Risk for Tuberculosis among Children

Risk among children is underestimated in countries with a high incidence of this disease

Cutaneous C-polymodal fibers lacking TRPV1 are sensitized to heat following inflammation, but fail to drive heat hyperalgesia in the absence of TPV1 containing C-heat fibers

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that the TRPV1 ion channel plays a critical role in the development of heat hyperalgesia after inflammation, as inflamed TRPV1-/- mice develop mechanical allodynia but fail to develop thermal hyperalgesia. In order to further investigate the role of TRPV1, we have used an ex vivo skin/nerve/DRG preparation to examine the effects of CFA-induced-inflammation on the response properties of TRPV1-positive and TRPV1-negative cutaneous nociceptors.</p> <p>Results</p> <p>In wildtype mice we found that polymodal C-fibers (CPMs) lacking TRPV1 were sensitized to heat within a day after CFA injection. This sensitization included both a drop in average heat threshold and an increase in firing rate to a heat ramp applied to the skin. No changes were observed in the mechanical response properties of these cells. Conversely, TRPV1-positive mechanically insensitive, heat sensitive fibers (CHs) were not sensitized following inflammation. However, results suggested that some of these fibers may have gained mechanical sensitivity and that some previous silent fibers gained heat sensitivity. In mice lacking TRPV1, inflammation only decreased heat threshold of CPMs but did not sensitize their responses to the heat ramp. No CH-fibers could be identified in naïve nor inflamed TRPV1-/- mice.</p> <p>Conclusions</p> <p>Results obtained here suggest that increased heat sensitivity in TRPV1-negative CPM fibers alone following inflammation is insufficient for the induction of heat hyperalgesia. On the other hand, TRPV1-positive CH fibers appear to play an essential role in this process that may include both afferent and efferent functions.</p

Spectral Analysis of the Supreme Court

The focus of this paper is the linear algebraic framework in which the spectral analysis of voting data like that above is carried out. As we will show, this framework can be used to pinpoint voting coalitions in small voting bodies like the United States Supreme Court. Our goal is to show how simple ideas from linear algebra can come together to say something interesting about voting. And what could be more simple than where our story begins— with counting

The Grizzly, September 18, 1981

Thomas P. Glassmoyer Elected Board President • APO Retains Highest GPA Last Spring • Chemistry, Economics, History and English Departments Receive New Faculty • Forum Programs Now \u27til Christmas • Editorial: Just Like the Good Old Days? • Message From the President: Play an Active Part • Evening in Photography Offered • Evening School Expands Computer Program • New Staff Appointments • Dr. Schultze Represents UC in Conference • UC Buying Up Main Street: New Off-Campus Housing • Anarchy in America: Let\u27s Kill All the Lawyers • Decatur Follows Shakespeare to Germany • Electric Factory Does it Again • IFC Getting it All Together • USGA Notes • Six New Faculty • Improving Relationships and Self-Image Workshop • Lacrosse Club Announces Fall Season • Gridders Kick Off \u2781 Season With Victory • Field Hockey Looking Good • Cross Country Team Off to Fast Starthttps://digitalcommons.ursinus.edu/grizzlynews/1060/thumbnail.jp

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Where's all the 'good' sports journalism? Sports media research, the sociology of sport, and the question of quality sports reporting

Across newsrooms and journalism schools, questions as to what constitutes or ‘counts’ as excellent reporting are currently inciting much debate. Among the various frameworks being put forward to describe and encourage ‘excellent’ journalism in its various forms, sport is seldom mentioned – a legacy perhaps of its perennial dismissal as trivial subject matter. This essay grew from our curiosity as to whether the reverse was also true: that is, whether and what those who study sports journalism and sports media – in particular sociologists of sport – have contributed to understandings of ‘best’ and even excellent journalistic practice. We identified and analysed 376 articles from eight leading scholarly journals that feature sports media research with the aim of examining instances where ‘excellent’ sports reporting was either highlighted, described or advocated. After outlining the major themes that emerged from this analysis, we reflect on why so few of the sampled articles explicitly advise on what best practice sports journalism might look like – especially when it comes to coverage of the sport-related social issues that sociologists of sport tend to focus on – and why so little theoretical attention has been afforded to the question of excellent sports journalism more generally. While there are good sociological reasons for focusing on problematic sports reporting, on structural and systemic issues in which media are implicated, and on producing alternatives to hegemonic sports media, we conclude that it is high time for instances of excellent sports journalism to be afforded the theoretical and empirical attention long granted to their ‘bad’ journalistic counterparts

