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Embedded 3D printing processes involve extruding ink within a support matrix that supports the ink throughout printing and curing. In once class of embedded 3D printing, which we refer to as "removable embedded 3D printing," curable inks are printed, cured, then removed from the uncured support matrix. Removable embedded 3D printing is advantageous because low-viscosity inks can be patterned in freeform geometries which may not be feasible to create via casting and other printing processes. When printing solid-infill geometries, however, uncured support matrix becomes trapped within the prints, which may be undesirable. This study builds on previous work by formulating a support matrix for removable embedded 3D printing that cures when mixed with the printed silicone ink to solve the problem of trapped, uncured support matrix within solid-infill prints. Printed specimens are shown to have a nearly isotropic elastic modulus in directions perpendicular and parallel to the printed layers, and a decreased modulus and increased elongation at break compared to specimens cast from the ink. The rheological properties of the support matrix are reported. The capabilities of the printer and support matrix are demonstrated by printing a variety of geometries from four UV and addition-cure silicone inks. Shapes printed with these inks range by nearly two orders of magnitude in stiffness and have failure strains between approximately 50 and 250%, suggesting a wide range of potential applications for this printing process.Production-volume and cost requirements currently limit machine tool manufacturers' ability to produce application-specific tooling with traditional methods, motivating the development of innovative manufacturing technologies. To this end, we detail a manufacturing framework for the design and production of application-specific cutting tools based on industry standard tungsten carbide-cobalt (WC-Co)-based "carbide" cutting materials using additive manufacturing (AM). Herein, novel diamond-reinforced carbide structures were designed and manufactured via AM and subsequently tested in comparison to current commercial products that are traditionally-processed. The resulting diamond-reinforced composites were free from large scale cracking and maintained microstructures with multiple reinforcing phases. Diamond incorporation had a remarkable effect on the processing, microstructure, and machining performance of the WC-Co based material in comparison to a commercial carbide cutting tool of similar composition as well as the base WC-Co matrix. Detailed microstructure and phase analysis, as well as machining experiments, demonstrate the ability to exploit laser-based directed energy deposition (DED)-based AM to create multifunctional cutting tools that can be designed to meet ever-increasing manufacturing demands across many industries.As the epidemic of coronavirus disease (COVID-19) has spread rapidly, health organizations around the world has made wearing face mask obligatory to prevent the spread of the infections for the wellness of the society. As wearing face masks become a daily routine, the usage of cloth facemasks from textile fabric, is popular among the public. Since antiquity, textiles have been proven to be intertwined with human lives and the integrant of these crucial materials are fibers. Particularly, nanofiber fabrics manufactured by electrospinning have attracted attention, owing to the better filtration efficiency and breathability. In addition, the electrospinning process provide opportunities to fine tuning of the surface functionality through polymer chemistry and an encapsulation of bioactive agents in single step process. This review opens up a new horizon in possible textile applications especially, an active layer of bioactive agent (Curcumin and Moringa) loaded nanofibrous fabrics-based facemasks for day to day life.

Pain spans a broad spectrum of diseases and types that are highly prevalent and cause substantial disease burden for individuals and society. Up to 40% of people affected by pain receive no or inadequate treatment. Providing a scalable, time-, and location-independent way for pain diagnostic, management, prevention and treatment mobile health applications (MHA) might be a promising approach to improve health care for pain. However, the commercial app market is rapidly growing and unregulated, resulting in an opaque market. Studies investigating the content, privacy and security features, quality and scientific evidence of the available apps are highly needed, to guide patients and clinicians to high quality MHA.Contributing to this challenge, the present study investigates the content, quality, and privacy features of pain apps available in the European app stores.

An automated search engine was used to identify pain apps in the European Google Play and Apple App store. Pain apps were screened and checkedivacy issues, posing a potential threat to users. Further research on evidence and improvements privacy and security are needed. Overall, the potential of pain apps is not exploited.

A multitude of pain apps is available. Most MHA lack scientific evaluation and have serious privacy issues, posing a potential threat to users. Further research on evidence and improvements privacy and security are needed. Overall, the potential of pain apps is not exploited.Depression is highly prevalent among university students. Internet-based interventions have been found to be effective in addressing depressive symptoms, but it is open if this also applies to interventions directed at academic stress. It is also largely unclear if the techniques employed in such programs provide significant additional benefits when controlling for non-specific intervention effects. A sample of N = 200 students with elevated levels of depression (CES-D ≥ 16) of a large distance-learning university were randomly assigned to either an Internet- and App-based stress intervention group (IG; n = 100) or an active control group (CG; n = 100) receiving an Internet-based psychoeducational program of equal length. Self-report data was assessed at baseline, post-treatment (7 weeks) and three-month follow-up. The primary outcome was depression (CES-D) post-treatment. Secondary outcomes included mental health outcomes, modifiable risk factors, and academic outcomes. We found significant between-group eff11800 (https//www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011800).In many regulated industries there is an increasing pressure to provide timely and robust risk assessment data to support product launches. Real-time cell analysis (RTCA) is a tool that allows for the fast and relatively labour-free cytotoxic assessment of test compounds, compared to traditional methods. Here, we propose an application for the RTCA platform to provide a screening approach, to evaluate the cytotoxic potential of tobacco-free nicotine pouches, also termed modern oral product (MOP), to determine the contribution of differing nicotine strengths (4-11 mg) and a range of available flavour types from multiple markets, on overall product toxicity. Aqueous extracts were prepared for all products using 1 pouch in 20 mL cell culture media and applied to the cell system for 24 h. Test extract nicotine concentrations reflected the increases in product nicotine strength; however, these changes were not present in the same magnitude in the cytotoxicity data obtained from both primary human gingival fibroblasts (HGF) and an NCI-H292 human bronchial epithelial continuous cell line. Furthermore, across the range of flavours and product nicotine strengths tested, H292 cells whilst not the target organ for oral product use, accurately predicted the results seen in HGFs and could be considered a useful surrogate for fast screening studies. H292 cells are more easily cultured and for longer periods, offering a more compatible test system. In conclusion, the data demonstrate the utility of the RTCA platform for the quick assessment of a large range of product variants. Furthermore, for a cytotoxicity measure with this test product, the simple H292 cell line can predict outcomes in the more complex HGF and provide useful pre-clinical cytotoxicity screening data to inform the risk assessment of MOPs and the relative contribution of flavourings, nicotine and other components.

