Surgical excision remains the treatment of choice for facial cutaneous squamous cell carcinoma (cSCC) despite there being no generally accepted diameter of clear margins. Therefore, the aim of this ...study was to evaluate the impact of microscopic clear margins diameter (mCMD) with respect to the development of local recurrences (LR).
The medical records of 99 patients with a total of 142 cases of facial cSCC, who underwent surgical treatment between January 2010 and December 2015, were reviewed for demographic data and clinicopathological features.
100 cases were diagnosed as primary cSCC and 42 cases as secondary cSCC. Of these, nine (6.3%) developed LR. Mean time to LR was 20 months, with the cheek as the predominant site 55.5% (n = 5). Wound closure was either primary (56%) or secondary (44%), depending on the site. Although no significant correlation between mCMD and LR was found (rPearson = 0.029; rPearson = 0.015), >4.1 mm was shown to be a negative cut-off-value (horizontally and vertically) without LR (100% vs 0%).
Based on these results, however descriptive they are, the authors consider histological confirmation of clear margins to be necessary for reducing the formation of LR. Thus, consistent testing and histopathological reporting, in a multicentered effort, are needed to further clarify the role of mCMD in the development of cSCC-LR.
The association between obesity and perceived weight discrimination has been investigated in several studies. Although there is evidence that perceived weight discrimination is associated with ...negative outcomes on psychological well-being, there is a lack of research examining possible buffering effects of coping strategies in dealing with experiences of weight discrimination. The present study aims to fill that gap. We examined the relationship between perceived weight discrimination and depressive symptoms and tested whether problem-solving strategies and/or avoidant coping strategies mediated this effect.
Using structural equation modeling, we analyzed representative cross-sectional data of n=484 German-speaking individuals with obesity (BMI⩾30 kg m
), aged 18 years and older.
Results revealed a direct effect of perceived weight discrimination on depressive symptoms. Further, the data supported a mediational linkage for avoidant coping strategies, not for problem-solving strategies. Higher scores of perceived weight discrimination experiences were associated with both coping strategies, but only avoidant coping strategies were positively linked to more symptoms of depression.
Perceived weight discrimination was associated with increased depressive symptoms both directly and indirectly through situational coping strategies. Avoidant coping has the potential to exacerbate depressive symptoms, whereas problem-solving strategies were ineffective in dealing with experiences of weight discrimination. We emphasize the importance of coping strategies in dealing with experiences of weight discrimination and the need to distinguish between using a strategy and benefiting from it without detriment.
Bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) is a side effect primarily in patients receiving highly potent nitrogen-containing bisphosphonates. The exact etiopathology is unknown. In ...addition to reduced bone remodeling, there may also be an impact on soft tissues. The impact of nitrogen- (ibandronate, pamidronate, zoledronate) and non-nitrogen-containing bisphosphonates (clodronate) on human umbilicord vein endothelial cells (HUVEC), fibroblasts and osteogenic cells was analyzed employing cell viability testing and a scratch wound assay. The impact on the cell morphology of vital-stained osteogenic cells was investigated by cell visualization (confocal laser scanning microscopy). Pamidronate and zoledronate had the greatest negative impact on all cell lines, whereas the impact of ibandronate and clodronate was less distinct. The effect of clodronate on HUVEC and fibroblasts was particularly marginal. BP-ONJ could be a multifactorial event with multicellular impairments. This might result in altered wound healing. The increased impact of the highly potent bisphosphonates, particularly on non-bone cells, may explain the higher occurrence of BP-ONJ.
Background
Red blood cells (RBCs) are routinely stored in liquid state at temperatures below 6°C, and RBC unit core temperature should not exceed 10°C during transport. Since the critical temperature ...of 10°C was chosen mostly arbitrarily, this study investigated the effect of both constant temperature settings as well as multiple rewarming cycles on stored RBCs with respect to morphology, biochemical parameters and haemolysis.
Materials and Methods
Buffy coat‐depleted filtered RBCs were used as standard products. RBCs were stored at 1–6°C (reference group, n = 12), 13 and 22°C (test groups, n = 12 each) or stored at 1–6°C and warmed up five times to 10, 13, or 22°C for a period of 24 h each. Various biochemical parameters were measured weekly. RBCs were further investigated using electron microscopy.
Results
Red blood cells stored constantly at 13 or 22°C showed stable haemolysis rates until day 28 and day 14, respectively. RBCs stored at 1–6°C with five warming‐up periods to 10, 13 or 22°C each lasting 24 h (total 120 h) did not exceed the limit of the haemolysis rate at the end of storage. Differently shaped erythrocytes were found in all samples, but more crenate erythrocytes appeared after 42 days of storage independent of temperature profiles.
Conclusion
Red cells can be kept at constant temperatures above 6°C without apparent harmful effects at least until day 14, whereas multiple warming cycles for no longer than 24 h at 10, 13 or 22°C with subsequent cooling do not cause quality loss as assessed using the in vitro assays employed in this study.
Summary Bisphosphonate associated osteonecrosis of the jaw (BP-ONJ) is one of the main side effects of bisphosphonate therapy (BPT). To date, there is no effective therapy of the BP-ONJ. ...Nitrogen-containing bisphosphonates (N-BPs) are particularly able to inhibit pyrophosphate synthase (FPPS) in the mevalonate pathway (MVP). Consequent of decreased synthesis of the metabolite Geranylgeraniol (GGOH) is believed to largely account for the development of BP-ONJ. Negative effect of N-BPs could be shown, resulting in decreased viability and migration capacity of different cell types of hard and soft tissues such as osteoblasts, fibroblast und endothelial cells. Aim of our in vitro study was to demonstrate that the mevalonate pathway metabolite GGOH could reverse the negative biological effect of N-BPs. Biological effect of GGOH on bisphosphonate-treated human umbilicord vein endothelial cells (HUVEC), fibroblast and osteogenic cells was analyzed by a viability test and measuring the migration capacity in a scratch wound assay as well as a migration assay using Boyden chambers. The morphological cell architecture of the treated cells was analyzed by phallacidin staining. GGOH cell-treatment can rescue the negative effect of bisphosphonates. These results underline the hypothesis that systemic or local treatment with GGOH could lead to new therapeutic strategies for BP-ONJ.
Most marine mammals are hypothesized to routinely dive within their aerobic dive limit (ADL). Mammals that regularly perform deep, long-duration dives have locomotor muscles with elevated myoglobin ...concentrations that are composed of predominantly large, slow-twitch (Type I) fibers with low mitochondrial volume densities (V(mt)). These features contribute to extending ADL by increasing oxygen stores and decreasing metabolic rate. Recent tagging studies, however, have challenged the view that two groups of extreme deep-diving cetaceans dive within their ADLs. Beaked whales (including Ziphius cavirostris and Mesoplodon densirostris) routinely perform the deepest and longest average dives of any air-breathing vertebrate, and short-finned pilot whales (Globicephala macrorhynchus) perform high-speed sprints at depth. We investigated the locomotor muscle morphology and estimated total body oxygen stores of several species within these two groups of cetaceans to determine whether they (1) shared muscle design features with other deep divers and (2) performed dives within their calculated ADLs. Muscle of both cetaceans displayed high myoglobin concentrations and large fibers, as predicted, but novel fiber profiles for diving mammals. Beaked whales possessed a sprinter's fiber-type profile, composed of ~80% fast-twitch (Type II) fibers with low V(mt). Approximately one-third of the muscle fibers of short-finned pilot whales were slow-twitch, oxidative, glycolytic fibers, a rare fiber type for any mammal. The muscle morphology of beaked whales likely decreases the energetic cost of diving, while that of short-finned pilot whales supports high activity events. Calculated ADLs indicate that, at low metabolic rates, both beaked and short-finned pilot whales carry sufficient onboard oxygen to aerobically support their dives.
Metastatic basal cell carcinoma (BCC) is rare. We treated a 44-year-old woman with an extended facial metatypical BCC in whom staging showed no local or distant metastases, but one year after ...resection, we diagnosed a local recurrence. Re-staging, using a fludeoxyglucose positron emission tomography-computed tomogram, (FDG PET-CT) showed suspected accumulations of FDG in the whole axial skeleton. Bone punch biopsy examination confirmed extensive bony metastases, and after resection of the relapse, we began her on a systemic treatment with a Hedgehog-pathway inhibitor (vismodegib), which resulted in partial remission.
Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate ...responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis.
We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression.
Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000–0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002–0·012), memory (b=0·017, 0·006–0·028), and language (b=0·008, 0·000–0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006–0·026) and weekly community group engagement (b=0·030, 0·007–0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018–0·075) and executive function (b=0·047, 0·017–0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I2=0·00–15·11%) for all but two of the significant findings (association between slower memory decline and living with others I2=58·33% and community group engagement, I2=37·54–72·19%), suggesting robust results across studies.
Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline.
EU Joint Programme–Neurodegenerative Disease Research grant, funded by the National Health and Medical Research Council Australia, and the US National Institute on Aging of the US National Institutes of Health.
Blubber, the specialized hypodermis of cetaceans, provides thermal insulation through the quantity and quality of lipids it contains. Quality refers to percent lipid content; however, not all lipids ...are the same. Certain deep-diving cetacean groups possess blubber with lipids - wax esters (WE) - that are not typically found in mammals, and the insulative quality of 'waxy' blubber is unknown. Our study explored the influence of lipid storage class - specifically WE in pygmy sperm whales (Kogia breviceps; N=7) and typical mammalian triacylglycerols in short-finned pilot whales (Globicephala macrorhynchus; N=7) - on blubber's thermal properties. Although the blubber of both species had similar total lipid contents, the thermal conductivity of G. macrorhynchus blubber (0.20±0.01 W m(-1) °C(-1)) was significantly higher than that of K. breviceps (0.15±0.01 W m(-1) °C(-1); P=0.0006). These results suggest that lipid class significantly influences the ability of blubber to resist heat flow. In addition, because the lipid content of blubber is known to be stratified, we measured its depth-specific thermal conductivities. In K. breviceps blubber, the depth-specific conductivity values tended to vary inversely with lipid content. In contrast, G. macrorhynchus blubber displayed unexpected depth-specific relationships between lipid content and conductivity, which suggests that temperature-dependent effects, such as melting, may be occurring. Differences in heat flux measurements across the depth of the blubber samples provide evidence that both species are capable of storing heat in their blubber. The function of blubber as an insulator is complex and may rely upon its lipid class, stratified composition and dynamic heat storage capabilities.
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