The aim of this study is to present long-term results including patients' satisfaction, pelvic floor symptoms, regret and change in body image in a long-term follow-up after colpocleisis.; All women who underwent colpocleisis between September 2001 and February 2014 were identified from the hospital operating lists. These women were contacted for a telephone survey up to 13 years after surgery and asked to complete a structured questionnaire to assess patients' satisfaction, Quality of Life (QoL)...
1d
Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most...
1d
Intradermal MVA85A, a candidate vaccine against tuberculosis, induces high amounts of Ag85A-specific CD4 T cells in adults who have already received the BCG vaccine, but aerosol delivery of this vaccine might offer immunological and logistical advantages. We did a phase 1 double-blind trial to compare the safety and immunogenicity of aerosol-administered and intradermally administered MVA85A METHODS: In this phase 1, double-blind, proof-of-concept trial, 24 eligible BCG-vaccinated healthy UK adults...
1d
OBJECTIVE: Preoperative assessment of adnexal masses with ultrasound has been shown to be time-, cost-effective, and specific. When used in combination with the menopausal status and the tumor marker CA125, the risk of malignancy index (RMI) can be calculated, allowing appropriate preoperative triage of patients to a gynecologist or a gynecological oncologist. Moreover, it allows for accurate planning of the required surgical procedure (laparoscopy vs laparotomy). METHODS: A large general gynecologic...
1d
Bisecting GlcNAc on N-glycoproteins is described in E-cadherin-, EGF-, Wnt- and integrin- cancer-associated signaling pathways. However, the mechanisms regulating bisecting GlcNAc expression are not clear. Bisecting GlcNAc is attached to N-glycans through beta 1-4 N-acetylglucosaminyl transferase III (MGAT3), which is encoded by two exons flanked by high-density CpG islands. Despite a recently described correlation of MGAT3 and bisecting GlcNAc in ovarian cancer cells, it remains unknown whether...
1d
Effector memory (EM) CD4(+) T cells recirculate between normoxic blood and hypoxic tissues to screen for cognate Ag. How mitochondria of these cells, shuttling between normoxia and hypoxia, maintain bioenergetic efficiency and stably uphold antiapoptotic features is unknown. In this study, we found that human EM CD4(+) T cells had greater spare respiratory capacity (SRC) than did naive counterparts, which was immediately accessed under hypoxia. Consequently, hypoxic EM cells maintained ATP levels,...
1d
How systemic metabolic alterations during acute infections impact immune cell function remains poorly understood. We found that acetate accumulates in the serum within hours of systemic bacterial infections and that these increased acetate concentrations are required for optimal memory CD8(+) T cell function in vitro and in vivo. Mechanistically, upon uptake by memory CD8(+) T cells, stress levels of acetate expanded the cellular acetyl-coenzyme A pool via ATP citrate lyase and promoted acetylation...
1d
The first phase IIb safety and efficacy trial of a new tuberculosis vaccine since that for BCG was completed in October 2012. BCG-vaccinated South African infants were randomized to receive modified vaccinia virus Ankara, expressing the Mycobacterium tuberculosis antigen 85A (MVA85A), or placebo. MVA85A did not significantly boost the protective effect of BCG. Cryopreserved samples provide a unique opportunity for investigating the correlates of the risk of tuberculosis disease in this population....
1d
An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated...
1d
Transplant patients are at increased risk of viral complications due to impaired control of viral replication, resulting from HLA mismatching between graft and host and the immunosuppression needed to avert alloimmune reactions. In the past decade, quantitative viral load measurements have become widely available to identify patients at risk and to inform treatment decisions with respect to immunosuppressive drugs and antiviral therapies. Because viral loads are viewed as the result of viral replication...
1d
BACKGROUND: Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive. METHODS: We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients...
1d
The non-coding control region (NCCR) of polyomaviruses includes the promoters for early and late genes, a transcription enhancer and the origin of DNA replication. Particularly virulent variants of the human pathogens BKPyV and JCPyV, as well as of simian virus 40 (SV40), occur in vitro and in vivo. These strains often harbour rearrangements in their NCCR, typically deletions of some DNA segment(s) and/or duplications of others. Using an SV40-based model system we provide evidence that duplications...
1d
BACKGROUND: Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS: We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of >/=1 major mutation in a genotypic resistance test. To estimate the prevalence...
