Summary Objective Identifying individuals who are less likely to respond to a weight loss intervention allows better allocation or focus of resources to achieve better weight loss results. The ...current study investigated whether baseline levels of mindfulness would predict weight loss during a 12-month diet and exercise intervention. Methods The Five Facet Mindfulness Questionnaire (FFMQ) was administered and body weight measured, at baseline, three, six and 12 months in 140 participants with pre-diabetes or type 2 diabetes mellitus and a body mass index of ≥25 kg/m2 . 137 of 140 participants completed the FFMQ at baseline and were included in this study. Results There was no correlation between baseline mindfulness scores and weight loss. Mean baseline total FFMQ score was 112.2 95% confidence interval: 109.4, 115.1 which did not change over the course of the study. Mean baseline body weight was 95.1 kg (standard deviation (19.1 kg)). There was a significant decrease in weight at month 12 (−3.8 kg (±standard deviation 5.8 kg)). This is comparable to the weight loss achieved by participants in other interventions of the same duration. Conclusions The findings suggest that baseline dispositional mindfulness does not predict the amount of weight loss in a lifestyle (diet and exercise) intervention.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, ...including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs - whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp), while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83 - a homolog of human Hsp90 - as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF). Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC) and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We evaluated the MR findings in patients with temporal lobe epilepsy to determine the predictive value of MR imaging in assessing patient outcome.
MR studies from 186 of 274 consecutive patients who ...underwent temporal lobectomy for intractable epilepsy were reviewed retrospectively. Images were interpreted by an experienced neuroradiologist, who was blinded to the side of seizure activity and to pathologic findings.
MR imaging exhibited 93% sensitivity and 83% specificity in detecting hippocampal/amygdalar abnormalities (n = 121), and 97% sensitivity and 97% specificity in detecting abnormalities in the rest of the temporal lobe (n = 60). Abnormal high signal of the hippocampus on T2-weighted images had a sensitivity of 93% and specificity of 74% in predicting mesial temporal sclerosis (n = 115). The presence of hippocampal atrophy on MR correlated with the duration of seizures. Sensitivity and specificity of MR imaging in detecting temporal lobe tumors (n = 42) were 83% and 97%, respectively, based on abnormal signal and mass effect. After surgery, 63% of patients were seizure free and 28% had a significant reduction of seizure frequency at an average of 24 months (range, 12 to 78 months) after surgery. Patients with a single lesion in the anterior temporal lobe or hippocampus/amygdala had a better outcome than patients with multiple lesions (n = 22). Interrater agreement varied from 0.4 to 0.93, with best agreement for tumors or abnormal hippocampal signal on T2-weighted images.
MR imaging is highly sensitive in detecting and locating abnormalities in the temporal lobe and the hippocampus/amygdala in patients with temporal lobe epilepsy. Hippocampal atrophy appears to correspond to the duration of seizure disorder.
Visceral leishmaniasis (VL) affects millions of people across the world, largely in developing nations. It is fatal if left untreated and the current treatments are inadequate. As such, there is an ...urgent need for new, improved medicines. In this paper, we describe the identification of a 6-amino-
N
-(piperidin-4-yl)-1
H
-pyrazolo3,4-
d
pyrimidine scaffold and its optimization to give compounds which showed efficacy when orally dosed in a mouse model of VL.
The development of a chemical series with oral efficacy against visceral leishmaniasis is described.
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IJS, KILJ, NUK, UL, UM, UPUK
The development of a chemical series with oral efficacy against visceral leishmaniasis is described.
Visceral leishmaniasis (VL) affects millions of people across the world, largely in developing ...nations. It is fatal if left untreated and the current treatments are inadequate. As such, there is an urgent need for new, improved medicines. In this paper, we describe the identification of a 6-amino-
N
-(piperidin-4-yl)-1
H
-pyrazolo3,4-
d
pyrimidine scaffold and its optimization to give compounds which showed efficacy when orally dosed in a mouse model of VL.
Full text
Available for:
IJS, KILJ, NUK, UL, UM, UPUK
To determine the relation between 1) intra-alveolar concentrations of the proinflammatory cytokines (tumor necrosis factor, interleukin-1 beta, and interleukin-8) and the anti-inflammatory cytokines ...(interleukin-10 and interleukin-1 receptor antagonist) in patients with early adult respiratory distress syndrome (ARDS) and 2) subsequent patient mortality rates.
Prospective cohort study.
University medical center.
28 consecutive patients in whom ARDS was prospectively identified during hospitalization and 9 ventilated controls.
Concentrations of proinflammatory cytokines and anti-inflammatory cytokines in bronchoalveolar lavage fluid.
The concentrations of proinflammatory and anti-inflammatory cytokines within the alveolar air spaces were significantly elevated in patients with ARDS compared with controls (P = 0.01 for tumor necrosis factor median, 90 pg/mL (range, 0 to 2500 pg/mL) for patients with ARDS; median, 0 pg/mL (range, 0 to 118 pg/mL) for controls; P = 0.001 for interleukin-1 beta median, 179 pg/mL (range, 0 to 2200 pg/mL) for patients with ARDS; median, 0 pg/mL (range, 0 to 80 pg/mL) for controls; P = 0.0001 for interleukin-8 median, 628 pg/mL (range, 0 to 4700 pg/mL) for patients with ARDS; median, 0 pg/mL (range, 0 to 278 pg/mL) for controls; P = 0.0005 for interleukin-10 median, 100 pg/mL (range, 0 to 1600 pg/mL) for patients with ARDS; median, 0 pg/mL (range, 0 to 50 pg/mL) for controls, and P = 0.002 for interleukin-1 receptor antagonist median, 820 pg/mL (range, 0 to 18,900 pg/mL) for patients with ARDS; median, 50 pg/mL (range, 0 to 240 pg/mL) for controls). A highly significant correlation was found between low concentrations of anti-inflammatory cytokines and subsequent patient mortality rates (P = 0.003 for interleukin-10 median, 120 pg/mL (range, 30 to 1600 pg/mL) for survivors; median, 40 pg/mL (range, 0 to 110 pg/mL) for nonsurvivors; P = 0.008 for interleukin-1 receptor antagonist median, 1600 pg/mL (range, 80 to 18,900 pg/mL) for survivors; median, 90 pg/mL (range, 0 to 3400 pg/mL) for nonsurvivors. No significant correlation was found between the concentrations of the proinflammatory cytokines and mortality rates.
Low concentrations of the anti-inflammatory cytokines interleukin-10 and interleukin-1 receptor antagonist in bronchoalveolar lavage fluid obtained from patients with early ARDS are closely associated with poor prognosis. These findings support the hypothesis that failure to mount a localized intrapulmonary anti-inflammatory response early in the pathogenesis of ARDS contributes to more severe organ injury and worse prognosis. Our findings suggest that augmenting anti-inflammatory cytokine defenses would be a beneficial therapeutic approach to patients with ARDS and other inflammatory diseases.
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