Murine Axial Compression Tibial Loading Model to Study Bone Mechanobiology:Implementing the Model and Reporting Results

In vivo tibial loading in mice is increasingly used to study bone adaptation and mechanotransduction. To achieve standardized and defined experimental conditions, loading parameters and animal-related factors must be considered when performing in vivo loading studies. In this review we discuss these loading and animal-related experimental conditions, present methods to assess bone adaptation, and suggest reporting guidelines. This review originated from presentations by each of the authors at the workshop “Developing Best Practices for Mouse Models of In Vivo Loading” during the Preclinical Models Section at the Orthopaedic Research Society Annual Meeting, San Diego, CA, March 2017. Following the meeting, the authors engaged in detailed discussions with consideration of relevant literature. The guidelines and recommendations in this review are provided to help researchers perform in vivo loading experiments in mice, and thus further our knowledge of bone adaptation and the mechanisms involved in mechanotransduction

Cтехиометрия и структура планктонных сообществ в литорали и пелагиали двух озер разного трофического статуса в Беларуси

Stoichiometric C : N : P ratios were compared between primary producers in littoral and pelagic ecosystems of mesotrophic relatively shallow lake Obsterno and shallow macrophyte covered low trophic lake Nobisto from May to October over the next two years. Elemental seston ratios of lake Obsterno revealed smaller differences between littoral and pelagic zones in comparison with lake Nobisto in 2017. During the studied period, in the both lakes, the seston C : N and C : P ratios were higher than the Redfield ratio (106 : 16 : 1 C : N : P) on most dates and N : P was always more than 16. Pelagic C : P and N : P ratios in lake Obsterno were the highest in May in 2017, July and September in 2018 with significant differences between littoral and pelagic zones. N : P ratios decreased in October but there were no significant differences among habitats. In lake Nobisto in 2018, seston C : P and N : P ratios increased from May to July in littoral and pelagic zones but then decreased in September to October. Our research shows differences in stoichiometric ratios in littoral and pelagic zones of these two lakes, which indicates food quality (seston C : N : P ratios) differences for zooplankton species depending on season and location.Изучали стехиометрию сестона (соотношения C : N : P) двух мелководных озер разной трофности – мезотрофного озера Обстерно и дистрофного макрофитного типа озера Нобисто в течение двух последовательных лет. Сравнивали сезонные изменения в стехиометрии продуцентов в литоральной и пелагической зонах. Соотношения элементов в сестоне оз. Обстерно выявили меньшие различия между литоральной и пелагической зонами по сравнению с оз. Нобисто в 2017 г. В течение исследуемого периода в обоих озерах соотношения C : N и C : P в сестоне были выше классического соотношения Редфилда (C106  : N16  : P1), а соотношение N : P всегда превышало 16. Соотношения C : P в пелагиали оз. Обстерно имели самые высокие показатели в мае 2017 г., а N : P в июле и сентябре 2018 г. со значимыми различиями между литоральной и пелагической зонами, но соотношения N : P уменьшились в октябре и не различались между местообитаниями. В оз. Нобисто в 2018 г. соотношения C : P и N : P в сестоне увеличивались с мая по июль в прибрежной и пелагической зонах, но затем снижались осенью. Как показали наши исследования, сезонные различия в стехиометрии сестона двух озер (соотношение C : N : P как показатель качества пищи) в разных местообитаниях отражают видовой состав фитопланктона, а также структуру сообществ зоопланктона, изменяющуюся в течение сезона и между местообитаниями

Colouration in amphibians as a reflection of nutritional status : the case of tree frogs in Costa Rica

Colouration has been considered a cue for mating success in many species; ornaments in males often are related to carotenoid mobilization towards feathers and/or skin and can signal general health and nutrition status. However, there are several factors that can also link with status, such as physiological blood parameters and body condition, but there is not substantial evidence which supports the existence of these relationships and interactions in anurans. This study evaluated how body score and blood values interact with colouration in free-range Agalychnis callidryas and Agalychnis annae males. We found significant associations between body condition and plasmatic proteins and haematocrit, as well as between body condition and colour values from the chromaticity diagram. We also demonstrated that there is a significant relation between the glucose and plasmatic protein values that were reflected in the ventral colours of the animals, and haematocrit inversely affected most of those colour values. Significant differences were found between species as well as between populations of A. callidryas, suggesting that despite colour variation, there are also biochemical differences within animals from the same species located in different regions. These data provide information on underlying factors for colouration of male tree frogs in nature, provide insights about the dynamics of several nutrients in the amphibian model and how this could affect the reproductive output of the animals

The study on the outsourcing of Taiwan's hospitals: a questionnaire survey research

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the outsourcing situation in Taiwanese hospitals and compares the differences in hospital ownership and in accreditation levels.</p> <p>Methods</p> <p>This research combined two kinds of methods: a questionnaire survey and the in-depth interview to two CEOs of the sample hospitals. One hospital is not-for-profit, while the other is a public hospital and the research samples are from the hospital data from Taiwan's 2005 to 2007 Department of Health qualifying lists of hospital accreditation. The returned questionnaires were analyzed with STATISTICA^®7.1 version software.</p> <p>Results</p> <p>The results for non-medical items showed medical waste and common trash both have the highest rate (94.6 percent) of being outsourced. The gift store (75 percent) and linen (73 percent) follow close behind, while the lowest rate of outsourcing is in utility maintenance (13.5 percent). For medical items, the highest rate of outsourcing is in the ambulance units (51.4 percent), while the hemodialysis center follows close behind with a rate of 50 percent. For departments of nutrition, pharmacy, and nursing however, the outsourcing rate is lower than 3 percent. This shows that Taiwan's hospitals are still conservative in their willingness to outsource for medical items. The results of the satisfaction paired t-test show that the non-medical items have a higher score than the medical items. The factor analysis showed the three significant factors in of non medical items' outsourcing are "performance", "finance", and "human resource". For medical items, the two factors are "operation" and satisfaction". To further exam the factor validity and reliability of the satisfaction model, a confirmative factor analysis (CFA) was conducted using structure equation modeling (SEM) method and found the model fitting well.</p> <p>Conclusion</p> <p>Hospitals, especially for public hospitals, can get benefits from outsourcing to revive the full-time-equivalent and human resource limitation.</p

Quality of life in patients with breast cancer before and after diagnosis: an eighteen months follow-up study

<p>Abstract</p> <p>Background</p> <p>Measuring quality of life in breast cancer patients is of importance in assessing treatment outcomes. This study examined the impact of breast cancer diagnosis and its treatment on quality of life of women with breast cancer.</p> <p>Methods</p> <p>This was a prospective study of quality of life in breast cancer patients. Quality of life was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its breast cancer supplementary measure (QLQ-BR23) at three points in time: baseline (pre diagnosis), three months after initial treatment and one year after completion of treatment (in all 18 months follow-up). At baseline the questionnaires were administered to all suspected identified patients while both patients and the interviewer were blind to the final diagnosis. Socio-demographic and clinical data included: age, education, marital status, disease stage and initial treatment. Repeated measure analysis was performed to compare quality of life differences over the time.</p> <p>Results</p> <p>In all, 167 patients diagnosed with breast cancer. The mean age of breast cancer patients was 47.2 (SD = 13.5) years and the vast majority (82.6%) underwent mastectomy. At eighteen months follow-up data for 99 patients were available for analysis. The results showed there were significant differences in patients' functioning and global quality of life at three points in time (P < 0.001). Although there were deteriorations in patients' scores for body image and sexual functioning, there were significant improvements for breast symptoms, systematic therapy side effects and patients' future perspective (P < 0.05).</p> <p>Conclusion</p> <p>The findings suggest that overall breast cancer patients perceived benefit from their cancer treatment in long-term. However, patients reported problems with global quality of life, pain, arm symptoms and body image even after 18 months following their treatments. In addition, most of the functional scores did not improve.</p

Murine Missing in Metastasis (MIM) Mediates Cell Polarity and Regulates the Motility Response to Growth Factors

Missing in metastasis (MIM) is a member of the inverse BAR-domain protein family, and in vitro studies have implied MIM plays a role in deforming membrane curvature into filopodia-like protrusions and cell dynamics. Yet, the physiological role of the endogenous MIM in mammalian cells remains undefined.We have examined mouse embryonic fibroblasts (MEFs) derived from mice in which the MIM locus was targeted by a gene trapping vector. MIM(-/-) MEFs showed a less polarized architecture characterized by smooth edges and fewer cell protrusions as compared to wild type cells, although the formation of filopodia-like microprotrusions appeared to be normal. Immunofluorescent staining further revealed that MIM(-/-) cells were partially impaired in the assembly of stress fibers and focal adhesions but were enriched with transverse actin filaments at the periphery. Poor assembly of stress fibers was apparently correlated with attenuation of the activity of Rho GTPases and partially relieved upon overexpressing of Myc-RhoA(Q63L), a constitutively activated RhoA mutant. MIM(-/-) cells were also spread less effectively than wild type cells during attachment to dishes and substratum. Upon treatment with PDGF MIM(-/-) cells developed more prominent dorsal ruffles along with increased Rac1 activity. Compared to wild type cells, MIM(-/-) cells had a slower motility in the presence of a low percentage of serum-containing medium but migrated normally upon adding growth factors such as 10% serum, PDGF or EGF. MIM(-/-) cells were also partially impaired in the internalization of transferrin, fluorescent dyes, foreign DNAs and PDGF receptor alpha. On the other hand, the level of tyrosine phosphorylation of PDGF receptors was more elevated in MIM depleted cells than wild type cells upon PDGF treatment.Our data suggests that endogenous MIM protein regulates globally the cell architecture and endocytosis that ultimately influence a variety of cellular behaviors, including cell polarity, motility, receptor signaling and membrane ruffling

Linking magmatism with collision in an accretionary orogen

A compilation of U-Pb age, geochemical and isotopic data for granitoid plutons in the southern Central Asian Orogenic Belt (CAOB), enables evaluation of the interaction between magmatism and orogenesis in the context of Paleo-Asian oceanic closure and continental amalgamation. These constraints, in conjunction with other geological evidence, indicate that following consumption of the ocean, collision-related calc-alkaline granitoid and mafic magmatism occurred from 255 ± 2 Ma to 251 ± 2 Ma along the Solonker-Xar Moron suture zone. The linear or belt distribution of end-Permian magmatism is interpreted to have taken place in a setting of final orogenic contraction and weak crustal thickening, probably as a result of slab break-off. Crustal anatexis slightly post-dated the early phase of collision, producing adakite-like granitoids with some S-type granites during the Early-Middle Triassic (ca. 251-245 Ma). Between 235 and 220 Ma, the local tectonic regime switched from compression to extension, most likely caused by regional lithospheric extension and orogenic collapse. Collision-related magmatism from the southern CAOB is thus a prime example of the minor, yet tell-tale linking of magmatism with orogenic contraction and collision in an archipelago-type accretionary orogen

Coordination of Membrane and Actin Cytoskeleton Dynamics during Filopodia Protrusion

Leading edge protrusion of migrating cells involves tightly coordinated changes in the plasma membrane and actin cytoskeleton. It remains unclear whether polymerizing actin filaments push and deform the membrane, or membrane deformation occurs independently and is subsequently stabilized by actin filaments. To address this question, we employed an ability of the membrane-binding I-BAR domain of IRSp53 to uncouple the membrane and actin dynamics and to induce filopodia in expressing cells. Using time-lapse imaging and electron microscopy of IRSp53-I-BAR-expressing B16F1 melanoma cells, we demonstrate that cells are not able to protrude or maintain durable long extensions without actin filaments in their interior, but I-BAR-dependent membrane deformation can create a small and transient space at filopodial tips that is subsequently filled with actin filaments. Moreover, the expressed I-BAR domain forms a submembranous coat that may structurally support these transient actin-free protrusions until they are further stabilized by the actin cytoskeleton. Actin filaments in the I-BAR-induced filopodia, in contrast to normal filopodia, do not have a uniform length, are less abundant, poorly bundled, and display erratic dynamics. Such unconventional structural organization and dynamics of actin in I-BAR-induced filopodia suggests that a typical bundle of parallel actin filaments is not necessary for generation and mechanical support of the highly asymmetric filopodial geometry. Together, our data suggest that actin filaments may not directly drive the protrusion, but only stabilize the space generated by the membrane deformation; yet, such stabilization is necessary for efficient protrusion

Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection

<p>Abstract</p> <p>Background</p> <p>Oral vancomycin (125 mg qid) is recommended as treatment of severe <it>Clostridium difficile </it>infection (CDI). Higher doses (250 or 500 mg qid) are sometimes recommended for patients with very severe CDI, without supporting clinical evidence. We wished to determine to what extent faecal levels of vancomycin vary according to diarrhoea severity and dosage, and whether it is rational to administer high-dose vancomycin to selected patients.</p> <p>Methods</p> <p>We recruited hospitalized adults suspected to have CDI for whom oral vancomycin (125, 250 or 500 mg qid) had been initiated. Faeces were collected up to 3 times/day and levels were measured with the AxSYM fluorescence polarization immunoassay.</p> <p>Results</p> <p>Fifteen patients (9 with confirmed CDI) were treated with oral vancomycin. Patients with ≥4 stools daily presented lower faecal vancomycin levels than those with a lower frequency. Higher doses of oral vancomycin (250 mg or 500 mg qid) led to consistently higher faecal levels (> 2000 mg/L), which were 3 orders of magnitude higher than the MIC₉₀of vancomycin against <it>C. difficile</it>. One patient receiving 125 mg qid had levels below 50 mg/L during the first day of treatment.</p> <p>Conclusions</p> <p>Faecal levels of vancomycin are proportional to the dosage administered and, even in patients with increased stool frequency, much higher than the MIC₉₀. Patients given the standard 125 mg qid dosage might have low faecal levels during the first day of treatment. A loading dose of 250 mg or 500 mg qid during the first 24-48 hours followed by the standard dosage should be evaluated in larger studies, since it might be less disruptive to the colonic flora and save unnecessary costs.</p