Chimeric tymovirus-like particles displaying foot-and-mouth disease virus non-structural protein epitopes and its use for detection of FMDV-NSP antibodies

Expression of Physalis mottle tymovirus (PhMV) coat protein (CP) in Escherichia coli (E. coli) was earlier shown to self-assemble into empty capsids that are nearly identical to the capsids formed in vivo. Aminoacid substitutions were made at the N-terminus of wild-type PhMV CP with single or tandem repeats of infection related B-cell epitopes of foot-and-mouth disease virus (FMDV) non-structural proteins (NSPs) 3B1, 3B2, 3AB, 3D and 3ABD of lengths 48, 66, 49, 51 and 55, respectively to produce chimeras pR-Ph-3B1, pR-Ph-3B2, pR-Ph- 3AB, pR-Ph-3D and pR-Ph-3ABD. Expression of these constructs in E. coli resulted in chimeric proteins which self-assembled into chimeric tymovirus-like particles (TVLPs), Ph-3B1, Ph-3B2, Ph-3AB, Ph-3D and Ph-3ABD as determined by ultracentrifugation and electron microscopy. Ph-3B1, Ph-3B2, Ph-3AB and Ph-3ABD reacted with polyclonal anti-3AB antibodies in ELISA and electroblot immunoassay, while wild-type PhMV TVLP and Ph-3D antigens did not react. An indirect ELISA (I-ELISA) was developed using Ph-3AB to detect FMDV-NSP antibodies in sera of animals that showed clinical signs of FMD. Field serum samples from cattle, buffalos, sheep, goats and pigs were examined by using these chimeric TVLPs for the differentiation of FMDV infected animals from vaccinated animals (DIVA). The assay was demonstrated to be highly specific (100%) and reproducible with sensitivity levels (94%) comparable to the Ceditest kit (P>0.05).     

Improving physical functional status in patients with fibromyalgia: a brief cognitive behavioral intervention

OBJECTIVE: Sustained improvement in physical functional status was the primary goal of a brief, 6 session cognitive behavioral therapy (CBT) protocol for fibromyalgia (FM). METHODS: One hundred forty-five patients with FM were randomly assigned to either (1) standard medical care that included pharmacological management of symptoms and suggestions for aerobic fitness, or (2) the same standard medical treatment plus 6 sessions of CBT aimed at improving physical functioning. Outcome measures included the Medical Outcome Study Short Form-36 Physical Component Score and McGill ratings of pain. Outcomes were treated dichotomously using a preestablished criterion for clinically significant success based upon the reliability of change index from baseline to one year posttreatment. RESULTS: Twenty-five percent of the patients receiving CBT were able to achieve clinically meaningful levels of longterm improvement in physical functioning, whereas only 12% of the patients receiving standard care achieved the same level of improvement. There were no lasting differences on pain ratings between groups. CONCLUSION: Lasting improvements in physical functioning have been among the most difficult outcomes to obtain in studies of FM. These data suggest that the inclusion of CBT to a standard medical regimen for FM can favorably influence physical functioning in a subset of patients.     

Characteristics of HER2-positive breast cancer diagnosed following the introduction of universal HER2 testing

The aim of this study was to determine the impact of universal HER2 testing on the clinico-pathologic profile of HER2+ breast cancer. Data were extracted from breast cancer pathology reports spanning two periods: before (2003/4, n = 379), and after (2008/9, n = 560) the introduction of universal testing. In 2003/4, 43.3% of breast cancers were tested for HER2 with 16% of tested cases HER2+. In 2008/9, 98.4% of cases were tested with 14.7% HER2+. In 2008/9, HER2+ status was associated with younger age, higher grade, increased tumour size, lymph node involvement, negative oestrogen and/or progesterone receptor status. HER2+ cases diagnosed in 2003/4 were not significantly different in respect of these features. The rate of HER2+ breast cancer amongst screen detected cases in 2008/9 was 8.3%. The phenotype of HER2+ breast cancer was stable following the introduction of universal testing. The overall rate of HER2+ breast cancer was influenced by screen detection.     

Corneal biomechanical properties and their correlates with refractive error

Purpose: The aim was to study the link between refractive error and corneal biomechanical properties. Methods: Corneal hysteresis and corneal resistance factor were measured using the Ocular Response Analyser in 117 participants. The spherical equivalent refractive error of the participants ranged between ‐9.00 and +3.00 D. Results: Corneal hysteresis and corneal resistance factor showed a considerable degree of variability between individuals. Corneal hysteresis was not found to correlate significantly with refractive error (p = 0.82). Corneal resistance factor showed a weak but significant correlation with spherical equivalent refractive error (r²= 0.04; p = 0.03), with myopic participants exhibiting a higher corneal resistance factor compared with non‐myopes. Conclusions: Refractive error accounted for four per cent of the variance in corneal resistance factor measurements, indicating that patients with mild to moderate myopia have higher corneal resistance compared with non‐myopes.     

Slums and Malnourishment: Evidence From Women in India

Objectives. We examined the association between slum residence and nutritional status in women in India by using competing classifications of slum type.Methods. We used nationally representative data from the 2005–2006 National Family Health Survey (NFHS-3) to create our citywide analysis sample. The data provided us with individual, household, and community information. We used the body mass index data to identify nutritional status, whereas the residential status variable provided slum details. We used a multinomial regression framework to model the 3 nutrition states—undernutrition, normal, and overnutrition.Results. After we controlled for a range of attributes, we found that living in a census slum did not affect nutritional status. By contrast, living in NFHS slums decreased the odds of being overweight by 14% (95% confidence interval [CI] = 0.79, 0.95) and increased the odds of being underweight by 10% (95% CI = 1.00, 1.22).Conclusions. The association between slum residence and nutritional outcomes is nuanced and depends on how one defines a slum. This suggests that interventions targeted at slums should look beyond official definitions and include current living conditions to effectively reach the most vulnerable.More than 50% of the world population was classified as urban for the first time in 2009 and is expected to reach around 69% in 2050.1 The proportion of the urban population in the developing world is expected to increase from 45% to 66% during the same period. One of the immediate consequences of population pressure in urban spaces is the growth of slums or urban communities that are characterized by poor access to civic services, inadequate housing, and overcrowding.2 It has been estimated that slum populations would double before 2035 in the low- and middle-income countries.3One of the main concerns regarding the growth of slum populations is that the living conditions of the slum dwellers could become a public health issue. The attention gained by the relation between poor health outcomes and living conditions is neither new nor restricted to the developing world. As early as the 19th century, the Public Health Acts of Britain aimed to improve water systems and sanitation facilities in slums.2 This was also true of other developed countries—notably, France and the United States—which attempted to regulate residential dwellings to contain the spread of disease among other things.Although the pace of urbanization in India historically has been slow, it is increasing rapidly. India’s urban population grew by about 230 million between 1971 and 2008, and it is estimated that 250 million more will swell the urban population within the next 2 decades.4 This urban growth has led to a population explosion in cities, and India boasts of 2 cities with a population of at least 10 million (Delhi and Mumbai).Literature from the developing world suggests that both communicable and noncommunicable diseases are a major concern for urban populations, particularly the slum populations. Already malnourished slum dwellers may experience additional stress because of overcrowding and poor living conditions and are more likely to have poor health outcomes. However, India-specific research findings paint a mixed picture. A study on urban slums in Maharashtra in 1999 indicated that women living in slums were more disadvantaged with respect to antenatal care than were women not living in slums.5 This was reaffirmed by another study that compared the health status of poor populations in slums and in resettlement colonies in Delhi and Chennai and found that slum dwellers had worse health outcomes than those in resettlement colonies.6 Recent research in Chandigarh that used primary data collected in 2006 showed that immunization status of children younger than 5 years was poorer in slum areas than in the rural and urban areas.7 In contrast, a 2005–2006 National Family Health Survey (NFHS-3) report suggested that slum residents were not necessarily worse off than nonslum residents on several deprivation dimensions including poor health.8 These studies have used prevalence rates of all illnesses, morbidity rates, incidence of hospitalization, and other health indicators as various proxies of health status.Our study examined the distribution of women’s malnutrition in 8 cities across slum and nonslum populations. Malnutrition is a significant problem among Indian women. According to several studies that used the NFHS-3, only 52% of the women were within the normal weight range for a given height.8,9 Following the World Health Organization, we defined malnutrition to include the dual burden of undernutrition and overnutrition. Until recently, attention has been exclusively focused on undernutrition. However, recent trends indicate that Indian women are facing a double burden of malnutrition because of the increasing prevalence of overnutrition largely caused by changing lifestyle and diet patterns.10Being underweight could affect productivity and pose health risks, particularly for women, by increasing the likelihood of negative maternal health outcomes, including low-birth-weight infants.11 However, being overweight also could lead to poor health outcomes because of the increased risk of diabetes, cardiovascular diseases, hypertension, and respiratory-related mortality.12Figures 1 and ​and22 show the prevalence of underweight and overweight women, respectively, in 8 cities in India by slum residence status. Women residing in nonslum areas were more likely to be overweight, whereas those residing in slum areas were more likely to be underweight. In cities such as Delhi, these gaps appear to be large, with 36% being overweight in nonslum areas as opposed to 26% in slum areas; in Indore, 38% were undernourished in slums, but only 28% appear to be undernourished in nonslum areas. These numbers suggest that undernutrition is a larger problem in slums, and overnutrition is mainly a nonslum problem. Therefore, slums could be used as a valid unit to study undernutrition-related policies, and nonslum areas could be used to study overweight-related problems.Open in a separate windowFIGURE 1—Distribution of underweight women in 8 cities in India by slum status: 2005–2006 National Family Health Survey (NFHS-3).Note. Prevalence was calculated with 2005–2006 NFHS-3 data that were weighted with the provided weights. The prevalence ratios were calculated as follows: the numerator is the number of people who have body mass index (BMI) < 18.5 kg/m², and the denominator is those with normal weight (BMI = 18.5–24.99 kg/m²). The slum variable includes both census-defined slums and those identified as slums by NFHS field staff.Open in a separate windowFIGURE 2—Distribution of overweight women in 8 cities in India by slum status: 2005–2006 National Family Health Survey (NFHS-3).Note. Prevalence was calculated with 2005–2006 NFHS-3 data that were weighted with the provided weights. The prevalence ratios were calculated as follows: the numerator is the number of people who have body mass index (BMI) ≥ 25 kg/m², and the denominator is those with normal weight (BMI = 18.5–24.99 kg/m²). The slum variable includes both census-defined slums and those identified as slums by NFHS field staff.However, such differences in prevalence may be attributed to differences in the configuration of infrastructure, socioeconomic and other amenities that distinguish a slum from a nonslum area, or individual characteristics between those who live in slums and those who live in nonslum areas. Individual differences tend to matter more for malnutrition outcomes than do slum characteristics.     

The anemia impact measure (AIM): development and content validation of a patient-reported outcome measure of anemia symptoms and symptom impacts in cancer patients receiving chemotherapy

Purpose

To develop a patient-reported outcome instrument for measuring anemia symptoms and their impact in patients with chemotherapy-induced anemia (CIA).

Methods

Qualitative research was conducted using six focus groups and 24 interviews with 46 CIA patients, eight interviews in patients receiving chemotherapy with no CIA history and two interviews in patients successfully treated for CIA. Atlas.ti 5.0 was used to organize key concepts. Cognitive interviews with 16 CIA patients and assessment of relevance of each item to CIA by 10 clinicians were also conducted to evaluate content validity.

Results

Most CIA patients were white (76%) and female (83%), and the average age was 60?years. The most common cancer types were breast cancer (54%) and lung cancer (17%). Tiredness was the most prevalent symptom and rated as the most important by 83% of CIA patients; weakness, shortness of breath, lightheadedness, and dizziness were ranked next in importance. The final anemia impact measure (AIM) contains: (1) daily CIA symptom diary (9 items), and (2) impact of CIA-related tiredness (29 items covering daily living activities, social activities, cognitive function, and emotions). Cognitive interviews found that the AIM was relevant and easy to understand.

Conclusions

The AIM assesses important patient-perceived CIA symptoms and their impact and was developed using extensive patient qualitative data.     

Chromosome 11q23 translocations in both infant and adult acute leukemias are detected by in situ hybridization with a yeast artificial chromosome.

The yeast artificial chromosome (YAC-13HH4), which spans a 440-kb region of DNA just distal to the CD3 locus on chromosome 11 at band q23, has been used to characterize a range of chromosomal translocations in acute leukemias from both adults and infants. In situ hybridization was performed on metaphase cells from bone marrow of 17 leukemias and two cell lines with a variety of chromosome 11q23 abnormalities. It was established that in infant leukemias the translocations t(11;19), t(4;11), and t(5;11) had occurred in the region defined by YAC 13HH4. Additionally, the translocations t(4;11), t(6;11), t(9;11), t(X;11), and t(10;11) in other leukemias were found to disrupt the same region of chromosome 11q23, although an exception was found in one t(6;11) translocation for which the breakpoint was distal to the YAC. One patient had a t(9;11) translocation in a therapy-related leukemia, suggesting that this class of etoposide-related malignancy has similar breakpoints to those occurring in de novo leukemias. An example of a lymphoma-derived translocation t(4;11) was shown to involve a deletion of the region defined by YAC 13HH4. A leukemia with a deletion on chromosome 11 (q23-q25) was also studied and it was shown that the YAC sequence was unaffected. It was concluded that, with a few exceptions, the translocations at 11q23 in a wide range of acute infant and adult leukemias occur in a common region and may result from a common underlying mechanism.     

Hypermutation of HIV type 1 genomes isolated from infants soon after vertical infection

Hypermutation involving excessive G-to-A substitutions in the dinucleotide context GA or GG is common among the lentiviruses and results in multiple stop codons across the genome. Hypermutated viruses have been associated with slower disease progression and might reflect an antiviral cell-defense mechanism. However, it is unclear how soon G-to-A substitutions are generated after infection and whether they occur randomly along the genome. In this report we describe for the first time hypermutated sequences detected at delivery and in the first weeks of life, which suggests that they could be either generated in utero and soon after birth and/or vertically transmitted. Hypermutated C2-C5 env clones were harbored in 13.2% of 243 infants and 18.6% of 199 mothers. A lower extent of hypermutation was found in infants than in mothers (Fisher's exact p = 0.034), but there was no relationship between the percent hypermutated Gs and viral subtype or transmission status of the mother. Analyses of six hypermutated full-length HIV-1 clones showed that although all genes could be affected by G-to-A substitutions, there was a significant drop in the extent of hypermutation between the central polypurine tract and the beginning of env, indicating that hypermutation across the HIV-1 genome might occur in a specific pattern. The genomic regions most affected by hypermutation were pol and env while both polypurine tracts remained unaffected. A better understanding of the mechanism of hypermutation may reveal novel virus-host interactions that could be targeted in drug development.