Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

ObjectiveIt has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women.Methods20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions.ResultsEpisodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri.ConclusionsDiet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.Key Words: Functional magnetic resonance imaging, Episodic memory, Obesity, Diet interventions, Hippocampus     

Clinical significance of corpus callosum atrophy in a mixed elderly population

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.     

Second primary cancer after treatment of invasive carcinoma of the uterine cervix, compared with those arising after treatment for in situ carcinomas. An effect of irradiation? A cancer registry study

A cancer registry cohort of 16,704 cases of invasive carcinoma of the uterine cervix and 56,116 cases of in situ carcinomas of the uterine cervix was followed up and second new primary cancers were recorded. The invasive carcinomas contributed 127,118 woman-years at risk and the in situ carcinomas contributed 453,362 woman-years at risk. The main treatment for the invasive carcinomas had been radiotherapy and for the in situ carcinomas, conization and other types of surgical intervention. 767 new primaries occurred after treatment of invasive carcinoma of the uterine cervix, compared with 644.5 expected. O/E is 1.19. After the in situ carcinomas, 1,421 malignant tumors were observed, vs. 1,188.0 expected (O/E 1.19). If, however, cases of invasive carcinoma of the uterine cervix after in situ carcinomas are excluded, the ratio observed/expected is 1.10. For some sites the increased observed/expected ratios were found after both invasive and in situ carcinomas, which speaks for some common carcinogenic effect other than irradiation (for instance, in bronchus and trachea, pharynx, nose, sinus and larynx, but also in rectum, urinary bladder, other female genital organs, pancreas, lymphosarcoma, as well as acute and non-lymphatic leukemia). A lower risk than expected--after both in situ and invasive carcinoma of the uterine cervix--is observed for breast cancer, cancer of the corpus uteri and for multiple myeloma. However, analyses based on time since treatment provide evidence of a carcinogenic effect of irradiation, especially in intensively irradiated organs such as bladder, rectum, corpus uteri and ovary, and also for acute and non-lymphatic leukemia.     

DNA mismatch binding in human lung tumor cell lines

Defects in mismatch repair (MMR) genes have been involved in several types of sporadic and hereditary cancers. In order to elucidate the role of MMR in human lung carcinogenesis we examined DNA mismatch binding in cell-free extracts of seven lung tumor cell lines and five corresponding lymphoblastoid cell lines from lung cancer patients. Using the technique of bandshift assay we have demonstrated that 2/7 of the tumor cell lines are aberrant in binding to specific DNA mismatches while all lymphoblastoid cell lines were proficient in binding to all tested mismatches. Both extracts were aberrant in binding to G/T mismatch whereas one of the cell lines showed deficiency in binding to the C:A mismatches as well. Immunoblotting analysis showed that all known DNA mismatch repair (MMR) proteins were present in these extracts. The cell line deficient in binding to both G:T and C:A mismatches showed microsatellite instability (MSI) in tumor DNA and higher resistance to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). This report indicates that DNA mismatch binding deficiencies may be implicated in at least a subgroup of human lung cancer.     

Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics

Recent studies using mass spectrometry have discovered candidate biomarkers for amyotrophic lateral sclerosis (ALS). However, those studies utilized small numbers of ALS and control subjects. Additional studies using larger subject cohorts are required to verify these candidate biomarkers. Cerebrospinal fluid (CSF) samples from 100 patients with ALS, 100 disease control, and 41 healthy control subjects were examined by mass spectrometry. Sixty‐one mass spectral peaks exhibited altered levels between ALS and controls. Mass peaks for cystatin C and transthyretin were reduced in ALS, whereas mass peaks for posttranslational modified transthyretin and C‐reactive protein (CRP) were increased. CRP levels were 5.84 ± 1.01 ng/ml for controls and 11.24 ± 1.52 ng/ml for ALS subjects, as determined by enzyme‐linked immunoassay. This study verified prior mass spectrometry results for cystatin C and transthyretin in ALS. CRP levels were increased in the CSF of ALS patients, and cystatin C level correlated with survival in patients with limb‐onset disease. Our biomarker panel predicted ALS with an overall accuracy of 82%. Muscle Nerve 42: 104–111, 2010     

Palliation of bone pain in prostate cancer using chemotherapy and strontium-89. A randomized phase II study

Strontium-89 is an established alternative for the alleviation of bone pain in prostate cancer. There are few data evaluating the effect on pain of palliative chemotherapy. The aim of this randomized phase II study was to assess and compare the analgesic efficacy of strontium-89 and chemotherapy (FEM=5-FU, epirubicin, and mitomycin C) in 35 patients with disseminated, hormone-refractory prostate cancer suffering from persisting bone pain despite analgesic treatment. In order to minimize the risk for imbalances regarding the two patient groups, a double-blind randomization was performed. A significant reduction in pain intensity and pain frequency was registered in both patient groups (P < 0.01 in both groups after 3 weeks). Side effects were generally mild in the strontium-89 group and significantly more severe in the FEM group. The effect of FEM on pain is surprising as chemotherapy has generally only limited effect on tumor growth in bone metastases due to prostate cancer. A possible explanation is that FEM has an inhibitory activity on the inflammatory component of metastases.