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Purpose: ATM is the most commonly mutated DNA damage and repair gene in non–small cell lung cancer (NSCLC); however, limited characterization has been pursued. Experimental Design: Clinicopathologic, genomic, and treatment data were collected for 5,172 patients with NSCLC tumors which underwent genomic profiling. ATM IHC was performed on 182 NSCLCs with ATM mutations. Multiplexed immunofluorescence was performed on a subset of 535 samples to examine tumor-infiltrating immune cell subsets. Results: A total of 562 deleterious ATM mutations were identified in 9.7% of NSCLC samples. ATM-mutant (ATMMUT) NSCLC was significantly associated with female sex (P = 0.02), ever smoking status (P < 0.001), non-squamous histology (P = 0.004), and higher tumor mutational burden (DFCI, P < 0.0001; MSK, P < 0.0001) compared with ATM–wild-type (ATMWT) cases. Among 3,687 NSCLCs with comprehensive genomic profiling, co-occurring KRAS, STK11, and ARID2 oncogenic mutations were significantly enriched among ATMMUT NSCLCs (Q < 0.05), while TP53 and EGFR mutations were enriched in ATMWT NSCLCs. Among 182 ATMMUT samples with ATM IHC, tumors with nonsense, insertions/deletions, or splice site mutations were significantly more likely to display ATM loss by IHC (71.4% vs. 28.6%; P < 0.0001) compared with tumors with only predicted pathogenic missense mutations. Clinical outcomes to PD-(L)1 monotherapy (N = 1,522) and chemo-immunotherapy (N = 951) were similar between ATMMUT and ATMWT NSCLCs. Patients with concurrent ATM/TP53 mutations had significantly improved response rate and progression-free survival with PD-(L)1 monotherapy. Conclusions: Deleterious ATM mutations defined a subset of NSCLC with unique clinicopathologic, genomic, and immunophenotypic features. Our data may serve as resource to guide interpretation of specific ATM mutations in NSCLC.

The current landscape of targeted therapies directed against oncogenic driver alterations in non–small cell lung cancer (NSCLC) is expanding. Patients with EGFR-mutant NSCLC can derive significant benefit from EGFR tyrosine kinase inhibitor (TKI) therapy, including the third-generation EGFR TKI osimertinib. However, invariably, all patients will experience disease progression with this therapy mainly due to the adaptation of cancer cells through primary or secondary molecular mechanisms of resistance. The comprehension and access to tissue and cell-free DNA next-generation sequencing have fueled the development of innovative therapeutic strategies to prevent and overcome resistance to osimertinib in the clinical setting. Herein, we review the biological and clinical implications of molecular mechanisms of osimertinib resistance and the ongoing development of therapeutic strategies to overcome or prevent resistance.

The skin of the child presents significant differences compared to that of the adult; this diversity is even more marked if the skin of the newborn is taken into consideration. In fact, this is immature, as is its immune response. This results in weak responses to microorganisms. Therefore, the use of antibacterial dressings is necessary to manage the microbial load at the skin surface level. To this end, international consensus documents suggest that the use of products with a physical and mechanical action to remove bacteria is indicated. Bacterial uptake dressings that exploit DACC technology are bacteriostatic and non-bactericidal dressings; this "passive" control of the bacterial load avoids the rupture of the bacterial cell wall and the consequent release of endotoxins, which worsen the inflammatory state and prevent the healing of the lesion. Thanks to its purely physical principle, it also does not release any antimicrobial agent, which could create the risk of bacterial resistance and allergies. This treatment proposal aims to highlight the advantage and benefit of advanced dressings with DACC technology, for the prevention and treatment of pediatric and neonatal infected wounds.

Background: Many transversal mechanisms act synergistically at different time-points in the cascade of Alzheimer’s disease (AD), since amyloid-β (Aβ) deposition, tau pathology, and neuroinflammation influence each other. Objective: We explored the contributions of microglia and astrocytes in patients with symptomatic sporadic AD stratified according to AT(N) system and APOE genotype. Methods: We compared the cerebrospinal fluid (CSF) levels of sTREM-2 and markers of astrocytic activation (GFAP; β-S100) from 71 patients with AD (23 A+T–,48 A+T+; 38 APOE ɛ3, 33 APOE ɛ4) and 30 healthy controls (HC). With multivariate analyses we investigated associations between glial biomarkers, Aβ42, and p-tau in all subgroups. Results: CSF sTREM-2 was higher in A+T+ [1.437 (0.264)] and A+T– [1.355 (0.213)] than in HC [1.042 (0.198); both p

Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). To expand our understanding of the molecular features underlying response to checkpoint inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including (1) favorable (for example, ATM altered) and unfavorable (for example, TERT amplified) genomic subgroups, (2) a prominent association between expression of inducible components of the immunoproteasome and response and (3) a dedifferentiated tumor-intrinsic subtype with enhanced response to checkpoint blockade. Taken together, results from this cohort demonstrate the complexity of biological determinants underlying immunotherapy outcomes and reinforce the discovery potential of integrative analysis within large, well-curated, cancer-specific cohorts.

Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide.Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected.Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity.Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes. Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide.Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected.Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity.Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes.

Abstract: A critical review was conducted to examine whether the peripheral hearing status of participants with neurological and psychological disorders was documented in published clinical studies of the auditory P300 response. Literature searches were conducted with three databases: PubMed, PsycINFO, and Scopus. Studies of participants with seven neurological or psychological disorders were included in the study. Each disorder was coupled with the main search phrase in separate searches on each database. Of the total 102 papers which met the inclusion criteria, the majority (64%) did not describe the peripheral hearing sensitivity of participants. In this review with studies that included participants at risk for hearing impairment, particularly age-related hearing loss, only a single publication adequately described formal hearing evaluation. Peripheral hearing status is rarely defined in studies of the P300 response. The inclusion of participants with a hearing loss likely affects the validity of findings for these studies. We recommend formal hearing assessment prior to inclusion of participants in studies of the auditory P300 response. The findings of this study may increase the awareness among researchers outside the field of audiology of the effects of peripheral hearing loss on the auditory P300.

La prescrizione dell’attività fisica, quando indicata, deve essere un compito imprescindibile del cardiologo, il quale deve fornire al paziente precise indicazioni su tipologia, frequenza, intensità e durata dell’esercizio da svolgere. Questa pratica è spesso trascurata nonostante i benefici dell’attività fisica in prevenzione primaria e secondaria siano ampiamente documentati. L’obiettivo di questo lavoro è di presentare un nuovo modello organizzativo per la prescrizione di esercizio fisico che coinvolge la figura professionale del chinesiologo dell’attività motoria preventiva ed adattata al fianco del cardiologo ambulatoriale.

Coronal shear fractures of the distal humerus are uncommon injuries representing 6% of distal humeral fractures. There is no univocal consensus about the correct management of this type of fracture. A national survey was conducted to gain more insight into the current classification, diagnosis and treatment of coronal shear fractures in Italy.A postal survey was sent to all AO Italian members including residency orthopaedic surgeons. The survey consisted of general questions about personal experience in the management of these fractures: types of classification systems used, surgical approaches, treatment options and rehabilitation programs.114 orthopaedic surgeons answered a 13-items questionnaire. The most used classification system was AO/OTA (72,8%). Independent screws and if necessary plates were the most answered regarding surgical treatment (81,6%). The most encountered post-surgical complication was stiffening of the elbow (81,6%).An algorithm of treatment has been proposed. To better classify coronal shear fractures, the authors recommended the integration of two classification systems: AO and Dubberley classifications. In the case of posterior wall comminution, a Kocher extensile approach is recommended, otherwise, if a posterior wall is intact, Kocher or Kaplan approach can be used. The posterior transolecranic approach can be reserved to Dubberley type III or AO 13B3.3. The best treatment choice is represented by independent screws and plates placed according to fracture patterns while arthroplasty is indicated when a stable ORIF is not possible. Mobilization is postponed for about 2 weeks.

Purpose: The aim of this study was to describe extended high-frequency (EHF) pure-tone audiometry monitoring of ototoxicity in a longitudinal treatment program for drug-resistant tuberculosis (DRTB). Method: This was a retrospective record review of longitudinal conventional (0.25–8 kHz) and EHF (9–16 kHz) audiometry for ototoxicity monitoring of DRTB patients undergoing treatment at community-based clinics between 2013 and 2017. Data from 69 patients with an average age of 37.9 years ( SD = 11.2, range: 16.0–63.8 years) were included. Patients were assessed by primary health care audiologists (87%) or community health workers (13%) using portable audiological equipment. The average length of time between initial and exit assessments was 84.6 days ( SD = 74.2, range: 2–335 days). Results: EHF ototoxicity of a mild or greater degree of hearing loss (> 25 dB HL in one or both ears across frequencies) was evident in 85.5% of patients' posttreatment, compared with 47.8% of patients across conventional frequencies. EHF audiometry demonstrated an ototoxic shift (American Speech-Language-Hearing Association criteria) in 56.5% of cases compared with 31.9% when only conventional audiometry was considered. Mean hearing deterioration for patients was significant across EHFs (9–16 kHz) bilaterally ( p < .05). Absent EHF thresholds at the initial assessment, owing to maximum output limits, was a limitation that occurred most frequently at 16 kHz (17.4%, 24/138). Conclusions: EHF audiometry is most sensitive for the early detection of ototoxicity and should be included in monitoring programs. Clinical ototoxicity monitoring protocols should consider shortened assessment approaches that target frequencies most sensitive to ototoxicity, including EHFs. Supplemental Material: https://doi.org/10.23641/asha.21651242

In recent years, there has been an increasing interest in the development of arthroplasty registries, therefore, in our country, the Italian Arthroplasty Registry (RIAP), was issued by the National Law No. 221/2012. In the last decade, however, some European countries -namely Sweden, Denmark, Norway, and Germany (in development)- have introduced another nationwide orthopaedic registry than arthroplasty registers: the fracture registry. The development of this new tool aims to improve quality and safety in fracture management, thus trying to provide a better postoperative quality of life in trauma patients. Based on these findings, the AO-Trauma Italy Council encouraged the development of a national fracture registry in Italy. The present study aims to (1) provide an overview of the fracture registries in Europe and (2) to develop, for the first time, a pilot Italian Fracture Registry (RIFra). Thirteen AO-Trauma Italy members, chairmen of Level-I orthopaedic and trauma centres, diffused throughout Italy, were involved in the RIFra project. The RIFra form, developed between November 2019 and March 2020, consists of 5 main sections, namely: epidemiologic data, previous surgical procedure (if any), patient and fracture features, surgical procedure, surgical implant details. This study constitutes the first step to start, in future years, the bureaucratic procedure leading to the final establishment of a RIAP-like fracture registry in Italy.

Periprosthetic femoral re-fractures (PFRFs) represent an emerging challenge for orthopaedic surgeons, since their incidence is growing in the last years, but very few experiences about their management have been currently published. The present study aims to (1) introduce, for the first time, an etiologic classification for PRFRs and (2) to provide surgical and pharmacological tips for the correct management of these injuries. Periprosthetic femoral re-fractures (PFRFs) could be classified into traumatic-PFRFs (T-PFRFs) and pathological-PFRFs (P-PFRFs). T-PFRFs, i.e. the "true" periprosthetic re-fractures, present as new fracture lines occurring proximally or distally to a previous periprosthetic fracture, that has correctly healed. They are generally unpredictable injuries but, in selected cases, it is possible to predict them by analyzing the construct used in the treatment of the previous periprosthetic fracture. P-PFRFs, on the other hand, define re-fractures occurring on a previous periprosthetic non-union or delayed union: the new fracture line appears in the same district of the old one. According to the etiologic factors influencing the P-PFRFs pathogenesis, it is possible to define re-fractures caused by mechanical failures, biological failures, septic failures and multifactorial failures, i.e., a combination of the previously mentioned concerns. A successful postoperative outcome, following the surgical management of PFRFs, requires the correct identification of all the underlying causes, which should be promptly and appropriately managed.

We report an observational, double-blind study that examined puppies’ behaviors while engaged in solving an experimental food retrieval task (food retrieval task instrument: FRTI). The experimental setting included passive social distractors (i.e., the dog’s owner and a stranger). The focus was on how the social and physical environment shapes puppies’ behaviors according to sex. The dependent variables were the number of tasks solved on an apparatus (Performance Index) and the time required to solve the first task (Speed). Sex and Stress were set as explanatory factors, and Social Interest, FRTI interactions, other behavior, and age as covariates. The main findings were that male puppies solved the first task faster than females. On the other hand, females displayed significantly more social interest and did so more rapidly than males. Males showed delayed task resolution. This study demonstrates sex differences in a problem-solving task in dog puppies for the first time, thus highlighting that sexually dimorphic behavioral differences in problem-solving strategies develop early on during ontogenesis.

This survey aimed to understand how far the Italian infectious diseases (ID) specialists are confident in the "Undetectable = Untransmittable" (U = U) message and translate this concept into clinical practice. An anonymous survey was distributed by e-mail to 286 clinicians to collect their opinions regarding six situations potentially at risk of HIV transmission between virologically suppressed patients and seronegative individuals who possibly require postexposure prophylaxis (PEP). Overall, 51% of ID specialists deemed zero risk of HIV transmission through condomless sex for undetectable patients. This answer was more frequent among HIV specialists (30% vs. 21%, p = .01) and clinicians working in teaching hospitals (35% vs. 16%, p = .03). Remarkably, 61% of participants would advise taking PEP for the HIV-negative partner in case of sexual intercourse with a seropositive person with a recent blip occurrence or absence of an HIV RNA test performed within the last 6 months (63%). Seventy-three percent of respondents deemed it essential to know patients' history of adherence to interpreting an HIV RNA test, regardless of its timing. When applying the U = U concept to daily clinical decisions, we observed an overall cautious attitude among physicians. Concerns mainly regarded the timing of the last HIV RNA test to the exposure event, especially in the absence of details on the patient's adherence. Wider diffusion and application of the U = U message are needed.

Introduction: Chronic pain is a distressing condition that should be treated in specialized pain clinics. Pain clinics offer a holistic, evidence-based approach, including pharmacological, complementary, and invasive treatments. This study aimed to provide preliminary information regarding chronic pain treatments and identify reasons for accessing an important hub-spoke pain clinic network. Methods: A retrospective multicenter cross-sectional study was carried out. A total of 1606 patients’ records were included. Patients were selected from the 26 pain clinics of a single region in Italy. Univariate and multivariate logistic regression models were used. Results: Multivariate models showed that the use of opioids were considered effective for severe or moderate pain [odds ratio (OR) 0.41; 95% 0.33–0.51], while the use of invasive treatments (OR 2.45; 95% 1.95–3.06) and the use of complementary therapy (OR 1.87; 95% 1.38–2.51) were associated with severe or moderate pain. Overall, age, sex, nonsteroidal anti-inflammatory drugs (NSAID) use, a combination of NSAIDs, complementary therapies, and a combination of opioids and invasive treatments did not seem to be significantly associated with the nature of pain. Multivariate models confirmed that clinical parameters such as the nature of pain, multi-diagnosis, more than one site of pain, treatments, and general practitioner, but not the severity of pain and use of invasive treatments, had an impact on the choice of a pain clinic. Conclusion: Opioids are useful in managing moderate or severe chronic pain. Multimodal approaches are used for the management of chronic pain. Moreover, it is not clear how patients are addressed to access different pain clinics (spoke versus hub) networks. More widespread adoption is needed for an interdisciplinary approach to managing chronic pain and adopting guideline recommendations, and rigorous research is required to provide more substantial evidence and support clinical practice.

Introduction: Several mobile health applications (MHAs) have been developed to assist and improve the quality of life of patients affected by premature ejaculation, but the scientific quality and adherence to guidelines are not yet addressed. Materials and methods: On 25 May 2022, we conducted a search in the Apple App Store and Google Play Store. We reviewed all mobile apps from Apple App Store and Google Play Store for premature ejaculation and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines. Results: In total 9 MHA were reviewed. All MHAs are geared towards the patient and provide information about diagnoses and treatment of PE. The mean score were 2.87, 3.69, 2.77, 2.55, 2.86 for Engagement, Functionality, Aesthetics, Information, and Subjective quality respectively. MHAs reported low and medium adherence to EAU guidelines. Conclusions: MHAs provide different services in many medical fields, including male sexual dysfunction. Their development is constantly increasing, but the problems of scientific validation, content, and quality are not yet solved. Much future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps.

Background Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. Methods We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. Results In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. Conclusions PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the “statin effect” of TDF.

The accumulation of fallout radionuclides (FRNs) from nuclear weapons testing and nuclear accidents has been evaluated for over half a century in natural environments; however, until recently their distribution and abundance within glaciers have been poorly understood. Following a series of individual studies of FRNs, specifically 137Cs, 241Am and 210Pb, deposited on the surface of glaciers, we now understand that cryoconite, a material commonly found in the supraglacial environment, is a highly efficient accumulator of FRNs, both artificial and natural. However, the variability of FRN activity concentrations in cryoconite across the global cryosphere has never been assessed. This study thus aims to both synthesize current knowledge on FRNs in cryoconite and assess the controls on variability of activity concentrations. We present a global database of new and previously published data based on gamma spectrometry of cryoconite and proglacial sediments, and assess the extent to which a suite of environmental and physical factors can explain spatial variability in FRN activity concentrations in cryoconite. We show that FRNs are not only found in cryoconite on glaciers within close proximity to specific sources of radioactivity, but across the global cryosphere, and at activity concentrations up to three orders of magnitude higher than those found in soils and sediments in the surrounding environment. We also show that the organic content of cryoconite exerts a strong control on accumulation of FRNs, and that activity concentrations in cryoconite are some of the highest ever described in environmental matrices outside of nuclear exclusion zones, occasionally in excess of 10,000 Bq kg−1. These findings highlight a need for significant improvements in the understanding of the fate of legacy contaminants within glaciated catchments. Future interdisciplinary research is required on the mechanisms governing their accumulation, storage, and mobility, and their potential to create time-dependent impacts on downstream water quality and ecosystem sustainability.

Sleep impairment is one of the most common comorbidities affecting people with epilepsy (PWE). The bidirectional relation between epilepsy and sleep has been widely established. Several studies investigated subjective sleep quality and daytime vigilance in PWE, highlighting frequent complaints of sleep fragmentation, difficulties in falling asleep, and daytime sleepiness. The present study aimed to deevaluate sleep structure in drug-naive PWE, distributed on the basis of epilepsy type, and compared to controls.This observational study included adult patients newly diagnosed with epilepsy and drug-naive as well as a control group of healthy subjects. All PWE and controls underwent a dynamic 24-hour EEG with signals for sleep recording in order to evaluate sleep architecture, structure, continuity and fragmentation.Twenty-four PWE were included and distributed in two groups based on epilepsy type. Eleven patients were included in the generalized epilepsy group (63.6% male; 34.91 ± 9.80 years) and 13 patients in the focal epilepsy group (53.8% male; 38.69 ± 12.74 years). The control group included 16 subjects (56.3% male; 32.75 ± 12.19 years). Patients with generalized or focal epilepsy had a significantly lower sleep efficiency than controls. Moreover, both patient groups presented the alteration of markers of sleep fragmentation and lack of continuity, with higher indices of sleep stage transitions and arousal. Finally, the two patient groups presented less REM sleep than controls.This study highlighted the alteration of sleep quality, continuity and stability in both patients with focal or generalized epilepsy compared to controls, also in the absence of ictal events. This sleep impairment resulted in the reduction of REM sleep. Therefore, these findings may be explained by the increase in awakenings and sleep stage shifts, which may be attributed to both sleep networks impairment and neurotransmission dysfunction in PWE, and also possibly triggered by paroxysmal interictal abnormalities.

In the hilly area of Gioia Tauro (Calabria, Southern Italy), lemon orchards are grown in consociation with centuries-old olive trees. Lemons are partially shaded by olive canopies and the microclimate at the level of their canopies is suitable for plants growth and quality productions. Under these conditions, lemon trees are grown even without irrigation, providing, despite this limitation, a quality product. This study aimed to i) investigate the qualitative characterisation of two clonal selections of the lemon cultivar Femminello, F. Siracusano (S) and F. Zagara bianca (ZB), from the described intercropping, on irrigated (I) and non-irrigated (NI) crops; ii) assess the quality preservation during cold storage, in order to evaluate the availability of lemons for marketing in a period of shortage such as the summer season. Fruits were harvested at commercial maturity, and cold stored at 10±1°C and RH 85-90%, for 60 days. Decay incidence, physiological disorders, weight loss, and the main physical-chemical parameters were assessed at harvest (T0) and every 15 days (T15, T30, T45, T60). The absence of decay and physiological disorders was observed throughout the 60-day storage period, in both clonal selections under the two management conditions. The weight loss was greater in fruits from irrigated lemon groves of both S and ZB. S_I showed significantly lower fruits weight and higher titratable acidity than S_NI. Total soluble solids and titratable acidity were statistically lower for ZB_I than for NI fruits.

One of the cornerstones for enhancing the patient safety culture is the incident reporting system (IRS). It is a process for detecting, reporting, collecting, and summarizing adverse events (AEs) and near-misses in healthcare, and so it represents a vital tool for clinical risk management. We analyzed the 5-year experience of a third-level hospital's IRSs, showing its trends and highlighting its main strengths and weaknesses. Patients’ falls and physical or verbal aggression toward the providers or between patients are the most reported events. Underreporting is the main limitation of the system, especially among nurses. Visible actions, forceful analysis of the reports, operators’ education, no-blame culture promotion, and organizational adjustments may improve operators’ adherence to IRS. Providers do not willingly inform patients’ relatives about fatal incidents. Despite that, the IRS is far from its potential, and the number of data collected has increased.

Imaging flow cytometry (IFC) combines conventional flow cytometry with optical microscopy, allowing for high-throughput, multi-parameter screening of single-cell specimens with morphological and spatial information.

The subsurface oxygen maximum (SOM) is observed in oligotrophic oceans and is associated with different physical and biological processes. This study characterizes the SOM in the Mediterranean Sea at the basin scale and investigates its driving mechanisms by analysing the output of the 1/24∘ resolution biogeochemical reanalysis provided by the Copernicus Marine Service for the 1999–2019 time period. We validated the model-derived oxygen concentration in the epipelagic layer at different spatial and temporal scales, including novel process comparisons with estimates from in situ observations. Moreover, using Biogeochemical Argo (BGC-Argo) float observations, we estimated the model uncertainty in reproducing the SOM concentration and depth in summer (13 mmol O2 m−3 and 13 m, respectively). The western and eastern Mediterranean Sea depicts different SOM signatures in summer, with higher oxygen values and shallower depths in the western Mediterranean. The concentrations and depths (in the ranges of 230–250 mmol O2 m−3 and 30–100 m, respectively) are in agreement with the estimations from the literature and show mesoscale variability patterns. The western Mediterranean also shows a stronger biological activity, specifically oxygen production and consumption, along the whole epipelagic layer and higher oxygen concentrations at the surface throughout the year, but heavy undersaturated waters are associated with winter deep convection in the northwestern Mediterranean Sea. A 1-year analysis conducted on selected areas that are representative of the heterogeneity of summer SOM highlighted that the SOM can actually be sustained by biological production (as in northwestern Mediterranean areas), or it can be a residual of the confinement of spring production (as in the central Ionian area) and vertical motions influence its depth (as in the Levantine subduction area).

