Now showing items 21-40 of 1842

    • Nocebo effects in clinical studies: Hints for pain therapy

      Klinger, R.; Blasini, M.; Schmitz, J. (Lippincott Williams and Wilkins, 2017)
      Introduction: Nocebo-induced algesic responses occurring within clinical contexts present a challenge for health care practitioners working in the field of pain medicine. Objectives: Following the recent research on algesic nocebo effects, the scope of this review is to develop ethically acceptable strategies to help avoid, or at least reduce, nocebo responses within clinical settings. Methods: We reviewed relevant clinical studies that depict how patient-practitioner interactions may contribute to the reduction of nocebo responses. Results: A strong algesic nocebo effect may adversely impact a patient�s condition by causing decreases in both the efficacy and effectiveness of interventions, as well as by promoting treatment nonadherence and discontinuation. These effects may be triggered through multiple channels and can lead to significant alterations in a patient�s perception of pain, consequently producing a weakening of the specific positive effects of pharmacological, psychological, or physical pain-management interventions. Conclusion: To minimize nocebo effects in clinical settings, we identified and discussed five contextual aspects relevant to the treatment of patients with chronic pain: (1) negative patient�clinician communication and interaction during treatment; (2) emotional burden of patients during treatment with analgesic medication; (3) negative information provided via informational leaflets; (4) cued and contextual conditioning nocebo effects; and (5) patient�s lack of positive information. Through an understanding of these elements, many preventive and ethically acceptable clinical actions can be taken to improve multidisciplinary pain treatment outcomes. Copyright Copyright 2017 The Authors.
    • Unabated occupational risk in a patient with rheumatoid pulmonary fibrosis

      Holden, V.K.; Kligerman, S.J.; Hastings, T.G. (Oxford University Press, 2017)
      Background This case highlights the importance of considering hypersensitivity pneumonitis (HP) in the differential diagnosis of interstitial lung disease (ILD) and of obtaining an occupational history so that remediable risk factors may be identified and managed. Aims To report a case of a chicken sexer with severe rheumatoid arthritis (RA) who developed progressively worsening dyspnoea and restrictive lung disease associated with pulmonary fibrosis. Methods Clinical investigation included physical examination, occupational history, pulmonary function tests (PFTs), chest imaging and bronchoalveolar lavage (BAL), as well as serological tests including standard IgE bird feather mixture and local IgG precipitin preparation to chicken excrement. Lung histopathology was examined post-mortem. Results The patient had worked as a chicken sexer for 29 years with limited control of exposure to chicken bioaerosols. PFTs initially showed mild restriction with a moderate gas transfer defect and computerized tomography of the chest exhibited extensive interstitial infiltrates throughout with severe honeycombing at the bases. Cytology from a BAL revealed multinucleated giant cells (MNGs). Specific serologic tests for bird antigens were negative. Histopathology demonstrated diffuse interstitial fibrosis with honeycombing, poorly formed granulomas and MNGs. Conclusions Findings were consistent with a diagnosis of HP with RA-associated ILD. The patient's history of severe RA biased the diagnosis to one of RA-associated ILD and her occupational risk had been less emphatically addressed. Obtaining a thorough occupational history can uncover exposures to workplace respiratory hazards and may create opportunities for intervention to limit morbidity from chronic lung disease. Copyright The Author 2017.
    • A Placebo-Controlled Trial of Riboflavin for Enhancement of Ultramarathon Recovery

      Hoffman, M.D.; Valentino, T.R.; Stuempfle, K.J. (Springer, 2017)
      Background: Riboflavin is known to protect tissue from oxidative damage but, to our knowledge, has not been explored as a means to control exercise-related muscle soreness. This study investigated whether acute ingestion of riboflavin reduces muscle pain and soreness during and after completion of a 161-km ultramarathon and improves functional recovery after the event. Methods: In this double-blind, placebo-controlled trial, participants of the 2016 161-km Western States Endurance Run were assigned to receive a riboflavin or placebo capsule shortly before the race start and when reaching 90�km. Capsules contained either 100�mg of riboflavin or 95�mg of maltodextrin and 5�mg of 10% �-carotene. Subjects provided muscle pain and soreness ratings before, during, and immediately after the race and for the 10 subsequent days. Subjects also completed 400-m runs at maximum speed on days 3, 5, and 10 after the race. Results: For the 32 (18 in the riboflavin group, 14 in the placebo group) race finishers completing the study, muscle pain and soreness ratings during and immediately after the race were found to be significantly lower (p =.043) for the riboflavin group. Analysis of the 400-m run times also showed significantly faster (p <.05) times for the riboflavin group than the placebo group at post-race days 3 and 5. Both groups showed that muscle pain and soreness had returned to pre-race levels by 5�days after the race and that 400-m run times had returned to pre-race performance levels by 10�days after the race. Conclusions: This preliminary work suggests that riboflavin supplementation before and during prolonged running might reduce muscle pain and soreness during and at the completion of the exercise and may enhance early functional recovery after the exercise. Copyright 2017, The Author(s).
    • Ethanol Induces Enhanced Vascularization Bioactivity of Endothelial Cell-Derived Extracellular Vesicles via Regulation of MicroRNAs and Long Non-Coding RNAs

      Lamichhane, T.N.; Leung, C.A.; Douti, L.Y. (Nature Publishing Group, 2017)
      Extracellular vesicles (EVs), such as exosomes, have been identified as regulators of vascular remodeling and have promise as therapeutics for vascularization applications. Towards development of EVs as therapeutics, it has been demonstrated that physiological stimuli of angiogenic phenotypes in EV-producing cells can enhance the potency of EVs for vascularization. The goal of this study was to assess whether ethanol, which induces angiogenic phenotypes in endothelial cells, could be employed to enhance endothelial-derived EV vascularization bioactivity. The results indicate that ethanol conditioning of endothelial cells increases the ability of endothelial EVs to induce a pro-vascularization response. This response is due in part to increased CD34 expression in recipient endothelial cells that may result from downregulation of microRNA-106b in EVs isolated from ethanol-conditioned producer endothelial cells. Further, ethanol-induced upregulation of long non-coding RNAs (lncRNAs) HOTAIR and MALAT1 in endothelial EVs was observed to play a significant role in mediating pro-angiogenic effects of these vesicles. Overall, these studies validate ethanol conditioning as a method to enhance the bioactivity of endothelial EVs via regulation of EV-associated microRNAs (miRNAs) and, especially, lncRNAs. Further, the results suggest that alcohol consumption may activate endothelial EVs towards a pro-vascularization phenotype, which could have implications for alcohol-induced tumor angiogenesis. Copyright 2017 The Author(s).
    • Comparison of multi-institutional Varian ProBeam pencil beam scanning proton beam commissioning data

      Langner, U.W.; Eley, J.G.; Dong, L. (AAPM - American Association of Physicists in Medicine, 2017)
      Purpose: Commissioning beam data for proton spot scanning beams are compared for the first two Varian ProBeam sites in the United States, at the Maryland Proton Treatment Center (MPTC) and Scripps Proton Therapy Center (SPTC). In addition, the extent to which beams can be matched between gantry rooms at MPTC is investigated. Method: Beam data for the two sites were acquired with independent dosimetry systems and compared. Integrated depth dose curves (IDDs) were acquired with Bragg peak ion chambers in a 3D water tank for pencil beams at both sites. Spot profiles were acquired at different distances from the isocenter at a gantry angle of 0� as well as a function of gantry angles. Absolute dose calibration was compared between SPTC and the gantries at MPTC. Dosimetric verification of test plans, output as a function of gantry angle, monitor unit (MU) linearity, end effects, dose rate dependence, and plan reproducibility were compared for different gantries at MPTC. Results: The IDDs for the two sites were similar, except in the plateau region, where the SPTC data were on average 4.5% higher for lower energies. This increase in the plateau region decreased as energy increased, with no marked difference for energies higher than 180 MeV. Range in water coincided for all energies within 0.5 mm. The sigmas of the spot profiles in air were within 10% agreement at isocenter. This difference increased as detector distance from the isocenter increased. Absolute doses for the gantries measured at both sites were within 1% agreement. Test plans, output as function of gantry angle, MU linearity, end effects, dose rate dependence, and plan reproducibility were all within tolerances given by TG142. Conclusion: Beam data for the two sites and between different gantry rooms were well matched.
    • Parents of children with food allergy: Gender differences in perceived impact and perceived food allergy severity

      Hoehn, J.L.; Dahlquist, L.M.; Hahn, A.L. (Oxford University Press, 2017)
      Objective To compare fathers' and mothers' perceptions of the impact and severity of their child's food allergy and their levels of involvement in allergy-related care. Methods One hundred parents of children with food allergy (50 mother-father pairs) rated the severity of their child's food allergies and completed the Food Allergy Impact Scale. A subset of 52 parents reported how often they engaged in food allergy-related care. Results Mothers reported more impact than fathers for meal preparation, family social activities, and stress and free time, and significantly greater involvement in allergy-related care. Fathers who reported more frequent medical appointment attendance perceived meal preparation as being significantly more impacted by food allergy than fathers who were less involved. Conclusions Fathers who are less involved may be buffered from experiencing the impact of their child's health condition. Differences in involvement rather than other gender differences may explain discrepancies in mothers' and fathers' illness perceptions. Copyright The Author 2016.
    • Potential Mediators between Fibromyalgia and C-Reactive protein: Results from a Large U.S. Community Survey

      Feinberg, T.; Sambamoorthi, U.; Lilly, C. (BioMed Central Ltd., 2017)
      Background: Fibromyalgia, a potentially debilitating chronic pain syndrome of unknown etiology, may be characterized by inflammation. In this study, we investigated the relation of FMS to serum C-reactive protein (CRP) in a large population of adults (18+) and investigated the influence of other factors on this relationship, including BMI, comorbidities, as well as mood and sleep disturbance. Methods: Participants were 52,535 Ohio Valley residents (Fibromyalgia n = 1125). All participants completed a comprehensive health survey (2005-2006) part of the C8 Health Project; serum levels of CRP were obtained, as was history of Fibromyalgia physician diagnosis. Logistic and linear regressions were used for this cross-sectional analysis. Results: Mean CRP was higher among participants reporting Fibromyalgia than those without (5.54 � 9.8 vs.3.75 � 7.2 mg/L, p <.0001)). CRP level showed a strong, positive association with FMS (unadjusted odds ratio (OR) for highest vs. lowest quartile = 2.5 (CI 2.1,3.0;p for trend <.0001)); adjustment for demographic and lifestyle factors attenuated but did not eliminate this association (AOR for highest vs. lowest quartile = 1.4 (CI 1.1,1.6;p for trend <.0001)). Further addition of body mass index (BMI) and comorbidities to the model markedly weakened this relationship (AORs, respectively, for highest vs lowest CRP quartile = 1.2 (CI 1.0,1.4) and 1.1 (CI 0.9,1.3). In contrast, inclusion of mood and sleep impairment only modestly reduced the adjusted risk estimate (AORs for highest vs. lowest quartile = 1.3 (CI 1.1,1.5) for each)). Conclusions: Findings from this large cross-sectional study indicate a significant positive cross-sectional association of Fibromyalgia to serum C-reactive protein may be explained, in part, by BMI and comorbidity. Prospective research is needed to confirm this, and clarify the potential mediating influence of obesity and comorbid conditions on this relationship. Copyright 2017 The Author(s).
    • Heparin and heparin-derivatives in post-subarachnoid hemorrhage brain injury: A multimodal therapy for a multimodal disease

      Hayman, E.G.; Patel, A.P.; James, R.F. (MDPI AG, 2017)
      Pharmacologic efforts to improve outcomes following aneurysmal subarachnoid hemorrhage (aSAH) remain disappointing, likely owing to the complex nature of post-hemorrhage brain injury. Previous work suggests that heparin, due to the multimodal nature of its actions, reduces the incidence of clinical vasospasm and delayed cerebral ischemia that accompany the disease. This narrative review examines how heparin may mitigate the non-vasospastic pathological aspects of aSAH, particularly those related to neuroinflammation. Following a brief review of early brain injury in aSAH and heparin's general pharmacology, we discuss potential mechanistic roles of heparin therapy in treating post-aSAH inflammatory injury. These roles include reducing ischemia-reperfusion injury, preventing leukocyte extravasation, modulating phagocyte activation, countering oxidative stress, and correcting blood-brain barrier dysfunction. Following a discussion of evidence to support these mechanistic roles, we provide a brief discussion of potential complications of heparin usage in aSAH. Our review suggests that heparin's use in aSAH is not only safe, but effectively addresses a number of pathologies initiated by aSAH.
    • Data Descriptor: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

      Flannick, J.; Fuchsberger, C.; Pollin; Toni, I., (Nature Publishing Groups, 2017)
      To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ?82 K Europeans via the exome chip, and ?90% of low-frequency non-coding variants in ?44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D. Copyright The Author(s) 2017.
    • Constitutively active SPAK causes hyperkalemia by activating NCC and remodeling distal tubules

      Grimm, P.R.; Coleman, R.; Delpire, E. (American Society of Nephrology, 2017)
      Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassiumexcretory renal outermedullary potassium(ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was specifically targeted to the earlyDCT using a DCT-driven Cre recombinase. CA-SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and consequent restoration of sodium excretion did not immediately restore urinary potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN remodeling, involving a reduction in connecting tubule mass and attenuation of epithelial sodium channel (ENaC) and ROMK expression and apical localization. Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC and ROMK expression, concurrentwith the restoration of urinary potassiumexcretion. These findings verify that NCC hyperactivity underlies FHHt but also reveal that NCC-dependent changes in the driving force for potassium secretion are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process controls potassium balance in health and becomes aberrantly activated in FHHt.
    • The metabolic phenotype of prostate cancer

      Eidelman, E.; Twum-Ampofo, J.; Ansari, J. (Frontiers Media S.A., 2017)
      Prostate cancer is the most common non-cutaneous cancer in men in the United States. Cancer metabolism has emerged as a contemporary topic of great interest for improved mechanistic understanding of tumorigenesis. Prostate cancer is a disease model of great interest from a metabolic perspective. Prostatic tissue exhibits unique metabolic activity under baseline conditions. Benign prostate cells accumulate zinc, and this excess zinc inhibits citrate oxidation and metabolism within the citric acid cycle, effectively resulting in citrate production. Malignant cells, however, actively oxidize citrate and resume more typical citric acid cycle function. Of further interest, prostate cancer does not exhibit the Warburg effect, an increase in glucose uptake, seen in many other cancers. These cellular metabolic differences and others are of clinical interest as they present a variety of potential therapeutic targets. Furthermore, understanding of the metabolic profile differences between benign prostate versus low- and high-grade prostate cancers also represents an avenue to better understand cancer progression and potentially develop new diagnostic testing. In this paper, we review the current state of knowledge on the metabolic phenotypes of prostate cancer.
    • Impact of protein O-GlcNAcylation on neural tube malformation in diabetic embryopathy

