The anatomical and cellular basis of immune surveillance in the central nervous system

The central nervous system (CNS) comprises the brain, spinal cord, optic nerves and retina, and contains post-mitotic, delicate cells. As the rigid coverings of the CNS render swelling dangerous and destructive, inflammatory reactions must be carefully controlled in CNS tissues. Nevertheless, effector immune responses that protect the host during CNS infection still occur in the CNS. Here, we describe the anatomical and cellular basis of immune surveillance in the CNS, and explain how this shapes the unique immunology of these tissues. The Review focuses principally on insights gained from the study of autoimmune responses in the CNS and to a lesser extent on models of infectious disease. Furthermore, we propose a new model to explain how antigen-specific T cell responses occur in the CNS.

Diseases in neonatal foals. Part 2: potential risk factors for a higher incidence of infectious diseases during the first 30 days post partum

REASON FOR PERFORMING STUDY: The development of clinical illness in foals is usually predetermined by perinatal history, management or stressful environmental conditions. OBJECTIVES: To determine potential risk factors for an increased incidence of infectious diseases during the first 30 days post partum. METHODS: The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). They were followed for their first 30 days. Factors suspected to influence the incidence of infectious neonatal diseases were examined in a logistic regression approach for each of the 3 outcomes (total infectious diseases, systemic disease with diarrhoea and total infectious diseases excluding diarrhoea). All 28 factors were either foal or mare or stud farm related. RESULTS: Several significant risk factors for a higher disease incidence, such as birth complications, colostrum intake by stomach tube and leucocytosis 12-48 h post partum were identified. The factor 'boarding stud' seemed to be protective against disease. CONCLUSION: Some factors, such as the mare's time at stud before foaling, the mare's rotavirus vaccination schedule and fibrinogen-values that empirically had been linked to the outcome previously were not confirmed as relevant. This included the reported useful prophylactic treatment with antimicrobial drugs. POTENTIAL RELEVANCE: Factors to be considered when evaluating newborn foals include: stud management, the birth process, route of colostrum intake, white and red blood cells, and the date of birth. These may help to detect foals at risk to develop an infection so that targeted prophylactic measures can be initiated.

Laribacter hongkongensis: a potential cause of infectious diarrhea

In this study, we describe the isolation of Laribacter hongkongensis, a recently described genus and species of bacterium, in pure culture on charcoal cefoperazone deoxycholate agar from the stool of six patients with diarrhea. Three patients were residents of Hong Kong, and three of Switzerland. In none of the stool samples obtained from these six patients was Salmonella, Shigella, enterohemorrhagic Escherichia coli, Vibrio, Aeromonas, Plesiomonas, or Campylobacter recovered. Rotavirus antigen detection, electron microscopic examination for viruses, and microscopic examinations for ova and cysts were all negative for the stool samples obtained from the three patients in Hong Kong. Enterotoxigenic E. coli was recovered from one of the patients in Hong Kong. Unlike L. hongkongensis type strain HKU1, all the six strains were motile with bipolar flagellae. Sequencing of the 16S ribosomal RNA genes of the six strains showed that they all had sequences with only 0-2 base differences to that of the type strain. Pulsed field gel electrophoresis of the SpeI digested genomic DNA of the six isolates and that of the type strain revealed that the seven isolates were genotypically unrelated strains. More extensive epidemiologic studies should be carried out to ascertain the causative association between L. hongkongensis and diarrhea and to define the reservoir and modes of transmission of L. hongkongensis.

Is the development of infectious keratoconjunctivitis in Alpine ibex and Alpine chamois influenced by topographic features?

Infectious keratoconjunctivitis (IKC) caused by Mycoplasma conjunctivae is a widespread ocular affection of free-ranging Caprinae in the Alpine arc. Along with host and pathogen characteristics, it has been hypothesized that environmental factors such as UV light are involved in the onset and course of the disease. This study aimed at evaluating the role of topographic features as predisposing or aggravating factors for IKC in Alpine chamois (Rupicapra rupicapra rupicapra) and Alpine ibex (Capra ibex ibex). Geospatial analysis was performed to assess the effect of aspect (northness) and elevation on the severity of the disease as well as on the mycoplasmal load in the eyes of affected animals, using data from 723 ibex and chamois (583 healthy animals, 105 IKC-affected animals, and 35 asymptomatic carriers of M. conjunctivae), all sampled in the Swiss Alps between 2008 and 2010. An influence of northness was not found, except that ibex with moderate and severe signs of IKC seem to prefer more north-oriented slopes than individuals without corneal lesions, possibly hinting at a sunlight sensitivity consequent to the disease. In contrast, results suggest that elevation influences the disease course in both ibex and chamois, which could be due to altitude-associated environmental conditions such as UV radiation, cold, and dryness. The results of this study support the hypothesis that environmental factors may play a role in the pathogenesis of IKC.

Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID): an extension of the STROBE statement

Molecular data are now widely used in epidemiological studies to investigate the transmission, distribution, biology, and diversity of pathogens. Our objective was to establish recommendations to support good scientific reporting of molecular epidemiological studies to encourage authors to consider specific threats to valid inference. The statement Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) builds upon the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. The STROME-ID statement was developed by a working group of epidemiologists, statisticians, bioinformaticians, virologists, and microbiologists with expertise in control of infection and communicable diseases. The statement focuses on issues relating to the reporting of epidemiological studies of infectious diseases using molecular data that were not addressed by STROBE. STROME-ID addresses terminology, measures of genetic diversity within pathogen populations, laboratory methods, sample collection, use of molecular markers, molecular clocks, timeframe, multiple-strain infections, non-independence of infectious-disease data, missing data, ascertainment bias, consistency between molecular and epidemiological data, and ethical considerations with respect to infectious-disease research. In total, 20 items were added to the 22 item STROBE checklist. When used, the STROME-ID recommendations should advance the quality and transparency of scientific reporting, with clear benefits for evidence reviews and health-policy decision making.

Outpatient Parenteral Antimicrobial Therapy Practices among Adult Infectious Disease Physicians

Objective. To identify current outpatient parenteral antibiotic therapy practice patterns and complications. Methods. We administered an 11-question survey to adult infectious disease physicians participating in the Emerging Infections Network (EIN), a Centers for Disease Control and Prevention-sponsored sentinel event surveillance network in North America. The survey was distributed electronically or via facsimile in November and December 2012. Respondent demographic characteristics were obtained from EIN enrollment data. Results. Overall, 555 (44.6%) of EIN members responded to the survey, with 450 (81%) indicating that they treated 1 or more patients with outpatient parenteral antimicrobial therapy (OPAT) during an average month. Infectious diseases consultation was reported to be required for a patient to be discharged with OPAT by 99 respondents (22%). Inpatient (282 [63%] of 449) and outpatient (232 [52%] of 449) infectious diseases physicians were frequently identified as being responsible for monitoring laboratory results. Only 26% (118 of 448) had dedicated OPAT teams at their clinical site. Few infectious diseases physicians have systems to track errors, adverse events, or "near misses" associated with OPAT (97 [22%] of 449). OPAT-associated complications were perceived to be rare. Among respondents, 80% reported line occlusion or clotting as the most common complication (occurring in 6% of patients or more), followed by nephrotoxicity and rash (each reported by 61%). Weekly laboratory monitoring of patients who received vancomycin was reported by 77% of respondents (343 of 445), whereas 19% of respondents (84 of 445) reported twice weekly laboratory monitoring for these patients. Conclusions. Although use of OPAT is common, there is significant variation in practice patterns. More uniform OPAT practices may enhance patient safety.

Influence of polyvascular disease on cardiovascular event rates. Insights from the REACH Registry

Cardiovascular event rates have been shown to increase substantially with the number of symptomatic disease locations. We sought to assess the risk profile, management and subsequent event rates of polyvascular disease patients. Consecutive outpatients were assessed for atherosclerotic risk factors and medications in the REACH Registry. A total of 19,117 symptomatic patients in Europe completed a 2-year follow-up: 77.2% with single arterial bed disease (coronary artery or cerebrovascular or peripheral arterial disease) and 22.8% with polyvascular disease (>/= 1 disease location). Polyvascular disease patients were older (68.5 +/- 9.4 vs 66.3 +/- 9.9 years, p < 0.0001), more often current or former smokers (64.9% vs 58.7%, p < 0.0001), and more often suffered from hypertension (59.5% vs 46.6%, p < 0.0001) and diabetes (34.5% vs 25.9%, p < 0.0001) than single arterial bed disease patients. Despite more intense medical therapy, risk factors (smoking, hypertension, low fasting glucose, and low fasting total cholesterol) were less often controlled in polyvascular disease patients. This was associated with substantially more events over 2 years compared with single arterial bed disease patients (cMACCE [cardiovascular death/non-fatal stroke/non-fatal MI] odds ratio, 1.63 [95% CI, 1.45-1.83], p < 0.0001). In conclusion, polyvascular disease patients have more cardiovascular risk factors, and the prognosis for these patients is significantly worse than for patients with single arterial bed disease. This suggests a need to improve detection and consequent medical treatment of polyvascular disease.

Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study

We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5-1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese.

Prognostic value of microvascular invasion in predicting the cancer specific survival and risk of metastatic disease in renal cell carcinoma: a multicenter investigation

While microvascular invasion is an accepted risk factor in various cancers, its prognostic role in renal cell carcinoma is still unclear. Therefore, a large multicenter study examining the experience of 5 international institutions was performed to evaluate the prognostic value of microvascular invasion in the occurrence of metastases and cancer specific survival.

A Comparison of Psychosocial Risk Factors Between 3 Groups of Cardiovascular Disease Patients Referred for Outpatient Cardiac Rehabilitation

Few studies have examined psychosocial risk factors for cardiovascular disease (CVD) between diagnostic groups of CVD patients. We compared levels of depression, anxiety, hostility, exhaustion, positive affect, and social support, and the prevalence of type D personality between patient groups with a primary diagnosis of coronary heart disease (CHD), chronic heart failure (CHF), or peripheral arterial disease (PAD).

Zurich Fabry study - prevalence of Fabry disease in young patients with first cryptogenic ischaemic stroke or TIA

BACKGROUND AND PURPOSE: The etiology of stroke in young patients remains undetermined in up to half of the cases. Data on prevalence of Fabry disease (FD) in young people with cryptogenic ischaemic stroke are limited and controversial. We aimed to evaluate the frequency of unrecognized FD in a cohort of stroke patients at a tertiary stroke center. METHODS: Patients suffering from first cryptogenic ischaemic stroke or transient ischaemic attack (TIA) at the age of 18-55 years were screened for the presence of FD. We measured the serum activity of α-galactosidase (α-GAL) in all patients. In addition, sequencing of α-GAL gene was performed in men with low enzyme activity and in all women. RESULTS: Between January, 2006, and October, 2009, we recruited 150 patients (102 men, 48 women) with a mean age of 43 ± 9 years at symptom onset (135 ischaemic stroke, 15 TIA). The α-GAL activity was low in nine patients (6%; six men and three women). Genetic sequencing in six men with low enzyme activity and all 48 women detected no α-GAL gene mutation. CONCLUSION: Our study suggests that the yield of screening for FD in patients with first cryptogenic ischaemic stroke or TIA is very low. Further large-scale studies are needed to investigate the importance of FD amongst patients with recurrent cryptogenic strokes.

Owner assessment in judging the efficacy of airway disease treatment

REASONS FOR PERFORMING STUDY: Efficacy of medications for recurrent airway obstruction is typically tested using clinical, cytological and lung function examinations of severely affected animals. These trials are technically challenging and may not adequately reflect the spectrum of disease and owner complaints encountered in clinical practice. OBJECTIVE: To determine if owners of horses with chronic airway disease are better able to detect drug efficacy than a veterinarian who clinically examines horses infrequently. METHOD: In a double-blinded randomised controlled trial, owners and a veterinarian compared the efficacy of dexamethasone (0.1 mg/kg bwt per os, q. 24 h, for 3 weeks; n = 9) to placebo (n = 8) in horses with chronic airway disease. Before and after treatment, owners scored performance, breathing effort, coughing and nasal discharge using a visual analogue scale (VAS). The clinician recorded vital parameters, respiratory distress, auscultation findings, cough and nasal discharge, airway mucus score, bronchoalveolar lavage fluid (BALF) cytology and arterial blood gases. RESULTS: The VAS score improved significantly in dexamethasone- but not placebo-treated horses. In contrast, the clinician failed to differentiate between dexamethasone- and placebo-treated animals based on clinical observations, BALF cytology or endoscopic mucus score. Respiratory rate (RR) and arterial oxygen pressure (PaO(2)) improved with dexamethasone but not placebo. CONCLUSIONS AND CLINICAL RELEVANCE: In the design of clinical trials of airway disease treatments, more emphasis should be placed on owner-assessed VAS than on clinical, cytological and endoscopic observations made during brief examinations by a veterinarian. Quantifiable indicators reflecting lung function such as RR and PaO(2) provide a good assessment of drug efficacy.

Safe high-pressure freezing of infectious micro-organisms

We describe how high-pressure freezing of infectious biological material can safely be accomplished with the help of membrane carriers. The method described is easy to perform; however, careful manipulations are required. Existing safety regulations must still be followed. However, the procedure reduces the risk of dissemination of infectious material.