Immunomodulation of murine collagen-induced arthritis by N, N-dimethylglycine and a preparation of Perna canaliculus

<p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel <it>Perna canaliculus </it>(Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses.</p> <p>Methods</p> <p>In our initial studies, we treated lipopolysaccahride (LPS) stimulated THP-1 monocytes <it>in vitro </it>with increasing concentrations of Perna extract or DMG. Additionally, we treated rat peripheral blood neutrophils with increasing concentrations of Perna extract and measured superoxide burst. In subsequent <it>in vivo </it>experiments, CIA was induced by administration of type II collagen; rats were prophylactically treated with either Perna or DMG, and then followed for disease severity. Finally, to test whether Perna and/or DMG could block or inhibit an ongoing pathologic disease process, we induced CIA in mice and treated them therapeutically with either of the two immunomodulators.</p> <p>Results</p> <p>Following LPS stimulation of THP-1 monocytes, we observed dose-dependent reductions in TNF-α and IL-12p40 production in Perna treated cultures. DMG treatment, however, showed significant increases in both of these cytokines in the range of 0.001–1 μM. We also demonstrate that <it>in vitro </it>neutrophil superoxide burst activity is dose-dependently reduced in the presence of Perna. Significant reductions in disease incidence, onset, and severity of CIA in rats were noted following prophylactic treatment with either of the two immunomodulators. More importantly, amelioration of mouse CIA was observed following therapeutic administration of Perna. In contrast, DMG appeared to have little effect in mice and may act in a species-specific manner.</p> <p>Conclusion</p> <p>These data suggest that Perna, and perhaps DMG, may be useful supplements to the treatment of RA in humans.</p

Acquired Resistance to KRAS (G12C) Inhibition in Cancer

BACKGROUND: Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS(G12C)). The mechanisms of acquired resistance to these therapies are currently unknown. METHODS: Among patients with KRAS(G12C) -mutant cancers treated with adagrasib monotherapy, we performed genomic and histologic analyses that compared pretreatment samples with those obtained after the development of resistance. Cell-based experiments were conducted to study mutations that confer resistance to KRAS(G12C) inhibitors. RESULTS: A total of 38 patients were included in this study: 27 with non-small-cell lung cancer, 10 with colorectal cancer, and 1 with appendiceal cancer. Putative mechanisms of resistance to adagrasib were detected in 17 patients (45% of the cohort), of whom 7 (18% of the cohort) had multiple coincident mechanisms. Acquired KRAS alterations included G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and high-level amplification of the KRAS(G12C) allele. Acquired bypass mechanisms of resistance included MET amplification; activating mutations in NRAS, BRAF, MAP2K1, and RET; oncogenic fusions involving ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN. In two of nine patients with lung adenocarcinoma for whom paired tissue-biopsy samples were available, histologic transformation to squamous-cell carcinoma was observed without identification of any other resistance mechanisms. Using an in vitro deep mutational scanning screen, we systematically defined the landscape of KRAS mutations that confer resistance to KRAS(G12C) inhibitors. CONCLUSIONS: Diverse genomic and histologic mechanisms impart resistance to covalent KRAS(G12C) inhibitors, and new therapeutic strategies are required to delay and overcome this drug resistance in patients with cancer. (Funded by Mirati Therapeutics and others; ClinicalTrials.gov number, NCT03785249.)