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Background: Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion. Herein, we assessed clinical, serological and histopathological findings of a single-center, large cohort of CD patients diagnosed and followed-up over forty years. Methods: From January 1980 to December 2020, 1547 CD patients (1170 females; age range: 8–81 years; F:M ratio = 3.1:1) were diagnosed in an Italian tertiary referral center. Comorbidities and complications were recorded at diagnosis and during follow-up. Results: CD diagnoses quadrupled after 2000. The most frequent phenotype was the non-classical CD (63.3%), and the most prevalent histotype was Marsh 3C (44.7%). Gastrointestinal manifestations, detectable in 51% of patients, were diarrhea (24.3%), bloating (28%) and aphthous stomatitis (19.7%). The most common CD-associated disorder was osteopenia (59.9%), predominant in females (64.3%); extraintestinal manifestations included anemia (35.8% iron-deficiency; 87% folic acid malabsorption), cryptogenic hypertransaminasemia (27.9%), and recurrent miscarriages (11.5%). Thyroiditis (26.9%), type 1 diabetes mellitus (2.9%), and dermatitis herpetiformis (1.4%) were the most common CD-related autoimmune disorders. Six patients had inflammatory bowel disease. Complications and mortality rate occurred in 1.8% and 1.9%, respectively. Conclusions: This single-center, large cohort analysis confirmed that CD presentation changed over the years, with an increase of non-classical and subclinical clinical phenotypes. [ABSTRACT FROM AUTHOR]

Peyronie's disease (PD) affects the penile albuginea, resulting in penile deformity, pain, erectile dysfunction (ED), and an anxious–depressive state. PD diagnosis involves a thorough medical history, penile palpation, documentation of the penile deformation, a dynamic penile echo color Doppler ultrasound (PCDU), and the completion of questionnaires for the evaluation of pain, ED, and psychometric tests. The aim of this study was to evaluate the symptoms of PD and their prevalence in PD patients in the active phase who had access to our andrology clinic. Inclusion criteria: availability of data on patients diagnosed with PD, including detailed medical history, blood tests, penile palpation, photographic documentation of penile deformity, and penile PCDU. Exclusion criteria: PD patients in the stable phase or those without the specified tests and data mentioned above. Our study found a higher prevalence of PD in younger patients (24.2%), a higher coexistence of PD with chronic prostatitis (35.6%), a higher percentage of cases of association between penile deformity and penile curvature (84.4%), a higher prevalence of "significant anxiety" (88.4%), a higher presence of plaque calcification (35.6%), and the detection of a longer duration of the first phase of PD (>18 months). The most frequently observed type of penile curvature was dorsal, followed by left lateral, right lateral, and, less commonly, ventral. We observed a significant statistical correlation between patient age and IIEF score, indicating that patients over the age of 40 years are at a higher risk of experiencing ED. We found a strong statistical relationship between VAS score and age. As age increases, the VAS score decreases, suggesting that younger patients reported more penile pain compared to those who were older than 40 years. Furthermore, we found that penile pain has a significant impact on the psychological state of PD patients. We also found that 38.8% of PD patients suffered from severe anxiety. In relation to this, psychotherapy should be integrated into PD treatment to improve the quality of life and treatment adherence. [ABSTRACT FROM AUTHOR]

Sex and gender are fundamental health determinants and their role as modifiers of treatment response is increasingly recognized. Norepinephrine is a cornerstone of septic shock management and its use is based on the highest level of evidence compared to dopamine. The related 2021 Surviving Sepsis Campaign (SCC) recommendation is presumably applicable to both females and males; however, a sex- and gender-based analysis is lacking, thus not allowing generalizable conclusions. This paper was aimed at exploring whether sex- and gender-disaggregated data are available in the evidence supporting this recommendation. For all the studies underpinning it, four pairs of authors, including a woman and a man, extracted data concerning sex and gender, according to the Sex and Gender Equity in Research guidelines. Nine manuscripts were included with an overall population of 2126 patients, of which 43.2% were females. No sex analysis was performed and gender was never reported. In conclusion, the present manuscript highlighted that the clinical studies underlying the SCC recommendation of NE administration in septic shock have neglected the likely role of sex and gender as modifiers of treatment response, thus missing the opportunity of sex- and gender-specific guidelines. [ABSTRACT FROM AUTHOR]

Elastography is a noninvasive method that utilizes ultrasound imaging to assess the elasticity and stiffness of soft tissue. Peyronie's disease (PD) is a chronic inflammatory condition that affects the male penis, causing the formation of fibrous plaques. This alters the penis's elasticity and can lead to changes in its shape. Ultrasound elastography (UE) is an important advancement in the diagnosis of PD. It not only identifies plaques, but it also measures their rigidity, providing crucial information to monitor changes during and after treatment. We conducted a narrative review of the scientific literature to identify articles that discuss the use of elastography in the diagnostic study of PD. The purpose of this study was to describe the "state of the art" in the diagnostic use of ultrasound in combination with elastography to highlight any benefits in the diagnosis of PD. We found 12 relevant articles after searching PubMed, Embase, and Google Scholar using the keywords "ultrasound elastography" and "Peyronie's disease", including eight clinical studies, two case reports, and two review articles. The results of our review indicate that UE is a useful technique for identifying Peyronie-related plaques, particularly when they are not detectable using a standard ultrasound or physical examination. It is also helpful in monitoring improvements during and after conservative treatments. More research is required to confirm the effectiveness of ultrasound elastography in diagnosing Peyronie's disease and to determine whether it is better than traditional ultrasound. [ABSTRACT FROM AUTHOR]

The golden rule in tissue engineering is the creation of a synthetic device that simulates the native tissue, thus leading to the proper restoration of its anatomical and functional integrity, avoiding the limitations related to approaches based on autografts and allografts. The emergence of synthetic biocompatible materials has led to the production of innovative scaffolds that, if combined with cells and/or bioactive molecules, can improve tissue regeneration. In the last decade, silk fibroin (SF) has gained attention as a promising biomaterial in regenerative medicine due to its enhanced bio/cytocompatibility, chemical stability, and mechanical properties. Moreover, the possibility to produce advanced medical tools such as films, fibers, hydrogels, 3D porous scaffolds, non-woven scaffolds, particles or composite materials from a raw aqueous solution emphasizes the versatility of SF. Such devices are capable of meeting the most diverse tissue needs; hence, they represent an innovative clinical solution for the treatment of bone/cartilage, the cardiovascular system, neural, skin, and pancreatic tissue regeneration, as well as for many other biomedical applications. The present narrative review encompasses topics such as (i) the most interesting features of SF-based biomaterials, bare SF's biological nature and structural features, and comprehending the related chemo-physical properties and techniques used to produce the desired formulations of SF; (ii) the different applications of SF-based biomaterials and their related composite structures, discussing their biocompatibility and effectiveness in the medical field. Particularly, applications in regenerative medicine are also analyzed herein to highlight the different therapeutic strategies applied to various body sectors. [ABSTRACT FROM AUTHOR]

