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Isolated orbital floor fractures are more frequent due to low bone thickness (2 mm). The aim of this study was to conduct a retrospective epidemiological analysis on these fractures, investigating demographic variables and fractures' features and their statistical correlation. A total of 120 patients with isolated orbital floor fracture, admitted at the Maxillofacial Surgery Unit of University of Naples Federico II, from 2010 to 2022 were enrolled in the study. Patients were evaluated for age, sex, smoke, comorbidities, post-traumatic clinical manifestation,s and defect side and size. Statistical analysis was conducted using the Pearson regression coefficient (r). The fractures were more frequent in men (male:female 2.2:1) because of road accidents (30% of cases). The average age was 48 years. Enophthalmos, diplopia and ocular motility anomalies were observed in 31%, 23% and 21% of cases, respectively. Statistical analysis revealed that age was related to fracture area; in particular, older patients showed larger fractures (p < 0.001). Interpersonal violence and traffic accidents were related to younger age (p < 0.001). Data analysis revealed that isolated orbital floor fractures are more frequent in young men (<40 years) because of road accidents or interpersonal violence. There is a statistical correlation between fracture area and patient age; in particular, older age corresponds to larger defects. [ABSTRACT FROM AUTHOR]

This study aims to describe our refined technique of submental intubation to avoid the recorded intraoperative complications related to tube passage and pilot balloon rupture. This is a retrospective case series of 21 patients with complex maxillofacial trauma who underwent submental intubation from January 2019 to January 2023. All the patients underwent to the same procedure with a new technique of pilot balloon protection: the pilot balloon was not deflated because, once the connector was removed, only the tube was curved and passed through the incision extraorally while the cuff remained inflated. The wire of the pilot balloon was passed behind the last tooth so as not to interfere with the maxillary-mandibular fixation, remaining extraorally under the anesthetist's view. Only 2 patients (9.5%) reported complications related to submental intubation: in particular a patient (4.8%) reported oral floor infection, and in another patient (4.8%) an unesthetic skin scar was observed. No patients reported intraoperative complications related to the procedure. The technique of pilot balloon protection that we have proposed seems to be effective in reducing the intraoperative complications related to the passage of the pilot balloon, such as rupture, damage or early extubation. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial functions are exploited in cancer and provide a validated therapeutic target. However, how this process is regulated has remained mostly elusive and the identification of new pathways that control mitochondrial integrity in cancer is an urgent priority. Methods: We studied clinically-annotated patient series of primary and metastatic prostate cancer, representative cases of multiple myeloma (MM) and publicly available genetic databases. Gene regulation studies involved chromatin immunoprecipitation, PCR amplification and Western blotting of conditional Myc-expressing cell lines. Transient or stable gene silencing was used to quantify mitochondrial functions in bioenergetics, outer membrane permeability, Ca2+ homeostasis, redox balance and cell death. Tumorigenicity was assessed by cell proliferation, colony formation and xenograft tumour growth. Findings: We identified Mitochondrial Fission Factor (MFF) as a novel transcriptional target of oncogenic Myc overexpressed in primary and metastatic cancer, compared to normal tissues. Biochemically, MFF isoforms, MFF1 and MFF2 associate with the Voltage-Dependent Anion Channel-1 (VDAC1) at the mitochondrial outer membrane, in vivo. Disruption of this complex by MFF silencing induces general collapse of mitochondrial functions with increased outer membrane permeability, loss of inner membrane potential, Ca2+ unbalance, bioenergetics defects and activation of cell death pathways. In turn, this inhibits tumour cell proliferation, suppresses colony formation and reduces xenograft tumour growth in mice. Interpretation: An MFF-VDAC1 complex is a novel regulator of mitochondrial integrity and actionable therapeutic target in cancer. Keywords: Mitochondria, MFF, Cell death, Tumour metabolism, VDAC1, Cancer therapy

Abstract Background Lung cancer is still the main cause of cancer death worldwide despite the availability of targeted therapies and immune-checkpoint inhibitors combined with chemotherapy. Cancer cell heterogeneity and primary or acquired resistance mechanisms cause the elusive behaviour of this cancer and new biomarkers and active drugs are urgently needed to overcome these limitations. p65BTK, a novel isoform of the Bruton Tyrosine Kinase may represent a new actionable target in non-small cell lung cancer (NSCLC). Methods p65BTK expression was evaluated by immunohistochemistry in 382 NSCLC patients with complete clinico-pathological records including smoking habit, ALK and EGFR status, and in metastatic lymph nodes of 30 NSCLC patients. NSCLC cell lines mutated for p53 and/or a component of the RAS/MAPK pathway and primary lung cancer-derived cells from Kras/Trp53 null mice were used as a preclinical model. The effects of p65BTK inhibition by BTK Tyrosine Kinase Inhibitors (TKIs) (Ibrutinib, AVL-292, RN486) and first-generation EGFR-TKIs (Gefitinib, Erlotinib) on cell viability were evaluated by MTT. The effects of BTK-TKIs on cell growth and clonogenicity were assessed by crystal violet and colony assays, respectively. Cell toxicity assays were performed to study the effect of the combination of non-toxic concentrations of BTK-TKIs with EGFR-TKIs and standard-of-care (SOC) chemotherapy (Cisplatin, Gemcitabine, Pemetrexed). Results p65BTK was significantly over-expressed in EGFR-wild type (wt) adenocarcinomas (AdC) from non-smoker patients and its expression was also preserved at the metastatic site. p65BTK was also over-expressed in cell lines mutated for KRAS or for a component of the RAS/MAPK pathway and in tumors from Kras/Trp53 null mice. BTK-TKIs were more effective than EGFR-TKIs in decreasing cancer cell viability and significantly impaired cell proliferation and clonogenicity. Moreover, non-toxic doses of BTK-TKIs re-sensitized drug-resistant NSCLC cell lines to both target- and SOC therapy, independently from EGFR/KRAS status. Conclusions p65BTK results as an emerging actionable target in non-smoking EGFR-wt AdC, also at advanced stages of disease. Notably, these patients are not eligible for EGFR-TKIs-based therapy due to a lack of EGFR mutation. The combination of BTK-TKIs with EGFR-TKIs is cytotoxic for EGFR-wt/KRAS-mutant/p53-null tumors and BTK-TKIs re-sensitizes drug-resistant NSCLC to SOC chemotherapy. Therefore, our data suggest that adding BTK-TKIs to SOC chemotherapy and EGFR-targeted therapy may open new avenues for clinical trials in currently untreatable NSCLC.

