Canadian Health Research Funding Patterns for Sexual and Gender Minority Populations Reflect Exclusion of Women.

Purpose: We explored the funding areas of Two-Spirit, lesbian, gay, bisexual, transgender (trans), queer or questioning, and intersex individuals (2S/LGBTQI)-specific health research funded by the Canadian Institutes of Health Research (CIHR) mentioned in the grant abstracts. Methods: We analyzed the publicly available database of grant abstracts funded by CIHR from 2009-2020 to examine what types of 2S/LGBTQI-specific health outcomes would be studied and in what populations. Results: We found that 58% of awarded grant abstracts mentioned studying sexually transmitted diseases, the majority of which was on human immunodeficiency virus. Of the funded 2S/LGBTQI grant abstracts that specified the gender of the population to be studied (n=23), less then 9% mentioned studying cisgender women. Almost 40% mentioned including trans women/girls, and 30% mentioned including trans men/boys. None of the studies examined mentioned work with the Two-Spirit community. Conclusion: These results reflect larger social and health inequities that require structural level changes in research to support the 2S/LGBTQI community.

The Concealment of Health Information at the Intersection of Sexual Orientation and Race.

Purpose: Sexually and racially minoritized people often have mistrust toward the healthcare system due to both perceived and actual experiences of discrimination. This may result in increased privacy concerns and a reluctance to share health-related information with health care providers. Drawing upon minority stress and an intersectionality framework, this study examines how rates of concealing health information differ between non-Hispanic White heterosexual people, non-Hispanic White lesbian, gay, and bisexual (LGB) people, racially minoritized heterosexual people, and those who are both sexually and racially minoritized. Methods: Using nationally representative cross-sectional data from the Health Information National Trends Survey from 2017 and 2018 (n = 4575), we fit logistic regression models to examine (1) whether sexually and racially minoritized people conceal health information from their providers more than their counterparts and (2) whether this tendency increases for those with multiple marginalized identities. Furthermore, we fit linear regression models to examine whether and how concealing health information from providers are linked to health outcomes. Results: Sexually and racially minoritized people had higher odds of concealing health information from providers than their counterparts. Those with multiple marginalized identities had even higher odds of withholding health information than other groups. Finally, we found a significant negative association between concealing health information and mental health. Conclusion: Our findings underscore the need to consider how the intersection of multiple marginalized identities shape health experiences and concerns over privacy in health care matters. We call for further research to better understand the complex dynamics of patient-provider relationships for marginalized populations.

Cultivating insight and engagement: exploring the role of Trait Emotional Intelligence in Chinese art education.

Background: The present study focuses on the unique role of insight and Trait Emotional Intelligence in the realm of art education in China. Insight, traditionally associated with clinical outcomes such as mastering symptoms, developing adaptive behaviors, and enhancing quality of life, is newly contextualized in this study within the framework of art education. The expansion of insight research into areas like Social Psychology reflects its relevance beyond clinical settings, particularly in educational environments where creativity and emotional intelligence are pivotal. Aim: In Chinese art education, insight is crucial not just for personal growth but also for professional development, integrating the understanding of emotions, culture, and artistic expression. This study explores how Trait Emotional Intelligence fosters insight and engagement in art students, underscoring its transformative impact on their educational and professional journey in the art world. Methods: Using a sample of Chinese art education students at University level (N = 881), that answered a quantitative self-report questionnaire, statistical procedures are applied to test the relationships between Trait Emotional Intelligence, Insight orientation, and students' academic engagement. Results: In the structural model, the path from Trait Emotional Intelligence to Insight Orientation was significant, indicating a positive relationship. Students' Engagement was significantly predicted by Insight Orientation and Trait Emotional Intelligence. Implications: This finding corroborates theoretical assertions that individuals with higher emotional intelligence are more inclined to have enhanced insight. The findings of the present study extend beyond the field of Art education, allowing us to provide a broad spectrum of social implications for Higher Education institutions.

Evaluation of sterile glove usage on digital tactile sensitivity using the Grating Orientation Task.

Introduction: Surgical glove use may be associated with a decrease in tactile sensitivity, with thicker gloves or double-gloving techniques further altering sensation. This study evaluates digital tactile sensitivity by use of a Grating Orientation Task (GOT) with multiple sterile gloving techniques (no gloves, single standard gloving, double standard gloving, orthopedic gloves, and micro-thickness gloves). Methods: Each participant performed the GOT at increasing grating widths until correctly noting orientation in ≥8 of 10 trials with multiple glove types or double-gloving technique. Glove order was randomly assigned and participants were blinded to the orientation and dome size. Results: All gloves except micro-thickness gloves showed increased threshold sensitivity values (i.e. worse fingertip sensitivity) when compared to control (micro:control, p = 0.105, others:control, p < 0.05). Single-layer gloves showed no significant difference in sensitivity when compared to orthopedic (p = 0.06) or double-layer latex gloves (p = 0.26). Discussion: Standard latex gloves decreased fingertip sensitivity when evaluated with the GOT. Double-layer and orthopedic latex gloves do not decrease sensitivity when compared with single-layer gloving. Micro-thickness gloves may provide similar tactile sensitivity to no surgical glove.

Prevalence of Sexual Strangulation/Choking Among Australian 18-35 Year-Olds.

In Australia, strangulation has been explicitly criminalized in all states and territories. However, it continues to be a "normalized" sexual practice despite its potentially fatal consequences and associated short and long-term sequelae. This research aimed to establish the prevalence of strangulation during sex and examine predictors of positive perceptions toward sexual strangulation in Australia. Confidential, cross-sectional online surveys were conducted with 4702 Australians aged 18-35 years. Participants were 47% cis-men, 48% cis-women, and 4% trans or gender diverse. A total of 57% reported ever being sexually strangled (61% women, 43% men, 79% trans or gender diverse) and 51% reported ever strangling a partner (40% women, 59% men, 74% trans or gender diverse). Differences were found across genders on all variables of sexual strangulation, including frequency of engagement, level of pressure on the neck, consequences, wanting and enjoyment, and how consent was given/received. However, when split by gender, sexual orientation of men and women revealed further differences in behaviors, consequences, and wanting, particularly among straight and bisexual women. After accounting for exposure to strangulation in pornography and previous experience of sexual strangulation, positive perceptions of being strangled (R2 = .51) and strangling a partner (R2 = .53) were predicted by ratings that it could be done safely and social normative factors. These findings suggest strangulation is common during sex among young Australians. Non-stigmatizing education strategies are needed to engage with young people so they have a better understanding of the risks involved and how to negotiate consent and safety regarding sexual strangulation.

Interdependency or submission to authority? The impacts of horizontal and vertical collectivist orientation on vaccine attitudes in mainland China.

Culture has a profound impact on preventive measures during the COVID-19 pandemic. Previous research has revealed that collectivism is associated with more effective responses to COVID-19 on the national or regional level. However, the impact of different components of collectivist orientation on vaccine attitudes remains insufficiently explored on the individual level. Two survey studies conducted in August 2021 in mainland China consistently found that individual-level horizontal collectivist orientation, rather than vertical collectivist orientation, was linked with more favourable vaccine attitudes. Specifically, Study 1 (N = 731) indicated that horizontal collectivist orientation was positive associated with vaccination intention indirectly via risk perception, and horizontal collectivist orientation was also positively associated with vaccination persuasion both directly and indirectly via risk perception. Study 2 (N = 1481), employing multilevel modelling, demonstrated that the link between horizontal collectivist orientation and confidence in vaccines remained robust regardless of provincial-level variations in socioeconomic development and cultural tightness. These findings convergently suggest that the positive vaccine attitudes among mainland Chinese are primarily driven by an amplified risk perception due to concern for others, rather than submission to authority.

Optimizing Crystal Orientation and Defect Mitigation in Antimony Selenide Thin-Film Solar Cells through Buffer Layer Energy Band Adjustment.

Antimony selenide (Sb2Se3) has sparked significant interest in high-efficiency photovoltaic applications due to its advantageous material and optoelectronic properties. In recent years, there has been considerable development in this area. Nonetheless, defects and suboptimal [hk0] crystal orientation expressively limit further device efficiency enhancement. This study used Zinc (Zn) to adjust the interfacial energy band and strengthen carrier transport. For the first time, it is discovered that the diffusion of Zn in the cadmium sulfide (CdS) buffer layer can affect the crystalline orientation of the Sb2Se3 thin films in the superstrate structure. The effect of Zn diffusion on the morphology of Sb2Se3 thin films with CdxZn1-xS buffer layer has been investigated in detail. Additionally, Zn doping promotes forming Sb2Se3 thin films with the desired [hk1] orientation, resulting in denser and larger grain sizes which will eventually regulate the defect density. Finally, based on the energy band structure and high-quality Sb2Se3 thin films, this study achieves a champion power conversion efficiency (PCE) of 8.76%, with a VOC of 458 mV, a JSC of 28.13 mA cm-2, and an FF of 67.85%. Overall, this study explores the growth mechanism of Sb2Se3 thin films, which can lead to further improvements in the efficiency of Sb2Se3 solar cells.

Diffusion Model-based FOD Restoration from High Distortion in dMRI.

Fiber orientation distributions (FODs) is a popular model to represent the diffusion MRI (dMRI) data. However, imaging artifacts such as susceptibility-induced distortion in dMRI can cause signal loss and lead to the corrupted reconstruction of FODs, which prohibits successful fiber tracking and connectivity analysis in affected brain regions such as the brain stem. Generative models, such as the diffusion models, have been successfully applied in various image restoration tasks. However, their application on FOD images poses unique challenges since FODs are 4-dimensional data represented by spherical harmonics (SPHARM) with the 4-th dimension exhibiting order-related dependency. In this paper, we propose a novel diffusion model for FOD restoration that can recover the signal loss caused by distortion artifacts. We use volume-order encoding to enhance the ability of the diffusion model to generate individual FOD volumes at all SPHARM orders. Moreover, we add cross-attention features extracted across all SPHARM orders in generating every individual FOD volume to capture the order-related dependency across FOD volumes. We also condition the diffusion model with low-distortion FODs surrounding high-distortion areas to maintain the geometric coherence of the generated FODs. We trained and tested our model using data from the UK Biobank (n = 1315). On a test set with ground truth (n = 43), we demonstrate the high accuracy of the generated FODs in terms of root mean square errors of FOD volumes and angular errors of FOD peaks. We also apply our method to a test set with large distortion in the brain stem area (n = 1172) and demonstrate the efficacy of our method in restoring the FOD integrity and, hence, greatly improving tractography performance in affected brain regions.

Hydrophobic Ion Barrier-Enabled Ultradurable Zn (002) Plane Orientation towards Long-Life Anode-Less Zn Batteries.

Gradual disability of Zn anode and high negative/positive electrode (N/P) ratio usually depreciate calendar life and energy density of aqueous Zn batteries (AZBs). Herein, within original Zn2+-free hydrated electrolytes, a steric hindrance/electric field shielding-driven "hydrophobic ion barrier" is engineered towards ultradurable (002) plane-exposed Zn stripping/plating to solve this issue. Guided by theoretical simulations, hydrophobic adiponitrile (ADN) is employed as a steric hindrance agent to ally with inert electric field shielding additive (Mn2+) for plane adsorption priority manipulation, thereby constructing the "hydrophobic ion barrier". This design robustly suppresses the (002) plane/dendrite growth, enabling ultradurable (002) plane-exposed dendrite-free Zn stripping/plating. Even being cycled in Zn‖Zn symmetric cell over 2150 h at 0.5 mA cm-2, the efficacy remains well-kept. Additionally, Zn‖Zn symmetric cells can be also stably cycled over 918 h at 1 mA cm-2, verifying uncompromised Zn stripping/plating kinetics. As-assembled anode-less Zn‖VOPO4·2H2O full cells with a low N/P ratio (2:1) show a high energy density of 75.2 Wh kg-1full electrode after 842 cycles at 1 A g-1, far surpassing counterparts with thick Zn anode and low cathode loading mass, featuring excellent practicality. This study opens a new avenue by robust "hydrophobic ion barrier" design to develop long-life anode-less Zn batteries.

White matter microstructure alterations of the posterior limb of internal capsule in first-episode drug naive schizophrenia patients.

OBJECTIVES: Previous studies have shown that microstructural alterations in white matter (WM) could contribute to the symptom manifestation and support the dysconnectivity hypothesis in schizophrenia patients. These alterations were pervasive, non-specific, and reported inconsistently across the literature. This study aimed to specifically investigate the microstructure alterations of the posterior limb of the internal capsule (PLIC) in first-episode, drug-naive schizophrenia patients. Utilizing a multicompartmental biophysical model, we further explored the correlation between these alterations and syndrome scale scores. METHODS: Thirty-two individuals with first-episode, drug-naive schizophrenia (FES) and thirty demographically matched healthy controls were enrolled. High-resolution multi-shell diffusion MRI data were collected, followed by the application of a three-compartment Neurite Orientation Dispersion and Density Imaging (NODDI) model to scrutinize the alterations in white matter microstructure. Changes in sensory and motor fibers within the PLIC were specifically focused on. Additionally, the correlation between these pathological changes and scores on the Positive and Negative Syndrome Scale (PANSS) was investigated. RESULTS: The Neurite density index (NDI) in the left PLIC was significantly lower in FES patients compared to healthy individuals, and positively correlated with PANSS positive syndrome scores (r = 0.0379, p = 0.046). In the sensory component (left superior thalamic radiation within PLIC, STR_P), the NDI was significantly elevated (p < 0.0001). Conversely, the NDI in the motor component (left corticospinal tract within PLIC, CST_P) was reduced (p = 0.007) in FES patients compared to healthy individuals, and strongly correlated with PANSS positive syndrome scores (p < 0.020) and PANSS total scores (p < 0.045). Moreover, the NDI deviation of STR from total PLIC (fSTR_P) and NDI deviation in STR_P and CST_P compared to PLIC region (fPLIC) were significantly higher in FES patients than in healthy controls (p < 0.00001), with an area under the curve (AUC) of fPLIC reaching 0.872. CONCLUSION: The study's findings provided new insights into the discrepancy of white matter microstructure changes associated with the sensory and motor fibers in the PLIC region in FES patients. These results contribute to the growing body of evidence suggesting that WM microstructural alterations play a critical role in schizophrenia pathophysiology.

Barriers and Facilitators to Accessing PrEP and Other Sexual Health Services Among Immigrant Latino Men Who Have Sex with Men in Los Angeles County.

In the United States, immigrant Latino men who have sex with men (ILMSM) are, compared to white MSM, disproportionately burdened by HIV and lack access to highly effective HIV prevention strategies, such as pre-exposure prophylaxis (PrEP). Qualitative research centered on exploring barriers that ILMSM experience in accessing PrEP and other sexual services is extremely limited, despite a high prevalence of HIV in this population. In this study, a purposive sample of ILMSM (n = 25) was recruited to participate in a semi-structured in-depth interview to identify the distinct barriers and facilitators ILMSM experience in accessing sexual health services given their complex intersectional identities of being an immigrant, Latino, and a sexual minority man. Using a thematic analysis approach, nine themes were generated from the data representing barriers and facilitators. Barriers included: (1) cost and a lack of health insurance, (2) complexity of PrEP assistance programs; (3) challenges related to the immigrant experience; (4) impact of gay stigma; and (5) communication challenges. Facilitators included: (1) improving affordability and accessibility of PrEP services; (2) receiving services from LGBT- or Latine LGBT-centered clinics; (3) receiving services from medical providers who are gay and/or Latino; and (4) providing targeted community outreach, education, and promotion of PrEP to ILMSM. While many of the barriers illuminated in the study were structural (e.g., cost and lack of health insurance), and not easy to overcome, the findings highlight a range of facilitators that can support access to PrEP and other sexual health services for ILMSM. Considering these findings, we suggest strategies that may enhance access to needed sexual health services among ILMSM.

"Just for pregnant women, not for you": a qualitative evaluation of the sexual and reproductive healthcare experiences of transgender and gender diverse cancer survivors.

