthesis (e.g. meta-analysis). Here, we report the first meta-analysis of the response of soil microbial alpha-diversity to the experimental addition of cadmium (Cd) and copper (Cu). We considered studies conducted between 2013 and 2022 using DNA metabarcoding of bacterial and fungal communities to overcome limitations of other cultivation- and electrophoresis-based techniques. Fungi were discarded due to the limited study number (i.e. 6 studies). Bacterial studies resulted in 66 independent experiments reported in 32 primary papers from four continents. We found a negative dose-dependent response for Cu but not for Cd for bacterial alpha-diversity in the environments, only for Cu additions exceeding 29.6 mg kg−1 (first loss of − 0.06% at 30 mg kg−1). The maximal loss of bacterial alpha-diversity registered was 13.89% at 3837 mg kg−1. Our results first highlight that bacterial communities behave differently to soil pollution depending on the metal. Secondly, our study suggests that even extreme doses of Cu do not cause a dramatic loss in alpha-diversity, highlighting how the behaviour of bacterial communities diverges from soil macro-organisms. [ABSTRACT FROM AUTHOR]

Thickened feeds may be useful in supporting improved suck–swallow–breath coordination and airway protection in infants with dysphagia. Unfortunately, the stability of thickened feeds for infant formulas is unpredictable, which makes use of this strategy challenging. This study aimed to propose a set of Level 1 (slightly thick) recipes for Australian infant formulas/thickeners. A secondary aim was to test whether formula could be batch prepared. A set of powdered, ready-to-feed, and specialized formulas were mixed with two thickening products (Aptamil Feed Thickener® and Supercol®) and tested at 5-, 10-, 15-, 20-, 25-, 30-, and 45-min intervals using the International Dysphagia Diet Standardization Initiative (IDDSI) Flow Test. Formula/thickener samples were mixed following manufacturer instructions, but recipes were adapted to determine an ideal recipe for Level 1 (slightly thick) consistency that would be maintained over a feed. Samples were refrigerated, reheated after 12 h, and retested. Each combination was tested six times. Overall, 1,353 IDDSI Flow Tests were conducted using 14 formula/thickener combinations. In all combinations, recipe alterations were made using metric spoon measurements as opposed to the manufacturer-provided scoop. All samples were most variable at the 5-min timepoint. Formulas thickened with Supercol® generally reached a more stable consistency by 10 min, whereas formulas thickened with Aptamil Feed Thickener® were more stable by 15 min. Samples tested after 12 h were more variable with Aptamil Feed Thickener®. This study provides practical recommendations for clinicians working with infants requiring thickened feeds for dysphagia management. Further study under controlled laboratory conditions is required. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcomes of REPA and establish if any differences in complications and evolution are present between males and females. Methods: A retrospective study including consecutive patients operated by REPA approach between November 2017 and April 2019 was conducted. Demographic data, operative times, postoperative complications, and hospital stay were analyzed. The EuraHS-QoL score was used to assess postoperative pain, daily activity constraints, and aesthetic discomfort. The results were compared between sexes. Statistical analysis was performed using SPSS 19. Results: Fifty-four patients were included and 53.7% were male. Patients had a mean age of 50.7 years and a mean BMI of 28.7. The average RAD (Rectus Abdominis Diastasis) size was 2.6 cm (range of 2–5 cm). Seroma was significantly more frequent in males, with an incidence of 55.2 and 24% for females (p = 0.02). Three cases required reintervention (5.5% of total cases), which corresponded to a cystic seroma, an abdominal wall hematoma, and a hernia recurrence. The three cases were males and a p value of 0.04 was obtained when comparing reintervention rates between males and females. No cases of surgical wound infection nor cutaneous necrosis were recorded. No conversions were needed. The mean postoperative pain was 2.25, the mean daily activity constraints score was 2.63, and the degree of aesthetic discomfort was 1.23 with no significant differences between groups. Conclusion: The correction of small midline defect associated with minor RAD using REPA seems feasible and reproducible. REPA had achieved good results in females, but in males, the outcomes were poorer. [ABSTRACT FROM AUTHOR]

Rationale: Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results. Objectives and methods: To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5–50 mg/kg, intragastric—i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg). Results: MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally—i.p. for 4 days), with ketanserin, a 5-HT2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT1A receptor antagonist (0.1 mg/kg, subcutaneous—s.c.) and ondansetron, a 5-HT3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT2A, 5 -HT2C, and 5-HT4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice. Conclusion: In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression. [ABSTRACT FROM AUTHOR]

Several shreds of evidence indicate that visual deprivation does not alter numerical competence neither in adults nor in children. However, studies reporting non-impaired numerical abilities in the visually impaired population present some limitations: (a) they mainly assessed the ability to process numbers (e.g. mathematical competence) rather than represent numbers (e.g. mental number line); (b) they principally focused on positive rather than negative number estimates; (c) they investigated numerical abilities in adult individuals except one focusing on children (Crollen et al. in Cognition 210:104586, 2021). Overall, this could limit a comprehensive explanation of the role exerted by vision on numerical processing when vision is compromised. Here we investigated how congenital visual deprivation affects the ability to represent positive and negative numbers in horizontal and sagittal planes in visually impaired children (thirteen children with low vision, eight children with complete blindness, age range 6–15 years old). We adapted the number-to-position paradigm adopted by Crollen et al. (Cognition 210:104586, 2021), asking children to indicate the spatial position of positive and negative numbers on a graduated rule positioned horizontally or sagittally in the frontal plane. Results suggest that long-term visual deprivation alters the ability to identify the spatial position of numbers independently of the spatial plane and the number polarity. Moreover, results indicate that relying on poor visual acuity is detrimental for low vision children when asked to localize both positive and negative numbers in space, suggesting that visual experience might have a differential role in numerical processing depending on number polarity. Such findings add knowledge related to the impact of visual experience on numerical processing. Since both positive and negative numbers are fundamental aspects of learning mathematical principles, the outcomes of the present study inform about the need to implement early rehabilitation strategies to prevent the risk of numerical difficulties in visually impaired children. [ABSTRACT FROM AUTHOR]

The identification of the protospacer adjacent motif (PAM) sequences of Cas9 nucleases is crucial for their exploitation in genome editing. Here we develop a computational pipeline that was used to interrogate a massively expanded dataset of metagenome and virome assemblies for accurate and comprehensive PAM predictions. This procedure allows the identification and isolation of sequence-tailored Cas9 nucleases by using the target sequence as bait. As proof of concept, starting from the disease-causing mutation P23H in the RHO gene, we find, isolate and experimentally validate a Cas9 which uses the mutated sequence as PAM. Our PAM prediction pipeline will be instrumental to generate a Cas9 nuclease repertoire responding to any PAM requirement. Cas9 proteins require a target-adjacent sequence, the PAM, in order to cleave DNA. Here the authors develop a pipeline to accurately predict PAM sequences in order to facilitate the identification of Cas9s targeting specific sequences, including mutations. [ABSTRACT FROM AUTHOR]

It is now well accepted that cancer cells change their microenvironment from normal to tumor-supportive state to provide sustained tumor growth, metastasis and drug resistance. These processes are partially carried out by exosomes, nano-sized vesicles secreted from cells, shuttled from donor to recipient cells containing a cargo of nucleic acids, proteins and lipids. By transferring biologically active molecules, cancer-derived exosomes may transform microenvironmental cells to become tumor supportive. Telomerase activity is regarded as a hallmark of cancer. We have recently shown that the transcript of human telomerase reverse transcriptase (hTERT), is packaged in cancer cells derived- exosomes. Following the engulfment of the hTERT transcript into fibroblasts, it is translated into a fully active enzyme [after assembly with its RNA component (hTERC) subunit]. Telomerase activity in the recipient, otherwise telomerase negative cells, provides them with a survival advantage. Here we show that exosomal telomerase might play a role in modifying normal fibroblasts into cancer associated fibroblasts (CAFs) by upregulating α SMA and Vimentin, two CAF markers. We also show that telomerase activity changes the transcriptome of microRNA in these fibroblasts. By ectopically expressing microRNA 342, one of the top identified microRNAs, we show that it may mediate the proliferative phenotype that these cells acquire upon taking-up exosomal hTERT, providing them with a survival advantage. [ABSTRACT FROM AUTHOR]

Purpose: Obesity has an especial implication for women of childbearing age because of a higher risk of adverse outcomes during pregnancy and labor. This report aimed to analyze complications of pregnancy after sleeve gastrectomy (SG) concerning the time after surgery. Methods: A retrospective descriptive-analytical study was conducted including women of childbearing age who underwent sleeve gastrectomy (SG) from 2006 to 2017. Patients were divided into two groups regarding the time elapsed from SG to pregnancy: less than and greater than one year (group A /group B, respectively). Results: During the studied time, 51 pregnancies with complete clinical records were found. The mean weight and gestational age (GA) of the newborn (NB) were normal. The mean time from surgery to pregnancy was 30.4 ± 21 months. Patients from Group A and B presented 28.6% and 16.7% respectively of preterm NB (p = 0.5). Group A registered no low birth weight (LBW) babies (3.0 ± 0.4 kg) with a GA of 37.2 ± 2.1 weeks, while in Group B, 8.6% of NB were at LBW 2.1 ± 0.1 kg and GA of 33.3 ± 3.8 weeks (p = NS). Conclusion: After SG, no differences in terms of maternal and neonatal complications were found concerning the time between surgery and pregnancy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. Saudi Arabia was significantly impacted by COVID-19. In March 2021, 381,000 cases were reported with 6539 deaths. This study attempts to quantify the impact of remdesivir on healthcare costs in Saudi Arabia, in terms of intensive care unit admissions, mechanical ventilation, and death prevention. Methods: A forecasting model was designed to estimate the impact of remdesivir on the capacity of intensive care units and healthcare costs with patients requiring low flow oxygen therapy. The forecasting model was applied in the Saudi context with a 20-week projection between 1 February and 14 June, 2021. Model inputs were collected from published global and Saudi literature, available forecasting resources, and expert opinions. Three scenarios were assumed: the effective pandemic infection rate (Rt) remains at 1, the Rt increases up to 1.2, and the Rt declines from 1 to 0.8 over the study period. Results: The model estimated that the use of remdesivir in hospitalized patients, in the optimistic and pessimistic scenarios, could prevent between 1520 and 3549 patient transfers to intensive care units and mechanical ventilation, prevent between 815 and 1582 deaths, and make potential cost savings between $US154 million and $US377 million owing to the reduction in intensive care unit capacity, respectively. Conclusions: The treatment with remdesivir may improve patient outcomes and reduce the burden on healthcare resources during this pandemic. [ABSTRACT FROM AUTHOR]

Background: The University of California system has a novel tenure-track education-focused faculty position called Lecturer with Security of Employment (working titles: Teaching Professor or Professor of Teaching). We focus on the potential difference in implementation of active-learning strategies by faculty type, including tenure-track education-focused faculty, tenure-track research-focused faculty, and non-tenure-track lecturers. In addition, we consider other instructor characteristics (faculty rank, years of teaching, and gender) and classroom characteristics (campus, discipline, and class size). We use a robust clustering algorithm to determine the number of clusters, identify instructors using active learning, and to understand the instructor and classroom characteristics in relation to the adoption of active-learning strategies. Results: We observed 125 science, technology, engineering, and mathematics (STEM) undergraduate courses at three University of California campuses using the Classroom Observation Protocol for Undergraduate STEM to examine active-learning strategies implemented in the classroom. Tenure-track education-focused faculty are more likely to teach with active-learning strategies compared to tenure-track research-focused faculty. Instructor and classroom characteristics that are also related to active learning include campus, discipline, and class size. The campus with initiatives and programs to support undergraduate STEM education is more likely to have instructors who adopt active-learning strategies. There is no difference in instructors in the Biological Sciences, Engineering, or Information and Computer Sciences disciplines who teach actively. However, instructors in the Physical Sciences are less likely to teach actively. Smaller class sizes also tend to have instructors who teach more actively. Conclusions: The novel tenure-track education-focused faculty position within the University of California system represents a formal structure that results in higher adoption of active-learning strategies in undergraduate STEM education. Campus context and evolving expectations of the position (faculty rank) contribute to the symbols related to learning and teaching that correlate with differential implementation of active learning. [ABSTRACT FROM AUTHOR]

Background and Objectives: In March 2020, the World Health Organization announced a state of emergency due to the appearance of a pandemic caused by the Coronavirus 2 (SARS-CoV-2), a severe acute respiratory syndrome, known as Covid-19. Most governments chose to implement precautionary measures, e.g., physical distancing and use of protective devices, which can in part limit the transmission of the virus. However, the healthcare system experienced numerous structural problems in managing the Covid-19 patients given the limited human and technical resources in critical areas, such as the intensive care units (ICUs). Different therapeutic solutions should therefore be assessed, which can potentially minimize the negative impact of the disease on patients, favoring their recovery and optimizing healthcare resources. The objective of this study is to simulate the impact of remdesivir treatment on the pandemic course in the long term. Methods: A forecasting model is designed to estimate how remdesivir would impact the ICU capacity and the healthcare costs from the hospital perspective when managing COVID-19 patients. This model is applied in the Portuguese context with a 20-week projection starting on May 1st and concluding on September 18th, 2021. The data inputs were carefully collected by consulting different sources, such as published global literature, official governmental reports, and available infectious diseases databases, i.e., Our World in Data, Portuguese Ministry of Health, and experts' opinions. Results: The model showed that the introduction of remdesivir-based treatment in patients with Covid-19 pneumonia requiring supplemental oxygen therapy generates a significant reduction in both the number of ICU admissions and deaths, which would produce more than €23 million in cost savings and avoid more than 261 ICUs admissions and 166 deaths. Conclusion: It is demonstrated that alternative treatments such as remdesivir can reduce both the health burden for healthcare facilities, optimize their management, and improve patients' clinical conditions. However, the model is centered on Rt values, which cannot be generalized to the entire country; hence, the results of this research should be considered as a "hypothetical study". [ABSTRACT FROM AUTHOR]

The metabolism of polyunsaturated fatty acids (PUFAs) plays an important role in male reproduction. Linoleic and alpha-linolenic acids need to be provided in the diet and they are converted into long chain polyunsaturated fatty acids by steps of elongation and desaturation, exerted by elongases 2 (ELOVL2) and 5 (ELOVL5) and Δ5- (FADS1) and Δ6-desaturase (FADS2). This study aims to assess the gene expression and localization of enzymes involved in the synthesis of n-3 and n-6 long-chain PUFAs in control rabbits and those fed diets containing 10% extruded flaxseed. Enzyme and PUFA localization were assessed in the testes and epididymis by immunofluorescence. Testes showed high gene expression of FADS2, ELOVL2 and ELOVL5 and low expression of FADS1. Intermediate metabolites, enzymes and final products were differently found in Leydig, Sertoli and germinal cells. FADS2 was localized in interstitial cells and elongated spermatids; ELOVL5 in meiotic cells; FADS1 was evident in interstitial tissue, Sertoli cells and elongated spermatids; ELOVL2 in interstitial cells. Epididymal vesicles were positive for FADS1, ELOVL2 and ELOVL5 as well as docosahexaenoic, eicosapentaenoic, and arachidonic acids. This knowledge of fatty acids (FA) metabolism in spermatogenesis and the influence of diet on FA profile could help identify causes of male infertility, suggesting new personalized therapy. [ABSTRACT FROM AUTHOR]

