A Comparative Study of the Triphenyltetrazolium Chloride (Uroscreen) Test and Conventional Methods for the Detection of Bacteriuria

Acute urinary tract infection may be preceded by and active pyelonephritis may be associated with asymptomatic bacteriuria. Treatment of asymptomatic bacteriuria may prevent or arrest active, chronic pyelonephritis and its sequelae. Consequently, there is a need for a reliable and simple screening procedure to detect asymptomatic bacteriuria in large segments of the population.The reliability and practicability of tests advocated for the detection of bacteriuria, including the new chemical triphenyltetrazolium chloride (T.T.C.) (Uroscreen) test, were evaluated. Reliability was assessed by correlating results of these tests with bacterial counts of tested urines. Significant bacteriuria is defined as the presence of 100,000 or more organisms per ml. of urine.The T.T.C. (Uroscreen) test was positive in 92.5% of cases of bacteriuria; there were 7.5% false-negative and 2.8% false-positive results. Bacteria on Gram-stained smear were found in 95.5% of the cases of bacteriuria and in 14.6% of those with non-infected urine; pyuria (more than three leukocytes per high-power field), in 60% of those with bacteriuria and in 15.9% of those with presumably non-infected urine. Bacteria were conspicuous in the urinary sediment in 91.1% of cases of bacteriuria and in 3.7% of presumably non-infected urines.The T.T.C. (Uroscreen) test fulfilled the criteria for a reliable and simple screening procedure. It should be used concomitantly with other screening tests when the urine is examined routinely.     

Screening methods for covert bacteriuria in schoolgirls.

Screening tests for bacteriuria based on two different principles were evaluated in1582 schoolgirls aged 5-11 years, and in 26 girls aged 3-16 years attending hospitalwith symptomatic urinary tract infection. Tests for hypoglucosuria, performed by a semi-automated fluorometric method and with Uriglox strips on early-morning urine samples voided after overnight fasting, gave unacceptably high false-negative rates (16.7% and 20.8% respectively). Oxoid and Uricult dipslides were immersed in fresh midstreamspecimens of urine obtained at school and read overnight incubation at 37 degrees C.Both gave comparable results, with low false-positive rates and no false-negative responses. The higher cost of screening by dipslides was halved by using the "dipstream" technique, which also gave no false-negative results. Its false-positive rate of 13.5% could be reduced to 1.8% by disregarding colony counts of 10-8 non-faecal organisms and over per litre, which appear unimportant in schoolchildren. Bacteriuria was found in 2.3% of the schoolgirls; 39% of them had symptons, compared with 7.2% of the healthy girls, and 25% showed vesicoureteric reflux, which in 17% was associated with renalscarring. Since the natural history of covert bacteriuria and its relationship withreflux and scarring remain undetermined further research is required. The dipstreamtechnique offers a simple, reliable, and comparatively cheap screening method which could also be applied in general practice.     

Bacteriuria amongst Pregnant Women in the Buea Health District,Cameroon: Prevalence,Predictors, Antibiotic Susceptibility Patterns and Diagnosis

Background

Bacteriuria is associated with significant maternal and foetal risks. However, its prevalence is not known in our community.

Objectives

This study was carried out to determine the prevalence and predictors of bacteriuria in pregnant women of the Buea Health District (BHD) as well as the antibiotic sensitivity patterns of bacterial isolates. It also sought to determine the diagnostic performance of the nitrite and leucocyte esterase tests in detecting bacteriuria in these women.

Methods

An observational analytic cross-sectional study was carried out amongst pregnant women attending selected antenatal care centres in Buea. We recruited 102 consenting pregnant women for the study. Demographic and clinical data were collected using structured questionnaires. Clean catch midstream urine was collected from each participant in sterile leak proof containers. Samples were examined biochemically, microscopically and by culture. Significant bacteriuria was defined as the presence of ≥10⁸ bacteria/L of cultured urine. Identification and susceptibility of isolates was performed using API 20E and ATB UR EU (08) (BioMerieux, Marcy l''Etoile, France).

Results

Significant bacteriuria was found in the urine of 24 of the 102 women tested giving a bacteriuria prevalence of 23.5% in pregnant women of the BHD. Asymptomatic bacteriuria was detected in 8(7.8%) of the women. There was no statistically significant predictor of bacteriuria. Escherichia coli were the most isolated (33%) uropathogens and were 100% sensitive to cefixime, cefoxitin and cephalothin. The nitrite and leucocyte esterase tests for determining bacteriuria had sensitivities of 8%, 20.8% and specificities of 98.7% and 80.8% respectively.

Conclusion

Bacteriuria is frequent in pregnant women in the BHD suggesting the need for routine screening by urine culture. Empiric treatment with cefixime should be instituted until results of urine culture and sensitivity are available. Nitrite and leucocyte esterase tests were not sensitive enough to replace urine culture as screening tests.     

Regular health checks: cross-sectional survey

Objective

To investigate whether Danish providers of general health checks present a balanced account of possible benefits and harms on their websites and whether the health checks are evidence-based.

Methods and Design

Cross-sectional study. The search engines Google and Jubii (Danish) were in July and August 2009 used to identify 56 websites using Danish search terms for “health check” and “health examination”. The content of the websites were evaluated using a checklist with 15 officially recommended information items. All tests offered through the websites were registered. The evidence for tests offered through at least 10% of the websites was identified in structured searches using PubMed and The Cochrane Library.

Results

We found 36 different tests on 56 websites offering health checks. Twenty one tests were offered on at least 10% of the websites. Seventeen (81%) of these tests were unsupported by evidence, or there was evidence against them for screening purposes. We found evidence supporting screening using body-mass-index, blood pressure, cholesterol, and faecal occult blood testing. None of the websites mentioned possible risks or harms. The websites presented a median of 1 of the 15 information items; the highest number from any provider was 2.

Conclusions

Information from Danish providers of health checks was sparse and tests were often offered against existing evidence or despite lack of evidence. None of the included websites mentioned potential risks or harms.     

The Dip-slide in Urology

To assess the value of the Uricult dip-slide in a hospital urological unit, bacteriological examination of 1,033 urine specimens was compared by this technique and by conventional methods. In 87% of cases identical results were obtained using the dip-slides and the standard laboratory culture plates. Insignificant differences occurred in 10%, and a serious discrepancy between the two methods was found in only 3%. The Uricult dip-slide technique is valuable as a bacteriological screening procedure in urological practice but subculturing from the slide is not recommended except in special circumstances.     

Profiling dizziness in older primary care patients: an empirical study

Background

The diagnostic approach to dizzy, older patients is not straightforward as many organ systems can be involved and evidence for diagnostic strategies is lacking. A first differentiation in diagnostic subtypes or profiles may guide the diagnostic process of dizziness and can serve as a classification system in future research. In the literature this has been done, but based on pathophysiological reasoning only.

Objective

To establish a classification of diagnostic profiles of dizziness based on empirical data.

Design

Cross-sectional study.

Participants and Setting

417 consecutive patients of 65 years and older presenting with dizziness to 45 primary care physicians in the Netherlands from July 2006 to January 2008.

Methods

We performed tests, including patient history, and physical and additional examination, previously selected by an international expert panel and based on an earlier systematic review. We used the results of these tests in a principal component analysis for exploration, data-reduction and finally differentiation into diagnostic dizziness profiles.

Results

Demographic data and the results of the tests yielded 221 variables, of which 49 contributed to the classification of dizziness into six diagnostic profiles, that may be named as follows: “frailty”, “psychological”, “cardiovascular”, “presyncope”, “non-specific dizziness” and “ENT”. These explained 32% of the variance.

Conclusions

Empirically identified components classify dizziness into six profiles. This classification takes into account the heterogeneity and multicausality of dizziness and may serve as starting point for research on diagnostic strategies and can be a first step in an evidence based diagnostic approach of dizzy older patients.     

Evaluation of Miniature Test for Bacteriuria Using Dehydrated Media and Nitrite Pads

A new dip-inoculum method for detecting bacteriuria which utilizes dehydrated media pads and a nitrite pad attached to a small plastic strip was evaluated in hospitalized patients. Discrepant interpretations were made by independent observers in 9.3% of the specimens with > 10(5) colonies per ml. The media pads failed to support growth of yeast and gave variable results with Staphylococcus epidermidis and non-group D streptococci. False-negative culture results commonly occurred if the patients were receiving antibiotics. The nitrite test occasionally remained positive for brief periods after the elimination of bacteriuria by antibiotics. Conditions and drugs (especially phenazopyridine) which discolor urine interfered with reading both the culture and nitrite tests. Although not suitable for hospital use, or for monitoring therapy, the test strip is probably as reliable as the calibrated loop-streak plate culture for office screening.     

Evaluation of four slide test kits for the detection of human chorionic gonadotropin in urine

Three “indirect-type” slide tests utilizing the principle of hemagglutination inhibition and one new “direct-type” slide test employing direct agglutination were evaluated for their sensitivity in detecting human chorionic gonadotropin (HCG) in urine. The results of positive tests in a group of woman in very early pregnancy were correlated with the “days after last menses”. In this series the direct slide test was the most accurate. A control must be used with each direct test to indicate interfering substances and when such are present a different test must be used. All tests were found to be of the relative sensitivity stated by the manufacturer.     

Performance of the CareStart? G6PD Deficiency Screening Test,a Point-of-Care Diagnostic for Primaquine Therapy Screening

Development of reliable, easy-to-use, rapid diagnostic tests (RDTs) to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency at point of care is essential to deploying primaquine therapies as part of malaria elimination strategies. We assessed a kit under research and development called CareStart™ G6PD deficiency screening test (Access Bio, New Jersey, USA) by comparing its performance to quantitative G6PD enzyme activity using a standardized spectrophotometric method (‘gold standard’). Blood samples (n = 903) were collected from Cambodian adults living in Pailin province, western Cambodia. G6PD enzyme activities ranged from 0 to 20.5 U/g Hb (median 12.0 U/g Hg). Based on a normal haemoglobin concentration and wild-type G6PD gene, the normal values of G6PD enzymatic activity for this population was 3.6 to 20.5 U/g Hg (95^th percentiles from 5.5 to 17.2 U/g Hg). Ninety-seven subjects (10.7%) had <3.6 U/g Hg and were classified as G6PD deficient. Prevalence of deficiency was 15.0% (64/425) among men and 6.9% (33/478) among women. Genotype was analyzed in 66 G6PD-deficient subjects and 63 of these exhibited findings consistent with Viangchang genotype. The sensitivity and specificity of the CareStart™ G6PD deficiency screening test was 0.68 and 1.0, respectively. Its detection threshold was <2.7 U/g Hg, well within the range of moderate and severe enzyme deficiencies. Thirteen subjects (1.4%, 12 males and 1 female) with G6PD enzyme activities <2 U/g Hg were falsely classified as “normal” by RDT. This experimental RDT test here evaluated outside of the laboratory for the first time shows real promise, but safe application of it will require lower rates of falsely “normal” results.     

Simple Disposable Method for Quantitative Cultures of Urine

A disposable kit was tested as a means of detecting significant bacteriuria by quantitative culture of urine. The total error in 3,563 specimens tested by five investigators was less than 1%. The method was very effective in differentiating significant bacteriuria, i.e., more than 100,000 bacteria per ml of urine from uninfected urine. In specimens from patients with urinary tract abnormalities who had mixed bacterial flora, the absolute numbers obtained with the dip-inoculum method had a 10% variation when compared to results obtained by calibrated loop or dilution pour plate methods. Therefore, the main utility of the kit is for screening and following patients after therapy. A significant delay in time between inoculation of the medium in the kit with the freshly voided urine and incubation of the kit to promote growth did not affect the reliability of the kit as a method of doing quantitative urine cultures to detect bacteriuria.     

Routine HIV screening in France: clinical impact and cost-effectiveness

Background

In France, roughly 40,000 HIV-infected persons are unaware of their HIV infection. Although previous studies have evaluated the cost-effectiveness of routine HIV screening in the United States, differences in both the epidemiology of infection and HIV testing behaviors warrant a setting-specific analysis for France.

Methods/Principal Findings

We estimated the life expectancy (LE), cost and cost-effectiveness of alternative HIV screening strategies in the French general population and high-risk sub-populations using a computer model of HIV detection and treatment, coupled with French national clinical and economic data. We compared risk-factor-based HIV testing (“current practice”) to universal routine, voluntary HIV screening in adults aged 18–69. Screening frequencies ranged from once to annually. Input data included mean age (42 years), undiagnosed HIV prevalence (0.10%), annual HIV incidence (0.01%), test acceptance (79%), linkage to care (75%) and cost/test (€43). We performed sensitivity analyses on HIV prevalence and incidence, cost estimates, and the transmission benefits of ART. “Current practice” produced LEs of 242.82 quality-adjusted life months (QALM) among HIV-infected persons and 268.77 QALM in the general population. Adding a one-time HIV screen increased LE by 0.01 QALM in the general population and increased costs by €50/person, for a cost-effectiveness ratio (CER) of €57,400 per quality-adjusted life year (QALY). More frequent screening in the general population increased survival, costs and CERs. Among injection drug users (prevalence 6.17%; incidence 0.17%/year) and in French Guyana (prevalence 0.41%; incidence 0.35%/year), annual screening compared to every five years produced CERs of €51,200 and €46,500/QALY.

Conclusions/Significance

One-time routine HIV screening in France improves survival compared to “current practice” and compares favorably to other screening interventions recommended in Western Europe. In higher-risk groups, more frequent screening is economically justifiable.     

Culture,cultural factors and psychiatric diagnosis: review and projections

This paper aims to provide conceptual justifications for the inclusion of culture and cultural factors in psychiatric diagnosis, and logistic suggestions as to the content and use of this approach. A discussion of the scope and limitations of current diagnostic practice, criticisms from different quarters, and the role and relevance of culture in the diagnostic encounter, precede the examination of advantages and disadvantages of the approach. The cultural content of psychiatric diagnosis should include the main, well-recognized cultural variables, adequate family data, explanatory models, and strengths and weaknesses of every individual patient. The practical aspects include the acceptance of “cultural discordances” as a component of an updated definition of mental disorder, and the use of a refurbished cultural formulation. Clinical “telescoping” strategies to obtain relevant cultural data during the diagnostic interview, and areas of future research (including field trials on the cultural formulation and on “culture bound syndromes”), are outlined.     

Colorectal cancer screening for average-risk North Americans: an economic evaluation

Background

Colorectal cancer (CRC) fulfills the World Health Organization criteria for mass screening, but screening uptake is low in most countries. CRC screening is resource intensive, and it is unclear if an optimal strategy exists. The objective of this study was to perform an economic evaluation of CRC screening in average risk North American individuals considering all relevant screening modalities and current CRC treatment costs.

Methods and Findings

An incremental cost-utility analysis using a Markov model was performed comparing guaiac-based fecal occult blood test (FOBT) or fecal immunochemical test (FIT) annually, fecal DNA every 3 years, flexible sigmoidoscopy or computed tomographic colonography every 5 years, and colonoscopy every 10 years. All strategies were also compared to a no screening natural history arm. Given that different FIT assays and collection methods have been previously tested, three distinct FIT testing strategies were considered, on the basis of studies that have reported “low,” “mid,” and “high” test performance characteristics for detecting adenomas and CRC. Adenoma and CRC prevalence rates were based on a recent systematic review whereas screening adherence, test performance, and CRC treatment costs were based on publicly available data. The outcome measures included lifetime costs, number of cancers, cancer-related deaths, quality-adjusted life-years gained, and incremental cost-utility ratios. Sensitivity and scenario analyses were performed. Annual FIT, assuming mid-range testing characteristics, was more effective and less costly compared to all strategies (including no screening) except FIT-high. Among the lifetimes of 100,000 average-risk patients, the number of cancers could be reduced from 4,857 to 1,782 and the number of CRC deaths from 1,393 to 457, while saving CAN$68 per person. Although screening patients with FIT became more expensive than a strategy of no screening when the test performance of FIT was reduced, or the cost of managing CRC was lowered (e.g., for jurisdictions that do not fund expensive biologic chemotherapeutic regimens), CRC screening with FIT remained economically attractive.

Conclusions

CRC screening with FIT reduces the risk of CRC and CRC-related deaths, and lowers health care costs in comparison to no screening and to other existing screening strategies. Health policy decision makers should consider prioritizing funding for CRC screening using FIT. Please see later in the article for the Editors'' Summary     

Genomes, race and health. Racial profiling in medicine might just be a stepping stone towards personalized health care

Considering a patient''s ethnic background can make some diagnoses easier. Yet, ‘racial profiling'' is a highly controversial concept and might soon be replaced by the advent of individualized medicine.In 2005, the US Food and Drug Administration (FDA; Bethesda, MD, USA) approved BiDil—a combination of vasodilators to treat heart failure—and hailed it as the first drug to specifically treat an ethnic group. “Approval of a drug to treat severe heart failure in self-identified black population is a striking example of how a treatment can benefit some patients even if it does not help all patients,” announced Robert Temple, the FDA''s Director of Medical Policy. “The information presented to the FDA clearly showed that blacks suffering from heart failure will now have an additional safe and effective option for treating their condition” (Temple & Stockbridge, 2007). Even the National Medical Association—the African-American version of the American Medical Association—advocated the drug, which was developed by NitroMed, Inc. (Lexington, MA, USA). A new era in medicine based on racial profiling seemed to be in the offing.By January 2008, however, the ‘breakthrough'' had gone bust. NitroMed shut down its promotional campaign for BiDil—a combination of the vasodilators isosorbide dinitrate, which affects arteries and veins, and hydralazine hydrochloride, which predominantly affects arteries. In 2009, it sold its BiDil interests and was itself acquired by another pharmaceutical company.In the meantime, critics had largely discredited the efforts of NitroMed, thereby striking a blow against the drug if not the concept of racial profiling or race-based medicine. Jonathan Kahn, a historian and law professor at Hamline University (St Paul, MN, USA), described the BiDil strategy as “a leap to genetics.” He demonstrated that NitroMed, motivated to extend its US patent scheduled to expire in 2007, purported to discover an advantage for a subpopulation of self-identified black people (Kahn, 2009). He noted that NitroMed conducted a race-specific trial to gain FDA approval, but, as there were no comparisons with other populations, it never had conclusive data to show that BiDil worked in black people differently from anyone else.“If you want to understand heart failure, you look at heart failure, and if you want to understand racial disparities in conditions such as heart failure or hypertension, there is much to look at that has nothing to do with genetics,” Kahn said, adding “that jumping to race as a genetic construct is premature at best and reckless generally in practice.” The USA, he explained, has a century-old tradition of marketing to racial and ethnic groups. “BiDil brought to the fore the notion that you can have ethnic markets not only in things like cigarettes and food, but also in pharmaceuticals,” Kahn commented.“BiDil brought to the fore the notion that you can have ethnic markets not only in things like cigarettes and food, but also in pharmaceuticals”However, despite BiDil''s failure, the search for race-based therapies and diagnostics is not over. “What I have found is an increasing, almost exponential, rise in the use of racial and ethnic categories in biotechnology-related patents,” Kahn said. “A lot of these products are still in the pipeline. They''re still patent applications, they''re not out on the market yet so it''s hard to know how they''ll play out.”The growing knowledge of the human genome is also providing new opportunities to market medical products aimed at specific ethnic groups. The first bumpy steps were taken with screening for genetic risk factors for breast cancers. Myriad Genetics (Salt Lake City, UT, USA) holds broad patents in the USA for breast-cancer screening tests that are based on mutations of the BRCA1 and BRCA2 genes, but it faced challenges in Europe, where critics raised concerns about the high costs of screening.The growing knowledge of the human genome is also providing new opportunities to market medical products aimed at specific ethnic groupsThe European Patent Office initially granted Myriad patents for the BRCA1 and BRCA2-based tests in 2001, after years of debate. But it revoked the patent on BRCA1 in 2005, which was again reversed in 2009. In 2005 Myriad decided to narrow the scope of BRCA2 testing on the basis of ethnicity. The company won a patent to predict breast-cancer risk in Ashkenazi Jewish women on the basis of BRCA2 mutations, which occur in one in 100 of these women. Physicians offering the test are supposed to ask their patients whether they are in this ethnic group, and then pay a fee to Myriad.Kahn said Myriad took this approach to package the test differently in order to protect its financial interests. However, he commented, the idea of ethnic profiling by asking women whether they identify themselves as Ashkenazi Jewish and then paying extra for an ‘ethnic'' medical test did not work in Europe. “It''s ridiculous,” Kahn commented.After the preliminary sequence of the human genome was published a decade ago, experts noted that humans were almost the same genetically, implying that race was irrelevant. In fact, the validity of race as a concept in science—let alone the use of the word—has been hotly debated. “Race, inasmuch as the concept ought to be used at all, is a social concept, not a biological one. And using it as though it were a biological one is as a much an ethical problem as a scientific problem,” commented Samia Hurst, a physician and bioethicist at Geneva University Medical School in Switzerland.​Switzerland.Open in a separate window© Monalyn Gracia/CorbisCiting a popular slogan: “There is no gene for race,” she noted, “there doesn''t seem to be a single cluster of genes that fits with identification within an ethnic group, let alone with disease risks as well. We''re also in an increasingly mixed world where many people—and I count myself among them—just don''t know what to check on the box. If you start counting up your grandparents and end up with four different ethnic groups, what are you going to do? So there are an increasing number of people who just don''t fit into those categories at all.”Still, some dismiss criticism of racial profiling as political correctness that could potentially prevent patients from receiving proper care. Sally Satel, a psychiatrist in Washington, DC, USA, does not shy away from describing herself as a racially profiling physician and argues that it is good medicine. A commentator and resident scholar at the nonpartisan conservative think tank, the American Enterprise Institute (Washington, DC, USA), Satel wrote the book PC, M.D.: How Political Correctness is Corrupting Medicine. “In practicing medicine, I am not color blind. I take note of my patient''s race. So do many of my colleagues,” she wrote in a New York Times article entitled “I am a racially profiling doctor” (Satel, 2002).…some dismiss criticism of racial profiling as political correctness that could potentially prevent patients from receiving proper careSatel noted in an interview that it is an undeniable fact that black people tend to have more renal disease, Native Americans have more diabetes and white people have more cystic fibrosis. She said these differences can help doctors to decide which drugs to prescribe at which dose and could potentially lead researchers to discover new therapies on the basis of race.Satel added that the mention of race and medicine makes many people nervous. “You can dispel that worry by taking pains to specify biological lineage. Simply put, members of a group have more genes in common than members of the population at large. Some day geneticists hope to be able to conduct genomic profiles of each individual, making group identity irrelevant, but until then, race-based therapeutics has its virtues,” she said. “Denying the relationship between race and medicine flies in the face of clinical reality, and pretending that we are all at equal risk for health problems carries its own dangers.”However, Hurst contended that this approach may be good epidemiology, rather than racial profiling. Physicians therefore need to be cautious about using skin colour, genomic data and epidemiological data in decision making. “If African Americans are at a higher risk for hypertension, are you not going to check for hypertension in white people? You need to check in everyone in any case,” she commented.Hurst said European physicians, similarly to their American colleagues, deal with race and racial profiling, albeit in a different way. “The way in which we struggle with it is strongly determined by the history behind what could be called the biases that we have. If you have been a colonial power, if the past is slavery or if the past or present is immigration, it does change some things,” she said. “On the other hand, you always have the difficulty of doing fair and good medicine in a social situation that has a kind of ‘them and us'' structure. Because you''re not supposed to do medicine in a ‘them and us'' structure, you''re supposed to treat everyone according to their medical needs and not according to whether they''re part of ‘your tribe'' or ‘another tribe''.”Indeed, social factors largely determine one''s health, rather than ethnic or genetic factors. August A. White III, an African-American orthopaedic surgeon at Harvard Medical School (Boston, MA, USA) and author of the book Seeing Patients: Unconscious Bias In Health Care, noted that race is linked to disparities in health care in the USA. A similar point can be made in Europe where, for example, Romani people face discrimination in several countries.White said that although genetic research shows that race is not a scientific concept, the way people are labelled in society and how they are treated needs to be taken into account. “It''d be wonderful at some point if we can pop one''s key genetic information into a computer and get a printout of which medications are best of them and which doses are best for them,” he commented. “In the meantime though, I advocate careful operational attempts to treat everyone as human beings and to value everyone''s life, not devalue old people, or devalue women, or devalue different religious faiths, etc.”Notwithstanding the scientific denunciation, a major obstacle for the concept of racial profiling has been the fact that the word ‘race'' itself is politically loaded, as a result of, among other things, the baggage of eugenics and Nazi racism and the legacies of slavery and colonialism. Richard Tutton, a sociologist at Lancaster University in the UK, said that British scientists he interviewed for a Wellcome Trust project a few years ago prefer the term ethnicity to race. “Race is used in a legal sense in relation to inequality, but certainly otherwise, ethnicity is the preferred term, which obviously is different to the US” he said. “I remember having conversations with German academics and obviously in Germany you couldn''t use the R-word.”Jan Helge Solbakk, a physician, theologian and medical ethicist at the University of Oslo in Norway, said the use of the term race in Europe is a non-starter because it makes it impossible for the public and policy-makers to communicate. “I think in Europe it would be politically impossible to launch a project targeting racial differences on the genetic level. The challenge is to find not just a more politically correct concept, but a genetically more accurate concept and to pursue such research questions,” he said. According to Kahn, researchers therefore tend to refer to ethnicity rather than race: “They''re talking about European, Asian and African, but they''re referring to it as ethnicity instead of race because they think somehow that''s more palatable.”Regardless, race-based medicine might just be a stepping stone towards more refined and accurate methods, with the advent of personalized medicine based on genomics, according to Leroy Hood, whose work has helped to develop tools to analyse the human genome. The focus of his company—the Institute for Systems Biology (Seattle, WA, USA)—is to identify genetic variants that can inform and help patients to pioneer individualized health care.“Race as a concept is disappearing with interbreeding,” Hood said. “Race distinction is going to slowly fade away. We can use it now because we have signposts for race, which are colour, fairness, kinkiness of hair, but compared to a conglomeration of things that define a race, those are very few features. The race-defining features are going to be segregating away from one another more and more as the population becomes racially heterogeneous, so I think it''s going to become a moot point.”Hood instead advocates “4P” health care—“Predictive, Personalized, Preventive and Participatory.” “My overall feeling about the race-based correlations is that it is far more important to think about the individual and their individual unique spectra of health and wellness,” he explained. “I think we are not going to deal in the future with racial or ethnic populations, rather medicine of the future is going to be focused entirely on the individual.”Yet, Arthur Caplan, Director of the Center for Bioethics at the University of Pennsylvania (Philadelphia, PA, USA), is skeptical about the prospects for both race-based and personalized medicine. “Race-based medicine will play a minor role over the next few years in health care because race is a minor factor in health,” he said. “It''s not like we have a group of people who keel over dead at 40 who are in the same ethnic group.”Caplan also argued that establishing personalized genomic medicine in a decade is a pipe dream. “The reason I say that is it''s not just the science,” he explained. “You have to redo the whole health-care system to make that possible. You have to find manufacturers who can figure out how to profit from personalized medicine who are both in Europe and the United States. You have to have doctors that know how to prescribe them. It''s a big, big revamping. That''s not going to happen in 10 years.”Hood, however, is more optimistic and plans to advance the concept with pilot projects; he believes that Europe might be the better testing ground. “I think the European systems are much more efficient for pioneering personalized medicine than the United States because the US health-care system is utterly chaotic. We have every combination of every kind of health care and health delivery. We have no common shared vision,” he said. “In the end we may well go to Europe to persuade a country to really undertake this. The possibility of facilitating a revolution in health care is greater in Europe than in the United States.”     

Twin Town in South Brazil: A Nazi's Experiment or a Genetic Founder Effect?

Cândido Godói (CG) is a small municipality in South Brazil with approximately 6,000 inhabitants. It is known as the “Twins'' Town” due to its high rate of twin births. Recently it was claimed that such high frequency of twinning would be connected to experiments performed by the German Nazi doctor Joseph Mengele. It is known, however, that this town was founded by a small number of families and therefore a genetic founder effect may represent an alternatively explanation for the high twinning prevalence in CG. In this study, we tested specific predictions of the “Nazi''s experiment” and of the “founder effect” hypotheses. We surveyed a total of 6,262 baptism records from 1959–2008 in CG catholic churches, and identified 91 twin pairs and one triplet. Contrary to the “Nazi''s experiment hypothesis”, there is no spurt in twinning between the years (1964–1968) when Mengele allegedly was in CG (P = 0.482). Moreover, there is no temporal trend for a declining rate of twinning since the 1960s (P = 0.351), and no difference in twinning among CG districts considering two different periods: 1927–1958 and 1959–2008 (P = 0.638). On the other hand, the “founder effect hypothesis” is supported by an isonymy analysis that shows that women who gave birth to twins have a higher inbreeding coefficient when compared to women who never had twins (0.0148, 0.0081, respectively, P = 0.019). In summary, our results show no evidence for the “Nazi''s experiment hypothesis” and strongly suggest that the “founder effect hypothesis” is a much more likely alternative for explaining the high prevalence of twinning in CG. If this hypothesis is correct, then this community represents a valuable population where genetic factors linked to twinning may be identified.     

Crystal structure of a trimeric form of the KV7.1 (KCNQ1) A‐domain tail coiled‐coil reveals structural plasticity and context dependent changes in a putative coiled‐coil trimerization motif

Coiled-coils are widespread protein–protein interaction motifs typified by the heptad repeat (abcdefg)_n in which “a” and “d” positions are hydrophobic residues. Although identification of likely coiled-coil sequences is robust, prediction of strand order remains elusive. We present the X-ray crystal structure of a short form (residues 583–611), “Q1-short,” of the coiled-coil assembly specificity domain from the voltage-gated potassium channel Kv7.1 (KCNQ1) determined at 1.7 Å resolution. Q1-short lacks one and half heptads present in a previously studied tetrameric coiled-coil construct, Kv7.1 585–621, “Q1-long.” Surprisingly, Q1-short crystallizes as a trimer. In solution, Q1-short self-assembles more poorly than Q1-long and depends on an R-h-x-x-h-E motif common to trimeric coiled-coils. Addition of native sequences that include “a” and “d” positions C-terminal to Q1-short overrides the R-h-x-x-h-E motif influence and changes assembly state from a weakly associated trimer to a strongly associated tetramer. These data provide a striking example of a naturally occurring amino sequence that exhibits context-dependent folding into different oligomerization states, a three-stranded versus a four-stranded coiled-coil. The results emphasize the degenerate nature of coiled-coil energy landscapes in which small changes can have drastic effects on oligomerization. Discovery of these properties in an ion channel assembly domain and prevalence of the R-h-x-x-h-E motif in coiled-coil assembly domains of a number of different channels that are thought to function as tetrameric assemblies raises the possibility that such sequence features may be important for facilitating the assembly of intermediates en route to the final native state.     

围小丛壳Glomerella cingulata子囊孢子交配繁殖、生物学特性及致病性

炭疽叶枯病（Glomerella leaf spot）是我国苹果上新发现的一种病害。为了解围小丛壳Glomerella cingulata子囊孢子的交配方式、生物学特性和致病性,从安徽砀山、山东牟平等地采集病害样品,经分离培养和纯化获得单孢菌株。在适宜条件下单孢菌株可产生子囊和子囊孢子,经过毛细管破子囊壁后单孢分离,获得12个子囊,每个子囊有8个子囊孢子。其中10个子囊中有4个“正”孢子（+）和4个“负”孢子（-）,2个子囊中只有“负”孢子。子囊孢子单孢菌株培养72h,“正”菌株菌落白色,以营养生长为主;“负”菌株菌落灰白色,直径略小于正菌株,菌丝稀疏,边缘菌丝白色,中部有大量橙色的分生孢子堆。“正”、“负”菌株异宗配合后,可产生大量可育子囊壳;单独的“正”菌株有性生殖产生稀疏丛簇状的可育子囊壳;单个的“负”菌株只能产生分散且不育的子囊壳。“正”、“负”菌株菌落的生长速度没有差异,对温度、营养、光照和pH值的敏感性也没有差异,但“正”、“负”菌株的致病性存在差异。正菌株的有性生殖没有导致rDNA-ITS、β-tubulin基因碱基序列变异。     

Growth and asymmetry of soil microfungal colonies from "Evolution Canyon," Lower Nahal Oren, Mount Carmel, Israel

Background

Fluctuating asymmetry is a contentious indicator of stress in populations of animals and plants. Nevertheless, it is a measure of developmental noise, typically obtained by measuring asymmetry across an individual organism''s left-right axis of symmetry. These individual, signed asymmetries are symmetrically distributed around a mean of zero. Fluctuating asymmetry, however, has rarely been studied in microorganisms, and never in fungi.

Objective and Methods

We examined colony growth and random phenotypic variation of five soil microfungal species isolated from the opposing slopes of “Evolution Canyon,” Mount Carmel, Israel. This canyon provides an opportunity to study diverse taxa inhabiting a single microsite, under different kinds and intensities of abiotic and biotic stress. The south-facing “African” slope of “Evolution Canyon” is xeric, warm, and tropical. It is only 200 m, on average, from the north-facing “European” slope, which is mesic, cool, and temperate. Five fungal species inhabiting both the south-facing “African” slope, and the north-facing “European” slope of the canyon were grown under controlled laboratory conditions, where we measured the fluctuating radial asymmetry and sizes of their colonies.

Results

Different species displayed different amounts of radial asymmetry (and colony size). Moreover, there were highly significant slope by species interactions for size, and marginally significant ones for fluctuating asymmetry. There were no universal differences (i.e., across all species) in radial asymmetry and colony size between strains from “African” and “European” slopes, but colonies of Clonostachys rosea from the “African” slope were more asymmetric than those from the “European” slope.

Conclusions and Significance

Our study suggests that fluctuating radial asymmetry has potential as an indicator of random phenotypic variation and stress in soil microfungi. Interaction of slope and species for both growth rate and asymmetry of microfungi in a common environment is evidence of genetic differences between the “African” and “European” slopes of “Evolution Canyon.”