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Aim: To investigate whether high-intensity interval training (HIIT) improves physical performance, systolic blood pressure, and markers of oxidative stress and inflammation in skeletal muscle of spontaneously hypertensive rats (SHR). Methods: Nineteen male SHR rats were randomly assigned to two groups: sedentary (SHRC) and trained (SHR+T). The SHR+T group trained five times a week for eight weeks on a treadmill, while the SHR group remained without any exercise stimulus throughout the experimental period. Maximum physical performance and systolic blood pressure (SBP) were assessed before and after the training period. The following variables were measured in the tibialis anterior (TA) muscle: gene expression of the NADPH oxidase complex (NOX2, NOX4, p22phox, p47phox) and the NF-kB pathway (NF-kB and Ik-B), lipid peroxidation (malonaldehyde; MDA), protein carbonylation, hydrophilic antioxidant capacity (HAC) and pro-inflammatory cytokines (IL-6 and TNF-α). Results: SHR+T rats showed higher physical performance and levels of IL-6, and lower SBP and protein carbonylation (p<0.05), compared with SHRC rats. No significant differences (p>0.05) were observed in the other variables. Significance: Our results indicate that HIIT is an effective non-pharmacologic strategy to improve physical performance, reduce SBP, and modulate the skeletal muscle oxidative damage and inflammation in hypertensive rats. [ABSTRACT FROM AUTHOR]

The effects of glass bead size in the conical space of flow-through cells on the dissolution profiles were investigated in a USP apparatus 4. Dissolution tests of disintegrating and non-disintegrating tablets in flow-through dissolution systems were performed using semi-high precision glass beads with diameters ranging from 0.5 mm to 1.5 mm. Computational fluid dynamics (CFD) was used to evaluate the effect of shear stress from the dissolution media flow. The use of smaller glass beads in a larger cell resulted in a faster dissolution of the model formulations under certain test conditions. The effect on the dissolution was highly dependent on the size of the beads in the top layer, including those in contact with the tablets. The absence of a bead-size effect on the dissolution of an orodispersible tablet in a small cell can be explained by the floating fragments during the test. CFD analysis showed that smaller bead diameters led to greater shear stress on the tablet, which was correlated with the dissolution rate. Hence, fluid flow through the narrow gaps between the small beads generated strong local flows, causing shear stress. The size of the glass beads used in flow-through cells affects the dissolution rate of tablets by altering the shear stress on the tablets in certain cases (e.g., direct deposition of the formulation on glass beads, large cells, and very low flow rates). Thus, glass bead size must be considered for a robust dissolution test in a flow-through cell system. [ABSTRACT FROM AUTHOR]

The mucus layer in the small intestine is generally regarded as a barrier to drug absorption. However, the mucus layer is a complex system, and presently, only a few studies have been conducted to elucidate its physicochemical properties. The current study hypothesizes that the mucus layer contains solubility-enhancing surfactants and thus might aid the oral absorption of poorly water-soluble drugs. Mucus was sampled from sections of the small intestine of fasted rats to analyze the rheological properties and determine the mucus pH and concentrations of proteins and endogenous surfactants, i.e., bile salts, polar lipids, and neutral lipids. The mucus layer in the two proximal sections of the small intestine exhibited different rheological properties such as higher zero-shear viscosity and lower loss tangent and higher protein concentrations compared to all subsequent sections of the small intestine. The pH of the mucus layer was stable at ~ 6.5 throughout most of the small intestine, but increased to 7.5 in the ileum. The bile salt concentrations increased from the duodenum (16.0 ± 2.2 mM) until the mid jejunum (55.1 ± 9.5 mM), whereas the concentrations of polar lipids and neutral lipids decreased from the duodenum (17.4 ± 2.2 mM and 37.8 ± 1.6 mM, respectively) until the ileum (4.8 ± 0.4 mM and 10.7 ± 1.1 mM, respectively). In conclusion, the mucus layer of the rat small intestine contains endogenous surfactants at levels that might benefit solubilization and absorption of orally administered poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]

Resuscitative thoracotomy (RT) is a critical procedure performed in certain trauma patients in extremis, with extremely low survival rates. Currently, there is a paucity of data pertaining to prehospital variables and their predictive role in survival outcomes in traumatic cardiac arrest (TCA) patients requiring RT. The aim of the study was to determine the impact of prehospital intubation and out-of-hospital time (OOHT) on return of spontaneous circulation (ROSC) and survival in TCA requiring RT. This was a retrospective cohort study of trauma patients presenting to two level-1 trauma centers, St. Michael's Hospital and Sunnybrook Health Sciences Center, in Toronto, Canada (January 1, 2005-December 31, 2020). Our exposures of interest were any prehospital intubation attempt and OOHT. Primary and secondary outcome measures were ROSC post-RT and survival to hospital discharge, respectively, and data analysis was performed using univariate logistic regression. A total of 195 patients were included, of which 86% were male, and the mean age was 33 years. ROSC and survival to hospital discharge were achieved in 30% and 5% of patients, respectively. Of those who survived to discharge, 89% sustained penetrating trauma. There was no association between OOHT and ROSC (OR = 1.00, 95% CI 0.97–1.03) or survival (OR = 0.99, 95% CI 0.94–1.05). The odds of ROSC were lower in penetrating trauma in the presence of any prehospital intubation attempt (OR = 0.39, 95% CI 0.19–0.82, p = 0.01). ROSC was less likely among all patients with no prehospital signs of life (SOL) compared to those who had prehospital SOL (OR = 0.30, 95% CI 0.13–0.69, p < 0.01). There was a significant association between prehospital intubation and lower likelihoods of ROSC in the penetrating TCA population requiring RT, as well as with the absence of prehospital SOL in all patients. OOHT did not appear to significantly impact ROSC or survival. [ABSTRACT FROM AUTHOR]

Gastroduodenal artery aneurysms are a rare type of visceral aneurysm that can lead to rupture and death. We present a 75-year-old male with history of hypertension, diabetes, and hyperlipidemia with an incidental finding of a 3.2 × 3.7 cm gastroduodenal aneurysm found on abdominal computed tomography angiography (CTA). After refusing surgical intervention, he was seen two years later and presented with an enlarged gastroduodenal aneurysm, now 5.0 × 5.1 cm, visible on a repeat abdominal CTA. Upon his continued refusal for an open surgery, we elected for endovascular repair of this GDA aneurysm via coil embolization. [ABSTRACT FROM AUTHOR]

Emergency Resuscitative Thoracotomy (ERT) is a lifesaving procedure in selected patients. Outcome mostly in blunt trauma is believed to be poor. The primary aim of this study was to determine the predictors of postoperative mortality following ERT. We retrospectively reviewed 34 patients ≥ 18 years who underwent ERT at San Camillo—Forlanini Hospital (Rome, Italy) between January 2009 and December 2022 with traumatic arrest for blunt or penetrating injuries. Of 34 ERT, 28 (82.4%) were for blunt trauma and 6 (17.6%) were for penetrating trauma. Injury Severity Score (p-value 0.014), positive E-FAST (p-value 0.023), Systolic Blood Pressure (p-value 0.001), lactate arterial blood (p-value 0.012), pH arterial blood (p-value 0.007), and bicarbonate arterial blood (p-value < 0.001) were significantly associated with postoperative mortality in a univariate model. After adjustment, the only independent predictor of postoperative mortality was Injury Severity Score (p-value 0.048). Our experience suggests that ERT is a technique that should be utilized for patients with critical penetrating injuries and blunt trauma in patients in extremis. Our study highlights as negative prognostic factors high values of ISS and lactate arterial blood, a positive E-FAST, and low values of Systolic Blood Pressure, pH arterial blood and bicarbonate arterial blood. [ABSTRACT FROM AUTHOR]

Copyright of Taiwan Journal of Publich Health / Taiwan Gong Gong Wei Sheng Za Zhi is the property of Taiwan Public Health Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Oral colon delivery has widely been pursued exploiting naturally occurring polysaccharides degraded by the resident microbiota. However, their hydrophilicity may hinder the targeting performance. The aim of the present study was to manufacture and evaluate a double-coated delivery system leveraging intestinal microbiota, pH, and transit time for reliable colonic release. This system comprised a tablet core, a hydroxypropyl methylcellulose (HPMC) inner layer and an outer coating based on Eudragit® S and guar gum. The tablets were loaded with paracetamol, selected as a tracer drug because of the well-known analytical profile and lack of major effects on bacterial viability. The HPMC and Eudragit® S layers were applied by film-coating. Tested for in vitro release, the double-coated systems showed gastroresistance in 0.1 N HCl followed by lag phases of consistent duration in phosphate buffer pH 7.4, imparted by the HPMC layer and synergistically extended by the Eudragit® S/guar gum one. In simulated colonic fluid with fecal bacteria from an inflammatory bowel disease patient, release was faster than in the presence of β-mannanase and in control culture medium. The bacteria-containing fluid was obtained by an experimental procedure making multiple tests possible from a single sampling and processing run. Thus, the study conducted proved the feasibility of the delivery system and ability of guar gum to trigger release in the presence of colon bacteria without impairing the barrier properties of the coating. Finally, it allowed an advantageous simulated colonic fluid preparation procedure to be set up, reducing the time, costs, and complexity of testing and enhancing replicability. [ABSTRACT FROM AUTHOR]

