Phosphodiesterase 4D inhibition improves the functional and molecular outcome in a mouse and human model of Charcot Marie Tooth disease 1 A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited peripheral neuropathy caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. It is primarily marked by Schwann cell dedifferentiation and demyelination, leading to motor and sensory deficits. Cyclic adenosine monophosphate (cAMP) is crucial for Schwann cell differentiation and maturation.

Therapeutic indications for HDAC6 inhibitors in the peripheral and central nervous disorders.

Introduction: Inhibition of the enzymatic function of HDAC6 is currently being explored in clinical trials ranging from peripheral neuropathies to cancers. Advances in selective HDAC6 inhibitor discovery allowed studying highly efficacious brain penetrant and peripheral restrictive compounds for treating PNS and CNS indications.

Areas Covered: This review explores the multifactorial role of HDAC6 in cells, the common pathological hallmarks of PNS and CNS disorders, and how HDAC6 modulates these mechanisms.

Analyzing the L4-5 Segmental Alignment Change of Two Minimally Invasive Prone-Based Interbody Fusions.

Study Design: Retrospective Cohort Study.

Objective: Restoration of lumbar lordosis (LL) is a principal objective during spinal fusion procedures, traditionally focusing on achieving an LL within 10° of the pelvic incidence (PI). Recent studies have demonstrated a relatively constant L4-S1 alignment of 35-40° at L4-S1 and at least 15° at L4-5, regardless of PI.

A Quality Improvement Project to Increase Infection Control Compliance Among Endoscopy Staff at a Large Urban Medical Center.

Although nurses and other healthcare professionals play a key role in preventing hospital-associated infections, studies show that infection control compliance rates have remained low. The purpose of this quality improvement project was to increase infection control compliance of hand hygiene and procedure room disinfection among endoscopy staff at a large urban medical center in Cincinnati, Ohio. This quality improvement project provided an education session on current evidence-based infection control guidelines to 20 participants, including registered nurses and technicians within the endoscopy department.

Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.

Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date.

Single-Position Prone Lateral Lumbar Interbody Fusion Technique Guide: Surgical Tips and Tricks.

Lateral lumbar interbody fusion (LLIF) is a popular technique as it allows for the placement of a large interbody implant through a retroperitoneal, transpsoas working corridor. Historically, the interbody is placed with the patient in lateral decubitus and then repositioned to prone for the posterior instrumentation. While this has been an effective and successful technique, removing the interoperative flip would improve the efficiency of these cases.

Implementation of a best-practice guideline: Early enteral nutrition in a neuroscience intensive care unit.

Current evidence suggests that early enteral nutrition is a best practice and leads to improved clinical outcomes. An evidence-based practice project was implemented in a busy neurointensive care unit in a midwestern tertiary care facility that was designed to improve care by implementing the early nutrition portion of Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine and the American Society for Enteral and Parenteral Nutrition. The Registered Nurses' Association of Ontario's (RNAO) Toolkit: Implementation of Best Practice Guidelines (BPGs) was selected and followed to guide implementation and achieve optimal results.

HDAC3 Inhibition Stimulates Myelination in a CMT1A Mouse Model.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy, with currently no effective treatment or cure. CMT1A is caused by a duplication of the PMP22 gene, which leads to Schwann cell differentiation defects and dysmyelination of the peripheral nerves. The epigenetic regulator histone deacetylase 3 (HDAC3) has been shown to negatively regulate myelination as well as its associated signaling pathways, PI3K-AKT and MAPK-ERK.

Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems.

Methods for highly multiplexed RNA imaging are limited in spatial resolution and thus in their ability to localize transcripts to nanoscale and subcellular compartments. We adapt expansion microscopy, which physically expands biological specimens, for long-read untargeted and targeted in situ RNA sequencing. We applied untargeted expansion sequencing (ExSeq) to the mouse brain, which yielded the readout of thousands of genes, including splice variants.

Quantification of cranberry proanthocyanidins by normal-phase high-performance liquid chromatography using relative response factors.

Introduction: American cranberries (Vaccinium macrocarpon) contain primarily A-type proanthocyanidins (PACs), which have been shown to prevent urinary tract infection. Currently, the accurate quantification of cranberry PACs is still lacking.

Objective: A normal-phase high-performance liquid chromatography (NP-HPLC) method using relative response factors was developed and validated to quantify cranberry PAC oligomers and polymers.

Conceptual Organization is Revealed by Consumer Activity Patterns.

Computational models using text corpora have proved useful in understanding the nature of language and human concepts. One appeal of this work is that text, such as from newspaper articles, should reflect human behaviour and conceptual organization outside the laboratory. However, texts do not directly reflect human activity, but instead serve a communicative function and are highly curated or edited to suit an audience.

Implementation of a clinical practice guideline in a primary care setting for the prevention and management of obesity in adults.

