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1.
Neurosci Biobehav Rev ; 163: 105744, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38825259

ABSTRACT

Every species' brain, body and behavior is shaped by the contingencies of their evolutionary history; these exert pressures that change their developmental trajectories. There is, however, another set of contingencies that shape us and other animals: those that occur during a lifetime. In this perspective piece, we show how these two histories are intertwined by focusing on the individual. We suggest that organisms--their brains and behaviors--are not solely the developmental products of genes and neural circuitry but individual centers of action unfolding in time. To unpack this idea, we first emphasize the importance of variation and the central role of the individual in biology. We then go over "errors in time" that we often make when comparing development across species. Next, we reveal how an individual's development is a process rather than a product by presenting a set of case studies. These show developmental trajectories as emerging in the contexts of the "the actual now" and "the presence of the past". Our consideration reveals that individuals are slippery-they are never static; they are a set of on-going, creative activities. In light of this, it seems that taking individual development seriously is essential if we aspire to make meaningful comparisons of neural circuits and behavior within and across species.


Subject(s)
Biological Evolution , Brain , Brain/physiology , Brain/growth & development , Animals , Humans
3.
Aliment Pharmacol Ther ; 59(12): 1527-1538, 2024 06.
Article in English | MEDLINE | ID: mdl-38629442

ABSTRACT

BACKGROUND: Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. AIM: We aimed to evaluate disease progression and outcomes in NCPH. METHODS: Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. RESULTS: Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. CONCLUSIONS: Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.


Subject(s)
Disease Progression , Hypertension, Portal , Humans , Hypertension, Portal/physiopathology , Hypertension, Portal/complications , Hypertension, Portal/diagnosis , Male , Female , Prospective Studies , Middle Aged , Adult , Platelet Count , Liver/pathology , Liver/physiopathology , Aged , Liver Cirrhosis/complications , Liver Cirrhosis/physiopathology , Biopsy
4.
Int J Gen Med ; 17: 1297-1310, 2024.
Article in English | MEDLINE | ID: mdl-38590998

ABSTRACT

Background: Fungal infections, especially those caused have emerged as a significant medical concern over the past three decades, particularly among immunocompromised patients. However, recent studies have highlighted the increasing prevalence of fungal infections resembling yeast other than Candida, such as trichosporonosis, especially among immunosuppressed individuals worldwide. Trichosporon has been identified as a significant contributor to superficial and invasive infections. Invasive trichosporonosis, primarily affecting immunocompromised patients, poses a significant threat with high mortality rates. Purpose: The current study aimed to explore the clinical epidemiology of Trichosporon spp at King Abdulaziz University Hospital (KAUH) in Saudi Arabia. Methods: This retrospective study aimed to assess the clinical epidemiology of Trichosporon spp. infections in microbiology cultures obtained from KAUH in Saudi Arabia. The study analyzed data from patients over a five-year period, focusing on demographic, clinical, and microbiological characteristics. Results: This study encompassed 21 participants, categorized into four distinct age groups. Moreover, this study indicated T. asahii as the predominant species isolated, accounting for 90.5% of infections, followed by T. mucoides (9.5%). ICU hospitalization, diabetes mellitus, taking immunosuppressive drugs, and antifungal drugs, and the use of invasive medical equipment were identified as prominent risk factors for trichosporonosis. Urinary tract infections were the most common clinical presentation, particularly among male and elderly patients. Mortality rates were high, especially among older individuals. Conclusion: This study contributes valuable epidemiological insights into trichosporonosis, highlighting the need for enhanced surveillance and preventive strategies in healthcare settings. Further research is warranted to optimize treatment approaches and infection control measures, ultimately reducing the burden of Trichosporon infections on patient outcomes.

5.
Aliment Pharmacol Ther ; 59(9): 1020-1032, 2024 05.
Article in English | MEDLINE | ID: mdl-38497159

ABSTRACT

BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.


Subject(s)
Carcinoma, Hepatocellular , Fontan Procedure , Liver Neoplasms , Child , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/surgery , Incidence , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Liver Neoplasms/surgery , Fontan Procedure/adverse effects , Liver Cirrhosis/etiology , Liver Cirrhosis/complications , Risk Factors
6.
ACS Nano ; 18(8): 6215-6228, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38345911

ABSTRACT

MoS2-based field-effect transistors (FETs) and, in general, transition metal dichalcogenide channels are fundamentally limited by high contact resistance (RC) and intrinsic defects, which results in low drive current and lower carrier mobilities, respectively. This work addresses these issues using a technique based on CF4 plasma treatment in the contacts and further cyclic field-assisted drift and activation of the fluorine ions (F-), which get introduced into the contact region during the CF4 plasma treatment. The F- ions are activated using cyclic pulses applied across the source-drain (S/D) contacts, which leads to their migration to the contact edges via the channel. Further, using ab initio molecular dynamics and density functional theory simulations, these F- ions are found to bond at sulfur (S) vacancies, resulting in their passivation and n-type doping in the channel and near the S/D contacts. An increase in doping results in the narrowing of the Schottky barrier width and a reduction in RC by ∼90%. Additionally, the passivation of S vacancies in the channel enhances the mobility of the FET by ∼150%. The CF4 plasma treatment in contacts and further cyclic field-assisted activation of F- ions resulted in an ON-current (ION) improvement by ∼90% and ∼480% for exfoliated and CVD-grown MoS2, respectively. Moreover, this improvement in ION has been achieved without any deterioration in the ION/IOFF, which was found to be >7-8 orders.

7.
J Inherit Metab Dis ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38421058

ABSTRACT

The balance between a protective and a destructive immune response can be precarious, as exemplified by inborn errors in nucleotide metabolism. This class of inherited disorders, which mimics infection, can result in systemic injury and severe neurologic outcomes. The most common of these disorders is Aicardi Goutières syndrome (AGS). AGS results in a phenotype similar to "TORCH" infections (Toxoplasma gondii, Other [Zika virus (ZIKV), human immunodeficiency virus (HIV)], Rubella virus, human Cytomegalovirus [HCMV], and Herpesviruses), but with sustained inflammation and ongoing potential for complications. AGS was first described in the early 1980s as familial clusters of "TORCH" infections, with severe neurology impairment, microcephaly, and basal ganglia calcifications (Aicardi & Goutières, Ann Neurol, 1984;15:49-54) and was associated with chronic cerebrospinal fluid (CSF) lymphocytosis and elevated type I interferon levels (Goutières et al., Ann Neurol, 1998;44:900-907). Since its first description, the clinical spectrum of AGS has dramatically expanded from the initial cohorts of children with severe impairment to including individuals with average intelligence and mild spastic paraparesis. This broad spectrum of potential clinical manifestations can result in a delayed diagnosis, which families cite as a major stressor. Additionally, a timely diagnosis is increasingly critical with emerging therapies targeting the interferon signaling pathway. Despite the many gains in understanding about AGS, there are still many gaps in our understanding of the cell-type drivers of pathology and characterization of modifying variables that influence clinical outcomes and achievement of timely diagnosis.

8.
J Immunol ; 212(6): 982-991, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38265261

ABSTRACT

Multiple sclerosis, and its murine model experimental autoimmune encephalomyelitis (EAE), is a neurodegenerative autoimmune disease of the CNS characterized by T cell influx and demyelination. Similar to other autoimmune diseases, therapies can alleviate symptoms but often come with side effects, necessitating the exploration of new treatments. We recently demonstrated that the Cullin-RING E3 ubiquitin ligase 4b (CRL4b) aided in maintaining genome stability in proliferating T cells. In this study, we examined whether CRL4b was required for T cells to expand and drive EAE. Mice lacking Cul4b (Cullin 4b) in T cells had reduced EAE symptoms and decreased inflammation during the peak of the disease. Significantly fewer CD4+ and CD8+ T cells were found in the CNS, particularly among the CD4+ T cell population producing IL-17A, IFN-γ, GM-CSF, and TNF-α. Additionally, Cul4b-deficient CD4+ T cells cultured in vitro with their wild-type counterparts were less likely to expand and differentiate into IL-17A- or IFN-γ-producing effector cells. When wild-type CD4+ T cells were activated in vitro in the presence of the recently developed CRL4 inhibitor KH-4-43, they exhibited increased apoptosis and DNA damage. Treatment of mice with KH-4-43 following EAE induction resulted in stabilized clinical scores and significantly reduced numbers of T cells and innate immune cells in the CNS compared with control mice. Furthermore, KH-4-43 treatment resulted in elevated expression of p21 and cyclin E2 in T cells. These studies support that therapeutic inhibition of CRL4 and/or CRL4-related pathways could be used to treat autoimmune disease.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Mice , Animals , Interleukin-17/metabolism , Cullin Proteins/metabolism , CD4-Positive T-Lymphocytes , Mice, Inbred C57BL
9.
Am J Transplant ; 24(1): 46-56, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37739347

ABSTRACT

Kidney paired donation (KPD) is a major innovation that is changing the landscape of kidney transplantation in the United States. We used the 2006-2021 United Network for Organ Sharing data to examine trends over time. KPD is increasing, with 1 in 5 living donor kidney transplants (LDKTs) in 2021 facilitated by KPD. The proportion of LDKT performed via KPD was comparable for non-Whites and Whites. An increasing proportion of KPD transplants are going to non-Whites. End-chain recipients are not identified in the database. To what extent these trends reflect how end-chain kidneys are allocated, as opposed to increase in living donation among minorities, remains unclear. Half the LDKT in 2021 in sensitized (panel reactive antibody ≥ 80%) and highly sensitized (panel reactive antibody ≥ 98%) groups occurred via KPD. Yet, the proportion of KPD transplants performed in sensitized recipients has declined since 2013, likely due to changes in the deceased donor allocation policies and newer KPD strategies such as compatible KPD. In 2021, 40% of the programs reported not performing any KPD transplants. Our study highlights the need for understanding barriers to pursuing and expanding KPD at the center level and the need for more detailed and accurate data collection at the national level.


Subject(s)
Kidney Transplantation , Tissue and Organ Procurement , Humans , United States , Living Donors , Tissue and Organ Harvesting , Kidney
10.
bioRxiv ; 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38106107

ABSTRACT

Active sensing is a behavioral strategy for exploring the environment. In this study, we show that contact vocal behaviors can be an active sensing mechanism that uses sampling to gain information about the social environment, in particular, the vocal behavior of others. With a focus on the realtime vocal interactions of marmoset monkeys, we contrast active sampling to a vocal accommodation framework in which vocalizations are adjusted simply to maximize responses. We conducted simulations of a vocal accommodation and an active sampling policy and compared them with real vocal exchange data. Our findings support active sampling as the best model for marmoset monkey vocal exchanges. In some cases, the active sampling model was even able to predict the distribution of vocal durations for individuals. These results suggest a new function for primate vocal interactions in which they are used by animals to seek information from social environments.

11.
Malays Orthop J ; 17(3): 26-32, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38107363

ABSTRACT

Introduction: Forearm fractures are common in children. The remodelling capacity of growing long bones in children makes these potentially forgiving injuries, recovering with good outcomes despite minimal intervention. Clinicians rely on radiological characteristics that vary with age to guide treatment decisions and minimise adverse sequelae. The purpose of this review was to consolidate the evidence base of radiological indications for intervention in paediatric mid-shaft forearm fractures. Materials and methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed for this review. Citable research output reporting radiological criteria for mid-shaft forearm fractures in paediatric patients (age ≤16 years) was screened and analysed to ascertain acceptable radiological criteria for non-operative management. Results: A total of 2,059 papers were initially identified; 14 were selected following screening. Sagittal angulation >15°, coronal angulation >10°, and/or >50% (or >1cm) translation were the most common radiological indications for intervention in children aged 0 to 10 years. For children over 10 years of age, the most common radiological indication for intervention was sagittal angulation >10°, coronal angulation >10°, and/or >50% (or >1cm) translation. Conclusion: This study revealed a scarcity of high-quality evidence to guide management and significant variation in outcome reporting throughout the published literature. Since Noonan and Price's 1998 recommendations, there has been no significant evolution in the evidence-base guided threshold for intervention in paediatric mid-shaft forearm fractures. There remains a pressing need for a robust multicentre observational study using the patient-reported outcome measurement information system (PROMIS) to address this complex and controversial area of uncertainty in paediatric trauma management.

12.
Nat Commun ; 14(1): 7098, 2023 11 04.
Article in English | MEDLINE | ID: mdl-37925424

ABSTRACT

During infection, virus-specific CD8+ T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8+ T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b). Following activation, c-Myc increases the levels of Cul4b and other members of the Cullin RING Ligase 4 (CRL4) complex. Despite expressing c-Myc at high levels, Cul4b-deficient CD8+ T cells do not expand and clear the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) in vivo. Cul4b-deficient CD8+ T cells accrue DNA damage and succumb to proliferative catastrophe early after antigen encounter. Mechanistically, Cul4b knockout induces an accumulation of p21 and Cyclin E2, resulting in replication stress. Our data show that c-Myc supports cell proliferation by maintaining genome stability via Cul4b, thereby directly coupling these two interdependent pathways. These data clarify how CD8+ T cells use c-Myc and Cul4b to sustain their potential for extraordinary population expansion, longevity and antiviral responses.


Subject(s)
CD8-Positive T-Lymphocytes , Cullin Proteins , Lymphocytic choriomeningitis virus , Proto-Oncogene Proteins c-myc , CD8-Positive T-Lymphocytes/immunology , Cell Cycle , Cullin Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Proto-Oncogene Proteins c-myc/metabolism
13.
Clin Radiol ; 78(10): e773-e781, 2023 10.
Article in English | MEDLINE | ID: mdl-37550131

ABSTRACT

AIM: To gauge current final year medical students' exposure to interventional radiology (IR)and assess their perceptions of IR as a prospective career option. MATERIALS AND METHODS: An online questionnaire comprising of questions that gauge final-year medical students' understanding of and exposure to IR based on the recommendations set out by the British Society of Interventional Radiology (BSIR), was sent out to final-year students across 34 UK medical schools. RESULTS: Five hundred and ten responses were collected from 33 out of 34 eligible medical schools. Sixty-four per cent of respondents rated their own IR knowledge as inadequate. On average, only 50% of all subtopics proposed in the BSIR undergraduate curriculum was covered during medical school and 32.7% of respondents were not exposed to any fundamental IR principles and techniques recommended by the BSIR during medical school. Regarding careers, 2.7% of respondents reported a definite interest in pursuing a career in IR. Most respondents (89.8%) felt that there was insufficient undergraduate teaching on IR and that they lacked information to consider pursuing a career in IR (87.5%). CONCLUSION: Insufficient exposure and teaching on IR throughout medical schools have led to a lack of awareness and consideration of IR as a future career choice amongst UK medical students. The re-evaluation of IR teaching in the medical school curricula is needed. In the long-term, such recommendations could provide the much-needed solution to the workforce shortages seen in IR.


Subject(s)
Education, Medical, Undergraduate , Students, Medical , Humans , Prospective Studies , Radiology, Interventional/education , Education, Medical, Undergraduate/methods , Curriculum , Surveys and Questionnaires , Career Choice
14.
Transplantation ; 107(9): 2043-2046, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37271866

ABSTRACT

BACKGROUND: Simultaneous heart-kidney transplant (SHK) is an established option for patients with severe heart failure and chronic kidney disease. Recent studies in simultaneous liver-kidney transplantation demonstrate favorable outcomes achieved by delaying implantation of the kidney for over 24 h. This report describes a case series of consecutive patients listed for SHK who had planned delayed implantation of the kidney graft. METHODS: This case series represents a retrospective analysis of SHK patients extracted from the transplant database at a single center. RESULTS: There were 7 patients who underwent SHK during the study period. In all cases, kidney grafts were maintained on hypothermic ex vivo pulsatile perfusion for delayed implantation (mean cold ischemia 53 h [range, 31-69]). The first 5 patients had 100% 1-y heart and kidney graft survival with good function. Patient 6 was unstable on extracorporeal membrane oxygenation post-heart transplant. The kidney was implanted at 69 h, and the patient died soon thereafter. Patient 7 was also unstable on extracorporeal membrane oxygenation after heart transplant. The decision was made to implant the kidney into a backup kidney recipient. The heart transplant recipient subsequently died several days later, whereas the kidney was successfully transplanted in the alternate candidate. CONCLUSIONS: This case series highlights the potential utility of delayed kidney implantation in SHK patients. SHK with delayed renal transplant may provide an improved physiologic environment for renal transplant, which may result in improved early renal graft function. Delayed kidney transplant also provides the opportunity to transplant the kidney graft into an alternate candidate.


Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Kidney , Graft Survival , Perfusion , Delayed Graft Function
15.
Appl Opt ; 62(12): 3028-3041, 2023 Apr 20.
Article in English | MEDLINE | ID: mdl-37133149

ABSTRACT

This computational study investigates the effects of common defects that occur while fabricating arrays of plasmonic metal nanoparticles (NPs) on the absorbing layer of the solar cells for enhancing their opto-electronic performance. Several "defects" in an array of plasmonic NP arrays on solar cells were studied. The results demonstrated no major changes in the performance of solar cells in the presence of "defective" arrays when compared to a "perfect" array with defect-free NPs. The results indicate that relatively inexpensive techniques may be used to fabricate "defective" plasmonic NP arrays on solar cells and still obtain a significant enhancement in opto-electronic performance.

16.
Mol Pharm ; 20(7): 3471-3483, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37254498

ABSTRACT

Crystal engineering is one green alternative to organic synthesis that can be used to manipulate molecular behavior promptly and economically. We report the preparation and characterization of the pharmaceutical organic salt (FLC-C) of fluconazole (FLC) and organosulfonate (NDSA-2H), based on the sulfonate-pyridinium supramolecular synthon. Structural studies validate the crystallization of the two-component stoichiometric crystal with two molecules of water in the triclinic P1̅ space group. The anticipated proton transfer between the crystal forms leads to ionic interactions, augmenting the organic salt's thermal stability. Hirshfeld studies of FLC-C help to understand the role and significance of different types of intermolecular interactions responsible for crystal packing. The structural and theoretical studies indicate the absence of π-π interactions in FLC-C, which account for the incipience of solid-state emission in the product. The solubility studies establish augmented aqueous solubility of FLC-C over pristine FLC at physiological pH values of 2 and 7. Interestingly, in in vitro studies, FLC-C appears to serve as a potential alternative to FLC, displaying a wide spectrum of antifungal activity. FLC-C is active against several human pathogenic yeast strains, including the leading and emerging Candida strains (Candida albicans and Candida auris, respectively), at comparable and/or lower drug concentrations without showing any enhanced host cell toxicity. Interestingly, the pharmaceutical co-crystal also displays fluorescence properties inside the Candida cells.


Subject(s)
Antifungal Agents , Fluconazole , Humans , Fluconazole/pharmacology , Microbial Sensitivity Tests , Drug Synergism , Antifungal Agents/pharmacology , Candida albicans , Candida , Sodium Chloride , Pharmaceutical Preparations , Drug Resistance, Fungal
17.
J Clin Pharmacol ; 63(8): 961-967, 2023 08.
Article in English | MEDLINE | ID: mdl-37042314

ABSTRACT

Tacrolimus is a calcineurin inhibitor with a narrow therapeutic range and is metabolized by cytochrome P450 (CYP) isoenzymes CYP3A4 and CYP3A5. The Clinical Pharmacogenetic Implementation Consortium published evidence-based guidelines for CYP3A5 normal/intermediate metabolizers prescribed tacrolimus, yet few transplant centers have implemented routine testing. The objective of this study was to implement preemptive CYP3A genotyping into clinical practice in a large kidney transplant program and to evaluate workflow feasibility, potential clinical benefit, and reimbursement to identify barriers and determine sustainability. Preemptive pharmacogenetic testing for CYP3A5 and CYP3A4 was implemented in all patients listed for a kidney transplant as part of standard clinical care. Genotyping was performed at the listing appointment, results were reported as discrete data in the electronic medical record, and education and clinical decision support alerts were developed to provide pharmacogenetic-recommended tacrolimus dosing. During this initial phase, all patients were administered standard tacrolimus dosing, and clinical and reimbursement outcomes were collected. Greater than 99.5% of genotyping claims were reimbursed by third-party payers. CYP3A5 normal/intermediate metabolizers had significantly fewer tacrolimus trough concentrations within the target range and a significantly longer time to their first therapeutic trough compared to poor metabolizers. The challenge of tacrolimus dosing is magnified in the African American population. The US Food and Drug Administration drug label recommends increased starting doses in African ancestry, yet only ≈66% of African Americans in our cohort were normal/intermediate metabolizers who required higher doses. Routine CYP3A5 genotyping may overcome this issue by using genotype over race as a more accurate predictor of drug response.


