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Abstract We introduce a purely geometric formulation for two different measures addressed to quantify the entanglement between different parts of a tripartite qubit system. Our approach considers the entanglement–polytope defined by the smallest eigenvalues of the reduced density matrices of the qubit-components. The measures identify global and genuine entanglement, and are respectively associated with the projection and rejection of a given point of the polytope on the corresponding biseparable segments. Solving the so called ‘inverse problem’, we also discuss a way to force the system to behave in a particular form, which opens the possibility of controlling and manipulating entanglement for practical purposes.

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods:Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 coun-tries were analyzed descriptively, with a Delphi process used for expert recommendations. Results:Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoosper-mia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differ-entiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions:Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Purpose: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele. Materials and Methods: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist. Results: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p

Purpose: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and metaanalysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). Materials and Methods: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). Results: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD –1.125, 95% confidence interval [CI] –1.410, –0.840; p

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intraperson before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. Materials and Methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. Results: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). Conclusions: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method.Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Purpose: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. Materials and Methods: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). Results: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p

Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several “omics” technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its “Middle Ages” to its “Renaissance”, a golden age of andrology.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS. Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines. Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair. Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.

Purpose: This study provides a comprehensive analysis of research trends on the etiology, mechanisms, potential risk factors, diagnosis, prognosis, surgical and non-surgical treatment of varicocele, and clinical outcomes before and after varicocele repair. Materials and Methods: Varicocele studies published between 1988 and 2020 were retrieved from the Scopus database on April 5, 2021. Original studies on human varicocele were included, irrespective of language. Retrieved articles were manually screened for inclusion in various sub-categories. Bibliometric data was subjected to scientometric analysis using descriptive statistics. Network, heat and geographic mapping were generated using relevant software. Results: In total, 1,943 original human studies on varicocele were published. These were predominantly from the northern hemisphere and developed countries, and published in journals from the United States and Germany. Network map analysis for countries showed several interconnected nodal points, with the USA being the largest, and Agarwal A. from Cleveland Clinic, USA, being a center point of worldwide varicocele research collaborations. Studies of adolescents were underrepresented compared with studies of adults. Studies on diagnostic and prognostic aspects of varicocele were more numerous than studies on varicocele prevalence, mechanistic studies and studies focusing on etiological and risk factors. Varicocele surgery was more investigated than non-surgical approaches. To evaluate the impact of varicocele and its treatment, researchers mainly analyzed basic semen parameters, although markers of seminal oxidative stress are being increasingly investigated in the last decade, while reproductive outcomes such as live birth rate were under-reported in the literature. Conclusions: This study analyzes the publication trends in original research on human varicocele spanning over the last three decades. Our analysis emphasizes areas for further exploration to better understand varicocele’s impact on men’s health and male fertility.

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the im-mune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relation-ship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this ar-ticle, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for as-sessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are pre-sented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility.

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management.

Abstract Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and z-score data obtained at Dual-Energy X-ray Absorptiometry (DXA) during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced z-score at DXA (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z-score (p

Introduction: The use of platelet-rich plasma is a very useful procedure in complex lesions when epithelialization is achieved by this condition. Objective: To determine the clinical characteristics of patients treated with heterologous platelet-rich plasma as an alternative treatment in avulsive wounds. Method: An observational descriptive study was carried out. The universe consisted of 27 patients with a diagnosis of avulsive wound; 19 injured patients who met the inclusion criteria were chosen. The variables age, sex, causes of avulsive lesions, start of treatment, healing time, adverse reactions and evolution of treatment were analyzed. Absolute frequencies, percentage and ratio were used as a summary measure. Results: The male sex predominated with 68.4 %, at a ratio of 4:1.8 men per women. It is observed with a higher incidence between 18-30 years, for 47.37 %. The cause of injury was motorcycle accidents with 52.6 %. The patients had an excellent response to treatment with very rapid healing for 58.0 % of the total, with a favorable clinical course after 30 days of treatment for 89.47 %. Conclusions: Avulsive wounds predominated in males, and a high frequency is observed in youth. It is related to motorcycle accidents. Early treatment allows an excellent healing response, presenting a favorable evolution. Adverse reactions are minimal.

Introduction: Long bone fractures are common; among them the tibia presents a high incidence. They are not only common, but often difficult to treat. Its subcutaneous location causes complications such as open fractures, pseudoarthrosis and defective consolidations. Objective: To determine the clinical-epidemiological characteristics of patients with open fracture of the tibia treated with external fixation. Method: A cross-sectional descriptive study was carried out. The universe consisted of 134 patients with a diagnosis of open fracture of the tibia. Sixty-four injured patients who met the inclusion criteria were chosen. The variables age, sex, etiology, anatomical location, classification and fracture line were analyzed, in addition to the type of external fixator used and complications. Results: The most affected age group was 28-37 years old, with 60.9 % of the total. There was a predominance of the male sex for 95.3 %. The car accident prevailed as the cause of the injury with 54.7 %. The Ilizarov external fixator is the most used model for 89.7 % to treat open fracture of the tibia and associated complications. Conclusions: The open fracture of the tibia predominates in males between the third and fourth decade of life; traffic accidents are the main cause of this traumatic injury, and the Ilizarov external fixator is the most widely used model for treating open tibial fractures and associated complications.

Introducción: El uso de plasma rico en plaquetas resulta un procedimiento de mucha utilidad en lesiones complejas al lograrse la epitelización. Objetivo: Determinar las características clínicas de los pacientes tratados con plasma rico en plaquetas heterólogo, como tratamiento alternativo en heridas avulsivas. Método: Se realizó un estudio observacional descriptivo. El universo estuvo constituido por 27 pacientes con diagnóstico de herida avulsiva. Se escogió a 19 lesionados que cumplieron con los criterios de inclusión. Se analizaron las variables edad, sexo, causas de lesiones avulsivas, inicio del tratamiento, tiempo de cicatrización, reacciones adversas y evolución del tratamiento. Se utilizaron frecuencias absolutas, el porcentaje y la razón como medidas resumen. Resultados: Predominó el sexo masculino con un 68,4 %, a razón de 4:1,8 hombres por mujer. Se observa con mayor frecuencia entre los 18 y 30 años, para un 47,37 %. La causa de lesión fueron los accidentes de motocicletas, con 52,6 %. Los pacientes tuvieron una excelente respuesta al tratamiento con una cicatrización muy rápida para el 58,0 % del total, con evolución clínica favorable a los 30 días de tratamiento para un 89,47 %. Conclusiones: Las heridas avulsivas predominan en el sexo masculino, con mayor frecuencia en la juventud. Se relaciona con los accidentes en motocicletas. El tratamiento precoz permite una excelente respuesta de cicatrización, presenta una evolución favorable. Las reacciones adversas son mínimas.

In 2019, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is transmitted via the airborne route, caused a new pandemic namely, “coronavirus disease 2019” (COVID-19). Although the effectiveness of face masks to prevent the transmission of SARS-CoV-2 is debated, no study has evaluated the virus-blocking efficacy of masks used by patients. We aimed to evaluate this efficacy of masks used by SARS-CoV-2-infected individuals. Data, masks used, and nasopharyngeal swab samples were obtained from these patients. Forty-five paired samples of nasopharyngeal swabs and masks were obtained and processed; the majority of masks were woven. Viral RNAs were amplified using quantitative reverse‐transcription polymerase chain reaction and detected only on the inner parts of masks. Median viral load (VL) values of swabs and masks were 1.954x106 and 2,51x103, respectively. Statistically, there was a difference of approximately 1000 RNA copies/mL between swabs and masks and no significant difference in VL values among different types of masks. There were statistically significant differences in VL values between men and women and between symptomatic and asymptomatic patients. Our findings suggest the blocking of virus transmission by different types of masks and reinforce the use of masks by both infected and non-infected individuals.

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing with various household disinfection products (Soap powder, Lysoform®, Hypochlorite sodium and 70% Alcohol), rinse numbers, and exposure times. Afterward, the fabrics were washed in sterile water, and viral RNA was extracted and amplified using RT-qPCR. Finally, viral replication in cell cultures was examined. Our findings show that all biocidal treatments successfully disinfected the tissue tested. Some products showed less reduction in viral loads, such as soap powder (1.60 × 104, 1.04 × 103), soap powder and Lysoform® (1.60 × 104, 1.04 × 103), and alcohol 70% (1.02 × 103, 5.91 × 101), respectively. However, when sodium hypochlorite was used, this reduction was significantly increased (viral inactivation in 100% of the washes). After the first wash, the reduction in the number of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51,759, p < 0.05). In conclusion, the role of sodium hypochlorite in cloth mask disinfection may also have implications for future health emergencies as well as recommendation by WHO.

With the development of SARS-CoV-2 vaccines, many authors started evaluating the immunization efficacy of the available vaccines mainly through sero-positivity tests or by a quantitative assessment of the IgG against the spike protein of SARS-CoV-2 virus in vaccinated subjects. In this work, we compared the titers resulting from vaccination and tried to understand the potential factors affecting the immune response to the available SARS-CoV-2 vaccines. This study was conducted on 670 volunteers employed at the University of Pisa and undergoing a health surveillance program at the University Hospital of Pisa. For each participant, 10 mL of blood, information about contacts with confirmed cases of COVID-19, age, sex, SARS-CoV-2 vaccination status, previous SARS-CoV-2 infection and symptoms, type of vaccine and the date of administration were collected. In the multivariate analysis, the type of vaccine, the presence of symptoms in SARS-CoV-2 positive individuals, and the distance from the second dose significantly affected the antibody titer; the combined vaccination resulted in a faster decay over time compared with the other types of vaccination. No significant differences were observed between Spikevax and Comirnaty (p > 0.05), while the antibody levels remain more stable in subjects undergoing Vaxzevria vaccination (p < 0.01) compared with mRNA-based ones.

