Pediatric Learning Health Networks in Solid Organ Transplantation-Engaging all Stakeholders to Achieve Health for Children Who Require Transplantation.

BACKGROUND: Learning Health Networks (LHN) have evolved within medicine over the past two decades, but their integration into transplantation has been more recent. OBJECTIVES AND METHODS: In this paper, we describe three LHNs in end-stage organ disease/transplantation, their common and unique features, and how their "actor-oriented" architecture allowed for rapid adaptation to meet the needs of their patients and practitioners during the recent COVID-19 pandemic. RESULT: The structure and focus of the Improving Renal Outcomes Collaborative (IROC), Starzl Network for Excellence in Pediatric Transplantation (SNEPT), and the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) are reviewed. We discuss the critical role of patient and family engagement, focusing on collaboration with Transplant Families. Finally, we review challenges common to the LHN concept and potential common areas of alignment to achieve the goal of more rapid and sustained progress to improve health in pediatric transplantation. CONCLUSION: LHN in transplantation are essential to accelerate knowledge dissemination and improve outcomes.

A narrative review of sperm selection technology for assisted reproduction techniques.

Background and Objective: In-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) has become increasingly prevalent even in cases without significant male factor infertility; however, stagnant live-birth rates, both nationally and internationally, have driven more research into sperm selection. To date, nothing has replaced swim-up and density-gradient preparation methods and therefore we sought to review the state of the science. Methods: A PubMed search was performed between years of 1989 and 2024 for English research articles reporting data on sperm selection technology in assisted reproductive technology. Key Content and Findings: IVF with ICSI is increasingly prevalent even in men with normal semen parameters. Despite technologic advances and widespread use, reproductive outcomes with ICSI have been stagnant. This market for opportunity growth has allowed for sperm selection techniques to grow exponentially with heterogeneity in utilization and a paucity of positive reproductive outcomes. Swim-up and density-gradient centrifugation remain the most utilized sperm selection techniques. Various future technologies show promise including epigenetics, sperm biomarkers and a potential role of artificial intelligence; however, more research is needed. Conclusions: Given unchanged IVF success rates, sperm selection technologies hold promise to improve reproductive outcomes beyond traditional ICSI. At present, no technique has shown superiority to swim up and density centrifugation.

Frequency and Sex-Specific Associations of Metabolic Syndrome in Rwandans Seeking Outpatient Care: A Cross Sectional, Single Centre Study.

Background: The prevalence of cardiometabolic diseases is escalating in sub-Saharan Africa (SSA) alongside the prevailing high burden of communicable diseases. Although many countries in SSA, including Rwanda, have existing data on the prevalence of individual components of the MetS, many SSA countries have insufficient data to guide policy makers on the magnitude of MetS. This study sought to determine the magnitude of MetS and its associated risk factors by sex at a referral teaching hospital in Rwanda. Methods: A cross-sectional, study was conducted among adults aged 35 to 65 years presenting at Ruhengeri Referral Teaching Hospital, Rwanda. We collected socio-clinicodemographic data using the World Health Organization (WHO) STEPwise tool for non-communicable diseases. We used the National Cholesterol Education Program Adult Treatment Panel III criteria for MetS. Results: Overall, 99 (23.5%) males and 322 (76.5%) female participants with mean ± SD age 47.5 ± 8.2 years were enrolled. The overall frequency of MetS was 51.9% (95% CI: 47.0-56.8) and was significantly higher (p < 0.001) in females 193 (59.4%) compared to males 26 (26.3%). Significant differences by sex were also noted in the proportions of visceral obesity; 70.4% vs 7.1% (p < 0.001), hypoalphalipoproteinaemia 36.1% vs 69.7% (p < 0.0001), type 2 diabetes mellitus; 18.4% vs 31.6% (p = 0.020) and body mass index 25.9 ± 15.6 vs 28.2 ± 6.4 (p = 0.032). On multivariate logistic regression, older age (odds ratio (OR) 1.05; 95% confidence interval ((CI) 1.01-1.10)), higher body weight (OR 1.06; 95% CI 1.04-1.08) and higher total cholesterol (1.25; 95% CI 1.05 -1.74) were significantly associated with MetS in females; whereas only higher body weight (OR1.10; 95% CI 1.04-1.18) was significantly associated with MetS in males. Conclusion: A high frequency of MetS was observed in the present study, which was higher among females. Our findings emphasize the need for tailored prevention and intervention strategies to mitigate the long-term impact of MetS.

Nicorandil treatment improves survival and spatial learning in aged granulin knockout mice.

Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the "K+ATP" channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral performance, neuropathology, and gene expression. Mortality was significantly higher for aged Grn-KO mice (particularly females), but there was a conspicuous improvement in survival for both sexes treated with nicorandil. Grn-KO mice performed worse on some cognitive tests than WT mice, but Morris Water Maze performance was improved with nicorandil treatment. Neuropathologically, Grn-KO mice had significantly increased levels of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytosis but not ionized calcium binding adaptor molecule 1 (IBA-1)-immunoreactive microgliosis, indicating cell-specific inflammation in the brain. Expression of several astrocyte-enriched genes, including Gfap, were also elevated in the Grn-KO brain. Nicorandil treatment was associated with a subtle shift in a subset of detected brain transcript levels, mostly related to attenuated inflammatory markers. Nicorandil treatment improved survival outcomes, cognition, and inflammation in aged Grn-KO mice.

nSMase2-mediated exosome secretion shapes the tumor microenvironment to immunologically support pancreatic cancer.

The pleiotropic roles of nSMase2-generated ceramide include regulation of intracellular ceramide signaling and exosome biogenesis. We investigated the effects of eliminating nSMase2 on early and advanced PDA, including its influence on the microenvironment. Employing the KPC mouse model of pancreatic cancer, we demonstrate that pancreatic epithelial nSMase2 ablation reduces neoplasia and promotes a PDA subtype switch from aggressive basal-like to classical. nSMase2 elimination prolongs survival of KPC mice, hinders vasculature development, and fosters a robust immune response. nSMase2 loss leads to recruitment of cytotoxic T cells, N1-like neutrophils, and abundant infiltration of anti-tumorigenic macrophages in the pancreatic preneoplastic microenvironment. Mechanistically, we demonstrate that nSMase2-expressing PDA cell small extracellular vesicles (sEVs) reduce survival of KPC mice; PDA cell sEVs generated independently of nSMase2 prolong survival of KPC mice and reprogram macrophages to a proinflammatory phenotype. Collectively, our study highlights previously unappreciated opposing roles for exosomes, based on biogenesis pathway, during PDA progression.

Impact of COVID-19 Pandemic on Reusable Device Pre-Cleaning Training for Front-line Staff.

High-level disinfection and sterilization are complex processes, requiring initial and ongoing training of frontline staff.1 A key component of appropriate disinfection and sterilization is point-of-use pre-cleaning performed by front-line staff. Our facility implemented an annual hospital-wide education and competency program for staff that perform pre-cleaning of reusable medical devices.

Mutation of a highly conserved isoleucine residue in loop 2 of several ß-coronavirus macrodomains indicates that enhanced ADP-ribose binding is detrimental for replication.

All coronaviruses (CoVs) encode for a conserved macrodomain (Mac1) located in non-structural protein 3. Mac1 is an ADP-ribosylhydrolase that binds and hydrolyzes mono-ADP-ribose from target proteins. Previous work has shown that Mac1 is important for virus replication and pathogenesis. Within Mac1, there are several regions that are highly conserved across CoVs, including the glycine-isoleucine-phenylalanine motif. While we previously demonstrated the importance of the glycine residue for CoV replication and pathogenesis, the impact of the isoleucine and phenylalanine residues remains unknown. To determine how the biochemical activities of these residues impact CoV replication, the isoleucine and the phenylalanine residues were mutated to alanine (I-A/F-A) in both recombinant Mac1 proteins and recombinant CoVs, including murine hepatitis virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The F-A mutant proteins had ADP-ribose binding and/or hydrolysis defects that correlated with attenuated replication and pathogenesis of F-A mutant MERS-CoV and SARS-CoV-2 viruses in cell culture and mice. In contrast, the I-A mutant proteins had normal enzyme activity and enhanced ADP-ribose binding. Despite only demonstrating increased ADP-ribose binding, I-A mutant MERS-CoV and SARS-CoV-2 viruses were highly attenuated in both cell culture and mice, indicating that this isoleucine residue acts as a gate that controls ADP-ribose binding for efficient virus replication. These results highlight the function of this highly conserved residue and provide unique insight into how macrodomains control ADP-ribose binding and hydrolysis to promote viral replication. IMPORTANCE: The conserved coronavirus (CoV) macrodomain (Mac1) counters the activity of host ADP-ribosyltransferases and is critical for CoV replication and pathogenesis. As such, Mac1 is a potential therapeutic target for CoV-induced disease. However, we lack a basic knowledge of how several residues in its ADP-ribose binding pocket contribute to its biochemical and virological functions. We engineered mutations into two highly conserved residues in the ADP-ribose binding pocket of Mac1, both as recombinant proteins and viruses for Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Interestingly, a Mac1 isoleucine-to-alanine mutant protein had enhanced ADP-ribose binding which proved to be detrimental for virus replication, indicating that this isoleucine controls ADP-ribose binding and is beneficial for virus replication and pathogenesis. These results provide unique insight into how macrodomains control ADP-ribose binding and will be critical for the development of novel inhibitors targeting Mac1 that could be used to treat CoV-induced disease.

Association between allostatic load and accelerated white matter brain aging: findings from the UK biobank.

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting and doubly robust methods, were used to evaluate the impact of AL on WM BAG adjusting for age, sex, socioeconomic, and lifestyle behaviors. We found increasing one AL score unit significantly increased WM BAG by 0.29 years in association analysis and by 0.33 years in Mendelian analysis. The age- and sex-stratified analysis showed consistent results among participants 45-54 and 55-64 years old, with no significant sex difference. This study demonstrated that higher chronic stress was significantly associated with accelerated brain aging, highlighting the importance of stress management in reducing dementia and neurodegenerative disease risks.

Formulation and Release of Active Pharmaceutical Ingredients using a Supramolecular Self-healing Two-component Gel.

A two-component low-molecular-weight gelator (LMWG) formed from a modified amino acid and an aldehyde was formulated with active pharmaceutical ingredients (APIs). Basic APIs (propranolol, atropine) can be mixed with the LMWG prior to gel assembly while acidic APIs (naproxen, rosuvastatin) inhibit assembly by disrupting the LMWG imine bond and were loaded by diffusion after gel assembly. For diffusion-loaded gels, the API in the liquid-like phase was rapidly released, with the remainder, interacting with gel fibres, retained in the gel. Rosuvastatin release was particularly low with STD NMR indicating interactions between the aromatic ring and the self-assembled gel network. Propranolol also interacted with the gel via its aromatic unit, and its release led to gel erosion. Using agarose as a polymer gelator additive reinforced the gel, restricting erosion. In contrast, atropine was readily released over a period of hours - it is primarily in the liquid-like phase with STD NMR indicating no interactions with the gel network. The atropine-loaded gel retained its thixotropic properties. Overall, APIs must be carefully chosen to optimise formulation/release. Of the APIs investigated, atropine has most potential for further development. Atropine has applications in treating myopia, and our results suggest potential ophthalmic applications of supramolecular gels.

Characterizing coagulation responses in humans and nonhuman primates following kidney xenotransplantation-A narrative review.

The recent report of the first pig kidney transplant in a living human brings hope to thousands of people with end-stage kidney failure. The scientific community views this early success with caution as kidney xenotransplantation exhibits many challenges and barriers. One of these is coagulation dysregulation. This includes (i) pig von Willebrand Factor (vWF) interaction with human platelets, which can induce abnormal clotting responses, heightening the risk of graft failure, (ii) the inefficiency of pig thrombomodulin in activating human protein C, which emphasizes the species-specific variations that aggravate coagulation challenges, and (iii) the development of thrombotic microangiopathy in the pig grafts and the occurrence of systemic consumptive coagulopathy in the recipients. Indeed, coagulation dysregulation largely results from differences in endothelial cell response and incompatibilities between pig and human coagulation-anticoagulation pathways. These barriers can be resolved by modifications to pig vWF and the expression of human thrombomodulin and endothelial protein C receptors in pig cells, serving as strategic interventions to align the coagulation systems of the two species more closely. These coagulation challenges have clinical implications in how they affect graft survival and patient outcome. Genetic engineering of the organ-source pig and the administration of various drugs have assisted in correcting this coagulation dysregulation. Hence, comprehending and controlling coagulation dysregulation is crucial for progress in xenotransplantation as a viable option for treating patients with terminal kidney disease.

Using cross-country datasets for association mapping in Arachis hypogaea L.

Groundnut (Arachis hypogaea L.) is one of the most important climate-resilient oil crops in sub-Saharan Africa. There is a significant yield gap for groundnut in Africa because of poor soil fertility, low agricultural inputs, biotic and abiotic stresses. Cross-country evaluations of promising breeding lines can facilitate the varietal development process. The objective of our study was to characterize popular test environments in Uganda (Serere and Nakabango) and Malawi (Chitala and Chitedze) and identify genotypes with stable superior yields for potential future release. Phenotypic data were generated for 192 breeding lines for yield-related traits, while genotypic data were generated using skim-sequencing. We observed significant variation (p < 0.001; p < 0.01; p < 0.05) across genotypes for all yield-related traits: days to flowering (DTF), pod yield (PY), shelling percentage, 100-seed weight, and grain yield within and across locations. Nakabango, Chitedze, and Serere were clustered as one mega-environment with the top five most stable genotypes being ICGV-SM 01709, ICGV-SM 15575, ICGV-SM 90704, ICGV-SM 15576, and ICGV-SM 03710, all Virginia types. Population structure analysis clustered the genotypes in three distinct groups based on market classes. Eight and four marker-trait associations (MTAs) were recorded for DTF and PY, respectively. One of the MTAs for DTF was co-localized within an uncharacterized protein on chromosome 13, while another one (TRv2Chr.11_3476885) was consistent across the two countries. Future studies will need to further characterize the candidate genes as well as confirm the stability of superior genotypes across seasons before recommending them for release.

Tissue resident memory T cells contribute to protectionagainst heterologousSARS-CoV-2 challenge.

Widespread vaccination and natural infection have resulted in greatly decreased rates of severe disease, hospitalization and death after subsequent infection or reinfection with SARS-CoV-2. New vaccine formulations are based on circulating strains of virus, which have tended to evolve to more readily transmit human to human and to evade the neutralizing antibody response. An assumption of this approach is that ancestral strains of virus will not recur. Recurrence of these strains could be a problem for individuals not previously exposed to ancestral spike protein by vaccination or infection. Here, we addressed this question by infecting mice with recent SARS-CoV-2 variants and then challenging them with a highly pathogenic mouse-adapted virus closely related to the ancestral Wuhan-1 strain (SARS2-N501YMA30). We found that challenged mice were protected from death and substantial weight loss, even though they generally had low or no neutralizing antibody response to SARS2-N501YMA30 at the time of reinfection. T cell depletion from the previously infected mice did not diminish infection against clinical disease, although it did result in delayed kinetics of virus clearance in the nasal turbinate and in some cases, in the lungs. Levels of tissue resident memory T cells were significantly elevated in the nasal turbinate of previously infected mice compared to mice that had no previous exposure to SARS-CoV-2. However, this phenotype was not seen in lung tissues. Together, these results indicate that the immune response to newly circulating variants afforded protection against re-infection with the ancestral virus that was at least in part T cell based.

Comparing direct medical care costs of patients with bladder cancer who received an ileal conduit vs. neobladder in the year following cystectomy.

PURPOSE: Bladder cancer is 1 of the most costly cancers, however there is limited research on medical care costs by type of urinary diversion. The objective of our study was to compare medical care costs of the 2 most common urinary diversions in the year following radical cystectomy. METHODS: The Bladder Cancer Quality of Life Study included patients diagnosed with bladder cancer who underwent radical cystectomy and received an ileal conduit (IC, n = 821) or neobladder (NB, n = 181) in 3 integrated health systems. Medical care costs per patient per quarter were estimated for the year following cystectomy. Multivariable generalized linear models with a gamma distribution and log link were used to estimate mean monthly medical care costs (2022 USD$), adjusted for patient demographic and clinical characteristics. RESULTS: In multivariable analysis, mean monthly costs per quarter were not significantly different between IC and NB patients in the 12 months following cystectomy. Overall, mean monthly costs in IC and NB patients were highest during the first quarter and decreased thereafter. Factors associated with higher mean costs across all quarters included presence of any complications and advanced tumor stage at cystectomy (all P < 0.001). CONCLUSION: Our study addresses an important knowledge gap by quantifying the medical costs of bladder cancer patients by urinary diversion type and comparing costs of different treatment approaches. Studies that assess patient-reported outcomes and out-of-pocket costs, by urinary diversion type, are warranted to inform treatment decision-making and cost conversations.

Is Allosensitization Detrimental to Pig Organ Xenotransplantation, and Is Xenosensitization Detrimental to Subsequent Organ Allotransplantation? A Debate Organized by the International Xenotransplantation Association (IXA).

This report summarizes the content of a debate sponsored by eGenesis Bio, organized by the International Xenotransplantation Association (IXA), and attended by more than 150 delegates in the context of the IPITA-IXA-CTRMS Joint Congress held in San Diego in October 2023. The debate centered around two important immunological topics relating to xenotransplantation. The first was a debate relating to the statement that "HLA-sensitized patients are at higher risk for rejecting a pig xenograft." Stuart Knechtle provided evidence to support this statement and Massimo Mangiola opposed it. Before the debate, a majority (>80%) of the audience agreed with this statement. After listening to the debate, this percentage was reduced to approximately 60%. The second debated statement was "Recipients of pig xenografts who develop anti-pig antibodies are at higher risk for rejecting a subsequent allograft." This was proposed by A. Joseph Tector and opposed by Léo H. Bühler. Before the debate, once again a majority of the audience (approximately 60%) believed that prior sensitization to a pig xenograft would be detrimental to the survival of a subsequent allograft. However, after listening to the debate, only about 40% believed this statement to be correct. The topics discussed remain complex and answers are not yet conclusive. However, the present evidence suggests that allosensitization may prove detrimental to subsequent xenotransplantation, whilst sensitization to pig antigens may not be detrimental to subsequent allotransplantation.

Impact of SGLT2-Inhibitor Therapy on Survival in Patients with Transthyretin Amyloid Cardiomyopathy: Analysis of a Prospective Registry Study.

Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) represent a high-risk heart failure population with continued unmet therapeutic needs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction, and first evidence regarding their safety and effectiveness in patients with ATTR-CM is arising. This study investigates the association between SGLT2i therapy and clinical outcomes in these patients. Methods: This is an analysis of a prospective registry conducted at a referral centre for hypertrophic cardiomyopathies including 116 patients with confirmed ATTR-CM. Fifty-one patients (44%) were treated with SGLT2i while 65 patients (56%) remained SGLT2i-naïve. Results: During a median follow-up of 2.6 (1.7-3.7) years, 38 patients (33%) died, of whom 11 patients (9%) received SGLT2i treatment and 27 patients (23%) were treatment-naïve. SGLT2i therapy was significantly associated with lower mortality (HR 0.457, 95%CI 0.227-0.922, p = 0.029). This association persisted after adjusting for age and sex (HR 0.479, 95%CI 0.235-0.977, p = 0.043) and after additional adjustment for eGFR, NT-proBNP, LVEF, and concomitant therapy with tafamidis (HR 0.328, 95%CI 0.141-0.760, p = 0.009). However, when potential immortal time bias was considered, this association lost statistical significance (HR 1.075, 95%CI 0.524-2.206, p = 0.843). No significant associations between SGLT2i therapy and worsening heart-failure hospitalization or cardiovascular mortality were observed. Conclusions: In crude analysis, SGLT2i therapy associates with better survival in patients with ATTR-CM. However, after adjustment for immortal time, this association becomes statistically insignificant. Hence, to draw final conclusions on the effectiveness of SGLT2i therapy in these patients, a randomized controlled trial is warranted.

Treatment of a patient with inoperable tumoral calcinosis associated with end stage kidney disease: A case report.

We describe a case of severe symptomatic tumoral calcinosis in a young man with end stage kidney disease secondary to antineutrophil cytoplasmic antibodies-associated vasculitis with longstanding hyperphosphatemia and secondary hyperparathyroidism while on several years of peritoneal dialysis. The use of intravenous sodium thiosulfate, optimization of clearance with five times weekly hemodialysis, and intradialytic nutrition were used to treat his inoperable tumoral calcinosis. Over 3 months, he had a remarkable reduction in the size of his calcified masses and associated improvement in pain. He subsequently received a living donor kidney transplant.

Referral Sources Across Racial and Ethnic Groups at Alzheimer's Disease Research Centers.

Background: Despite the need to increase engagement of underrepresented groups (URG) in Alzheimer's disease and related dementias (ADRD) studies, enrollment remains low. Objective: Compare referral sources across racial and ethnic groups among participants enrolled in ADRC studies. Methods: Data for this cross-sectional secondary analysis were extracted from the National Alzheimer's Coordinating Center Uniform Data Set. We performed mixed effects logistic regression models using generalized estimating equations for professional referral versus non-professional referral by racial and ethnic group, adjusted for age, gender, education, visit year, and Clinical Dementia Rating scale (CDR) with a random effect for study site. Results: Included in the analysis were 48,330 participants across 46 ADRCs (mean [SD] age, 71.3 [10.5] years; 20,767 female [57%]; 4,138 Hispanic [8.6%]; 1,392 non-Hispanic Asian [2.9%]; 6,766 non-Hispanic Black [14%] individuals; and 676 individuals [1.4%] of other races. Non-Hispanic Black and Asian participants had lower odds of being referred by a professional contact compared to non-Hispanic White participants (Black: adjusted OR = 0.61, 95% CI = 0.44-0.86, p = 0.005; Asian: adjusted OR = 0.65, 95% CI, p = 0.004). In participants who had completed an MRI, there was no significant difference in referral source across ethnic and racial groups. Conclusions: Further studies are needed to better understand the systemic and structural factors that contribute to differences in referral sources and disparities in recruitment of URG into ADRD studies.

Reference genome for the endangered, genetically subdivided, northern tidewater goby, Eucyclogobius newberryi.

The federally endangered sister species, Eucyclogobius newberryi (northern tidewater goby) and E. kristinae (southern tidewater goby) comprise the California endemic genus Eucyclogobius, which historically occurred in all coastal California counties. Isolated lagoons that only intermittently connect to the sea are their primary habitat. Reproduction occurs during lagoon closure, minimizing marine dispersal and generating the most genetically subdivided vertebrate genus on the California coast. We present a new genome assembly for E. newberryi using HiFi long reads and Hi-C chromatin-proximity sequencing. The 980Mb E. newberryi reference genome has an N50 of 34Mb with 22 well-described scaffolds comprising 88% of the genome and a complete BUSCO score of 96.7%. This genome will facilitate studies addressing selection, drift, and metapopulation genetics in subdivided populations, as well as the persistence of the critically endangered E. kristinae, where reintroduction will be an essential element of conservation actions for recovery. It also provides tools critical to the recovery of the genetically distinct management units in the northern tidewater goby, as well as broader ecological and evolutionary studies of gobies, the most speciose family of fishes in the world.

Austrian consensus statement on the diagnosis and management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease that is characterized by left ventricular hypertrophy unexplained by secondary causes. Based on international epidemiological data, around 20,000-40,000 patients are expected to be affected in Austria. Due to the wide variety of clinical and morphological manifestations the diagnosis can be difficult and the disease therefore often goes unrecognized. HCM is associated with a substantial reduction in quality of life and can lead to sudden cardiac death, especially in younger patients. Early and correct diagnosis, including genetic testing, is essential for comprehensive counselling of patients and their families and for effective treatment. The latter is especially true as an effective treatment of outflow tract obstruction has recently become available in the form of a first in class cardiac myosin ATPase inhibitor, as a noninvasive alternative to established septal reduction therapies. The aim of this Austrian consensus statement is to summarize the recommendations of international guidelines with respect to the genetic background, pathophysiology, diagnostics and management in the context of the Austrian healthcare system and resources, and to present them in easy to understand algorithms.