Tracing of noradrenergic projections using manganese-enhanced MRI

We examined the applicability of manganese-enhanced MRI (MEMRI) to the in vivo tracing of diffuse neuromodulatory projections by means of simultaneous iontophoretic injections of an extremely low, non-toxic concentration of MnCl₂ (10 mM) and fluorescent dextran in the locus coeruleus (LC) in the rat. We validated the use of the iontophoretic injection by reproducing previously reported results from pressure injections of MnCl₂ in primary somatosensory cortex. Twenty four hours after injection in LC, Mn^2 + labeling was detected in major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor and somatosensory cortices, hippocampus and amygdala. Although the injections were in most cases centered in the core of LC, the pattern of Mn^2 + labeling greatly varied across rats. In addition, despite a certain degree of overlap of the labeling obtained with both MEMRI and classical tracing, MEMRI tracing consistently failed to reliably label not only several minor but also major targets of LC, notably the thalamus. The lack of Mn^2 + labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. Inversely, a number of brain regions, particularly contralateral motor cortex, that were not or only sparsely labeled with fluorescent dextran were strongly labeled by Mn^2 +. This discrepancy could be partly due to both the activity-dependent and transsynaptic nature of Mn^2 + transport. The overall labeling produced using MEMRI with iontophoretic injections in LC indicates that the Mn^2 + imaging of highly diffuse projections is in principle feasible. However, the labeling pattern of each individual case needs to be carefully interpreted particularly before submitting data for group analysis or in the case of longitudinal examination of discrete changes in functional connectivity under various physiological or behavioral conditions.     

Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case-control studies

Poor oral health has been reported as a risk factor in the etiology of head and neck cancer. Data on oral health were ascertained as part of two multicenter case-control studies comprising 924 cases and 928 controls in central Europe and 2,286 cases and 1,824 controls in Latin America. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and esophagus, as well as age (in quinquennia)- and sex frequency-matched controls, were enrolled from 1998 to 2003. Poor condition of the mouth (central Europe: odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.74, 4.81; Latin America: OR = 1.89, 95% CI: 1.47, 2.42), lack of toothbrush use (Latin America: OR = 2.36, 95% CI: 1.28, 4.36), and daily mouthwash use (Latin America: OR = 3.40, 95% CI: 1.96, 5.89) emerged as risk factors for head and neck cancer, independent of tobacco use and alcohol consumption. Missing between six and 15 teeth was an independent risk factor for esophageal cancer (central Europe: OR = 2.84, 95% CI: 1.26, 6.41; Latin America: OR = 2.18, 95% CI: 1.04, 4.59). These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck, and esophagus.     

Evidence for an important role of alcohol- and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract.

BACKGROUND: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region. METHODS: A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2). RESULTS: The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer. CONCLUSIONS: Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption.     

Yeast ts secretory mutation rgs1 is suppressed by the SEC4 gene of Saccharomyces cerevisiae

Yeast rgs1 cells accumulate secretory vesicles in the cytoplasm and stop the secretion of proteins at the restrictive temperature. The ts mutation rgs1 may be suppressed by several different genes; the S. cerevisiae SEC4 gene, encoding the small G-protein involved in the late secretory stage, is one of them. Synthetic lethality of the double rgs1 sec4 mutant is demonstrated.     

Correlation of the Epworth Sleepiness Scale with respiratory sleep parameters in patients with sleep-related breathing disorders and upper airway pathology

The aim of the study was to test whether a correlation between the Epworth Sleepiness Scale (ESS) and respiratory sleep parameters recorded by polysomnography (PSG) in patients with sleep-related breathing disorders and upper airway pathology exists. The PSG records of 130 patients (average age 52.6 ± 10.7 years) with upper airway pathology suspected of having obstructive sleep apnea (OSA) have been retrospectively evaluated. Upper airway pathology included deviation of the nasal septum, inferior nasal turbinate hypertrophy, soft palate webbing, elongated uvula, tonsillar hypertrophy, macroglossia, hypertrophy of the tongue base, unfavorable palate position relative to the tongue base. To test for a possible correlation in this patient population between ESS score and arithmetic values of AHI, SPO₂, ODI and Arousal Index, the Spearman’s correlation coefficient was calculated. No correlation between ESS and AHI, minimal SpO₂ and ODI was proven and only a weak positive correlation between Arousal Index and ESS was found in this particular patient population. We concluded that in patients with upper airway pathology, it is not possible to predict solely on the basis of the ESS score the existence of OSA or of other disturbances in Arousal Index, minimal SpO₂ and ODI. Nevertheless, historical data evaluated by questionnaires, such as the ESS provide for additional information combined with the clinical findings to select patients who are candidates for further detailed sleep studies.     

The Cancer and Deity Questionnaire: A New Religion and Cancer Measure

We evaluated a new measure, the Cancer and Deity Questionnaire (CDQ), which assesses perceived relations with God after a cancer diagnosis. Based on object relations theory, the 12-item CDQ assesses benevolent and abandoning God representations. Sixty-one older participants with recent cancer diagnoses completed the questionnaire at baseline, and 52 of these participants completed the same questionnaire at follow-up. Internal consistency was excellent for the Benevolence scale (α = .97) and good for the Abandonment scale (α = .80). Moderate correlations with the Spiritual Well-Being Scale support divergent validity. Correlations between CDQ scales and the Styles of Religious Coping scales support convergent validity. The CDQ is brief, easily scored, practical for psycho-oncology research, and adaptable for use with other illnesses.