[Association of physical activity with fatigue and functional capacity in patients with rheumatoid arthritis]. / Zusammenhang von körperlicher Aktivität mit Fatigue und Funktionskapazität bei Patienten mit rheumatoider Arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) tend to be less physically active. Physical activity has been shown to have a positive impact on disease activity and quality of life and is recommended by the European League Against Rheumatism (EULAR) as an integral component of standard treatment. OBJECTIVE: A cross-sectional analysis of RA patients was carried out assessing disease activity, functional capacity and fatigue associated with physical activity. MATERIAL AND METHODS: Physical activity, functional capacity and the global fatigue index (GFI) were examined using standardized questionnaires: the international physical activity questionnaire short form (IPAQ-SF), the functional questionnaire Hannover (FFbH) and the multidimensional assessment of fatigue (MAF). The data were evaluated using SPSS 26 (IBM, Armonk, NY, USA). The level of significance was tested with bivariate and partial correlations and nonparametric tests. RESULTS: In total 164 patients were included in the study. The majority of the patients were female (127/164; 77%) and the median age of the cohort was 58.3 years (range 21-86 years). The median duration of disease-related symptoms at inclusion was 169 months (range 0-713 months). Physical activity was low in 39%, moderate in 37% and high in 24%. Patients reporting higher levels of physical activity reported significantly lower GFI (p < 0.001), functional limitations (p < 0.001) and disease activity (p = 0.045) scores than those with less physical activity. CONCLUSION: Physical activity in RA patients was significantly correlated with functional capacity and levels of fatigue. In order to reduce the proportion of patients with low physical activity, the possibilities for functional training should be expanded and the patients should be encouraged to undertake sporting activities.

Hyperostosis frontalis interna - a marker of social status? Evidence from the Bronze-Age "high society" of Qatna, Syria.

In 1719 Morgagni described a condition, today known as hyperostosis frontalis interna (HFI), as one sign within a triad consisting of HFI, virilism, and obesity. Today, HFI is predominantly found in older women. Although the etiology of HFI has not yet been determined precisely, the condition has been linked to metabolic disorders. HFI is reported to be rare in the archaeological record and the frequency of the condition is thought to have increased during the 19th and 20th centuries. We present preliminary results on the occurrence of HFI in the commingled human bone assemblage from "tomb VII" discovered underneath the Bronze Age royal palace of the ancient city of Qatna, Syria. A preliminary minimal number of individuals of 70 has been estimated for the as yet not fully analyzed skeletal remains. Skull fragments of nine individuals exhibit endocranial bone formations consistent with HFI. Rarity of stress indicators in the skeletons, the rich grave goods, and the burial place within the area of the Royal palace are suggestive of a high social status and an economically favorable situation of the buried individuals. Assuming that their life style included a high calorie diet in combination with little physical activity, acquired metabolic disorders may have been present in many individuals. The comparatively high number of individuals presenting HFI in the studied sample might therefore be viewed as being related to their high social status. Multiple occurrences of HFI in archaeological skeletal assemblages might serve as a proxy for social status.

Impaired neurotrophin-3 signaling in a TrkAII mutant associated with hereditary polyneuropathy.

Mutations of the neurotrophin receptor tyrosine kinase TrkA (NTRK1) cause congenital sensory neuropathy with insensitivity to pain and anhydrosis (CIPA), also called hereditary sensory and autonomous neuropathy type IV (HSAN IV). The neuronal splice variant of TrkA, TrkAII, binds two neurotrophin ligands, nerve growth factor (NGF) and neurotrophin-3 (NT3). Several studies have demonstrated NGF signaling defects in CIPA-associated TrkA mutants. To date, however, no study has examined NT3/TrkA signaling of CIPA mutants. As the interaction of NT3 and TrkA temporally and spatially precedes the interaction of NGF with TrkA, we examined the signaling of NT3 in a CIPA-associated TrkA mutant. Intriguingly, we revealed remarkable defects in NT3-induced ERK1/2 phosphorylation and neurite outgrowth. The impact of our findings is twofold. First, our data call for a re-examination of previously described TrkAII CIPA mutants regarding their NT3 signaling capability. Second, we envision that CIPA/HSAN IV polyneuropathies might fall into two different subgroups: one with diminished NT3/TrkAII signaling, in which axons actually do not reach their targets, and a second group with sufficient NT3/TrkAII signaling but diminished NGF/TrkAII signaling, in which axons do reach their targets, yet degenerate after successful target engagement.

Tracking TrkA's trafficking: NGF receptor trafficking controls NGF receptor signaling.

Growth factors such as the neurotrophins promote neuronal survival and shape neuronal morphology. Neurotrophin receptors are located on the surface of axons and dendrites and must convey their signal retrogradely to the nucleus to influence transcription of target genes. The distance between the site of receptor activation and the nucleus is tremendous. How is the retrograde transmission of survival signals being achieved? Recent work showed that signaling endosomes containing neurotrophin receptors and associated downstream kinases undergo retrograde vesicular transport along microtubules, propelled by the molecular motor dynein. The next objective in the "neurotrophin receptor trafficking meets signal transduction field" will be to elucidate the traffic control mechanisms governing the directed movement of signaling endosomes. Much is already known on the trafficking of the receptor for epidermal growth factor, EGFR. We will summarize the known traffic control mechanisms for EGFR and hypothesize whether EGFR-relevant traffic control mechanisms might also be relevant for neurotrophin receptor traffic control. Moreover, we speculate about potential implications of neurotrophin receptor traffic jams for neurodegenerative diseases.

Technical note: development of a transcervical oocyte recovery procedure for sheep.

An oocyte recovery procedure was developed and evaluated to determine whether a transcervical embryo recovery procedure is feasible with our method, which includes estradiol-17beta (E2) and oxytocin (OT) treatments, for dilating the cervix in ewes. On d 6 of an estrous cycle, oocytes were recovered either transcervically or with a laparotomy procedure. In the laparotomy group, ovulation rate was determined during the procedure and was used to calculate the percentage ofoocytes recovered. The laparotomy procedure was a standard uterine flush, and 12 mL of PBS was used to flush each uterine horn. In the transcervical group, the ovaries in each ewe were evaluated ultrasonically to determine ovulation rate. For transcervical recovery, 100 microg of E2 were injected i.v. on d 5 to increase cervical OT receptors, and 100 USP units of OT were injected i.v. 10 to 12 h later to dilate the cervix. Approximately 25 min after OT, ewes were placed in dorsal recumbency in a Commodore cradle, and a modified Foley catheter was passed through the cervix and into the uterus for injection (80 to 210 mL) and aspiration of PBS. The PBS was aspirated with a vacuum pump. The percentage of PBS recovered was greater (P<.01) at laparotomy than with the transcervical procedure (85.8 vs. 36.2%). Despite that difference, oocyte recovery did not differ significantly between the two groups (67% for laparotomy vs. 50% for transcervical; [oocytes recovered/number of corpora lutea] x 100), and there was no evidence that the transcervical procedure damaged the oocytes; the zona pellucida remained intact around all of the oocytes. In conclusion, a procedure that includes E2-OT-induced cervical dilation, passage of a modified Foley catheter into the uterus, and incremental infusion and aspiration of media through the catheter can be used to recover oocytes transcervically from ewes. This procedure may make transcervical embryo recovery feasible for sheep.

Reduced tolerance for heat stress environments caused by protective lotions.

There have been complaints of excessive heat after applying skin protective lotions. The purpose of this study was to determine if oil-base or alcohol-base protective lotions interfere with the body's cooling mechanisms during moderate work in heat stress conditions, and if so, then to identify the mechanisms. This was accomplished by evaluating the effect of lotions on thermoregulation as measured by rectal temperatures, local sweat rates, and total water losses during exercise at elevated temperatures. In comparison to the control, after about thirty minutes, the skin lotion tests resulted in a more hyperthermic condition, as measured by rectal temperatures.