Riluzole attenuates acute neural injury and reactive gliosis, hippocampal-dependent cognitive impairments and spontaneous recurrent generalized seizures in a rat model of temporal lobe epilepsy.

Background: Riluzole exhibits neuroprotective and therapeutic effects in several neurological disease models associated with excessive synaptic glutamate (Glu) release. We recently showed riluzole prevents acute excitotoxic hippocampal neural injury at 3 days in the kainic acid (KA) model of temporal lobe epilepsy (TLE). Currently, it is unknown if preventing acute neural injury and the neuroinflammatory response is sufficient to suppress epileptogenesis.

An in vitro study of orthodontic brackets bonded to transition dental zirconia: Shear bond strength, adhesive remnant index, and surface irregularities.

Purpose: Orthodontic treatment often involves bonding brackets to teeth, and the protocols for natural enamel differ from those for prosthodontically restored teeth. With the rising number of adult orthodontic patients, many present with zirconia crowns. This study aimed to evaluate the shear bond strength (SBS) of ceramic orthodontic brackets bonded to transition dental zirconia, which combines 3Y-TZP and 5Y-TZP powders.

Trends in Phototherapy Utilization, Payments, and Geographic Distribution: An Analysis of United States Medicare Part B From 2000 to 2021.

Background: Trends in phototherapy utilization in the context of new therapeutics have not been evaluated.

Objective: This study aimed to evaluate phototherapy utilization, payments, and geographic distribution for Medicare beneficiaries from 2000 to 2021.

Patients/methods: A longitudinal analysis of the Medicare Part B National Summary Data Files was conducted to obtain phototherapy utilization and payment amounts.

The Role of Glucagon-Like Peptide-1 Agonists in the Treatment of Multiple Sclerosis: A Narrative Review.

Multiple sclerosis (MS) is a chronic, progressive autoimmune disease modulated by autoantibodies that inflame and destroy the myelin sheath encasing neuronal axons, impairing proper axonal conduction and function. Glucagon-like peptide-1 (GLP-1) receptor agonists have been demonstrated to exert anti-inflammatory and neuroprotective effects, making these drugs particularly exciting prospects in the treatment of MS. While the exact mechanism remains unclear, GLP-1 receptor agonists may modulate inflammatory responses by targeting GLP-1 receptors present on immune cells such as macrophages, monocytes, and lymphocytes.

Emerging Treatments and Therapies for Autism Spectrum Disorder: A Narrative Review.

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity.

Differential effect of an evolving amyloid and tau pathology on brain phospholipids and bioactive lipid mediators in rat models of Alzheimer-like pathology.

Background: Brain inflammation contributes significantly to the pathophysiology of Alzheimer's disease, and it is manifested by glial cell activation, increased production of cytokines/chemokines, and a shift in lipid mediators from a pro-homeostatic to a pro-inflammatory profile. However, whether the production of bioactive lipid mediators is affected at earlier stages, prior to the deposition of Aβ plaques and tau hyperphosphorylation, is unknown. The differential contribution of an evolving amyloid and tau pathology on the composition and abundance of membrane phospholipids and bioactive lipid mediators also remains unresolved.

Immediate implant placement in extraction sockets with buccal bone dehiscence: A case study.

Background: Immediate implant placement (IIP) has been associated with a higher risk of esthetic complications and particularly buccal mucosal recession, which can be more pronounced in non-intact sockets or in the presence of thin phenotype in the esthetic zone. Nevertheless, multiple techniques have been published to address IIP in non-intact alveolar sockets with favorable outcomes. The purpose of this study is to present an approach on IIP in sites with buccal bone dehiscence.

In vitro comparison of zinc-based, chlorhexidine, and essential oil mouth rinses.

Background: Chlorhexidine (CHX)-based mouth rinses are frequently prescribed following periodontal surgeries. A more recently available brand of zinc-based mouth rinses advertises one of its mouth rinses as a substitute for chlorhexidine. The purpose of this study was to evaluate, in vitro, the effects of this brand of zinc-based mouth rinses on cell survival, cell motility, and gene expression of human gingival fibroblasts (HGFs).

Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region.

Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids' addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses.

Clinical Considerations and Outcomes of Robotic Urologic Surgery in Obese Patients.

Obesity is associated with many significant physiological changes. These considerations are important to surgery, especially in urological procedures. Obese patients often undergo surgical procedures and are at higher risk of complications.

Chest Tube Size Selection: Evaluating Provider Practices, Treatment Efficacy, and Complications in Management of Thoracic Trauma.

Background: The standard for managing traumatic pneumothorax (PTX), hemothorax (HTX), and hemopneumothorax (HPTX) has historically been large-bore (LB) chest tubes (>20-Fr). Previous studies have shown equal efficacy of small-bore (SB) chest tubes (≤19-Fr) in draining PTX and HTX/HPTX. This study aimed to evaluate provider practice patterns, treatment efficacy, and complications related to the selection of chest tube sizes for patients with thoracic trauma.

Bactericidal Efficacy of the Combination of Maresin-like Proresolving Mediators and Carbenicillin Action on Biofilm-Forming Burn Trauma Infection-Related Bacteria.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes.

Nonhormonal Pharmacotherapies for the Treatment of Postmenopausal Vasomotor Symptoms.

An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset. However, despite increasing prevalence, these hot flashes remain hard to treat and have a negative effect on the quality of life. Though hormone replacement therapy is commonly utilized as a standard treatment for VMSs, this therapy is not recommended for all women.

Adherence Rate to Alliance for Clinical Trials in Oncology Z0011 Trial Based on Breast Cancer Subtype.

