ResearchPad - short-reports https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Thalamic, cortical, and amygdala involvement in the processing of a natural sound cue of danger]]> https://www.researchpad.co/article/elastic_article_7872 When others stop and silence ensues, animals respond as if threatened. This study highlights the brain areas involved in listening to the dangerous silence.

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<![CDATA[Sonographic measurements of normal C5‐C8 nerve roots in children]]> https://www.researchpad.co/article/elastic_article_6788 The aim of this study was to use ultrasound to measure the cervical nerve roots in normal children to determine normal reference values.MethodsA total of 441 children of different ages at the Children's Hospital of Chongqing Medical University were examined by ultrasound. The diameter, circumference, and cross‐sectional area of the nerve roots were measured.ResultsUltrasonographic measurements were consistent with the ranking C5 < C6 < C7. The C8 nerve root was thicker than C7 in 60% of the participants. The nerve root measurements increased with increasing age, height, weight, and body surface area.DiscussionNormal reference ranges of the cervical nerve roots in children of different ages were established, and can serve as the basis for measurement in future studies. ]]> <![CDATA[Infected teratoma of lower posterior mediastinum in a six-year-old boy]]> https://www.researchpad.co/article/Nd8de182f-842b-4caf-acbe-4a1d8811a8a4

A six-year old boy presented with prolonged unexplained fever caused by an infected teratoma of the lower posterior mediastinum. Modern imaging, combining ultrasonography with computed tomography, enabled the correct diagnosis of topography, extension and nature of this rare lesion to be made and explained the clinical features. Follow-up CT showed regression of the abscess after antibiotics thus permitting elective surgery.

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<![CDATA[Patterns of detectable viral load in a cohort of HIV‐positive adolescents on antiretroviral therapy in South Africa]]> https://www.researchpad.co/article/N8f88141f-1b3b-4fe0-9868-94246a756af0

Abstract

Introduction

Despite improved treatment and access to care, adolescent AIDS deaths are decreasing more slowly than in any other age group. There is lack of longitudinal data around adolescent adherence and the dynamics of viraemia over time. We aimed to describe patterns of detectable viral load (VL) in a cohort of adolescents attending an ARV clinic in Cape Town, South Africa.

Methods

We conducted a retrospective cohort study of all patients on antiretroviral therapy aged 10 to 19 years.

Participants were included if they underwent at least two VL measurements and remained in care at the Groote Schuur Hospital HIV Clinic for at least 24 months between 2002 and 2016.

The primary outcome was two consecutive HIV VL >100 copies/mL, in line with the lower limit of detection of assays in use over the follow‐up period.

Results and discussion

Of the 482 screened participants, 327 met inclusion criteria. Most participants had perinatally acquired HIV (n = 314; 96%), and 170 (52%) were males. Overall, there were 203 episodes of confirmed detectable VL involving 159 (49% (95% CI 43% to 54%)) participants during the follow‐up period. Six participants had genotyped resistance to protease inhibitors. Four of these never suppressed, while two suppressed on salvage regimens.

Total follow‐up time was 1723 person years (PY), of which 880 (51%) were contributed by the 159 participants who experienced detectable VL. Overall time with detectable VL was 370 PY. This comprised 22% of total follow‐up time, and 42% of the follow‐up time contributed by those who experienced detectable VL.

The rate of detectable VL was 11.8 (95% CI 10.3 to 13.5) episodes per 100 PY. The risk increased by 24% for each year of increasing age (Relative Risk 1.24 (95% CI 1.17 to 1.31); p < 0.0001).

There was no sex difference with respect to duration (p = 0.4), prevalence (p = 0.46) and rate (p = 0.608) of detectable VL.

Conclusions

Clinicians need to be alert to the high prevalence of detectable VL during adolescence so as to pre‐empt it and act swiftly once it is diagnosed. This study helps to highlight the risk of detectable VL that is associated with increase in age as well the high proportion of time that poorly adherent adolescents spend in this state.

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<![CDATA[Decreasing time to antiretroviral therapy initiation after HIV diagnosis in a clinic‐based observational cohort study in four African countries]]> https://www.researchpad.co/article/N7dc668f2-3362-4909-ada2-509349864eb5

Abstract

Introduction

World Health Organization (WHO) guidelines have shifted over time to recommend earlier initiation of antiretroviral therapy (ART) and now encourage ART initiation on the day of HIV diagnosis, if possible. However, barriers to ART access may delay initiation in resource‐limited settings. We characterized temporal trends and other factors influencing the interval between HIV diagnosis and ART initiation among participants enrolled in a clinic‐based cohort across four African countries.

Methods

The African Cohort Study enrols adults engaged in care at 12 sites in Uganda, Kenya, Tanzania and Nigeria. Participants provide a medical history, complete a physical examination and undergo laboratory assessments every six months. Participants with recorded dates of HIV diagnosis were categorized by WHO guideline era (<2006, 2006 to 2009, 2010 to 2012, 2013 to 2015, ≥2016) at the time of diagnosis. Cox proportional hazard modelling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for time to ART initiation.

Results and discussion

From January 2013 to September 2019, a total of 2888 adults living with HIV enrolled with known diagnosis dates. Median time to ART initiation decreased from 22.0 months (interquartile range (IQR) 4.0 to 77.3) among participants diagnosed prior to 2006 to 0.5 months (IQR 0.2 to 1.8) among those diagnosed in 2016 and later. Comparing those same periods, CD4 nadir increased from a median of 166 cells/mm3 (IQR: 81 to 286) to 298 cells/mm3 (IQR: 151 to 501). In the final adjusted model, participants diagnosed in each subsequent WHO guideline era had increased rates of ART initiation compared to those diagnosed before 2006. CD4 nadir ≥500 cells/mm3 was independently associated with a lower rate of ART initiation as compared to CD4 nadir <200 cells/mm3 (HR: 0.32; 95% CI: 0.28 to 0.37). Age >50 years at diagnosis was independently associated with shorter time to ART initiation as compared to 18 to 29 years (HR: 1.38; 95% CI: 1.19 to 1.61).

Conclusions

Consistent with changing guidelines, the interval between diagnosis and ART initiation has decreased over time. Still, many adults living with HIV initiated treatment with low CD4, highlighting the need to diagnose HIV earlier while improving access to immediate ART after diagnosis.

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<![CDATA[Infantile Onset of Spinocerebellar Ataxia Type 5 (SCA-5) in a 6 Month Old with Ataxic Cerebral Palsy]]> https://www.researchpad.co/article/N9c660c6a-4d1f-4368-8c0a-f755b72d2d48

Spinocerebellar ataxia type 5 (SCA-5) is a predominantly slowly progressive adult onset ataxia. We describe a child with a presentation of ataxic cerebral palsy (CP) and developmental delay at 6 months of age. Genetic testing confirmed a c.812C>T p.(Thr271Ile) mutation within the SPTBN2 gene. Seven previous cases of infantile onset SCA-5 are reported in the literature, four of which had a CP presentation. Early onset of SCA-5 presents with ataxic CP and is a rare cause of cerebral palsy.

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<![CDATA[Pharmacokinetics of intravenous and inhaled salbutamol and tobramycin: An exploratory study to investigate the potential of exhaled breath condensate as a matrix for pharmacokinetic analysis]]> https://www.researchpad.co/article/N2701b20f-be2c-460b-a729-2c6b8696106a

Concentrations of drugs acting in the lungs are difficult to measure, resulting in relatively unknown local pharmacokinetics. The aim of this study is to assess the potential of exhaled breath condensate (EBC) as a matrix for pharmacokinetic analysis of inhaled and intravenous medication. A 4‐way crossover study was conducted in 12 volunteers with tobramycin and salbutamol intravenously and via inhalation. EBC and plasma samples were collected postdose and analysed for drug concentrations. Sample dilution, calculated using urea concentrations, was used to estimate the epithelial lining fluid concentration. Salbutamol and tobramycin were largely undetectable in EBC after intravenous administration and were detectable after inhaled administration in all subjects in 50.8 and 51.5% of EBC samples, respectively. Correction of EBC concentrations for sample dilution did not explain the high variability. This high variability of EBC drug concentrations seems to preclude EBC as a matrix for pharmacokinetic analysis of tobramycin and salbutamol.

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<![CDATA[High HIV prevalence and associated risk factors among transgender women in China: a cross‐sectional survey]]> https://www.researchpad.co/article/N49e8cbe4-469c-467b-a63c-041569fc09ad

Abstract

Introduction

Transgender women may face the highest prevalence of HIV of any population, experiencing a disproportionate burden of disease frequently confirmed in surveys throughout the developing and developed world. However, few studies have been conducted specifically for transgender women in China. This study aimed to measure HIV prevalence and explore risk factors for infection in a diverse sample of Chinese transgender women to help advocate for prevention and care interventions for this population.

Methods

From July 2018 to May 2019, we adapted a respondent‐driven sampling (RDS) approach to recruit a diverse sample of 250 transgender women through chains of peer referrals in two cities of eastern China, Nanjing and Suzhou. Eligible participants (i.e. 18 years of age or older, living in Jiangsu province and assigned male sex at birth but currently self‐identified as a gender different from male) completed a self‐administered questionnaire on a mobile phone to collect demographic characteristics and risk behaviours and underwent HIV testing.

Results and discussion

The survey sample was young (82% under age 35 years), with 28.8% having a university degree, 39.2% reporting work at entertainment venues, 47.6% ever having taken hormones and 6.4% being diagnosed with an STI in the last year. One in five (20.8%) reported having engaged in sex work. HIV prevalence was 14.8% (95% CI 10.6 to 19.8), with 75.6% of those testing HIV positive reporting they were already aware of their serostatus. In multivariate analysis, HIV prevalence was significantly higher among transgender women above the age of 24 years, those who work at entertainment venues, who never have taken hormones, and who had been diagnosed with an STI in the last year.

Conclusions

The prevalence of HIV among transgender women in our study, at 14.8%, is among the highest detected in any population in eastern China. Chinese transgender women may therefore follow the disparity in the burden of HIV noted worldwide. Data support policies to prioritize transgender women for HIV testing outreach, for in‐depth research to better understand the specific drivers of infection in this population, and for trans‐friendly HIV care and prevention programmes to address their specific needs.

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<![CDATA[Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real‐life study in Brazil]]> https://www.researchpad.co/article/N46254f2e-1eac-438d-b7a3-062b27088cd1

Abstract

Introduction

The relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements at pre‐specified timepoints after ART onset. However, data from real‐life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil.

Methods

Retrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir‐boosted atazanavir (regimen 3)).

Results and Discussion

We included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 (p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12‐month cumulative viraemia. The model predicted a 45‐unit increase in log10 copy‐days/mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70‐unit increase in log10 copy‐days/mL cumulative viraemia for regimen 3 as compared with regimen 1 (95%CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir‐lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders.

Conclusions

Our findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.

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<![CDATA[Microglia exit the CNS in spinal root avulsion]]> https://www.researchpad.co/article/5c79a3e5d5eed0c4841d1bf2

Microglia are central nervous system (CNS)-resident cells. Their ability to migrate outside of the CNS, however, is not understood. Using time-lapse imaging in an obstetrical brachial plexus injury (OBPI) model, we show that microglia squeeze through the spinal boundary and emigrate to peripheral spinal roots. Although both macrophages and microglia respond, microglia are the debris-clearing cell. Once outside the CNS, microglia re-enter the spinal cord in an altered state. These peripheral nervous system (PNS)-experienced microglia can travel to distal CNS areas from the injury site, including the brain, with debris. This emigration is balanced by two mechanisms—induced emigration via N-methyl-D-aspartate receptor (NMDA) dependence and restriction via contact-dependent cellular repulsion with macrophages. These discoveries open the possibility that microglia can migrate outside of their textbook-defined regions in disease states.

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<![CDATA[A polyploid admixed origin of beer yeasts derived from European and Asian wine populations]]> https://www.researchpad.co/article/5c88240dd5eed0c48463962a

Strains of Saccharomyces cerevisiae used to make beer, bread, and wine are genetically and phenotypically distinct from wild populations associated with trees. The origins of these domesticated populations are not always clear; human-associated migration and admixture with wild populations have had a strong impact on S. cerevisiae population structure. We examined the population genetic history of beer strains and found that ale strains and the S. cerevisiae portion of allotetraploid lager strains were derived from admixture between populations closely related to European grape wine strains and Asian rice wine strains. Similar to both lager and baking strains, ale strains are polyploid, providing them with a passive means of remaining isolated from other populations and providing us with a living relic of their ancestral hybridization. To reconstruct their polyploid origin, we phased the genomes of two ale strains and found ale haplotypes to both be recombinants between European and Asian alleles and to also contain novel alleles derived from extinct or as yet uncharacterized populations. We conclude that modern beer strains are the product of a historical melting pot of fermentation technology.

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<![CDATA[A season for all things: Phenological imprints in Wikipedia usage and their relevance to conservation]]> https://www.researchpad.co/article/5c882408d5eed0c4846395ce

Phenology plays an important role in many human–nature interactions, but these seasonal patterns are often overlooked in conservation. Here, we provide the first broad exploration of seasonal patterns of interest in nature across many species and cultures. Using data from Wikipedia, a large online encyclopedia, we analyzed 2.33 billion pageviews to articles for 31,751 species across 245 languages. We show that seasonality plays an important role in how and when people interact with plants and animals online. In total, over 25% of species in our data set exhibited a seasonal pattern in at least one of their language-edition pages, and seasonality is significantly more prevalent in pages for plants and animals than it is in a random selection of Wikipedia articles. Pageview seasonality varies across taxonomic clades in ways that reflect observable patterns in phenology, with groups such as insects and flowering plants having higher seasonality than mammals. Differences between Wikipedia language editions are significant; pages in languages spoken at higher latitudes exhibit greater seasonality overall, and species seldom show the same pattern across multiple language editions. These results have relevance to conservation policy formulation and to improving our understanding of what drives human interest in biodiversity.

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<![CDATA[Pathogen diversity drives the evolution of generalist MHC-II alleles in human populations]]> https://www.researchpad.co/article/5c5ca310d5eed0c48441f094

Central players of the adaptive immune system are the groups of proteins encoded in the major histocompatibility complex (MHC), which shape the immune response against pathogens and tolerance to self-peptides. The corresponding genomic region is of particular interest, as it harbors more disease associations than any other region in the human genome, including associations with infectious diseases, autoimmune disorders, cancers, and neuropsychiatric diseases. Certain MHC molecules can bind to a much wider range of epitopes than others, but the functional implication of such an elevated epitope-binding repertoire has remained largely unclear. It has been suggested that by recognizing more peptide segments, such promiscuous MHC molecules promote immune response against a broader range of pathogens. If so, the geographical distribution of MHC promiscuity level should be shaped by pathogen diversity. Three lines of evidence support the hypothesis. First, we found that in pathogen-rich geographical regions, humans are more likely to carry highly promiscuous MHC class II DRB1 alleles. Second, the switch between specialist and generalist antigen presentation has occurred repeatedly and in a rapid manner during human evolution. Third, molecular positions that define promiscuity level of MHC class II molecules are especially diverse and are under positive selection in human populations. Taken together, our work indicates that pathogen load maintains generalist adaptive immune recognition, with implications for medical genetics and epidemiology.

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<![CDATA[Heterochromatin delays CRISPR-Cas9 mutagenesis but does not influence the outcome of mutagenic DNA repair]]> https://www.researchpad.co/article/5c1ab83fd5eed0c48402748f

Genome editing occurs in the context of chromatin, which is heterogeneous in structure and function across the genome. Chromatin heterogeneity is thought to affect genome editing efficiency, but this has been challenging to quantify due to the presence of confounding variables. Here, we develop a method that exploits the allele-specific chromatin status of imprinted genes in order to address this problem in cycling mouse embryonic stem cells (mESCs). Because maternal and paternal alleles of imprinted genes have identical DNA sequence and are situated in the same nucleus, allele-specific differences in the frequency and spectrum of mutations induced by CRISPR-Cas9 can be unequivocally attributed to epigenetic mechanisms. We found that heterochromatin can impede mutagenesis, but to a degree that depends on other key experimental parameters. Mutagenesis was impeded by up to 7-fold when Cas9 exposure was brief and when intracellular Cas9 expression was low. In contrast, the outcome of mutagenic DNA repair was unaffected by chromatin state, with similar efficiencies of homology-directed repair (HDR) and deletion spectra on maternal and paternal chromosomes. Combined, our data show that heterochromatin imposes a permeable barrier that influences the kinetics, but not the endpoint, of CRISPR-Cas9 genome editing and suggest that therapeutic applications involving low-level Cas9 exposure will be particularly affected by chromatin status.

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<![CDATA[Errors as a primary cause of late-life mortality deceleration and plateaus]]> https://www.researchpad.co/article/5c254543d5eed0c48442c3c0

Several organisms, including humans, display a deceleration in mortality rates at advanced ages. This mortality deceleration is sufficiently rapid to allow late-life mortality to plateau in old age in several species, causing the apparent cessation of biological ageing. Here, it is shown that late-life mortality deceleration (LLMD) and late-life plateaus are caused by common demographic errors. Age estimation and cohort blending errors introduced at rates below 1 in 10,000 are sufficient to cause LLMD and plateaus. In humans, observed error rates of birth and death registration predict the magnitude of LLMD. Correction for these sources of demographic error using a mixed linear model eliminates LLMD and late-life mortality plateaus (LLMPs) without recourse to biological or evolutionary models. These results suggest models developed to explain LLMD have been fitted to an error distribution, that ageing does not slow or stop during old age in humans, and that there is a finite limit to human longevity.

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<![CDATA[Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions]]> https://www.researchpad.co/article/5b60363a463d7e4090b7ce28

Bones at different anatomical locations vary dramatically in size. For example, human femurs are 20-fold longer than the phalanges in the fingers and toes. The mechanisms responsible for these size differences are poorly understood. Bone elongation occurs at the growth plates and advances rapidly in early life but then progressively slows due to a developmental program termed “growth plate senescence.” This developmental program includes declines in cell proliferation and hypertrophy, depletion of cells in all growth plate zones, and extensive underlying changes in the expression of growth-regulating genes. Here, we show evidence that these functional, structural, and molecular senescent changes occur earlier in the growth plates of smaller bones (metacarpals, phalanges) than in the growth plates of larger bones (femurs, tibias) and that this differential aging contributes to the disparities in bone length. We also show evidence that the molecular mechanisms that underlie the differential aging between different bones involve modulation of critical paracrine regulatory pathways, including insulin-like growth factor (Igf), bone morphogenetic protein (Bmp), and Wingless and Int-1 (Wnt) signaling. Taken together, the findings reveal that the striking disparities in the lengths of different bones, which characterize normal mammalian skeletal proportions, is achieved in part by modulating the progression of growth plate senescence.

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<![CDATA[Structure of the herpes simplex virus portal-vertex]]> https://www.researchpad.co/article/5b49ab6f463d7e11e6cdb2e9

Herpesviruses include many important human pathogens such as herpes simplex virus, cytomegalovirus, varicella-zoster virus, and the oncogenic Epstein–Barr virus and Kaposi sarcoma–associated herpesvirus. Herpes virions contain a large icosahedral capsid that has a portal at a unique 5-fold vertex, similar to that seen in the tailed bacteriophages. The portal is a molecular motor through which the viral genome enters the capsid during virion morphogenesis. The genome also exits the capsid through the portal-vertex when it is injected through the nuclear pore into the nucleus of a new host cell to initiate infection. Structural investigations of the herpesvirus portal-vertex have proven challenging, owing to the small size of the tail-like portal-vertex–associated tegument (PVAT) and the presence of the tegument layer that lays between the nucleocapsid and the viral envelope, obscuring the view of the portal-vertex. Here, we show the structure of the herpes simplex virus portal-vertex at subnanometer resolution, solved by electron cryomicroscopy (cryoEM) and single-particle 3D reconstruction. This led to a number of new discoveries, including the presence of two previously unknown portal-associated structures that occupy the sites normally taken by the penton and the Ta triplex. Our data revealed that the PVAT is composed of 10 copies of the C-terminal domain of pUL25, which are uniquely arranged as two tiers of star-shaped density. Our 3D reconstruction of the portal-vertex also shows that one end of the viral genome extends outside the portal in the manner described for some bacteriophages but not previously seen in any eukaryote viruses. Finally, we show that the viral genome is consistently packed in a highly ordered left-handed spool to form concentric shells of DNA. Our data provide new insights into the structure of a molecular machine critical to the biology of an important class of human pathogens.

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<![CDATA[A sensory-motor neuron type mediates proprioceptive coordination of steering in C. elegans via two TRPC channels]]> https://www.researchpad.co/article/5b28b93c463d7e146ff345d4

Animal locomotion is mediated by a sensory system referred to as proprioception. Defects in the proprioceptive coordination of locomotion result in uncontrolled and inefficient movements. However, the molecular mechanisms underlying proprioception are not fully understood. Here, we identify two transient receptor potential cation (TRPC) channels, trp-1 and trp-2, as necessary and sufficient for proprioceptive responses in C. elegans head steering locomotion. Both channels are expressed in the SMDD neurons, which are required and sufficient for head bending, and mediate coordinated head steering by sensing mechanical stretches due to the contraction of head muscle and orchestrating dorsal head muscle contractions. Moreover, the SMDD neurons play dual roles to sense muscle stretch as well as to control muscle contractions. These results demonstrate that distinct locomotion patterns require dynamic and homeostatic modulation of feedback signals between neurons and muscles.

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<![CDATA[Receptors of intermediates of carbohydrate metabolism, GPR91 and GPR99, mediate axon growth]]> https://www.researchpad.co/article/5b07d0e7463d7e0d4a37a6ed

During the development of the visual system, high levels of energy are expended propelling axons from the retina to the brain. However, the role of intermediates of carbohydrate metabolism in the development of the visual system has been overlooked. Here, we report that the carbohydrate metabolites succinate and α-ketoglutarate (α-KG) and their respective receptor—GPR91 and GPR99—are involved in modulating retinal ganglion cell (RGC) projections toward the thalamus during visual system development. Using ex vivo and in vivo approaches, combined with pharmacological and genetic analyses, we revealed that GPR91 and GPR99 are expressed on axons of developing RGCs and have complementary roles during RGC axon growth in an extracellular signal–regulated kinases 1 and 2 (ERK1/2)-dependent manner. However, they have no effects on axon guidance. These findings suggest an important role for these receptors during the establishment of the visual system and provide a foundational link between carbohydrate metabolism and axon growth.

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<![CDATA[Potentially fatal new trend in performance enhancement: a cautionary note on nitrite]]> https://www.researchpad.co/article/5989da8aab0ee8fa60b9d93f

Background

Considerable interest has been shown by athletes and scientists in the potential for nitric oxide and associated vasodilators to enhance performance. This study aims to explore potential misuse of vasodilators by the athletes, and to highlight the growing concern over these agents.

Methods

Retrospective analyses of anonymous inquiries recorded in the Drug Information Database™ (DID™) between January 2006 and June 2008 (inclusive). In this 30-month period, the DID™ recorded 198,023 inquiries, of which 118,724 were UK Licensed Pharmaceutical products with a further 79,299 inquiries made for substance not found in the database.

Results

Phosphodiesterase type 5 (PDE-5) inhibitors, dominated by Viagra®, ranked 16th among the substance groups. The proportion of the inquiries made regarding PDE-5 inhibitors, especially in comparison to antibiotics, painkillers or alcohol, appears to be above the level that would normally be expected from medical need. No significant change in the months leading up to the Beijing Olympics was observed. On the contrary, the Nitric/Nitrate group showed a notable increase between 2006-2007 and 2008, suggesting a potential increase in interest in using nitric oxide among athletes.

Conclusions

With patents recently filed for the use of agents containing sodium nitrite/nitrate to enhance blood flow for performance enhancement in sport, coupled with anecdotal evidence from internet athlete forums and media, there is a concern that athletes may endanger their health by using vasodilators to enhance athletic performance. PDE-5 inhibitors or chemicals in the nitrate/nitrate group are currently not prohibited or tested for by the doping control agencies but some are highly dangerous to health and can lead to cardiovascular collapse, coma and death. Its promotion among athletes as a performance enhancing supplement is ethically and medically questionable.

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