Microbiotically activated ileo-colonic delivery of budesonide from compression coated tablets with considerably reduced carboxymethyl chitosan (CMCH) concentration was designed and investigated. CMCH was synthesized from chitosan dissolved in 20%w/v sodium hydroxide (NaOH) with monochloroacetic at 40 ± 5 °C and characterized by proton NMR, FTIR and Degree of Substitution. The microbiotically activated compression coated tablets (MACC-TABs) were prepared by wet granulation and compression coated with Eudragit S100: HPMC K100M in different ratios for enteric protection and ileo-colon selectivity. Dissolution studies without enzymes and in the presence of enzymes such as pepsin at pH 1.2, diastase and pancreatin at pH 6.8, the F1C3 did not show significant changes. Addition of colonic enzymes at the tenth hour resulted in significant increase in release of budesonide. The % Cumulative Drug Release was 98.49 ± 1.42%, due to the enzymatic triggering (produced by the colonic microflora) leading to the lysis of glycosidic bonds. Scanning electron microscopy revealed the pores formed after dissolution was due to the water-soluble nature of CMCH to release budesonide. The evidence during in-vitro dissolution studies confirmed the pH sensitivity along with microbiotic activation of the MACC-TABs tablets to efficiently and reproducibly release budesonide in the ileo-colon site in the presence of the bacterial enzymes. [ABSTRACT FROM AUTHOR]

Far infrared (FIR) irradiation is commonly used as a convenient, non-contact, non-invasive treatment for diseases such as myocardial ischemia, diabetes, and chronic kidney disease. In this review, we focus on reviewing the potential therapeutic mechanisms of FIR and its cutting-edge applications in cancer detection. Firstly, we searched the relevant literature in the last decade for systematic screening and briefly summarized the biophysical properties of FIR. We then focused on the possible mechanisms of FIR in wound healing, cardiovascular diseases, and other chronic diseases. In addition, we review recent applications of FIR in cancer detection, where Fourier transform infrared spectroscopy and infrared thermography provide additional diagnostic methods for the medical diagnosis of cancer. Finally, we conclude and look into the future development of FIR for disease treatment and cancer detection. As a high-frequency non-ionizing wave, FIR has the advantages of safety, convenience, and low cost. We hope that this review can provide biological information reference and relevant data support for those who are interested in FIR and related high-frequency non-ionizing waves, to promote the further application of FIR in the biomedical field. [ABSTRACT FROM AUTHOR]

Semaglutide is a drug, available in injection and oral forms, which exhibits hypoglycemic action in a blood glucosedependent manner through the glucagon-like peptide-1 (GLP-1) receptor. Gastrointestinal issues such as diarrhea, constipation, and nausea may initially occur as major side effects, but many of these symptoms improve with continued use of the medication. This case reports a patient who had improved glycemic control after treatment with subcutaneous semaglutide. However, the treatment could not be continued due to persistent nausea and vomiting. After switching to oral semaglutide, the patient experienced an improvement in gastrointestinal symptoms. In cases where semaglutide injection has a sufficient hypoglycemic effect but cannot be continued due to adverse gastrointestinal symptoms, changing to oral semaglutide may be effective. However, although oral semaglutide had positive outcomes in this case, the effectiveness of oral semaglutide is highly dependent on adherence to the dosing regimen. [ABSTRACT FROM AUTHOR]

Purpose: The effectiveness of open cardiopulmonary resuscitation (OCPR) remains controversial for trauma patients. In this current study, the role of OCPR in managing chest trauma patients is evaluated using nationwide real-world data. Methods: From 2014 to 2015, the National Trauma Data Bank was retrospectively queried for chest trauma patients with out-of-hospital cardiac arrest status. The emergency department (ED) and overall survival of patients without signs of life were analyzed. Multivariate logistic regression (MLR) analysis was performed to evaluate independent factors of mortality for the target group. Furthermore, a subset group of patients who survived after the ED were studied, focusing on the duration of survival after leaving the ED. Results: A total of 911 patients were enrolled in this study (OCPR vs. non-OCPR: 161 patients vs. 750 patients). The average overall mortality rate was 98.6% (N = 898). Among penetrating chest trauma patients, non-survivors in the ED had significantly higher proportions of gunshot injuries (83.9% vs. 69.7%, p = 0.001) and lower proportions of OCPR (20.7% vs. 44.4%, p < 0.001). MLR analysis showed that gunshot injuries and non-OCPR were significantly related to ED mortality in penetrating trauma patients without signs of life (odds ratio = 2.039, p = 0.006 and odds ratio = 2.900, p < 0.001, respectively). However, the overall survival rate of patients after ED survival (n = 99) was 9.9%, and only 21.2% (n = 21) of them survived more than 1 day after leaving the ED. Conclusion: OCPR could be considered in situations where appropriate indications exist. The survival benefit was observed in critically ill patients with penetrating chest trauma who show no signs of life. By enhancing ED survival, OCPR may also contribute to overall survival improvement. [ABSTRACT FROM AUTHOR]

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AIM: To test whether intramuscular injection of 30 microg adrenaline decreased the incidence of respiratory distress and hypoglycaemia in term infants delivered by elective caesarean section before active labour. METHOD: The study was randomised and double-blinded. A total of 270 neonates were assigned to intramuscular treatment with saline (0.30 ml) or 30 microg adrenaline (0.30 ml) immediately after birth. The primary endpoint was referral to the neonatal ward because of respiratory distress or a blood glucose level <1.8 mmol/l measured 2 h after birth. The first 50 infants were monitored with pulse oximetry to disclose potential side effects. RESULTS: Pulse-oximetry recordings revealed a modest systemic effect by intramuscular adrenaline as the heart rate and the haemoglobin oxygen saturation were significantly higher in infants who received adrenaline. In contrast, the incidence of respiratory distress and hypoglycaemia was 14% among infants treated with adrenaline compared with 7% in those who received saline injection (p = 0.048). CONCLUSION: Intramuscular injection of 30 microg adrenaline does not reduce the incidence of respiratory distress or hypoglycaemia after elective caesarean section. [ABSTRACT FROM AUTHOR]

Background. The sinonasal tract is the second most common site of human papillomavirus (HPV)-related carcinomas in the head and neck. Published data on the association between sinonasal tumors and HPV are quite inconsistent among different regions. Material and methods. We performed high-risk HPV DNA in situ hybridization (ISH) and p16 immunohistochemistry on sinonasal carcinomas diagnosed between 2006 and 2016. Results. Of 105 sinonasal carcinomas, we found only two (2%) HPV-positive cases; both had non-keratinizing morphology and were diffusely positive for p16. By histologic type, HPV DNA positivity rate was 14% in non-keratinizing squamous cell carcinomas, and we did not detect HPV DNA in any other type of sinonasal carcinomas. Thirteen HPV-negative tumors (7 salivary gland carcinomas, 3 sinonasal undifferentiated carcinomas, 2 keratinizing squamous cell carcinomas, and 1 non-keratinizing squamous cell carcinoma) were positive for p16. In nine carcinomas arising from an underlying sinonasal papilloma, p16 and HPV DNA ISH were evaluated in both carcinoma and papilloma areas and all were negative. Follow-up information was available for 104 patients; 46 (44%) were alive and 58 (55%) died of disease. One of the two HPV-positive patients died of the disease; the other was alive at 100 months of follow-up. Conclusions. We detected a much lower percentage of HPV positivity in sinonasal carcinomas when compared to the literature. We believe that our results support various rates of HPV-related carcinomas depending on the geographic and ethnic characteristics. [ABSTRACT FROM AUTHOR]

Purpose of Review: In addition to disease-modifying anti-rheumatic drug (DMARD) treatment, exercise is increasingly promoted in patients with rheumatoid arthritis (RA). Although both are known to reduce disease activity, few studies have investigated the combined effects of these interventions on disease activity. The aim of this scoping review was to provide an overview of the reported evidence on whether a combined effect—i.e., a greater reduction in disease activity outcome measures—can be detected in studies where an exercise intervention was performed in addition to the DMARD treatment in patients with RA. This scoping review followed the PRISMA guidelines. A literature search was performed for exercise intervention studies in patients with RA treated with DMARDs. Studies without a non-exercise control group were excluded. Included studies reported on (components of) DAS28 and DMARD use and were assessed for methodological quality using version 1 of the Cochrane risk-of-bias tool for randomized trials. For each study, comparisons between groups (i.e., exercise + medication vs. medication only) were reported on disease activity outcome measures. Study data related to the exercise intervention, medication use, and other relevant factors were extracted to assess what may have influenced disease activity outcomes in the included studies. Recent Findings: A total of 11 studies were included of which 10 between-group studies on DAS28 components were made. The remaining one study focused on within-group comparisons only. Median duration of the exercise intervention studies was 5 months, and the median number of participants was 55. Six out of the 10 between-group studies reported no significant differences between groups in DAS28 components between exercise + medication vs. medication only. Four studies showed significant reductions in disease activity outcomes for the exercise + medication group compared with the medication-only group. Most studies were not adequately designed methodologically in order to investigate for comparisons of DAS28 components and had a high risk of multi-domain bias. Summary: Whether the simultaneous application of exercise therapy and DMARD medication in patients with RA has a combined effect on disease outcome remains unknown, due to weak methodological quality of existing studies. Future studies should focus on the combined effects by having disease activity as the primary outcome. [ABSTRACT FROM AUTHOR]

Among the numerous thermoelectric compounds, β-Zn4Sb3 has gained significant interest as a promising thermoelectric material due to its effective working temperature range and enhanced figure of merit (ZT) values. In this work, the effect of Se doping in β-Zn4Sb3 system has been studied. The structure refinement of the prepared Zn3.9Se0.1Sb3 solid solution was carried out using Rietveld refinement analysis, which confirms that the compound crystallizes in hexagonal rhombohedric structure with R-3c space group. Temperature-dependent electrical conductivity (σ) of the sample has been measured in the temperature range of 300–610 K. At room temperature, the electrical conductivity value of the sample was found to be high (~1919 S m−1) and it tends to decrease upon increasing the temperature up to 514 K and thereafter slightly increases, which indicates the typical metallic to semiconductor transition behaviour of the prepared compound. The positive Hall coefficient (RH) value reveals that the holes are the dominant charge carriers (p-type) in the prepared sample. The power factor value (σS2) of the sample increases linearly with increase in temperature up to 610 K. Hence the Se substitution in pristine Zn4Sb3 possesses greater effect in inducing superior thermoelectric power factor values. Temperature-dependent total thermal conductivity (κtotal) of Zn3.9Se0.1Sb3 sample is measured in the temperature range of 300 to 610 K. At room temperature, the κtotal value of the sample was found to be very low (~1 Wm−1 K−1) and it decreases linearly with increasing the temperature. At 610 K, the sample shows merely ultra-low-thermal conductivity value (~0.6 Wm−1 K−1). A peak ZT value of ~0.3 was obtained in Zn3.9Se0.1Sb3 solid solution at 610 K, which was found to be quite competitive with the current thermoelectric materials. [ABSTRACT FROM AUTHOR]

