Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto’s thyroiditis

Hashimoto’s thyroiditis (HT) is the most common of all thyroid diseases and is characterized by abundant lymphocyte infiltrate and thyroid impairment, caused by various cell- and antibody-mediated immune processes. Viral infections have been suggested as possible environmental triggers, but conclusive data are not available. We analyzed the presence and transcriptional state of human herpesvirus 6 (HHV-6) in thyroid fine needle aspirates (FNA) and peripheral blood mononuclear cells (PBMCs) from 34 HT patients and 28 controls, showing that HHV-6 DNA prevalence (82% vs. 10%, p≤0.001) and viral load were significantly increased in FNA from HT patients, and thyrocytes from HT FNA displayed a 100-fold higher HHV-6 DNA load compared to infiltrating lymphocytes. In addition, while HHV-6 was strictly latent in positive samples from controls, a low grade acute infection was detected in HT samples. HHV-6 variant characterization was carried out in 10 HT FNA samples, determining that all specimens harbored HHV-6 Variant A. The tropism of HHV-6 for thyroid cells was verified by infection of Nthy-ori3-1, a thyroid follicular epithelial cell line, showing that thyrocytes are permissive to HHV-6 replication, which induces de novo expression of HLA class II antigens. Furthermore, HHV-6-infected Nthy-ori3-1 cells become targets for NK-mediated killing, NK cells from HT patients show a significantly more efficient killing of HHV-6 infected thyroid cells than healthy controls, and HT patients have increased T-cell responses to HHV-6 U94 protein, associated to viral latency. These observations suggest a potential role for HHV-6 (possibly variant A) in the development or triggering of HT

Predictors of high level of burden and distress in caregivers of demented patients : results of an Italian multicenter study

Background Considerable suffering is experienced by carers of patients with dementia. Most existing studies do not consider the coexistence of subjective and objective aspects that cause, interacting to each other, this suffering. Objectives In this study we: (1) define the high-risk group of caregivers on the bases of the scores obtained on the four scales evaluating burden, distress, depression and anxiety (BDDA) taken into account simultaneously and (2) evaluate risk factors related to the high level of BDDA. Subjects and methods 419 elderly outpatients with dementia and their caregivers were enrolled. Patients were evaluated for their cognitive, neuropsychological and functional impairment and for comorbidity. Caregivers were evaluated with four scales for the assessment of burden, distress related to neuropsychological disturbances, depression and anxiety. Cluster analysis was used to identify the group with the High level of BDDA (HBDDA). Results By multiple logistic analysis, disability, specific behavioural disturbances of the patients as well as caregiver's age, type of relationship and living in the south of Italy were observed to be a major risk factor for HBDDA. Conclusion The targeted use of scales specifically assessing BDDA of the caregiver and the identification of particular patient and caregiver characteristics are able to allow a precise and early definition of caregivers at high risk of burden and distress. This might be helpful in planning the correct social/clinical/rehabilitative approach. Copyright (C) 2005 John Wiley Sons, Ltd

The Caregiver Burden Inventory in evaluating the burden of caregivers of elderly demented patients : results from a multicenter study

The burden perceived by caregivers of patients with dementia is a fundamental prognostic aspect in the history of the disease. The aim of this study was to demonstrate the internal consistency of the Caregiver Burden Inventory (CBI), a scale used to quantify burdens in different aspects of a caregiver's life, and the influence of patients' and caregivers' characteristics on its different dimensions. METHODS: In this cross-sectional study, 419 demented patients and their caregivers were evaluated in 16 geriatric centers in Italy. Cognitive status and behavioral disturbances were assessed by the Mini Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI), respectively. Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were also evaluated. Comorbidity was assessed by the Cumulative Illness Rating Scale (CIRS). The severity of dementia was evaluated by the Clinical Dementia Rating (CDR) score. Caregiver distress due to the behavioral problems of the patient was assessed by the Neuropsychiatric Inventory-Distress, a subscale of the NPI which evaluates stress caused by each behavioral disturbance of the patient, and by the Brief Symptom Inventory which evaluates anxiety and depression. Burden was evaluated by the CBI. RESULTS: The CBI showed very high internal consistency (Cronbach's alpha value > 0.80). Factor analysis showed that the items clustered into four dimensions, and not five as originally proposed. Multiple regression analysis revealed that patients' behavioral disturbances and disability were the major predictors of the time-dependent burden; the psychophysical burden was explained mainly by caregiver anxiety and depression. CONCLUSIONS: The CBI proved to be an effective multidimensional tool for evaluating the impact of burden on many aspects of caregivers' lives

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort

149nonenonePellegrini C.; Botta F.; Massi D.; Martorelli C.; Facchetti F.; Gandini S.; Maisonneuve P.; Avril M.-F.; Demenais F.; Bressac-de Paillerets B.; Hoiom V.; Cust A.E.; Anton-Culver H.; Gruber S.B.; Gallagher R.P.; Marrett L.; Zanetti R.; Dwyer T.; Thomas N.E.; Begg C.B.; Berwick M.; Puig S.; Potrony M.; Nagore E.; Ghiorzo P.; Menin C.; Manganoni A.M.; Rodolfo M.; Brugnara S.; Passoni E.; Sekulovic L.K.; Baldini F.; Guida G.; Stratigos A.; Ozdemir F.; Ayala F.; Fernandez-de-Misa R.; Quaglino P.; Ribas G.; Romanini A.; Migliano E.; Stanganelli I.; Kanetsky P.A.; Pizzichetta M.A.; Garcia-Borron J.C.; Nan H.; Landi M.T.; Little J.; Newton-Bishop J.; Sera F.; Fargnoli M.C.; Raimondi S.; Alaibac M.; Ferrari A.; Valeri B.; Sicher M.; Mangiola D.; Nazzaro G.; Tosti G.; Mazzarol G.; Giudice G.; Ribero S.; Astrua C.; Mazzoni L.; Orlow I.; Mujumdar U.; Hummer A.; Busam K.; Roy P.; Canchola R.; Clas B.; Cotignola J.; Monroe Y.; Armstrong B.; Kricker A.; Litchfield M.; Tucker P.; Stephens N.; Switzer T.; Theis B.; From L.; Chowdhury N.; Vanasse L.; Purdue M.; Northrup D.; Rosso S.; Sacerdote C.; Leighton N.; Gildea M.; Bonner J.; Jeter J.; Klotz J.; Wilcox H.; Weiss H.; Millikan R.; Mattingly D.; Player J.; Tse C.-K.; Rebbeck T.; Walker A.; Panossian S.; Setlow R.; Mohrenweiser H.; Autier P.; Han J.; Caini S.; Hofman A.; Kayser M.; Liu F.; Nijsten T.; Uitterlinden A.G.; Kumar R.; Bishop T.; Elliott F.; Lazovich D.; Polsky D.; Hansson J.; Pastorino L.; Gruis N.A.; Bouwes Bavinck J.N.; Aguilera P.; Badenas C.; Carrera C.; Gimenez-Xavier P.; Malvehy J.; Puig-Butille J.A.; Tell-Marti G.; Blizzard L.; Cochrane J.; Branicki W.; Debniak T.; Morling N.; Johansen P.; Mayne S.; Bale A.; Cartmel B.; Ferrucci L.; Pfeiffer R.; Palmieri G.; Kypreou K.; Bowcock A.; Cornelius L.; Council M.L.; Motokawa T.; Anno S.; Helsing P.; Andresen P.A.; Guida S.; Wong T.H.Pellegrini, C.; Botta, F.; Massi, D.; Martorelli, C.; Facchetti, F.; Gandini, S.; Maisonneuve, P.; Avril, M. -F.; Demenais, F.; Bressac-de Paillerets, B.; Hoiom, V.; Cust, A. E.; Anton-Culver, H.; Gruber, S. B.; Gallagher, R. P.; Marrett, L.; Zanetti, R.; Dwyer, T.; Thomas, N. E.; Begg, C. B.; Berwick, M.; Puig, S.; Potrony, M.; Nagore, E.; Ghiorzo, P.; Menin, C.; Manganoni, A. M.; Rodolfo, M.; Brugnara, S.; Passoni, E.; Sekulovic, L. K.; Baldini, F.; Guida, G.; Stratigos, A.; Ozdemir, F.; Ayala, F.; Fernandez-de-Misa, R.; Quaglino, P.; Ribas, G.; Romanini, A.; Migliano, E.; Stanganelli, I.; Kanetsky, P. A.; Pizzichetta, M. A.; Garcia-Borron, J. C.; Nan, H.; Landi, M. T.; Little, J.; Newton-Bishop, J.; Sera, F.; Fargnoli, M. C.; Raimondi, S.; Alaibac, M.; Ferrari, A.; Valeri, B.; Sicher, M.; Mangiola, D.; Nazzaro, G.; Tosti, G.; Mazzarol, G.; Giudice, G.; Ribero, S.; Astrua, C.; Mazzoni, L.; Orlow, I.; Mujumdar, U.; Hummer, A.; Busam, K.; Roy, P.; Canchola, R.; Clas, B.; Cotignola, J.; Monroe, Y.; Armstrong, B.; Kricker, A.; Litchfield, M.; Tucker, P.; Stephens, N.; Switzer, T.; Theis, B.; From, L.; Chowdhury, N.; Vanasse, L.; Purdue, M.; Northrup, D.; Rosso, S.; Sacerdote, C.; Leighton, N.; Gildea, M.; Bonner, J.; Jeter, J.; Klotz, J.; Wilcox, H.; Weiss, H.; Millikan, R.; Mattingly, D.; Player, J.; Tse, C. -K.; Rebbeck, T.; Walker, A.; Panossian, S.; Setlow, R.; Mohrenweiser, H.; Autier, P.; Han, J.; Caini, S.; Hofman, A.; Kayser, M.; Liu, F.; Nijsten, T.; Uitterlinden, A. G.; Kumar, R.; Bishop, T.; Elliott, F.; Lazovich, D.; Polsky, D.; Hansson, J.; Pastorino, L.; Gruis, N. A.; Bouwes Bavinck, J. N.; Aguilera, P.; Badenas, C.; Carrera, C.; Gimenez-Xavier, P.; Malvehy, J.; Puig-Butille, J. A.; Tell-Marti, G.; Blizzard, L.; Cochrane, J.; Branicki, W.; Debniak, T.; Morling, N.; Johansen, P.; Mayne, S.; Bale, A.; Cartmel, B.; Ferrucci, L.; Pfeiffer, R.; Palmieri, G.; Kypreou, K.; Bowcock, A.; Cornelius, L.; Council, M. L.; Motokawa, T.; Anno, S.; Helsing, P.; Andresen, P. A.; Guida, S.; Wong, T. H