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

UTILIZZO DELLE CELLULE STAMINALI CONCENTRATE IN ORTOPEDIA ONCOLOGICA E RICOSTRUTTIVA

RIASSUNTO ANALITICO Scopo di questo studio è la valutazione dei risultati ottenuti nel trattamento di tre patologie attraverso metodiche che prevedono l’utilizzo delle cellule staminali concentrate, le cui proprietà rigenerative sono il fulcro della medicina rigenerativa e dell’ingegneria tissutale. Dal mese di Giugno 2000 al mese di Giugno 2016 sono stati trattati presso l’Azienda Ospedaliera Universitaria Careggi, CTO, Firenze, Dipartimento di Ortopedia Oncologica e Chirurgia Ricostruttiva, 248 pazienti. Questi sono stati suddivisi in tre gruppi: 140 cisti/lesioni pseudotumorali: 53 femmine di età compresa tra i 5 ed i 67 anni, 87 maschi di età compresa tra gli 8 ed i 39 anni; compresi 12 casi di displasia fibrosa (1 non guarito), 3 casi di condroblastoma, 2 casi di condrosarcoma, 3 casi di istiocitoma, 8 casi di TGC (1 non guarito); 72 casi localizzati negli arti inferiori (soprattutto femore e tibia), 68 casi negli arti superiori (soprattutto omero prossimale); 80 pseudoartrosi: di cui 20 femmine di età compresa tra gli 8 ed i 79 anni, 60 maschi tra i 13 e gli 83 anni; arti superiori 17 ed arti inferiori 63 di cui 29 femore, 34 tibia; 28 osteonecrosi epifisarie del femore: 8 femmine dai 23 ai 58 anni e 20 maschi di età compresa tra 23 e 55 anni. La guarigione è stata dell’87,9% per le lesioni pseudotumorali, 81,2% per le PSA e 57% per le ON. I risultati ottenuti permettono di affermare che l’utilizzo delle cellule staminali mesenchimali rappresenti un valido supporto per l’ortopedia oncologica e ricostruttiva ed in futuro rivestirà un ruolo sempre maggiore in questo ed in altri ambiti della medicina purché in grado di fornire al paziente strategie sicure, a lungo termine e sostanzialmente più efficaci di qualsiasi altro trattamento disponibile. ABSTRACT The purpose of this study is to evaluate the results obtained in the treatment of three pathologies through methods that involve the use of concentrated stem cells whose regenerative properties are the core of regenerative medicine and tissue engineering. From June 2000 to June 2016, 248 patients were treated at the Careggi Hospital, CTO, Florence, Department of Orthopedic Oncology and Reconstructive Surgery. These were divided into three groups: 140 cysts / pseudo-tumor lesions: 53 females aged 5 to 67, 87 males aged 8 to 39; Including 12 cases of fibrous dysplasia (only 1 failed), 3 cases of chondroblastoma, 2 cases of condrosarcoma, 3 cases of histiocytoma, 8 cases of TGC (1 failed); 72 cases located in the lower limbs (especially femur and tibia), 68 cases in the upper limbs (especially proximal humerus); 80 pseudoarthrosis: 20 females aged 8 to 79 years, 60 males between 13 and 83 years; Upper limbs 17 and lower limbs 63; 28 femoral head osteonecrosis: 8 females aged 23 to 58 and 20 males aged 23 to 55 years. Healing was 87.9% for pseudotumoral injuries, 81.2% for PSA and 57% for ON. We can conclude that the use of mesenchymal stem cells is a valid support for oncological and reconstructive orthopedics and it will play an increasing role in this and other areas of medicine as long as it can provide to the patient secure strategies, long term healing and basically more effective than any other available treatment

Optoeletronic properties of poly(N-alkenyl-carbazole)s driven by polymer stereoregularity

Stereoregular polymers like isotactic poly(N-butenyl-carbazole) (i-PBK), isotactic and syndiotactic poly(N-pentenyl-carbazole) (i-PPK and s-PPK), and poly(N-hexenyl-carbazole) (i-PHK and s-PHK) are synthesized using the stereospecific homogeneous â\u80\u9csingle siteâ\u80\u9d Ziegler-Natta (Z-N) catalysts: rac-dimethylsilylbis(1-indenyl)zirconium dichloride (1)/methylaluminoxane (MAO) and diphenylmethylidene(cyclopentadienyl)-(9-fluorenyl)zirconium dichloride (2)/MAO. Catalytic activity is rationalized by density functional theory (DFT) calculations. All synthesized polymers are fully characterized by NMR, thermal, wide-angle X-ray diffraction, and fourier transform infrared spectroscopy analysis. Fluorescence measurements on isotactic and syndiotactic polymer films indicate that all polymers give rise to excimers, both â\u80\u9csandwich-likeâ\u80\u9d and â\u80\u9cpartially overlapping.â\u80\u9d Excimer formation is essentially driven by the polymer tacticity. Isotactic polymers generate both sandwich-like and partially overlapping excimers, while syndiotactic polymers give rise especially to partially overlapping ones. A theoretical combined molecular dynamicsâ\u80\u93time dependent DFT approach is also used to support the experimental results. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 242â\u80\u93251

Kinetics of TTV Loads in Peripheral Blood Mononuclear Cells of Early Treated Acute HIV Infections

Torquetenovirus (TTV) is the most abundant component of the human blood virome and its replication is controlled by a functioning immune system. In this study, TTV replication was evaluated in 21 people with acute HIV infection (AHI) and immune reconstitution following antiretroviral therapy (ART). PBMC-associated TTV and HIV-1 DNA, as well as plasma HIV-1 RNA, were measured by real-time PCR. CD4 and CD8 differentiation, activation, exhaustion, and senescence phenotypes were analyzed by flow cytometry. Thirteen healthy donors (HD) and twenty-eight chronically infected HIV individuals (CHI), late presenters at diagnosis, were included as control groups. TTV replication in AHI seems to be controlled by the immune system being higher than in HD and lower than in CHI. During ART, a transient increase in TTV DNA levels was associated with a significant perturbation of activation and senescence markers on CD8 T cells. TTV loads were positively correlated with the expansion of CD8 effector memory and CD57+ cells. Our results shed light on the kinetics of TTV replication in the context of HIV acute infection and confirm that the virus replication is strongly regulated by the modulation of the immune system

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele