A prospective study on single-port versus multiport patient-reported surgical outcomes.

Introduction: We sought to determine potential patient reported advantages of the da Vinci single-port (SP) robotic system for urological procedures compared with the previous model, the da Vinci multiport (MP) system. The SP model utilizes a single 30 to 40 mm incision rather than multiple 5 to 22 mm incisions. This project aims to prospectively investigate the impact of the novel SP system on patient reported cosmetic and psychometric surgical outcomes. Methods: We conducted a prospective study of patients who underwent uro-oncologic surgery by three urologists at the University of Illinois Chicago from April to November 2021. Study participants completed a Patient Scar Assessment Questionnaire 20 and 90 days post-procedure. The Patient Scar Assessment Questionnaire is a reliable measure of surgical scars that includes five subscales: Appearance, Symptoms, Consciousness, Satisfaction with Appearance, and Satisfaction with Symptoms. Higher scores represented worse reported outcomes. Results: On Postoperative Day 20, there were 77 responses (53 SP and 24 MP). Patients receiving SP procedures reported more favourable outcomes in terms of appearance, symptoms, consciousness, and pain medication. On Day 90, there were 37 responses (24 SP and 13 MP). Patients receiving SP procedures reported more favourable outcomes in terms of appearance. No significant differences were seen on Day 90 in terms of pain, medication, symptoms, consciousness, or satisfaction. Conclusions: This study demonstrates the superiority of the SP in patient reported cosmetic and pain outcomes on short- and long-term follow-up after uro-oncological surgical procedures. Symptomatic and cosmetic advantages are present at the 20 day follow-up, with better scar appearance being significant 90 days after surgery.

SGLT2 inhibitors therapy protects glucotoxicity-induced ß-cell failure in a mouse model of human KATP-induced diabetes through mitigation of oxidative and ER stress.

Progressive loss of pancreatic ß-cell functional mass and anti-diabetic drug responsivity are classic findings in diabetes, frequently attributed to compensatory insulin hypersecretion and ß-cell exhaustion. However, loss of ß-cell mass and identity still occurs in mouse models of human KATP-gain-of-function induced Neonatal Diabetes Mellitus (NDM), in the absence of insulin secretion. Here we studied the temporal progression and mechanisms underlying glucotoxicity-induced loss of functional ß-cell mass in NDM mice, and the effects of sodium-glucose transporter 2 inhibitors (SGLT2i) therapy. Upon tamoxifen induction of transgene expression, NDM mice rapidly developed severe diabetes followed by an unexpected loss of insulin content, decreased proinsulin processing and increased proinsulin at 2-weeks of diabetes. These early events were accompanied by a marked increase in ß-cell oxidative and ER stress, without changes in islet cell identity. Strikingly, treatment with the SGLT2 inhibitor dapagliflozin restored insulin content, decreased proinsulin:insulin ratio and reduced oxidative and ER stress. However, despite reduction of blood glucose, dapagliflozin therapy was ineffective in restoring ß-cell function in NDM mice when it was initiated at >40 days of diabetes, when loss of ß-cell mass and identity had already occurred. Our data from mouse models demonstrate that: i) hyperglycemia per se, and not insulin hypersecretion, drives ß-cell failure in diabetes, ii) recovery of ß-cell function by SGLT2 inhibitors is potentially through reduction of oxidative and ER stress, iii) SGLT2 inhibitors revert/prevent ß-cell failure when used in early stages of diabetes, but not when loss of ß-cell mass/identity already occurred, iv) common execution pathways may underlie loss and recovery of ß-cell function in different forms of diabetes. These results may have important clinical implications for optimal therapeutic interventions in individuals with diabetes, particularly for those with long-standing diabetes.

Single-port Versus Multi-port Robotic-assisted Procedures From the Patient's Perspective: A Retrospective Cohort Study.

INTRODUCTION: The da Vinci SP® single-port system, differently from prior platforms, utilizes a single 2.5 cm incision to accommodate 1 flexible camera and 3 articulated robotic arms. Potential advantages include shorter hospitalization, improved cosmesis, and reduced postoperative pain. This project investigates the impact of the novel single-port system on cosmetic and psychometric patient assessment. METHODS: The Patient Scar Assessment Questionnaire (a validated patient-reported outcomes measure for surgical scar) has been administered retrospectively to patients who underwent either an SP or Xi® urological procedure at a single center. Four domains were assessed: Appearance, Consciousness, Satisfaction With Appearance, and Satisfaction With Symptoms. Higher scores represent worse reported outcomes. RESULTS: Compared to 78 Xi procedure recipients (mean 15.28), 104 SP procedure recipients (mean 13.84) reported significantly better cosmetic scar appearance U(NSP=104, NMP=78) = 3,739 (P = .007) where U is the difference between the 2 rank totals, and NSP and NMP represent the number of single-port and multi-port procedure recipient respondents, respectively. Similarly, the SP cohort (mean 8.80) compared to the Xi group (mean 9.87) demonstrated significantly better consciousness of their surgical scar, U(NSP=104, NMP=78) = 3,329 (P = .045), and higher satisfaction with the cosmetic appearance of their surgical scar, U(NSP=103, NMP=78) = 3,232 (P = .022), with the SP group (mean 11.35) attaining better scores than the Xi group (mean 12.54). No significant difference was found for "Satisfaction With Symptoms," U(NSP=103, NMP=78) = 3,969 (P = .88), despite the SP group (mean 6.58) attaining lower scores than the Xi group (mean 6.74). CONCLUSIONS: This study demonstrates patients' favorable perception of SP versus XI surgery in terms of aesthetic outcomes. An ongoing study is investigating the relationship between cosmetic satisfaction and length of stay, postoperative pain, and narcotic use.

Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.

Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals.

In vivo depletion of CD4(+)CD25(hi) regulatory T cells is associated with improved antiviral responses in cats chronically infected with feline immunodeficiency virus.

Regulatory T (Treg) cells are activated and suppress immune responses during infection, and are characterized as CD4(+)CD25(hi)FOXP3(+). Ex vivo studies demonstrate that Treg cells potentially suppress anti-HIV-1 T cell responses. Lentivirus-induced CD4(+)CD25(hi) Treg cells were first described in feline immunodeficiency virus (FIV)-infected cats. In the present study we demonstrate that anti-feline CD25 monoclonal antibody (mAb) therapy depletes Treg cells in FIV-infected cats for 4 weeks and does not exacerbate viral replication or proinflammatory cytokine production. Significant FIV-specific immune responses are revealed in Treg cell-depleted cats. These anti-FIV effector cells exist prior to Treg cell depletion and are not expanded while Treg cells are depleted. Importantly, cats receiving the Treg cell-depleting mAb are able to produce a robust humoral response to new antigen. We propose that short-term in vivo Treg cell depletion during chronic HIV-1 infection could provide a window of opportunity for therapeutic vaccination in individuals with controlled viral replication.

Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats.

BACKGROUND: The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL), therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses. RESULTS: Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL). Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia. CONCLUSIONS: Our results indicate that mucosal immune pathogenesis could be used as a rapid indicator of vaccine success or failure when combined with a physiologically relevant low dose mucosal challenge. We also show that innate immune responses may play an important role in controlling viral replication following acute mucosal infection, which has not been previously identified.

beta-Adrenergic receptor stimulated Ncx1 upregulation is mediated via a CaMKII/AP-1 signaling pathway in adult cardiomyocytes.

The Na(+)-Ca(2+) exchanger gene (Ncx1) is upregulated in hypertrophy and is often found elevated in end-stage heart failure. Studies have shown that the change in its expression contributes to contractile dysfunction. beta-Adrenergic receptor (beta-AR) signaling plays an important role in the regulation of calcium homeostasis in the cardiomyocyte, but chronic activation in periods of cardiac stress contributes to heart failure by mechanisms which include Ncx1 upregulation. Here, using a Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIdelta(c)) null mouse, we demonstrate that beta-AR-stimulated Ncx1 upregulation is dependent on CaMKII. beta-AR-stimulated Ncx1 expression is mediated by activator protein 1 (AP-1) factors and is independent of cAMP-response element-binding protein (CREB) activation. The MAP kinases (ERK1/2, JNK and p38) are not required for AP-1 factor activation. Chromatin immunoprecipitation demonstrates that beta-AR stimulation activates the ordered recruitment of JunB homodimers, which then are replaced by c-Jun homodimers binding to the proximal AP-1 elements of the endogenous Ncx1 promoter. In conclusion, this work has provided insight into the intracellular signaling pathways and transcription factors regulating Ncx1 gene expression in a chronically beta-AR-stimulated heart.

Safety and immunogenicity of the Mycobacterium tuberculosis DeltalysA DeltapanCD vaccine in domestic cats infected with feline immunodeficiency virus.

Feline immunodeficiency virus (FIV)-positive and FIV-negative cats (n=4/group) received 2 x 10(6) CFU Mycobacterium tuberculosis DeltalysA DeltapanCD intramuscularly. Vaccination elicited antibody responses, albeit at lower levels in FIV-positive cats than in FIV-negative cats. Delayed-type hypersensitivity responses were minimal in both groups. No adverse reactions were found.

The clinical response to brain death: a policy proposal.

The ethical and scientific literature reflects a certain amount of controversy and confusion surrounding the concept of death by neurological criteria, or brain death. The issues surrounding brain death occur with limited frequency for those working in acute critical care settings. Even so, the literature and our own experiences evidence the discomfort of caregivers and policymakers when dealing with brain-dead patients and their family and loved ones. One particular area in which there seems to be significant diversity of opinion is what should occur when death by neurological criteria is pronounced. At some hospitals, when the patient is pronounced dead by neurological criteria, the support equipment is removed from the body immediately and the body is prepared for visitation by family or is transported to the morgue. In other hospitals, support equipment is maintained for a certain limited period to allow the family to be present when the equipment is ultimately removed. In general, however, it appears that institutional guidelines and policy are vague, at best, or often silent about the issue of when, how, and, to some extent, who decides what is done with the body. This policy paper discusses the confusion of care providers as well as lay persons related to the general concepts of death by neurological criteria. In addition, alternative approaches to the withdrawal of support equipment are examined. This article may also allow nursing administrators to better understand the importance of establishing specific clinical guidelines for their staff related to patients declared dead by neurological criteria. Our conclusion is that a universal policy should be adopted whereby all institutions develop the same guidelines concerning when and how treatment modalities should be withdrawn on their brain-dead patients. Such policy guidelines may not extinguish the misconceptions, misunderstandings, and discomforts that are present with a diagnosis of brain death, but it would certainly allow for more consistent actions on the part of the caregivers. Consistency would substantially benefit caregivers, families, and society alike.

Comparing ethics education in medicine and law: combining the best of both worlds.

This article compares various models of ethics education and how these models are employed by both medical schools and law schools. The authors suggest ways in which each profession can enhance their ethical teaching and argue that ethics education in both medicine and law should combine the best elements of each education model, thereby producing graduates who are more knowledgeable and appreciative of ethical issues in practice.