Wounds with embedded metal fragments are an unfortunate consequence of armed conflicts. In many cases the exact identity of the metal(s) and their long-term health effects, especially on the kidney, are not known.

The aim of this study was to quantitate the urinary levels of metals solubilized from surgically implanted metal pellets and to assess the effect of these metals on the kidney using a battery of biomarker assays.

Using a rodent model system developed in our Institute to simulate embedded fragment injuries, eight metals considered likely components of an embedded fragment wound were individually implanted into the gastrocnemius muscle of male Sprague-Dawley rats. The rats were followed for 12 months post-implantation with urine collected prior to surgery then at 1-, 3-, 6-, 9-, and 12-months post-implantation to provide a within-subjects cohort for examination. Urinary metal levels were determined using inductively coupled plasma-mass spectrometry and urinary biomarkers assessed using commercial fragment wounds.

This study showed that metal pellets surgically implanted into the leg muscle of Sprague-Dawley rats rapidly solubilized with significant levels of the implanted metal found in the urine. Although kidney biomarker results were inconsistent, the changes observed along with the relatively low amounts of metal implanted, suggest that metal-induced renal effects need to be considered when caring for individuals with embedded metal fragment wounds.The electronic cigarettes mimic combustible cigarettes through a heating technology that vaporizes a refill liquid consisting of solvents, flavors, and nicotine. E-cigarettes are sometimes still used as a support for smoking cessation, even if in 2019 an acute lung injury outbreak occurred in the USA, affecting mainly adolescents and young adults, and was correlated to eCigs. Therefore, due to the lack of a definite knowledge about the mechanism(s) of refill liquid toxicity and considering that previous investigations gave controversial results, the aim of the present study was the cytotoxicity assessment of different refill liquids on human endothelial cells, evaluated by means of two different in vitro approaches, i.e. the resazurin and the LDH release assays. Our results clearly demonstrated that different refill liquids (6 samples) display different levels of cytotoxicity in our cellular model, although their cytotoxicity was always lower than that observed for the condensate obtained from traditional cigarettes (3 samples). These results suggest that accurate evaluations should be provided for refill liquids, in particular to correlate their toxicity to their chemical composition, with the final aim of obtaining useful information for the agencies involved in the regulation of their components.The intensive application of pesticides without proper disposal management has led their excess residues to reach the neighbouring aquatic ecosystem and its inhabitants mainly fish. In natural water body pesticides get diluted, and therefore to study the silent toxic effect, a low dose of malathion (0.4 mg/L; 1/20th of 96-h LC50 value) for the different duration (1, 4, 8, 12 days) was evaluated through biochemical and histopathological biomarkers of the blood and hepatorenal tissues of Channa punctatus. With the increase in pesticide exposure periods, the biometric indices Condition Factor (K), HSI and KSI and hepatorenal tissues weight decreased. Among the biochemical alterations in malathion exposed fish, serum glucose levels reduced by 72.23 % while protein amounts increased by 29.03 % in 12 days malathion exposed fish. Other parameters, viz., cholesterol, albumin, and phosphorous, remained the same as control fish after malathion exposure. Though serum bilirubin (total and direct) followed a biphasic respure, and therefore utmost care should be taken to prevent their seepage into the water bodies.3-Monochloropropane-1,2-diol (3-MCPD) is a food processing contaminant in some infant formula products and other foods in the United States. Although rodent studies have demonstrated that 3-MCPD and its palmitic esters have the potential to induce nephrotoxicity, our recent human cell culture studies using the human renal proximal tubule cell line HK-2 have not strongly supported this finding. Considering this disparity, we sought to examine whether changes in transporter gene expression on proximal tubule cells could be modulated by these compounds and allow us to glean mechanistic information on a possible indirect path to proximal tubule injury in vivo. If fundamental processes like water and solute transport could be disrupted by 3-MCPD compounds, then a new avenue of toxicity could be further explored in both infant and adult models. In our current study, we used HK-2 cells as an in vitro cellular model of human proximal tubule cells to investigate the effects of low (10 μM) and high (100 μM) 3-MCPD compound exposures to these cells for 24 hours (h) on the expression of 20 transporter genes that are known to be relevant to proximal tubules. Although we detected consistent upregulation of AQP1 expression at the RNA transcript level following HK-2 treatment with both low and high doses of several ester-bound 3-MCPD compounds, these increases were not associated with statistically significant elevations in their protein expression levels. Moreover, we observed a lack of modulation of other members of the AQP protein family that are known to be expressed by human proximal tubule cells. Overall, our study suggests the possibility that 3-MCPD-related nephrotoxicity could be associated with indirect modes of action relating to aquaporin homeostasis, but additional studies with other human-derived models would be pertinent to further explore these findings and to better understand transporter expression differences under different stages of proximal tubule development.Ciprofloxacin (CIP) is an antimicrobial "pseudo-persistent" in aquatic ecosystems. Once dispersed in the water compartments, it can also affect the microalgae. Thus, the evaluation of its long-term ecotoxicological effects is necessary. CIP interactions with other pharmaceuticals are not well known. In this study, we investigated the toxic effects of CIP alone and combined with caffeine (CAF), using the modified Gompertz model parameters and the chlorophyll-a production of the microalga Raphidocelis subcapitata as endpoints, throughout a 16-day exposure assay. The exposure to CIP alone led to significant reductions of the growth rate and the cell density of the microalgae compared to control groups. The combination with CAF lowered the adverse effects of CIP to R. subcapitata. However, as the toxicity is dynamic, our results indicated that the toxic effects in respect to the studied endpoints changed throughout the exposure period, reinforcing the need for longer-term ecotoxicity assessments.Theophrastus Bombastus Von Hohenheim known as Paracelsus was a German-Swiss homo universalis, or Renaissance man, whose interests included medicine, chemistry and toxicology. Characterized as a rebellious and great reformer of established medicine of his era, Paracelsus preferred observing nature, over studying ancient texts to find appropriate treatments for various diseases. He also used unconventional curative methods, such as minerals and other inorganic substances, which caused much controversy among his contemporaries. The main purpose of this article is to highlight his contribution on toxicology and the use of mercury.Nitromethane is a volatile organic compound categorized as a Group 2B carcinogen by the International Agency for Research on Cancer. It has been detected in mainstream cigarette smoke, but few reliable methods have been reported for accurate quantification. We developed, a sensitive, selective, fully validated method for the targeted determination of nitromethane in mainstream tobacco smoke in ten U.S. domestic brands and two quality control materials (3R4F and CM6). The vapor phase portion of machine-generated cigarette mainstream smoke, under modified ISO 33082000 regime (ISO) and modified intense regime (HCI), from single cigarettes was collected using airtight polyvinylfluoride sampling bags. The bags' contents were extracted using methanol containing an isotopically labeled internal standard followed by gas chromatography-tandem mass spectrometry. This approach is sufficiently sensitive to measure nitromethane levels in the nanogram range, with a method limit of detection of 72.3 ng/cig. Within-product variability estimated from the replicate analysis of 10 products ranged from 4.6%-16.3% (n = 6) over the two different smoking regimes, and method reproducibility estimated from two products used as quality control materials (3R4F and CM6) yielded intermediate precision values ranging from 16.6 to 20.8% (n = 20). Under HCI, nitromethane yields in machine-generated cigarette smoke from ten different domestic cigarette products ranged from 3.2 to 12 μg/cig; under ISO yields ranged from 1.6 to 4.9 μg/cig under standardized smoking machine conditions. Nitromethane yields are related to both the smoke regime (blocking of vent holes, puff duration and puff volume) and the heterogeneity of tobacco mixtures. This method provides a selective and fully validated technique to accurately quantify nitromethane in mainstream cigarette smoke, with minimal waste generation. It is an improvement over previous methods with regards to specificity, throughput, and simplicity of the sample collection process.

(dodder) belonging to the family Convolvulaceae has many ethno-medicinal uses such as antidiarrheal and antiemetic. This plant has been employed to treat diarrhea, where the antidiarrheal use of this plant is well established in different communities around the world without scientific bases. In addition, the antibacterial, anthelmintic, anticholinergic, and antihistaminic effects of this parasitic vine are partly responsible for the folkloric antidiarrheal use of this plant. In the present study, the antidiarrheal activity

was evaluated in pigeons (

) using the juice (JCR), aqueous (CRAE), and methanol (CRME) extracts.

The antidiarrheal effect of

was evaluated using different reported research models, with few modifications. In pigeons, diarrhea was induced by administration of castor oil (6 mL/kg, PO), ampicillin (250 mg/kg, IP), magnesium sulfate (2 gm/kg, PO), and cisplatin (6 mg/kg, IV). In these experiments, loperamide (2 mg/kg, IM) was used as a positive control, whereas JCR (1 mL/kg (1%) a of

exhibit significant anti-motility and anti-secretory potential. These findings may explain the medicinal use of

folk medicine as an antidiarrheal medicinal plant.

Taken all together, results from this study reveal that the juice, aqueous, and methanol extract of C. reflexa exhibit significant anti-motility and anti-secretory potential. These findings may explain the medicinal use of C. reflexa in folk medicine as an antidiarrheal medicinal plant.The aim of this study was to assess the integrity and kidney overall functional capacity of subjects exposed to landfill emissions. Urine and blood levels of Pb and Cd, and several of the newly biomarkers of nephrotoxicity (Kim Injury Molecule 1 (KIM-1), alpha-1 Microglobulin (α1 M), beta-2 Microglobulin (β2 M), Cystatin-C (Cyst C), Clusterin, alpha-glutathione S-transferase (GSTα), pi-glutathione S-transferase (GSTπ), Tissue Inhibitor of Metalloproteinase-1 (TIMP1), Calbindin, Neutrophil Gelatinase-Associated Lipocalin (NGAL), Osteopontin (OPN), (Retinol Binding Protein(RBP), Liver-type Fatty Acid-Binding Protein (FABP-1), Trefoil Factor 3 (TFF3), Collagen VI) were measured in order to assess glomerular and tubule damage in adults living near a landfill. Our results indicate glomerular dysfunction in exposed subjects, and supported evidence of necrosis of proximal and distal tubule epithelial cells as specific biomarkers began to appear in the urine. Positive correlation by Pearson test were obtained between blood Pb and B-OPN, B-Cyst C, Calbindin, U-KIM-1, TIMP1, U-OPN, and U-Clusterin; and also, between urinary Cd and TIMP1, B-Clusterin, U-OPN, FABP-1, Albumin, and U-Clusterin. The relation between biomarkers of Cd/Pb exposure and early effect biomarkers in this study clearly predicts the future risk of severe kidney injury in subjects living close to the landfill.

Few human studies have explored the mechanisms of smoking-induced insulin resistance.

To prospectively examine the metabolic changes of smoking reduction.

Cigarette smokers (n=22; ½-2 packs per day) were enrolled in a smoking reduction program (counseling plus bupropion×8weeks; Phase I) followed by monitoring only (no counseling or bupropion×16weeks; Phase II). We serially measured exhaled carbon monoxide (CO) and urine nicotine metabolites; fat distribution, and metabolic parameters by hyperinsulinemic clamps including hepatic glucose output (HGO) and indirect calorimetry, adjusted for total caloric intake and expenditure.

CO and nicotine metabolite levels fell with smoking reduction during Phase I (all p<0.05), without any further changes through Phase II. Central-to-peripheral fat ratio increased during Phase I, but then fell during Phase II (all p<0.05). Over 24weeks, basal HGO fell (p=0.02); and falling CO and nicotine metabolite levels correlated inversely with changes in glucose oxidation, and directly with changes in weight (all p<0.05).

Smoking reduction produced a transient worsening of central fat redistribution followed by a more significant improvement; along with other net beneficial metabolic effects.

Smoking reduction produced a transient worsening of central fat redistribution followed by a more significant improvement; along with other net beneficial metabolic effects.Renal artery aneurysm is a rare condition. Most patients are asymptomatic. This case presented to the emergency with colicky pain and underwent left transurethral lithotripsy for left ureteral stone, due to simultaneous renal stone candidates for percutaneous nephrolithotomy. In the review of the imaging, we found a large renal artery aneurysm, so vascular surgery consult was done and the patient managed with coil embolization Misdiagnosis of this condition could be led to life-threatening bleeding if percutaneous nephrolithotomy was done. It is recommended that renal artery aneurysm should be considered in the differential diagnosis of renal rim-like opaque lesions.Primary carcinoma of the ureteral stump following a radical nephrectomy is rare, and it is even rarer that the cause of the nephrectomy is renal cell carcinoma (RCC). Treatment by complete ureterectomy with a bladder cuff is considered as the standard treatment. We report a case of a 70-year-old female with urothelial carcinoma with glandular differentiation that occurred in the ureteral stump after nephrectomy for left RCC. We performed a novel technique of pure laparoscopic resection of the ureteral stump with a bladder cuff.Renal metastases are very rare condition in the clinical practice. The treatment is individualized and it depends on general status of the patient, involving of other organs and also the control of primary tumor. We are presenting a 64 years old woman, who had episodes of intermittent hematuria for two weeks. CT scan showed a large heterogeneous left kidney mass. The patient underwent open transabdominal radical left nephrectomy and the final diagnosis was isolated lung adenocarcinoma metastasis of the kidney.

The genetic prevalence of Pompe disease was estimated based on the proportion of individuals who have a causative genotype in a general population database. In addition, clinical severity for causative genotypes was assessed based on currently available locus-specific databases (LSDBs), which contain information on both genotype and clinical severity.

Genetic variants in the

gene in the Genome Aggregation Database (gnomAD) (v2.1.1) were analyzed in combination with LSDBs of ClinVar, ClinGen Evidence Repository, Pompe disease

variant database, and the Pompe Registry. Carrier frequency (CF) and predicted genetic prevalence (pGP) were estimated.

Of 7 populations, East Asian and African showed higher proportions of pathogenic or likely pathogenic variants (PLPVs) associated with classic infantile-onset Pompe disease. Total CF and pGP in the overall population were 1.3% (1 in 77) and 123,232, respectively. The highest pGP was observed in the East Asian population at 112,125, followed by Non-Finnish European (113,756), Ashkenazi Jewish (122,851), African/African-American (126,560), Latino/Admixed American (157,620), South Asian (193,087), and Finnish (11,056,444).

Pompe disease has a higher pGP (123,232) than earlier accepted (140,000). The pGP for Pompe disease was expectedly wide by population and consistent with previous reports based on newborn screening programs (approximately 110,000-130,000).

Pompe disease has a higher pGP (123,232) than earlier accepted (140,000). The pGP for Pompe disease was expectedly wide by population and consistent with previous reports based on newborn screening programs (approximately 110,000-130,000).

