Simultaneous detection of West Nile and Japanese encephalitis virus RNA by duplex TaqMan RT-PCR

West Nile virus (WNV) and Japanese encephalitis virus (JEV) are important mosquito-borne viruses of the Flaviviridae family, associated with encephalitis, mainly in humans and horses. WNV is also pathogen for many bird species. The incidence of human and animal WNV infections in Europe has risen, mostly in recent years, and JEV was detected in 2011 in mosquitoes collected in Italy and may emerge in Europe in the same way as other flaviviruses had emerged recently (USUTU and Bagaza virus) and should be regarded as a potential threat to public health.     

Tau phosphorylation affects its axonal transport and degradation

Phosphorylated forms of microtubule-associated protein tau accumulate in neurofibrillary tangles in Alzheimer's disease. To investigate the effects of specific phosphorylated tau residues on its function, wild type or phosphomutant tau was expressed in cells. Elevated tau phosphorylation decreased its microtubule binding and bundling, and increased the number of motile tau particles, without affecting axonal transport kinetics. In contrast, reducing tau phosphorylation enhanced the amount of tau bound to microtubules and inhibited axonal transport of tau. To determine whether differential tau clearance is responsible for the increase in phosphomimic tau, we inhibited autophagy in neurons which resulted in a 3-fold accumulation of phosphomimic tau compared with wild type tau, and endogenous tau was unaffected. In autophagy-deficient mouse embryonic fibroblasts, but not in neurons, proteasomal degradation of phosphomutant tau was also reduced compared with wild type tau. Therefore, autophagic and proteasomal pathways are involved in tau degradation, with autophagy appearing to be the primary route for clearing phosphorylated tau in neurons. Defective autophagy might contribute to the accumulaton of tau in neurodegenerative diseases.     

Bone marrow plasma cell infiltration in light chain amyloidosis: impact on organ involvement and outcome

Abstract

Objectives: Prognosis of immunoglobulin light-chain (AL) amyloidosis depends mainly on the presence of cardiac involvement and the disease burden. A higher bone marrow plasma cell (BMPC) burden has been recognized as an adverse prognostic factor. The aim of our study was to analyze the correlation between the BMPC infiltration, clinical features and outcomes in patients with AL amyloidosis.

Methods: The clinical records of 79 patients with AL amyloidosis treated at a single institution.

Results: Median BMPC infiltration at diagnosis was 11% and significantly correlated with the serum free light-chain difference (p?<?.001). Patients with more than 10% BMPCs had more frequent cardiac involvement (86 vs. 63%; p?=?.015), a trend towards a higher early mortality (27 vs. 11%; p?=?.08) and a significantly shorter progression-free survival (PFS) (median of 18 vs. 48?months, p?=?.02) and overall survival (median of 33?months vs. not reached; p?=?.046). In the multivariate analysis, a BMPC infiltration over 10% retained its adverse prognostic value for PFS (HR?=?2.26; 95% CI, 1.048–4.866; p?=?.038). The use of new drugs seemed to overcome the negative prognostic impact of a higher BMPC infiltration.

Conclusion: Higher BMPC infiltration in AL amyloidosis might be associated with increased systemic organ damage, particularly cardiac involvement and is rarely related to the development of myeloma features.     

Laser Doppler flowmetry for assessing localized scleroderma in children

OBJECTIVE: Assessment of disease activity is a major challenge in the management of children with localized scleroderma. The aim of this study was to evaluate the role of laser Doppler flowmetry (LDF) in comparison with infrared thermography in the detection of scleroderma disease activity. METHODS: In 41 children with localized scleroderma, 111 lesions were assessed on 2 separate occasions, by clinical examination, LDF, and thermography. Measurements from contralateral areas of unaffected skin served as intrapatient controls, and differences in blood flow and temperature were calculated between the corresponding sites. The sensitivity and specificity to detect clinically active lesions were compared between LDF and thermography. RESULTS: Seventy-five active lesions (34%) and 147 inactive lesions (66%) were identified clinically. The median relative increase in blood flow measured by LDF was +89% (range -69% to +449%) for clinically active lesions and +11% (range -46% to +302%) for clinically inactive lesions (P < 0.001). Thermography showed a median difference in temperature of +0.5 degrees C (range -0.1 degrees C to +4.1 degrees C) and +0.3 degrees C (range -1.9 degrees C to +2.7 degrees C) for clinically active lesions and clinically inactive lesions, respectively (P = 0.024). Using a cutoff level of 39% to indicate increase in blood flow, a sensitivity of 80% and specificity of 77% to detect clinically active lesions were observed; for thermography, no useful cutoff level was identified. The correlation between differences in blood flow and differences in temperature was small, but significant (r2 = 0.120, P < 0.001). CONCLUSION: LDF is a helpful, noninvasive diagnostic technique that can be used to discriminate disease activity in children with localized scleroderma, and is more accurate than thermography for this purpose.     

Comparison of atorvastatin versus fenofibrate in reaching lipid targets and influencing biomarkers of endothelial damage in patients with familial combined hyperlipidemia

Statins and fibrates have different effects on lipid abnormalities of familial combined hyperlipidemia (FCHL); thus, the selection of the first-line drug is troublesome. We evaluated to what extent monotherapy with a potent statin is more effective than fibrate in reaching the recommended lipid targets in FCHL. Fifty-six patients were randomized to receive optimal dosage of atorvastatin (n = 27) or 200 mg/d micronized fenofibrate (n = 29) for 24 weeks. To reach the optimal dosage, atorvastatin was up-titrated at each follow-up visit if low-density lipoprotein (LDL) cholesterol >130 mg/dL (>100 mg/dL in patients with coronary or cerebrovascular disease). The effects of fenofibrate and atorvastatin on lipoprotein fractions as well as on plasma levels of endothelin-1 (ET-1) and adrenomedullin (AM) were also evaluated. At end of trial, a greater proportion of patients on atorvastatin (average dosage, 20.8 mg/d) reached lipid targets in comparison with those on fenofibrate (64% vs 32.1%, P = .02). Atorvastatin was significantly more effective in reducing total cholesterol, LDL cholesterol, apolipoprotein B, and non-high-density lipoprotein (HDL) cholesterol. Conversely, triglycerides decreased and HDL increased more during fenofibrate. Nevertheless, atorvastatin produced a marked reduction in very low-density lipoprotein and very low-density lipoprotein remnants. Atorvastatin lowered all LDL subtypes, although fenofibrate appeared to be more effective on denser LDL. Compared with 43 normolipemic controls, FCHL patients presented increased baseline plasma levels of ET-1 (P = .007) but not of AM. Fenofibrate, but not atorvastatin, significantly lowered ET-1 levels by 16.7% (P < .05). Neither drug significantly affected plasma concentrations of AM. In summary, although fenofibrate showed superiority in raising HDL and reducing ET-1, atorvastatin was more effective in reaching lipid targets in FCHL so that it can be proposed as the first-line option in the management of this atherogenic hyperlipidemia.     

A high n-6 polyunsaturated fatty acid diet reduces muscarinic M2/M4 receptor binding in the rat brain

The aim of this study was to examine the influence of different fat diets on muscarinic acetylcholine receptor binding. Nineteen male Sprague–Dawley rats were divided into four groups and fed a diet of either high saturated fat, n-6 polyunsaturated fatty acid (PUFA), n-3 PUFA or low fat (control) for 8 weeks. Using quantitative autoradiography, [³H]pirenzepine binding to muscarinic M1/M4 receptors and [³H]AF-DX384 binding to M2/M4 receptors were measured throughout the brain in all four groups. The main findings were that compared to the low fat control group, M2/M4 receptor binding was significantly reduced in the dorsolateral, dorsomedial and ventromedial parts of the caudate putamen (61–64%, p < 0.05), anterior cingulate cortex (59%, p < 0.01), dentate gyrus and CA1–3 fields of the hippocampus (32–43%, p < 0.01) of rats on a high n-6 PUFA diet; however, no differences in M1/M4 receptor binding densities between the four groups were observed. These results suggest that a diet high in n-6 PUFA, but not of n-3 PUFAs or saturated fat, may selectively alter M2/M4 receptor-mediated signal transduction in the rat brain.     

Assistance received by employed caregivers and their care recipients: who helps care recipients when caregivers work full time?

PURPOSE: This study examined the association among caregiver labor force participation, employees' caregiving activities, and the amount and quality of care received by care recipients. DESIGN AND METHODS: Telephone interviews were conducted with 478 adults who were employed full time and 705 nonemployed adults who provided care to a family member or friend aged 50 or older, identified through random sampling of California households. We assessed care recipient impairment and service problems; the amounts and types of assistance received from caregivers, family and friends, and paid providers; and caregiver utilization of support services. RESULTS: Care recipients of caregivers employed full time were less likely to receive large amounts of care from their caregivers, more likely to receive personal care from paid care providers, more likely to use community services, and more likely to experience service problems than were care recipients of nonemployed caregivers. Employed caregivers were more likely to use caregiver support services than were nonemployed caregivers. IMPLICATIONS: Accommodation to caregiver full-time employment involves selective supplementation by caregivers and their care recipients, reflecting increased reliance on formal support services as well as increased vulnerability to service problems and unmet care recipient needs. These findings suggest the need for greater attention to the well-being of disabled elders whose caregivers are employed full time.     

Endoscopic submucosal dissection for the treatment of neoplastic lesions in the gastrointestinal tract

AIM: To investigate the indications, resection rate, and safety of endoscopic submucosal dissection (ESD) for neoplastic lesions in the gastrointestinal tract at a European referral center. METHODS: We carried out a retrospective analysis of the ESD procedures performed in our center for mucosal neoplastic and submucosal lesions of the gastrointestinal tract. The duration of the procedure, en bloc and complete (R0) resection rates, and complication rates were evaluated. Variables were reported as mean ± SD or simple proportions. Univariate analysis and comparisons of procedure times and resection rates were performed using Mann-Whitney U tests, or χ2 tests for dichotomous variables.RESULTS: Between 2007 and 2011, ESD was performed in a total of 103 patients (46.7% male, mean age 64.0 ± 12.7 years). The indications for the procedure were epithelial tumor (n = 54), submucosal tumor (n = 42), or other (n = 7). The total en bloc resection rate was 90.3% (93/103) and R0 resection rate 80.6% (83/103). The median speed of the procedure was 15.0 min/cm2 . The complete resection rate was lower for submucosal tumors arising from the muscle layer (68%, 15/22, P < 0.05). Resection speed was quicker for submucosal tumors localized in the submucosal layer than for lesions arising from the muscularis propria layer (8.1 min/cm 2 vs 17.9 min/cm 2 , P < 0.05). The R0 resection rate and speed were better in the last 24 mo (90.1%, 49/54 and 15.3 min/cm 2 ) compared to the first 3 years of treatment (73.5%, 36/49, P < 0.05 and 22.0 min/cm2 , P < 0.05). Complications occurred in 14.6% (n = 15) of patients, including perforation in 5.8% (n = 6), pneumoperitoneum in 3.9% (n = 4), delayed bleeding in 1.9% (n = 2), and other in 2.9% (n = 3). Only one patient with delayed perforation required surgical treatment. During the mean follow-up of 26 ± 15.3 mo, among patients with R0 resection, recurrence occurred in one patient (1.2%).CONCLUSION: ESD is an effective and safe method for resection of neoplastic lesions with low re