Lazy Sundays: role of day of the week and reactivity on objectively measured physical activity in older people.

BACKGROUND: The aim of this study was to assess the effect of day of the week and wearing a device (reactivity) on objectively measured physical activity (PA) in older people. METHODS: Walking duration as a measure for PA was recorded from 1333 German community-dwelling older people (≥65 years, 43.8% women) over 5 days using accelerometers (activPAL). Least-square means of PA with 95%-confidence intervals (95%-CI) from multi-level analysis were calculated for each day of the week and each measurement day (days after sensor attachment). RESULTS: Walking duration on Sundays was significantly lower compared to working days (Sunday vs. Monday-Friday: - 12.8 min (95%-CI: - 14.7; - 10.9)). No statistically significant difference compared to working days was present for Saturdays. The linear slope for measurement day and walking duration was marginal and not statistically significant. CONCLUSIONS: Studies using PA sensors in older people should assess Sundays and working days to adequately determine the activity level of the participants.

Neutrophils in Tissue Trauma of the Skin, Bone, and Lung: Two Sides of the Same Coin.

Following severe tissue injury, patients are exposed to various danger- and microbe-associated molecular patterns, which provoke a strong activation of the neutrophil defense system. Neutrophils trigger and modulate the initial posttraumatic inflammatory response and contribute critically to subsequent repair processes. However, severe trauma can affect central neutrophil functions, including circulation half-life, chemokinesis, phagocytosis, cytokine release, and respiratory burst. Alterations in neutrophil biology may contribute to trauma-associated complications, including immune suppression, sepsis, multiorgan dysfunction, and disturbed tissue regeneration. Furthermore, there is evidence that neutrophil actions depend on the quality of the initial stimulus, including trauma localization and severity, the micromilieu in the affected tissue, and the patient's overall inflammatory status. In the present review, we describe the effects of severe trauma on the neutrophil phenotype and dysfunction and the consequences for tissue repair. We particularly concentrate on the role of neutrophils in wound healing, lung injury, and bone fractures, because these are the most frequently affected tissues in severely injured patients.

Diabetes mellitus and the skin.

Diabetes is a debilitating, life-threatening disease accounting in 2015 for the death of 5 million people worldwide. According to new estimations, 415 million adults currently suffer from the disease, and this number is expected to rise to 642 million by 2040. High glucose blood levels also affect the skin among systemic organs, and skin disorders can often predict the onset of this metabolic disorder. In this review, we address the pathomechanistic effects of diabetes on the skin and give an overview on the most common skin diseases associated with diabetes.

[Wound healing in the elderly]. / Wundheilung im Alter.

Restoration of tissue integrity is essential for host defense and protection of the organism. The efficacy and quality of skin repair varies significantly over a person's lifetime. Whereas prenatal wound healing is characterized by regeneration and scarless healing, scarring, fibrosis, and loss of function are features of postnatal repair. In fact, aging is the prominent risk factor for chronic wounds, skin fragility, infections, comorbidities, and decreased quality of life. Current strategies for restoration of tissue integrity and wound therapy are not sufficient and require further investigation of the underlying pathomechanisms and the development of causal-based concepts.

[Skin aging: Molecular understanding of extrinsic and intrinsic processes]. / Hautalterung : Molekulares Verständnis der ex- und intrinsischen Vorgänge.

In an ever-aging society, a better understanding of the underlying mechanisms accompanying skin aging has become essential. Most age-related morphological skin changes are triggered by a combination of intrinsic factors (e.g., genetics, hormones) and extrinsic ones (e.g., ultarviolet/infrared light exposure, smoking, pollution). In this article, new insights on the latest findings regarding the pathogenesis of skin aging are summarised, addressing the extent to which the aforementioned factorsmay influence the progress of skin aging and identifying the consequences on the morphology and physiology of skin.

Interplay of H2A deubiquitinase 2A-DUB/Mysm1 and the p19(ARF)/p53 axis in hematopoiesis, early T-cell development and tissue differentiation.

Monoubiquitination of core histone 2A (H2A-K119u) has a critical role in gene regulation in hematopoietic differentiation and other developmental processes. To explore the interplay of histone H2A deubiquitinase Myb-like SWIRM and MPN domain containing1 (2A-DUB/Mysm1) with the p53 axis in the sequential differentiation of mature lymphocytes from progenitors, we systematically analyzed hematopoiesis and early T-cell development using Mysm1(-/-) and p53(-/-)Mysm1(-/-) mice. Mysm1(-/-) thymi were severely hypoplastic with <10% of wild-type cell numbers as a result of a reduction of early thymocyte progenitors in context with defective hematopoietic stem cells, a partial block at the double-negative (DN)1-DN2 transition and increased apoptosis of double-positive thymocytes. Increased rates of apoptosis were also detected in other tissues affected by Mysm1 deficiency, including the developing brain and the skin. By quantitative PCR and chromatin immunoprecipitation analyses, we identified p19(ARF), an important regulator of p53 tumor suppressor protein levels, as a potential Mysm1 target gene. In newly generated p53(-/-)Mysm1(-/-) double-deficient mice, anomalies of Mysm1(-/-) mice including reduction of lymphoid-primed multipotent progenitors, reduced thymocyte numbers and viability, and interestingly defective B-cell development, growth retardation, neurological defects, skin atrophy, and tail malformation were almost completely restored as well, substantiating the involvement of the p53 pathway in the alterations caused by Mysm1 deficiency. In conclusion, this investigation uncovers a novel link between H2A deubiquitinase 2A-DUB/Mysm1 and suppression of p53-mediated apoptotic programs during early lymphoid development and other developmental processes.

[Papulovesicular exanthem after a safari in South Africa]. / Papulovesikuläres Exanthem nach einer Südafrika-Safari.

A 68-year-old man presented with a papulovesicular exanthem, fever and malaise after a safari in South Africa. Based on the history, the typical clinical picture with an exanthema and eschar as well as the detection of antibodies against rickettsioses of the spotted fever group, we diagnosed African tick-bite fever which is due to R. africae. During treatment with doxycycline 200 mg/d, all symptoms resolved completely within 11 days. Rickettsioses should always be considered in patients presenting with exanthema, fever and malaise. Particularly the presence of one or multiple eschars on the skin manifesting as erythematous plaques with central necrosis is a pathognomic sign. The serological detection of antibodies against rickettsia species of the spotted fever group is the established diagnostic standard. Due to extensive cross-reactions it is not possible to distinguish between the members of one rickettsial group. Furthermore antibody titers rise late in the disease, frequently 2 or 3 weeks after the onset of symptoms. This underscores the importance of the clinical diagnosis.

Mice with heterozygous deficiency of manganese superoxide dismutase (SOD2) have a skin immune system with features of "inflamm-aging".

Dendritic cells (DC) are central in regulating skin immunity. Immunosenescence is associated with a chronic inflammatory state. Little is known about the contribution of DC to "inflamm-aging". When determining langerhans cell (LC) numbers, we found a 60 % reduction of LC in aged epidermis. Reactive oxygen species(ROS) are linked with aging. The mitochondrial manganese superoxide dismutase (SOD2) is in the first line of antioxidant defense. We investigated the function of DC from SOD2 heterozygous mice (SOD2+/-) and found that at 4 months of age LC numbers are not altered, but activated LC have impaired expression of MHC-II and CD44. Immature SOD2+/- DC produced increased proinflammatory IL-6 and chemokines CXCL1 and CXCL2. Upon challenge SOD2+/- DC accumulated ROS. When activating SOD2+/- DC by LPS they less efficiently upregulated MHC-II, CD86 and CD44. Surprisingly, in vivo contact hypersensitivity (CHS) was enhanced in SOD2+/- mice although SOD2+/- DC were less potent in stimulating wt T cells. However, SOD2+/- T cells showed increased proliferation, even when stimulated with SOD2+/- DC, possibly explaining the increased CHS. Our findings suggest that SOD2 is a molecular candidate in the regulation of "inflamm-aging" conveying both immunosuppressive and proinflammatory signals through alteration of DC and T cell functions.

Efficacy of bath psoralen plus ultraviolet A (PUVA) vs. system PUVA in psoriasis: a prospective, open, randomized, multicentre study.

BACKGROUND: Plaque psoriasis is an inflammatory disease affecting approximately 2% of the population. The clinical hallmarks of psoriasis are sharply demarcated, erythematous plaques with thick scales. Photochemotherapy (psoralen plus ultraviolet A, PUVA) is one of the most effective therapies of psoriasis. The photosensitizer 8-methoxypsoralen (8-MOP) can be applied either orally (system PUVA) or topically in a warm water bath (bath PUVA). OBJECTIVES: To compare bath PUVA and system PUVA in the treatment of plaque psoriasis. METHODS: This was a randomized, open, prospective, multicentre trial. We included 74 patients with moderate-to-severe plaque psoriasis during a 6-week treatment and a 4-week follow-up period. Of the patients enrolled in the study, 38 received bath PUVA and 36 system PUVA. RESULTS: Both treatment modalities significantly reduced the median Psoriasis Area and Severity Index (PASI) score in the intention-to-treat population. Within 6 weeks bath PUVA reduced the median PASI by 74% (16·4 to 4·2) while system PUVA did so by 62% (15·3 to 5·8). The difference between the two modalities was not significant with regard to treatment efficacy (P = 0·389). CONCLUSION: There is no difference between bath PUVA and system PUVA in the treatment of psoriasis.

Identifying congenital hearing impairment: preliminary results from a comparative study using objective and subjective audiometric protocols.

To compare objective and subjective protocols assessing hearing loss in young children and evaluate frequency-specific hearing impairment through a comparison between auditory steady state responses (ASSR), auditory brainstem responses (ABR), transient otoacoustic emissions and conditioned orientation reflex responses (COR). Thirty-five hearing-impaired children (20 male and 15 female), aged between 14 months and 4 years, participated in the study. Hearing threshold levels and peripheral auditory function were assessed by measurements of ABR, ASSR, otoacoustic emissions and COR. The analysis of the COR and ASSR variables showed significant correlations in the majority of tested frequencies. The data highlight a characteristic of the COR procedure, which is an underestimation of the hearing threshold in comparison to the ASSR estimate. The data show that the COR threshold assessment follows the pattern of the other two established electrophysiological methods (ABR, ASSR). The correlation analyses did not permit evaluation of the precision of these estimates. Considering that the ASSR variables show a better relationship with ABR (higher correlation values) than COR, it might be advantageous to utilize the ASSR to gain frequency-specific information.

Automatic removal of sonomotor waves from auditory brainstem responses.

We have developed a computerized technique for automatic detection and removal of sonomotor waves (SMWs) from auditory brainstem responses (ABRs). Our approach is based on adaptive decomposition using a redundant set of Gaussian and 1-cycle-limited Gabor functions. In order to find optimal parameters and evaluate the efficiency of the methods, simulated data were first used before applying it to clinical data. Results were good and confirmed by an expert with years of clinical experience in ABR evaluation.

Exercise-induced adaptations of cardiac redox homeostasis and remodeling in heterozygous SOD2-knockout mice.

A reduced expression of the manganese-dependent superoxide dismutase (SOD2) is characterized by increased cardiac oxidative stress. Oxidative stress has also been described in situations of physical exercise. We investigated the influence of physical exercise (EX; treadmill 1 h/day at 15 m/min, 5 days/wk, at an angle of 5° for a duration of 8 wk) on cardiac function [heart frequency (HF), echocardiography, morphometry], oxidative stress [reactive oxygen species (ROS)], and antioxidative defence capacity (peroxiredoxin 1-6) in male SOD2-knockout (SOD2_EX) and wild-type mice (WT_EX) compared with untrained age-matched animals (WT_CON; SOD2_CON). In SOD2_CON, heart weight, cardiomyocyte diameter, and cardiac ROS were significantly larger and peroxiredoxin isoforms 4-6 lower than in WT_CON. The vessel-to-cardiomyocyte ratio, cardiac VEGF-concentration, and cardiac function were similar in SOD2_CON and WT_CON. Both groups tolerated the exercise protocol well. In WT, exercise significantly increased vessel-to-cardiomyocyte ratio and ROS-generation and downregulated peroxiredoxin isoforms 4-6 and VEGF generation. The vessel-to-cardiomyocyte ratio, cardiac VEGF concentration, and cardiac ROS were not altered in SOD2_EX compared with SOD2_CON, but a significant upregulation of cardiac peroxiredoxin 1 and 4 was observed. Similar to the result observed in WT_EX, peroxiredoxin 3 was upregulated in SOD2_EX. Chronic exercise shifted the (mal)adaptive hypertrophic into a compensated dilated cardiac phenotype in SOD2_EX. In conclusion, downregulation of SOD2 induces a maladaptive cardiac hypertrophy. In this situation, physical exercise results in a further deterioration of cardiac remodeling despite an upregulation of the antioxidative defense system.

Identification of defense-related genes newly-associated with tomato flower abscission.

The current abscission model suggests the formation of a post-abscission trans-differentiation of a protective layer as the last step of the process. The present report expands the repertoire of genes activated in the tomato flower abscission zone (AZ), which are likely to be involved in defense responses. We identified four different defense-related genes, including: Cysteine-type endopeptidase, α-Dioxygenase 1 (α-DOX1), HopW-1-1-Interacting protein2 (WIN2), and Stomatal-derived factor-2 (SDF2), that are newly-associated with the late stage of the abscission process. The late expression of these genes, induced at 8-14 h after flower removal when pedicel abscission was already in progress, was AZ-specific, and was inhibited by treatments that prevented pedicel abscission, including 1-methylcyclopropene pretreatment or IAA application. This information supports the activation of different defense responses and strategies at the late abscission stages, which may enable efficient protection of the exposed tissue toward different environmental stresses.