Correction: Farnfield, M.M., et al. Whey Protein Ingestion Activates mTOR-dependent Signalling after Resistance Exercise in Young Men: A Double-Blinded Randomized Controlled Trial. Nutrients 2009, 1, 263-275.

We found an error in our paper recently published in Nutrients [1]

Pharmacologic Inhibition of COX-1 and COX-2 in Influenza A Viral Infection in Mice

BACKGROUND: We previously demonstrated that cyclooxygenase (COX)-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560), a COX-2 inhibitor (celecoxib) or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU) and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL) fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice

Randomized Clinical Trial Comparing Basal Insulin Peglispro and Insulin Glargine in Patients With Type 2 Diabetes Previously Treated With Basal Insulin: IMAGINE 5

OBJECTIVE To evaluate the efficacy and safety of basal insulin peglispro (BIL) versus insulin glargine in patients with type 2 diabetes (hemoglobin A1c [HbA1c] ≤9% [75 mmol/mol]) treated with basal insulin alone or with three or fewer oral antihyperglycemic medications. RESEARCH DESIGN AND METHODS This 52-week, open-label, treat-to-target study randomized patients (mean HbA1c 7.42% [57.6 mmol/mol]) to BIL ( n = 307) or glargine ( n = 159). The primary end point was change from baseline HbA1c to 26 weeks (0.4% [4.4 mmol/mol] noninferiority margin). RESULTS At 26 weeks, reduction in HbA1c was superior with BIL versus glargine (−0.82% [−8.9 mmol/mol] vs. −0.29% [−3.2 mmol/mol]; least squares mean difference −0.52%, 95% CI −0.67 to −0.38 [−5.7 mmol/mol, 95% CI −7.3 to −4.2; P < 0.001); greater reduction in HbA1c with BIL was maintained at 52 weeks. More BIL patients achieved HbA1c <7% (53 mmol/mol) at weeks 26 and 52 ( P < 0.001). With BIL versus glargine, nocturnal hypoglycemia rate was 60% lower, more patients achieved HbA1c <7% (53 mmol/mol) without nocturnal hypoglycemia at 26 and 52 weeks ( P < 0.001), and total hypoglycemia rates were lower at 52 weeks ( P = 0.03). At weeks 26 and 52, glucose variability was lower ( P < 0.01), basal insulin dose was higher ( P < 0.001), and triglycerides and aminotransferases were higher with BIL versus glargine ( P < 0.05). Liver fat content (LFC), assessed in a subset of patients ( n = 162), increased from baseline with BIL versus glargine ( P < 0.001), with stable levels between 26 and 52 weeks. CONCLUSIONS BIL provided superior glycemic control versus glargine, with reduced nocturnal and total hypoglycemia, lower glucose variability, and increased triglycerides, aminotransferases, and LFC

Comparative genomics of Mycobacterium avium complex reveals signatures of environment-specific adaptation and community acquisition

Nontuberculous mycobacteria, including those in the Mycobacterium avium complex (MAC), constitute an increasingly urgent threat to global public health. Ubiquitous in soil and water worldwide, MAC members cause a diverse array of infections in humans and animals that are often multidrug resistant, intractable, and deadly. MAC lung disease is of particular concern and is now more prevalent than tuberculosis in many countries, including the United States. Although the clinical importance of these microorganisms continues to expand, our understanding of their genomic diversity is limited, hampering basic and translational studies alike. Here, we leveraged a unique collection of genomes to characterize MAC population structure, gene content, and within-host strain dynamics in unprecedented detail. We found that different MAC species encode distinct suites of biomedically relevant genes, including antibiotic resistance genes and virulence factors, which may influence their distinct clinical manifestations. We observed that M. avium isolates from different sources-human pulmonary infections, human disseminated infections, animals, and natural environments-are readily distinguished by their core and accessory genomes, by their patterns of horizontal gene transfer, and by numerous specific genes, including virulence factors. We identified highly similar MAC strains from distinct patients within and across two geographically distinct clinical cohorts, providing important insights into the reservoirs which seed community acquisition. We also discovered a novel MAC genomospecies in one of these cohorts. Collectively, our results provide key genomic context for these emerging pathogens and will facilitate future exploration of MAC ecology, evolution, and pathogenesis

Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer

AbstractAdipocytes promote progression of multiple cancers, but their role in pancreatic intraepithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC) is poorly defined. Nutrient transfer is a mechanism underlying stromal cell-cancer crosstalk. We studied the role of adipocytes in regulating in vitro PanIN and PDAC cell proliferation with a focus on glutamine metabolism. Murine 3T3L1 adipocytes were used to model adipocytes. Cell lines derived from PKCY mice were used to model PanIN and PDAC. Co-culture was used to study the effect of adipocytes on PanIN and PDAC cell proliferation in response to manipulation of glutamine metabolism. Glutamine secretion was measured with a bioanalyzer. Western blotting was used to study the effect of PanIN and PDAC cells on expression of glutamine-related enzymes in adipocytes. Adipocytes promote proliferation of PanIN and PDAC cells, an effect that was amplified in nutrient-poor conditions. Adipocytes secrete glutamine and rescue PanIN and PDAC cell proliferation in the absence of glutamine, an effect that was glutamine synthetase-dependent and involved PDAC cell-induced down-regulation of glutaminase expression in adipocytes. These findings suggest glutamine transfer as a potential mechanism underlying adipocyte-induced PanIN and PDAC cell proliferation

A Network-Individual-Resource Model for HIV Prevention

HIV is transmitted through dyadic exchanges of individuals linked in transitory or permanent networks of varying sizes. A theoretical perspective that bridges key individual level elements with important network elements can be a complementary foundation for developing and implementing HIV interventions with outcomes that are more sustainable over time and have greater dissemination potential. Toward that end, we introduce a Network-Individual-Resource (NIR) model for HIV prevention that recognizes how exchanges of resources between individuals and their networks underlies and sustains HIV-risk behaviors. Individual behavior change for HIV prevention, then, may be dependent on increasing the supportiveness of that individual’s relevant networks for such change. Among other implications, an NIR model predicts that the success of prevention efforts depends on whether the prevention efforts (1) prompt behavior changes that can be sustained by the resources the individual or their networks possess; (2) meet individual and network needs and are consistent with the individual’s current situation/developmental stage; (3) are trusted and valued; and (4) target high HIV-prevalence networks

Impact of American Joint Committee on Cancer Eighth Edition clinical stage and smoking history on oncologic outcomes in human papillomavirus‐associated oropharyngeal squamous cell carcinoma

BackgroundThe purpose of this study was to evaluate the AJCC eighth edition clinical staging system for human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma and to further understand how clinical stage and smoking history affect oncologic outcomes. The purpose of this study was to present the understanding of how clinical stage and smoking history affect oncologic outcomes in human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (SCC) is critical for selecting patients for treatment deintensification.MethodsKaplan‐Meier and Cox regression were used to evaluate overall survival (OS), locoregional recurrence‐free survival (LRFS), and distant recurrence‐free survival (DRFS). Concordance statistics (C‐indices) were used to compare discriminating ability.ResultsThe OS and DRFS but not LRFS were significantly distributed using the American Joint Committee on Cancer (AJCC) seventh and eighth editions criteria. The C‐indices for OS, LRFS, and DRFS were 0.57, 0.54, and 0.60, respectively, using the AJCC seventh edition, and 0.63, 0.53, and 0.65, respectively, using the AJCC eighth edition. On multivariate analysis, 1 + pack‐year smoking history correlated with OS (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.2‐3.1; P < .01) but not LRFS or DRFS.ConclusionThese results support implementation of the AJCC eighth edition for HPV‐associated oropharyngeal SCC. Clinical stage may be more important than smoking history in selection for deintensification.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148352/1/hed25336_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148352/2/hed25336.pd

Eruptive papules during efalizumab (anti-CD11a) therapy of psoriasis vulgaris: a case series

BACKGROUND: Newer biological therapies for moderate-to-severe psoriasis are being used more frequently, but unexpected effects may occur. CASE PRESENTATIONS: We present a group of 15 patients who developed inflammatory papules while on efalizumab therapy (Raptiva, Genentech Inc, anti-CD11a). Immunohistochemistry showed that there were increased CD11b(+), CD11c(+ )and iNOS(+ )cells (myeloid leukocytes) in the papules, with relatively few CD3(+ )T cells. While efalizumab caused a decreased expression of CD11a on T cells, other circulating leukocytes from patients receiving this therapy often showed increased CD11b and CD11c. In the setting of an additional stimulus such as skin trauma, this may predispose to increased trafficking into the skin using these alternative β2 integrins. In addition, there may be impaired immune synapse formation, limiting the development of these lesions to small papules. There is little evidence for these papular lesions being "allergic" in nature as there are few eosinophils on biopsy, and they respond to minimal or no therapy even if efalizumab is continued. CONCLUSION: We hypothesize that these papules may represent a unique type of "mechanistic" inflammatory reaction, seen only in the context of drug-induced CD11a blockade, and not during the natural disease process

Sodium Chloride Inhibits the Growth and Infective Capacity of the Amphibian Chytrid Fungus and Increases Host Survival Rates

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0–5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1–4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation