Early respiratory viral infections in infants with cystic fibrosis

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood. Methods Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life. Results Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0–10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances. Conclusions Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF

A novel method to analyze leukocyte rolling behavior in vivo

Leukocyte endothelial cell interaction is a fundamentally important process in many disease states. Current methods to analyze such interactions include the parallel-plate flow chamber and intravital microscopy. Here, we present an improvement of the traditional intravital microscopy that allows leukocyte-endothelial cell interaction to be studied from the time the leukocyte makes its initial contact with the endothelium until it adheres to or detaches from the endothelium. The leukocyte is tracked throughout the venular tree with the aid of a motorized stage and the rolling and adhesive behavior is measured off-line. Because this method can involve human error, methods to automate the tracking procedure have been developed. This novel tracking method allows for a more detailed examination of leukocyte-endothelial cell interactions

Arthroscopic treatment of a medial meniscal cyst using a posterior trans-septal approach: a case report

Arthroscopic partial menisectomy followed by cyst decompression is currently recommended for treatment of a meniscal cyst. However, it is doubtful whether partial menisectomy should be performed on cysts communicating with the joint in cases without a meniscal tear on its surface since meniscal function will be sacrificed. In this report, a meniscal cyst arising from the posterior horn of the medial meniscus without meniscal tear on its surface was resected using an arthroscopic posterior trans-septal approach. A 59 year-old male presented to our hospital with popliteal pain when standing up after squatting down. Magnetic resonance imaging revealed a multilobulated meniscal cyst arising from the posterior horn of the medial meniscus extending to the posterior septum with a grade 2 meniscal tear by Mink's classification. The medial meniscus was intact on the surface on arthroscopic examination. The meniscal cyst and posterior septum were successfully resected using a posterior trans-septal approach without harming the meniscus. This is the first report on a meniscal cyst being resected using an arthroscopic posterior trans-septal approach with a 9-month follow-up period

The Be Our Ally Beat Smoking (BOABS) study, a randomised controlled trial of an intensive smoking cessation intervention in a remote aboriginal Australian health care setting

Background: Australian Aboriginal and Torres Strait Islander peoples (Indigenous Australians) smoke at much higher rates than non-Indigenous people and smoking is an important contributor to increased disease, hospital admissions and deaths in Indigenous Australian populations. Smoking cessation programs in Australia have not had the same impact on Indigenous smokers as on non-Indigenous smokers. This paper describes the outcome of a study that aimed to test the efficacy of a locally-tailored, intensive, multidimensional smoking cessation program. Methods: A randomised controlled trial of Aboriginal researcher delivered tailored smoking cessation counselling during face-to-face visits, aiming for weekly for the first four weeks, monthly to six months and two monthly to12 months. The control (“usual care”) group received routine care relating to smoking cessation at their local primary health care service. Data collection occurred at enrolment, six and 12 months. The primary outcome was self-reported smoking cessation with urinary cotinine confirmation at final follow-up (median 13 (interquartile range 12–15) months after enrolment).Results: Participants in the intervention (n = 55) and usual care (n = 108) groups were similar in baseline characteristics, except the intervention group was slightly older. At final follow-up the smoking cessation rate for participants assigned to the intervention group (n = 6; 11%), while not statistically significant, was double that of usual care (n = 5; 5%; p = 0.131). A meta-analysis of these findings and a similarly underpowered but comparable study of pregnant Indigenous Australian women showed that Indigenous Australian participants assigned to the intervention groups were 2.4 times (95% CI, 1.01-5.5) as likely to quit as participants assigned to usual care. Conclusions: Culturally appropriate, multi-dimensional Indigenous quit smoking programs can be successfully implemented in remote primary health care. Intensive one-on-one interventions with substantial involvement from Aboriginal and Torres Strait Islander workers are likely to be effective in these settings. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12608000604303)

Should all acutely ill children in primary care be tested with point-of-care CRP: A cluster randomised trial

Background: Point-of-care blood C-reactive protein (CRP) testing has diagnostic value in helping clinicians rule out the possibility of serious infection. We investigated whether it should be offered to all acutely ill children in primary care or restricted to those identified as at risk on clinical assessment. Methods: Cluster randomised controlled trial involving acutely ill children presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium. Practices were randomised to undertake point-of-care CRP testing in all children (1730 episodes) or restricted to children identified as at clinical risk (1417 episodes). Clinical risk was assessed by a validated clinical decision rule (presence of one of breathlessness, temperature ≥ 40 °C, diarrhoea and age 12-30 months, or clinician concern). The main trial outcome was hospital admission with serious infection within 5 days. No specific guidance was given to GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20, 80 and 200 mg/L. Results: Restricting CRP testing to those identified as at clinical risk substantially reduced the number of children tested by 79.9 % (95 % CI, 77.8-82.0 %). There was no significant difference between arms in the number of children with serious infection who were referred to hospital immediately (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP < 5 mg/L had an illness requiring admission (a child with viral gastroenteritis admitted for rehydration). However, of the 80 children referred to hospital to rule out serious infection, 24 (30.7 %, 95 % CI, 19.6-45.6 %) had a CRP < 5 mg/L. Conclusions: CRP testing should be restricted to children at higher risk after clinical assessment. A CRP < 5 mg/L rules out serious infection and could be used by GPs to avoid unnecessary hospital referrals

Adipocyte mitochondrial genes and the forkhead factor FOXC2 are decreased in type 2 diabetes patients and normalized in response to rosiglitazone

<p>Abstract</p> <p>Background</p> <p>FOXC2 has lately been implicated in diabetes and obesity as well as mitochondrial function and biogenesis and also as a regulator of mtTFA/Tfam. In this study, the expression of FOXC2 and selected genes involved in mitochondrial function and biogenesis in healthy subjects and in a matched cohort with type 2 diabetes patients before and after treatment with rosiglitazone was determined. Quantitative real time PCR was used to analyze both RNA and DNA from biopsies from subcutaneous adipose tissue.</p> <p>Methods</p> <p>Blood samples and subcutaneous abdominal fat biopsies were collected from 12 T2D patients, of which 11 concluded the study, pre-treatment and 90 days after initiation of rosiglitazone treatment, and from 19 healthy control subjects on the first and only visit from healthy subjects. Clinical parameters were measured on the blood samples. RNA and DNA were prepared from the fat biopsies and gene expression was measured with real time PCR.</p> <p>Results</p> <p>The expression level of genes in the mitochondrial respiratory complexes I - IV were significantly downregulated in the diabetic patients and restored in response to rosiglitazone treatment. Rosiglitazone treatment also increased the relative number of mitochondria in diabetic patients compared with controls. Furthermore, the transcription factors FOXC2 and mtTFA/Tfam displayed a response pattern identical to the mitochondrial genes.</p> <p>Conclusions</p> <p>FOXC2, mtTFA/Tfam and subunits of the respiratory complexes I - IV show equivalent regulation in gene expression levels in response to TZD treatment. This, together with the knowledge that FOXC2 has a regulatory function of mtTFA/Tfam and mitochondrial biogenesis, suggests that FOXC2 has a possible functional role in the TZD activated mitochondrial response.</p

Endocrine therapy in epithelial ovarian cancer

INTRODUCTION: The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers. Expert commentary: The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents. The low toxicity profile of these agents is favourable although their use is unlicensed and the optimal setting undefined. Prospective clinical trials of endocrine agents in the early relapse and maintenance settings are urgently required to establish their definitive role in the management of epithelial ovarian cancer

Soil and Cultivar Type Shape the Bacterial Community in the Potato Rhizosphere

The rhizospheres of five different potato cultivars (including a genetically modified cultivar) obtained from a loamy sand soil and two from a sandy peat soil, next to corresponding bulk soils, were studied with respect to their community structures and potential function. For the former analyses, we performed bacterial 16S ribosomal RNA gene-based PCR denaturing gradient gel electrophoresis (PCR-DGGE) on the basis of soil DNA; for the latter, we extracted microbial communities and subjected these to analyses in phenotype arrays (PM1, PM2, and PM4, Biolog), with a focus on the use of different carbon, sulfur and phosphorus sources. In addition, we performed bacterial PCR-DGGE on selected wells to assess the structures of these substrate-responsive communities. Effects of soil type, the rhizosphere, and cultivar on the microbial community structures were clearly observed. Soil type was the most determinative parameter shaping the functional communities, whereas the rhizosphere and cultivar type also exerted an influence. However, no genetically modified plant effect was observed. The effects were imminent based on general community analysis and also single-compound analysis. Utilization of some of the carbon and sulfur sources was specific per cultivar, and different microbial communities were found as defined by cultivar. Thus, both soil and cultivar type shaped the potato root-associated bacterial communities that were responsive to some of the substrates in phenotype arrays