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During the past ten years or more, sustainable fashion and slow lifestyle has received a growing amount of attention from design scholars, creative practitioners and fashion brands. In addition to new technologies of material development, the recent incorporation of repair-inspired designs into current fashion practice is also notable. Among the origins of global repair traditions, the Japanese patchwork boro receives a shared interest from a global creative network of fashion designers, textile collectors and artisans in their exploration of sustainable materials and reinvention of ancient craftsmanship. Born from humbleness, boro signifies a class of Japanese textiles that have been extensively mended and patched together by people who could not get or afford proper clothes. The recent resurrection of boro as a style and an eco-friendly fashion statement follows the trend for sustainable design, and also benefits from the recognition of Japanese aesthetics in western fashion and design industries. By investigating the boro-influenced patchwork menswear brand KUON from Japan, this case study acknowledges and exemplifies the historical and contemporary ideological alignment of sustainable fashion with Japanese repair culture, aesthetics and material interpretations. This research considers boro as an alternative solution to the current development of new material technologies, and the discussion of boro offers future possibilities to reimagine the meanings and representations of this traditional repair craft which may inspire creative practitioners to participate and contribute to sustainable fashion design.

Background: Uncontrollable inflammatory response following ectopic engineered cartilage implantation is devastating to the aesthetic and functional outcomes of the recipients. Adipose stem cells (ASCs) have a good immunomodulatory capacity via a paracrine mechanism. However, works of literature are scarce regarding ASC modulation in ectopic engineered cartilage regeneration in vivo. This study aims to explore how ASCs modulate the inflammatory response after engineered cartilage implantation and affect the implants in a nonchondrogenic milieu in large immunocompetent animals. Methods: Porcine engineered elastic cartilages were cultured in vitro for 3 weeks with chondrocyte cell sheeting technology and then assigned into two groups: ASCs and Control (saline injection). All samples (n= 6 per group) were autologously implanted into different subcutaneous pockets, and a single dose of ASCs was injected at three points around the implant. All samples were harvested after 2 weeks in vivo for analysis. Results: In the examination of inflammation, we observed reduced inflammatory cell infiltration and improved M2 macrophage polarization in the implanted engineered cartilage with ASC injection compared to the control. There were also enhanced anti-inflammatory cytokines and reduced proinflammatory cytokines inside and adjacent to the implants, while in serum, there were no significant differences. In the examination of the cartilage quality, there were significant increases in cartilage extracellular matrix and chondrogenic factors, and the elastic cartilage phenotype was maintained compared to control. Conclusion: This study finds that a single dose of ASCs can promote ectopic cartilage regeneration by modulating inflammation and enhancing cartilage matrix synthesis in a porcine model.

Patients with familial hypercholesterolemia (FH) have a markedly increased risk of premature cardiovascular disease. However, there are effective lipid-lowering therapies available to reduce the risk of cardiovascular disease. This makes it important to diagnose these patients. The most cost-effective strategy to diagnose patients with FH is to perform cascade screening. However, cascade screening as part of ordinary healthcare has not been very successful. Thus, there is a need to implement more efficient cascade screening strategies.Cascade screening for FH should be organized at a national level and should be run by dedicated health personnel such as genetic counsellors. As part of a national organization a national registry of patients with FH needs to be established. Moreover, for cascade screening to be effective, diagnosis of FH must be based on identifying the underlying mutation. There should preferably only be one genetics centre in each country for diagnosing FH, and this genetics centre should be an integrated part of the national cascade screening program.Cascade screening for FH is very effective and should be organized at a national level. Even a modest national cascade screening program can result in a large number of patients being identified.

In recent years, new energy vehicles, as a high-tech industry, have developed rapidly. This paper uses “number of new energy project personnel” and “hours of R&D (research and development) personnel” as design indicators to evaluate the investment of innovative talents in enterprises. This paper first introduces the supporting factors of the innovation environment in the input of innovation resources, and conducts research from four perspectives: human resources, innovation R&D, technology acquisition, and environmental support. In the construction of the innovation output index system, this paper outlines that the technological innovation (TI) achievements of enterprises are related to factors such as technological capabilities, profits, and market competitiveness of enterprises. Finally, this paper evaluates it from three aspects: the research and development achievements, the economic benefits obtained and the competitive benefits of the enterprise. The results show that from 2018 to 2022, the average technological innovation efficiency of new energy enterprises is 1.06; TI’s efficiency indicators in the past five years are all above 1, and the overall improvement trend of TI is relatively stable. The new energy vehicle collaborative innovation system constructed in this paper will promote the overall development of the new energy vehicle industry.

Revision operation of the unsatisfactory microtia reconstruction is 1 of the most difficult revision operations in plastic surgery. This study discussed the cases about revision operation of the unsatisfactory or failed ear reconstruction using autologous costal cartilage and residual.A prospectively maintained database of all consecutive patients who underwent secondary total ear reconstruction from 2013 to 2020 was reviewed. Demographic data and outcomes were assessed.Thirty-six patients with microtia met the inclusion criteria. The age of the patients who underwent secondary reconstruction ranged 6 to 56 years. The follow-up duration was from 1 to 8 years. Primary reconstruction using costal cartilage was performed in 34 cases, and Medpor (porous high-density polyethylene) were used in 2 cases. All 36 cases were treated with costal cartilage as the revision. One-stage revision was performed in 27 cases, including scaffold covered by superficial temporal fascia flap in 9 cases, retroauricular fascia flap in 12 cases and superficial temporal plus retroauricular fascia flap in 5 cases. Nine cases were renovated with expanders by stages, of which 8 cases were covered by retroauricular fascia and 1 case was covered by expanded skin flap. Complications occurred in 2 cases, and 1 patient was not satisfied with the partial scaffold repair.The effect of revision operation of ear reconstruction with costal cartilage is satisfactory, and different methods of ear reconstruction are indicated in different operation conditions, and the revision surgery requires adequate preoperative evaluation.Level of Evidence: Level IV, therapeutic study.

Pathological scars are dermal fibroproliferative disorders due to rapid inflammatory response after dermal injury. The altered metabolites could reflect pathophysiological changes directly. However, it has not cleared how the metabolites change scars.To explore new ideas of pathological scars from the altered metabolites by using ultra-performance liquid chromatography coupled to tandem mass spectrometry and identifying the key genes.Keloid (KS, n = 10), hypertrophic scar (HS, n = 10), and normal skin (NS, n = 10) were collected. Ultra-performance liquid chromatography coupled to tandem mass spectrometry was used to identify and characterize metabolites. Differential metabolites were analyzed by orthogonal partial least square discriminant analysis and Student t test. The key pathways were analyzed via Kyoto Encyclopedia of Genes and Genomes, and the related enzymes were verified by real-time Polymerase Chain Reaction, both in tissues and their dermal fibroblasts.Two hundred fourteen metabolites were detected in total, mostly were fatty acids and amino acids. In the KS and NS groups, 65 different metabolites were screened ( P0.05), and the polyunsaturated fatty acids (PUFAs) metabolism and butyric acid in keloid should be concerned. The messenger Ribonucleic Acid expression of fatty acid desaturase 1 and fatty acid desaturase 2, which are the key enzyme of PUFA metabolism, were lower in KS and keloid-derived fibroblasts, P0.05. In HS group, 17 metabolites were significantly different and branched chain amino acids degradation was the key pathway. Moreover, branched chain keto acid dehydrogenase E1 subunit alpha was lower expressed in HS and their fibroblasts compared with NS, P0.05.Polyunsaturated fatty acids and butyric acid may be associated with the generation of keloids. The pathogenesis of hypertrophic scars may be involved in branched chain amino acids degradation, which is worth paying attention to.

This study used aluminum powder as a raw material to fabricate a wick for loop heat pipes by the powder metallurgy method and took advantage of the excellent corrosion resistance, low density and low cost of aluminum. The average pore diameter, porosity and permeability of the aluminum wicks were 9 ?m, 47.65%, and 2.1 ? 10?13 m?2, respectively. Then, to verify the feasibility of the aluminum wick, it was installed into a loop heat pipe to test the heat transfer performance. The experimental results showed that the loop heat pipe could transport a heating load of 130 W with a thermal resistance of 0.04 K/W under horizontal condition. A steady-state loop heat pipe mathematical model was developed, and the numerical results were compared with the experimental data. The results show that the model data are consistent with the experimental data, which means that Al wicks are suitable for use in the case of a high heating load and light weight.

Familial hypercholesterolemia (FH) is a common, inherited disease characterized by high levels of low-density lipoprotein Cholesterol (LDL-C) from birth. Any diseases associated with increased LDL-C levels including atherosclerotic cardiovascular diseases (ASCVDs) would be expected to be overrepresented among FH patients. There are several clinical scoring systems aiming to diagnose FH, however; most individuals who meet the clinical criteria for a FH diagnosis do not have a mutation causing FH. In this review, we aim to summarize the literature on the risk for the various forms of ASCVD in subjects with a proven FH-mutation (FH+). We searched for studies on FH+ and cardiovascular diseases and also included our and other groups published papers on FH + on a wide range of cardiovascular and other diseases of the heart and vessels. FH + patients are at a markedly increased risk of a broad range of ASCVD. Acute myocardial infarction (AMI) is the most common in absolute numbers, but also aortic valve stenosis is by far associated with the highest excess risk. Per thousand patients, we observed 3.6 incident AMI per year compared to 1.9 incident aortic valve stenosis, however, standardized incidence ratio (SIR) for incident AMI was 2.3 compared to 7.9 for incident aortic valve stenosis. Further, occurrence of ischemic stroke seems not to be associated with increased risk in FH+. Clinicians should be aware of the excess risk of almost all kind of ASCVD in FH+, and the neutral risk of stroke need to be studied further in FH + patients. publishedVersion

The wick is the most crucial element of loop heat pipes (LHPs). At present, wick materials are limited to copper, stainless steel, nickel, and so on. Little research has been carried out on new wick materials. This paper reports the fabrication of aluminum wicks and performance tests of LHPs using aluminum wicks. Experimental data show that this LHP is capable of transferring a heating load of 130 W, while the thermal resistance is only approximately 0.04 K/W. Then, the experimental data were compared with those for LHPs using a polytetrafluoroethylene (PTFE) wick. Based on the SIMPLE algorithm, a 2-D unsteady-state heat transfer model and a 2-D steady-state flow model of the wicks are established to analyze the effects of wick material, pore size and porosity on the performance of the evaporator. The experimental data for LHPs with PTFE wicks are from the literature. The simulation results show that a PTFE wick can effectively reduce heat leakage, while an aluminum wick has better temperature uniformity and a lower casing temperature. However, wicks with large porosities have lower flow resistance.

Freeze-drying is an effective method for aortal preservation. However, there are few studies on heat and mass transfer of aortal freeze-drying. In this study, the contactless weighing device was us...

This study was aimed at determining wastewater sewage sludge moisture sorption characteristics using a static gravimetric method at 303 K, 313 K and 323 K. Eleven mathematical models were adopted to simulate the experimental data, and the optimal model was analysed. The indexes included the net isosteric heat of adsorption (qst), differential entropy (△S), spreading pressure (π), net integral enthalpy (qin) and net integral entropy (△Sin) to evaluate the thermodynamic properties of the sludge. The isotherm curves exhibited type II behaviour according to the Brunauer--Emmett--Teller classification. The sorption isotherm fitting showed that the Gugghenheim--Anderson--de Boer model was able to reproduce the equilibrium moisture content evolution with water activity for a moisture range varying from 6% to 89% (0.991

Congenital microtia is a severe physiological defect and is among the most common craniofacial defects. It is characterized by severe auricle dysplasia, external auditory canal atresia or stenosis, and middle ear malformation, though inner ear development is mostly normal with some hearing occurring through bone conduction. Auricular reconstruction is the only treatment for congenital microtia. In this study, the authors integrated messenger ribonucleic acid and mass spectrometry data of cartilage obtained from the affected and unaffected sides of 16 unilateral microtia patients who had undergone ear reconstruction surgery. The authors next performed functional analyses to investigate differences in the proteome of the affected and unaffected ears to elicit molecular pathways involved in microtia pathogenesis. The authors collected 16 pairs samples. Proteomic and transcriptomic analyses identified 47 genes that were differentially expressed in affected and unaffected cartilage. Integrated pathway analysis implicated the involvement of genes related to cell adhesion, extracellular matrix organization, and cell migration in disease progression. Through the integration of gene and protein expression data in human primary chondrocytes, the authors identified molecular markers of microtia progression that were replicated across independent datasets and that have translational potential.

Freeze-drying is one of the most commonly used methods of bacteria preservation. During this process, cryoprotectants can greatly reduce cellular damage. Micromolecular cryoprotectants have been widely adopted but have limited selectivity and protective effects. Therefore, explorations of other types of cryoprotectants are needed. This study aimed to explore the possibility of the macromolecular cryoprotectants and combinations of cryoprotectants to maintain bacterial activity. We found that the survival rate of Lactiplantibacillus plantarum AR113 after freeze-drying was 19% higher in the presence of soy polysaccharides than with trehalose, the best-performing micromolecular cryoprotectant. Moreover, a 90.52% survival rate of L. plantarum WCFS1 was achieved using the composite cryoprotectant containing soy polysaccharide and trehalose, which increased by 31.48 and 36.47% compared with adding solely trehalose or soy polysaccharide, respectively. These results demonstrate that macromolecular and micromolecular cryoprotectants have similar effects, and that combinations of macromolecular and micromolecular cryoprotectants have better protective effects. We further observed that the composite cryoprotectant can increase Lactobacilli survival by improving cell membrane integrity and lactate dehydrogenase activity. Our finding provides a new type of cryoprotectant that is safer and more effective, which can be extensively applied in the relevant food industry.

Background and aims A first-time acute myocardial infarction (AMI) is a severe diagnosis that leads to initiation or intensification of lipid-lowering medication to prevent recurrent events. Individuals with familial hypercholesterolemia (FH) already use high-intensity lipid-lowering medication at the time of an incident AMI due to their diagnosis. Hence, we hypothesized that compared with matched non-FH controls, individuals with genetically verified FH have increased mortality and risk of recurrent AMI after their first event. Methods The study population comprised 4871 persons with genetically verified FH, and 96,251 age and sex matched controls randomly selected from the Norwegian population. Data were obtained from the Cardiovascular Disease in Norway Project, the Norwegian Patient Registry and the Norwegian Cause of Death Registry. Incidence of AMI, all-cause mortality and recurrent AMI after incident AMI were analyzed for the period 2001–2017. Incidence and mortality were compared using hazard ratios (HR) from Cox regression. Risk of recurrent AMI was compared using sub-hazard ratios (SHR) from competing risk regression with death as a competing event. Results We identified 232 individuals with FH and 2118 controls with an incident AMI [HR 2.10 (95% CI 1.83–2.41)]. Among survivors ≥29 days after the incident AMI, both mortality [HR = 1.45 (95% CI: 1.07–1.95)] and recurrent AMI [SHR = 2.53 (95% CI: 1.88–3.41)] were significantly increased among individuals with FH compared with non-FH controls. Conclusions Individuals with FH have increased mortality and increased risk of recurrent AMI after the first AMI event compared with controls. These findings call for intensive follow-up of individuals with FH following an AMI.

Reconstruction of auricular deformities and facial scars after burns is a challenging undertaking for surgeons. Excessive scar tissue, a poor blood supply and the paucity of available skin are all substantial difficulties that should be considered before the operation. Expanded neck flaps provide comparatively larger and thinner flaps for the simultaneous treatment of auricular deformities and facial scars in burn patients. In this article, the authors introduced the use of an expanded neck flap as coverage tissue for ear reconstruction and face resurfacing in 2 burn patients. The operation consisted of 3 stages. In the first stage, the expander was implanted subcutaneously under the skin of the neck to create adequate skin and soft tissue. In the second stage, the expander was removed, and the expanded flap was transferred to cover defects on the auricle and face. The third operation to repair the reconstructed ear and thick flap could be performed according the willingness of the patients and surgeons. Esthetically satisfactory results were achieved in both of the patients. The flaps survived completely, and the skin color, texture, and flexibility were well matched to those of the peripheral tissue. Six months postoperatively, the flaps did not shrink, and subsequent contractures did not recur. Both of the patients experienced high satisfaction, and no adverse effects were detected.

Freeze-drying is an effective method for preservation of aortas. In order to maintain the original properties of aortas, the sublimation drying process requires accurate monitoring. In this study, ...

In this study, the performance of a two-stage compression transcritical cycle with an expander (TCE) and a conventional single-stage compression transcritical cycle with a throttling valve (SCT) using pure CO2 and CO2/ethane (0.78/0.22, mass fraction) azeotropy mixture as a refrigerant in an air-source heat pump water heater (ASHPWH) system is investigated. From the point of the first and second laws of thermodynamics, the theoretical analysis of cycle characteristics based on the two systems with both refrigerants are carried out and compared in detail. The results show that the COP of TCE cycle with CO2 and CO2/ ethane are at least 57.4% and 81.6% higher than those of the SCT cycle under the studied conditions. The main attractiveness of the CO2/ethane azeotropy refrigerant is connected with its lower discharge temperature compared with the pure CO2, which can prolong the compressor lifetime. In addition, the CO2/ethane azeotropy refrigerant can obviously reduce the evaporation temperature, which is conducive to the ASHPWH system in cold region.

Objectives: Ear deformity caused by burns is one of the most difficult types of deformity to treat with plastic surgery, and the reconstruction of burned ears undoubtedly remains a substantial challenge. This study aims to report the therapeutic regime of using a superficial temporal fascial flap to cover the framework in burned ear reconstruction. Methods: Autologous costal cartilage was used to form the ear framework in all of the reconstruction cases. A superficial temporal fascial flap was used as soft tissue to cover the ear scaffold. Results: Five patients with 6 ears were included in our study. The external ear healed well and the location, size, and shape of both ears were generally symmetrical. No complication was observed in any of the patients. Conclusions: The superficial temporal fascial flap is a good choice for covering the autogenous cartilage framework when treating ear deformities after burns.

Due to the low boiling point of organic fluids, the organic Rankine cycle (ORC) is an effective way to improve the recovery efficiency of low-temperature waste heat. An ORC power plant was established with an actual generating capacity of 16.3 kW. As the ORC technology is in the initial stage of commercial application, a technical and economic analysis has been conducted in this paper. Through analysis of each part investment of the power generation plant, it is found that the ORC system part accounts for 61% of the total initial investment, and the larger the power generation scale, the larger the proportion. An economic model has been proposed to study the economic feasibility of low-temperature industrial waste heat conversion in this plant. The influences of the installation of cooling water system, preheater, superheater, loan ratio, interest rate on electricity production cost (EPC) and profit are analyzed. According to the analysis, the lowest EPC of the plant is 0.46 Yuan/(kW • h).

Background This study presents the results of complete excision of giant congenital melanocytic nevi (GCMN) on the auricle, forehead, or periorbital area combined with tissue expansion, and skin graft transplantation performed in two stages based on 10 years of experience. Aims To solve the giant congenital melanocytic nevi on the auricle, forehead, or periorbital area with two-stage operation. Patients/methods A total of 21 patients with GCMN were included in this study. The operation combined tissue expander and skin graft transplantation. Result All GCMNs were successfully and completely excised. No patient in the study group had experienced skin contraction or auricular deformation at 3 years after treatment. Conclusion Two-stage operation is effective for removing GCMN on the auricle or face and can achieve good oncological and cosmetic results.

Pain is a serious problem for patients with leg ulcers. Research mainly focuses on dressing‐related pain; however, chronic background pain may be just as devastating. Our main objective was to describe the prevalence and characteristics of wound‐related background pain in persons with chronic venous leg ulcers. We performed a systematic review to synthesise data from quantitative studies. Studies were eligible if they reported original baseline‐ or cross‐sectional data on background pain in chronic venous leg ulcers. The initial search identified 2454 publications. We included 36 descriptive and effect studies. The pooled prevalence of wound‐related background pain (from 10 studies) was 80% (95% CI 65‐92%). The mean pain intensity score (from 27 studies) was 4 (0‐10 numeric rating scale) (95% CI 3.4‐4.5). Other pain characteristics could not be synthesised. We identified few sufficiently high‐quality studies on prevalence and intensity of wound‐related background pain in patients with chronic venous leg ulcers. Four of five persons experience mild to moderate pain. Because of poor quality of pain assessment and report, we believe that the available research does not provide a sufficiently nuanced understanding of background pain in this patient group.

Aims To describe results from genetic testing for cardiomyopathies in a national laboratory for genetic testing in Norway since 2003. Methods and results Retrospective data collection from the laboratory information management system at Unit for Cardiac and Cardiovascular Genetics, Oslo University hospital. Data from 4408 probands and 3008 relatives were available. Three probands had two variants, nine had incidental findings of variants not related to their cardiomyopathy diagnosis. Of the remaining 4396 probands, 65.1% were males, age at genetic testing was 50.9 (±18.1) years and 6.1% were under the age of 18. A likely pathogenic or pathogenic variant (216 different variants including 67 novel) was detected in 574 probands, corresponding to a hit-rate of genetic testing of 13.1% in total, 11.9% in hypertrophic, 14.1% in dilated, and 14.9% in arrhythmogenic right ventricular cardiomyopathy. Of the 3008 relatives, 47.6 % were males, age at genetic testing was 39.3 (±20.5) years, 17.9% were under the age of 18, and 43.2% were positive for the variant found in their family. Probands and relatives combined, 1/2809 persons in Norway were found to be heterozygous for a cardiomyopathy variant. Next Generation Sequencing provided more findings in dilated cardiomyopathy, especially in TTN accounting for 44.2% of all variants. Otherwise, the majority of variants were found in the classical sarcomeric and desmosomal genes. Conclusion Genetic testing provided a genetic basis of the cardiomyopathy in 13.1% of probands, and subsequent family testing identified almost three times as many variant-positive relatives which could be offered preventive follow-up.

Background and aims Individuals with familial hypercholesterolemia (FH), causing severely elevated LDL-C, are expected to have a higher risk of ischemic stroke. The risk of hemorrhagic stroke and impact of statin use are, however, not known. We aimed to investigate the risk of incident total, ischemic and hemorrhagic stroke in individuals with FH compared to controls, and to explore the association between cumulative statin use and risk of total stroke in FH. Methods This prospective cohort study consists of 4186 individuals with genetically verified FH and 82 180 age and sex matched controls followed from 2008 to 2018 for incident stroke. Daily defined doses (DDD) described cumulative statin exposure: 0–5000 DDD (“low”), 5000–10,000 DDD (“intermediate”), and >10 000 DDD (“high”). Results were presented as hazard ratio (95% CI) derived from Cox proportional hazards models. Results Individuals with FH did not have a higher risk of total stroke (1.16 (0.95–1.43) nor ischemic stroke (1.11 (0.88–1.38). Excess risk of hemorrhagic stroke was observed (1.63 (1.07, 2.48) but attenuated after adjusting for antithrombotic medication (1.25 (0.81, 1.93). Among individuals with FH, there was no association between statin use and total stroke for intermediate vs. low DDD [0.69 (0.32, 1.48)] or for high vs. low DDD [0.83 (0.41, 1.67)]. Conclusions No significant excess risk of incident total and ischemic stroke in FH, and no difference in total stroke risk among the FH population with low, intermediate, and high statin exposure were observed. The observed relationship between FH and hemorrhagic stroke was no longer significant after adjusting for use of anti-thrombotic medication. publishedVersion

This exploratory descriptive study aimed to describe characteristics and management of background pain related to chronic leg ulcers. A total of 121 participants were recruited from two wound care clinics using a consecutive sampling method. Data were obtained through screening interview, clinical examination, and questionnaires. The mean average background pain intensity was 4.5 (SD 2.56) (CI 95% 4.0-5.0). Pain interfered mostly with general activity (mean 4.3), sleep (mean 4.1), and walking ability (mean 4.0) (0-10 NRS). The most frequently reported descriptors of background pain were ‘tender’, ‘stabbing’, ‘aching’, and ‘hot-burning’. Most of the participants stated that the pain was intermittent. Less than 60% had analgesics prescribed specifically for ulcer related pain, and the respondents reported that pain management provided a mean pain relief of 45.9% (SD 33.9, range 0-100). The findings indicate that ulcer related background pain is a significant problem that interferes with daily function, and that pain management in wound care is still inadequate.

In this paper, a thin film evaporation model that includes expressions for energy, mass, and momentum conservation was established through the augmented Young–Laplace model. Based on this model, the effects of pore size and superheating on heat transfer during thin film evaporation were analyzed. The influence of the wick diameter of the loop heat pipe (LHP) on the critical heat flux of the evaporator is analyzed theoretically. The results show that pore size and superheating mainly influence evaporation through changes in the length of the transition film and intrinsic meniscus. The contribution of the transition film area is mainly reflected in the heat transfer coefficient, and the contribution of the intrinsic meniscus area is mainly apparent in the quantity of heat that is transferred. When an LHP evaporator is operating in a state of surface evaporation, a higher heat transfer coefficient can be achieved using a smaller pore size.

Lysosomal acid lipase (LAL) plays an important role in lipid metabolism by performing hydrolysis of triglycerides and cholesteryl esters in the lysosome. Based upon characteristics of LAL purified from human liver, it has been proposed that LAL is a proprotein with a 55 residue propeptide that may be essential for proper folding, intracellular transport, or enzymatic function. However, the biological significance of such a propeptide has not been fully elucidated. In this study, we have performed a series of studies in cultured HepG2 and HeLa cells to determine the role of the putative propeptide. However, by Western blot analysis and subcellular fractionation, we have not been able to identify a cleaved LAL lacking the N-terminal 55 residues. Moreover, mutating residues surrounding the putative cleavage site at Lys76 ↓ in order to disrupt a proteinase recognition sequence, did not affect LAL activity. Furthermore, forcing cleavage at Lys76 ↓ by introducing the optimal furin cleavage site RRRR↓EL between residues 76 and 77, did not affect LAL activity. These data, in addition to bioinformatics analyses, indicate that LAL is not a proprotein. Thus, it is possible that the previously reported cleavage at Lys76 ↓ could have resulted from exposure to proteolytic enzymes during the multistep purification procedure.

The cell-surface low-density lipoprotein receptor (LDLR) internalizes low-density lipoprotein (LDL) by receptor-mediated endocytosis and plays a key role in the regulation of plasma cholesterol levels. The ligand-binding domain of the LDLR contains seven ligand-binding repeats of approximately 40 residues each. Between ligand-binding repeats 4 and 5, there is a 10-residue linker region that is subject to enzymatic cleavage. The cleaved LDLR is unable to bind LDL. In this study, we have screened a series of enzyme inhibitors in order to identify the enzyme that cleaves the linker region. These studies have identified bone morphogenetic protein 1 (BMP1) as being the cleavage enzyme. This conclusion is based upon the use of the specific BMP1 inhibitor UK 383367, silencing of the BMP1 gene by the use of siRNA or CRISPR/Cas9 technology and overexpression of wild-type BMP1 or the loss-of-function mutant E214A-BMP1. We have also shown that the propeptide of BMP1 has to be cleaved at RSRR120↓ by furin-like proprotein convertases for BMP1 to have an activity towards the LDLR. Targeting BMP1 could represent a novel strategy to increase the number of functioning LDLRs in order to lower plasma LDL cholesterol levels. However, a concern by using BMP1 inhibitors as cholesterol-lowering drugs could be the risk of side effects based on the important role of BMP1 in collagen assembly.

In this paper, the azeotropic mixture of CO2/R170 (0.78/0.22, mass fraction) is presented as a refrigerant to replace R134a in an ASHPWH system. On the basis of the first and second laws of thermodynamics, system performance and the exergy efficiency analysis are carried out for the system using both refrigerants. The results show that both the COPheat (coefficient of heating performance) and exergy efficiency of the system using the CO2/R170 mixture refrigerant are higher than that using the R134a, and the values can be increased by 31.3% and 30.6%, respectively. Moreover, the compressor discharge temperature for CO2/R170 is about 34.3–49.8 °C lower and the compression ratio of compressor also has a significant reduction (from 12.0417 to 3.2734), which leads to a higher lifetime for the compressors. So, the CO2/R170 mixture may be a good choice to substitute for R134a in ASHPWH systems. Also, a CO2/R170 ASHPWH system may be more suitable in cold region.

Hepatic hemangioma is common among benign liver tumors and usually grows slowly. About 50-70% of hepatic hemangiomas are asymptomatic, and management is not necessary; however, management should be considered in symptomatic patients. The optimal management of symptomatic hepatic hemangioma depends on multiple factors. Invasive management of symptomatic hepatic hemangioma mainly consists of surgery and interventional radiology, including transarterial embolization, ablation, percutaneous sclerotherapy, and percutaneous argon-helium cryotherapy. Although both surgery and interventional radiology are promising in the management of symptomatic hepatic hemangioma, multiple and/or giant hemangiomas represent a clinical dilemma because the complication rate and recurrence rate are relatively high, and symptom relief is not always achieved. However, a review of recent advances in treatment is lacking. We therefore summarized the current invasive management techniques for symptomatic hepatic hemangioma to potentially facilitate clinical decision-making.

The presence of bubbles exerts a strong influence on pressure drop, heat transfer, flow pattern, and many other flow characteristics. Due to the complexity of two-phase flow boiling, it is not easy to carry out experimental research. An experimental setup based on ultrasonic detection method is built up in this paper. The present study investigates bubble size distribution and vapor quality in liquid-gas two-phase flow in a vertical narrow channel with the cross section of 3×20 mm. Bubble size distribution is heavily affected by the heat power and mass flux, which means that different flow patterns show different bubble size distributions. Vapor quality is also obtained by the ultrasonic attenuation method, which is compared to the theoretical calculation. The ultrasonic detection model is mainly applied in the bubble-coalesced flow. As the vapor quality is small, the detection value is close to the theoretical value, and this detection model is suitable for nucleate boiling. As the vapor quality is increased, the deviation is larger. By comparison with the theoretical calculations, it is necessary to modify the ultrasonic detection model to fit different flow patterns, which is helpful to study the liquid entrainment mechanism in the micro-channel (especially when the inner diameter is less than 5 mm) in the future.

Hong Qu Huangjiu (HQW) is distinguished by its inclusion of Monascus pigments, meaning that photosensitivity strongly affects the sensory quality of the wine. In this study, the effects of Flos sophorae immaturus (FSI) on the stability of Monascus pigments, the flavor profiles, and the sensory characteristics of HQW were investigated. After sterilization, the addition of FSI increased the preservation rate of Monascus pigments in HQW by up to 93.20%, which could be accounted for by the synergy of rutin and quercetin in FSI. The total content of the volatile flavor compounds in HQW increased significantly as the added amounts of FSI were increased, especially 3-methyl-1-butanol, 2-methyl-1-propanol, and short-chain fatty acid ethyl esters (SCFAEE). Sensory evaluation and partial least-squares regression revealed that the concentration of FSI significantly affected the aroma characteristics of HQW but had little effect on the mouthfeel. The addition of 0.9 mg/mL FSI yielded a satisfactory HQW with high scores in terms of mouthfeel and aroma. The strong correlation between fruit-aroma, full-body, and SCFAEE suggests that FSI might alter the aroma of HQW by enhancing the synthesis of SCFAEE. Summarily, treatment with FSI represents a new strategy for improving the stability of photosensitive pigments and thus adjusting the aroma of HQW or similar beverages.

Background The most cost-effective strategy to diagnose patients with autosomal dominant hypercholesterolemia (ADH) is to perform cascade genetic screening. Objective To present the cascade genetic screening program for ADH in Norway. Methods A national cascade genetic screening program for ADH in Norway has been operating at Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital for twenty years. This program has been run by just one genetic counsellor. We now present the main findings of this cascade genetic screening program. Results After genetic counselling, 8182 at-risk relatives have consented to genetic testing for the mutation that causes ADH in the family. Of these, 3076 (37.6%) relatives have tested positive. Among mutation-positive relatives 31.3% were on lipid-lowering therapy at the time of genetic testing. However, only 9.8% of these relatives had a value for low density lipoprotein (LDL) cholesterol below 2.5 mmol/l (97 mg/dl). At follow-up six months after genetic testing, reductions in the levels of total serum cholesterol and LDL cholesterol of 12% and 17%, respectively were observed. A total of 8811 ADH heterozygotes have been diagnosed in Norway. Thus, the number of patients diagnosed by this modest cascade genetic screening program constitutes 35% of all Norwegian ADH patients provided with a molecular genetic diagnosis. Conclusion Cascade genetic screening for ADH is very effective and should be organized at a national level. Even a modest cascade genetic screening program with small resources, can result in a large number of patients being identified.

BACKGROUND The period of regular contractions before 4 cm of cervical dilatation is often referred to as the latent phase or early labor. Women find it challenging to prepare for and cope with this phase of labor, and easily accessed web-based information from reliable sources may be useful in this preparation. OBJECTIVE The aim of this study is to describe the development of a Norwegian website, Latens.no, for people seeking information on early labor and to explore users’ experiences with the website to increase its user-friendliness. METHODS We developed a website using an iterative process involving a multidisciplinary research team, health personnel, users, a graphic designer, and an expert in software development. We explored the website’s user-friendliness using semistructured individual interviews and the think-aloud method. All interviews were audio recorded and transcribed. We then analyzed the participants’ feedback on the website. RESULTS Participants included women who had recently given birth to their first baby (n=2), women who were pregnant with their first baby (n=4), and their partners (n=2). Results from participants’ experiences completing tasks included positive feedback related to the content of Latens.no, positive feedback related to the website’s design, and suggestions for improvement. Participants wanted to find information on early labor on the internet. Moreover, they found the information on the website relevant, trustworthy, and easy to read, and the design was attractive and easy to use. Overall, the participants performed the tasks easily, with few clicks and minimal effort. CONCLUSIONS The think-aloud method, while performing tasks, allowed for detailed feedback. The participants confirmed the user-friendliness of the website but at the same time provided information enabling improvement. We expect that changes made based on this user-centered design study will further increase the usability and acceptability of Latens.no. CLINICALTRIAL

