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Yann F Mahe,1 Marie-Jesus Perez,1 Charlotte Tacheau,1 Chantal Fanchon,2 Richard Martin,3 Françoise Rousset,1 Sophie Seite4 1L’Oreal Research and Innovation, Clichy, 2L’Oréal Research and Innovation, Chevilly Larue, 3L’Oréal Research and Innovation Tours, 4La Roche-Posay Pharmaceutical Laboratories, Asnières, France Abstract: Vitreoscilla filiformis (VF) biomass (VFB) has been widely used in cosmetic preparations and shown to modulate the major inducible free-radical scavenger mitochondrial superoxide dismutase in skin cells. By adding La Roche-Posay (LRP) thermal spring water to the VF culture medium, we obtained a biomass (LRP-VFB) with a similar mitochondrial superoxide dismutase activation capacity to VF. Also, the new biomass more powerfully stimulated mRNA expression and antimicrobial peptides in reconstructed epidermis. Interestingly, a predictive computer model that analyzed transducing events within skin epidermal cells suggested that this protective activity may involve the Toll-like receptor 2/protein kinase C, zeta transduction pathway. Protein kinase C, zeta inhibition was effectively shown to abolish VFB-induced gene stimulation and confirmed this hypothesis. This thus opens new avenues for investigation into the improvement of skin homeostatic defense in relation to the control of its physiological microbiota and innate immunity. Keywords: innate skin defenses, TLR2, PKCz, La Roche-Posay, mitochondrial superoxide dismutase, SOD2

This study examined the prevalence of hepatitis A (HAV), B (HBV), C (HCV), and Human Immunodeficiency Virus (HIV) co-infection among Injection Drug Users (IDUs) in Los Angeles County, California, and predictors of multiple infections in this population. Six hundred seventy-nine IDUs were recruited from October 2002 through June 2004. Participants completed questionnaires to elicit demographic, drug and sex risk information, and were tested for hepatitis A, B, C and HIV.A linear regression model predicting the total number of infections (0 to 4 possible) was constructed. Significant associations were found between HAV and HBV infection, HAV and HCV infection, and HBV and HCV infection. Predictors of total co-infections included age of first injection, lifetime years in jail, and Hispanic ethnicity. Latinos had the highest proportion of HAV and HBV co-infection with HCV. The total number of co-infections, especially those co-infected with all three of the hepatitis infections, was unexpectedly high. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and the timing of pregnancy termination relative to the type of central nervous system (CNS) malformations. Design Retrospective cohort study. Setting: Multidisciplinary centre for prenatal diagnosis in the Languedoc-Roussillon region, France. Population: A cohort of 481 pregnancy terminations performed between 2005 and 2009. Methods: Detailed post-termination fetal and neuropathological analyses were carried out to identify the CNS malformations. Then, the prevalence and timing of pregnancy termination were assessed relative to the identified malformations. Results: About one-third of pregnancy terminations (143/481) were performed for severe CNS malformations. Up to 24 weeks of gestation (WG), pregnancy terminations (56.6%) were carried out mainly for defects occurring during the two major first steps of CNS development (neurulation and differentiation of cerebral vesicles). After 24 WG, pregnancy terminations (43.3%) were mainly performed for corpus callosum agenesis (16/17), vermian agenesis (10/12) and gyral anomalies (13/15). For hindbrain malformations and gyral anomalies, there was a significant relationship between the timing of pregnancy termination and the presence of a severe ventriculomegaly at prenatal diagnosis (p=0.002 and p=0.02, respectively). Conclusion: By classifying CNS malformations according to the neuropathological analysis, the authors show that the timing and prevalence of pregnancy termination are distributed in a manner that is consistent with what is currently known on the development of brain. They are also influenced by the French prenatal screening policy and the variable expressivity of the brain malformations and associated lesions. [ABSTRACT FROM AUTHOR]

There is an urgent need for antiviral compounds effective against currently known and future viral threats. The development of host-targeting antivirals (HTAs) appears as an alternative strategy to fight viral infections minimizing the potential of resistant mutant development and potentially leading to the identification of broad-spectrum antiviral agents. Among the host factors explored for HTA strategy, lipids constitute an attractive target as many viruses, even genetically diverse, hijack specific lipids during their lifecycle. Multiple repurposing efforts have been performed to analyze the antiviral properties of lipid-targeting compounds. These studies include the analysis of the effects of cholesterol lowering drugs such as statins, cholesterol transport inhibitors, sphingolipid modulators, de novo lipogenesis inhibitors blocking fatty acid synthesis, compounds targeting glycerophospholipids or drugs interfering with lipid droplet metabolism. This review is focused on the current status of lipid-based or lipid-targeting antiviral strategies and their potential for the development of antiviral therapies, with special emphasis on those studies that have reached advanced stages of development such as efficacy studies in animal models or clinical trials. Whereas there is still a long way to go, multiple proof-of-concept studies and clinical evidence reinforce the therapeutic potential of these strategies warranting their further development into effective antiviral therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre-diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case-control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. LCN2 was measured in 1267 incident CRC cases matched to 1267 controls using incidence density sampling. Conditional logistic regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) according to tumor subsite and sex. Weighted Cox proportional hazard regression was used to explore associations by adiposity status. In multivariable-adjusted analyses, the IRR [95% CI] per doubling in LCN2 concentration was 1.16 [0.98-1.37] for CRC overall, 1.26 [1.00-1.59] for colon cancer, and 1.08 [0.85-1.38] for rectal cancer. The association for colon cancer was more pronounced in women (IRR [95% CI], 1.66 [1.20-2.30]) and for proximal colon cancer (IRR [95% CI], 1.96 [1.15-3.34]), whereas no association was seen in men and distal colon cancer. The association for colon cancer was positive in individuals with high waist circumference (hazard ratio [95% CI], 1.69 [1.52-1.88]) and inverse in individuals with low waist circumference (hazard ratio [95% CI], 0.86 [0.76-0.98], P interaction<0.01). Overall, these data suggest that pre-diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: This study examines the impact of the COVID-19 pandemic on both routine and non-routine vaccinations in infants during their initial 18 months of life, concurrently exploring the complex influence of sociodemographic factors., Methods: A cohort study was conducted, involving 2007 children in two distinct periods: pre-pandemic (January-June 2018) and pandemic (March 2020-May 2021). Participants were classified into two cohorts: 962 children in the 2018 group and 1045 children in the 2020-21 group. Utilizing unconditional logistic regression, the association between vaccination (complete or non-routine) and socioeconomic factors was examined, with adjustments for potential confounding variables such as age, breastfeeding, gestational age, and twins., Results: The study's analysis reveals that in the post-pandemic period, mothers were three times more likely to opt for non-routine vaccines (95% CI 2.25-4.23). However, no significant alterations were observed in routine vaccination rates. Protective factors for complete vaccination included having an employed mother, higher education, and a medium-to-high income. Conversely, a higher income was associated with a reduced likelihood of complete vaccination (OR 0.34, 95% CI 0.20-0.59)., Conclusion: Contrary to initial expectations, this study concludes that the COVID-19 pandemic did not have a substantial impact on childhood complete vaccination rates. Nevertheless, a noticeable increase in the choice of non-routine vaccination was observed. Sociodemographic factors, such as maternal education, income, and employment status, emerged as key influencers, particularly in the context of deciding on non-routine vaccinations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Recently, there have been several calls for psychologists to dismantle systemic racism within the field (e.g., Buchanan et al., 2021; Dupree & Boykin, 2021; Wilcox et al., 2022). In this article, we discuss why incorporating critical histories into psychology curricula can be beneficial to this effort. We focus on three potential pathways: critical histories provide counterstories that challenge racist narratives, critical histories promote contexts that encourage antiracism practices (antiracist affordances), and critical histories can signal identity safety and belonging. To adequately integrate critical histories into psychology curricula, we make three recommendations. First, create and support a departmental curriculum that engages critical histories in the field of psychology at the undergraduate and graduate level (we offer some example topics and readings). Second, based on our own training experiences, we recommend that psychology graduate programs facilitate opportunities to take interdisciplinary courses that cover the history of race and racism in domestic and/or global contexts. Finally, we recommend funding research and supporting student projects that produce critical histories in psychology to expand the knowledge base of our field. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Since 1978 many children are born thanks to assisted reproductive technology (ART). However, the long-term effects of these therapies are still not fully known. Our objective is to evaluate the risk of cerebral palsy (CP) after ART compared with that in those spontaneously conceived (SC) and to examine this risk in single, multiple, and preterm births and the evolution of the risk over the years., Methods: PubMed, Embase, and Web of Science databases were searched until December 2022. Studies were included if they studied CP cases in children born through ART. 16 studies were finally selected. Quality of studies was assessed using Newcastle Ottawa Scale. Pooled OR was estimated by weighting individual OR/RR by the inverse of their variance. A random-effect model was applied. To assess the causes of heterogeneity, we performed meta-regression analyses., Results: A significantly high risk of CP was found (OR = 1.27; 95% CI 1.12 to 1.43) in children born through ART compared with those SC. This risk increased in singletons (OR = 1.48; 95% CI 1.23 to 1.79) but disappeared in multiple (OR = 1.05; 95% CI 0.93 to 1.18) and preterm births (OR = 1.09; 95% CI 0.87 to 1.37). We found a higher risk of CP in children born before the year 2000 (OR = 3.40; 95% CI 2.49 to 4.63)., Conclusions: ARTs slightly increase the risk of CP once the effect of multiple gestation is controlled. Further studies are needed to clarify whether the techniques themselves, fertility problems, or associated maternal comorbidities are responsible for this risk., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Irreversible Electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated. Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer. The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect)., (Copyright © 2023 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

SARS-CoV-2 is a large, enveloped and positive sense single stranded RNA virus. Its genome codes for 16 non-structural proteins. The largest protein of this complex is nsp3, that contains a well conserved Macro1 domain. Viral Macro domains were shown to bind to mono-ADP-ribose (MAR) and poly-ADP-ribose (PAR) in their free form or conjugated to protein substrates. They carry ADP-ribose hydrolase activities implicated in the regulation of innate immunity. SARS-CoV-2 and SARS-CoV show widely different induction and handling of the host interferon response. Herein, we have conducted a mutational study on the key amino-acid residue F156 in SARS-CoV-2, pinpointed by bioinformatic and structural studies, and its cognate residue N157 in SARS-CoV. Our data suggest that the exchange of these residues slightly modifies ADP-ribose binding, but drastically impacts de-MARylation activity. Alanine substitutions at this position hampers PAR binding, abolishes MAR hydrolysis of SARS-CoV-2, and reduces by 70% this activity in the case of SARS-CoV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This article reviews the evidence regarding the safety and efficacy of intra-cytoplasmic sperm injection (ICSI). It provides evidence-based clinical and laboratory guidelines and recommendations for use of ICSI within an assisted reproductive technology (ART) service. The guidelines address the evidence for the use of ICSI rather than conventional IVF (cIVF); the use of ART techniques supplementary to ICSI; and risks associated with ICSI. This article is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs and medical history of the patient, available resources, and institutional or clinical practice limitations.

Sun et al. demonstrate that defects in autophagy cause nicotinamide adenine dinucleotide (NAD) depletion and neurotoxicity. 1 Restoring NAD levels rescues cytotoxicity in autophagy-deficient neurons, providing a potential therapy for neurodegenerative and lysosomal storage diseases associated with autophagy defects., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Mutations in GBA1, the gene encoding the lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher's disease, are the most frequent genetic risk factor for Parkinson's disease (PD). Here, we employ global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from the cytosol into the mitochondria via recognition of internal mitochondrial targeting sequence-like signals. In mitochondria, GCase promotes the maintenance of mitochondrial complex I (CI) integrity and function. Furthermore, GCase interacts with the mitochondrial quality control proteins HSP60 and LONP1. Disease-associated mutations impair CI stability and function and enhance the interaction with the mitochondrial quality control machinery. These findings reveal a mitochondrial role of GCase and suggest that defective CI activity and energy metabolism may drive the pathogenesis of GCase-linked neurodegeneration., (© 2023. The Author(s).)

Background: COVID-19 pandemic has changed the way pregnancies have been controlled as well as working conditions. In countries with paid leave of work, leaving earlier has been a relevant measure for controlling the pandemic. No study has been published on factors associated with earlier leaving work in pregnancy and the consequences it could have on pregnancy outcomes., Objective: We aimed to identify woman and pregnancy characteristics associated with leaving work earlier and its consequences on pregnancy results., Method: A cohort study was carried out in Cantabria, Northern Spain, including 760 women who were pregnant in 2020 and were working at the beginning of their pregnancy. Data on pregnancy characteristics and results were obtained from medical records and gestational age at leaving work was self-reported. In a logistic regression analysis, leaving work before 26th week of pregnancy was the main effect variable., Results: Several factors were associated with lower probability of leaving work before 26th week, including university studies (OR = 0.49, 95% CI: 0.36, 0.68), having presential work (OR = 0.57, 95% CI: 0.40, 0.81), women born in non-European countries (OR = 0.55, 95% CI: 0.30, 1.01) and non-smokers (OR for smokers = 1.79, 95% CI: 1.12, 2.87). Neither type of delivery, gestational age at delivery nor other pregnancy results were associated with the gestational age of leaving work., Conclusion: Several pregnancy and women characteristics were associated with leaving work earlier in the COVID-19 pandemic, although it was not associated with any pregnancy outcome., (© 2023. The Author(s).)

The treatment of hepatitis C virus (HCV) has been a revolution in hepatology. Since the beginning of transplantation, liver cirrhosis and hepatocarcinoma on HCV cirrhosis has been the main etiology of liver transplantation. We set out to analyze the impact that C virus treatment has had on liver transplantation. To do so, we divided our cohort into 2 periods, one before virus treatment (from 2000-2014) and one after the onset of treatment (2014-2020). Taking into account this differentiation, we analyzed the percentage of patients transplanted for hepatocarcinoma over cirrhotic liver by HCV in both groups. Among the patients transplanted for HCV, we analyzed whether there were differences in hepatocarcinoma recurrences according to their serologic status at the time of transplantation., (Published by Elsevier Inc.)

Background: Clinical trials of the messenger RNA COVID-19 vaccines excluded individuals with active reproductive needs (attempting to conceive, currently pregnant, and/or lactating). Women comprise three-quarters of healthcare workers in the United States-an occupational field among the first to receive the vaccine. Professional medical and government organizations have encouraged shared decision-making and access to vaccination among those with active reproductive needs., Objective: This study aimed to characterize the information sources used by pregnancy-capable healthcare workers for information about the COVID-19 vaccines and to compare the self-reported "most important" source by the respondents' active reproductive needs, if any., Study Design: This was a web-based national survey of female, US-based healthcare workers in January 2021. Recruitment was done using social media and subsequent sharing via word of mouth. We classified the respondents into 6 groups on the basis of self-reported reproductive needs as follows: (1) preventing pregnancy, (2) attempting pregnancy, (3) currently pregnant, (4) lactating, (5) attempting pregnancy and lactating, and (6) currently pregnant and lactating. We provided respondents with a list of information sources (friends, family, obstetrician-gynecologists, pediatrician, news, social media, government organizations, their employer, and "other") and asked respondents which source(s) they used when looking for information about the vaccine and their most important source. We used descriptive statistics to characterize the information sources and compared the endorsement of government organizations and obstetrician-gynecologists, which were the most important information source between reproductive groups, using the chi-square test. The effect size was calculated using Cramér V., Results: Our survey had 11,405 unique respondents: 5846 (51.3%) were preventing pregnancy, 955 (8.4%) were attempting pregnancy, 2196 (19.3%) were currently pregnant, 2250 (19.7%) were lactating, 67 (0.6%) were attempting pregnancy and lactating, and 91 (0.8%) were currently pregnant and lactating. The most endorsed information sources were government organizations (88.7%), employers (48.5%), obstetrician-gynecologists (44.9%), and social media (39.6%). Considering the most important information source, the distribution of respondents endorsing government organizations was different between reproductive groups (P<.001); it was most common among respondents preventing pregnancy (62.6%) and least common among those currently pregnant (31.5%). We observed an inverse pattern among the respondents endorsing an obstetrician-gynecologist as the most important source; the source was most common among currently pregnant respondents (51.4%) and least common among those preventing pregnancy (5.8%), P<.001. The differences in the endorsement of social media as an information source between groups were significant but had a small effect size., Conclusion: Healthcare workers use government and professional medical organizations for information. Respondents attempting pregnancy and those pregnant and/or lactating are more likely to use social media and an obstetrician-gynecologist as information sources for vaccine decision-making. These data can inform public health messaging and counseling for clinicians., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dysregulated metabolism characterizes both animal and human forms of pulmonary hypertension (PH). Enzymes involved in fatty acid metabolism have previously not been assessed in human pulmonary arteries affected by pulmonary arterial hypertension (PAH), and how inhibition of fatty acid oxidation (FAO) may attenuate PH remains unclear. Fatty acid metabolism gene transcription was quantified in laser-dissected pulmonary arteries from 10 explanted lungs with advanced PAH (5 idiopathic, 5 associated with systemic sclerosis), and 5 donors without lung diseases. Effects of oxfenicine, a FAO inhibitor, on female Sugen 5416-chronic hypoxia (SuHx) rats were studied in vivo using right heart catheterization, and ex vivo using perfused lungs and pulmonary artery ring segments. The impact of pharmacologic (oxfenicine) and genetic (carnitine palmitoyltransferase 1a heterozygosity) FAO suppression was additionally probed in mouse models of Schistosoma and hypoxia-induced PH. Potential mechanisms underlying FAO-induced PH pathogenesis were examined by quantifying ATP and mitochondrial mass in oxfenicine-treated SuHx pulmonary arterial cells, and by assessing pulmonary arterial macrophage infiltration with immunohistochemistry. We found upregulated pulmonary arterial transcription of 26 and 13 FAO genes in idiopathic and systemic sclerosis-associated PAH, respectively. In addition to promoting de-remodeling of pulmonary arteries in SuHx rats, oxfenicine attenuated endothelin-1-induced vasoconstriction. FAO inhibition also conferred modest benefit in the two mouse models of PH. Oxfenicine increased mitochondrial mass in cultured rat pulmonary arterial cells, and decreased the density of perivascular macrophage infiltration in pulmonary arteries of treated SuHx rats. In summary, FAO inhibition attenuated experimental PH, and may be beneficial in human PAH.

Problem: Physicians' voices are valued in society and should be present in mainstream social media where they can provide valuable public health messaging and patient education as well as increase opportunities for medical education, mentoring, and collaboration. However, lack of formal education on effective use of social media prevents many physicians from using it., Approach: The authors developed a physician-led social media training program to address the need for formal instruction on social media use. The program was presented to medical students, trainees, and faculty at an academic medical institution in August and September 2020. The virtual format included 5 hour-long sessions with presentations by peer experts in social media. Peer physicians with experience using social media presented on a range of topics, including introductions to platforms, how to reach and grow audiences, and use of social media to advance patient education, medical education, and advocacy., Outcomes: There were 425 cumulative registrations for the 5 sessions of the Social Media Summit. The number of registrants increased for each session, suggesting that interest increased over time. Qualitative and quantitative participant feedback was collected via a brief, voluntary survey. All of the participants who completed the survey (n = 24) reported they were "very satisfied" (58.3%) or "somewhat satisfied" (41.7%) with the Summit., Next Steps: Physician involvement in social media presents opportunities for public health knowledge, medical education, scientific collaboration, and career advancement. Physicians who have been successful in using social media for these purposes are excellent peer educators and can fill the medical education void in social media training. Future plans include building sustainability of the program, collecting additional quantitative and qualitative feedback to guide improvement, and encouraging reproducibility., (Copyright © 2022 by the Association of American Medical Colleges.)