Here we described the virological and serological assessment of 23 COVID-19 patients hospitalized and followed up in Milan, Italy, during the first wave of COVID-19 pandemic. Nasopharyngeal (NPS), anal swabs, and blood samples were collected from 23 COVID-19 patients, at hospital admission, and periodically up to discharge, for a median time of 20 days (3–83 days). RNA was isolated and tested for SARS-CoV-2 by qRT-PCR; anti-SARS-CoV-2 IgM and IgG antibody titers were evaluated in serum samples by ELISA. SARS-CoV-2 genome was detected in the NPS swabs of the 23 patients, at the admission, and 8/19 (42.1%) were still positive at the discharge. Anal swabs were positive to SARS-CoV-2 RNA detection in 20/23 (86.9%) patients; 6/19 (31.6%) were still positive at discharge. The mean time of RNA negative conversion was 17 days (4–36 days) and 33 days (4–77 days), for NPS and anal swabs, respectively. SARS-CoV-2-RNA was detected in the blood of 6/23 (26.1%) patients. Thirteen/23 (56.5%) and 17/23 (73.9%) patients were seropositive for IgM and IgG, respectively, at the admission, and the median IgM and IgG levels significantly (p < 0.05) increased after 13 days. Although the limited cohort size, our report provides evidence that SARS-CoV-2 is shed through multiple routes, with important implications in healthcare settings. [ABSTRACT FROM AUTHOR]

Varroa destructor is one of the most important sanitary threats for the beekeeping industry and so far disease control is based mainly on chemical treatment. However, a long-term solution may arise from studying natural surviving colonies of Apis mellifera. We compared the Varroa infestation rate in six commercial colonies that received annual treatment against mites and six non-treated colonies that survived in absence of any treatment for the last 6 years. In addition, we evaluated two potential mechanisms that might be involved in colony survival: hygienic (HYG) and Varroa-sensitive hygiene behavior (VSH) by means of pin-killed and mite artificial infestation, respectively. HYG and VSH were negatively correlated with mite infestation independently of the colony group (treated or non-treated). Furthermore, colonies expressing high levels of pupae removal (≥ 80%) showed higher %HYG and lower mite infestation compared to colonies showing low pupae removal (< 80%). The analysis of reproductive status of mites from the non-removed infested cells evidenced that more infertile mites are found in colonies with more than 80% of pupae removal. To study non-treated colonies that survive for several years, it is a suitable approach for identifying the underlying mechanisms related to Varroa-resistance. [ABSTRACT FROM AUTHOR]

A quantitative risk assessment for exposure to aflatoxin M1 (AFM1) related to the consumption of milk and traditional dairy products of Argentina was developed. The frequency and concentration of AFM1 was modelled at various stages through the milk processes, considering Argentinean practices. Concentration of AFM1 (0.046 μg/l, 95%CI = 0.002–0.264 μg/l) in raw milk was estimated. The AFM1 concentration in milk was sensitive to the carry-over rate (r = 0.80), and milk yield in the first third of lactation during the spring–summer season (r = 0.11). AFB1 levels in silage (r = 0.22), pasture during the spring–summer season (r = 0.11), concentrate (r = 0.08), and cotton seed (r = 0.05) were the factors most correlated with AFM1 concentrations. Although the results showed that MoE values for the mean and median exposure to AFM1 were < 10,000 in infants, toddlers, and other children, the additional cancer risk due to exposure to AFM1 in infants, toddlers, and other children was 0.007, 0.005, and 0.0009 additional cases per year per 100,000 individuals, respectively, which indicates no health concern. In addition, the percentages of the population exceeding HI values (HI > 1) for exposure to AFM1 for infants, toddlers, and other children were 45%, 49.1%, and 40.6%, respectively. Under this scenario, the most susceptible population at risk was children < 10 years old; therefore, it is necessary to establish measures to prevent contamination of AFM1 in milk and milk products. [ABSTRACT FROM AUTHOR]

Background and Objectives: Current evidence shows that tapentadol hydrochloride prolonged-release is more cost effective than other opioids. However, the introduction into the market of generic formulations of traditional comparators, leading to potential savings due to their lower price, creates space for further research. The objective of this study is to evaluate and compare the efficacy of tapentadol versus oxycodone/naloxone and the economic impact of the two alternatives in both branded and generic formulations. Methods: A cost-effectiveness analysis was performed using the third-payer perspective (TPP), with specific reference to the Italian National Health Service. A Markov model was implemented to simulate transitions between states, comparing two arms: The first arm simulated the administration of tapentadol, while the second simulated the administration of oxycodone/naloxone, both branded and generic. The results were reported in terms of net monetary benefit (NMB). The willingness to pay (WPT) was estimated at €35,000/quality-adjusted life year. Results: Tapentadol was dominant in all scenarios, assuming a population of 1000 individuals over a 1-year time horizon. In all cases, although the prices of oxycodone/naloxone generic formulations were lower, the costs associated with treatment discontinuation were always higher than those associated with tapentadol. The comparison with the branded formulation of oxycodone/naloxone was associated with the highest savings of €431.77 per patient, and with the highest NMB of €1943.77 per patient. Conclusion: The results of this pharmacoeconomic evaluation promote the use of tapentadol in comparison with oxycodone/naloxone, confirming the results obtained in previous studies with reference to the generic formulations. [ABSTRACT FROM AUTHOR]

Palladium was incorporated into carboxymethylated cellulose fibers as a support, thereby becoming an efficient and stable catalyst for low temperature gas phase reaction. Thus, NO was used as test molecule of Greenhouse Gas to be catalytically reduced with hydrogen on an eco-friendly sustainable material containing palladium as the active site. Prior to the catalytic test, the catalysts were reduced with glucose as an eco-friendly reagent. The material characterization was performed by SEM–EDS, XRD, LRS, TGA and FTIR. The catalytic results showed that at 170 °C, NO conversion was 100% with a selectivity of 70% to nitrogen. While NOX species were completely converted into N2 at temperatures higher than 180 °C. The starting commercial dissolving pulp was also studied, but its performance resulted lower than the ones of functionalized fibers. The use of this strategy, i.e., the functionalization of cellulose fibers followed by in-situ formation of metallic nanoparticles, can be further applied for the design of a wide range of materials with interesting applications for gas and liquid phase reactions under mild conditions. [ABSTRACT FROM AUTHOR]

The objective of this work was to determine the antibacterial effect of Lactobacillus plantarum strains of pork origin against Campylobacter coli strains, and to conduct experimental colonization pilot models in mice for both microorganisms. Inhibition assays allowed evaluation and selection of L. plantarum LP5 as the strain with the highest antagonistic activity against C. coli and with the best potential to be used in in vivo study. Adult 6-week-old female Balb/cCmedc mice were lodged in two groups. The treated group was administered with 9.4 log10CFU/2 times/wk of L. plantarum LP5. L. plantarum LP5 was recovered from the feces and cecum of the inoculated mice. However, when bacteria stopped being administered, probiotic counts decreased. Experimental colonization with C. coli was carried out in five groups of mice. All animals were treated with antibiotics in their drinking water to weaken the indigenous microbiota and to allow colonization of C. coli. Four groups were administered once with different C. coli strains (DSPV458: 8.49 log10CFU; DSPV567: 8.09 log10CFU; DSPV570: 8.46 log10CFU; DSPV541: 8.86 log10CFU, respectively). After 8 h, mice inoculated with different C. coli strains were colonized because the pathogen was detected in their feces. L. plantarum LP5 tolerated the gastrointestinal conditions of murine model without generating adverse effects on the animals. C. coli DSPV458 colonized the mice without causing infection by lodging in their digestive tract, thus generating a reproducible colonization model. Both models combined could be used as protection murine models against pathogens to test alternative control tools to antibiotics. [ABSTRACT FROM AUTHOR]

Cytokines are physiological seminal components and their abnormal levels, reported in different pathological conditions, negatively influence the sperm function. We analysed the relationship between interleukin (IL)-6 and IL-33 levels and lipid peroxidation (LPO), measured both in semen and sperm lysate, in 44 human semen samples. The semen analysis was performed following the WHO guidelines. Seminal IL-6 and IL-33 concentrations were assessed by ELISA and LPO was evaluated measuring malondialdehyde (MDA) both in seminal plasma and viable spermatozoa. Two small groups of patients with varicocele and infection were extrapolated from the cases analysed and the variables compared with those of a group of control. IL-33 levels were undetectable in all samples and IL-6 levels were positively correlated with both seminal and sperm MDA concentrations (p < 0.01) and negatively with sperm parameters (p < 0.01). Seminal and sperm MDA levels were both negatively correlated with sperm parameters (p < 0.01). IL-6 and semen MDA showed an exponential positive relationship, whereas MDA values measured in viable spermatozoa were low until IL-6 amount reached a concentration of >30 pg/mL, rising consistently. By comparing the variables in the groups, we confirmed that a high IL-6 concentration in the varicocele and infection groups was concomitant with an increase of seminal MDA levels, but also with MDA measured in viable spermatozoa, which represents the novelty of this study. We identified the IL-6 threshold, beyond which sperm MDA concentration rises concomitantly with the increase of IL-6 concentration. Other studies are needed, considering the increasing number of patients with different pathologies affecting male infertility. [ABSTRACT FROM AUTHOR]