1d
BACKGROUND: BK polyomavirus (BKPyV)-associated nephropathy remains a challenge to the success of kidney transplantation, but its impact varies in different transplant programmes. METHODS: We investigated current practice through a web-based questionnaire made available by the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 90 physicians (23% of 391 active members) from 27 countries participated in the study. BKPyV-associated nephropathy is seen in 1-5% of patients annually...
1d
BK polyomavirus (BKPyV) infection represents a major problem in transplantation, particularly for renal recipients developing polyomavirus-associated nephropathy (PyVAN). The possibility that BKPyV may also be oncogenic is not routinely considered. Twenty high-grade renourinary tumors expressing polyomavirus large T antigen in the entirety of the neoplasm in 19 cases, including the metastases in six, have been reported in transplant recipients with a history of PyVAN or evidence of BKPyV infection....
1d
Abstract Saccharomyces cerevisiae ribosomal DNA, the repeated region where rRNAs are synthesized by about 150 encoding units, hosts all the protein machineries responsible for the main DNA transactions such as replication, transcription and recombination. This and its repetitive nature make rDNA a unique and complex genetic locus compared to any other. All the different molecular machineries acting in this locus need to be accurately and finely controlled and coordinated and for...
1d
Abstract A persistent dogma in neuroscience supported the idea that terminally differentiated neurons permanently withdraw from the cell cycle. However, since the late 1990s, several studies have shown that cell cycle proteins are expressed in post-mitotic neurons under physiological conditions, indicating that the cell cycle machinery is not restricted to proliferating cells. Moreover, many studies have highlighted a clear link between cell cycle-related proteins and neurological...
1d
Abstract Purpose Early prediction of clinical response to conventional chemotherapy is a significant factor in determining an overall treatment strategy for osteosarcoma. Methods Cells were extracted from treatment-naïve biopsies from 16 osteosarcoma patients who received a doxorubicin and cisplatin-based neoadjuvant chemotherapy regimen and their sensitivities...
1d
Aggression and suicidality prior to the initiation of treatment are frequent phenomena in psychosis patients. Increased scores in the Brief Psychiatric Rating Scale Excited Component (BPRS-EC) have been shown to predict involuntary treatment, aggression, and suicide in first-episode psychosis (FEP) patients. However, it is unclear if an agitated-aggressive syndrome as measured with the BPRS-EC is already present in at-risk mental state (ARMS).; BPRS-EC scores from 43 ARMS patients, 50 FEP patients,...
1d
Despite the reform efforts of the last decades modern acute psychiatry still stands between conflicting priorities in everyday practice. The protection of patient autonomy might conflict with a regulatory mandate of psychiatry in societal contexts and the necessity of coercive measures and involuntary treatment might become problematic with respect to presumed but contentious interests of the patient. The conflicts particularly concern questions of involuntary commitment, door closing, coercive and...
1d
Change of treatment policy from closed to open ward settings has been shown to reduce coercive measures. The aim of the current study was to examine the effects of the change from closed to open wards on the frequency of seclusion and forced medication in a hospital-wide setting.; 2-year, longitudinal observational study with 2838 inpatient cases.; On a hospital-wide level, the percentage of patients with at least one seclusion was decreased significantly (χ(2)(1) = 5.8; p = .016), while there was...
1d
Atomic force microscopy (AFM) has been proposed as a tool to evaluate the structural and mechanical properties of cartilage tissue. Here, we aimed at assessing whether AFM can be employed to quantify spatially resolved elastic response of tissue engineered cartilage (TEC) to short exposure to IL-1β, thus mimicking the initially inflammatory implantation site. TEC generated by 14 days of pellet-culture of expanded human chondrocytes was left untreated (ctr) or exposed to IL-1β for 3 days. TEC pellets...
1d
Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication...
1d
Final data analysis of SPARTAN trial demonstrates large benefit in overall survival when compared with ADT plus placebo. (Source: CancerNetwork)
1d
Overall survival (OS) benefit derived from frontline treatment with nivolumab plus ipilimumab combined with 2 cycles of platinum-doublet chemotherapy in patients with metastatic or recurrent non-small cell lung cancer was further improved after at least 12 months of follow-up. (Source: CancerNetwork)
1d
A phase III study using cediranib and olaparib to treat recurrent platinum-sensitive ovarian cancer did not meet its primary endpoint of progression-free survival but did produce comparable activity to standard of care platinum-based chemotherapy treatment. (Source: CancerNetwork)
1d
Results showed that axicabtagene ciloleucel demonstrated significant and durable clinical benefit in patients with relapsed or refractory indolent non-Hodgkin lymphoma. (Source: CancerNetwork)
1d
When compared to currently approved therapies, KTE-X19 demonstrated comparable pharmacologic and clinical outcomes in patients with high-risk MCL characteristics versus lower-risk characteristics defined by tumor protein TP53 mutation or high Ki-67 proliferation index. (Source: CancerNetwork)
1d
The MD Anderson Cancer Center expert discussed why there is an unmet need for more treatments in patients with IDH1-mutated acute myeloid leukemia. (Source: CancerNetwork)
1d
Publication date: Available online 30 May 2020Source: Experimental Cell ResearchAuthor(s): Fang Tian, Pengjun Jiang, Min Wu, Yun Xing, Li Liu, Xinbin Dai, Hua Tang, Zhong-Fa Yang, Lixin Wang, Xuejun Zhu
1d
Publication date: Available online 30 May 2020Source: Experimental Cell ResearchAuthor(s): Gowru Srivani, Santosh Kumar Behera, Begum Dariya, Sheik Aliya, Afroz Alam, Ganji Purnachandra Nagaraju
1d
Rearrangements or point mutations in the noncoding control region (NCCR) of BK polyomavirus (BKPyV) have been associated with higher viral loads and more pronounced organ pathology in immunocompromised patients. The respective alterations affect a multitude of transcription factor binding sites (TFBS) but consistently cause increased expression of the early viral gene region (EVGR) at the expense of late viral gene region (LVGR) expression. By mutating TFBS, we identified three phenotypic groups...
1d
Respiratory tract infection (RTI) involves a variety of viruses and bacteria, which can be conveniently detected by multiplex nucleic acid amplification testing (NAT). To compare the novel Luminex-based NxTAG-Respiratory Pathogen Panel (NxTAG-RPP) with the routine multiplex-ligation-NAT based RespiFinder-22(R) (RF-22), 282 respiratory specimens including nasopharyngeal swabs (71%), broncho-alveolar lavage (27%), throat swabs, tracheal secretions, and sputum (2%) from 116 children and 155 adults were...
1d
Intrathymic T-cell development is critically dependent on cortical and medullary thymic epithelial cells (TECs). Both epithelial subsets originate during early thymus organogenesis from progenitor cells that express the thymoproteasome subunit beta5t, a typical feature of cortical TECs. Using in vivo lineage fate mapping, we demonstrate in mice that beta5t(+) TEC progenitors give rise to the medullary TEC compartment early in life but significantly limit their contribution once the medulla has completely...
1d
Thymic epithelial cell differentiation, growth and function depend on the expression of the transcription factor Foxn1; however, its target genes have never been physically identified. Using static and inducible genetic model systems and chromatin studies, we developed a genome-wide map of direct Foxn1 target genes for postnatal thymic epithelia and defined the Foxn1 binding motif. We determined the function of Foxn1 in these cells and found that, in addition to the transcriptional control of genes...
1d
The induction of innate and adaptive immunity is essential for controlling viral infections. Limited or overwhelming innate immunity can negatively impair the adaptive immune response. Therefore, balancing innate immunity separately from activating the adaptive immune response would result in a better antiviral immune response. Recently, we demonstrated that Usp18-dependent replication of virus in secondary lymphatic organs contributes to activation of the innate and adaptive immune responses. Whether...
1d
The cold-inducible RNA-binding motif protein 3 (RBM3) is involved in the protection of neurons in hypoxic-ischemic and neurodegenerative disorders. RBM3 belongs to a small group of proteins whose synthesis increases during hypothermia while global protein production is slowed down. To investigate the molecular mechanisms underlying RBM3 action, we subjected hippocampal organotypic slice cultures from RBM3 knockout mice to various stressors and found exuberant signaling of the endoplasmic reticulum...
1d
Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo and extra-terminal) inhibitors and their significant activity in diverse tumor models have rapidly translated into clinical studies and have motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of BRD protein complexes complicates predictions of the consequences of their pharmacological targeting. To address this...
1d
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου