A novel minimally invasive neurosurgical cranial fixation device for improved accuracy of intraventricular catheter placement: an experimental animal study.

Background: External ventricular drain (EVD) insertion is one of the most commonly performed neurosurgical procedures. Herein, we introduce a new concept of a cranial fixation device for insertion of EVDs, that reduces reliance on freehand placement and drilling techniques and provides a simple, minimally invasive approach that provides strong fixation to minimal thickness skulls.

Methods: An experimental device for catheter insertion and fixation was designed and tested in both ex-vivo and in-vivo conditions to assess accurate cannulation of the ventricle and to test the strength of fixation to the skull.

Banana fruit (Musa sp.) DNA-magnetite nanoparticles: Synthesis, characterization, and biocompatibility assays on normal and cancerous cells.

Magnet-mediated gene therapy has gained considerable interest from researchers as a novel alternative for treating genetic disorders, particularly through the use of superparamagnetic iron oxide nanoparticles (NPs)-such as magnetite NPs (Fe3O4NPs)-as non-viral genetic vectors. Despite their commercial availability for specific genetic transfection, such as in microglia cell lines, many potential uses remain unexplored. Still, ethical concerns surrounding the use of human DNA often impede genetic research.

Excitotoxic spinal damage induced by kainic acid impairs locomotion, alters nociception, and reduces CREB nuclear translocation.

Our previous in vitro studies showed that excitotoxicity evoked by glutamate analogue kainate (KA) significantly decreased the number of rat spinal neurons and triggered high release of glutamate leading to locomotor network block. Our current objective was to assess the role of CREB as a predictive marker of damage following chemically-induced spinal cord injury by using in vivo and in vitro models. Thus, in vivo excitotoxicity in Balb/c adult mice was induced by KA intraspinal injection, while in vitro spinal cord excitotoxicity was produced by bath-applied KA.

Chemotherapy-induced neuropathy and pain in pediatric oncology patients: impact of combination therapies.

Unlabelled: Chemotherapy-induced peripheral neuropathy (CIPN) and associated pain are prevalent adverse effects of pediatric cancer treatment, significantly affecting the patient's quality of life. Their impact and risk factors have yet to be assessed in our country. This study aimed to assess the prevalence and clinical characteristics of CIPN, as well as to explore associations with patient- and treatment-related variables, within a cohort of Argentinean pediatric oncology patients.

Unlocking Transplant Tolerance with Biomaterials.

For patients suffering from organ failure due to injury or autoimmune disease, allogeneic organ transplantation with chronic immunosuppression is considered the god standard in terms of clinical treatment. However, the true "holy grail" of transplant immunology is operational tolerance, in which the recipient exhibits a sustained lack of alloreactivity toward unencountered antigen presented by the donor graft. This outcome is resultant from critical changes to the phenotype and genotype of the immune repertoire predicated by the activation of specific signaling pathways responsive to soluble and mechanosensitive cues.

Resveratrol evokes neuroprotective effects and improves foot stance following kainate-induced excitotoxic damage to the mouse spinal cord.

Excitotoxicity, characterized by over-activation of glutamate receptors, is a major contributor to spinal cord injury (SCI) pathophysiology, resulting in neuronal death and loss of locomotor function. In our previous in vitro studies, we showed that excitotoxicity induced by the glutamate analogue kainate (KA) leads to a significant reduction in the number of neurons, providing a model for SCI. Our current objective was to assess the neuroprotective role of resveratrol (RESV), a natural polyphenol, following KA-induced SCI.

Bending the Rules: Amplifying PD-L1 Immunoregulatory Function Through Flexible Polyethylene Glycol Synthetic Linkers.

Immune checkpoint signaling, such as programmed cell death protein-1 (PD-1), is a key target for immunotherapy due to its role in dampening immune responses. PD-1 signaling in T cells is regulated by complex physicochemical and mechanical cues. However, how these mechanical forces are integrated with biochemical responses remains poorly understood.

VEGF-delivering PEG hydrogels promote vascularization in the porcine subcutaneous space.

For cell therapies, the subcutaneous space is an attractive transplant site due to its large surface area and accessibility for implantation, monitoring, biopsy, and retrieval. However, its poor vascularization has catalyzed research to induce blood vessel formation within the site to enhance cell revascularization and survival. Most studies focus on the subcutaneous space of rodents, which does not recapitulate important anatomical features and vascularization responses of humans.

An Optimal Integral Controller for Adaptive Optics Systems.

Integral controllers are commonly employed in astronomical adaptive optics. This work presents a novel tuning procedure for integral controllers in adaptive optics systems which relies on information about the measured disturbances. This tuning procedure consists of two main steps.

Delayed graft rejection in autoimmune islet transplantation via biomaterial immunotherapy.

The induction of operational immune tolerance is a major goal in beta-cell replacement strategies for the treatment of type 1 diabetes. Our group previously reported long-term efficacy via biomaterial-mediated programmed death ligand 1 (PD-L1) immunotherapy in islet allografts in nonautoimmune models. In this study, we evaluated autoimmune recurrence and allograft rejection during islet transplantation in spontaneous nonobese diabetic (NOD) mice.

Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates.

The transplanting islets to the liver approach suffers from an immediate posttransplant loss of islets of more than 50%, progressive graft dysfunction over time, and precludes recovery of grafts should there be serious complications such as the development of teratomas with grafts that are stem cell-derived islets (SC-islets). The omentum features an attractive extrahepatic alternative site for clinical islet transplantation. We explore an approach in which allogeneic islets are transplanted onto the omentum, which is bioengineered with a plasma-thrombin biodegradable matrix in three diabetic non-human primates (NHPs).

Modulation of the Inflammatory Response by Pre-emptive Administration of IMT504 Reduces Postoperative Pain in Rats and has Opioid-Sparing Effects.

Despite the available knowledge on underlying mechanisms and the development of several therapeutic strategies, optimal management of postoperative pain remains challenging. This preclinical study hypothesizes that, by promoting an anti-inflammatory scenario, pre-emptive administration of IMT504, a noncoding, non-CpG oligodeoxynucleotide with immune modulating properties, will reduce postincisional pain, also facilitating therapeutic opioid-sparing. Male adult Sprague-Dawley rats with unilateral hindpaw skin-muscle incision received pre-emptive (48 and 24 hours prior to surgery) or postoperative (6 hours after surgery) subcutaneous vehicle (saline) or IMT504.

Risk stratification, prognosis, and survival in a pulmonary arterial hypertension cohort in Latin America. A multicenter study.

Background: Pulmonary arterial hypertension (PAH) guidelines suggest that achieving a low-risk profile should be the treatment goal. Our aim was to assess a risk assessment strategy based on three non-invasive variables from the ESC/ERS 2015 guidelines in a Latin American cohort.

Methods: 92 incident patients (mean [SD] age 47, 77% female, 53% idiopathic PAH) were included in this retrospective, multicenter study.

An update to pain management after spinal cord injury: from pharmacology to circRNAs.

Neuropathic pain (NP) following a spinal cord injury (SCI) is often hard to control and therapies should be focused on the physical, psychological, behavioral, social, and environmental factors that may contribute to chronic sensory symptoms. Novel therapeutic treatments for NP management should be based on the combination of pharmacological and nonpharmacological options. Some of them are addressed in this review with a focus on mechanisms and novel treatments.

Changes in the expression of endocannabinoid system components in an experimental model of chemotherapy-induced peripheral neuropathic pain: Evaluation of sex-related differences.

Chemotherapy-induced neuropathic pain is a serious clinical problem and one of the major side effects in cancer treatment. The endocannabinoid system (ECS) plays a crucial role in regulating pain neurotransmission, and changes in the expression of different components of the ECS have been reported in experimental models of persistent pain. In addition, sex differences have been observed in ECS regulation and function.

Sex-related differences in oxaliplatin-induced changes in the expression of transient receptor potential channels and their contribution to cold hypersensitivity.

Transient receptor potential (TRP) channels are involved in the development of oxaliplatin-induced neuropathic pain, a frequent and debilitating side effect of cancer therapy. Here we explored whether oxaliplatin-induced changes in the expression of TRP channels, as well as the development of pain-related behaviours, differed between male and female animals. Adult rats were injected with oxaliplatin or saline and mechanical and cold allodynia were evaluated using Von Frey and Choi Tests.

A hydrogel platform for co-delivery of immunomodulatory proteins for pancreatic islet allografts.

Type 1 diabetes (T1D), an autoimmune disorder in which the insulin-producing β-cells in the islets of Langerhans in the pancreas are destroyed, afflicts over 1.6 million Americans. Although pancreatic islet transplantation has shown promise in treating T1D, continuous use of required immunosuppression regimens limits clinical islet transplantation as it poses significant adverse effects on graft recipients and does not achieve consistent long-term graft survival with 50%-70% of recipients maintaining insulin independence at 5 years.

The conundrum in endoscopic management of duodenal polyps: a tertiary cancer center experience.

Background: Endoscopic mucosal resection of duodenal polyps (EMR) is a challenging intervention. The aim of this study was to review the patient characteristics, techniques, procedure outcomes, adverse events, and recurrence of duodenal polyps.

Research Design And Methods: Patients were included if they had pathologically confirmed non-ampullary duodenal polyps and had received EMR with at least one follow-up EGD for surveillance.

Full-thickness resection: troubleshooting, tips, and tricks for success in the colorectum.

Video 1Difficult scenarios encountered during colorectal full thickness resection and their management: (1) Inability to advance device to target lesion; (2) injury to extraluminal structures; (3) anal trauma; (4) anal stenosis; (5) luminal edema after resection; (6) difficulty in grasping lesion; (7) recommendation for "mini time-out"; (8) Summary.

Host type 2 immune response to xenogeneic serum components impairs biomaterial-directed osteo-regenerative therapies.

The transformative potential of cells as therapeutic agents is being realized in a wide range of applications, from regenerative medicine to cancer therapy to autoimmune disorders. The majority of these therapies require ex vivo expansion of the cellular product, often utilizing fetal bovine serum (FBS) in the culture media. However, the impact of residual FBS on immune responses to cell therapies and the resulting cell therapy outcomes remains unclear.

FasL microgels induce immune acceptance of islet allografts in nonhuman primates.

Islet transplantation to treat insulin-dependent diabetes is greatly limited by the need for maintenance immunosuppression. We report a strategy through which cotransplantation of allogeneic islets and streptavidin (SA)-FasL-presenting microgels to the omentum under transient rapamycin monotherapy resulted in robust glycemic control, sustained C-peptide levels, and graft survival in diabetic nonhuman primates for >6 months. Surgical extraction of the graft resulted in prompt hyperglycemia.

Hydrolytically Degradable Microgels with Tunable Mechanical Properties Modulate the Host Immune Response.

Hydrogel microparticles (microgels) are an attractive approach for therapeutic delivery because of their modularity, injectability, and enhanced integration with the host tissue. Multiple microgel fabrication strategies and chemistries have been implemented, yet manipulation of microgel degradability and its effect on in vivo tissue responses remains underexplored. Here, the authors report a facile method to synthesize microgels crosslinked with ester-containing junctions to afford tunable degradation kinetics.

How much progress have we made?: a 20-year experience regarding esophageal stents for the palliation of malignant dysphagia.

Esophageal stents are widely used for the palliation of malignant esophageal obstruction. Advances in technology have made esophageal stenting technically feasible and widespread for such obstruction, but complications remain frequent. We present outcomes of a large cohort undergoing esophageal stent placement for malignant esophageal obstruction at a tertiary care cancer center.