Development of a Health-Protective Drinking Water Level for Perchlorate

We evaluated animal and human toxicity data for perchlorate and identified reduction of thyroidal iodide uptake as the critical end point in the development of a health-protective drinking water level [also known as the public health goal (PHG)] for the chemical. This work was performed under the drinking water program of the Office of Environmental Health Hazard Assessment of the California Environmental Protection Agency. For dose–response characterization, we applied benchmark-dose modeling to human data and determined a point of departure (the 95% lower confidence limit for 5% inhibition of iodide uptake) of 0.0037 mg/kg/day. A PHG of 6 ppb was calculated by using an uncertainty factor of 10, a relative source contribution of 60%, and exposure assumptions specific to pregnant women. The California Department of Health Services will use the PHG, together with other considerations such as economic impact and engineering feasibility, to develop a California maximum contaminant level for perchlorate. We consider the PHG to be adequately protective of sensitive subpopulations, including pregnant women, their fetuses, infants, and people with hypothyroidism

Frequent, Geographically Structured Heteroplasmy in the Mitochondria of a Flowering Plant, Ribwort Plantain (Plantago lanceolata)

Recent research has convincingly documented cases of mitochondrial heteroplasmy in a small set of wild and cultivated plant species. Heteroplasmy is suspected to be common in flowering plants and investigations of additional taxa may help understand the mechanisms generating heteroplasmy as well as its effects on plant phenotypes. The role of mitochondrial heteroplasmy is of particular interest in plants as cytoplasmic male sterility is controlled by mitochondrial genotypes, sometimes leading to co-occurring female and hermaphroditic individuals (gynodioecy). Paternal leakage may be important in the evolution of mating systems in such populations. We conducted a genetic survey of the gynodioecious plant Plantago lanceolata, in which heteroplasmy has not previously been reported, and estimated the frequencies of mitochondrial genotypes and heteroplasmy. Sanger sequence genotyping of 179 individuals from 15 European populations for two polymorphic mitochondrial loci, atp6 and rps12, identified 15 heteroplasmic individuals. These were distributed among 6 of the 10 populations that had polymorphisms in the target loci and represented 8% of all sampled individuals and 15% of the individuals in those 6 populations. The incidence was highest in Northern England and Scotland. Our results are consistent with geographic differences in the incidence of paternal leakage and/or the rates of nuclear restoration of male fertility

Cost-effectiveness of postural exercise therapy versus physiotherapy in computer screen-workers with early non-specific work-related upper limb disorders (WRULD); a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Exercise therapies generate substantial costs in computer workers with non-specific work-related upper limb disorders (WRULD).</p> <p>Aims</p> <p>To study if postural exercise therapy is cost-effective compared to regular physiotherapy in screen-workers with early complaints, both from health care and societal perspective.</p> <p>Methods</p> <p>Prospective randomized trial including cost-effectiveness analysis; one year follow-up. Participants: Eighty-eight screen-workers with early non-specific WRULD; six drop-outs. Interventions: A ten week postural exercise program versus regular physiotherapy. Outcome measures: Effectiveness measures: Pain: visual analogous scale (VAS), self-perceived WRULD (yes/no). Functional outcome: Disabilities of Arm, Shoulder and Hand- Dutch Language Version (DASH-DLV). Quality of life outcome: EQ-5D.</p> <p>Economic measures: health care costs including patient and family costs and productivity costs resulting in societal costs. Cost-effectiveness measures: health care costs and societal costs related to the effectiveness measures. Outcome measures were assessed at baseline; three, six and twelve months after baseline.</p> <p>Results</p> <p>At baseline both groups were comparable for baseline characteristics except scores on the Pain Catastrophizing Scale and comparable for costs. No significant differences between the groups concerning effectiveness at one year follow-up were found. Effectiveness scores slightly improved over time. After one year 55% of participants were free of complaints. After one year the postural exercise group had higher mean total health care costs, but lower productivity costs compared to the physiotherapy group. Mean societal costs after one year (therefore) were in favor of postural exercise therapy [- €622; 95% CI -2087; +590)]. After one year, only self- perceived WRULD seemed to result in acceptable cost-effectiveness of the postural exercise strategy over physiotherapy; however the probability of acceptable cost-effectiveness did not exceed 60%.</p> <p>Considering societal costs related to QALYs, postural exercise therapy had a probability of over 80% to be cost-effective over a wide range of cost-effectiveness ceiling ratios; however based on a marginal QALY-difference of 0.1 over a 12 month time frame.</p> <p>Conclusion</p> <p>Although our trial failed to find significant differences in VAS, QALYs and ICERs based on VAS and QALYs at one-year follow-up, CEACs suggest that postural exercise therapy according to Mensendieck/Cesar has a higher probability of being cost-effective compared to regular physiotherapy; however further research is required.</p> <p>Trial registration</p> <p>ISRCTN 15872455</p

