Steroid hormone regulation of ribosomal RNA in rat hypothalamus: early detection using in situ hybridization and precursor-product ribosomal DNA probes.
In the female rat, behavioral and endocrine aspects of reproduction are controlled, in part, by the action of the steroid hormone estradiol on several regions of the brain, including the ventrolateral portion of the ventromedial hypothalamus (VL-VMN) and the arcuate nucleus of the hypothalamus (ARC). Quantitative assessment of the effects of estradiol on the regulation of ribosomal RNA in rat hypothalamus was accomplished in this study by tandem in situ hybridization experiments with 2 ribosomal DNA probes specific to the initial transcript (precursor) or mature, stable (product) rRNA. This novel approach allowed the regulation of RNA processing by steroid hormones to be analyzed in the individual neuron, a particularly important concern in heterogeneous tissue such as the brain. Estradiol was administered subcutaneously to ovariectomized rats for 15 min, 30 min, or 2 hr, or a discontinuous schedule of 2 hr on/7 hr off/2 hr on. Levels of precursor and product rRNA were measured in VL-VMN and ARC neurons using a computerized image-analysis system. Significant increases in the levels of precursor rRNA were observed only in the VL-VMN as early as 30 min after hormone exposure, with a doubling in the amount of precursor rRNA occurring at 2 hr. No changes in product rRNA were observed in either brain region at these early times. These data, in conjunction with our previous findings of increases in product rRNA after longer hormone exposure times, lead us to conclude that rRNA gene transcription is activated in rat hypothalamic neurons within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)


[Resilience in COVID-19 times: general considerations on the recovery of a 93-year-old patient on haemodialysis treatment].
We report the case of a 93-year-old woman on haemodialysis treatment for more than 30 months and with multiple comorbidities who recovered from a Covid-19 infection without any significant clinical problems. The patient has shown a delay in viral clearance with swab test negativization (confirmed) after 33 days; after testing positive again, she has resulted persistently negative, (confirmed after 49 days). After the first negative swab, IgG and IgM antibodies have been found; these have remained persistently positive after a month. As well as highlighting an unexpected resilience in an extremely fragile context, the analysis of this case draws attention to patients' management and, potentially, to the need to arrange dialysis treatments in isolation for some time after their "laboratory recovery".


Localisation of mRNA and co-expression and molecular forms of GRP gene products in endocrine cells of fetal human lung.
The presence of bombesin (gastrin-releasing peptide, GRP)-like immunoreactivity in mucosal endocrine cells of human fetal lung is well established. In this study we have investigated the localisation of pro-GRP mRNA and GRP gene products and compared the distribution and levels of extractable GRP- and C-terminal flanking peptide of human pro-GRP-like immunoreactivity in order to verify synthesis and to investigate their coexistence and molecular forms. Human fetal lungs (14 to 23 weeks gestation) were immunostained, and extracts were assayed using region-specific antisera to pro-GRP. Additional antisera to chromogranin and protein gene product 9.5 (PGP 9.5) were used for immunostaining by the peroxidase anti-peroxidase technique and for double immunofluorescence staining using antisera raised in two species. Immunoreactivity for both bombesin (GRP) and flanking peptide was seen mainly in the same endocrine cells, but more cells were stained with antisera to flanking peptide than with antiserum to bombesin (GRP). In situ hybridisation showed that pro-GRP mRNA was present and thus synthesis of the peptides was taking place. Endocrine cells and nerve fibres were PGP 9.5-immunoreactive, and a subset of cells was immunoreactive for bombesin gene products. Radioimmunoassay and chromatography show that pro-GRP is present in both the uncleaved and cleaved forms, and, in agreement with immunocytochemistry results, that an excess of C-terminal peptide of pro-GRP is detectable. It is therefore concluded that GRP-like peptides and flanking peptide are co-localised in human pulmonary endocrine cells, but the latter is found in larger concentrations than free GRP. Thus GRP-like peptides may be secreted separately from the flanking peptide(s) of pro-GRP.(ABSTRACT TRUNCATED AT 250 WORDS)


Aloe vera in dermatology: a brief review.
Aloe vera Linne or aloe barbadensis Miller is a succulent from the Aloe family (400 different species), a tropical plant which is easily grown in hot and dry climates and widely distributed in Asia, Africa and other tropical areas. The use of aloe vera is being promoted for a large variety of conditions. The aim of this systematic review was to summarize all dermatology-oriented in vitro and in vivo experiments and clinical trials on aloe vera preparations. Extensive literature search were carried out to identify all in vitro and in vivo studies as well as clinical trials on the subject. Data were extracted from these in a predefined standardized manner. Forty studies were located. The results suggest that oral administration of aloe vera in mice is effective on wound healing, can decrease the number and size of papillomas and reduce the incidence of tumors and leishmania parasitemia by >90% in the liver, spleen, and bone marrow. Topical application of aloe vera is not an effective prevention for radiation-induced injuries and has no sunburn or suntan protection. It can be effective for genital herpes, psoriasis, human papilloma virus, seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus, frostbite, burn, wound healing and inflammation. It can also be used as a biological vehicle and an anti-microbial and antifungal agent and also as a candidate for photodynamic therapy of some kinds of cancer. Even though there are some promising results with the use of aloe vera for diverse dermatologic conditions, clinical effectiveness of oral and topical aloe vera is not sufficiently and meticulously explored as yet.


Mortality in Iraq associated with the 2003-2011 war and occupation: findings from a national cluster sample survey by the university collaborative Iraq Mortality Study.
Previous estimates of mortality in Iraq attributable to the 2003 invasion have been heterogeneous and controversial, and none were produced after 2006. The purpose of this research was to estimate direct and indirect deaths attributable to the war in Iraq between 2003 and 2011. We conducted a survey of 2,000 randomly selected households throughout Iraq, using a two-stage cluster sampling method to ensure the sample of households was nationally representative. We asked every household head about births and deaths since 2001, and all household adults about mortality among their siblings. We used secondary data sources to correct for out-migration. From March 1, 2003, to June 30, 2011, the crude death rate in Iraq was 4.55 per 1,000 person-years (95% uncertainty interval 3.74-5.27), more than 0.5 times higher than the death rate during the 26-mo period preceding the war, resulting in approximately 405,000 (95% uncertainty interval 48,000-751,000) excess deaths attributable to the conflict. Among adults, the risk of death rose 0.7 times higher for women and 2.9 times higher for men between the pre-war period (January 1, 2001, to February 28, 2003) and the peak of the war (2005-2006). We estimate that more than 60% of excess deaths were directly attributable to violence, with the rest associated with the collapse of infrastructure and other indirect, but war-related, causes. We used secondary sources to estimate rates of death among emigrants. Those estimates suggest we missed at least 55,000 deaths that would have been reported by households had the households remained behind in Iraq, but which instead had migrated away. Only 24 households refused to participate in the study. An additional five households were not interviewed because of hostile or threatening behavior, for a 98.55% response rate. The reliance on outdated census data and the long recall period required of participants are limitations of our study. Beyond expected rates, most mortality increases in Iraq can be attributed to direct violence, but about a third are attributable to indirect causes (such as from failures of health, sanitation, transportation, communication, and other systems). Approximately a half million deaths in Iraq could be attributable to the war. Please see later in the article for the Editors' Summary.


Protective effects of Bee pollen extract on the Caco-2 intestinal barrier dysfunctions induced by dextran sulfate sodium.
Bee pollen (BP) is a natural medicine from the hive with various potential health-promoting benefits, but until now there is no study to determine its protective roles in inflammatory bowel disease (IBD). The aim of this study was to reveal the in vitro gastrointestinal protective effects of BP against IBD using molecular and metabolic methods. Dextran sulfate sodium (DSS) challenged Caco-2 cell monolayers were applied to mimic intestinal epithelial cell dysfunctions and metabolic disorders. The pretreatment with BP extract rich in polyphenols ameliorated DSS-induced cell viability losses. It also exerted protective effects against intestinal barrier impairment by strengthening epithelial integrity and tight junction losses induced by DSS. BP up-regulated anti-oxidant (NQO1, Txnrd1, Nrf2) and down-regulated inflammatory (TNF-α and IL-6) mRNA expressions, in accompany with MAPK signaling inhibition. Furthermore, metabolomics analysis based on UPLC-Q-TOF/MS revealed that BP, and DSS treated Caco-2 cells have different metabolomic profiles, with significant changes on key metabolites involved in glycerophospholipid metabolism. Our results showed that BP has great therapeutic potential throughout the early stages of DSS-induced colitis.


Cooperative effects of exercise and occlusive stimuli on muscular function in low-intensity resistance exercise with moderate vascular occlusion.
To obtain insight into the relative contributions of exercise and occlusive stimuli to these muscular adaptations, the present study investigated the short- and long-term effects of varied combinations of low-intensity exercise and vascular occlusion. The subjects were separated into 3 groups (n = 6 for each group): low-intensity with vascular occlusion (LIO), low-intensity without vascular occlusion (LI), and vascular occlusion without exercise (VO). LIO and LI groups performed bilateral knee extension exercises in seated positions with an isotonic extension machine. In the LIO group, both sides of the thigh were pressure-occluded at the proximal end by means of a tourniquet during the entire session of exercise (approximately 10 min), whereas only the occlusion with the same pressure and duration was given in the VO group. The mean occlusion pressure was 218 +/- 8.1 mmHg (mean +/- SE). The exercise session consisted of five sets of exercise at an intensity of 10-20% 1RM and was performed twice a week for 8 wk. After the period of exercise training, isometric and isokinetic strengths at all velocities examined increased significantly in the LIO group (p < 0.05), whereas no significant change in strength was seen in the LI and VO groups. The increase in muscular strength in LIO was associated with a significant increase in the cross-sectional area of knee extensor muscles by 10.3 +/- 1.6%. The plasma growth hormone concentration measured 15 min after the session of exercise showed a marked increase only in LIO. The results showed that the low-intensity exercise and occlusive stimuli have cooperative effects in the long-term adaptation of muscle and an acute response to growth hormone.


Sociopsychological tailoring to address colorectal cancer screening disparities: a randomized controlled trial.
Interventions tailored to sociopsychological factors associated with health behaviors have promise for reducing colorectal cancer screening disparities, but limited research has assessed their impact in multiethnic populations. We examined whether an interactive multimedia computer program (IMCP) tailored to expanded health belief model sociopsychological factors could promote colorectal cancer screening in a multiethnic sample. We undertook a randomized controlled trial, comparing an IMCP tailored to colorectal cancer screening self-efficacy, knowledge, barriers, readiness, test preference, and experiences with a nontailored informational program, both delivered before office visits. The primary outcome was record-documented colorectal cancer screening during a 12-month follow-up period. Secondary outcomes included postvisit sociopsychological factor status and discussion, as well as clinician recommendation of screening during office visits. We enrolled 1,164 patients stratified by ethnicity and language (49.3% non-Hispanic, 27.2% Hispanic/English, 23.4% Hispanic/Spanish) from 26 offices around 5 centers (Sacramento, California; Rochester and the Bronx, New York; Denver, Colorado; and San Antonio, Texas). Adjusting for ethnicity/language, study center, and the previsit value of the dependent variable, compared with control patients, the IMCP led to significantly greater colorectal cancer screening knowledge, self-efficacy, readiness, test preference specificity, discussion, and recommendation. During the followup period, 132 (23%) IMCP and 123 (22%) control patients received screening (adjusted difference = 0.5 percentage points, 95% CI -4.3 to 5.3). IMCP effects did not differ significantly by ethnicity/language. Sociopsychological factor tailoring was no more effective than nontailored information in encouraging colorectal cancer screening in a multiethnic sample, despite enhancing sociopsychological factors and visit behaviors associated with screening. The utility of sociopsychological tailoring in addressing screening disparities remains uncertain.


Tissue Expanders and Proton Beam Radiotherapy: What You Need to Know.
Proton beam radiotherapy (PBR) has gained acceptance for the treatment of breast cancer because of unique beam characteristics that allow superior dose distributions with optimal dose to the target and limited collateral damage to adjacent normal tissue, especially to the heart and lungs. To determine the compatibility of breast tissue expanders (TEs) with PBR, we evaluated the structural and dosimetric properties of 2 ex vivo models: 1 model with internal struts and another model without an internal structure. Although the struts appeared to have minimal impact, we found that the metal TE port alters PBR dynamics, which may increase proton beam range uncertainty. Therefore, submuscular TE placement may be preferable to subcutaneous TE placement to reduce the interaction of the TE and proton beam. This will reduce range uncertainty and allow for more ideal radiation dose distribution.


Targeting immunotherapy for bladder cancer by using anti-CD3 × CD155 bispecific antibody.
To investigate whether CD155 is an attractive target for T cell-mediated immunotherapy against human bladder cancer, we examined the novel bispecific antibody anti-CD3 x anti-CD155 (CD155Bi-Ab) for its ability to redirect activated T cells (ATCs) to target bladder cancer cells was examined. Expression of CD155 was detected by flow cytometry on the surface of bladder cancer cells, including T24 and Pumc-91 cells, and their chemotherapeutic drug-resistant counterparts. ATCs generated from healthy donors were stimulated with anti-CD3 monoclonal antibody, anti-CD28 monoclonal antibody and interleukin-2 (IL-2) for 14 days. The cytotoxic activity of ATCs armed with CD155Bi-Ab against bladder cancer cells was detected by LDH and luciferase quantitative assay. Furthermore, ATCs generated from bladder cancer patients were also armed with CD155Bi-Ab to verity the cell killing by the same methods. In contrast to unarmed ATCs, CD155Bi-armed ATCs against bladder cancer cells were increased cytotoxic activity at effector/target (E/T) ratios of 5:1, 10:1, and 20:1, with more IFN-γ, TNF-α secreting. It is worth noting that in spite of the presence of immunosuppression in bladder cancer patients and the drug resistance in chemotherapeutic drug-resistant cancer cell lines, not only the anti-tumor effect of CD155Bi-armed ATCs generated from bladder cancer patients still showed significantly but only higher level of activation marker CD69 was expressed. Taken together, our results suggest that CD155 is an effective target for the CD155-positive bladder cancer. And CD155Bi-Ab-armed ATCs are promisingly to provide a novel strategy for current CD155-positive bladder cancer therapy.


Significant Predictors of Sports Performance in Elite Men Judo Athletes Based on Multidimensional Regression Models.
This research aimed to identify the most significant predictors of sports level using regression modeling. This study examined 16 judokas (aged 23 (±2.5)) from four weight categories, with four athletes in each category (66 kg, 73 kg, 81 kg and 90 kg). Each athlete was a member of the Polish National Team, an international master class (IM) or national master class (M). The tests were carried out twice (every two weeks) during the pre-competitive season in the morning, after a 10-min warm-up. The tests were performed according to the following protocol: Explosive Strength Lower Limbs (ExSLL) [W], Strength Endurance Lower Limbs (SELL) [%], Explosive Strength Upper Limbs (ExSUL) [W], Strength Endurance Upper Limbs (SEUL) [%]. The relationships between the dependent variable (ranking score) and the other analyzed variables (predictors) were estimated using the one-factor ridge regression analysis. There were significant intergroup and intragroup differences in the results of explosive strength and strength endurance of the lower and upper limbs. The best predictors were identified using regression modeling: ExSLL, SELL, and SEUL. Increasing the value of these predictors by a unit should significantly affect the scores in the ranking table. Correlation analysis showed that all variables that are strongly correlated with the Polish Judo Association (PJA) ranking table scores may have an effect on the sports performance.


Dynamic substrate based on photocleavable poly(ethylene glycol): zeta potential determines the capability of geometrical cell confinement.
Dynamic substrates whose cell adhesiveness changes in response to an external stimulus are useful not only for patterning cells in various geometries but also for inducing cell migration or arraying heterotypic cells. The requirements for such applications are high switching efficiency in cell adhesiveness and long-term persistence of the created cellular patterns. In this study, we prepared a dynamic substrate bearing photocleavable poly(ethylene glycol) (PEG) and examined the effect of the surface PEG density and the charge of cationic base materials on the above-mentioned key requirements. An amino-terminated substrate with a certain amino group density and charge was functionalized with photocleavable PEG5K, with and without subsequent backfilling of photocleavable PEG2K. The PEG chains made the surface non-cell-adhesive, but subsequent near-UV irradiation of the substrate induced photocleavage of the PEG, eventually making the surface cell-adhesive. The substrates were analyzed by atomic force microscopy, contact angle measurements, ellipsometry, and zeta potential measurements, complemented with protein adsorption observations. Although the density of amino group in the base material affected both the grafting efficiency of the backfilling PEG and the electrokinetic potential mainly in the positive range, the latter mainly determined the protein- and cell-repelling abilities of the substrates. Furthermore, varying the surface compositions had almost no effect on the switching efficiency in the early stage of the culture, but it became more significant after culturing cells for a longer time; the cells fouled the nonirradiated PEGylated regions earlier on the surfaces with higher positive zeta potentials. These results indicate that the zeta potential is an essential factor in the long-term persistence of cellular patterns on photoactivatable substrates. This study not only provides a recipe for the development of a dynamic substrate with an adequate time frame but also clarifies how the interfacial nanoarchitectures, composed of the nanometer-scale PEG brushes and charged base materials, affect the biocompatibility.


A Recyclable Metal-Organic Framework as a Dual Detector and Adsorbent for Ammonia.
Recyclable materials for simultaneous detection and uptake of ammonia (NH3 ) are of great interest due to the hazardous nature of NH3 . The structural versatility and porous nature of metal-organic frameworks (MOFs) make them ideal candidates for NH3 capture. Herein, the synthesis of a water-stable and porous 3-dimensional CuII -based MOF (SION-10) displaying a ship-in-a-bottle structure is reported; the pores of the host SION-10 framework accommodate mononuclear CuII -complexes. SION-10 spontaneously uptakes NH3 as a result of two concurrent mechanisms: chemisorption due to the presence of active CuII sites and physisorption (bulk permanent porosity). The color of the material changes from green to blue upon NH3 capture, with the shifts of the UV/Vis absorption bands clearly seen at NH3 concentrations as low as 300 ppm. SION-10 can be recovered upon immersion of SION-10⊃NH3 in water and can be further reused for NH3 capture for at least three cycles.


Neural processing of vision and language in kindergarten is associated with prereading skills and predicts future literacy.
The main objective of this longitudinal study was to investigate the neural predictors of reading acquisition. For this purpose, we followed a sample of 54 children from the end of kindergarten to the end of second grade. Preliterate children were tested for visual symbol (checkerboards, houses, faces, written words) and auditory language processing (spoken words) using a passive functional magnetic resonance imaging paradigm. To examine brain-behavior relationships, we also tested cognitive-linguistic prereading skills at kindergarten age and reading performance of 48 of the same children 2 years later. Face-selective response in the bilateral fusiform gyrus was positively associated with rapid automatized naming (RAN). Response to both spoken and written words at preliterate age was negatively associated with RAN in the dorsal temporo-parietal language system. Longitudinally, neural response to faces in the ventral stream predicted future reading fluency. Here, stronger neural activity in inferior and middle temporal gyri at kindergarten age was associated with higher reading performance. Our results suggest that interindividual differences in the neural system of language and reading affect literacy acquisition and thus might serve as a marker for successful reading acquisition in preliterate children.