Hong Qu Huangjiu (HQW) is distinguished by its inclusion of Monascus pigments, meaning that photosensitivity strongly affects the sensory quality of the wine. In this study, the effects of Flos sophorae immaturus (FSI) on the stability of Monascus pigments, the flavor profiles, and the sensory characteristics of HQW were investigated. After sterilization, the addition of FSI increased the preservation rate of Monascus pigments in HQW by up to 93.20%, which could be accounted for by the synergy of rutin and quercetin in FSI. The total content of the volatile flavor compounds in HQW increased significantly as the added amounts of FSI were increased, especially 3-methyl-1-butanol, 2-methyl-1-propanol, and short-chain fatty acid ethyl esters (SCFAEE). Sensory evaluation and partial least-squares regression revealed that the concentration of FSI significantly affected the aroma characteristics of HQW but had little effect on the mouthfeel. The addition of 0.9 mg/mL FSI yielded a satisfactory HQW with high scores in terms of mouthfeel and aroma. The strong correlation between fruit-aroma, full-body, and SCFAEE suggests that FSI might alter the aroma of HQW by enhancing the synthesis of SCFAEE. Summarily, treatment with FSI represents a new strategy for improving the stability of photosensitive pigments and thus adjusting the aroma of HQW or similar beverages.

Background and aims In this study, we present the status regarding molecular genetic testing for mutations in the genes encoding the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) as causes of autosomal dominant hypercholesterolemia (ADH) in Norway. Methods We have extracted data from the laboratory information management system at Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital for the period 1993–2020. This laboratory is the sole laboratory performing molecular genetic testing for ADH in Norway. Results A total of 29,449 unrelated hypercholesterolemic patients have been screened for mutations in the LDLR gene, in the APOB gene and in the PCSK9 gene. Of these, 2818 (9.6%) were heterozygotes and 11 were homozygotes or compound heterozygotes. Most of the 264 different mutations identified were found in the LDLR gene. Only two and three mutations were found in the APOB gene or in the PCSK9 gene, respectively. Several founder mutations were identified. After testing of 14,230 family members, a total of 8811 heterozygous patients have been identified. Of these, 94.0% had a mutation in the LDLR gene, 5.4% had a mutation in the APOB gene and 0.6% had a mutation in the PCSK9 gene. Conclusions A large proportion of Norwegian ADH patients have been provided with a molecular genetic diagnosis. Norway is probably only second to the Netherlands in this respect. A molecular genetic diagnosis may form the basis for starting proper preventive measures and for identifying affected family members by cascade genetic screening.

Background The clinical features of keloids consist of aberrant proliferation, secretion, differentiation and apoptosis of keloid dermis-derived fibroblasts (KFBs). Notably, the apoptosis rate of KFBs is lower than the proliferation rate. Though the anti-fibrotic effect of adipose-derived stem cells (ADSCs) on keloids has become a hot topic of research, the exact anti-fibrotic mechanism of the paracrine effect remains unclear. This study aimed to find out how the conditioned medium of ADSCs (ADSC-CM) exerts an anti-fibrotic effect in KFBs. Methods KFBs and ADSCs were extracted and cultured. Then, ADSC-CM was prepared. Whether ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8, an 5-Ethynyl-2-deoxyuridine (Edu) kit and flow cytometry. The expressions of cyclooxygenase-1 (COX-1), COX-2, caspase 3 and B-cell lymphoma-2 (Bcl-2) in ADSC-CM-cultured KFBs were tested by real-time PCR and western blotting. To clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis, a specific COX-2 inhibitor, celecoxib, was applied to KFBs cultured in ADSC-CM. Moreover, we tested the production of arachidonic acid (AA) and prostaglandin E2 (PGE2) by ELISA. Then, we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in vivo. Results The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly increased. Caspase 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured KFBs. Furthermore, ADSC-CM strikingly elevated COX-2 mRNA and protein expressions, but COX-1 expression was unaltered. COX-2 inhibitors reduced ADSC-CM-induced apoptosis. Additionally, COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 expression. ADSC-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 inhibition. In the nude mouse model, expressions of AA, COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injection than in the controls. Conclusions We showed activation of the COX-2/PGE2 cascade in KFBs in response to ADSC-CM. By employing a specific COX-2 inhibitor, COX-2/PGE2 cascade activation played a crucial role in mediating the ADSC-CM-induced KFB apoptosis and anti-proliferation effects.

Background Recent evidence suggests that an implantable cardioverter defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit. We aimed to investigate if etiology of heart failure and strain echocardiography can improve risk stratification of life threatening ventricular arrhythmia (VA) in heart failure patients. Methods This prospective multi-center follow-up study consecutively included NICM and ischemic cardiomyopathy (ICM) patients with left ventricular ejection fraction (LVEF) 70 ms had highest VA incidence with an event rate of 16%/year. Conclusion Patients with NICM and normal MD had low arrhythmic event rate, comparable to the general population. Patients with ICM and MD >70 ms had the highest risk of VA. Combining heart failure etiology and strain echocardiography may classify heart failure patients in low, intermediate and high risk of VA and thereby aid ICD decision strategies.

