No abstract

The objectives of this retrospective, naturalistic study were to provide preliminary data on the effects of 6 months treatment with risperidone, olanzapine and quetiapine on behavioral disturbances, within a sample of outpatients with mild to moderate Alzheimer's disease, and on predictors of response. Between July 2005 and December 2005, data were collected from 58 consecutive outpatients with a DSM-IV-TR diagnosis of Alzheimer's disease with behavioral disturbances, who received a 6-month treatment with risperidone, olanzapine or quetiapine. Primary outcome measures were Neuropsychiatric Inventory (NPI) total score and its items forming the basic core of behavioral disturbances in Alzheimer's disease: delusions, hallucinations and agitation/aggressiveness. Secondary outcome measures were Mini-Mental State Examination (MMSE), Activities of Daily Living, Instrumental Activities of Daily Living and Clinical Insight Rating scale. Correlations between baseline MMSE score and improvements in behavioral disturbances were investigated. At 6 months mean NPI total score had fallen 43.5% in the risperidone group, 45.6% in the olanzapine group and 33.3% in the quetiapine group, with no significant between-group differences. Global cognitive function showed no significant change from baseline to end-point. Incidence of adverse events was low. A significant correlation was found between MMSE score and NPI total score and NPI item agitation decreases. Risperidone, olanzapine and quetiapine produced significant improvements in behavioral disturbances and were well tolerated. No significant differences emerged among treatments. The preliminary results also suggest that baseline cognitive function might influence treatment response.

Polysaccharides and other cationic polymers have recently been used in pharmaceutical research and industry for their properties to control the release of antibiotics, DNA, proteins, peptide drugs or vaccines, and they have also been extensively studied as non-viral DNA carriers for gene delivery and therapy. Among them, chitosan is the most used since it can promote long-term release of incorporated drugs. This work is focused on the preparation of chitosan and chitosan/DNA nanospheres by using a novel and simple osmosis-based method, recently patented. The morphology of chitosan/DNA particles is spherical (as observed by scanning electron microscopy, SEM) and the nanospheres' average diameter is 38 ± 4 nm (obtained by dynamic light scattering, DLS). With this method, DNA is incorporated with high yield (up to 30%) and the release process is gradual and prolonged in time. The novelty of the reported method resides in the general applicability to various synthetic or natural biopolymers. Solvent, temperature and membrane cut-off are the physicochemical parameters that one is able to use to control the overall osmotic process, leading to several nanostructured systems with different size and shape that may be used in several biotechnological applications.

Microsatellite instability (MSI) has been identified in several tumors arising from either germline or somatic aberration. The presence of MSI in cancer predicts the sensitivity to immune checkpoint inhibitors (ICIs), particularly PD1/PD-L1 inhibitors. To date, the predictive role of MSI is currently used in the selection of colorectal cancer patients for immunotherapy; moreover, the expansion of clinical trials into other cancer types may elucidate the predictive value of MSI for non-colorectal tumors. In clinical practice, several assays are used for MSI testing, including immunohistochemistry (IHC), polymerase chain reaction (PCR) and next-generation sequencing (NGS). In this review, we provide an overview of MSI in various cancer types, highlighting its potential predictive/prognostic role and the clinical trials performed. Finally, we focus on the comparison data between the different assays used to detect MSI in clinical practice.

(1) Background: Fine-needle aspiration cytology is often used for the pre-operative diagnosis of melanoma metastases. The diagnosis may not be confidently established based on morphology alone, and immunocytochemistry is mandatory. The choice of the most advantageous immunocytochemical antibodies is critical, as the sample may be scant, and the presence of pigmented histiocytes may be confounding. However, the diagnostic performance of melanocytic markers in this setting is poorly investigated. Moreover, PRAME (preferentially expressed antigen in melanoma) recently emerged as a novel marker for the diagnosis of melanoma. The current work aimed to evaluate the sensitivity and specificity of PRAME for the diagnosis of melanoma metastases in cytological samples, compared to other melanocytic markers. (2) Methods: PRAME, S100, Melan-A, HMB45 and SOX10 were tested on cell block sections of 48 cases of melanoma metastases diagnosed from cytological samples, and 20 cases of reactive lymphadenopathy. (3) Results: S100 and SOX10 showed the highest sensitivity (100%), while the sensitivity of PRAME was 85.4%. PRAME, Melan-A, SOX10 and HMB45 showed a specificity of 100%, while the specificity of S100 was lower (85%), as it marked some histiocytes. (4) Conclusion: PRAME immunocytochemistry is highly specific for the diagnosis of melanoma metastasis from a cytological sample, but is less sensitive compared with other melanocytic markers.