articles+ search results

LOW-fat diet and BLOOD cholesterol

Examines the effect of dietary cholesterol on plasma cholesterol concentration in subjects following low fat diet in Great Britain. Ratio of polyunsaturated to saturated fatty acids; Comparison of the cholesterol concentration among subjects; Importance of dietary cholesterol for the reduction of saturated fats.

ARCHAEOLOGICAL excavations, ARCHAEOLOGICAL surveying, ARCHAEOLOGY, INTERMENT, and IRON Age

Geophysical survey and excavation have demonstrated that iron age settlement features and early Anglo-Saxon burials discovered during road construction in 1983 were part o[ an extensive multi-period site, now a Scheduled Ancient Monument. This paper presents the results of the archaeological investigations. The bulk of the report is concerned with the early Anglo-Saxon burials, which included a grave containing a balance, weights and runic inscription. The evidence for late mesolithic, neolithic -- early bronze age, iron age and post-medieval activity is also discussed, and the site is considered in its regional and wider context. [ABSTRACT FROM AUTHOR]

BEER, INTERNATIONAL economic relations, and INTERNATIONAL trade

Demonstrates how United States and Canadian controls on the alcohol market affect public health. US-Canadian alcohol control; Public health implications; How the trade agreements (GATT, FTA, NAFTA) work; Trade disputes since 1985; The larger meaning of the disputes; Chronology of the US-Canada beer dispute; Glossary; Summary.

ALCOHOL drinking

In a national sample of 11 634 Canadians aged 15 years and above, risk curves for harm to six life-areas from one's own drinking and for assault by another drinker rose steadily with the respondent's volume of alcohol consumption. While drinking five or more drinks on an occasion at least once a month substantially raised the risk at a given volume of drinking, the risk rose with volume even among those not regularly drinking five or more drinks. These relationships remained in logistic regressions which controlled for gender, age and educational level. Younger respondents, those without higher education and men reported more harm for a given level of their own drinking although differences by gender disappeared above one-third of one drink per day. Three sets of guidelines for low-risk drinking-two from Canada, and one generally used in Britain-were compared in terms of the proportions of respondents reporting harm from their own drinking among those who had kept within the guideline in the previous 7 days' drinking. More restrictiveness in the guidelines was associated with substantial reductions in reported drinking-related harm. [ABSTRACT FROM AUTHOR]

TUBERCULOSIS prevention, MEDICAL care of HIV-positive persons, ISONIAZID, PTERIDINES, and DRUG efficacy

Studies the effectiveness of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1 positive individuals. Methods for comparing efficacy of the chemoprophylaxis regimens; Findings; Interpretation. INSET: Disease categories.

PERSONALITY, ANGER, CITY traffic, AFRICAN Americans, AUTOMOBILE drivers, ATTITUDE (Psychology), and PSYCHOLOGICAL burnout

This study evaluates the psychosocial correlates of anger-related traits. Participants include New York City traffic enforcement agents (TEAs), who issue summonses for vehicular and parking violations and are frequently confronted by angry motorists. This sample of TEAs is 53% African American and 57% female. Participants completed surveys at 2 points, 4 months apart, which measured attitudinal, affective, and expressive components of hostility and anger, as well as dimensions of workplace psychosocial response. Results indicate that trait anger-in was positively associated with frequency of conflict, anger intensity, and burnout in cross-sectional analyses; and positively associated with frequency of conflict in prospective analyses. Trait anger was positively associated with an increase in burnout over a 4-month period. These findings provide support for the transactional model of hostility and health and have implications for worksite interventions promoting cardiovascular health. [ABSTRACT FROM AUTHOR]

COMMUNITY health services, NATIONAL health insurance, and MEDICAL care

A series of 12 studies (five historic cohort and seven randomized trials) examined clients in community settings in Southern Ontario suffering from a variety of chronic physical and mental health conditions. These studies are appraised using a framework for evaluating possible outcomes of economic evaluation. In the 12 studies, sample composition and size varied. Each study was designed to quantify the well-being outcomes and expenditures associated with different community-based approaches to care provided in the context of a system of national health insurance. As a collective, these studies represent increasing methodological rigour. Multiple-perspective client well-being outcome measures were used. In two studies, caregiver burden also was analysed. A common approach to quantification and evaluation of expenditures for service consumption was used in all 12 studies. The nature of community-based health services (health vs. disease care orientation) was found to have direct and measurable impact on total expenditures for health service utilization and client well-being outcomes. In most cases, a recurring pattern of equal or better client outcomes, yet lower expenditures for use of community based health services, was associated with well-integrated health oriented services. Integrated services aimed at factors which determine health are superior when compared to individual, fragmented, disease oriented, and focused approaches to care. The main lessons from the 12 studies are that it is as or more effective and as or less expensive to offer complete, proactive, community health services to persons living with chronic circumstance than to provide focused, on-demand, piecemeal services. Complete services would have a psychosocial and mental health focus included with the physical care approach. Furthermore, people with coexisting risk factors (age, living arrangements, mental distress and problem-solving ability) are the ones who most benefit at lower expense... [ABSTRACT FROM AUTHOR]

PERIODONTAL disease and KERATOSIS

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7-9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between DllS4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers. [ABSTRACT FROM AUTHOR]

SUBSTANCE abuse prevention, ETHNICITY, MEDICAL communication, ETHNIC groups, PATHOLOGICAL psychology, and SOCIAL psychology

The rationale for targeted and tailored substance use prevention programs derives from essentially three observations: 1) differences in substance use prevalence rates across racial/ethnic groups; 2) differences in the prevalence of the risk factors for substance use across racial/ethnic groups; and 3) differences in the predictors of substance use across groups. This article provides a model for understanding cultural sensitivity as it pertains to substance use prevention. Cultural sensitivity is defined by two dimensions, surface and deep structure. Surface structure involves matching intervention materials and messages to observable, “superficial” characteristics of a target population. This may involve using people, places, language, product brands, music, food, locations, and clothing familiar to, and preferred by, the target audience. Surface structure refers to how well interventions fit within a specific culture. Deep structure involves incorporating the cultural, social, historical, environmental, and psychologic forces that influence the target health behavior in the proposed target population. For example, peer influences may exert a greater influence on substance use initiation among White and Hispanic than among African American youth, while parental influences may be stronger among African Americans. Whereas surface structure generally increases the "receptivity" or "acceptance" of messages, deep structure conveys salience. Techniques for developing culturally sensitive interventions, borrowed from social marketing and health communication theory, are described. © 2000 John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

GENETICS of multiple sclerosis, APOLIPOPROTEIN E, GENETIC polymorphisms, and GENETICS of disease susceptibility

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, with a complex etiology that includes a strong genetic component. The contribution of the major histocompatibility complex (MHC) has been established in numerous genetic linkage and association studies. In addition to the MHC, the chromosome 19q13 region surrounding the apolipoprotein E (APOE) gene has shown consistent evidence of involvement in MS when family-based analyses were conducted. Furthermore, several clinical reports have suggested that the APOE-4 allele may be associated with more-severe disease and faster progression of disability. To thoroughly examine the role of APOE in MS, we genotyped its functional alleles, as well as seven single-nucleotide polymorphisms (SNPs) located primarily within 13 kb of APOE, in a data set of 398 families. Using family-based association analysis, we found statistically significant evidence that an SNP haplotype near APOE is associated with MS susceptibility (P = .005 ). An analysis of disease progression in 614 patients with MS from 379 families indicated that APOE-4 carriers are more likely to be affected with severe disease (P = .03 ), whereas a higher proportion of APOE-2 carriers exhibit a mild disease course (P = .02 ). [ABSTRACT FROM AUTHOR]

CONDENSATION, PYRYLIUM compounds, and CARBANIONS

The condensation reaction between γ-unsubstituted pyrylium salts and carbanions of Fischer-type carbene complexes allowed the synthesis of new γ-methylenepyran carbene complexes. NMR data, single crystal X-ray analysis, and DFT calculations suggest that these complexes have a partial pyrylium character due to the π electron-accepting ability of the carbenic fragment and to the electron-releasing properties of the methylenepyran part. [Copyright &y& Elsevier]

XYLANASES and ASPERGILLUS

The heterologous production of Arthromyces ramosus peroxidase (ARP) was analysed in the filamentous fungus Aspergillus awamori under control of the inducible endoxylanase promoter. Secretion of active ARP was achieved up to 800 mg l−1 in shake flask cultures. Western blot analysis showed that an rARP product of the correct molecular weight was produced. In contrast to several other studies about heterologous production of heme containing peroxidases, our results suggest that in A. awamori no heme limitation exists during overproduction of ARP. [Copyright &y& Elsevier]

CELL differentiation, APOPTOSIS, FATTY acids, and PROTEINS

We previously reported that the enterocytic differentiation of human colonic Caco-2 cells correlated with alterations in integrin signaling. We now investigated whether differentiation and apoptosis of Caco-2 cells induced by the short-chain fatty acid butyrate (NaBT) was associated with alterations in the integrin-mediated signaling pathway with special interest in the expression and activity of focal adhesion kinase (FAK), of the downstream phosphatidylinositol 3'-kinase (PI 3-kinase)Akt pathway and in the role of the nuclear factor κB (NF-κB). NaBT increased the level of sucrase. It induced apoptosis as shown by: (1) decreased Bcl-2 and Bcl-XL proteins and increased Bax protein; (2) activation of caspase-3; and (3) increased shedding of apoptotic cells in the medium. This effect was associated with defective integrin-mediated signaling as shown by: (1) down-regulation of β1 integrin expression; 2) decreased FAK expression and tyrosine phosphorylation; (3) concerted alterations in cytoskeletal and structural focal adhesions proteins (talin, ezrin); and (4) decreased FAK ability to associate with PI 3-kinase. However, in Caco-2 cells, β1-mediated signaling failed to be activated downstream of FAK and PI 3-kinase at the level of Akt. Transfection studies show that NaBT treatment of Caco-2 cells promoted a significant activation of the NF-κB which was probably involved in the NaBT-induced apoptosis. Our results indicate that the prodifferentiating agent NaBT induced apoptosis of Caco-2 cells probably through NF-κB activation together with a defective β1 integrin-FAK-PI 3-kinase pathways signaling. J. Cell. Physiol. 197: 336347, 2003© 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

NEURONS, ELECTROPHYSIOLOGY, SENSORY receptors, HAIR cells, and COCHLEA

Type I and type II spiral ganglion neurons convey auditory information from the sensory receptors in the cochlea to the CNS. The numerous type I neurons have been extensively characterized, but the small population of type II neurons with their unmyelinated axons are undetectable with most recording methods. Despite the paucity of information about the type II neurons, it is clear that they must have a significant role in sound processing because they innervate the large number of outer hair cells that are critical for maintaining normal responses to stimuli. To elucidate the function of type II neurons, we have developed an approach for studying their electrophysiological features in vitro. Type II neurons obtained from postnatal day 6-7 mice displayed distinctly different firing properties than type I neurons. They showed slower accommodation, lower action potential thresholds, and more prolonged responses to depolarizing current injection than the type I neurons. These differences were most evident in neurons from the basal, high-frequency region of the cochlea. The basal type I neurons displayed uniformly fast firing features, whereas the basal type II neurons showed particularly slow accommodation and responses to depolarization. Interestingly, neurons from the apical, low-frequency region of the cochlea showed the opposite trend. These data suggest that the type I and type II neurons have specialized electrophysiological characteristics tailored to their different roles in auditory signal processing. In particular, the type II neuron properties are consistent with cells in other sensory systems that receive convergent synaptic input for high-sensitivity stimulus detection. [ABSTRACT FROM AUTHOR]

HABITAT selection, GLOBAL Positioning System, HABITATS, VEGETATION & climate, RADIO telemetry, and ANIMAL radio tracking

Journal of Applied Ecology (2004) 41, 201–212 [ABSTRACT FROM AUTHOR]

Objectives: To compare the effects of low vs. high tidal volume (Vt) with three positive end-expiratory pressure (PEEP) strategies on activated neutrophil influx into the lung.Design: Prospective, randomized controlled animal study.Setting: Animal laboratory in a university hospital.Subjects: Newborn piglets.Interventions: Surfactant-depleted piglets were randomized in littermate pairs; to PEEP of either 0 (zero end-expiratory pressure [ZEEP]; n = 6), 8 cm H2O (PEEP 8; n = 5), or 1 cm H2O above the lower inflection point (LIP) (PEEP>LIP; n = 6). Within each pair piglets were randomized to a low VT (5-7 mL/kg) or high VT strategy (17-19 mL/kg). After 4 hrs of mechanical ventilation, 18-fluorodeoxyglucose (18FDG) was injected and positron emission tomography scanning was performed.Measurements and Main Results: VT and PEEP changes on influx constants of 18FDG were assessed by analysis of variance. A within-litter comparison of Vt was nonsignificant (p = .50). A between-litter comparison, ordered in linear trend rank, from ZEEP, to PEEP 8, to PEEP>LIP, showed a strong effect of PEEP on influx constant (p = .019).Conclusions: PEEP set above the LIP on the inspiratory limb of the pressure-volume curve affords a stronger lung protection than VT strategy. [ABSTRACT FROM AUTHOR]

MENTAL depression, QUALITY of life, PSYCHOLOGICAL adaptation, HIV-positive persons, AIDS patients, and SOCIAL services

Examines the prevalence of depression, and its association with quality–of–life, coping strategies, social support, and use of health and social services among people living with HIV and AIDS in Ontario. Indication of the prevalence of depression; Increase of the use of crisis health care and related services among subjects; Improvement of the quality of life through expanding the capacity of medical workers to recognize and address depression.

BOOKS, LIBRARIES, INFORMATION science, HEALTH services administration, HEALTH of physicians, and MEDICAL care

The article presents a special report on the book "Standards for Hospital Libraries 2002." The 2004 revisions of the book include an expansion of standard 6, which is a glossary definition of "library," and updates to the bibliography. The expanded standard 6 defines appropriate resources, technology, and services that must be provided. The updates to the bibliography include the latest edition of the Joint Commission on Accreditation of Healthcare Organizations Comprehensive Accreditation Manual for Hospitals, the Medical Library Association policy statement on the role of expert searching in health sciences libraries, and updates of some Website addresses. The librarian uses a variety of tools and techniques, both formal and informal, to assess the knowledge-based information needs of the hospital and medical staff. The needs assessment should address the timeliness of information services and document delivery. In response, resources and services are made available to meet those identified needs.

SHEEHAN'S syndrome, SOMATOTROPIN, INTELLECTUAL disabilities, ETIOLOGY of diseases, TRANSCRIPTION factors, and PATHOLOGICAL psychology

Duplications of Xq26-27 have been implicated in the etiology of X-linked hypopituitarism associated with mental retardation (MR). Additionally, an expansion of a polyalanine tract (by 11 alanines) within the transcription factor SOX3 (Xq27.1) has been reported in patients with growth hormone deficiency and variable learning difficulties. We report a submicroscopic duplication of Xq27.1, the smallest reported to date (685.6 kb), in two siblings with variable hypopituitarism, callosal abnormalities, anterior pituitary hypoplasia (APH), an ectopic posterior pituitary (EPP), and an absent infundibulum. This duplication contains SOX3 and sequences corresponding to two transcripts of unknown function; only Sox3 is expressed in the infundibulum in mice. Next, we identified a novel seven-alanine expansion within a polyalanine tract in SOX3 in a family with panhypopituitarism in three male siblings with an absent infundibulum, severe APH, and EPP. This mutation led to reduced transcriptional activity, with impaired nuclear localization of the mutant protein. We also identified a novel polymorphism (A43T) in SOX3 in another child with hypopituitarism. In contrast to findings in previous studies, there was no evidence of MR or learning difficulties in our patients. We conclude that both over- and underdosage of SOX3 are associated with similar phenotypes, consisting of infundibular hypoplasia and hypopituitarism but not necessarily MR. [ABSTRACT FROM AUTHOR]

AZEPINES, HETEROCYCLIC compounds, EPIDERMAL growth factor, and PROTEIN-tyrosine kinase inhibitors

Abstract: A novel class of pyrimido[4,5-b]-1,4-benzoxazepines is described as inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase. Two compounds display potent EGFR inhibitory activity of less than 1μM in cellular phosphorylation assays (IC50 0.47–0.69μM) and are highly selective against a small kinase panel. Such compounds demonstrate anti-EGFR activity within a class that is different from any known EGFR inhibitor scaffolds. They also provide a basis for the design of kinase inhibitors with the desired selectivity profile. [Copyright &y& Elsevier]

SEPTEMBER 11 Terrorist Attacks, 2001, PARTICLES, TOXINS, GLASS fibers, POLYCYCLIC aromatic hydrocarbons, DIOXINS, and PUBLIC health

In the aftermath of the September 11 World Trade Center (WTC) attack, a large number of people sustained potential exposures to smoke, dust, particulate matter, and a variety of toxins, including asbestos, pulverized concrete, glass fibers, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated furans and dioxins. Additionally, many had exposure to psychological traumatogens. The most common effects seen to date are respiratory and mental health consequences. The long-term consequences of exposures are not yet known, and there remains concern about the potential for late-emerging diseases such as cancers. This article reviews WTC-related health effects, the spectrum of exposures and how they were documented, and discusses future preventive efforts. [ABSTRACT FROM AUTHOR]

HEALTH promotion, NURSING, HOME care services, PREVENTIVE health services, and FRAIL elderly

Aim. This paper reports a study evaluating the comparative effects and costs of a proactive nursing health promotion intervention in addition to usual home care for older people compared with usual home care services alone. Background. An ageing population, budget constraints and technological advances in many countries have increased the pressure on home care resources. The result is a shift in nursing services from health promotion to meet the more pressing need for postacute care. For frail older people with long-term needs, these changes combine to create a fragmented system of health service delivery, characterized by providing nursing on demand rather than proactively. Methods. A two-armed, single-blind, randomized controlled trial was carried out with older people ≥75 years and eligible for personal support services through a home care programme in Ontario, Canada. Participants were randomly allocated either to usual home care (control) or to a nursing (experimental) group. In addition to usual home care, the nursing group received a health assessment combined with regular home visits or telephone contacts, health education about management of illness, coordination of community services, and use of empowerment strategies to enhance independence. The data were collected in 2001–2002. Results. Of the 288 older people who were randomly allocated at baseline, 242 (84%) completed the study (120 nursing group; 122 control group). Proactively providing older people with nursing health promotion, compared with providing nursing services on-demand, resulted in better mental health functioning ( P = 0·009), a reduction in depression ( P = 0·009), and enhanced perceptions of social support ( P = 0·009) at no additional cost from a societal perspective. Conclusions. Home based nursing health promotion, proactively provided to frail older people with chronic health needs, enhances quality of life while not increasing the overall costs of health care. The results underscore the need to re-invest in nursing services for health promotion for older clients receiving home care. [ABSTRACT FROM AUTHOR]

DIAZEPINES, EPIDERMAL growth factor, CYTOKINES, and PROTEIN-tyrosine kinases

Abstract: Novel tricyclic derivatives containing an oxazepine, thiazepine, or diazepine ring were studied for their EGFR tyrosine kinase inhibitory activity. While the oxazepines were in general more potent than thiazepines, the diazepines displayed somewhat different structure–activity relationships. Moreover, the diazepines, in contrast to the oxazepines, showed appreciable inhibitory activity against the KDR tyrosine kinase. Furthermore, both oxazepines and diazepines demonstrated significant ability to inhibit autophosphorylation of EGFR in DiFi cells (generally, IC50 values in the single-digit micromolar to submicromolar range). [Copyright &y& Elsevier]

COMMUNITY health nurses, HEALTH promotion, HOME care of older people, HOME care services, and COMMUNITY health services

Despite the large potential role that community nurses have in providing individualized health promotion to older people, there is a lack of consensus in the literature regarding this role's effectiveness and efficiency. This article presents a literature review and synthesis of 12 randomized controlled trials selected from 344 published studies on preventive home visitation programs for older people. The findings suggest that a diversity of home visiting interventions carried out by nurses can favorably affect health and functional status, mortality rates, use of hospitalization and nursing homes, and costs. Further research is needed that focuses on the outcomes of quality of life, mental health, social support, caregiver burden, the acceptability of intervention, and specific subgroups of clients who benefit most. Findings also indicate the need for a theoretical foundation, increased emphasis on health-promotion strategies, and more research using a more complete economic evaluation to establish efficiency. [ABSTRACT FROM AUTHOR]