Background: The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011 or Z11) trial demonstrated no survival advantage with completion axillary lymph node dissection (ALND) for patients with T1-2 breast cancer, 1 to 2 positive SLNs who received adjuvant chemoradiation therapy. More than 70% of the cohort had estrogen receptor (ER)+ tumors. There is paucity of data on the adherence rate to Z11, as well as a dearth of data on the applicability of Z11 for the different subtypes.

Ca-regulated expression of high affinity methylaminoisobutryic acid transport in hippocampal neurons inhibited by riluzole and novel neuroprotective aminothiazoles.

High affinity methylaminoisobutyric acid(MeAIB)/glutamine(Gln) transport activity regulated by neuronal firing occurs at the plasma membrane in mature rat hippocampal neuron-enriched cultures. Spontaneous Ca-regulated transport activity was similarly inhibited by riluzole, a benzothiazole anticonvulsant agent, and by novel naphthalenyl substituted aminothiazole derivatives such as SKA-378. Here, we report that spontaneous transport activity is stimulated by 4-aminopyridine (4-AP) and that phorbol-myristate acetate (PMA) increases high K stimulated transport activity that is inhibited by staurosporine.

Elovanoid-N34 modulates TXNRD1 key in protection against oxidative stress-related diseases.

The thioredoxin (TXN) system is an NADPH + H/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34.

Awakening neural survival mechanisms after stroke: Lipid metabolism in brain-autonomous repair.

In this issue of Neuron, Nakamura et al. report the discovery that neuronally secreted phospholipase PLA2G2E releases dihomo-γ-linolenic acid (DGLA) that generates 15-hydroxy-eicosatrienoic acid (15-HETrE), which in turn induces peptidyl arginine deiminase 4 (PAD4/PADI4) to elicit neuronal pro-survival and pro-reparative events following ischemic brain injury.

Integrated inflammatory signaling landscape response after delivering Elovanoid free-fatty-acid precursors leading to experimental stroke neuroprotection.

Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood-brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6.

Rod-specific downregulation of omega-3 very-long-chain polyunsaturated fatty acid pathway in age-related macular degeneration.

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging.

Advances in Metabolic Engineering of Plant Monoterpene Indole Alkaloids.

Monoterpene indole alkaloids (MIAs) encompass a diverse family of over 3000 plant natural products with a wide range of medical applications. Further utilizations of these compounds, however, are hampered due to low levels of abundance in their natural sources, causing difficult isolation and complex multi-steps in uneconomical chemical syntheses. Metabolic engineering of MIA biosynthesis in heterologous hosts is attractive, particularly for increasing the yield of natural products of interest and expanding their chemical diversity.

aBnormal motION capture In aCute Stroke (BIONICS): A Low-Cost Tele-Evaluation Tool for Automated Assessment of Upper Extremity Function in Stroke Patients.

Background: The incidence of stroke and stroke-related hemiparesis has been steadily increasing and is projected to become a serious social, financial, and physical burden on the aging population. Limited access to outpatient rehabilitation for these stroke survivors further deepens the healthcare issue and estranges the stroke patient demographic in rural areas. However, new advances in motion detection deep learning enable the use of handheld smartphone cameras for body tracking, offering unparalleled levels of accessibility.

Age-Related Differences in the Contribution of Systolic Blood Pressure and Biomarkers to Cardiovascular Disease Risk Prediction: The Atherosclerosis Risk in Communities (ARIC) Study.

We sought to determine how biomarkers known to be associated with hypertension-induced end-organ injury complement the use of systolic blood pressure (SBP) for cardiovascular disease (CVD) risk prediction at different ages. Using data from visits 2 (1990 to 1992) and 5 (2011 to 2013) of the Atherosclerosis Risk in Communities (ARIC) study, 3 models were used to predict CVD (composite of coronary heart disease, stroke, and heart failure). Model A included traditional risk factors (TRFs) except SBP, model B-TRF plus SBP, and model C-TRF plus biomarkers (high-sensitivity troponin T [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]).

Elovanoids are neural resiliency epigenomic regulators targeting histone modifications, DNA methylation, tau phosphorylation, telomere integrity, senescence programming, and dendrite integrity.

Cellular identity, developmental reorganization, genomic structure modulation, and susceptibility to diseases are determined by epigenomic regulation by multiple signaling interplay. Here we demonstrate that elovanoids (ELVs), mediators derived from very-long-chain polyunsaturated fatty acids (VLC-PUFAs, n-3, C > 28), and their precursors in neurons in culture overcome the damage triggered by oligomeric amyloid-beta (OAβ), erastin (ferroptosis-dependent cell death), or other insults that target epigenomic signaling. We uncover that ELVs counteract damage targeting histones H3K9 and H3K27 methylation and acetylation; tau hyperphosphorylation (pThr181, pThr217, pThr231, and pSer202/pThr205 (AT8)); senescence gene programming (p16INK4a, p27KIP, p21CIP1, and p53); DNA methylation (DNAm) modifying enzymes: TET (DNA hydroxymethylase), DNA methyltransferase, DNA demethylase, and DNAm (5mC) phenotype.

Duodenal Metastasis From Primary Lung Adenocarcinoma: A Diagnostic and Therapeutic Challenge.

Distant metastasis from primary lung cancer is mostly seen in the liver, brain, adrenal glands and bones. Small bowel, specifically duodenum is a relatively unusual site for distant metastasis from lung carcinoma. This case reports a rare scenario of upper gastrointestinal bleeding caused by duodenal metastasis by a primary lung adenocarcinoma.