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BackgroundPatients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. SPS inherited genetic basis is mostly unknown. We aimed to identify new germline predisposition factors for SPS by functionally evaluating a candidate gene and replicating it in additional SPS cohorts.MethodsAfter a previous whole-exome sequencing in 39 SPS patients from 16 families (discovery cohort), we sequenced specific genes in an independent validation cohort of 211 unrelated SPS cases. Additional external replication was also available in 297 SPS cases. The WNK2gene was disrupted in HT-29 cells by gene editing, and WNK2variants were transfected using a lentiviral delivery system. Cells were analysed by immunoblots, real-time PCR and functional assays monitoring the mitogen-activated protein kinase (MAPK) pathway, cell cycle progression, survival and adhesion.ResultsWe identified 2 rare germline variants in the WNK2gene in the discovery cohort, 3 additional variants in the validation cohort and 10 other variants in the external cohorts. Variants c.2105C>T (p.Pro702Leu), c.4820C>T (p.Ala1607Val) and c.6157G>A (p.Val2053Ile) were functionally characterised, displaying higher levels of phospho-PAK1/2, phospho-ERK1/2, CCND1, clonogenic capacity and MMP2.ConclusionAfter whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in the WNK2gene. Functional studies suggested germline WNK2variants affect protein function in the context of the MAPK pathway, a molecular hallmark in this disease.

More than 34 million people are hearing impaired, but few nurses receive training on how to best communicate with them. Here are some tips on what it takes-from a nurse [...]

Hereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1and CTNNA1. The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOLVE-RD consortium, re-analysis of whole-exome sequencing data from unresolved gastric cancer cases (n= 83) identified a mosaic missense variant in PIK3CAin a 25-year-old female with diffuse gastric cancer (DGC) without familial history for cancer. The variant, c.3140A>G p.(His1047Arg), a known cancer-related somatic hotspot, was present at a low variant allele frequency (18%) in leukocyte-derived DNA. Somatic variants in PIK3CAare usually associated with overgrowth, a phenotype that was not observed in this patient. This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC.

Utilizing the pyridinediimine ligand [(2,6-iPrC6H3)NCMe)(N(iPr)2C2H4)NCMe)C5H3N] (didpa), the zinc(II) and iron(II) complexes Zn(didpa)Cl2(1), Fe(didpa)Cl2(2), [Zn(Hdidpa)Cl2][PF6] (3), [Fe(Hdidpa)Cl2][PF6] (4), Zn(didpa)Br2(5), and [Zn(Hdidpa)Br2][PF6] (6), Fe(didpa)(CO)2(7), and [Fe(Hdidpa)(CO)2][PF6] (8) were synthesized and characterized. These complexes allowed for the study of the secondary coordination sphere pendant base and the redox-activity of the didpa ligand scaffold. The protonated didpa ligand is capable of forming metal halogen hydrogen bonds (MHHBs) in complexes 3, 4, and 6. The solution behavior of the MHHBs was probed via pKa measurements and 1H NMR titrations of 3and 6with solvents of varying H-bond accepting strength. The H-bond strength in 3and 6was calculated in silicoto be 5.9 and 4.9 kcal/mol, respectively. The relationship between the protonation state and the ligand-based redox activity was probed utilizing 7and 8, where the reduction potential of the didpa scaffold was found to shift by 105 mV upon protonation of the reduced ligand in Fe(didpa)(CO)2.

Since doctors receive only about two hours of training in nutrition, it's rare that a person leaves a doctor's office with a prescription for a medication and a list of [...]

'MY NAME IS Burton Goldberg, and I've been a businessman for over forty years. My interest is in results, so let us get right to the point. 'Two systems of [...]

This study addresses the field-scale architecture and static connectivity of fluvial sandstones of the lower Williams Fork Formation through analysis and reservoir modeling of analogous outcrop data from Coal Canyon, Piceance Basin, Colorado. The Upper Cretaceous lower Williams Fork Formation is a relatively low net-to-gross ratio (commonly <30%) succession of fluvial channel sandstones, crevasse splays, flood-plain mudstones, and coals that were deposited by meandering river systems within a coastal-plain setting. The lower Williams Fork outcrops serve as proximal reservoir analogs because the strata dip gently eastward into the Piceance Basin where they form natural gas reservoirs. Three-dimensional architectural-element models (3-D reservoir models) of the lower Williams Fork Formation that are constrained to outcrop-derived data (e.g., sandstone body types, dimensions, stratigraphic position) from Coal Canyon show how static sandstone body connectivity is sensitive to sandstone body width and varies with net-to-gross ratio and well spacing. With a low well density (e.g., 160-ac well spacing), connectivity is low for net-to-gross ratios less than 20%, connectivity increases between net-to-gross ratios of 20 to 30%, and levels off above a net-to-gross ratio of 30%. As well density increases, static connectivity increases more linearly with an increasing net-to-gross ratio. For a 20-ac well spacing, static connectivity can range from approximately 35 to 75% and 45 to 80% for net-to-gross ratios of 10 and 15%, respectively, depending on sandstone body width. Given the lower net-to-gross ratio and continuity of lower Williams Fork deposits, this underscores the importance of representative sandstone body statistics (e.g., sandstone body type, dimensions) to aid in subsurface correlation and mapping and to constrain reservoir models. [ABSTRACT FROM AUTHOR]

This study addresses the field-scale architecture and dimensions of fluvial deposits of the lower Williams Fork Formation through analysis of outcrops in Coal Canyon, Piceance Basin, Colorado. The lower Williams Fork Formation primarily consists of mud rock with numerous isolated, lenticular to channel-form sandstone bodies that were deposited by meandering river systems within a coastal-plain setting. Field descriptions, global positioning system traverses, and a combination of high-resolution aerial light detection and ranging data, digital orthophotography, and ground-based photomosaics were used to map and document the abundance, stratigraphic position, and dimensions of single-story and multistory channel bodies and crevasse splays. The mean thickness and apparent width of the 688 measured sandstone bodies are 12.1 ft (3.7 m) and 364.9 ft (111.2 m), respectively. Single-story sandstone bodies (N = 116) range in thickness from 3.9 to 29.9 ft (1.2 to 9.1 m) and from 44.1 to 1699.8 ft (13.4 to 518.1 m) in apparent width. Multistory sandstone bodies (N = 273) range in thickness from 5.0 to 47.1 ft (1.5 to 14.4 m) and from 53.2 to 2791.1 ft (16.2 to 850.7 m) in apparent width. Crevasse splays (N = 279) range in thickness from 0.5 to 15.0 ft (0.2 to 4.6 m) and from 40.1 to 843.3 ft (12.2 to 257.0 m) in apparent width. These data show that most sandstone bodies are smaller than the distance between wells at 10-ac spacing (660 ft [201 m]). Analyses of interwell sandstone-body connectivity suggest that even at 10-ac spacing, only half of the sandstone bodies are intersected and few are intersected by more than one well. [ABSTRACT FROM AUTHOR]

This article reports that the primary focus of the Arts in Medicine (AIM) program at Shands hospital in Gainesville, Florida is to bring the arts, music, dance, theater, writing, and visual arts, to patients at this university-related medical center with patients from all over the southeast. The community spend so much time together, both at the hospital and supporting each other in a variety of social and artistic endeavors, that by all definitions, except that their houses are scattered throughout the county and beyond, the community might as well be considered an intentional community. When an AIM staff member or volunteer gets sick or suffers any loss, the community springs to life, home-cooked food is delivered, dogs are walked, aging parents or spouses are cared for.

To describe a case of lightning injury restricted to the eyes and facial skin.Case history describing the clinical examination of a 54-year-old woman.Following a lightning stroke the patient suffered from a sharply demarcated facial skin burn and bilateral iridocyclitis with raised intraocular pressure. Initially she had amnesia regarding the incident. She recovered on symptomatic treatment, with dry eyes as the only sequela.We suggest that a lightning current travelled over the outside of the patient's body facilitated by her wet raincoat, a so-called flash-over. Thereby, she was spared from more severe injury, and only the exposed areas of the face and eyes were affected.

Reports on the results of a national survey conducted on primary care physicians in the United States. Attitudes of primary care physicians on alternative therapies.

Recounts how the author learned to like to exercise, and modified her routine to accommodate her congenital hip injury and mitral valve prolapse (MVP). Tells how exercise has helped her physically.

Several letters to the editor are presented in response to articles in the previous issues which include one on Bosnia and Hercegovina's war and political situation by Scott Anderson, one on the work of producer Damon Lindelof, and "How Do You Heal a Traumatized Mind?" in the May 25, 2014.