Feline leukemia virus C receptor 1a (FLVCR1a), initially identified as a retroviral receptor and localized on the plasma membrane, has emerged as a crucial regulator of heme homeostasis. Functioning as a positive regulator of δ-aminolevulinic acid synthase 1 (ALAS1), the rate-limiting enzyme in the heme biosynthetic pathway, FLVCR1a influences TCA cycle cataplerosis, thus impacting TCA flux and interconnected metabolic pathways. This study reveals an unexplored link between FLVCR1a, heme synthesis, and cholesterol production in endothelial cells. Using cellular models with manipulated FLVCR1a expression and inducible endothelial-specific Flvcr1a-null mice, we demonstrate that FLVCR1a-mediated control of heme synthesis regulates citrate availability for cholesterol synthesis, thereby influencing cellular cholesterol levels. Moreover, alterations in FLVCR1a expression affect membrane cholesterol content and fluidity, supporting a role for FLVCR1a in the intricate regulation of processes crucial for vascular development and endothelial function. Our results underscore FLVCR1a as a positive regulator of heme synthesis, emphasizing its integration with metabolic pathways involved in cellular energy metabolism. Furthermore, this study suggests that the dysregulation of heme metabolism may have implications for modulating lipid metabolism. We discuss these findings in the context of FLVCR1a's potential heme-independent function as a choline importer, introducing additional complexity to the interplay between heme and lipid metabolism. [ABSTRACT FROM AUTHOR]

Since the rise of awareness of gluten/wheat-related disorders in the academic and clinical field in the last few decades, misinformation regarding the gluten-free diet (GFD) and its impact on health has been spreading among the general population. Despite the established link between gluten and celiac disease (CD), where a GFD is mandatory to reach clinical and histological remission, things are more complicated when it comes to non-celiac gluten/wheat sensitivity (NCGWS) and other autoimmune/dysimmune disorders. In the last conditions, a beneficial effect of gluten withdrawal has not been properly assessed, but still is often suggested without strong supporting evidence. In this context, women have always been exposed, more than men, to higher social pressure related to nutritional behaviors and greater engagement in controlling body weight. With this narrative review, we aim to summarize current evidence on the adherence to a GFD, with particular attention to the impact on women's health. [ABSTRACT FROM AUTHOR]

Peyronie's disease (PD) is a chronic inflammatory disease affecting the penile albuginea. Oxidative stress (OS) is important for the development of the disease; therefore, it seemed interesting to us to directly measure OS at both the site of the disease and in peripheral blood. For a precise OS study, it is necessary to evaluate not only the single results of the total oxidant status (TOS) and total antioxidant status (TAS) but also their ratio: OS index (OSI) (arbitrary unit) = TOS/TAS × 100. This study included 49 PD patients examined and diagnosed in our Peyronie's care center and a control group of 50 cases. We collected blood samples from both the penis and a vein in the upper extremity; we used d-ROMs and PAT-test (FRAS kit) for OS measurement. Pearson's study found a statistical correlation between penile OSI values and PD plaque volumes: p-value = 0.002. No correlation was found between systemic OSI values and PD plaque volumes: p-value = 0.27. Penile OSI values were significantly reduced after the elimination of the PD plaque (p < 0.00001). The mean value of the penile OSI indices in the PD patients after plaque elimination corresponded to 0.090 ± 0.016 (p = 0.004). The comparison between the penile OSI values of the PD patients (with plaque elimination) and the control group revealed no statistically significant differences (p = 0.130). The absence of a correlation between Peyronie's plaque volume and systemic OSI values indicates that it is preferable to carry out the OS study by taking a sample directly from the site of the disease. By carrying out a penile OSI study, it would be possible to obtain a precise plaque-volume-dependent oxidative marker. Even if the study did not demonstrate any correlation between OSI indices and anxious–depressive state, we detected a high prevalence of anxiety (81.6%) and depression (59.1%) in PD patients. [ABSTRACT FROM AUTHOR]

Clinical prediction models for spine surgery applications are on the rise, with an increasing reliance on machine learning (ML) and deep learning (DL). Many of the predicted outcomes are uncommon; therefore, to ensure the models' effectiveness in clinical practice it is crucial to properly evaluate them. This systematic review aims to identify and evaluate current research-based ML and DL models applied for spine surgery, specifically those predicting binary outcomes with a focus on their evaluation metrics. Overall, 60 papers were included, and the findings were reported according to the PRISMA guidelines. A total of 13 papers focused on lengths of stay (LOS), 12 on readmissions, 12 on non-home discharge, 6 on mortality, and 5 on reoperations. The target outcomes exhibited data imbalances ranging from 0.44% to 42.4%. A total of 59 papers reported the model's area under the receiver operating characteristic (AUROC), 28 mentioned accuracies, 33 provided sensitivity, 29 discussed specificity, 28 addressed positive predictive value (PPV), 24 included the negative predictive value (NPV), 25 indicated the Brier score with 10 providing a null model Brier, and 8 detailed the F1 score. Additionally, data visualization varied among the included papers. This review discusses the use of appropriate evaluation schemes in ML and identifies several common errors and potential bias sources in the literature. Embracing these recommendations as the field advances may facilitate the integration of reliable and effective ML models in clinical settings. [ABSTRACT FROM AUTHOR]

The hinterland of the Taranto Gulf in Basilicata (Southern Italy) provides a great opportunity for the study of coarse-grained coastal systems belonging to a staircase of Quaternary terraced marine-deposits. Among gravelly successions, beach deposits abound in the stratigraphic record, offering exceptional outcrops useful for providing detailed information on their facies features. In this paper, we describe sedimentary facies, textural variations, and the depositional architecture of these deposits in order to: (1) demonstrate that the area is an excellent training ground for the study of gravelly beaches in microtidal settings; (2) discuss the use of beach deposits as a proxy for even small relative sea-level variations. [ABSTRACT FROM AUTHOR]

Background: Renowned since ancient times for its medical properties, liquorice is nowadays mainly used for flavoring candies or soft drinks. Continuous intake of large amounts of liquorice is a widely known cause of pseudo-hyperaldosteronism leading to hypertension and hypokalemia. These manifestations are usually mild, although in some cases may generate life-threatening complications, i.e., arrhythmias, muscle paralysis, rhabdomyolysis, and coma. In addition, liquorice has an important estrogenic-like activity. Methods: We summarized the current knowledge about liquorice and reviewed 104 case reports in both the English and Italian languages from inception to June 2023 concerning complications due to an excess of liquorice intake. Results: In contrast to most published data, female sex and old age do not appear to be risk factors. However, hypertension and electrolyte imbalance (mainly hypokalemia) are prevalent features. The detection of glycyrrhetinic acid in blood is very uncommon, and the diagnosis is essentially based on an accurate history taking. Conclusions: Although there is not a significant mortality rate, liquorice toxicity often requires hospitalization and therefore represents a significant health concern. Major pharmaceutical drug regulatory authorities should solicit public awareness about the potentially dangerous effects caused by excessive use of liquorice. [ABSTRACT FROM AUTHOR]

Background: Gamma-hydroxybutyric acid (GHB) at low dosages has anxiolytic effects and promotes REM sleep and low-wave deep sleep. In the U.S., the legal form of GHB is prescribed to adults suffering from narcolepsy-associated cataplexy; the sodium salt of GHB is reserved for alcohol-addiction treatment. GHB is also a molecule of abuse and recreational use, it is a controlled substance in several countries, so gamma-valerolactone (GVL) has frequently been used as a legal substitute for it. GHB's abuse profile is most likely attributable to its anxiolytic, hypnotic, and euphoric properties, as well as its widespread availability and inexpensive/low cost on the illicit market. Methods: Our study is focused on evaluating the potential effects on the mouse brain after repeated/prolonged administration of GHB and GVL at a pharmacologically active dose (100 mg/kg) through behavioral study and immunohistochemical analysis using the markers tetraspanin 17 (TSPAN17), aldehyde dehydrogenase 5 (ALDH5A1), Gamma-aminobutyric acid type A receptor (GABA-A), and Gamma-aminobutyric acid type B receptor (GABA-B). Results: Our findings revealed that prolonged administration of GHB and GVL at a pharmacologically active dose (100 mg/kg) can have effects on a component of the mouse brain, the intensity of which can be assessed using immunohistochemistry. The findings revealed that long-term GHB administration causes a significant plastic alteration of the GHB signaling system, with downregulation of the putative binding site (TSPAN17) and overexpression of ALDH5A1, especially in hippocampal neurons. Our findings further revealed that GABA-A and GABA-B receptors are downregulated in these brain locations, resulting in a greater decrease in GABA-B expression. Conclusions: The goal of this study, from the point of view of forensic pathology, is to provide a new methodological strategy for better understanding the properties of this controversial substance, which could help us better grasp the unknown mechanism underlying its abuse profile. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is the most common form of muscle degenerative hereditary disease. Muscular replacement by fibrosis and calcification are the principal causes of progressive and severe musculoskeletal, respiratory, and cardiac dysfunction. To date, the D2.B10-Dmdmdx/J (D2-mdx) model is proposed as the closest to DMD, but the results are controversial. In this study, the cardiac structure and function was characterized in D2-mdx mice from 16–17 up to 24–25 weeks of age. Echocardiographic assessment in conscious mice, gross pathology, and histological and cardiac biomarker analyses were performed. At 16–17 weeks of age, D2-mdx mice presented mild left ventricular function impairment and increased pulmonary vascular resistance. Cardiac fibrosis was more extended in the right ventricle, principally on the epicardium. In 24–25-week-old D2-mdx mice, functional and structural alterations increased but with large individual variation. High-sensitivity cardiac Troponin T, but not N-terminal pro-atrial natriuretic peptide, plasma levels were increased. In conclusion, left ventricle remodeling was mild to moderate in both young and adult mice. We confirmed that right ventricle epicardial fibrosis is the most outstanding finding in D2-mdx mice. Further long-term studies are needed to evaluate whether this mouse model can also be considered a model of DMD cardiomyopathy. [ABSTRACT FROM AUTHOR]

This descriptive article explores the use of smart devices for health and wellness in the context of telehealth, highlighting rapidly evolving technologies such as the Internet of Things (IoT) and Artificial Intelligence (AI). Key innovations, benefits, challenges, and opportunities related to the adoption of these technologies are outlined. The article provides a descriptive and accessible approach to understanding the evolution and impact of smart devices in the tele-exercise reality. Nowadays, technological advances provide solutions that were unthinkable just a few years ago. The habits of the general population have also changed over the past few years. Hence, there is a need to investigate this issue and draw the attention of the scientific community to this topic by describing the benefits and challenges associated with each topic. If individuals no longer go to exercise, the exercise must go to their homes instead. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether the presence of Staphylococcus aureus (SA) producing the Panton–Valentine leukocidin (PVL) affects the outcome of Prosthetic Joint Infection (PJI). Patients with acute and chronic PJI sustained by SA were prospectively enrolled at the orthopedic unit of "Casa di Cura Santa Maria Maddalena", from January 2019 to October 2021. PJI diagnosis was reached according to the diagnostic criteria of the International Consensus Meeting on PJI of Philadelphia. Synovial fluid obtained via joint aspirations was collected in order to isolate SA. The detection of PVL was performed via real-time quantitative PCR (RT-qPCR). The outcome assessment was performed using the criteria of the Delphi-based International Multidisciplinary Consensus. Twelve cases of PJI caused by SA were included. Nine (75%) cases were acute PJI treated using debridement, antibiotic and implant retention (DAIR); the remaining three (25%) were chronic PJI treated using two-stage (n = 2) and one-stage revision (n = 1), respectively. The SA strains that tested positive for PVL genes were 5/12 (41.6%,). Treatment failure was documented in three cases of acute PJI treated using DAIR, all supported by SA–PVL strains (p < 0.045). The remaining two cases were chronic PJI treated with a revision arthroplasty (one and two stage, respectively), with a 100% eradication rate in a medium follow-up of 24 months. Although a small case series, our study showed a 100% failure rate in acute PJI, probably caused by SA PVL-producing strains treated conservatively (p < 0.04). In this setting, toxin research should guide radical surgical treatment and targeted antibiotic therapy. [ABSTRACT FROM AUTHOR]

Sepsis is a time-dependent and life-threating condition related to macro- and micro-circulatory impairment leading to anaerobic metabolism and lactate increase. We assessed the prognostic accuracy of capillary lactates (CLs) vs. serum ones (SLs) on 48-h and 7-day mortality in patients with suspected sepsis. This observational, prospective, single-centre study was conducted between October 2021 and May 2022. Inclusion criteria were: (i) suspect of infection; (ii) qSOFA ≥ 2; (iii) age ≥ 18 years; (iv) signed informed consent. CLs were assessed with LactateProTM2®. 203 patients were included: 19 (9.3%) died within 48 h from admission to the Emergency Department, while 28 (13.8%) within 7 days. Patients deceased within 48 h (vs. survived) had higher CLs (19.3 vs. 5 mmol/L, p < 0.001) and SLs (6.5 vs. 1.1 mmol/L, p = 0.001). The best CLs predictive cut-off for 48-h mortality was 16.8 mmol/L (72.22% sensitivity, 94.02% specificity). Patients within 7 days had higher CLs (11.5 vs. 5 mmol/L, p = 0.020) than SLs (2.75 vs. 1.1 mmol/L, p < 0.001). The multivariate analysis confirmed CLs and SLs as independent predictors of 48-h and 7-day mortality. CLs can be a reliable tool for their inexpensiveness, rapidity and reliability in identifying septic patients at high risk of short-term mortality. [ABSTRACT FROM AUTHOR]

