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ABSTRACT The use of clinically validated human papillomavirus (HPV) assays is recommended in cervical cancer screening, and extended genotyping is getting attention as a triage biomarker because of the different oncogenic risk of the high-risk HPV genotypes. We compared the results of the Becton & Dickinson (BD) Onclarity HPV assay, on the residual baseline cervico-vaginal specimens of the NTCC2 trial, to those of the screening HPV-DNA assay (Cobas 4800 or HC2) and to cytology, p16/ki67 and E6/E7 mRNA triage results. We genotyped virtually all HPV-positive women and a consecutive sample of HPV-negatives. Among the 3,129 baseline-positives, 75.5% (k = 0.368) were BD-positive, as were 5 of the 333 baseline-negatives (1.5%). The concordance between BD and HPV-DNA screening test was 87% for Cobas (1,250/1,436) and 65.9% for HC2 (1,115/1,693). A higher than the recommended positivity threshold for Onclarity would increase the agreement but would not improve concordance in the overall screening population. Among the baseline-positive cases, we observed an increasing trend of BD positivity with cytology severity (from 71.6% in negative for intraepithelial lesion of malignancy to 95.1% in ASC-H+ samples), with histologically confirmed CIN3 (96.9%), with p16/ki67 dual staining positivity (90.9% among the positive and 69.6% among the negative specimens), and with E6/E7 mRNA positivity (93.4% in the mRNA-positive cases vs 39.7% among the mRNA-negatives). Our findings confirm some disagreement among different HPV assays used for screening. Nevertheless, the agreement is substantial for women with high-grade cytology, histologically confirmed CIN3, and p16/ki67 or mRNA positivity at triage, thus confirming a good clinical performance of all the tests used.The NTCC2 trial is registered as Clinicaltrials.gov identifier NCT01837693.IMPORTANCELarge randomized clinical trials have demonstrated that human papillomavirus (HPV) testing for high-risk types is more effective than cytology in detecting pre-cancerous lesions and preventing cervical cancer. Its use is being implemented in cervical cancer screening in several countries. The most recent guidelines recommend a risk-based management. It is therefore important to assess the individual risk of having/developing high-grade lesions of women testing high-risk HPV-positive. A crucial viral factor influencing the risk is the HPV genotype since different types are associated to different carcinogenetic risks. Understanding the degree of concordance among different assays targeting either HPV presence/type(s) or cellular morphology and proteins’ expression provides knowledge useful to better define how these tests can be used in screening protocols for an effective triage and to anticipate the possible implementation issues. Our study shows that the concordance between tests is higher when the infections have a higher probability of producing a clinically relevant lesion.

IntroductionSurgical-related injuries are frequent, in fact the reported percentage of musculoskeletal disorders in surgeons is between 47% and 87%. These conditions are caused by long periods of standing, incorrect postures, repeated movements, little rest between operations, the lack of integrated operator rooms, the correct number and arrangement of monitors and the use of non-ergonomic instruments. This survey aims to assess the Italian overview both highlighting how prevalent surgical-related injury is in our surgeons and whether there is an operating room ergonomics education program in Italian surgical specialty schools.MethodsAn anonymous questionnaire was designed through SurveyMonkey© web application. This survey was composed of 3 different sections concerning the general characteristics of the participants, their surgical background and any training performed, and any injuries or ailments related to the surgical activity. The survey was carried out in the period 1th of December 2022 and the 6th of February 2023.ResultsAt the close of our survey, 300 responses were collected. Among the participants, the two most represented specialties were Gynecology and Obstetrics (42.3%) and General Surgery (39.7%) and surgeons were mainly employed in the Northern regions of Italy (54.8%). Analyzing the participants’ background, 61.7% of the respondents had laparoscopic training during their training and only 53.1% had a pelvic trainer during their residency. In accordance with 98.7% of the respondents, during surgery we have the feeling of being in an uncomfortable position that causes discomfort or muscle pain, and regarding the frequency of these discomforts, the majority of our study population experiences these problems monthly (46.2%), while in 29.6% it is experienced weekly, 12.1% annually and finally 12.1% daily. The surgical approach that is most correlated with these disorders is laparoscopy (62.7%) while the one that causes the least discomfort is robotic surgery (1.4%). These discomforts cause 43.9% of our population to take a break or do short exercises to reduce pain during surgery, and the body areas most affected are the back (61.6%), neck (40.6%) and shoulders (37.8%).ConclusionDespite this, our survey allows us to highlight some now-known gaps present in the surgical training program of our schools and the lack of protection toward our surgeons during their long career.

Groin hernia repair is the most common procedure performed by general surgeons. The open mesh technique generally represents the main technique for an inguinal repair, but a different approach is often required. Laparoscopy was found to be the answer to minimizing the impact of the preperitoneal open techniques described by Nyhus and Stoppa. The introduction of the totally extraperitoneal hernia repair (TEP) and transabdominal preperitoneal repair (TAPP) in the early 1990s started a new chapter in groin hernia surgery. The minimally invasive techniques vs. open mesh, and then one against the other, soon became a hot topic among abdominal wall surgeons. With time, the number of procedures and indications increased and are still increasing. This review aims to provide an overview of the two main laparoscopic techniques for groin hernia repair, answering the following questions: Who should perform them? What is the learning curve required to minimize complications and optimize operative time? When is a minimally invasive approach indicated, and which one (both in elective and in emergency setting)? How are they performed? The standard techniques have been described in detail, and personal observations from an abdominal wall surgery referral center were added. The main reviews from the early 2000s up to date, which compared the techniques, were analyzed, and the results reported, confirming the comparable safety and efficacy of both these techniques.

Summary: Background: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. Methods: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. Findings: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. Interpretation: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years. Funding: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support.

Dietary patterns high in fat and sugar promote brain dysfunction, but the preventive efficacy of probiotics has been little explored. This study investigated whether the administration of Limosilactobacillus reuteri DSM 17938 (L.reuteri; 108 CFU/day) counteracts cognitive dysfunction and brain redox unbalance induced in male Wistar rats fed a western diet (WD) for 8 weeks.The results showed that L. reuteri prevented the WD-associated impairment in brain memory function, as evaluated by NOR test, and consistently increased specific molecular markers of synaptic plasticity. The condition of oxidative stress induced by WD, namely enhanced oxidation to proteins and lipids, increased oxidants-producing enzymes as well as reduced nuclear Nrf2 and Nrf2-dependent antioxidant enzymes, was ameliorated by the probiotic. Unexpectedly, mitochondria displayed a diet-induced increase in oxidative capacity, not modified by the probiotic. A protective effect of the probiotic on gut absorption of fructose and its further delivery to brain was evidenced as mechanism involved in cortex redox homeostasis. These findings evidence the potential utility of L. reuteri against WD-induced brain dysfunction and implicate the Nrf2 pathway as a potential mechanism for this effect.

Abstract We show that holographic thermal two-sided two-point correlators take the form of a product over quasi-normal modes (QNMs). Due to this fact, the two-point function admits a natural dispersive representation with a positive discontinuity at the location of QNMs. We explore the general constraints on the structure of QNMs that follow from the operator product expansion, the presence of the singularity inside the black hole, and the hydrodynamic expansion of the correlator. We illustrate these constraints through concrete examples. We suggest that the product formula for thermal correlators may hold for more general large N chaotic systems, and we check this hypothesis in several models.

Background: The present study was conducted to evaluate the impact of enhanced recovery after surgery (ERAS) pathway in patients undergoing laparoscopic adrenalectomy (LA) for primary and secondary adrenal disease, in reducing the length of primary hospital stay and return to daily activities. Materials and Methods: This retrospective study was carried out on 61 patients who underwent LA. A total of 32 patients formed the ERAS group. A total of 29 patients received conventional perioperative care and were assigned as the control group. Groups were compared in terms of patient's characteristics (sex, age, pre-operative diagnosis, side of tumour, tumour size and co-morbidities), post-operative compliance (anaesthesia time, operative time, post-operative stay, post-operative numeric rating scale (NRS) score, analgesic assumption and days to return to daily activities) and post-operative complications. Results: No significant differences in anaesthesia time (P = 0.4) and operative time (P = 0.6) were reported. NRS score 24 h postoperatively was significantly lower in the ERAS group (P < 0.05). The analgesic assumption in post-operative period in the ERAS group was lower (P < 0.05). ERAS protocol led to a significantly shorter length of post-operative stay (P < 0.05) and to return to daily activities (P < 0.05). No differences in peri-operative complications were reported. Discussion: ERAS protocols seem safe and feasible, potentially improving perioperative outcomes of patients undergoing LA, mainly improving pain control, hospital stay and return to daily activities. Further studies are needed to investigate overall compliance with ERAS protocols and their impact on clinical outcomes.

