Brain connectivity changes in autosomal recessive Parkinson Disease: a model for the sporadic form

Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients' cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptom

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

SEGNALAZIONI E NOVIT\uc0 PER EDOARDO ARBORIO MELLA A CASALE, GALLIATE E VERCELLI

Alla luce delle ricerche e della catalogazione condotte nell\u2019ambito del Dipartimento di Studi Umanistici dell\u2019Universit\ue0 del Piemonte Orientale, gli autori ricostruiscono e analizzano, incrociando risultanze archivistiche e studio dei disegni del Fondo Arborio Mella dell\u2019Archivio di Stato di Vercelli, tre progetti di Edoardo Arborio Mella (1808-1884): il pulpito ligneo per il Duomo di Sant\u2019Evasio a Casale Monferrato, il complesso arredo ligneo per la chiesa parrocchiale dei SS Pietro e Paolo a Galliate, la lapide in pietra di Saltrio oggi murata nel cortile anticamente detto \u201cdella Podesteria\u201d del Palazzo Comunale di Vercelli, realizzata per commemorare il VII centenario della Battaglia di Legnano nel 1876

La chirurgia conservativa nel cancro della mammella

Breast-conserving surgery is the treatment of choice for the breast cancer T< 3 cm. The local recurrence is a problem of diagnosis and consequent treatment. We enrolled, from 1987 to 2004, 1504 breast cancer. In 803 (53,4%) tumor with T < 3 cm we performed conserving surgery. The sentinel lymph node (SN) technique induce to limit the axillary dissection in patients T1a-b to the SN only if non metastatic and located to the first level, the dissection of the 1st level of the axilla in patients T1c-T2 < 3 cm and SN negative, complete axillary dissection in patients with metastatic SN or located to the 2nd level. Our percentage of local recurrence in the follow-up was 3,5% at 5 years and 6% at 10 years

Carcinoma duttale in situ della mammella

Gli Autori riportano la loro esperienza relativa a 127 casi di carcinoma duttale in situ (CDIS) della mammella ed analizzano, anche alla luce della letteratura internazionale, i risultati ottenuti. L?intervento chirurgico è stato diversificato in rapporto ad alcuni fattori principali, dei quali i più importanti sono: il rilievo solo radiologico o clinico, l?estensione della neoplasia, la varietà istologica, il grading e lo studio dei margini di sezione. Nel corso degli anni è stata sostanzialmente modificata la strategia terapeutica del CDIS. Si è passati dalla mastectomia come intervento preferenziale alla quadrantectomia con attento studio della estensione della malattia e dei margini di sezione chirurgica. Anche la linfectomia di principio è stata abbandonata e gli Autori riportano, negli ultimi 7 anni, il costante impiego della tecnica del linfonodo sentinella. La terapia adiuvante (radioterapia e ormonoterapia) è attualmente limitata a casi selezionati. Con questa strategia terapeutica gli Autori riportano, seppure con un follow up medio ancora breve (6,1 anni), una percentuale di ripresa omolaterale della malattia dell?8,1%. English version The Authors report their experience about 127 ductal carcinoma in situ (DCIS) of the breast. Guidelines for surgical treatment are: radiological or clinical diagnosis, tumor?s extension, histological classification , grading and margin status. At the present the Authors prefer breast conserving surgery with tumor margin?s study. They report their experience in the last seven years about sentinel node biopsy. Radiotherapy and endocrine therapy are indicated for selected patients; local recurrence after DCIS therapy is 8,1% on a 6,1 years follow-up