Low concentrations of adiponectin, the protein product of the APM1 gene, have been reported to be associated with obesity and insulin resistance. However, contrasting results have been described on the genetic variability in APM1 and characteristics of the metabolic syndrome and adiponectin serum concentrations. In the present study, we investigated the association of the two most well-known SNPs of APM1 ( þ 45T4G and þ 276G4T) and their haplotypes, with serum adiponectin concentrations, metabolic parameters and intima-media thickness of the carotid arteries in 1745 well-phenotyped asymptomatic unrelated Caucasian subjects of the SAPHIR cohort. The common T-allele (88.5%) of SNP þ 45T4G and the common G-allele (70.5%) of SNP þ 276G4T were associated with significantly lower serum adiponectin levels (P ¼ 0.0008 and P ¼ 0.00005, respectively). The most frequent haplotype TG (59.0%) defined by both loci showed a strong association with lower serum adiponectin concentrations (P ¼ 0.000000002). A clear effect per copy of the respective haplotype was observed. This association was most pronounced in lean and insulin-sensitive subjects. The two less common haplotypes TT (29.5%) and GG (11.5%) were associated with higher serum adiponectin levels in a dose-dependent association. Interestingly, no significant association between the adiponectin 45-276 haplotypes and the majority of parameters of the metabolic syndrome or intima-media thickness of the carotid arteries was found in our study. In summary, we replicated a strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy Caucasians. However, we could not confirm an association of this gene locus with metabolic parameters of the insulin resistance syndrome.

Archival paraffin-embedded tumor specimens offer a wealth of information for both cancer research and for routine clinical applications. However, the use of formalin-fixed, paraffin-embedded specimens for quantitative real-time PCR is not yet a standard diagnostic method in many laboratories, in particular for the quantification of human papillomavirus (HPV). Particularly high-risk HPV types are involved in almost 100% of the carcinogenesis of cervical cancer. We compared the diagnostic applicability and sensitivity of real-time PCR to that of chromogenic tyramide-signal-amplified in situ hybridization and conventional PCR for the detection of HPV from archival tissue in 164 cases of carcinoma in situ and cervical cancer. Furthermore, we examined whether the viral load of HPV is of prognostic relevance. Our findings indicate that patients in tumor stage I with a lower viral load of HPV type 16 (HPV16; up to 1,000 copies/ng of DNA) had a significantly better survival than HPV 16-negative patients (P ‫؍‬ 0.037). We observed a greater sensitivity of both real-time PCR and conventional PCR for the detection of HPV16 and -18 compared to signal amplified in situ hybridization. We found a considerable concordance between HPV16 ( ‫؍‬ 0.661) and HPV18 ( ‫؍‬ 0.781) status as measured by real-time PCR and conventional PCR, indicating similar sensitivities. We recognized an inhibitory effect of formalin fixation and paraffin embedding on the evaluation of real-time PCR quantification.Formalin-fixed, paraffin-embedded (FFPE) tissues retained in pathology archives are an important resource for molecular pathology studies and for diagnostic applications. The use of in situ hybridization (ISH) and PCR assays have both been reported for DNA analysis in formalin-fixed archival tissues (6,7,25,40,42,48). Both assays have the advantage that only small amounts of tissue are required, and both tolerate the degradation of target nucleic acids due to the formalin fixation and paraffin-embedding procedures. Each assay per se has its own advantages and disadvantages.For a pathologist, the retention of morphology and the histological context of a tumor is very important. Especially in the case of cervical carcinoma, the phenomenon of koilocytosis indicates an infection with human papillomavirus (HPV) (4) that can only be detected by microscopic analysis of tissue sections. Moreover, episomal and integrated viral DNA can only be differentiated by ISH due to the staining pattern (8). With the use of chromogenic tyramide-signal-amplified ISH (CISH) it is even possible to detect and localize single or very few HPV copies within infected nuclei (15,36,49). However, this technique is rather cost-intensive and quite involved for routine applications.Conventional PCR is held to be the most sensitive detection method available (9,16,20,27,37,41). Although this is probably true, it has some limitations, as does ISH, in that it cannot quantify viral load in a prognostic-diagnostic significant manner. This restriction can be circumvented by the use o...

Two subjects participated in a 216 km ultramarathon with outside temperatures above 50 degrees C while several physiological and psychological parameters (cognitive performance assessed by a mental calculation task and an attentional task, subjective bodily experience, and lactate level) were evaluated throughout the race. Severe stress from dehydration, sleep deprivation, and total physical exhaustion are combined in a unique manner, allowing evaluation of their effects in a range far outside that obtainable in a laboratory setting. During the race the subjects answered a questionnaire about their actual bodily experiences, underwent 8 medical examinations, and performed two cognitive tests approximately every 35 kilometers. Analysis showed cognitive performance did not decrease steadily in a simple and gradual way but reached a peak in the morning of Day 2 after a short sleeping period and then decreased. In the early morning of Day 3, in general cognitive performance exhibited the worst results but increased differentially between the subjects again in the last test 1 km before the finish line.

There are only a few studies using human electroencephalograms (EEGs) to investigate bioelectrical changes in the brain during exercise (running or cycling). These studies report an increase in EEG alpha amplitude during and immediately after exercise. However, only exercises within a relatively short time interval of approximately 1 hour have been investigated. Thus, we focussed on long-lasting exercise and report three single case studies, performed on the same participant, during extended exercise and under different thermal conditions. EEG was recorded during a 12-, 24-, and 56-hour ultramarathon. The 56-hour race was performed under extreme thermal stress in Death Valley, CA, with temperatures well above 55uC/131uF. Analyzing the centre gravity frequency of the EEG alpha rhythm yielded a gradual decrease with time for the 12-and 24-hour races. In the 56-hour race, the centre frequency decreased only until the first sleeping period. Alpha amplitude, on the other hand, did not vary systematically. For all three races, the lowest alpha amplitude was observed during the last test session. This decrease is most likely due to cognitive and emotional changes but not to thermal stress, exhaustion, or sleep deprivation.

In a single-case study, the effects of very long-lasting physical exercise, namely a 24-h-long ultramarathon, on the human electroencephalogram (EEG) were evaluated. While only effects of relatively short exercise have been reported earlier, we focused on the changes induced by these long-lasting physical requires. EEG was recorded repeatedly using an auditory oddball paradigm, and event-related potentials (ERPs), as well as changes in the current oscillatory brain activity (in particular, event-related desynchronization, ERD), were repeatedly monitored. While an increase in several attention-related ERP parameters was reported for shorter exercises, the results of our study show that cognitive performance-related EEG phenomena slowly decreased throughout the race. The P300 amplitude decreased, and the P300 latency increased with ongoing exercise duration. In addition, the difference between standard and target tones at N200b, as well as the difference in the lower alpha ERD, decreased with time, indicating a reduced automatic stimulus evaluation.