Porcine acellular dermal matrix (PADM) vascularises after exposure in open necrotic wounds seen after complex hernia repair.

Biological alternatives to synthetic meshes are increasingly utilised in complex abdominal wall reconstruction. There is a lack of evidence demonstrating that non-cross-linked porcine acellular dermal matrix vascularizes and integrates with human tissue in suboptimal wound conditions. We aimed to evaluate these properties in Strattice™ (Life Cell Inc., Branchburg, NJ) following ventral hernia repair. A retrospective review of patients with high-risk ventral hernia repair utilising Strattice™ as an onlay after open component separation was conducted. Patients with postoperative wound exploration and exposure of the onlay were included in this review. One patient underwent punch biopsy for histological analysis. Eleven patients with wound complications necessitating postoperative debridement and exposure of Strattice™ onlay were identified. The onlay was partially debrided in two cases, and one case required complete excision. Vascularisation was clinically evident in 10 of 11 cases (91%) as demonstrated by the presence of granulation tissue and/or the ability to support a skin graft. Histological analysis of one onlay 3 months postoperatively showed neovascularisation and collagen remodelling with minimal inflammatory response. Strattice™ demonstrated resistance to rejection, ability to undergo vascularisation and incorporation into host tissues in sub-optimal wound conditions following ventral hernia repair.

The impact of guided versus supportive coaching on mental health app engagement and clinical outcomes.

Although mobile mental health apps have the unique potential to increase access to care, evidence reveals engagement is low unless coupled with coaching. However, most coaching protocols are limited in their scalability. This study assesses how human support and guidance from a Digital Navigator (DN), a scalable coach, can impact mental health app engagement and effectiveness on anxiety and depressive symptoms. This study aims to detach components of coaching, specifically personalized recommendations versus general support, to inform scalability of coaching models for mental health apps. 156 participants were split into the DN Guide versus DN Support groups for the 6-week study. Both groups utilized the mindLAMP app for the duration of the study and had equal time with the DN, but the Guide group received personalized app recommendations. The Guide group completed significantly more activities than the Support group. 34% (49/139) of all participants saw a 25% decrease in PHQ-9 scores and 38% (53/141) saw a 25% decrease in GAD-7 scores. These findings show mental health apps, especially when supported by DNs, can reduce depression and anxiety symptoms when coupled with coaching, suggesting a feasible path for large-scale deployment.

Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC.

INTRODUCTION: In KRAS-mutant NSCLC, co-occurring alterations in LKB1 confer a negative prognosis compared with other mutations such as TP53. LKB1 is a tumor suppressor that coordinates several signaling pathways in response to energetic stress. Our recent work on pharmacologic and genetic inhibition of histone deacetylase 6 (HDAC6) revealed the impaired activity of numerous enzymes involved in glycolysis. On the basis of these previous findings, we explored the therapeutic window for HDAC6 inhibition in metabolically-active KRAS-mutant lung tumors. METHODS: Using cell lines derived from mouse autochthonous tumors bearing the KRAS/LKB1 (KL) and KRAS/TP53 mutant genotypes to control for confounding germline and somatic mutations in human models, we characterize the metabolic phenotypes at baseline and in response to HDAC6 inhibition. The impact of HDAC6 inhibition was measured on cancer cell growth in vitro and on tumor growth in vivo. RESULTS: Surprisingly, KL-mutant cells revealed reduced levels of redox-sensitive cofactors at baseline. This is associated with increased sensitivity to pharmacologic HDAC6 inhibition with ACY-1215 and blunted ability to increase compensatory metabolism and buffer oxidative stress. Seeking synergistic metabolic combination treatments, we found enhanced cell killing and antitumor efficacy with glutaminase inhibition in KL lung cancer models in vitro and in vivo. CONCLUSIONS: Exploring the differential metabolism of KL and KRAS/TP53-mutant NSCLC, we identified decreased metabolic reserve in KL-mutant tumors. HDAC6 inhibition exploited a therapeutic window in KL NSCLC on the basis of a diminished ability to compensate for impaired glycolysis, nominating a novel strategy for the treatment of KRAS-mutant NSCLC with co-occurring LKB1 mutations.

