BACKGROUND

The efficacy of amodiaquine (AQ), sulphadoxine-pyrimethamine (SP) and the combination of SP+AQ in the treatment of Cameroonian children with clinical malaria was investigated. The prevalence of molecular markers for resistance to these drugs was studied to set the baseline for surveillance of their evolution with time.

METHODS

Seven hundred and sixty children aged 6-59 months with uncomplicated falciparum malaria were studied in three ecologically different regions of Cameroon - Mutengene (littoral equatorial forest), Yaoundé (forest-savannah mosaic) and Garoua (guinea-savannah). Study children were randomized to receive either AQ, SP or the combination AQ+SP. Clinical outcome was classified according to WHO criteria, as either early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) or adequate clinical and parasitological response (ACPR). The occurrence of mutations in pfcrt, pfmdr1, dhfr and dhps genes was studied by either RFLP or dot blot techniques and the prevalence of these mutations related to parasitological and therapeutic failures.

RESULTS

After correction for the occurrence of re-infection by PCR, ACPRs on day 28 for AQ, SP and AQ+SP were 71.2%, 70.1% and 80.9%, in Garoua, 79.2%, 62.5%, and 81.9% in Mutengene, and 80.3%, 67.5% and 76.2% in Yaoundé respectively. High levels of Pfcrt 76T (87.11%) and Pfmdr1 86Y mutations (73.83%) were associated with quinoline resistance in the south compared to the north, 31.67% (76T) and 22.08% (86Y). There was a significant variation (p < 0.001) of the prevalence of the SGK haplotype between Garoua in the north (8.33%), Yaoundé (36.29%) in the savannah-forest mosaic and Mutengene (66.41%) in the South of Cameroon and a weak relation between SGK haplotype and SP failure. The 540E mutation on the dhps gene was extremely rare (0.3%) and occurred only in Mutengene while the pfmdr1 1034K and 1040D mutations were not detected in any of the three sites.

CONCLUSIONS

In this study the prevalence of molecular markers for quinoline and anti-folate resistances showed high levels and differed between the south and north of Cameroon. AQ, SP and AQ+SP treatments were well tolerated but with low levels of efficacy that suggested alternative treatments were needed in Cameroon since 2005.

We have studied the production of serum albumin by somatic hybrids between well-differentiated 2s and 1s rat hepatoma cells (Faza), which produce serum albumin, and sub-diploid mouse leukemic lymphoblasts (Lc), which do not produce albumin. We determined the rat or mouse origin of the albumin by double immunodiffusion, using immuno-adsorbed noncrossreacting antisera. Each of 12 karyologically identified 2s hybrid clones (Lc2F) produces both rat and mouse albumin. Moreover, unlike 1s hybrids reported previously, eight of nine 1s hybrids (LcF) also produce mouse albumin; six of them produce rat albumin as well. One clone from the 1s cross produces only rat albumin.

At sites of inflammation, mononuclear cells are in close contact with aggregated platelets. Although the physiologic role of this association is not clear, this proximity suggests that platelet-derived mediators may play a role in chemoattraction of T lymphocytes. In the current study we investigated serotonin receptor-bearing lymphocyte modulation of T cell migration. Serotonin-stimulated human blood mononuclear cells secrete lymphocyte chemoattractant activity with selective activity for CD4+ T cells. This chemoattractant activity was observed within 2 h of exposure to serotonin and was blocked by serotonin type 2 receptor antagonists. Molecular sieve chromatography of supernatant from serotonin-stimulated PBMCs revealed a single peak of T cell chemoattractant activity with an apparent molecular mass of 56 kDa and a pl of 9.1. Neutralizing experiments with specific mAbs indicated that the serotonin-induced chemotactic factor was the previously characterized lymphocyte chemoattractant factor (LCF), recently designated IL-16. Serotonin induced secretion of IL-16 from CD8+, not CD4+, T cells which did not require the de novo protein synthesis. These studies suggest that serotonin, via serotonin type 2 receptors, may promote the recruitment of CD4+ T lymphocytes into an inflammatory focus.

OBJECTIVE

High power of pre-stimulus cortical alpha rhythms (about 8-12 Hz) underlies conscious perception in normal subjects. Here we tested the hypothesis that these rhythms are abnormal in persistent vegetative state (PVS) patients, who are awake but not aware of self and environment.

METHODS

Clinical and resting-state, eyes-closed electroencephalographic (EEG) data were taken from a clinical archive. These data were recorded in 50 PVS subjects (level of cognitive functioning--LCF score: I-II) and in 30 cognitively normal subjects. Rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical sources were estimated by low-resolution electromagnetic tomography (LORETA). Based on LCF score at 3-months follow-up, PVS patients were retrospectively divided into three groups: 30 subjects who did not recover (NON-REC patients; follow-up LCF: I-II), 8 subjects classified as minimally conscious state patients (MCS patients; follow-up LCF: III-IV), and 12 subjects who recovered (REC patients; follow-up LCF: V-VIII).

RESULTS

Occipital source power of alpha 1 and alpha 2 was high in normal subjects, low in REC patients, and practically null in NON-REC patients. A Cox regression analysis showed that the power of alpha source predicted the rate of the follow up recovery, namely the higher its power, the higher the chance to recover consciousness. Furthermore, the MCS patients showed intermediate values of occipital alpha source power between REC and NON-REC patients.

CONCLUSIONS

These results suggest that cortical sources of alpha rhythms are related to the chance of recovery at a 3-months follow-up in patients in persistent vegetative state.

CONCLUSIONS

Cortical sources of resting alpha rhythms might predict recovery in PVS patients.

Following surgical removal of glioblastoma multiforme (GBM), radiochemotherapy impedes neoplastic outgrowth and relapse formation. Macrophages/microglial cells are believed to be potent mediators of the host defense system in GBM. However, little is known about their alteration by postsurgical therapies. We have now analyzed expression of LCA (leucocyte common antigen), CD68 (phagocytic cells), HLA-DR, -DP, -DQ (MHC class II), MRP-8 (myeloid-related protein, S100A8), MRP-14 (S100A9), LCF (lymphocyte chemoattractant factor, IL-16) and NOS II (inducible nitric oxide synthase) in macrophages/microglial cells in 39 GBM relapses and their matched primary tumors. Following surgery of the primary tumors, 15 patients received irradiation and chemotherapy, 17 irradiation and 7 no treatment. In irradiated relapses, we observed significantly more macrophages/microglial cells expressing MRP-14 compared to untreated GBM relapses. Furthermore, we observed a significant increase of CD68 expressing macrophages/microglial cells in patients without postsurgical treatment, but not in those with radiochemotherapy. In conclusion, our findings suggest that radiochemotherapy alters the number of MRP-14 expressing cells. The lacking increase of CD68 expressing cells in patients with radiochemotherapy suggests depletion of this cell type by postsurgical therapy.

OBJECTIVE

To compare corneal thickness measurements using Orbscan II (OII) and ultrasonic (US) pachymetry in normal and in keratoconic eyes.

METHODS

Eye Department, Heartlands and Solihull NHS Trust, Birmingham, United Kingdom.

METHODS

Central corneal thickness (CCT) was measured by means of OII and US pachymetry in 1 eye of 72 normal subjects and 36 keratoconus patients. The apical corneal thickness (ACT) in keratoconus patients was also evaluated using each method. The mean of the difference, standard deviation (SD), and 95% limits of agreement (LoA = mean +/- 2 SD), with and without applying the default linear correction factor (LCF), were determined for each sample. The Student t test was used to identify significant differences between methods, and the correlation between methods was determined using the Pearson bivariate correlation. Bland-Altman analysis was performed to confirm that the results of the 2 instruments were clinically comparable.

RESULTS

In normal eyes, the mean difference (+/- 95% LoA) in CCT was 1.04 microm +/- 68.52 (SD) (P>.05; r = 0.71) when the LCF was used and 46.73 +/- 75.40 microm (P =.0001; r = 0.71) without the LCF. In keratoconus patients, the mean difference (+/- 95% LoA) in CCT between methods was 42.46 +/- 66.56 microm (P<.0001: r = 0.85) with the LCF, and 2.51 +/- 73.00 microm (P>.05: r = 0.85) without the LCF. The mean difference (+/- 95% LoA) in ACT for this group was 49.24 +/- 60.88 microm (P<.0001: r = 0.89) with the LCF and 12.71 +/- 68.14 microm (P =.0077; r = 0.89) when the LCF was not used.

CONCLUSIONS

This study suggests that OII and US pachymetry provide similar readings for CCT in normal subjects when an LCF is used. In keratoconus patients, OII provides a valid clinical tool for the noninvasive assessment of CCT when the LCF is not applied.

Cholecystokinin (CCK), peptide YY (PYY), and ghrelin have been proposed to act as satiety hormones. CCK and PYY are stimulated during meal intake by the presence of nutrients in the small intestine, especially fat, whereas ghrelin is inhibited by eating. The sequence of events (fat intake followed by fat hydrolysis and CCK release) suggests that this process is crucial for triggering the effects. The aim of this study was therefore to investigate whether CCK mediated the effect of intraduodenal (ID) fat on ghrelin secretion and PYY release via CCK-1 receptors. Thirty-six male volunteers were studied in three consecutive, randomized, double-blind, cross-over studies: 1) 12 subjects received an ID fat infusion with or without 120 mg orlistat, an irreversible inhibitor of gastrointestinal lipases, compared with vehicle; 2) 12 subjects received ID long-chain fatty acids (LCF), ID medium-chain fatty acids (MCF), or ID vehicle; and 3) 12 subjects received ID LCF with and without the CCK-1 receptor antagonist dexloxiglumide (Dexlox) or ID vehicle plus intravenous saline (placebo). ID infusions were given for 180 min. The effects of these treatments on ghrelin concentrations and PYY release were quantified. Plasma hormone concentrations were measured in regular intervals by specific RIA systems. We found the following results. 1) ID fat induced a significant inhibition in ghrelin levels (P < 0.01) and a significant increase in PYY concentrations (P < 0.004). Inhibition of fat hydrolysis by orlistat abolished both effects. 2) LCF significantly inhibited ghrelin levels (P < 0.02) and stimulated PYY release (P < 0.008), whereas MCF were ineffective compared with controls. 3) Dexlox administration abolished the effect of LCF on ghrelin and on PYY. ID fat or LCF significantly stimulated plasma CCK (P < 0.006 and P < 0.004) compared with saline. MCF did not stimulate plasma CCK release. In summary, fat hydrolysis is essential to induce effects on ghrelin and PYY through the generation of LCF, whereas MCF are ineffective. Furthermore, LCF stimulated plasma CCK release, suggesting that peripheral CCK is the mediator of these actions. The CCK-1 receptor antagonist Dexlox abolished the effect of ID LCF, on both ghrelin and PYY. Generation of LCF through hydrolysis of fat is a critical step for fat-induced inhibition of ghrelin and stimulation of PYY in humans; the signal is mediated via CCK release and CCK-1 receptors.

OBJECTIVE

To compile a minimum data set for the follow-up of traumatic brain injury patients from discharge from hospital to one year post injury to assess functioning and participation in the physical, cognitive and psychosocial domains, and in quality of life.

METHODS

Repeated questionnaire interviews by two observers to establish inter-observer reliability of the measurement instruments at discharge and at one year post injury, as well as their sensitivity to change over time in traumatic brain injury patients.

METHODS

Department of neurosurgery of an academic hospital, department of a rehabilitation centre, and at the patients' homes in the Netherlands.

METHODS

The study at discharge included 25 patients aged 18-50 years with a moderate to severe traumatic brain injury (Glasgow Coma Scale score 3-14), whereas the one year post injury study included 14 patients aged 19-51 years. MAIN (OUTCOME) MEASURES: Physical domain: Barthel Index (BI), Functional Independence Measurement (FIM), Glasgow Outcome Scale (GOS), GOS Extended (GOSE). Cognitive domain: Disability Rating Scale (DRS), Functional Assessment Measurement (FAM), Levels of Cognitive Functioning Scale (LCFS), Neurobehavioural Rating Scale (NRS). Psychosocial domain: Community Integration Questionnaire (CIQ), Employability Rating Scale (ERS), Frenchay Activity Index (FAI), Multi Health Locus of Control (MHLC), Rehabilitation Activities Profile (RAP), Social Support List (SSL), Supervision Rating Scale (SRS), Wimbledon Self Reporting Rating Scale (WSRS). Quality of life: Coop/Wonca Charts (Coop), Rand SF-36 (Rand-36), Sickness Impact Profile-68 (SIP-68).

RESULTS

At both discharge and at one year post injury, in the physical domain the FIM showed excellent squared weighted kappa (SWK ranging from 0.75 to 0.80), and intraclass correlation coefficient (ICC ranging from 0.75 to 0.92), and a relatively small standard error of measurement (SEM 3.22) and smallest detectable difference (SDD 8.92). In the cognitive domain the FAM and the NRS showed excellent SWK, and ICC, and a relatively small SEM and SDD. In the psychosocial domain the FAI showed excellent SWK (0.89), and ICC (0.87), and a relatively small SEM (2.64) and SDD (7.31). For quality of life, at both discharge and at one year post injury the SIP-68 and the Coop showed excellent SWK (0.87), and ICC (0.89), and a relatively small SEM (3.79) and SDD (10.51). At both time points SWK and ICC ranged from 0.80 to 0.89, SEM ranged from 1.47 to 1.98, and the SDD was 4.07.

CONCLUSIONS

An example of a reliable minimum data set that is also able to detect changes over time is: the FIM, the FAM and the Coop for the early stages in recovery, extended with the NRS, the FAI, and the SIP-68 later in recovery, thereby covering all relevant domains after traumatic brain injury.

BACKGROUND

A combination of artesunate (AS) plus sulphadoxine/pyrimethamine (SP) as first-line and artemether-lumefantrine (AL) as second-line treatment are currently recommended against uncomplicated P. falciparum infection in Sudan. However, there is limited information on the efficacy of ACTs in the country and only one report of PCR-corrected results for AS/SP only.

METHODS

The WHO protocol for the assessment of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria was employed. Artesunate plus sulphadoxine/pyrimethamine (AS/SP) was compared to artemether-lumefantrine (AL) in a 28-day follow up. Samples that were classified as early treatment failure (ETF), late treatment failure (LCF) or late parasitological failure (LPF) were genotyped for msp-1 and msp-2 genes to differentiate recrudescence from reinfection.

RESULTS

A total of 178 patients were screened and 160 met the enrollment criteria and were recruited to the study of which 157 (98.1%) completed the follow up and had an analysed treatment outcome. On the AS/SP arm, three (0.038%) patients were lost during the follow-up, two on day 1 and one on day 7, and 77 (96.3) completed the study, while all 80 (100%) patients completed the follow up in the AL arm. In the per protocol analysis for AS/SP the treatment outcome for patients who completed the follow-up were as follows: adequate clinical and parasitological response (ACPR); 84.4% ETF; 1.3%, LCF; 3.9%, (LPF); 10.4%. For the AL arm the out come was as follows, ACPR; 90%, ETF; 0%, LCF; 6.3% and LPF; 3.8%. However, when PCR-corrected, 6.5% (5/77) of patients treated with AS/SP maintained parasites from their primary infection, while (7/80) in the AL group maintained their initial parasite genotype. Therefore, PCR-corrected efficacy was 93.5% in the AS/SP treated group and for AL it was 91.3%.

CONCLUSIONS

Both AS/SP and AL are highly effective for the treatment of uncomplicated falciparum malaria in eastern Sudan. However, AS/SP appears to have a slightly higher efficacy than AL, this may be due to patient compliance with the repeated dose rather than drug efficacy.

OBJECTIVE

To investigate the prognostic value of standard electroencephalogram (EEG) in predicting the improvement of the level of consciousness in patients suffering from severe disturbances of consciousness following coma caused by acute brain injuries.

METHODS

A standard EEG was recorded at admission in our rehabilitation department in a total of 46 patients with impaired consciousness states following coma (22 patients with traumatic brain injuries, 24 patients with non-traumatic brain injuries). We quantified the EEG abnormalities using the scale of Synek (1988) and correlated them with the basal level of cognitive functioning (LCF) scale score and with its variation after three months.

RESULTS

EEG scores correlated with LCF scores at admission (p<0.01) and with LCF scores' variation after three months (p<0.01) in patients with traumatic brain injury; EEG scores correlated only with LCF scores variation after three months (p<0.01) in patients with non-traumatic brain injury.

CONCLUSIONS

Standard EEG, analysed using the Synek scale, has a good prognostic value in both groups of patients with disorders of consciousness.

CONCLUSIONS

This work may have implications for clinical care, rehabilitative programs and medical-legal decisions in patients with impaired consciousness states following coma due to acute brain injuries.

OBJECTIVE

To evaluate the clinical value of combining one-view mammography (cranio-caudal, CC) with the complementary view tomosynthesis (mediolateral-oblique, MLO) in comparison to standard two-view mammography (MX) in terms of both lesion detection and characterization.

METHODS

A free-response receiver operating characteristic (FROC) experiment was conducted independently by six breast radiologists, obtaining data from 463 breasts of 250 patients. Differences in mean lesion detection fraction (LDF) and mean lesion characterization fraction (LCF) were analysed by analysis of variance (ANOVA) to compare clinical performance of the combination of techniques to standard two-view digital mammography.

RESULTS

The 463 cases (breasts) reviewed included 258 with one to three lesions each, and 205 with no lesions. The 258 cases with lesions included 77 cancers in 68 breasts and 271 benign lesions to give a total of 348 proven lesions. The combination, DBT(MLO)+MX(CC), was superior to MX (CC+MLO) in both lesion detection (LDF) and lesion characterization (LCF) overall and for benign lesions. DBT(MLO)+MX(CC) was non-inferior to two-view MX for malignant lesions.

CONCLUSIONS

This study shows that readers' capabilities in detecting and characterizing breast lesions are improved by combining single-view digital breast tomosynthesis and single-view mammography compared to two-view digital mammography.

CONCLUSIONS

• Digital breast tomosynthesis is becoming adopted as an adjunct to mammography (MX) • DBT (MLO) +MX (CC) is superior to MX (CC+MLO) in lesion detection (overall and benign lesions) • DBT (MLO) +MX (CC) is non-inferior to MX (CC+MLO) in cancer detection • DBT (MLO) +MX (CC) is superior to MX (CC+MLO) in lesion characterization (overall and benign lesions) • DBT (MLO) +MX (CC) is non-inferior to MX (CC+MLO) in characterization of malignant lesions.

The Glasgow Coma Scale (GCS) is routinely used in the acute care setting after traumatic brain injury (TBI) to guide decisions in triage, based on its ability to predict morbidity and mortality. Although the GCS has been previously demonstrated to predict mortality, efficacy in prediction of functional outcome has not been established. The purpose of this study was to assess the value of the acute GCS in predicting functional outcome in survivors of TBI. This study used the Multicenter National Institute on Disability and Rehabilitation Research TBI Model Systems database of 501 patients who had received acute medical care and inpatient rehabilitation within a coordinated neurotrauma program for treatment of TBI. Initial and lowest 24 hr GCS scores were correlated with the following outcome measures: the Disability Rating Scale (DRS), Rancho Los Amigos Levels of Cognitive Functioning Scale (LCFS), and cognitive and motor components of the Functional Independence Measure (FIM(SM)-COG and FIM(SM)-M). Outcome data were collected at admission to and discharge from the inpatient TBI rehabilitation unit. Correlation analysis revealed only modest, but statistically significant, relationships between initial and lowest GCS scores and outcome variables. Initial and lowest GCS score comparison with outcome demonstrated the following correlation coefficients: admission DRS, -0.25 and -0.28; discharge DRS, -0.24 and -0.24; admission LCFS, 0.31 and 0.33; discharge LCFS, 0.27 and 0.25; admission FIM-COG, 0.36 and 0.37; discharge FIM-COG, 0.23 and 0.23; admission FIM-M, 0.31 and 0.31; discharge FIM-M, 0.25 and 0.21. The GCS as a single variable may have limited value as a predictor of functional outcome.

Jasmonates are ubiquitously occurring plant growth regulators with high structural diversity that mediate numerous developmental processes and stress responses. We have recently identified 12-O-β-D-glucopyranosyljasmonic acid as the bioactive metabolite, leaf-closing factor (LCF), which induced nyctinastic leaf closure of Samanea saman. We demonstrate that leaf closure of isolated Samanea pinnae is induced upon stereospecific recognition of (-)-LCF, but not by its enantiomer, (+)-ent-LCF, and that the nonglucosylated derivative, (-)-12-hydroxyjasmonic acid also displays weak activity. Similarly, rapid and cell type-specific shrinkage of extensor motor cell protoplasts was selectively initiated upon treatment with (-)-LCF, whereas flexor motor cell protoplasts did not respond. In these bioassays related to leaf movement, all other jasmonates tested were inactive, including jasmonic acid (JA) and the potent derivates JA-isoleucine and coronatine. By contrast, (-)-LCF and (-)-12-hydroxyjasmonic acid were completely inactive with respect to activation of typical JA responses, such as induction of JA-responsive genes LOX2 and OPCL1 in Arabidopsis (Arabidopsis thaliana) or accumulation of plant volatile organic compounds in S. saman and lima bean (Phaseolus lunatus), generally considered to be mediated by JA-isoleucine in a COI1-dependent fashion. Furthermore, application of selective inhibitors indicated that leaf movement in S. saman is mediated by rapid potassium fluxes initiated by opening of potassium-permeable channels. Collectively, our data point to the existence of at least two separate JA signaling pathways in S. saman and that 12-O-β-D-glucopyranosyljasmonic acid exerts its leaf-closing activity through a mechanism independent of the COI1-JAZ module.

BACKGROUND

The objective of this study was to investigate the effects of feeding a high-concentrate corn straw diet on the release of endotoxin in the rumen and the changes of pro-inflammatory cytokines in the mammary gland of dairy cows in comparison with a low-concentrate corn straw diet and a low-concentrate mixed forage diet. Thirty second-parity Chinese Holstein cows in mid-lactation with a body condition score of 2.86 ± 0.29, weighing 543 ± 57 kg and producing 24.32 ± 3.86 kg milk per day were randomly assigned to 1 of the 3 diets (n = 10 per treatment): 1) low-concentrate mixed forage diet (LCF) with a concentrate to roughage ratio of 46 : 54; 2) high-concentrate corn straw diet (HCS) with a concentrate to roughage ratio of 65 : 35; 3) low-concentrate corn straw diet (LCS) with the same concentrate to roughage ratio (46 : 54) as LCF. The experiment lasted 6 weeks, and samples were collected in the last week. Milk samples were analyzed for conventional components, rumen fluid samples were analyzed for pH and endotoxin, and mammary arterial and venous plasma samples were analyzed for concentrations of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α).

RESULTS

Concentrations of endotoxin in rumen fluid and feces of cows fed HCS were significantly higher than those of cows fed LCS and LCF. Feeding HCS increased the release of IL-1β, IL-6 and IL-8 in the mammary gland compared with feeding LCS. Concentrations of cytokines (IL-1β and IL-8) in mammary venous plasma had a negative correlation with milk production efficiencies.

CONCLUSIONS

Results indicated that the high-concentrate corn straw diet increased the concentrations of endotoxin in rumen fluid and feces. Furthermore, feeding the high-concentrate corn straw diet stimulated the mammary gland to release more pro-inflammatory cytokines. The results suggest that feeding a high-concentrate corn straw diet induce a higher pro-inflammatory response in the mammary gland and thus may partly decrease the milk production efficiencies in dairy cows.

OBJECTIVE

To determine which outcome measures are best and least suited for assessing long-term functional outcome of individuals with traumatic brain injury (TBI) in the community.

METHODS

Survey of participants in the community an average of 5 years after TBI. A battery of outcome measures was given.

METHODS

Community in northern California after inpatient rehabilitation.

METHODS

Forty-eight adult individuals with prior moderate to severe TBI. All subjects had received inpatient rehabilitation 2 to 9 years previously and could be reached for telephone interview.

METHODS

The Community Integration Questionnaire, Neurobehavioral Functioning Inventory (NFI), Patient Competency Rating Scale (PCRS), Level of Cognitive Functioning Scale (LCFS), FIM instrument, Functional Assessment Measure (FIM+FAM), Supervision Rating Scale (SRS), Disability Rating Scale (DRS), Revised Craig Handicap Assessment and Reporting Technique (R-CHART), and Glasgow Outcome Scale (GOS). The number of maximal scores on each of the surveys was studied to determine which instruments continued to reveal deficits years after TBI.

RESULTS

Most individuals obtained maximum scores, ie, functional independence, on these scales: LCFS, FIM motor subscale and total score, R-CHART physical independence subscale, FIM+FAM, GOS, and the SRS. Measures with the fewest maximum scores (<36%, measuring deficits still extant in the group) were the R-CHART cognition subscale and the NFI memory/attention and communication subscales, and employment subscales. Items, subscales, and total scores that showed good variability and correlated most highly and frequently with other scales also demonstrating good variability were the PCRS, the DRS and FIM+FAM employment items, the R-CHART cognition subscale, and the NFI motor, memory/attention, communication, and depression subscales (the R-CHART cognition subscale and NFI memory/attention subscale were highly correlated with the PCRS;.84,.83).

CONCLUSIONS

Measures that appeared to contribute little to assessing functional status of a TBI sample years postinjury were the FIM, FIM+FAM, SRS, GOS, and LCFS. Measures that showed a range of deficits across participants were DRS employability, the NFI, PCRS, and the R-CHART cognition subscale.

In Mexico cutaneous leishmaniasis (CL) occurs in 17 of 32 States, and is a serious public health problem. This is a report of treatment of CL patients in the State of Tabasco, Mexico with a localized current field-radio frequency (LCF-RF) device to generate precisely controlled heat as an alternative to prohibitively expensive drug treatment. It was not a controlled clinical trial, but rather an evaluation of the feasibility of this form of treatment for all CL patients encountered in the endemic area. A total of 201 previously diagnosed patients with CL caused by Leishmania mexicana were treated with a portable Thermosurgery LCF-RF generator powered by rechargeable batteries. The ages of the patients ranged from two to 75 years; the sex distribution was 63% males and 37% females. A single device was used in five different municipalities. Lesions were first anesthetized with 1% lidocaine HCl and moistened with normal saline solution. Treatment consisted of a single application that produced 50 degrees C for 30 sec. After four weeks, 122 patients were available for evaluation, of which 95% were totally cured; (even those involving ear cartilage, which respond poorly to antimonials). At eight weeks post-treatment, 191 patients were evaluated, with a total cure rate of 90%. This form of treatment proved to be effective and convenient for use in primary health care facilities in Mexico and has many advantages over traditional forms of therapy.

Field and laboratory investigations into the effect of the parasitic isopod Anilocra pomacentri (Cymothoidae) on the population dynamics of the reef fish Chromis nitida (Pomacentridae) were carried out at Heron Island, Great Barrier Reef, Australia. Fish carried a single adult parasite just posterior and dorsal to the eye either to the right or to the left of the midline. The adult parasite was overdispersed among fish on patch reefs (dispersion factor, k = 0.69). Sequential field observations on a single cohort of fish showed that parasites significantly depressed growth, reproduction, and survivorship. The von Bertalanffy growth coefficients (a measure of somatic growth) were 0.10 for parasitized fish compared with 0.17 for non-parasitized fish. Female fish carrying the parasite produced only 12% of the number of eggs produced by non-parasitized fish of the same size. In the field, the mortality of infected juvenile C. nitida (LCF 15-30 mm) was estimated to be at least 88% in the first 70 days after recruitment of the fish. The mortality of uninfected recruits over the same period was 66%. In laboratory trials, the mortality associated with the infection of juvenile fish by larval parasites ranged from 78% for small fish (mean LCF 15.0 mm) to 28% for larger fish (mean LCF 24.9 mm) within 4 days of experimental infection. This is one of the few studies that evaluates the effect of a parasite on a population of fish in the field.

Lymphocyte chemoattractant factor (LCF) is a polypeptide cytokine which induces both cell motility and activation of T lymphocytes. These LCF-induced events demonstrate an absolute requirement for the cell surface expression of CD4. Because many CD4-mediated T lymphocyte activation events have been demonstrated to require the association of the src-related tyrosine kinase p56lck with the cytoplasmic domain of CD4, we examined the role of p56lck in LCF-induced lymphocyte migration in a murine T cell hybridoma line expressing transfected human CD4. LCF induces the catalytic activity of CD4 associated p56lck at chemoattractant concentrations of cytokine. Hybridoma cells that express CD4 with cytoplasmic point mutations which uncouple the CD4-lck association lack both lck enzymatic activity and chemotactic responses to LCF. The enzymatic activity of lck however does not appear to be required for CD4-mediated migratory signal. First, the protein tyrosine kinase inhibitor herbimycin A blocked LCF-induced p56lck activation but had no effect on the LCF-induced motile response. Second, T cell hybridomas expressing a chimeric receptor combining the extracellular domain of human CD4 and murine p56lck which lacked the kinase domain had a normal LCF-induced motile response. We conclude from these observations that CD4-lck coupling is essential for LCF-induced T lymphocyte migration but the motile response is independent of the enzymatic activity of CD4-associated p56lck.

OBJECTIVE

To evaluate microtubule-associated proteins (MAP-2), a dendritic marker of both acute damage and chronic neuronal regeneration after injury, in serum of survivors after severe TBI and examine the association with long-term outcome.

METHODS

Serum concentrations of MAP-2 were evaluated in 16 patients with severe TBI (Glasgow Coma Scale score [GCS] ≤ 8) 6 months post-injury and in 16 controls. Physical and cognitive outcomes were assessed, using the Glasgow Outcome Scale Extended (GOSE) and Levels of Cognitive Functioning Scale (LCFS), respectively.

RESULTS

Severe TBI patients had significantly higher serum MAP-2 concentrations than normal controls with no history of TBI (p = 0.008) at 6 months post-injury. MAP-2 levels correlated with the GOSE (r = 0.58, p = 0.02) and LCFS (r = 0.65, p = 0.007) at month 6. Significantly lower serum levels of MAP-2 were observed in patients in a vegetative state (VS) compared to non-VS patients (p < 0.05). A trend tracking the level of consciousness was observed.

CONCLUSIONS

Severe TBI results in a chronic release of MAP-2 into the peripheral circulation in patients with higher levels of consciousness, suggesting that remodelling of synaptic junctions and neuroplasticity processes occur several months after injury. The data indicate MAP-2 as a potential marker for emergence to higher levels of cognitive function.

Foraging theory predicts that mobile predators should target high profitability areas with plentiful resources and minimize time spent moving between these areas. This has led to a focus in recent literature on the identification of "hotspots" important for migratory marine predators, i.e., regions where predators spend disproportionate amounts of time ostensibly due to high prey abundance; and determination of the environmental features characteristic of such areas. We investigated factors predicting foraging success in southern bluefin tuna (SBT; Thunnus maccoyii), by integrating telemetry-based feeding and movement data (n = 19 fish, length to caudal fork [LCF] = 99 +/- 3 cm) with environmental data over the scale of their annual oceanic migrations during 1998-2000. We used widely available statistical modeling techniques, generalized linear models, and generalized linear mixed models, formulated to represent feeding as a Markov process. The results showed increased feeding and predictability of feeding occurs in the coastal waters of southern Australia, providing some evidence that this area represents a fixed foraging "hotspot" for juvenile tuna during the austral summer. However, in oceanic waters southern bluefin tuna did not fit the common model of migration, but rather showed a pattern of relatively high foraging success throughout their migratory range, especially during periods of continuous travel. Interestingly, foraging "coldspots" (prolonged low-feeding periods) as well as "hotspots" were apparent across individual tracks, predicted most strongly by warm ocean temperatures. These results provide a new perspective on the ecology of large-scale feeding migrations within the context of the heterogeneous ocean environment, where the continuous and opportunistic feeding of generalist predators may be more common, particularly in predatory large pelagic fishes, than is currently documented.

OBJECTIVE

The purpose of this study was to examine differences in novel markers of cardiovascular disease (CVD) in women with type 2 diabetes stratified according to cardiorespiratory fitness.

METHODS

A total of 28 women (mean age 57 +/- 6 years) with type 2 diabetes who were free from overt CVD were placed into low cardiorespiratory fitness (LCF) or average cardiorespiratory fitness (ACF) groups based on a graded exercise test to exhaustion. A group of eight women without type 2 diabetes were also examined and served as healthy control subjects. The median VO(2peak) value was used as a cutoff for group determination. We assessed both conventional CVD risk factors, including blood pressure, BMI, and lipid profile, as well as novel CVD risk factors, such as left ventricular filling dynamics, arterial stiffness, fasting insulin, and C-reactive protein (CRP).

RESULTS

VO(2peak) values were 69 +/- 14 and 91 +/- 24% of predicted values for sedentary age-matched healthy individuals in the LCF and ACF groups, respectively. BMI was significantly greater in the LCF group (P < 0.05); however, no differences were observed in age, lipid profile, or resting hemodynamics. CRP was 3.3-fold higher in the LCF group (6.3 +/- 41. vs. 1.9 +/- 1.7 mg/l, P < 0.05), whereas other novel markers of CVD were not significantly different between the groups. Significant negative relationships were observed between VO(2peak) and both CRP (r = -0.49) and the homeostasis model assessment index (r = -0.48) (P < 0.05).

CONCLUSIONS

The novel finding of this investigation is that low cardiorespiratory fitness is associated with elevated CRP and reduced fasting glucose control in women with type 2 diabetes.

OBJECTIVE

This study was conducted to compare the differences in adipocytokines and fatty acid composition between two fraction sizes of small and large cells from subcutaneous and visceral fat of mice receiving a high-fat diet (HFD).

METHODS

Body weight, blood glucose and cholesterol levels, and adipocyte diameter distribution were examined. Total adipocyte fractions could be separated into the small-cell fraction (SCF) and the large-cell fraction (LCF). Adipocytokine expression, fatty acid composition and stearoyl-CoA desaturase (SCD) expression were compared between SCF and LCF.

RESULTS

In HFD mice, body weight, glucose and cholesterol levels were significantly higher than in NCD mice. The adipocyte diameter of HFD mice continuously increased throughout the feeding period regardless of the fat depot. The expression of adipocytokine genes such as angiotensinogen, plasminogen activator inhibitor-1, adipsin, leptin, TNF-alpha and adiponectin was higher in LCF than SCF. The ratio of stearic acid to the total fatty acid content was lower in SCF than LCF, whereas oleic acid composition was higher in LCF. SCD expression was higher in LCF than SCF.

CONCLUSIONS

Our results indicate that large adipocytes strongly express adipocytokine genes and show high oleic acid composition via SCD upregulation. Based on these findings, the differences in fatty acid composition between adipocyte sizes may be related to adipocytokine expression.

The structural features of dinoflagellate nuclei are distinct from those of other eukaryotes in several respects, and the mechanisms of DNA replication and transcription are almost completely unknown. In this study we investigated the structure and organization of the gene coding for luciferase (LCF), the enzyme catalyzing the bioluminescent reaction in the dinoflagellate Gonyaulax polyedra. The genomic lcf sequence, including its flanking regions, were completely determined. The transcription initiation site was identified using primer extension and RNase protection assays. Sequence analysis shows that, like the luciferin-binding protein gene (lbp) from G. polyedra, lcf does not contain introns. Analysis of results from genomic Southern blots, inverse PCR, and sequencing revealed that the lcf gene is organized as tandem repeats in the genome. The spacer region between the lcf genes, which very likely contains the promoter elements necessary for transcription initiation, has no TATA box or other known promoter elements or consensus sequences. However, a conserved sequence motif was identified by comparing the two intergene spacer regions of lcf and the peridinin chlorophyll protein gene, pcp; a novel 13 nt sequence, CGTGAACGCAGTG, which might be a dinoflagellate promoter, was found to be present in both.

OBJECTIVE

In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors.

METHODS

Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption.

RESULTS

Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE).

CONCLUSIONS

This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D.