Morphology of peripheral nerves, their sheaths, and their vascularization

This review aims to update our understanding of peripheral nerves, including the nature and function of their sheaths and, finally, their vascularization. The peripheral nervous system is made up of nerves whose function is to gather stimuli from the periphery as well as to transport the motor, secretory or vegetative responses that are triggered to the periphery. The connective tissue surrounding peripheral nerves all along their extension is made up of endoneurial, perineurial and epineurial. The endoneurium surrounds individual axons, which are grouped in fasciculi, each of which is surrounded by the perineurium and finally, the group of fasciculi that comprise all the axons present in this nerve are surrounded by the epineurium. Axons form an intraneural plexus such that they occupy positions in the various fasciculi along the trajectory of the plexus. The number and size of fasciculi vary along the trajectory of a nerve as a result of the plexus positioning of the axons. Peripheral nerves are richly vascularized throughout their length, with multiple anastomoses forming the intraneural vascular network, which is made up mainly of arterioles, capillaries, postcapillary venules and venules. Regarding the blood-nerve barrier and the existence of capillary permeability: endoneural capillaries have junctions that are stronger than those of the endothelial cells of vessels in the epineurium and perineurium. Two distinct lymph channels networks are present in the peripheral nerve stems and are separated by the perineural barrier. The nervi-nervorum are special nerves of a sympathetic and sensory nature that arise from the nerve itself and the perivascular plexuses.     

Mechanistic Insight into Sonoporation with Ultrasound-Stimulated Polymer Microbubbles

Sonoporation is emerging as a feasible, non-viral gene delivery platform for the treatment of cardiovascular disease and cancer. Despite promising results, this approach remains less efficient than viral methods. The objective of this work is to help substantiate the merit of polymeric microbubble sonoporation as a non-viral, localized cell permeation and payload delivery strategy by taking a ground-up approach to elucidating the fundamental mechanisms at play. In this study, we apply simultaneous microscopy of polymeric microbubble sonoporation over its intrinsic biophysical timescales–with sub-microsecond resolution to examine microbubble cavitation and millisecond resolution over several minutes to examine local macromolecule uptake through enhanced endothelial cell membrane permeability–bridging over six orders of magnitude in time. We quantified microbubble behavior and resulting sonoporation thresholds at transmit frequencies of 0.5, 1 and 2 MHz, and determined that sonic cracking is a necessary but insufficient condition to induce sonoporation. Further, sonoporation propensity increases with the extent of sonic cracking, namely, from partial to complete gas escape from the polymeric encapsulation. For the subset that exhibited complete gas escape from sonic cracking, a proportional relationship between the maximum projected gas area and resulting macromolecule uptake was observed. These results have revealed one aspect of polymeric bubble activity on the microsecond time scale that is associated with eliciting sonoporation in adjacent endothelial cells, and contributes toward an understanding of the physical rationale for sonoporation with polymer-encapsulated microbubble contrast agents.     

Outcomes of Donation After Circulatory Death Heart Transplantation in Australia

Background

Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice.

Is Robotic Revisional Bariatric Surgery Justified? An MBSAQIP Analysis

Background

The laparoscopic approach is utilized in greater than 90% of bariatric surgeries. With the growing prevalence of robotic-assisted surgery in bariatrics, there has been limited consensus on the superiority of either laparoscopic or robotic approaches, especially in revisional procedures (conversion from sleeve gastrectomy (SG) to Roux-en-Y gastric bypass (RYGB)).

Methods

A retrospective analysis was performed of the MBSAQIP PUF database of patients who underwent conversion from SG to RYGB procedures in either laparoscopic or robotic-assisted approaches. The groups underwent 2:1 propensity matching and primary outcomes included post-conversion days until discharge (POD), conversion operation length, total and major morbidity, 30-day readmission, 30-day reoperation, 30-day reintervention, and 30-day mortality after conversion.

Results

After 2:1 propensity score matching, 3411 patients (2274 laparoscopic vs 1137 robotic) were included in the study. Intraoperatively, no significant difference was found in total morbidity (6.5% lap vs 5.9% robotic) or major morbidity (1.9% lap vs 1.7% robotic); however, the operative times were significantly longer robotically (126 min vs 164 min). Post-operatively, no significant differences were found in discharge day (1.8 lap vs 1.8 robotic), 30-day readmission (7.6% lap vs 8.6% robotic), reoperation rate (2.9% lap vs 3.7% robotic), additional intervention rate (2.5% lap vs 3.3% robotic), or 30-day mortality (0.1% vs 0.1%).

Conclusion

There is no significant difference in perioperative or intraoperative outcomes between laparoscopic and robotic-assisted SG to RYGB conversion procedures other than a longer operative time in the robotic approach, suggesting increased efficiency with the laparoscopic approach.

Graphical abstract

     

Alcohol Modulation of Human Normal T-Cell Activation, Maturation, and Migration

We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4⁺ cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and 0-endor-phin pretreatment on the activation of CD4⁺ lymphocytes endowed with the homing receptor CD62L.     

Induction and treatment of anergy in murine leprosy

Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial‐specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG‐inoculated and MLM‐inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell‐mediated immune response (CMI) that was temporary in the MLM‐inoculated group and long‐lasting in the BCG‐inoculated group. DLE were prepared from the spleens of MLM‐ and BCG‐inoculated mice at the peak of CMI. Independent MLM intradermally‐inoculated groups were treated every other day with HLT‐DLE, BCG‐DLE or MLM‐DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 10⁶ splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy.     

Pulmonary mass and multiple lung nodules mimicking a lung neoplasm as amiodarone-induced pulmonary toxicity

Amiodarone is an effective anti-arrhythmic agent. However, during long-term therapy, patients can develop severe adverse pulmonary reactions that are potentially life-threatening. A case of amiodarone-induced pulmonary toxicity is presented in a 78-year-old woman. She developed dyspnea and a pulmonary mass with associated multiple lung nodules mimicking a lung cancer following 5 years of treatment with amiodarone for atrial fibrillation. After drug withdrawal, and without any additional treatment, clinical and radiological improvement was observed, and radiological findings resolved completely within 6 months.