Therapeutic yoga reduces pro-tumorigenic cytokines in cancer survivors.

INTRODUCTION: Chronic inflammation can remain many years after the completion of cancer treatment and is associated with cancer recurrence. The purpose of this study was to examine how a 16-week therapeutic yoga program (TYP) modulates the cytokine profile in heterogeneous cancer survivors. METHODS: Eligible participants were 18 years of age or older and clinically diagnosed with cancer. Consenting participants were asked to attend three, 75-min sessions weekly of TYP with meditation. Seventeen patients provided blood samples at baseline and end of study. Eight cytokines (interferon (IFN)-γ; interleukin (IL)-1b, IL-1ra, IL-4, IL-6, IL-8, IL-10; and tumor necrosis factor (TNF)-α), three receptors (sIL-6R, sTNFRI, sTNFRII), and C-reactive protein (CRP) were quantified. RESULTS: Patients were 59.6 ± 7.3 years old; over half (56%) were overweight or obese BMI ≥ 25 kg/m2); majority were female (71%) and breast cancer survivors (65%), of which 44% were Hispanic. Marked reductions were observed in all cytokines except IL-4, with significant reductions (p < 0.05) found in IL-1b (- 13%) and IL-1ra (- 13%). No significant changes were observed in soluble cytokine receptors or CRP. CONCLUSIONS: TYP led to significant reduction in circulating cytokines associated with chronic inflammation in a heterogeneous sample of cancer survivors.

Temporal multispectral and 3D analysis of Cerro de Pasco, Peru.

Mining operations across the world often lead to contamination of land, water resources, ecosystems and in some cases, entire communities.Results of recent health and ground sampling studies revealed extensive lead contamination within the populace and around the City of Cerro de Pasco, Peru. Tailings excavated from a large open pit zinc mine in the center of the city have been aggregated in four large stockpiles within close proximity to neighborhoods, schools, and hospitals. Visual comparison of ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) imagery from 2001 and Sentinel-2 imagery from 2018 suggests a size increase in one tailing stockpile in particular near the neighborhood of Paragsha. Due to ongoing mining efforts, the hypothesis motivating the work presented here is that Pb-bearing minerals would be detectable through multispectral analysis, an increase in Pb mineral percent abundance would be observed and tailing stockpile volume would be detectable between 2001 and 2016. This hypothesis is tested using Spectral Angle Mapper (SAM), Adaptive Coherence Estimator (ACE), and Jeffries-Matusita distance calculation on ASTER (2001) and Sentinel-2 (2018) VNIR and SWIR bands. Volume and area estimate of tailing stockpiles were calculated using a photogrammetrically derived point cloud. SAM detected the presence of five Pb-bearing minerals around Cerro de Pasco and Paragsha. The results of the temporal SAM analysis displayed an increase of approximately 17% of Pb-bearing minerals around the greater Cerro de Pasco city area and approximately 11% for the neighborhood of Paragsha. Jeffries-Matusita distance results suggest clear correlation between contamination sources and affected locations. Total tailing stockpile volume was measured to be approximately 200,300,000 m3. Volume for Pile 4 was estimated to have increased by approximately 46,000,000 m3 between 2001 and 2018. These presented results will hopefully inspire and guide future remote sensing campaigns, perhaps involving a UAV or aircraft-based hyperspectral instrument.

The health status of people claiming compensation for musculoskeletal injuries following road traffic crashes is not altered by an early intervention programme: a comparative study.

OBJECTIVE: To compare health outcomes among claimants compared to those who were ineligible or choose not to lodge a compensation claim. We also evaluated the effect of an early intervention programme on the health outcomes of the participants. DESIGN: Prospective comparative study using sequential cohorts. SUBJECTS: People presenting to hospital emergency departments with mild to moderate musculoskeletal injuries following road traffic crashes. INTERVENTION: referral to an early intervention programme for assessment by musculoskeletal physician, pain management education, promotion of self-management and encouragement of early activity. MAIN OUTCOMES: The 36-Item Short-Form Survey (SF-36); Hospital Anxiety and Depression Scale (HADS) and Functional Rating Index (FRI) scores were assessed at post-crash and at 12 months. RESULTS: At 12 months, mean scores in six and five of the SF-36 domains were significantly lower among participants who claimed compensation versus those who chose not to claim or were ineligible, respectively. Differences in mean SF-36 scores ranged from 3.0 ('general health perception') to 8.0 units ('role limitations due to physical problems'). Participants who claimed compensation had 6.3- and 4.6-units lower SF-36 physical component score compared to those who were ineligible (p=0.001) or chose not to claim (p=0.01), respectively. Participants who claimed compensation reported a worse HADS-depression score of 6.46 versus 4.97 and 4.69 observed in those who were ineligible (p=0.04) or did not claim (p=0.01). Claimants had worse FRI scores compared to non-claimants (p=0.01) and those who were ineligible (p=0.01). The early intervention did not improve health outcomes, 12 months after injury. CONCLUSIONS: Claiming compensation was associated with a worse health status for people with soft tissue injuries caused by road traffic crashes. The health status in people claiming compensation was not altered by an early intervention programme.

An early intervention programme had no detectable influence on the health status of people with musculoskeletal injuries following road traffic crashes: comparative study.

OBJECTIVE: To compare the health status of people with minor injuries from road traffic crashes that are exposed to an early, active intervention programme (intervention group) with those receiving usual care (control group) over a 12 month period. DESIGN: Prospective comparative study using sequential cohorts. SUBJECTS: People presenting to hospital emergency departments with mild to moderate musculoskeletal injuries following road traffic crashes. MAIN OUTCOME MEASURES: Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form 36 (SF-36) health status measure; Hospital Anxiety and Depression Scale (HADS) and the Functional Rating Index (FRI) recorded immediately post-crash, at 6 months and at 12 months after injury. RESULTS: There were 95 participants allocated to the control group and 98 allocated to the intervention group. Participants were enrolled at a mean of 9.3 days following the crash. There were no significant differences in baseline health measures between the groups. Apart from a small improvement in anxiety for the intervention group, there were no significant differences in health status between the groups. Twenty percent of participants in the intervention group received treatment from external healthcare providers that was inconsistent with the recommendations of the intervention programme. CONCLUSIONS: The intervention programme failed to result in a clinically significant improvement in health outcomes compared with usual care. There is some evidence to suggest that the intervention had some psychological benefits, as evidenced by the small improvement in anxiety levels. Limited adherence, frequent use of co-interventions, or other factors (such as intervention content or intensity) may have reduced its effect.

Expression of transglutaminase-2 isoforms in normal human tissues and cancer cell lines: dysregulation of alternative splicing in cancer.

The multiple enzymatic activities and functions of transglutaminase type 2 (TG2) may be attributed to alternative TG2 molecules produced by differential splicing of TG2 mRNA. Different RNA transcripts of the human TG2 gene (TGM2) have been identified, but the expression of TG2 multiple transcripts has never been systematically addressed. We have confirmed and rationalized the main TG2 variants and developed a screening assay for the detection of alternative splicing of TG2, based on real-time reverse-transcription PCR. We have quantified the multiple TG2 transcripts in a wide range of normal tissues and in cancer cell lines from four different sites of origin. Our data show a significant correlation in the expression of canonical and alternative TG2 isoforms in normal human tissue, but differences in alternative splicing of TG2 in cancer cell lines, suggesting that in cancer cells the alternative splicing of TG2 is a more active process.

The influence of fault on health in the immediate post-crash period following road traffic crashes.

OBJECTIVE: To compare the early health status of people who sustained injuries during road traffic crashes (RTC) in which they were at fault (AF), with people who sustained injuries in RTC in which they were not at fault (NAF). DESIGN: Prospective cohort study. SUBJECTS: People presenting to the emergency department with mild to moderate musculoskeletal injuries following RTC. MAIN OUTCOME MEASURES: Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form 36 (SF-36) health status measure; Hospital Anxiety and Depression Scale (HADS) and the Functional Rating Index (FRI) recorded immediately post-crash. RESULTS: 193 people participated in the study and were enrolled a mean of 9.3 days following the crash. The mean age was 37 years and 60% were female. 71% were NAF. There was a significantly higher number of females in the NAF group (65% compared with 35% males; p<0.001). Neck and back injuries were reported by 90.4% of the NAF group compared to 69.1% of the AF group (p<0.001). There were no significant differences in PCS, FRI or pain intensity between the two groups at a mean of 9.3 days after the crash. The mean MCS for the NAF group was significantly worse than for the AF group (31.4 compared to 37.3; p = 0.005). The SF-36 domain revealed a significantly worse adjusted mean role emotional score for the NAF group (23.4 compared to 32.5, p = 0.002). Females had significantly worse MCS score than males (30.6 and 38.1 respectively; p<0.001) and worse adjusted mean anxiety and depression scores (10 compared to 7.8; p = 0.002 and 7.6 compared to 5.5; p = 0.002 respectively). CONCLUSIONS: Despite there being no difference in physical health status, the NAF group demonstrated more emotional and mental disturbance than the AF group; and this was significantly worse for females. Treatment strategies should focus on addressing early pain and disability as well as providing appropriate psychological interventions, particularly for people not at fault following RTC.

The association of compensation on longer term health status for people with musculoskeletal injuries following road traffic crashes: emergency department inception cohort study.

OBJECTIVE: To compare the health status of people claiming compensation for injuries sustained in road traffic crashes (RTC), with people who do not claim compensation. DESIGN: Prospective cohort study. SETTING: Australian Capital Territory, Australia and a fault based common law compensation scheme. SUBJECTS: People presenting to the emergency department with mild to moderate musculoskeletal injury following RTC. MAIN OUTCOME MEASURES: Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form 36 (SF-36) health status measure, Hospital Anxiety and Depression Scale (HADS) and the Functional Rating Index (FRI). These measures are recorded immediately post crash, at 6 and 12 months post crash. RESULTS: 95 people participated in the study and were enrolled a mean of 8.6 (median 8) days following the crash. 86% were followed up to 12 months after injury. Mean age was 37 years, 61% were female and 91% were employed at the time of their injury.33%ultimately claimed compensation, and 25% engaged a lawyer. There were no major differences in baseline personal characteristics or injury related factors between the groups. As expected, involvement as a passenger and in multiple vehicle crashes, were more frequent in the group claiming compensation. Over the duration of the study claiming compensation was associated with lower SF-36 PCS (5.5 (95%CI 8.6 to 2.4), p = 0.001), greater HADS-Anxiety (1.7 (95%CI 0.2­3.3), p = 0.048), and worse FRI (11.2 (95%CI 3.9­18.5), p = 0.003). There was a highly significant improvement in health status between baseline and 6 months after injury, but no further significant change between 6 and 12 months after injury. There was no difference in rate of improvement between the groups. Claiming compensation and psychological factors were independent predictors of worse health status at 12 months. CONCLUSION: In this study the group claiming compensation had overall worse health status following mild to moderate musculoskeletal injuries over the course of the study. There was no difference in rate of improvement between the groups. However, it is not possible to determine whether this negative effect was due to claiming compensation itself or the presence of other unmeasured factors.

Role of imaging in the diagnosis of acute bacterial meningitis and its complications.

Acute bacterial meningitis is a common neurological emergency and a leading cause of death and neurological disability worldwide. Diagnosis is based on clinical and microbiological findings with neuroimaging in the form of CT reserved for those with specific adverse clinical features or when an underlying cause such as mastoiditis is suspected. MRI is extremely useful for detecting and monitoring the complications of meningitis. These can be remembered by the mnemonic HACTIVE (hydrocephalus, abscess, cerebritis/cranial nerve lesion, thrombosis, infarct, ventriculitis/vasculopathy and extra-axial collection). Diffusion weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) are useful to distinguish abscess from other ring enhancing lesions.

ZP genes in avian species illustrate the dynamic evolution of the vertebrate egg envelope.

The vertebrate egg envelope is composed of a set of related proteins, encoded by the ZP genes. The apparent simplicity of the egg envelope is in contrast to the number of ZP genes identified by conventional cloning and data mining of genome sequences from a number of vertebrates. The vertebrate ZP genes fall into five classes, ZP1, ZP2, ZP3, ZPD and ZPAX. Analysis of chicken genome and EST sequence data has revealed the presence of seven distinct ZP genes, falling into these classes that are expressed in the female reproductive system. Comparison with the repertoire of ZP genes in other vertebrates suggests a major source of diversity in the composition of the egg envelope is a continual process of amplification, diversification and attrition of ZP gene sequences.

When physiology becomes pathology: the role of magnetic resonance imaging in evaluating bone marrow oedema in the humerus in elite tennis players with an upper limb pain syndrome.

Upper limb stresses are well recognised in tennis, and the normal physiological responses of the humerus to externally applied forces are well defined. Changes to both the microscopic and macroscopic bony architecture are often not apparent on plain radiographs in the early stages of a stress reaction. Bone scintigraphy is more sensitive, but not very specific to subtle changes, as is computer aided tomography. Magnetic resonance imaging (MRI) scans are now used to assess many musculoskeletal injuries, and may allow earlier recognition of changes. This study reports on eight high level tennis players (seven professionals, one highly ranked amateur), who all presented during the course of the 2002 Australian Open and its lead up events. All had an upper limb pain syndrome centred around the elbow. Each underwent an MRI scan. A group of asymptomatic players also had scans of the same area to serve as controls. All symptomatic patients had various levels of bone marrow oedema in their distal humerus, some with periosteal reactions, although most without. No scans revealed a cortical breach. The management of these reactions is problematic in players on an international circuit, as review is sporadic and not always coordinated. The timetabling of international tournaments means it is difficult for top players to obtain adequate rest to avoid injury. Awareness of this early overuse reaction needs to be raised to allow preventive and therapeutic options to be considered to reduce the incidence of this humeral stress response producing an upper limb pain syndrome.

Cracking the egg: increased complexity in the zona pellucida.

A functional zona pellucida is critical for both fertilization and the early stages of embryo development. Recent data from genomic and proteomic studies have questioned our simplistic view of the zona as being composed of three proteins whose functions are clearly defined. In the human, for example, the zona pellucida is composed of four proteins, not three. The increased complexity of the zona pellucida in humans and other species across the evolutionary tree now demands that we reconsider our reliance on the mouse model for understanding early fertilization events. Additionally, we are now well placed to examine, for the first time, potential defects in zona genes and their proteins associated with defined pathology.

Four zona pellucida glycoproteins are expressed in the human.

BACKGROUND: The zona pellucida (ZP) is an extracellular glycoprotein matrix which surrounds all mammalian oocytes. Recent data have shown the presence of four human zona genes (ZP1, ZP2, ZP3 and ZPB). The aim of the study was to determine if all four ZP proteins are expressed and present in the human. METHODS: cDNA derived from human oocytes were used to amplify by PCR the four ZP genes. In addition, isolated native human ZP were heat-solubilized, trypsin-digested and subjected to tandem mass spectrometry (MS/MS). RESULTS: All four genes were expressed and the respective proteins present in the human ZP. Moreover, a bioinformatics approach showed that the mouse ZPB gene, although present, is likely to encode a non-functional protein. CONCLUSIONS: Four ZP genes are expressed in human oocytes (ZP1, ZP2, ZP3 and ZPB) and preliminary data show that the four corresponding ZP proteins are present in the human ZP. Therefore, this is a fundamental difference with the mouse model

Analysis of fish ZP1/ZPB homologous genes--evidence for both genome duplication and species-specific amplification models of evolution.

The vertebrate egg envelope is composed of a family of related proteins, the zona pellucida (ZP) proteins, which are characterized by the presence of a conserved zona pellucida domain. Analysis of teleost fish ZP gene sequences has demonstrated that there are no direct orthologues of the mammalian ZPB and ZP1 genes, but that teleost fish contain multiple copies of two classes of genes (ZPXa and ZPXb) that are equally related to ZPB and ZP1. The two classes of genes are further distinguished by expression in liver or ovary, respectively, indicating there was probably an initial duplication event, followed by a switch to hepatic expression of one of the paralogues. This switch was followed in some species by additional amplification of one of the paralogues with the subsequent loss of the other. It is proposed that the expansion of the number of ZPXa and ZPXb genes and the acquisition of dual sites of synthesis are the result of an ancient polyploidization event, followed by additional species-specific gene amplifications.

Alternative splicing of the human VEGFGR-3/FLT4 gene as a consequence of an integrated human endogenous retrovirus.

The vascular endothelial growth factor receptor 3 (VEGFR-3/FLT4) is a receptor tyrosine kinase that regulates angiogenesis and vasculogenesis in response to the binding of the ligands VEGF-C and VEGF-D. Mutations in VEGFR-3 have been identified in patients with primary lymphoedema. It has been noted previously that whilst in the mouse there is only a single Vegfr-3 transcript, in humans there are two transcripts of 5.8 and 4.5 kb, of which the shorter encodes a protein that lacks the C-terminal 65 amino acids. These two isoforms also differ in their biological activity. Analysis of the human VEGFR-3 cDNA and genomic sequence reveals that these two isoforms arise by alternative splicing of the terminal exons. The shorter transcript is generated by splicing into the long terminal repeat of a human endogenous retrovirus located between the last two exons, thus explaining the lack of the shorter transcript in the mouse. The retention of the retroviral sequences in the FLT4 locus suggests that this retrotransposition event has contributed significant additional function to this gene. This provides support for a role for integrated retroviruses in modulating gene activity and participating in evolutionary processes.

The impact of managed care on children's access, satisfaction, use, and quality of care.

OBJECTIVE: To examine the impact of managed care on children's access, satisfaction, use, and quality of care using nationally representative household survey data. DATA SOURCE: The 1996 Medical Expenditure Panel Survey (MEPS). STUDY DESIGN: Bivariate and multivariate analyses are used to detect independent effects of managed care on access, satisfaction, utilization, and quality of pediatric health services. DATA COLLECTION/EXTRACTION METHODS: Data were obtained from rounds 1, 2, and 3 of the 1996 MEPS. MEPS collects data on health care use, insurance, access, and satisfaction, along with basic demographic and health status information for a representative sample of the U. S. civilian, noninstitutionalized population. Our sample consists of 5,995 children between the ages of 0 and 17. FINDINGS: Among the 18 outcome indicators examined, the bivariate analysis revealed only three statistically significant differences between children enrolled in managed care and children in traditional health plans: children enrolled in managed care were more likely to receive physician services, more likely to have access to office-based care during evening or weekend hours, and less likely to report being very satisfied with overall quality of care. However, after controlling for confounding factors, none of these differences remained statistically significant. CONCLUSIONS: Our findings suggest that there are no statistically significant differences in self-reported outcomes for children enrolled in managed care and traditional health plans. This conclusion is provisional, however, because of limitations in the data set.

A simple diagnostic index for asthma.

BACKGROUND: Asthma is becoming increasingly prevalent and a number of research groups are investigating its genetic and environmental basis. OBJECTIVE: To produce a brief screening tool suitable for determining phenotype in asthma research. METHODS: The scores from eight questions on symptoms and history were obtained from 678 adults and 244 children from high asthma-incidence caucasian families. An independent physician diagnosis was also obtained with the use of a modified NHLBI-CSGA questionnaire and pulmonary function test. Stepwise logistic regression was applied to determine which of the eight questions had greatest predictive value for asthma, and the quality of the resultant models was evaluated using an independent set of 643 adults and 239 children. RESULTS: For adults, the most parsimonious model used responses from three of the eight questions. It had sensitivity and specificity of 0.94 and 0.96, respectively. For children, responses to two questions gave a model with sensitivity and specificity of 0.97. For both age groups, negative predictive values were above 0.87. Positive predictive values were 0.58 and 0.78 for adults and children respectively. The latter emphasize the need for conformation, by physician, of "affected" calls made by this initial screen. CONCLUSION: The brief questionnaires described are potentially useful in a research setting, as a preliminary screening mechanism of low cost. Their use will reduce the numbers of subjects that must undergo detailed phenotyping.

The unmet health needs of America's children.

OBJECTIVE: Unmet need for health care is a critical indicator of access problems. Among children, unmet need for care has special significance inasmuch as the failure to obtain treatment can affect health status and functioning in the near- and long-term. The purpose of this study was to present current prevalence estimates and descriptive characteristics of children with unmet health needs using nationally representative household survey data. METHODS: We analyzed 4 years of National Health Interview Survey data spanning 1993 through 1996. Our analysis included 97 206 children <18 years old. Measures of unmet need for medical care, dental care, prescription medications, and vision care were obtained from an adult household member (usually the mother) responding for the child. Bivariate and multivariate analyses were used to assess the degree to which unmet need was related to the demographic and socioeconomic characteristics of the child and family. RESULTS: Overall, 7.3% (4.7 million) of US children experienced at least 1 unmet health care need. Dental care was the most prevalent unmet need. After adjustment for confounding factors, near-poor and poor children were both about 3 times more likely to have an unmet need as nonpoor children (adjusted odds ratio [95% confidence interval] = 2.89 [2.52, 3.32], 3.0 [2.53, 3.56], respectively). Uninsured children were also about 3 times more likely to have an unmet need as privately insured children (adjusted odds ratio [95% confidence interval] = 2. 92 [2.58, 3.32]). CONCLUSIONS: Despite the nation's great wealth, unmet health needs remain prevalent among US children. A combined public policy that addresses financial and nonfinancial barriers to care is required to reduce the prevalence of unmet need for health care.

Impact of correlated factors on bone density in individuals with a family history of osteoporosis.

Previous studies have suggested that 14-47% of the variation in bone mineral density (BMD) can be predicted using clinical risk factors. The aim of our study was to determine, for the first time, the importance of these factors in individuals with evidence of a genetic predisposition to the disease. The subjects studied were 147 female and 86 male Caucasians, all with a family history of osteoporosis. Linear regression was used to determine whether age, height, weight, and years of reduced estrogen exposure were significant predictors of BMD. Males and females were examined separately, and BMD was measured at the hip and spine. The results show that these risk factors, known to be at work in the general population, are equally important in those with a family history of osteoporosis. It is clear, therefore, that they must be taken into account, and corrected for in genetic studies of the disease.