Frailty: A global measure of the multisystem impact of COPD

Chronic obstructive pulmonary disease (COPD) is a multisystem disease that resembles the accumulation of multiple impairments seen in aging. A comprehensive geriatric assessment (CGA) captures multisystem deficits, from which a frailty index (FI) can be derived. We hypothesized that patients with COPD would be frailer than a comparator group free from respiratory disease. In this cross-sectional analysis, the CGA questionnaire was completed and used to derive an FI in 520 patients diagnosed with COPD and 150 comparators. All subjects were assessed for lung function, body composition, 6-minute walking distance (6MWD), and handgrip strength. Patients completed validated questionnaires on health-related quality of life and respiratory symptoms. Patients and comparators were similar in age, gender, and body mass index, but patients had a greater mean ± SD FI 0.16 ± 0.08 than comparators 0.05 ± 0.03. In patients, a stepwise linear regression 6MWD (β = −0.43), number of comorbidities (β = −0.38), handgrip (β = −0.11), and number of exacerbations (β = 0.11) were predictors of frailty (all p < 0.01). This large study suggests patients with COPD are frailer than comparators. The FI derived from the CGA captures the deterioration of multiple systems in COPD and provides an overview of impairments, which may identify individuals at increased risk of morbidity and mortality in COPD

Eating dysfunction associated with oromandibular dystonia: clinical characteristics and treatment considerations

BACKGROUND: In oromandibular dystonia (OMD) abnormal repetitive contractions of masticatory, facial, and lingual muscles as well as the presence of orobuccolingual (OBL) dyskinesias may interfere with the appropriate performance of tasks such as chewing and swallowing leading to significant dysphagia and weight loss. We present here the clinical characteristics and treatment variables of a series of patients that developed an OMD-associated eating dysfunction. METHODS: We present a series of patients diagnosed and followed-up at the Movement Disorders Clinic of the Department of Neurology of University of Miami, Miller School of Medicine over a 10-year period. Patients were treated with botulinum toxin injections according to standard methods. RESULTS: Five out of 32 (15.6%) OMD patients experienced symptoms of eating dysfunction associated with OMD. Significant weight loss was reported in 3/5 patients (ranged for 13–15 lbs). Two patients regained the lost weight after treatment and one was lost to follow-up. Tetrabenazine in combination with other antidystonic medication and/or botulinum toxin injections provided substantial benefit to the patients with dysphagia caused by OMD. CONCLUSION: Dystonic eating dysfunction may occasionally complicate OMD leading to weight loss. Its adequate characterization at the time of history taking and clinical examination should be part of outcome measurements of the anti-dystonic treatment in clinical practice

Computing the vertices of tropical polyhedra using directed hypergraphs

We establish a characterization of the vertices of a tropical polyhedron defined as the intersection of finitely many half-spaces. We show that a point is a vertex if, and only if, a directed hypergraph, constructed from the subdifferentials of the active constraints at this point, admits a unique strongly connected component that is maximal with respect to the reachability relation (all the other strongly connected components have access to it). This property can be checked in almost linear-time. This allows us to develop a tropical analogue of the classical double description method, which computes a minimal internal representation (in terms of vertices) of a polyhedron defined externally (by half-spaces or hyperplanes). We provide theoretical worst case complexity bounds and report extensive experimental tests performed using the library TPLib, showing that this method outperforms the other existing approaches.Comment: 29 pages (A4), 10 figures, 1 table; v2: Improved algorithm in section 5 (using directed hypergraphs), detailed appendix; v3: major revision of the article (adding tropical hyperplanes, alternative method by arrangements, etc); v4: minor revisio

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Hypnotic analgesia reduces brain responses to pain seen in others.

Brain responses to pain experienced by oneself or seen in other people show consistent overlap in the pain processing network, particularly anterior insula, supporting the view that pain empathy partly relies on neural processes engaged by self-nociception. However, it remains unresolved whether changes in one's own pain sensation may affect empathic responding to others' pain. Here we show that inducing analgesia through hypnosis leads to decreased responses to both self and vicarious experience of pain. Activations in the right anterior insula and amygdala were markedly reduced when participants received painful thermal stimuli following hypnotic analgesia on their own hand, but also when they viewed pictures of others' hand in pain. Functional connectivity analysis indicated that this hypnotic modulation of pain responses was associated with differential recruitment of right prefrontal regions implicated in selective attention and inhibitory control. Our results provide novel support to the view that self-nociception is involved during empathy for pain, and demonstrate the possibility to use hypnotic procedures to modulate higher-level emotional and social processes

Anaerobic Carbon Monoxide Dehydrogenase Diversity in the Homoacetogenic Hindgut Microbial Communities of Lower Termites and the Wood Roach

Anaerobic carbon monoxide dehydrogenase (CODH) is a key enzyme in the Wood-Ljungdahl (acetyl-CoA) pathway for acetogenesis performed by homoacetogenic bacteria. Acetate generated by gut bacteria via the acetyl-CoA pathway provides considerable nutrition to wood-feeding dictyopteran insects making CODH important to the obligate mutualism occurring between termites and their hindgut microbiota. To investigate CODH diversity in insect gut communities, we developed the first degenerate primers designed to amplify cooS genes, which encode the catalytic (β) subunit of anaerobic CODH enzyme complexes. These primers target over 68 million combinations of potential forward and reverse cooS primer-binding sequences. We used the primers to identify cooS genes in bacterial isolates from the hindgut of a phylogenetically lower termite and to sample cooS diversity present in a variety of insect hindgut microbial communities including those of three phylogenetically-lower termites, Zootermopsis nevadensis, Reticulitermes hesperus, and Incisitermes minor, a wood-feeding cockroach, Cryptocercus punctulatus, and an omnivorous cockroach, Periplaneta americana. In total, we sequenced and analyzed 151 different cooS genes. These genes encode proteins that group within one of three highly divergent CODH phylogenetic clades. Each insect gut community contained CODH variants from all three of these clades. The patterns of CODH diversity in these communities likely reflect differences in enzyme or physiological function, and suggest that a diversity of microbial species participate in homoacetogenesis in these communities

Characteristics of transposable element exonization within human and mouse

Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs) revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. SNP density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on RNA editing for their exonization. These results shed light on TE fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure