M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis

BACKGROUND: The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis. METHODS: M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months. RESULTS: M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity. CONCLUSIONS: This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Forecasting Non-Stationary Diarrhea, Acute Respiratory Infection, and Malaria Time-Series in Niono, Mali

BACKGROUND: Much of the developing world, particularly sub-Saharan Africa, exhibits high levels of morbidity and mortality associated with diarrhea, acute respiratory infection, and malaria. With the increasing awareness that the aforementioned infectious diseases impose an enormous burden on developing countries, public health programs therein could benefit from parsimonious general-purpose forecasting methods to enhance infectious disease intervention. Unfortunately, these disease time-series often i) suffer from non-stationarity; ii) exhibit large inter-annual plus seasonal fluctuations; and, iii) require disease-specific tailoring of forecasting methods. METHODOLOGY/PRINCIPAL FINDINGS: In this longitudinal retrospective (01/1996-06/2004) investigation, diarrhea, acute respiratory infection of the lower tract, and malaria consultation time-series are fitted with a general-purpose econometric method, namely the multiplicative Holt-Winters, to produce contemporaneous on-line forecasts for the district of Niono, Mali. This method accommodates seasonal, as well as inter-annual, fluctuations and produces reasonably accurate median 2- and 3-month horizon forecasts for these non-stationary time-series, i.e., 92% of the 24 time-series forecasts generated (2 forecast horizons, 3 diseases, and 4 age categories = 24 time-series forecasts) have mean absolute percentage errors circa 25%. CONCLUSIONS/SIGNIFICANCE: The multiplicative Holt-Winters forecasting method: i) performs well across diseases with dramatically distinct transmission modes and hence it is a strong general-purpose forecasting method candidate for non-stationary epidemiological time-series; ii) obliquely captures prior non-linear interactions between climate and the aforementioned disease dynamics thus, obviating the need for more complex disease-specific climate-based parametric forecasting methods in the district of Niono; furthermore, iii) readily decomposes time-series into seasonal components thereby potentially assisting with programming of public health interventions, as well as monitoring of disease dynamics modification. Therefore, these forecasts could improve infectious diseases management in the district of Niono, Mali, and elsewhere in the Sahel

Femoroacetabular impingement: normal values of the quantitative morphometric parameters in asymptomatic hips.

OBJECTIVE: To determine the means and the reference intervals of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in normal hips with high-resolution computed tomography (CT). METHODS: We prospectively included 94 adult individuals who underwent CT for thoracic, abdominal or urologic pathologies. Patients with a clinical history of hip pathology and/or with osteoarthritis on CT were excluded. We calculated means and 95 % reference intervals for imaging signs of cam-type (alpha angle at 90° and 45° and femoral head-neck offset) and pincer-type impingement (acetabular version angle, lateral centre-edge angle and acetabular index). RESULTS: The 95 % reference interval limits were all far beyond the abnormal thresholds found in the literature for cam-type and to a lesser extent for pincer-type FAI. The upper limits of the reference intervals for the alpha angles (at 90°/45°) were 68°/83° (men) and 69°/84° (women), compared to thresholds from the literature (50°, 55° or 60°). Reference intervals were similar between genders for cam-type parameters, and slightly differed for pincer-type. CONCLUSION: The 95 % reference intervals of morphometric measurements of FAI in asymptomatic hips were beyond the abnormal thresholds, which was especially true for cam-type FAI. Our results suggest the need for redefining the current morphometric parameters used in the diagnosis of FAI. KEY POINTS: ? 95 % reference intervals limits of FAI morphotype were beyond currently defined thresholds. ? Reference intervals of pincer-type morphotype measurements were close to current definitions. ? Reference intervals of cam-type morphotype measurements were far beyond the current definitions. ? Current morphometric definitions of cam-type morphotype should be used with care

Respiratory maneuvers in echocardiography: a review of clinical applications

During echocardiographic examination, respiration induces cyclic physiological changes of intracardiac haemodynamics, causing normal variations of the right and left ventricle Doppler inflows and outflows and physiological variation of extracardiac flows. The respiration related hemodynamic variation in intra and extracardiac flows may be utilized in the echocardiography laboratory to aid diagnosis in different pathological states. Nevertheless, physiologic respiratory phases can cause excessive translational motion of cardiac structures, lowering 2D image quality and interfering with optimal Doppler interrogation of flows or tissue motion

Ethnic-Racial Socialization in Early Childhood: The Implications of Color-Consciousness and Colorblindness for Prejudice Development

This chapter outlines how early childhood teachers can bring children into conversations surrounding race and racism by drawing on literature on how parents of color discuss these topics. Although educators’ practices surrounding race and racism remain largely unexplored, decades of developmental psychological research indicate that parents of color engage in ethnic-racial socialization practices that are beneficial for children (Hughes et al., 2006). The established dimensions of parental ethnic-racial socialization include (1) cultural socialization, or teaching children about their ethnic heritage and instilling ethnic pride; (2) preparation for bias, or teaching children about racism and preparing them to face discrimination; (3) promotion of mistrust, or warning children about the need to distance themselves from other racial groups; and (4) egalitarianism, or emphasizing the similarities between and equality of all races (Hughes et al. 2006). One consideration to take into account from a developmental perspective is that children’s level of cognitive development impacts how they interpret messages about race. This chapter draws a link between parental ethnic-racial socialization and extends this body of work to school settings, with a focus on teachers. The ideologies of colorblindness and color-consciousness are discussed throughout

Analysis of Gene expression in soybean (Glycine max) roots in response to the root knot nematode Meloidogyne incognita using microarrays and KEGG pathways

<p>Abstract</p> <p>Background</p> <p>Root-knot nematodes are sedentary endoparasites that can infect more than 3000 plant species. Root-knot nematodes cause an estimated $100 billion annual loss worldwide. For successful establishment of the root-knot nematode in its host plant, it causes dramatic morphological and physiological changes in plant cells. The expression of some plant genes is altered by the nematode as it establishes its feeding site.</p> <p>Results</p> <p>We examined the expression of soybean (<it>Glycine max</it>) genes in galls formed in roots by the root-knot nematode, <it>Meloidogyne incognita</it>, 12 days and 10 weeks after infection to understand the effects of infection of roots by <it>M. incognita</it>. Gene expression was monitored using the Affymetrix Soybean GeneChip containing 37,500 <it>G. max </it>probe sets. Gene expression patterns were integrated with biochemical pathways from the Kyoto Encyclopedia of Genes and Genomes using PAICE software. Genes encoding enzymes involved in carbohydrate and cell wall metabolism, cell cycle control and plant defense were altered.</p> <p>Conclusions</p> <p>A number of different soybean genes were identified that were differentially expressed which provided insights into the interaction between <it>M. incognita </it>and soybean and into the formation and maintenance of giant cells. Some of these genes may be candidates for broadening plants resistance to root-knot nematode through over-expression or silencing and require further examination.</p