Background: Cancer cells use specific V-ATPase subunits to activate oncogenic pathways. Therefore, we investigated V-ATPase deregulation in aggressive gliomas and associated signaling. Methods: V-ATPase genes expression and associated pathways were analyzed in different series of glioma available from public databases, as well as in patients' cohort. Activation of pathways was analyzed at gene and protein expression levels. A genetic model of glioma in Drosophila melanogaster and mice with GBM patients-derived orthotopic xenografts were used as in vivo models of disease. Findings: GBM and recurrent gliomas display a specific V-ATPase signature. Such signature resolves the heterogeneous class of IDH-wild type lower-grade gliomas, identifying the patients with worse prognosis independently from clinical and molecular features (p = 0·03, by Cox proportional-hazards model). In vivo, V-ATPase subunits deregulation significantly impacts tumor growth and proliferation. At the molecular level, GBM-like V-ATPase expression correlates with upregulation of Homeobox genes. Interpretation: Our data identify a V-ATPase signature that accompanies glioma aggressiveness and suggest new entry points for glioma stratification and follow-up. Fund: This work was supported by Fondazione Cariplo (2014–1148 to VV), Fondazione IRCCS Ca' Granda, and Fondazione INGM Grant in Molecular Medicine 2014 (to VV). Keywords: V-ATPase, IDHwt/lower-grade glioma, Homeobox genes, Glioma stem cells

Background: The V-ATPase proton pump controls acidification of intra and extra-cellular milieu in both physiological and pathological conditions. We previously showed that some V-ATPase subunits are enriched in glioma stem cells and in patients with poor survival. In this study, we investigated how expression of a GBM-like V-ATPase pump influences the non-neoplastic brain microenvironment. Methods: Large oncosome (LO) vesicles were isolated from primary glioblastoma (GBM) neurospheres, or from patient sera, and co-cultured with primary neoplastic or non-neoplastic brain cells. LO transcript and protein contents were analyzed by qPCR, immunoblotting and immunogold staining. Activation of pathways in recipient cells was determined at gene and protein expression levels. V-ATPase activity was impaired by Bafilomycin A1 or gene silencing. Findings: GBM neurospheres influence their non-neoplastic microenvironment by delivering the V-ATPase subunit V1G1 and the homeobox genes HOXA7, HOXA10, and POU3F2 to recipient cells via LO. LOs reprogram recipient cells to proliferate, grow as spheres and to migrate. Moreover, LOs are particularly abundant in the circulation of GBM patients with short survival time. Finally, impairment of V-ATPase reduces LOs activity. Interpretation: We identified a novel mechanism adopted by glioma stem cells to promote disease progression via LO-mediated reprogramming of their microenvironment. Our data provide preliminary evidence for future development of LO-based liquid biopsies and suggest a novel potential strategy to contrast glioma progression. Fund: This work was supported by Fondazione Cariplo (2014-1148 to VV) and by the Italian Minister of Health-Ricerca Corrente program 2017 (to SF). Keywords: V-ATPase, Homeobox genes, Glioma stem cells, Large oncosome

Urban pollution is usually monitored via fixed stations that provide detailed and reliable information, thanks to equipment quality and effective measuring protocols, but these sampled data are gathered from very limited areas and through discontinuous monitoring campaigns. Currently, the spread of mobile devices has fostered the development of new approaches, like Mobile Crowd Sensing (MCS), increasing the chances of using smartphones as suitable sensors in the urban monitoring scenario, because it potentially contributes massive ubiquitous data at relatively low cost. However, MCS is useless (or even counter-productive), if contributed data are not trustworthy, due to wrong data-collection procedures by non-expert practitioners. Contextualizing monitored data with those coming from phone-embedded sensors and from time/space proximity can improve data trustworthiness. This work focuses on the development of an algorithm that exploits context awareness to improve the reliability of MCS collected data. It has been validated against some real use cases for noise pollution and promises to improve the trustworthiness of end users generated data.

