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Teaching urgent situation treatments residents health equity by means of simulation immersion.
Stress fractures occur as a result of microscopic injuries sustained when bone is subjected to repeated submaximal stresses. Overtime, with repeated cycles of loading, accumulation of such injuries can lead to macro-structural failure and frank fracture. There are numerous stress fractures about the foot and ankle of which a trauma and orthopaedic surgeon should be aware. These include metatarsal, tibia, calcaneus, navicular, fibula, talus, medial malleolus, sesamoid, cuneiform and cuboid. Awareness of these fractures is important as the diagnosis is frequently missed and appropriate treatment delayed. Late identification can be associated with protracted pain and disability, and may predispose to non-union and therefore necessitate operative intervention. This article outlines the epidemiology and risk factors, aetiology, presentation and management of the range of stress fractures in the foot and ankle.Due to their ability to knock down the expression of any gene, siRNAs have been heralded as ideal candidates for treating a wide variety of diseases, including those involving "undruggable" targets. However, the therapeutic potential of siRNAs remains severely limited by a lack of effective delivery vehicles. Recently, lipid nanoparticles (LNPs) containing ionizable cationic lipids have been developed for hepatic siRNA delivery. However, their suitability for delivery to other cell types has not been determined. We have modified LNPs for preferential targeting to dendritic cells (DCs), central regulators of immune responses. To achieve directed delivery, we coated LNPs with a single-chain antibody (scFv; DEC-LNPs), specific to murine DEC205, which is highly expressed on distinct DC subsets. Here we show that injection of siRNAs encapsulated in DEC-LNPs are preferentially delivered to DEC205(+) DCs. Gene knockdown following uptake of DEC-LNPs containing siRNAs specific for the costimulatory molecules CD40, CD80, and CD86 dramatically decreases gene expression levels. We demonstrate the functionality of this knockdown with a mixed lymphocyte response (MLR). SHP099 Overall, we report that injection of LNPs modified to restrict their uptake to a distinct cell population can confer profound gene knockdown, sufficient to inhibit powerful immune responses like the MLR.Vectors based on the clade E family member adeno-associated virus (AAV) serotype 8 have shown promise in patients with hemophilia B and have emerged as best in class for human liver gene therapies. We conducted a thorough evaluation of liver-directed gene therapy using vectors based on several natural and engineered capsids including the clade E AAVrh10 and the largely uncharacterized and phylogenically distinct AAV3B. Included in this study was a putatively superior hepatotropic capsid, AAVLK03, which is very similar to AAV3B. Vectors based on these capsids were benchmarked against AAV8 and AAV2 in a number of in vitro and in vivo model systems including C57BL/6 mice, immune-deficient mice that are partially repopulated with human hepatocytes, and nonhuman primates. Our studies in nonhuman primates and human hepatocytes demonstrated high level transduction of the clade E-derived vectors and equally high transduction with vectors based on AAV3B. In contrast to previous reports, AAVLK03 vectors are not superior to either AAV3B or AAV8. link2 Vectors based on AAV3B should be considered for liver-directed gene therapy when administered following, or before, treatment with the serologically distinct clade E vectors.A major unmet clinical need is a universal method for subcellular targeting of bioactive molecules to lysosomes. Delivery to this organelle enables either degradation of oncogenic receptors that are overexpressed in cancers, or release of prodrugs from antibody-drug conjugates. Here, we describe a general method that uses receptor crosslinking to trigger endocytosis and subsequently redirect trafficking of receptorcargo complexes from their expected route, to lysosomes. By incubation of plasma membrane receptors with biotinylated cargo and subsequent addition of streptavidin to crosslink receptorcargo-biotin complexes, we achieved rapid and selective lysosomal targeting of transferrin, an anti-MHC class I antibody, and the clinically approved anti-Her2 antibody trastuzumab. These three protein ligands each target a receptor with a distinct cellular function and intracellular trafficking profile. Importantly, we confirmed that crosslinking of trastuzumab increased lysosomal degradation of its cognate oncogenic receptor Her2 in breast cancer cell lines SKBR3 and BT474. These data suggest that crosslinking could be exploited for a wide range of target receptors, for navigating therapeutics through the endolysosomal pathway, for significant therapeutic benefit.
Diaries written by nurses for the critically ill patient help the relatives cope and support the patient. Relatives may participate in writing a diary for the critically ill and when they do this is appreciated by the patients. However, the relative's perception of writing a diary has not previously been explored.

To explore how relatives perceive writing a diary for the critically ill patient.

In a phenomenological-hermeneutic study building on the theory of Ricoeur interviews with seven relatives were conducted and interpreted.

When relatives wrote a diary for the critically patients, they experienced that writing and reading the diary allowed for the unloading of emotions and expression of feelings. Writing a diary was a meaningful activity while enduring a situation of uncertainty and furthermore it created a distance that allowed understanding of the critical situation.

Involving relatives in writing a diary may support relatives and help them cope with the critical situation.

Relatives are distressed and struggle to understand what is happening during the patient's course of illness. Involving relatives in writing a diary for the critically ill could be one way to meet their needs in the critical situation.
Relatives are distressed and struggle to understand what is happening during the patient's course of illness. Involving relatives in writing a diary for the critically ill could be one way to meet their needs in the critical situation.
To identify cases of severe maternal morbidity (SMM) during pregnancy and childbirth, their characteristics, and to test the feasibility of scaling up World Health Organization criteria for identifying women at risk of a worse outcome.

Multicentre cross-sectional study.

Twenty-seven referral maternity hospitals from all regions of Brazil.

Cases of SMM identified among 82 388 delivering women over a 1-year period.

Prospective surveillance using the World Health Organization's criteria for potentially life-threatening conditions (PLTC) and maternal near-miss (MNM) identified and assessed cases with severe morbidity or death.

Indicators of maternal morbidity and mortality; sociodemographic, clinical and obstetric characteristics; gestational and perinatal outcomes; main causes of morbidity and delays in care.

Among 9555 cases of SMM, there were 140 deaths and 770 cases of MNM. The main determining cause of maternal complication was hypertensive disease. Criteria for MNM conditions were more frequent as the severity of the outcome increased, all combined in over 75% of maternal deaths.

This study identified around 9.5% of MNM or death among all cases developing any severe maternal complication. Multicentre studies on surveillance of SMM, with organised collaboration and adequate study protocols can be successfully implemented, even in low-income and middle-income settings, generating important information on maternal health and care to be used to implement appropriate health policies and interventions.

Surveillance of severe maternal morbidity was proved to be possible in a hospital network in Brazil.
Surveillance of severe maternal morbidity was proved to be possible in a hospital network in Brazil.Nano-sized SAPO-34 zeolites with high crystallinity are obtained in 10 minutes by fast heating the reaction gel in a stainless steel tubular reactor combined with the seed-assisted method, which show outstanding performance in methanol-to-olefin (MTO) reaction.Macrophage activation is one of the major immunological events in the pathogenesis of various diseases. Recent studies have disclosed that complicated mechanisms are involved in macrophage activation and polarization, and many published research articles have been based on the M1/M2 polarization concept. It is considered that M1- and M2-like macrophages are associated with T helper (Th)1-type and Th2-type immune responses, respectively, via several immune mediators. In this article, we summarize the correlations between macrophage polarization and metabolic disorders in both humans and mice and discuss the contribution of macrophage polarization to the pathogenic process of metabolic diseases.
The association between aging and insulin resistance has been unclear. We evaluated the effects of aging on visceral fat area (VFA) and subcutaneous fat area (SFA) measured by computed tomography, homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) among participants in a comprehensive health checkup.

This study included 1,050 male and 700 female Japanese participants aged 35-84 years in our comprehensive health checkup program during a 2-year period. Participants who were on medication for diabetes mellitus or those who met the pre-determined exclusion criteria were excluded. The participants were divided into five groups according to age.

As age increased from Group 1 to Group 5, both VFA and VFA/SFA ratio significantly increased in both male and female participants, whereas log[HOMA-IR] linearly and significantly decreased (p＜0.0001 for each). link3 Body mass index (BMI), waist circumference (WC), and SFA increased with age in female participants but decreased in male participants. Although age was not or only weakly correlated with log[glucose] and log[HbA1c] in both male and female participants, age showed significant negative correlations with log[insulin], log[HOMA-IR], and log[HOMA-β] even after adjusting for BMI and WC (p＜0.0001 for each). Serum high-molecular-weight adiponectin (HMW-ADPN) levels were measured in 114 male and 87 female participants, and log[HMW-ADPN] was negatively correlated with log[HOMA-IR] and positively correlated with age in both male and female participants.

In the present study, both male and female participants showed increases in VFA and VFA/SFA ratio and decreases in insulin, HOMA-IR, and HOMA-β with age.
In the present study, both male and female participants showed increases in VFA and VFA/SFA ratio and decreases in insulin, HOMA-IR, and HOMA-β with age.
In our team, free flap and especially serratus anterior muscle is the first option for the coverage of lower limb post-traumatic defects. For complex tissue loss, it may be advantageous to harvest the free serratus anterior with rib myo-osseous composite flap. We performed 20osteomuscular serratus anterior composite flap between 2008 and 2010.

We retrospectively studied the records of 20patients, by separately analyzing the characteristics of the bone defect and the soft tissue loss. Patients have been recently reviewed by an independent operator. We compared our results to other reconstruction techniques and other similar series reported in the literature.

The average age of our patients was 43years and 11months. In all cases, defect was traumatic. The average follow-up was 5years (4.5 to 5.8). The average flap area was 135cm(2) and the average rib length was 9.21cm. Our microsurgical success rate is 95%. Our global consolidation rate is 82%.

Use of vascularized rib in the treatment of lower limb traumatic defects is rare.
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