Purpose : Oral delivery of therapeutic peptides has been challenging due to multiple physiological factors and physicochemical properties of peptides. We report a systematic approach to identify formulation compositions combining a permeation enhancer and a peptidase inhibitor that minimize proteolytic degradation and increase absorption of a peptide across the small intestine. Methods: An acylated glucagon-like peptide-1/glucagon co-agonist peptide (4.5 kDa) was selected as a model peptide. Proteolytic stability of the peptide was investigated in rat and pig SIF. Effective PEs and multiple component formulations were identified in rats. Relative bioavailability of the peptide was determined in minipigs via intraduodenal administration (ID) of enteric capsules. Results: The peptide degraded rapidly in the rat and pig SIF. Citric acid, SBTI, and SBTCI inhibited the enzymatic degradation. The peptide self-associated into trimers in solution, however, addition of PEs monomerized the peptide. C10 was the most effective PE among tested PEs (DPC, LC, rhamnolipid, C12-maltosides, and SNAC) to improve intestinal absorption of the peptide in the rat IJ-closed loop model. A combination of C10 and SBTI or SBTCI increased the peptide exposure 5–tenfold compared to the exposure with the PE alone in the rat IJ-cannulated model, and achieved 1.06 ± 0.76% bioavailability in minipigs relative to subcutaneous via ID administration using enteric capsules. Conclusion: We identified SBTI and C10 as an effective peptidase inhibitor and PE for intestinal absorption of the peptide. The combination of SBTI and C10 addressed the peptide physiochemical properties and provides a formulation strategy to achieve intestinal delivery of this peptide. [ABSTRACT FROM AUTHOR]

Oral administration is the most preferred route for drug administration in clinic. However, due to unsatisfactory physicochemical properties of drugs and various physiological barriers, the oral bioavailability of most poorly water-soluble and macromolecules drugs is low and the therapeutic effect is unsatisfactory. Ionic liquids (ILs), molten salts with unique properties, show amazing potential for oral delivery. In addition to being able to form active pharmaceutical ingredients based ILs (API-ILs) to overcome drug solubility and polymorphism issues, ILs have also been used to enhance the solubility of poorly soluble drugs, enhance drug stability in the gastrointestinal environment, improve drug permeability in intestinal mucus, and facilitate drug penetration across the intestinal epithelial barrier. Furthermore, ILs were attempted as formulation components to develop novel oral drug delivery systems. This review focus on the application progress of ILs in oral drug delivery and the mechanisms. The challenges and perspectives of the development of ILs-based oral delivery systems are also discussed. This article reviews the latest advances of ionic liquids for oral drug delivery, focusing on the application and related mechanisms of ionic liquids in improving the drug physicochemical properties and enhancing drug delivery across physiological barriers. [ABSTRACT FROM AUTHOR]

Objective: Sinonasal inverted papilloma (IP) and its clinical features have been widely studied, but there are few studies delving into its etiology and risk factors. A narrative review was conducted to summarize a contemporary understanding of the potential etiologies of IP, including immunologic/inflammatory, viral, genetic, and environmental causes. Study Design: Review. Methods: A MEDLINE search was conducted through August 11, 2021, focusing on studies investigating the etiology and risk factors for sinonasal IP and its malignant transformation. Results: High‐ and low‐risk human papillomavirus have been connected with the formation of IP, but conflicting evidence exists regarding their role. Occupational and industrial exposures may also contribute to IP formation, while smoking may increase the odds of malignant progression. Exon 20 mutations in EGFR are an active area of research in IP with mixed evidence. Finally, several cell cycle and angiogenic factors such as Ki67, VEGF, and Akt/mTOR have been implicated in the development and progression of IP. Conclusion: There continues to be conflicting evidence around the development of IP, but significant progress has been made in recent years. Further study is needed for all these potential etiologies to elucidate risk factors and therapeutic strategies. [ABSTRACT FROM AUTHOR]

With the need for tools that assess microvascular status in diabetic foot disease (DFD) being clear, near infrared spectroscopy (NIRS) is a putative method for noninvasive testing of the diabetic foot. The use of NIRS in patients with peripheral arterial disease (PAD) has extended to its role in studying the pathophysiology of DFD. NIRS generates metrics such as recovery time, deoxygenation, oxygen consumption (VO2 ), tissue oxygen saturation (StO2 ), total haemoglobin (HbT), and oxyhaemoglobin area under the curve (O2 HbAUC ). NIRS may potentially help the multidisciplinary team stratify limbs as high-risk, especially in diabetic patients with symptoms masked by peripheral neuropathy. NIRS may be useful for assessing treatment effectiveness and preventing deterioration of patients with PAD. [ABSTRACT FROM AUTHOR]

The intestinal tract is an ecosystem in which the resident microbiota lives in symbiosis with its host. This symbiotic relationship is key to maintaining overall health, with dietary habits of the host representing one of the main external factors shaping the microbiome-host relationship. Diets high in fiber and low in fat and sugars, as opposed to Western and high-fat diets, have been shown to have a beneficial effect on intestinal health by promoting the growth of beneficial bacteria, improve mucus barrier function and immune tolerance, while inhibiting pro-inflammatory responses and their downstream effects. On the contrary, diets low in fiber and high in fat and sugars have been associated with alterations in microbiota composition/functionality and the subsequent development of chronic diseases such as food allergies, inflammatory bowel disease, and metabolic disease. In this review, we provided an updated overview of the current understanding of the connection between diet, microbiota, and health, with a special focus on the role of Western and highfat diets in shaping intestinal homeostasis by modulating the gut microbiota. [ABSTRACT FROM AUTHOR]

Purpose: Semaglutide is the only oral GLP-1 RA in the market, but oral bioavailability is generally limited in range of 0.4–1%. In this study, a new GLP-1RA named SHR-2042 was developed to gain higher oral bioavailability than semaglutide. Method: Self-association of SHR-2042, semaglutide and liraglutide were assessed using SEC-MALS. The intestinal perfusion test in SD rats was used to select permeation enhancers (PEs) including SNAC, C10 and LCC. ITC, CD and DLS were used to explore the interaction between SHR-2042 and SNAC. Gastric administrated test in SD rats was used to screen SHR-2042 granules with different SHR-2042/SNAC ratios. The oral bioavailability of SHR-2042 was studied in rats and monkeys. Result: The designed GLP-1RA, SHR-2042, gives a better solubility and lipophilicity than semaglutide. While it forms a similar oligomer with that of semaglutide. During the selection of PEs, SNAC shows better exposure than the other competing PEs including C10 and LCC. SHR-2042 and SNAC bind quickly and exhibit hydrophobic interaction. SNAC could promote monomerization of SHR-2042 and form micelles to trap the monomerized SHR-2042. The oral bioavailability of SHR-2042 paired with SNAC is 0.041% (1:0, w/w), 0.083% (1:10, w/w), 0.32% (1:30, w/w) and 2.83% (1:60, w/w) in rats. And the oral bioavailability of SHR-2042 matched with SNAC is 3.39% (1:30, w/w) in monkeys, which is over 10 times higher than that of semaglutide. Conclusion: We believe that the design and development of oral SHR-2042 will provide a new way to design more and more GLP-1RAs with high oral bioavailability in the future. [ABSTRACT FROM AUTHOR]

Selective permeability of biological membranes represents a significant barrier to the delivery of therapeutic substances into both microorganisms and mammalian cells, restricting the access of drugs into intracellular pathogens. Cell-penetrating peptides usually 5–30 amino acids with the characteristic ability to penetrate biological membranes have emerged as promising antimicrobial agents for treating infections as well as an effective delivery modality for biological conjugates such as nucleic acids, drugs, vaccines, nanoparticles, and therapeutic antibodies. However, several factors such as antimicrobial resistance and poor drug delivery of the existing medications justify the urgent need for developing a new class of antimicrobials. Herein, we review cell-penetrating peptides (CPPs) used to treat microbial infections. Although these peptides are biologically active for infections, effective transduction into membranes and cargo transport, serum stability, and half-life must be improved for optimum functions and development of next-generation antimicrobial agents. [ABSTRACT FROM AUTHOR]

Cancer is a severe disease that substantially jeopardizes global health. Although considerable efforts have been made to discover effective anti-cancer therapeutics, the cancer incidence and mortality are still growing. The personalized anti-cancer therapies present themselves as a promising solution for the dilemma because they could precisely destroy or fix the cancer targets based on the comprehensive genomic analyses. In addition, genome editing is an ideal way to implement personalized anti-cancer therapy because it allows the direct modification of pro-tumor genes as well as the generation of personalized anti-tumor immune cells. Furthermore, non-viral delivery system could effectively transport genome editing tools (GETs) into the cell nucleus with an appreciable safety profile. In this manuscript, the important attributes and recent progress of GETs will be discussed. Besides, the laboratory and clinical investigations that seek for the possibility of combining non-viral delivery systems with GETs for the treatment of cancer will be assessed in the scope of personalized therapy. [ABSTRACT FROM AUTHOR]

In the present work, polyvinylpyrrolidone (PVP)-assisted bismuth telluride (Bi2Te3) fibers were synthesized by electrospinning technique. These fibers were then compacted at a very slow rate at a constant temperature of 283 K. The as-prepared and compacted fibers were structurally and morphologically characterized via X-ray diffraction (XRD) and scanning electronic microscopy (SEM). Thermogravimetric analysis (TGA) along with differential scanning calorimetry (DSC) were also carried out up to 800 K for the thermal analysis of the as-prepared and compacted composite fibers. Thermoelectric characterizations (Seebeck coefficient, electrical conductivity and thermal conductivity) along with diffusive reflectance spectroscopy (DRS) were performed to study the thermoelectric properties and optical properties of the as-synthesized and compacted electrospun fibers. High Seebeck coefficient value of 3062µVK−1 and an ultra-low thermal conductivity value of 0.5 Wm−1 K−1 have been observed for the fibers at room temperature. The compacted samples have shown much better thermoelectric performance, and their zT increased significantly from 10−12 to 10−2 due to the compaction. [ABSTRACT FROM AUTHOR]

Background: The efficacy of simulation-based training in surgical education is well known. However, the development of training programs should start with problem identification and a general needs assessment to ensure that the content is aligned with current surgical trainee needs. The objective of the present study is to identify the technical skills and clinical procedures that should be included in a simulation-based curriculum in general surgery. Methods: A national, three-round Delphi process was conducted to achieve consensus on which technical skills and clinical procedures should be included in a simulation-based curriculum in general surgery. In total, 87 key opinion leaders were identified and invited to the study. Results: Round 1 of the Delphi process had a response rate of 64% (56/87) and a total of 245 suggestions. Based on these suggestions, a consolidated list of 51 technical skills or clinical procedures was made. The response rate in Delphi round 2 was 62% (54/87) resulting in a pre-prioritized order of procedures for round 3. The response rate in Delphi round 3 was 65% (35/54). The final list included 13 technical skills and clinical procedures. Training was predominantly requested within general open surgical skills, laparoscopic skills, and endoscopic skills, and a few specific procedures such as appendectomy and cholecystectomy were included in the final prioritized list. Conclusion: Based on the Delphi process 13 technical skills and clinical procedures were included in the final prioritized list, which can serve as a point of departure when developing simulation-based training in surgery. [ABSTRACT FROM AUTHOR]

The temperature dependences of the electrical conductivity σ(T), Seebeck coefficient σ(T), and heat capacity Cp(T) of polycrystalline samples of Bi2Te3, Bi2Te3+1%CuI, and Bi2Te3+1%(CuI+1/2Pb) are investigated in the temperature range below room temperature. Based on the temperature dependences of all investigated physical properties, it is discovered that phase transition occurs at 120–200 K. Investigation of single crystals shows that anomalies in the electrical resistivity (ρ(T)=1/σ(T)) occur only across the crystal growth axis (across the well‐conducting Bi–Te plane). Investigation of the low‐temperature dependence of electrical conductivity shows that all polycrystalline samples exhibit quasi‐two‐dimensional electron transport. Additionally, quasi‐two‐dimensional transport is detected in single crystals based on anisotropy analysis ρ⊥(T)/ρ‖(T):10 (where ρ‖(T) is the resistivity along the crystal growth axis, and ρ⊥(T) is resistivity across the crystal growth axis) and temperature dependence ρ(T):T2 below 50 K. The Fermi energy EF is estimated using the temperature dependence of S(T). It is discovered that an increase in EF at T > 200 K is associated with the phase transition. For single‐crystal samples, the maximum thermoelectric figure of merit ZT, as observed along the crystal growth axis, increases with doping. A maximum ZT value of ∼1.1 is observed for the Bi2Te3+1%(CuI+1/2Pb) sample at room temperature (T=300K). [ABSTRACT FROM AUTHOR]

The purpose of this research is to investigate the suitability of acquiring improved dissolution profile and sustained release of Fluvastatin sodium to reduce dosage frequency via a novel combination of freeze dried microspheres and Eudragit polymers-based matrix tablet technologies. Fluvastatin sodium microspheres were prepared using polyvinyl pyrollidone K-30 and Poloxamer 407 through solvent evaporation via freeze drying. We adopted a central composite design to examine the influence of independent variables viz. drug:polymer (X1) and surfactant (X2) on the t50 % (Y1), Q90 (Y2) and percentage drug content (Y3) along with determination of an optimized composition for production of an optimal Fluvastatin sodium microspheres. Design expert software illustrated that an optimized Fluvastatin sodium microspherescould be achieved using 1:3.496 drug:polymer and 3.102 % poloxamer 407 which would illustrates t50 % (36.33 min), Q90 (79.99 %) and percentage drug content (81.589 %). The mean diameter and polydispersity index of Fluvastatin sodium microspheres using dynamic light scattering was found 0.78 μm and 0.287, respectively. Sustained release tablet of optimized Fluvastatin sodium microspheres (Fluvastatin sodium microspheres-sustained release tablet) was manufactured using Eudragit RS 100 and Eudragit RL 100 based granules by wet granulation technique. In vitro drug release kinetics studies were executed to assess the drug release mechanism from optimized Fluvastatin sodium microspheres and Fluvastatin sodium microspheres-sustained release tablet. The dissolution level of Fluvastatin sodium was 3.58-fold improved wthin 2 h through the freeze dried microspheres. Fluvastatin sodium microspheres-sustained release tablet showed sustained drug release over 24 h and was matched properly to Korsmeyer-Peppas model with release exponent of 0.5318, which indicated drug release through diffusion and erosion mechanism. Conclusively, it has been demonstrated that novel combination of freeze dried microspheres and their Eudragit polymers-based matrix tablet techniques could find great potential for improving drug dissolution and sustained release of water insoluble drugs along with reduced dosage frequency. [ABSTRACT FROM AUTHOR]

Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation's ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach. Trials registration: NCT04975360. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is an established prognostic marker in oropharyngeal squamous cell carcinoma. Currently, the role of HPV in sinonasal carcinoma is being explored. This systematic review addresses the role of HPV in sinonasal cancer, establishing the occurrence of HPV-positive cancers and the influence of HPV-positivity on prognosis in sinonasal cancer as well as the utility of the putative surrogate marker of HPV (p16) in sinonasal cancer. Studies were identified with searches of Medline via PubMed and Embase via OVID (4 May 2020). Articles on original research concerning sinonasal cancer and HPV in humans written in English were included. Case reports with less than five cases were excluded. Initially, 545 articles were identified; 190 duplicate articles were removed leaving 355 articles for title/abstract screening. Title/abstract screening excluded 243 articles, leaving 112 studies assessed for eligibility. After full-text screening, 57 studies were included. All articles investigated the significance of HPV in sinonasal carcinomas. HPV was reported in approximately 30% of sinonasal squamous cell carcinoma (SNSCC), where it was associated with a better prognosis. In sinonasal cancer, p16 is associated with diagnostic pitfalls and a putative utility of p16 in SNSCC has yet to be established. HPV was not frequently reported in other types of sinonasal carcinomas, besides the recently described subtype, HPV-dependent Multiphenotypic Sinonasal Carcinoma. In other types of sinonasal carcinoma, HPV is not frequently found. Approximately 30% of SNSCC are HPV-positive. HPV-positivity in SNSCC is associated with improved survival. HPV occurs only rarely in other sinonasal cancers. There is currently not sufficient evidence for p16 as a surrogate marker of HPV in SNSCC. [ABSTRACT FROM AUTHOR]

Objectives: In this paper, we explore and compare types and longitudinal trends of hospital adverse events in Norway and Sweden in the years 2013–2018 with special reference to AEs that contributed to death. Design: Acute care hospitals in both countries performed medical record reviews on randomly selected medical records from all eligible admissions. Analysis: Comparison between Norway and Sweden of linear trends from 2013–2018, and percentage rates of admissions with at least one AE according to types and severities. Setting: Norway and Sweden have similar socio-economic and demographic characteristics, which constitutes a relevant context for cooperation, comparison and mutual learning. This setting has promoted the use of GTT to monitor national rates of AEs in hospital care in the two countries. Participants: 53 367 medical records in Norway and 88 637 medical records in Sweden were reviewed. Results: 13.2% of hospital admissions in Norway and 13.1% in Sweden were associated with an AE of all severities (E-I). 0.23% of hospital admissions in Norway and 0.26% in Sweden were associated with an AE that contributed to death (I). The differences between the two countries were not statistically significant. Conclusions: There were no significant differences in overall rates (E-I) of AEs in Norway and Sweden, nor in rates of AEs that contributed to death (I). There was no significant change in AEs or fatal AEs in either country over the six-year time period. [ABSTRACT FROM AUTHOR]

Background: Resuscitative emergency thoracotomy is a potential life-saving procedure but is rarely performed outside of busy trauma centers. Yet the intervention cannot be deferred nor centralized for critically injured patients presenting in extremis. Low-volume experience may be mitigated by structured training. The aim of this study was to describe concurrent development of training and simulation in a trauma system and associated effect on one time-critical emergency procedure on patient outcome. Methods: An observational cohort study split into 3 arbitrary time-phases of trauma system development referred to as 'early', 'developing' and 'mature' time-periods. Core characteristics of the system is described for each phase and concurrent outcomes for all consecutive emergency thoracotomies described with focus on patient characteristics and outcome analyzed for trends in time. Results: Over the study period, a total of 36 emergency thoracotomies were performed, of which 5 survived (13.9%). The "early" phase had no survivors (0/10), with 2 of 13 (15%) and 3 of 13 (23%) surviving in the development and mature phase, respectively. A decline in 'elderly' (>55 years) patients who had emergency thoracotomy occurred with each time period (from 50%, 31% to 7.7%, respectively). The gender distribution and the injury severity scores on admission remained unchanged, while the rate of patients with signs on life (SOL) increased over time. Conclusion: The improvement over time in survival for one time-critical emergency procedure may be attributed to structured implementation of team and procedure training. The findings may be transferred to other low-volume regions for improved trauma care. [ABSTRACT FROM AUTHOR]