Herb Extracellular Vesicle-Chitosan-PEGylated Graphene Oxide Conjugate Delivers Estrogen Receptor α Targeting siRNA to Breast Cancer Cells.

Herb-based extracellular vesicles (EV), inherently replete with bioactive proteins, RNA, lipids, and other medicinal compounds, are noncytotoxic and uniquely capable of cellular delivery to meet the ever-stringent challenges of ongoing clinical applications. EVs are abundant in nature, affordable, and scalable, but they are also incredibly fragile and stuffed with many biomolecules. To address the low drug binding abilities and poor stability of EVs, we demonstrated herb-based EVs (isolated from neem, mint, and curry leaves) conjugated with chitosan (CS) and PEGylated graphene oxide (GP) that led to their transformation into robust and efficient vectors. The designed conjugates successfully delivered estrogen receptor α (ERα1)-targeting siRNA to breast cancer MCF7 cells. Our data revealed that neem-based EV-CS-GP conjugates were most efficient in cellular siRNA delivery, which could be attributed to hyaluronic acid-mediated recognition of neem EVs by MCF7 cells via CD44 receptors. Our approach shows a futuristic direction in designing clinically viable, sustainable, nontoxic EV-based vehicles that can deliver a variety of functional siRNA cargos.

Glucose-Responsive Chitosan Nanoparticle/Poly(vinyl alcohol) Hydrogels for Sustained Insulin Release In Vivo.

Stimuli-responsive hydrogels (HGs) with a controlled drug release profile are the current challenge for advanced therapeutic applications. Specifically, antidiabetic drug-loaded glucose-responsive HGs are being investigated for closed-loop insulin delivery in insulin-dependent diabetes patients. In this direction, new design principles must be exploited to create inexpensive, naturally occurring, biocompatible glucose-responsive HG materials for the future. In this work, we developed chitosan nanoparticle/poly(vinyl alcohol) (PVA) hybrid HGs (CPHGs) for controlled insulin delivery for diabetes management. In this design, PVA and chitosan nanoparticles (CNPs) are cross-linked with a glucose-responsive formylphenylboronic acid (FPBA)-based cross-linker in situ. Leveraging the structural diversity of FPBA and its pinacol ester-based cross-linkers, we fabricate six CPHGs (CPHG1-6) with more than 80% water content. Using dynamic rheological measurements, we demonstrate elastic solid-like properties of CPHG1-6, which are dramatically reduced under low-pH and high-glucose environments. An in vitro drug release assay reveals size-dependent glucose-responsive drug release from the CPHGs under physiological conditions. It is important to note that the CPHGs show appreciable self-healing and noncytotoxic properties. Promisingly, we observe a significantly slower insulin release profile from the CPHG matrix in the type-1 diabetes (T1D) rat model. We are actively pursuing scaling up of CPHGs and the in vivo safety studies for clinical trial in the near future.

In Situ-Forming Protein-Polymer Hydrogel for Glucose-Responsive Insulin Release.

Phenylboronic acid (PBA)-containing hydrogels (HGs), capable of glucose-responsive insulin release, have shown promise in diabetes management in preclinical studies. However, sustainable material usage and attaining an optimum insulin release profile pose a significant challenge in such HG design. Herein, we present the development of a straightforward fabrication strategy for glucose-responsive protein-polymer hybrid HGs (PPHGs). We prepare PPHGs by crosslinking polyvinyl alcohol (PVA) with various nature-abundant proteins, such as bovine serum albumin (BSA), egg albumin, casein, whey protein, and so forth, using formylphenylboronic acid (FPBA)-based crosslinkers. We showcase PPHGs with diverse bulk rheological properties that are appropriately modulated by the positions of aldehyde, boronic acid, and fluorine substitutions in the FPBA-crosslinker. The orthogonal imine and boronate ester bonds formed by FPBAs are susceptible to the acidic pH environment and glucose concentrations, leading to the glucose-responsive dissolution of the PPHGs. We further demonstrate that by an appropriate selection of FPBAs, glucose-responsive insulin release profiles of the PPHGs can be precisely engineered at the molecular level. Importantly, PPHGs are injectable, incur no cytotoxicity, and, therefore, hold great potential as smart insulin for in vivo applications in the near future.

Breast cancer: presentation, investigation and management.

Breast cancer is the most common global malignancy and the leading cause of cancer deaths. Despite this, undergraduate and postgraduate exposure to breast cancer is limited, impacting on the ability of clinicians to accurately recognise, assess and refer appropriate patients. This article provides a comprehensive review of the pathology, epidemiology, clinical presentation, referral pathways and management of breast cancer in the UK. It also describes how to conduct a thorough clinical breast examination.

Segmentation of Change in Surface Geometry Analysis for Cultural Heritage Applications.