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Incidence of synchronous appendiceal neoplasm in patients with colorectal cancer and its clinical significance

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to evaluate the incidence of synchronous appendiceal neoplasm in patients with colorectal cancer, and to determine its clinical significance.</p> <p>Methods</p> <p>Pathological reports and medical records were reviewed of patients with colorectal adenocarcinoma who underwent oncological resection of the tumor together with appendectomy at the Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand between September 2000 and April 2008.</p> <p>Results</p> <p>This study included 293 patients with an average age of 62 years (range 19–95) and 51 percent were male. Of the patients studied, 228 (78 percent) had right hemicolectomy, whereas the others (22 percent) had surgery for left-sided colon cancer or rectal cancer. One patient (0.3 percent) had epithelial appendiceal neoplasm (mucinous cystadenoma) and 3 patients (1.0 percent) had metastatic colorectal cancer in the mesoappendix. However, the presence of synchronous appendiceal tumors and/or metastasis did not alter postoperative management, as these patients had received adjuvant therapy and were scheduled for surveillance program because of nodal involvement.</p> <p>Conclusion</p> <p>The incidence of synchronous primary appendiceal neoplasm and secondary (metastatic) appendiceal neoplasm in colorectal cancer patients was 0.3 and 1.0 percent, respectively. However, these findings did not change the postoperative clinical management.</p

Repeated Radionuclide therapy in metastatic paraganglioma leading to the highest reported cumulative activity of 131I-MIBG

131I-MIBG therapy for neuroendocrine tumours may be dose limited. The common range of applied cumulative activities is 10-40 GBq. We report the uneventful cumulative administration of 111 GBq (= 3 Ci) 131I-MIBG in a patient with metastatic paraganglioma. Ten courses of 131I-MIBG therapy were given within six years, accomplishing symptomatic, hormonal and tumour responses with no serious adverse effects. Chemotherapy with cisplatin/vinblastine/dacarbazine was the final treatment modality with temporary control of disease, but eventually the patient died of progression. The observed cumulative activity of 131I-MIBG represents the highest value reported to our knowledge, and even though 12.6 GBq of 90Y-DOTATOC were added intermediately, no associated relevant bone marrow, hepatic or other toxicity were observed. In an individual attempt to palliate metastatic disease high cumulative activity alone should not preclude the patient from repeat treatment

Quantifying morbidities by Adjusted Clinical Group system for a Taiwan population: A nationwide analysis

<p>Abstract</p> <p>Background</p> <p>The Adjusted Clinical Group (ACG) system has been used in measuring an individual's and a population's morbidities. Although all required inputs for running the ACG system are readily available, patients' morbidities and their associations to health care utilizations have been rarely studied in Taiwan. Therefore, the objective of this study was using the ACG system to quantify morbidities for Taiwanese population and to examine their relationship to ambulatory utilizations and costs.</p> <p>Methods</p> <p>This secondary analysis examined claims data for ambulatory services provided to 2.71 million representative Taiwanese in 2002 and 2003. People were grouped by the ACG system according to age, gender, and all ambulatory diagnosis codes in a given year. The software collapses the full set of ACGs into six morbidity categories (Non-users, Healthy, Low-morbidity, Moderate-, High- and Very-high) termed Resource Utilization Bands (RUBs). Each ACG was assigned a relative weight (RW), which was calculated as the ratio of mean ambulatory cost for each ACG to that for the overall. The distribution of morbidities was compared between years 2002 and 2003. The consistency of the distributions of visits, costs, and RWs of each ACG were examined for a two-year period. The relationship between people's morbidities and their ambulatory utilizations and costs was assessed.</p> <p>Results</p> <p>Ninety-eight percent of the subjects were correctly assigned to ACGs. Except for non-users (7.9 ~ 8.3%), most subjects were assigned to ACGs of acute and minor diseases and ACGs of moderate-to-high-morbid chronic diseases. The distributions of ACG-based morbidities were highly consistent (r = 0.949, <it>p < 0.001</it>) between 2002 and 2003. The ACG-specific visits (r = 0.955, <it>p < 0.001</it>), costs (r = 0.966, <it>p < 0.001</it>) and RWs (r = 0.991, <it>p < 0.001</it>) were correlated across two years. People grouped to the high-morbid ACGs had more visits and costs than those grouped to the low-morbid ACGs. Forty-six percent of the total ambulatory costs were spent by eighteen percent of the population, who were grouped to the High- and Very-high-morbidity RUBs.</p> <p>Conclusion</p> <p>This study demonstrated the feasibility, validity, and reliability of using the ACG system to measure morbidities in a Taiwan population and to explain their associations with ambulatory utilizations and costs for the whole country.</p

Choroid plexus tumours

Choroid plexus tumours are rare epithelial brain tumours and limited information is available regarding their biology and the best treatment. A meta-analysis was done to determine prognostic factors and the influence of various treatment modalities. A thorough review of the medical literature (1966–1998) revealed 566 well-documented choroid plexus tumours. These were entered into a database, which was analysed to determine prognostic factors and treatment modalities. Most patients with a supratentorial tumour were children, while the most common sites in adults were the fourth ventricle and the cerebellar pontine angle. Cerebellar pontine angle tumours were more frequently benign. Histology was the most important prognostic factor, as one, five, and 10-year projected survival rates were 90, 81, and 77% in choroid plexus-papilloma (n=353) compared to only 71, 41, and 35% in choroid plexus-carcinoma respectively (P<0.0005). Surgery was prognostically relevant for both choroid plexus-papilloma (P=0.0005) and choroid plexus-carcinoma (P=0.0001). Radiotherapy was associated with significantly better survival in choroid plexus-carcinomas. Eight of 22 documented choroid plexus-carcinomas responded to chemotherapy. Relapse after primary treatment was a poor prognostic factor in choroid plexus-carcinoma patients but not in choroid plexus-papilloma patients. Treatment of choroid plexus tumours should start with radical surgical resection. This should be followed by adjuvant treatment in case of choroid plexus-carcinoma, and a ‘wait and see’ approach in choroid plexus-papilloma

Advantage of rare infanticide strategies in an invasion experiment of behavioural polymorphism

Killing conspecific infants (infanticide) is among the most puzzling phenomena in nature. Stable polymorphism in such behaviour could be maintained by negative frequency-dependent selection (benefit of rare types). However, it is currently unknown whether there is genetic polymorphism in infanticidal behaviour or whether infanticide may have any fitness advantages when rare. Here we show genetic polymorphism in non-parental infanticide. Our novel invasion experiment confirms negative frequency-dependent selection in wild bank vole populations, where resource benefits allow an infanticidal strategy to invade a population of non-infanticidal individuals. The results show that infanticidal behaviour is highly heritable with genetic correlation across the sexes. Thus, a positive correlative response in male behaviour is expected when selection operates on females only and vice versa. Our results, on one hand, demonstrate potential benefits of infanticide, and on the other, they open a new perspective of correlative evolution of infanticide in females and males