Patients' expectation of postoperative course and satisfaction following cardiac surgery.

INTRODUCTION: In patients undergoing cardiac surgery, preoperative concerns, expectations of the impact of surgery, anticipated recovery timelines, and pre- and postoperative education, which impact recovery and quality-of-life, are not well documented. These factors are important with the increase in virtual consultations, the availability of internet-based information and increased use of minimally invasive surgical procedures. METHODS: Patients who underwent cardiac surgery between January 2016 and December 2019 took part in an online survey examining preoperative concerns, information provision, use of digital channels, satisfaction with surgery, impact on health and resumption of daily activity. 80 patients completed the survey. RESULTS: There was a high rate of overall post-surgical satisfaction (86%); 71% of respondents reported an improvement in physical health, 45% in mental health and 70% in their quality-of-life. The usefulness of information provided by the National Health Service varies across different stages of the patient experience. Although approximately 90% of respondents found the information provided at each stage at least 'somewhat' helpful, the proportion who found the information 'very' helpful was lower (68% for pre-procedure; 55% for post-discharge). The majority (79%) said that they felt prepared for their operation. Survey responses highlighted areas of lower understanding, including survival rate, levels of postoperative pain, duration of hospital stay and when the patient could return to normal physical activity. CONCLUSIONS: Levels of satisfaction with the outcomes of heart surgery are high, and the majority of patients report positive health outcomes. However, there is room for improvement in patients' understanding of survival rate and level of pain post-procedure. There is also a clear desire among patients for a more surgical team-based face-to-face consultation.

Noninvasive body sculpting technologies with an emphasis on high-intensity focused ultrasound.

BACKGROUND: Body-sculpting procedures are becoming increasingly popular in the United States. Although surgical lipoplasty remains the most common body sculpting procedure, a demand exists for noninvasive alternatives capable of reducing focal adiposity without the risks of adverse events (AEs) associated with invasive excisional body-sculpting procedures. METHODS: This report describes the mechanism of action, efficacy, safety, and tolerability of cryolipolysis, radiofrequency ablation, low-level external laser therapy, injection lipolysis, low-intensity nonthermal ultrasound, and high-intensity focused ultrasound (HIFU), with an emphasis on thermal HIFU. The articles cited were identified via a PubMed search, with additional article citations identified by manual searching of the reference lists of articles identified through the literature search. RESULTS: Each of the noninvasive treatments reviewed can be administered on an outpatient basis. These treatments generally have fewer complications than lipoplasty and require little or no anesthesia or analgesia. However, HIFU is the only treatment that can produce significant results in a single treatment, and only radiofrequency, low-level laser therapy, and cryolipolysis have been approved for use in the United States. Early clinical data on HIFU support its efficacy and safety for body sculpting. In contrast, radiofrequency, laser therapy, and injection lipolysis have been associated with significant AEs. CONCLUSIONS: The published literature suggests that noninvasive body-sculpting techniques such as radiofrequency ablation, cryolipolysis, external low-level lasers, laser ablation, nonthermal ultrasound, and HIFU may be appropriate options for nonobese patients requiring modest reduction of adipose tissue.

Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine.

Venlafaxine and its metabolite desvenlafaxine are serotonin-norepinephrine reuptake inhibitors currently prescribed for the treatment of depression. Previously, it was reported that venlafaxine is an inducer of MDR1, the gene responsible for P-glycoprotein (P-gp). The present study expanded upon these findings by examining the effect of venlafaxine and desvenlafaxine on the expression of both P-gp and the breast cancer resistance protein (BCRP) in human brain endothelial cells (HBMEC), an in vitro model of the blood-brain barrier (BBB). The HBMEC were treated for 1 h with various concentrations (500 nM to 50 µM) of venlafaxine and desvenlafaxine. Western blot analysis revealed treatment with venlafaxine significantly induced the expression of P-gp (2-fold) and BCRP (1.75-fold) in a dose-dependent manner, while treatment with desvenlafaxine had no effect on drug efflux transporter expression. To determine the functional significance of this effect, the permeability of a known drug efflux probe, rhodamine 123, across the BBB model and Caco-2 cells, a model of intestinal absorption, were examined. Treatment with venlafaxine (1-50 µM) for 1 h significantly reduced the apical-to-basolateral permeability of R123 across the BBB model (30%) and Caco-2 cell monolayers (25%), indicative of increased drug efflux transporter expression at the apical membrane. Conversely, desvenlafaxine had no effect on R123 permeability in either cellular model. These studies indicate that venlafaxine, but not desvenlafaxine is an inducer of drug efflux transporter expression, which consequently increases the potential for clinical drug-drug interactions. Therefore, based on these preliminary results, caution should be taken when prescribing venlafaxine with other P-gp substrates.

Anti-Tumoral Activity of a Short Decapeptide Fragment of the Alzheimer's Abeta Peptide.

The inhibition of angiogenesis is regarded as a promising avenue for cancer treatment. Although some antiangiogenic compounds are in the process of development and testing, these often prove ineffective in vivo, therefore the search for new inhibitors is critical. We have recently identified a ten amino acid fragment of the Alzheimer Abeta peptide that is anti-angiogenic both in vitro and in vivo. In the present study, we investigated the antitumoral potential of this decapeptide using human MCF-7 breast carcinoma xenografts nude mice. We observed that this decapeptide was able to suppress MCF-7 tumor growth more potently than the antiestrogen tamoxifen. Inhibition of tumor vascularization as determined by PECAM-1 immunostaining and decreased tumor cell proliferation as determined by Ki67 immunostaining were observed following treatment with the Abeta fragment. In vitro, this peptide had no direct impact on MCF-7 tumor cell proliferation and survival suggesting that the inhibition of tumor growth and tumor cell proliferation observed in vivo is related to the antiangiogenic activity of the peptide. Taken together these data suggest that this short Abeta derivative peptide may constitute a new antitumoral agent.

Assessment of recovery time for the collagen products Dermicol-P35 27G and 30G.

BACKGROUND: Dermicol-P35 27G and 30G are purified advanced collagen dermal fillers that are effective and well tolerated for cosmetic procedures. OBJECTIVE: The primary objectives of this study were to: (1) document recovery time and return to daily activities after treatment with Dermicol-P35 27G, 30G, or both; and (2) assess the immediate adverse effects of these products and monitor their time to resolution. METHODS: In all, 30 patients were treated with Dermicol-P35 27G, 30G, or both in nasolabial folds, lips, corners of the mouth, vermillion border, marionette lines, or a combination of these and monitored for 7 days. Comfort with resuming daily routine, adverse events, and satisfaction with results were documented by patients in diaries. The clinician assessed aesthetic improvement and rated satisfaction with results. RESULTS: The majority of patients (63.4%) were very comfortable or comfortable returning to their daily routine immediately postprocedure. Most patients (86.7%) participated in normal work or social events within 2 days of treatment. Adverse events were mild to moderate and were resolved or tolerable by day 7. The clinician assessed that most patients had between 50% and 100% improvement over baseline for all procedures at all time points. Clinician and patients were very satisfied or satisfied with aesthetic results at days 2 and 7 postprocedure. LIMITATIONS: The limitations of this study were the small number of patients, the assessment of short-term results, and the lack of touch-up injections. CONCLUSIONS: Treatment with Dermicol-P35 27G, 30G, or both allowed for rapid return to daily activities and produced only transient and tolerable adverse events.

Reduction of beta-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer's disease.

BACKGROUND: Abeta deposits represent a neuropathological hallmark of Alzheimer's disease (AD). Both soluble and insoluble Abeta species are considered to be responsible for initiating the pathological cascade that eventually leads to AD. Therefore, the identification of therapeutic approaches that can lower Abeta production or accumulation remains a priority. NFkappaB has been shown to regulate BACE-1 expression level, the rate limiting enzyme responsible for the production of Abeta. We therefore explored whether the known NFkappaB inhibitor celastrol could represent a suitable compound for decreasing Abeta production and accumulation in vivo. METHODS: The effect of celastrol on amyloid precursor protein (APP) processing, Abeta production and NFkappaB activation was investigated by western blotting and ELISAs using a cell line overexpressing APP. The impact of celastrol on brain Abeta accumulation was tested in a transgenic mouse model of AD overexpressing the human APP695sw mutation and the presenilin-1 mutation M146L (Tg PS1/APPsw) by immunostaining and ELISAs. An acute treatment with celastrol was investigated by administering celastrol intraperitoneally at a dosage of 1 mg/Kg in 35 week-old Tg PS1/APPsw for 4 consecutive days. In addition, a chronic treatment (32 days) with celastrol was tested using a matrix-driven delivery pellet system implanted subcutaneously in 5 month-old Tg PS1/APPsw to ensure a continuous daily release of 2.5 mg/Kg of celastrol. RESULTS: In vitro, celastrol dose dependently prevented NFkappaB activation and inhibited BACE-1 expression. Celastrol potently inhibited Abeta1-40 and Abeta1-42 production by reducing the beta-cleavage of APP, leading to decreased levels of APP-CTFbeta and APPsbeta. In vivo, celastrol appeared to reduce the levels of both soluble and insoluble Abeta1-38, Abeta1-40 and Abeta1-42. In addition, a reduction in Abeta plaque burden and microglial activation was observed in the brains of Tg PS1/APPsw following a chronic administration of celastrol. CONCLUSIONS: Overall our data suggest that celastrol is a potent Abeta lowering compound that acts as an indirect BACE-1 inhibitor possibly by regulating BACE-1 expression level via an NFkappaB dependent mechanism. Additional work is required to determine whether chronic administration of celastrol can be safely achieved with cognitive benefits in a transgenic mouse model of AD.