Protective role of gamma-aminobutyric acid against chronic renal failure in rats.
The protective effect of gamma-aminobutyric acid (GABA) against chronic renal failure (CRF) was investigated using a remnant kidney model with 5/6 nephrectomized rats. Nephrectomy led to renal dysfunction, which was evaluated via several parameters including serum urea nitrogen, creatinine (Cr) and Cr clearance. However, the administration of GABA ameliorated renal dysfunction, and a longer administration period of GABA increased its protective effect. In addition, nephrectomized control rats showed an elevation in the fractional excretion of sodium (FE(Na)) with an increase in urinary sodium, while GABA led to a significant decline in FE(Na). Moreover, nephrectomy resulted in a decrease of serum albumin and an increase of urinary protein with a change in the urinary protein pattern, whereas the rats administered GABA showed improvement in these changes associated with CRF caused by nephrectomy. This suggests that GABA would inhibit the disease progression and have a protective role against CRF. As one of the risk factors for CRF progression, hypertension was also regulated by GABA. The results also indicate that GABA may play a protective role against CRF through improvement of the serum lipid profile, with reductions in triglyceride and total cholesterol. Furthermore, nephrectomy led to renal oxidative stress with a decrease in the activity of antioxidative enzymes and elevation of lipid peroxidation. The administration of GABA attenuated oxidative stress induced by nephrectomy through an increase in superoxide dismutase and catalase, and decrease in lipid peroxidation. The histopathological lesions, including glomerular, tubular and interstitial lesions, under nephrectomy were also improved by GABA with the inhibition of fibronectin expression. This study demonstrated that GABA attenuated renal dysfunction via regulation of blood pressure and lipid profile, and it also ameliorated the oxidative stress induced by nephrectomy, suggesting the promising potential of GABA in protecting against renal failure progression.


Processing of primary microRNAs by the Microprocessor complex.
Mature microRNAs (miRNAs) are generated via a two-step processing pathway to yield approximately 22-nucleotide small RNAs that regulate gene expression at the post-transcriptional level. Initial cleavage is catalysed by Drosha, a nuclease of the RNase III family, which acts on primary miRNA transcripts (pri-miRNAs) in the nucleus. Here we show that Drosha exists in a multiprotein complex, the Microprocessor, and begin the process of deconstructing that complex into its constituent components. Along with Drosha, the Microprocessor also contains Pasha (partner of Drosha), a double-stranded RNA binding protein. Suppression of Pasha expression in Drosophila cells or Caenorhabditis elegans interferes with pri-miRNA processing, leading to an accumulation of pri-miRNAs and a reduction in mature miRNAs. Finally, depletion or mutation of pash-1 in C. elegans causes de-repression of a let-7 reporter and the appearance of phenotypic defects overlapping those observed upon examination of worms with lesions in Dicer (dcr-1) or Drosha (drsh-1). Considered together, these results indicate a role for Pasha in miRNA maturation and miRNA-mediated gene regulation.


Parental supply of alcohol as a predictor of adolescent alcohol consumption patterns: A prospective cohort.
Recent research has not supported the idea that parental supply of alcohol to adolescents prevents later alcohol-related harm. Yet the specific role of parental supply in shaping patterns of drinking over time remains unclear. This study investigated the role of parental supply of alcohol in patterns of drinking across adolescence, and assessed whether that role remained consistent over time. Using a longitudinal cohort of 1927 adolescents (mean age 12.9 years), recruited in 2010 and 2011 from schools across Australia and followed up annually until 2016, we assessed three outcomes using mixed-effect negative binomial regression: frequency of consumption, typical quantity consumed, and overall alcohol consumption in the year (frequency * quantity). Child, parental, familial, and peer confounders of adolescent alcohol consumption were measured and adjusted for in the analyses. Parental supply was associated with greater overall consumption in earlier adolescence: Grade 7-8 (incidence rate ratio [IRR]: 3.61; 95% CI: 2.55, 5.12; no supply IRR: 1.00), Grade 8-9 (IRR: 4.84; 95% CI: 3.66, 6.39; no supply IRR: 1.44) and Grade 9-10 (IRR: 8.33; 95% CI: 6.28, 11.05; no supply IRR: 4.75). Alcohol consumption continued to increase in later adolescence regardless of whether parental supply occurred. Parental supply of alcohol was associated with increased alcohol consumption by their children during early adolescence. While parental supply appears to have less impact on drinking in later adolescence, there was no evidence to suggest it is protective. Parents should be advised to avoid supplying children with alcohol, particularly in early adolescence.


[Reproductive risk factors associated with breast cancer in Colombian women].
As of 1992, breast cancer has been the second cause of death in Columbian women, with a rising trend in mortality due to this type of neoplasm (average annual rate 4.5*/100.000 inhabitants). Information about potential risk factors for breast cancer in Latin American countries is scarce. The objectives of the project were to test the breastfeeding protection against breast cancer and to establish the reproductive factors associated with breast cancer in Columbia. A hospital case-control study was carried out from July 1995 to March 1996 in Bogotá, Columbia, using paring by age groups. The study population consisted of 171 histopathologically confirmed cases and 171 controls. Reproductive history and sociodemographic data were collected through a questionnaire, and logistic regression models were used for statistical analysis of the data. The following associated factors were found as principal results: nuli-parousness as compared with women with over 3 children (OR=3.35 CI 1.40-8.0), age at first birth (OR=1.83 CI 0.70- 4.80), breast cancer history, breastfeeding the first child (OR=0.09 CI 0.01-0.64 for 1-11 months) and with a highly significant trend for accumulated breastfeeding above 24 months (p=0.001). This study indicates the importance of focusing on the promotion of prolonged breastfeeding by women identified as being at higher risk, and confirms that socio-economic level can determine life styles and reproductive events among women (such as breastfeeding time); this could explain the increase in breast cancer mortality in Latin American countries, similar to that in developed countries in terms of fertility and risk factors for breast cancer. The epidemiological information produced by this study will be useful for planning and carrying out early diagnosis and treatment of breast cancer in women identified as being at high risk of this disease.


Cow characteristics and their association with udder health after different dry period lengths.
Shortening or omitting the dry period (DP) in dairy cows is of interest because of potential beneficial effects on energy balance and metabolic health. Reported effects of a short or omitted dry period on udder health are ambiguous. This study aimed to evaluate the effect of no DP (0d), a short DP (30d), or a conventional DP (60 d) on the occurrence of intramammary infections (IMI) during the precalving period and on somatic cell counts (SCC), elevations of SCC (SCC≥200,000 cells/mL), and clinical mastitis in the subsequent lactation. The study also aimed to analyze which prepartum cow characteristics are associated with udder health after different DP lengths. Holstein-Friesian dairy cows (n=167) were randomly assigned to a DP length (0, 30, or 60 d). Cows with a 0-d DP had a greater occurrence of chronic IMI and a lower occurrence of cured IMI during the precalving period than cows with a 30-d or 60-d DP. Postpartum average SCC for lactation was greater in cows with a 0-d DP than in cows with a 30-d or 60-d DP. The number of cows with at least 1 elevation of SCC, the number of elevations of SCC per affected cow, the number of cows treated for clinical mastitis, and the number of cases of mastitis per affected cow did not differ among DP lengths. Cow characteristics related to postpartum average SCC for lactation were DP length, parity, and the following interactions: DP length with prepartum elevation of SCC, DP length with fat- and protein-corrected milk (FPCM) reduction between 150 and 67d prepartum, DP length with parity and with average SCC for lactation, and last FPCM before the conventional drying-off day with average SCC for lactation. Cows with prepartum parity 1 had a lower occurrence of at least 1 elevation of SCC in subsequent lactation compared with cows with parity >2. Last SCC before the conventional drying-off day was positively associated with occurrence of clinical mastitis in the subsequent lactation. In this study, DP length was not a risk factor for either elevation of SCC or occurrence of clinical mastitis in the subsequent lactation. The identified cow characteristics could be used in a decision support model to optimize DP length for individual cows.


Association between genotype and drug resistance profiles of Mycobacterium tuberculosis strains circulating in China in a national drug resistance survey.
We describe the population structure of a representative collection of 3,133 Mycobacterium tuberculosis isolates, collected within the framework of a national resistance survey from 2007 in China. Genotyping data indicate that the epidemic strains in China can be divided into seven major complexes, of which 92% belonged to the East Asian (mainly Beijing strains) or the Euro-American lineage. The epidemic Beijing strains in China are closely related to the Beijing B0/W148 strain earlier described in Russia and a large cluster of these strains has spread national wide. The density of Beijing strains is high in the whole of China (average 70%), but the highest prevalence was found North of the Yellow river. The Euro-American lineage consists of three sublineages (sublineage_1, 2, and 3) and is more prevalent in the South. Beijing lineage showed the highest cluster rate of 48% and a significantly higher level of resistance to rifampicin (14%, p<0.001), ethambutol (9%, p = 0.001), and ofloxacin (5%, p = 0.011). Within the Euro-American Lineage, sublineage_3 revealed the highest cluster rate (28%) and presented a significantly elevated level of resistance to streptomycin (44%, p<0.001). Our findings suggest that standardised treatment in this region may have contributed to the successful spread of certain strains: sublineage_3 in the Euro-American lineage may have thrived when streptomycin was used without rifampicin for treatment, while later under DOTS based treatment, in which rifampicin plays a key role, Beijing lineage appears to be spreading.


Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand.
Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly. Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits. The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious Diseases.).


Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Regional and diagnostic specificity.
Multiple lines of evidence indicate that the prefrontal cortex is a site of dysfunction in schizophrenia. However, the apparent absence of gross structural abnormalities in this area suggests that the pathophysiological characteristics of schizophrenia may involve more subtle disturbances in prefrontal cortical circuitry, such as alterations in synaptic connectivity and transmission. In this study, immunoreactivity for synaptophysin, an integral membrane protein of small synaptic vesicles, was used to assess the integrity of cortical synaptic circuitry in schizophrenia. Using immunocytochemical techniques and adjusted optical density measurements, we examined synaptophysin immunoreactivity in prefrontal cortical areas 9 and 46 and in area 17 (the primary visual cortex) from 10 pairs of case subjects with schizophrenia and control subjects. matched on a pairwise basis for age, sex, race, and postmortem interval, and in 5 matched pairs of nonschizophrenic psychiatric case subjects and normal control subjects. Compared with levels found in matched control subjects, synaptophysin immunoreactivity in areas 46 and 9 was significantly decreased (P < .001 and P < .008, respectively) across all cortical layers in the case subjects with schizophrenia. In contrast, no differences were observed in area 17. In addition, levels of synaptophysin immunoreactivity in areas 46, 9, and 17 did not differ between 5 nonschizophrenic psychiatric case subjects and their matched controls, suggesting that decreased synaptophysin levels in the prefrontal cortex of patients with schizophrenia may be specific to that disorder. Additional studies are required to determine if the decrease in levels of synaptophysin immunoreactivity is caused by a decrease in the number or size of presynaptic terminals, a decrease in the number of synaptic vesicle per terminal, or a decrease in the expression of synaptophysin. However, all of these potential explanations are consistent with a disturbance in synaptic transmission in the prefrontal cortex of patients with schizophrenia.


Feasibility test of a UK-scalable electronic system for regular collection of patient-reported outcome measures and linkage with clinical cancer registry data: the electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system.
Cancer survivors can face significant physical and psychosocial challenges; there is a need to identify and predict which survivors experience what sorts of difficulties. As highlighted in the UK National Cancer Survivorship Initiative, routine post-diagnostic collection of patient reported outcome measures (PROMs) is required; to be most informative, PROMs must be linked and analysed with patients' diagnostic and treatment information. We have designed and built a potentially cost-efficient UK-scalable electronic system for collecting PROMs via the internet, at regular post-diagnostic time-points, for linking these data with patients' clinical data in cancer registries, and for electronically managing the associated patient monitoring and communications; the electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system. This study aims to test the feasibility of the ePOCS system, by running it for 2 years in two Yorkshire NHS Trusts, and using the Northern and Yorkshire Cancer Registry and Information Service. Non-metastatic breast, colorectal and prostate cancer patients (largest survivor groups), within 6 months post-diagnosis, will be recruited from hospitals in the Yorkshire Cancer Network. Participants will be asked to complete PROMS, assessing a range of health-related quality-of-life outcomes, at three time-points up to 15 months post-diagnosis, and subsequently to provide opinion on the ePOCS system via a feedback questionnaire. Feasibility will be examined primarily in terms of patient recruitment and retention rates, the representativeness of participating patients, the quantity and quality of collected PROMs data, patients' feedback, the success and reliability of the underpinning informatics, and the system running costs. If sufficient data are generated during system testing, these will be analysed to assess the health-related quality-of-life outcomes reported by patients, and to explore if and how they relate to disease, treatment and/or individual differences characteristics. There is currently no system in the UK for collecting PROMs online and linking these with patients' clinical data in cancer registries. If feasible, ePOCS has potential to provide an affordable UK-scalable technical platform to facilitate and support longitudinal cohort research, and improve understanding of cancer survivors' experiences. Comprehensive understanding of survivorship difficulties is vital to inform the development and provision of supportive services and interventions.


Identification of Leukocytes Associated With Midday Fogging in the Post-Lens Tear Film of Scleral Contact Lens Wearers.
Midday fogging is a frequent complaint among scleral contact lens (ScCL) wearers, and the mechanism and cause of this is unknown. The purpose of this investigation was to understand the relation between midday fogging, ocular surface leukocytes, and ScCL fitting characteristics. Subjects arrived at a clinical exam having worn ScCLs for at least 4 hours. ScCL were removed, and 150 μL of phosphate-buffered saline (PBS) was used to wash the bowl of the ScCL. Eyes were washed post-ScCL removal with 5 mL PBS per eye. Wash solutions were collected and leukocytes were then isolated and counted, followed by assessment with flow cytometry. Samples from the post-lens tear fluid were stained with fluorescently labeled antibodies to detect leukocyte distributions. Thirty-nine eyes from 19 adapted, full-time, ScCL wearers were included, and 46% presented with midday fogging. ScCL corneal clearance was 246 ± 61 μm for nonfoggers, while it was 308 ± 98 μm for those with fogging (P < 0.05). On average, the number of leukocytes collected from the ScCL bowl (9551 ± 18,926) was greater than the number of leukocytes recovered from the eye wash (2195 ± 4384, P < 0.02). ScCL corneal clearance was associated with the presence of fogging, with an odds ratio of 2.24 (95% confidence interval = 1.48-3.38, P < 0.001). Leukocytes, predominated by neutrophils, are present in the post-lens tear film of ScCL wearers, and in particular wearers with greater ScCL corneal clearance have greater odds of having midday fogging.


Native chemical ligation for conversion of sequence-defined oligomers into targeted pDNA and siRNA carriers.
Native chemical ligation (NCL) was established for the conversion of sequence-defined oligomers of different topologies into targeted and PEG shielded pDNA and siRNA carriers. From an existing library of non-targeted oligoethanamino amides, six oligomers containing N-terminal cysteines were selected as cationic cores, to which monodisperse polyethylene glycol (PEG) containing terminal folic acid as targeting ligand (or terminal alanine as targeting negative control ligand) were attached by NCL. Ligated conjugates plus controls (in sum 18 oligomers) were evaluated for pDNA or siRNA gene delivery. Biophysical characteristics including nucleic acid binding in the absence or presence of serum, as well as biological activities in cellular uptake and gene transfer (or gene silencing, respectively) were determined. In most cases, the folic acid-PEG-ligated oligomers displayed a strongly improved cellular binding, uptake and gene transfer into receptor-positive KB cells as compared to the alanine-PEG controls. Changing the topological structures by increasing the number of cationic arms, adding tyrosine trimers as polyplex stabilizing domains, or histidines facilitating endosomal escape resulted in beneficial gene transfer characteristics. The screen revealed different requirements for pDNA and siRNA delivery. A folate-PEG ligated histidinylated four-arm oligomer was most effective for pDNA delivery but inactive for siRNA, whereas a folate-PEG-ligated three-arm oligomer with tyrosine trimer modifications was most effective in siRNA mediated gene silencing. The results demonstrate the site-selective NCL reaction as powerful method to modify existing oligomers. Thus multifunctional targeted carriers can be obtained with ease and used to identify lead structures for subsequent in vivo delivery.


The European Brain Injury Consortium survey of head injuries.
To provide a picture of contemporary practice, a survey was carried out of severely and moderately head injured patients admitted to 67 'neuro' centres in 12 European countries. 1,005 adult head injuries were recruited over a three month period. Sixty items of information on demography, clinical features, investigations, management and early complications were captured on a simple, two-page questionnaire and, information on outcome at six months on a third page. The median age of the subjects was 38 years, 74% were male and 51% injured in road traffic accidents; 57% of patients were transferred to the 'neuro' centre from another hospital. Assessment of clinical responsiveness was limited by the use of sedation and intubation and information from four early time points (pre-hospital, arrival at the Accident and Emergency department, post-resuscitation, and arrival at the 'neuro' unit) was combined to stratify the subjects as severe (58%), moderate (17%) or intermediate (19%). In 48% of patients classified the CT scan showed features of a 'mass lesion' and in 40% showed a subarachnoid haemorrhage. Fifty-five centres provided the data on outcome for 94% of the cases recruited in these centres six months after injury. 31% died, 3% were vegetative, 16% severely disabled, 20% moderately disabled and 31% had made a good recovery. Comparison of the data from different parts of Europe showed differences in the frequency of secondary transfer, cause of injury, occurrence of major extracranial injury, CT scan findings, intracranial operation, clinical severity of injury and utilisation of the components of intensive care and the occurrence of a favourable outcome, although the latter difference was not statistically significant when variations in the initial severity of injury were taken into account. The findings in the present survey are compared with newly analysed information for three previous large series: the International Data Bank involving the UK, the Netherlands and the USA, the North American Traumatic Coma Data Bank, and data from four centres in the UK. The comparisons showed substantial similarities and also differences that may reflect variations in policy for admission of the head injury to 'neuro' units, and evolution in methods of assessment, investigation and management. The effects of these differences on outcome requires further, rigorous prospective study.


Post-operative pain after knee arthroscopy and related factors.
The aim of this study was to explore the intensity of post-arthroscopy knee pain during the first 24 hours, and to study the influence of pre-operative pain, tourniquet time and amount of surgical trauma on post-arthroscopy pain. In 78 male patients that underwent elective arthroscopic menisectomy or diagnostic arthroscopy of the knee, preoperative and post-operative pain were registered using the Visual Analogue Scale. Variance for repeated measures and for independent observations was analysed. Supplementary analgesia was required for 23% of the patients, more often in the recovery room and between 2 and 8 hours postoperatively. Of all factors analyzed, only time was statistically significant in determining the level of post-operative pain. Supplementary analgesia was required only in patients that underwent operative arthroscopy, and more often in patients with tourniquet time of more than 40 minutes. In conclusions, post-operative time is the most significant factor related to the post-arthroscopy knee pain.


Irradiated wild-type and Spa mutant Staphylococcus aureus induce anti-S. aureus immune responses in mice which do not protect against subsequent intravenous challenge.
Staphylococcus aureus remains an important human and animal pathogen. Its pathogenicity is determined in part by expression of the Spa-immune subversion protein, neutralising the activity of which provides partial protection in murine models, as does experimental infection with live S. aureus with Spa gene deletions followed by antibiotic-mediated cure in mice. Together, these data raise the question of whether Spa mutant S. aureus might represent a viable vaccine. Here, we find that gamma-irradiated S. aureus strains, both wild-type and null mutant of spa, are immunogenic in mice when administered intramuscularly, eliciting large amounts of anti-S. aureus antibodies, as judged by whole-cell immunoassay on fixed microorganisms. We used an intravenous challenge system to assess vaccine efficacy, the sensitivity of which was increased by studying renal bacterial concentrations in both kidneys. Despite this, protection from intravenous challenge was not observed (mean difference between vaccinated and unvaccinated mice 0.27 log(10) with 95% confidence interval -0.922 to 1.467). Surprisingly, antibody responses elicited against a panel of protective cell surface proteins were very low, indicating that most antibody induced is not protective. Additionally, these data suggest a limited role for irradiated wild-type or spa mutant S. aureus as vaccines.


Updates in the management of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and its increasing incidence worldwide is a cause for concern. Fortunately, advances in diagnostic and therapeutic approaches have contributed to earlier detection and treatment. As cancer epidemiology studies continue to elucidate the natural history of liver diseases, greater understanding of HCC has led to improved risk stratification and earlier enrollment of high-risk patients in cancer screening and surveillance programs. Improved survival rates among HCC patients also reflect significant advances in available treatment options. Advances in surgical techniques are pushing the boundaries of resection for localized disease, and progress in the field of transplantation has led to refinements in listing criteria and improved post-transplantation outcomes. The evolving field of locoregional therapies-including percutaneous ablation and transarterial chemoembolization-continues to provide novel therapeutic options that can be used in place of, or in addition to, surgical approaches. Recent advances in systemic multikinase inhibitor therapies have also demonstrated significant benefits for advanced-stage disease, and these therapies also show promise as adjuvant treatments for earlier-stage disease. This article provides an update on the management of HCC, with a focus on revised guidelines for screening and an in-depth discussion of emerging novel therapies.


Ecological Overlap and Horizontal Gene Transfer in Staphylococcus aureus and Staphylococcus epidermidis.
The opportunistic pathogens Staphylococcus aureus and Staphylococcus epidermidis represent major causes of severe nosocomial infection, and are associated with high levels of mortality and morbidity worldwide. These species are both common commensals on the human skin and in the nasal pharynx, but are genetically distinct, differing at 24% average nucleotide divergence in 1,478 core genes. To better understand the genome dynamics of these ecologically similar staphylococcal species, we carried out a comparative analysis of 324 S. aureus and S. epidermidis genomes, including 83 novel S. epidermidis sequences. A reference pan-genome approach and whole genome multilocus-sequence typing revealed that around half of the genome was shared between the species. Based on a BratNextGen analysis, homologous recombination was found to have impacted on 40% of the core genes in S. epidermidis, but on only 24% of the core genes in S. aureus. Homologous recombination between the species is rare, with a maximum of nine gene alleles shared between any two S. epidermidis and S. aureus isolates. In contrast, there was considerable interspecies admixture of mobile elements, in particular genes associated with the SaPIn1 pathogenicity island, metal detoxification, and the methicillin-resistance island SCCmec. Our data and analysis provide a context for considering the nature of recombinational boundaries between S. aureus and S. epidermidis and, the selective forces that influence realized recombination between these species.


Recognition of essential purines by the U1A protein.
The RNA recognition motif (RRM) is one of the largest families of RNA binding domains. The RRM is modulated so that individual proteins containing RRMs can specifically recognize RNA targets with diverse sequences and structures. Understanding the principles governing this specificity will be important for the rational modification and design of RRM-RNA complexes. In this paper we have investigated the origins of specificity of the N terminal RRM of the U1A protein for stem loop 2 (SL2) of U1 snRNA by substituting modified bases for essential purines in SL2 RNA. In one series of modified bases, hydrogen bond donors and acceptors were replaced by aliphatic groups to probe the importance of these functional groups to binding. In a second series of modified bases, hydrogen bond donors and acceptors were incorrectly placed on the purine bases to analyze the origins of discrimination between cognate and non-cognate RNA. The results of these experiments show that three different approaches are used by the U1A protein to gain specificity for purines. Specificity for the first base in the loop, A1, is based primarily on discrimination against RNA containing the incorrect base, specificity for the fourth base in the loop, G4, is based largely on recognition of the donors and acceptors of G4, while specificity for the sixth base in the loop, A6, results from a combination of direct recognition of the base and discrimination against incorrectly placed functional groups. These investigations identify different roles that hydrogen bond donors and acceptors on bases in both cognate and non-cognate RNA play in the specific recognition of RNA by the U1A protein. Taken together with investigations of other RNA-RRM complexes, the results contribute to a general understanding of the origins of RNA-RRM specificity and highlight, in particular, the contribution of steric and electrostatic repulsion to binding specificity.


Structures of dCTP deaminase from Escherichia coli with bound substrate and product: reaction mechanism and determinants of mono- and bifunctionality for a family of enzymes.
dCTP deaminase (EC 126.96.36.199) catalyzes the deamination of dCTP forming dUTP that via dUTPase is the main pathway providing substrate for thymidylate synthase in Escherichia coli and Salmonella typhimurium. dCTP deaminase is unique among nucleoside and nucleotide deaminases as it functions without aid from a catalytic metal ion that facilitates preparation of a water molecule for nucleophilic attack on the substrate. Two active site amino acid residues, Arg(115) and Glu(138), were identified by mutational analysis as important for activity in E. coli dCTP deaminase. None of the mutant enzymes R115A, E138A, or E138Q had any detectable activity but circular dichroism spectra for all mutant enzymes were similar to wild type suggesting that the overall structure was not changed. The crystal structures of wild-type E. coli dCTP deaminase and the E138A mutant enzyme have been determined in complex with dUTP and Mg(2+), and the mutant enzyme also with the substrate dCTP and Mg(2+). The enzyme is a third member of the family of the structurally related trimeric dUTPases and the bifunctional dCTP deaminase-dUTPase from Methanocaldococcus jannaschii. However, the C-terminal fold is completely different from dUTPases resulting in an active site built from residues from two of the trimer subunits, and not from three subunits as in dUTPases. The nucleotides are well defined as well as Mg(2+) that is tridentately coordinated to the nucleotide phosphate chains. We suggest a catalytic mechanism for the dCTP deaminase and identify structural differences to dUTPases that prevent hydrolysis of the dCTP triphosphate.


Climate oscillations reflected within the microbiome of Arabian Sea sediments.
Selection of microorganisms in marine sediment is shaped by energy-yielding electron acceptors for respiration that are depleted in vertical succession. However, some taxa have been reported to reflect past depositional conditions suggesting they have experienced weak selection after burial. In sediments underlying the Arabian Sea oxygen minimum zone (OMZ), we performed the first metagenomic profiling of sedimentary DNA at centennial-scale resolution in the context of a multi-proxy paleoclimate reconstruction. While vertical distributions of sulfate reducing bacteria and methanogens indicate energy-based selection typical of anoxic marine sediments, 5-15% of taxa per sample exhibit depth-independent stratigraphies indicative of paleoenvironmental selection over relatively short geological timescales. Despite being vertically separated, indicator taxa deposited under OMZ conditions were more similar to one another than those deposited in bioturbated intervals under intervening higher oxygen. The genomic potential for denitrification also correlated with palaeo-OMZ proxies, independent of sediment depth and available nitrate and nitrite. However, metagenomes revealed mixed acid and Entner-Dourdoroff fermentation pathways encoded by many of the same denitrifier groups. Fermentation thus may explain the subsistence of these facultatively anaerobic microbes whose stratigraphy follows changing paleoceanographic conditions. At least for certain taxa, our analysis provides evidence of their paleoenvironmental selection over the last glacial-interglacial cycle.


Rural health care in Mexico?
A very large percentage of Mexico's population living in rural areas lacks resources for health care. Any new effort to provide such care must emphasize the health of the infant population because of the high percentage of infants in the country. Plans made at the national level have not been correlated with the conditions that exist in rural areas. For example, the majority of university programs are oriented toward urban medical practice, and the construction of more schools of medicine to solve the problem of doctors in rural areas is based on a mistaken premise. This problem has not been solved even in developed countries such as the United States where, as in Mexico, graduates in medicine migrate to the cities where optimal conditions are met for practicing the type of medicine for which they have been trained. Furthermore, it is both expensive and illogical to maintain urban doctors in rural areas where they cannot practice their profession for lack of resources; to do so is to deny the purpose of their education (27). Conventional schools of medicine, for reasons of investment and of structure, should teach only very selected groups of students who, on finishing their training, are fully capacitated to practice specialized medicine. A different system is required if we are to provide adequate health care in the rural communities. A system such as that described herein, adapted to the real need of rural communities, would avoid the necessity to create dysfunctional bureaucracies and would not destroy those institutions which have proved useful in the past. This study should be considered as one of the many pilot programs that should be initiated in order to determine the type of program that would best solve the problem of health care in rural Mexico. Other programs already being considered at the National Autonomous University of Mexico include the A36 plan of the Faculty of Medicine, now in operation; the work of C. Biro carried out in Netzahualcoyotl City (both focused on providing medical care to the urban poor); and the Open University program. Unless an efficient program designed to meet the needs of rural communities is quickly put into operation, Mexico will, in the near future, be facing the same problems now confronting Southeast Asia.


Intrauterine Fetal Traumatic Brain Injury Following Motor Vehicle Accident; A Case Report and Review of the Literature.
Trauma, especially traumatic injuries due to car accidents are one of the causes of maternal and fetal mortality and morbidity during pregnancy. Fetus brain injuries are usually caused fetus death. We herein report a pregnant woman in 28 weeks of gestation. The fetus was found to be normal during in-hospital. At birth, the female neonate demonstrated developmental delay and neurological deficits (hypotonicity). Neuroimaging after birth revealed extreme dilatation of lateral ventricles, hypoplasia and aplasia of the brain. In 4 months, she had multiple morbidities including developmental delay, hypotonia, blindness, oropharyngeal dysphagia and simple partial seizure. Motor and response to stimulation was normal. Appropriate seatbelt usage can protect the fetus from sustaining severe intracranial injuries.


Effects of exergaming based exercise on urban children's physical activity participation and body composition.
Exergaming has been considered a fun solution to promoting a physically active lifestyle. This study examined the impact of an exergaming-based program on urban children's physical activity participation, body composition and perceptions of the program. A sample of 185 children's physical activity was measured in August 2009 (pretest), and percent body fat was used as index of body composition. Fourth graders were assigned to intervention group engaging in 30 minutes exergaming-based activities 3 times per week, while third and fifth graders were in comparison group. Measurements were repeated 9 months later (posttest). Interviews were conducted among 12 intervention children. ANCOVA with repeated measures revealed a significant main effect for intervention, F(1, 179) = 10.69, P < .01. Specifically, intervention children had significantly greater increased physical activity levels than comparison children. Logistic regression for body composition indicated intervention children did not differ significantly in percent body fat change from comparison children, Chi square = 5.42, P = .14. Children interviewed reported positive attitudes toward the intervention. The implementation of exergaming-based program could have a significantly positive effect on children's physical activity participation and attitudes. Meanwhile, long-term effect of the program on children's body composition deserves further investigation.


Low seroprevalence of HIV and syphilis in pregnant women in refugee camps on the Thai-Burma border.
Refugee and migrant populations are considered to be at high risk from sexually transmitted infection (STI) and HIV. Cross-sectional surveys for syphilis and HIV were conducted in antenatal clinics (ANCs) on the Thai-Burmese border. In Mae La refugee camp, the seroprevalence of HIV and syphilis were 0.2% (one of 500) (95% CI 0-1.1) and 0% (0 of 404) (95% CI 0-0.9) in 1997; and 0.4% (two of 500) (95% CI 0.1-1.4) and 0.4% (three of 741) (95% CI 0.1-1.2) in 2005, respectively; syphilis seroprevalence in migrant women in 2005 was 0 (0 of 234) (95% CI 0-1.6). The seroprevalence was lower than that reported from surrounding ANCs for Thai or Burmese women. Focus group discussions with HIV-negative and -positive pregnant refugee women established that aspects of Karen culture and isolation (geographical and political) had a significant protective role from HIV and STI. This survey has resulted in programmatic changes in services to pregnant women in this area.


Mechanoactive materials in cardiac science.
Over 4000 people in the US are on the heart transplant waiting list. The lack of donor hearts and complications with ventricular assist devices motivates the development of alternative solutions for end stage heart disease patients. Mechanically active biomaterials such as shape memory materials, liquid crystal elastomers, dielectric elastomer actuators, and conductive polymers could be used in mechanical devices to augment heart function or condition cardiac cells and artificial tissues for regenerative medicine solutions. These materials are likened to natural muscle, with applications varying from intraventricular devices, ventricular support, and annuloplasty rings. Other novel materials in cardiac science are also discussed along with their potential application for the treatment of cardiac diseases.


Experimental investigation on influence of smoke venting velocity and vent height on mechanical smoke exhaust efficiency.
A set of burning experiments were conducted to investigate the influence of smoke vent height and exhausting velocity on mechanical smoke exhausting efficiency. Results have shown that the smoke exhausting process becomes more efficient due to the increased smoke vent height and the decreased exhausting velocity, which eliminate the plug-holing issue with fewer disturbances on the smoke layer interface. For each certain exhausting velocity, there is a critical value of distance between the vent and the bottom of the smoke layer. When the distance is less than the critical value, the smoke exhausting is inefficient, and the efficiency decreases sharply as the distance decreases. Contrarily, when the distance is greater than the critical value, a good efficiency can be acquired and the exhausted smoke increased relatively slowly as the distance increases. A critical Froude number, proposed by Hinkley to predict the onset of plug-holing effect in gravity venting systems, was validated in the experiments. However, the experimental results indicate that in the tests without the plug-holing, the fresh air entrained due to smoke exhausting is up to 48% of the mechanical exhausting rate.


Asymmetry loss is local rather than global in adolescent onset schizophrenia.
Meta-analyses in adult-onset schizophrenia report loss of normal planum temporale (PT) asymmetry, posited to relate to language and symptoms, but are inconclusive regarding global "cerebral torque". PT asymmetry has been reported unchanged in childhood onset schizophrenia. Here the discrepancy is examined in adolescence. Unbiased PT asymmetry and torque measures were obtained on 35 adolescents with schizophrenia or schizoaffective disorder and 31 adolescent controls. Patients had less PT asymmetry than controls, but torque was unchanged. Taken with previous reports, these results in adolescent onset psychosis suggest that local disturbance of cerebral asymmetry increases with patient age; it could indicate that differential rate of change at the cortical surface in the two hemispheres is the mechanism of symptom generation.


Slow muscle power output of yellow- and silver-phase European eels (Anguilla anguilla L.): changes in muscle performance prior to migration.
Eels swim in the anguilliform mode in which the majority of the body axis undulates to generate thrust. For this reason, muscle function has been hypothesised to be relatively uniform along the body axis relative to some other teleosts in which the caudal fin is the main site of thrust production. The European eel (Anguilla anguilla L.) has a complex life cycle involving a lengthy spawning migration. Prior to migration, there is a metamorphosis from a yellow (non-migratory) to a silver (migratory) life-history phase. The work loop technique was used to determine slow muscle power outputs in yellow- and silver-phase eels. Differences in muscle properties and power outputs were apparent between yellow- and silver-phase eels. The mass-specific power output of silver-phase slow muscle was greater than that of yellow-phase slow muscle. Maximum slow muscle power outputs under approximated in vivo conditions were 0.24 W kg(-1) in yellow-phase eel and 0.74 W kg(-1) in silver-phase eel. Power output peaked at cycle frequencies of 0.3--0.5 Hz in yellow-phase slow muscle and at 0.5--0.8 Hz in silver-phase slow muscle. The time from stimulus offset to 90 % relaxation was significantly greater in yellow- than in silver-phase eels. The time from stimulus onset to peak force was not significantly different between life-history stages or axial locations. Yellow-phase eels shifted to intermittent bursts of higher-frequency tailbeats at a lower swimming speed than silver-phase eels. This may indicate recruitment of fast muscle at low speeds in yellow-phase eels to compensate for a relatively lower slow muscle power output and operating frequency.


Iron, oxidative stress and the example of solar ultraviolet A radiation.
Iron has outstanding biological importance as it is required for a wide variety of essential cellular processes and, as such, is a vital nutrient. The element holds this central position by virtue of its facile redox chemistry and the high affinity of both redox states (iron II and iron III) for oxygen. These same properties also render iron toxic when its redox-active chelatable 'labile' form exceeds the normal binding capacity of the cell. Indeed, in contrast to iron bound to proteins, the intracellular labile iron (LI) can be potentially toxic especially in the presence of reactive oxygen species (ROS), as it can lead to catalytic formation of oxygen-derived free radicals such as hydroxyl radical that ultimately overwhelm the cellular antioxidant defense mechanisms and lead to cell damage. While intracellular iron homeostasis and body iron balance are tightly regulated to minimise the presence of potentially toxic LI, under conditions of oxidative stress and certain pathologies, iron homeostasis is severely altered. This alteration manifests itself in several ways, one of which is an increase in the intracellular level of potentially harmful LI. For example acute exposure of skin cells to ultraviolet A (UVA, 320-400 nm), the oxidising component of sunlight provokes an immediate increase in the available pool of intracellular LI that appears to play a key role in the increased susceptibility of skin cells to UVA-mediated oxidative membrane damage and necrotic cell death. The main purpose of this overview is to bring together some of the new findings related to intracellular LI distribution and trafficking under physiological and patho-physiological conditions as well as to discuss mechanisms and consequences of oxidant-induced alterations in the intracellular pool of LI, as exemplified by UVA radiation.


Population structure, genetic diversity and selection signatures within seven indigenous Pakistani goat populations.
Goat farming in Pakistan depends on indigenous breeds that have adapted to specific agro-ecological conditions. Pakistan has a rich resource of goat breeds, and the genetic diversity of these goat breeds is largely unknown. In this study, genetic diversity and population structure were characterized from seven indigenous goat breeds using the goat 50K SNP chip. The genetic diversity analysis showed that Bugi toori goats have the highest inbreeding level, consistent with the highest linkage disequilibrium, lowest diversity and long run of heterozygosity segments. This indicates that this breed should be prioritized in future conservation activities. The population structure analysis revealed four fairly distinct clusters (including Bugi toori, Bari, Black Tapri and some Kamori) and three other breeds that are seemingly the results of admixture between these or related groups (some Kamori, Pateri, Tapri and White Tapri). The selection signatures were evaluated in each breed. A total of 2508 putative selection signals were reported. The 26 significant windows were identified in more than four breeds, and selection signatures spanned several genes that directly or indirectly influence traits included coat colour variation (KIT), reproduction (BMPR1B, GNRHR, INSL6, JAK2 and EGR4), body size (SOCS2), ear size (MSRB3) and milk composition (ABCG2, SPP1, CSN1S2, CSN2, CSN3 and PROLACTIN).


Cell phone usefulness to improve the skin cancer screening: preliminary results and critical analysis of mobile app development.
The high incidence of skin cancer in Brazil has resulted in an urgent need for more efficient methods of reducing the time between initial diagnosis and therapy. Such delays are significant in large countries like Brazil, where a considerable proportion of the population live in remote areas with limited access to specialized medical care. To address this problem the use of mobile phones as screening devices for suspicious skin lesions has been incorporated as long-distance teledermatology services. Digital photography is now a convenient ancillary option to minimize treatment delays caused by the distance between the specialist doctor and patients. The authors have developed a friendly mobile application and website to take high quality digital images of suspicious lesions, and to capture patient data easily and quickly to be analyzed by skin cancer professionals at another location. This was a prospective study of a population of 39 individuals monitored by routine skin cancer screening by the Cancer Prevention Department at Barretos Cancer Hospital during 2016. All patients were evaluated in the dermatology clinic, where a differential diagnosis was made based on the clinical information and direct examination of suspicious lesions. A second dermatologist assessed the same clinical information and digital images of all lesions captured by teledermatology, and provided an independent diagnostic opinion on the likelihood of the lesions being benign or suggestive of malignancy. The diagnostic efficiencies of teledermatology and standard dermatology were then compared to the histopathological findings of each biopsy as the diagnostic gold standard, and then statistical parameters of each approach were evaluated. The lesions studied in this comparison were mostly found on the face (69%), followed by upper limbs (15%), scalp (8%), trunk (6%) and lower limbs (2%). Final histopathological analyses of the biopsies in the study group showed that 71% of lesions were malignant, with 32% being squamous cell carcinoma and 68% being classified as basal cell carcinoma, and 29% were considered benign lesions. The overall sensitivities of teledermatology in comparison to face-to-face evaluation in the clinic were similar (clinic, 80.0%; teledermatology, 80.8%). Other comparisons including accuracy (clinic, 78.9%; teledermatology, 79.5%); specificity (clinic, 76.9%; teledermatology, 76.9%); positive predictive value (clinic, 87.0%; teledermatology, 87.5%); and negative predictive value (clinic, 66.7.0%; teledermatology, 66.7%) all showed equivalence. The inter-observer kappa value between face-to-face examination and teledermatology showed excellent agreement at 0.958. These preliminary findings indicate that the cell phone application developed to aid the diagnosis of skin cancer showed great potential and reliability, and can therefore be considered as an ancillary option in countries like Brazil, with isolated communities that have limited access to dermatology clinics.