      Kim, G.; Cao, L.; Reece, E.A. (Nature Publishing Group, 2017)
      Diabetes mellitus in early pregnancy can cause neural tube defects (NTDs) in embryos by perturbing protein activity, causing cellular stress, and increasing programmed cell death (apoptosis) in the tissues required for neurulation. Hyperglycemia augments a branch pathway in glycolysis, the hexosamine biosynthetic pathway (HBP), to increase uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc). GlcNAc can be added to proteins by O-GlcNAc transferase (OGT) to regulate protein activity. In the embryos of diabetic mice, OGT is highly activated in association with increases in global protein O-GlcNAcylation. In neural stem cells in vitro, high glucose elevates O-GlcNAcylation and reactive oxygen species, but the elevations can be suppressed by an OGT inhibitor. Inhibition of OGT in diabetic pregnant mice in vivo decreases NTD rate in the embryos. This effect is associated with reduction in global O-GlcNAcylation, alleviation of intracellular stress, and decreases in apoptosis in the embryos. These suggest that OGT plays an important role in diabetic embryopathy via increasing protein O-GlcNAcylation, and that inhibiting OGT could be a candidate approach to prevent birth defects in diabetic pregnancies. Copyright 2017 The Author(s).
    • Equination (inoculation of horsepox): An early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine

      Esparza, J.; Schrick, L.; Damaso, C.R.; Nitsche, A. (Elsevier Ltd, 2017)
      For almost 150 years after Edward Jenner had published the �Inquiry� in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was not until 1939 when it was shown that vaccinia, the smallpox vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus. A favorite candidate for a vaccinia ancestor has been the horsepox virus. Edward Jenner himself suspected that cowpox derived from horsepox and he also believed that �matter� obtained from either disease could be used as preventative of smallpox. During the 19th century, inoculation with cowpox (vaccination) was used in Europe alongside with inoculation with horsepox (equination) to prevent smallpox. Vaccine-manufacturing practices during the 19th century may have resulted in the use of virus mixtures, leading to different genetic modifications that resulted in present-day vaccinia strains. Horsepox, a disease previously reported only in Europe, has been disappearing on that continent since the beginning of the 20th century and now seems to have become extinct, although the virus perhaps remains circulating in an unknown reservoir. Genomic sequencing of a horsepox virus isolated in Mongolia in 1976 indicated that, while closely related to vaccinia, this horsepox virus contained additional, potentially ancestral sequences absent in vaccinia. Recent genetic analyses of extant vaccinia viruses have revealed that some strains contain ancestral horsepox virus genes or are phylogenetically related to horsepox virus. We have recently reported that a commercially produced smallpox vaccine, manufactured in the United States in 1902, is genetically highly similar to horsepox virus, providing a missing link in this 200-year-old mystery.
    • Polyplexes assembled from self-peptides and regulatory nucleic acids blunt toll-like receptor signaling to combat autoimmunity

      Hess, K.L.; Andorko, J.I.; Tostanoski, L.H. (Elsevier Ltd, 2017)
      Autoimmune diseases occur when the immune system incorrectly recognizes self-molecules as foreign; in the case of multiple sclerosis (MS), myelin is attacked. Intriguingly, new studies reveal toll-like receptors (TLRs), pathways usually involved in generating immune responses against pathogens, play a significant role in driving autoimmune disease in both humans and animal models. We reasoned polyplexes formed from myelin self-antigen and regulatory TLR antagonists might limit TLR signaling during differentiation of myelin-specific T cells, inducing tolerance by biasing T cells away from inflammatory phenotypes. Complexes were formed by modifying myelin peptide with cationic amino acids to create peptides able to condense the anionic nucleic-acid based TLR antagonist. These immunological polyplexes eliminate synthetic polymers commonly used to condense polyplexes and do not rely on gene expression; however, the complexes mimic key features of traditional polyplexes such as tunable loading and co-delivery. Using these materials and classic polyplex analysis techniques, we demonstrate condensation of both immune signals, protection from enzymatic degradation, and tunable physicochemical properties. We show polyplexes reduce TLR signaling, and in primary dendritic cell and T cell co-culture, reduce myelin-driven inflammation. During mouse models of MS, these tolerogenic polyplexes improve the progression, severity, and incidence of disease. Copyright 2016 The Authors
    • A Review of HIV Pre-Exposure Prophylaxis: The Female Perspective

      Bailey, J.L.; Molino, S.T.; Vega, A.D. (Springer Healthcare, 2017)
      When taken consistently, pre-exposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) with once daily tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) has been shown to safely reduce the incidence of HIV infection in high-risk individuals by more than 90%. Yet, according to the Centers for Disease Control and Prevention, there were about 2.1 million new cases of HIV reported worldwide in 2015. Undoubtedly, there is significant room for improvement to prevent the transmission of HIV. Research to date has been heavily focused on the high-risk men who have sex with men (MSM) population, yet, many women worldwide remain at high risk of HIV transmission. PrEP offers women a protection method that is discrete, does not require partner consent, and may be compatible with both contraception or conception as desired. However, women often remain under-represented in HIV prevention literature and are reported to have lower real-world uptake in comparison to men. Furthermore, clinical trials that do focus on the female population demonstrate mixed efficacy results that highlight the adherence challenges in this population. It is essential to identify factors that contribute to PrEP non-adherence as well as barriers to preventative treatment. This review will discuss the clinical evidence behind PrEP in women, current barriers to use afflicting this population, pharmacotherapy considerations for the female patient, alternative and future agents, and the current real-world application of PrEP. Copyright 2017, The Author(s).
    • Framework for enhancing clinical practice guidelines through continuous patient engagement

      Armstrong, M.J.; Rueda, J.-D.; Gronseth, G.S. (Blackwell Publishing Ltd, 2017)
      Background: Patient engagement in clinical practice guideline (CPG) development is recommended by multiple institutions and instruments measuring guideline quality. Approaches to engaging patients, however, vary between oversight organizations, quality tools and guideline developers. Objective: We propose a ten-step framework outlining steps and options for patient engagement in guideline development with the goal of highlighting steps for patient engagement and methods by which this can be achieved. Discussion: This framework provides a model for continuous patient engagement in CPGs by outlining ten steps of guideline development occurring at the levels of the developer/committee and the individual guideline project. At the developer level, patients can assist in topic nomination (step 1), topic prioritization (step 2) and guideline development group selection (step 3). Within specific guideline projects, patients� opinions may be incorporated when framing the question (step 4), creating an analytic framework and research plan (step 5), conducting the systematic review and conclusion formation (step 6), development of recommendations (step 7) and dissemination and implementation (step 8). At the end of process, patients can again be engaged at the developer level by helping determine when guidelines need updating (step 9) and evaluating the developer's approach to patient engagement (step 10). Conclusions: Patient engagement at each CPG development step has different purposes, mechanisms, advantages and disadvantages, and implications for resource utilization. This framework can serve as a resource for guideline developers desiring to increase patient engagement and reference for researchers investigating engagement methodology at different steps of the CPG lifecycle. Copyright 2016 The Authors.
    • Does Active Oral Sex Contribute to Female Infertility?

      Bavoil, P.M.; Marques, P.X.; Brotman, R. (Oxford University Press, 2017)
      Based on recent, historical, and circumstantial evidence, we present a multifactorial hypothesis that has potential direct implications on the epidemiology and management of chlamydial infection and disease in humans. We propose that (1) like its veterinary relatives, the oculogenital pathogen Chlamydia trachomatis evolved as a commensal organism of the human gastrointestinal (GI) tract primarily transmissible via the fecal-oral route; (2) in the modern era, C. trachomatis causes "opportunistic" infection at non-GI sites under conditions driven by improved sanitation/hygiene and reduced fecal-oral transmission; and (3) the rise in the practice of oral sex is contributing to the increased prevalence of C. trachomatis in the human GI tract. Infectious organisms produced in the GI tract and reaching the rectum may then chronically contaminate and infect the female urogenital tract, thereby potentially contributing to the most serious sequelae of chlamydial infection in women: pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility. Copyright 2017 The Author.
    • Effects of Exercise Training and Weight Loss on Plasma Fetuin-A Levels and Insulin Sensitivity in Overweight Older Men

      Blumenthal, J.B.; Gitterman, A.; Ryan, A.S. (Hindawi Limited, 2017)
      Aerobic exercise training and weight loss (AEX+WL) improves insulin sensitivity in overweight adults; however, the underlying pathways are incompletely understood. Fetuin-A, a hepatokine that inhibits insulin signaling, may be involved in the salutary effects of AEX+WL. Therefore, we examined the effects of 6-month AEX+WL on plasma fetuin-A levels (36-48 hours after the last bout of exercise), aerobic capacity (VO2max), body composition, glucose tolerance, and insulin sensitivity (M) in 16 sedentary, overweight-obese older men (age = 60 � 2 years, BMI = 31 � 1 kg/m2) with no history of cardiovascular disease or diabetes. At baseline, fetuin-A levels correlated directly with adiposity and had a borderline inverse correlation with M. After AEX+WL, body weight decreased by 10 kg, while both VO2max and M increased by 16% (P&lt;0.005 for all). Contrary to our hypothesis, plasma fetuin-A levels increased after AEX+WL (1.16 � 0.10 g/L versus 1.70 � 0.19 g/L, P=0.006). This increase was unrelated to changes in body composition or glucose metabolism, but directly correlated with changes in VO2max (r=0.57, P&lt;0.05). Thus, in overweight-to-obese older men, AEX+WL appears to increase plasma fetuin-A levels. Although not associated with improvements in insulin sensitivity, this increase in fetuin-A was related to improvements in aerobic capacity and could be representative of the cardioprotective effects of AEX+WL in older men. Copyright 2017 Jacob B. Blumenthal et al.
    • Inhibition of fracture healing in the presence of contamination by Staphylococcus aureus: Effects of growth state and immune response

      Blanchette, K.A.; Prabhakara, R.; Shirtliff, M.E. (John Wiley and Sons Inc., 2017)
      Extremity injuries comprise a significant portion of trauma, affecting quality of life, financial burden, and return to duty. Bacterial contamination is commonly associated with failure to heal, despite antibiotic treatment, suggesting that additional therapies must be developed to combat these complications. Treatment failure is likely due to the presence of resistant microbial communities known as biofilms. Biofilm bacteria are able to elicit a direct inhibition of healing through a multitude of known factors. However, they likely also inhibit healing through alteration of the inflammatory response. As inflammation is a critical step in fracture healing, how the presence of biofilm bacteria shifts this response to one that is suboptimal for healing is an important consideration that is currently understudied. The profile of inflammatory factors in response to biofilm bacteria is unique and distinct from those induced during normal healing or by planktonic bacteria alone. This review will examine the presence of inflammatory factors during normal healing and those induced by contaminating bacteria, and will discuss how these differences may ultimately lead to nonunion. Specifically, this review will focus on the Th1/Th2/Th17 type inflammatory responses and how shifts in the balance of these responses during infection can lead to both ineffective clearance and disruption of fracture healing.
    • Tick humoral responses: Marching to the beat of a different drummer

      Ch�vez, A.S.O.; Shaw, D.K.; Munderloh, U.G. (Frontiers Media S.A., 2017)
      Ticks transmit a variety of human pathogens, including Borrelia burgdorferi, the etiological agent of Lyme disease. Multiple pathogens that are transmitted simultaneously, termed "coinfections," are of increasing importance and can affect disease outcome in a host. Arthropod immunity is central to pathogen acquisition and transmission by the tick. Pattern recognition receptors recognize pathogen-associated molecular patterns and induce humoral responses through the Toll and Immune Deficiency (IMD) pathways. Comparative analyses between insects and ticks reveal that while the Toll pathway is conserved, the IMD network exhibits a high degree of variability. This indicates that major differences in humoral immunity exist between insects and ticks. While many variables can affect immunity, one of the major forces that shape immune outcomes is the microbiota. In light of this, we discuss how the presence of commensal bacteria, symbionts and/or coinfections can lead to altered immune responses in the tick that impact pathogen persistence and subsequent transmission. By investigating non-insect arthropod immunity, we will not only better comprehend tick biology, but also unravel the intricate effects that pathogen coinfections have on vector competence and tick-borne disease transmission. Copyright 2017 Oliva Ch�vez, Shaw, Munderloh and Pedra.