Correlation between improved leptin signaling and cognitive function post bariatric surgery.

Determining whether changes in leptin signaling plays a role in the improvement of cognitive function post-bariatric surgery may aid in the understanding and development of novel therapeutic approaches targeting cognitive dysfunction through the greater understanding of processes connecting obesity and brain health. Several studies have explored the effects of cognition post bariatric surgery, and others have studied leptin and its changes post surgery. However the amalgamation of the effects of leptin signaling in relation to cognition post bariatric surgery have yet to be considered as key tools in the understanding of cognitive dysfunction in obese subjects with leptin resistance or insensitivity. This review serves to highlight the potential correlations, to further elucidate the effect of improved leptin signaling on cognition post bariatric surgery, and to propose a direct cause for the improvement of cognitive function via the amelioration of the leptin Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway as a result of the reversal of inflammatory processes involved in diseased individuals.

Malignant cerebral infarction after ChAdOx1 nCov-19 vaccination: a catastrophic variant of vaccine-induced immune thrombotic thrombocytopenia.

Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine. Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination. The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes. None of the patients had ever received heparin in the past before stroke onset. Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.

Lymphographic-Like Technique for the Treatment of Microcystic Lymphatic Malformation Components of <3 mm.

BACKGROUND AND PURPOSE: The treatment of microcystic lymphatic malformations remains challenging. Our aim was to describe the lymphographic-like technique, a new technique of slow bleomycin infusion for the treatment of microcyst components of <3 mm, performed at our institution. MATERIALS AND METHODS: A retrospective analysis of a prospectively collected lymphatic malformation data base was performed. Patients with at least 1 microcystic lymphatic malformation component demonstrated on MR imaging treated by lymphographic-like technique bleomycin infusion were included in the study. Patient interviews and MR imaging were performed to assess subjective and objective (microcystic lymphatic malformation size decrease of >30%) clinical improvement, respectively. Patients were reviewed 3 months after each sclerotherapy session. Lymphographic-like technique safety and efficacy were assessed. RESULTS: Between January 2012 and July 2016, sixteen patients (5 males, 11 females; mean age, 15 years; range, 1-47 years) underwent the bleomycin lymphographic-like technique for microcystic lymphatic malformations. Sixty sclerotherapy sessions were performed, with a mean of 4 sessions per patient (range, 1-8 sessions) and a mean follow-up of 26 months (range, 5-58 months). We observed no major and 3 minor complications: 1 eyelid infection, 1 case of severe postprocedural nausea and vomiting, and 1 case of skin discoloration. One patient was lost to follow-up. Overall MR imaging objective improvement was observed in 5/16 (31%) patients; overall improvement of clinical symptoms was obtained in 93% of treated patients. CONCLUSIONS: The bleomycin lymphographic-like technique for microcystic lymphatic malformations is safe and feasible with objective improvement in about one-third of patients. MR signal intensity changes after the lymphographic-like technique are associated with subjective improvement of the patient's symptoms.

Preoperative embolization of meningiomas with polyvinyl alcohol particles: The benefits are not outweighed by risks.

PURPOSE: The purpose of this study was to define the feasibility, the efficacy and the safety of preoperative embolization (POE) of meningiomas using polyvinyl alcohol (PVA) particles. MATERIALS AND METHODS: Between January 2006 and June 2014, 191 consecutive patients were referred to our institution for the treatment of meningiomas; of these 57 patients were excluded from the study. A total of 64 patients (22 men and 42 women) with a mean age of 58.4±10.8 [SD] years (range: 14-82years) who underwent POE with PVA particles, achieving extensive (>90%) devascularization were ultimately included and compared to 70 patients who had surgery without POE. Surgical time and intraoperative blood loss were compared between the two groups. The duration of procedures and complications related to POE were analyzed. RESULTS: No differences were found between the two groups with respect to intraoperative blood loss. A significant reduction in surgical time was observed for the group who had POE (207.4±79.5 [SD] min vs. 226.9±117.6 [SD] min; P=0.028). In a subgroup analysis, the size and location of meningiomas did not influence these results. The duration of procedures was 41.4±10.5 [SD] min. Minor complications related to POE occurred in 3 out of 64 patients (4.7%). CONCLUSION: POE of meningiomas using PVA particles is effective in reducing surgical time, when extensive tumor devascularization is achieved. However, radiation exposure, the duration of procedures and complications related to POE with PVA particles do not justify this technique in most patients.

Tolerance to silver of an Aspergillus fumigatus strain able to grow on cyanide containing wastes.

We studied the strategy of an Aspergillus fumigatus strain able to grow on metal cyanide wastes to cope with silver. The tolerance test revealed that the Minimum Inhibitory Concentration of Ag(I) was 6mM. In 1mM AgNO3 aqueous solution the fungus was able to reduce and sequestrate silver into the cell in the form of nanoparticles as evidenced by the change in color of the biomass and Electron Microscopy observations. Extracellular silver nanoparticle production also occurred in the filtrate solution after previous incubation of the fungus in sterile, double-distilled water for 72h, therefore evidencing that culture conditions may influence nanoparticle formation. The nanoparticles were characterized by UV-vis spectrometry, X-ray diffraction and Energy Dispersion X-ray analysis. Atomic absorption spectrometry revealed that the optimum culture conditions for silver absorption were at pH 8.5.The research is part of a polyphasic study concerning the behavior of the fungal strain in presence of metal cyanides; the results provide better understanding for further research targeted at a rationale use of the microorganism in bioremediation plans, also in view of possible metal recovery. Studies will be performed to verify if the fungus maintains its ability to produce nanoparticles using KAg(CN)2.

Reduced NFAT1 protein expression in human umbilical cord blood T lymphocytes.

Umbilical cord blood (UCB) stem cells from related and unrelated allogeneic donors have emerged as novel treatment for patients with hematologic malignancies. The incidence and severity of acute graft-versus-host disease (GVHD) after UCB transplantation compares favorably with that observed in recipients of matched unrelated donor allogeneic grafts, but remains a major cause of morbidity and mortality. It has been shown that stimulated lymphocytes from UCB have reduced production of cytokines including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which play a role in GVHD pathophysiology. We investigated the molecular mechanisms underlying this reduced cytokine production by analyzing expression of nuclear factor of activated T cells-1 (NFAT1) in UCB T cells. We detected no constitutive expression of NFAT1 protein in unstimulated UCB T cells compared with adult T cells. Moreover, although NFAT1 expression in UCB T cells was upregulated after prolonged (40 hours) T-cell stimulation, it was only partially upregulated when compared with adult controls. Our observation of minimal NFAT1 expression after stimulation correlated with reduced cytoplasmic IFN-gamma and TNF-alpha production in UCB T cells studied simultaneously. Reduced NFAT1 expression may blunt amplification of donor UCB T-cell alloresponsiveness against recipient antigens, thereby potentially limiting GVHD incidence and severity after allogeneic UCB transplantation.

Dendritic cells improve the generation of Epstein-Barr virus-specific cytotoxic T lymphocytes for the treatment of posttransplantation lymphoma.

BACKGROUND: The use of immunosuppressive therapies after solid organ transplantation has been shown to increase a patient's risk for Epstein-Barr virus (EBV)-associated lymphoma. A potential therapy for this disorder is the adoptive transfer of EBV-specific cytotoxic T lymphocytes (CTLs). We proposed that dendritic cells (DCs) could be loaded with EBV antigens and be used to improve the in vitro generation of EBV-specific CTLs. METHODS: Autologous EBV-transformed B-lymphoblastoid cell lines (BLCLs) were generated from normal donors, and CTLs were initiated by culturing peripheral blood mononuclear cells with DCs alone, disrupted BLCLs alone, intact, irradiated BLCLs alone, and DCs loaded with disrupted BLCLs. Lytic activities were determined with a 4-hour chromium-release assay against autologous BLCLs, and statistical calculations were performed by a Student t test assuming equal variance. RESULTS: The lytic activity of CTLs generated with DCs loaded with disrupted BLCLs reached 78% and was statistically significant (P < .01) at all effector/target ratios compared with CTLs generated with DCs alone, disrupted BLCLs alone, or intact BLCLs alone. Total numbers of CTLs were also greater than those of control groups for DCs loaded with disrupted BLCLs. CONCLUSIONS: DCs improved the in vitro generation of EBV-specific CTLs as evidenced by this group's significantly increased lytic activity over that of the control group. The improved lytic activity of DC-generated EBV-CTLs suggests that adoptive transfer of these cells could lead to a more effective immunotherapeutic response against posttransplantation EBV-associated lymphoma.

Active immunotherapy with transiently transfected cytokine-secreting tumor cells inhibits breast cancer metastases in tumor-bearing animals.

BACKGROUND: Metastatic disease remains the most frequent cause of treatment failure in the management of patients with breast cancer. A novel method that allows delivery of a gene into primary tumor cells was used to generate tumor cell vaccines to inhibit metastasis formation in tumor-bearing hosts. METHODS: Inoculation of 2.5 x 10(4) 4T1 murine breast cancer cells into the footpads of BALB/c mice reliably leads to tumor growth and pulmonary metastases. Interleukin-2 (IL-2)-secreting 4T1 cells (4T1-pMP6A/IL-2) and control transduced 4T1 cells (4T1-pMP6A) were generated by lipofection with a cationic liposome complexed to an adeno-associated viral plasmid bearing the IL-2 gene (pMP6A/IL-2). Unmodified 4T1 cells were inoculated into the footpads on day 0, and weekly immunization with phosphate-buffered saline solution or 2 x 10(6) irradiated 4T1, 4T1-pMP6A, or 4T1-pMP6A/IL-2 cells commenced on day 21. Hindlimb amputation was performed when tumors measured 6 mm in diameter. Mice were killed 24 days after amputation, and metastatic disease was determined by weighing lungs at time of harvest. RESULTS: A significant reduction was seen in the pulmonary metastatic load of mice receiving IL-2 gene-modified tumor cell immunization (4T1-pMP6A/IL2) when compared with mice given control immunizations. CONCLUSIONS: These results suggest that active immunization strategies with cytokine gene-modified tumor cells generated by clinically relevant gene delivery systems may prove useful in inhibiting the development of metastases from primary breast cancer.

A null mutation in the first enzyme of flavonoid biosynthesis does not affect male fertility in Arabidopsis.

Flavonoids are a major class of secondary metabolites that serves a multitude of functions in higher plants, including a recently discovered role in male fertility. Surprisingly, Arabidopsis plants deficient in flavonoid biosynthesis appear to be fully fertile. Using RNA gel blot analysis and polymerase chain reaction-based assays, we have shown that a mutation at the 3' splice acceptor site in the Arabidopsis chalcone synthase gene completely disrupts synthesis of the active form of the enzyme. We also confirmed that this enzyme, which catalyzes the first step of flavonoid biosynthesis, is encoded by a single-copy gene. HPLC analysis of whole flowers and stamens was used to show that plants homozygous for the splice site mutation are completely devoid of flavonoids. This work provides compelling evidence that despite the high levels of these compounds in the pollen of most plant species, flavonoids are not universally required for fertility. The role of flavonoids in plant reproduction may therefore offer an example of convergent functional evolution in secondary metabolism.