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Nicola Luigi Bragazzi,1– 4 Hicham Khabbache,5 Khalid Ouazizi,6 Driss Ait Ali,6 Hanane El Ghouat,6 Laila El Alami,6 Hisham Atwan,7 Ruba Tuma,8– 10 Nomy Dickman,10 Raymond Farah,10,11 Rola Khamisy-Farah9,10 1Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Parma, Italy; 2Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON, Canada; 3Postgraduate School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; 4United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair, Health Anthropology Biosphere and Healing Systems, University of Genoa, Genoa, Italy; 5Director of the UNESCO Chair “Lifelong Learning Observatory” (UNESCO/UMSBA), Fez, Morocco; 6Department of Psychology, Faculty of Arts and Human Sciences Fès-Saïss, Sidi Mohamed Ben Abdellah University, Fez, Morocco; 7Department of Internal Medicine, Kaplan Medical Centre, Hebrew University, Rehovot, Israel; 8Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Galilee, Israel; 9Clalit Health Services, Akko, Israel; 10Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; 11Department of Internal Medicine B, Ziv Medical Center, Safed, IsraelCorrespondence: Nicola Luigi Bragazzi, Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Via Volturno 39, Parma, 43125, Italy, Tel +39 0521 903121, Email nicolaluigi.bragazzi@unipr.itPurpose: Sex and Gender-Based Medicine (SGBM) addresses the influence of sex and gender on health and healthcare, emphasizing personalized care. Integrating SGBM into medical education is challenging. This study examines the implementation of an SGBM course in an Israeli university during the first year of the medical school.Methods: The course integrated lectures, group work, online gender studies resources, workshops, teacher training, and essential literature. The curriculum spanned pre-clinical and clinical aspects, featuring seven 90-minute sessions. Surveys assessed course structure, content, and lecturers using a 5-point Likert scale and qualitative feedback. Quantitative analysis involved descriptive statistics, and thematic analysis was used for qualitative data.Results: Of the 84 students surveyed, 35 (41.7%) responded to the first part, and 30 (35.7%) to the second. The SGBM course received high satisfaction with an average score of 3.63, surpassing other first-year courses (average 3.21). Students appreciated the supportive academic atmosphere (mean score 4.20) and diverse teaching methods (mean score 4.03), while the development of feminist thinking was less appreciated (average score 3.49). Lecturers received high ratings (average score 4.33). Qualitative feedback highlighted the value of group work, the significance of the subject matter, and the helpfulness of supplementary videos. Students requested more content on contemporary issues like gender transition and patient perspectives. The feminist medicine aspect was contentious, with students seeking better gender balance and scientific evidence.Conclusion: Introducing SGBM into the first-year curriculum yielded positive results with high student satisfaction for content and lecturers. An expanded course module is planned, to be assessed at the end of the next academic year.Keywords: sex- and gender-based medicine, medical education, medical training, curriculum integration

Nicola Luigi Bragazzi,1–4 Hicham Khabbache,5 Khalid Ouazizi,6 Driss Ait Ali,6 Hanane El Ghouat,6 Laila El Alami,6 Hisham Atwan,7 Ruba Tuma,8–10 Nomy Dickman,10 Raymond Farah,10,11 Rola Khamisy-Farah9,10 1Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Parma, Italy; 2Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON, Canada; 3Postgraduate School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; 4United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair, Health Anthropology Biosphere and Healing Systems, University of Genoa, Genoa, Italy; 5Director of the UNESCO Chair “Lifelong Learning Observatory” (UNESCO/UMSBA), Fez, Morocco; 6Department of Psychology, Faculty of Arts and Human Sciences Fès-Saïss, Sidi Mohamed Ben Abdellah University, Fez, Morocco; 7Department of Internal Medicine, Kaplan Medical Centre, Hebrew University, Rehovot, Israel; 8Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Galilee, Israel; 9Clalit Health Services, Akko, Israel; 10Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; 11Department of Internal Medicine B, Ziv Medical Center, Safed, IsraelCorrespondence: Nicola Luigi Bragazzi, Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Via Volturno 39, Parma, 43125, Italy, Tel +39 0521 903121, Email nicolaluigi.bragazzi@unipr.it

Background: The COVID-19 pandemic has significantly strained health care systems globally, leading to an overwhelming influx of patients and exacerbating resource limitations. Concurrently, an "infodemic" of misinformation, particularly prevalent in women's health, has emerged. This challenge has been pivotal for health care providers, especially gynecologists and obstetricians, in managing pregnant women's health. The pandemic heightened risks for pregnant women from COVID-19, necessitating balanced advice from specialists on vaccine safety versus known risks. In addition, the advent of generative artificial intelligence (AI), such as large language models (LLMs), offers promising support in health care. However, they necessitate rigorous testing., Objective: This study aimed to assess LLMs' proficiency, clarity, and objectivity regarding COVID-19's impacts on pregnancy., Methods: This study evaluates 4 major AI prototypes (ChatGPT-3.5, ChatGPT-4, Microsoft Copilot, and Google Bard) using zero-shot prompts in a questionnaire validated among 159 Israeli gynecologists and obstetricians. The questionnaire assesses proficiency in providing accurate information on COVID-19 in relation to pregnancy. Text-mining, sentiment analysis, and readability (Flesch-Kincaid grade level and Flesch Reading Ease Score) were also conducted., Results: In terms of LLMs' knowledge, ChatGPT-4 and Microsoft Copilot each scored 97% (32/33), Google Bard 94% (31/33), and ChatGPT-3.5 82% (27/33). ChatGPT-4 incorrectly stated an increased risk of miscarriage due to COVID-19. Google Bard and Microsoft Copilot had minor inaccuracies concerning COVID-19 transmission and complications. In the sentiment analysis, Microsoft Copilot achieved the least negative score (-4), followed by ChatGPT-4 (-6) and Google Bard (-7), while ChatGPT-3.5 obtained the most negative score (-12). Finally, concerning the readability analysis, Flesch-Kincaid Grade Level and Flesch Reading Ease Score showed that Microsoft Copilot was the most accessible at 9.9 and 49, followed by ChatGPT-4 at 12.4 and 37.1, while ChatGPT-3.5 (12.9 and 35.6) and Google Bard (12.9 and 35.8) generated particularly complex responses., Conclusions: The study highlights varying knowledge levels of LLMs in relation to COVID-19 and pregnancy. ChatGPT-3.5 showed the least knowledge and alignment with scientific evidence. Readability and complexity analyses suggest that each AI's approach was tailored to specific audiences, with ChatGPT versions being more suitable for specialized readers and Microsoft Copilot for the general public. Sentiment analysis revealed notable variations in the way LLMs communicated critical information, underscoring the essential role of neutral and objective health care communication in ensuring that pregnant women, particularly vulnerable during the COVID-19 pandemic, receive accurate and reassuring guidance. Overall, ChatGPT-4, Microsoft Copilot, and Google Bard generally provided accurate, updated information on COVID-19 and vaccines in maternal and fetal health, aligning with health guidelines. The study demonstrated the potential role of AI in supplementing health care knowledge, with a need for continuous updating and verification of AI knowledge bases. The choice of AI tool should consider the target audience and required information detail level., (©Nicola Luigi Bragazzi, Michèle Buchinger, Hisham Atwan, Ruba Tuma, Francesco Chirico, Lukasz Szarpak, Raymond Farah, Rola Khamisy-Farah. Originally published in JMIR Formative Research (https://formative.jmir.org), 05.02.2025.)