Inhibiting GLUTtony in cancer.

In this issue of Cell Chemical Biology, Olszewski et al. (2022) address the challenge of developing small molecules to inhibit glucose uptake in cancer. They characterize a novel pan-GLUT inhibitor that suppresses tumor growth and uncover how cancer cells can adapt to glucose restriction.

Dexamethasone implant migration in an eye with congenital glaucoma: A case report and review of the literature.

INTRODUCTION: The dexamethasone (DEX) implant is an FDA approved treatment for diabetic macular edema, non-infectious posterior uveitis, and macular edema secondary to branch or central retinal vein occlusions. We describe a case of anterior chamber (AC) migration of a DEX implant in a patient with a history of congenital glaucoma and perform a review of the literature on this particular complication, summarizing the common risk factors, subsequent complications, and management options. CASE DESCRIPTION: A 46-year-old female with a history of congenital glaucoma, status post cataract extraction with insertion of intraocular lens, pars plana vitrectomy, and Baerveldt tube implant in the left eye was referred for post-operative cystoid macular edema (CME). The patient underwent insertion of a DEX implant, resulting in improvement in her CME. After the fourth implant was injected, the patient noticed a white line in her eye while looking in the mirror after doing jumping jacks. Slit lamp examination confirmed migration of the implant into the AC. Ultimately, the patient was taken to the operating room, where her implant was removed via bimanual vitrectomy through an anterior approach. CONCLUSION: This case report and literature review explores the ophthalmic structural changes specific to congenital glaucoma which may have predisposed this eye to anterior migration of the DEX implant. The purpose of this review is to detail the anatomic changes that may increase the risk of anterior chamber implant migration in patients with congenital glaucoma so that physicians may be aware of these risks when selecting patients for this implant.

Equine-related eye injury: a case report of globe rupture and vision loss in a post-stroke hippotherapy patient.

INTRODUCTION: Hippotherapy has recently emerged as a horse-based rehabilitative therapy to improve balance, coordination, and strength in patients with a wide range of medical conditions. Although several studies have demonstrated its effectiveness in restoring balance and gait in patients who have suffered cerebrovascular accidents (CVA), few studies have reported on adverse events associated with the treatment. CASE PRESENTATION: This case report describes a female post-stroke patient who fell from a horse during a hippotherapy session. She suffered a closed right zygomaticomaxillary complex fracture and ruptured globe injury. The patient's orbital injuries were surgically repaired, yet ultimately left her with no light perception in the affected eye and required enucleation. CONCLUSION: Ocular and orbital injuries following hippotherapy are potentially blinding yet preventable. As such, practitioners should weigh the risks and benefits of hippotherapy, particularly in patients with unstable gait, and advise that additional safety precautions are taken to avoid these devastating injuries.

Different Neuronal Activity Patterns Induce Different Gene Expression Programs.

A vast number of different neuronal activity patterns could each induce a different set of activity-regulated genes. Mapping this coupling between activity pattern and gene induction would allow inference of a neuron's activity-pattern history from its gene expression and improve our understanding of activity-pattern-dependent synaptic plasticity. In genome-scale experiments comparing brief and sustained activity patterns, we reveal that activity-duration history can be inferred from gene expression profiles. Brief activity selectively induces a small subset of the activity-regulated gene program that corresponds to the first of three temporal waves of genes induced by sustained activity. Induction of these first-wave genes is mechanistically distinct from that of the later waves because it requires MAPK/ERK signaling but does not require de novo translation. Thus, the same mechanisms that establish the multi-wave temporal structure of gene induction also enable different gene sets to be induced by different activity durations.