Mitochondrial echoes of first settlement and genetic continuity in El Salvador

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador. Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas. Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade

Austro-Asiatic Tribes of Northeast India Provide Hitherto Missing Genetic Link between South and Southeast Asia

Northeast India, the only region which currently forms a land bridge between the Indian subcontinent and Southeast Asia, has been proposed as an important corridor for the initial peopling of East Asia. Given that the Austro-Asiatic linguistic family is considered to be the oldest and spoken by certain tribes in India, Northeast India and entire Southeast Asia, we expect that populations of this family from Northeast India should provide the signatures of genetic link between Indian and Southeast Asian populations. In order to test this hypothesis, we analyzed mtDNA and Y-Chromosome SNP and STR data of the eight groups of the Austro-Asiatic Khasi from Northeast India and the neighboring Garo and compared with that of other relevant Asian populations. The results suggest that the Austro-Asiatic Khasi tribes of Northeast India represent a genetic continuity between the populations of South and Southeast Asia, thereby advocating that northeast India could have been a major corridor for the movement of populations from India to East/Southeast Asia

Theoretical basis for reducing time-lines to the determination of positive Mycobacterium tuberculosis cultures using thymidylate kinase (TMK) assays

<p>Abstract</p> <p>Background</p> <p><it>In vitro </it>culture of pathogens on growth media forms a "pillar" for both infectious disease diagnosis and drug sensitivity profiling. Conventional cultures of <it>Mycobacterium tuberculosis </it>(M.<it>tb</it>) on Lowenstein Jensen (LJ) medium, however, take over two months to yield observable growth, thereby delaying diagnosis and appropriate intervention. Since DNA duplication during interphase precedes microbial division, "para-DNA synthesis assays" could be used to predict impending microbial growth. Mycobacterial thymidylate kinase (TMKmyc) is a phosphotransferase critical for the synthesis of the thymidine triphosphate precursor necessary for M.<it>tb </it>DNA synthesis. Assays based on high-affinity detection of secretory TMKmyc levels in culture using specific antibodies are considered. The aim of this study was to define algorithms for predicting positive TB cultures using antibody-based assays of TMKmyc levels <it>in vitro</it>.</p> <p>Methods and results</p> <p>Systems and chemical biology were used to derive parallel correlation of "M.<it>tb </it>growth curves" with "TMKmyc curves" theoretically in four different scenarios, showing that changes in TMKmyc levels in culture would in each case be predictive of M.<it>tb </it>growth through a simple quadratic curvature, |tmk| = at²+ bt + c, consistent with the "S" pattern of microbial growth curves. Two drug resistance profiling scenarios are offered: isoniazid (INH) resistance and sensitivity. In the INH resistance scenario, it is shown that despite the presence of optimal doses of INH in LJ to stop M.<it>tb </it>proliferation, bacilli grow and the resulting phenotypic growth changes in colonies/units are predictable through the TMKmyc assay. According to our current model, the areas under TMKmyc curves (AUC, calculated as the integral ∫(at²+ bt + c)dt or ~1/3 at³+ 1/2 bt²+ct) could directly reveal the extent of prevailing drug resistance and thereby aid decisions about the usefulness of a resisted drug in devising "salvage combinations" within resource-limited settings, where second line TB chemotherapy options are limited.</p> <p>Conclusion</p> <p>TMKmyc assays may be useful for reducing the time-lines to positive identification of <it>Mycobacterium tuberculosis </it>(M.<it>tb</it>) cultures, thereby accelerating disease diagnosis and drug resistance profiling. Incorporating "chemiluminiscent or fluorescent" strategies may enable "photo-detection of TMKmyc changes" and hence automation of the entire assay.</p

Psychosocial stress and strategies for managing adversity: measuring population resilience in New South Wales, Australia

<p>Abstract</p> <p>Background</p> <p>Populations around the world are facing an increasing number of adversities such as the global financial crisis, terrorism, conflict, and climate change. The aim of this paper was to investigate self-reported strategies and sources of support used to get through "tough times" in an Australian context and to identify patterns of response in the general population and differences in potentially vulnerable subgroups.</p> <p>Methods</p> <p>Data were collected through a cross-sectional survey of the New South Wales population in Australia. The final sample consisted of 3,995 New South Wales residents aged 16 years and above who responded to the question: "What are the things that get you through tough times?"</p> <p>Results</p> <p>Respondents provided brief comments that were coded into 14 main subject-area categories. The most frequently reported responses were family and self (52%); friends and neighbors (21%); use of positive emotional and philosophical strategies (17%), such as sense of humor, determination, and the belief that things would get better; and religious beliefs (11%). The responses of four population subgroups were compared, based on gender, household income, level of psychological distress, and whether a language other than English was spoken at home. Women reported greater use of friends and neighbors and religious or spiritual beliefs for support, whereas men reported greater use of drinking/smoking and financial supports. Those with lower incomes reported greater reliance on positive emotional and philosophical strategies and on religious or spiritual beliefs. Those with high levels of psychological distress reported greater use of leisure interests and hobbies, drinking/smoking, and less use of positive lifestyle strategies, such as adequate sleep, relaxation, or work/life balance. Those who spoke a language other than English at home were less likely to report relying on self or others (family/friends) or positive emotional and philosophical strategies to get through tough times.</p> <p>Conclusions</p> <p>Understanding strategies and sources of support used by the population to get through adversity is the first step toward identifying the best approaches to build and support strengths and reduce vulnerabilities. It is also possible to reflect on how large-scale threats such as pandemics, disasters, conflict, bereavement, and loss could impact individual and population resilience.</p

Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

<p>Abstract</p> <p>Background</p> <p>Ionizing radiation-induced hematopoietic injury could occur either due to accidental exposure or due to diagnostic and therapeutic interventions. Currently there is no approved drug to mitigate radiation toxicity in hematopoietic cells. This study investigates the potential of ON 01210.Na, a chlorobenzylsulfone derivative, in ameliorating radiation-induced hematopoietic toxicity when administered after exposure to radiation. We also investigate the molecular mechanisms underlying this activity.</p> <p>Methods</p> <p>Male C3H/HeN mice (n = 5 mice per group; 6-8 weeks old) were exposed to a sub-lethal dose (5 Gy) of γ radiation using a ¹³⁷Cs source at a dose rate of 0.77 Gy/min. Two doses of ON 01210.Na (500 mg/kg body weight) were administered subcutaneously at 24 h and 36 h after radiation exposure. Mitigation of hematopoietic toxicity by ON 01210.Na was investigated by peripheral white blood cell (WBC) and platelet counts at 3, 7, 21, and 28 d after radiation exposure. Granulocyte macrophage colony forming unit (GM-CFU) assay was done using isolated bone marrow cells, and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) was performed on bone marrow sections at 7 d post-exposure. The DNA damage response pathway involving ataxia telangiectasia mutated (ATM) and p53 was investigated by Western blot in bone marrow cells at 7 d post-exposure.</p> <p>Results</p> <p>Compared to the vehicle, ON 01210.Na treated mice showed accelerated recovery of peripheral WBC and platelet counts. Post-irradiation treatment of mice with ON 01210.Na also resulted in higher GM-CFU counts. The mitigation effects were accompanied by attenuation of ATM-p53-dependent DNA damage response in the bone marrow cells of ON 01210.Na treated mice. Both phospho-ATM and phospho-p53 were significantly lower in the bone marrow cells of ON 01210.Na treated than in vehicle treated mice. Furthermore, the Bcl2:Bax ratio was higher in the drug treated mice than the vehicle treated groups.</p> <p>Conclusions</p> <p>ON 01210.Na treatment significantly mitigated the hematopoietic toxicity induced by a sub-lethal radiation dose. Mechanistically, attenuation of ATM-p53 mediated DNA damage response by ON 01210.Na is contributing to the mitigation of radiation-induced hematopoietic toxicity.</p

Use of the Internet for health information by physicians for patient care in a teaching hospital in Ibadan, Nigeria

BACKGROUND: The Internet is the world's largest network of information, communication and services. Although the Internet is widely used in medicine and has made significant impact in research, training and patient care, few studies had explored the extent to which Nigerian physicians use Internet resources for patient care. The objective of this study was to assess physicians' use of the Internet for health information for patient care. METHOD: 172 physicians at the University College hospital (UCH) Ibadan, Nigeria; completed a 31-item, anonymous, standardized questionnaire. The Epi-Info software was used for data analysis. RESULTS: The mean age of the respondents was 31.95 years (SD 4.94). Virtually all (98%) the respondents had used the Internet; 76% accessed it from cyber cafes. E-mail was the most commonly used Internet service (64%). Ninety percent of the respondents reported they had obtained information from the Internet for patient care; of this number, 76.2% had searched a database. The database most recently searched was MEDLINE/PubMed in 99% of cases. Only 7% of the respondents had ever searched the Cochrane Library. More than half (58.1%) perceived they had no confidence to download full-text articles from online sources such as the Health Internetwork Access to Research Initiative (HINARI). Multiple barriers to increased use of the Internet were identified including poor availability of broadband (fast connection speed) Internet access, lack of information searching skills, cost of access and information overload. CONCLUSION: Physicians' use of the Internet for health information for patient care was widespread but use of evidenced-based medicine resources such as Cochrane Library, Up-to-date and Clinical Evidence was minimal. Awareness and training in the use of EBM resources for patient care is needed. Introduction of EBM in the teaching curriculum will enhance the use of EBM resources by physicians for patient care

Informed Switching Strongly Decreases the Prevalence of Antibiotic Resistance in Hospital Wards

Antibiotic resistant nosocomial infections are an important cause of mortality and morbidity in hospitals. Antibiotic cycling has been proposed to contain this spread by a coordinated use of different antibiotics. Theoretical work, however, suggests that often the random deployment of drugs (“mixing”) might be the better strategy. We use an epidemiological model for a single hospital ward in order to assess the performance of cycling strategies which take into account the frequency of antibiotic resistance in the hospital ward. We assume that information on resistance frequencies stems from microbiological tests, which are performed in order to optimize individual therapy. Thus the strategy proposed here represents an optimization at population-level, which comes as a free byproduct of optimizing treatment at the individual level. We find that in most cases such an informed switching strategy outperforms both periodic cycling and mixing, despite the fact that information on the frequency of resistance is derived only from a small sub-population of patients. Furthermore we show that the success of this strategy is essentially a stochastic phenomenon taking advantage of the small population sizes in hospital wards. We find that the performance of an informed switching strategy can be improved substantially if information on resistance tests is integrated over a period of one to two weeks. Finally we argue that our findings are robust against a (moderate) preexistence of doubly resistant strains and against transmission via environmental reservoirs. Overall, our results suggest that switching between different antibiotics might be a valuable strategy in small patient populations, if the switching strategies take the frequencies of resistance alleles into account

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