Uptake, Whole-Body Distribution, and Depuration of Nanoplastics by the Scallop Pecten maximus at Environmentally Realistic Concentrations.
Previous studies of uptake and effects of nanoplastics by marine organisms have been conducted at what may be unrealistically high concentrations. This is a consequence of the analytical challenges in tracking plastic particles in organisms at environmentally relevant concentrations and highlights the need for new approaches. Here, we present pulse exposures of 14C-radiolabeled nanopolystyrene to a commercially important mollusk, Pecten maximus, at what have been predicted to be environmentally relevant concentrations (<15 μg L-1). Uptake was rapid and was greater for 24 nm than for 250 nm particles. After 6 h, autoradiography showed accumulation of 250 nm nanoplastics in the intestine, while 24 nm particles were dispersed throughout the whole-body, possibly indicating some translocation across epithelial membranes. However, depuration was also relatively rapid for both sizes; 24 nm particles were no longer detectable after 14 days, although some 250 nm particles were still detectable after 48 days. Particle size thus apparently influenced the biokinetics and suggests a need for chronic exposure studies. Modeling extrapolations indicated that it could take 300 days of continued environmental exposure for uptake to reach equilibrium in scallop body tissues although the concentrations would still below 2.7 mg g-1. Comparison with previous work in which scallops were exposed to nonplastic (silver) nanomaterials of similar size (20 nm), suggests that nanoparticle composition may also influence the uptake tissue distributions somewhat.


The enhancement of activity rescues the establishment of Mecp2 null neuronal phenotypes.
MECP2 mutations cause Rett syndrome (RTT), a severe and progressive neurodevelopmental disorder mainly affecting females. Although RTT patients exhibit delayed onset of symptoms, several evidences demonstrate that MeCP2 deficiency alters early development of the brain. Indeed, during early maturation, Mecp2 null cortical neurons display widespread transcriptional changes, reduced activity, and defective morphology. It has been proposed that during brain development these elements are linked in a feed-forward cycle where neuronal activity drives transcriptional and morphological changes that further increase network maturity. We hypothesized that the enhancement of neuronal activity during early maturation might prevent the onset of RTT-typical molecular and cellular phenotypes. Accordingly, we show that the enhancement of excitability, obtained by adding to neuronal cultures Ampakine CX546, rescues transcription of several genes, neuronal morphology, and responsiveness to stimuli. Greater effects are achieved in response to earlier treatments. In vivo, short and early administration of CX546 to Mecp2 null mice prolongs lifespan, delays the disease progression, and rescues motor abilities and spatial memory, thus confirming the value for RTT of an early restoration of neuronal activity.


Detection, quantification, and microlocalisation of targets of pesticides using microchannel plate autoradiographic imagers.
Organophosphorus (OP) compounds are a diverse chemical group that includes nerve agents and pesticides. They share a common chemical signature that facilitates their binding and adduction of acetylcholinesterase (AChE) within nerve synapses to induce cholinergic toxicity. However, this group diversity results in non-uniform binding and inactivation of other secondary protein targets, some of which may be adducted and protein activity influenced, even when only a relatively minor portion of tissue AChE is inhibited. The determination of individual OP protein binding targets has been hampered by the sensitivity of methods of detection and quantification of protein-pesticide adducts. We have overcome this limitation by the employment of a microchannel plate (MCP) autoradiographic detector to monitor a radiolabelled OP tracer compound. We preincubated rat thymus tissue in vitro with the OP pesticides, azamethiphos-oxon, chlorfenvinphos-oxon, chlorpyrifos-oxon, diazinon-oxon, and malaoxon, and then subsequently radiolabelled the free OP binding sites remaining with 3H-diisopropylfluorophosphate (3H-DFP). Proteins adducted by OP pesticides were detected as a reduction in 3H-DFP radiolabelling after protein separation by one dimensional polyacrylamide gel electrophoresis and quantitative digital autoradiography using the MCP imager. Thymus tissue proteins of molecular weights -28 kDa, 59 kDa, 66 kDa, and 82 kDa displayed responsiveness to adduction by this panel of pesticides. The 59 kDa protein target (previously putatively identified as carboxylesterase I) was only significantly adducted by chlorfenvinphos-oxon (p < 0.001), chlorpyrifos-oxon (p < 0.0001), and diazinon-oxon (p < 0.01), the 66 kDa protein target (previously identified as serum albumin) similarly only adducted by the same three pesticides (p < 0.0001), (p < 0.001), and (p < 0.01), and the 82 kDa protein target (previously identified as acyl peptide hydrolase) only adducted by chlorpyrifos-oxon (p < 0.0001) and diazinon-oxon (p < 0.001), when the average values of tissue AChE inhibition were 30%, 35%, and 32% respectively. The -28 kDa protein target was shown to be heterogeneous in nature and was resolved to reveal nineteen 3H-DFP radiolabelled protein spots by two dimensional polyacrylamide gel electrophoresis and MCP autoradiography. Some of these 3H-DFP proteins spots were responsive to adduction by preincubation with chlorfenvinphos-oxon. In addition, we exploited the useful spatial resolution of the MCP imager (-70 mm) to determine pesticide micolocalisation in vivo, after animal dosing and autoradiography of brain tissue sections. Collectively, MCP autoradiographic imaging provided a means to detect targets of OP pesticides, quantify their sensitivity of adduction relative to tissue AChE inhibition, and highlighted that these common pesticides exhibit specific binding character to protein targets, and therefore their toxicity will need to be evaluated on an individual compound basis. In addition, MCP autoradiography afforded a useful method of visualisation of the localisation of a small radiolabelled tracer within brain tissue.


NRAGE, a p75 neurotrophin receptor-interacting protein, induces caspase activation and cell death through a JNK-dependent mitochondrial pathway.
The p75 neurotrophin receptor (p75NTR) mediates signaling events leading to activation of the JNK pathway and cell death in a variety of cell types. We recently identified NRAGE, a protein that directly interacts with the p75NTR cytosolic region and facilitates p75NTR-mediated cell death. For the present study, we developed an inducible recombinant NRAGE adenovirus to dissect the mechanism of NRAGE-mediated apoptosis. Induced NRAGE expression resulted in robust activation of the JNK pathway that was not inhibited by the pharmacological mixed lineage kinase (MLK) inhibitor CEP1347. NRAGE induced cytosolic accumulation of cytochrome c, activation of Caspases-3, -9 and -7, and caspase-dependent cell death. Blocking JNK and c-Jun action by overexpression of the JNK-binding domain of JIP1 or dominant-negative c-Jun ablated NRAGE-mediated caspase activation and NRAGE-induced cell death. These findings identify NRAGE as a p75NTR interactor capable of inducing caspase activation and cell death through a JNK-dependent mitochondrial apoptotic pathway.


Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes.
Altered tyrosine kinase signalling has been implicated in several diseases, paving the way for the development of small-molecule TKIs (tyrosine kinase inhibitors). TKIs such as imatinib, sunitinib and dasatinib are clinically used for treating chronic myeloid leukaemia, gastrointestinal stromal tumours and other malignancies. In addition to their use as anti-cancer agents, increasing evidence points towards an anti-diabetic effect of these TKIs. Imatinib and other TKIs counteract diabetes not only in non-obese diabetic mice, but also in streptozotocin diabetic mice, db/db mice, high-fat-treated rats and humans with T2D (Type 2 diabetes). Although the mechanisms of protection need to be investigated further, the effects of imatinib and other TKIs in human T2D and the rapidly growing findings from animal models of T1D (Type 1 diabetes) and T2D are encouraging and give hope to improved treatment of human diabetes. In the present article, we review the anti-diabetic effects of TKIs which appear to involve both protection against beta-cell death and improved insulin sensitivity. Considering the relatively mild side effects of TKIs, we hypothesize that TKIs could be used to treat new-onset T1D, prevent T1D in individuals at high risk of developing the disease, treat the late stages of T2D and improve the outcome of islet transplantation.


ST segment monitoring with a derived 12-lead electrocardiogram is superior to routine cardiac care unit monitoring.
Prior studies have shown that a derived 12-lead electrocardiogram with a simple electrode configuration is comparable with the standard electrocardiogram for arrhythmia analysis. A prospective, comparative, within subjects design was used to compare the value of the derived 12-lead electrocardiogram with that of routine monitoring of leads V1 and II for detection of transient myocardial ischemia in 250 patients treated for unstable angina or myocardial infarction. During 11,532 hours of derived 12-lead ST segment monitoring, 55 (22%) of 250 patients had 176 episodes of ischemia. Of the 55 patients with ischemia, 75% reported no chest pain and 64% had no ischemic ST changes with routine monitoring leads. All five patients who developed angiographically confirmed abrupt reocclusion after percutaneous transluminal coronary angioplasty had ischemic ST changes with the derived electrocardiogram (sensitivity, 100%), compared with only two patients with routine monitoring (sensitivity, 40%). Serious complications occurred in 17% of angina patients with ischemic events compared to 3% of those without ischemia. Length of stay in the cardiac care unit was twice as long in angina patients who had ischemic events. In patients with acute myocardial infarction, ischemic events were not associated with a more complicated hospital course; however, length of stay in the cardiac care unit was longer in patients with recurrent ischemia. The findings show that derived 12-lead ST monitoring is superior to routine monitoring of leads V1 and II for detecting transient myocardial ischemia. ST monitoring of the derived 12-lead electrocardiogram may identify high-risk patients with unstable angina and provide prognostic information that would not be otherwise available from the usual clinical measures.


Serotyping of Dutch Staphylococcus aureus strains from carriage and infection.
International epidemiological studies have shown that clinical isolates of Staphylococcus aureus are usually capsulated with either type 5 or 8 capsular polysaccharides (CPs). Because all noncapsulated strains were found to be cross-reactive with polysaccharide 336 (336PS) antibodies, the noncapsulated strains were denoted as type 336PS. The capsular types of 162 Dutch methicillin-susceptible S. aureus strains derived from individuals living in the Rotterdam area were determined. The serotype distribution was 28.4% serotype 5, 53.7% type 8, and 17.9% type 336PS. Serotyping was in agreement with genotyping by amplified fragment length polymorphism (AFLP) and multi locus sequence typing (MLST). Among 49 nasal carriage isolates from healthy children 24.5% belonged to serotype 5, 67.3% were type 8 and 8.2% were type 336PS. For 28 adult patients on chronic ambulatory peritoneal dialysis (CAPD) the serotype incidences among carriage isolates obtained from the nose, catheter exit-site, and abdominal skin were 45.1%, 41.2% and 13.7%, respectively. Among S. aureus strains deriving from blood cultures, the serotype incidences were 17.7% serotype 5, 53.2% type 8, and 29.0% type 336PS. Apparently, type 336PS strains are more prevalent (P=0.017) among bacteraemia isolates as compared with the nasal carriage isolates obtained from healthy children and CAPD patients. In conclusion, all Dutch S. aureus isolates belonged to types 5, 8, or 336PS, which is in agreement with data from other countries. Thus, addition of the 336PS conjugate to a type 5- and type 8-CP protein conjugate vaccine would significantly extend the vaccine coverage.


Specific or general health outcome measures in the evaluation of total hip replacement. A comparison between the Harris hip score and the Nottingham Health Profile.
We assessed 100 patients with a primary total hip replacement using the Harris hip score and the Nottingham Health Profile at one, three and five years after operation. They were derived from two prospective randomised series of cemented and uncemented replacements. Both scoring systems correlated highly and were each heavily influenced by the system of functional classification defined by Charnley. After five years both reflected the function of the implant and the general state of the patient. A higher degree of sensitivity is needed to show differences in the performance of an implant in the short and medium term. We do not yet have an ideal system of clinical assessment and the overall function must always be properly assessed.


Changes to the cardiac biomarkers of non-elite athletes completing the 2009 London Marathon.
Many studies have demonstrated a rise in troponin and brain natriuretic peptide (BNP) levels following prolonged and/or strenuous exercise. Only one study looked at athletes who collapse and this showed no difference in cardiac biomarkers between those who collapsed and those who completed without requiring medical attention. We set out to describe and quantify the changes in troponin and BNP in three groups of non-elite runners at the 2009 London marathon: those with and without known structural heart disease (SHD) and those who collapsed on completion. The first group (recruited group, RG) was recruited at the prerace exhibition. This group had two subsets, runners with SHD and without (non-SHD). A second group was recruited from those who collapsed (collapsed group, CG). Blood was taken for troponin I (TnI), troponin T (TnT), high sensitivity TnT (HSTnT) and BNP. Cardiac biomarker levels increased in all groups following the marathon. No statistically significant difference was seen between the SHD and non-SHD subgroups. When comparing the RG and CG the number and degree of rise was greater in those who collapsed. A trend for the degree of rise of HSTnT was demonstrated. We identified runners with troponin levels that, in other circumstances, would raise concern for myocardial necrosis. However absence of adverse clinical sequelae would suggest this rise is physiological. The cause and clinical significance of the increased HSTnT levels seen in those that collapsed is yet to be fully elucidated.


Epidemiologic and genetic follow-up study of 544 Minnesota breast cancer families: design and methods.
In 1944, a case-control family study was initiated at the Dight Institute for Human Genetics at the University of Minnesota to study the influences of childbearing breastfeeding, and hereditary susceptibility on the occurrence and age-of-onset of breast cancer. Index cases (probands) were women ascertained at the Tumor Clinic of the University of Minnesota Hospital. Medical history and life style information were obtained on probands and relatives, and all cancers were histologically verified. A total of 544 families were studied, with probands diagnosed between 1931 and 1952. All of the records and pathology slides have been maintained from the original study; for most probands this includes the original tissue blocks. We are conducting a historical cohort study of selected of selected first- and second-degree female relatives (sisters, daughters, nieces, granddaughters) of the probands and a group of control women identified as the spouses of all male first- and second-degree relatives (brothers, sons, grandsons, and nephews). The subsequent development of breast cancer is being determined to quantify the absolute risk associated with a positive family history. Current disease status is ascertained with mammography, and stromal density is measured using digital imaging. Segregation analysis will be applied to examine how non-genetic factors such as diet, exogenous hormone use, and body fat distribution influence risk in women at high risk because of family history. A subset of families are being selected for molecular analysis of the BRCA1 gene or for linkage analyses to identify putative susceptibility loci other than BRCA1. Documented cancer histories were known for at least three generations, and the current study extends the pedigrees up to four or five generations for every family, allowing a detailed description of familial risk. This cohort study of breast cancer families is likely to be important in both quantity and quality of data and will serve as a major genetic epidemiologic resource, being free of selection bias and having relevant non-genetic exposure determined in at least four generations.


High-resolution behavioral mapping of electric fishes in Amazonian habitats.
The study of animal behavior has been revolutionized by sophisticated methodologies that identify and track individuals in video recordings. Video recording of behavior, however, is challenging for many species and habitats including fishes that live in turbid water. Here we present a methodology for identifying and localizing weakly electric fishes on the centimeter scale with subsecond temporal resolution based solely on the electric signals generated by each individual. These signals are recorded with a grid of electrodes and analyzed using a two-part algorithm that identifies the signals from each individual fish and then estimates the position and orientation of each fish using Bayesian inference. Interestingly, because this system involves eavesdropping on electrocommunication signals, it permits monitoring of complex social and physical interactions in the wild. This approach has potential for large-scale non-invasive monitoring of aquatic habitats in the Amazon basin and other tropical freshwater systems.


Risk factors for coronary heart disease in diabetic and nondiabetic Native Americans. The Strong Heart Study.
The Strong Heart Study is a study of cardiovascular disease and its risk factors among diabetic and nondiabetic Native Americans. The study includes 12 tribes in Arizona, Oklahoma, and North and South Dakota. Phase I, initiated in October 1988, included a mortality survey to determine CVD death rates in individuals 35-74 yr old between 1984 and 1988, and a medical record review to determine rates of myocardial infarction and stroke for individuals ages 45-74 during the same time. In addition, a physical examination was performed on persons 45-74 yr old to measure the prevalence of cardiovascular and peripheral vascular diseases and known and suspected risk factors. In Phase II, CVD mortality and morbidity rates will be determined in the examined cohort by surveillance. CVD risk factors, changes in risk factors over time, and the relationship between risk factors and CVD incidence will be assessed longitudinally. This study provides data on the relative importance of cardiovascular risk factors in nondiabetic and diabetic Native Americans and will provide insight into possible variations in the quantitative or qualitative importance of CVD risk factors among diverse population groups.


Two-Dimensional Lead Halide Perovskites Templated by a Conjugated Asymmetric Diammonium.
We report novel two-dimensional lead halide perovskite structures templated by a unique conjugated aromatic dication, N,N-dimethylphenylene-p-diammonium (DPDA). The asymmetrically substituted primary and tertiary ammoniums in DPDA facilitate the formation of two-dimensional network (2DN) perovskite structures incorporating a conjugated dication between the PbX42- (X = Br, I) layers. These 2DN structures of (DPDA)PbI4 and (DPDA)PbBr4 were characterized by single-crystal X-ray diffraction, showing uniquely low distortions in the Pb-X-Pb bond angle for 2D perovskites. The Pb-I-Pb bond angle is very close to ideal (180°) for a 2DN lead iodide perovskite, which can be attributed to the ability of the rigid diammonium DPDA to insert into the PbX62- octahedral pockets. Optical characterization of (DPDA)PbI4 shows an excitonic absorption peak at 2.29 eV (541 nm), which is red-shifted in comparison to similar 2DN lead iodide structures. Temperature-dependent photoluminescence of both compounds reveals both a self-trapped exciton and free exciton emission feature. The reduced exciton absorption energy and emission properties are attributed to the dication-induced structural order of the inorganic PbX42- layers. DFT calculation results suggest mixing of the conjugated organic orbital component in the valence band of these 2DN perovskites. These results demonstrate a rational new strategy to incorporate conjugated organic dications into hybrid perovskites and will spur spectroscopic investigations of these compounds as well as optoelectronic applications.


Multiple pathways of plasmid DNA transfer in Helicobacter pylori.
Many Helicobacter pylori (Hp) strains carry cryptic plasmids of different size and gene content, the function of which is not well understood. A subgroup of these plasmids (e.g. pHel4, pHel12), contain a mobilisation region, but no cognate type IV secretion system (T4SS) for conjugative transfer. Instead, certain H. pylori strains (e.g. strain P12 carrying plasmid pHel12) can harbour up to four T4SSs in their genome (cag-T4SS, comB, tfs3, tfs4). Here, we show that such indigenous plasmids can be efficiently transferred between H. pylori strains, even in the presence of extracellular DNaseI eliminating natural transformation. Knockout of a plasmid-encoded mobA relaxase gene significantly reduced plasmid DNA transfer in the presence of DNaseI, suggesting a DNA conjugation or mobilisation process. To identify the T4SS involved in this conjugative DNA transfer, each individual T4SS was consecutively deleted from the bacterial chromosome. Using a marker-free counterselectable gene deletion procedure (rpsL counterselection method), a P12 mutant strain was finally obtained with no single T4SS (P12ΔT4SS). Mating experiments using these mutants identified the comB T4SS in the recipient strain as the major mediator of plasmid DNA transfer between H. pylori strains, both in a DNaseI-sensitive (natural transformation) as well as a DNaseI-resistant manner (conjugative transfer). However, transfer of a pHel12::cat plasmid from a P12ΔT4SS donor strain into a P12ΔT4SS recipient strain provided evidence for the existence of a third, T4SS-independent mechanism of DNA transfer. This novel type of plasmid DNA transfer, designated as alternate DNaseI-Resistant (ADR) mechanism, is observed at a rather low frequency under in vitro conditions. Taken together, our study describes for the first time the existence of three distinct pathways of plasmid DNA transfer between H. pylori underscoring the importance of horizontal gene transfer for this species.