Criminal trials and claims against physicians for malpractice-related damages have increased dramatically in recent years, and, with Obstetrics and Gynecology being one of the medical specialties that is at the highest risk, we carried out a retrospective analysis aimed at examining all Obstetrics- and Gynecology-related medical professional liability prosecutions within the General Register of Criminal Records of the Rome Public Prosecutor's Office between the years 2000 and 2014. The number of prosecutions increased steadily in the years 2000–2005, with varying trends in the following years. A total of 727 healthcare professionals were involved in criminal charges, and most prosecuted crimes were related to Articles 590 and 589 of the Italian Penal Code, followed by violations of Article 17 of Law 194/78. In most cases, filing was requested and granted without opposition. In 95 cases, an expert witness was appointed by the Court, and in 68 cases, the technical consultants of the State Prosecutor found culpable conduct. Public hospitals, private nursing homes and outpatient clinics, or private practices were mostly involved; in 45% of the cases, the physicians were hospital employees. In this setting, Italy is prepared to introduce new measures and regulations to address the issues posed by defensive medicine and charges of professional liability for healthcare providers. [ABSTRACT FROM AUTHOR]

Background: Sepsis/septic shock is a life-threatening and time-dependent condition that requires timely management to reduce mortality. This review aims to update physicians with regard to the main pillars of treatment for this insidious condition. Methods: PubMed, Scopus, and EMBASE were searched from inception with special attention paid to November 2021–January 2023. Results: The management of sepsis/septic shock is challenging and involves different pathophysiological aspects, encompassing empirical antimicrobial treatment (which is promptly administered after microbial tests), fluid (crystalloids) replacement (to be established according to fluid tolerance and fluid responsiveness), and vasoactive agents (e.g., norepinephrine (NE)), which are employed to maintain mean arterial pressure above 65 mmHg and reduce the risk of fluid overload. In cases of refractory shock, vasopressin (rather than epinephrine) should be combined with NE to reach an acceptable level of pressure control. If mechanical ventilation is indicated, the tidal volume should be reduced from 10 to 6 mL/kg. Heparin is administered to prevent venous thromboembolism, and glycemic control is recommended. The efficacy of other treatments (e.g., proton-pump inhibitors, sodium bicarbonate, etc.) is largely debated, and such treatments might be used on a case-to-case basis. Conclusions: The management of sepsis/septic shock has significantly progressed in the last few years. Improving knowledge of the main therapeutic cornerstones of this challenging condition is crucial to achieve better patient outcomes. [ABSTRACT FROM AUTHOR]

JWH-018 is the most known compound among synthetic cannabinoids (SCs) used for their psychoactive effects. SCs-based products are responsible for several intoxications in humans. Cardiac toxicity is among the main side effects observed in emergency departments: SCs intake induces harmful effects such as hypertension, tachycardia, chest pain, arrhythmias, myocardial infarction, breathing impairment, and dyspnea. This study aims to investigate how cardio-respiratory and vascular JWH-018 (6 mg/kg) responses can be modulated by antidotes already in clinical use. The tested antidotes are amiodarone (5 mg/kg), atropine (5 mg/kg), nifedipine (1 mg/kg), and propranolol (2 mg/kg). The detection of heart rate, breath rate, arterial oxygen saturation (SpO2), and pulse distention are provided by a non-invasive apparatus (Mouse Ox Plus) in awake and freely moving CD-1 male mice. Tachyarrhythmia events are also evaluated. Results show that while all tested antidotes reduce tachycardia and tachyarrhythmic events and improve breathing functions, only atropine completely reverts the heart rate and pulse distension. These data may suggest that cardiorespiratory mechanisms of JWH-018-induced tachyarrhythmia involve sympathetic, cholinergic, and ion channel modulation. Current findings also provide valuable impetus to identify potential antidotal intervention to support physicians in the treatment of intoxicated patients in emergency clinical settings. [ABSTRACT FROM AUTHOR]

The number of legal disputes in the field of medical liability has increased exponentially in the last decades. The aim of this study is to investigate the outcomes of criminal cases against healthcare professionals in Italian criminal courts. The hypothesis is that the majority of cases are dismissed and/or most professionals in these cases are acquitted. This retrospective analysis considers criminal proceedings related to medical professional liability registered with the general register of crime reports of the Public Prosecutor's Office of Rome in the time interval between 1 January 2000 and 31 December 2015. A total of 4793 criminal proceedings were ultimately identified. Proceedings related to the field of orthopedic trauma were then examined and identified. A complete analysis of 132 of the identified files (76.7%) was carried out. The field with the highest risk of disputes was determined to be the field of trauma. The most frequent complaint was found to arise from unsatisfactory surgical outcomes following elective surgery. The most affected anatomical district is the lower limb in both elective and trauma cases, followed by the upper limb in traumatology and spine cases. The surgeon is the most frequently quoted role of the professional involved. The number of physicians actually convicted (3.93%) and for whom liability was thus recognized, i.e., the existence of a causal link between their conduct and the event that took place was established, appears to be extremely small when compared with the far more significant values related to dismissals (53%) and acquittals (14.2%). Adequate legal reform aiming to reduce this disproportion is necessary to ensure physicians experience a more relaxed daily profession and to restore the original connotations of the doctor–patient relationship with the abolition of defensive medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: This review reports the risk and management of the hepatotoxicity of all the approved protein kinase inhibitors (PKIs) for cancer. Hepatotoxicity is one of the major safety concerns of these drugs, as reflected by the discontinuation of the development of some of them due to liver injury, or by the significant number of warnings for hepatotoxicity reported in drug labeling. Although these side effects are usually reversible by dose adjustment or therapy suspension, or by switching to an alternative PKI, and fatality is uncommon, all patients undergoing these drugs should be carefully pre-evaluated and monitored during treatment. Small molecule protein kinase inhibitors (PKIs) have become an effective strategy for cancer patients. However, hepatotoxicity is a major safety concern of these drugs, since the majority are reported to increase transaminases, and few of them (Idelalisib, Lapatinib, Pazopanib, Pexidartinib, Ponatinib, Regorafenib, Sunitinib) have a boxed label warning. The exact rate of PKI-induced hepatoxicity is not well defined due to the fact that the majority of data arise from pre-registration or registration trials on fairly selected patients, and the post-marketing data are often based only on the most severe described cases, whereas most real practice studies do not include drug-related hepatotoxicity as an end point. Although these side effects are usually reversible by dose adjustment or therapy suspension, or by switching to an alternative PKI, and fatality is uncommon, all patients undergoing PKIs should be carefully pre-evaluated and monitored. The management of this complication requires an individually tailored reappraisal of the risk/benefit ratio, especially in patients who are responding to therapy. This review reports the currently available data on the risk and management of hepatotoxicity of all the approved PKIs. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD. [ABSTRACT FROM AUTHOR]

The main aim of this study was to create a new test to assess the motor skills of children of preschool and early school age and to determine its reliability and validity. Thirty children (5–6 years old) were tested on two occasions 14 days apart. The testing procedures included measuring the participants' performance on the Four Station Fundamental Motor Test (4-SFMT). The newly constructed 4-SFMT tested four fundamental skills/tasks: space covering (ROLL), overcoming resistance (PULL), object control (BALL), and overcoming obstacles (CLIMB). The performance was evaluated with a 22-point scale with different criteria for each skill, and the time taken to perform the test was measured. The concurrent validity was assessed by determining the correlation with a Test of Gross Motor Development (TGMD-2). The level of agreement across trials was statistically significant for all three raters, with two variables presenting excellent reliability (ICC > 0.9) and two variables having good reliability (ICC > 0.75 and <0.9). No significant differences were found between the test and retest scores, indicating the test's high reliability. A factor analysis isolated only one motor factor (accounting for 43.99% of the variance with the eigenvalue of 1.768) from the four tasks. There was a large correlation (r = −0.576, p < 0.01) between the process- and product-oriented assessments of the 4-SFMT. Moreover, significant correlations were found between the 4-SFMT and TGMD-2 regarding the scores (r = 0.824, p < 0.001) and time taken to perform the tasks (r = −0.652, p < 0.001), which indicates the good concurrent validity of the newly constructed test. Small to moderate correlations between tasks (0.016 to 0.497) and no differences between boys and girls in the total score (p = 0.943) and time taken to complete the tasks (p = 0.49) were determined. The 4-SFMT appears to be a valid and reliable tool that can be used to evaluate motor skills performance in children between the ages of 5 and 6 and is reasonably simple to use. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients. This narrative review aims to resume the current knowledge of female-related features in clinical manifestations, development, and therapy, as well as sexual and psychological implications related to inflammatory bowel disease. The final attempt is to provide gastroenterologists with a roadmap of female-specific differences, to improve patients' diagnosis, management, and treatment. [ABSTRACT FROM AUTHOR]

Secretory IgA (sIgA), which may play an important role in the early defense against SARS-CoV-2 infection, were detected in the eye of COVID-19 patients. However, an evaluation of the sIgA response in the tears of vaccinated or non-vaccinated COVID-19 subjects is still lacking. Aimed at characterizing sIgA mucosal immunity in the eye, this study analyzed tear samples from 77 COVID-19 patients, including 63 vaccinated and 14 non-vaccinated subjects. The groups showed similar epidemiological features, but as expected, differences were observed in the percentage of asymptomatic/pauci-symptomatic subjects in the vaccinated vs. non-vaccinated cohort (46% and 29% of the total, respectively). Consistent with this, ocular sIgA values, evaluated by a specific quantitative ELISA assay, were remarkably different in vaccinated vs. non-vaccinated group for both frequency (69.8% vs. 57.1%, respectively) and titer (1372.3 U/mL vs. 143.7 U/mL, respectively; p = 0.01), which was significantly differently elevated depending on the type of administered vaccine. The data show for the first time significant differences of available vaccines to elicit sIgA response in the eye and suggest that quantitative tear-based sIgA tests may potentially serve as a rapid and easily accessible biomarker for the assessment of the development of a protective mucosal immunity toward SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Several new psychoactive substances (NPS) are responsible for intoxication involving the cardiovascular and respiratory systems. Among NPS, synthetic cannabinoids (SCs) provoked side effects in humans characterized by tachycardia, arrhythmias, hypertension, breathing difficulty, apnoea, myocardial infarction, and cardiac arrest. Therefore, the present study investigated the cardio-respiratory (MouseOx Plus; EMKA electrocardiogram (ECG) and plethysmography TUNNEL systems) and vascular (BP-2000 systems) effects induced by 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018; 0.3–3–6 mg/kg) and Δ9-tetrahydrocannabinol (Δ9-THC; 0.3–3–6 mg/kg), administered in awake CD-1 male mice. The results showed that higher doses of JWH-018 (3–6 mg/kg) induced deep and long-lasting bradycardia, alternated with bradyarrhythmia, spaced out by sudden episodes of tachyarrhythmias (6 mg/kg), and characterized by ECG electrical parameters changes, sustained bradypnea, and systolic and transient diastolic hypertension. Otherwise, Δ9-THC provoked delayed bradycardia (minor intensity tachyarrhythmias episodes) and bradypnea, also causing a transient and mild hypertensive effect at the tested dose range. These effects were prevented by both treatment with selective CB1 (AM 251, 6 mg/kg) and CB2 (AM 630, 6 mg/kg) receptor antagonists and with the mixture of the antagonists AM 251 and AM 630, even if in a different manner. Cardio-respiratory and vascular symptoms could be induced by peripheral and central CB1 and CB2 receptors stimulation, which could lead to both sympathetic and parasympathetic systems activation. These findings may represent a starting point for necessary future studies aimed at exploring the proper antidotal therapy to be used in SCs-intoxicated patient management. [ABSTRACT FROM AUTHOR]

Background: Peyronie's disease (PD) is a chronic inflammatory condition affecting adult males, involving the tunica albuginea of the corpora cavernosa of the penis. PD is frequently associated with penile pain, erectile dysfunction, and a secondary anxious–depressive state. The etiology of PD has not yet been completely elucidated, but local injury is generally recognized to be a triggering factor. It has also been widely proven that oxidative stress is an essential, decisive component in all inflammatory processes, whether acute or chronic. Current conservative medical treatment comprises oral substances, penile injections, and physical therapy. Aim: This article intends to show how antioxidant therapy is able to interfere with the pathogenetic mechanisms of the disease. Method: This article consists of a synthetic narrative review of the current scientific literature on antioxidant therapy for this disease. Results: The good results of the antioxidant treatment described above also prove that the doses used were adequate and the concentrations of the substances employed did not exceed the threshold at which they might have interacted negatively with the mechanisms of the redox regulation of tissue. Conclusions: We believe new, randomized, controlled studies are needed to confirm the efficacy of treatment with antioxidants. However, we consider the experiences of antioxidant treatment which can already be found in the literature useful for the clinical practice of urologists in the treatment of this chronic inflammatory disease. [ABSTRACT FROM AUTHOR]

Peyronie's disease (PD) is a fibrotic disorder of the penile tunica albuginea. To date, only a few cases of recovery from PD following medical treatment have been reported in the literature. In this article, we describe three new cases of PD where patients achieved complete resorption of plaque following multimodal antioxidant treatment. In all three cases, treatment included the following antioxidants: bilberry, propolis, ginkgo biloba, silymarin, and vitamin E. Only in case nos. 1 and 2 did we also use the following antioxidant substances: L-carnitine, coenzyme Q10, and Boswellia. In all three cases, we also used a local therapy with diclofenac gel. Only in case no. 2 did we also use periodic perilesional injections with pentoxifylline. Although the sample of cases presented here was small, these patients incontrovertibly experienced complete plaque disappearance and recovery (in one case, only after a short course of treatment). Therefore, it is our conviction that urologists may find our experiences of considerable interest in their clinical practices. [ABSTRACT FROM AUTHOR]

Severe gut motility disorders are characterized by the ineffective propulsion of intestinal contents. As a result, the patients develop disabling/distressful symptoms, such as nausea and vomiting along with altered bowel habits up to radiologically demonstrable intestinal sub-obstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility. This syndrome occurs due to changes altering the morpho-functional integrity of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), the interstitial cells of Cajal (ICC) (mesenchymopathy), and smooth muscle cells (myopathy). In the last years, several genes have been identified in different subsets of CIPO patients. The focus of this review is to cover the most recent update on enteric dysmotility related to CIPO, highlighting (a) forms with predominant underlying neuropathy, (b) forms with predominant myopathy, and (c) mitochondrial disorders with a clear gut dysfunction as part of their clinical phenotype. We will provide a thorough description of the genes that have been proven through recent evidence to cause neuro-(ICC)-myopathies leading to abnormal gut contractility patterns in CIPO. The discovery of susceptibility genes for this severe condition may pave the way for developing target therapies for enteric neuro-(ICC)-myopathies underlying CIPO and other forms of gut dysmotility. [ABSTRACT FROM AUTHOR]

Background: Lipodystrophy is one of the most frequent complications in people with diabetes following subcutaneous insulin therapy, and poor management can lead to several problems, such as impaired glycemic control and adherence to therapy, anxiety, and depression. Poor injection technique represents the main risk factor for lipodystrophies. In order to enhance the patient's insulin injection technique to heal lipodystrophy, improve psychological indices, and promote involvement in their health and care, the efficacy of emerging person-centered care called the IARA model was tested. Methods: A total of 49 patients were randomly allocated to the IARA group (Experimental; n = 25) or standard education (Control; n = 24). The following questionnaires were used in a mixed-method design: (i) State Anxiety Scale; (ii) Beck Depression Inventory; (iii) Italian Summary of Diabetes Self-Care Activities. An ad hoc open-ended questionnaire was structured for the qualitative analysis. Finally, photos were taken in order to verify if injection sites were changed until the follow-up at 12 months. The number of patients who participated until the completion of the study was 17 in the IARA and 11 in the Control group. Results: State anxiety was significantly reduced in people who followed IARA to follow-up at 3 and 6 months (p < 0.05). The IARA group also demonstrated better compliance in blood glucose monitoring and foot-care compared to Control at follow-up at 12 months. The management of insulin injections dramatically improved in participants who received IARA intervention. Conclusions: IARA could be considered an effective strategy to improve well-being and compliance in people affected with diabetes mellitus and lipodystrophy complications. [ABSTRACT FROM AUTHOR]

At the onset of the SARS-CoV-2 pandemic, individual and social measures were strengthened through restrictive non-pharmaceutical interventions, labelled with the term "lockdown". In Italy, there were two lockdowns (9 March 2020–3 May 2020 and 3 November 2020–27 March 2021). As part of preventive measures, healthcare workers and the administrative staff population of Policlinico A. Gemelli underwent nasopharyngeal swab tests from 1 March 2020 to 9 February 2022, a long time interval that includes the two aforementioned lockdowns. The population included 8958 people from 1 March 2020 to 31 December 2020; 8981 people from 1 January 2021 to 31 December 2021; and 8981 people from 1 January 2022 to 9 February 2022. We then analysed pseudo-anonymized data, using a retrospective observational approach to evaluate the impact of the lockdown on the incidence of SARS-CoV-2 infections within the population. Given the 14 day contagious period, the swab positivity rate (SPR) among the staff decreased significantly at the end of the first lockdown, every day prior to 18 May 2020, by 0.093 (p < 0.0001, CI = (−0.138–−0.047)). After the fourteenth day post the end of the first lockdown (18 May 2020), the SPR increased daily at a rate of 0.024 (p < 0.0001, 95% CI = (0.013–0.034)). In addition, the SPR appeared to increase significantly every day prior to 17 November 2020 by 0.024 (p < 0.0001, CI = (0.013–0.034)). After the fourteenth day post the start of the second lockdown (17 November 2020), the SPR decreased daily at a rate of 0.039 (p < 0.0001, 95% CI = (−0.050–−0.027)). These data demonstrate that, in our Institution, the lockdowns helped to both protect healthcare workers and maintain adequate standards of care for COVID and non-COVID patients for the duration of the state of emergency in Italy. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the changes in internal training intensity, well-being, and countermovement jump (CMJ) performance and to determine their relationship across five weeks of the pre-season training phase in professional soccer players. A total of 22 professional male soccer players (age = 21.7 ± 4 years, body height = 185.9 ± 6.3 cm, body weight = 79 ± 6.3 kg, BMI = 22.8 ± 1.4 kg·m−2; VO2max = 52.9 ± 3.2) from the Croatian Second League voluntary participated in this study. The players spent 2230 ± 117 min in 32 technical/tactical and strength/conditioning training sessions, mostly at the low intensity zone (61%), and played 8 friendly matches at a high intensity (>90%). A one-way repeated measure of analysis ANOVA revealed a significant difference between weeks in CMJ performance (F(1,22) = 11.8, p < 0.001), with CMJ height in weeks 4 and 5 being likely to very likely higher than that noted in week 1. Moreover, significant differences between weeks were found in all internal training intensity measures (average [F(1,22) = 74.8, p < 0.001] and accumulated weekly internal training intensity [F(1,22) = 55.4, p < 0.001], training monotony [F(1,22) = 23.9, p < 0.001], and training strain [F(1,22) = 34.5, p < 0.001]). Likewise, differences were observed for wellness status categories (fatigue [F(1,22) = 4.3, p = 0.003], sleep [F(1,22) = 7.1, p < 0.001], DOMS [F(1,22) = 5.7, p < 0.001], stress [F(1,22) = 15.6, p < 0.001]), mood [F(1,22) = 12.7, p < 0.001], and overall well-being status score (F(1,22) = 13.2, p < 0.001). Correlation analysis showed large negative correlations between average weekly internal training intensity and fatigue (r = −0.63, p = 0.002), DOMS (r = −0.61, p = 0.003), and WBI (r = −0.53, p = 0.011). Additionally, fatigue was significantly associated (large negative correlation) with accumulated weekly internal training intensity (r = −0.51, p = 0.014) and training strain (r = −0.61, p = 0.003). Small, but non-significant, correlations were found between CMJ performance and wellness status measures. These findings highlight the utility and simplicity of monitoring tools to improve athletes' performance. [ABSTRACT FROM AUTHOR]

Peyronie's disease (PD) is a fibrotic disorder of the tunica albuginea of the penis. Conservative medical therapy includes oral and/or injective active substances. Until now, only two PD patients who recovered after medical treatment are described in the literature. This article describes three new cases of PD patients who achieved complete resorption of plaque following antioxidant treatment. Case Presentations: Case 1. The patient was a 34-year-old man, a smoker, with lateral-left penile curvature (40 degrees), penile pain, and good penile rigidity. The patient was treated with combined therapy (oral antioxidants + Propolis creme). At follow-up, after about 29 months of treatment, we observed the disappearance of the acquired penile deformity. The ultrasound examination no longer showed any plaque. Case 2. The patient was a 32-year-old man with chronic prostatitis, penile lichen sclerosus, lateral-left penile curvature (10 degrees), a palpable lump, and good penile rigidity. The patient was treated with combined therapy (oral antioxidants + Propolis creme + penile injections of pentoxifylline). After 33 months of treatment, at follow-up, we observed the disappearance of the penile deformity. Ultrasound examinations no longer showed any plaque. Case 3. The patient was a 33-year-old man with penile pain, dorsal penile curvature (30 degrees), and good penile rigidity. The patient was treated with combined therapy (oral antioxidants + Propolis creme + penile injections of pentoxifylline). At follow-up, after 41 months of treatment, the penile pain was no longer present, and the ultrasound study no longer showed any plaque. Conclusions: Although our study presents a limited number of cases, it is a matter of fact that these patients obtained full regression in the affected area. We believe our experience may be very useful for urological clinical practice. [ABSTRACT FROM AUTHOR]

The education of children is important because it determines the future of the world. Teachers have a great responsibility for this, which applies to every subject taught. In this regard, teachers usually specialize in a specific area and greatly influence how the subject is taught and how students gain a view of the subject. The present study aimed to investigate teachers' attitudes about subjects in primary school, with a particular focus on physical education. The sample of participants (N = 111) included Croatian female primary school teachers with a mean age of 47.88 (±8.11 SD) years and a mean teaching experience of 21.83 (±10.24 SD) years. The variable sample consisted of a three-criteria questionnaire for the assessment of classroom subjects: (i) the importance of a subject (importance); (ii) the level of qualifications obtained during study for a subject (qualification); and (iii) the teacher's competence for teaching (competence). Significant differences were found in the assessment of classroom subjects. The group of core academic subjects has noticeably higher assessments than the group of practical and artistic subjects. The assessment of teachers' competence in PE teaching is the lowest of all the classroom subjects. Further research of classroom teachers' attitudes towards the implementation of physical education is advised, with an increased number of participants and the inclusion of new measures. [ABSTRACT FROM AUTHOR]

In the current study, using portable optical coherence tomography, we evaluated 46 corneas of 23 individuals in a multicenter setting during the first 17 h after death. Twenty-three eyes were kept open, and twenty three were kept closed. Furthermore, the experiment was carried out for 12 samples in summer and 11 in winter. Our data show that postmortem corneal alterations largely depend on the phenomena of dehydration (in particular in open eyes) and swelling of the stroma in closed eyes, probably due in the first phase to hypoxia/anoxia and subsequently to the passage by osmosis of the aqueous humor from the anterior chamber to the corneal tissue. Our findings could have significant repercussions in forensic pathology for estimating the postmortem interval and transplantation to optimize the conservation of the tissue before the explant. [ABSTRACT FROM AUTHOR]

Background: Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) has caused millions of deaths worldwide and is the second most serious pandemic after the Spanish flu. Despite SARS-CoV-2 infection having a dominant effect on morbidity and life-threatening outcomes, the role of bacterial co-infection in patients with COVID-19 is poorly understood. The present study aimed to verify the existence of bacterial co-infections and their possible role as cofactors worsening COVID-19-related clinical manifestations. Methods: All patients with suspected SARS-CoV-infection, hospitalised in COVID-19 wards at the Sant'Anna University Hospital of Ferrara, were retrospectively included in this single-centre study and their specific bacterial serologies were assessed. Univariate and logistic regression analyses were performed. Results: A total of 1204 individual records were retrieved. Among them, 959 were excluded because of a negative nasopharyngeal swab or missing data; of the eligible 245 patients, 51 were co-infected. Compared to patients with SARS-CoV-2 infection alone, those with Chlamydia pneumoniae or Mycoplasma pneumoniae co-infections had worse respiratory/radiological features and more intensive care unit admissions. However, the co-infection did not result in a higher mortality rate. Conclusions: The present study, comparing clinical, laboratory and radiological findings between patients with COVID-19 vs. those with co-infections (C. pneumoniae or M. pneumoniae) showed that, on admission, these features were worse in co-infected patients, although the mortality rate did not differ between the two groups. [ABSTRACT FROM AUTHOR]

Background: Living in socio-economically disadvantaged neighborhoods can predispose persons to numerous health conditions. The purpose of this study was to report the general health conditions of persons living in disadvantaged neighborhoods in Rome, Italy, a large European metropolitan city. Participants were reached through the mobile facilities of the primary care services of the Dicastery for the Charity Services, Vatican City. Methods: People living in disadvantaged neighborhoods were reached with mobile medical units by doctors, nurses, and paramedics. Demographic characteristics, degree of social integration, housing conditions, and history of smoking and/or alcohol use were investigated. Unstructured interviews and general health assessments were performed to investigate common acute and/or chronic diseases, and history of positivity to COVID-19. Basic health parameters were measured; data were collected and analyzed. Results: Over a 10-month period, 436 individuals aged 18–95 years were enrolled in the study. Most lived in dormitories, whereas a few lived in unsheltered settings. Most participants (76%) were unemployed. Smoking and drinking habits were comparable to the general population. The most common pathological conditions were cardiovascular diseases in 103 subjects (23.39%), diabetes in 65 (14.9%), followed by musculoskeletal system disorders (11.7%), eye diseases (10.5%), psychiatric conditions such as anxiety and depression (9.2%), and chronic respiratory conditions (8.7%). Conclusions: Subjects in our sample showed several pathologic conditions that may be related to their living conditions, thus encouraging the development of more efficient and effective strategies for a population-tailored diagnosis and treatment. [ABSTRACT FROM AUTHOR]

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE. [ABSTRACT FROM AUTHOR]

3-(1-Naphthalenylmethyl)-1-pentyl-1H-indole (JWH-175) is a synthetic cannabinoid illegally marketed for its psychoactive cannabis-like effects. This study aimed to investigate and compare in vitro and in vivo pharmacodynamic activity of JWH-175 with that of 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018), as well as evaluate the in vitro (human liver microsomes) and in vivo (urine and plasma of CD-1 male mice) metabolic profile of JWH-175. In vitro binding studies showed that JWH-175 is a cannabinoid receptor agonist less potent than JWH-018 on mouse and human CB1 and CB2 receptors. In agreement with in vitro data, JWH-175 reduced the fESPS in brain hippocampal slices of mice less effectively than JWH-018. Similarly, in vivo behavioral studies showed that JWH-175 impaired sensorimotor responses, reduced breath rate and motor activity, and increased pain threshold to mechanical stimuli less potently than JWH-018. Metabolic studies demonstrated that JWH-175 is rapidly bioactivated to JWH-018 in mice blood, suggesting that in vivo effects of JWH-175 are also due to JWH-018 formation. The pharmaco-toxicological profile of JWH-175 was characterized for the first time, proving its in vivo bio-activation to the more potent agonist JWH-018. Thus, it highlighted the great importance of investigating the in vivo metabolism of synthetic cannabinoids for both clinical toxicology and forensic purposes. [ABSTRACT FROM AUTHOR]

As the literature highlights, many health behavior theories try to explain both social and psychological variables influencing an individual's health behavior. This study integrates insights relative to the antecedents of getting vaccinated from health behavior theories, particularly including the health belief model (HBM), the theory of planned behavior (TPB), and the different socio-demographic factors. Furthermore, we considered the possible mechanism of impact of distrust in science on individuals' hesitance and resistance to taking up SARS-CoV-2 vaccination in subjects living in Italy. A correlational study of 1095 subjects enrolled when the national vaccination campaign for the third dose was launched. A questionnaire was used to measure: Italian Risk Perception; subjective norm; trust in science, trust in the vaccine; fear of COVID-19; fear of the vaccine; perceived knowledge about SARS-CoV-2; booster vaccination intention. Principal results show that: (i) the positive relationship provided by HBM theory between perceptions of SARS-CoV-2 risk (vulnerability and severity) and intention to have the vaccine, through fear of COVID-19; (ii) the positive relationship between subjective norms and both trust in science and vaccination intention; (iii) that trust in science plays a crucial role in predicting vaccination intention. Finally, the results provided indications about a positive relationship between subjective norms and fear of COVID-19, and a full mediation role of trust in science in the relationships between determinants of both TPA and HBM, fear of COVID-19, and vaccination intention. In conclusion, an individual's intention (not) to get vaccinated requires the consideration of a plethora of socio-psychological factors. However, overall, trust in science appears to be a key determinant of vaccination intention. Additional strategies promoting healthy behavior are needed. [ABSTRACT FROM AUTHOR]

In the last decades, nanotechnology-based tools have attracted attention in the scientific community, due to their potential applications in different areas from medicine to engineering, but several toxicological effects mediated by these advanced materials have been shown on the environment and human health. At present, the effects of engineered nanomaterials on gametogenesis have not yet been well understood. In the present study, we addressed this issue using the yeast Saccharomyces cerevisiae as a model eukaryote to evaluate the effects of cadmium sulfide quantum dots (CdS QDs) on sporulation, a process equivalent to gametogenesis in higher organisms. We have observed that CdS QDs cause a strong inhibition of spore development with the formation of aberrant, multinucleated cells. In line with these observations, treatment with CdS QDs down-regulates genes encoding crucial regulators of sporulation process, in particular, the transcription factor Ndt80 that coordinates different genes involved in progression through the meiosis and spore morphogenesis. Down-regulation of NDT80 mediated by CdS QDs causes a block of the meiotic cell cycle and a return to mitosis, leading to the formation of aberrant, multinucleated cells. These results indicate that CdS QDs inhibit gametogenesis in an irreversible manner, with adverse effects on cell-cycle progression. [ABSTRACT FROM AUTHOR]

According to the latest data from the World Health Organization (WHO), since the start of the COVID-19 pandemic, there have been 761,402,282 confirmed cases worldwide and 6,887,000 deaths reported so far as a result of pneumonia complicated by SARS-CoV-2 [[2]]. These papers provided insights into epidemiology, pathogenesis, epigenetics [[3]] COVID-19 emergencies in hospital settings [[5]], advanced diagnosis [[6], [8]], vaccination [[9]], and SARS-CoV-2 infection in the experimental setting [[11]]. Coronavirus Disease 2019 (COVID-19) is a life-threatening disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus which was first reported in late 2019 in China, from where it then spread worldwide [[1]]. A fair number of manuscripts concerning the diagnosis of SARS-CoV-2 infection have been the subject of publication in this Special Issue. [Extracted from the article]

Lithium titanium oxide (Li4Ti5O12, LTO) is an attractive negative electrode for the development of safe—next-generation—lithium-ion batteries (LIBs). LTO can find specific applications complementary to existing alternatives for LIBs thanks to its good rate capability at high C-rates, fast lithium intercalation, and high cycling stability. Furthermore, LIBs featuring LTO electrodes are inherently safer owing to the LTO's operating potential of 1.55 V vs. Li+/Li where the commonly used organic-based electrolytes are thermodynamically stable. Herein, we report the combined use of water-soluble sodium alginate (SA) binder and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI)-tetraglyme (1m-T) electrolyte and we demonstrate the improvement of the electrochemical performance of LTO-based electrodes with respect to those operating in conventional electrolyte 1M LiPF6-ethylene carbonate: dimethyl carbonate (LP30). We also tackle the analysis of the impact of combining the binder/electrolyte on the long-term cycling performance of LTO electrodes featuring SA or conventional polyvinylidene fluoride (PVdF) as binders. Therefore, to assess the impact of the combination of binder/electrolyte on performance, we performed post-mortem characterization by ex situ synchrotron diffraction experiments of LTO electrodes after cycling in LP30 and 1m-T electrolytes. [ABSTRACT FROM AUTHOR]