High-Performance Dopamine-Based Supramolecular Bio-Adhesives.

The need for wound closure or surgical procedures has been commonly met by the application of sutures. Unfortunately, these are often invasive or subject to contamination. Alternative solutions are offered by surgical adhesives that can be applied and set without major disruption; a new class of supramolecular-based adhesives provides potential solutions to some of these challenges. In this study, a series of polymers utilizing dopamine as a self-assembling unit are synthesized. It is found that these motifs act as extremely effective adhesives, with control over the mechanical strength of the adhesion and materials' tensile properties enabled by changing monomer feed ratios and levels of cross-linking. These materials significantly outperform commercially available bio-adhesives, showing yield strengths after adhesion at least two times higher than that of BioGlue and Tisseel, as well as the ability to re-adhere with significant recovery of adhesion strength. Promisingly, the materials are shown to be non-cytotoxic, with cell viability > 90%, and able to perform in aqueous environments without significant loss in strength. Finally, the removal of the materials, is possible using benign organic solvents such as ethanol. These properties all demonstrate the effectiveness of the materials as potential bio-adhesives, with potential advantages for use in surgery.

The inflatable carrot-An orthosis for fingertip wound healing in flexion contractures of the hand: A case report.

STUDY DESIGN: Case report. INTRODUCTION: Severe flexure contractures of the hand secondary to upper limb spasticity (ULS) cause pain, palmar hyperhidrosis, ulceration, and nail plate deformities. Nonoperative management includes traditional orthotic devices that can be very painful for severe contractures and Botox injections, which provide a temporary solution. Surgical treatment comprises of soft tissue releases, tendon transfers, and release of the flexor and intrinsic muscles, which can cause permanent functional problems. CASE DESCRIPTION: In a 28-year-old male, unfit for surgery, we present the first documented case report in literature of flexion contractures of the hand secondary to upper limb spasticity managed using the "Inflatable Carrot" orthosis, where other conservative measures failed. RESULTS: At 4 weeks, the pulp to palm distance improved from 0 to 2 cm. At 3 months, the patient regained normal nail plate architecture, improved hand hygiene, reduced infection and pain. The patient reported improved psychological well-being and motivation to engage further with our therapists. CONCLUSIONS: The inflatable carrot provided an alternative nonsurgical solution for management of flexion contractures of the hand when surgical intervention was not considered in the patient's best interests. Awareness of this orthosis among hand therapists and surgeons will broaden our armamentarium for this challenging clinical problem.

Adrenaline Auto-injector injuries to digits; a systematic review and recommendations for emergency management.

AIMS: Accidental injury to digits with Adrenaline Auto-injectors (AAIs) is becoming increasingly common. Digital AAI injury causes painful ischaemia that can lead to necrosis and patient anxiety. There is a lack of understanding amongst surgeons regarding how to manage these injuries. We aimed to determine an optimal treatment algorithm for their management. METHODS: We conducted a systematic review using the search engines MEDLINE, PubMed, EMBASE, CINAHL, BNI, AMED, Google Scholar. Search items included ("epinephrine OR adrenaline") AND ("Digit" OR "Finger" OR "Thumb") AND ("Injury" OR "Accidental"). RESULTS: A total of 49 articles were identified describing 111 cases. In 58 cases; 52% of cases were managed with phentolamine, 24% were managed with nitroglycerine and 7% were treated with warm soaks. The remaining 17% of cases were managed with a variety of alternative treatments. Mean recovery time following treatment with phentolamine infiltration was 33 min, whilst symptoms persisted for several hours in some cases with observation/warm soaks and nitroglycerine. Phentolamine was more effective when injected into the AAI puncture site (mean resolution time: 17 min) in comparison to injection as a digital block (74 min). CONCLUSION: Phentolamine is the most effective method of reversing symptoms and treating ischaemic digits when compared to alternative therapies. Symptoms resolved much quicker when phentolamine was infiltrated into the site of injury compared to being infiltrated as a digital block. We propose a treatment algorithm for management of these injuries. Hand surgeons should be aware of AAI injuries and be able to advise on their management.

Quality Assessment of Expired Naloxone Products from First-Responders' Supplies.

Objective: Naloxone is an opioid receptor antagonist that reverses life-threatening effects of opioid overdose. Since the 1970s, naloxone products have been developed as injectable solutions, and more recently as nasal sprays. Naloxone products have saved many lives in emergency settings. These products are routinely carried by public safety first-responders including fire fighters (FF), law enforcement officers (LEO), and emergency medical services (EMS). Now, they are also distributed through community access programs to the public. While public safety medications are monitored, those publically distributed are not, so expired products can be possibly found on-hand in an emergency. This study analyzed the quality and stability of expired Naloxone HCl Solutions for Injection, to assess their remaining efficacies and potential risks. Methods: The samples were collected from EMS or law enforcement training supplies and expired returns, with expiration dates ranging from 1990 to 2018. Using standardized techniques, the remaining naloxone was quantified, and the main degradation products, nornaloxone (also known as noroxymorphone) and other possible species, were monitored and quantified systematically. Results: Most tested samples were found containing more than 90% of labeled naloxone, including those stored for nearly 30 years. The naloxone degradation was slow, but generally correlated with storage time length. There was no significant amount of degradation products detected across all samples. Nornaloxone was detected from some older samples, but all less than 1%. Therefore, although it is an opioid agonist, the risk caused by nornaloxone should be low. Conclusion: This quality assessment demonstrates that expired naloxone products may still meet USP standards, even after many years. Further pharmaceutical, clinical, and regulatory investigation should be conducted to confirm our findings, especially for new naloxone products with different formulations and routes of administration. Extending the shelf-life of naloxone products may have important financial and public health consequences in addressing future drug shortages and meeting the needs for this critical drug.

The effect of anaesthetist grade and frequency of insertion on epidural failure: a service evaluation in a United Kingdom teaching hospital.

BACKGROUND: Despite being a commonly performed procedure, epidural catheter insertion has a significant failure rate. There is a lack of guidance as to how regularly the procedure should be performed in order to maintain competence. This study aimed to quantify whether increasing frequency of practice is associated with a reduction in failure rates. METHODS: Data were collected prospectively on all patients undergoing intra-abdominal or thoraco-abdominal surgery who received epidural analgesia as part of their post-operative analgesic regimen over a 36 month period. Records were examined to identify the reason for epidural catheter removal, classified according to standardised definitions, the seniority of the inserting anaesthetist, and whether or not they were a permanent member of the anaesthetic department. Data were analysed using independent t tests, Mann-Whitney tests and Fisher's test. RESULTS: 881 epidurals were inserted during the study period. 48 hour failure rate was 27.2%, whilst by 96 hours 33.9% of epidurals had failed. Increasing frequency of epidural insertion did not show a significant decrease in failure rate at either 48 (p = 0.36) or 96 hours (p = 0.28). However, long-term survival of epidurals at 96 hours was greater if inserted by permanent rather than temporary members of staff (non-permanent 60/141, 42.6% vs permanent 228/715, 31.9%, OR 1.58 (CI 1.09-2.29) p = 0.02). CONCLUSION: This study demonstrates that failure rates for postoperative epidural analgesia in major surgery are not dependent upon the frequency with which practitioners insert epidural catheters. However, failure rates are dependent on permanency of anaesthetic staff. These findings are significant when placed in the context of the General Medical Council's requirements for clinicians to maintain competence in their clinical practice, suggesting that institutional factors may have greater bearing on epidural success or failure than frequency of task performance.

Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity.

Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two percent of the overall population in the United States. Tetraspanin CD9 is a cell surface protein that has been thoroughly demonstrated to be a molecular facilitator of cellular phenotype. CD9 expression varies in two human lymphoma cell lines, Raji and BJAB. In this report, we investigated the functional relationship between CD9 and cell proliferation regulated by histone deacetylase (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji cells resulted in significantly increased cell proliferation and HDAC activity compared to Mock transfected Raji cells. The increase in CD9-Raji cell proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment. Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also displayed decreased cell proliferation after HDACi treatment. These results suggest a significant relationship between CD9 expression and cell proliferation in human lymphoma cells that may be modulated by HDAC activity.

Assessment of Patient-Reported Outcomes for Closed-Incision Negative Pressure Therapy with Wide-Coverage Dressings in Simple Mastectomy and Immediate Implant-Based Breast Reconstruction.

Objective: A new configuration of closed-incision negative pressure therapy (ciNPT) dressings now covers the incision and a broader area of peri-incisional tissues. We have implemented these ciNPT dressings following simple mastectomy (SM) or skin-sparing mastectomy with implant-based reconstruction (IBR). This study assesses patient-reported outcomes of this new protocol. Approach: Patients underwent SM or IBR for breast cancer. ciNPT with wide-coverage dressings were placed over the entire breast, and -125 mmHg was applied for 14 days. Upon dressing removal, patients rated their experience using the Wound-Q™ Suction Device Scale and recorded their satisfaction on a Likert scale ranging 1-5. Results: Thirteen SM patients and 12 IBR patients were included in the study. The median age was 62 years, and SM patients were significantly older (p < 0.01). Patients rated the ciNPT device highest on items relating to its function and appearance, and lowest on noise and interference with sleep and physical activity. The overall mean score for the combined cohort was 64.8/100. The mean score for SM patients (74.8 ± 19.9) was significantly greater than for IBR patients (53.9 ± 9.6, p < 0.01). The mean overall patient satisfaction rating was 3.92 on a 5-point scale; 4.0 in the SM group and 3.8 in the IBR group. Innovation: This study is the first to report on the patient experience with these newly available wide-coverage ciNPT dressings. Conclusion: Overall, the dressing was well-tolerated by patients, and satisfaction was high. The positive reception of ciNPT with wide-coverage dressings supports continued use at our hospital.

Conjugated Microporous Polymers for Catalytic CO2 Conversion.

Rising carbon dioxide (CO2) levels in the atmosphere are recognized as a threat to atmospheric stability and life. Although this greenhouse gas is being produced on a large scale, there are solutions to reduction and indeed utilization of the gas. Many of these solutions involve costly or unstable technologies, such as air-sensitive metal-organic frameworks (MOFs) for CO2 capture or "non-green" systems such as amine scrubbing. Conjugated microporous polymers (CMPs) represent a simpler, cheaper, and greener solution to CO2 capture and utilization. They are often easy to synthesize at scale (a one pot reaction in many cases), chemically and thermally stable (especially in comparison with their MOF and covalent organic framework (COF) counterparts, owing to their amorphous nature), and, as a result, cheap to manufacture. Furthermore, their large surface areas, tunable porous frameworks and chemical structures mean they are reported as highly efficient CO2 capture motifs. In addition, they provide a dual pathway to utilize captured CO2 via chemical conversion or electrochemical reduction into industrially valuable products. Recent studies show that all these attractive properties can be realized in metal-free CMPs, presenting a truly green option. The promising results in these two fields of CMP applications are reviewed and explored here.

Selective CO2 Electroreduction from Tuneable Naphthalene-Based Porous Polyimide Networks.

A series of porous polyimides (pPIs) are synthesized, and their surface areas and pore sizes are optimized by the previously reported Bristol-X'an-Jiatong (BXJ) approach. How this approach can be used to tune and optimize the porous network properties to target and tune their ability to capture CO2 is demonstrated. Once optimized, these porous organic frameworks are utilized, for the first time, as electrocatalysts for the conversion of CO2 . The excellent Faradaic efficiencies (FEs) for the conversion of CO2 to formate (91%) and methanol (85%) present exciting opportunities for the metal-free generation of useful fuels and feedstocks from CO2 . In addition, the ability to directly address and select the conversion products through tuning of the porous materials' properties highlights the potential of this approach, and more generally for a wide range of organic frameworks as future metal-free CO2 reduction catalysts.

Controlled Removal of Organic Dyes from Aqueous Systems Using Porous Cross-Linked Conjugated Polyanilines.

Porous organic materials, as a broad class of functional materials, offer a promising route for low-cost purification of contaminated wastewaters. We have synthesized a range of highly cross-linked conjugated porous polyanilines and optimized their porosity and water dispersibility by tuning reactant feed ratios, previously unreported in the synthesis of such networks. To demonstrate their ability to adsorb model dyes used in the textile industry, we exposed the networks to a range of cationic aromatic dyes, leading to absorption capacities of >100 mg/g, reported for the first time with respect to polyaniline networks. The versatility of the networks was further demonstrated by the preparation of gel composites, producing active gels for efficient and facile removal and recycling, ideal for real-world applications. Finally, chemical modifications of the networks were undertaken to target the removal of model anionic organic dye pollutants, showing the wide applicability of our approach.

Chemically Driven Oscillating Soft Pneumatic Actuation.

Pneumatic actuators are widely studied in soft robotics as they are facile, low cost, scalable, and robust and exhibit compliance similar to many systems found in nature. The challenge is to harness high energy density chemical and biochemical reactions that can generate sufficient pneumatic pressure to actuate soft systems in a controlled and ecologically compatible manner. This investigation evaluates the potential of chemical reactions as both positive and negative pressure sources for use in soft robotic pneumatic actuators. Considering the pneumatic actuation demands, the chemical mechanisms of the pressure sources, and the safety of the system, several gas evolution/consumption reactions are evaluated and compared. Furthermore, the novel coupling of both gas evolution and gas consumption reactions is discussed and evaluated for the design of oscillating systems, driven by the complementary evolution and consumption of carbon dioxide. Control over the speed of gas generation and consumption is achieved by adjusting the initial ratios of feed materials. Coupling the appropriate reactions with pneumatic soft-matter actuators has delivered autonomous cyclic actuation. The reversibility of these systems is demonstrated in a range of displacement experiments, and practical application is shown through a soft gripper that can move, pick up, and let go of objects. Our approach presents a significant step toward more autonomous, versatile soft robots driven by chemo-pneumatic actuators.

Inhibitory effects of antagonists of growth hormone releasing hormone on experimental prostate cancers are associated with upregulation of wild-type p53 and decrease in p21 and mutant p53 proteins.

BACKGROUND: The tumor suppressor gene p53 is implicated in cell cycle control and apoptosis. Antagonists of growth hormone-releasing hormone (GHRH) have been shown to inhibit human experimental prostate cancers. METHODS: We investigated the involvement of p53 apoptotic pathways in this effect. Nude mice bearing xenografted PC-3, DU-145, and MDA-PCa-2b human prostate cancer lines were treated with a new potent GHRH antagonist MZ-J-7-138. To determine whether tumor inhibition by MZ-J-7-138 involves apoptotic mechanisms such as p53 and p21, we evaluated by Western Blot the expression of mutant mt-p53 in PC-3 and DU-145 and of wild type (wt-p53) in MDA-PCa-2b prostate cancers as well as p21. RESULTS: MZ-J-7-138 significantly inhibited the growth of PC-3, DU-145, and MDA-PCa-2b xenografts in nude mice. Androgen deprivation with the LHRH antagonist Cetrorelix enhanced the anti-proliferative effect of GHRH antagonist MZ-J-7-138 on MDA-PCa-2b tumors. The expression of mutant (mt-p53) and p21 protein in PC-3 and DU-145 tumors was significantly decreased by treatment with MZ-J-7-138, whereas wild type wt-p53 expression in MDA-PCA-2b tumors was up regulated by treatment with Cetrorelix. All three models investigated expressed specific, high affinity GHRH receptors. CONCLUSIONS: Our findings indicate that the anti-proliferative effects of GHRH antagonist MZ-J-7-138 and LHRH antagonist Cetrorelix on prostate cancers involve p53 and p21 signaling.

Optimising UK training in aesthetic surgery: A prospective national study using operative logbooks and questionnaires to determine factors associated with trainee participation.

