Rapid identification of emerging pathogens: coronavirus

We describe a new approach for infectious disease surveillance that facilitates rapid identification of known and emerging pathogens. The process uses broad-range polymerase chain reaction (PCR) to amplify nucleic acid targets from large groupings of organisms, electrospray ionization mass spectrometry for accurate mass measurements of PCR products, and base composition signature analysis to identify organisms in a sample. We demonstrate this principle by using 14 isolates of 9 diverse Coronavirus spp., including the severe acute respiratory syndrome-associated coronavirus (SARS-CoV). We show that this method could identify and distinguish between SARS and other known CoV, including the human CoV 229E and OC43, individually and in a mixture of all 3 human viruses. The sensitivity of detection, measured by using titered SARS-CoV spiked into human serum, was approximate, equals1 PFU/mL. This approach, applicable to the surveillance of bacterial, viral, fungal, or protozoal pathogens, is capable of automated analysis of >900 PCR reactions per day.     

Superselective catheterization and embolization as first-line therapy for lower gastrointestinal bleeding

Emergent operative intervention for lower gastrointestinal bleeding (LGIB) is associated with significant morbidity and mortality. Advances in endovascular techniques have made superselective catheterization and embolization (SSCE) of small visceral arterial branches possible. We hypothesized that SSCE for LGIB would be an effective first-line therapy and associated with low mortality. We identified all patients that underwent visceral angiography at our institution from 1997 to 2003. Records from all patients with documented LGIB and in whom SSCE was used as first-line therapy were reviewed. Twenty-three patients (69 +/- 11 years) were treated with SSCE as an initial intervention for LGIB. A definitive bleeding site was identified in 95 per cent of cases (22/23). Eleven patients (48%) developed an early complication [recurrent bleeding (n=5; two required surgery), asymptomatic ischemic colonic mucosa (n=3), acute renal insufficiency (n=1; resolved), and femoral pseudo-aneurysm (n=2; one treated operatively)]. Long-term (mean 19 months) follow-up was available for 17 patients. Five patients (22%) experienced recurrent LGIB, and three patients had evidence of colonic ischemic. One patient required endoscopic dilation of a stricture, and three underwent surgical resection. There was no mortality in our series. In this series, SSCE was an effective first-line therapy for LGIB. Rebleeding and ischemia rates were low.     

Continuous monitoring of cervical dilatation during labour by ultrasonic transit-time measurement

Instrumentation for continuously measuring cervical dilatation during labour based upon measuring the transit time of a short pulse of ultrasound across the intracervical space is described. 1 mm × 1 mm × 5 mm ultrasonic transducers are attached to diametrically opposite sides of the cervical rim by spring-loaded clips, and their separation increases as the cervix dilates. The velocity of ultrasound in the intracervical space has been determined to be 1·48 mm/μs, making it possible to convert the transit-time measurements between the transducers to displacement. Samples are taken once a second, allowing a continuous recording to be made throughout labour. Examples of cervical dilatation recordings from primigravid and multiparous patients are presented.     

Anxiety, nostalgia and melancholy. A few remarks on psychoanalysis and tango

Our work is based on the application of psychoanalytic techniques, in order to unveil this cultural phenomenon called tango, related with sexuality and unconscious processes. As a way of introduction, it deals with a brief theory of the birth of tango, the possible terminological source of its name, its main creators and interpreters, as well as the chronological classification into the first wave tangos, Guardia Vieja, and the newer wave tangos, Guardia Nueva. The former ones were awash with festive themes of the centennial years, expressed in behaviors that denote sexuality and love, whereas the latter ones, expose the great bewilderment of the thirties' crisis, due to the imminent downfall of the country, the denunciation of materialism, the crumbling of ideas; which led up to feelings of utter pessimism, loneliness and abandonment. From this point onwards, through the use of techniques provided by psychoanalysis applied to tango lyrics, we are able to unravel the unconscious processes of the drama of its characters; the immigrant, hopeful and at same time nostalgic for the loss of his mother country; the porteno -urban man from Buenos Aires city- who, overwhelmed by immigrants, has to give way to the new compatriots; the inland inhabitant, who was dragged to the city because of the new conditions of rural work; and finally the conventillo, tenement house, as a melting pot that fulfilled the integration of these groups. Like in a painter's palette, which contains various colors and shades, the interpretations about nostalgia, grief and loneliness become apparent, along with the father-son rivalry, the conflict with the absent mother, the relationship between sexes, male chauvinism, infatuation, identity, the fear of death, the rebirth to a new life, the passage from gaucho to guapo, from a shrewd horseman to a daring, bullying braggart.     

Gender and medication use: an exploratory, multi-site study

OBJECTIVE: This comparative study in four countries was designed to explore differences in women's and men's patterns of medication use. METHODS: A total of 539 individuals, 303 women and 236 men, aged 15 years and older, were interviewed in Mexico, the Philippines, Uganda, and the US. Country-specific variables and codes adapted questions and answers to local contexts, and the instrument alternated between closed- and open-ended questions. RESULTS: In all sites, women reported using medications more frequently than men. Differences in reported use between women and men over the month preceding the survey were significant in Mexico and Uganda, but not in the two countries with the highest medication use, the Philippines and the USA. Gender differences are explained in part by differences in the frequencies with which major symptoms/conditions are reported, as women were generally more likely to report these conditions then men, but not more likely to treat symptoms or conditions with medications. This analysis also found gendered patterns of communication and information about health: women are central to the process of communication about health and therapies and they appear to draw on a richer repertoire of knowledge, perceptions and attitudes regarding medications. CONCLUSIONS: This study documents differences in patterns of medication use, with women reporting higher use than men overall. It also finds gendered patterns of use, manifested in information and perceptions surrounding medications.     

Novel mutations of APOB cause ApoB truncations undetectable in plasma and familial hypobetalipoproteinemia

Familial hypobetalipoproteinemia (FHBL) is a genetic disorder characterized by low levels of apoB-100 and LDL cholesterol. Truncation-producing mutations of apoB (chromosome 2) are among several potential causes of FHBL in patients. Ten new families with FHBL linked to chromosome 2 were identified. In Family 8, a 4432delT in exon 26 produces a frame-shift and a premature stop codon predicted to produce a truncated apoB-30.9. Even though this truncation is just 10 amino acid shorter than the well-documented apoB-31, which is readily detectable in plasma, apoB-30.9 is undetectable. Most truncations shorter than apoB-30 are not detectable in plasma. In Family 34, an acceptor splicing mutation at position -1 of exon 14 changes the acceptor splice site AG to AA. Two families (Family 50 and 52) had mutations (apoB-9 and apoB-29) reported previously. In Family 98, a novel point mutation in exon 26 (11163T>G) causes a premature stop codon, and produces a truncated apoB-80.5 readily detectable in plasma. Sequencing of the ApoB gene in families 1, 5, 18, 58, and 59 did not reveal mutations.     

Apoptosis in diseases of the liver

Apoptosis, or programmed cell death, and the elimination of apoptotic cells are crucial factors in the maintenance of liver health Apoptosis allows hepatocytes to die without provoking a potentially harmful inflammatory response In contrast to necrosis, apoptosis is tightly controlled and regulated via several mechanisms, including Fas/Fas ligand interactions, the effects of cytokines such as tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), and the influence of pro- and antiapoptotic mitochondria-associated proteins of the B-cell lymphoma-2 (Bcl-2) family. Efficient elimination of apoptotic cells in the liver relies on Kupffer cells and endothelial cells and is thought to be regulated by the expression of certain cell surface receptors. Liver disease is often associated with enhanced hepatocyte apoptosis, which is the case in viral and autoimmune hepatitis, cholestatic diseases, and metabolic disorders. Disruption of apoptosis is responsible for other diseases, for example, hepatocellular carcinoma. Use and abuse of certain drugs, especially alcohol, chemotherapeutic agents, and acetaminophen, have been associated with increased apoptosis and liver damage. Apoptosis also plays a role in transplantation-associated liver damage, both in ischemia/reperfusion injury and graft rejection. The role of apoptosis in various liver diseases and the mechanisms by which apoptosis occurs in the liver may provide insight into these diseases and suggest possible treatments.     

Reliability and stability of a semistructured DSM-IV interview designed for family studies

OBJECTIVE: To determine the interrater reliability and stability of diagnoses, and to compare the results of in-person versus telephone administration of the Missouri Assessment of Genetics Interview for Children (the MAGIC), a new, semistructured, glossary-based diagnostic interview for children and adolescents. METHOD: The interview was developed for a large-scale epidemiological family genetics study. For reliability measures, parent report on offspring, child self-report, and adolescent self-report interviews were independently scored by two different raters on a population-based sample of respondents. The stability of diagnoses was assessed by comparing repeat interviews of parents, children, and adolescents, separated on average by 13 months. Frequencies of parent and adolescent report of disorders were determined for telephone and in-person interviews. RESULTS: High interrater reliabilities were achieved for individual DSM-IV symptoms and diagnoses and for individual characteristics of diagnostic domains, including number, clustering, duration, and impairment of symptoms. The stability of diagnoses was also high for parents and adolescents. No significant differences in the prevalence of attention-deficit/hyperactivity disorder and major depressive disorder were found for interviews administered in person or by telephone. CONCLUSIONS: The MAGIC demonstrates high interrater reliability and stability for DSM-IV symptoms and diagnoses.     

Mutational analysis of the nicotinic acetylcholine receptor alpha 4 subunit gene in attention deficit/hyperactivity disorder: evidence for association of an intronic polymorphism with attention problems

Recent studies suggest the presence of genetically distinct subtypes of attention deficit/hyperactivity disorder (ADHD) and that attention problems can be treated with receptor subtype selective nicotine agonists. In this study, individuals with two independent familial subtypes of ADHD defined by latent class analysis were systematically screened for sequence variations in the coding regions and intron/exon junctions of the nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4). Common polymorphisms were used for transmission disequilibrium test (TDT) analyses. A significant association was found for a 5' intron 2 single nucleotide polymorphism and severe inattention problems (P = 0.007, effect size = 4, 95% CI 1.3-14.1). The location of the polymorphism is compatible with it affecting pre-mRNA stability or splicing.     

中药抗疲I号对训练Wistar大鼠急进高原并运动力竭后心肌及其酶谱的影响

目的通过训练大鼠急进高原模型从心肌组织形态和酶谱改变,研究训练对心肌损伤的防护。方法于海拔1520m实地环境设实验组(EG)采用中药抗疲I号加入常规饲料中喂养,对照组(CG)常规饲料喂养,EG、CG各40只游泳训练4周后,各选35只3h急进海拔3850m实地静息1.5h,从中各选10只作为静息对照采集标本,EG、CG各20只游泳至力竭后1h、24h采集标本;测定比较各组心肌酶谱指标等,镜下观察比较各组心肌形态变化。结果EG血中心肌酶谱指标1h、24h指标均优于CG1h、24h结果;心肌组织学结构从纵断面看,EG心肌结构清晰,肌丝细密,横纹清楚,核周无空隙;横断面心肌纤维群间隙小,毛细血管平均为10～12个/HPF;CG心肌纤维界限不清晰,肌丝分散,横纹不清楚,横断面心肌纤维群间隙增宽,毛细血管平均为3～5个/HPF,毛细血管腔扩张,红细胞堆积,提示有水肿。结论急进高海拔地区运动后可使心肌纤维缺氧水肿,血中心肌酶谱增高,同时会使心肌营养不良而发生结构改变,对心肌的供氧能力好坏必然决定运动能力强弱,过度训练、改变运动集训环境或强体力劳动均可引起心肌供血能力下降,本研究是通过抗疲I号加入食品干预训练大鼠的,有利于改善心肌营养与供氧状况,并能降低心肌纤维水肿发生。