Transcription factors of the bHLH-PAS family play vital roles in animal development, physiology, and disease. Two members of the family require binding of low-molecular weight ligands for their activity: the vertebrate aryl hydrocarbon receptor (AHR) and the insect juvenile hormone receptor (JHR). In the fly Drosophila melanogaster, the paralogous proteins GCE and MET constitute the ligand-binding component of JHR complexes. Whilst GCE/MET and AHR are phylogenetically heterologous, their mode of action is similar. JHR is targeted by several synthetic agonists that serve as insecticides disrupting the insect endocrine system. AHR is an important regulator of human endocrine homeostasis, and it responds to environmental pollutants and endocrine disruptors. Whether AHR signaling is affected by compounds that can activate JHR has not been reported. To address this question, we screened a chemical library of 50,000 compounds to identify 93 novel JHR agonists in a reporter system based on Drosophila cells. Of these compounds, 26% modulated AHR signaling in an analogous reporter assay in a human cell line, indicating a significant overlap in the agonist repertoires of the two receptors. To explore the structural features of agonist-dependent activation of JHR and AHR, we compared the ligand-binding cavities and their interactions with selective and common ligands of AHR and GCE. Molecular dynamics modeling revealed ligand-specific as well as conserved side chains within the respective cavities. Significance of predicted interactions was supported through site-directed mutagenesis. The results have indicated that synthetic insect juvenile hormone agonists might interfere with AHR signaling in human cells., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “DS and MJ have co-founded a start-up Preagon Biotech, s.r.o”., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Idiopathic polyhydramnios is associated with adverse neonatal outcome. The aim of this study was to examine the value of the middle cerebral artery pulsatility index (MCA-PI) in predicting adverse perinatal outcome in pregnancies affected by idiopathic polyhydramnios., Methods: A retrospective study was performed during 2013-2022 at a tertiary-care university affiliated hospital. The study included singleton pregnancies with idiopathic polyhydramnios. Obstetrical and perinatal outcomes were compared between women with MCA-PI <10th percentile and women with MCA-P ≥ 10th percentile. A composite adverse perinatal outcome was defined as an Apgar score <7 at 5 minutes, umbilical artery pH <7.15, emergent caesarean delivery (CD) or operative delivery due to foetal distress, neonatal intensive care admission or foetal death., Results: Among 45,459 pregnancies, 128 (0.3%) had idiopathic polyhydramnios; 27 exhibited MCA-PI <10th percentile. Among the latter, compared to pregnancies with MCA-PI ≥10th percentile group, the rates were higher of emergent CD (25.9% vs. 7.9%, p = 0.017) and adverse perinatal outcomes (37.0% vs. 15.8%, p = 0.020). These differences persisted in a subgroup analysis of women with moderate or severe polyhydramnios. In the MCA-PI <10th percentile group, the median MCA-PI and cerebroplacental ratio were lower: 0.9 vs. 1.7, p  < 0.001 and 0.7 vs. 2.1, p  < 0.001, respectively. Receiver operating characteristic curve analysis indicated a significant association of MCA-PI with emergent CD/operative delivery for foetal distress (area under curve = 0.672, p = 0.031); the sensitivity was 46.7% and specificity 82.3%. Cerebroplacental ratio values were not associated with adverse perinatal outcomes., Conclusions: Idiopathic polyhydramnios might be associated with foetal cerebral blood flow redistribution, potentially contributing to an increased risk of adverse neonatal outcomes. Prospective studies are required to establish the role of foetal Doppler studies in the antenatal surveillance of idiopathic polyhydramnios, and to determine whether evidence of abnormal MCA-PI serves as a reliable predictor of perinatal outcomes, potentially necessitating labour induction.

Background: The integration of gender and sexuality awareness in health care is increasingly recognized as vital for patient outcomes. Despite this, there is a notable lack of comprehensive data on the current state of physicians' training and perceptions in these areas, leading to a gap in targeted educational interventions and optimal health care delivery., Objective: The study's aim was to explore the experiences and perceptions of attending and resident physicians regarding the inclusion of gender and sexuality content in medical school curricula and professional practice in Israel., Methods: This cross-sectional survey targeted a diverse group of physicians across various specializations and experience levels. Distributed through Israeli Medical Associations and professional networks, it included sections on experiences with gender and sexuality content, perceptions of knowledge, the impact of medical school curricula on professional capabilities, and views on integrating gender medicine in medical education. Descriptive and correlational analyses, along with gender-based and medical status-based comparisons, were used, complemented, and enhanced by qualitative analysis of participants' replies., Results: The survey, encompassing 189 respondents, revealed low-to-moderate exposure to gender and sexuality content in medical school curricula, with a similar perception of preparedness. A need for more comprehensive training was widely recognized. The majority valued training in these areas for enhancing professional capabilities, identifying 10 essential gender-related knowledge areas. The preference for integrating gender medicine throughout medical education was significant. Gender-based analysis indicated variations in exposure and perceptions., Conclusions: The study highlights a crucial need for the inclusion of gender and sexuality awareness in medical education and practice. It suggests the necessity for curriculum development, targeted training programs, policy advocacy, mentorship initiatives, and research to evaluate the effectiveness of these interventions. The findings serve as a foundation for future directions in medical education, aiming for a more inclusive, aware, and prepared medical workforce., (©Rola Khamisy-Farah, Eden Biras, Rabie Shehadeh, Ruba Tuma, Hisham Atwan, Anna Siri, Manlio Converti, Francesco Chirico, Łukasz Szarpak, Carlo Biz, Raymond Farah, Nicola Bragazzi. Originally published in JMIR Medical Education (https://mededu.jmir.org), 08.10.2024.)

Juvenile hormone (JH) signaling is realized at the gene regulatory level by receptors of the bHLH-PAS transcription factor family. The sesquiterpenoid hormones and their synthetic mimics are agonist ligands of a unique JH receptor (JHR) protein, methoprene-tolerant (MET). Upon binding an agonist to its PAS-B cavity, MET dissociates from a cytoplasmic chaperone complex including HSP83 and concomitantly switches to a bHLH-PAS partner taiman, forming a nuclear, transcriptionally active JHR heterodimer. This course of events resembles the vertebrate aryl hydrocarbon receptor (AHR), activated by a plethora of endogenous and synthetic compounds. Like in AHR, the pliable PAS-B cavity of MET adjusts to diverse ligands and binds them through similar mechanisms. Despite recent progress, we only begin to discern agonist-induced conformational shifts within the PAS-B domain, with the ultimate goal of understanding how these localized changes stimulate the assembly of the active JHR complex and, thus, fully grasp the mechanism of JHR signaling., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: Marek Jindra and David Sedlak are co-founders of Preagon Biotech, a company aiming to develop specific JHR agonists as selective insecticides., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The cerebroplacental ratio is a sonographic tool used to predict poor pregnancy outcomes. Data are insufficient regarding its use in postdate pregnancy. We evaluated the cerebroplacental ratio's prediction of unfavorable pregnancy outcomes in women at 40-42 weeks gestation with normal amniotic fluid index., Methods: This prospective observational study included 101 women with low-risk singleton pregnancy and gestational age > 40 weeks who delivered in a university affiliated hospital during 2020-2021. The middle cerebral artery pulsatility index, the umbilical artery pulsatility index, and the cerebroplacental ratio, which is their quotient, were compared between women with favorable and unfavorable pregnancy outcomes. The latter included: meconium-stained amniotic fluid, cesarean or vacuum-assisted delivery due to pathological cardiotocography (category 2 or 3), 5-min Apgar score < 7, umbilical cord pH < 7.1, neonatal intensive care unit admission, and neonatal death., Results: Fetal Doppler, performed at a median gestational age of 40.3 (40.0-41.6), did not differ between 75 (74.3%) women with favorable obstetrical outcomes and 26 (25.7%) with unfavorable outcomes. In multivariate analysis, advanced maternal age and a history of a cesarean section were correlated with unfavorable outcomes, while Doppler indices were not found to be predictive. Among women at 41-42 weeks' gestation, for those with intrapartum fetal monitor category 2-3 vs. category 1, the mean umbilical artery pulsatility index was higher: 0.92 ± 0.34 vs. 0.71 ± 0.11 (p = 0.044)., Conclusion: According to the study results, fetal Doppler indices, including the cerebroplacental ratio, are not predictive of unfavorable outcome in women with pregnancies exceeding 40 weeks. Larger prospective studies are needed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Copper indium sulfide (CIS) nanocrystals constitute a promising alternative to cadmium- and lead-containing nanoparticles. We report a synthetic method that yields hydrophilic, core-only CIS quantum dots, exhibiting size-dependent, copper-deficient composition and optical properties that are suitable for direct coupling to biomolecules and nonradiative energy transfer applications. To assist such applications, we complemented previous studies covering the femtosecond-picosecond time scale with the investigation of slower radiative and nonradiative processes on the nanosecond time scale, using both time-resolved emission and transient absorption. As expected for core particles, relaxation occurs mainly nonradiatively, resulting in low, size-dependent photoluminescence quantum yield. The nonradiative relaxation from the first excited band is wavelength-dependent with lifetimes between 25 and 150 ns, reflecting the size distribution of the particles. Approximately constant lifetimes of around 65 ns were observed for nonradiative relaxation from the defect states at lower energies. The photoluminescence exhibited a large Stokes shift. The band gap emission decays on the order of 10 ns, while the defect emission is further red-shifted, and the lifetimes are on the order of 100 ns. Both sets of radiative lifetimes are wavelength-dependent, increasing toward longer wavelengths. Despite the low radiative quantum yield, the aqueous solubility and long lifetimes of the defect states are compatible with the proposed role of CIS quantum dots as excitation energy donors to biological molecules., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: The cavum septi pellucidi (CSP) is a brain-enclosed cavity located on the midline between the two leaflets of the septum pellucidum that separates the lateral ventricles. This structure develops in the fetus from week 18 and can be seen up to week 37 in almost all cases and then begins to disappear., Objectives: To measure and determine the normative values of the CSP volume in fetuses between 20 to 40 weeks of gestation., Methods: The study comprised 161 consecutive pregnant women between 20 to 40 weeks of gestation with single viable fetuses. All patients had normal, disease-free pregnancies. Transvaginal or transabdominal ultrasound was used according to the fetal presentation. The fetal head was assessed in mid-sagittal sections. Once the CSP was visualized, its volume was measured using three-dimensional ultrasound with Virtual Organ Computer-aided Analysis software. The width of the CSP was also measured at the biparietal diameter (BPD) plane., Results: Of the 161 fetuses, the CSP volume was measured in 158. In three patients the CSP was not identified. The CSP volume correlated poorly with gestational age (r=0.229) and with the BPD (r=0.295). The mean CSP volume was 0.508 ± 0.372 ml (range: 0.03-1.78 ml). The simple measurement of the CSP width correlated better with gestational age (r=0.535) and the BPD (r=0.484)., Conclusions: The CSP volume had a poor correlation with gestational age; however, the volume did not exceed 2 ml regardless of gestational age. This information can be used to assess pathologies involving the CSP.

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported., Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome., Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir., Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes., Competing Interests: Potential conflicts of interest. M.W.D. advises, is on the speakers’ bureau for Gilead, AbbVie, GSK, and Merck, and has received grants from Gilead and AbbVie. J.G. advises, is on the speakers’ bureau for, and received grants from Gilead; he advises and is on the speakers’ bureau for AbbVie and MSD. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The Sec translocon is a highly conserved membrane assembly for polypeptide transport across, or into, lipid bilayers. In bacteria, secretion through the core channel complex-SecYEG in the inner membrane-is powered by the cytosolic ATPase SecA. Here, we use single-molecule fluorescence to interrogate the conformational state of SecYEG throughout the ATP hydrolysis cycle of SecA. We show that the SecYEG channel fluctuations between open and closed states are much faster (~20-fold during translocation) than ATP turnover, and that the nucleotide status of SecA modulates the rates of opening and closure. The SecY variant PrlA4, which exhibits faster transport but unaffected ATPase rates, increases the dwell time in the open state, facilitating pre-protein diffusion through the pore and thereby enhancing translocation efficiency. Thus, rapid SecYEG channel dynamics are allosterically coupled to SecA via modulation of the energy landscape, and play an integral part in protein transport. Loose coupling of ATP-turnover by SecA to the dynamic properties of SecYEG is compatible with a Brownian-rachet mechanism of translocation, rather than strict nucleotide-dependent interconversion between different static states of a power stroke., (© 2023. The Author(s).)

