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Amyotrophic lateral sclerosis (ALS) patients might present with cognitive and behavioural abnormalities resembling frontotemporal dementia (FTD). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was developed as an easy to administer cognitive screen for detecting these symptoms. The aim of the present study was to develop and validate a Japanese version of the ECAS.

In this single centreobservational study, 35 ALS patients and 28 healthy controls were enrolled. Three patients in the ALS group fulfilled the criteria for behavioural variant FTD (ALS-FTD) and the rest were grouped as ALS without FTD. Participants were subjected to the Japanese version of the ECAS. ALS patients were also subjected to the Montreal Cognitive Assessment, Frontal Assessment Battery, ALS Functional Rating Scale-Revised, and respiratory function testing. Demographic and disease characteristics (e.g., sex, age at examination, and years of education) were also recorded.

Internal consistency and correlations with general cognitive screenings were sufficient in the Japanese adaptation. Executive functions were the most commonly affected ECAS domain, followed by fluency and language. Compared to control subjects, ALS patients without FTD had low scores in the ECAS ALS-specific functions but not in ALS-nonspecific functions. Meanwhile ALS-FTD patients markedly underperformed both in the ECAS ALS-specific and ALS-nonspecific functions. Furthermore, the Japanese ECAS score correlated positively with years of education and negatively with age at onset.

The Japanese version of the ECAS is a valid and useful screening tool to identify multiple types of cognitive impairment in ALS patients.

The Japanese version of the ECAS is a valid and useful screening tool to identify multiple types of cognitive impairment in ALS patients.Aim To assess time-to-treatment failure (TTF) in US patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib-osimertinib treatment in the global, observational GioTag study. Patients & methods Patients had EGFR T790M mutation-positive disease after first-line afatinib and subsequently received osimertinib. The primary outcome was TTF. Selleckchem Perhexiline Results In 129 patients at US centers, median TTF was 28.4 months (90% CI 27.0-34.1). Median overall survival was 47.6 months (90% CI 35.5-51.5). Conclusion Sequential afatinib-osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with EGFR mutation-positive NSCLC not presenting with active brain metastases or de novo T790M. Clinical Trial Registration NCT03370770 (ClinicalTrials.gov).

Cisplatin is a highly effective chemotherapeutic agent against a variety of solid tumors in adults and in children. Unfortunately, a large percentage of patients suffer permanent sensorineural hearing loss. Up to 60% of children and at least 50% of adults suffer this complication that seriously compromises their quality of life. Hearing loss is due to damage to the sensory cells in the inner ear. The mechanisms of cochlear damage are still being investigated. However, it appears that inner ear damage is triggered by reactive oxygen species (ROS) formation and inflammation 34.

We discuss a number of potential therapeutic targets that can be addressed to provide hearing protection. These strategies include enhancing the endogenous antioxidant pathways, heat shock proteins, G protein coupled receptors and counteracting ROS and reactive nitrogen species, and blocking pathways that produce inflammation, including TRPV1 and STAT1 36.

Numerous potential protective agents show promise in animal models by systemic or local administration. However, clinical trials have not shown much efficacy to date with the exception of sodium thiosulfate. There is an urgent need to discover safe and effective protective agents that do not interfere with the efficacy of cisplatin against tumors yet preserve hearing 151.

Numerous potential protective agents show promise in animal models by systemic or local administration. However, clinical trials have not shown much efficacy to date with the exception of sodium thiosulfate. There is an urgent need to discover safe and effective protective agents that do not interfere with the efficacy of cisplatin against tumors yet preserve hearing 151.Pseudogout, also known as calcium pyrophosphate dihydrate (CPPD) deposition disease or chondrocalcinosis, is caused by crystalline deposits of CPPD within the extracellular matrix of articular hyaline cartilage and fibrocartilage, and within articular and periarticular connective tissue. Using a variety of laboratory techniques, we diagnosed pseudogout in the right hindlimb digit V of a 12-y-old Standard Poodle. Histologically, the joint, bone, tendon, and dermis were expanded and effaced by masses of mineralized, rhomboid crystals surrounded by macrophages, multinucleate giant cells, fibrous connective tissue, and chondroid and osseous matrix. Rhomboid crystals exhibiting weak-positive birefringence were identified under polarized light using a first-order red compensator filter. Scanning electron microscopy with energy-dispersive x-ray analysis (SEM-EDXA) revealed that the rhomboid crystals were composed of calcium, phosphorus, and oxygen. Fourier-transform infrared (FTIR) microspectroscopy confirmed the presence of calcium pyrophosphate. In dogs, tophaceous pseudogout, which was the variant of pseudogout in our case, occurs as a single, tumor-like periarticular mass that can be invasive and mimic neoplasia. Having ancillary confirmatory testing (SEM-EDXA and FTIR), particularly in unusual histologic scenarios, such as tophaceous pseudogout in dogs, is desirable for confirming the correct diagnosis, even though it is available only at certain reference centers. The pathogenesis of pseudogout is unknown.

The objective of this study was to investigate the cumulative fraction of response (CFR) of various tigecycline dosing regimens in patients with hepatic or renal impairment.

Monte Carlo simulations were performed using pharmacokinetic parameters and microbiological data to evaluate various tigecycline regimens in patients with hepatic or renal impairment.

For HAP and cIAI, the regimen of 25 mg q12h achieved CFR values of >90% in Child-Pugh C patients against Gram-positive bacteria and partial Gram-negative bacteria (

and

). However, dose increases of tigecycline was mostly required for

,

and

. The conventional tigecycline regimen (50 mg q12h) was effective for HAP and cIAI caused by Gram-positive bacteria and

in patients with renal impairment. For HAP caused by

and

, patients with severe renal failure can use the standard dose regimen 50 mg q12h, and other patients need to increase the dose of tigecycline. However, when treating cSSSI caused by

,

and

, all tigecycline maintenance doses have a CFR <90%.

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