Gender assessment through three-dimensional analysis of maxillary sinuses by means of Cone Beam Computed Tomography

OBJECTIVE: The availability of a low dose radiation technology such as Cone Beam Computed Tomography (CBCT) in dental practice has increased the number of scans available for forensic purposes. Moreover, specific software allows for three-dimensional (3D) characterization of the maxillary sinuses. This study was performed to determine whether sinus maxillary volumes can be useful to identify gender after validating the use of the Dolphin software as a tool for volumetric estimation of maxillary sinus volumes. PATIENTS AND METHODS: The validation was performed by four different operators measuring the volume of six phantoms, where the real volume was already known. The maxillary sinus volumes of 52 patients (26 males and 26 females) mean age 24.3 were calculated and compared between genders and sagittal skeletal class subdivision. The measurements for patients and phantoms were based on CBCT scans (ILUMA™) processed by Dolphin 3D software. RESULTS: No statistical difference was observed between the real volume and the volume measurements performed by the operators. No statistical difference was found in patient's maxillary sinus volumes between gender. CONCLUSIONS: Based on our results, it is not possible to support the use of maxillary sinuses to discern sexual difference in corpse identification

Suspected limited mobility of a Middle Pleistocene woman from Southern Italy: strontium isotopes of a human deciduous tooth

We present the Sr isotopic composition of enamel of the most ancient deciduous tooth ever discovered in Italy to assess human mobility in Middle Pleistocene. Reconstructing ancient mobility is crucial for understanding human strategy at exploiting temporally and spatially patchy resources, with most studies focusing on indirect evidences, ultimately affecting our interpretation on hominin territoriality and energetic costs invested by hominin groups. Here, we use the high spatial resolution and micro-destructivity options offered by the Laser Ablation Multi-Collector Inductively Coupled Plasma Mass Spectrometry technique, to determine the (87)Sr/ (86)Sr intra-tooth variability of a human deciduous incisor from the Middle Pleistocene layers of the Isernia La Pineta site (Italy). We compared these data with the Sr isotopic signature of local micro-mammals, the broadest home-range of the macro-mammals and with modern plant samples. Our study reveals that while macro-mammals have possibly migrated through the landscape for up to 50\u2009km, the pregnant woman from Isernia was probably local, given that the isotopic ratio of the enamel falls within the local range and is comparable with the signature of the local plants in a radius of 10\u2009km. This is the first case study of Sr isotopic composition determination in such ancient deciduous tooth

Trend of change of sperm count and concentration over the last two decades: A systematic review and meta‐regression analysis

Background: Since the 1970s, several studies found that sperm concentration (SC) and total sperm count (TSC) constantly worsened over time, mainly in high-income countries. Objectives: To evaluate whether the decreasing trend in sperm count is continuing in Western European countries and USA, we performed a systematic review and meta-regression analysis. Materials and methods: Embase and Pubmed/Medline were searched papers published in English in the 2000-2020 period limiting the search to data collected in the USA and Western European countries. Results: We identified 62 articles and pooled information on 24,196 men (range 10-2,523), collected from 1993 to 2018. Considering all the studies, random-effects meta-regression analyses showed no significant trend for SC (slope per year -0.07 mil/mL, p-value = 0.86). Negative trends of SC were detected in Scandinavian countries (slope per year -1.11 mil/mL, 95% CI: -2.40 to +0.19; p-value = 0.09), but the findings were statistically not significant. No significant trends of SC were detected in Central Europe (slope per year +0.23, 95% CI -2.51 to +2.96; p-value = 0.87), the USA (slope per year +1.08, 95% CI -0.42 to +2.57; p-value = 0.16), and Southern Europe (slope per year +0.19, 95% CI -0.99 to +1.37; p-value = 0.75). We have analyzed separately findings from studies including sperm donors, fertile men, young unselected men (unselected men, study mean age < 25 years) and unselected men (unselected men, study mean age ≥ 25 years). No significant trends of SC were observed among sperm donors (slope per year -2.80, 95% CI -6.76 to +1.17; p-value 0.16), unselected men (slope per year -0.23, 95% CI -1.58 to +1.12; p-value 0.73), young unselected men (slope per year -0.49, 95% CI -1.76 to +0.79; p-value 0.45), fertile men (slope per year +0.29, 95% CI -1.09 to +1.67; p-value 0.68). Discussion and conclusion: The results of this analysis show no significant trends in SC, in USA, and selected Western European countries

Characterization of AAV integrations and rearrangements from long and short reads with RAAVioli

Recombinant Adeno Associated Viral (rAAV)-based gene therapy (GT) applications have been successfully exploited for the treatment of several disorders. rAAV mainly remains episomal in the nucleus of transduced cells, however, numerous studies demonstrated integration of fragmented or full-length AAV DNA within the transduced cell genome where double-strand DNA breaks (DSBs) or nicks have occurred. Yet, preclinical studies revealed the occurrence of hepatocellular carcinoma and clonal expansion events consequent to rAAV insertions, posing safety concerns for their clinical use. However, bioinformatics tools able to identify AAV integration sites (IS) and characterize vector rearrangements are still missing. Here, we collected data from a humanized liver mouse model, where human primary hepatocytes have been transduced ex-vivo or in-vivo with a tomato expressing AAV. PCR amplicons or DNA fragments containing AAV vector portions were sequenced by both short paired- end and long reads and then analyzed by RAAVioli (Recombinant Adeno-Associated Viral IntegratiOn analysis), to characterize vector rearrangements and IS. Python and R scripts parse the alignments to identify IS and reconstruct rearrangements using CIGAR strings. We retrieved 811 and 370 IS from short paired-end Illumina reads and long PacBio reads respectively, confirming the higher efficiency of PCR-based approach in IS retrieval. The distribution of AAV IS was sparse in the human genome similarly in both datasets, and Albumin gene was the most targeted gene as expected. Furthermore, 32 ISs were in common between the two datasets, demonstrating the reliability of RAAVioli independently from sequencing platform adopted. Both datasets showed a similar percentage (~25%) of fragments with AAV rearrangements, however more than 2 rearrangements per fragment were retrieved only in long PacBio reads. Precision and accuracy of RAAVioli pipeline was assessed through simulated datasets obtaining scores >0.95 in IS identification and rearrangement characterization. These data demonstrated that RAAVioli is a comprehensive and flexible bioinformatic tool that can efficiently map AAV IS using long and short paired ends sequencing reads. These approaches are fundamental to characterize AAV integration and recombination events in gene therapy and gene editing applications, allowing and improving the assessment of safety in AAV studies

PARLOMA – A Novel Human-Robot Interaction System for Deaf-blind Remote Communication

Deaf-blindness forces people to live in isolation. Up to now there is no existing technological solution enabling two (or many) Deaf-blind persons to communicate remotely among them in tactile Sign Language (t-SL). When resorting to t-SL, Deaf-blind persons can communicate only with persons physically present in the same place, because they are required to reciprocally explore their hands to exchange messages. We present a preliminary version of PARLOMA, a novel system to enable remote communication between Deaf-blind persons. It is composed of a low-cost depth sensor as the only input device, paired with a robotic hand as output device. Essentially, any user can perform handshapes in front of the depth sensor. The system is able to recognize a set of handshapes that are sent over the web and reproduced by an anthropomorphic robotic hand. PARLOMA can work as a “telephone” for Deaf-blind people. Hence, it will dramatically improve life quality of Deaf-blind persons. PARLOMA has been designed in strict collaboration with the main Italian Deaf-blind associations, in order to include end-users in the design phase

Revision of previous Fontan connections to total extracardiac cavopulmonary anastomosis: A multicenter experience

AbstractBackground: Conversion to total extracardiac cavopulmonary anastomosis is an option for managing patients with dysfunction of a prior Fontan connection. Methods: Thirty-one patients (19.9 ± 8.8 years) underwent revision of a previous Fontan connection to total extracardiac cavopulmonary anastomosis at four institutions. Complications of the previous Fontan connection included atrial tachyarrhythmias (n = 20), progressive heart failure (n = 17), Fontan pathway obstruction (n = 10), effusions (n = 10), pulmonary venous obstruction by an enlarged right atrium (n = 6), protein-losing enteropathy (n = 3), right atrial thrombus (n = 2), subaortic stenosis (n = 1), atrioventricular valve regurgitation (n = 3), and Fontan baffle leak (n = 5). Conversion to an extracardiac cavopulmonary connection was performed with a nonvalved conduit from the inferior vena cava to the right pulmonary artery, with additional procedures as necessary. Results: There have been 3 deaths. Two patients died in the perioperative period of heart failure and massive effusions. The third patient died suddenly 8 months after the operation. All surviving patients were in New York Heart Association class I (n = 20) or II (n = 7), except for 1 patient who underwent heart transplantation. Early postoperative arrhythmias occurred in 10 patients: 4 required pacemakers, and medical therapy was sufficient in 6. In 15 patients, pre-revision arrhythmias were improved. Effusions resolved in all but 1 of the patients in whom they were present before revision. The condition of 2 patients with protein-losing enteropathy improved within 30 days. Conclusions: Conversion of a failing Fontan connection to extracardiac cavopulmonary connection can be achieved with low morbidity and mortality. Optimally, revision should be undertaken early in symptomatic patients before irreversible ventricular failure ensues. (J Thorac Cardiovasc Surg 2000;119:340-6

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT

SARS-CoV-2 vaccination modelling for safe surgery to save lives : data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.Peer reviewe

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p