Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). ...TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30-40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options.
Co-morbid depression and anxiety symptoms are frequently under-recognised and under-treated in heart disease and this negatively impacts self-management.
The purpose of this study was to determine ...the prevalence, correlates and predictors of depression and anxiety in cardiac rehabilitation programmes, the impact of cardiac rehabilitation on moderate depression, anxiety and stress symptoms, and the relationship between moderate depression, anxiety and stress symptoms and cardiac rehabilitation adherence.
This was a retrospective cohort study of 5908 patients entering cardiac rehabilitation programmes from 2006-2017, across two Sydney metropolitan teaching hospitals. Variables included demographics, diagnoses, cardiovascular risk factors, medication use, participation rates, health status (Medical Outcomes Study Short Form-36) and psychological health (Depression Anxiety Stress Scales) subscale scores.
Moderate depression, anxiety or stress symptoms were prevalent in 18%, 28% and 13% of adults entering cardiac rehabilitation programmes, respectively. Adults with moderate depression (24% vs 13%), anxiety (32% vs 23%) or stress (18% vs 10%) symptoms were significantly less likely to adhere to cardiac rehabilitation compared with those with normal-mild symptoms (
< 0.001). Anxiety (odds ratio 4.395, 95% confidence interval 3.363-5.744,
< 0.001) and stress (odds ratio 4.527, 95% confidence interval 3.315-6.181,
< 0.001) were the strongest predictors of depression. Depression (odds ratio 3.167, 95% confidence interval 2.411-4.161) and stress (odds ratio 5.577, 95% confidence interval 4.006-7.765,
< 0.001) increased the risk of anxiety on entry by more than three times, above socio-demographic factors, cardiovascular risk factors, diagnoses and quality of life.
Monitoring depression and anxiety symptoms on entry and during cardiac rehabilitation can assist to improve adherence and may identify the need for additional psychological health support. Exploring the relevance and use of adjunct psychological support strategies within cardiac rehabilitation programmes is warranted.
Elevations in levels of total, low-density lipoprotein, and non-high-density lipoprotein cholesterol; lower levels of high-density lipoprotein cholesterol; and, to a lesser extent, elevated ...triglyceride levels are associated with risk of cardiovascular disease in adults.
To update the 2007 US Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in children, adolescents, and young adults.
The USPSTF reviewed the evidence on screening for lipid disorders in children and adolescents 20 years or younger--1 review focused on screening for heterozygous familial hypercholesterolemia, and 1 review focused on screening for multifactorial dyslipidemia.
Evidence on the quantitative difference in diagnostic yield between universal and selective screening approaches, the effectiveness and harms of long-term treatment and the harms of screening, and the association between changes in intermediate outcomes and improvements in adult cardiovascular health outcomes are limited. Therefore, the USPSTF concludes that the balance of benefits and harms cannot be determined.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger. (I statement).
New US Preventive Services Task Force (USPSTF) recommendation on screening for autism spectrum disorder (ASD) in young children.
The USPSTF reviewed the evidence on the accuracy, benefits, and ...potential harms of brief, formal screening instruments for ASD administered during routine primary care visits and the benefits and potential harms of early behavioral treatment for young children identified with ASD through screening.
This recommendation applies to children aged 18 to 30 months who have not been diagnosed with ASD or developmental delay and for whom no concerns of ASD have been raised by parents, other caregivers, or health care professionals.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for ASD in young children for whom no concerns of ASD have been raised by their parents or a clinician. (I statement).
In 2014, 19,999 cases of syphilis were reported in the United States. Left untreated, syphilis can progress to late-stage disease in about 15% of persons who are infected. Late-stage syphilis can ...lead to development of inflammatory lesions throughout the body, which can lead to cardiovascular or organ dysfunction. Syphilis infection also increases the risk for acquiring or transmitting HIV infection.
To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for syphilis infection in nonpregnant adults. Screening for syphilis in pregnant women was updated in a separate recommendation statement in 2009 (A recommendation).
The USPSTF reviewed the evidence on screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents, including patients coinfected with other sexually transmitted infections (such as HIV).
The USPSTF found convincing evidence that screening for syphilis infection in asymptomatic, nonpregnant persons at increased risk for infection provides substantial benefit. Accurate screening tests are available to identify syphilis infection in populations at increased risk. Effective treatment with antibiotics can prevent progression to late-stage disease, with small associated harms, providing an overall substantial health benefit.
The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation).
Aim: To test the extent to which the vertical structure of tropical forests is determined by environment, forest structure or biogeographical history. Location: Pan-tropical. Methods: Using height ...and diameter data from 20,497 trees in 112 non-contiguous plots, asymptotic maximum height (H AM ) and height—diameter relationships were computed with nonlinear mixed effects (NLME) models to: (1) test for environmental and structural causes of differences among plots, and (2) test if there were continental differences once environment and structure were accounted for; persistence of differences may imply the importance of biogeography for vertical forest structure. NLME analyses for floristic subsets of data (only/excluding Fabaceae and only/excluding Dipterocarpaceae individuals) were used to examine whether family-level patterns revealed biogeographical explanations of cross-continental differences. Results: H AM and allometry were significantly different amongst continents. H AM was greatest in Asian forests (58.3 ± 7.5 m, 95% CI), followed by forests in Africa (45.1 ± 2.6 m), America (35.8 ± 6.0 m) and Australia (35.0 ± 7.4 m), and height—diameter relationships varied similarly; for a given diameter, stems were tallest in Asia, followed by Africa, America and Australia. Precipitation seasonality, basal area, stem density, solar radiation and wood density each explained some variation in allometry and H AM yet continental differences persisted even after these were accounted for. Analyses using floristic subsets showed that significant continental differences in H AM and allometry persisted in all cases. Main conclusions: Tree allometry and maximum height are altered by environmental conditions, forest structure and wood density. Yet, even after accounting for these, tropical forest architecture varies significantly from continent to continent. The greater stature of tropical forests in Asia is not directly determined by the dominance of the family Dipterocarpaceae, as on average non-dipterocarps are equally tall. We hypothesise that dominant large-statured families create conditions in which only tall species can compete, thus perpetuating a forest dominated by tall individuals from diverse families.
There is convincing evidence that breastfeeding provides substantial health benefits for children. However, nearly half of all US mothers who initially breastfeed stop doing so by 6 months, and there ...are significant disparities in breastfeeding rates among younger mothers and in disadvantaged communities.
To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on primary care interventions to promote breastfeeding.
The USPSTF reviewed the evidence on the effectiveness of interventions to support breastfeeding on breastfeeding initiation, duration, and exclusivity. The USPSTF also briefly reviewed the literature on the effects of these interventions on child and maternal health outcomes.
The USPSTF found adequate evidence that interventions to support breastfeeding, including professional support, peer support, and formal education, change behavior and that the harms of these interventions are no greater than small. The USPSTF concludes with moderate certainty that interventions to support breastfeeding have a moderate net benefit.
The USPSTF recommends providing interventions during pregnancy and after birth to support breastfeeding. (B recommendation).
The lymphatic system continues to gain importance in a range of conditions, and therefore, imaging of lymphatic vessels is becoming more widespread for research, diagnosis, and treatment. Fluorescent ...lymphatic imaging offers advantages over other methods in that it is affordable, has higher resolution, and does not require radiation exposure. However, because the lymphatic system is a one-way drainage system, the successful delivery of fluorescent tracers to lymphatic vessels represents a unique challenge. Each fluorescent tracer used for lymphatic imaging has distinct characteristics, including size, shape, charge, weight, conjugates, excitation/emission wavelength, stability, and quantum yield. These characteristics in combination with the properties of the target tissue affect the uptake of the dye into lymphatic vessels and the fluorescence quality. Here, we review the characteristics of visible wavelength and near-infrared fluorescent tracers used for
in vivo
lymphatic imaging and describe the various techniques used to specifically target them to lymphatic vessels for high-quality lymphatic imaging in both clinical and pre-clinical applications. We also discuss potential areas of future research to improve the lymphatic fluorescent tracer design.
Summary
Background
Regulated alteration of connexin expression has been shown to be integral to acute wound repair. Downregulation of the gap‐junction protein connexin 43 at the wound edge has been ...correlated with keratinocyte and fibroblast migration, while abnormal overexpression of connexin 43 significantly perturbs healing, as shown in the streptozotocin diabetic rodent impaired healing model.
Objectives
To examine the protein expression levels of connexin 43, in addition to connexins 26 and 30, in a variety of human chronic wounds.
Methods
Wound‐edge punch biopsies and a matched control from the arm were taken from a cohort of patients with venous leg, diabetic foot or pressure ulcers. Wound connexin expression in each patient was compared with that in a matched, nonwounded arm punch. Tissue was sectioned, stained and imaged by confocal microscopy using identical parameters per patient to permit quantification.
Results
Epidermal connexin 43, connexin 26 and connexin 30, and dermal connexin 43 were discovered to be strikingly upregulated in every ulcer from all three wound types, pointing to connexin upregulation as a common feature between chronic wounds.
Conclusions
This result supports efforts to target connexin 43 to promote cell migration and wound healing in chronic ulcers.
What's already known about this topic?
Connexin 43 (Cx43) protein levels are reduced at the wound edge, enabling migration of keratinocytes and fibroblasts to aid wound healing.
In wounded diabetic rats, Cx43 is elevated in the wound edge and healing is delayed.
In human diabetic epidermal wound edge, Cx43, Cx26 and Cx30 are detectable.
What does this study add?
We quantify the wound‐edge expression of Cx43, Cx26 and Cx30 in chronic venous, diabetic foot and pressure ulcers and show their tissue distribution.
Cx43 is massively upregulated in the epidermis and dermis.
Linked Comment: Martin, Br J Dermatol 2015; 173: 1123–24.
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