Characteristics Associated With Nonreceipt of Surveillance Testing and the Relationship With Survival in Stage II and III Colon Cancer.

We investigated characteristics of patients with colon cancer that predicted nonreceipt of posttreatment surveillance testing and the subsequent associations between surveillance status and survival outcomes. This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Patients diagnosed between 2002 and 2009 with disease stages II and III and who were between 66 and 84 years of age were eligible. A minimum of 3 years' follow-up was required, and patients were categorized as having received any surveillance testing (any testing) versus none (no testing). Poisson regression was used to obtain risk ratios with 95% confidence intervals for the relative likelihood of No Testing. Cox models were used to obtain subdistribution hazard ratios with 95% confidence intervals for 5- and 10-year cancer-specific and noncancer deaths. There were 16,009 colon cancer cases analyzed. Patient characteristics that predicted No Testing included older age, Black race, stage III disease, and chemotherapy. Patients in the No Testing group had an increased rate of 10-year cancer death that was greater for patients with stage III disease (subdistribution hazard ratio = 1.79, 95% confidence interval: 1.48, 2.17) than those with stage II disease (subdistribution hazard ratio = 1.41, 95% confidence interval: 1.19, 1.66). Greater efforts are needed to ensure all patients receive the highest quality medical care after diagnosis of colon cancer.

Phenotypic characterization of KCTD3-related developmental epileptic encephalopathy.

The association between KCTD3 gene and neurogenetic disorders has only been published recently. In this report, we describe the clinical phenotype associated with 2 pathogenic variants in KCTD3 gene. Seven individuals (including one set of monozygotic twin) from 4 consanguineous families presented with developmental epileptic encephalopathy, global developmental delay, central hypotonia, progressive peripheral hypertonia, and variable dysmorphic facial features. Posterior fossa abnormalities (ranging from Dandy-Walker malformation to isolated hypoplasia of the cerebellar vermis) were consistently observed in addition to other variable neuroradiological abnormalities such as hydrocephalus and abnormal brain myelination. One patient also had a multicystic kidney. Whole exome sequencing revealed 2 probably pathogenic homozygous variants in KCTD3 gene that fully segregated with the disease. KCTD3 gene belongs to a family of accessory subunits that regulate the biophysical properties of ion channels, and is highly expressed in the kidney and brain. In this largest series to date on KCTD3-mutated patients, we show that biallelic loss of function mutations in KCTD3 lead to a consistent phenotype of developmental epileptic encephalopathy and abnormal cerebellum on brain imaging.

Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.

Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring.

The effect of in-utero environment on fetal health and survival is long-lasting, and this is known as the fetal origin hypothesis. The oxidative stress state during gestation could play a pivotal role in fetal programming and development of diseases such as diabetes. In this study, we investigated the effect of intra-uterine obesity and malnutrition on oxidative stress markers in pancreatic and peripheral tissues of F1 offspring both prenatally and postnatally. Furthermore, the effect of postnatal diet on oxidative stress profile was evaluated. The results indicated that intra-uterine obesity and malnourishment significantly increased oxidative stress in F1 offspring. Moreover, the programming effect of obesity was more pronounced and protracted than malnutrition. The obesity-induced programming of offspring tissues was independent of high-caloric environment that the offspring endured; however, high-caloric diet potentiated its effect. In addition, pancreas and liver were the most affected tissues by fetal reprogramming both prenatally and postnatally. In conclusion, maternal obesity and malnutrition-induced oxidative stress could predispose offspring to insulin resistance and diabetes.

Bimetallic nickel/manganese phosphate-carbon nanofiber electrocatalyst for the oxidation of formaldehyde in alkaline medium.

The development of earth-abundant transition metal-based catalysts, supported by a conductive carbonaceous matrix, has received great attention in the field of conversion of formaldehyde derivatives into toxic-free species. Herein, we report a comprehensive investigation of bimetallic electrocatalyst activity towards the electrooxidation of formaldehyde. The bimetallic phosphate catalyst is prepared by co-precipitation of Ni and Mn phosphate precursors using a simple reflux approach. Then the bimetallic catalyst is produced by mixing the Ni/Mn with carbon fibres (CNFs). The structural properties and crystallinity of the catalyst were investigated by using several techniques, such as scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and Brunauer Emmett-Teller theory. The system performance was studied under potentiostatic conditions. Some theoretical thermodynamic and kinetic models were applied to assess the system performance. Accordingly, key electrochemical parameters, including surface coverage (Γ) of active species, charge transfer rate (k s), diffusion coefficient of the formaldehyde (D), and catalytic rate constant (k cat) were calculated at Γ = 1.690 × 10-4 mmol cm-2, k s = 1.0800 s-1, D = 1.185 × 10-3 cm2 s-1 and k cat = 1.08 × 105 cm3 mol-1 s-1. These findings demonstrate the intrinsic electrocatalytic activity of formaldehyde electrooxidation on nickel/manganese phosphate- CNFs in alkaline medium.

Controlling the sugar beet fly Pegomyia mixta Vill. with entomopathogenic nematodes.

Sugar beet, Beta vulgaris L. is a strategic crop of sugar industry in Egypt. It is threatened by several insect pests among most important of them is the beet fly Pegomyia mixta. This work deals with the biological control of this insect using four entomopathogenic nematodes (EPNs). The nematodes included Steinernema carpocapsae S2, Steinernema feltiae, Heterorhabditis bacteriophora (HB1-3) and Heterorhabditis bacteriophora S1. Daily mortality of larvae and pupae of P. mixta were recorded after treatment with serial concentrations (500, 1000, 2000 and 4000 infective juveniles (IJs)/ml) of each of four studied EPNs. In the laboratory all tested nematodes killed the larvae inside their mines in the sugar beet leaves and developed in their bodies in different extends. They also killed the insect pupae in the soil and developed in their bodies. Young larvae were more susceptible than old ones. New pupae were more susceptible than old ones. In the field a single spray of S. feltiae or H. bacteriophora caused 81.3 or 75.9% reduction in the larval population of the in sugar beet leaves.

The photoprotective properties of α-tocopherol phosphate against long-wave UVA1 (385 nm) radiation in keratinocytes in vitro.

UVA1 radiation (340-400 nm), especially longwave UVA1 (> 370 nm), is often ignored when assessing sun protection due to its low sunburning potential, but it generates reactive oxygen species (ROS) and is poorly attenuated by sunscreens. This study aimed to investigate if α-tocopherol phosphate, (α-TP) a promising new antioxidant, could protect against long-wave UVA1 induced cell death and scavenge UVA1 induced ROS in a skin cell model. HaCaT keratinocyte cell viability (24 h) was assessed with Alamar Blue and Neutral Red assays. The metabolism of α-TP into α-T, assessed using mass spectrometry, and the compound's radical scavenging efficacy, assessed by the dichlorodihydrofluorescein (H2DCFDA) ROS detection assay, was monitored in HaCaTs. The mechanism of α-TP ROS scavenging was determined using non-cell based DPPH and ORAC assays. In HaCaT keratinocytes, irradiated with 226 J/cm2 UVA1 in low-serum (2%, starved) cell culture medium, pretreatment with 80 µM α-TP significantly enhanced cell survival (88%, Alamar Blue) compared to control, whereas α-T pre-treatment had no effect survival (70%, Alamar Blue). Pre-treatment of cells with 100 µM α-TP or 100 µM α-T before 57 J/cm2 UVA1 also significantly reduced ROS generation over 2 h (24.1% and 23.9% respectively) compared to the control and resulted in α-TP bioconversion into α-T. As α-TP displayed weak antioxidant activity in the cell-free assays thus its photoprotection was assigned to its bioconversion to α-T by cellular phosphatases. Through this mechanism α-TP prevented long-wave UVA1 induced cell death and scavenged UVA1 induced ROS in skin cells when added to the starved cell culture medium before UVA1 exposure by bioconversion into α-T.

Trends in Breast Cancer Survival by Race-Ethnicity in Florida, 1990-2015.