A chicken in every pot: at what price?

The poultry industry is one of the fastest growing industries in the United States. "Big chicken," however, has created big problems. Consumers and the environment, as well as people who grow, catch, slaughter, and process chicken are all impacted by the practices and policies of the poultry industry. This paper sheds some light on serious problems caused by production practices that put profits above human dignity, food safety, and the environment and proposes some needed regulations and actions.

Management of pterygia 20 years later.

Over a 20-year period, I excised 205 pterygia. A single, low dose of beta irradiation applied to the site of excision before surgical closure of the conjunctiva significantly reduced the rate of recurrence. Follow-up for as long as 20 years in this series revealed no complications. I discuss possible reasons for the few recurrences.

Chloroquine affects biosynthesis of Ia molecules by inhibiting dissociation of invariant (gamma) chains from alpha-beta dimers in B cells.

Biosynthetic conversion of Ia oligomers from three chains (alpha, beta, gamma) to two (alpha, beta) before surface expression was inhibited in B lymphoid cells by treatment with chloroquine, resulting in the accumulation of Ia complexes composed of mature alpha and beta chains, and gamma chains at various states of sialylation. Other stages of Ia biosynthesis and processing appeared unaffected, indicating that chloroquine selectively interfered with the gamma chain dissociating mechanism itself. Similar effects were also observed with ammonium chloride. Because of the nature of such lysosomotropic agents, these results suggest that an intracellular acidic compartment may be involved in processing Ia oligomers to accomplish dissociation from gamma chains. Since chloroquine is known to inhibit Ia-restricted antigen presentation in accessory cells, our results raise the possibility that the pathways of antigen processing and Ia biosynthesis may use some common intracellular compartments.

Preparation of experimental animal tissue for SEM.

Methods for preparing experimental animal tissues for the scanning electron microscope (SEM) have evolved from so many sources, with such lack of standardization that interpretation of the results is difficult, and inter-investigation comparisons usually impossible. To distinguish the surface changes inherent in any protocol for the preparation of bulk tissue blocks from those produced by experimentation or disease, the preparative procedures must become standardized at least to the extent that preparation for light microscopy (LM) and transmission electron microscopy (TEM) is standardized. Rationales for the selection of a particular preparative procedure which will result in minimal alteration from the living tissue are discussed. The methods for handling the specimen, stabilization, dehydration and drying, rendering the surface conductive, and exposing the surface of interest are described for a wide variety of experimental animals. The use of SEM to yield maximum morphological information in the secondary electron mode is also described, as are the methods used for evaluating the results in terms of minimal distortion due to preparative procedures.

SEM of micro-corrosion casts.

The production of micro-corrosion casts suitable for scanning electron microscopy (SEM) is described in this tutorial. The casts are produced by filling an internal luminal system or space with a liquid medium which becomes solid in situ. The surrounding tissue is then removed (corroded) and the resulting replica is dried, rendered conductive, and examined in the SEM. An historical review describes the evolution of the technique and provides perspective for the SEM applications. The criteria which should be fulfilled by the injection medium are listed, and the procedures used for those media which have proven successful, together with their inherent artefacts are described in detail. The two groups of media most commonly used are the rubber compounds and the polymer resins. The latter so faithfully replicate luminal surfaces that a distinction between arteries and veins can be made on the basis of endothelial cell impressions on the surface of the replica. A review of currently used non-SEM techniques provides a comprehensive analysis of the methods used to determine success with SEM micro-corrosion casting, as well as complementary methods for the visualization of vascular and alveolar systems. The paper is illustrated mainly with material from the rat brain vascular system.