We assess tensile performance of Steel Reinforced Grout (SRG) and Fabric Reinforced Cementitious Matrix/Textile Reinforced Mortar, upon exposure to aggressive environments. Galvanized and brass-coated Ultra High Tensile Strength Steel fabrics are considered for SRG, while carbon, AR-glass, basalt and PBO fabrics are investigated for TRM, in a common cement mortar. Exposure to the aggressive environments is realized by specimen immersion for 1000 h (41.6 days) at controlled temperature in distilled water as well as alkaline, saline and acid solutions. Mechanical performance of rectangular 1-ply coupons is assessed in uni-axial traction: Ultimate strength and elongation, dissipated energy at failure and environmental conversion factors for design values are calculated and compared. It is found that significant performance difference exists in dependence of the aggressive environment under consideration. As a result, careful selection of the reinforcing fabric leads to substantial advantage in terms of durability, that should be capitalized upon at the design stage. A simple material selection matrix is presented which suggests the best reinforcing textile/aggressive environment combination for design purposes. [ABSTRACT FROM AUTHOR]

A longitudinal study was carried out in order to evaluate Nosema spp. spore counts in two key moments of the year (late autumn and spring) in honeybee colonies from five eco-regions of Argentina. Three hundred and sixty colonies were randomly selected and the infestation level of Nosema spp. and Varroa destructor was assessed in autumn and spring of 2015. In addition, a questionnaire concerning all management practices applied in the colonies was answered by the beekeepers. Generalized linear mixed effect models were performed to determine the relationship between risk factors associated with Nosema spp. spore counts in each eco-region. Data were scanned to identify colonies cluster with a higher probability of achieving high values of Nosema spp. abundance for each sampling period. Spatial distribution of colonies with a higher risk of achieving high Nosema spp. abundance seems to be explained by geographical conditions associated to climatic conditions and some management practices implemented in each eco-region. [ABSTRACT FROM AUTHOR]

We investigate antiplane Stoneley waves, localized at the discontinuity surface between two perfectly bonded half-spaces. Both half-spaces are elastic linear isotropic and possess a microstructure that is described within the theory of couple stress materials with micro-inertia. We show that the microstructure deeply affects wave propagation, which is permitted under broad conditions. This outcome stands in marked contrast to classical elasticity, where antiplane Stoneley waves are not supported and in-plane Stoneley waves exist only under very severe conditions on the material properties of the bonded half-spaces. Besides, Stoneley waves may propagate only beyond a threshold frequency (cuton), for which an explicit expression is provided. For a given frequency above cuton, this expression lends the admissible range of material parameters that allows propagation (passband). In particular, significant contrast between the adjoining materials is possible, provided that Stoneley waves propagate at high enough frequency. Therefore, micro-inertia plays an important role in determining the features of propagation. Considerations concerning existence and uniqueness of antiplane Stoneley waves are given: it is found that evanescent and decaying/exploding modes are also admitted. Results may be especially useful when accounting for the microstructure in non-destructive testing (NDT) and seismic propagation. [ABSTRACT FROM AUTHOR]

