Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model

The entorhinal cortex (EC) has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer’s disease (AD), a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving animals indicates gamma oscillations (30–100 Hz) as critical for mediating interactions in the circuit between EC and hippocampus. However, it is still unclear whether gamma oscillations have causal relationship with memory impairment in AD. Here we provide the first evidence that in vivo gamma oscillations in the EC are impaired in an AD mouse model. Cross-frequency coupling of gamma (30–100 Hz) oscillations to theta oscillations was reduced in the medial EC of anesthetized amyloid precursor protein knock-in (APP-KI) mice. Phase locking of spiking activity of layer II/III pyramidal cells to the gamma oscillations was significantly impaired. These data indicate that the neural circuit activities organized by gamma oscillations were disrupted in the medial EC of AD mouse model, and point to gamma oscillations as one of possible mechanisms for cognitive dysfunction in AD patients

Local and regional therapy for primary and locally recurrent melanoma.

In the vast majority of cases, cutaneous melanoma presents as localized disease and is treated with wide excision and sentinel lymph node biopsy, with shared decision making regarding completion lymph node dissection and adjuvant systemic therapy. The treatment of recurrent and in-transit disease is more complex, with further options for regional and systemic therapies and multiple variables to be factored into decisions. Rates of overall and complete response to regional therapies can be quite high in carefully chosen patients, which limits the need for systemic therapies and their inherent side effects. Ongoing trials aim to assess the efficacy of combination regional and systemic therapies and assist in deciding among these options. This review discusses the treatment of primary melanoma and regional nodal disease and offers an in-depth discussion of options for the treatment of recurrent melanoma and in-transit melanoma

In-transit metastatic cutaneous melanoma: current management and future directions.

Management of in-transit melanoma encompasses a variety of possible treatment pathways and modalities. Depending on the location of disease, number of lesions, burden of disease and patient preference and characteristics, some treatments may be more beneficial than others. After full body radiographic staging is performed to rule out metastatic disease, curative therapy may be performed through surgical excision, intraarterial regional perfusion and infusion therapies, intralesional injections, systemic therapies or various combinations of any of these. While wide excision is limited in indication to superficial lesions that are few in number, the other listed therapies may be effective in treating unresectable disease. Where intraarterial perfusion based therapies have been shown to successfully treat extremity disease, injectable therapies can be used in lesions of the head and neck. Although systemic therapies for in-transit melanoma have limited specific data to support their primary use for in-transit disease, there are patients who may not be eligible for any of the other options, and current clinical trials are exploring the use of concurrent and sequential use of regional and systemic therapies with early results suggesting a synergistic benefit for oncologic response and outcomes

Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model.

The entorhinal cortex (EC) has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer's disease (AD), a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving animals indicates gamma oscillations (30-100 Hz) as critical for mediating interactions in the circuit between EC and hippocampus. However, it is still unclear whether gamma oscillations have causal relationship with memory impairment in AD. Here we provide the first evidence that in vivo gamma oscillations in the EC are impaired in an AD mouse model. Cross-frequency coupling of gamma (30-100 Hz) oscillations to theta oscillations was reduced in the medial EC of anesthetized amyloid precursor protein knock-in (APP-KI) mice. Phase locking of spiking activity of layer II/III pyramidal cells to the gamma oscillations was significantly impaired. These data indicate that the neural circuit activities organized by gamma oscillations were disrupted in the medial EC of AD mouse model, and point to gamma oscillations as one of possible mechanisms for cognitive dysfunction in AD patients

Atypical Fibroxanthoma: Outcomes from a Large Single Institution Series.

BACKGROUND: Atypical fibroxanthomas (AFX) are rare malignant cutaneous neoplasms. Unfortunately, limited clinicopathologic and outcomes data on this cancer exists. OBJECTIVE: We report the clinical, pathologic, and treatment characteristics, as well as oncologic outcomes in this single-institution retrospective analysis. METHODS: This retrospective cohort study compiled clinical, pathologic, treatment, and outcome data for all patients with AFX on definitive excision diagnosed, evaluated, and treated primarily by surgical resection at a single institution between 2000-2020. Descriptive statistics evaluated clinical and pathologic characteristics. Kaplan-Meier method and Cox proportional-hazards models were used to evaluate overall survival and recurrence-free survival. RESULTS: 78 patients with AFX were identified. The majority were elderly, immunocompetent, Caucasian men. 85% of tumors were located on the head and neck. 63% of patients were correctly diagnosed only after complete resection of the index lesion. The median surgical margin was 1.0 cm. Overall, only 1.3% (1/78) of patients developed a local recurrence (RFS). No patients died of disease. CONCLUSION: This study suggests that resection margins of 1 cm achieve excellent local control with close to 99% RFS and 100% disease-specific survival

Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model

The entorhinal cortex (EC) has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer's disease (AD), a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving animals indicates gamma oscillations (30-100 Hz) as critical for mediating interactions in the circuit between EC and hippocampus. However, it is still unclear whether gamma oscillations have causal relationship with memory impairment in AD. Here we provide the first evidence that in vivo gamma oscillations in the EC are impaired in an AD mouse model. Cross-frequency coupling of gamma (30-100 Hz) oscillations to theta oscillations was reduced in the medial EC of anesthetized amyloid precursor protein knock-in (APP-KI) mice. Phase locking of spiking activity of layer II/III pyramidal cells to the gamma oscillations was significantly impaired. These data indicate that the neural circuit activities organized by gamma oscillations were disrupted in the medial EC of AD mouse model, and point to gamma oscillations as one of possible mechanisms for cognitive dysfunction in AD patients