Meeting report - Desmosome dysfunction and disease: Alpine desmosome disease meeting.

Desmosome diseases are caused by dysfunction of desmosomes, which anchor intermediate filaments (IFs) at sites of cell-cell adhesion. For many decades, the focus of attention has been on the role of actin filament-associated adherens junctions in development and disease, especially cancer. However, interference with the function of desmosomes, their molecular constituents or their attachments to IFs has now emerged as a major contributor to a variety of diseases affecting different tissues and organs including skin, heart and the digestive tract. The first Alpine desmosome disease meeting (ADDM) held in Grainau, Germany, in October 2022 brought together international researchers from the basic sciences with clinical experts from diverse fields to share and discuss their ideas and concepts on desmosome function and dysfunction in the different cell types involved in desmosome diseases. Besides the prototypic desmosomal diseases pemphigus and arrhythmogenic cardiomyopathy, the role of desmosome dysfunction in inflammatory bowel diseases and eosinophilic esophagitis was discussed.

Molecular regulators of exercise-mediated insulin sensitivity in non-obese individuals.

Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.

HIV and type 2 diabetes: An evolving story.

INTRODUCTION: Diabetes is widely reported to be more common in people living with HIV (PLWH). Much of the data supporting this originated during the earlier HIV era. The perceived increased risk of type 2 diabetes is reflected in HIV clinical guidelines that recommend screening for diabetes in PLWH on anti-retroviral therapy (ART). However, international HIV clinical guidelines do not agree on the best marker of glycaemia to screen for diabetes. This stems from studies that suggest HbA1c underestimates glycaemia in PLWH. METHODS: Within this review we summarise the literature surrounding the association of HIV and type 2 diabetes and how this has changed over time. We also present the evidence on HbA1c discrepancy in PLWH. CONCLUSION: We suggest there is no basis to any international guidelines to restrict HbA1c based on HIV serostatus. We recommend, using the current evidence, that PLWH should be screened annually for diabetes in keeping with country specific guidance. Finally, we suggest future work to elucidate phenotype and natural history of type 2 diabetes in PLWH across all populations.

Type 1 diabetes and frailty: A scoping review.

AIMS: Advances in type 1 diabetes management are enabling more to reach older ages. Frailty is known to complicate type 2 diabetes. However, frailty in people with type 1 diabetes has not been extensively researched. This review summarises the available evidence on frailty in those with type 1 diabetes. METHODS: A systematic search strategy was applied to multiple databases (Medline, Embase, CINAHL and Cochrane) including grey literature (Scopus, OAIster, OpenGrey, dissertation and thesis database). All evidence types were considered. English articles published after 2001 were eligible. For inclusion, participants must have been over 55 with type 1 diabetes. Frailty must have been clearly defined or assessed. The results were synthesised into a descriptive format to identify key themes. RESULTS: Of 233 papers subject to full-text review, 23 were included. Older adult diabetes research frequently does not specify the type of diabetes; 100 articles were excluded for this reason. No articles were found specifically researching frailty in older adults with type 1 diabetes. Fourteen different definitions and nine assessments of frailty were outlined. Generally, the papers supported relaxation of glucose targets and greater adoption of diabetes technology. CONCLUSIONS: This review highlights the paucity of evidence in older adults with type 1 diabetes and frailty. Consensus on standardised definitions and assessments of frailty would aid future research, which is urgently needed as more people with type 1 diabetes reach older ages. Identifying and addressing the key issues in this population is vital to support individuals through the challenges of ageing.

Developing a risk management framework to improve public health outcomes by enumerating and serotyping Salmonella in ground turkey.

Salmonella enterica continues to be a leading cause of foodborne morbidity worldwide. A quantitative risk assessment model was developed to evaluate the impact of pathogen enumeration and serotyping strategies on public health after consumption of undercooked contaminated ground turkey in the USA. The risk assessment model predicted more than 20,000 human illnesses annually that would result in ~700 annual reported cases. Removing ground turkey lots contaminated with Salmonella exceeding 10 MPN/g, 1 MPN/g, and 1 MPN/25 g would decrease the mean number of illnesses by 38.2, 73.1, and 95.0%, respectively. A three-class mixed sampling plan was tested to allow the detection of positive lots above threshold levels with 2-6 (c = 1) and 3-8 samples per lot (c = 2) using 25-g and 325-g sample sizes for a 95% probability of rejecting a contaminated lot. Removal of positive lots with the presence of highly virulent serotypes would decrease the number of illnesses by 44.2-87.0%. Based on these model prediction results, risk management strategies should incorporate pathogen enumeration and/or serotyping. This would have a direct impact on illness incidence linking public health outcomes with measurable food safety objectives, at the cost of diverting production lots.

Community cervical cancer screening and precancer risk in women living with HIV in Jos Nigeria.

BACKGROUND: High HIV prevalence, and lack of organized screening for the indigent population receiving care and treatment within HIV clinics in low-resource settings increases cervical cancer incidence. We sought to determine predictors of cervical precancer in women living with HIV and receiving cervical cancer screening in Jos, Nigeria. METHODS: A cross-sectional study of women living with HIV and receiving care and treatment in adult HIV/AIDS clinics in Jos-Metropolis, Nigeria between June 2020 and April 2023. Ethical approvals were obtained from the ethics committee in Jos, Nigeria and Northwestern University IRB, USA. Informed consent was obtained from eligible participants, and data on socio-demographics, cancer risk factors, and cytology reports were collected. The outcome variables were cervical precancer lesions. The independent variables were prior Pap smear status, socio-demographics, income, educational, and other reproductive health factors. Descriptive statistics was done to obtain means ± sd, frequencies, and percentages for the variables. Univariate and bivariate analyses were done to determine predictors of cervical dysplasia. Analyses were performed using R software. RESULTS: Of 957 women screened, 570 were living with HIV and 566 women had cytology report and were included in the final analysis. The mean age was 45.08 ± 8.89 years and 81.6% had no prior evidence of Pap test (under-screened). Prevalence of cervical dysplasia was 24% (mild and severe dysplasia were 12.9% and 11.1%, respectively). Age above 45 years (aOR = 3.48, p = 0.009), postmenopausal status (aOR = 7.69, p = 0.000), and women with no history of prior IUCD use (aOR = 5.94, p = 0.0001), were predictors for severe dysplasia. Women who had history of STI (aOR = 0.17, p = 0.000), prior use of IUCD (aOR = 0.32, p = 0.004), prior use of condom (aOR = 2.50, p = 0.003) and had co-morbidities (aOR = 0.46, p = 0.009) were more likely to have had a Pap test in the past. CONCLUSIONS: The majority of indigent women receiving care at HIV clinics had their first Pap test screening, and lack of organized screening among older and post-menopausal women with HIV, puts women at a higher risk of developing severe cervical precancer lesions.

Direct immunofluorescence on formalin-fixed, paraffin-embedded versus fresh frozen human renal biopsies: a comparative study.

BACKGROUND: The data referring to the value of direct immunofluorescence on formalin-fixed, paraffin-embedded tissue (IF-Paraffin) in the diagnosis of renal diseases is controversial. The aim of this study was to investigate whether renal biopsies evaluated by routine immunofluorescence on frozen tissue (IF-Frozen) would yield adequate findings to confirm diagnoses when the IF-Paraffin technique was applied. METHODS: To show immunoglobulins, complement components, and light chains, 55 native renal biopsies were subjected to IF-Paraffin and IF-Frozen staining techniques. The intensity of the staining was compared, and the sensitivity and specificity were calculated. RESULTS: The IF-Paraffin technique showed a sensitivity of 89%, 81%, 86%, 30%, 71%, 60%, and 77% for IgG, IgM, IgA, C1q, C3, κ, and λ, respectively, whereas specificity was 91%, 100%, 100%, 96%, 94%, 98%, and 100%. It showed diagnostic findings in 87% of cases. Compared to cases that had both IF-Paraffin and IF-Frozen staining techniques, 43 of 55 showed either equal intensity for the diagnostic immunoglobulin/complement or a little difference. CONCLUSIONS: Direct immunofluorescence on formalin-fixed, paraffin-embedded sections cannot replace immunofluorescence on frozen sections in the assessment of renal biopsies, but may be a "salvage technique" when frozen tissue is insufficient or unavailable and must be interpreted with great caution.

Photonics-powered augmented reality skin electronics for proactive healthcare: multifaceted opportunities.

Rapid technological advancements have created opportunities for new solutions in various industries, including healthcare. One exciting new direction in this field of innovation is the combination of skin-based technologies and augmented reality (AR). These dermatological devices allow for the continuous and non-invasive measurement of vital signs and biomarkers, enabling the real-time diagnosis of anomalies, which have applications in telemedicine, oncology, dermatology, and early diagnostics. Despite its many potential benefits, there is a substantial information vacuum regarding using flexible photonics in conjunction with augmented reality for medical purposes. This review explores the current state of dermal augmented reality and flexible optics in skin-conforming sensing platforms by examining the obstacles faced thus far, including technical hurdles, demanding clinical validation standards, and problems with user acceptance. Our main areas of interest are skills, chiroptical properties, and health platform applications, such as optogenetic pixels, spectroscopic imagers, and optical biosensors. My skin-enhanced spherical dichroism and powerful spherically polarized light enable thorough physical inspection with these augmented reality devices: diabetic tracking, skin cancer diagnosis, and cardiovascular illness: preventative medicine, namely blood pressure screening. We demonstrate how to accomplish early prevention using case studies and emergency detection. Finally, it addresses real-world obstacles that hinder fully realizing these materials' extraordinary potential in advancing proactive and preventative personalized medicine, including technical constraints, clinical validation gaps, and barriers to widespread adoption.

Operando Neutron Imaging.

In the past, neutron imaging has been the little brother of advanced neutron spectroscopy techniques due to its apparent simplicity. However, this simplicity allows the studying of complex chemical and electrochemical processes and related devices even under harsh reaction conditions such as high pressure, high temperature, corrosive and/or air sensitive environments. We review a number of highly relevant case studies as archetypal examples of modern energy technology; that is heat storage, power-to-X, batteries, fuel cells, and catalysis. The promising results trigger the further development of neutron imaging towards a chemical imaging method.

Bringing precision medicine to the management of pregnancy in women with glucokinase-MODY: a study of diagnostic accuracy and feasibility of non-invasive prenatal testing.

AIMS/HYPOTHESIS: In pregnancies where the mother has glucokinase-MODY (GCK-MODY), fetal growth is determined by fetal genotype. When the fetus inherits a maternal pathogenic GCK variant, normal fetal growth is anticipated, and insulin treatment of maternal hyperglycaemia is not recommended. At present, fetal genotype is estimated from measurement of fetal abdominal circumference on ultrasound. Non-invasive prenatal testing of fetal GCK genotype (NIPT-GCK) using cell-free DNA in maternal blood has recently been developed. We aimed to compare the diagnostic accuracy of NIPT-GCK with that of ultrasound, and determine the feasibility of using NIPT-GCK to guide pregnancy management. METHODS: We studied an international cohort of pregnant women with hyperglycaemia due to GCK-MODY. We compared the diagnostic accuracy of NIPT-GCK with that of measurement of fetal abdominal circumference at 28 weeks' gestation (n=38) using a directly genotyped offspring sample as the reference standard. In a feasibility study, we assessed the time to result given to clinicians in 43 consecutive pregnancies affected by GCK-MODY between July 2019 and September 2021. RESULTS: In terms of diagnostic accuracy, NIPT-GCK was more sensitive and specific than ultrasound in predicting fetal genotype (sensitivity 100% and specificity 96% for NIPT-GCK vs sensitivity 53% and specificity 61% for fetal abdominal circumference 75th percentile). In terms of feasibility, a valid NIPT-GCK fetal genotype (≥95% probability) was reported in all 38 pregnancies with an amenable variant and repeated samples when needed. The median time to report was 5 weeks (IQR 3-8 weeks). For the 25 samples received before 20 weeks' gestation, results were reported at a median gestational age of 20 weeks (IQR 18-24), with 23/25 (92%) reported before 28 weeks. CONCLUSIONS/INTERPRETATION: Non-invasive prenatal testing of fetal genotype in GCK-MODY pregnancies is highly accurate and is capable of providing a result before the last trimester for most patients. This means that non-invasive prenatal testing of fetal genotype is the optimal approach to management of GCK-MODY pregnancies.

Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria.

BACKGROUND: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). METHODS: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. RESULTS: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. CONCLUSION: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

Gastro-Protective and Therapeutic Effect of Punica granatum against Stomach Ulcer Caused by Helicobacter Pylori.

Gastric ulcer is a chronic condition that occurs when the mucosa of the stomach is broken. There is a physiological equilibrium between aggressive factors and mucosal defense. The purpose of this research was to compare the prevention level and efficiency of herbal medicinal plants (Punica granatum) to the omeprazole drug. Many groups were prepared from Albino male rats, the first control group (inoculate with H. pylori and fed with standard pellet), the Second group, rats inoculated by H. pylori and prevented with Punica granatum aqueous extracts (PGAE) in two dosages (250mg/kg, 500mg/kg), and last group inoculated by H. pylori and prevented with standard drug omeprazole at the dose (20mg/kg). The results showed that the Ulcer Inhibition % of Punica granatum with a high dose of 500mg/kg and a low dose of 250mg/kg was 84.60±5.48 and 42.87±7.14, respectively. While in the omeprazole treatment group, Ulcer Inhibition % was 24.50±6.35 and this Ulcer Inhibition %  in the Punica granatum treatment groups was significant compared to the omeprazole treatment group and the control group (P=0.0001). PGAE displayed a significant lessening in stomach index and infectious cell proliferation with much cell damage. Although the result of the current study improves, a high dosage of aqueous extracts of plants has more effectiveness than a low dosage of aqueous extracts plants.

Novel image analyser-assisted morphometric methodology offer unique opportunity for selection of embryos with potential for implantation.

BACKGROUND: Previous studies looked into the connections between pregnancy and the Zona Pellucida (ZP) thickness and Zona Pellucida Thickness Variation (ZPTV), as well as the embryo's radius, circumference, perimeter and global symmetry. However, no research has linked embryo implantation and pregnancy to the percentage of ZP thinning, the reduction in ooplasm volume, and the increase in perivitelline space (PVS) volume. Our objective is to correlate the percentage of ZP thinning, the percentage of ooplasm volume shrinkage and the percentage of PVS increase to the implantation. These data will be used for embryo selection as well as it can be put into a software that will assist embryo selection. MATERIALS AND METHODS: Retrospective study included 281 patients, all of them had 2 embryos transferred, 149 patients got pregnant with two gestation sacs and 132 patients did not get pregnant. All of the transferred embryos had the ZP thickness measured several times from time of ICSI till Embryo Transfer (ET), the ooplasm volume was calculated from time of ICSI till two Pronuclei (2PN) fading and the PVS was calculated from the ICSI time till the 2PN fading. RESULTS: The first characteristic is the change in the average ZP thickness that decreased by 32.7% + 5.3% at 70 h for the implanted embryos (Group 1) versus 23.6% + 4.8% for non-implanted embryos (Group 2) p = 0.000. The second characteristic is the average reduction in the volume of the ooplasm which is 20.5% + 4.3% in Group 1 versus 15.1% + 5.2% in Group 2, p = 0.000. The third characteristic is the increase in the volume of the PVS which was 38.1% + 7.6% in Group 1 versus 31.6% + 9.7% in Group 2 p = 0.000. CONCLUSION: The implanted embryos showed higher percent of ZP thinning, higher percent of ooplasm reduction and higher percent of PVS increase.

Factors associated with the prevalence of depression and anxiety among parents of children with neurodevelopmental disorders in Saudi Arabia.

BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of conditions that include attention-deficit/hyperactivity disorders, specific learning disorders, autism spectrum disorder, intellectual disability, and other disorders. Raising a child with an NDD can be difficult because it affects the social lives of the parents and their relationships. It also requires the parents to develop another set of skills to deal with their child. These factors increase their risk of depression and anxiety. AIM: To measure the prevalence rates of depression and anxiety among parents of children with different NDDs, compare the rates between mothers and fathers, and measure the relevant associated factors. METHODOLOGY: This study was a prospective, qualitative, cross-sectional, anonymous questionnaire-based study. The participants were 416 parents of children with NDDs in Saudi Arabia. The sample size was determined using the Richard Geiger equation with a 5% margin of error, a 95% confidence level, and a 50% response distribution. The screening was performed using a validated Arabic version of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7). These are short and understandable screening tools that assist in identifying and grading the severity of depression and anxiety symptoms. The participants were reached by distributing the questionnaire to parents who followed up with Saudi NDD-related associations, clinics, and psychiatric clinics from November 20 to May 8, 2022. The data were collected, reviewed, and then entered into SPSS 21. RESULTS: In total, 416 parents of children with NDDs in Saudi Arabia participated in the study. We demonstrated that 85.1% of parents of children with NDDs had depression and that 85.8% had anxiety. Mothers and fathers had similar rates of depression and anxiety. No significant difference was found between the type of NDD and rates of depression and anxiety in parents. CONCLUSION: Children with NDDs affect their parents' mental health in terms of increased rates of depression and anxiety. This increase is not correlated with a specific etiology. Healthcare professionals who care for children with NDDs should also assess parental mental health and seek an early diagnosis of mental illness to ensure that the appropriate interventions are provided for parents.

Ultrasonography for the Busy Orthopaedic Surgeon: The Upper Extremity.

Ultrasonography is increasingly used in the diagnosis and treatment of musculoskeletal conditions and injuries. Ultrasonography possesses multiple advantages compared with other methods of imaging, including low cost, lack of radiation exposure, speed, and means for dynamic examination. Because of these advantages, many orthopaedic surgeons are routinely using ultrasonography to diagnose musculoskeletal conditions of the upper extremity. Musculoskeletal ultrasonography is technically challenging, but with proper guidance and practice, every orthopaedic surgeon can confidently integrate ultrasonography into their clinical practice.

Ultrasonography for the Busy Orthopaedic Surgeon: The Lower Extremity.

Ultrasonography has the potential to become a fundamental component of the diagnosis and management of musculoskeletal conditions and injuries. Moreover, in the context of modern healthcare systems that are focused on optimizing value, ultrasonography has the advantage of minimizing costs when compared with other advanced imaging modalities. Because of its low cost, lack of radiation exposure, speed, and capability to diagnose dynamic conditions, more orthopaedic surgeons are routinely integrating musculoskeletal ultrasonography into their daily practice. It is important to provide a comprehensive review of and approach to common musculoskeletal conditions of the lower extremity for the busy orthopaedic surgeon.

Clinical Profiles of Childhood Astrovirus-, Sapovirus-, and Norovirus-Associated Acute Gastroenteritis in Pediatric Emergency Departments in Alberta, 2014-2018.

BACKGROUND: Infections by previously underdiagnosed viruses astrovirus and sapovirus are poorly characterized compared with norovirus, the most common cause of acute gastroenteritis. METHODS: Children <18 years old with acute gastroenteritis were recruited from pediatric emergency departments in Alberta, Canada between 2014 and 2018. We described and compared the clinical course of acute gastroenteritis in children with astrovirus, sapovirus, and norovirus. RESULTS: Astrovirus was detected in 56 of 2688 (2.1%) children, sapovirus was detected in 146 of 2688 (5.4%) children, and norovirus was detected in 486 of 2688 (18.1%) children. At illness onset, ~60% of astrovirus cases experienced both diarrhea and vomiting. Among sapovirus and norovirus cases, 35% experienced diarrhea at onset and 80% of 91% (sapovirus/norovirus) vomited; however, diarrhea became more prevalent than vomiting at approximately day 4 of illness. Over the full course of illness, diarrhea was 18% (95% confidence interval [CI], 8%- 29%) more prevalent among children with astrovirus than norovirus infections and had longer duration with greater maximal events; there were a median of 4.0 fewer maximal vomiting events (95% CI, 2.0-5.0). Vomiting continued for a median of 24.8 hours longer (95% CI, 9.6-31.7) among children with sapovirus versus norovirus. Differences between these viruses were otherwise minimal. CONCLUSIONS: Sapovirus infections attended in the emergency department are more similar to norovirus than previously reported, whereas astrovirus infections have several distinguishable characteristics.

Single-Cell RNA Sequencing Uncovers Paracrine Functions of the Epicardial-Derived Cells in Arrhythmogenic Cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) manifests with sudden death, arrhythmias, heart failure, apoptosis, and myocardial fibro-adipogenesis. The phenotype typically starts at the epicardium and advances transmurally. Mutations in genes encoding desmosome proteins, including DSP (desmoplakin), are major causes of ACM. METHODS: To delineate contributions of the epicardium to the pathogenesis of ACM, the Dsp allele was conditionally deleted in the epicardial cells in mice upon expression of tamoxifen-inducible Cre from the Wt1 locus. Wild type (WT) and Wt1-CreERT2:DspW/F were crossed to Rosa26mT/mG (R26mT/mG) dual reporter mice to tag the epicardial-derived cells with the EGFP (enhanced green fluorescent protein) reporter protein. Tagged epicardial-derived cells from adult Wt1-CreERT2:R26mT/mG and Wt1-CreERT2: R26mT/mG:DspW/F mouse hearts were isolated by fluorescence-activated cell staining and sequenced by single-cell RNA sequencing. RESULTS: WT1 (Wilms tumor 1) expression was progressively restricted postnatally and was exclusive to the epicardium by postnatal day 21. Expression of Dsp was reduced in the epicardial cells but not in cardiac myocytes in the Wt1-CreERT2:DspW/F mice. The Wt1-CreERT2:DspW/F mice exhibited premature death, cardiac dysfunction, arrhythmias, myocardial fibro-adipogenesis, and apoptosis. Single-cell RNA sequencing of ≈18 000 EGFP-tagged epicardial-derived cells identified genotype-independent clusters of endothelial cells, fibroblasts, epithelial cells, and a very small cluster of cardiac myocytes, which were confirmed on coimmunofluorescence staining of the myocardial sections. Differentially expressed genes between the paired clusters in the 2 genotypes predicted activation of the inflammatory and mitotic pathways-including the TGFß1 (transforming growth factor ß1) and fibroblast growth factors-in the epicardial-derived fibroblast and epithelial clusters, but predicted their suppression in the endothelial cell cluster. The findings were corroborated by analysis of gene expression in the pooled RNA-sequencing data, which identified predominant dysregulation of genes involved in epithelial-mesenchymal transition, and dysregulation of 146 genes encoding the secreted proteins (secretome), including genes in the TGFß1 pathway. Activation of the TGFß1 and its colocalization with fibrosis in the Wt1-CreERT2:R26mT/mG:DspW/F mouse heart was validated by complementary methods. CONCLUSIONS: Epicardial-derived cardiac fibroblasts and epithelial cells express paracrine factors, including TGFß1 and fibroblast growth factors, which mediate epithelial-mesenchymal transition, and contribute to the pathogenesis of myocardial fibrosis, apoptosis, arrhythmias, and cardiac dysfunction in a mouse model of ACM. The findings uncover contributions of the epicardial-derived cells to the pathogenesis of ACM.

Complex floral traits shape pollinator attraction to ornamental plants.

BACKGROUND AND AIMS: Ornamental flowering plant species are often used in managed greenspaces to attract and support pollinator populations. In natural systems, selection by pollinators is hypothesized to result in convergent multimodal floral phenotypes that are more attractive to specific pollinator taxa. In contrast, ornamental cultivars are bred via artificial selection by humans, and exhibit diverse and distinct phenotypes. Despite their prevalence in managed habitats, the influence of cultivar phenotypic variation on plant attractiveness to pollinator taxa is not well resolved. METHODS: We used a combination of field and behavioural assays to evaluate how variation in floral visual, chemical and nutritional traits impacted overall attractiveness and visitation by pollinator taxonomic groups and bee species to 25 cultivars of five herbaceous perennial ornamental plant genera. KEY RESULTS: Despite significant phenotypic variation, cultivars tended to attract a broad range of pollinator species. Nonetheless, at the level of insect order (bee, fly, butterfly, beetle), attraction was generally modulated by traits consistent with the pollination syndrome hypothesis. At the level of bee species, the relative influence of traits on visitation varied across plant genera, with some floral phenotypes leading to a broadening of the visitor community, and others leading to exclusion of visitation by certain bee species. CONCLUSIONS: Our results demonstrate how pollinator choice is mediated by complex multimodal floral signals. Importantly, the traits that had the greatest and most consistent effect on regulating pollinator attraction were those that are commonly selected for in cultivar development. Though variation among cultivars in floral traits may limit the pollinator community by excluding certain species, it may also encourage interactions with generalist taxa to support pollinator diversity in managed landscapes.

Impact of packing arrangement on the optical properties of C60 cluster aggregates.

The packing arrangement of organic π-conjugated molecules in a nanoscale material can have a strong impact on their optical properties. Here, using real-time-propagation time dependent density functional theory (rt-TDDFT) calculations with the support of transition contribution maps, we study how modifications in the packing arrangement (cubic-like and chain-like aggregates composed of eight C60 molecules) and packing density (assembled at close distances with center-to-center inter-fullerene distances (d) varying from 9 Å to 11 Å) of C60 molecules affect the optical properties of cluster aggregates. The important conclusions drawn from this work are summarized as follows. For d = 9 Å, the charge transfer excitons produced by cubic and chain-like C60 cluster aggregates have highly different optical characteristics, as evidenced by the transition contribution maps. On the other hand, for d = 10 Å and 11 Å, both kinds of aggregates produce qualitatively similar optical features with the emergence of Wannier-like delocalized excitons having distinct degrees of localization and spatial distribution. The theoretical findings in this study elucidate the optical excitations in C60 cluster aggregates and could help in the design of more efficient organic devices.