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Background: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA., Methods: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment., Results: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen., Conclusions: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone., (© 2023 The Author. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Importance: In cardiac surgery, albumin solution may maintain hemodynamics better than crystalloids and reduce the decrease in platelet count and excessive fluid balance, but randomized trials are needed to compare the effectiveness of these approaches in reducing surgical complications., Objective: To assess whether 4% albumin solution compared with Ringer acetate as cardiopulmonary bypass prime and perioperative intravenous volume replacement solution reduces the incidence of major perioperative and postoperative complications in patients undergoing cardiac surgery., Design, Setting, and Participants: A randomized, double-blind, single-center clinical trial in a tertiary university hospital during 2017-2020 with 90-day follow-up postoperatively involving patients undergoing on-pump coronary artery bypass grafting; aortic, mitral, or tricuspid valve surgery; ascending aorta surgery without hypothermic circulatory arrest; and/or the maze procedure were randomly assigned to 2 study groups (last follow-up was April 13, 2020)., Interventions: The patients received in a 1:1 ratio either 4% albumin solution (n = 693) or Ringer acetate solution (n = 693) as cardiopulmonary bypass priming and intravenous volume replacement intraoperatively and up to 24 hours postoperatively., Main Outcomes and Measures: The primary outcome was the number of patients with at least 1 major adverse event: death, myocardial injury, acute heart failure, resternotomy, stroke, arrhythmia, bleeding, infection, or acute kidney injury., Results: Among 1407 patients randomized, 1386 (99%; mean age, 65.4 [SD, 9.9] years; 1091 men [79%]; 295 women [21%]) completed the trial. Patients received a median of 2150 mL (IQR, 1598-2700 mL) of study fluid in the albumin group and 3298 mL (IQR, 2669-3500 mL) in the Ringer group. The number of patients with at least 1 major adverse event was 257 of 693 patients (37.1%) in the albumin group and 234 of 693 patients (33.8%) in the Ringer group (relative risk albumin/Ringer, 1.10; 95% CI, 0.95-1.27; P = .20), an absolute difference of 3.3 percentage points (95% CI, -1.7 to 8.4). The most common serious adverse events were pulmonary embolus (11 [1.6%] in the albumin group vs 8 [1.2%] in the Ringer group), postpericardiotomy syndrome (9 [1.3%] in both groups), and pleural effusion with intensive care unit or hospital readmission (7 [1.0%] in the albumin group vs 9 [1.3%] in the Ringer group)., Conclusions and Relevance: Among patients undergoing cardiac surgery with cardiopulmonary bypass, treatment with 4% albumin solution for priming and perioperative intravenous volume replacement solution compared with Ringer acetate did not significantly reduce the risk of major adverse events over the following 90 days. These findings do not support the use of 4% albumin solution in this setting., Trial Registration: ClinicalTrials.gov Identifier: NCT02560519.

Background: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK., Methods: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively., Results: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened., Conclusions: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered., (© 2021. The Author(s).)

Objectives: Dried bonito dashi , a traditional Japanese fish broth made from dried bonito tuna, enhances food palatability due to its specific umami flavor characteristics. However, the pattern of brain activation following dashi ingestion has not been previously investigated. Methods: We mapped activation sites of the rat brain after intragastric loads of dried bonito dashi by measuring neuronal levels of the Fos protein, a functional marker of neuronal activation. Results: Compared to intragastric saline, intragastric dashi administration produced enhanced Fos expression in four forebrain regions: the medial preoptic area, subfornical organ, habenular nucleus, and central nucleus of the amygdala. Interestingly, the medial preoptic area was found to be the only feeding-related hypothalamic area responsive to dashi administration. Moreover, dashi had no effect in the nucleus accumbens and ventral tegmental area, two connected sites known to be activated by highly palatable sugars and fats. In the hindbrain, dashi administration produced enhanced Fos expression in both visceral sensory (caudal nucleus of the solitary tract, dorsal part of the lateral parabrachial nucleus, and area postrema) and autonomic (rostral ventrolateral medulla, and caudal ventrolateral medulla) sites. Discussion: The results demonstrate the activation of discrete forebrain and hindbrain regions following intragastric loads of dried bonito dashi . Our data suggest that the gut-brain axis is the principal mediator of the postingestive effects associated with the ingestion of dashi .

Purpose: The objective of this work was to systematically evaluate the effects of formulation composition on subcutaneous injection site pain (ISP) using matrices comprising of common pharmaceutical excipients., Methods: Two randomized, blinded, crossover studies in healthy subjects were conducted at a single site, where subjects received 1 mL SC injections of the buffer matrices. ISP intensity was measured using a 100 mm visual analogue scale (VAS), which was then analyzed via heatmap, categorical grouping, subgroup analysis, and paired delta analysis., Results: Buffer type, buffer concentration and tonicity agent showed a substantial impact on ISP. Citrate buffer demonstrated a higher ISP than acetate buffer or saline). The 20 mM citrate buffer was more painful than 10 or 5 mM citrate buffers. NaCl and propylene glycol were significantly more painful than sugar alcohols (mannitol, sucrose, trehalose or glycerol). Histidine buffers exhibited ISP in the descending order of 150 mM > 75 mM > 25 mM > 0 mM NaCl, while histidine buffers containing Arginine-HCl at 0, 50, or 150 mM all showed very low ISP. Histidine buffer at pH 6.5 showed a lower ISP than pH 5.7., Conclusions: This systematic study via orthogonal analyses demonstrated that subcutaneous ISP is significantly influenced by solution composition.

Purpose: Interface motion and hydrodynamic shear of the liquid slosh during the insertion of syringes upon autoinjector activation may damage the protein drug molecules. Experimentally validated computational fluid dynamics simulations are used in this study to investigate the interfacial motion and hydrodynamic shear due to acceleration and deceleration of syringes. The goal is to explore the role of fluid viscosity, air gap size, syringe acceleration, syringe tilt angle, liquid-wall contact angle, surface tension and fill volume on the interface dynamics caused by autoinjector activation., Methods: A simplified autoinjector platform submerged in water is built to record the syringe and liquid motion without obstruction of view. The syringe kinematics is imported to the simulations based on OpenFOAM InterIsoFoam solver, which is used to study the effects of various physical parameters., Results: The simulations agree with experiments on the air-liquid interface profile and interface area. The interfacial area and the volume of fluid subject to high strain rate decrease with the solution viscosity, increase with the air gap height, syringe velocity, tilt angle and syringe wall hydrophobicity, and hardly change with the surface tension and liquid column height. The hydrodynamic shear mainly occurs near the syringe wall and entrained bubbles., Conclusion: For a given dose of drug solution, the syringe with smaller radius and larger length will generate less liquid slosh. Reducing the air volume and syringe wall hydrophobicity are also helpful to reduce interface area and effective shear. The interface motion is reduced when the syringe axis is aligned with the gravitational direction.

Background: Studies have shown complications of normal saline infusion because of its high-chloride content. Therefore, in the present study, we aimed to explore whether the use of low- versus high-chloride solutions benefited the unselected and specifically perioperative patients and was associated with different outcomes., Methods: Studies on the use of low- versus high-chloride content intravenous solutions for perioperative patients, published up to July 15, 2019, were systematically reviewed, and primary and secondary outcomes were quantitatively summarized., Results: A total of 14 eligible randomized controlled trials with 943 perioperative patients were included. Five studies reported all-cause mortality, and eight studies provided detailed data on renal replacement therapy (RRT). The pooled result suggested no statistically significant difference in the effect of low- versus high-chloride solutions on all-cause mortality (risk ratio (RR) = 1.39; 95%confidence interval (CI) = 0.23-8.26) and RRT (RR = 1.05; 95%CI = 0.63-1.76). The pooled results on acute kidney injury (AKI) and the use of allogenic blood transfusion ( P > 0.05) were similar., Conclusion: Among specific perioperative patients, the use of low- versus high-chloride content intravenous solutions did not reduce the all-cause mortality, risk of severe AKI, or rate of RRT use. Further large randomized clinical trials are needed to confirm or refute this finding., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Xuan Song et al.)

Background: Blood derivative injections have been recently proposed to address osteoarthritis (OA) with overall positive results, although long-term data on their efficacy are lacking. A novel blood derivative has been developed to concentrate growth factors and antagonists of inflammatory cytokines and shown promising early findings., Purpose: To investigate if the positive effects of a single intra-articular injection of autologous protein solution (APS) in patients affected by knee OA-previously documented at 1 year in a multicenter double-blind randomized saline-controlled trial-last up to 3 years., Study Design: Case series; Level of evidence, 4., Methods: A total of 46 patients with Kellgren-Lawrence 2 or 3 knee OA were randomized into 2 groups: 1 ultrasound-guided APS injection (n = 31) or 1 saline injection (n = 15). At 1 year, the saline group was allowed to cross over. Patients were re-evaluated at 24 and 36 months through the visual analog scale for pain (VAS), Western Ontario and McMaster Universities Osteoarthritis Index Likert 3.1 (WOMAC LK 3.1), Knee injury and Osteoarthritis Outcome Score (KOOS), 36-Item Short Form Health Survey (SF-36), and Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder rate. Magnetic resonance imaging evaluation was performed with the MRI Osteoarthritis Knee Score (MOAKS) before and at 24 months after treatment, and radiographs were assessed per Kellgren-Lawrence before and annually after treatment., Results: In the APS cohort, WOMAC pain improved from 11.5 ± 2.4 (mean ± SD) to 4.3 ± 4.0 at 1 year and to 5.7 ± 5.0 at 3 years ( P < .0001 vs baseline). The APS cohort also showed a statistically significant improvement in its KOOS pain score from 39.4 ± 13.1 to 70.6 ± 21.5 at 1 year and to 64.1 ± 24.6 at 3 years ( P < .0001 vs baseline) and VAS pain scores from 5.5 ± 2.2 to 2.6 ± 2.5 at 1 year and to 3.4 ± 2.9 at 3 years ( P = .0184 vs baseline). VAS pain score significantly worsened from 12 to 36 months ( P = .0411). All patients in the saline group decided to cross over to APS, and their final scores were better than baseline, although not significantly better than at the crossover point. Overall, 7 of 26 (26.9%) APS cases and 4 of 14 (28.6%) crossover cases were considered failures as patients underwent further injective treatments or surgical procedures between the 12- and 36-month follow-up. MOAKS findings showed no statistically significant differences. Patients with better cartilage had greater WOMAC pain improvement when their baseline scores were worse, whereas the trend was reversed for patients with cartilage loss at baseline., Conclusion: Intra-articular use of APS for mild to moderate knee OA was safe, and significant pain improvement was documented 3 years after a single injection. Patients with better cartilage status seem to respond better than patients with more cartilage loss, with more clinical improvement even when starting from more painful conditions., Registration: NCT02138890 (ClinicalTrials.gov identifier).

Purpose of Review: The use of commercially or naturally thickened liquids is a well-established treatment for patients with dysphagia to fluids, the aim of which is to improve swallow safety by minimizing risk of aspiration. Although the most recent systematic reviews conclude that this treatment lacks evidential support and leads to patient-reported worsening health and quality of life, thickened liquids continue to be used with patients with dysphagia across clinical settings. This review briefly summarizes the evidence and considers potential reasons for the apparent mismatch between the evidence and clinical practice., Recent Findings: Continuing practice with thickened liquids is influenced by a range of factors, including gaps in clinical knowledge, inadequate patient involvement, a culture of common practice and a reliance on invalid surrogate studies or research lacking a credible association between thickened liquids and clinically meaningful endpoints., Summary: While awaiting further research, clinical decision-making about thickened liquids can be improved by considering the evidence of clinically meaningful endpoints, promoting shared decision-making with patients and underpinning practice with knowledge about the complex relationship between dysphagia, aspiration and pneumonia.

Background: Exclusive use of Del Nido cardioplegia administration in all adult patients undergoing cardiac surgery has been studied for operative, postoperative and myocardial protection outcomes., Methods: From November 2016 to October 2017, Del Nido cardioplegia was used in 131 consecutive patients (DN group). Using a propensity score, DN group was compared to 251 patients having received intermittent cold blood cardioplegia (CB group)., Results: Preoperative characteristics were similar in DN and CB groups. Operative outcomes were statistically different (p < 0.0001): cardiopulmonary bypass (CPB) time (DN 105.9 ± 46.5, CB 131.2 ± 38.8); aortic cross-clamp time (DN 80.8 ± 35.5, CB 102.2 ± 31.3); operative time (DN 203.1 ± 65.0, CB 241.5 ± 54.7); total cardioplegia volume (DN 1328 ± 879, CB 3773 ± 1226); and peak glycemia on CPB (DN 8.2 ± 2.3, CB 9.0 ± 1.8). No statistical differences were noted in intensive care unit stay, hospital stay and hospital death. Myocardial protection outcomes were similar: discharge left ventricular ejection fraction (DN 52 ± 11, CB 51 ± 10); Troponin levels at the end of the surgery (DN 871 ± 1623, CB 1958 ± 854), day 1 (DN 853 ± 1139, CB 993 ± 8234) and day 4 (DN 442 ± 540, CB 463 ± 317)., Conclusion: Del Nido cardioplegia use in all adult cardiac surgeries is associated with improved surgical efficiency. The design of larger trials including adults combined cardiac procedures and emergencies is needed.

Molluscum contagiosum is a common childhood condition, and although it is self-limited, treatments are often prescribed. Several medications are available, but there is no consensus regarding the optimal choice in the pediatric population. We report a child who underwent potassium hydroxide 5% treatment resulting in superficial diffuse erosions caused by the inappropriate application. This underlines the importance of parent education before use of this medication with well-known caustic properties., (© 2019 Wiley Periodicals, Inc.)

Primary cultures of neurons of the peripheral nervous system have been successfully used for studying many aspects of neuronal development and survival, including investigations into the mechanisms of axon degeneration. In this chapter, we describe how to prepare and microinject dissociated cultures of sympathetic neurons of the superior cervical ganglion (SCG) specifically for use in highly controlled and targeted assays of axon survival and degeneration.

Hemorrhoidal disease is the most common proctologic disease and the search for new treatment methods, as well as an in-depth understanding of the mechanisms underlying effects of well-known agents on disease pathogenesis still remain relevant. There have been long recognized the effects of the E.coli bacterial culture suspension (BCS) as a therapeutic means eliciting decreased exudation during inflammation, wound healing, tissue regeneration, and stimulated immunity. Here, based on recent findings related to innate and adaptive immune cells, we set out to present mechanisms accounting for some effects coupled to commensal bacteria, particularly inactivated E.coli BCS, which are important for understanding pathogenesis-related action of drug Posterisan and Posterisan forte, and outline their broad application in therapy of hemorrhoids. Based on the analysis, it was concluded that such effects are mediated via multi-pronged and complementary interactions between diverse human receptors expressed in the anorectal region cells and microbial components: NOD ligands, metabolites, enzymes, heat shock proteins and nucleic acids, which lead to production of pro-inflammatory cytokines by anodermal colonocytes, innate and adaptive immune cells, neurons in the submucosal plexus covered by transitional zone epithelium, and hemorrhoid plexus endothelium. Based on current concepts, it may be plausible that E.coli BCS-derived biologically active components contained in drug Posterisan are capable of exerting both positive local and systemic effects, which extend our understanding and substantiate its use in hemorrhoidal disease. The effectiveness of using Posterisan and Posterisan forte is corroborated by their indications in real-life clinical practice, both as a conservative therapy as well as after surgical interventions.

Background: Patients with an ileostomy often experience fluid and electrolyte depletion because of gastrointestinal loss. This study aimed to compare how an iso-osmolar and a hyperosmolar oral supplement affect ileostomy output, urine production, and natriuresis as proxy measurements of water-electrolyte balance., Methods: In a randomised, double-blinded, active comparator, crossover intervention study, we included eight adult ileostomy patients who were independent of parenteral support. We investigated how an iso-osmolar (279 mOsm/kg) and a hyperosmolar (681 mOsm/kg) oral supplement affected ileostomy output mass, urine volume, and natriuresis. In addition to their habitual diet, each participant ingested 800 mL/day of either the iso-osmolar or hyperosmolar supplement in each of two study periods. Each period started with 24-hour baseline measurements, and the supplements were ingested during the following 48 h. All measurements were repeated in the last 24 h., Results: No statistically significant changes in ileostomy output were detected following the intake of either oral supplement (median (range) 67 (-728 to 290) g/day, p = 0.25) despite increased fluid intake. Compared with the hyperosmolar supplement, the iso-osmolar supplement induced a statistically significant increase in urine volume (470 (0-780) mL/day, p = 0.02) and natriuresis (36 (0-66) mmol/day, p = 0.02)., Conclusion: Intake of the two oral supplements did not affect ileostomy output during this short intervention. Natriuresis increased following intake of the iso-osmolar supplement compared to that after ingesting the hyperosmolar supplement, indicating that patients with an ileostomy may benefit from increasing their ingestion of iso-osmolar fluids. ClinicalTrials.gov identifier:NCT03348709., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Cardiac hypertrophy often causes impairment of cardiac function. Xenon (Xe), a naturally occurring noble gas, is known to provide neurological and myocardial protection without side effects. The conventional method of Xe delivery by inhalation is not feasible on a chronic basis. We have developed an orally deliverable, effective Xe formulation for long-term administration. We employed 2-hydroxypropyl)-β-cyclodextrin (HPCD), which was dissolved in water to increase the Xe concentration in solution. The beneficial effects of long-term oral administration of Xe-enriched solutions on cardiovascular function were evaluated in vivo. HPCD increased Xe solubility from 0.22 mM to 0.67 mM (3.8-fold). Aged ApoE knockout mice fed high-fat diet for 6 weeks developed hypertension, and myocardial hypertrophy with impaired cardiac function. Oral Xe prevented this ischemic damage, preserving normal blood pressure, while maintaining normal left ventricular mass and wall thickness. This novel formulation allows for gastrointestinal delivery and cardiovascular stabilization.

Background: Biofilms represent a complex milieu of matrix-enclosed microorganisms, which can significantly contribute to the pathology of chronic wounds. In this study, we compare the activity of 3 commercial antimicrobial wound care solutions, Vashe (HOCl based), PhaseOne (HOCl based), and Sulfamylon (mafenide acetate), for their in vitro activity against bacterial and fungal biofilms., Methods: Reference and clinical isolates of 6 Gram-negative bacterial species (36 total strains), 3 Gram-positive bacteria (21 strains), and 3 Candida species (9 strains) were used to create biofilms. Various working concentrations of the 3 antiseptic agents were incubated with the biofilms in microwell plates; they were monitored from 1 minute to 24 hours to compare bacterial and fungal viability through colony forming unit analysis., Results: Vashe and PhaseOne displayed excellent bactericidal and fungicidal activity, whereas Sulfamylon demonstrated minimal activity against the biofilms tested. With the exception of Candida albicans, all biofilms were eliminated at either 1 or 10 minutes using Vashe and PhaseOne solutions. In most cases, mafenide was unable to eliminate both bacterial and fungal biofilms, even with 24 hours of treatment., Conclusions: Biofilms represent a major clinical challenge, with no clear consensus for treatment of chronic wounds or prosthetic devices. Our results suggest that hypochlorous acid-based wound solutions such as Vashe and PhaseOne are more efficacious than mafenide in eliminating bacterial and fungal biofilms. Further studies are necessary to investigate and compare the in vivo efficacy of these products in clinical care.

Background: A critical barrier to successful limb replantation and allotransplantation is the maximum allowable limb ischemia time of 4 to 6 hours. The current gold standard is to preserve amputated limbs on an ice slurry. Experimental machine perfusion has yielded promising results as an alternative. In particular, hypothermic acellular perfusion has enabled preservation of amputated limbs for up to 12 hours thus far., Methods: Amputated forelimbs of Yorkshire pigs were preserved on static cold storage at 4°C for 4 hours (static cold storage group) or perfused at 8°C for 24 hours (perfusion group) with oxygenated modified STEEN Solution perfusate before replantation. Animals were followed up for 7 days after replantation., Results: Eight animals underwent replantation (cold storage group, n = 4; perfusion group, n = 4). Seventy-five and 100 percent of animals in the static cold storage and perfusion groups survived for 7 days, respectively. Glycogen and adenosine triphosphate remained stable throughout perfusion. Heart and respiratory rate after replantation were increased in the static cold storage group. There was increased damage in muscle biopsy specimens obtained from animals in the static cold storage group after 7 days when compared with those from animals in the perfusion group., Conclusions: Hypothermic acellular ex vivo perfusion of limbs for up to 24 hours enables tissue preservation comparable to that obtained with conventional static cold storage for 4 hours and may reduce muscle damage and systemic reactions on limb replantation. Translation to human limbs may help improve limb replantation and allotransplantation outcomes.

Objective: In neonates on total parenteral nutrition (TPN), amino acids may be a risk factor for developing total parenteral nutrition-associated cholestasis (TPNAC). We aimed, first, to compare methionine, cysteine, and taurine plasma levels between neonates on TPN who were receiving an intravenous amino acid solution based on a breast milk aminogram and those on an intravenous solution of pediatric amino acids based on an umbilical cord aminogram, and second, to determine the frequency of TPNAC., Methods: A double-blind randomized controlled trial was conducted. Ninety-four neonates with a birthweight of 1000g or more and a gestational age of 30 wk or older were admitted and enrolled. Blood samples were obtained at 0, 7, and 14 d of TPN, and plasma amino acid concentrations were determined by ultra-high-resolution liquid chromatography. Continuous variables were compared using the Wilcoxon rank-sum test or Student's t test; categorical variables were compared using the Fisher exact test., Results: Thirty-five neonates completed the study (Primene, n = 14; TrophAmine, n = 21). On day 14, methionine plasma concentrations were significantly lower in the Primene group than in the TrophAmine group (27 µmol/L versus 32.9 µmol/L, P = 0.044); the taurine concentration was significantly higher in the same group (72.4 µmol/L versus 45.3 µmol/L, P < 0.0001). There were no differences in TPNAC incidence., Conclusions: Administering an intravenous solution of pediatric amino acids based on the umbilical cord aminogram yielded a higher taurine and lower methionine plasma concentration than did administering a similar solution based on the breast milk aminogram., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: We evaluate whether the consumption of fructose for 8 weeks affects enzymes and transcription factors of the lipogenic and inflammatory pathways in the hypothalamus of Wistar rats. Methods: At 30 days, the animals were divided into groups: Control (C) and Fructose (F) and maintained with free access to feed and filtered water (C) or aqueous solution of purified fructose at 20% (F). RT-PCR and Western blotting were performed for the target genes and proteins. Results: In F group, results showed a lower feed intake, an increase in glycemia (146.20 ± 6.09 vs. 102.32 ± 4.58; n : 9) and triacylglycerol (F: 191.65 ± 13.51 vs. C: 131.69 ± 6.49; n : 9) and there was no difference in water and energy consumption. We identified a higher content of acetyl-CoA carboxylase (ACC) (F: 133.93 ± 5.58 vs. C: 100 ± 0.0; n : 9-10) and NFκB (F: 125.5 ± 8.85 vs. C: 100 ± 0; n : 14) in group F, whereas fatty acid synthase (FAS) was lower (F: 85.90 ± 4.81 vs. C: 100 ± 0.0; n : 4-6). SREBP-1c gene expression was higher in F vs. C group (F: 4.08 ± 0.44 vs. C: 1.13 ± 0.15; n : 5-6), although we did not found difference between groups in the gene expression for ACC, SREBP-2, and NFκB. Discussion: Dietary fructose can change important lipogenic and inflammatory factors in the hypothalamus of rats and it leads to regulation of transcription factors before changes in body mass are evident.

Background: Hemorrhagic shock could induce acute lung injury (ALI), which is associated with cell hypoxia, lung tissue inflammation, free radical damage, and excessive cell apoptosis. Our previous studies demonstrated that hyperoxygenated solution could alleviate cell hypoxia. Furthermore, hydrogen-rich solution (HS) could relieve lung tissue inflammation, free radical damage and excessive cell apoptosis. Therefore we hypothesize that Hyperoxygenated Hydrogen-rich solution (HOHS) can protect the lung against ALI., Materials and Methods: SD rats were randomly divided into five groups (n = 6 at each time point in each group) and were exposed to Hemorrhagic shock induced ALI, and then treated with lactated Ringer's solution (LRS), hyperoxygenated solution, HS, and HOHS, respectively. The protective effects of these solutions were assessed using methods as follows: arterial blood samples were collected for blood gas analysis; Bronchoalveolar lavage fluid was collected for cell count and protein quantification; lung tissue samples were collected to measure wet/dry ratio, as well as levels of T-SOD, MDA, TNF-α, and IL-6; Caspase-3 and TUNEL-positive cells, and pathological changes were observed under light microscope; ALI was scored using the Smith scoring method; ultrastructural changes of lung tissues were further observed with transmission electron microscopy., Results: The results indicated that PaO2, PaCO2, and T-SOD increased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group; and conversely that the levels of lactate, MDA, TNF-α and IL-6, cell count, protein content, caspase-3 and TUNEL-positive cells as well as ALI score decreased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group. Morphological observation with optical microscope and electron microscopy showed that compared with the LRS group, cell damage in the three treatment groups improved to a varying extent, especially evident in the HOHS group., Conclusions: These findings demonstrate that HOHS can protect the lung against ALI induced by hemorrhagic shock., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the acceptability, tolerability, and effects on vulvovaginitis symptoms and signs of a non-soap, herbal-based intimate solution (Zelesse®)., Methods: We conducted a prospective, observational, multicenter study including adult women with symptoms and signs of vulvovaginitis with various etiologies, including candidiasis, trichomoniasis, bacterial vaginosis, and atrophic and irritative vaginitis. The presence and intensity of signs (edema, erythema, vaginal discharge) and symptoms (pruritus) of vulvovaginitis were evaluated before and after 5-15 days of daily use of Zelesse® alone or as a coadjuvant in antimicrobial therapy. Variables following a normal distribution and categorical variables were analyzed using the Student t-test and chi-square or Fisher's exact test, respectively., Results: A total 137 women were enrolled in the study; 87 (63.5%) women received concomitant antimicrobials and 50 (36.5%) used Zelesse® only. Global symptom scores and frequency of patients with vulvovaginitis signs and symptoms, and their mean intensity, decreased after treatment in both patient groups. Vaginal pH and (in the Zelesse®-only group) vaginal flora remained unaltered. The product was safe, well tolerated, and highly accepted by patients., Conclusions: Zelesse®, the non-soap herbal-based solution in this study, may represent a safe and effective option for symptomatic relief of vulvovaginitis.

Background: Atrophic acne facial scars still pose a treatment challenge. Needle-free high-pressure pneumatic injection has recently been introduced; however, few studies exist regarding its effectiveness., Objective: To evaluate the efficacy and safety of pneumatic injection for treating atrophic acne scars using a 3-dimensional optical profiling system., Methods and Materials: A pneumatic injection device with a 0.2-mm nozzle diameter, 50% pressure power, and 85-μL injection volume was used. The degree of depression was examined and analyzed using a 3-dimensional optical profiling system and clinical photographs. The patients also evaluated any side effects. Each subject underwent a single treatment session and was followed up after 1 and 2 months., Results: A total of 13 atrophic acne scars from 10 Korean men and women aged 20 to 29 (mean age 25.8 ± 2.4) years were studied. The mean scar volume values were 0.964, 0.741, and 0.566 mm, respectively, at baseline, 1 month, and 2 months after the injection. Scar volumes after 2 months were significantly different compared with baseline volumes. However, there was no significant difference between the baseline and 1-month volumes., Conclusion: Treatment with pneumatic injection is safe and effective in reducing atrophic acne facial scars; it results in quantitative improvement in scar volumes.

Background: As an alternative to advection, solute transport by shear-augmented dispersion within oscillatory cerebrospinal fluid flow was investigated in small channels representing the basement membranes located between cerebral arterial smooth muscle cells, the paraarterial space surrounding the vessel wall and in large channels modeling the spinal subarachnoid space (SSS)., Methods: Geometries were modeled as two-dimensional. Fully developed flows in the channels were modeled by the Darcy-Brinkman momentum equation and dispersion by the passive transport equation. Scaling of the enhancement of axial dispersion relative to molecular diffusion was developed for regimes of flow including quasi-steady, porous and unsteady, and for regimes of dispersion including diffusive and unsteady., Results: Maximum enhancement occurs when the characteristic time for lateral dispersion is matched to the cycle period. The Darcy-Brinkman model represents the porous media as a continuous flow resistance, and also imposes no-slip boundary conditions at the walls of the channel. Consequently, predicted dispersion is always reduced relative to that of a channel without porous media, except when the flow and dispersion are both unsteady., Discussion/conclusions: In the basement membranes, flow and dispersion are both quasi-steady and enhancement of dispersion is small even if lateral dispersion is reduced by the porous media to achieve maximum enhancement. In the paraarterial space, maximum enhancement R max  = 73,200 has the potential to be significant. In the SSS, the dispersion is unsteady and the flow is in the transition zone between porous and unsteady. Enhancement is 5.8 times that of molecular diffusion, and grows to a maximum of 1.6E+6 when lateral dispersion is increased. The maximum enhancement produces rostral transport time in agreement with experiments.

The study was designed to assess a practical mode of postdilution continuous venovenous hemofiltration (CVVH) with regional citrate anticoagulation (RCA) using a calcium-containing replacement solution, and to compare it with a CVVH mode with no anticoagulation (NA). Both methods were employed in our center for acute kidney injury (AKI) patients at high risk of bleeding. Fifty-six patients were equally allocated into the RCA-CVVH group and the NA-CVVH group. The study displayed no significant differences between groups involving baseline characteristics, severity level, blood gas analysis, hepatic/renal/coagulative functions, electrolytes, hemoglobin concentration, and platelet counts before or after continuous renal replacement therapy (CRRT). Compared to the NA-CVVH group, the RCA-CVVH group had a lower level of transfused packed red blood cells and platelet as well as a longer filter lifespan. The result showed no substantial differences between groups in terms of the mean supporting time and cost involving CRRT per person, the length of ICU and hospital stays, and the ICU survival. Homeostasis was basically preserved at a target range during the RCA post-CVVH procedure. Serious complications did not arise during the RCA process. RCA postdilutional CVVH is a safe and effective mode for application in AKI patients with a high risk of bleeding, and it can extend the filter lifespan and decrease blood loss, compared with the NA mode for CRRT. Further studies are needed to evaluate this mode for CRRT. (Retrospective Registration number ChiCTR1800016462, Registration date 2/6/2018).

Introduction: Leak tests using air or methylene blue (MB) for gastrojejunal anastomoses are often performed during gastric bypass surgeries to avoid leaks due to technical errors. Still, early leaks have been reported in the literature. Indocyanine green (ICG) fluorescence with laser excitement makes this dye easily visible even in small amounts, and, thus, may be an excellent agent for leak testing., Methods: During robotic gastric bypass surgery, a leak test of a gastrojejunal anastomosis was performed with air through a nasogastric tube under manual occlusion of the jejunum. Afterward, 50 ml of a mix of 100 ml sterile water, 2 mg of MB, and 5 mg ICG was injected through the same tube. The entire anastomosis was inspected for integrity under both fluorescent and normal light modes., Results: Leak tests with air and the blend of MB and ICG have been performed in 95 patients from January 2017 to April 2018. No intraoperative leak test-related adverse events occurred. Zero (0%) patients had a positive leak test with air, 0 patients showed MB excretion, and an ICG leak was observed in four (4.2%) patients. No anastomotic complications, including leaks and/or strictures, were found 30 days postoperatively., Conclusions: Leak tests using a blend of MB and ICG appear to be more sensitive for small defect detection of gastrojejunal anastomoses during robotic gastric bypass surgery. Larger datasets and research that is more stringent are needed to determine the exact clinical value of this new method.

Background: Tumescent local anesthesia (TLA) consists of infiltration of saline solution with lidocaine and epinephrine into the tissues to obtain regional anesthesia and vasoconstriction. The use of TLA in augmentation mammoplasty has been described for sub-glandular positioning. We describe a modified TLA technique for primary sub-muscular breast augmentation reporting our experience during the past 7 years., Methods: From 2010 to 2017, 300 patients underwent bilateral primary sub-muscular breast augmentation under TLA and conscious sedation. The tumescent solution was prepared with 25 mL of 2% lidocaine, 8 mEq of sodium bicarbonate, and 1 mL of epinephrine (1 mg/1 mL) in 1000 mL of 0.9% saline solution. Firstly, the solution was infiltrated between the pectoral fascia and the mammary gland, secondarily, during surgery, under the pectoralis major muscle., Results: The average amount of tumescent solution infiltrated while performing TLA was 740 mL per breast. No signs of adrenaline or lidocaine toxicity were reported and conversion to general anesthesia was never required. In all patients, no pain nor discomfort was reported during the pre-operating infiltration and surgical procedure. We reported a major complication rate of 3.3% (4 hematomas and 6 seromas) and a minor complication rate of 6.0% (8 implant dislocation and 10 dystrophic scars formation)., Conclusions: TLA represents a safe and efficacious technique for performing breast augmentation surgery with sub-muscular implant positioning. This technique guarantees good pain control during and after surgery and has low incidence of postoperative side effects. Patients subjected to sub-muscular breast augmentation with TLA were satisfied., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intravenous (IV) infusion of therapeutic proteins typically involves dilution of the formulated product into infusion media such as normal saline or dextrose, 5% m/v in water. We report results from a rigorous evaluation of imaged capillary isoelectric focusing (iCIEF) for monitoring dextrose-mediated glycation of proteins in IV infusion solutions. In addition to detecting stable Amadori glycation products, iCIEF was able to detect the labile Schiff base (SB) glycation adducts since the equilibrium with free dextrose is maintained on capillary. Method parameters such as sample dilution factor and ampholyte composition (but not urea) were found to influence the observed level of SB glycation adducts. The impacts of dextrose and urea on the apparent pI values are also reported. iCIEF results were compared with results from cation exchange chromatography, which was found to preferentially detect the more stable Amadori glycation products due to the on-column decomposition of the SB adducts resulting from the separation of the protein from free dextrose which in turn altered the SB adduct- free dextrose equilibrium. These results demonstrate the need for careful consideration when selecting the analytical methodology to investigate protein sensitivity to dextrose and to monitor protein stability in dextrose-containing infusion solutions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: Structural and functional analysis of cells from purulent-necrotic wounds in patients with diabetic foot syndrome undergoing ultrasonic treatment with 0.2% Lavasept solution., Material and Methods: It is presented morphological/ultrastructural analysis of wound specimens in 90 (DFS) patients aged 27-80 years with diabetic foot syndrome and purulent-necrotic complications who were hospitalized in the department of wounds and wound infections of the Vishnevsky Institute of Surgery in 2013-2016. Main group consisted of 75 patients, control group - 15 patients. Mean age was 58.4±8.2 years. All patients had diabetes mellitus type II for previous 13±4.5 years. Severity of foot tissue damage was assessed according to Wagner classification (F. Wagner, 1981). 46 (51.1%) patients had Wagner III-IV, 44 (48.9%) patients - Wagner II. Complex treatment included radical surgical management of purulent lesion, surgical revascularization for critical limb ischemia and foot reconstruction at the final stage. Additional measures were complete unloading of the foot, correction of carbohydrate metabolism and concomitant diseases. Topical treatment between surgical stages included dressing with 1.0% betadine solution (once a day). Ultrasonic cavitation was additionally applied in the main group. Electron microscopic examination of specimens was used before treatment, after 3-5 and 7-10 days in order to assess effectiveness of ultrasound cavitation for purulent-necrotic complications of DFS., Results: Ultrasound cavitation with 0.2% Lavasept solution effectively cleans wounds from microbial and cellular detritus, destroys cellular membranes of biofilm-forming microorganisms, prevents their redo development and reinfection of the wound. Effective management of the wounds accelerates reparative processes that allows to perform foot reconstruction early.

Background: Effective alcohol-based hand rubs (ABHRs) and healthcare worker compliance with hand hygiene guidelines are important in the prevention of infection transmission in healthcare settings. Compliance to hand hygiene guidelines is affected by many factors including education, ABHR availability, time pressure, skin health, and user acceptance of the sensory properties of ABHRs during and after application., Aim: To examine the effect of ABHR format (gel/foam/liquid) and dose (0.7 mL, 1.5 mL, 3 mL) on its sensory properties and acceptability, and to consider how this might affect healthcare workers' hand hygiene compliance., Methods: Sensory descriptive analysis established key sensory differences between ten market-leading ABHRs (three gels, four foams, two liquids, one aerosol foam). Focus groups reinforced these differences., Findings: All formats were less desirable at the highest dose as they were more difficult to handle than the lower doses. Foams and gels became stickier, less clean-feeling and slower to dry at higher doses. Liquids gave a cleaner, smoother, more moisturized feel, but the increased difficulty in handling and applying the product negated these benefits. Overall, the gel and foam formats were more desirable than the liquid. The key desirable properties include: fast absorption, soft/moisturized hand feel, not sticky, clean feel, and low smell., Conclusion: The 1.5 mL dose yielded the most acceptable properties with no extreme negative consequences. The foam provided the benefits of both the liquid and gel and combined them into a more widely acceptable format that may lead to greater hand hygiene compliance., (Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objective To evaluate the efficacy, tolerability and acceptability of Zelesse®, an intimate hygiene wash solution, in the relief of the symptoms and signs of non-specific vulvovaginitis in paediatric patients. Methods The NINESSE Study was a prospective, observational, multicentre study involving females aged 2-8 years who attended paediatric offices with symptoms suggestive of non-specific vulvovaginitis. They were administered Zelesse® as a single treatment for 15 ± 5 days. Pruritus, burning, dysuria, erythema, leucorrhoea and oedema were evaluated before and after treatment. Results A total of 71 paediatric patients were enrolled in the study (mean ± SD age, 4.5 ± 1.9 years). The most significant effects were observed for pruritus and burning, where 98.4% (62 of 63) and 96.9% (63 of 65) of the patients improved after treatment, respectively. Zelesse® demonstrated a beneficial effect on dysuria, erythema, leucorrhoea and oedema. The effects on the symptoms and signs were observed within the first week of treatment; although 44.9% (31 of 69) of patients experienced improvements after 2-3 days. Zelesse® was well accepted and tolerated by most patients. No serious adverse events were reported. Conclusions Zelesse® was very effective for the relief of the symptoms and signs of non-specific vulvovaginitis, in particular pruritus, burning and erythema, in females aged 2-8 years.

Background: A recently developed transdermal fentanyl solution was hypothesized to be effective for non-invasive postoperative analgesia in rats., Materials and Methods: Thirty-nine male Sprague-Dawley rats were treated once with 0.1, 0.33 or 1.0 mg/kg transdermal fentanyl solution at the skin of the scruff 1 h prior to subjected to hind-paw surgery, and compared to non-treated animals. All rats were tested for nociceptive response in the electronic von Frey (EVF) test between 1 and 72 h postoperatively, and assessed daily with regards to facial expression, body weight changes and welfare score., Results: Fentanyl treatment at all doses significantly reduced nociceptive response in the EVF test throughout the 72 h of experimentation, reduced facial expressions on all days postoperatively, slightly reduced the body weight and improved postoperative welfare parameters., Conclusion: The present study indicates that transdermal fentanyl solution seems to be an effective, non-invasive and long-lasting analgesic regimen in male rats., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aims: A submucosal cushion of sodium hyaluronate facilitates gastric and colorectal endoscopic submucosal dissection (ESD). However, few studies have evaluated the utility of sodium hyaluronate for ESD of esophageal lesions. The aim of this study is to evaluate the utility and safety of sodium hyaluronate for ESD of superficial esophageal squamous cell neoplasms (ESCN)., Material and Methods: We retrospectively reviewed 111 ESCN in 86 patients treated by ESD between September 2007 and April 2013. There were four double cancers, with 107 ESD procedures analyzed., Results: The en bloc resection rate was 99% (106/107). The R0 resection rate was 93% (99/107). Of 106 specimens resected en bloc, four specimens had a positive horizontal margin, two specimens had non-assessable horizontal margins and one specimen had non-assessable horizontal and vertical margins. One patient with a non-assessable horizontal margin developed local recurrence seven months later, treated by repeat ESD. Delayed bleeding occurred in two procedures (2%), and intra-procedural perforation occurred in four (4%). None required operative repair. Endoscopy trainees performed 33 of 107 (31%) ESD procedures. Post-ESD stenosis requiring dilation occurred following five procedures (5%)., Conclusions: Sodium hyaluronate for ESD of ESCN achieves a high R0 resection rate with a low rate of adverse events.

The accumulation and differentiation of adipocytes contribute to the development of obesity and metabolic diseases. It is well-known that interactions of transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and endoplasmic reticulum (ER) stress are required for adipogenesis. Recently, use of nonthermal atmospheric plasma (NTP) is expanding from the biomedical field into various other fields. In this study, we investigated whether nonthermal plasma-treated solution (NTS) has an inhibitory effect on adipogenesis and elucidated its mechanisms. Our results demonstrated that NTS significantly inhibited pre-adipocyte differentiation into adipocytes based on Oil Red O staining and triglyceride accumulation. Moreover, NTS treatment suppressed the mRNA and protein expression levels of key adipogenic transcription factors, and adipocyte-specific genes. NTS also down-regulated endoplasmic reticulum stress-related proteins. Consistent with in vitro studies, an animal study using a mouse model of diet-induced obesity showed that NTS treatment reduced body weight and fat, ER stress/UPR, triglyceride, and adipogenic marker level without altering food intake. These findings indicate that NTS inhibits adipogenic differentiation, and provide a mechanistic explanation of the inhibitory effect of NTS on adipogenesis. Taken together, our results suggest that NTS might be useful to treat obesity and obesity-related diseases.

Objectives: Test the performance of topical antimicrobial wound solutions against microbial biofilms using in vitro, ex vivo and in vivo model systems at clinically relevant exposure times., Methods: Topical antimicrobial wound solutions were tested under three different conditions: (in vitro) 4% w/v Melaleuca oil, polyhexamethylene biguanide, chlorhexidine, povidone iodine and hypochlorous acid were tested at short duration exposure times for 15 min against 3 day mature biofilms of Staphylococcus aureus and Pseudomonas aeruginosa; (ex vivo) hypochlorous acid was tested in a porcine skin explant model with 12 cycles of 10 min exposure, over 24 h, against 3 day mature P. aeruginosa biofilms; and (in vivo) 4% w/v Melaleuca oil was applied for 15 min exposure, daily, for 7 days, in 10 patients with chronic non-healing diabetic foot ulcers complicated by biofilm., Results: In vitro assessment demonstrated variable efficacy in reducing biofilms ranging from 0.5 log10 reductions to full eradication. Repeated instillation of hypochlorous acid in a porcine model achieved <1 log10 reduction (0.77 log10, P = 0.1). Application of 4% w/v Melaleuca oil in vivo resulted in no change to the total microbial load of diabetic foot ulcers complicated by biofilm (median log10 microbial load pre-treatment = 4.9 log10 versus 4.8 log10, P = 0.43)., Conclusions: Short durations of exposure to topical antimicrobial wound solutions commonly utilized by clinicians are ineffective against microbial biofilms, particularly when used in vivo. Wound solutions should not be used as a sole therapy and clinicians should consider multifaceted strategies that include sharp debridement as the gold standard., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Purpose: The aim of this study was to investigate the diagnostic efficacy and image quality of magnetic resonance enterography (MRE) using oral mannitol solution for the evaluation Crohn disease (CD)., Materials and Methods: We retrospectively evaluated MRE examinations of 153 patients with an assumed or definitive diagnosis of CD. There were 65 men and 88 women, with a mean age of 35.7 years (range: 6-73years). MRE findings of the patients were compared to histopathologic results obtained by surgery-fiberoptic endoscopy. The sensitivity, specificity and diagnostic efficacy rate were calculated. Additionally, image quality of MRE was evaluated using a four-point scale (1=excellent, 4=poor/non-diagnostic)., Results: Sensitivity, specificity and diagnostic efficacy were 92.5%, 93% and 92.8%, respectively. Six patients had false-positive and five patients had false-negative findings. Three falsely positive patients had ulcerative colitis and three had non-specific terminal ileitis. A total of 765 small bowel segments were analyzed; 475 (62%) had an image quality score of 1 and 15 (2%), an image quality score of 4., Conclusion: MRE using oral mannitol solution provides excellent image quality for MRE and has high degrees of diagnostic efficacy in CD patients., (Copyright © 2017 Editions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Prolonged labor has been demonstrated to increase adverse maternal and neonatal outcome. A practice that may decrease the risk of prolonged labor is the modification of fluid intake during labor., Objective: Several studies demonstrated that increased hydration in labor as well as addition of dextrose-containing fluids may be associated with a decrease in length of labor. The purpose of our study was to characterize whether high-dose intravenous fluids, standard-dose fluids with dextrose, or high-dose fluids with dextrose show a difference in the duration of labor in nulliparas., Study Design: Nulliparous subjects with singletons who presented in active labor were randomized to 1 of 3 groups of intravenous fluids: 250 mL/h of normal saline, 125 mL/h of 5% dextrose in normal saline, or 250 mL/h of 2.5% dextrose in normal saline. The primary outcome was total length of labor from initiation of intravenous fluid in vaginally delivered subjects. Secondary outcomes included cesarean delivery rate and length of second stage of labor, among other maternal and neonatal outcomes., Results: In all, 274 subjects who met inclusion criteria were enrolled. There were no differences in baseline characteristics among the 3 groups. There was no difference in the primary outcome of total length of labor in vaginally delivered subjects among the 3 groups. First stage of labor duration, second stage of labor duration, and cesarean delivery rates were also equivalent. There were no differences identified in other secondary outcomes including clinical chorioamnionitis, postpartum hemorrhage, blood loss, Apgar scores, or neonatal intensive care admission., Conclusion: There is no difference in length of labor or delivery outcomes when comparing high-dose intravenous fluids, addition of dextrose, or use of high-dose intravenous fluids with dextrose in nulliparous women who present in active labor., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To review the history of moist therapy used to regenerate traumatic tympanic membrane perforations., Study Design: Literature review., Methods: The literature on topical agents used to treat traumatic tympanic membrane perforations was reviewed, and the advantages and disadvantages of moist therapy were analysed., Results: A total of 76 studies were included in the analysis. Topical applications of certain agents (e.g. growth factors, Ofloxacin Otic Solution, and insulin solutions) to the moist edges of traumatic tympanic membrane perforations shortened closure times and improved closure rates., Conclusion: Dry tympanic membrane perforation edges may be associated with crust formation and centrifugal migration, delaying perforation closure. On the contrary, moist edges inhibit necrosis at the perforation margins, stimulate proliferation of granulation tissue and aid eardrum healing. Thus, moist perforation margins upon topical application of solutions of appropriate agents aid the regeneration of traumatic tympanic membrane perforations.

Objective: To assess the types of maintenance fluids used in our hospital, comparing their volume and composition to the standards recommended by the guidelines., Material and Methods: Observational, cross-sectional study. Volume and type of fluid therapy administered during 24h to patients admitted to various hospital departments were recorded. Patients receiving fluid therapy because of water-electrolyte imbalance were excluded., Results: Out of 198 patients registered, 74 (37.4%) were excluded because they did not meet the criteria for inclusion. Mean administered volume was 2,500cc/day. Mean daily glucose dose was 36g per 24h (SD: 31.4). The most frequent combination included normal saline solution (NSS) and glucose 5% (64.4%). Mean daily dose of sodium and chlorine was, respectively, 173mEq (SD: 74.8) and 168mEq (SD: 75), representing a surplus daily dose of +87.4mEq and +85mEq. Potassium, magnesium and calcium daily deficit was, respectively, -50mEq, -22mEq and -21mEq per day. Buffer administration was exceptional, bicarbonate (2.29%), acetate (1.29%), lactate (1.15%) and gluconate (1.10%) being the buffering agents most frequently used., Conclusion: NNS is the most frequently used solution. In contrast to excess doses of sodium and chlorine, there is a great deficit of other ions, buffering agents and caloric intake in the fluid therapy regimens that are usually prescribed., (Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Focal abnormalities most commonly acquired within the uterine cavity include endometrial polyps (arising from the endometrium) and submucous fibroids (arising from the myometrium). These benign abnormalities can cause several problems, including abnormal uterine bleeding (AUB) and subfertility. Two-dimensional saline infusion sonography (2D SIS) is a minimally invasive test that can be used to diagnose these pathologies, but it is less accurate than hysteroscopy, which is a more invasive procedure by which an endoscope allows direct visualisation of the uterine cavity. Three-dimensional (3D) SIS appears to enhance sonographic visualisation within the uterine cavity, thereby offering a potentially more accurate minimally invasive diagnostic test., Objectives: Primary objectives • To evaluate the diagnostic accuracy of 3D SIS (index test 1) compared with 2D SIS for the diagnosis of focally growing lesions (presence or not) in women with AUB or subfertility, with hysteroscopy performed as the reference test. • To evaluate the diagnostic accuracy of 2D+3D SIS (index test 2) compared with 2D SIS for the diagnosis of focally growing lesions (presence or not) in women with AUB or subfertility, with hysteroscopy performed as the reference test. In this case, any abnormality on either modality was regarded as a positive result ('OR' approach). Secondary objectives • To evaluate the diagnostic accuracy of 3D SIS (index test 1) compared with 2D SIS according to type of abnormality and discrimination between uterine polyps and submucous fibroids in women with AUB or subfertility, with hysteroscopy and histology used as the reference.• To evaluate the diagnostic accuracy of 2D+3D SIS (index test 2) compared with 2D SIS according to type of abnormality and discrimination between uterine polyps and submucous fibroids in women with AUB or subfertility, with hysteroscopy and histology used as the reference., Search Methods: We searched the following databases: Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PubMed, Cochrane Gynaecology and Fertility Group (CGF) Specialised Register and CGFG Diagnostic Test Accuracy (DTA) Specialised Register, clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Screening reference lists of appropriate studies was also performed. We screened for eligibility all studies identified from inception until March 2016. We performed searches with no date or language restrictions., Selection Criteria: The population of interest consisted of premenopausal women with AUB or subfertility and postmenopausal women with AUB. Diagnostic test accuracy studies, randomised controlled trials (RCTs) and prospective cohort studies were eligible for inclusion if they evaluated the accuracy of both 2D SIS and 3D SIS for the diagnosis of acquired intracavitary abnormalities with hysteroscopy used as the reference standard. In light of the lack of data for 3D SIS, we also included studies that evaluated the accuracy of 3D SIS alone., Data Collection and Analysis: Two review authors read all potentially eligible references after performing a first screening by title and abstract (LLN and FJRH). They independently extracted data to construct 2×2 tables from eligible studies and assessed studies for methodological quality using the QUADAS-2 tool (revised tool for quality assessment of diagnostic accuracy studies). To describe and visually present results, we produced in RevMan forest plots showing pairs of sensitivity and specificity together with 95% confidence intervals from each study, as well as raw receiver operating characteristic (ROC) plots. We displayed paired analyses in an ROC plot by linking sensitivity-specificity pairs from each study by using a dashed line. To compare 3D SIS versus 2D SIS, we restricted analyses to studies that provided 2×2 tables for both tests and used the bivariate meta-analysis of sensitivity and specificity., Main Results: Thirteen studies (1053 women) reported the accuracy of 3D SIS for focal uterine abnormalities; 11 of these (846 women) were suitable for meta-analysis, and eight reported accuracy according to the type of focal abnormality. The design of the included studies seems applicable. The main problem involving the quality of included studies is insufficient reporting of study methods, resulting in unclear risk of bias for several of the quality domains assessed. Therefore, we considered the overall quality of the evidence as low. The summary estimate (11 studies reporting absence or presence of abnormality at 3D SIS) for sensitivity was 94.5% (95% confidence interval (CI) 90.6% to 96.9%) and for specificity 99.4% (95% CI 96.2% to 99.9%). Meta-analysis of the eight studies (N = 716) directly comparing 2D SIS versus 3D SIS showed summary sensitivity of 96.9% (95% CI 91.9% to 98.8%) and summary specificity of 99.5% (95% CI 96.1% to 100%) for 3D SIS. For 2D SIS, summary sensitivity was 90.9% (95% CI 81.2% to 95.8%) and summary specificity was 96.3% (95% CI 86.1% to 99.1%). The difference in accuracy between 2D SIS and 3D SIS was non-significant (P values of 0.07 for sensitivity and 0.10 for specificity)., Authors' Conclusions: Low-quality evidence suggests that 3D SIS may be very accurate in detecting intracavitary abnormalities. Meta-analysis revealed no statistically significant differences between 2D SIS and 3D SIS. Summary sensitivity and summary specificity are higher for 3D SIS, but margins of improvement are limited because 2D SIS is already very accurate. When the technology and appropriate expertise are available, 3D SIS offers an alternative to 2D SIS. Both 2D SIS and 3D SIS should be considered alternatives to diagnostic hysteroscopy when intracavitary pathology is suspected in subfertile women and in those with abnormal uterine bleeding.

Objective: To examine factors that might affect the ability of patients to accurately halve tablets or measure a 5-ml liquid dose., Methods: Eighty-eight participants split four different placebo tablets by hand and using a tablet splitter, while 85 participants measured 5 ml of water, 0.5% methylcellulose (MC) and 1% MC using a syringe and dosing cup. Accuracy of manipulation was determined by mass measurements., Key Findings: The general population was less able than pharmacy students to break tablets into equal parts, although age, gender and prior experience were insignificant factors. Greater accuracy of tablet halving was observed with tablet splitter, with scored tablets split more equally than unscored tablets. Tablet size did not affect the accuracy of splitting. However, >25% of small scored tablets failed to be split by hand, and 41% of large unscored tablets were split into >2 portions in the tablet splitter. In liquid measurement, the syringe provided more accurate volume measurements than the dosing cup, with higher accuracy observed for the more viscous MC solutions than water., Conclusion: Formulation characteristics and manipulation technique have greater influences on the accuracy of medication modification and should be considered in off-label drug use in vulnerable populations., (© 2016 Royal Pharmaceutical Society.)

We measured the distribution of sugar solution within groups of caged honey bees (Apis mellifera) under standard in vitro laboratory conditions using 14C polyethylene glycol as a radioactive marker to analyze ingestion by individual bees after group feeding. We studied the impact of different experimental setups by varying the number of bees, age of bees, origin of bees, duration of experiment, the amount of available diet, and the influence of the neurotoxic pesticide imidacloprid in the diet on the feeding and food sharing behavior (trophallaxis). Sugar solution was non-uniformly distributed in bees in 36 out of 135 cages. As a measure of the extent to which the sugar diet was equally distributed between caged bees, we calculated the (inner 80%) intake ratio by dividing the intake of the 90th percentile bee by the intake of the 10th percentile bee. This intake ratio ranged from 1.3 to 94.8 in 133 individual cages, further supporting a non-uniform distribution of food among caged bees. We can expect a cage with 10 or 30 bees containing one bee that ingests, on average, the 8.8-fold of the bee in the same cage ingesting the smallest quantity of food. Inner 80% intake ratios were lower in experiments with a permanent or chronic offering of labelled sugar solution compared to temporary or acute feedings. After pooling the data of replicates to achieve a higher statistical power we compared different experimental setups. We found that uniform food distribution is best approached with 10 newly emerged bees per cage, which originate from a brood comb from a single colony. We also investigated the trophallaxis between caged honey bees which originally consumed the diet and newly added bees. Color marked bees were starved and added to the cages in a ratio of 10:5 or 20:20 after the initial set of bees consumed all the labelled sugar solution. The distribution of the labelled sugar solution by trophallaxis within 48 hours to added bees was 25% (10:5) or 45% (20:20) of the initial sugar solution. Imidacloprid at its median lethal dose (LD50) in the sugar solution reduced this post-feeding food transmission to 27% (20:20). Our results show that differences in food intake exist within caged bees that may lead to differential exposure that can influence the interpretation of toxicity tests.