Toll‐Like Receptor 3 and 7/8 Function Is Impaired in Hepatitis C Rapid Fibrosis Progression Post‐Liver Transplantation

Recurrence of hepatitis C (HCV) postliver transplant is universal, with a subgroup developing rapid hepatic fibrosis. Toll‐like receptors (TLRs) are critical to innate antiviral responses and HCV alters TLR function to evade immune clearance. Whether TLRs play a role in rapid HCV recurrence posttransplant is unknown. We stimulated peripheral blood mononuclear cells (PBMCs) from 70 patients with HCV postliver transplant with TLR subclass‐specific ligands and measured cytokine production, TLR expression and NK cell function. Rate of fibrosis progression was calculated using posttransplant liver biopsies graded by Metavir scoring (F0–4; R = fibrosis stage/year posttransplant; rapid fibrosis defined as >0.4 units/year). Thirty of 70 (43%) patients had rapid fibrosis progression. PBMCs from HCV rapid‐fibrosers produced less IFNα with TLR7/8 stimulation (p = 0.039), less IL‐6 at baseline (p = 0.027) and with TLR3 stimulation (p = 0.008) and had lower TLR3‐mediated monocyte IL‐6 production (p = 0.028) compared with HCV slow fibrosers. TLR7/8‐mediated NKCD56 dim cell secretion of IFNγ was impaired in HCV rapid fibrosis (p = 0.006) independently of IFNα secretion and TLR7/8 expression, while cytotoxicity remained preserved. Impaired TLR3 and TLR7/8‐mediated cytokine responses may contribute to aggressive HCV recurrence postliver transplantation through impaired immune control of HCV and subsequent activation of fibrogenesis.     

Can a Specific Neck Strengthening Program Decrease Cervical Spine Injuries in a Men's Professional Rugby Union Team? A Retrospective Analysis

Cervical spine injuries in Rugby Union are a concerning issue at all levels of the game. The primary aim of this retrospective analysis conducted in a professional Rugby Union squad was to determine whether a 26-week isometric neck strengthening intervention program (13-week strengthening phase and 13-week maintenance phase) was effective in reducing the number and severity of cervical spine injuries. The secondary aim was to determine whether at week five, where the program had been the similar for all players, there was increased isometric neck strength. All 27 players who were common to both the 2007-2008 and 2008-2009 seasons were included in this analysis and data was extracted from a Sports Medicine/Sports Science database which included the squad''s injury records. Primary outcome variables included; the number of cervical spine injuries and the severity of these injuries as determined by the total number of days lost from training and competition. Secondary outcome variables included isometric neck strength in flexion, extension and left and right lateral flexion. Using non-parametric statistical methods, no significant differences were evident for the total number of cervical spine injuries (n = 8 in 2007-2008, n = 6 in 2008-2009) or time loss due to these injuries (100 days in 2007-2008, 40 days in 2008-2009). However, a significant (p = 0.03) reduction in the number of match injuries was evident from 2007-2008 (n = 11) to 2008-09 (n = 2). Non-significant increases in isometric neck strength were found in all directions examined. A significant reduction in the number of match injuries was evident in this study. However, no other significant changes to primary outcome variables were achieved. Further, no significant increases in isometric neck strength were found in this well-trained group of professional athletes.

Key Points

• While many authors have proposed that neck strengthening could be an effective strategy in preventing cervical spine injuries in Rugby Union, there is currently little information in the literature pertaining to how such a study might be conducted.
• A significant decrease in the number of injuries recorded in matches can be achieved using a specific neck strengthening program at the elite level.
• In an elite rugby union team as investigated in this study a significant increase in neck strength is difficult to achieve in a short period of time such as five weeks.

Key words: Rugby Union, cervical spine, injury, isometric, neck strength     

Genomic and proteomic expression analysis of Leishmania promastigote and amastigote life stages: the Leishmania genome is constitutively expressed