Human papillomavirus (HPV) is a small, non-enveloped, double-stranded DNA virus, belonging to the family of Papillomaviridae. It is a highly common infectious agent, which causes one of the most widespread sexually transmitted infections (STIs), involving approximately 20% of sexually active female adolescents and up to 80% of female adults aged 50 years. There exist two major preventative strategies: namely, anti-HPV vaccination and cervical screening. Healthcare providers, including nurses, can play a crucial role in HPV immunization campaigns, counteracting vaccine hesitancy and doing advocacy and counseling. To explore the overall knowledge of HPV and HPV-related issues, as well as the attitudes and practices of Israeli nurses, a modified and adapted, previously validated knowledge, attitudes, and practices (KAP) questionnaire was administered to a sample of 565 participants, 481 female (85.1%) and 84 male (14.9%). Most of them were married (n = 428, 75.8%), with more than 5 years of experience (n = 405, 71.7%), working in the general/internal medicine ward (n = 432, 76.5%), and Jewish (n = 352, 62.3%). Only 87 nurses (15.4%) got vaccinated against HPV. Forty-four (9.1%) of the female nurses never underwent a Pap smear. Higher percentages of right replies were reported only for the item related to available preventative strategies for cervical cancer (82.1% versus 17.9%). Higher percentages of wrong replies were reported for items related to body regions that can be infected by HPV (60.5% versus 39.5%), percentage of girls aged 15-18 years being sexually active (68.0% versus 32.0%). Similar percentages of right and wrong replies were reported for items related to whom the Pap test is recommended (52.7% versus 47.3%), Israeli Ministry of Health's guidelines for anti-HPV vaccination (50.4% versus 49.6%), and percentage of boys aged 15-18 years being sexually active (44.4% versus 55.6%). Concerning the reliability of the third section of the questionnaire, Cronbach's alpha was deemed to be acceptable (α = 0.64). Statistically significant determinants of reporting lower scores in HPV-related attitudes and practices were religion (OR 1.44 [95%CI 1.02-2.04]), and male offspring (OR 1.22 [1.03-1.44]). This study has important implications for policy- and decision-makers in that they should be aware of the overall poor and unsatisfactory level of HPV-related knowledge among Israeli nurses and implement multipronged HPV vaccine promotion programs, taking into account the challenges of a multicultural and diverse society like Israel., (© 2023. The Author(s) under exclusive licence to American Association for Cancer Education.)