This work proposes a change-based segmentation method for applications to cultural heritage (CH) imaging to perform monitoring and assess changes at each surface point. It can be used as a support or component of the 3D sensors to analyze surface geometry changes. In this research, we proposed a new method to identify surface changes employing segmentation based on 3D geometrical data acquired at different time intervals. The geometrical comparison was performed by calculating point-to-point Euclidean distances for each pair of surface points between the target and source geometry models. Four other methods for local distance measurement were proposed and tested. In the segmentation method, we analyze the local histograms of the distances between the measuring points of the source and target models. Then the parameters of these histograms are determined, and predefined classes are assigned to target surface points. The proposed methodology was evaluated by considering two different case studies of restoration issues on CH surfaces and monitoring them over time. The results were presented with a colormap visualization for each category of the detected change in the analysis. The proposed segmentation method will help in the field of conservation and restoration for the documentation and quantification of geometrical surface change information. This analysis can help in decision-making for the assessment of damage and potential prevention of further damage, and the interpretation of measurement results.

Current margin practice and effect on re-excision rates following the publication of the SSO-ASTRO consensus and ABS consensus guidelines: a national prospective study of 2858 women undergoing breast-conserving therapy in the UK and Ireland.

INTRODUCTION: There is variation in margin policy for breast conserving therapy (BCT) in the UK and Ireland. In response to the Society of Surgical Oncology and American Society for Radiation Oncology (SSO-ASTRO) margin consensus ('no ink on tumour' for invasive and 2 mm for ductal carcinoma in situ [DCIS]) and the Association of Breast Surgery (ABS) consensus (1 mm for invasive and DCIS), we report on current margin practice and unit infrastructure in the UK and Ireland and describe how these factors impact on re-excision rates. METHODS: A trainee collaborative-led multicentre prospective study was conducted in the UK and Ireland between 1st February and 31st May 2016. Data were collected on consecutive BCT patients and on local infrastructure and policies. RESULTS: A total of 79 sites participated in the data collection (75% screening units; average 372 cancers annually, range 70-900). For DCIS, 53.2% of units accept 1 mm and 38% accept 2-mm margins. For invasive disease 77.2% accept 1 mm and 13.9% accept 'no ink on tumour'. A total of 2858 patients underwent BCT with a mean re-excision rate of 17.2% across units (range 0-41%). The re-excision rate would be reduced to 15% if all units applied SSO-ASTRO guidelines and to 14.8% if all units followed ABS guidelines. Of those who required re-operation, 65% had disease present at margin. CONCLUSION: There continues to be large variation in margin policy and re-excision rates across units. Altering margin policies to follow either SSO-ASTRO or ABS guidelines would result in a modest reduction in the national re-excision rate. Most re-excisions are for involved margins rather than close margins.

Evolution of male rectal prolapse surgery and initial experience of robotic rectopexy in men.

Laparoscopic ventral mesh rectopexy (LVMR) has proven benefit in the treatment of external rectal prolapse and symptomatic internal rectal prolapse in women. However, there is a recurrence rate of 4-50% depending on indication. Some of this recurrence is attributable to persistent lateral and posterior prolapses. Modifications of LVMR (modified Orr-Loygue rectopexies) describe an additional narrow posterior rectal mesh fixed to the mesorectal fat, which is inherently insecure. Additional complications in men include sexual dysfunction caused by nerve damage from the ventral rectal dissection. There is one case series in men, published by a surgeon with an unusually large practice, showing LVMR to have a good success rate with low rates of sexual dysfunction. Other series have contained small numbers of men, but subgroup analysis to determine success and complication rates is not possible. Robotic surgery is more precise than laparoscopic surgery, allows stereotactic vision, and has a stable platform. We have developed a robotic modified Orr-Loygue rectopexy in an attempt to deal with the persistent components of posterior rectal prolapse by placing a mesh posteriorly through a narrow dissection and securing the mesh to the distal rectal muscle tube. Mesh-to-muscle fixation is more secure than mesh-to-mesorectal fat fixation. The robotic platform also improves the accuracy of ventral dissection and reduces the risk of sexual dysfunction in men. Our initial results indicate that robotic modified Orr-Loygue rectopexy is a safe and feasible option for rectal prolapse in men, with no more complications or recurrences than the best published outcomes for LVMR.

Safety of radioactive sentinel node biopsy for breast cancer and the pregnant surgeon - A review.

INTRODUCTION: Sentinel node biopsy is an established key element in the surgical management of breast cancer and melanoma. Several studies have assessed radiation exposure during sentinel node biopsy and confirmed it to be safe for health workers. Recent demographic changes amongst surgeons has resulted in increasing numbers of women of childbearing age performing sentinel node procedures as a regular part of their surgical practice. We aimed to assess the radiation risk posed by sentinel node biopsy in breast cancer surgery to pregnant surgeons. METHODS: A search of indexed citations from PUBMED and Cochrane databases for studies assessing the radiation exposure to the primary surgeon during sentinel node biopsy was undertaken. Due to the variability of melanoma location in relation to nodal basins, we have focused on sentinel node biopsy for breast cancer where surgeon positioning, radiopharmaceutical injection and nodal dissection sites are consistent. RESULTS: From the eleven studies totalling 344 procedures, exposure doses to the abdomens and fingers of surgeons undertaking sentinel node biopsy were within the guideline maximum recommended exposure limit of 1 mSv as set out by the International Committee on Radiation Protection (ICRP) 107 recommendations as long as fewer than one hundred procedures are performed throughout the duration of the pregnancy. Of note the radiation doses in the newer studies were much lower and used more sensitive instruments to detect radiation exposure. CONCLUSIONS: Providing the numbers of procedures are within defined limits, the radiation risks posed to pregnant surgeons undertaking sentinel node procedures are limited and within the regulatory guidelines for pregnancy.

Efficacy of topical local anaesthesia to reduce perioperative pain for endovenous laser ablation of varicose veins: a double-blind randomized controlled trial.

OBJECTIVES: Tumescent local anaesthesia via multiple injections in the perivenous space leads to intraoperative and postoperative pain during endovenous laser ablation (EVLA). We considered whether the application of topical local anaesthesia reduces pain caused by these injections. METHODS: Eligible patients undergoing local anaesthetic EVLA were recruited and randomized to either application of topical local anaesthesia or water-based gel (placebo) to the inner thigh over the marked great saphenous vein. Varicose vein severity was classified using the American venous forum clinical etiological anatomical pathological (CEAP) classification score for chronic venous disorders and the Aberdeen varicose vein questionnaire (AVVQ) score. Visual analogue pain scores attributable to the varicose veins or tumescent injections were recorded before the procedure, immediately postprocedure and prior to discharge. Secondary outcome measures were extra analgesia requirement during or immediately postoperatively. Analysis was performed using the unpaired Student's t test and Wilcoxon signed-rank test. RESULTS: A total of 52 patients underwent the procedure. Eight patients were excluded from analysis due to failure to complete the procedure or incomplete data. In the remaining 44 patients (24 local anaesthesia, 20 placebo), no statistical difference was noted in age, gender distribution or the severity of varicose veins assessed preoperatively by the clinician (CEAP classification score, median = 2 in both groups) and patient (AVVQ, mean placebo = 21.59, local anaesthesia = 17.53, p = 0.264) between the two groups. There was no statistical difference in pain scores between the placebo and topical local anaesthetic group at baseline (23.0 versus 20.44, p = 0.57), immediately postoperatively (23.35 versus. 19.75, p = 0.44) or predischarge (20.9 versus 13.75, p = 0.68). CONCLUSIONS: Topical local anaesthesia is of no benefit in EVLA of varicose vein to reduce patient experience of perioperative pain.

Manubriosternal joint dislocation: an unusual risk of trampolining.

BACKGROUND: Manubriosternal joint (MSJ) dislocation is a rare but potentially serious injury that can be associated with concurrent injuries to ribs, lungs, or myocardium. Two distinct types of MSJ dislocation have been described in the literature: type I, involving posterior dislocation of the sternum due solely to direct trauma; and type II, involving the sternum being pushed anteriorly as a result of indirect trauma. Until now, the relationship between the nature of the forces acting on the sternum and the type of MSJ dislocation that results has been absolute, whereby indirect forces never cause a type I dislocation, and direct forces never result in a type II dislocation. OBJECTIVES: To describe a case demonstrating that type I MSJ dislocation can occur without direct trauma. CASE REPORT: A 14-year-old boy developed sternal pain accompanied by an audible crack while executing a maneuver on a trampoline that required hyperflexion of the thorax. A lateral chest radiograph demonstrated a type I manubriosternal dislocation normally associated with direct trauma, as opposed to the more typical type II dislocation pattern one would expect to find in a hyperflexion injury. CONCLUSION: MSJ dislocations are classified into two groups, depending on the position of the sternum in relation to the manubrium. Each type of dislocation has been ascribed to either direct forces (for type I dislocation) or indirect forces (for type II dislocation). This case highlights that it is possible to have a type I dislocation in the absence of any direct sternal trauma.

An unusual groin mass. Seminal vesicle abscess: a case report.

The rare pathology of seminal vesicle abscess is usually diagnosed with computerised tomography scan and confirmed with transrectal ultrasound. We report a recently encountered case where diagnosis proved difficult owing to the non-specific clinical presentation.