Abstract We study the analytic structure of the heavy-heavy-light-light holographic correlators in the supergravity approximation of the AdS3 × S 3/CFT2 duality. As an explicit example, we derive the correlator where the heavy operator is a classical microstate of the 5D supersymmetric black hole and its dual geometry interpolates as a function of a continuous parameter between global AdS3 and the extremal BTZ black hole. The simplest perturbation of this interpolating geometry by a light field is described by the Heun equation and we exploit the relation of its connection coefficients to the Liouville CFT to analytically compute the correlator in the two limits, focusing in particular on the black hole regime. In this limit we find that the real poles of the correlator become dense and can be approximated by a cut. We show that, when the charges of the heavy state are in the black hole regime, the discontinuity across the cut has complex poles corresponding to the quasi-normal modes of BTZ. This behaviour is qualitatively similar to what is expected for the large central charge limit of a typical black hole microstate.

Byline: Giulio. Lelli, Alessandra. Micalizzi, Angelo. Iossa, Alessia. Fassari, Antonio. Concistre, Francesco. Circosta, Luigi. Petramala, Francesco. De Angelis, Claudio. Letizia, Giuseppe. Cavallaro Background: The present study was conducted to evaluate [...]

Abstract Exposure to extreme temperatures can negatively affect animal reproduction, by disrupting the ability of individuals to produce any offspring (fertility), or the number of offspring produced by fertile individuals (fecundity). This has important ecological consequences, because reproduction is the ultimate measure of population fitness: a reduction in reproductive output lowers the population growth rate and increases the extinction risk. Despite this importance, there have been no large‐scale summaries of the evidence for effect of temperature on reproduction. We provide a systematic map of studies testing the relationship between temperature and animal reproduction. We systematically searched for published studies that statistically test for a direct link between temperature and animal reproduction, in terms of fertility, fecundity or indirect measures of reproductive potential (gamete and gonad traits). Overall, we collated a large and rich evidence base, with 1654 papers that met our inclusion criteria, encompassing 1191 species. The map revealed several important research gaps. Insects made up almost half of the dataset, but reptiles and amphibians were uncommon, as were non‐arthropod invertebrates. Fecundity was the most common reproductive trait examined, and relatively few studies measured fertility. It was uncommon for experimental studies to test exposure of different life stages, exposure to short‐term heat or cold shock, exposure to temperature fluctuations, or to independently assess male and female effects. Studies were most often published in journals focusing on entomology and pest control, ecology and evolution, aquaculture and fisheries science, and marine biology. Finally, while individuals were sampled from every continent, there was a strong sampling bias towards mid‐latitudes in the Northern Hemisphere, such that the tropics and polar regions are less well sampled. This map reveals a rich literature of studies testing the relationship between temperature and animal reproduction, but also uncovers substantial missing treatment of taxa, traits, and thermal regimes. This database will provide a valuable resource for future quantitative meta‐analyses, and direct future studies aiming to fill identified gaps.

Background: There is still no consensus on perioperative pain control techniques in patients undergoing laparoscopic surgery; protocols of conventional therapy can be improved by the use of perioperative anaesthesiologic techniques, such as epidural or loco-regional analgesic administration as transversus abdominis plane (TAP) block. The aim of this evaluation was to investigate the role of laparoscopic-assisted TAP block during repair of diastasis recti associated with primary midline hernias in term of post-operative pain relief. Materials and Methods: This was a retrospective evaluation of a prospectively maintained database including patients undergoing laparoscopic repair of diastasis recti associated with primary ventral hernia. Patients were divided into two groups: Group A patients (n = 34) received laparoscopic-assisted bilateral TAP-block of 7.5 mg/ml ropivacaine for each side and Group B patients (n = 29) received conventional post-operative therapy. All patients received 24 h infusion of 20 mg morphine; pain was checked at 6, 24 and 48 h after surgery by numeric rating scale (NRS) score. A rescue analgesia by was given if NRS score was >4 or on patient request. Results: No differences in operative time, complications and post-operative stay, no complications related to TAP-block technique were found. Post-operative pain scores (determined by NRS) were found to be significantly different between groups. Group A patients showed a significant reduction in NRS score at 6, 24 and 48 h (P < 0.005) and in the number of patients requiring further analgesic drugs administration (P < 0.005) compared to Group B patients. Conclusions: Laparoscopic-guided TAP-block can be considered safe and effective in the management of post-operative pain and in the reduction of analgesic need in patients undergoing laparoscopic repair of diastasis recti and ventral hernias. The non-randomised nature of the study and the lack of a consistent series of patients require further evaluations.

IntroductionMicroencapsulation of probiotic bacteria is an efficient and innovative new technique aimed at preserving bacterial survival in the hostile conditions of the gastrointestinal tract. However, understanding whether a microcapsule preserves the effectiveness of the bacterium contained within it is of fundamental importance.MethodsMale Wistar rats aged 90 days were fed a control diet or a Western diet for 8 weeks, with rats fed the Western diet divided into three groups: one receiving the diet only (W), the second group receiving the Western diet and free L. reuteri DSM 17938 (WR), and the third group receiving the Western diet and microencapsulated L. reuteri DSM 17938 (WRM). After 8 weeks of treatment, gut microbiota composition was evaluated, together with occludin, one of the tight junction proteins, in the ileum and the colon. Markers of inflammation were also quantified in the portal plasma, ileum, and colon, as well as markers for gut redox homeostasis.ResultsThe Western diet negatively influenced the intestinal microbiota, with no significant effect caused by supplementation with free and microencapsulated L. reuteri. However, L. reuteri, in both forms, effectively preserved the integrity of the intestinal barrier, thus protecting enterocytes from the development of inflammation and oxidative stress.ConclusionFrom these whole data, it emerges that L. reuteri DSM 17938 can be an effective probiotic in preventing the unhealthy consequences of the Western diet, especially in the gut, and that microencapsulation preserves the probiotic effects, thus opening the formulation of new preparations to be able to improve gut function independent of dietary habits.

This review focuses on ablative techniques for small renal masses (SRMs), including radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), and irreversible electroporation (IRE), and discusses recurrence management. Through an extensive literature review, we outline the procedures, outcomes, and follow-up strategies associated with each ablative method. The review provides a detailed examination of these techniques—RFA, CA, MWA, and IRE—elucidating their respective outcomes. Recurrence rates vary among them, with RFA and CA showing comparable rates, MWA demonstrating favorable short-term results, and IRE exhibiting promise in experimental stages. For managing recurrences, various strategies are considered, including active surveillance, re-ablation, or salvage surgery. Surveillance is preferred post-RFA and post-CA, due to slow SRM growth, while re-ablation, particularly with RFA and CA, is deemed feasible without additional complications. Salvage surgery emerges as a viable option for larger or resistant tumors. While ablative techniques offer short-term results comparable to surgery, further research is essential to understand their long-term effects fully. Decisions concerning recurrence management should consider individual and tumor-specific factors. Imaging, notably contrast-enhanced ultrasounds, plays a pivotal role in assessing treatment success, emphasizing the necessity of a multidisciplinary approach for optimal outcomes. The lack of randomized trials highlights the need for further research.

Since the 2018 revision of the Posting of Workers Directive, the debate on posting has once again been heated. The spark comes particularly from disputes concerning cross-border mobility of highly mobile workers employed in transnational logistics services (Dobersberger, FNV, Rapidsped, and to a different extent Gruber and Samidani and AFMB). In this set of case law, the Court of Justice of the EU had to consider whether or not, and to what extent, the workers in question should be considered posted workers. Thus, the case law came to revolve around the spatial and territorial attributes, and the cross-border nature of the work performed. By resorting to the analytical tools provided by legal geography, and in particular to the concept of ‘chronotopes of law’ elaborated by Mariana Valverde, the aim of this piece is to reflect upon assumptions and implications of the aforementioned rulings with a view of discussing both structural and contingent elements that possibly favour exploitation of posted work in the transnational logistics industry.