Dermal αSMA+ myofibroblasts orchestrate skin wound repair via ß1 integrin and independent of type I collagen production.

Skin wound repair is essential for organismal survival and failure of which leads to non-healing wounds, a leading health issue worldwide. However, mechanistic understanding of chronic wounds remains a major challenge due to lack of appropriate genetic mouse models. αSMA+ myofibroblasts, a unique class of dermal fibroblasts, are associated with cutaneous wound healing but their precise function remains unknown. We demonstrate that genetic depletion of αSMA+ myofibroblasts leads to pleiotropic wound healing defects, including lack of reepithelialization and granulation, dampened angiogenesis, and heightened hypoxia, hallmarks of chronic non-healing wounds. Other wound-associated FAP+ and FSP1+ fibroblasts do not exhibit such dominant functions. While type I collagen (COL1) expressing cells play a role in the repair process, COL1 produced by αSMA+ myofibroblasts is surprisingly dispensable for wound repair. In contrast, we show that ß1 integrin from αSMA+ myofibroblasts, but not TGFßRII, is essential for wound healing, facilitating contractility, reepithelization, and vascularization. Collectively, our study provides evidence for the functions of myofibroblasts in ß1 integrin-mediated wound repair with potential implications for treating chronic non-healing wounds.

Naloxone Versus Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Patients.

BACKGROUND: Opioid-induced constipation (OIC) may occur in up to 81% of critically ill patients and can lead to many complications. Opioid antagonists are a reasonable approach and may be used for managing OIC. OBJECTIVE: The purpose of this study was to assess the efficacy of enteral naloxone (NLX) versus subcutaneous methylnaltrexone (MNTX) for the management of OIC in critically ill patients. METHODS: A retrospective analysis was conducted on adult patients who received NLX or MNTX and a continuous opioid infusion for at least 48 hours. The primary end point was time to resolution of constipation, defined as hours to first bowel movement (BM) after the first dose of an opioid antagonist. Reversal of analgesia was assessed by comparing the total number of morphine milligram equivalents (MME) 24 hours preopioid and postopioid antagonist administration. Univariate and multivariate analyses were conducted to assess treatment response within 48 hours. RESULTS: Baseline characteristics were similar between patients receiving NTX (n = 89) and MNTX (n = 71). However, the time to the first BM with NLX was 18 hours compared with 41 hours with MNTX (P = 0.004). There was no difference in MME requirements 24 hours pre/post NLX or MNTX administration. Naloxone administration was identified as a statistically significant predictor of BM within 48 hours (odds ratio [OR] = 2.68 [1.33-5.38]). CONCLUSION AND RELEVANCE: The time to first BM was shorter with enteral NLX. Both NLX and MNTX appear to be effective for the management of OIC without causing reversal of analgesia. Future controlled, prospective trials comparing these agents are warranted.

3D particle tracking using transport of intensity equation (TIE).

This article presents a simple and high-speed approach for tracking colloidal spheres in three dimensions. The method uses the curvature of the wavefront as determined by the transport of intensity equation (TIE) technique. Due to the fact that the TIE is applicable under partially coherent light, our technique is fully compatible with standard bright field microscopes, requiring no demanding environmental stability requirements or restrictions on the noise produced by related laser speckles. The method was validated experimentally to determine the sedimentation and diffusion coefficients of two different sizes of microspheres, 20 and 3 microns. The 3D position of the microspheres was calculated with an accuracy greater than 350 nm. Moreover, we examined the calculated 3D positions to determine the parameters of the microsphere interaction with its surrounding media, such as the sedimentation and diffusion coefficients. The results show that the measured sedimentation and diffusion of the microspheres have a good agreement with predicted values of about 2% and 10%, respectively, demonstrating the robustness of our proposed method.

A transferable prediction model of molecular adsorption on metals based on adsorbate and substrate properties.

Surface adsorption is one of the fundamental processes in numerous fields, including catalysis, the environment, energy and medicine. The development of an adsorption model which provides an effective prediction of binding energy in minutes has been a long term goal in surface and interface science. The solution has been elusive as identifying the intrinsic determinants of the adsorption energy for various compositions, structures and environments is non-trivial. We introduce a new and flexible model for predicting adsorption energies to metal substrates. The model is based on easily computed, intrinsic properties of the substrate and adsorbate, which are the same for all the considered systems. It is parameterised using machine learning based on first-principles calculations of probe molecules (e.g., H2O, CO2, O2, N2) adsorbed to a range of pure metal substrates. The model predicts the computed dissociative adsorption energy to metal surfaces with a correlation coefficient of 0.93 and a mean absolute error of 0.77 eV for the large database of molecular adsorption energies provided by Catalysis-Hub.org which have a range of 15 eV. As the model is based on pre-computed quantities it provides near-instantaneous estimates of adsorption energies and it is sufficiently accurate to eliminate around 90% of candidates in screening study of new adsorbates. The model, therefore, significantly enhances current efforts to identify new molecular coatings in many applied research fields.

Diffractometry-based vortex beams fractional topological charge measurement.

In this Letter, we investigate the Fresnel diffraction of vortex beams from a phase plate and propose a novel (to the best of our knowledge) method to determine the fractional part of the topological charge of vortex beams. When a vortex beam with a fractional topological charge illuminates the edge region of a transparent plate, the visibility of the diffraction pattern on two sides of the beam is different. Rotation of the phase plate changes the visibility on the left and right sides of the beam, periodically. By measuring three consecutive angles of the minimum visibilities, the fractional part of the topological charge is obtained. The proposed method is verified experimentally and is shown to be independent of the phase plate and vortex beam parameters. The precision of the method is obtained better than 0.01.

Prospective evaluation of the value of dynamic contrast enhanced (DCE) imaging for prostate cancer detection, with pathology correlation.

INTRODUCTION: The aim of this study was to evaluate the value of dynamic contrast enhanced (DCE) imaging in multi-parametric prostate MRI (mpMRI) for the detection and staging of prostate cancer in comparison with T2W and DWI images alone in biparametric MRI (bpMRI) in treatment naïve patients. MATERIALS AND METHODS: One hundred consecutive patients who underwent a prostate MRI at our institution from June-August 2017, as well as a systematic ultrasound-guided prostate biopsy or prostatectomy, were included. Strictly following PIRADSv2, the MRI studies were independently interpreted by a body radiologist and a body-imaging fellow on two different occasions 8-10 weeks apart. Initially, with all mpMRI sequences and then without the DCE sequence (bpMRI). The readers were blinded to the clinical information. Ethics approval was obtained. RESULTS: One hundred treatment-naïve patients were included (median age 64, age range 48-81, mean PSA 10.3). There was almost perfect intra-observer agreement for mpMRI versus bpMRI for both readers [Cohen's Kappa (k) 0.88-0.86] and substantial inter-observer agreement (k = 0.74 for mpMRI and 0.76 for bpMRI). The sensitivity and specificity did not significantly change between multi-parametric and bi-parametric MRI (Sensitivity 91.7% and 90%, Specificity of 85.5% and 85% for mpMRI and bpMRI, respectively). CONCLUSION: Based on our findings, prostate MRI without DCE (bpMRI) is of comparable diagnostic accuracy to mpMRI in treatment-naïve patients. Performing prostate MRI without DCE (bpMRI) will reduce acquisition time, decrease cost and potentially improve patient safety.

Regenerative effects of glycyrrhizin and/or platelet rich plasma on type-II collagen induced arthritis: Targeting autophay machinery markers, inflammation and oxidative stress.