Leishmania are protozoan parasites that cause a wide spectrum of clinical diseases in humans and are a major public health risk in several countries. Leishmania life cycle consists of an extracellular flagellated promastigote stage within the midgut of a sandfly vector, and a morphological distinct intracellular amastigote stage within macrophages of a mammalian host. This study reports the use of DNA oligonucleotide genome microarrays representing 8160 genes to analyze the mRNA expression profiles of L. major promastigotes and lesion derived amastigotes. Over 94% of the genes were expressed in both life stages. Advanced statistical analysis identified a surprisingly low degree of differential mRNA expression: 1.4% of the total genes in amastigotes and 1.5% in promastigotes. These microarray results demonstrate that the L. major genome is essentially constitutively expressed in both life stages and suggest that Leishmania is constitutively adapted for survival and replication in either the sandfly vector or macrophage host utilizing an appropriate set of genes for each vastly different environment. Quantitative proteomics, using the isotope coded affinity tag (ICAT) technology and mass spectrometry, was used to identify L. infantum promastigote and axenic amastigote differentially expressed proteins. Of the 91 distinct proteins identified, 8% were differentially expressed in the amastigote stage, 20% were differentially expressed in the promastigote stage, and the remaining 72% were considered constitutively expressed. The differential expression was validated by the identification of previously reported stage specific proteins and identified several amastigote and promastigote novel stage specific proteins.     

Development of Stabilizing Formulations of a Trivalent Inactivated Poliovirus Vaccine in a Dried State for Delivery in the Nanopatch™ Microprojection Array

The worldwide switch to inactivated polio vaccines (IPVs) is a key component of the overall strategy to achieve and maintain global polio eradication. To this end, new IPV vaccine delivery systems may enhance patient convenience and compliance. In this work, we examine Nanopatch? (a solid, polymer microprojection array) which offers potential advantages over standard needle/syringe administration including intradermal delivery and reduced antigen doses. Using trivalent IPV (tIPV) and a purpose-built evaporative dry-down system, candidate tIPV formulations were developed to stabilize tIPV during the drying process and on storage. Identifying conditions to minimize tIPV potency losses during rehydration and potency testing was a critical first step. Various classes and types of pharmaceutical excipients (～50 total) were then evaluated to mitigate potency losses (measured through D-antigen ELISAs for IPV1, IPV2, and IPV3) during drying and storage. Various concentrations and combinations of stabilizing additives were optimized in terms of tIPV potency retention, and 2 candidate tIPV formulations containing cyclodextrin and a reducing agent (e.g., glutathione), maintained ≥80% D-antigen potency during drying and subsequent storage for 4 weeks at 4°C, and ≥60% potency for 3 weeks at room temperature with the majority of losses occurring within the first day of storage.     

National estimates of severe sepsis in United States emergency departments

OBJECTIVE: The emergency department (ED) often serves as the first site for the recognition and treatment of patients with suspected severe sepsis. However, few evaluations of the national epidemiology and distribution of severe sepsis in the ED exist. We sought to determine national estimates of the number, timing, ED length of stay, and case distribution of patients presenting to the ED with suspected severe sepsis. DESIGN: Analysis of 2001-2004 ED data from the National Hospital Ambulatory Medical Care Survey. SETTING: National multistage probability sample of United States ED data. PATIENTS: Adult (age, >or=18 yrs) patients with suspected severe sepsis, defined as the concurrent presence of an infec-tion (ED International Classification of Diseases, 9th Revision; ICD-9) diagnosis of infection, or a triage temperature <96.8 degrees F or >or=100.4 degrees F) and organ dysfunction (ED ICD-9) diagnosis of organ dysfunction, intubation, or a triage systolic blood pressure 6 hrs in the ED. Of suspected severe sepsis patients, 20.6% presented to a low-volume ED (相似文献   

The placement of osseointegrated dental implants in a patient with type IV B osteogenesis imperfecta: a 9-year follow-up

Osteogenesis imperfecta (OI) is a rare autosomal dominant connective tissue and metabolic disorder. Typically, patients with OI exhibit bone fragility, with the sclera, joints, skin, and tooth dentin being affected to varying degrees. Despite existing classifications, there is an extreme phenotypic variation within this population, and at times the mild forms of OI may be difficult to diagnose. Comprehensive management of the severe types of OI involves aggressive physical and surgical orthopaedic treatment to improve muscle structure and joint mobility. For those patients with associated dentinogenesis imperfecta (DI), early and definitive management can help prevent excessive tooth wear and sensitivity. A case of a late diagnosis of type IV OI with DI successfully treated with implant-supported dentures is reported. To date, 9 years after implant surgery and prosthetic loading, the patient continues to be clinically and radiographically normal.     

An OxPLORE Initiative Evaluating Children’s Surgery Resources Worldwide: A Cross-sectional Implementation of the OReCS Document

World Journal of Surgery - The Global Initiative for Children's Surgery (GICS) group produced the Optimal Resources for Children’s Surgery (OReCS) document in 2019, listing standards of...