WORLD Trade Center Bombing, New York, N.Y., 1993, RESCUE work, EMERGENCY medical services, SEPTEMBER 11 Terrorist Attacks, 2001, TERRORISM, MEDICAL screening, HEALTH risk assessment, DIAGNOSTIC services, and MEDICAL care

BACKGROUND: Approximately 40,000 rescue and recovery workers were exposed to caustic dust and toxic pollutants following the 11 September 2001 attacks on the World Trade Center (WTC). These workers included traditional first responders, such as firefighters and police, and a diverse population of construction, utility, and public sector workers. METHODS: To characterize WTC-related health effects, the WTC Worker and Volunteer Medical Screening Program was established. This multicenter clinical program provides free standardized examinations to responders. Examinations include medical, mental health, and exposure assessment questionnaires; physical examinations; spirometry; and chest X rays. RESULTS: Of 9,442 responders examined between July 2002 and April 2004, 69% reported new or worsened respiratory symptoms while performing WTC work. Symptoms persisted to the time of examination in 59% of these workers. Among those who had been asymptomatic before September 11, 61% developed respiratory symptoms while performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital capacity (FVC) was low in 21%; and obstruction was present in 5%. Among nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S. population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities were significantly associated with early arrival at the site. CONCLUSION: WTC responders had exposure-related increases in respiratory symptoms and pulmonary function test abnormalities that persisted up to 2.5 years after the attacks. Long-term medical monitoring is required to track persistence of these abnormalities and identify late effects, including possible malignancies. Lessons learned should guide future responses to civil disasters. [ABSTRACT FROM AUTHOR]

NEUROMUSCULAR diseases, HUMAN chromosome abnormality diagnosis, GENETIC mutation, and GENETIC testing

Mutations in DOK7 have recently been shown to underlie a recessive congenital myasthenic syndrome (CMS) associated with small simplified neuromuscular junctions (‘synaptopathy’) but normal acetylcholine receptor and acetylcholinesterase function. We identified DOK7 mutations in 27 patients from 24 kinships. Mutation 1124_1127dupTGCC was common, present in 20 out of 24 kinships. All patients were found to have at least one allele with a frameshift mutation in DOK7 exon 7, suggesting that loss of function(s) associated with the C-terminal region of Dok-7 underlies this disorder. In 15 patients, we were able to study the clinical features in detail. Clinical onset was usually characterized by difficulty in walking developing after normal motor milestones. Proximal muscles were usually more affected than distal, leading to a ‘limb-girdle’ pattern of weakness; although ptosis was often present from an early age, eye movements were rarely involved. Patients did not show long-term benefit from anticholinesterase medication and sometimes worsened, and where tried responded to ephedrine. The phenotype can be distinguished from ‘limb-girdle’ myasthenia associated with tubular aggregates, where DOK7 mutations were not detected and patients respond to anticholinesterase treatments. CMS due to DOK7 mutations are common within our UK cohort and is likely to be under-diagnosed; recognition of the phenotype will help clinical diagnosis, targeted genetic screening and appropriate management. [ABSTRACT FROM AUTHOR]

HEALTH of poor children, MOTOR ability in children, PHYSIOLOGICAL control systems, LOCOMOTOR control, AFRICAN American children, MOTOR ability -- Research, SOCIOECONOMIC factors, and PHYSIOLOGY

Children from poor, urban, and disadvantaged environments often demonstrate poor motor skill competence in both object control (OC) and locomotor skills (Goodway & Rudisill, 1996; Hamilton et al., 1999). This study examined the motor skill competence of disadvantaged, African American preschoolers. Further, it investigated the effects of a 9-week OC intervention on OC competence. Two instructional approaches were compared: low autonomy (LA) consisting of direct-instruction and a mastery motivational climate (MMC). Participants were randomly assigned to a LA (n = 36), MMC (n = 38), or comparison (no motor intervention) group (n = 39). The LA and MMC groups participated in 18 30-min OC sessions and the comparison group participated in the same amount of unstructured recess. All children were pre-and posttested on the OC subscale of the TGMD-2 (Ulrich, 2001). Preintervention OC competence was low based on percentile ranks (LA = 23%, MMC = 20%, comparison = 20%). A 3 (Group) x 2 (Sex) ANOVA on pre-OC scores revealed no significant group differences (p = .90) or Group x Sex interaction (p = .60). However, a significant sex main effect was found with boys having greater OC competence than girls, F(1, 107) = 29.34, p < .001. A 3 (Group) x 2 Time x 2 (Sex) ANOVA with repeated measures revealed a significant Group x Time interaction, F(2, 107) = 210.97, p < .001, indicating the OC intervention was effective. Post hoc Tukey HSD analysis reported the LA (p ≤ = < .001) and MMC (p ≤ = < .001) groups had significantly better OC competence than the Comparison group from pre- to postintervention. There was no difference between the LA and MMC groups (p = .88). A nonsignificant Group x Time x Sex interaction (p = .94) showed that there were no sex differences within groups from pre- to postintervention. Clearly, disadvantaged preschoolers had low OC competence and needed motor intervention. When instruction was provided by either LA or MMC, preschool children improved their OC skills. [ABSTRACT FROM AUTHOR]

CYTOKINES, CELLULAR immunity, APOPTOSIS, CELL death, GENETIC mutation, and LIGANDS (Biochemistry)

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a cytokine that preferentially induces apoptosis in tumor cells compared with normal cells through two receptors (DR4 and DR5). Somatic mutations in these receptors have been found in different kinds of cancer; however, it is poorly under- stood how the mutations affect signaling. We found that point mutations (L334F, E326K, E338K, and K386N) that were identified in human tumors result in the DR5 receptor losing its ability to form a functional death-inducing signaling complex and induce apoptosis. The mutant receptors also have a ‘dominant negative’ effect whereby they inhibit the ability of TRAIL to induce apoptosis through functional DR4 receptors. This dominant negative mechanism is achieved through competition for TRAIL binding as shown by experiments where the ability of the mutant DR5 receptor to bind with the ligand was abolished, thus restoring TRAIL signaling through DR4. The inhibitory effect on signaling through the wild-type DR4 protein can be overcome if the inhibitory mechanism is bypassed by using a DR4-agonistic antibody that is not subject to this competition. This study provides a molecular basis for the use of specific therapeutic agonists of TRAIL receptors in people whose tumors harbor somatic DR5 mutations. [ABSTRACT FROM AUTHOR]

PROTEINS, NEURONS, SENSE organs, AUDITORY pathways, SENSORY receptors, and COCHLEA

A unifying principle of sensory system organization is feature extraction by modality-specific neuronal maps in which arrays of neurons show systematically varied response properties and receptive fields. Only beginning to be understood, however, are the mechanisms by which these graded systems are established. In the peripheral auditory system, we have shown previously that the intrinsic firing features of spiral ganglion neurons are influenced by brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). We now show that is but a part of a coordinated package of neurotrophin actions that also includes effects on presynaptic and postsynaptic proteins, thus encompassing the input, transmission, and output functions of the spiral ganglion neurons. Using immunocytochemical methods, we determined that proteins targeted to opposite ends of the neuron were organized and regulated in a reciprocal manner. AMPA receptor subunits GluR2 and GluR3 were enriched in base neurons compared with their apex counterparts. This distribution pattern was enhanced by exposure to BDNF but reduced by NT-3. SNAP-25 and synaptophysin were distributed and regulated in the mirror image: enriched in the apex, enhanced by NT-3 and reduced by BDNF. Moreover, we used a novel coculture to identify potential endogenous sources of neurotrophins by showing that sensory receptors from different cochlear regions were capable of altering presynaptic and postsynaptic protein levels in these neurons. From these studies, we suggest that BDNF and NT-3, which are systematically distributed in complementary gradients, are responsible for orchestrating a comprehensive set of electrophysiological specializations along the frequency contour of the cochlea. [ABSTRACT FROM AUTHOR]

ORTHOGRAPHY & spelling, LEARNING, LITERACY, SECOND grade (Education), SCHOOL children, TEACHING, and GENES

As part of a longitudinal twin study of literacy and language, we conducted a behaviour-genetic analysis of orthographic learning, spelling and decoding in Grade 2 children (225 identical and 214 fraternal twin pairs) in the United States and Australia. Each variable showed significant genetic and unique environment influences. Multivariate analyses revealed very high genetic correlations among the variables, indicating that the same genes are involved in their aetiology. These genes are partly independent of those contributing to intelligence. A further analysis indicated that the covariation between decoding and orthographic learning is mediated by shared genes rather than by a direct causal path. The authors argue that a learning parameter, most directly assessed by orthographic learning in this study, underlies all three literacy variables. The results are also discussed in relation to Share's self-teaching hypothesis, which may require modification. [ABSTRACT FROM AUTHOR]

SEPTEMBER 11 Terrorist Attacks, 2001, HAZARDOUS substance exposure, MEDICAL screening, HAZARDS, and HEALTH risk assessment

The attack on the World Trade Center (WTC) on September 11th, 2001 exposed thousands of individuals to an unprecedented mix of chemicals, combustion products and micronized building materials. Clinicians at the Mount Sinai Irving Selikoff Center for Occupational and Environmental Medicine, in partnership with affected stakeholder organizations, developed a medical screening program to evaluate the health status of workers and volunteers who spent time at the WTC site and thus sustained exposure in the aftermath of September 11th. Standardized questionnaires were adapted for use in this unique population and all clinicians underwent training to ensure comparability. The WTC Worker and Volunteer Medical Screening Program (MSP) received federal funding in April 2002 and examinations began in July 2002. The MSP and the follow up medical monitoring program has successfully recruited nearly 22,000 responders, and serves as a model for the rapid development of a medical screening program to assess the health of populations exposed to environmental hazards as a result of natural and man-made disasters. The MSP constitutes a successful screening program for WTC responders. We discuss the challenges that confronted the program; the absence of a prior model for the rapid development of a program to evaluate results from mixed chemical exposures; little documentation of the size of the exposed population or of who might have been exposed; and uncertainty about both the nature and potential severity of immediate and long-term health effects. [ABSTRACT FROM AUTHOR]

DISASTERS, FIRST responders, HEALTH risk assessment, and SEPTEMBER 11 Terrorist Attacks, 2001

Studies of long-term health consequences of disasters face unique methodologic challenges. The authors focused on studies of the health of cleanup and recovery workers, who are often poorly enumerated at the outset and difficult to follow over time. Comparison of the experience at the World Trade Center disaster with 4 past incidents of chemical and radiation releases at Seveso, Italy; Bhopal, India; Chernobyl, Ukraine; and Three Mile Island, USA, provided useful contrasts. Each event had methodologic advantages and disadvantages that depended on the nature of the disaster and the availability of records on area residents, and the emergency-response and cleanup protocol. The World Trade Center Worker Monitoring Program has well-defined eligibility criteria but lacks information on the universe of eligible workers to characterize response proportions or the potential for distortion of reported health effects. Nonparticipation may result from lack of interest, lack of awareness of the program, availability of another source of medical care, medical conditions precluding participation, inability to take time off from work, moving out of the area, death, or shift from initially ineligible to eligible status. Some of these considerations suggest selective participation by the sickest individuals, whereas others favor participation by the healthiest. The greatest concern with the validity of inferences regarding elevated health risks relative to external populations is the potential for selective enrollment among those who are affected. If there were a large pool of nonparticipating workers and those who suffered ill health were most motivated to enroll, the rates of disease among participants would be substantially higher than among all those eligible for the program. Future disaster follow-up studies would benefit substantially by having access to accurate estimates of the number of workers and information on the individuals who contributed to the cleanup and recovery effort. [ABSTRACT FROM AUTHOR]

MENTAL health, VOLUNTEERS, SEPTEMBER 11 Terrorist Attacks, 2001, EMOTIONAL trauma, and MENTAL health services

Background: Disaster workers responding to the events of September 11th were exposed to traumatic events. No study has systematically investigated the diverse mental health status and needs of the heterogeneous population of disaster workers responding to the events of September 11th. Methods: Using PubMed and Medline and the search terms of "September 11, 2001" or "September 11" or "9/11" or "WTC" or "World Trade Center", the authors reviewed all articles that examined the mental health outcomes of workers at one of the three September 11th crash sites or the Fresh Kills landfill in New York City. Results: In total, 25 articles met study inclusion criteria, often using different methodologies. The articles described varying degrees of mental health symptomatology, risk factors for adverse mental health outcomes, and utilization of mental health services. Conclusions: The mental health needs of workers exposed to the events of September 11th ranged from little to no care to pharmacotherapy. A range of risk factors, including exposures at the WTC site and occupational activities, impacted on these needs but the role of specific mental health interventions was less clear. These findings suggest the need for a future program for disaster workers consisting of an accessible mental health treatment service supported by comprehensive postdisaster surveillance and emphasis on pre-disaster mental wellness. A number of areas for further consideration and study were identified, including the need for a more diverse exploration of involved responder populations as well as investigation of potential mental health outcomes beyond post-traumatic stress disorder (PTSD). [ABSTRACT FROM AUTHOR]

Background: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/microL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART.Methods: Patients who were either ART naive (n=249) or who had not been receiving ART for >or= 6 months (n=228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii).Results: A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for 6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56; p=.02); outcome (ii), 3.26 (95% CI, 1.04-10.25; p=.04); outcome (iii), 7.02 (95% CI, 1.57-31.38; p=.01); and outcome (iv), 4.19 (95% CI, 1.69-10.39; p=.002 ).Conclusions: Initiation of ART at CD4+ cell counts >350 cells/microL compared with <250 cells/microL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial. [ABSTRACT FROM AUTHOR]

PROTEIN kinases, OLIGODENDROGLIA, GENETIC translation, MESSENGER RNA, NUCLEOPROTEINS, and RNA

Central nervous system myelination requires the synthesis of large amounts of myelin basic protein (MBP) at the axon-glia contact site. MBP messenger RNA (mRNA) is transported in RNA granules to oligodendroglial processes in a translationally silenced state. This process is regulated by the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binding to the cis-acting A2 response element (A2RE). Release of this repression of MBP mRNA translation is thus essential for myelination. Mice deficient in the Src family tyrosine kinase Fyn are hypomyelinated and contain reduced levels of MBP. Here, we identify hnRNP A2 as a target of activated Fyn in oligodendrocytes. We show that active Fyn phosphorylates hnRNP A2 and stimulates translation of an MBP A2RE-containing reporter construct. Neuronal adhesion molecule L1 binding to oligodendrocytes results in Fyn activation, which leads to an increase in hnRNP A2 phosphorylation. These results suggest that Fyn kinase activation results in the localized translation of MBP mRNA at sites of axon-glia contact and myelin deposition. [ABSTRACT FROM AUTHOR]

EARLY childhood education, LITERACY programs, ACTIVITY programs in kindergarten, and SCHOOL attendance

Abstract: Genetic and environmental influences on early reading and spelling at the end of kindergarten and Grade 1 were compared across three twin samples tested in the United States, Australia, and Scandinavia. Proportions of variance due to genetic influences on kindergarten reading were estimated at .84 in Australia, .68 in the U.S., and .33 in Scandinavia. The effects of shared environment on kindergarten reading were estimated at .09 in Australia, .25 in the U.S., and .52 in Scandinavia. A similar pattern of genetic and environmental influences was obtained for kindergarten spelling. One year later when twins in all three samples had received formal literacy instruction for at least one full school year, heritability was similarly high across country, with estimated genetic influences varying between .79 and .83 for reading and between .62 and .79 for spelling. These findings indicate that the pattern of genetic and environmental influences on early reading and spelling development varies according to educational context, with genetic influence increasing as a function of increasing intensity of early instruction. Longitudinal analyses revealed genetic continuity for both reading and spelling between kindergarten and Grade 1 across country. However, a new genetic factor comes into play accounting for independent variance in reading at Grade 1 in the U.S. and Scandinavia, suggesting a change in genetic influences on reading. Implications for response-to-instruction are discussed. [Copyright &y& Elsevier]

CERVICAL cancer treatment, RADIOTHERAPY, RADIOISOTOPE brachytherapy, and COMORBIDITY

Purpose: To assess the outcome of patients treated with radical radiotherapy for cervical cancer who received an external beam boost, in place of intracavitary brachytherapy (ICT), after irradiation to the whole pelvis. Methods and Materials: Case notes were reviewed for all patients treated in this way in a single center between 1996 and 2004. Patient and tumor details, the reasons why ICT was not possible, and treatment outcome were documented. Results: Forty-four patients were identified. The mean age was 56.4 years (range, 26–88 years). Clinical International Federation of Gynecology and Obstetrics or radiologic stage for Stages I, II, III, and IV, respectively, was 16%, 48%, 27%, and 7%. A total radiation dose of 54–70 Gy was given (75% received ≥60 Gy). Reasons for ICT not being performed were technical limitations in 73%, comorbidity or isolation limitations in 23%, and patient choice in 4%. The median follow-up was 2.3 years. Recurrent disease was seen in 48%, with a median time to recurrence of 2.3 years. Central recurrence was seen in 16 of the 21 patients with recurrent disease. The 5-year overall survival rate was 49.3%. The 3-year cancer-specific survival rate by stage was 100%, 70%, and 42% for Stages I, II, and III, respectively. Late Grades 1 and 2 bowel, bladder, and vaginal toxicity were seen in 41%. Late Grade 3 toxicity was seen in 2%. Conclusion: An external beam boost is a reasonable option after external beam radiotherapy to the pelvis when it is not possible to perform ICT. [Copyright &y& Elsevier]

ENVIRONMENTAL toxicology research, SEPTEMBER 11 Terrorist Attacks, 2001 -- Psychological aspects, POST-traumatic stress disorder, COMORBIDITY, and MENTAL health

BACKGROUND: The World Trade Center (WTC) attacks exposed thousands of workers to hazardous environmental conditions and psychological trauma. In 2002, to assess the health of these workers, Congress directed the National Institute for Occupational Safety and Health to establish the WTC Medical Monitoring and Treatment Program. This program has established a large cohort of WTC rescue, recovery, and cleanup workers. We previously documented extensive pulmonary dysfunction in this cohort related to toxic environmental exposures. OBJECTIVES: Our objective in this study was to describe mental health outcomes, social function impairment, and psychiatric comorbidity in the WTC worker cohort, as well as perceived symptomatology in workers' children. METHODS: Ten to 61 months after the WTC attack, 10,132 WTC workers completed a self-administered mental health questionnaire. RESULTS: Of the workers who completed the questionnaire, 11.1% met criteria for probable posttraumatic stress disorder (PTSD), 8.8% met criteria for probable depression, 5.0% met criteria for probable panic disorder, and 62% met criteria for substantial stress reaction. PTSD prevalence was comparable to that seen in returning Afghanistan war veterans and was much higher than in the U.S. general population. Point prevalence declined from 13.5% to 9.7% over the 5 years of observation. Comorbidity was extensive and included extremely high risks for impairment of social function. PTSD was significantly associated with loss of family members and friends, disruption of family, work, and social life, and higher rates of behavioral symptoms in children of workers. CONCLUSIONS: Working in 9/11 recovery operations is associated with chronic impairment of mental health and social functioning. Psychological distress and psychopathology in WTC workers greatly exceed population norms. Surveillance and treatment programs continue to be needed. [ABSTRACT FROM AUTHOR]

PYRIDAZINES, VASCULAR endothelial growth factor antagonists, DRUG bioavailability, ORGANIC synthesis, ENZYME inhibitors, MITOGENS, and LABORATORY mice

Abstract: A series of arylphthalazine derivatives were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in two steps from commercially available starting materials, was found to be a potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays (comparable activity to ZD-6474). Additionally, 57 inhibited the related receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed orally to female CD-1 mice. [Copyright &y& Elsevier]

IMIDAZOLES, PROTEIN kinase C, ENZYME inhibitors, TARGETED drug delivery, IMMUNOLOGIC diseases, and INFLAMMATION

Abstract: The inhibition of PKC-ζ has been proposed to be a potential drug target for immune and inflammatory diseases. A series of 2-(6-phenyl-1H indazol-3-yl)-1H-benzo[d]imidazoles with initial high crossover to CDK-2 has been optimized to afford potent and selective inhibitors of protein kinase c-zeta (PKC-ζ). The determination of the crystal structures of key inhibitor:CDK-2 complexes informed the design and analysis of the series. The most selective and potent analog was identified by variation of the aryl substituent at the 6-position of the indazole template to give a 4-NH2 derivative. The analog displays good selectivity over other PKC isoforms (α, βII, γ, δ, ε, μ, θ, η and ι/λ) and CDK-2, however it displays marginal selectivity against a panel of other kinases (37 profiled). [Copyright &y& Elsevier]

OCCUPATIONAL diseases, LUNG diseases, SPIROMETRY, VITAL capacity (Respiration), and WEIGHT gain

The article presents a study that evaluates prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up assessment in participants in the World Trade Center Worker and Volunteer Medical Monitoring Program in New York City. The research found that elevated rates of spirometric abnormalities were present in two examinations, with reduced forced vital capacity most common.

CLEFT lip, CLEFT palate, GENES, MYOSIN, GENETIC disorders, and HUMAN genetics

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth anomaly that requires prolonged multidisciplinary rehabilitation. Although variation in several genes has been identified as contributing to NSCLP, most of the genetic susceptibility loci have yet to be defined. To identify additional contributory genes, a high-throughput genomic scan was performed using the Illumina Linkage IVb Panel platform. We genotyped 6008 SNPs in nine non-Hispanic white NSCLP multiplex families and a single large African-American NSCLP multiplex family. Fourteen chromosomal regions were identified with LOD>1.5, including six regions not previously reported. Analysis of the data from the African-American and non-Hispanic white families revealed two likely chromosomal regions: 8q21.3–24.12 and 22q12.2–12.3 with LOD scores of 2.98 and 2.66, respectively. On the basis of biological function, syndecan 2 (SDC2) and growth differentiation factor 6 (GDF6) in 8q21.3–24.12 and myosin heavy-chain 9, non-muscle (MYH9) in 22q12.2–12.3 were selected as candidate genes. Association analyses from these genes yielded marginally significant P-values for SNPs in SDC2 and GDF6 (0.01≤P<0.05). Evidence for an altered transmission was found for four MYH9 SNPs (P<0.01). SNP rs1002246 exhibited altered transmission by all analytic methods. However, analysis of two SNP MYH9 haplotypes did not identify a single high-risk haplotype. Our results confirm a previous report that 8q21.3–24.12 may harbor a clefting gene and identify 22q12.2–12.3 as a new candidate region that contains MYH9. Most importantly, we confirm the previous report of an association with MYH9.European Journal of Human Genetics (2009) 17, 195–204; doi:10.1038/ejhg.2008.149; published online 20 August 2008 [ABSTRACT FROM AUTHOR]

THYROID gland, REGULATION of blood pressure, HYPERTENSION, ENDOCRINE glands, and HYPOTHALAMUS

Introduction Thyroid function and genetic variation in the hypothalamus–pituitary–thyroid axis have been implicated in blood pressure regulation and susceptibility to hypertension. However studies conducted thus far were small with controversial results. Objective To examine whether serum thyroid parameters and polymorphisms in the type 2 deiodinase and the TSH receptor are associated with blood pressure and the presence of hypertension in two large cohorts of elderly subjects. Design and participants We studied a random sample of 1444 subjects of the Rotterdam study, and 997 subjects of the Rotterdam Scan study, two population-based cohort studies among elderly individuals aged 55–90 years. Outcome measurements Data on blood pressure and hypertension were obtained, and serum thyroid parameters, D2-Thr92Ala, D2-ORFa-Gly3Asp and TSHR-Asp727Glu polymorphisms were determined. Results In contrast to previous findings, no consistent and/or significant associations were found between serum TSH and FT4 and blood pressure in both cohorts. In addition, the D2-Thr92Ala, D2-ORFa-Gly3Asp and TSHR-Asp727Glu polymorphisms were not associated with blood pressure or the risk of hypertension. Conclusions In two large populations of elderly subjects, neither serum thyroid parameters nor polymorphisms in the type 2 deiodinase and the TSH receptor, were associated with blood pressure or the presence of hypertension. Our data suggest that thyroid function is not an important determinant of hypertension in elderly Dutch subjects. [ABSTRACT FROM AUTHOR]

MULTIPLE myeloma, B cell lymphoma, FIRST responders, and SEPTEMBER 11 Terrorist Attacks, 2001

The article presents a study which examines cases of multiple myeloma (MM) observed in World Trade Center (WTC) responders registered in the World Trade Center Medical Program in New York City. Eight cases of MM were observed among 28, 252 responders of known sex and age. The findings concluded that it is important to maintain surveillance for cancer and other emerging diseases among WTC responders.

FISHES, MICROBIOLOGICAL synthesis, ANTIBIOTICS, PATHOGENIC microorganisms, PATHOGENIC bacteria, and FERMENTATION

Lactococcus lactis subsp, lactis strain CWBI B1410, which produces various antibacterial compounds including organic acids and nisin, was used as a starter culture to improve the traditional Senegalese fish fermentation in which fish are mostly transformed to guedj by spontaneous fermentation for 24 to 48 h at ambient temperatures near 30°C followed by salting (with NaCI) and sun drying. Assays were performed on lean fish (Podamasys jubelini) and fat fish (Arius heudelotii) purchased at a local market. The total viable microbial counts in raw fillets of P. jubelini and A. heudelotii were 5.78 and 5.39 log CFU/g respectively. Populations of enteric bacteria (which can include pathogenic bacteria) in P. jubelini and A. heudelotii were 4.08 and 4.12 log CFU/g, respectively. Spontaneous fermentation of raw fillets at 30°C led to the proliferation of enteric bacteria to 9 log CFU/g after 24 h in fermented P. jubelini and A. heudelotii fillets with pH values of 6.83 and 7.50, respectively. When raw fish fillets were supplemented with glucose (1%, wt/wt) and inoculated with Lactococcus lactis (107 CFU/g), the pH decreased to about 4.60 after 10 h at 30°C, and nisin activity was detected in juice from the fillets. Traditionally fermented fillets of P. jubelini and A. heudelotii contained enteric bacteria at higher levels of 4 and 2 log CFU/g, respectively, than did fillets of the same fish supplemented with glucose and fermented with the starter culture. These data suggest that this new fish fermentation strategy combined with salting and drying can be used to enhance the safety of guedj. [ABSTRACT FROM AUTHOR]

PATHOLOGICAL psychology, MENTAL health, MEDICAL screening, TERRORISM, and MENTAL health services

A qualitative study of the experiences of rescue and recovery workers/volunteers at Ground Zero following the terrorist attacks of 9/11/01 is reported. Information was extracted from a semi-structured clinical evaluation of 416 responders who were the initial participants in a large scale medical and mental health screening and treatment program for 9/11 responders. Qualitative analysis revealed themes that spanned four categories— occupational roles, exposures, attitudes/experiences, and outcomes related to the experience of Ground Zero. Themes included details regarding Ground Zero roles, grotesque experiences such as smells, the sense of the surreal nature of responding, and a turning to rituals to cope after leaving Ground Zero. These findings personalize the symptom reports and diagnoses that have resulted from the 9/11 responders’ exposure to Ground Zero, yielding richer information than would otherwise be available for addressing the psychological dimensions of disasters. This work shows that large scale qualitative surveillance of trauma-exposed populations is both relevant and feasible. [ABSTRACT FROM AUTHOR]

ORGANOPHOSPHORUS compounds, BUTYRYLCHOLINESTERASE, ALBUMINS, OXIMES, TYROSINE, BIOMARKERS, and CHOLINESTERASES

Organophosphorus nerve agents inhibit the activity of cholinesterases by phosphylation of the active site serine. In addition, sarin, cyclosarin, soman and tabun have been shown to phosphylate a tyrosine residue in albumin. Therapies against nerve agent poisoning include the use of oximes to reactivate inhibited cholinesterases by displacement of the phosphyl moiety and hence detectable levels of adducts with cholinesterases may be reduced. Adducts with tyrosine have been shown to be persistent in the guinea pig in the presence of oxime therapy. Plasma samples obtained from an animal study aimed at improving therapy against nerve agent poisoning were used to compare the suitability of tyrosine and butyrylcholinesterase (BuChE) adducts as biomarkers of nerve agent exposure after treatment with therapeutic oximes. Under the terms of the project licence, these samples could be collected only on death of the animal, which occurred within hours of exposure or when culled at 23 or 24 days. Tyrosine adducts were detected in all samples collected following intra-muscular administration of twice the LD50 dose of the respective nerve agent. Aged BuChE adducts were detected in samples collected within a few hours after administration of soman and tabun, but not after 23 or 24 days. No BuChE adducts were detected in animals exposed to sarin and cyclosarin where samples were collected only after 23 or 24 days. [ABSTRACT FROM AUTHOR]

ACIDIFICATION, LACTIC acid bacteria, FATTY acids, LACTOBACILLUS, SORBITOL, MONOSODIUM glutamate, GLYCERIN, ADDITIVES, and FERMENTATION

The protective effects of the fatty acid composition and membrane action of the acidification activity of two strains of Lactobacillus kept at 20?C were studied. The addition of sorbitol, monosodium glutamate and glycerol during storage is causing the decline of acidification and increased concentrations of unsaturated fatty acids observed in both strains. The addition of sorbitol and monosodium glutamate does not alter the fatty acid composition, whatever the strain, but increases the resistance to freeze-drying of L. plantarum CWBI-B1419 and improves survival during storage. The addition of these preservatives and decreased activity of acidification improves the ratio unsaturated. These results indicate that the survival during storage and freeze-drying resistance are closely related to the composition of membrane fatty acids. This behaviour can be interpreted as an adaptation of L. plantarum B1419-CWBI supplemented by cryoprotectant additives such as sorbitol or monosodium glutamate sorbitol and monosodium glutamate as an additive. L. plantarum CWBI-B1419 presents a greater adaptation to culture conditions than L. paracasei ssp. paracasei LMG9192T. [ABSTRACT FROM AUTHOR]

PROTEIN-tyrosine kinases, CRYSTALLIZATION, PHOSPHORYLATION, CYTOKINES, INFLAMMATION, ONCOLOGY, and MICROFLUIDICS

Abstract: Janus-associated kinases (JAKs) play critical roles in cytokine signaling, and have emerged as viable therapeutic targets in inflammation and oncology related diseases. To date, targeting JAK proteins with highly selective inhibitor compounds have remained elusive. We have expressed the active kinase domains for both JAK2 and JAK3 and devised purification protocols to resolve the non-, mono- (Y1007) and diphosphorylated (Y1007 and Y1008) states of JAK2 and non- and monophosphorylated states of JAK3 (Y980). An optimal purified protein yield of 20, 29 and 69mg per 20L cell culture was obtained for the three JAK2 forms, respectively, and 12.2 and 2.3mg per 10L fermentation for the two JAK3 forms allowing detailed biochemical and biophysical studies. To monitor the purification process we developed a novel HPLC activity assay where a sequential order of phosphorylation was observed whereby the first tyrosine residue was completely phosphorylated prior to phosphorylation of the tandem tyrosine residue. A Caliper-based microfluidics assay was used to determine the kinetic parameters (K m and k cat) for each phosphorylated state, showing that monophosphorylated (Y1007) JAK2 enzyme activity increased 9-fold over that of the nonphosphorylated species, and increased an additional 6-fold for the diphosphorylated (Y1007/Y1008) species, while phosphorylation of JAK3 resulted in a negligible increase in activity. Moreover, crystal structures have been generated for each isolated state of JAK2 and JAK3 with resolutions better than 2.4Å. The generation of these reagents has enabled kinetic and structural characterization to inform the design of potent and selective inhibitors of the JAK family. [Copyright &y& Elsevier]

MICROFABRICATION, GAS chromatography, PHOTOIONIZATION, SEPARATION (Technology), VOLATILE organic compounds, HYDROFLUORIC acid, GLASS, SURFACES (Technology), VAN der Waals forces, and DIMETHYLPOLYSILOXANES

Abstract: We report the development of a microfabricated gas chromatography system suitable for the separation of volatile organic compounds (VOCs) and compatible with use as a portable measurement device. Hydrofluoric acid etching of 95×95mm Schott B270 wafers has been used to give symmetrical hemi-spherical channels within a glass substrate. Two matching glass plates were subsequently cold bonded with the channels aligned; the flatness of the glass surfaces resulted in strong bonding through van der Waals forces. The device comprised gas fluidic interconnections, injection zone and 7.5 and 1.4m long, 320μm internal diameter capillaries. Optical microscopy confirmed the capillaries to have fully circular channel profiles. Direct column heating and cooling could be achieved using a combination of resistive heaters and Peltier devices. The low thermal conductivity of glass allowed for multiple uniform temperature zones to be achieved within a single glass chip. Temperature control over the range 10–200°C was achieved with peak power demand of approximately 25W. The 7.5m capillary column was static coated with a 2μm film of non-polar dimethylpolysiloxane stationary phase. A standard FID and a modified lightweight 100mW photoionization detector (PID) were coupled to the column and performance tested with gas mixtures of monoaromatic and monoterpene species at the parts per million concentration level. The low power GC-PID device showed good performance for a small set of VOCs and sub ng detection sensitivity to monoaromatics. [Copyright &y& Elsevier]