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease manifested by joint destruction and deformity, hence decreasing patient's life quality. The aim of the present work is to explore the mechanistic effects of glycyrrhizin (GL)and/or platelet rich plasma (PRP) treatment on collagen induced arthritis. 75 female Wistar rats were allocated into five equal groups. Group I: control group. Group II: arthritis group (A group); arthritis was induced by type-II collagen Group III: Glycyrrhizin treated group(A + GL group), Group IV: platelet rich plasma treated group(A + PRP group)and Group V: combined treatment group(A + GL + PRP group). Hind paw joint tissue levels of high-mobility group box 1 protein (HMGB-1), beclin-1 and nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity were detected by ELISA. Activities of myeloperoxidase (MPO) and catalase enzymes were determined spectrophotometrically. mRNA expression levels of microtubule associated protein light chain 3 (LC3) was detected by quantitative real time PCR. After 8 weeks treatment, there was improvement of inflammation and autophagy biomarkers by the significant reduction of HMGB-1 and beclin-1 levels, down regulation ofLC3mRNA expression. On the other hand, we monitored restoration of the anti-oxidant status through the inhibited MPO activity besides induction of both catalase and Nrf2-DNA binding activities. It could be concluded that, the mutual use of both PRP and GL had a greater effect than each alone against arthritis which is considered a novel finding that can highlight the regenerative and ameliorative effects of this combined treatmentthus launching promising avenues for RA treatment.

Fresnel diffraction due to phase gradient singularity.

In this Letter, a singularity in the phase gradient is introduced as a new origin of the diffraction from phase objects. The continuity in the amplitude and phase of the wave and the singularity in the phase gradient are assumed to describe this phenomenon. Fresnel diffraction of Fresnel double mirror and biprism are studied as practical examples, and the diffracted intensity distribution is calculated. We show that the intensity of the diffracted field varies with an almost constant period along the average propagation direction. Using this value and the fringe spacing of the interference pattern on a plane normal to the average propagation direction, the angle between two interfering beams and the wavelength of the incident light could be simultaneously derived. The diffraction pattern of the Fresnel double mirror and Fresnel biprism were obtained experimentally, which were in good agreement with the theoretical results.

Digital holography based submicron thermometry.

Here we introduce a phase-shifting digital holography-based method to determine the temperature profile around an irradiated (sub-)micron spherical bead. The method utilizes a Mach-Zehnder interferometer implemented into an open setup microscope. The results of irradiated gold spheres with diameter of 400 nm and also silver-coated micron-sized silica beads embedded in silicone oil are presented. We show that the applied method is able to accurately determine the surface temperature with accuracy of 1 °C. Our experimental results perfectly confirm the theoretical prediction of temperature profile around the irradiated bead.

Communication gaps associated with donor-derived infections.

The detection and management of potential donor-derived infections is challenging, in part due to the complexity of communications between diverse labs, organ procurement organizations (OPOs), and recipient transplant centers. We sought to determine if communication delays or errors occur in the reporting and management of donor-derived infections and if these are associated with preventable adverse events in recipients. All reported potential donor-derived transmission events reviewed by the Organ Procurement and Transplantation Network Ad Hoc Disease Transmission Advisory Committee from January 2008 to June 2010 were evaluated for communication gaps between the donor center, OPO and transplant centers. The impact on recipient outcomes was then determined. Fifty-six infection events (IEs; involving 168 recipients) were evaluated. Eighteen IEs (48 recipients) were associated with communication gaps, of which 12 resulted in adverse effects in 69% of recipients (20/29), including six deaths. When IEs and test results were reported without delay, appropriate interventions were taken, subsequently minimizing or averting recipient infection (23 IEs, 72 recipients). Communication gaps in reported IEs are frequent, occur at multiple levels in the communication process, and contribute to adverse outcomes among affected transplant recipients. Conversely, effective communication minimized or averted infection in transplant recipients.

Vascular heterogeneity of tight junction Claudins guides organotropic metastasis.

Carcinomas are associated with metastasis to specific organs while sparing others. Breast cancer presents with lung metastasis but rarely kidney metastasis. Using this difference as an example, we queried the mechanism(s) behind the proclivity for organ-specific metastasis. We used spontaneous and implant models of metastatic mammary carcinoma coupled with inflammatory tissue fibrosis, single-cell sequencing analyses and functional studies to unravel the causal determinants of organ-specific metastasis. Here we show that lung metastasis is facilitated by angiopoietin 2 (Ang2)-mediated suppression of lung-specific endothelial tight junction protein Claudin 5, which is augmented by the inflammatory fibrotic microenvironment and prevented by anti-Ang2 blocking antibodies, while kidney metastasis is prevented by non-Ang2-responsive Claudins 2 and 10. Suppression of Claudins 2 and 10 was sufficient to induce the emergence of kidney metastasis. This study illustrates the influence of organ-specific vascular heterogeneity in determining organotropic metastasis, independent of cancer cell-intrinsic mechanisms.

Multiple intracranial dural arteriovenous fistula.

Dural arteriovenous fistula (DAVF) is also known as dural arteriovenous malformation. Two forms of DAVF have been introduced, however, here we present an exceptional case of DAVF with unique origin and drainage. In this study, we present a rare case of multiple DAVFs in a 50 year old man with right parietal intraparenchymal hemorrhage. MRI showed two round right parieto-occipital masses with flow void intensity adjacent to superior sagittal sinus (SSS). Another pathology connected to SSS by an abnormal cortical vein was detected anterior to first lesion. This study showed that both DAVFs were simultaneously drained in SSS in our patient.

Awake Airtraq intubation in an immobile neck--a case report.

A 78 year old patient, whose neck was fixed with polyaxial lateral mass screws and rod was planned for an incisional hernia repair under general anaesthesia. Securing the airway in such an immobile neck is a challenge to the anesthesiologist. Although awake fibreoptic intubation is considered as the gold standard for such challenging patients, we successfully used the Airtraq optical laryngoscope for performing an awake intubation in this case. This example paves the way for the management of similar cases in the future.

Role of Heme Oxygenase, Leptin, Coenzyme Q10 and Trace Elements in Pre-eclamptic Women.

The objective of this study to evaluate heme oxygenase (COHb), leptin and coenzyme Q10 (CoQ10) in pre-eclamptic women. Also Zinc, copper, Iron, total iron binding capacity, Ferritin and uric acid were assessed. 120 female subjects were included in this study. They were divided into, 60 female with normal pregnancy attending the outpatient clinic, 60 pre-eclamptic patients were recruited from obstetrics and gynaecology department El-kasr El-Aini hospital. The results showed that in pre-eclampatic group, leptin level was significantly increased while COHb and CoQ10 was significantly decreased. It is concluded that hemeoxygenase, leptin and coenzyme CoQ10 can be considered as new markers for prediction of pre-eclampsia.

New onset diabetes mellitus in post-COVID-19 patients.

Background: Diabetes, is known to have a bilateral relationship with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Precise mechanism of diabetes onset in COVID-19 patients remains unclear. Aim: To analyse the incidence of new onset diabetes (NODM) among COVID-19 patients, as well as the effect of body mass index (BMI), family history, and steroid use on the incidence of the disease. Methods: Adult, not known diabetic patients, tested positive with Rapid Antigen Test or RT-PCR admitted to a tertiary care hospital and research institute were included in the present prospective observational study. The patients who developed NODM and NOPD (New Onset Pre-diabetes) during the three months follow-up and the risk factors associated were assessed. Patients with HbA1c >6.4% were diagnosed with NODM. An HbA1c of 5.7% to 6.4% was used to characterize NOPD. Results: Out of 273 previously not known diabetic COVID-19 infected individuals, a total of 100 were studied for three months after consent. Mean age of the patients 48.31 ± 19.07 years with male predominance (67%). Among these, 58% were non-diabetics and 42% were pre-diabetics. 6 (10.3%) of the 58 non-diabetics developed NOPD, and 8 (13.8%) developed NODM. 6 (14.2%) of the 42 pre-diabetics became non-diabetic, and 16.6% (7) developed NODM. Family history of DM (P < 0.001), severity at admission (P < 0.006), diabetic ketoacidosis (P < 0.0275), and persistent symptoms were associated significantly with NODM. Those with NODM had significantly greater BMI, O2 duration, steroid duration, FBS, and PPBS (P < 0.001 for all). Nearly 67% of the patients who developed NOPD had shortness of breath as the common symptom at time of admission (P = 0.0165). Conclusion: The incidence of NODM was strongly influenced by positive family history of DM, higher BMI, steroid dosage, and its duration. Hence, patients with COVID-19 need to be under surveillance for blood glucose screening.

Synthesis and characterization of berberine-loaded chitosan nanoparticles for the protection of urethane-induced lung cancer.

Lung cancer is one of the most common types of malignant tumors of the respiratory system and has the highest rates of incidence and mortality of malignant tumors. This study aimed to synthesize and characterize berberine-loaded chitosan nanoparticles (BBR-COSNPs) and to evaluate their protective effects against urethane-induced lung cancer. Forty male albino mice were divided into four groups, with the first serving as a negative control and the other three groups were injected intraperitoneally with urethane (1 mg/kg b.w) each other day for 1 week then group 2 was served as a positive control, however, groups 3 and 4 were treated orally with a daily dose of BBR or BBR-COSNPs (75 mg/kg b.w) for 10 consecutive weeks. Blood and lung tissue samples are collected for laboratory assay. The BBR-COSNPs were spherical, with an average particle size of 45.56 nm and zeta potential of 39.82 1.82 mV. The in vivo data demonstrated that mice given urethane alone had a significant increase in MDA, NO, NF-κB level, HIF1-α, and COX-2-positive expression in the lung tissue and serum VEGFR2, ALT, AST, urea, and creatinine accompanied with a significant decrease in GSH, SOD, caspase 9 in the lung tissue and serum BAX. Co-treatment with BBR-COSNPs suppressed lung cancer growth and promoted apoptosis by modulating serum BAX and lung caspase 9 gene expressions. In addition, BBR-COSNPs inhibited tumor angiogenesis by reduction in levels of serum VEGFR2 and lung HIF 1 gene expression. It is possible to conclude that BBR-COSNPs can be used in oral administration formulations for lunganticancer therapy.

Reconstructing the phase distribution of two interfering wavefronts by analysis of their nonlocalized fringes with an iterative method.

This paper presents a technique for reconstructing two interfering wavefronts by analyzing their 3D interference field pattern. The method is based on the numerical inverse problem and will present a robust algorithm for reconstructing of wavefronts. Several simulations are done to validate the proposed method.

Hepatic perfusional changes on CT and MRI: a radiology primer.

Hepatic perfusional changes are common in response to, or as a result of, a multitude of pathological processes. These can be neoplastic, inflammatory, fibrotic, or ischemic in origin, to name a few. The liver, having a dual blood supply, is a unique organ to study using contrast-enhanced CT and MRI imaging due to its varied appearance on multiphasic imaging. Knowledge of the CT and MRI appearance of hepatic perfusional changes, in addition to the clinical presentation, can often result in an accurate differential diagnosis. Many of the conditions that cause these changes in hepatic blood flow result in similar appearances on imaging. As a result, it is important that radiologists be aware of common pitfalls when dealing with hepatic perfusional changes to prevent misdiagnosis or delayed diagnosis. As such, this review will focus on some of the various causes of hepatic perfusional changes and how to accurately identify and diagnose them based on their CT and MRI appearance.

The impact of cow dung augmentation on soil restoration and bio-accumulation of metals (Lead and Cadmium) in Pheretima posthuma (Annelida: Clitellata).

To investigate the role of cow dung in soil reclamation and bio assimilation along with bio accumulation of heavy metals in earthworm (P. posthuma) (N=900) earthworms were used and treatment groups of CD-soil mixture of different proportion of cow dung were designed. Nonlethal doses of lead acetate and cadmium chloride were added in treatment groups. Mature P. posthuma were released in each experimental pot maintaining the favorable conditions. The pH, carbon, nitrogen, phosphorus, exchangeable cations, and heavy metal level of each mixture was evaluated. The results indicated that bio-assimilation of Pb and Cd by P. posthuma were significantly (P ˂ 0.01) higher in different soil-CD treatments compared to control. Highest bio-assimilation of both metals was observed in T1 of both groups (Pb = 563.8 mg/kg and Cd = 42.95 mg/kg). The contents of both metals were significantly (P ˂ 0.05) lowered in casting. The nutrient concentration in the final castings of all soil-CD treatments were also equally transformed from less or insoluble to more soluble and available for plants, except for carbon level which increased with CD proportion. It is concluded that cow dung as organic matter has a positive effect on soil reclamation and bio-assimilation of metals by P. posthuma.