Avian (ortho)reovirus (ARV), which belongs to Reoviridae family, is a major domestic fowl pathogen and is the causative agent of viral tenosynovitis and chronic respiratory disease in chicken. ARV replicates within cytoplasmic inclusions, so-called viral factories, that form by phase separation and thus belong to a wider class of biological condensates. Here, we evaluate different optical imaging methods that have been developed or adapted to follow formation, fluidity and composition of viral factories and compare them with the complementary structural information obtained by well-established transmission electron microscopy and electron tomography. The molecular and cellular biology aspects for setting up and following virus infection in cells by imaging are described first. We then demonstrate that a wide-field version of fluorescence recovery after photobleaching is an effective tool to measure fluidity of mobile viral factories. A new technique, holotomographic phase microscopy, is then used for imaging of viral factory formation in live cells in three dimensions. Confocal Raman microscopy of infected cells provides "chemical" contrast for label-free segmentation of images and addresses important questions about biomolecular concentrations within viral factories and other biological condensates. Optical imaging is complemented by electron microscopy and tomography which supply higher resolution structural detail, including visualization of individual virions within the three-dimensional cellular context., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Juvenile hormones (JHs) control insect metamorphosis and reproduction. JHs act through a receptor complex consisting of methoprene-tolerant (Met) and taiman (Tai) proteins to induce transcription of specific genes. Among chemically diverse synthetic JH mimics (juvenoids), some of which serve as insecticides, unique peptidic juvenoids stand out as being highly potent yet exquisitely selective to a specific family of true bugs. Their mode of action is unknown. Here we demonstrate that, like established JH receptor agonists, peptidic juvenoids act upon the JHR Met to halt metamorphosis in larvae of the linden bug, Pyrrhocoris apterus . Peptidic juvenoids induced ligand-dependent dimerization between Met and Tai proteins from P. apterus but, consistent with their selectivity, not from other insects. A cell-based split-luciferase system revealed that the Met-Tai complex assembled within minutes of agonist presence. To explore the potential of juvenoid peptides, we synthesized 120 new derivatives and tested them in Met-Tai interaction assays. While many substituents led to loss of activity, improved derivatives active at sub-nanomolar range outperformed hitherto existing peptidic and classical juvenoids including fenoxycarb. Their potency in inducing Met-Tai interaction corresponded with the capacity to block metamorphosis in P. apterus larvae and to stimulate oogenesis in reproductively arrested adult females. Molecular modeling demonstrated that the high potency correlates with high affinity. This is a result of malleability of the ligand-binding pocket of P. apterus Met that allows larger peptidic ligands to maximize their contact surface. Our data establish peptidic juvenoids as highly potent and species-selective novel JHR agonists.

This case report describes the efficacy and advantages of using a high-power diode laser in non-contact mode to remove racial melanin pigmentation from the oral mucosa in an aesthetically sensible area to reduce thermal damage and promote better postoperative results. In the presented case, the lesion was removed under local anesthesia in a single session using high-power diode equipment with circular movements over the lesion (10 seconds maximum for each irradiation cycle, with 30 seconds for thermal relaxation, for a total of two cycles), maintaining an average distance of 2-3 mm from the target tissue without fiber activation (continuous wave, 2 W, delivered by quartz fiber with 300 µ). The patient did not report immediate postoperative pain; however, analgesic use was recorded during the first day after the surgical procedure. The biological response and cosmetic results were satisfactory, with proper lesion removal and adequate cicatrization observed during a two-year follow-up period, without complications or compromise of periodontal tissue esthetics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hiramatsu Azevedo et al.)

The helicase domain of nonstructural protein 3 (NS3H) unwinds the double-stranded RNA replication intermediate in an ATP-dependent manner during the flavivirus life cycle. While the ATP hydrolysis mechanism of Dengue and Zika viruses NS3H has been extensively studied, little is known in the case of the tick-borne encephalitis virus NS3H. We demonstrate that ssRNA binds with nanomolar affinity to NS3H and strongly stimulates the ATP hydrolysis cycle, whereas ssDNA binds only weakly and inhibits ATPase activity in a noncompetitive manner. Thus, NS3H is an RNA-specific helicase, whereas DNA might act as an allosteric inhibitor. Using modeling, we explored plausible allosteric mechanisms by which ssDNA inhibits the ATPase via nonspecific binding in the vicinity of the active site and ATP repositioning. We captured several structural snapshots of key ATP hydrolysis stages using X-ray crystallography. One intermediate, in which the inorganic phosphate and ADP remained trapped inside the ATPase site after hydrolysis, suggests that inorganic phosphate release is the rate-limiting step. Using structure-guided modeling and molecular dynamics simulation, we identified putative RNA-binding residues and observed that the opening and closing of the ATP-binding site modulates RNA affinity. Site-directed mutagenesis of the conserved RNA-binding residues revealed that the allosteric activation of ATPase activity is primarily communicated via an arginine residue in domain 1. In summary, we characterized conformational changes associated with modulating RNA affinity and mapped allosteric communication between RNA-binding groove and ATPase site of tick-borne encephalitis virus helicase., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)