Importance Hypercholesterolemia, which is a cardiovascular risk factor, may also be associated with dementia risk. The benefit of statin treatment on dementia risk is controversial. Objective To determine whether individuals with familial hypercholesterolemia (FH), who have been exposed to lifelong hypercholesterolemia, have an excess risk of dementia and whether statin use is associated with dementia risk. Design, Setting, and Participants This was a prospective cohort study performed from 2008 to 2018 in Norway. Statistical analysis was performed from January 2021 to February 2022. This study included individuals with genetically verified FH and age-matched and sex-matched controls obtained from the general Norwegian population. Exposures Dementia was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-03 and G30. Main Outcomes and Measures Incident cases of total dementia, vascular dementia, Alzheimer disease–dementia in Alzheimer disease, and data on lipid-lowering medication were obtained from the Norwegian Patient Registry, Cause of Death Registry, and the Norwegian Prescription Database. Hazard ratios (HRs) for risk of dementia for individuals with FH vs matched controls were calculated using Cox regression. The cumulative sum of defined daily doses (DDDs) of statins prescribed during study follow-up was calculated for individuals with FH and was analyzed as a time-varying covariate with 3 levels: 1 to 4999 DDDs, 5000 to 10 000 DDDs, and more than 10 000 DDDs. Results Among the 3520 individuals with FH (1863 women [52.9%]; mean [SD] age at the start of follow-up, 51.8 [11.5] years) and the 69 713 controls (36 958 women [53.0%]; mean [SD] age at the start of follow-up, 51.7 [11.5] years), 62 patients with FH (39 women [62.9%]) and 1294 controls (801 women [61.9%]) had developed dementia over the course of 10 years of follow-up. Most dementia cases occurred among individuals aged 70 years and older (39 patients with FH [62.9%] and 870 patients [67.2%] in the control group). We found no excess risk of dementia in patients with FH vs matched controls (HR for total dementia, 0.9; 95% CI, 0.7-1.2). There was no association between cumulative DDDs of statins and total dementia in patients with FH with HRs of 1.2 (95% CI, 0.4-3.8) for cumulative DDDs of 5000 to 10 000 and 1.9 (95% CI, 0.7-5.0) for cumulative DDDs greater than 10 000. Conclusions and Relevance These findings suggest that individuals with FH have no excess risk of dementia compared with age-matched and sex-matched controls and that there is no association between use of statins and risk of dementia in patients with FH. publishedVersion

Background:The objective of this study was to delineate the characteristics and incidence of congenital heart disease (CHD) in patients with isolated microtia and to determine whether the prevalence of CHD among patients with isolated microtia increases with the severity of microtia.Methods:A total of 804 consecutive patients had a pre-operative colour Doppler echocardiographic examination. A retrospective study was performed with the clinical and imaging data from November, 2017 to January, 2019. The χ2 test was performed to analyse the interaction between isolated microtia and CHD.Results:With the colour Doppler echocardiographic examination’s data from 804 consecutive isolated microtia patients, we found CHD, including atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus, and others, occurred in 52 of 804 patients (6.5%). Atrial septal defect prevalence in patients with isolated microtia was significantly higher than ventricular septal defect (24/804 versus 11/804, p < 0.05) and patent ductus arteriosus (24/804 versus 2/804, p < 0.001). Ventricular septal defect prevalence in patients with isolated microtia was significantly higher than patent ductus arteriosus (11/804 versus 2/804, p < 0.05). All four types of microtia (concha-type microtia, small concha-type microtia, lobule-type microtia, and anotia) had similar incidences of CHD with no difference in the incidences among these types (p > 0.05 respectively). Furthermore, there was no significant difference in the incidence of the atrial septal defect among the four subtypes (p > 0.05 respectively). Similarly, ventricular septal defect and patent ductus arteriosus also showed no differences (p > 0.05 respectively).Conclusions:The overall incidences of CHD and three most common CHD subtypes (atrial septal defect, ventricular septal defect, and patent ductus arteriosus) in patients with isolated microtia are higher than general population. The prevalence of CHD among patients with isolated microtia does not increase with the severity of microtia. According to our experience in this study, we suggest colour Doppler echocardiographic imaging should be performed for isolated microtia patients soon after birth if possible. Furthermore, for the plastic surgeon and anaesthesiologist, it is important to take pre-operative colour Doppler echocardiographic images which can help evaluate heart function to ensure the safety of the peri-operative period. Future studies when investigating CHDs associated with isolated microtia could focus on genetic and molecular mechanisms.

Introduction: During the last 30 years, treatment of familial hypercholesterolemia (FH) has been revolutionized, but it is not known if both sexes equally benefit in these advances, and whether this could have affected the sex difference in risk of coronary heart disease (CHD). We aimed to study sex difference in the risk of CHD between men and women with FH compared to non-FH men and women. Methods: We obtained data on CHD hospitalization and death from Norwegian health registries in 4,525 individuals diagnosed with FH between 1992 and 2014 and an age and sex matched control population of 88,892. The sex distribution was about 50/50 between women and men, and the mean age at start of follow-up was 36 years. Results: The cumulative incidence of CHD (FH vs. non-FH controls) in women and men are shown in Figure 1 with a clear increased risk in FH compared to controls. The cumulative incidence starts to increase at a younger age in men compared with women, both in FH and non-FH controls. This corresponds to an age adjusted 2.6-fold higher risk of CHD in men compared with women in both the FH and control population. In the FH population, men aged 20-39 years had a hazard ratio (HR) of 5.3 (95% CI: 2.6-10.9) compared with women, whereas the corresponding HR between women and men in non-FH controls was 3.7 (95% CI: 2.6-5.3). There was no significant interaction between sex and FH status, indicating that the excess risk in men was similar in FH and non-FH controls. Stratified by sex and adjusted for age, we found that both men and women with FH had a 2-fold higher risk of CHD than controls. The highest excess risk was observed in ages 20-30 years with a of HR= 4.5 (95% CI: 2.2-9.2) and a HR of= 5.5 (95%CI: 4.60-9.34) in women and men, respectively. Conclusions: The risk of CHD among individuals with FH was higher in men than in women in all age groups presented, with no differences between the FH sample and the non-FH controls. However, the relative risk in FH compared with controls was similar for both sexes.