Stabilization of high-order solutions of the cubic Nonlinear Schrodinger Equation

In this paper we consider the stabilization of non-fundamental unstable stationary solutions of the cubic nonlinear Schrodinger equation. Specifically we study the stabilization of radially symmetric solutions with nodes and asymmetric complex stationary solutions. For the first ones we find partial stabilization similar to that recently found for vortex solutions while for the later ones stabilization does not seem possible

Limb amputations; etiopathogenesis, diagnosis and the multidisciplinary therapeutic approach

Despite remarkable advances in medicine, limb amputations remain a therapeutic measure that saves the lives of many patients. Given the varied etiopathogenesis, such operations are performed both as an emergency and as an elective procedure. Such interventions address either only the distal segments of a limb, or even the entire limb, having a great psychological, functional and social impact on the patient. Due to these multiple implications, limb amputations must be performed by specialized teams, in order to achieve the best possible functional and aesthetic results to be compatible with the correction of the remaining deficit with a prosthesis. The main causes leading to amputations and the corresponding preventive measures are presented, as well as the general principles of amputations as a therapeutic solution of last resort. In conclusion, reducing the number of traffic/workplace accidents and effective treatment of chronic diseases affecting the vascular system can contribute to decreasing the need for amputations, a life-saving therapeutic solution, but with a devastating impact on the patient and society

Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo

We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3(+) T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34(+) progenitor cells derived from 1 further patient and I healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34(+) progenitors during transduction. In contrast to those in CD34(+) cells, RISs recovered from engrafted CD3(+)T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation

Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency

BACKGROUND: X-linked inhibitor of apoptosis protein (XIAP) deficiency is a severe immunodeficiency with clinical features including hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) due to defective NOD2 responses. Management includes immunomodulatory therapies and hematopoietic stem cell transplant (HSCT). However, this cohort is particularly susceptible to the chemotherapeutic regimens and acutely affected by graft-vs-host disease (GvHD), driving poor long-term survival in transplanted patients. Autologous HSC gene therapy could offer an alternative treatment option and would abrogate the risks of alloreactivity. METHODS: Hematopoietic progenitor (Lin-ve) cells from XIAPy/- mice were transduced with a lentiviral vector encoding human XIAP cDNA before transplantation into irradiated XIAP y/- recipients. After 12 weeks animals were challenged with the dectin-1 ligand curdlan and recovery of innate immune function was evaluated though analysis of inflammatory cytokines, body weight, and splenomegaly. XIAP patient-derived CD14+ monocytes were transduced with the same vector and functional recovery was demonstrated using in vitro L18-MDP/NOD2 assays. RESULTS: In treated XIAPy/- mice, ~40% engraftment of gene-corrected Lin-ve cells led to significant recovery of weight loss, splenomegaly, and inflammatory cytokine responses to curdlan, comparable to wild-type mice. Serum IL-6, IL-10, MCP-1, and TNF were significantly reduced 2-h post-curdlan administration in non-corrected XIAPy/- mice compared to wild-type and gene-corrected animals. Appropriate reduction of inflammatory responses was observed in gene-corrected mice, whereas non-corrected mice developed an inflammatory profile 9 days post-curdlan challenge. In gene-corrected patient CD14+ monocytes, TNF responses were restored following NOD2 activation with L18-MDP. CONCLUSION: Gene correction of HSCs recovers XIAP-dependent immune defects and could offer a treatment option for patients with XIAP deficiency

Upper gastrointestinal bleeding during the COVID-19 pandemic; particularities of diagnosis and therapy

SARS-COV 2 recently caused a global pandemic, with the first case being reported in Romania in February 2020. Important restrictive measures were imposed, so that the addressability of patients to medical services decreased. Upper gastrointestinal bleeding had more severe forms of evolution at the time of presentation, which required additional methods of diagnosis and treatment. This is a retrospective study performed on 268 patients, which aims to evaluate the type and effectiveness of different treatment methods for upper gastrointestinal bleeding during the COVID 19 pandemic. Severity assessment was performed by measuring the Rockall score and additional methods of diagnosis. The association of COVID-19 with upper gastrointestinal bleeding can lead to much more severe outcomes for the patient, so treatment must be sustained and fast established. If the initial therapeutic methods fail, the other available therapeutic measures should be introduced progressively and without delay to achieve the best possible outcomes

Current principles for the surgical treatment of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma is one of the most aggressive forms of cancer. It is usually diagnosed in advanced stages of the disease, mainly because it is asymptomatic for a long time after the onset. Consequently, intrahepatic cholangiocarcinoma still represents an important problem of diagnosis and treatment. In the multidisciplinary treatment of these patients, oncological surgery is essential, as the accuracy of resection is one of the most important prognostic factors for the long-term results of these patients. Therefore, there has been a continuing concern to improve surgical techniques, with the aim of maximizing the chances of achieving the best possible long-term survival. The purpose of this paper is to discuss the surgical standard of care in intrahepatic cholangiocarcinoma, with particular attention being paid to resection margins and lymph node dissection. For unresectable cholangiocarcinoma, locoregional therapy can be used such as transarterial chemoembolization, transarterial radioembolization, thermal ablation, radiotherapy and hepatic artery infusion pump chemotherapy

Diabetes mellitus and associated complications in the digestive tract

Diabetes mellitus presents an increasing prevalence and severe multisystemic complications, with notable personal, professional and social implications. Diabetes is generally known by hyperglycemia and subsequent metabolic disorders. In addition to hyperglycemia, it appears that other factors (related to anthropometric-pathophysiology and genome-based subphenotyping) are involved not only in the clinical course but also in the occurrence of diabetes complications. This review presents several diabetes-induced complications on the digestive tract (periodontal disease, xerostomia, oral infections, dental caries, taste disturbances, gastroesophageal reflux disease, gastroparesis, gastric ulcer and cancer, diabetic enteropathy, inflammatory bowel diseases, colorectal cancer, etc.), many of them with major implications and unfavorable long-term prognosis. Consequently, prompt recognition and treatment of diabetes and its complications, as well as strict follow-up education, still remain essential for the effective management of this complex metabolic disease

Pancreatic cancer; from effective prevention and early diagnosis to personalized therapy

Despite substantial improvements in survival rates for most cancers, pancreatic cancer still remains a leading cause of death from malignancy. The disease has no symptoms in the initial stages, it can early invade the surrounding organs, and treatment methods have poor long-term prognosis. In addition, this neoplasia is starting to be diagnosed more and more frequently in young people. High incidences have been found in developed regions such as Europe, North America, Australia, but recent data show that this condition is increasing in other regions as well. Pancreatic cancer involves multiple factors such as cigarette smoking, obesity, diabetes, alcohol consumption, inherited genetic factors, recent studies also correlating pancreatic cancer with abnormal metabolism of human microorganisms, blood type, as well as glucose and lipid levels. This review aims to update knowledge on the epidemiology, pathophysiology, diagnosis and treatment of pancreatic cancer. The goal is to encourage screening and early diagnosis methods, as well as to stimulate further research on this oncological topic, insufficiently studied to date

Thymus transplantation for complete DiGeorge syndrome: European experience

Background: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods: Twelve patients with cDGS were transplanted with allogeneic cultured thymus. Objective: To confirm and extend the results previously obtained in a single centre. Results: Two patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x10663 /L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per106 65 T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1). Conclusions: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors