Adult Prg4+ progenitors repair long-term articular cartilage wounds in vivo.

The identity and origin of the stem/progenitor cells for adult joint cartilage repair remain unknown, impeding therapeutic development. Simulating the common therapeutic modality for cartilage repair in humans, i.e., full-thickness microfracture joint surgery, we combined the mouse full-thickness injury model with lineage tracing and identified a distinct skeletal progenitor cell type enabling long-term (beyond 7 days after injury) articular cartilage repair in vivo. Deriving from a population with active Prg4 expression in adulthood while lacking aggrecan expression, these progenitors proliferate, differentiate to express aggrecan and type II collagen, and predominate in long-term articular cartilage wounds, where they represent the principal repair progenitors in situ under native repair conditions without cellular transplantation. They originate outside the adult bone marrow or superficial zone articular cartilage. These findings have implications for skeletal biology and regenerative medicine for joint injury repair.

Varenicline for cognitive impairment in people with schizophrenia: systematic review and meta-analysis.

BACKGROUND: People with schizophrenia frequently have cognitive dysfunction, which does not respond to pharmacological interventions. Varenicline has been identified as a potential treatment option for nicotinic receptor dysfunction with a potential to treat cognitive impairment in schizophrenia. METHODS: We conducted a systematic review of Pubmed, Embase, Psycinfo, CINAHL and the Cochrane Schizophrenia Trial Registry for randomised controlled trials of varenicline in people with schizophrenia for cognitive dysfunction. We excluded trials among people with dementia. We then undertook a meta-analysis with the primary outcome of difference in change of cognitive measures between varenicline and placebo as well as secondary outcomes of difference in rates of adverse events. We conducted a sensitivity analysis on smoking status and study duration. RESULTS: We included four papers in the meta-analysis (n = 339). Varenicline was not superior to placebo for overall cognition (SMD = -0.022, 95% CI -0.154-0.110; Z = -0.333; p = 0.739), attention (SMD = -0.047, 95% CI -0.199-0.104; Z = -0.613; p = 0.540), executive function (SMD = -0.060, 95% CI -0.469-0.348; Z =- 0.290; p = 0.772) or processing speed (SMD = 0.038, 95% CI -0.232-0.308; Z = 0.279; p = 0.780). There was no difference in psychotic symptoms, but varenicline was associated with higher rates of nausea. Sensitivity analyses for smoking status and study duration did not alter the results. CONCLUSION: Within the present literature, varenicline does not appear to be a useful target compound for improving cognitive impairment in schizophrenia. Based on these results, a trial would need over 2500 participants to be powered to show statistically significant findings.

Backbone 1H, 13C, and 15N resonance assignments of deubiquitinase A in non-phosphorylated and phosphorylated forms.

Ubiquitination is one of the most prevalent forms of post-translational modifications that are important for regulating many cellular processes in eukaryotes. Deubiquitinases are proteases that hydrolyze the isopeptide or peptide bonds formed between ubiquitin and the target proteins or within a polyubiquitin chain. Deubiquitinase A (DUBA) is a deubiquitinase known to be a negative regulator of innate immune responses in humans by suppressing production of type I interferons (INF-I). Excess INF-I production has been associated with autoimmune diseases. Phosphorylation of a single serine residue at position 177 is essential for the protease activity of DUBA. The structural and mechanistic basis of DUBA activation by phosphorylation and substrate specificity is not well understood. Here, we report the backbone resonance assignments of the isoform 2 of DUBA in both non-phosphorylated and phosphorylated forms. The reported assignments form the basis for future NMR studies on the structural and dynamical properties of both active and inactive forms of DUBA.

Compliance of metabolic monitoring at rehabilitation facilities.

OBJECTIVES: To examine compliance with routine metabolic monitoring at four rehabilitation facilities within the Metro South Addiction and Mental Health Services in Queensland. METHODS: A retrospective chart audit was undertaken on 63 residents of rehabilitation facilities with electronic health records from 1 October 2014 to 30 March 2015. RESULTS: Evidence of any metabolic monitoring was recorded for 87% of residents. Compliance rates differed for monitoring waist circumference (97%), blood pressure (97%), high-density lipoprotein (79%), triglycerides (81%) and plasma glucose (83%). Evidence of communication with residents and primary healthcare providers were each found in 41% of the sample. CONCLUSIONS: In current clinical practice, metabolic monitoring is high for residents of rehabilitation facilities in Queensland with serious mental illness. However, many residents do not receive adequate communication regarding their results and, disturbingly, results are not forwarded to their primary healthcare providers. This can result in people not receiving treatment for modifiable factors of metabolic syndrome.

NC10 bacteria in marine oxygen minimum zones.

