Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified ...associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, α-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
Background
Treatment of chronic wounds using traditional surgical procedures is challenging because of the low graft take rates. This study investigated the combination approach of split‐thickness ...autografts with harvested skin cell suspension for chronic wound treatment.
Methods
This randomized clinical trial enrolled patients with chronic wounds between March 2012 and December 2013. Patients who were assigned randomly to the active treatment received a split‐thickness autograft combined with harvested skin cell suspension. Control patients received the split‐thickness autograft alone. The primary outcome was the rate of complete wound closure by postoperative day 28. Analysis was by intention to treat. Patients who achieved wound closure were followed up for a minimum of 6 months to evaluate the quality of healing.
Results
A total of 88 patients were included, 44 in each group. More patients achieved complete wound closure in the skin cell group than in the control group (41 versus 34 patients; P = 0·035). Complete wound closure was observed at a median of 14 (95 per cent c.i. 12·0 to 16·0) days in the skin cell group and 20 (15·7 to 24·3) days in the control group (P = 0·001). The skin cell group had significantly fewer complications (4 versus 11 patients; P = 0·047). The autografted sites displayed better physical attributes and a reduced tendency for wound recurrence in the skin cell group.
Conclusion
Complementary split‐thickness autologous skin grafting with autologous skin cells harvested using ReCell® (Avita Medical, Cambridge, UK) technology improved the healing rate of chronic wounds. Registration number: UMIN000011966 (http://www.umin.ac.jp/ctr).
Adjunct to skin grafting
Origami structures are mechanical metamaterials with properties that arise almost exclusively from the geometry of the constituent folds and the constraint of piecewise isometric deformations. Here ...we characterize the geometry and planar and nonplanar effective elastic response of a simple periodically folded Miura-ori structure, which is composed of identical unit cells of mountain and valley folds with four-coordinated ridges, defined completely by two angles and two lengths. We show that the in-plane and out-of-plane Poisson's ratios are equal in magnitude, but opposite in sign, independent of material properties. Furthermore, we show that effective bending stiffness of the unit cell is singular, allowing us to characterize the two-dimensional deformation of a plate in terms of a one-dimensional theory. Finally, we solve the inverse design problem of determining the geometric parameters for the optimal geometric and mechanical response of these extreme structures.
Subclinical hypothyroidism (SCH) has been shown to be associated with microbiota. However, the association between SCH and oral microbiota has not yet been elucidated. The results of our previous ...clinical studies showed that Prevotella intermedia was abundant in the oral microbiota of SCH patients. This study aimed to investigate the relationship between SCH and oral microbiota, verify the pathogenicity of P. intermedia in SCH, and preliminarily explore the possible mechanism. The SCH mouse model with oral application of P. intermedia was established, and the variance in the mouse oral microbiota and changes in thyroid function and metabolism were detected in mice. Student’s t test and analysis of variance were used for statistical analysis. Oral application of P. intermedia changed the composition of the oral microbiota of SCH mice, which enhanced the damage to the thyroid and decreased the expression of functional genes of the thyroid. Moreover, P. intermedia decreased oxygen consumption and aggravated glucose and lipid metabolism disorders in SCH mice. Glucose tolerance and insulin tolerance decreased, and the triglyceride content of the liver and inflammatory infiltration in adipose tissue increased in SCH mice after P. intermedia stimulation. Mechanistically, P. intermedia increased the proportion of CD4+ T cells in cervical lymph nodes and thyroids in SCH mice. Th1 cells were suggested to play an important role in the pathogenesis of SCH involving P. intermedia. In conclusion, P. intermedia aggravated SCH manifestations, including thyroid dysfunction and glucose and lipid metabolism disorders, by causing immune imbalance in mice. This study sheds new light on the pathogenesis of SCH from the perspective of oral microbiota.
Introduction
Postoperative delirium (POD) is a common complication in elderly surgical patients. Patients undergoing hip fractures surgery who are often characterized by advanced age could be ...particularly prone to suffering POD. We performed a meta-analysis to assess the association between POD and mortality in elderly patients undergoing hip fractures surgery.
Summary
This meta-analysis included twenty-one cohort studies, and the pooled outcomes demonstrated that approximated one-fourth of patients undergoing hipfracture surgery would develop POD, and delirium increased the mortality in these patients.
Methods
We searched PubMed, Embase, Web of Science, and Scopus for studies that investigated the effect of POD on mortality in elderly patients undergoing hip fracture surgery. Two reviewers independently selected studies, assessed quality, and extracted data. Statistical analyses were performed by STATA 14.0 and RevMan 5.3. Risk ratios (RRs) with 95% confidence intervals (CIs) were derived using random or fixed-effects model.
Results
Twenty-one cohort studies enrolling a total of 6288 patients were included, and the pooled prevalence (95% CI) of POD was 28% (23–34%). POD was associated with an increase in perioperative mortality (30-day or in-hospital mortality) 12 studies, 3123 patients, relative risk (RR) (95% CI) 2.79 (1.97–3.93), 6-month mortality 6 studies, 1673 patients, 2.51 (1.99–3.16), 1-year mortality 6 studies, 1896 patients, 1.98 (1.62–2.41), and more than 1-year mortality 8 studies, 1926 patients, 2.06 (1.60–2.64).
Conclusions
Our meta-analysis demonstrated that approximated one-fourth of patients undergoing hip fracture surgery would develop POD, and delirium increased the short-term and long-term mortality in these patients.
A continuous function defined on a closed interval can be of unbounded variation with certain fractal dimension. Fractal interpolation functions are often used to approximate such functions whose ...structure seem self affine. In the present paper, a continuous function with non-integer Box dimension has been approximated by certain linear fractal interpolation functions. Both the original function and the linear fractal interpolation functions have the same Box dimension. The interpolation approximation of integer dimensional continuous functions has also been discussed elementary.
The objective of this study is to examine the trends in body mass index (BMI), waist circumference (WC) and prevalence of overweight (BMI 25–27.49 kg m−2), general obesity (BMI ≥ 27.5 kg m−2) and ...abdominal obesity (WC ≥ 90 cm for men and ≥80 cm for women) among Chinese adults from 1993 to 2009. Data were obtained from the China Health and Nutrition Survey, which was conducted from 1993 to 2009 and included a total of 52,621 Chinese adults. During the period of 1993–2009, mean BMI values increased by 1.6 kg m−2 among men and 0.8 kg m−2 among women; mean WC values increased by 7.0 cm among men and 4.7 cm among women. The prevalence of overweight increased from 8.0 to 17.1% among men (P < 0.001) and from 10.7 to 14.4% among women (P < 0.001); the prevalence of general obesity increased from 2.9 to 11.4% among men (P < 0.001) and from 5.0 to 10.1% among women (P < 0.001); the prevalence of abdominal obesity increased from 8.5 to 27.8% among men (P < 0.001) and from 27.8 to 45.9% among women (P < 0.001). Similar significant trends were observed in nearly all age groups and regions for both men and women. The prevalence of overweight, general obesity and abdominal obesity among Chinese adults has increased greatly during the past 17 years.
Elevated temperature in the machining process is detrimental to cutting tools-a result of the effect of thermal softening and material diffusion. Material diffusion also deteriorates the quality of ...the machined part. Measuring or predicting machining temperatures is important for the optimization of the machining process, but experimental temperature measurement is difficult and inconvenient because of the complex contact phenomena between tools and workpieces, and because of restricted accessibility during the machining process. This paper presents an original analytical model for fast prediction of machining temperatures at two deformation zones in orthogonal cutting, namely the primary shear zone and the tool⁻chip interface. Temperatures were predicted based on a correlation between force and temperature using the mechanics of the cutting process and material constitutive relation. Minimization of the differences between calculated material flow stresses using a mechanics model and a constitutive model yielded an estimate of machining temperatures. Experimental forces, cutting condition parameters, and constitutive model constants were inputs, while machining forces were easily measurable by a piezoelectric dynamometer. Machining temperatures of AISI 1045 steel were predicted under various cutting conditions to demonstrate the predictive capability of each presented model. Close agreements were observed by verifying them against documented values in the literature. The influence of model inputs and computational efficiency were further investigated. The presented model has high computational efficiency that allows real-time prediction and low experimental complexity, considering the easily measurable input variables.
Coronavirus disease of 2019 (COVID-19) has resulted in millions of cases worldwide. As the pandemic has progressed, the understanding of this disease has evolved.
This first in a two-part series on ...COVID-19 updates provides a focused overview of the presentation and evaluation of COVID-19 for emergency clinicians.
COVID-19, caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality worldwide. Several variants exist, including a variant of concern known as Delta (B.1.617.2 lineage) and the Omicron variant (B.1.1.529 lineage). The Delta variant is associated with higher infectivity and poor patient outcomes, and the Omicron variant has resulted in a significant increase in infections. While over 80% of patients experience mild symptoms, a significant proportion can be critically ill, including those who are older and those with comorbidities. Upper respiratory symptoms, fever, and changes in taste/smell remain the most common presenting symptoms. Extrapulmonary complications are numerous and may be severe, including the cardiovascular, neurologic, gastrointestinal, and dermatologic systems. Emergency department evaluation includes focused testing for COVID-19 and assessment of end-organ injury. Imaging may include chest radiography, computed tomography, or ultrasound. Several risk scores may assist in prognostication, including the 4C (Coronavirus Clinical Characterisation Consortium) score, quick COVID Severity Index (qCSI), NEWS2, and the PRIEST score, but these should only supplement and not replace clinical judgment.
This review provides a focused update of the presentation and evaluation of COVID-19 for emergency clinicians.
Summary
Background
Keloid and hypertrophic scar (HS) are two pathological forms of excessive dermal fibrosis, which are due to aberrant wound‐healing responses. Accumulating evidence suggests that ...aberrant activity of growth factors and increased numbers of growth factor receptors play an important role in the formation of pathological scar.
Aim
We examined the expression level of insulin‐like growth factor‐1 receptor (IGF‐IR) in keloid, HS and normal skin.
Methods
IGF‐IR expression was analyzed by immunohistochemistry, real‐time PCR and western blotting on tissues and fibroblasts from 30 patients, comprising 10 patients with keloid and 20 with HS (10 with immature and 10 with mature HS), and from 10 age‐matched and sex‐matched healthy controls.
Results
Immunoreactivity to IGF‐IR was found in dermal fibroblasts of keloid (90%), immature HS, (80%) and mature HS (30%), but not in normal skin. There was no statistically significant difference in immunoreactivity scores between keloid and immature HS, but there was a significant difference (P < 0.01) between mature and immature HS. Real‐time PCR and western blot analysis confirmed that there was high expression of IGF‐IR in keloid and immature HS fibroblasts, but not in mature HS or normal skin fibroblasts. IGF‐IR was expressed in the overlying epidermis, and there was no significant difference between the groups.
Conclusions
IGF‐IR may be involved in the pathogenesis of keloid and HS. Given that IGF‐IR are predominantly expressed on dermal fibroblasts, targeting of IGF‐IR in fibroblasts may be of benefit to prevent scarring.
PDF