Over two-thirds of American adults have obesity or overweight, increasing the risk of comorbidities, mortality, and healthcare costs. Despite this growing issue, screening and counseling for an unhealthy weight are not common in primary care and clinical practice guidelines (CPGs) for prevention and management of obesity are underutilized. Following the stepwise approach outlined in the Registered Nurses' Association of Ontario Toolkit: Implementation of Best Practice Guidelines, the Institute for Clinical Systems Improvement: Prevention and Management of Obesity for Adults were implemented in a primary care office in Lexington, KY.

Computer algorithm compared with routine clinical practice in screening for deep venous thrombosis in the leg in an emergency department.

Objective: To audit routine clinical practice in screening patients admitted to an accident and emergency department for deep venous thrombosis in the leg (DVT) and compare it with a computer algorithm.

Design: Retrospective study of case notes with data subsequently entered into a computer algorithm followed by a comparison of the diagnosis and recommended management from each modality.

Setting: Emergency department at a London teaching hospital.

Assessment of Mortality and Smoking Rates Before and After Reduction in Community-wide Prevention Programs in Rural Maine.

Importance: It is unclear whether effective population-wide interventions that reduce risk factors and improve health result in sustained benefits to a community's health. If benefits do persist after a program is ended, interventions could be brief rather than maintained long term.

Objective: To measure mortality and smoking rates in a rural community over decades before, during, and after prevention program reductions.

HDAC6 as a potential therapeutic target for peripheral nerve disorders.

Peripheral neuropathies are a heterogeneous group of diseases that are characterized by a progressive, ascending loss of nerve function arising from the peripheral regions of the limbs. The phenotypic overlap between different types of hereditary and acquired peripheral neuropathies indicates that similar pathophysiological processes are at play. Many downstream pathways in peripheral neurons, such as axonal transport, protein degradation, and interactions with Schwann cells, organelle damage, channelopathies, and neuroinflammatory signaling, have been proposed and each affects peripheral nerves in a negative way.

Prevention of Atherosclerosis by Berries: The Case of Blueberries.

Berry consumption has been associated with cardiovascular disease prevention in recent years. Atherosclerosis is one of the major causes of cardiovascular diseases. However, research on the prevention of atherosclerosis through consuming individual whole berries, specifically direct evidence, remains scarce.

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration.

Assessing the functionality of the nerve axon provides detailed information on the progression of neuromuscular disorders. Electrophysiological recordings provide a sensitive approach to measure nerve conduction in humans and rodent models. To broaden the technical possibilities for electromyography in mice, the measurement of compound muscle action potentials (CMAPs) from the brachial plexus nerve in the forelimb using needle electrodes is described here.

HDAC6 is a therapeutic target in mutant GARS-induced Charcot-Marie-Tooth disease.

Peripheral nerve axons require a well-organized axonal microtubule network for efficient transport to ensure the constant crosstalk between soma and synapse. Mutations in more than 80 different genes cause Charcot-Marie-Tooth disease, which is the most common inherited disorder affecting peripheral nerves. This genetic heterogeneity has hampered the development of therapeutics for Charcot-Marie-Tooth disease.

Current Advances and Limitations in Modeling ALS/FTD in a Dish Using Induced Pluripotent Stem Cells.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two age-dependent multifactorial neurodegenerative disorders, which are typically characterized by the selective death of motor neurons and cerebral cortex neurons, respectively. These two diseases share many clinical, genetic and pathological aspects. During the past decade, cell reprogramming technologies enabled researchers to generate human induced pluripotent stem cells (iPSCs) from somatic cells.

Single-Laboratory Validation for Determination of Total Soluble Proanthocyanidins in Cranberry Using 4-Dimethylaminocinnamaldehyde.

American cranberry (Vaccinium macrocarpon) is native to Eastern North America. Recent studies have suggested that the A-type proanthocyanidins (PACs) in cranberries are effective in preventing urinary tract infection. To meet the growing interest in the cranberry market, an accurate, reliable, and simple method to determine PAC concentration is needed.

Stabilization of anthocyanins in blackberry juice by glutathione fortification.

Blackberry anthocyanins provide attractive color and antioxidant activity. However, anthocyanins degrade during juice processing and storage, so maintaining high anthocyanin concentrations in berry juices may lead to greater antioxidant and health benefits for the consumer. This study evaluated potential additives to stabilize anthocyanins during blackberry juice storage.

Impact of three different fungicides on fungal epi- and endophytic communities of common bean (Phaseolus vulgaris) and broad bean (Vicia faba).

In this study, the impacts of three different fungicides to fungal phyllosphere communities on broad bean (Vicia faba, Fabaceae) and common bean (Phaseolus vulgaris, Fabaceae) were analyzed. The fungicides included copper, sulfur, and azoxystrobin. The plants were sowed, grown, and treated under conditions occurring in conventional and organic farming.