INTRODUCTION: No previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values). METHODS: Embase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis. RESULTS: Of 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria. Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4-94; specificity 98.5-99; accuracy 97.2-97.7; PPV 88.9-99.1; NPV 95.8-98.9). CONCLUSIONS: Xpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance. Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB.

The apparent effect of superior semicircular canal dehiscence (SSCD) on middle ear- and cochlear impedance has led researchers to investigate the use of wideband acoustic immittance as a screening tool when SSCD is suspected. The purpose of the study was to describe the absorbance characteristics and tympanometric values of ears with confirmed SSCD measured at tympanometric peak pressure (TPP) and at ambient pressure.Wideband Acoustic Immittance was performed at ambient pressure and at TPP on ten participants (12 ears) with confirmed SSCD, as well as on an age- and gender matched control group (12 ears). Inferential statistics were used to determine whether statistical differences existed for the absorbance values at each of the averaged frequencies, the resonance frequency (RF) and tympanometric data between the SSCD and control groups.The mean absorbance of the SSCD group reached a maximum at 890.9 Hz and a minimum at 6349.6 Hz. When testing absorbance at TPP, a statistically significant increase/peak in the absorbance values of the SSCD group (compared to those of the control group) was found from 630 to 890.9 Hz and a decrease from 4489.8 to 6349.6 Hz. Similar patterns were observed for absorbance at ambient pressure. A lower mean RF for ears with SSCD as well as an increased mean admittance magnitude (AM) value at RF was found compared to those of the control group.The use of SSCD as a screening tool when SSCD is suspected was strengthened by results similar to those of previous studies. As a result of the significant difference in RF of SSCD ears compared to the RF of the control group, the potential value of measuring the RF of the middle ear to differentiate between mass-and stiffness dominated pathologies, was also illustrated.

Resumo Este artigo objetiva buscar no romance Dora Bruder (1997), de Patrick Modiano, o significado e a relevância do apagamento visual como recurso narrativo, materializado na ausência das imagens fotográficas e no uso da écfrase para tratar do trauma deixado pela perseguição e morte de judeus durante a Segunda Guerra Mundial. A opção do autor por negar ao leitor a exposição da menina judia desaparecida em Paris durante a ocupação alemã é a metáfora da eliminação, do apagamento, do silenciamento e da morte da memória social de um povo. Em resposta a essa amnésia imposta, a memória é usada como meio de interrogar um passado que se transforma em narrativa para permitir a reelaboração de experiências dolorosas tornadas mais compreensíveis porque dizíveis.

Objectives: The aim of this study was to assess the incidence of being overweight and metabolic syndrome (MS) among people living with HIV (PHIV) in three different cross-sectional studies conducted over three different periods: 2005, 2011 and 2015. Methods: This was a multi-centre, nationwide study. Data were collected in three studies from the CISAI group - SIMOne, HIV-HY and STOPSHIV - and included a total of 3014 PHIV. Logistic regression [odds ratio (OR), 95% confidence interval (CI)] was used to account for age and gender difference among three groups when comparing MS prevalence and being overweight; potential confounders were accounted for by including them in the regression equation. Results: Overall, the mean age was 46.9±10.2years, and men comprised 73.3% of participants. Comparing 2005, 2011 and 2015, MS was present in 34.5%, 33.0% and 29.3% of PHIV, respectively. Adjusted OR for MS was 0.64 (95% CI: 0.52-0.78) in 2011 and 0.56 (95% CI: 0.46-0.69) in 2015 compared with 2005, while BMI (kg/m2 ) increased from 23.6 in 2005, 24.5 in 2011 and 24.5 in 2015, with a concomitant increase of being overweight from 29.4% to 39.5% to 39.6% (p&nbsp

We report an observational, double-blind, experimental study that examines the effects of human emotional odors on puppies between 3 and 6 months and adult dogs (one year and upwards). Both groups were exposed to control, human fear, and happiness odors in a between subjects’ design. The duration of all behaviors directed to the apparatus, the door, the owner, a stranger, and stress behaviors was recorded. A discriminant analysis showed that the fear odor activates consistent behavior patterns for both puppies and adult dogs. However, no behavioral differences between the control and happiness odor conditions were found in the case of puppies. In contrast, adult dogs reveal distinctive patterns for all three odor conditions. We argue that responses to human fear chemosignals systematically influence the behaviors displayed by puppies and adult dogs, which could be genetically prefigured. In contrast, the effects of happiness odors constitute cues that require learning during early socialization processes, which yield consistent patterns only in adulthood.

There is increasing evidence that thyroid hormones (THs) work in an integrative fashion with androgen receptors (ARs) to regulate gonadal differentiation and reproductive function. Studies reveal that THs have interactions with the AR promoter region and increase AR expression. THs also have a role in the regulation of enzymes involved in the biosynthesis of androgens, such as 5α-reductase, which is essential in the conversion of testosterone into its active form, 5α-dihydrotestosterone. Additionally, the presence of androgen response elements (AREs) in the promoter regions of TH-related genes, such as deiodinases and thyroid hormone receptor isoforms have been identified in some vertebrates, indicating a mutual interaction between THs and ARs. Since the androgen signaling pathway, mediated by ARs, plays a key role in the formation and progression of prostate cancer (PCa), the existence of crosstalk between THs and ARs supports the epidemiologic and experimental evidence indicating a relationship between the high incidence of Prostate Cancer (PCa) and hyperthyroidism. This article aims to review the role of androgen-thyroid hormone crosstalk in PCa and its implication in the clinical management. As life expectancy is growing these days, it can increase the number of patients with PCa and the critical relevance of the disease. In order to gain better knowledge about PCa and to improve the clinical management, it is essential to get better insight into the key factors related to the formation and progression of this cancer.

A 6-month-old baby girl, with a history of 2 months of intensive care management and two episodes of cardiac arrest, was transferred from another European country to initiate the “Giessen approach” for end-stage heart failure in children. At the admission, left ventricular ejection fraction was 20%. Severe mitral valve regurgitation and severe left atrial dilatation were present. Right ventricular function was preserved, and tricuspid valve regurgitation was mild. As a result, the patient underwent surgical pulmonary artery banding. Additionally, unloading of the left atrium was achieved by implanting an 8 mm atrial flow regulator device through a hybrid per-atrial approach. Two months after the procedure, the patient was progressively weaned from the inotropes and transferred to the ward.

BACKGROUND Gastroenteropancreatic neuroendocrine tumors are often diagnosed when metastatic. The liver is the main site of metastases. Unfortunately, optimal management of neuroendocrine liver metastases remains a topic of debate. The aim of this study was to make a systematic review of the current literature about the results of the different treatments of neuroendocrine liver metastases. METHODS A systematic review was conducted for English language publications from 1995 to 2021. Outcomes were analyzed according to survival, disease-free survival, and in the case of systemic therapies, progression-free survival. RESULTS 5509 patients were analyzed in the review. 67% of patients underwent surgery achieving 5 years overall survival despite only 30% percent without a recurrence. 60% of patients that had received a transplant reached 5 years survival with a low disease-free survival rate (20%). Five-year survival rate was 36.2% for patients undergoing loco-regional therapies. CONCLUSION Surgical resection is the best treatment when metastases are resectable, with the highest rate of survival, although liver transplantation shows good results for patients not eligible for surgery. Loco-regional therapies may be useful when surgical resection is contraindicated, or selectively used as a bridge to surgery or transplantation. Systemic therapies are indicated in patients for whom curative treatment cannot be obtained.