INTRODUCTION: We aimed to determine the proportion of UK aesthetic surgery training taking place in the independent sector, how this experience is gained, and factors associated with trainee participation. We also aimed to draw comparisons between training in the National Health Services (NHS) and independent sectors. METHODS: Plastic Surgery Trainees were asked to complete a 10-item questionnaire, in addition to their usual operative entry on eLogbook, when logging a procedure with an aesthetic operative code, prospectively over a 6-month period. Anonymised data was exported and analysed using SPSS. RESULTS: A total of 285 questionnaires were completed; all UK training regions were represented. The majority were for NHS procedures (88%), of which 56% were for breast surgery, 23% facial surgery, 19% body contouring, and 2% non-surgical. Trainees were significantly more likely to participate in procedures when they were performed in the NHS (odds ratio, OR, 9.7, p < 0.01) or when they were body contouring surgery (OR 1.5, p < 0.01). Trainees were more likely to participate in perioperative care in an NHS setting (p < 0.01). When trainees attend the independent sector, it was usually within contracted training hours (57%) with their consultant trainer with whom they are working in the NHS (63%). CONCLUSIONS: The majority of aesthetic surgery training occurs in the NHS but this is not representative of UK aesthetic practice. There is a need to engage the independent sector to provide formal aesthetic surgery training as part of the plastic surgery training programme, including procedural participation and perioperative care. Additional aesthetic fellowships and mechanisms for mentorship by established consultants should be developed.

Comparative UK Cross-sectional Study of Breast Cancer Patient-Reported Outcomes for Breast-Conserving Surgery and Immediate Reconstruction, Including Contribution to an International Collaborative Pilot Study.

INTRODUCTION: Breast-conserving surgery (BCS) with adjuvant radiotherapy is oncologically comparable to mastectomy with immediate breast reconstruction (IBR) in treating breast cancer. This tertiary UK centre cross-sectional study compared BCS patient-reported outcomes with those of immediate implant-based (IBR) and free flap reconstruction (FFR), and included a contribution to a pilot international collaboration co-ordinated through the Organisation for Economic Cooperation and Development (OECD). METHODS: Validated BREAST-Q™ 'satisfaction with breasts' modules were administered to 271 consecutive patients for six months after unilateral BCS, IBR, or FFR were conducted between June and October 2018. Risk adjustment data were collected on age, body mass index, smoking, radiotherapy, specimen weight, and tumour burden. RESULTS: A total of 190 women returned completed questionnaires (131 BCS, 42 IBR, 17 FFR; 70% response rate). BCS scores (mean 68, standard deviation (SD) 23) were higher than those for IR overall (62, SD 23, p=0.04) and IBR (61, 24, p=0.03) but equivalent to those for FFR (66, SD 23, p=0.33). There was no significant difference in Q-Scores between the IBR and FFR groups (p=0.77). Scores were only minimally changed by risk adjustment and comparable to OECD mean international scores for IBR (61) and FFR (66). CONCLUSIONS: This is the first study to compare BCS and IR outcomes using a validated scale. BREAST-Q™ 'satisfaction with breasts' scores were comparable between BCS and FFR but significantly lower following IBR.

Implant-Based Reconstruction following Mastectomy in Patients Who Have Had a Previous Breast Augmentation: Lessons from the National Multicenter Implant Breast Reconstruction Evaluation Study.

BACKGROUND: Breast augmentation is the most commonly performed cosmetic procedure, and increasingly women in this group present with breast cancer or request risk-reducing surgery, but their optimal management is unclear. The authors explored the clinical and patient-reported outcomes of patients undergoing immediate implant-based breast reconstruction following previous augmentation and compared these with outcomes of patients who had not had cosmetic implants in the Implant Breast Reconstruction Evaluation (iBRA) Study. METHODS: Patients undergoing immediate implant-based breast reconstruction were prospectively recruited from breast and plastic surgical units across the United Kingdom. Demographic, operative, and oncologic data, and information regarding complications within 3 postoperative months were collected. Patient-reported outcomes at 18 months were assessed using the BREAST-Q. The clinical and patient-reported outcomes of patients undergoing immediate implant-based breast reconstruction with and without previous breast augmentation were compared. RESULTS: A total of 2108 women were included in the iBRA Study, of whom 49 had undergone a previous augmentation. Women in the augmentation group were younger (median age, 45 years versus 50 years; p = 0.01), had a lower body mass index (22.8 kg/m2 versus 24.9 kg/m2; p < 0.01), and had smaller tumors (15 mm versus 25 mm; p = 0.01) than patients without augmentation. No differences were seen in operative technique between the groups. Complications at 3 months were similar in both groups and there were no significant differences in patient-reported outcomes at 18 months. CONCLUSIONS: The clinical and patient-reported outcomes of patients undergoing immediate implant-based breast reconstruction following previous augmentation are consistent with those observed in the wider iBRA Study cohort, supporting the safety of this approach.

