Application of a target array Comparative Genomic Hybridization to prenatal diagnosis

<p>Abstract</p> <p>Background</p> <p>While conventional G-banded karyotyping still remains a gold standard in prenatal genetic diagnoses, the widespread adoption of array Comparative Genomic Hybridization (array CGH) technology for postnatal genetic diagnoses has led to increasing interest in the use of this same technology for prenatal diagnosis. We have investigated the value of our own designed DNA chip as a prenatal diagnostic tool for detecting submicroscopic deletions/duplications and chromosome aneuploidies.</p> <p>Methods</p> <p>We designed a target bacterial artificial chromosome (BAC)-based aCGH platform (MacArray™ M-chip), which specifically targets submicroscopic deletions/duplications for 26 known genetic syndromes of medical significance observed prenatally. To validate the DNA chip, we obtained genomic DNA from 132 reference materials generated from patients with 22 genetic diseases and 94 clinical amniocentesis samples obtained for karyotyping.</p> <p>Results</p> <p>In the 132 reference materials, all known genomic alterations were successfully identified. In the 94 clinical samples that were also subjected to conventional karyotyping, three cases of balanced chromosomal aberrations were not detected by aCGH. However, we identified eight cases of microdeletions in the Yq11.23 chromosomal region that were not found by conventional karyotyping. This region harbors the DAZ gene, and deletions may lead to non-obstructive spermatogenesis.</p> <p>Conclusions</p> <p>We have successfully designed and applied a BAC-based aCGH platform for prenatal diagnosis. This platform can be used in conjunction with conventional karyotyping and will provide rapid and accurate diagnoses for the targeted genomic regions while eliminating the need to interpret clinically-uncertain genomic regions.</p

Foodways in transition: food plants, diet and local perceptions of change in a Costa Rican Ngäbe community

Background Indigenous populations are undergoing rapid ethnobiological, nutritional and socioeconomic transitions while being increasingly integrated into modernizing societies. To better understand the dynamics of these transitions, this article aims to characterize the cultural domain of food plants and analyze its relation with current day diets, and the local perceptions of changes given amongst the Ngäbe people of Southern Conte-Burica, Costa Rica, as production of food plants by its residents is hypothesized to be drastically in recession with an decreased local production in the area and new conservation and development paradigms being implemented. Methods Extensive freelisting, interviews and workshops were used to collect the data from 72 participants on their knowledge of food plants, their current dietary practices and their perceptions of change in local foodways, while cultural domain analysis, descriptive statistical analyses and development of fundamental explanatory themes were employed to analyze the data. Results Results show a food plants domain composed of 140 species, of which 85 % grow in the area, with a medium level of cultural consensus, and some age-based variation. Although many plants still grow in the area, in many key species a decrease on local production–even abandonment–was found, with much reduced cultivation areas. Yet, the domain appears to be largely theoretical, with little evidence of use; and the diet today is predominantly dependent on foods bought from the store (more than 50 % of basic ingredients), many of which were not salient or not even recognized as ‘food plants’ in freelists exercises. While changes in the importance of food plants were largely deemed a result of changes in cultural preferences for store bought processed food stuffs and changing values associated with farming and being food self-sufficient, Ngäbe were also aware of how changing household livelihood activities, and the subsequent loss of knowledge and use of food plants, were in fact being driven by changes in social and political policies, despite increases in forest cover and biodiversity. Conclusions Ngäbe foodways are changing in different and somewhat disconnected ways: knowledge of food plants is varied, reflecting most relevant changes in dietary practices such as lower cultivation areas and greater dependence on food from stores by all families. We attribute dietary shifts to socioeconomic and political changes in recent decades, in particular to a reduction of local production of food, new economic structures and agents related to the State and globalization

Primary liposarcoma of the ascending colon: a rare case of mixed type presenting as hemoperitoneum combined with other type of retroperitoneal liposarcoma

<p>Abstract</p> <p>Background</p> <p>Liposarcoma occurs most commonly in the extremities and retroperitoneum, however, it has been rarely observed in the colon.</p> <p>Case Presentation</p> <p>A case is reported a 41-year-old man with liposarcoma of ascending colon which was presented as hemoperitoneum and combined with a different histological type of retroperitoneal liposarcoma. He visited hospital with right lower abdominal pain and palpable mass. Laboratory data including tumor markers were within normal limits, and computed tomography revealed a 15 × 10 cm sized enhancing soft mass. Right hemicolectomy was performed, and after that, a further large retroperitoneal mass was revealed and this was also radically excised. Mixed-type colon liposarcoma and well differentiated type of retroperitoneal liposarcoma were diagnosed in pathologic report. The patient has remained free of disease for 24 months.</p> <p>Conclusions</p> <p>No standardized guidelines have been established for its treatment because too small a number of cases have been reported, but surgical resection was considered the treatment of choice.</p

Consumer use of “Dr Google”: a survey on health information-seeking behaviors and navigational needs

BACKGROUND: The Internet provides a platform to access health information and support self-management by consumers with chronic health conditions. Despite recognized barriers to accessing Web-based health information, there is a lack of research quantitatively exploring whether consumers report difficulty finding desired health information on the Internet and whether these consumers would like assistance (ie, navigational needs). Understanding navigational needs can provide a basis for interventions guiding consumers to quality Web-based health resources. OBJECTIVE: We aimed to (1) estimate the proportion of consumers with navigational needs among seekers of Web-based health information with chronic health conditions, (2) describe Web-based health information-seeking behaviors, level of patient activation, and level of eHealth literacy among consumers with navigational needs, and (3) explore variables predicting navigational needs. METHODS: A questionnaire was developed based on findings from a qualitative study on Web-based health information-seeking behaviors and navigational needs. This questionnaire also incorporated the eHealth Literacy Scale (eHEALS; a measure of self-perceived eHealth literacy) and PAM-13 (a measure of patient activation). The target population was consumers of Web-based health information with chronic health conditions. We surveyed a sample of 400 Australian adults, with recruitment coordinated by Qualtrics. This sample size was required to estimate the proportion of consumers identified with navigational needs with a precision of 4.9% either side of the true population value, with 95% confidence. A subsample was invited to retake the survey after 2 weeks to assess the test-retest reliability of the eHEALS and PAM-13.RESULTS: Of 514 individuals who met our eligibility criteria, 400 (77.8%) completed the questionnaire and 43 participants completed the retest. Approximately half (51.3%; 95% CI 46.4-56.2) of the population was identified with navigational needs. Participants with navigational needs appeared to look for more types of health information on the Internet and from a greater variety of information sources compared to participants without navigational needs. However, participants with navigational needs were significantly less likely to have high levels of eHealth literacy (adjusted odds ratio=0.83, 95% CI 0.78-0.89, P<.001). Age was also a significant predictor (P=.02). CONCLUSIONS: Approximately half of the population of consumers of Web-based health information with chronic health conditions would benefit from support in finding health information on the Internet. Despite the popularity of the Internet as a source of health information, further work is recommended to maximize its potential as a tool to assist self-management in consumers with chronic health conditions

Primary care follow up of patients discharged from the emergency department: a retrospective study

BACKGROUND: The visit to the emergency department (ED) constitutes a brief, yet an important point in the continuum of medical care. The aim of our study was to evaluate the continuity of care of adult ED visitors. METHODS: We retrospectively reviewed all ED discharge summaries for over a month 's period. The ED chart, referral letter and the patient's primary care file were reviewed. Data collected included: age, gender, date and hour of ED visit, documentation of ED referral and ED discharge letter in the primary care file. RESULTS: 359 visits were eligible for the study. 192 (53.5%) of the patients were women, average age 54.1 ± 18.7 years (mean ± SD). 214 (59.6%) of the visits were during working hours of primary care clinics ("working hours"), while the rest were "out of hours" visits. Only 196 (54.6%) of patients had a referral letter, usually from their family physician. A third (71/214) of "working hours" visits were self referrals, the rate rose to 63.5% (92/145) of "out of hours" visits (p < 0.0001). The ED discharge letter was found in 50% (179/359) of the primary care files. A follow-up visit was documented in only 31% (111/359). Neither follow up visit nor discharge letter were found in 43% of the files (153/359). CONCLUSIONS: We have found a high rate of ED self referrals throughout the day together with low documentation rates of ED visits in the primary care charts. Our findings point to a poor continuity of care of ED attendees

The Effect of Insecticide Synergists on the Response of Scabies Mites to Pyrethroid Acaricides

Synergists are commonly used in combination with pesticides to suppress metabolism-based resistance and increase the efficacy of the agents. They are also useful as tools for laboratory investigation of specific resistance mechanisms based on their ability to inhibit specific metabolic pathways. To determine the role of metabolic degradation as a mechanism for acaricide resistance in human scabies, PBO (piperonyl butoxide), DEF (S,S,S-tributyl phosphorotrithioate) and DEM (diethyl maleate) were used with permethrin as synergists in a bioassay of mite killing. A statistically significant difference in survival time of permethrin-resistant Sarcoptes scabiei variety canis was noted when any of the three synergists were used in combination with permethrin compared to survival time of mites exposed to permethrin alone (p<0.0001). These results indicate the potential utility of synergists in reversing tolerance to pyrethroid-based acaricides (i.e. the addition of synergists to permethrin-containing topical acaricide cream commonly used to treat scabies). To further verify specific metabolic pathways being inhibited by these synergists, enzyme assays were developed to measure esterase, glutathione S-transferase (GST) and cytochrome P450 monooxygenase activity in scabies mites. Results of in vitro enzyme inhibition experiments showed lower levels of esterase activity with DEF; lower levels of GST activity with DEM and lower levels of cytochrome monooxygenase activity with PBO. These findings indicate a metabolic mechanism as mediating pyrethroid resistance in scabies mites

Acoustic signals in the sand fly Lutzomyia (Nyssomyia) intermedia (Diptera: Psychodidae)

<p>Abstract</p> <p>Background</p> <p>Acoustic signals are part of the courtship of many insects and they often act as species-specific signals that are important in the reproductive isolation of closely related species. Here we report the courtship songs of the sand fly <it>Lutzomyia (Nyssomyia) intermedia</it>, one of the main vectors of cutaneous leishmaniasis in Brazil.</p> <p>Findings</p> <p>Recordings were performed using insects from three localities from Eastern Brazil: Posse and Jacarepaguá in Rio de Janeiro State and Corte de Pedra in Bahia State. The three areas have remnants of the Brazilian Atlantic forest, they are endemic for cutaneous leishmaniasis and <it>L. intermedia </it>is the predominant sand fly species. We observed that during courtship <it>L. intermedia </it>males from all populations produced pulse songs consisting of short trains. No significant differences in song parameters were observed between the males of the three localities.</p> <p>Conclusions</p> <p><it>L. intermedia </it>males produce acoustic signals as reported for some other sand flies such as the sibling species of the <it>Lutzomyia longipalpis </it>complex. The lack of differences between the males from the three localities is consistent with previous molecular studies of the <it>period </it>gene carried out in the same populations, reinforcing the idea that <it>L. intermedia </it>is not a species complex in the studied areas and that the three populations are likely to have similar vectorial capacities.</p

Switching to letrozole or exemestane improves hot flushes, mood and quality of life in tamoxifen intolerant women

We report an open-label, prospective, crossover study involving 184 post-menopausal women experiencing hot flushes on adjuvant tamoxifen (T). Six weeks after switching to an AI, the primary end point, hot flush score, improved by 47.3% (P<0.001) compared to those reported on T. The mean mood rating scale (MRS) score improved by 9.7% (P=0.01). The total mean combined FACT (b+es) score improved from 134.2 (95% CI ±2.96) to 143.5 (95% CI ±2.96 <0.001), and the endocrine subscale improved by 9.8% from 51.73 (95% CI ±1.38) to 57.34 (CI ±1.38, P<0.001). At 6 weeks, significantly more women chose to remain on an AI: 133 (72%), vs 40 (22%) (P<0.001) preferring T. At 3 months, 107 (58%) preferred to remain on an AI, 55(30%) on T, and 22 (12%) withdrew. The overall arthralgia rate at 3 months was 47% on AI and 30% on T (P=0.001). In all 182 (99%) women reported appreciating the opportunity to experience both drugs. These data suggest that if patients suffering significant adverse effects on T are given the opportunity to try an AI, this empowers them to prioritise relative side-effects, improving wellbeing in a significant proportion. These data also highlight the need for hospital follow-up in this intolerant cohort

Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice

The ability to genetically manipulate mice has led to rapid progress in our understanding of the roles of different gene products in human disease. Transgenic mice have often been created in the FVB/NJ (FVB) strain due to its high fecundity, while gene-targeted mice have been developed in the 129/SvJ-C57Bl/6J strains due to the capacity of 129/SvJ embryonic stem cells to facilitate germline transmission. Gene-targeted mice are commonly backcrossed into the C57Bl/6J (B6) background for comparison with existing data. Genetic modifiers have been shown to modulate mammary tumor latency in mouse models of breast cancer and it is commonly known that the FVB strain is susceptible to mammary tumors while the B6 strain is more resistant. Since gene-targeted mice in the B6 background are frequently bred into the polyomavirus middle T (PyMT) mouse model of breast cancer in the FVB strain, we have sought to understand the impact of the different genetic backgrounds on the resulting phenotype. We bred mice deficient in the inducible nitric oxide synthase (iNOS) until they were congenic in the PyMT model in the FVB and B6 strains. Our results reveal that the large difference in mean tumor latencies in the two backgrounds of 53 and 92 days respectively affect the ability to discern smaller differences in latency due to the Nos2 genetic mutation. Furthermore, the longer latency in the B6 strain enables a more detailed analysis of tumor formation indicating that individual tumor development is not stoichastic, but is initiated in the #1 glands and proceeds in early and late phases. NO production affects tumors that develop early suggesting an association of iNOS-induced NO with a more aggressive tumor phenotype, consistent with human clinical data positively correlating iNOS expression with breast cancer progression. An examination of lung metastases, which are significantly reduced in PyMT/iNOS(−/−) mice compared with PyMT/iNOS(+/+) mice only in the B6 background, is concordant with these findings. Our data suggest that PyMT in the B6 background provides a useful model for the study of inflammation-induced breast cancer