PURPOSE: To identify opportunities to improve sexual and reproductive health (SRH) care for transgender and gender diverse (TGD) cancer survivors by describing (1) challenges experienced when navigating SRH care and (2) strategies to help overcome these challenges. METHODS: We enrolled a purposive sample of 17 adult TGD cancer survivors and 5 co-survivors. We aimed for a diverse sample across cancer experience, age, racial/ethnic background, sexual orientation, and gender identity. We conducted 90-min individual interviews via videoconference and used reflexive thematic analysis, guided by a focus on three social determinants of health. RESULTS: Themes describing challenges were as follows: (1) Cancer treatment's impact on sexual health was insufficiently addressed by cancer care providers; (2) fertility-related information and conversations were complicated by gendered expectations and ultimately did not meet survivors' needs; (3) feeling excluded and uncared-for in healthcare settings due to gendered language and lack of supportive services that met their needs; and (4) TGD survivors commonly reported high financial burden, negatively impacting their access to care. Strategies to overcome these challenges were (1) a solid social support network that can be integrated into the care team to meet the unique SRH needs of TGD survivors and (2) gender-affirming healthcare providers and environments to address SRH care needs and concerns. CONCLUSIONS: TGD survivors and co-survivors desire improved access to gender-affirming SRH care in cancer survivorship. IMPLICATIONS FOR CANCER SURVIVORS: Key opportunities to improve gender-affirming SRH care in cancer survivorship include fostering and engaging TGD survivors' support networks and implementing system-level changes in cancer care settings.

The Effect of Digital Platform Strategies on Firm Value in the Banking Industry.

After digital platforms have become successful in the information technology (IT) industry, incumbents from traditional industries increasingly implement digital platform strategies. However, there is mixed evidence on whether these incumbents benefit from digital platform strategies. To provide systematic insights, we focus on the banking industry. With the emergence of open banking, banks have begun implementing digital platforms to unlock the innovative power of third-party developers. We conducted an event study based on the announcement of digital platform strategies in a global sample of 165 banks. We show that, on average, investors react positively to the announcements. Contrary to our expectations, this effect is more substantial for banks from emerging markets than those from developed markets. Prior artificial intelligence (AI) orientation only partly contributes to investors' favorable perception of a digital platform strategy. These results point to the complex interplay of AI orientation and digital platform strategies, yielding questions for future research.

Molecular Orientation Regulation of Hole Transport Semicrystalline-Polymer Enables High-Performance Carbon-Electrode Perovskite Solar Cells.

Carbon-based perovskite solar cells (PSCs) coupled with solution-processed hole transport layers (HTLs) have shown potential owing to their combination of low cost and high performance. However, the commonly used poly(3-hexylthiophene) (P3HT) semicrystalline-polymer HTL dominantly shows edge-on molecular orientation, in which the alkyl side chains directly contact the perovskite layer, resulting in an electronically poor contact at the perovskite/P3HT interface. The study adopts a synergetic strategy comprising of additive and solvent engineering to transfer the edge-on molecular orientation of P3HT HTL into 3D molecular orientation. The target P3HT HTL possesses improved charge transport as well as enhanced moisture-repelling capability. Moreover, energy level alignment between target P3HT HTL and perovskite layer is realized. As a result, the champion devices with small (0.04 cm2) and larger areas (1 cm2) deliver notable efficiencies of 20.55% and 18.32%, respectively, which are among the highest efficiency of carbon-electrode PSCs.

Liner orientation change of dual mobility cup determined via 3D ultrasound imaging and motion analysis: A cadaver study.

BACKGROUND: A mobile polyethylene liner enables the dual mobility cup (DMC) to contribute to restoring hip joint range-of-motion, decreasing wear and increasing implant stability. However, more data is required on how liner orientation changes with hip joint movement. As a first step towards better understanding liner orientation change in vivo, this cadaver study focuses on quantifying DMC liner orientation change after different hip passive movements, using ultrasound imaging and motion analysis. HYPOTHESIS: The liner does not always go back to its initial orientation and its final orientation depends mainly on hip movement amplitude. METHODS: 3D ultrasound imaging and motion analysis were used to define liner and hip movements for four fresh post-mortem human subjects with six implanted DMC. Abduction and anteversion angles of the liner plane relative to the pelvis were measured before and after hip flexion, internal rotation, external rotation, abduction, adduction. RESULTS: Liner orientation changes were generally defined by angle variation smaller than 5°, with the liner nearly going back to its initial orientation. However, hip flexion caused liner abduction and anteversion angle variations greater than 15°. Except for hip adduction, only weak or no correlation was found between the final angle of the liner and the maximal hip joint movement amplitude. DISCUSSION: This study is the first attempt to quantify liner orientation change for implanted DMC via ultrasound imaging and constitutes a step forward in the understanding of liner orientation change and its relationship with hip joint movement. The hypothesis that the final liner abduction and anteversion angles depend mainly on hip movement amplitude was not confirmed, even if hip flexion was the movement generating the most liner orientation changes over 15°. This approach should be extended to in vivo clinical investigations, as measured liner angle variation could provide important support for the wear and stability claims made for DMC. LEVEL OF EVIDENCE: IV; cadaveric study.

Blade-Coating (100)-Oriented α-FAPbI3 Perovskite Films via Crystal Surface Energy Regulation for Efficient and Stable Inverted Perovskite Photovoltaics.

Photoactive formamidinium lead triiodide (α-FAPbI3) perovskite has dominated the prevailing high-performance perovskite solar cells (PSCs), normally for those spin-coated, conventional n-i-p structured devices. Unfortunately, α-FAPbI3 has not been made full use of its advantages in inverted p-i-n structured PSCs fabricated via blade-coating techniques owing to uncontrollable crystallization kinetics and complicated phase evolution of FAPbI3 perovskites. Herein, a customized crystal surface energy regulation strategy has been innovatively developed by incorporating 0.5 mol% of N-aminoethylpiperazine hydroiodide (NAPI) additive into α-FAPbI3 crystal-derived perovskite ink, which enabled the formation of phase-pure, highly-oriented α-FAPbI3 films. We deciphered the phase transformation mechanisms and crystallization kinetics of blade-coated α-FAPbI3 perovskite films via combining a series of in-situ characterizations. Interestingly, the strong chemical interactions between the NAPI and inorganic Pb-I framework help to reduce the surface energy of (100) crystal plane by 42%, retard the crystallization rate and lower the formation energy of α-FAPbI3. The resultant blade-coated inverted PSCs based on (100)-oriented α-FAPbI3 perovskite films realized promising efficiencies up to 24.16% (~26.5% higher than that of the randomly-oriented counterparts), accompanied by improved operational stability. This result represented one of the best performances reported to date for FAPbI3-based inverted PSCs fabricated via scalable deposition methods.

Inequality and health: Can medical practice address the consequences of inequalities?

BACKGROUND: The extent to which governments provide socioeconomic supports has been highlighted by their spending during the COVID-19 pandemic. This has implications for patterns of inequality, in particular on exacerbating unequal health and well-being. RESULTS: Inequity has expanded due to neoliberalism, a market-based approach that has endured for more than four decades. Together with COVID-19, it has developed and exposed many structural governance differences. DISCUSSION: There are a number of examples presented of the effects of inequalities on health and well-being. The role of general practice in addressing these is discussed and challenges are highlighted, especially those relating to payment systems and workforce constraints.

The role of activists' sexual orientation and gender identity in their participation in LGBT movements: a case study from Yunnan, China.

The role played by activists' sexual orientation and gender identity in their involvement and commitment to LGBT movements is an understudied area in the Chinese context. Using identity and dramaturgical theory, this qualitative study explored how activists' work and commitment toward promoting LGBT rights and services is shaped and influenced by their identities. The study draws on data from life history interviews conducted with 20 long-time LGBT activists in Yunnan, China. The findings indicate that their sexual orientation and gender identities were, in the long run, seen as assets by the activists that shaped their work and commitment in the LGBT movement. Despite initial challenges in establishing identity-based connections with co-workers/clients, the emergence of sense of inclusiveness through recognition of activists' efforts, particularly when working with diverse gender and sexual minorities, stands out as a prominent theme in this context. This dynamic is important in bolstering the longevity of activists' commitment and building the continued momentum of LGBT movements in the region and internationally.