Bacteria of the NC10 phylum link anaerobic methane oxidation to nitrite denitrification through a unique O2-producing intra-aerobic methanotrophy pathway. A niche for NC10 in the pelagic ocean has not been confirmed. We show that NC10 bacteria are present and transcriptionally active in oceanic oxygen minimum zones (OMZs) off northern Mexico and Costa Rica. NC10 16S rRNA genes were detected at all sites, peaking in abundance in the anoxic zone with elevated nitrite and methane concentrations. Phylogenetic analysis of particulate methane monooxygenase genes further confirmed the presence of NC10. rRNA and mRNA transcripts assignable to NC10 peaked within the OMZ and included genes of the putative nitrite-dependent intra-aerobic pathway, with high representation of transcripts containing the unique motif structure of the nitric oxide (NO) reductase of NC10 bacteria, hypothesized to participate in O2-producing NO dismutation. These findings confirm pelagic OMZs as a niche for NC10, suggesting a role for this group in OMZ nitrogen, methane and oxygen cycling.

Cold agglutinin activity in 2 dogs.

A 5-year-old neutered male Mastiff and an 8-year-old spayed female Labrador Retriever were presented to the University of Minnesota Veterinary Medical Center. The Mastiff was presented for evaluation of lameness and pyoderma one month prior in Missouri, where he tested positive for Ehrlichia canis by serum ELISA test, treated with doxycycline. PCR for Ehrlichia sp, Anaplasma sp, Babesia sp, and Bartonella sp, and PCR for antigen receptor rearrangement were negative, serum protein electrophoresis (SPE) revealed polyclonal gammopathy, and mildly reactive lymphoid cells were seen cytologically. The Labrador presented with a proliferative rostral mandibular gingival mass and lipomas for further presurgical evaluation of cold agglutinin activity documented by a commercial laboratory 2 years earlier prior to removal of a grade II mast cell tumor. This dog had a negative SNAP4Dx, normal SPE, and persistently increased serum ALP activity and polyuria/polydipsia suggestive for hyperadrenocorticism. Both dogs had markedly agglutinated RBC in the EDTA samples that dispersed with warming, and normal plasma color. Cold agglutinin activity was demonstrated by direct saline agglutination testing using whole blood and washed erythrocytes demonstrating agglutination at 30°C, 25°C, 15°C, and 4°C, but not at 37°C. CBC results (ADVIA 2120i) from the Mastiff revealed no significant differences in the RBC results obtained at room temperature (RT) and at 37°C; however, the RT run demonstrated negative bias in neutrophil and platelet concentrations attributed to rapid RBC settling. This uncommon hematologic condition may cause artifacts on the automated leukogram and platelet count, and may be subclinical for long periods.

The presence of diatom algae in a tracheal wash from a German Wirehaired Pointer with aspiration pneumonia.

A 7-year-old spayed female German Wirehaired Pointer was presented with difficulty breathing after being found seizing in a water-filled drainage ditch while out hunting. Aspirates from a tracheal wash contained numerous degenerate neutrophils, fewer macrophages, some of which contained basophilic debris, low numbers of extracellular diatoms, and a single intracellular short bacterial rod. As the dog continued to clinically decline and could not be weaned from oxygen support, the owners chose euthanasia. The major necropsy finding was a severe granulomatous bronchopneumonia that was likely due to aspiration of foreign material based on the microscopic presence of plant-like material, bi-refringent crystalline material, non-cellular debris, and occasional fungal structures. Diatoms are a class of algae that live primarily in water. Diatom analysis has been used, with some controversy, in human forensics to assist in documenting drowning as the cause of death. In this case, given the clinical history, the presence of diatoms and inflammation in the tracheal wash were interpreted as a likely result of the aspiration of surface water. To our knowledge, this is the first reported case of diatoms observed in a cytologic specimen in a nonhuman mammal with aspiration pneumonia.

A new ranavirus isolated from Pseudacris clarkii tadpoles in playa wetlands in the southern High Plains, Texas.

Mass die-offs of amphibian populations pose a challenging problem for conservation biologists. Ranaviruses often cause systemic infections in amphibians and, in North America, are especially virulent and lethal to larvae and metamorphs. In this paper we describe a novel ranavirus isolate as well as the first recorded occurrence of ranavirus in the southern High Plains of Texas and in associated populations of the spotted chorus frog Pseudacris clarkii. The breeding sites were playas, that is, wetlands that fill via isolated thunderstorms that can occur infrequently; thus, not every playa has water or breeding amphibians annually. We did not detect ranavirus in sympatric anurans, but other reports document ranaviruses in Pseudacris spp. elsewhere. The occurrence of multiple isolates of ranavirus in a number of Pseudacris species suggests that this genus of frogs is highly susceptible to ranaviruses and may experience exceptionally high mortality rates from infection. Thus, the virus may contribute to substantial seasonal population declines and low seasonal recruitment, with negative impacts on populations of breeding adults in successive years.

Improving influenza vaccine distribution in preparation for an H1N1 influenza pandemic: lessons from the field.

Vaccine distribution is an essential component of any healthcare organization's pandemic influenza plan. Variables surrounding distribution in these circumstances are often difficult to anticipate and require careful consideration. The 2009 H1N1 influenza pandemic provided organizations with an opportunity to test current models and overall organizational readiness for the next influenza pandemic. This article describes the experiences at a large, midwestern, multispecialty medical system in responding to the unique circumstances surrounding distribution of the 2009 H1N1 influenza vaccine. We discuss challenges, variables to consider when choosing a vaccine distribution model, institutional response, and lessons learned.