BACKGROUND: This study was conducted to evaluate trends in survival, by race-ethnicity, for women diagnosed with breast cancer in Florida over a 26-year period. METHODS: This was a retrospective cohort study of women diagnosed with invasive breast cancer in Florida between 1990 and 2015. Data were obtained from the Florida Cancer Data System. Women in the study were categorized according to race (white/black) and Hispanic ethnicity (yes/no). Cumulative incidence estimates of 5- and 10-year breast cancer-related death with 95% confidence intervals (CI) were obtained by race-ethnicity, according to diagnosis year. Subdistribution hazard models were used to obtain subdistribution HRs (sHR) for the relative rate of breast cancer death accounting for competing causes. RESULTS: Breast cancer mortality decreased for all racial-ethnic groups, and racial-ethnic minorities had greater absolute and relative improvement for nearly all metrics compared with non-Hispanic white (NHW) women. However, for the most recent time period (2010-2015), black women still experienced significant survival disparities with non-Hispanic black (NHB) women, having twice the rate of 5-year [sHR = 2.04; 95% confidence interval (CI), 1.91-2.19] and 10-year (sHR = 2.02; 95% CI, 1.89-2.16) breast cancer-related death. Adjustment for covariates substantially reduced the excess rate of breast cancer-related death for black women. CONCLUSIONS: Despite efforts to improve disparities in breast cancer outcomes for underserved women in Florida, black women continue to experience significant survival disparities. IMPACT: These results highlight the need for targeted approaches to eliminate disparities in breast cancer survival for black women.

Endometriosis: a possible cause of right shoulder pain.

Although endometriosis is a common condition it can present with a wide range of symptoms. We report a case of chronic right hypochondrial and shoulder pain which proved to be due to endometriosis.

Spectrum of mutations underlying Propionic acidemia and further insight into a genotype-phenotype correlation for the common mutation in Saudi Arabia.

Propionic acidemia (PA) is an autosomal recessive metabolic disorder. PA is characterized by deficiency of the mitochondrial enzyme propionyl CoA carboxylase (PCC) that results in the accumulation of propionic acid. Alpha and beta subunits of the PCC enzyme are encoded by the PCCA and PCCB genes, respectively. Pathogenic variants in PCCA or PCCB disrupt the function of the PCC enzyme preventing the proper breakdown of certain amino acids and metabolites. To determine the frequency of pathogenic variants in PA in our population, 84 Saudi Arabian patients affected with PA were sequenced for both the PCCA and PCCB genes. We found that variants in PCCA accounted for 81% of our cohort (68 patients), while variants in PCCB only accounted for 19% (16 patients). In total, sixteen different sequence variants were detected in the study, where 7 were found in PCCA and 9 in PCCB. The pathogenic variant (c.425G > A; p.Gly142Asp) in PCCA is the most common cause of PA in our cohort and was found in 59 families (70.2%), followed by the frameshift variant (c.990dupT; p.E331Xfs*1) in PCCB that was found in 7 families (8.3%). The p.Gly142Asp missense variant is likely to be a founder pathogenic variant in patients of Saudi Arabian tribal origin and is associated with a severe phenotype. All variants were inherited in a homozygous state except for one family who was compound heterozygous. A total of 11 novel pathogenic variants were detected in this study thereby increasing the known spectrum of pathogenic variants in the PCCA and PCCB genes.

Recurrent angiomyofibroblastoma of the vagina: a case report.

Angiomyofibroblastoma is a rare tumour of the superficial soft tissue of the pelvis and perineum. It is considered to be a slowly growing benign tumour. In the literature no evidence of recurrence has been reported up to eight years following local excision. We report a recurrent case of this tumour with no evidence of malignant transformation.

Abnormal cervical smears in adolescents: a ten-year comparative study of demographic criteria and management.

OBJECTIVE: Comparison of the demographic criteria and management of adolescents and other age groups referred to a colposcopy clinic with abnormal smears. METHODS: Retrospective study of newly referred cases to a colposcopy clinic in a UK district general hospital between 1996 and 2005. RESULTS: Most of the sociodemographic and sexual factors associated with HPV infection and cervical cancer were more obvious among adolescents than older women. There was a comparable incidence of high-grade cervical lesions in the two groups. CONCLUSIONS: A policy is needed to deal with adolescents who are exposed to all the risk factors associated with the development of HPV infection and high-grade cervical lesions. This has become an important issue for discussion recently in the UK after raising the age of onset of cervical screening to 25.

Spontaneous heterotopic pregnancy: a successful outcome.

Spontaneous heterotopic pregnancy is rare condition. We are reporting a case where the ectopic component was treated successfully laparoscopically and the intrauterine pregnancy continued to term uneventfully.

Factors associated with adherence to recommendations for screening mammography among American Indian women in Colorado.

OBJECTIVE: To compare adherence to screening mammography recommendations of American Indian and non-Hispanic White women in the Denver, Colorado, area. DESIGN/SETTING/PARTICIPANTS: This study retrospectively examined adherence patterns in 229 American Indian and 60,197 non-Hispanic White women > or = 40 years and older, with at least one screening mammogram in the Colorado Mammography Project (CMAP), from January 1, 1999, to December 31, 2003. The CMAP was a prospective study of women receiving mammograms at participating clinics around Denver. MAIN OUTCOME MEASURES: Using logistic mixed models, we defined two dependent variables as annual and biennial adherence from the intervals between screening mammograms for each woman. RESULTS: Biennial adherence was substantially higher than annual adherence for both American Indian and non-Hispanic White women in our analyses. American Indian women were less likely than non-Hispanic White women to adhere to biennial recommendations in multivariate models controlling for age, family history of breast cancer, and economic status (zip code): odds ratio (OR) .4 and 95% confidence interval (CI) .2-.6. The association between American Indian race/ethnicity and annual adherence was similar, although not as strong (OR .5, 95% CI .3-.8). CONCLUSIONS: American Indian women in the CMAP cohort were less likely than non-Hispanic White women to adhere to recommendations for screening mammography, both annually and biennially. Additional research is needed to explore the effect of biennial screening and other barriers among American Indian women.

Biodegradable/biocompatible coated metal implants for orthopedic applications.

Biocompatible metals have been suggested as revolutionary biomaterials for bone-grafting therapies. Although metals and their alloys are widely and successfully used in producing biomedical implants due to their good mechanical properties and corrosion resistance, they have a lack in bioactivity. Therefore coating of the metal surface with calcium phosphates (CaP) is a benign way to achieve well bioactivity and get controlled corrosion properties. The biocompatibility and bioactivity calcium phosphates (CaP) in bone growth were guided them to biomedical treatment of bone defects and fractures. Many techniques have been used for fabrication of CaP coatings on metal substrates such as magnesium and titanium. The present review will focus on the synthesis of CaP and their relative forms using different techniques especially electrochemical techniques. The latter has always been known of its unique way of optimizing the process parameters that led to a control in the structure and characteristics of the produced materials.

Factors influencing adherence to guidelines for screening mammography among women aged 40 years and older.

OBJECTIVE: To explore patterns of adherence to guidelines for screening mammography among participants in the Colorado Mammography Project (CMAP) surveillance database. METHODS: An algorithm was developed to assess factors associated with adherence to mammography screening guidelines. RESULTS: Of the 27,778 women ranging from 40-90 years of age included in the analysis, 41.4% were adherent with mammography screening guidelines. According to the model tested in this study, race/ethnicity (Black vs White, OR=0.76, 95% CI=0.64-0.91); educational attainment (high school vs 55,000 dollars vs <15,000 dollars, OR 1.14, 95% CI=1.03-1.26) were statistically significant predictors of adherence to guidelines. A significant interaction between age and family history of breast cancer (BC) was also found. Younger females with a family history of BC were less likely to be adherent than their counterparts without a family history (OR=0.93, 95% CI=0.90-0.96). In general, elderly women were more likely to be adherent compared with the youngest group in this cohort (OR=1.21, 95% CI=1.11-1.33). Inclusion or exclusion of women aged 70 years and older did not change the outcome of the analysis. CONCLUSION: Adherence with screening mammography guidelines was found to be associated with women's personal characteristics including race/ethnicity, age, and family history of BC. In addition, socioeconomic status, as measured by educational level and community economic status, are important predictors of adherence. Efforts to increase adherence may need to be specific to race/ethnic group and age, but the effect of age is mediated by family history of BC and vice versa.

Odds ratios for hip- and lower forearm fracture using peripheral bone densitometry; a case-control study of postmenopausal women.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) measured at the lumbar spine and particularly at the hip remain the gold-standard for diagnosing osteoporosis. However, devices for assessing the peripheral skeleton present several advantages in terms of lower price and portability. A major concern when using peripheral densitometry is the poor correlation with the central measurements. The main aim of this study is, therefore, to assess the possibility of expressing ultrasound measurements at the heel and bone mineral density (BMD) measured at the distal forearm as fracture odds ratios rather than an absolute measure of bone mass. METHODS: A total of 76 women with lower forearm fracture, 47 women with hip fracture and 231 age-matched women (controls) were included. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel using the DTU-one ultrasound scanner as well as BMD measured by dual X-ray absorptiometry on the DTX-200 at the distal forearm. RESULTS: BUA, SOS and BMD at the distal forearm were all significantly lower in fracture patients compared with their respective control groups. The odds ratio for lower forearm fracture was 3.1 (95% CI: 1.8; 5.2) for heel-BUA (T-score cutoff: -2.3), 4.1 (2.3; 7.4) for heel-SOS (-2.1) and 2.2 (1.3; 3.7) for lower forearm BMD (-2.7). The odds ratio for hip fracture was 3.4 (1.5-7.7) for heel-BUA (-2.7), 3.6 (1.6; 8.1) for heel-SOS (-2.6) and 3.2 (1.4; 7.4) for lower forearm BMD (-2.9). CONCLUSION: Peripheral densitometry can discriminate between hip- and lower forearm fracture patients and age-matched controls. Significantly elevated odds ratios for incurring these fractures can be calculated using device- and site specific t-score cutoff values. The results from this case-control study need to be confirmed by prospective cohort studies.

Ultrastructural features of vocal fold nodules and polyps.

Earlier investigation did not show any clear distinctive pathological features that differentiate vocal polyps from vocal nodules. The light microscopic distinctive features between the two lesions point in the direction of a more pronounced epithelial reaction and a more fibrous stromal change in vocal nodules. In the present study, 19 vocal polyps and 11 vocal nodules were subjected to ultrastructural examination aiming at finding distinctive features that may be pathognomic for each of these clinically distinct entities. The study was carried out by EM Philips 400 T. The results demonstrate that nodules showed epithelial changes in the form of gaping of the intercellular junctions and absence of the basal lamina in parts. These changes are less apparent in polyps, whereas the stromal changes are more pronounced and varied. The significance of these results and their interpretation are discussed.

Fundamental frequency stability in functional dysphonia.

Functional dysphonia is a term applied to voice disorders for which there is an absence of apparent structural change in the larynx. The aim of this work was to investigate how functional dysphonia may differ acoustically from other types of dysphonia. Fundamental frequency profiles for steady vowels were generated using a software program called GLIMPES (Glottal Imaging by Processing External Signals). The fundamental frequency variations were found to be unimodal in normal individuals. In contrast, the variations for dysphonic patients were sometimes bi-modal or multi-modal due to the presence of subharmonics or low-frequency modulations. The appearance of these patterns was generally related to the severity of the dysphonia rather than to its etiology.

Hepato-protective effect of daturaolone isolated from Solanum arundo.

The triterpene daturaolone was isolated for the first time from Solanum arundo Mattei. The structure has been elucidated by comparison of MS and 1H NMR spectra with the reported literature data, and was confirmed by 13C NMR. The compound proved its potency in reducing the harmful effects or in maintaining the normal hepatic physiological mechanisms in both acute and chronic hepato-toxic induced liver damage in rats.