Divergent Processes Drive Parallel Evolution in Marine and Freshwater Fishes.

Evolutionary comparisons between major environmental divides, such as between marine and freshwater systems, can reveal the fundamental processes governing diversification dynamics. Although processes may differ due to the different scales of their biogeographic barriers, freshwater and marine environments nevertheless offer similar opportunities for diversification in benthic, demersal, and pelagic habitats. Here, we compare the evolutionary patterns and processes shaping teleost diversity in each of these three habitats and between marine and freshwater systems. Using specimens from the National Museum of Natural History, we developed a data set of linear measurements capturing body shape in 2266 freshwater and 3344 marine teleost species. With a novel comparative approach, we contrast the primary axis of morphological diversification in each habitat with the major axis defined by phylogenetic signal. By comparing angles between these axes, we find that fish in corresponding habitats have more similar primary axes of morphological diversity than would be expected by chance, but that different historical processes underlie these parallel patterns in freshwater and marine environments. Marine diversification is more strongly aligned with phylogenetic signal and shows a trend toward lineages occupying separate regions of morphospace. In contrast, ecological signal appears to be a strong driver of diversification in freshwater lineages through repeated morphological evolution in densely packed regions of morphospace. In spite of these divergent histories, our findings reveal that habitat has driven convergent patterns of evolutionary diversification on a global scale. [Benthic-pelagic axis; body shape; convergent evolution; morphological diversification; phylogenetic signal.].

Muscle Atrophy in CKD: A Historical Perspective of Advancements in Its Understanding.

OBJECTIVE: This perspective reviews the seminal clinical and experimental observations that led to today's current mechanistic model of muscle protein loss (wasting) in patients with chronic kidney disease (CKD). RESULTS AND CONCLUSION: Early International Society of Renal Nutrition and Metabolism (ISRNM) meetings facilitated discussions and hypotheses about the causes of muscle wasting in CKD. It became widely recognized that wasting is common and correlated with increased risks of mortality and morbidity. Although anorexia and dietary restrictions contribute to muscle loss, several features of CKD-associated wasting cannot be explained by malnutrition alone. The protein catabolism-inducing actions of metabolic acidosis, inflammation, insulin resistance, endocrine disorders and uremic toxins were progressively identified. Continued research to understand the interactions of inflammation, anabolic resistance, mitochondrial dysfunction, exercise, and nutrition on muscle protein turnover in patients with CKD will hopefully accelerate discoveries and treatments to ameliorate muscle wasting as well as the progression of CKD.

Heart disease in women: a narrative review.

Cardiovascular disease is the worldwide leading cause of death in women. Biological differences between the sexes, a result of genetic, epigenetic and sex hormone-mediated factors, are complex and incompletely understood. These differences are compounded by socio-cultural factors and together account for the variation in the prevalence, presentation and natural history of cardiovascular disease between men and women. Although there is growing recognition of sex-specific determinants of outcomes, women remain under-represented in clinical trials, and sex-disaggregated diagnostic and management strategies are not currently recommended in clinical guidelines. Women remain more likely to experience delays in diagnosis, to be treated less aggressively and to have worse outcomes. As a consequence, cardiovascular disease in women remains understudied, underdiagnosed and undertreated. This review will focus on female-specific characteristics of cardiovascular disease and how these may impact on anaesthetic and peri-operative risk assessment and care. We highlight significant differences between the sexes in the natural history of cardiovascular disease, including those disease entities that are more common in women, such as sudden coronary artery dissection or microvascular dysfunction. Given the rapidly rising incidence of maternal cardiovascular disease and associated complications, special consideration is given to the risk assessment and management of these conditions during pregnancy. Increased awareness of these issues has the potential to improve the effectiveness of the multidisciplinary heart team and ultimately improve the care provided to women.

The International Society of Renal Nutrition and Metabolism Commentary on the National Kidney Foundation and Academy of Nutrition and Dietetics KDOQI Clinical Practice Guideline for Nutrition in Chronic Kidney Disease.

The Academy of Nutrition and Dietetics and the National Kidney Foundation collaborated to provide an update to the Clinical Practice Guidelines (CPG) for nutrition in chronic kidney disease (CKD). These guidelines provide a valuable update to many aspects of the nutrition care process. They include changes in the recommendations for nutrition screening and assessment, macronutrients, and targets for electrolytes and minerals. The International Society of Renal Nutrition and Metabolism assembled a special review panel of experts and evaluated these recommendations prior to public review. As one of the highlights of the CPG, the recommended dietary protein intake range for patients with diabetic kidney disease is 0.6-0.8 g/kg/day, whereas for CKD patients without diabetes it is 0.55-0.6 g/kg/day. The International Society of Renal Nutrition and Metabolism endorses the CPG with the suggestion that clinicians may consider a more streamlined target of 0.6-0.8 g/kg/day, regardless of CKD etiology, while striving to achieve intakes closer to 0.6 g/kg/day. For implementation of these guidelines, it will be important that all stakeholders work to detect kidney disease early to ensure effective primary and secondary prevention. Once identified, patients should be referred to registered dietitians or the region-specific equivalent, for individualized medical nutrition therapy to slow the progression of CKD. As we turn our attention to the new CPG, we as the renal nutrition community should come together to strengthen the evidence base by standardizing outcomes, increasing collaboration, and funding well-designed observational studies and randomized controlled trials with nutritional and dietary interventions in patients with CKD.

Factors influencing interprofessional team collaboration when delivering care to community-dwelling seniors: A metasynthesis of Canadian interventions.

The rapid growth in the proportion of adults over the age of 65 translates into greater need of complex, highly specialized care. Hence, coupled with other factors, healthcare expenditures in Canada have grown exponentially, creating tension for a high-quality care while managing costs. Interventions with community-based interprofessional teams have been piloted across Canada as a means to provide efficient specialized care. These teams must, however, work collaboratively for a more comprehensive and patient-centered care. This metasynthesis aimed to identify common factors or characteristics found to be essential for a collaborative practice among members of an interdisciplinary team delivering coordinated care to community-dwelling seniors in both rural and urban centers in Canada. Six databases (Medline, CINAHL, Sage, JSTOR, ProQuest, Web of Science) were searched for qualitative peer-reviewed articles on community-based interventions with interprofessional teams in Canada and published between 2005-2018. Six articles were included and appraised using the COREQ guidelines for quality, followed by a thematic analysis for common themes related to team collaboration. Overarching themes related to practices of interprofessional collaboration were trust and respect, communication, and shared vision. Sub-themes included trust in the relationship between health care professional, professional identity and role clarity, interprofessional communication, communication with the client or family, and common goals. Interprofessional teams work collaboratively when trust and respect, communication, and shared vision are valued and present. Agencies coordinating interprofessional teams for community-based care could be pivotal in ensuring an environment conducive to collaboration, such as learning and team building opportunities.

Body shape diversification along the benthic-pelagic axis in marine fishes.

Colonization of novel habitats can result in marked phenotypic responses to the new environment that include changes in body shape and opportunities for further morphological diversification. Fishes have repeatedly transitioned along the benthic-pelagic axis, with varying degrees of association with the substrate. Previous work focusing on individual lineages shows that these transitions are accompanied by highly predictable changes in body form. Here, we generalize expectations drawn from this literature to study the effects of habitat on body shape diversification across 3344 marine teleost fishes. We compare rates and patterns of evolution in eight linear measurements of body shape among fishes that live in pelagic, demersal and benthic habitats. While average body shape differs between habitats, these differences are subtle compared with the high diversity of shapes found within each habitat. Benthic living increases the rate of body shape evolution and has led to numerous lineages evolving extreme body shapes, including both exceptionally wide bodies and highly elongate, eel-like forms. By contrast, we find that benthic living is associated with the slowest diversification of structures associated with feeding. Though we find that habitat can serve as an impetus for predictable trait changes, we also highlight the diversity of responses in marine teleosts to opportunities presented by major habitats.

Exosome-Mediated miR-29 Transfer Reduces Muscle Atrophy and Kidney Fibrosis in Mice.

Our previous study showed that miR-29 attenuates muscle wasting in chronic kidney disease. Other studies found that miR-29 has anti-fibrosis activity. We hypothesized that intramuscular injection of exosome-encapsulated miR-29 would counteract unilateral ureteral obstruction (UUO)-induced muscle wasting and renal fibrosis. We used an engineered exosome vector, which contains an exosomal membrane protein gene Lamp2b that was fused with the targeting peptide RVG (rabies viral glycoprotein peptide). RVG directs exosomes to organs that express the acetylcholine receptor, such as kidney. The intervention of Exo/miR29 increased muscle cross-sectional area and decreased UUO-induced upregulation of TRIM63/MuRF1 and FBXO32/atrogin-1. Interestingly, renal fibrosis was partially depressed in the UUO mice with intramuscular injection of Exo/miR29. This was confirmed by decreased TGF-ß, alpha-smooth muscle actin, fibronectin, and collagen 1A1 in the kidney of UUO mice. When we used fluorescently labeled Exo/miR29 to trace the Exo/miR route in vivo and found that fluorescence was visible in un-injected muscle and in kidneys. We found that miR-29 directly inhibits YY1 and TGF-ß3, which provided a possible mechanism for inhibition of muscle atrophy and renal fibrosis by Exo/miR29. We conclude that Exo/miR29 ameliorates skeletal muscle atrophy and attenuates kidney fibrosis by downregulating YY1 and TGF-ß pathway proteins.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Barriers and facilitators to health visiting teams delivering oral health promotion to families of young children: a mixed methods study with vignettes.

OBJECTIVE: To explore the potential barriers and facilitators to health visiting (HV) teams delivering oral health promotion during the 9-12-month old child mandated visit in Ealing, England. BACKGROUND: HV schemes and their counterparts worldwide share similar priorities to discuss oral health at 6-12 months of age. The HV programme in England stipulates at 9-12 months old, diet and dental health should be discussed. HVs believe dental decay is important however oral health knowledge is varied. Further, little is understood about what drives HVs to deliver oral health advice. An appropriate theoretical model to explore these factors is the Theoretical Domains Framework (TDF). METHODS: An opportunistic sample of HV team members was drawn from three hubs to allow for maximum variation. First, participants completed a questionnaire to establish baseline knowledge. Secondly, participants were invited to take part in focus groups (FGs) with vignettes. Thirdly, face-to-face interviews were conducted. FGs were subject to thematic analysis and the interviews to framework analysis. RESULTS: Thirty-six participants provided written informed consent and completed baseline questionnaires. Three FGs were conducted with an average of seven participants (n=21) followed by 13 interviews. Perceived facilitators: good levels of knowledge and skills, sense of professional role, emotions, belief in capability, organisational structure and resources. Perceived barriers: gaps in knowledge, conflicting advice from other professionals, conflicting issues for parents/ carers, use of interpreters. CONCLUSIONS: These findings can be harnessed to support oral health promotion delivered by HV teams.

Post-concussion syndrome and pre-existing mood disorder: A case report.

Sport-related concussions in youth and adolescent athletes most commonly resolve within one week without residual symptoms, with athletes resuming full participation following return to play guidelines. A small percentage of athletes have persistent symptoms that cause significant morbidity, some of whom are ultimately diagnosed with post-concussion syndrome. In these athletes, symptoms in the emotional domain can be more prolonged than other domains, with athletes reporting anxiety and depression months to years following injury. A prior personal or family history of pre-existing mood disorder or attention-deficit/hyperactivity disorder increases the risk of a prolonged duration of symptoms. In this case series, we discuss two cases of post-concussion syndrome in adolescent athletes with a past personal or family history of attention-deficit/hyperactivity disorder, anxiety, and depression treated by a combination of cognitive behavioral therapy and medication with ongoing persistent symptoms. There is increased need for mental health screening in all athletes to identify individuals at risk for post-concussion syndrome. Early identification of at-risk individuals allows the interdisciplinary care team to discuss expectations for the athlete and family regarding duration of symptoms.

Glucocorticoid-induced CREB activation and myostatin expression in C2C12 myotubes involves phosphodiesterase-3/4 signaling.

Muscle atrophy in metabolic conditions like chronic kidney disease (CKD) and diabetes are associated with glucocorticoid production, dysfunctional insulin/Akt/FoxO3 signaling and increased myostatin expression. We recently found that CREB, a transcription factor proposed to regulate myostatin expression, is highly phosphorylated in some wasting conditions. Based on a novel Akt-PDE3/4 signaling paradigm, we hypothesized that reduced Akt signaling contributes to CREB activation and myostatin expression. C2C12 myotubes were incubated with dexamethasone (Dex), an atrophy-inducing synthetic glucocorticoid. Akt/CREB signaling and myostatin expression were evaluated by immunoblot and qPCR analyses. Inhibitors of Akt, phosphodiesterase (PDE)-3/4, and protein kinase A (PKA) signaling were used to test our hypothesis. Incubating myotubes with Dex for 3-24 h inhibited Akt phosphorylation and enhanced CREB phosphorylation as well as myostatin mRNA and protein. Inhibition of PI3K/Akt signaling with LY294002 similarly increased CREB phosphorylation. Isobutyl-methylxanthine (IBMX, a pan PDE inhibitor), milrinone (PDE3 inhibitor) and rolipram (PDE4 inhibitor) augmented CREB phosphorylation and myostatin expression. Inhibition of protein kinase A by PKI reverted Dex- or IBMX-induced CREB phosphorylation and myostatin expression. Our study provides evidence supporting a newly identified mechanism by which a glucocorticoid-related reduction in Akt signaling contributes to myostatin expression via CREB activation.

MicroRNA-23a and MicroRNA-27a Mimic Exercise by Ameliorating CKD-Induced Muscle Atrophy.

Muscle atrophy is a frequent complication of CKD, and exercise can attenuate the process. This study investigated the role of microRNA-23a (miR-23a) and miR-27a in the regulation of muscle mass in mice with CKD. These miRs are located in a gene cluster that is regulated by the transcription factor NFAT. CKD mice expressed less miR-23a in muscle than controls, and resistance exercise (muscle overload) increased the levels of miR-23a and miR-27a in CKD mice. Injection of an adeno-associated virus encoding the miR-23a/27a/24-2 precursor RNA into the tibialis anterior muscles of normal and CKD mice led to increases in mature miR-23a and miR-27a but not miR-24-2 in the muscles of both cohorts. Overexpression of miR-23a/miR-27a in CKD mice attenuated muscle loss, improved grip strength, increased the phosphorylation of Akt and FoxO1, and decreased the activation of phosphatase and tensin homolog (PTEN) and FoxO1 and the expression of TRIM63/MuRF1 and FBXO32/atrogin-1 proteins. Provision of miR-23a/miR-27a also reduced myostatin expression and downstream SMAD-2/3 signaling, decreased activation of caspase-3 and -7, and increased the expression of markers of muscle regeneration. Lastly, in silico miR target analysis and luciferase reporter assays in primary satellite cells identified PTEN and caspase-7 as targets of miR-23a and FoxO1 as a target of miR-27a in muscle. These findings provide new insights about the roles of the miR-23a/27a-24-2 cluster in CKD-induced muscle atrophy in mice and suggest a mechanism by which exercise helps to maintain muscle mass.

A multi-variable analysis of four factors affecting caries levels among five-year-old children; deprivation, ethnicity, exposure to fluoridated water and geographic region.

OBJECTIVE: To assess the role of factors posited to affect population caries levels across England. BASIC RESEARCH DESIGN: Multivariable regression analysis assessing four potential determinants of caries severity and prevalence: deprivation, exposure to fluoridated water, ethnicity and geographic region Participants: Random sample of 121,875 five-year-old children in England in the 2014/15 academic year. MAIN OUTCOME MEASURES: Decayed, missing and filled teeth, with decay measured at the dentinal level, (d3mft), presented as prevalence (dmft⟩0) and extent of decay among children who have any (d3mft if d3mft>0). INDEPENDENT VARIABLES: Parental reported ethnicity from school records, index of multiple deprivation (IMD) scores, region and exposure to water fluoridation calculated utilising home postcodes. RESULTS: The data support wider literature displaying associations between caries and deprivation across a social gradient. The important, new findings are deprivation, some ethnic groups and lack of exposure to water fluoridation are all associated with increased prevalence and severity of caries when considered together and independently. New evidence supports the impact of water fluoridation on health inequalities in that the greatest impact of exposure to fluoridated water was seen in the most deprived children and those from an Asian / Asian British ethnic group. CONCLUSIONS: Five-year-old children who were from the most deprived areas, not exposed to fluoridated water, of an Eastern European ethnic group and living in the North West demonstrated the highest prevalence and severity of caries in the survey under scrutiny. This is of public health importance, providing evidence for population groups to target with health improvement activities.

Comparison of ventricular drain location and infusion test in hydrocephalus.

OBJECTIVES: Suspected cerebrospinal fluid shunt (CSF) dysfunction in hydrocephalic patients poses a diagnostic uncertainty. The clinical picture can be non-specific and CT imaging alone is not always pathognomonic. Infusion tests are an increasingly used investigation for real-time hydrodynamic assessment of shunt patency. We report the correlation between infusion test results with the quality of ventricular drain placement on CT scans in a large retrospective group of hydrocephalic patients. MATERIALS & METHODS: Three hundred and six infusion test results performed in 200 patients were correlated with 306 corresponding CT head scans. Nominal logistic regression was used to correlate shunt catheter position on CT imaging to patency of ventricular drain as determined by infusion tests. RESULTS: Infusion test results of shunt patency are statistically congruent with the analysis of shunt catheter position on CT head scans. Catheter tips completely surrounded by either parenchyma or CSF on CT imaging are strongly associated with evidence of occlusion or patency from infusion tests, respectively (χ² = 51.68, P < 0.0001, n = 306 and χ² = 31.04, P < 0.0001, n = 306). CONCLUSIONS: The most important anatomical factor for shunt patency is the catheter tip being completely surrounded by CSF. Infusion tests provide functional and reliable assessment of shunt patency in vivo and are strongly correlated with the position of the ventricular catheter on CT imaging.

The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure.

The extracellular calcium-sensing receptor CaSR is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vascular smooth muscle cells (VSMC) were generated by breeding exon 7 LoxP-CaSR mice with animals in which Cre recombinase is driven by a SM22α promoter (SM22α-Cre). Wire myography performed on Cre-negative [wild-type (WT)] and Cre-positive (SM22α)CaSR(Δflox/Δflox) [knockout (KO)] mice showed an endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared with WT mice in response to KCl and to phenylephrine. Increasing extracellular calcium ion (Ca(2+)) concentrations (1-5 mM) evoked contraction in WT but only relaxation in KO aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with WT, as measured by both tail cuff and radiotelemetry. This hypotension was mostly pronounced during the animals' active phase and was not rescued by either nitric oxide-synthase inhibition with nitro-l-arginine methyl ester or by a high-salt-supplemented diet. KO animals also exhibited cardiac remodeling, bradycardia, and reduced spontaneous activity in isolated hearts and cardiomyocyte-like cells. Our findings demonstrate a role for CaSR in the cardiovascular system and suggest that physiologically relevant changes in extracellular Ca(2+) concentrations could contribute to setting blood vessel tone levels and heart rate by directly acting on the cardiovascular CaSR.

Comparative expression of the extracellular calcium-sensing receptor in the mouse, rat, and human kidney.

The calcium-sensing receptor (CaSR) was cloned over 20 years ago and functionally demonstrated to regulate circulating levels of parathyroid hormone by maintaining physiological serum ionized calcium concentration ([Ca(2+)]). The receptor is highly expressed in the kidney; however, intrarenal and intraspecies distribution remains controversial. Recently, additional functions of the CaSR receptor in the kidney have emerged, including parathyroid hormone-independent effects. It is therefore critical to establish unequivocally the localization of the CaSR in the kidney to relate this to its proposed physiological roles. In this study, we determined CaSR expression in mouse, rat, and human kidneys using in situ hybridization, immunohistochemistry (using 8 different commercially available and custom-made antibodies), and proximity ligation assays. Negative results in mice with kidney-specific CaSR ablation confirmed the specificity of the immunohistochemistry signal. Both in situ hybridization and immunohistochemistry showed CaSR expression in the thick ascending limb, distal tubule, and collecting duct of all species, with the thick ascending limb showing the highest levels. Within the collecting ducts, there was significant heterogeneity of expression between cell types. In the proximal tubule, lower levels of immunoreactivity were detected by immunohistochemistry and proximity ligation assays. Proximity ligation assays were the only technique to demonstrate expression within glomeruli. This study demonstrated CaSR expression throughout the kidney with minimal discrepancy between species but with significant variation in the levels of expression between cell and tubule types. These findings clarify the intrarenal distribution of the CaSR and enable elucidation of the full physiological roles of the receptor within this organ.

Ecomorphological convergence in planktivorous surgeonfishes.

Morphological convergence plays a central role in the study of evolution. Often induced by shared ecological specialization, homoplasy hints at underlying selective pressures and adaptive constraints that deterministically shape the diversification of life. Although midwater zooplanktivory has arisen in adult surgeonfishes (family Acanthuridae) at least four independent times, it represents a clearly specialized state, requiring the capacity to swiftly swim in midwater locating and sucking small prey items. Whereas this diet has commonly been associated with specific functional adaptations in fishes, acanthurids present an interesting case study as all nonplanktivorous species feed by grazing on benthic algae and detritus, requiring a vastly different functional morphology that emphasizes biting behaviours. We examined the feeding morphology in 30 acanthurid species and, combined with a pre-existing phylogenetic tree, compared the fit of evolutionary models across two diet regimes: zooplanktivores and nonzooplanktivorous grazers. Accounting for phylogenetic relationships, the best-fitting model indicates that zooplanktivorous species are converging on a separate adaptive peak from their grazing relatives. Driving this bimodal landscape, zooplanktivorous acanthurids tend to develop a slender body, reduced facial features, smaller teeth and weakened jaw adductor muscles. However, despite these phenotypic changes, model fitting suggests that lineages have not yet reached the adaptive peak associated with plankton feeding even though some transitions appear to be over 10 million years old. These findings demonstrate that the selective demands of pelagic feeding promote repeated - albeit very gradual - ecomorphological convergence within surgeonfishes, while allowing local divergences between closely related species, contributing to the overall diversity of the clade.