Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

<p>Abstract</p> <p>Background</p> <p>Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.</p> <p>Methods</p> <p>Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂= 80%) and hyperoxic (FiO₂= 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.</p> <p>Results</p> <p>Hypoxia enhanced hyperpnoea-induced P_di,twand P_ga,twreductions both immediately after hyperpnoea (P_di,tw: normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw: normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all <it>P </it>< 0.05) and after 30 min of recovery (P_di,tw: normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw: normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all <it>P </it>< 0.05). No significant difference in P_di,twor P_ga,twreductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.</p> <p>Conclusions</p> <p>These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂transport as during exercise in altitude or in hypoxemic patients.</p

Transmission of Chronic Wasting Disease Identifies a Prion Strain Causing Cachexia and Heart Infection in Hamsters

Chronic wasting disease (CWD) is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrPSc, prion infection of the central and peripheral neuroendocrine system, and PrPSc deposition in cardiac muscle. There was also prominent PrPSc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the ‘wasting’ or WST strain of hamster CWD

Low Dynamics, High Longevity and Persistence of Sessile Structural Species Dwelling on Mediterranean Coralligenous Outcrops

There is still limited understanding of the processes underlying benthic species dynamics in marine coastal habitats, which are of disproportionate importance in terms of productivity and biodiversity. The life-history traits of long-lived benthic species in these habitats are particularly poorly documented. In this study, we assessed decadal patterns of population dynamics for ten sponge and anthozoan species that play key structural roles in coralligenous outcrops (∼25 m depth) in two areas of the NW Mediterranean Sea. This study was based on examination of a unique long-term photographic series, which allowed analysis of population dynamics over extensive spatial and time spans for the very first time. Specifically, 671 individuals were censused annually over periods of 25-, 15-, and 5-years. This long-term study quantitatively revealed a common life-history pattern among the ten studied species, despite the fact they present different growth forms. Low mortality rates (3.4% yr−1 for all species combined) and infrequent recruitment events (mean value of 3.1±0.5 SE recruits yr−1) provided only a very small fraction of the new colonies required to maintain population sizes. Overall, annual mortality and recruitment rates did not differ significantly among years; however, some species displayed important mortality events and recruitment pulses, indicating variability among species. Based on the growth rates of these 10 species, we projected their longevity and, obtained a mean estimated age of 25–200 years. Finally, the low to moderate turnover rates (mean value 0.80% yr−1) observed among the coralligenous species were in agreement with their low dynamics and persistence. These results offer solid baseline data and reveal that these habitats are among the most vulnerable to the current increases of anthropogenic disturbances

There's No Place Like Home: Crown-of-Thorns Outbreaks in the Central Pacific Are Regionally Derived and Independent Events

One of the most significant biological disturbances on a tropical coral reef is a population outbreak of the fecund, corallivorous crown-of-thorns sea star, Acanthaster planci. Although the factors that trigger an initial outbreak may vary, successive outbreaks within and across regions are assumed to spread via the planktonic larvae released from a primary outbreak. This secondary outbreak hypothesis is predominantly based on the high dispersal potential of A. planci and the assertion that outbreak populations (a rogue subset of the larger population) are genetically more similar to each other than they are to low-density non-outbreak populations. Here we use molecular techniques to evaluate the spatial scale at which A. planci outbreaks can propagate via larval dispersal in the central Pacific Ocean by inferring the location and severity of gene flow restrictions from the analysis of mtDNA control region sequence (656 specimens, 17 non-outbreak and six outbreak locations, six archipelagos, and three regions). Substantial regional, archipelagic, and subarchipelagic-scale genetic structuring of A. planci populations indicate that larvae rarely realize their dispersal potential and outbreaks in the central Pacific do not spread across the expanses of open ocean. On a finer scale, genetic partitioning was detected within two of three islands with multiple sampling sites. The finest spatial structure was detected at Pearl & Hermes Atoll, between the lagoon and forereef habitats (<10 km). Despite using a genetic marker capable of revealing subtle partitioning, we found no evidence that outbreaks were a rogue genetic subset of a greater population. Overall, outbreaks that occur at similar times across population partitions are genetically independent and likely due to nutrient inputs and similar climatic and ecological conditions that conspire to fuel plankton blooms

Benign external hydrocephalus: a review, with emphasis on management

Benign external hydrocephalus in infants, characterized by macrocephaly and typical neuroimaging findings, is considered as a self-limiting condition and is therefore rarely treated. This review concerns all aspects of this condition: etiology, neuroimaging, symptoms and clinical findings, treatment, and outcome, with emphasis on management. The review is based on a systematic search in the Pubmed and Web of Science databases. The search covered various forms of hydrocephalus, extracerebral fluid, and macrocephaly. Studies reporting small children with idiopathic external hydrocephalus were included, mostly focusing on the studies reporting a long-term outcome. A total of 147 studies are included, the majority however with a limited methodological quality. Several theories regarding pathophysiology and various symptoms, signs, and clinical findings underscore the heterogeneity of the condition. Neuroimaging is important in the differentiation between external hydrocephalus and similar conditions. A transient delay of psychomotor development is commonly seen during childhood. A long-term outcome is scarcely reported, and the results are varying. Although most children with external hydrocephalus seem to do well both initially and in the long term, a substantial number of patients show temporary or permanent psychomotor delay. To verify that this truly is a benign condition, we suggest that future research on external hydrocephalus should focus on the long-term effects of surgical treatment as opposed to conservative management

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis. RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives. CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.)