Herpes Simplex Virus Type 1 Infection: Features of immune surveillance and antiviral resistance

__Abstract__ The family of Herpesviridae is highly disseminated in the animal world, with a wide range of host species. Because most animal species have at least one herpesvirus, the number of herpesviruses in nature is likely to exceed by far the 138 currently identifi ed members. To date, eight human herpesviruses have been identifi ed: human herpesvirus 1 to 8 (HHV1-HHV8). They are classifi ed on basis of their cell tropism and genome organization into subfamilies of Alpha-, Beta-, and Gammaherpesvirinae (Table 1). In addition to causing productive infections, a key feature of herpesviruses is their ability to establish latency. This non-productive phase lasts for the life time of the host, is characterized by a silent viral infection with intermittent reactivations, commonly clinical unapparent, resulting in intermittent shedding of infectious virus and spread throughout the population

Functional capillary density decreases after the first week of life in term neonates

Background: Changes in the microcirculation have been recognized to play a crucial role in many disease processes. In premature neonates, functional capillary density (FCD) decreases during the first months of life. Objectives: The aims of this study were to obtain microcirculatory parameters in term neonates and older children who did not present with compromised respir

Tapentadol treatment results in long-term pain relief in patients with chronic low back pain and associates with reduced segmental sensitization

Introduction:Chronic low back pain (CLBP) is one of the most common chronic pain conditions in pain practice.Objectives:In the current study, we describe phenotypes of patients with CLBP based on the status of their endogenous pain modulatory system.Methods:Conditioned pain modulation (a measure of central pain inhibition), temporal summation (TS, a measure of pain facilitation), and offset analgesia (a measure of temporal filtering of nociception) were evaluated in 53 patients with CLBP at painful and nonpainful sites. Next, in a double-blind, randomized, placebo-controlled trial, 40 patients with defective conditioned pain modulation responses received treatment with tapentadol prolonged-release or placebo for 3 months.Results:The majority of patients (87%) demonstrated loss of central pain inhibition combined with segmentally increased TS and reduced offset analgesia at the lower back region. During treatment, tapentadol reduced pain intensity more than placebo (tapentadol -19.5 2.1 mm versus placebo -7.1 +/- 1.8 mm, P = 0.025). Furthermore, tapentadol significantly decreased pain facilitation by reduction of TS responses at the lower back (tapentadol -0.94 +/- 1.9 versus placebo 0.01 +/- 1.5, P = 0.020), which correlated with pain reduction (P < 0.001).Conclusion:Patients with CLBP demonstrated different phenotypes of endogenous pain modulation. In patients with reduced conditioned pain modulation, tapentadol produced long-term pain relief that coincided with reduction of signs of pain facilitation. These data indicate that the endogenous pain system may be used as a biomarker in the pharmacological treatment of CLBP, enabling an individualized, mechanism-based treatment approach.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Usefulness and feasibility of comprehensive and less comprehensive vocational rehabilitation for patients with chronic musculoskeletal pain:perspectives from patients, professionals, and managers

Purpose: To explore the usefulness and feasibility of a comprehensive vocational rehabilitation (C-VR) program and less comprehensive (LC-VR) program for workers on sick leave due to chronic musculoskeletal pain, from the perspective of patients, professionals, and managers.Materials and methods: Semi-structured interviews were held with patients, professionals, and managers. Using topic lists, participants were questioned about barriers to and facilitators of the usefulness and feasibility of C-VR and LC-VR. Thirty interviews were conducted with thirteen patients (n = 6 C-VR, n = 7 LC-VR), eight professionals, and nine managers. All interviews were transcribed verbatim. Data were analyzed by systematic text condensation using inductive thematic analysis.Results: Three themes emerged for usefulness ("patient factors," "content," "dosage") and six themes emerged for feasibility ("satisfaction," "intention to continue use," "perceived appropriateness," "positive/negative effects on target participants," "factors affecting implementation ease or difficulty," "adaptations"). The patients reported that both programs were feasible and generally useful. The professionals preferred working with the C-VR, although they disliked the fixed and uniform character of the program. They also mentioned that this program is too extensive for some patients, and that the latter would probably benefit from the LC-VR program. Despite their positive intentions, the managers stated that due to the Dutch healthcare system, implementation of the LC-VR program would be financially unfeasible.Conclusions: The main conclusion of this study is that it is not useful to have one VR program for all patients with CMP and reduced work participation, and that flexible and tailored-based VR are warranted.Implications for rehabilitationBoth comprehensive and less comprehensive vocational rehabilitation are deemed useful for patients with chronic musculoskeletal pain and reduced work participation. Particular patient factors, for instance information uptake, discipline, willingness to change, duration of complaints, movement anxiety, obstructing thoughts, and willingness to return to work might guide the right program for the right patient.Both comprehensive and less comprehensive vocational rehabilitation are deemed feasible in practice. However, factors such as center logistic (schemes, rooms, professionals available) and country-specific healthcare insurance and sickness compensation systems should foster the implementation of less comprehensive programs

Test-Retest Reliability, Agreement and Responsiveness of Productivity Loss (iPCQ-VR) and Healthcare Utilization (TiCP-VR) Questionnaires for Sick Workers with Chronic Musculoskeletal Pain

PurposeThe purpose of this study was to assess test-retest reliability, agreement, and responsiveness of questionnaires on productivity loss (iPCQ-VR) and healthcare utilization (TiCP-VR) for sick-listed workers with chronic musculoskeletal pain who were referred to vocational rehabilitation. Methods Test-retest reliability and agreement was assessed with a 2-week interval. Responsiveness was assessed at discharge after a 15-week vocational rehabilitation (VR) program. Data was obtained from six Dutch VR centers. Test-retest reliability was determined with intraclass correlation coefficient (ICC) and Cohen's kappa. Agreement was determined by Standard Error of Measurement (SEM), smallest detectable changes (on group and individual level), and percentage observed, positive and negative agreement. Responsiveness was determined with area under the curve (AUC) obtained from receiver operation characteristic (ROC). Results A sample of 52 participants on test-retest reliability and agreement, and a sample of 223 on responsiveness were included in the analysis. Productivity loss (iPCQ-VR): ICCs ranged from 0.52 to 0.90, kappa ranged from 0.42 to 0.96, and AUC ranged from 0.55 to 0.86. Healthcare utilization (TiCP-VR): ICC was 0.81, and kappa values of the single healthcare utilization items ranged from 0.11 to 1.00. Conclusions The iPCQ-VR showed good measurement properties on working status, number of hours working per week and long-term sick leave, and low measurement properties on short-term sick leave and presenteeism. The TiCP-VR showed adequate reliability on all healthcare utilization items together and medication use, but showed low measurement properties on the single healthcare utilization items

Chemical fingerprints of emotional body odor

Chemical communication is common among animals. In humans, the chemical basis of social communication has remained a black box, despite psychological and neural research showing distinctive physiological, behavioral, and neural consequences of body odors emitted during emotional states like fear and happiness. We used a multidisciplinary approach to examine whether molecular cues could be associated with an emotional state in the emitter. Our research revealed that the volatile molecules transmitting different emotions to perceivers also have objectively different chemical properties. Chemical analysis of underarm sweat collected from the same donors in fearful, happy, and emotionally neutral states was conducted using untargeted two-dimensional (GC×GC) coupled with time of flight (ToF) MS-based profiling. Based on the multivariate statistical analyses, we find that the pattern of chemical volatiles (N = 1655 peaks) associated with fearful state is clearly different from that associated with (pleasant) neutral state. Happy sweat is also significantly different from the other states, chemically, but shows a bipolar pattern of overlap with fearful as well as neutral state. Candidate chemical classes associated with emotional and neutral sweat have been identified, specifically, linear aldehydes, ketones, esters, and cyclic molecules (5 rings). This research constitutes a first step toward identifying the chemical fingerprints of emotion.info:eu-repo/semantics/publishedVersio

Local CD4 and CD8 T-Cell Reactivity to HSV-1 Antigens Documents Broad Viral Protein Expression and Immune Competence in Latently Infected Human Trigeminal Ganglia

Herpes simplex virus type 1 (HSV-1) infection results in lifelong chronic infection of trigeminal ganglion (TG) neurons, also referred to as neuronal HSV-1 latency, with periodic reactivation leading to recrudescent herpetic disease in some persons. HSV-1 proteins are expressed in a temporally coordinated fashion during lytic infection, but their expression pattern during latent infection is largely unknown. Selective retention of HSV-1 reactive T-cells in human TG suggests their role in controlling reactivation by recognizing locally expressed HSV-1 proteins. We characterized the HSV-1 proteins recognized by virus-specific CD4 and CD8 T-cells recovered from human HSV-1-infected TG. T-cell clusters, consisting of both CD4 and CD8 T-cells, surrounded neurons and expressed mRNAs and proteins consistent with in situ antigen recognition and antiviral function. HSV-1 proteome-wide scans revealed that intra-TG T-cell responses included both CD4 and CD8 T-cells directed to one to three HSV-1 proteins per person. HSV-1 protein ICP6 was targeted by CD8 T-cells in 4 of 8 HLA-discordant donors. In situ tetramer staining demonstrated HSV-1-specific CD8 T-cells juxtaposed to TG neurons. Intra-TG retention of virus-specific CD4 T-cells, validated to the HSV-1 peptide level, implies trafficking of viral proteins from neurons to HLA class II-expressing non-neuronal cells for antigen presentation. The diversity of viral proteins targeted by TG T-cells across all kinetic and functional classes of viral proteins suggests broad HSV-1 protein expression, and viral antigen processing and presentation, in latently infected human TG. Collectively, the human TG represents an immunocompetent environment for both CD4 and CD8 T-cell recognition of HSV-1 proteins expressed during latent infection. HSV-1 proteins recognized by TG-resident T-cells, particularly ICP6 and VP16, are potential HSV-1 vaccine candidates

Clinical impact of HLA class I expression in rectal cancer

Contains fulltext : 69499.pdf (publisher's version ) (Open Access)PURPOSE: To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. EXPERIMENTAL DESIGN: Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10). RESULTS: Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with < or =50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival. CONCLUSIONS: Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient's prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed