Are Female-Breadwinner Couples Always Less Stable? Evidence from French Administrative Data.

The paper studies the association between partners' relative incomes and union dissolution among couples in France. With the increase in dual-earner couples and women's educational level, couples in which women earn more than their partners are structurally becoming more widespread. Because female breadwinning challenges long-lived social norms regarding traditional gender roles, scholars have theorized a higher risk of union dissolution among female-breadwinner couples compared to couples in other income arrangements. We estimate the risk of union dissolution using regression analyses on unique longitudinal data from French administrative sources containing an unconventionally high number of couples (4% of the population) and separation events (more than 100,000), as well as precise and reliable income measurement. Female-breadwinner couples face a higher risk of union dissolution compared to other couple types. This result is robust to various definitions of female breadwinning and controls for partners' employment status. Contrary to recent research on other countries, we find no sign of a fading effect among younger cohorts. However, among younger, cohabiting couples and couples in registered partnerships the risk of union dissolution is lowest when both partners are employed and provide a similar share of the total couple's income, suggesting the emergence of a new profile of stable couples. The female-breadwinner penalty in union dissolution is in place; also in France, it holds among married and cohabiting couples and registered partnerships, across all birth cohorts and levels of household income.

Pharmacological strategies and nutritional supplements for managing dysgeusia among chemotherapy patients: A systematic review.

BACKGROUND/OBJECTIVE: Among the side effects of chemotherapy, there is dysgeusia, which is an alteration or damage to the taste perception that negatively impacts the biopsychosocial sphere of the patient. Therefore, it is important to recognize and manage it appropriately. The objective of this study is to identify clinical pharmacological strategies to reduce dysgeusia in chemotherapy patients. METHODS: A systematic literature review was conducted following the PRISMA guidelines between February and May 2023, utilizing PubMed, Embase, Cochrane Library, CINAHL, and the British Nursing Database. Methodological quality and bias risk assessment were performed using the JBI framework, while evidence certainty was evaluated using the Oxford OCEBM methodology. RESULTS: Out of 1225 consulted records, 12 articles were included. The results underscore the efficacy of diverse pharmacological interventions in mitigating dysgeusia among chemotherapy patients. These include zinc supplementation with a daily dosage ranging between 50 and 220 mg (p ≤ 0.005), lactoferrin at 250 mg thrice daily (p < 0.001), delta-9-tetrahydrocannabinol at 2 mg per day (p < 0.05), and cannabidiol at 150 mg per day (p = 0.04). All studies analysed showed a low risk of bias. The zinc and Delta-9-Tetrahydrocannabinoid treatment proved particularly promising, compared to the other treatments considered, where sample sizes were smaller and the placebo effect was not always clear. CONCLUSION: Among the various pharmacological strategies identified, those that appear most promising concern the integration of zinc and Delta-9-Tetrahydrocannabinoid. Future studies should further explore the treatments identified in this review to expand the evidence base in this relatively underexplored field.

Non-pharmacological strategies to alleviate dysgeusia in patients undergoing chemotherapy: A systematic review.

PURPOSE: Dysgeusia is a common side effect in oncology patients, significantly impacting their quality of life. This systematic review aims to evaluate the effectiveness of non-pharmacological strategies in treating dysgeusia in patients undergoing chemotherapy or radiotherapy. METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search across five databases: PubMed, Embase, Cochrane Library, CINAHL, and the British Nursing Database. We used the Joanna Briggs Institute Critical Appraisal Tools to assess the quality of the included studies. A harvest plot was used to synthesise evidence about the differential effects of population-level interventions. RESULTS: Nine studies of non-pharmacological strategies to manage dysgeusia were included. These studies encompassed a variety of interventions, including oral applications and supplements, instrumental techniques, and educational programs. The review identified promising interventions such as cryotherapy and Miraculine supplementation, which showed potential in mitigating taste alterations. Instrumental techniques like photobiomodulation therapy and complementary and integrative medicine approaches, including acupuncture and herbs, were also found to be beneficial. Educational and self-management strategies emerged as effective interventions for empowering patients to manage dysgeusia. Despite the diversity of interventions and the limitations of the included studies, such as small sample sizes and geographical differences, these findings underscore the potential of non-pharmacological strategies in managing dysgeusia. CONCLUSION: The results support the integration of these strategies into clinical practice, highlighting the importance of multidisciplinary approaches to improve patient care. Further research should prioritize rigorous studies to enhance evidence and explore long-term effects.

High habitat richness reduces the risk of tick-borne encephalitis in Europe: A multi-scale study.

Background: The natural transmission cycle of tick-borne encephalitis (TBE) virus is enhanced by complex interactions between ticks and key hosts strongly connected to habitat characteristics. The diversity of wildlife host species and their relative abundance is known to affect transmission of tick-borne diseases. Therefore, in the current context of global biodiversity loss, we explored the relationship between habitat richness and the pattern of human TBE cases in Europe to assess biodiversity's role in disease risk mitigation. Methods: We assessed human TBE case distribution across 879 European regions using official epidemiological data reported to The European Surveillance System (TESSy) between 2017 and 2021 from 15 countries. We explored the relationship between TBE presence and the habitat richness index (HRI1) by means of binomial regression. We validated our findings at local scale using data collected between 2017 and 2021 in 227 municipalities located in Trento and Belluno provinces, two known TBE foci in northern Italy. Findings: Our results showed a significant parabolic effect of HRI on the probability of presence of human TBE cases in the European regions included in our dataset, and a significant, negative effect of HRI on the local presence of TBE in northern Italy. At both spatial scales, TBE risk decreases in areas with higher values of HRI. Interpretation: To our knowledge, no efforts have yet been made to explore the relationship between biodiversity and TBE risk, probably due to the scarcity of high-resolution, large-scale data about the abundance or density of critical host species. Hence, in this study we considered habitat richness as proxy for vertebrate host diversity. The results suggest that in highly diverse habitats TBE risk decreases. Hence, biodiversity loss could enhance TBE risk for both humans and wildlife. This association is relevant to support the hypothesis that the maintenance of highly diverse ecosystems mitigates disease risk.

Modified Technique to Rehabilitate American Society of Anesthesiology-III Patient, Through Flapless Procedure With Computed Tomography-Guided Surgery.

PURPOSE: The aim was to evaluate the safety and effectiveness of a computed tomography-guided surgery implant placement with a flapless technique and immediate functional loading in an American Society of Anesthesiology-III patient. METHODS: This technical note involved a 64-year-old American Society of Anesthesiology-III patient. Her hopeless teeth were extracted and a restorative evaluation was provided as a prosthetic reference. The surgical procedure was based on the flapless technique that let us to use local anesthesia. The authors used an All-on-4 concept restoration for maxilla and conventional fixed prosthesis procedures for jaw rehabilitation. The authors placed 4 tilted implants in the upper maxilla and 6 right implants in the jaw. Implants were loaded with a provisional prosthesis on the same day of surgery. Five months later, provisional restoration was removed; the authors placed into the ceramic crowns 2 Procera Implant Bridge (Nobel Biocare) frameworks, developed through computer-aided design/computer-aided manufacturing technology. CONCLUSIONS: Computed tomography-guided surgery is a minimally invasive technique that allows, through a flapless approach, safer and more predictable procedures. In this technical note, the authors achieved accurate implant placement and precise fit of restoration with natural looking appearance; this patient-oriented-treatment led to a reduced healing time with better compliance.

Use of Concentrated Growth Factor (CGF) in Prosthetic-Guided Reconstruction on Two-Wall Bone Defect after Cystectomy: An Alternative to Traditional Regeneration.

This clinical case report's objective was to describe an alternative technique executed to ensure bone regeneration after removing a cystic lesion in the upper jaw. The bone defect after the cystectomy was filled with autologous fibrin-rich clots containing concentrated growth factor (CGF). A 45-year-old female patient was presumed to have a cystic lesion with massive bone destruction on the vestibular and palatal walls between teeth 2.2 and 2.3. CGF was applied to fill the gap to promote the development of the bone. The tooth was asymptomatic and repair was still increasing steadily after a year, according to the results of the clinical and radiological follow-up assessment. This article describes a different way to treat a two-wall defect involving both the palatal and buccal bone, after removing a cystic lesion, with the use of CGF as an equivalent to the traditional use of autologous or heterologous bone. A promising substance for bone repair is CGF fibrin, which may encourage the growth of new bone in jaw deformities and promote bone tissue healing.

Haemochromatosis in children: A national retrospective cohort promoted by the A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica) study group.

Haemochromatosis (HC) encompasses a range of genetic disorders. HFE-HC is by far the most common in adults, while non-HFE types are rare due to mutations of HJV, HAMP, TFR2 and gain-of-function mutations of SLC40A1. HC is often unknown to paediatricians as it is usually asymptomatic in childhood. We report clinical and biochemical data from 24 paediatric cases of HC (10 cases of HFE-, 5 TFR2-, 9 HJV-HC), with a median follow-up of 9.6 years. Unlike in the adult population, non-HFE-HC constitutes 58% (14/24) of the population in our series. Transferrin saturation was significantly higher in TFR2- and HJV-HC compared to HFE-HC, and serum ferritin and LIC were higher in HJV-HC compared to TFR2- and HFE-HC. Most HFE-HC subjects had relatively low ferritin and LIC at the time of diagnosis, so therapy could be postponed for most of them after the age of 18. Our results confirm that HJV-HC is a severe form already in childhood, emphasizing the importance of early diagnosis and treatment to avoid the development of organ damage and reduce morbidity and mortality. Although phlebotomies were tolerated by most patients, oral iron chelators could be a valid option in early-onset HC.

The stated preferences of community-based volunteers for roles in the prevention of violence against women and girls in Ghana: A discrete choice analysis.

Violence against women and girls (VAWG) is a human rights violation with substantial health-related consequences. Interventions to prevent VAWG, often implemented at the community level by volunteers, have been proven effective and cost-effective. One such intervention is the Rural Response System in Ghana, a volunteer-run program which hires community based action teams (COMBATs) to sensitise the community about VAWG and to provide counselling services in rural areas. To increase programmatic impact and maximise the retention of these volunteers, it is important to understand their preferences for incentives. We conducted a discrete choice experiment (DCE) among 107 COMBAT volunteers, in two Ghanaian districts in 2018, to examine their stated preferences for financial and non-financial incentives that could be offered in their roles. Each respondent answered 12 choice tasks, and each task comprised four hypothetical volunteering positions. The first three positions included different levels of five role attributes. The fourth option was to cease volunteering as a COMBAT volunteer (opt-out). We found that, overall, COMBAT volunteers cared most for receiving training in volunteering skills and three-monthly supervisions. These results were consistent between multinomial logit, and mixed multinomial logit models. A three-class latent class model fitted our data best, identifying subgroups of COMBAT workers with distinct preferences for incentives: The younger 'go getters'; older 'veterans', and the 'balanced bunch' encompassing the majority of the sample. The opt-out was chosen only 4 (0.3%) times. Only one other study quantitatively examined the preferences for incentives of VAWG-prevention volunteers using a DCE (Kasteng et al., 2016). Understanding preferences and how they vary between sub-groups can be leveraged by programme managers to improve volunteer motivation and retention. As effective VAWG-prevention programmes are scaled up from small pilots to the national level, data on volunteer preferences may be useful in improving volunteer retention.

A Comparison of Small Rodent Assemblages after a 20 Year Interval in the Alps.

Human-induced environmental alterations in the Alps may importantly affect small mammal species, but evidence in this sense is limited. We live-trapped small rodents in the Central-Eastern Italian Alps in three close-by habitat types (rocky scree, alpine grassland, and heath) at 2100 m a.s.l. during summer-fall, in 1997 and 2016. We compared small rodent assemblages through a Redundancy Detrended Analysis (RDA). In both surveys, we detected two specialist species, i.e., the common vole (Microtus arvalis) and the snow vole (Chionomys nivalis), and, unexpectedly, the forest generalist bank vole (Myodes glareolus). In 1997, grassland was mainly occupied by the common vole, while the bank vole and the snow vole were sympatric in the other habitats. In 2016, the snow vole was detected only in the scree, while other species did not show distribution changes. We discuss a series of hypotheses that might have driven the differences observed across decades, among which is a species-specific response to abiotic and biotic environmental alterations, with the alpine habitat specialist moving out of sub-optimal habitats. We encourage further research on this topic, e.g., via long-term longitudinal studies.

DOAC in the treatment of cancer-associated venous thromboembolism: a retrospective cohort study beyond the guidelines.

BACKGROUND: The emerging use of direct oral anticoagulants (DOAC) in the management of cancer-associated venous thromboembolism (CAT) is significantly improving therapeutic adherence and quality of life. Despite this, many conditions can restrict the therapeutic index of these drugs. For all these reasons the latest guidelines recommend the use of heparins in the treatment of CAT as the preferred treatment in some clinical settings. OBJECTIVES: We evaluated the efficacy and the safety of DOAC, in terms of recurrent venous thromboembolism (VTE) and major bleeding (MB), as a composite primary outcome. Mortality and clinically relevant non-major bleeding (CRNMB) were evaluated as secondary outcomes. METHODS: We performed a retrospective study on 209 patients to compare the effects of DOAC versus heparins for the treatment of CAT. 127 patients with a high bleeding risk neoplasia were enrolled. RESULTS: A primary-outcome event occurred in 11.3% of patients treated with heparins and in 10.5% treated with DOAC (Relative Risk 0.92; 95% CI 0.42-2.01, p = 0.84). Recurrent VTE occurred in 6.1% in the heparins group and in 8.4% in the DOAC group (RR 1.37; 95% CI 0.51-3.64, p = 0.52). MB occurred in 5.2% in the heparins group and in 2.1% in the DOAC group (RR 0.40; 95% CI 0.08-1.93, p = 0.25). CONCLUSIONS: DOAC seem to be as effective and safe as heparins in the treatment of CAT. Most bleeding events occurred in patients with high-risk bleeding neoplasms regardless of the type of anticoagulant. Considering the characteristics and satisfaction of patients using DOAC in this setting, this approach should be considered as a first choice.

Pediatric immune myelofibrosis (PedIMF) as a novel and distinct clinical pathological entity.

Myelofibrosis is a rare myeloproliferative disorder. The detailed descriptions of myelofibrosis in children and adolescents is limited to a few case series and case reports describing fewer than 100 patients, thus suggesting the extreme rarity of this condition prior to adulthood. Though pediatric patients rarely present the typical features and outcomes usually observed in older people, pediatric myelofibrosis is not considered an independent entity. Here we aim to describe patients with pediatric myelofibrosis, showing different clinical and pathological features when compared to the World Health Organization 2016 Primary Myelofibrosis classification. We retrospectively collected and analyzed 14 consecutive pediatric myelofibrosis diagnosed in our Pediatric hematology outpatient clinic over a six-year period. According to clinical data and bone marrow biopsy findings, patients were classified into three subgroups: adult-like myelofibrosis, pediatric immune myelofibrosis, idiopathic myelofibrosis. Pediatric Immune Myelofibrosis was the predominant subgroup in our cohort (7/14). Pediatric Immune Myelofibrosis is characterized by peculiar bone marrow features (i.e., T lymphocyte infiltration) and a milder course compared to the other patients Pediatric Immune Myelofibrosis is a novel and distinct pathological entity. We suggest to carefully consider Pediatric Immune Myelofibrosis in case of bone marrow biopsies showing myelofibrosis that do not fulfill WHO criteria.

Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling.

Muscle satellite stem cells (MuSCs) are responsible for skeletal muscle growth and regeneration. Despite their differentiation potential, human MuSCs have limited in vitro expansion and in vivo migration capacity, limiting their use in cell therapies for diseases affecting multiple skeletal muscles. Several protocols have been developed to derive MuSC-like progenitors from human induced pluripotent stem (iPS) cells (hiPSCs) to establish a source of myogenic cells with controllable proliferation and differentiation. However, current hiPSC myogenic derivatives also suffer from limitations of cell migration, ultimately delaying their clinical translation. Here we use a multi-disciplinary approach including bioinformatics and tissue engineering to show that DLL4 and PDGF-BB improve migration of hiPSC-derived myogenic progenitors. Transcriptomic analyses demonstrate that this property is conserved across species and multiple hiPSC lines, consistent with results from single cell motility profiling. Treated cells showed enhanced trans-endothelial migration in transwell assays. Finally, increased motility was detected in a novel humanised assay to study cell migration using 3D artificial muscles, harnessing advanced tissue modelling to move hiPSCs closer to future muscle gene and cell therapies.

First Record of Hepatozoon spp. in Alpine Wild Rodents: Implications and Perspectives for Transmission Dynamics across the Food Web.

Among the Apicomplexa parasites, Hepatozoon spp. have been mainly studied in domestic animals and peri-urban areas. The epidemiology of Hepatozoon spp. is poorly investigated in natural systems and wild hosts because of their scarce veterinary and economic relevance. For most habitats, the occurrence of these parasites is unknown, despite their high ecosystemic role. To fill this gap for alpine small mammals, we applied molecular PCR-based methods and sequencing to determine the Hepatozoon spp. in 830 ear samples from 11 small mammal species (i.e., Apodemus, Myodes, Chionomys, Microtus, Crocidura and Sorex genera) live-trapped during a cross-sectional study along an altitudinal gradient in the North-Eastern Italian Alps. We detected Hepatozoon spp. with an overall prevalence of 35.9%. Two species ranging from 500 m a.s.l. to 2500 m a.s.l. were the most infected: My. glareolus, followed by Apodemus spp. Additionally, we detected the parasite for the first time in another alpine species: C. nivalis at 2000-2500 m a.s.l. Our findings suggest that several rodent species maintain Hepatozoon spp. along the alpine altitudinal gradient of habitats. The transmission pathway of this group of parasites and their role within the alpine mammal community need further investigation, especially in consideration of the rapidly occurring environmental and climatic changes.

Prevention of violence against women and girls: A cost-effectiveness study across 6 low- and middle-income countries.

BACKGROUND: Violence against women and girls (VAWG) is a human rights violation with social, economic, and health consequences for survivors, perpetrators, and society. Robust evidence on economic, social, and health impact, plus the cost of delivery of VAWG prevention, is critical to making the case for investment, particularly in low- and middle-income countries (LMICs) where health sector resources are highly constrained. We report on the costs and health impact of VAWG prevention in 6 countries. METHODS AND FINDINGS: We conducted a trial-based cost-effectiveness analysis of VAWG prevention interventions using primary data from 5 randomised controlled trials (RCTs) in sub-Saharan Africa and 1 in South Asia. We evaluated 2 school-based interventions aimed at adolescents (11 to 14 years old) and 2 workshop-based (small group or one to one) interventions, 1 community-based intervention, and 1 combined small group and community-based programme all aimed at adult men and women (18+ years old). All interventions were delivered between 2015 and 2018 and were compared to a do-nothing scenario, except for one of the school-based interventions (government-mandated programme) and for the combined intervention (access to financial services in small groups). We computed the health burden from VAWG with disability-adjusted life year (DALY). We estimated per capita DALYs averted using statistical models that reflect each trial's design and any baseline imbalances. We report cost-effectiveness as cost per DALY averted and characterise uncertainty in the estimates with probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEACs), which show the probability of cost-effectiveness at different thresholds. We report a subgroup analysis of the small group component of the combined intervention and no other subgroup analysis. We also report an impact inventory to illustrate interventions' socioeconomic impact beyond health. We use a 3% discount rate for investment costs and a 1-year time horizon, assuming no effects post the intervention period. From a health sector perspective, the cost per DALY averted varies between US$222 (2018), for an established gender attitudes and harmful social norms change community-based intervention in Ghana, to US$17,548 (2018) for a livelihoods intervention in South Africa. Taking a societal perspective and including wider economic impact improves the cost-effectiveness of some interventions but reduces others. For example, interventions with positive economic impacts, often those with explicit economic goals, offset implementation costs and achieve more favourable cost-effectiveness ratios. Results are robust to sensitivity analyses. Our DALYs include a subset of the health consequences of VAWG exposure; we assume no mortality impact from any of the health consequences included in the DALYs calculations. In both cases, we may be underestimating overall health impact. We also do not report on participants' health costs. CONCLUSIONS: We demonstrate that investment in established community-based VAWG prevention interventions can improve population health in LMICs, even within highly constrained health budgets. However, several VAWG prevention interventions require further modification to achieve affordability and cost-effectiveness at scale. Broadening the range of social, health, and economic outcomes captured in future cost-effectiveness assessments remains critical to justifying the investment urgently required to prevent VAWG globally.

Effective Penetration of a Liposomal Formulation of Bleomycin through Ex-Vivo Skin Explants from Two Different Species.

Bleomycin is a chemotherapy agent that, when administered systemically, can cause severe pulmonary toxicity. Bleosome is a novel formulation of bleomycin encapsulated in ultra-deformable (UD) liposomes that may be applicable as a topical chemotherapy for diseases such as non-melanoma skin cancer. To date, the ability of Bleosome to effectively penetrate through the skin has not been evaluated. In this study, we investigated the ability of Bleosome to penetrate through ex vivo skin explants from dogs and horses. We visualized the penetration of UD liposomes through the skin by transmission electron microscopy. However, to effectively image the drug itself we fluorescently labeled bleomycin prior to encapsulation within liposomes and utilized multiphoton microscopy. We showed that UD liposomes do not penetrate beyond the stratum corneum, whereas bleomycin is released from UD liposomes and can penetrate to the deeper layers of the epidermis. This is the first study to show that Bleosome can effectively penetrate through the skin. We speculate that UD liposomes are penetration enhancers in that UD liposomes carry bleomycin through the outer skin to the stratum corneum and then release the drug, allowing diffusion into the deeper layers. Our results are comparative in dogs and horses and warrant further studies on the efficacy of Bleosome as topical treatment.

Investigating the role of dystrophin isoform deficiency in motor function in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by DMD mutations leading to dystrophin loss. Full-length Dp427 is the primary dystrophin isoform expressed in muscle and is also expressed in the central nervous system (CNS). Two shorter isoforms, Dp140 and Dp71, are highly expressed in the CNS. While a role for Dp140 and Dp71 on DMD CNS comorbidities is well known, relationships between mutations expected to disrupt Dp140 and Dp71 and motor outcomes are not. METHODS: Functional outcome data from 387 DMD boys aged 4-15 years were subdivided by DMD mutation expected effects on dystrophin isoform expression; Group 1 (Dp427 absent, Dp140/Dp71 present, n = 201); Group 2 (Dp427/Dp140 absent, Dp71 present, n = 152); and Group 3 (Dp427/Dp140/Dp71 absent, n = 34). Relationships between isoform group and North Star ambulatory assessment (NSAA) scores, 10 m walk/run velocities and rise time velocities were explored using regression analysis. Western blot analysis was used to study Dp427, Dp140 and Dp71 production in myogenic cells (control and DMD human), control skeletal muscle, DMD skeletal muscle from the three isoform groups and cerebral cortex from mice (wild-type and DMD models). Grip strength and rotarod running test were studied in wild-type mice and DMD mouse models. DMD mouse models were mdx (Dp427 absent, Dp140/Dp71 present), mdx52 (Dp427/Dp140 absent, Dp71 present) and DMD-null (lacking all isoforms). RESULTS: In DMD boys, mean NSAA scores at 5 years of age were 6.1 points lower in Group 3 than Group 1 (P < 0.01) and 4.9 points lower in Group 3 than Group 2 (P = 0.05). Mean peak NSAA scores were 4.0 points lower in Group 3 than Group 1 (P < 0.01) and 1.6 points lower in Group 2 than Group 1 (P = 0.04). Mean four-limb grip strength was 1.5 g/g lower in mdx52 than mdx mice (P = 0.003) and 1.5 g/g lower in DMD-null than mdx mice (P = 0.002). Dp71 was produced in myogenic cells (control and DMD human) and skeletal muscle from humans in Groups 1 and 2 and mdx mice, but not skeletal muscle from human controls, myogenic cells and skeletal muscle from humans in Group 3 or skeletal muscle from wild-type, mdx52 or DMD-null mice. CONCLUSIONS: Our results highlight the importance of considering expected effects of DMD mutations on dystrophin isoform production when considering patterns of DMD motor impairment and the implications for clinical practice and clinical trials. Our results suggest a complex relationship between dystrophin isoforms expressed in the brain and DMD motor function.

Dystrophin deficiency affects human astrocyte properties and response to damage.

In addition to progressive muscular degeneration due to dystrophin mutations, 1/3 of Duchenne muscular dystrophy (DMD) patients present cognitive deficits. However, there is currently an incomplete understanding about the function of the multiple dystrophin isoforms in human brains. Here, we tested the hypothesis that dystrophin deficiency affects glial function in DMD and could therefore contribute to neural impairment. We investigated human dystrophin isoform expression with development and differentiation and response to damage in human astrocytes from control and induced pluripotent stem cells from DMD patients. In control cells, short dystrophin isoforms were up-regulated with development and their expression levels changed differently upon neuronal and astrocytic differentiation, as well as in 2-dimensional versus 3-dimensional astrocyte cultures. All DMD-astrocytes tested displayed altered morphology, proliferative activity and AQP4 expression. Furthermore, they did not show any morphological change in response to inflammatory stimuli and their number was significantly lower as compared to stimulated healthy astrocytes. Finally, DMD-astrocytes appeared to be more sensitive than controls to oxidative damage as shown by their increased cell death. Behavioral and metabolic defects in DMD-astrocytes were consistent with gene pathway dysregulation shared by lines with different mutations as demonstrated by bulk RNA-seq analysis. Together, our DMD model provides evidence for altered astrocyte function in DMD suggesting that defective astrocyte responses may contribute to neural impairment and might provide additional potential therapeutic targets.

COVID-19 lockdowns and demographically-relevant Google Trends: A cross-national analysis.

The spread of COVID-19 and resulting local and national lockdowns have a host of potential consequences for demographic trends. While impacts on mortality and, to some extent, short-term migration flows are beginning to be documented, it is too early to measure actual consequences for family demography. To gain insight into potential future consequences of the lockdown for family demography, we use cross-national Google Trends search data to explore whether trends in searches for words related to fertility, relationship formation, and relationship dissolution changed following lockdowns compared to average, pre-lockdown levels in Europe and the United States. Because lockdowns were not widely anticipated or simultaneous in timing or intensity, we exploit variability over time and between countries (and U.S. states). We use a panel event-study design and difference-in-differences methods, and account for seasonal trends and average country-level (or state-level) differences in searches. We find statistically significant impacts of lockdown timing on changes in searches for terms such as wedding and those related to condom use, emergency contraception, pregnancy tests, and abortion, but little evidence of changes in searches related to fertility. Impacts for union formation and dissolution tended to only be statistically significant at the start of a lockdown with a return to average-levels about 2 to 3 months after lockdown initiation, particularly in Europe. Compared to Europe, returns to average search levels were less evident for the U.S., even 2 to 3 months after lockdowns were introduced. This may be due to the fact, in the U.S., health and social policy responses were less demarcated than in Europe, such that economic uncertainty was likely of larger magnitude. Such pandemic-related economic uncertainty may therefore have the potential to slightly increase already existing polarization in family formation behaviours in the U.S. Alongside contributing to the wider literature on economic uncertainty and family behaviors, this paper also proposes strategies for efficient use of Google Trends data, such as making relative comparisons and testing sensitivity to outliers, and provides a template and cautions for their use in demographic research when actual demographic trends data are not yet available.

Engineering of human induced pluripotent stem cells via human artificial chromosome vectors for cell therapy and disease modeling.

Genetic engineering of induced pluripotent stem cells (iPSCs) holds great promise for gene and cell therapy as well as drug discovery. However, there are potential concerns regarding the safety and control of gene expression using conventional vectors such as viruses and plasmids. Although human artificial chromosome (HAC) vectors have several advantages as a gene delivery vector, including stable episomal maintenance and the ability to carry large gene inserts, the full potential of HAC transfer into iPSCs still needs to be explored. Here, we provide evidence of a HAC transfer into human iPSCs by microcell-mediated chromosome transfer via measles virus envelope proteins for various applications, including gene and cell therapy, establishment of versatile human iPSCs capable of gene loading and differentiation into T cells, and disease modeling for aneuploidy syndrome. Thus, engineering of human iPSCs via desired HAC vectors is expected to be widely applied in biomedical research.