Despite following a gluten-free diet, which is currently the only effective therapy for celiac disease, about 5% of patients can develop serious complications, which in the case of refractory type 2 could evolve towards intestinal lymphoma. In this study, we have identified a set of 15 microRNAs in serum discriminating between the two types of refractory disease. Upregulated miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p could be useful for the better stratification of patients and the monitoring of disease development, while miR-490-3p was found to be dysregulated in patients with refractory type 1. Finally, by using bioinformatic tools applied to the analysis of the targets of dysregulated microRNAs, we have completed a more precise assessment of their functions. These mainly include the pathway of response to Transforming Growth Factor β cell–cell signaling by Wnt; epigenetic regulation, especially novel networks associated with transcriptional and post-transcriptional alterations; and the well-known inflammatory profiles.

Viruses are potential vectors for horizontal gene transfer. Here, studying viral infection of sugar beet plants, the authors report the generation of virus-host circular DNA hybrids and provide a picture of the initial steps in virus-mediated horizontal transfer of chromosomal DNA between plant species.

La visión del trabajo científico ha cambiado, se asume una posición más amplia, los trabajos ya no son individuales tornándose difusas las fronteras de las disciplinas. Para llevarlos a cabo es necesaria la interdisciplinariedad, lo que requiere cambiar la modalidad tradicional de trabajo, la conformación de equipos y un lenguaje común. Despertar vocación por el estudio de las Ciencias implica cambiar su enseñanza. Es crear en los alumnos un espíritu inquisidor, constructor, participativo, capaz de resolver problemas, alentando la constitución de grupos de trabajo interdisciplinarios. Para conseguirlo es necesario desarrollar estrategias que tengan por objeto revalorizar y resignificar el estudio de las Ciencias. El presente trabajo es un informe de avance de una propuesta pedagógica para promover acciones concretas en el aula de la escuela media desde la Universidad, que posibilite cambios en las metodologías y en los conocimientos aplicados de las áreas de la Ciencia, a través del "diálogo entre ellas". La forma de trabajo propuesta requiere de tácticas que permitan facilitar los procesos de aprendizaje que mejoren las acciones educativas. No es fácil llevar a cabo un trabajo de este tipo, su éxito no está asegurado y exige que se cumplan condiciones que pueden conducir a dificultades. Una de ellas, detectada en esta investigación, es la falta de formación de los docentes, tanto del nivel secundario como universitario, en la modalidad "interdisciplinaria". La misma es una nueva concepción de trabajo y de enseñanza de las Ciencias. La experiencia realizada resultó positiva. Con este trabajo se iniciaron acciones que integran áreas, currículos y espacios educativos. Permitió la realización de prácticas de laboratorio de estudiantes de nivel secundario en el ámbito universitario para que puedan conocer otro modo de hacer Ciencias, sentando un precedente de modalidad educativa en la zona de influencia de la Universidad Nacional del Litoral.

Tomato spotted wilt virus (TSWV) is a devastating plant pathogen, causing huge crop losses worldwide. Unfortunately, due to its wide host range and emergence of resistance breaking strains, its management is challenging. Up to now, resistance to TSWV infection based on RNA interference (RNAi) has been achieved only in transgenic plants expressing parts of the viral genome or artificial microRNAs targeting it. Exogenous application of double-stranded RNAs (dsRNAs) for inducing virus resistance in plants, namely RNAi-based vaccination, represents an attractive and promising alternative, already shown to be effective against different positive-sense RNA viruses and viroids. In the present study, the protection efficacy of exogenous application of dsRNAs targeting the nucleocapsid (N) or the movement protein (NSm) coding genes of the negative-sense RNA virus TSWV was evaluated in Nicotiana benthamiana as model plant and in tomato as economically important crop. Most of the plants treated with N-targeting dsRNAs, but not with NSm-targeting dsRNAs, remained asymptomatic until 40 (N. benthamiana) and 63 (tomato) dpi, while the remaining ones showed a significant delay in systemic symptoms appearance. The different efficacy of N- and NSm-targeting dsRNAs in protecting plants is discussed in the light of their processing, mobility and biological role. These results indicate that the RNAi-based vaccination is effective also against negative-sense RNA viruses but emphasize that the choice of the target viral sequence in designing RNAi-based vaccines is crucial for its success.

Introduction: To evaluate the recovery rate of loss of smell (LOS) with objective olfactory testing in COVID-19 patients.Methods: Adults with confirmed COVID-19 and self-reported sudden LOS were prospectively recruited through a public call from the University of Mons (Belgium). Epidemiological and clinical data were collected using online patient-reported outcome questionnaires. Patients benefited from objective olfactory evaluation (Sniffin-Sticks-test) and were invited to attend for repeated evaluation until scores returned to normal levels.Results: From March 22 to May 22, 2020, 88 patients with sudden-onset LOS completed the evaluations. LOS developed after general symptoms in 44.6% of cases. Regarding objective evaluation, 22 patients (25.0%) recovered olfaction within 14 days following the onset of LOS. The smell function recovered between the 16th and the 70th day post-LOS in 48 patients (54.5%). At the time of final assessment at 2 months, 20.5% of patients (N = 18) had not achieved normal levels of olfactory function. Higher baseline severity of olfactory loss measured using Sniffin-Sticks was strongly predictive of persistent loss (p < 0.001).Conclusion: In the first 2 months, 79.5% of patients may expect to have complete recovery of their olfactory function. The severity of olfactory loss, as detected at the first Sniffin-Sticks-test, may predict the lack of mid-term recovery.

Treatment of chronic diseases, such as heart failure, requires complex protocols based on early diagnosis; self-monitoring of symptoms, vital signs and physical activity; regular medication intake; and education of patients and caregivers about relevant aspects of the disease. Smartphones and mobile health applications could be very helpful in improving the efficacy of such protocols, but several barriers make it difficult to fully exploit their technological potential and produce clear clinical evidence of their effectiveness. App suppliers do not help users distinguish between useless/dangerous apps and valid solutions. The latter are few and often characterised by rapid obsolescence, lack of interactivity and lack of authoritative information. Systematic reviews can help physicians and researchers find and assess the ‘best candidate solutions’ in a repeatable manner and pave the way for well-grounded and fruitful discussion on their clinical effectiveness. To this purpose, the authors assess 10 apps for heart failure self-care using the Intercontinental Marketing Statistics score and other criteria, discuss the clinical effectiveness of existing solutions and identify barriers to their use in practice and drivers for change.

The aim of this study was to investigate the effect of intramammary infusions of natural composition GLP 810 with immunomodulating properties on the local nonspecific cellular and humoral immune response in cows with subclinical mastitis. The composition GLP 810 consists of lactic acid, lysozyme, glycopeptides, and 0.9% solution of NaCl. The following parameters were studied: (1) leukocyte differential distribution in milk, (2) expression of cytokines in milk leukocytes, (3) antibacterial activity, and (4) milk quality. Nineteen mammary glands in five lactating cows were infused with 10 mL of GLP 810, and nineteen other glands from five control cows were treated with 10 mL 0.9% NaCl. The results showed that after intramammary administration of the composition GLP 810 three times with 48 h intervals, the following effects on leukocyte populations in milk were observed: (1) an increase in the number of polymorphonuclear leukocytes and lymphocytes and (2) a decrease in the number of macrophages. A reduction in the number of pathogenic bacteria was also detected. The analyses of tumour necrosis factor-alpha, interleukin-10, and beta-defensin-2 revealed that the production of the aforementioned cytokines significantly increased, whereas no significant effects on interleukin-1 and caspase-6 expression in milk leukocytes were recorded. However, there were significant differences between mammary glands with high and low milk somatic cell count. The results suggest that the composition GLP 810 has an immunomodulatory effect on mammary glands and it could be used for improving the immune response in cows with subclinical mastitis during lactation.

(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up.

Abstract Background Optimal cytoreduction (macroscopic Residual Tumor, RT = 0) is the best survival predictor factor in epithelial ovarian cancer (EOC). It doesn’t exist a consolidated criteria to predict optimal surgical resection at interval debulking surgery (IDS). The aim of this study is to develop a predictive model of complete cytoreduction at IDS. Methods We, retrospectively, analyzed 93 out of 432 patients, with advanced EOC, underwent neoadjuvant chemotherapy (NACT) and IDS from January 2010 to December 2016 in two referral cancer centers. The correlation between clinical-pathological variables and residual disease at IDS has been investigated with univariate and multivariate analysis. A predictive score of cytoreduction (PSC) has been created by combining all significant variables. The performance of each single variable and PSC has been reported and the correlation of all significant variables with progression free survival (PFS) has been assessed. Results At IDS, 65 patients (69,8%) had complete cytoreduction with no residual disease (R = 0). Three criteria independently predicted R > 0: age ≥ 60 years (p = 0.014), CA-125 before NACT > 550 UI/dl (p = 0.044), and Peritoneal Cancer Index (PCI) > 16 (p 16, a PSC ≥ 3 and the presence of R > 0 after IDS were all significantly associated with shorter PFS (p 0). The PSC should be prospectively validated in a larger series of EOC patients undergoing NACT-IDS.

Breast cancer tumors originating from mammary luminal epithelial cells are highly heterogeneous. Here, the authors show MYC-driven tumor initiation is reliant on cell reprogramming via an epigenetic program which leads to mammary luminal epithelial cells acquiring basal/stem cell-like properties.

Abstract Background The national antiretroviral therapy in the Republic of Chad provides free of charge antiretroviral regimens and therapeutic monitoring for patients receiving antiretroviral therapy nationwide. For a successful programmatic uptake, these efforts merit to be supported by thorough assessments of antiretroviral therapy response and HIV-1 drug resistance surveillance, especially with risks of cross-resistance due to the gradual stavudine phasing out in such national settings. We therefore evaluated the virological response to antiretroviral therapy, HIV-1 drug resistance emergence and circulating HIV-1 clades in a Chad context. A cross-sectional and prospective study was conducted among 116 patients (41 [δ ± 6.87] years, 59% female) receiving first-line antiretroviral therapy for ≥ 6 months in Ndjamena, Chad, in 2011–2012, enrolled consecutively. To ensure accuracy, plasma viral load was concomitantly measured using Abbott Real-Time and Cobas AmpliPrep/TaqMan (v2.0), and virological failure defined as ≥ 1000 HIV-1 RNA copies/ml. Plasma from patients experiencing virological failure were processed for sequencing of HIV-1 protease-reverse transcriptase using the ANRS-AC.11 resistance testing protocol; drug resistant mutations were interpreted using the ANRS-AC11 algorithm; and phylogenetic analysis was performed using MEGA.v.6. Results Majority of patients was receiving zidovudine plus lamivudine plus nevirapine (46%), stavudine plus lamivudine plus nevirapine (41%) and tenofovir plus emtricitabine plus efavirenz (11%), for a median time-on-treatment of 5 [IQR 4–7] years. The rate of virological failure was 43% (50/116), with 86% (43/50) sequencing performance. Overall, 32% (37/116) patients presented ≥ one major drug resistant mutation(s), with 29% (34/116) to nucleos(t)ide reverse transcriptase inhibitors (67% [29/43] M184V/I, 30% [13/43] T215Y/F, 19% [8/43] V75A/F/I/L/M, 9% [4/43] K70P/R/W, 9% [4/43] K219E/N/Q and 5% [2/43] A62V); 86% (37/43) to non-nulceos(t)ide reverse transcriptase inhibitors (30% [13/43] K103N/S/E, 26% [11/43] Y181C/V/F/L, 2% [1/43] L100I, 2% [1/43] F227L, 2% [1/43] P225H); and 2% (1/43) to protease inhibitors (M46I, I54V, V82S). Six HIV-1 subtypes were found: 30% circulating recombinant form (CRF02_AG), 30% J, 16% G, 9% A, 9% D, 5% F. Conclusions In Chad, almost half of patients are failing first-line antiretroviral therapy after 5 years, with considerable drug resistant mutations at failure. Absence of K65R supports the use of tenofovir-containing regimens as preferred first-line and as suitable drug for second-line combinations, in this setting with significant HIV-1 genetic diversity.

Abstract Background There is today no gold standard method to accurately define the time passed since infection at HIV diagnosis. Infection timing and incidence measurement is however essential to better monitor the dynamics of local epidemics and the effect of prevention initiatives. Methods Three methods for infection timing were evaluated using 237 serial samples from documented seroconversions and 566 cross sectional samples from newly diagnosed patients: identification of antibodies against the HIV p31 protein in INNO-LIA, SediaTM BED CEIA and SediaTM LAg-Avidity EIA. A multi-assay decision tree for infection timing was developed. Results Clear differences in recency window between BED CEIA, LAg-Avidity EIA and p31 antibody presence were observed with a switch from recent to long term infection a median of 169.5, 108.0 and 64.5 days after collection of the pre-seroconversion sample respectively. BED showed high reliability for identification of long term infections while LAg-Avidity is highly accurate for identification of recent infections. Using BED as initial assay to identify the long term infections and LAg-Avidity as a confirmatory assay for those classified as recent infection by BED, explores the strengths of both while reduces the workload. The short recency window of p31 antibodies allows to discriminate very early from early infections based on this marker. BED recent infection results not confirmed by LAg-Avidity are considered to reflect a period more distant from the infection time. False recency predictions in this group can be minimized by elimination of patients with a CD4 count of less than 100 cells/mm3 or without no p31 antibodies. For 566 cross sectional sample the outcome of the decision tree confirmed the infection timing based on the results of all 3 markers but reduced the overall cost from 13.2 USD to 5.2 USD per sample. Conclusions A step-wise multi assay decision tree allows accurate timing of the HIV infection at diagnosis at affordable effort and cost and can be an important new tool in studies analyzing the dynamics of local epidemics or the effects of prevention strategies.

Fe/Cu-based sintered friction materials are proven potential materials for heavy-duty applications. The current research explores the influence of rare earth oxide (Nd2O3) and graphite on the tribological characteristics of Fe/Cu-based friction materials. The constituents present in the friction material are Fe, Cu, Cg (1%, 3%, 5%, 7%), BaSO4, and Nd2O3 (5%). Optical microscopy and elemental mapping studies reveal the homogeneous distribution of elements in the matrix. Sintered density of the specimens showed a maximum of 70% of the theoretical density measured by Archimedes' principle. XRD analysis shows no new phase formation in all the sintered specimens. A peak microhardness result of 96 HV is obtained in specimen NG-01. The pin-on-disc tribotests are performed at an axial load of 50 N at a sliding velocity of 5.5 m/s. Specimen NG-03 with 3% graphite exhibited an optimum wear rate with a friction coefficient of 0.45. The surface morphology and elemental composition of the worn specimens are investigated. The morphological features inferred that the wear mechanism is predominantly mixed abrasive and adhesive. [ABSTRACT FROM AUTHOR]

Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013–2016 to 2017–2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013–2016 (33%) and 2017–2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013–2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

Statins could increase the effectiveness of Helicobacter pylori eradication therapies due to their anti-inflammatory effect. The aim of this study was to analyze the impact of this therapeutic association in real life. This is a multicenter, prospective, non-interventional study aimed at evaluating the management of H. pylori by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap from 2013 to 2020. The association between statin use and H. pylori eradication effectiveness was evaluated through multivariate analysis. Overall, 9988 and 705 patients received empirical and culture-guided treatment, respectively. Overall, statin use was associated with higher effectiveness in the empirical group (OR = 1.3; 95%CI = 1.1–1.5), but no association was found with first-line treatment effectiveness (N = 7738); as an exception, statin use was specifically associated with lower effectiveness of standard triple therapy (OR = 0.76; 95%CI = 0.59–0.99). In the rescue therapy empirical group (N = 2228), statins were associated with higher overall effectiveness (OR = 1.9; 95%CI = 1.4–2.6). However, sub-analyses by treatment schemes only confirmed this association for the single-capsule bismuth quadruple therapy (OR = 2.8; 95%CI = 1.3–5.7). No consistent association was found between statin use and H. pylori therapy effectiveness. Therefore, the addition of statins to the usual H. pylori treatment cannot be currently recommended to improve cure rates.

Facial palsy can severely compromise quality of life, significantly altering the harmony and symmetry of the face, which can be restored by surgical rehabilitation. The aim of the study was the quantification of facial symmetry following facial reanimation. Fifteen consecutive adult patients were surgically treated through triple innervation for reanimation of flaccid unilateral facial paralysis (contralateral facial nerve, masseteric nerve, and hypoglossal nerve) and fascia lata graft for definition of the nasolabial sulcus. In the preoperative stage and at least 11 months after the surgical treatment, three-dimensional facial images were recorded through stereophotogrammetry in a neutral (rest) position, and with Mona Lisa and full-denture (maximum) smiles. Labial commissure inclination relative to the interpupillary axis, and a surface assessment of local facial asymmetry at rest and while smiling were obtained for the upper, middle, and lower facial thirds. The angle between the interpupillary axis and the labial commissure significantly improved in post-surgical acquisitions, regaining symmetry at rest (t -test; p < 0.001). Facial symmetry increased significantly when passing from pre-to postsurgical facial scans, from the lower to the upper facial third, and from the full smile to the rest position (ANOVA; p < 0.001). After treatment, the full smile recovered more symmetry than the other two expressions. In summary, surgical treatment significantly reduced facial asymmetry, but this reduction differed significantly among the various animations and facial thirds. The results of this study confirmed clinical findings of significant static and dynamic improvements in facial symmetry after triple innervation reanimation surgery. [ABSTRACT FROM AUTHOR]

Tumors of the parathyroid glands are the second most common endocrine neoplasia. Epigenetic studies revealed an embryonic signature involved in parathyroid tumorigenesis. Here, we investigated the expression of the stem core genes SOX2, POU5F1/OCT4, and NANOG. Rare cells within normal parathyroid glands expressed POU5F1/OCT4 and NANOG, while SOX2 was undetectable. Nuclear SOX2 expression was detectable in 18% of parathyroid adenomas (PAds, n = 34) involving 5–30% of cells, while OCT4 and NANOG were expressed at the nuclear level in a more consistent subset of PAds involving 15–40% of cells. Most parathyroid carcinomas expressed the core stem genes. SOX2-expressing cells co-expressed parathormone (PTH). In PAds-derived primary cultures, silencing of the tumor suppressor gene MEN1 induced the expression of SOX2, likely through a MEN1/HAR1B/SOX2 axis, while calcium-sensing receptor activation increased SOX2 mRNA levels through YAP1 activation. In addition, inducing nuclear β-catenin accumulation in PAds-derived primary cultures by short-term incubation with lithium chloride (LiCl), SOX2 and POU5F1/OCT4 expression levels increased, while NANOG transcripts were reduced, and LiCl long-term incubation induced an opposite pattern of gene expression. In conclusion, detection of the core stem genes in parathyroid tumors supports their embryogenic signature, which is modulated by crucial genes involved in parathyroid tumorigenesis.

Demand for new biological technologies in agriculture is ever growing, particularly with respect to the need of restoring the soil organic matter and soil fertility. Products of natural origin are developed to stimulate plant growth and productivity. Humic substances (HS) are the decay products of living matter, with high molecular weight and complex structure. Nowadays, HS are industrially produced from various materials like peat, lignin, soil and compost. The objective of this study is to make a comparison of the impact of HS of different origin on plant development. In total, eight different HS were used; four were extracted from various materials and four were commercially available products. To evaluate the stimulating effect, three different species of plants were used (Triticum aestivum, Sinapis alba, Lepidum sativum). The tests were carried out on Phytotestkit plates, germinating the seeds in different solutions of HS in various concentrations in dark, with or without added nutrient solution. Then, the growth parameters were measured. All tested products showed increase in at least some concentrations compared with the control sample. Significant differences in the stimulating effect of HS depending on their origin were found.

Background: The objective of this study was to investigate the efficacy and safety of early administration of oral corticosteroids (OC) or nasal corticosteroids (NC) as an add-on to olfactory training (OT) versus OT alone in patients with olfactory dysfunction (OD) related to coronavirus disease 2019 (COVID-19). Methods: Patients with a positive diagnosis of COVID-19 and OD were prospectively recruited from March 22 to December 15, 2020 from 4 European hospitals. Patients had confirmed OD on psychophysical testing. All patients undertook OT, with add-on 10 days of OC (group 1: OC + OT), or 1 month of NC (group 2: NC + OT) or olfactory training alone (group 3: OT). Olfactory evaluations (Sniffin’Sticks tests) were carried out at the time of inclusion, 1 and 2 months after the start of the therapeutic course. Results: A total of 152 hyposmic or anosmic patients completed the study. Group 1, 2 and 3 included 59, 22 and 71 patients, respectively and all patient groups were comparable regarding baseline Sniffin’Sticks tests. The median Sniffin’Sticks test values significantly improved from pre- to post-intervention in all groups. The increase of Sniffin’Sticks test values was higher in group 1 (OC + OT) compared with groups 2 and 3 (p < 0.001) at one month after treatment but did not remain so at 2 months. Groups 1, 2 and 3, respectively, presented parosmia in 20/71 (28.2%), 9/22 (40.9%) and 42/71 (59.2%) patients. This difference was statistically significant between group 1 and 3 (p < 0.001). There were no patients with a worsening of the disease or an increase of the severity of the COVID-19 symptoms. Conclusions: The use of OCs in patients with OD related to mild COVID-19 is generally well-tolerated without any case of deterioration of symptoms. OC is associated with greater improvement in psychophysical olfactory evaluations at 1-month post-treatment but there was no difference at 2 months. Parosmia may be reduced following treatment with OC and NC. On the basis of these preliminary results, it is possible to state that considering the 2 months efficacy of OC and NC with respect to the OT alone and the risk-benefit ratio, the benefit to start a specific treatment of COVID-19 related OD cannot be demonstrated and there is a need for a randomised controlled trial to assess this further.

Background and Aims: The WHO has solicited all countries to eliminate HCV by 2030. The Italian government started routine screening for HCV infection in January 2021, initially targeting subjects born between 1969 and 1989. With the aim of achieving micro-elimination, we designed a hospital-wide project focusing on inpatients born from 1935 to 1985 and conducted it in our institution. Method: All inpatients aged 35 to 85, admitted from 10 February 2020 to 9 February 2021 for many different diseases and conditions underwent HCV antibody (HCVAb) testing by third-generation ELISA. When positive, reflex HCV RNA testing and genotyping were performed. Clinical history, fibrosis diagnosis, laboratory data and concomitant medications were available for all. Results: The HCV screening rate of inpatients was 100%. In total, 11,748 participants were enrolled, of whom 53.50% were male. The HCVAb positivity rate was 3.03%. The HCVAb rate increased with age and was higher for patients born between 1935 and 1944 (4.81%). The rate of HCV RNA positivity was 0.97%. The vast majority (80.70%) of HCV RNA-positive participants were 55 or older; in about 40% of cases, HCV RNA-positive patients were unaware of their infection. Although 16 patients died after HCV chronic infection diagnosis (two due COVID-19) or HCV treatment prescription (one due to COVID-19), 74.56% of patient HCV diagnoses were linked to HCV treatment, despite their co-morbidities. All patients older than 65 who died had an active HCV infection. Conclusion: The present study revealed a rate of active HCV infections among inpatients lower than what has been reported in the past in the general population; this appears to be a result of the widespread use of pangenotypic direct-acting antiviral agents (DAAs). The overall rate of active infection was lower than the rate observed in the 1935–1954 cohort. The high rate of inpatients unaware of HCV infections and the high number of deaths among subjects with an active HCV infection born from 1935 to 1954, suggest that, at least in southern Italy, targeted screening of this birth cohort may be required to reduce the number of undiagnosed cases and hidden infections.

Background/Aims: Curing Helicobacter pylori infection remains challenging for clinicians, as no proposed first-line therapy achieves bacterial eradication in all treated patients so that several patients need two or more consecutive treatments. Bacterial culture with antibiotics susceptibility testing is largely unachievable in Italy, and empiric second-line and rescue therapies are generally used. This study aimed to identify what eradication regimens perform better in Italy, following first-line therapy failure. Methods: We performed a literature search on PubMed for studies on standard therapy regimens used as second-line or rescue treatments performed in adult patients. Studies including modified drug combinations were not considered. Both intention-to-treat and per- protocol analyses were computed for each therapy subgroup. Results: Data from 35 studies with a total of 4830 patients were eventually considered. As a second-line therapy, Pylera® (90.6%) and a sequential regimen (89.8%) achieved eradication rates significantly higher than other therapies. For third-line therapy, a levofloxacin-based regimen and Pylera® achieved comparable eradication rates (88.2% vs. 84.7%; p = 0.2). Among therapies used as fourth (or more) attempts, Pylera® and a rifabutin-based therapy achieved 77.4% and 66.4% cure rates, respectively (p = 0.013). A therapy sequence based on the type of first-line therapy used was proposed. Conclusions: Data obtained through our review indicate that standard therapies for H. pylori eradication can be used when following an appropriate sequence, allowing clinicians to improve the cure rate without resorting to bacterial culture.

Mitochondria have a controversial role in cancer. Here, the authors demonstrate the reprogramming of a neuronal network of mitochondrial trafficking in tumor cells, and identify Syntaphilin as a key protein that suppresses organelle dynamics thereby blocking chemotaxis and metastasis in mice.

Background: Peritoneal carcinomatosis is a common metastatic pattern in ovarian, gastric, colorectal, and appendiceal cancer; systemic chemotherapy is the current standard of care for peritoneal metastatic disease; however, in a subset of patients its beneficial effect remains questionable. More effective perioperative chemotherapy is needed.Materials and methods: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It’s a safe and feasible approach that improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. Till now the drugs used in PIPAC for the treatment of the peritoneal carcinomatosis (PC) are cisplatin, doxorubicin, and oxaliplatin; as of yet, there are no in vivo data comparing different drug formulations and dosage schedules of PIPAC. Pegylated liposomal doxorubicin 1.5 mg/sm was aerosolized in PIPAC procedures.Results: Pharmacokinetics analysis of 10 procedures performed with conventional doxorubicin solution at the dose of 1.5 mg/m2 were compared to 15 procedures with the same dose of pegylated liposomal doxorubicin (PLD). Significant differences between experimental groups were detected by one-way ANOVA followed by Bonferroni correction; a p value < 0.05 was considered statistically significant. A statistically different doxorubicin tissue concentration was observed for the doxorubicin solution compared to pegylated liposomal doxorubicin in the right parietal peritoneum and right diaphragm. In the Caelyx® series a mean tissue concentration of 1.27 ± 1.33 mg/g was reported, while in the second one we registered a mean concentration of 3.1 ± 3.7 mg/g.Conclusions: The delivery of nano-particles in PIPAC was feasible, but pegylated liposomal concentrations are lower than standard doxorubicin formulation. Probably mechanical and physical properties of pressurized aerosol chemotherapy might alter their stability and cause structural disintegration.

Plant roots establish interactions with several beneficial soil microorganisms including arbuscular mycorrhizal fungi (AMF). In addition to promoting plant nutrition and growth, AMF colonization can prime systemic plant defense and enhance tolerance to a wide range of environmental stresses and below-ground pathogens. A protective effect of the AMF against above-ground pathogens has also been described in different plant species, but it seems to largely rely on the type of attacker. Viruses are obligate biotrophic pathogens able to infect a large number of plant species, causing massive losses in crop yield worldwide. Despite their economic importance, information on the effect of the AM symbiosis on viral infection is limited and not conclusive. However, several experimental evidences, obtained under controlled conditions, show that AMF colonization may enhance viral infection, affecting susceptibility, symptomatology and viral replication, possibly related to the improved nutritional status and to the delayed induction of pathogenesis-related proteins in the mycorrhizal plants. In this review, we give an overview of the impact of the AMF colonization on plant infection by pathogenic viruses and summarize the current knowledge of the underlying mechanisms. For the cases where AMF colonization increases the susceptibility of plants to viruses, the term “mycorrhiza-induced susceptibility” (MIS) is proposed.

Background. The occurrence of false losses of resistance may be one of the reasons for inadequate or failed epidural block. A CompuFlo® epidural instrument has been introduced to measure the pressure of human tissues in real time at the orifice of a needle and has been used as a tool to identify the epidural space. The aim of this study was to investigate the sensitivity and the specificity of the ability of CompuFlo® to differentiate the false loss of resistance from the true loss of resistance encountered during the epidural space identification procedure. Method. We performed epidural block with the CompuFlo® epidural instrument in 120 healthy women who requested labor epidural analgesia. The epidural needle was considered to have reached the epidural space when an increase in pressure (accompanied by an increase in the pitch of the audible tone) was followed by a sudden and sustained drop in pressure for more than 5 seconds accompanied by a sudden decrease in the pitch of the audible tone, resulting in the formation of a low and stable pressure plateau. We evaluate the sensitivity, specificity, and positive and negative predictive values of the ability of CompuFlo® recordings to correctly identify the true LOR from the false LOR. Results. The drop in pressure associated with the epidural space identification was significantly greater than that recorded after the false loss of resistance (73% vs 33%) (P=0.000001). The sensitivity was 0.83, and the AUC was 0.82. Discussion. We have confirmed the ability of CompuFlo® to differentiate the false loss of resistance from the true loss of resistance and established its specificity and sensitivity. Conclusion. An easier identification of dubious losses of resistance during the epidural procedure is essential to reduce the number of epidural attempts and/or needle reinsertions with the potential of a reduced risk of accidental dural puncture especially in difficult cases or when the procedure is performed by trainees.

Background and aims: Only a few antimicrobials are effective against H. pylori, and antibiotic resistance is an increasing problem for eradication therapies. In 2017, the World Health Organization categorized clarithromycin resistant H. pylori as a “high-priority” bacterium. Standard antimicrobial susceptibility testing can be used to prescribe appropriate therapies but is currently recommended only after the second therapeutic failure. H. pylori is, in fact, a “fastidious” microorganism; culture methods are time-consuming and technically challenging. The advent of molecular biology techniques has enabled the identification of molecular mechanisms underlying the observed phenotypic resistance to antibiotics in H. pylori. The aim of this literature review is to summarize the results of original articles published in the last ten years, regarding the use of Next Generation Sequencing, in particular of the whole genome, to predict the antibiotic resistance in H. pylori.Methods: a literature research was made on PubMed. The research was focused on II and III generation sequencing of the whole H. pylori genome. Results: Next Generation Sequencing enabled the detection of novel, rare and complex resistance mechanisms. The prediction of resistance to clarithromycin, levofloxacin and amoxicillin is accurate; for other antimicrobials, such as metronidazole, rifabutin and tetracycline, potential genetic determinants of the resistant status need further investigation.