Skull base osteomyelitis (SBO) is a potentially life-threatening inflammation of cranial base bony structures of variable origin. Criteria for diagnosis and treatment are still controversial. Demographics, predisposing factors, symptoms, imaging, and clinical, laboratory, histological, and microbiological data of patients managed for SBO at the University Hospital of Brescia (ASST Spedali Civili) between 2002 and 2017 were retrospectively reviewed. Patients were included in different etiological groups. The topographic distribution of magnetic resonance (MR) abnormalities was recorded on a bi-dimensional model of skull base, on which three different patterns of inflammatory changes (edematous, solid, or necrotic) were reported. In patients with a history of radiotherapy, the spatial distribution of SBO was compared with irradiation fields. The association between variables and etiological groups was verified with appropriate statistical tests. A classification tree analysis was performed with the aim of inferring a clinical-radiological diagnostic algorithm for SBO. The study included 47 patients, divided into 5 etiological groups: otogenic (n = 5), radio-induced (n = 16), fungal (n = 14), immune-mediated (n = 6), and idiopathic (n = 6). At MR, five types of topographical distribution were identified (central symmetric, central asymmetric, orbital apex, sinonasal, maxillary). In patients with a history of radiotherapy, the probability to develop SBO was significantly increased in areas receiving the highest radiation dosage. The analysis of patients allowed for design of a classification tree for the diagnosis of SBO. The integration of clinical and radiologic information is an efficient strategy to categorize SBO and potentially guide its complex management. [ABSTRACT FROM AUTHOR]

The evaluation of the seminal plasma plays a relevant role in the definition of male infertility and in assisted reproduction outcomes; for this reason, it would be recommended to find biochemical markers able to characterize sperm pathology. In this study, 53 infertile patients (grouped by the presence leukocytospermia, idiopathic infertility, or varicocele) and 10 fertile men were selected. Spermiogram was performed by light microscopy, and sperm ultrastructure was evaluated by transmission electron microscopy (TEM) mathematically elaborated. Testosterone (TESTO), estradiol (E2), ferritin (FERR), iron (Fe), transferrin (TRSF), triglycerides (TRG), cholesterol (CHOL), and isoprostanes (F2-IsoPs) were detected in seminal plasma. Sperm characteristics and biochemical components were correlated by Spearman's rank correlation coefficient in the whole population and in each group. The levels of TESTO and E2 were positively correlated with sperm quality in particular, and E2 was correlated with fertility index expressing the number of sperm free of ultrastructural defects evaluated by TEM. On the contrary, the indices of iron metabolism (FERR, Fe, and TRSF) were positively associated with low sperm quality and sperm necrosis, particularly in leukocytospermia and varicocele groups, pathologies in which an inflammatory status and oxidative stress condition are present. The study of the seminal plasma composition deserves attention because the levels of the various components seem to be associated with specific reproductive pathologies. [ABSTRACT FROM AUTHOR]

Introduction: Joubert syndrome (JS) is a recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including optic nerve morphologic abnormalities. The function of the visual pathways, including the optic nerve, can be objectively evaluated by visual evoked potential (VEP) recordings. Our work aims to employ VEP to evaluate the neural conduction along the visual pathways in JS patients with or without optic nerve morphologic abnormalities (ONMA). Methods: In this observational and prospective study, 18 children with genetic diagnosis of JS (mean age 8.78 ± 5.87 years) and 17 healthy age-similar control subjects (control group, 9.05 ± 6.02 years) were enrolled. Based on presence/absence of ONMA at fundus examination, JS patients were divided into two groups: the JS-A group (eight patients with ONMA) and JS-N group (ten patients without ONMA). Following the ISCEV standards, pattern VEPs were recorded in patients and controls in response to 60' and 15' checks to obtain a prevalent activation of large or small axons, respectively. Results: Compared to controls, both the JS-A and JS-N groups showed significant abnormalities in 60' and 15' VEP implicit time and amplitude. Only in the JS-N group were values of 15' VEP implicit significantly correlated with the corresponding values of visual acuity. Conclusions: Our results suggest that a visual pathways dysfunction (of both large and small axons) detectable by VEP may occur in JS patients regardless of the presence of ONMA. Since clinical trials are envisaged in the near future to address JS-related ocular problems, our results might provide information about the potential usefulness of VEP recordings to assess the efficacy of treatments targeted to improve the visual pathways' function. [ABSTRACT FROM AUTHOR]