Abstract Several of the identified genetic factors in Amyotrophic Lateral Sclerosis (ALS) point to dysfunction in RNA processing as a major pathogenic mechanism. However, whether a precise RNA pathway is particularly affected remains unknown. Evidence suggests that FUS, that is mutated in familial ALS, and SMN, the causative factor in Spinal Muscular Atrophy (SMA), cooperate to the same molecular pathway, i.e. regulation of alternative splicing, and that disturbances in SMN-regulated functions, either caused by depletion of SMN protein (as in the case of SMA) or by pathogenic interactions between FUS and SMN (as in the case of ALS) might be a common theme in both diseases. In this work, we followed these leads and tested their pathogenic relevance in vivo. FUS-associated ALS recapitulates, in transgenic mice, crucial molecular features that characterise mouse models of SMA, including defects in snRNPs distribution and in the alternative splicing of genes important for motor neurons. Notably, altering SMN levels by haploinsufficiency or overexpression does not impact the phenotypes of mouse or Drosophila models of FUS-mediated toxicity. Overall, these findings suggest that FUS and SMN functionally interact and that FUS may act downstream of SMN-regulated snRNP assembly in the regulation of alternative splicing and gene expression.

Introduction: The association of adhesive systems and desensitising agents could influence the values of the bond strength. That is because these desensitising agents cause the obliteration of the tubular holes and minimise the movement of the dentin fluids, promoted by environmental stimulus that tends to cause hydrolysis at the base of the hybrid layer over time. Aim: To evaluate the microtensile bond strength of total-etch (Single Bond II, SB, 3M ESPE, USA) and self-etch (Clearfil SE Bond, SE, Kuraray, Japan) adhesive systems in dentin conditioned after the application of oxalate-based and fluoridebased desensitising agents. Materials and Methods: Discs obtained from human molars were used, which had its occlusal enamel removed to expose flat surfaces of dentin. Six groups were formed, according to the materials used: G1 (control)- hybridization with SB; G2- desensitizer based on oxalate (BisBlock, BB) and SB; G3- desensitizer based on fluoride (Aqua Prep F, AF) and SB; G4 (control)- hybridization with SE; G5- BB and SE; G6- AF and SE. On these surfaces, blocks of composite resin Filtek Z350 of 5 mm high were prepared to obtain sticks of (1×1×10 mm). The samples were stored in deionized water at 37°C for 24h and submitted to microtensile mechanical trial at 1mm/min speed till the fracture. The results were statistically analysed by one-way ANOVA followed by Tukey’s post hoc test (p0.05). Regarding the fractures analysis, the mixed type prevailed. The fracture was on the base region of the hybrid layer for the totaletch adhesive system, and at the top of the hybrid layer for the self-etch system. Conclusion: There is no significant difference in bond strength between the combined use of desensitizers with total-etch and self-etch adhesive systems on human dentine.

Introduction: Loss of HBsAg is observed in only 3-4% of patients who receive interferon for chronic HBV+HCV hepatitis, and there are few reports of HBsAg loss induced by treatments other than interferon. We report a case of chronic HBV+HCV hepatitis, in which a positive outcome was achieved with a new therapeutic strategy. Case report: The patient was a 49-year-old Caucasian woman found to be HBsAg+ in 1978 and HCVAb+ in 1997. During 2000-2003, the patient had markedly increased AST/ALT, histology grade 5, stage 1 (Ishak) disease with HBsAg positivity, HBV-DNA 1,450 cp/mL, HCV-RNA 7.57x105 IU/mL (genotype 1b). In May 2003 she began a 48-week course of PEG-IFNa2b (80 mg/week) without ribavirin. The latter drug was not used because it had recently been observed that in some HBV/HCV-coinfected patients treated with the two drugs, the hepatic flares preceding the seroconversion to HBsAb caused fulminant liver failure. Neither the HBV and HCV infections responded to this treatment, but during follow-up the HBV-DNA dropped to 40 cp/mL and the patient presented persistently normal transaminase values (6th month) followed by loss of HBsAg (24th month) and the appearance of anti-HBs (36th month). By December 2008, the HBV negativity and HBsAg/anti-HBs seroconversion were well-established, but HCV replication persisted. The decision was therefore made to administer PEG-IFNa2a (180 mg/week) and ribavirin (1,000 mg/day). There was no evidence of an RVR or EVR, so therapy was continued for 48 weeks. At the scheduled 12-month treatment, the patientwas found to be HCV-RNA negative by TaqMan PCR. Conclusions: In our opinion this case is of great interest because: 1) it is the first report of a virological response in a HBV/HCV-coinfected CH patient treated with PEG-IFN; 2) control of the two viral infections was achieved with a new therapeutic strategy that included two phases: a) HBV-DNA loss at 6 months and HBsAg/anti-HBs seroconversion between months 24 and 36, after PEG-IFNa2b mono-therapy, which was administered when the HCV replication seemed to prevail over that of HBV; b) ETR for HCV after 72 weeks of PEG-IFNa2a+ribavirin, which was continued in spite of the lack of an EVR, as this does not preclude the possibility of a SVR.

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