Purpose
A growing proportion of inguinal hernia patients are at least 65 years old. Assessing operational benefits versus risks in this group of elderly patients merits research.
Methods
Patients in ...two prospective trials (1:
n
= 134, 89 elderly; 2:
n
= 398, 70 elderly) completed RAND-36 questionnaires preoperatively (response rate 100 and 98.5 %, respectively) and at 3 (98.5 %) or 12 months (89.6 %) after open inguinal hernia repair. In both groups, preoperative and postoperative quality of life data were statistically compared within age categories. Quality of life change was compared between age categories. Immediate complications were recorded.
Results
The dimensions physical functioning and pain improved significantly in the elderly and under 65-year-olds. Role functioning/physical and social functioning showed improvement as well, but less constantly. No statistical difference in complication rates was found across age groups.
Conclusion
Inguinal hernia surgery improves physical and social dimensions of quality of life among elderly and under 65-year-olds similarly.
In 59 cases (81%) brain tissue had been obtained at necropsy and verified to be normal based on a thorough neuropathological investigation made according to CERAD recommendations. 14 Amygdala, ...hippocampus, entorhinal cortex, substantia nigra, and five cortical gyri (medial frontal, rectus, cingulate, angular, medial temporal) were examined for senile plaques and neurofibrillary tangles using the modified Bielschowsky's silver staining method and for Lewy bodies using anti-ubiquitin immunostaining. Table 1 Genotype and allele frequencies of the IL1 gene cluster polymorphisms in AD, PD, and control patients Polymorphism AD (n=92) PD (n=52) Controls (n=73) IL1A (-889) *1/*1 42 (0.46) 28 (0.54) 33 (0.45) *1/*2 39 (0.42) 20 (0.38) 29 (0.40) *2/*2 11 (0.12) 4 (0.08) 11 (0.15) *1 123 (0.67) 76 (0.73) 95 (0.65) *2 61 (0.32) 28 (0.27) 51 (0.35) IL1B (-511) *1/*1 35 (0.38) 25 (0.48) 24 (0.32) *1/*2 47 (0.51) 25 (0.48) 30 (0.41) *2/*2 10 (0.11) 2 (0.04)dagger 19 (0.26) *1 117 (0.63) 75 (0.72) 78 (0.53) *2 67 (0.36) 29 (0.28) 68 (0.47) IL1RN (VNTR) *1/*1 47 (0.51) 28 (0.54) 30 (0.41) *1/*2 30 (0.33) 19 (0.36) 30 (0.41) *2/*2 8 (0.09) 0 (0.00) 9 (0.12) *1/*3 5 (0.05) 3 (0.06) 2 (0.03) *2/*3 2 (0.\n The C to T substitution at position -511 in the promoter region of IL1B may regulate the production of IL1β, and indeed the in vitro synthesis capacity of IL1B *1/*1 genotype carriers has been found to be lower than that of *1/*2 and *2/*2 carriers. 20 Our finding of IL1B*1 being associated with PD therefore suggests that the lower synthesis capacity of IL1β could be important in the development of PD. IL1β may thus be a safeguard against the disease as has been suggested by Nishimura et al. 12 On the other hand, the level of IL1β in the nigro-striatal regions of the brain has been reported to be increased in PD patients. 9 This increase of the IL1β level in the PD brain could, however, result, for instance, from a compensatory response to neurodegeneration in the course of the disease.
Background RA has a substantial societal effect in terms of costs, disability and lost productivity, with much of the costs occurring outside the healthcare system (1,2). However, the calculatedcosts ...of RA vary considerably depending on countries studied and methods used (3). Objectives The objective of this study wasto evaluate the influence of morning stiffness on productivity at work and to estimate the work-related economic consequences of morning stiffness in 11 European countries. Methods The original sample comprised 1061 RA patients from 11 European countries (Belgium, Denmark, Finland, France, Germany, Italy, Norway, Poland, Spain, Sweden and UK). They had symptoms of morning stiffness for more than six months, three or more times per week. Data were collected by interviews using a structured questionnaire translated into local languages. Women comprised 77.9% of the sample, the average age was 50.4 years and 84.3% had RA diagnosed for more than 2 years. Based on the average working time in EU countries (4) in all time-based cost estimates the numbers of active working hours per year was estimated to be 1568. The annual level of gross income reported by the patients was used to obtain individual time-based cost estimates. Results Overall costs of RA-related morning stiffness was calculated to be 27712€ per patient per year, varying from 4965€ in Spain to 66706€ in Norway. On average 96% (77-99%) of the overall production losses were attributed to early retirement, with a markedly lower level (77%) in Italy than in other countries (p<0.0001). The proportion of patients who reported retirement due to morning stiffness showed considerable variation across the countries represented in the study, being relatively low in Italy but much higher in Finland, Denmark, UK and Poland. Also the productivity losses caused by late work arrivals, sick leave and working while sick were considerable. Overall, the annual cost of late arrivals (6-847€) was approximately half of the costs attributed to sick leave (0-1506€) and working while sick (0-1090€). Conclusions Morning stiffness due to RA causes significant production losses and is a significant cost burden throughout Europe. There seem to be notable differences in the impact of morning stiffness on productivity between European countries. References Kobelt G, Jönsson B. The burden of rheumatoid arthritis and access to treatment: outcome and cost-utility of treatments. Eur J Healh Econ 2008;8 (Suppl 2):S95-S106. Merkersdal S, Ruof J, Huelsemann J et al. Development of a matrix of cost domains in economic evaluation of rheumatoid arthritis. J Rheumatol 2001;28:657-661. Lundqkvist J, Kastäng F, Kobelt G. The burden of rheumatoid arthritis and access to treatment: health burden and costs. Eur J Health Econ 2008; 8 (Suppl2):S49-S60. Eurostat yearbook 2011. http://epp.eurostat.ec.europa.eu/portal/page/portal/product_details/publication?p_product_code=CH_06_2011 / accessed 25.10.2012. Acknowledgements The survey was conducted by Ipsos MORI and sponsored by an educational grant from Mundipharma International Limited. Disclosure of Interest K. Mattila: None Declared, F. Buttgereit Grant/research support from: Merck Serono & Horizon Pharma, Consultant for: Merck Serono, Horizon Pharma (formerly Nitec Pharma) & Mundipharma International Limited, Speakers bureau: Mundipharma International Limited, R. Tuominen Consultant for: Mundipharma International Limited, Speakers bureau: Mundipharma International Limited
Profilin and cyclase-associated protein (CAP, known in yeast as Srv2) are ubiquitous and abundant actin monomer-binding proteins. Profilin catalyses the nucleotide exchange on actin monomers and ...promotes their addition to filament barbed ends. Srv2/CAP recycles newly depolymerized actin monomers from ADF/cofilin for subsequent rounds of polymerization. Srv2/CAP also harbors two proline-rich motifs and has been suggested to interact with profilin. However, the mechanism and biological role of the possible profilin-Srv2/CAP interaction has not been investigated. Here, we show that Saccharomyces cerevisiae Srv2 and profilin interact directly (KD ~1.3 μM) and demonstrate that a specific proline-rich motif in Srv2 mediates this interaction in vitro and in vivo. ADP-actin monomers and profilin do not interfere with each other's binding to Srv2, suggesting that these three proteins can form a ternary complex. Genetic and cell biological analyses on an Srv2 allele (srv2-201) defective in binding profilin reveals that a direct interaction with profilin is not essential for Srv2 cellular function. However, srv2-201 causes a moderate increase in cell size and partially suppresses the cell growth and actin organization defects of an actin binding mutant profilin (pfy1-4). Together these data suggest that Srv2 is an important physiological interaction partner of profilin.
Humpback whales Megaptera novaeangliae are seasonal migrants that mate and calve at low latitudes and feed at mid- to high latitudes. Connections between most Southern Hemisphere breeding and feeding ...areas are not well understood, but are critical for assessing stock structure and human impacts. Photo-identification was performed to identify the feeding grounds of an Endangered sub-population that breeds in the central South Pacific Ocean (CSP). Identification photographs were obtained from 159 ind. at American Samoa and compared to 3508 Southern Hemisphere humpback whales in the Antarctic Humpback Whale Catalogue (AHWC), including 1352 from Antarctic feeding grounds. Two individuals from American Samoa were seen on 3 occasions at the Antarctic Peninsula. This is the first known feeding site for American Samoa and one of few reliably identified for the CSP. AHWC #2950 was confirmed to have undertaken a round-trip movement of no less than 18840 km, spanning 108 longitudinal degrees. This represents the largest mammalian migration known to date and a departure from historical assumptions about CSP migratory patterns. The frequency, causes, and fitness implications of such movements have yet to be determined. However, distance is the only known extrinsic barrier to humpback whale movement within oceans, and so maximum individual range is 1 factor potentially affecting population exchange and colonization of new habitats. The movement documented here may place this Endangered sub-population at risk if conservation efforts are relaxed in unidentified parts of its range. Yet, the ability of humpback whales to undertake such extensive movements may have also contributed to the apparent recovery of some populations versus other historically exploited whale species.
Persistent smoking after cancer diagnosis is associated with increased overall mortality (OM) and cancer mortality (CM). According to the 2020 Surgeon General's report, smoking cessation may reduce ...CM but supporting evidence is not wide. Use of deep learning-based modeling that enables universal natural language processing of medical narratives to acquire population-based real-life smoking data may help overcome the challenge. We assessed the effect of smoking status and within-1-year smoking cessation on CM by an in-house adapted freely available language processing algorithm.
This cross-sectional real-world study included 29 823 patients diagnosed with cancer in 2009-2018 in Southwest Finland. The medical narrative, International Classification of Diseases-10th edition codes, histology, cancer treatment records, and death certificates were combined. Over 162 000 sentences describing tobacco smoking behavior were analyzed with ULMFiT and BERT algorithms.
The language model classified the smoking status of 23 031 patients. Recent quitters had reduced CM hazard ratio (HR) 0.80 (0.74-0.87) and OM HR 0.78 (0.72-0.84) compared to persistent smokers. Compared to never smokers, persistent smokers had increased CM in head and neck, gastro-esophageal, pancreatic, lung, prostate, and breast cancer and Hodgkin's lymphoma, irrespective of age, comorbidities, performance status, or presence of metastatic disease. Increased CM was also observed in smokers with colorectal cancer, men with melanoma or bladder cancer, and lymphoid and myeloid leukemia, but no longer independently of the abovementioned covariates. Specificity and sensitivity were 96%/96%, 98%/68%, and 88%/99% for never, former, and current smokers, respectively, being essentially the same with both models.
Deep learning can be used to classify large amounts of smoking data from the medical narrative with good accuracy. The results highlight the detrimental effects of persistent smoking in oncologic patients and emphasize that smoking cessation should always be an essential element of patient counseling.
•Deep learning/universal language modeling was used to extract smoking status of cancer patients. Good accuracy was observed.•Those who continue smoking after cancer diagnosis had increased CM compared to never smokers.•Recent within-1-year cessation reduced this mortality.•Detrimental effects of smoking were observed in multiple types of early- and advanced-stage cancers, including the elderly.•We conclude that smoking cessation support should always be included in cancer care.
Aims. We study an undocumented large translucent cloud, detected by means of its enhanced radiation in the SHASSA (Southern H-Alpha Sky Survey Atlas) survey. We consider whether its excess surface ...brightness can be explained by light scattered off the dust grains in the cloud, or whether emission from in situ ionized gas is required. In addition, we aim to determine the temperature of dust, the mass of the cloud, and its possible star formation activity. Methods. We compare the observed Hα surface brightness of the cloud with predictions of a radiative transfer model. We use the WHAM (Wisconsin H-Alpha Mapper) survey as a source for the Galactic Hα interstellar radiation field illuminating the cloud. Visual extinction through the cloud is derived using 2MASS J, H, and K band photometry. We use far-IR ISOSS (ISO Serendipitous Survey), IRAS, and DIRBE data to study the thermal emission of dust. The LAB (The Leiden/Argentine/Bonn Galactic HI Survey) is used to study 21 cm HI emission associated with the cloud. Results. Radiative transfer calculations of the Galactic diffuse Hα radiation indicate that the surface brightness of the cloud can be explained solely by radiation scattered off dust particles in the cloud. The maximum visual extinction through the cloud is about 1.2 mag. The cloud is found to be associated with 21 cm HI emission at a velocity ~-9 km s-1. The total mass of the cloud is about 550–1000 $M_{\odot}$. There is no sign of star formation in this cloud. The distance of the cloud is estimated from the Hipparcos data to be ~100 pc.
Knowledge of the effects of thermal conditions on animal movement and dispersal is necessary for a mechanistic understanding of the consequences of climate change and habitat fragmentation. In ...particular, the flight of ectothermic insects such as small butterflies is greatly influenced by ambient temperature. Here, variation in body temperature during flight is investigated in an ecological model species, the Glanville fritillary butterfly (Melitaea cinxia). Attention is paid on the effects of flight metabolism, genotypes at candidate loci, and environmental conditions. Measurements were made under a natural range of conditions using infrared thermal imaging. Heating of flight muscles by flight metabolism has been presumed to be negligible in small butterflies. However, the results demonstrate that Glanville fritillary males with high flight metabolic rate maintain elevated body temperature better during flight than males with a low rate of flight metabolism. This effect is likely to have a significant influence on the dispersal performance and fitness of butterflies and demonstrates the possible importance of intraspecific physiological variation on dispersal in other similar ectothermic insects. The results also suggest that individuals having an advantage in low ambient temperatures can be susceptible to overheating at high temperatures. Further, tolerance of high temperatures may be important for flight performance, as indicated by an association of heat‐shock protein (Hsp70) genotype with flight metabolic rate and body temperature at takeoff. The dynamics of body temperature at flight and factors affecting it also differed significantly between female and male butterflies, indicating that thermal dynamics are governed by different mechanisms in the two sexes. This study contributes to knowledge about factors affecting intraspecific variation in dispersal‐related thermal performance in butterflies and other insects. Such information is needed for predictive models of the evolution of dispersal in the face of habitat fragmentation and climate change.
Knowledge of the effects of thermal conditions on animal movement and dispersal is necessary for a mechanistic understanding of the consequences of climate change and habitat fragmentation. Here, variation in body temperature during flight in a butterfly is investigated. Attention is paid on the effects of flight metabolism, genotypes at candidate gene loci, and environmental conditions.
MIM/MTSS1 is a tissue-specific regulator of plasma membrane dynamics, whose altered expression levels have been linked to cancer metastasis. MIM deforms phosphoinositide-rich membranes through its ...I-BAR domain and interacts with actin monomers through its WH2 domain. Recent work proposed that MIM also potentiates Sonic hedgehog (Shh)-induced gene expression. Here, we generated MIM mutant mice and found that full-length MIM protein is dispensable for embryonic development. However, MIM-deficient mice displayed a severe urinary concentration defect caused by compromised integrity of kidney epithelia intercellular junctions, which led to bone abnormalities and end-stage renal failure. In cultured kidney epithelial (MDCK) cells, MIM displayed dynamic localization to adherens junctions, where it promoted Arp2/3-mediated actin filament assembly. This activity was dependent on the ability of MIM to interact with both membranes and actin monomers. Furthermore, results from the mouse model and cell culture experiments suggest that full-length MIM is not crucial for Shh signaling, at least during embryogenesis. Collectively, these data demonstrate that MIM modulates interplay between the actin cytoskeleton and plasma membrane to promote the maintenance of intercellular contacts in kidney epithelia.
Human mesenchymal stem cells (hMSCs) are multipotent cells that are found in the bone marrow. Inflammation and tissue damage mobilize MSCs and induce their migration towards the damaged site through ...mechanisms that are not well defined. Toll-like receptor-9 (TLR9) is a cellular receptor for microbial and vertebrate DNA. Stimulation of TLR9 induces inflammatory and invasive responses in TLR9-expressing cells. We studied here the expression of TLR9 in human MSCs and the effects of synthetic TLR9-agonists on their invasion. Constitutive expression of TLR9 was detected in human MSCs but the expression was suppressed when MSCs were induced to differentiate into osteoblasts. Using standard invasion assays and a novel organotypic culture model based on human myoma tissue, we discovered that stimulation with the TLR9 agonistic, CpG oligonucleotides increased the invasion capacity of undifferentiated MSCs. Simultaneously, an increase in MMP-13 synthesis and activity was detected in the CpG-activated MSCs. Addition of anti-MMP-13 antibody significantly diminished the CpG-induced hMSC invasion. We conclude that treatment with TLR9-ligands increases MSC invasiveness, and this process is at least partially MMP-13-mediated.
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