Orally Delivered Connexin43 Hemichannel Blocker, Tonabersat, Inhibits Vascular Breakdown and Inflammasome Activation in a Mouse Model of Diabetic Retinopathy.

Diabetic retinopathy (DR), a microvascular complication of diabetes, is associated with pronounced inflammation arising from the activation of a nucleotide-binding and oligomerization domain-like receptor (NLR) protein 3 (NLRP3) inflammasome. Cell culture models have shown that a connexin43 hemichannel blocker can prevent inflammasome activation in DR. The aim of this study was to evaluate the ocular safety and efficacy of tonabersat, an orally bioavailable connexin43 hemichannel blocker, to protect against DR signs in an inflammatory non-obese diabetic (NOD) DR mouse model.

Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial.

Background: Patients with non-small-cell lung cancer (NSCLC) that is resistant to PD-1 and PD-L1 (PD[L]-1)-targeted therapy have poor outcomes. Studies suggest that radiotherapy could enhance antitumour immunity. Therefore, we investigated the potential benefit of PD-L1 (durvalumab) and CTLA-4 (tremelimumab) inhibition alone or combined with radiotherapy.

Blocking connexin43 hemichannels prevents TGF-β2 upregulation and epithelial-mesenchymal transition in retinal pigment epithelial cells.

Epithelial-mesenchymal transition (EMT) occurs when polarised epithelial cells change to a mesenchymal phenotype. EMT plays a role in several chronic conditions, including ocular diseases with retinal pigment epithelium (RPE) EMT associated with retinal diseases such as diabetic retinopathy (DR). Here, EMT results in breakdown of the blood-retinal barrier (BRB) leading to sub-retinal fluid deposition and retinal detachment.

Uncovering a delicate balance between endonuclease RNase III and ribosomal protein S15 in E. coli ribosome assembly.

The bacterial ribosomal protein S15 is located in the platform, a functional region of the 30S ribosomal subunit. While S15 is critical for in vitro formation of E. coli small subunits (SSUs), it is dispensable for in vivo biogenesis and growth.

Craniosynostosis of the Metopic Suture in a Patient With CADASIL/Lehman Syndrome.

A 3-month-old patient presented for evaluation by plastic surgery with marked trigonocephaly and was subsequently diagnosed with metopic craniosynostosis. During presurgical evaluation, the patient was found to have two variants of the NOTCH3 gene, resulting in the diagnosis of lateral meningocele (Lehman) syndrome. Due to the increased possibility of stroke associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the patient underwent only anterior calvarial vault remodeling without fronto-orbital advancement for correction of her craniosynostosis.

Tonabersat Inhibits Connexin43 Hemichannel Opening and Inflammasome Activation in an In Vitro Retinal Epithelial Cell Model of Diabetic Retinopathy.

This study was undertaken to evaluate the connexin hemichannel blocker tonabersat for the inhibition of inflammasome activation and use as a potential treatment for diabetic retinopathy. Human retinal pigment epithelial cells (ARPE-19) were stimulated with hyperglycemia and the inflammatory cytokines IL-1β and TNFα in order to mimic diabetic retinopathy molecular signs in vitro. Immunohistochemistry was used to evaluate the effect of tonabersat treatment on NLRP3, NLRP1, and cleaved caspase-1 expression and distribution.

The influence of hyperglycemia on the safety of ultrasound in retinal pigment epithelial cells.

Ultrasound (US) assisted drug delivery is receiving interest in treating posterior eye diseases, such as diabetic retinopathy due to its ability to maximize drug penetration into difficult to reach tissues. Despite its promise, the technique has only been investigated using healthy cell and tissue models, with no evidence to date about its safety in active disease. As a result, the aim of this study was to evaluate the safety of US administration in vitro in retinal pigment epithelial cells under normal and high glucose conditions.

Morphological and functional properties distinguish the substance P and gastrin-releasing peptide subsets of excitatory interneuron in the spinal cord dorsal horn.

Excitatory interneurons account for the majority of neurons in the superficial dorsal horn, but despite their presumed contribution to pain and itch, there is still limited information about their organisation and function. We recently identified 2 populations of excitatory interneuron defined by expression of gastrin-releasing peptide (GRP) or substance P (SP). Here, we demonstrate that these cells show major differences in their morphological, electrophysiological, and pharmacological properties.

Creating an integrated care model for childhood obesity: a randomized pilot study utilizing telehealth in a community primary care setting.

In an integrated care model, involving primary care providers (PCPs) and obesity specialists, telehealth may be useful for overcoming barriers to treating childhood obesity. We conducted a pilot study comparing body mass index (BMI) changes between two arms (i) PCP in-person clinic visits plus obesity specialist tele-visits ( PCP visits + specialist tele-visits) and (ii) PCP in-person clinic visits only ( PCP visits only), with ongoing tele-consultation between PCPs and obesity specialists for both arms. Patients (N = 40, 10-17 years, BMI ≥ 95th percentile) were randomized to Group 1 or 2.

News from the Biological Stain Commission, No. 17.

In the 17(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the 20(th) meeting of ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on October 15 - 17, 2014 in Toronto, Canada, and from the 29(th) meeting of CEN/TC 140 In vitro diagnostic medical devices held on February 3, 2015 in Berlin, Germany.

Relationships between p53 status, apoptosis and induction of micronuclei in different human and mouse cell lines in vitro: Implications for improving existing assays.

Accumulated evidence has shown that in vitro mammalian cell genotoxicity assays produce high frequencies of "misleading" positive results, i.e. predicted hazard is not confirmed in in vivo and/or carcinogenicity studies [1], raising the question of relevance to human risk assessment.

News from the Biological Stain Commission, no. 16.

In the 16(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the 28(th) meeting of CEN/TC 140 In vitro diagnostic medical devices held on October 23, 2013 in Berlin, Germany. Information is also presented from the 19(th) meeting of ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on October 19 - 21, 2013 in Singapore.

Improvements in teaching behavior at two German medical schools resulting from a modified Flanders interaction analysis feedback intervention process.

Unlabelled: Abstract Background: Person-centered teachers who are more empathic and "indirect" (accept, encourage, praise and ask questions) tend to be more effective than those who are "direct" (lecture, give directions and criticize) (Amidon & Flanders 1991). The Flanders Interaction Analysis (FIA) is a tool for diagnosing these teaching aspects, though not yet used to improve lecturing in undergraduate medical education.

Aims: Does structured expert feedback to volunteer lecturers lead to improvement in person-centered teaching behavior as measured by a Modified Flanders Interaction Analysis (MFIA) and student questionnaires?

Methods: Twenty-one volunteer lecturers from two German medical faculties were stratified by past teaching experience and randomized into two groups.

News from the Biological Stain Commission no. 15.

In the 15(th) issue of News from the Biological Stain Commission (BSC), under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the plenary meetings of the International Standards Organization ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on August 22-24, 2012 in Berlin, Germany. An additional discussion of the use of food dyes in India also is included.

The N-terminal extension of S12 influences small ribosomal subunit assembly in Escherichia coli.

The small subunit (SSU) of the ribosome of E. coli consists of a core of ribosomal RNA (rRNA) surrounded peripherally by ribosomal proteins (r-proteins). Ten of the 15 universally conserved SSU r-proteins possess nonglobular regions called extensions.

Molecular confirmation of nine cases of Cornelia de Lange syndrome diagnosed prenatally.

Objectives: Cornelia de Lange syndrome (CdLS) is characterized by distinct facial features, growth retardation, upper limb reduction defects, hirsutism, and intellectual disability. NIPBL mutations have been identified in approximately 60% of patients with CdLS diagnosed postnatally. Prenatal ultrasound findings include upper limb reduction defects, intrauterine growth restriction, and micrognathia.

Replication and fine mapping of asthma-associated loci in individuals of African ancestry.

Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups.

A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry.

News from the Biological Stain Commission No. 14.

In the 14(th) issue of News from the Biological Stain Commission (BSC) the BSC's International Affairs Committee presents information from the meetings of ISO/TC 212/WG 3, In vitro diagnostic products, and from the final plenary meeting of ISO/TC 212, Clinical laboratory testing and in vitro diagnostic test systems, held on 17-19 October 2011 in Las Vegas, NV. Information is also presented from the 26th meeting of CEN/TC 140, In vitro diagnostic medical devices, held on 5 December 2011 in Berlin, Germany.

Correction: Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA.

[This corrects the article DOI: 10.1371/journal.pone.

News from the Biological Stain Commission no. 13.

In the 13(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the first plenary meeting of the International Standards Organization ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on 17-19 October 2011 in Las Vegas, Nevada.

Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.

Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.

Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations.

Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts.

News from the Biological Stain Commission no. 12.

In this 12(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the meetings of ISO/TC 212/WG 1 Quality and competence in the medical laboratory and ISO/TC 212/WG 3 In vitro diagnostic products both held on 2 - 3 June 2010, plus information on the second plenary meeting of ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on 4 June 2010. All meetings took place in Seoul, Republic of Korea. Finally, information is provided concerning the 25(th) meeting of CEN/TC 140 In vitro diagnostic medical devices held on 23 June 2010 in Berlin, Germany.

News from the Biological Stain Commission No. 11.

The 11th issue of News from the Biological Stain Commission (BSC) provides our first impressions of the REACH and ECHA programs. We intend to give a more thorough account of what these important programs actually mean in later editions of News from the Biological Stain Commission. Under the heading of Regulatory Affairs, the Biological Stain Commission's International Affairs Committee presents information from the opening session of the meeting of the International Standards Organization ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on 2-4 June 2010 in Seoul, Republic of Korea.

Genetic variants of TSLP and asthma in an admixed urban population.

Background: Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations.