Genome-wide meta-analysis associates donor-recipient non-HLA genetic mismatch with acute cellular rejection post-liver transplantation.

Background: Acute cellular rejection (ACR) remains a common complication causing significant morbidity post-liver transplantation. Non-human leukocyte antigen (non-HLA) mismatches were associated with an increased risk of ACR in kidney transplantation. Therefore, we hypothesized that donor-recipient non-HLA genetic mismatch is associated with increased ACR incidence post-liver transplantation.

Neurocognitive, Clinical and Reelin Activity in Rehabilitation Using Neurofeedback Therapy in Patients with Schizophrenia.

Reelin is a neuropeptide responsible for the migration and positioning of pyramidal neurons, interneurons, and Purkinje cells. In adulthood, it still supports neuroplasticity, especially dendritic spines formation and glutamatergic neurotransmission. Genetic studies have confirmed the involvement of reelin system failure in the etiopathogenesis of mental diseases, including schizophrenia.

Donor and recipient genetics: Implications for the development of posttransplant diabetes mellitus.

Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated.

Assessing the Utility of a Genotype-Guided Tacrolimus Equation in African American Kidney Transplant Recipients: A Single Institution Retrospective Study.

Tacrolimus metabolism is heavily influenced by the CYP3A5 genotype, which varies widely among African Americans (AA). We aimed to assess the performance of a published genotype-informed tacrolimus dosing model in an independent set of adult AA kidney transplant (KTx) recipients. CYP3A5 genotypes were obtained for all AA KTx recipients (n = 232) from 2010 to 2019 who met inclusion criteria at a single transplant center in Philadelphia, Pennsylvania, USA.

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity.

Dietary assessment of type 2 diabetic patients using healthful plant-based diet score in the Eastern Province of Saudi Arabia.

Background: Diabetes mellitus is a chronic disease characterized by a wide range of metabolic problems. The current study sought to assess nutritional habits of Saudi patients with type 2 diabetes (T2D) and to propose recommendations to improve these patients' dietary habits and delay possible disease complications.

Methods: Over a period of three years, (2017-2019) 577 patients with T2D attending the outpatient's diabetic clinics at King Fahd Hospital of the University, Al Khobar, Saudi Arabia were invited to participate in this study.

Reelin Signaling and Synaptic Plasticity in Schizophrenia.

Recent research emphasizes the significance of studying the quality of life of schizophrenia patients, considering the complex nature of the illness. Identifying neuronal markers for early diagnosis and treatment is crucial. Reelin (RELN) stands out among these markers, with genetic studies highlighting its role in mental health.

Brain-derived neurotrophic factor and matrix metalloproteinase-9 activity during rehabilitation therapy of schizophrenic patients - environmental pilot study.

Introduction And Objective: The aim of the study was to evaluate the peripheral level of brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) during rehabilitation therapy, combined with neurofeedback in schizophrenic patients, and to investigate whether these biomarkers are related to psychopathological symptoms, changes in auditory evoked potentials (AEPs), and quantitative EEG (QEEGs) mapping.

Material And Methods: The study involved two groups of patients diagnosed with paranoid schizophrenia in partial remission who participated in a 3-month structured rehabilitation programme combined with neurofeedback (REH group) and a standard support group (CON group). The following parameters were assessed: BDNF and MMP-9 serum levels, AEPs, QEEGs, and psychopathological symptoms (PANSS).

Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment.

Schizophrenia is a chronic and relapsing disorder that is characterized not only by delusions and hallucinations but also mainly by the progressive development of cognitive and social deficits. These deficits are related to impaired synaptic plasticity and impaired neurotransmission in the nervous system. Currently, technological innovations and medical advances make it possible to use various self-regulatory methods to improve impaired synaptic plasticity.

Whole-exome sequencing analyses in a Saudi Ischemic Stroke Cohort reveal association signals, and shows polygenic risk scores are related to Modified Rankin Scale Risk.

Ischemic stroke represents a significant societal burden across the globe. Rare high penetrant monogenic variants and less pathogenic common single nucleotide polymorphisms (SNPs) have been described as being associated with risk of diseases. Genetic studies in Saudi Arabian patients offer a greater opportunity to detect rare high penetrant mutations enriched in these consanguineous populations.

LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.

Background: Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect.

Relationship of Neuropeptide S (NPS) with Neurocognitive, Clinical, and Electrophysiological Parameters of Patients during Structured Rehabilitation Therapy for Schizophrenia.

Introduction: Neuropeptide S is a biomarker related to various neuropsychiatric and neurocognitive functions. Since the need to improve cognitive functions in schizophrenia is unquestionable, it was valuable to investigate the possible relationships of plasma levels of NPS with neurocognitive, psychopathological and EEG parameters in patients with schizophrenia.

Aim: Relationships between the serum NPS level and neurocognitive, clinical, and electrophysiological parameters were investigated in patients diagnosed with schizophrenia who underwent structured rehabilitation therapy.

The Course of LIRADS 3 and 4 Hepatic Abnormalities as Correlated With Explant Pathology: A Single Center Experience.

Background And Aims: The Liver Reporting and Data System (LI-RADS) is the standard classification of imaging findings of hepatic abnormalities for hepatocellular carcinoma (HCC) surveillance. We aimed to study the course of LI-RADS 3 and 4 (LR-3 and LR-4) abnormalities through correlations with explant pathology.

Methods: A single center retrospective study of liver transplant recipients between January 2016 and September 2019 with HCC on explant pathology was conducted.

Relationship of Neuropeptide S with Clinical and Metabolic Parameters of Patients during Rehabilitation Therapy for Schizophrenia.

Neuropeptide S (NPS) is a factor associated with the central regulation of body weight, stress, anxiety, learning, memory consolidation, wakefulness-sleep cycle, and anti-inflammatory and neuroplastic effects. Its stress-reducing, anti-anxiety, arousal without anxiety, and pro-cognitive effects represent an interesting option for the treatment of neuropsychiatric disorders. The purpose of the study was to examine the potential associations of NPS levels in the blood with clinical and metabolic parameters during the rehabilitation therapy of patients with schizophrenia.

Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes.

Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n = 1,581) and their donors (n = 1,555), and kidney recipients (n = 2,062) and their donors (n = 533).

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients.

Background: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y inhibitor.

Improving Clinical, Cognitive, and Psychosocial Dysfunctions in Patients with Schizophrenia: A Neurofeedback Randomized Control Trial.

Objectives: The aim of this study was to use neurofeedback (NF) training as the add-on therapy in patients with schizophrenia to improve their clinical, cognitive, and psychosocial condition. The study, thanks to the monitoring of various conditions, quantitative electroencephalogram (QEEG) and brain-derived neurotrophic factor (BDNF), was supposed to give an insight into mechanisms underlying NF training results.

Methods: Forty-four male patients with schizophrenia, currently in a stable, incomplete remission, were recruited into two, 3-month rehabilitation programs, with standard rehabilitation as a control group (R) or with add-on NF training (NF).

Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation.

Background: Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients.

Methods: Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected.

Joint testing of donor and recipient genetic matching scores and recipient genotype has robust power for finding genes associated with transplant outcomes.

Genetic matching between transplant donor and recipient pairs has traditionally focused on the human leukocyte antigen (HLA) regions of the genome, but recent studies suggest that matching for non-HLA regions may be important as well. We assess four genetic matching scores for use in association analyses of transplant outcomes. These scores describe genetic ancestry distance using identity-by-state, or genetic incompatibility or mismatch of the two genomes and therefore may reflect different underlying biological mechanisms for donor and recipient genes to influence transplant outcomes.

Predictors, Presentation, and Treatment Outcomes of Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Large Single Center Experience.

Background: Liver transplantation (LT) is an accepted therapeutic option for hepatocellular carcinoma (HCC) in patients with cirrhosis. Despite careful candidate selection, HCC recurrence occurs. We aimed to describe the predictors of recurrence, clinical presentation, and predictors of survival after HCC recurrence post-LT.

Genome-wide non-HLA donor-recipient genetic differences influence renal allograft survival via early allograft fibrosis.

Donor-recipient (D-R) differences at human leukocyte antigen (HLA) loci are currently incorporated into organ sharing, allocation and immunosuppression decisions. However, while acute rejection episodes have substantially diminished, progressive histologic damage occurs in allografts and improved long-term survival remains an unrealized goal among kidney recipients. Here we tested the hypothesis that non-HLA dependent, genome-wide D-R genetic differences could contribute to unchecked alloimmunity with histologic and functional consequences, culminating in long-term allograft failure.