Frequency and clinicopathological features of fibroelastotic changes in the gastrointestinal tract

Fibroelastotic changes (FEC) and especially elastotic polyps of the gastrointestinal (GI) tract are considered rare benign lesions. They consist of accumulations of elastic fibers within the mucosal, submucosal, or muscular layer, occurring in all parts of the GI tract and often appearing as polyps, but also as diffuse non-polyp-forming deposits. They have been the subject of only a few studies. To explore the clinical and histopathological features of FEC in the GI tract, a series of 162 elastotic lesions was collected within a 2-year period. The clinical data and endoscopic findings were correlated. FEC appeared as polyp-forming lesions of the large intestine in 23 samples (14 %), all other samples concerning histological findings without an identifiable gross mass. Frequently related findings were postinterventional status (9 %), previous irradiation (7 %), and history of GI lymphoma (4 %). Eight samples (5 %) presented endoscopically with lesions justifying surgical intervention. We identified three different histological patterns of FEC, which we have called fibroelastosis, angioelastosis, and elastofibroma. Consistent with previous studies, CD34 immunohistochemical staining (performed on 38 polypoid FEC specimens) showed an increase of CD34-positive mesenchymal cells in 95 % of immunostained samples, suggesting a potential role for CD34-positive mesenchymal cells in the accumulation of elastic fibers. In conclusion, FEC are more common in the GI tract than previously recognized. They often present as a benign polyp. Many accompany other diseases like ulcers and atrophic gastritis or represent a residual finding after an intervention.     

Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations

Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate with ataxia in the family. Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family. As there was no evidence for mutations in 23 additional consanguineous families, SPTBN2-related ARCA is probably rare.     

Mutation of POC1B in a Severe Syndromic Retinal Ciliopathy

We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next‐generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole‐exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106Pro_POC1B in a family with nonsyndromic cone‐rod dystrophy. The phenotype associated with homozygous p.Arg106Pro_POC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD.     

The description and definition of Emergency Department Pharmacist Practitioners in the United Kingdom (the ENDPAPER study)

International Journal of Clinical Pharmacy - Background Due to a shortage of emergency department doctors and nurses, hospitals have started to employ pharmacists who have additional clinical...     

Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project

Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment: 1.07 [95% CI: 1.04-1.09]) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI: 1.08-1.15) for men and 1.06 (95% CI: 1.02-1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women.     

Reasons for enhanced activity of doxorubicin on co-delivery with octa(3-aminopropyl)silsesquioxane

This paper presents results of spectroscopic (NMR, FTIR, fluorescence), Q-TOF mass spectrometry and Z-potential analyses of interactions between octa(3-aminopropyl)silsesquioxane hydrochloride (POSS-NH₂·HCl) and anticancer drug – doxorubicin hydrochloride. These studies aimed at explanation of the enhanced activity of doxorubicin on co-delivery with POSS-NH₂. The results point to the formation of active complexes via ionic interactions between the ammonium chloride groups of silsesquioxane and the drug, and not, as suggested earlier, via NH⋯N hydrogen bonding. It has also been shown that the main driving force for the formation of the complexes can be strengthened by π–π stacking and hydrogen bonds. The experimental results are supported by quantum mechanical calculations. This work has proven that co-delivery with POSS offers a potentially advantageous and simple approach for improved efficacy in chemotherapy, avoiding often complicated synthesis of conjugates, involving covalent bonding between drug, nanocarrier and targeting agents.

The interaction between polyhedral oligomeric silsesquioxane (POSS) and doxorubicin, leading to formation of active complexes involving POSS functional aminopropyl groups and anthracycline functional groups.