Subject(s)
Kidney Diseases , Kidney Transplantation , Humans , Tacrolimus , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/metabolism , Immunosuppressive Agents , Kidney Transplantation/methods , Genotype , Polymorphism, Single Nucleotide
18.
Am J Transplant ; 23(5): 597-607, 2023 05.
Article in English | MEDLINE | ID: mdl-36868514

ABSTRACT

The growing accessibility and falling costs of genetic sequencing techniques has expanded the utilization of genetic testing in clinical practice. For living kidney donation, genetic evaluation has been increasingly used to identify genetic kidney disease in potential candidates, especially in those of younger ages. However, genetic testing on asymptomatic living kidney donors remains fraught with many challenges and uncertainties. Not all transplant practitioners are aware of the limitations of genetic testing, are comfortable with selecting testing methods, comprehending test results, or providing counsel, and many do not have access to a renal genetic counselor or a clinical geneticist. Although genetic testing can be a valuable tool in living kidney donor evaluation, its overall benefit in donor evaluation has not been demonstrated and it can also lead to confusion, inappropriate donor exclusion, or misleading reassurance. Until more published data become available, this practice resource should provide guidance for centers and transplant practitioners on the responsible use of genetic testing in the evaluation of living kidney donor candidates.


Subject(s)
Kidney Transplantation , Humans , Living Donors , Donor Selection , Tissue and Organ Harvesting
19.
Cureus ; 15(2): e35050, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36942194

ABSTRACT

PURPOSE:  The aim of the study is to estimate the prevalence rate of carbapenem-resistant Enterobacteriaceae (CRE) and to determine the types of carbapenemase genes present in patients admitted to King Abdulaziz Medical City (KAMC-J) and King Abdulaziz University Hospital (KAUH), both in Jeddah, Saudi Arabia. METHODS:  A total of 180 isolates were analyzed which were included on the basis of retrospective chart review of patients from KAMC-J and KAUH between 1st April 2017 to 30th March 2019. The prevalence of carbapenemase genes ( blaIMP, blaVIM, blaKPC, blaNDM-1, and blaOXA-48) was evaluated by Xpert® Carba-R (Cepheid, Sunnyvale, CA, USA). We assessed the CRE prevalence and described their susceptibility to antimicrobial agents based on antibiogram reports.  Results: Klebsiella pneumoniae showed a higher frequency of bla OXA-48 (79%) than bla NDM (11.7%) genes (p=0.007). The CRE prevalence in KAUH was 8% in 2017 and increased to 13% in 2018. In KAMC-J, the prevalence was 57% in 2018 and 61% in 2019. K. pneumoniae was found to be the most frequently isolated causative organism followed by Escherichia coli . The  bla OXA-48 (76.1%) gene was predominant among overall isolates followed by bla NDM (13.9%); both genes coexisted in 6.1% of the isolates. CONCLUSION:  During the study period, the prevalence of CRE considerably rose in the two tertiary care institutions from western Saudi Arabia. In the CRE isolates, bla OXA-48 was discovered to be the most common gene. We recommend an antimicrobial resistance surveillance system to detect the emergence of resistant genes through use of new rapid diagnostic tests and monitor antimicrobial use in order to improve clinical outcomes of CRE infections given the severity of infection associated with the CRE isolates as well as the limited treatment options available.

20.
iScience ; 26(3): 106079, 2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36843846

ABSTRACT

The future of energy generation is well in tune with the critical needs of the global economy, leading to more green innovations and emissions-abatement technologies. Introducing concentrated photovoltaics (CPVs) is one of the most promising technologies owing to its high photo-conversion efficiency. Although most researchers use silicon and cadmium telluride for CPV, we investigate the potential in nascent technologies, such as perovskite solar cell (PSC). This work constitutes a preliminary investigation into a "large-area" PSC module under a Fresnel lens (FL) with a "refractive optical concentrator-silicon-on-glass" base to minimize the PV performance and scalability trade-off concerning the PSCs. The FL-PSC system measured the solar current-voltage characteristics in variable lens-to-cell distances and illuminations. The PSC module temperature was systematically studied using the COMSOL transient heat transfer mechanism. The FL-based technique for "large-area" PSC architectures is a promising technology that further facilitates the potential for commercialization.

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