To describe the clinical and molecular features of a group of Argentinian pediatric patients with mitochondrial DNA (mtDNA) disorders, and to evaluate the results of the implementation of a classical approach for the molecular diagnosis of mitochondrial diseases.

Clinical data from 27 patients with confirmed mtDNA pathogenic variants were obtained from a database of 89 patients with suspected mitochondrial disease, registered from 2014 to 2020. Clinical data, biochemical analysis, neuroimaging findings, muscle biopsy and molecular studies were analyzed.

Patients were 18 females and 9 males, with ages at onset ranging from 1week to 14years (median=4years). The clinical phenotypes were mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (

=11), Leigh syndrome (

=5), Kearns-Sayre syndrome (

=3), Chronic Progressive External Ophthalmoplegia (

=2), Leber hereditary optic neuropathy (n=2), myoclonic epilepsy associated with ragged-red fibers (

=1) and revers cases presented with classical phenotypes, being MELAS the most frequent. Applying classical molecular methods, it was possible to achieve a genetic diagnosis in 30% of the cases, suggesting that this is an effective first approach, especially for those centers from low-middle income countries, leaving NGS studies for those patients with inconclusive results.

Wearable robotic exoskeletons (WREs) have been globally developed to achieve gait reconstruction in patients with spinal cord injury (SCI). The present study aimed to enable evidence-based decision-making in selecting the optimal WRE according to residual motor function and to provide a new perspective on further development of appropriate WREs.

The current review was conducted by searching PubMed, Web of Science, and Google Scholar for relevant studies published from April 2015 to February 2020. Selected studies were analysed with a focus on the participants' neurological level of SCI, amount of training (number of training sessions and duration of the total training period), gait speed and endurance achieved, and subgroup exploration of the number of persons for assistance and the walking aid used among patients with cervical level injury.

A total of 28 articles (nine using Ekso, three using Indego, ten using ReWalk, one using REX, five using Wearable Power-Assist Locomotor) involving 228 patients werit reconstruction in patients with SCI, contributing to evidence-based device application and further development.

The present review reveals the current state of the clinical effectiveness of WREs for gait reconstruction in patients with SCI, contributing to evidence-based device application and further development.

Chondrons are composed of chondrocytes and the surrounding pericellular matrix (PCM) and function to enhance chondrocyte-mediated cartilage tissue engineering. This study aimed at investigating the potential effect of combined chondrocytes with chondrons on the production of proteoglycan and collagen-II (Col-2) and the repair of defective knee cartilage in rabbits.

Chondrocytes and chondrons were isolated from the knee cartilage of rabbits, and cultured alone or co-cultured for varying periods in vitro. Their morphology was characterized by histology. The levels of aggrecan (AGG), Col-2 and glycosaminoglycan (GAG) expression were quantified by qRT-PCR, Alcian blue-based precipitation and ELISA. The effect of combined chondrocytes with chondrons in alginate spheres on the repair of defective knee cartilage was examined in rabbits.

The isolated chondrocytes and chondrons displayed unique morphology and began to proliferate on day 3 and 6 post culture, respectively, accompanied by completely degenerated PCondrons and chondrocytes may be new therapeutic strategy for cartilage tissue engineering and repair of defective cartilage.

Trauma is the leading cause of death and disability worldwide, especially in the young population. Cardiac injuries are an independent predictor for a poor overall outcome after trauma. The aim of the present study was to analyze systemic inflammation as well as local cardiac inflammation after experimental limb-, neuro- and combined trauma in mice.

Male C57BL/6 mice received either a closed tibia fracture (Fx), isolated traumatic brain injury (TBI) or a combination of both (Fx​+​TBI). Control animals underwent sham procedure. After 6 and 24​h, systemic levels of inflammatory mediators were analyzed, respectively. Locally, cardiac inflammation and cardiac structural alterations were investigated in left ventricular tissue of mice 6 and 24​h after trauma.

Mice showed enhanced systemic inflammation after combined trauma, which was manifested by increased levels of KC, MCP-1 and G-CSF. Locally, mice exhibited increased expression of inflammatory cytokines (IL-1β, TNF) in heart tissue, which was probably meetabolism, which might be linked to increased systemic- and local cardiac inflammation after limb-, neuro- and combined trauma. These cardiac alterations might predispose individuals for secondary cardiac damage after trauma that might compromise cardiac function after TBI and long bone fracture.

Injuries to the head and extremities frequently occur after severe trauma. In our study, we analyzed the effects of closed tibia fracture, isolated TBI, and the combination of both injuries with regard to the development of post-traumatic secondary cardiac injuries.

Injuries to the head and extremities frequently occur after severe trauma. In our study, we analyzed the effects of closed tibia fracture, isolated TBI, and the combination of both injuries with regard to the development of post-traumatic secondary cardiac injuries.

Mesenchymal Stem Cells (MSCs) therapy has become a new coming focus of clinical research in regenerative medicine. However, only a small number of implanted MSCs could successfully reach the injured areas. The previous studies have shown that fracture healing time is inversely proportional to concentration of MSCs in injured tissue.

The migration and osteogenesis of MSCs were assessed by transwell assay and Alizarin Red S staining. Levels of gene and protein expression were checked by qPCR and Western Blot. On the other hand, the enhanced migration ability of MSCs induced by Cyasterone was retarded by CXCR4 siRNA. In addition, the rat model of femoral fracture was established to evaluate the effect of Cyasterone on fracture healing. What's more, we also checked the effect of Cyasterone on mobilisation of MSCs in vivo.

The results showed that Cyasteron increased the number of MSCs in peripheral blood. The concentrations of SDF-1α in serum at different time points were determined by ELISA assay. Micro-CT and histological analysis were used to evaluate the fractured femurs.Our results showed that Cyasterone could promote the migration and osteogenesis capacities of MSCs. The fractured femurs healed faster with treatment of Cyasterone. Meanwhile, Cyasterone could significantly increase the level of SDF-1α in rats with femur fracture.

Cyasterone could promote migration and osteogenesis of MSCs, and most importantly, it could accelerate bone fracture healing.Translational Potential statement These findings provide evidence that Cyasterone could be used as a therapeutic reagent for MSCs mobilisation and osteogenesis. What's more, it could acclerate fracture healing.

Cyasterone could promote migration and osteogenesis of MSCs, and most importantly, it could accelerate bone fracture healing.Translational Potential statement These findings provide evidence that Cyasterone could be used as a therapeutic reagent for MSCs mobilisation and osteogenesis. What's more, it could acclerate fracture healing.Trans-regulating elements such as noncoding RNAs are crucial in modifying cells, and has shown broad application in synthetic biology, metabolic engineering and RNA therapies. Although effective, titration of the regulatory levels of such elements is less explored. Encouraged by the need of fine-tuning cellular functions, we studied key parameters of the antisense RNA design including oligonucleotide length, targeting region and relative dosage to achieve differentiated inhibition. We determined a 30-nucleotide configuration that renders efficient and robust inhibition. We found that by targeting the core RBS region proportionally, quantifiable inhibition levels can be rationally obtained. A mathematic model was established accordingly with refined energy terms and successfully validated by depicting the inhibition levels for genomic targets. Additionally, we applied this fine-tuning approach for 4-hydroxycoumarin biosynthesis by simultaneous and quantifiable knockdown of multiple targets, resulting in a 3.58-fold increase in titer of the engineered strain comparing to that of the non-regulated. We believe the developed tool is broadly compatible and provides an extra layer of control in modifying living systems.Photoacoustic imaging (PAI) is a promising emerging imaging modality that enables spatially resolved imaging of optical tissue properties up to several centimeters deep in tissue, creating the potential for numerous exciting clinical applications. However, extraction of relevant tissue parameters from the raw data requires the solving of inverse image reconstruction problems, which have proven extremely difficult to solve. The application of deep learning methods has recently exploded in popularity, leading to impressive successes in the context of medical imaging and also finding first use in the field of PAI. Deep learning methods possess unique advantages that can facilitate the clinical translation of PAI, such as extremely fast computation times and the fact that they can be adapted to any given problem. In this review, we examine the current state of the art regarding deep learning in PAI and identify potential directions of research that will help to reach the goal of clinical applicability.

Herbal medicine has been used frequently in Korean medicine. We aimed to summarize the relevant regulations for herbal medicine clinical trials and to analyze their current status in the Republic of Korea.

We searched for legislation to find regulations on herbal medicine clinical trials. Additionally, the websites of the Korean Ministry of Food and Drug Safety (KMFDS) and Clinical Research Information Service (CRIS) were searched to investigate the current status of them.

To conduct herbal medicine clinical trials for new drugs or previously approved drugs outside of indications, investigational new drug (IND) approval should be obtained from the KMFDS. For clinical trials of herbal medicines that have been used for more than 3 years with 200 cases at the clinical trial institution, nonclinical data can be exempted from IND approval. Total 95 and 108 herbal medicine clinical trials from the KMFDS and CRIS websites were analyzed. The number of clinical trials showed an increasing trend each year, as didw drugs that reflect the clinical setting using relevant regulations, evaluate the efficacy and safety of the drugs, and strengthen insurance coverage.

Avascular necrosis (AVN) of femoral head is commonly seen in middle age groups and in its advanced stages, it is a common indication for total hip replacements (THRs). These patients invariably require revision surgeries in their lifetime and modalities to delay the first arthroplasty are necessary. Core decompression (CD) with bone marrow aspirate concentrate (BMAC) have proved successful in early stages of AVN, but their role in advanced stages remains unclear. The present review was done to assess the same.

Is CD and BMAC combination effective in delaying radiographic progression and THRs in post collapse stages of AVN hip?

A systematic review and meta-analysis was conducted to determine the overall efficacy of CD and BMAC in post collapse stages of AVN hip and to specifically compare primary outcomes like radiographic progression along with need of THR, with CD alone.Three data bases (PubMed, EMBASE and SCOPUS) were searched to identify relevant articles.

The present review included 12 studies witnted with bone strut grafts or tantalum rods, for supporting the articular cartilage. BMAC that has shown better results in early AVN, has not shown any additional benefits when compared to CD alone in advanced cases.

Among the various exposure technique used in total knee arthroplasty (TKA); the midline medial parapatellar knee approach is most commonly performed; which require mobilisation of patella for adequate surgical exposure. In this study, we compare the effect of patellar eversion with lateral retraction in simultaneous bilateral TKA to find out difference in postoperative clinical outcome between the two patellar mobilisation techniques.

We enrolled 41 patients who underwent bilateral simultaneous TKR (82 knees) from Nov 2016 to Dec 2018. During surgery patellar eversion was done in one knee and lateral retraction was done in other knee selecting them randomly to reduce the bias. During the follow up period achieving unassisted active straight leg raise (SLR), 90 flexion and complications were recorded. Measurement of Oxford knee society score (OKSS), American knee society score (AKSS), Visual Analogue Scale (VAS) score, and quadriceps strength (measured by handheld dynamometer) was done daily up to one weekrecovery after TKA; it delays achieving active SLR, 90∗ flexion and has unfavourable outcome in functional scores, quadriceps strength, and postoperative pain relief. However it has minimal effects on long term functional outcomes.Surgeries for Rotator Cuff (RC) pathologies are required for either trauma or degenerative related aetiologies. Various surgical techniques from open to arthroscopic repair, are being undertaken by orthopaedic surgeons. Peri-operative anaesthetic management of the patients undergoing rotator cuff repair requires understanding the surgical procedure and patient status for optimal anaesthetic planning. Such management mandates a thorough pre-operative evaluation, including clinical history, examination, and relevant investigations. Patients with acute trauma associated Rotator Cuff (RC) tears should be assessed for visceral injuries using appropriate injury evaluation systems before such repairs. On the other hand, patients with degenerative tears tend to be older with associated comorbidities. Hence pre-operative optimisation is necessary according to risk stratification. Anaesthetic techniques for Rotator Cuff (RC) surgery include general anaesthesia or regional anaesthesia. These are individualised according to patient assessment and surgical procedure planned. Knowledge of relevant surgical anatomy is essential for intra-operative, and post-operative neural blockade techniques since optimal peri-operative analgesia improve overall patient recovery. The occurrence of a peri-operative complication should be recognised as timely management improves the patient-related surgical outcomes. We describe the relevance of surgical anatomy, the effect of patient positioning, irrigating fluids, various anaesthetic techniques and an overview of regional and medical interventions to manage pain in patients undergoing for Rotator Cuff (RC) surgery.Parathyroid Hormone (PTH) has a significant role in calcium metabolism. Its intermittent administration has an anabolic effect on bone mineralization. Teriparatide (PTH 1-34), a recombinant form of parathyroid hormone, is useful in the treatment of osteoporosis, fracture healing, non-union, stress fracture, augmentation of implant fixation with bone, and chondroprotection in osteoarthritis. The present review article will elaborate on the potential approved uses of recombinant PTH in orthopedics and its evolving role in the management of fracture osteosynthesis and other common challenging bone pathologies.

Ankle fractures in diabetic patients are known to have an increased morbidity. This systematic review aims to evaluate the current evidence in terms of risk profile and inform treatment options.

Following the methodology of the Cochrane collaboration, an extensive literature search was conducted. Outcomes included, complications, operative and non-operative management and early weight-bearing.

A total of 40 studies were included. Complication rates were higher in diabetic patients and more so in poorly controlled diabetes, IDDM, or "complicated" diabetes. Supplementary fixation was associated with lower complication rates. Regarding early weight-bearing, similar results to non-diabetics in the stable fracture pattern were found providing there was no evidence of neuropathy.

Diabetes, especially complicated diabetes, presents an increased risk of complications. However non operative management of diabetic ankle fractures do poorly, and with the use of 'ORIF plus' techniques there is no increase in complications from early fixation. The use of external fixation for definitive fixation should be minimised as it is associated with high complication rates.

Diabetes, especially complicated diabetes, presents an increased risk of complications. However non operative management of diabetic ankle fractures do poorly, and with the use of 'ORIF plus' techniques there is no increase in complications from early fixation. The use of external fixation for definitive fixation should be minimised as it is associated with high complication rates.

Heel ulcers in patients with peripheral neuropathy and diabetes pose a significant challenge to treating physicians. Infection spreading to the os calcis is associated with a poor prognosis. There is no consensus on which method of surgical treatments results in better outcomes. The aim of this study was to assess patients' survival, rate of ulcer healing following surgical treatment, along with limb salvage rate, time taken for healing, ulcer recurrence and patients' functional outcome after healing.

We studied 29 patients (20 men, 9 women) presenting with diabetic neuropathic heel ulcers (30 feet) and no critical limb ischemia, were managed surgically in our unit and followed-up for a minimum of 12 months. We assessed their clinical and functional outcomes within a mean follow-up period of 28 months (12-83).

11 out of 29 patients died (38%) with mean duration of post op survival being 31months (range 4-70). 14 ulcers (50%) healed fully within a mean of 360 days (131-1676). Limb salvage was achieved incation and survival.Diabetic sensorimotor polyneuropathy (DSPN) is the commonest form of neuropathy which leads to insensate sole, diabetic foot ulcers (DFU) and its complications. We share our experience in recovery of sensation in the sole after prophylactic surgery such as nerve decompression (ND) or sensory neurotization by nerve transfer (NT) in patients having Diabetic sensorimotor polyneuropathy DSPN. 32 patients (46 feet) were selected for either nerve decompression or sensory neurotization depending upon presence or absence of Tinel's sign at tarsal tunnel. At 6 month post-operatively perception of touch and pain recovered in all feet; temperature and pressure perception recovered in ∼95% feet; average vibration perception threshold returned to normal range and 2-Point Discrimination came down significantly. There were no ulcers or amputation in operated limbs during follow up period of 6 months. Prophylactic surgery in the form of ND and NT can be offered with minimal complications which significantly improve sensations in the sole in selected cases of DSPN. These have the potential to improve the quality of life of patient and change the natural course of disease.

Various surgical techniques and implants are available for surgical treatment of significantly displaced proximal humerus fractures. We describe a minimally invasive technique using 3 curved wires, inserted in a retrograde fashion into the humeral head. These are aimed to diverge within the humeral head to provide three separate 3-point fixations to achieve good stability. We present the results of proximal humerus fractures managed with the modified palm tree technique.

A retrospective analysis of data collected prospectively including demographics, radiographs, clinical outcomes, complications and revision surgery for patients treated with the palm tree technique was performed.

Between 1998 and 2017, 132 patients underwent fixation with this technique. Average age was 61.8 years. Fifty-Eight fractures were 2 part, 46 were three part and 28 were four part. Average follow up was 26 months. In three to four part fractures, a bone graft substitute block was used behind the humeral head fragment for structinimally invasive technique which can be used for two, three and four part fractures with good functional outcomes and high union rates. No metalwork remains in the proximal humerus should another procedure like arthroplasty be required in case of avascular necrosis of the humeral head or fracture sequela.

ACL injuries are infamously known for disability in young adults and require surgical reconstruction. The need of time is to predict predisposing factors and prevent ACL injuries.The incidence of ACL injuries has been associated with various factors related to the morphology of distal femur and proximal tibia.Hence, purpose of this study was to assess the relationship of morphology of distal femur by assessing Notch Width(NW), Notch Width Index (NWI), and Notch shape calculated preoperatively on MRI in association with an ACL tear.

The following randomized control study had 60 patients enrolled with non contact injury to knee who were equally divided into 2 groups i.e. ACL injury group and control group. ACL group had patients who had MRI proven ACL tear along with clinical findings suggestive of ACL tear whereas control contained patients with intact ACL. Demographic data was collected and NW, NWI and Notch shape were determined on coronal sections of MRI sequences.

Positive correlation of ACL tear was, its important to counsel the subjects about the increased risk of ACL injuries in them and take preventive measures.

Tibial shaft fractures are a relatively common injury and contemporary treatment includes on-axis fixation with a locked intramedullary nail in the majority of cases. The conventional technique is via an infrapatellar approach but currently there is a trend towards the use of a suprapatellar approach. We compared key variables including operative time, radiation exposure and early patient reported outcomes when adopting a suprapatellar approach to tibial nailing in our unit versus our previous experience of infrapatellar tibial nailing.

Twenty-eight consecutive patients with tibial fracture underwent tibial nailing via the suprapatellar (SPN) approach. Six patients in the study group were excluded due polytrauma and need for dual orthopaedic and plastic surgery management. We compared outcomes with our most recent 20 consecutive patients who had undergone tibial nailing via an infrapatellar (IPN) approach. Primary surgical outcomes were operative time, radiation exposure and accuracy of entry point of theme, radiation exposure and superior patient reported outcomes when compared to the conventional infrapatellar approach.

Our study shows that adoption of the SPN approach requires minimal learning curve, and has the potential benefits of reduced operative time, radiation exposure and superior patient reported outcomes when compared to the conventional infrapatellar approach.Charcot Neuroarthropathy (CN) of the ankle/hindfoot is a devastating condition that results in a loss of alignment, bony malleolar protrusions and frequently leads to ulceration, infection, and amputation. Major limb amputations in this patient population has a 5-year mortality rate approximating 39%-68%. The treatment goal for CN of the ankle/hindfoot is to provide stability with a plantigrade foot that is infection free, shoeable and allows independent weight bearing. The use of a circular frame external fixator is often required when treating patients with CN of the ankle/hindfoot because they often present late with deformity, soft tissue compromise and infection which are contraindications to primary internal fixation. These patients require urgent surgical attention to salvage the limb or risk amputation. In this narrative review article we will discuss the indications, management options, surgical technique, evidence and describe our experience in the use of circular frame external fixation in patients with ankle/hindfoot Charcot Neuroarthropathy.Ramp lesions are important injuries that are difficult to detect on MRI and pose a challenge to diagnose on arthroscopy since they require inspection of the posteromedial compartment. No bony injury has been reported in the literature as an associated injury with the ramp lesion. We report a rare case of complete ramp tear of the posterior capsule-meniscal junction associated with fracture of the rim of the posterior medial tibial plateau and a double injury to the posterior medial meniscus forming a terrible triad with poor prognosis. This report has implications on the classifications of ramp lesions, posterior root injuries of the medial meniscus and meniscal tears as fracture of the rim adds a new dimension to these injuries.

Virtual Reality (VR) simulators are playing an increasingly prominent role in orthopaedic training and education. Face-validity - the degree to which reality is accurately represented - underpins the value of a VR simulator as a learning tool for trainees. Despite the importance of tactile feedback in arthroscopy, there is a paucity for evidence regarding the role of haptics in VR arthroscopy simulator realism.

To assess the difference in face validity between two high fidelity VR simulators employing passive and active haptic feedback technology respectively.

38 participants were recruited and divided into intermediate and expert groups based on orthopaedic training grade. Each participant completed a 12-point diagnostic knee arthroscopy VR module using the active haptic Simbionix ARTHRO Mentor and passive haptic VirtaMed ArthroS simulators. Subsequently, each participant completed a validated simulator face validity questionnaire.

The ARTHRO Mentor active haptic system failed to achieve face validity with mean scores for external appearance (6.

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