Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide

Background  

Insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex.     

Low penetrance of a SDHB mutation in a large Dutch paraganglioma family

Background

The role of the innate immune protein mannose-binding lectin (MBL) in host defence against severe respiratory infection remains controversial. Thoracic empyema is a suppurative lung infection that arises as a major complication of pneumonia and is associated with a significant mortality. Although the pathogenesis of thoracic empyema is poorly understood, genetic susceptibility loci for this condition have recently been identified. The possible role of MBL genotypic deficiency in susceptibility to thoracic empyema has not previously been reported.

Methods

To investigate this further we compared the frequencies of the six functional MBL polymorphisms in 170 European individuals with thoracic empyema and 225 healthy control individuals.

Results

No overall association was observed between MBL genotypic deficiency and susceptibility to thoracic empyema (2 × 2 Chi square = 0.02, P = 0.87). Furthermore, no association was seen between MBL deficiency and susceptibility to the Gram-positive or pneumococcal empyema subgroups. MBL genotypic deficiency did not associate with progression to death or requirement for surgery.

Conclusions

Our results suggest that MBL genotypic deficiency does not associate with susceptibility to thoracic empyema in humans.     

Caractérisation phénotypique et génotypique (randomly amplified polymorphic DNA analysis et multiple-locus variable-number tandem-repeat analysis) de 96 isolats cliniques de Pseudomonas aeruginosa à l’hôpital F. Bourguiba (Monastir,Tunisie)

Aim of the study

Phenotypic and genotypic characterization of 96 clinical isolates of Pseudomonas aeruginosa recovered in a Tunisian teaching hospital during a 16-month period.

Materials and methods

All the isolates were characterized by serotyping, antimicrobial susceptibility typing and genotyping with randomly amplified polymorphic DNA (RAPD) analysis and multiple-locus variable-number tandem-repeat analysis (MLVA).

Results

Forty-one isolates out of 96 (43%) were recovered from two intensive care units (medical and chirurgical). Most of the isolates (48%) belonged to serotype O:11. Among the 13 antibiotypes, three multidrug resistant ones were mostly observed within the two intensive care units. Genotyping showed 83 RAPD types and 52 MLVA types. Isolates showing the same serotype could show different genotypes. A limited number of clusters was highlighted with MLVA typing, of which an outbreak of nine cases within the surgical intensive care unit.

Conclusion

Except this outbreak of nine cases, the heterogeneity observed for most of the P. aeruginosa isolates showed that outbreak situations were rare in the F. Bourguiba hospital during the study period. MLVA genotyping is a good tool for genotyping P. aeruginosa clinical isolates.     

Different levels of humoral immunoreactivity to different wheat cultivars gliadin are present in patients with celiac disease and in patients with multiple myeloma

Background

Extensive allelic matching in the human leukocyte antigen (HLA) genes is regarded as a prerequisite for good clinical success of allogeneic haematopoietic stem cell transplantation (HSCT). Also other genetic factors can be assumed to play a role in preventing and controlling the complications associated with allogeneic HSCT, in particular graft-versus-host disease (GvHD). Interleukin-10 (IL-10) and its receptor (IL-10R), key regulators of the immune response, are among these candidates. We studied the association of IL-10 and IL-10Rβ gene polymorphisms with the occurrence of GvHD in 309 HLA-identical sibling donor and recipient pairs.

Results

The difference in genotypic IL-10 production between patient and donor in combination with patient IL-10Rβ A/A genotype predisposed strongly to acute GvHD (OR = 7.15, p = 0.000023). On the other hand, a combination of same genotypic IL-10 production with patient IL-10Rβ A/A genotype protected from chronic GvHD (OR = 0.407, p = 0.0097).

Conclusion

Our results suggest that IL-10 and IL-10Rβ genes have a synergistic effect on the risk of GvHD.     

Performance of statistical models to predict mental health and substance abuse cost

Background  

Providers use risk-adjustment systems to help manage healthcare costs. Typically, ordinary least squares (OLS) models on either untransformed or log-transformed cost are used. We examine the predictive ability of several statistical models, demonstrate how model choice depends on the goal for the predictive model, and examine whether building models on samples of the data affects model choice.     

B-Cell Reconstitution and BAFF After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis

Introduction  

Treatment with alemtuzumab is highly effective in relapsing–remitting multiple sclerosis; however, 30% of patients develop autoimmunity. Alemtuzumab (previously called Campath 1-H) induces a prolonged T-cell lymphopenia with memory cells dominating the reconstituting T-cell pool for at least 3 months.     

Entecavir plus tenofovir versus entecavir plus adefovir in chronic hepatitis B patients with a suboptimal response to lamivudine and adefovir combination therapy

Background/Aims

We compared the efficacies of entecavir (ETV) plus tenofovir (TDF) and ETV plus adefovir (ADV) in chronic hepatitis B (CHB) patients with genotypic resistance to lamivudine (LAM) who showed a suboptimal response to LAM and ADV combination therapy.

Methods

We reviewed 63 CHB patients with genotypic resistance to LAM who showed a suboptimal response to LAM and ADV combination therapy. Among these patients, 30 were treated with ETV + ADV and 33 were treated with ETV + TDF for 12 months.

Results

The only baseline characteristic that differed significantly between the two groups was the ETV resistance profile. The rate of a virologic response [serum hepatitis B virus (HBV) DNA level of <20 IU/mL] was significant higher for ETV+TDF than for ETV+ADV over 12 months (57.6% vs. 23.3%, P=0.006, at 6 months; 84.8% vs. 26.7%, P<0.001, at 12 months). The probability of a virologic response was significantly increased in ETV+TDF (P<0.001, OR=54.78, 95% CI=7.15-419.54) and decreased in patients with higher baseline viral loads (P=0.001, OR=0.18, 95% CI=0.07-0.50) in multivariate analysis. No serious adverse event occurred during the study period.

Conclusions

In patients with CHB who showed a suboptimal response to LAM and ADV combination therapy, ETV+TDF was superior to ETV+ADV in achieving a virologic response regardless of the HBV resistance profile. Further large-scale and long-term follow-up prospective studies are needed to explain these results.     

Continuing medical education challenges in chronic fatigue syndrome

Background  

Chronic fatigue syndrome (CFS) affects at least 4 million people in the United States, yet only 16% of people with CFS have received a diagnosis or medical care for their illness. Educating health care professionals about the diagnosis and management of CFS may help to reduce population morbidity associated with CFS.     

Maximising response to postal questionnaires – A systematic review of randomised trials in health research

Background  

Postal self-completion questionnaires offer one of the least expensive modes of collecting patient based outcomes in health care research. The purpose of this review is to assess the efficacy of methods of increasing response to postal questionnaires in health care studies on patient populations.     

Testing for hereditary thrombophilia: a retrospective analysis of testing referred to a national laboratory

Background  

Predisposition to venous thrombosis may be assessed through testing for defects and/or deficiencies of a number of hereditary factors. There is potential for confusion about which of these tests are appropriate in which settings. At least one set of recommendations has been published to guide such testing, but it is unclear how widely these have been disseminated.     

Previously described sequence variant in <Emphasis Type="Italic">CDK5RAP2</Emphasis>gene in a Pakistani family with autosomal recessive primary microcephaly

Background  

Autosomal Recessive Primary Microcephaly (MCPH) is a disorder of neurogenic mitosis. MCPH leads to reduced cerebral cortical volume and hence, reduced head circumference associated with mental retardation of variable degree. Genetic heterogeneity is well documented in patients with MCPH with six loci known, while pathogenic sequence variants in four respective genes have been identified so far. Mutations in CDK5RAP2 gene at MCPH3 locus have been least involved in causing MCPH phenotype.     

Lasso regularization for left-censored Gaussian outcome and high-dimensional predictors

Background

Biological assays for the quantification of markers may suffer from a lack of sensitivity and thus from an analytical detection limit. This is the case of human immunodeficiency virus (HIV) viral load. Below this threshold the exact value is unknown and values are consequently left-censored. Statistical methods have been proposed to deal with left-censoring but few are adapted in the context of high-dimensional data.

Methods

We propose to reverse the Buckley-James least squares algorithm to handle left-censored data enhanced with a Lasso regularization to accommodate high-dimensional predictors. We present a Lasso-regularized Buckley-James least squares method with both non-parametric imputation using Kaplan-Meier and parametric imputation based on the Gaussian distribution, which is typically assumed for HIV viral load data after logarithmic transformation. Cross-validation for parameter-tuning is based on an appropriate loss function that takes into account the different contributions of censored and uncensored observations. We specify how these techniques can be easily implemented using available R packages. The Lasso-regularized Buckley-James least square method was compared to simple imputation strategies to predict the response to antiretroviral therapy measured by HIV viral load according to the HIV genotypic mutations. We used a dataset composed of several clinical trials and cohorts from the Forum for Collaborative HIV Research (HIV Med. 2008;7:27-40). The proposed methods were also assessed on simulated data mimicking the observed data.

Results

Approaches accounting for left-censoring outperformed simple imputation methods in a high-dimensional setting. The Gaussian Buckley-James method with cross-validation based on the appropriate loss function showed the lowest prediction error on simulated data and, using real data, the most valid results according to the current literature on HIV mutations.

Conclusions

The proposed approach deals with high-dimensional predictors and left-censored outcomes and has shown its interest for predicting HIV viral load according to HIV mutations.

     

Motor function in Parkinson's disease and supranuclear palsy: simultaneous factor analysis of a clinical scale in several populations

Background  

In order to better understand the similarities and differences in the motor behaviour of different groups of patients, their scores on the Motor Examination section of the Unified Parkinson's Disease Rating Scale (UPDRS) were analysed simultaneously. The three groups consisted, respectively, of patients with Parkinson's disease (PD) on medication, patients with Parkinson's disease withdrawn from anti-parkinsonian medication for at least 12 hours, and patients diagnosed with a specific Parkinsonism syndrome: Progressive Supranuclear Palsy (PSP).     

Utility of temporal self-regulation theory in health and social behaviours: A meta-analysis

Purpose

Temporal self-regulation theory was developed to address an observed intention-behaviour gap across behaviours. However, a synthesis of studies has not yet been conducted to investigate the theory's utility to explain behaviour and bridge the intention-behaviour gap. This review aimed to evaluate the predictive ability of temporal self-regulation theory to understanding behaviour and pre-registered at PROSPERO (ID: CRD42021253174).

Method

Forward citation searches on the original theory publication through Google Scholar until May 2021 identified 37 eligible articles, including, 12,555 participants assessing at least two of the three theory constructs. Random-effects meta-analyses assessed the strength of associations between theory constructs on behaviour and random effects meta-regressions assessed moderators of behaviour.

Results

Findings provide support for temporal self-regulation theory to explain behaviour with very weak (self-regulatory capacity r = .039, CI = .00, –.07) to moderate (intention r = .331, CI = .26, .40; behavioural pre-potency r = .379, CI = .32, .44) effect sizes. Further, the strength of associations varied across behaviour types and contexts. However, there was high heterogeneity across studies and some moderating effects could not be assessed due to insufficient numbers of studies assessing interactions.

Conclusions

We urge researchers to assess and report interactions for better understanding of the drivers of behaviour to develop effective interventions for positive behaviour change.     

The obligation of physicians to medical outliers: a Kantian and Hegelian synthesis

Background  

Patients who present to medical practices without health insurance or with serious co-morbidities can become fiscal disasters to those who care for them. Their consumption of scarce resources has caused consternation among providers and institutions, especially as it concerns the amount and type of care they should receive. In fact, some providers may try to avoid caring for them altogether, or at least try to limit their institutional or practice exposure to them.     

Interactions between the <Emphasis Type="Italic">adducin 2</Emphasis>gene and antihypertensive drug therapies in determining blood pressure in people with hypertension

Background  

As part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy (GENOA) recruited 575 sibships (n = 1583 individuals) from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms (SNPs) typed in 7 positional candidate genes, including adducin 2 (ADD2).     

<Emphasis Type="Italic">MRPS18CP2</Emphasis> alleles and <Emphasis Type="Italic">DEFA3</Emphasis>absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene

Background  

Mitochondrial DNA (mtDNA) mutations account for at least 5% of cases of postlingual, nonsyndromic hearing impairment. Among them, mutation A1555G is frequently found associated with aminoglycoside-induced and/or nonsyndromic hearing loss in families presenting with extremely variable clinical phenotypes. Biochemical and genetic data have suggested that nuclear background is the main factor involved in modulating the phenotypic expression of mutation A1555G. However, although a major nuclear modifying locus was located on chromosome 8p23.1 and regardless intensive screening of the region, the gene involved has not been identified.     

Routine resite of peripheral intravenous devices every 3 days did not reduce complications compared with clinically indicated resite: a randomised controlled trial

Background  

Peripheral intravenous device (IVD) complications were traditionally thought to be reduced by limiting dwell time. Current recommendations are to resite IVDs by 96 hours with the exception of children and patients with poor veins. Recent evidence suggests routine resite is unnecessary, at least if devices are inserted by a specialised IV team. The aim of this study was to compare the impact of peripheral IVD 'routine resite' with 'removal on clinical indication' on IVD complications in a general hospital without an IV team.     

The Cognitive and Behavioural Responses to Symptoms Questionnaire (CBRQ): Development,reliability and validity across several long-term conditions

Objectives

Cognitive and behavioural responses to symptoms can worsen or maintain the severity of symptoms across long-term conditions (LTCs). Although the Cognitive and Behavioural Responses Questionnaire (CBRQ) has been used in research, its original development and psychometric properties as a transdiagnostic measure have not been reported. Our aim was to evaluate the psychometric properties of the CBRQ and a recently proposed short version, across different LTCs.

Design

Psychometric validation study.

Methods

Confirmatory factor analysis (CFA) tested the factor structure of the CBRQ in two datasets from the CBRQ's original development; (chronic fatigue syndrome, N = 230; and multiple sclerosis, N = 221) and in additional groups: haemodialysis (N = 174), inflammatory bowel disease (N = 182) and chronic dizziness (N = 185). Scale reliability and construct validity were assessed. The factor structure of the shortened CBRQ (CBRQ-SF) was also assessed.

Results

CFA revealed that a 7-or 8-factor structure had generally appropriate fit supporting the originally proposed 7 factors (Fear avoidance, Damage beliefs, Catastrophising, Embarrassment avoidance, Symptom focusing, All-or-nothing behaviour and Avoidance/Resting behaviour). Omega coefficients indicated satisfactory internal reliability. Correlations with related constructs suggested construct validity. The scale appeared sensitive to change. The CBRQ-SF also displayed good psychometric quality, with a better model fit than the CBRQ.

Conclusions

The CBRQ and the shortened version were shown to be reliable and valid at assessing a range of cognitive and behavioural responses to symptoms, highlighting the multi-symptom, transdiagnostic properties of this questionnaire. Further research is necessary to determine the test–retest reliability and sensitivity to change of the CBRQ and CBRQ-SF and a thorough evaluation of the content validity of the items.     

Multidetector CT imaging of arterial supply to sinuatrial and atrioventricular nodes

Purpose  

The aim of this study is to depict anatomic characteristics of sinuatrial nodal artery (SANA) and atrioventricular nodal artery (AVNA) of the heart with multidetector computed tomography.