Changes in Left Ventricular-Aortic Angulation Are Associated with the Development of Obstruction in Hypertrophic Cardiomyopathy.

OBJECTIVE: To characterize changes in ventricular morphology in patients with hypertrophic cardiomyopathy(HCM) who develop left ventricular outflow tract(LVOT) obstruction. METHODS: We reviewed HCM patients with LVOT obstruction who underwent septal myectomy from May 2012 to June 2023. Among 68 patients initially without obstruction, documented up to 7.6 years (IQR,6.3-9.4) before the operation, a comparison was made with 78 nonobstructive HCM patients over a similar period. Patients who did not develop obstruction were matched with those who did on sex, age, and maximum septal wall thickness during the initial echocardiography, identifying 41 matched pairs. Echocardiographic data, including 5 measures of angulation, were compared between the groups. RESULTS: The median interval between echocardiographic assessments was 7.5 years (IQR,6.3-8.1) among obstructive versus 7.3 years (IQR,6.2-9.0) in nonobstructive patients. Obstructive patients were more likely to have hypertension at both times. The maximum septal wall thickness increased within both groups (both p<0.001), but the magnitude of increase was not different between groups (p=0.130). Obstructive patients exhibited a greater increase in left ventricular (LV) mass (p<0.001) compared to nonobstructive patients (p=0.004). Aortic angulation significantly increased in 4 of the 5 measurements(all p<0.001) in obstructive patients, while nonobstructive patients showed no change. Anterior and posterior mitral valve(MV) leaflet lengths and coaptation lengths remained similar in both groups over time. CONCLUSIONS: The development of LVOT obstruction in patients with HCM was associated with progressive LVOT angulation and increased LV hypertrophy, as reflected by LV mass. Progression to obstruction was not related to changes in the MV leaflet morphology.

Impairment of α-tubulin and F-actin interactions of GJB3 induces aneuploidy in urothelial cells and promotes bladder cancer cell invasion.

BACKGROUND: We have previously identified an unsuspected role for GJB3 showing that the deficiency of this connexin protein induces aneuploidy in human and murine cells and accelerates cell transformation as well as tumor formation in xenograft models. The molecular mechanisms by which loss of GJB3 leads to aneuploidy and cancer initiation and progression remain unsolved. METHODS: GJB3 expression levels were determined by RT-qPCR and Western blot. The consequences of GJB3 knockdown on genome instability were assessed by metaphase chromosome counting, multinucleation of cells, by micronuclei formation and by the determination of spindle orientation. Interactions of GJB3 with α-tubulin and F-actin was analyzed by immunoprecipitation and immunocytochemistry. Consequences of GJB3 deficiency on microtubule and actin dynamics were measured by live cell imaging and fluorescence recovery after photobleaching experiments, respectively. Immunohistochemistry was used to determine GJB3 levels on human and murine bladder cancer tissue sections. Bladder cancer in mice was chemically induced by BBN-treatment. RESULTS: We find that GJB3 is highly expressed in the ureter and bladder epithelium, but it is downregulated in invasive bladder cancer cell lines and during tumor progression in both human and mouse bladder cancer. Downregulation of GJB3 expression leads to aneuploidy and genomic instability in karyotypically stable urothelial cells and experimental modulation of GJB3 levels alters the migration and invasive capacity of bladder cancer cell lines. Importantly, GJB3 interacts both with α-tubulin and F-actin. The impairment of these interactions alters the dynamics of these cytoskeletal components and leads to defective spindle orientation. CONCLUSION: We conclude that deregulated microtubule and actin dynamics have an impact on proper chromosome separation and tumor cell invasion and migration. Consequently, these observations indicate a possible role for GJB3 in the onset and spreading of bladder cancer and demonstrate a molecular link between enhanced aneuploidy and invasive capacity cancer cells during tumor cell dissemination.