The Oxford Finger Nail Appearance Score - a new scoring system for fingernail deformity following paediatric finger tip trauma.

Fingernail deformity is common, yet current methods used to define cosmetic appearance following trauma are mainly descriptive. In order to quantify the cosmetic appearance of the fingernail, we developed the Oxford Fingernail Appearance Score using a three stage iterative process. The score has five cosmetic components marked as binary outcomes composed of nail shape, nail adherence, eponychial appearance, nail surface appearance and presence of a split. In the first stage, two assessors independently assessed 25 photographs of fingernails taken at a minimum of four months following paediatric nail bed repair and compared them to the corresponding contralateral uninjured finger. Following refinement in the score, ten different assessors scored a further 62 photographs of fingernails taken after paediatric nail bed repair. Assessors completed each of the five components, and the overall component score was calculated by statisticians post-hoc, taking the ideal appearance of each component as 1 ("identical to opposite" for nail shape, eponychium and surface, "complete" for adherence, "absent" for split) and all the non-ideal appearances as 0. Assessors effectively scored the photographs' integer values between 0 (least optimal appearance) and 5 (most optimal appearance). Refinements in the scoring system resulted in an improvement in a weighted kappa statistic of 0.36 (95% CI:0.09,0.68) in the initial score to 0.52 (95% CI: 0.42, 0.61). The Oxford Fingernail Appearance Score is a user-friendly and reliable scoring system which has application in a clinical trial setting.

UC Pd: a new form of Pd/C for Sonogashira couplings.

Screening of different sources of Pd/C shows reagents of highly variable nanoparticle sizes and oxidation states of the metal. Typically, catalysts with higher surface area are viewed as likely to be the more reactive. In this paper a new form of Pd/C, "UC Pd" is described that is shown to contain larger nanoparticles yet it is the most reactive catalyst of those sold commercially for Sonogashira coupling reactions. UC Pd functions efficiently in the absence of a copper co-catalyst, under very mild and "green" conditions using inexpensive 95% EtOH at 50 degrees C. It is also the only form of Pd/C that can be recycled. In side-by-side reactions with several commercially available forms of Pd/C, none compete successfully with UC Pd under standardized conditions. Physical data obtained from extensive surface analysis using TEM, XRD, XPS, and CO-TPD measurements lead to an explanation behind the unique reactivity of this new recyclable form of Pd/C.

Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt.

Bombesin (BN) or gastrin-releasing peptide (GRP) can stimulate the growth of neoplasms such as breast cancer and small-cell lung carcinoma (SCLC). Antagonists of BN/GRP have been shown to inhibit these cancers. We evaluated whether antagonists of BN/GRP can suppress the growth of human non-SCLC (NSCLC) xenografted into nude mice. The effect of the administration of BN/GRP antagonist RC-3940-II on the growth of H460 and A549 NSCLC cell lines orthotopically xenografted into the intrapulmonary interstitium was examined. Protein levels of K-Ras, COX-2, Akt/pAkt, WT p53, Erk1/2, and lung resistance-related protein (LRP) in tumors were analyzed by Western blot analaysis, and receptors for BN/GRP were investigated by radioligand-binding studies. The effect of RC-3940-II on the proliferation of H460 and A549 cells in vitro was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. High-affinity receptors for BN/GRP were found on tumors. Treatment with RC-3940-II significantly (P < 0.001) inhibited growth of H460 and A549 NSCLC xenografts by 30-50% and led to an improved performance status, compared with controls. In H460 NSCLC, the antitumor effect was associated with a significant (P < 0.001) reduction in protein levels of K-Ras, COX-2, pAkt, and pERK1/2 and with a major augmentation in the expression of WT p53, compared with controls. In A549 NSCLC, pAkt and LRP were significantly down-regulated. Our findings demonstrate the efficacy of BN/GRP antagonist RC-3940-II for the treatment of NSCLC. The suppression of K-Ras, COX-2, pAkt, and LRP, as well as the up-regulation of WT p53 might contribute to the antitumor action of BN/GRP antagonists.