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1.
IJID Reg ; 11: 100378, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38947736

ABSTRACT

We present a case report about a 26-year-old female with a Mycobacterium wolinskyi surgical site infection after bilateral breast augmentation. In a unique approach compared with previously reported cases, the patient was successfully treated in an outpatient setting using only orally administered cotrimoxazole (trimethoprim-sulfamethoxazole) and ciprofloxacin with one-sided preservation of the breast prothesis. We also provide a comprehensive overview of all report cases of M. wolinskyi infections available in the PubMed database until December 2023 and compare the different diagnostic and therapeutic approaches.

2.
HCA Healthc J Med ; 5(2): 57-65, 2024.
Article in English | MEDLINE | ID: mdl-38984225

ABSTRACT

Background: Many abdominal-pelvic surgeries utilize incisions not along the linea alba, such as transverse, laparoscopic, ostomy reversal, or ostomy formation incisions. The prevalence of ventral incisional hernias (VIH) at these sites and the efficacy of prophylactic mesh in preventing VIH remains unclear. Methods: PubMed, Embase, Scopus, and Cochrane databases were systematically reviewed from inception to September 2022. We included published randomized controlled trials (RCTs) that compared prophylactic mesh reinforcement versus no mesh. The primary outcome was the incidence of VIH at postoperative follow-up equal to or greater than 24 months. Secondary outcomes included surgical site infection (SSI) and surgical site occurrence (SSO). Results: Of 3186 screened articles, only 3 RCTs with at least an 80% 2-year follow-up, encompassing a total of 901 patients, were included for analysis of non-midline VIH. Fifteen additional RCTs were included for analysis of secondary outcomes. The rate of parastomal hernias with prophylactic mesh was 21%, while it ranged from 44%-64% in the control group. The rate of incisional hernia after ostomy reversal with prophylactic mesh was 10%, and 16% in the control group. No clear evidence of a difference was found in rates of SSI or SSO between groups. Conclusion: There is limited evidence on the role of prophylactic mesh in preventing non-midline VIH. More studies at low risk for bias are needed to elucidate the balance of the long-term risks and benefits of prophylactic mesh for non-midline incisions.

3.
Mol Biol Evol ; 41(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38982580

ABSTRACT

South American coca (Erythroxylum coca and E. novogranatense) has been a keystone crop for many Andean and Amazonian communities for at least 8,000 years. However, over the last half-century, global demand for its alkaloid cocaine has driven intensive agriculture of this plant and placed it in the center of armed conflict and deforestation. To monitor the changing landscape of coca plantations, the United Nations Office on Drugs and Crime collects annual data on their areas of cultivation. However, attempts to delineate areas in which different varieties are grown have failed due to limitations around identification. In the absence of flowers, identification relies on leaf morphology, yet the extent to which this is reflected in taxonomy is uncertain. Here, we analyze the consistency of the current naming system of coca and its four closest wild relatives (the "coca clade"), using morphometrics, phylogenomics, molecular clocks, and population genomics. We include name-bearing type specimens of coca's closest wild relatives E. gracilipes and E. cataractarum. Morphometrics of 342 digitized herbarium specimens show that leaf shape and size fail to reliably discriminate between species and varieties. However, the statistical analyses illuminate that rounder and more obovate leaves of certain varieties could be associated with the subtle domestication syndrome of coca. Our phylogenomic data indicate extensive gene flow involving E. gracilipes which, combined with morphometrics, supports E. gracilipes being retained as a single species. Establishing a robust evolutionary-taxonomic framework for the coca clade will facilitate the development of cost-effective genotyping methods to support reliable identification.


Subject(s)
Phylogeny , Biological Evolution , Coca/genetics , Plant Leaves/anatomy & histology , Plant Leaves/genetics
4.
Endocr Pract ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39025300

ABSTRACT

OBJECTIVE: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with eGFR (estimated glomerular filtration rate) 15-29 mL/min/1.73m2 (CKD stage 4), eGFR<15 mL/min/1.73m2 (CKD stage 5) or on dialysis. METHODS: This is a retrospective Electronic Medical Record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between Jan 2018 and Jan 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired T-test, linear mixed effects models and Wilcoxon signed rank test. RESULTS: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of T2DM (96.0%), and most were male (53.9%). The mean age was 66.8 y (SD 11.5) with the mean BMI was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2(SD 24.2) to 101.3 (SD 27.3) kg (p<0.001). Eight patients (16%) with type 2 diabetes (T2DM) discontinued insulin after starting semaglutide. Mean HbA1c decreased from 8.0 % (SD 1.7) to 7.1 % (SD 1.3) (p<0.001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. CONCLUSIONS: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6 % of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity.

5.
bioRxiv ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39026749

ABSTRACT

NK cells express activating receptors that signal through ITAM-bearing adapter proteins. The phosphorylation of each ITAM creates binding sites for SYK and ZAP70 protein tyrosine kinases to propagate downstream signaling including the induction of Ca 2+ influx. While all immature and mature human NK cells co-express SYK and ZAP70, clonally driven memory or adaptive NK cells can methylate SYK genes and signaling is mediated exclusively using ZAP70. Here, we examined the role of SYK and ZAP70 in a clonal human NK cell line KHYG1 by CRISPR-based deletion using a combination of experiments and mechanistic computational modeling. Elimination of SYK resulted in more robust Ca ++ influx after cross-linking of the CD16 and NKp30 receptors and enhanced phosphorylation of downstream proteins, whereas ZAP70 deletion diminished these responses. By contrast, ZAP70 depletion increased proliferation of the NK cells. As immature T cells express both SYK and ZAP70 but mature T cells often express only ZAP70, we transduced the human Jurkat cell line with SYK and found that expression of SYK increased proliferation but diminished TCR-induced Ca 2+ flux and activation. We performed transcriptional analysis of the matched sets of variant Jurkat and KHYG1 cells and observed profound alterations caused by SYK expression. As depletion of SYK in NK cells increased their activation, primary human NK cells were transduced with a CD19-targeting CAR and were CRISPR edited to ablate SYK or ZAP70 . Deletion of SYK resulted in more robust cytotoxic activity and cytokine production, providing a new therapeutic strategy of NK cell engineering for cancer immunotherapy.

6.
PLoS One ; 19(6): e0304213, 2024.
Article in English | MEDLINE | ID: mdl-38935695

ABSTRACT

BACKGROUND: The mental health of children conceived using Assisted Reproductive Technologies (ARTs) such as In-Vitro-Fertilization (IVF) is a subject of significant controversy. Existing studies suggest children conceived through ART meet physical and cognitive developmental milestones at similar rates to their spontaneously conceived peers, however, a significant number of studies have connected ART conception with mental health conditions, particularly depression and attention-deficit hyperactivity disorder (ADHD) in adolescence. This study, therefore, aimed to determine whether maternal use of ARTs to achieve pregnancy is associated with an increased risk of mental disorders in these children, and whether these effects are sex-dependent or confounded by known covariates in the ART population. METHODS: Secondary data analysis was performed using Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) data; a nationally representative population-based cross-sequential cohort study. Multivariate logistic regression models examined the impact of ART (including IVF and other fertility drugs, from LSAC wave-1 and wave-2 conducted in 2004 and 2006, respectively) on mental health outcomes (i.e., autism, ADHD, anxiety and/or depression, from LSAC waves 8 conducted in 2018) in Australian adolescents aged 18-19 years in 2018 (n = 1735). Known sociological and obstetric covariates including maternal age, birth weight, smoking and drinking alcohol during pregnancy, maternal gestational diabetes, postnatal depression, hypertension, and socioeconomic status were considered to generate an adjusted logistic model. Variables with a p-value of <0.05 in the regression models were considered statistically significant. RESULTS: Of the 1735 mother-child dyads analysed, the maternal mean age was 35.6 years (Standard deviation = ±4.75), approximately 5% of mothers (n = 89) used ART to become pregnant, and 22% of adolescents (n = 384) had a mental disorder. Longitudinal analysis revealed no relationship between ART and children developing a mental disorder in the LSAC population. CONCLUSION: These results should reassure parents considering ART that there is no increased risk of psychological or neurodevelopmental problems in their ART conceived offspring.


Subject(s)
Mental Health , Reproductive Techniques, Assisted , Humans , Female , Adolescent , Longitudinal Studies , Australia/epidemiology , Male , Young Adult , Pregnancy , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/etiology , Child , Adult , Depression/epidemiology
7.
Mil Psychol ; 36(4): 393-402, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38913767

ABSTRACT

The concept of resilience is embedded within military culture and professional identity. To date, temporal changes in individuals' perceptions of their own resilience have not been systematically assessed in highstakes occupational contexts, like the military. The current study examined change in selfreported resilience over time by: (1) examining the longitudinal measurement invariance of the Brief Resilience Scale (BRS); (2) assessing the longitudinal pattern of resilience across a combat deployment cycle; and (3) examining predictors of postdeployment resilience and change in resilience scores across time. U.S. Army soldiers assigned to a combat brigade completed a survey at four time points over the course of a deployment cycle: (a) prior to deployment to Afghanistan; (b) during deployment; (c) immediately following return to home station; and (d) approximately 2-3 months thereafter. The longitudinal measurement invariance of the BRS was established. Growth curve modeling indicated that, on average, self-reported resilience decreased across the deployment cycle, but there was considerable individual variation in the rate of change. Of note, loneliness, as measured during deployment, predicted the rate of change in self-reported resilience over time. Results have implications for the longitudinal analysis of resilience and for the development of interventions with military personnel.


Subject(s)
Military Personnel , Resilience, Psychological , Humans , Military Personnel/psychology , Male , Adult , Female , Longitudinal Studies , Young Adult , Military Deployment/psychology , Afghan Campaign 2001- , United States
8.
PLoS One ; 19(6): e0297451, 2024.
Article in English | MEDLINE | ID: mdl-38857220

ABSTRACT

Traumatic brain injury has faced numerous challenges in drug development, primarily due to the difficulty of effectively delivering drugs to the brain. However, there is a potential solution in targeted drug delivery methods involving antibody-drug conjugates or nanocarriers conjugated with targeting antibodies. Following a TBI, the blood-brain barrier (BBB) becomes permeable, which can last for years and allow the leakage of harmful plasma proteins. Consequently, an appealing approach for TBI treatment involves using drug delivery systems that utilize targeting antibodies and nanocarriers to help restore BBB integrity. In our investigation of this strategy, we examined the efficacy of free antibodies and nanocarriers targeting a specific endothelial surface marker called vascular cell adhesion molecule-1 (VCAM-1), which is known to be upregulated during inflammation. In a mouse model of TBI utilizing central fluid percussion injury, free VCAM-1 antibody did not demonstrate superior targeting when comparing sham vs. TBI brain. However, the administration of VCAM-1-targeted nanocarriers (liposomes) exhibited a 10-fold higher targeting specificity in TBI brain than in sham control. Flow cytometry and confocal microscopy analysis confirmed that VCAM-1 liposomes were primarily taken up by brain endothelial cells post-TBI. Consequently, VCAM-1 liposomes represent a promising platform for the targeted delivery of therapeutics to the brain following traumatic brain injury.


Subject(s)
Blood-Brain Barrier , Brain Injuries, Traumatic , Nanoparticles , Vascular Cell Adhesion Molecule-1 , Animals , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/pathology , Vascular Cell Adhesion Molecule-1/metabolism , Mice , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Nanoparticles/chemistry , Liposomes , Male , Drug Delivery Systems , Mice, Inbred C57BL , Disease Models, Animal , Endothelial Cells/metabolism , Endothelial Cells/drug effects
9.
J Exp Biol ; 227(12)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38826150

ABSTRACT

Gravid female lizards often experience reduced thermal preferences and impaired locomotor performance. These changes have been attributed to the physical burden of the clutch, but some authors have suggested that they may be due to physiological adjustments. We compared the thermal biology and locomotor performance of the lizard Liolaemus wiegmannii 1 week before and 1 week after oviposition. We found that gravid females had a thermal preference 1°C lower than that of non-gravid females. This was accompanied by a change in the thermal dependence of maximum running speed. The thermal optimum for locomotor performance was 2.6°C lower before oviposition than after. At relatively low temperatures (22 and 26°C), running speeds of females before oviposition were up to 31% higher than for females after oviposition. However, at temperatures above 26°C, females achieved similar maximum running speeds (∼1.5 m s-1) regardless of reproductive stage. The magnitude of the changes in thermal parameters and locomotor performance of L. wiegmannii females was independent of relative clutch mass (clutches weighed up to 89% of post-oviposition body mass). This suggests that the changes are not simply due to the clutch mass, but are also due to physiological adjustments. Liolaemus wiegmannii females simultaneously adjusted their own physiology in a short period in order to improve locomotor performance and allocated energy for embryonic development during late gravid stage. Our findings have implications for understanding the mechanisms underlying life histories of lizards on the fast extreme of the slow-fast continuum, where physiological exhaustion could play an important role.


Subject(s)
Lizards , Oviposition , Reproduction , Animals , Lizards/physiology , Female , Reproduction/physiology , Oviposition/physiology , Temperature , Running/physiology , Locomotion/physiology
10.
Arch. cardiol. Méx ; 94(2): 127-132, Apr.-Jun. 2024. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1556908

ABSTRACT

Abstract Objective: Analyze sex hormone's influence during Chagas disease. Methods: Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups' data. P-values < 0.05 were considered statistically significant. Results: Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. Conclusions: Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´ infuence upon this infection to contribute with the handling of Chagas´ disease.


Resumen Objetivo: Analizar la influencia de las hormonas durante la enfermedad de Chagas. Métodos: Se separaron grupos de ratones macho y hembras BALB/c, todos infectados con T. cruzi (cepa NINOA), 4 grupos experimentales de machos (Sham, orquidectamizados, orquidectimezados y suplementados con estradiol, orquidectamizaos y suplementados con testosterona). 4 grupos experimentales de hembras (oforectomizadas, oforectomizadas y suplementadas con estradiol, oforectomizadas y suplementadas con testosterona y sham), and y dos grupos control para cada sexo (sin infección e infectados intraperitonealmente con T. cruzi (cepa NINOA). Los datos clínicos fueron registrados diariamente, la parasitemia fue evaluada durante toda la infección utilizando una cámara de Neubauer y el análisis histopatológico del corazón fue realizada con la técnica de inclusión en parafina. Para el análisis de las curvas de parasitemia y el área bajo la curva, se realizó una prueba de ANOVA de dos vías, p < 0.05 fueron considerados estadísticamente diferentes. Resultados: Las mayores tasas de mortalidad, cardiomegalia, hepatomegalia y mayor infiltrado inflamatorio, se encontró en los ratones con una mayor concentración de testosterona. En contraste los ratones con mayor concentración de estradiol presentaron paresia, postración edema y necrosis. Conclusiones: Nuestros resultados ponen en manifiesto que la testosterona incrementa la severidad del curso de la enfermedad de Chagas, mientras que el estradiol tuvo el efecto opuesto. Este trabajo mejora el entendimiento del rol que juegan las hormonas sexuales en esta infección para contribuir en un mejor manejo de la enfermedad de Chagas.

11.
PLoS One ; 19(5): e0302830, 2024.
Article in English | MEDLINE | ID: mdl-38722842

ABSTRACT

INTRODUCTION: The risk of major bleeding complications in catheter directed thrombolysis (CDT) for acute limb ischemia (ALI) remains high, with reported major bleeding complication rates in up to 1 in every 10 treated patients. Fibrinogen was the only predictive marker used for bleeding complications in CDT, despite the lack of high quality evidence to support this. Therefore, recent international guidelines recommend against the use of fibrinogen during CDT. However, no alternative biomarkers exist to effectively predict CDT-related bleeding complications. The aim of the POCHET biobank is to prospectively assess the rate and etiology of bleeding complications during CDT and to provide a biobank of blood samples to investigate potential novel biomarkers to predict bleeding complications during CDT. METHODS: The POCHET biobank is a multicentre prospective biobank. After informed consent, all consecutive patients with lower extremity ALI eligible for CDT are included. All patients are treated according to a predefined standard operating procedure which is aligned in all participating centres. Baseline and follow-up data are collected. Prior to CDT and subsequently every six hours, venous blood samples are obtained and stored in the biobank for future analyses. The primary outcome is the occurrence of non-access related major bleeding complications, which is assessed by an independent adjudication committee. Secondary outcomes are non-major bleeding complications and other CDT related complications. Proposed biomarkers to be investigated include fibrinogen, to end the debate on its usefulness, anti-plasmin and D-Dimer. DISCUSSION AND CONCLUSION: The POCHET biobank provides contemporary data and outcomes of patients during CDT for ALI, coupled with their blood samples taken prior and during CDT. Thereby, the POCHET biobank is a real world monitor on biomarkers during CDT, supporting a broad spectrum of future research for the identification of patients at high risk for bleeding complications during CDT and to identify new biomarkers to enhance safety in CDT treatment.


Subject(s)
Hemorrhage , Thrombolytic Therapy , Humans , Hemorrhage/etiology , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/methods , Prospective Studies , Biomarkers/blood , Male , Female , Fibrinogen/metabolism , Fibrinogen/analysis , Peripheral Arterial Disease/drug therapy , Peripheral Arterial Disease/blood , Aged , Arterial Occlusive Diseases/drug therapy , Arterial Occlusive Diseases/blood , Middle Aged
13.
Transpl Infect Dis ; : e14292, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728099

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) mismatched, donor IgG-positive/recipient IgG-negative, solid organ transplant recipients (SOTRs) are at high risk of CMV invasive disease. Post-prophylaxis disease is an issue in this population. Some programs employ surveillance after prophylaxis (SAP) to limit the incidence of post-prophylaxis disease. METHODS: This was a single-center retrospective cohort study that included all CMV mismatched SOTRs from 2003 to 2017. Patients underwent SAP with weekly CMV plasma viral load for 12 weeks. The subjects were classified into three post-prophylaxis DNAemia patterns: no DNAemia, one episode of DNAemia, and multiple episodes of DNAemia. We calculated the cumulative incidence of each DNAemia pattern. We also determined 5-year mortality based on DNAemia pattern stratified by organ transplant type. RESULTS: Post-prophylaxis recurrent DNAemia occurred in 63% of lung recipients and 32% of non-lung recipients (p =  .003). Tissue invasive CMV disease was diagnosed in 3% of the population and CMV syndrome was diagnosed in 33%. Recurrent DNAemia was not associated with 5-year mortality. CONCLUSION: In this cohort, undergoing SAP tissue invasive disease was uncommon and CMV DNAemia recurrence did not have an impact on long-term mortality.

14.
Nat Commun ; 15(1): 3937, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38729924

ABSTRACT

Human natural killer (NK) cell-based therapies are under assessment for treating various cancers, but cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. Using cryopreservation protocols optimized for T cells, here we find that ~75% of NK cells die within 24 h post-thaw, with the remaining cells displaying reduced cytotoxicity. Using CRISPR-Cas9 gene editing and confocal microscopy, we find that cryopreserved NK cells largely die via apoptosis initiated by leakage of granzyme B from cytotoxic vesicles. Pretreatment of NK cells with a combination of Interleukins-15 (IL-15) and IL-18 prior to cryopreservation improves NK cell recovery to ~90-100% and enables equal tumour control in a xenograft model of disseminated Raji cell lymphoma compared to non-cryopreserved NK cells. The mechanism of IL-15 and IL-18-induced protection incorporates two mechanisms: a transient reduction in intracellular granzyme B levels via degranulation, and the induction of antiapoptotic genes.


Subject(s)
Apoptosis , Cryopreservation , Granzymes , Interleukin-15 , Interleukin-18 , Killer Cells, Natural , Granzymes/metabolism , Interleukin-15/metabolism , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Humans , Interleukin-18/metabolism , Animals , Cryopreservation/methods , Mice , Cell Line, Tumor , CRISPR-Cas Systems
15.
Org Biomol Chem ; 22(20): 4135-4144, 2024 05 22.
Article in English | MEDLINE | ID: mdl-38712466

ABSTRACT

Herein, we present an innovative synthetic approach for producing a diverse set of biobased oligomers. This method begins with olive oil and employs a wide variety of commercially available amino acids (AAs) as bio-organocatalysts, in addition to tetrabutylammonium iodide (TBAI) as a cocatalyst, to synthesize various biobased oligomers. These biobased oligomers were strategically prepared starting from epoxidized olive oil (EOO) and a variety of cyclic anhydrides (phthalic, PA; maleic, MA; succinic, SA; and glutaric, GA). Among the amino acids tested as bio-organocatalysts, L-glutamic acid (L-Glu) showed the best performance for the synthesis of both poly(EOO-co-PA) and poly(EOO-co-MA), exhibiting 100% conversion at 80 °C in 2 hours, whereas the formation of poly(EOO-co-SA) and poly(EOO-co-GA) required more extreme reaction conditions (72 hours under toluene reflux conditions). Likewise, we have succeeded in obtaining the trans isomer exclusively for the MA based-oligomer within the same synthetic framework. The obtained oligomers were extensively characterized using techniques including NMR, FT-IR, GPC and TGA. A series of computational simulations based on density functional theory (DFT) and post-Hartree Fock (post-HF) methods were performed to corroborate our experimental findings and to obtain an understanding of the reaction mechanisms.


Subject(s)
Amino Acids , Polymerization , Catalysis , Amino Acids/chemistry , Amino Acids/chemical synthesis , Green Chemistry Technology , Plant Oils/chemistry , Polymers/chemistry , Polymers/chemical synthesis , Molecular Structure , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/chemical synthesis
16.
Nano Lett ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38598417

ABSTRACT

Two camps have emerged for targeting nanoparticles to specific organs and cell types: affinity moiety targeting and physicochemical tropism. Here we directly compare and combine both using intravenous (IV) lipid nanoparticles (LNPs) designed to target the lungs. We utilized PECAM antibodies as affinity moieties and cationic lipids for physicochemical tropism. These methods yield nearly identical lung uptake, but aPECAM LNPs show higher endothelial specificity. LNPs combining these targeting methods had >2-fold higher lung uptake than either method alone and markedly enhanced epithelial uptake. To determine if lung uptake is because the lungs are the first organ downstream of IV injection, we compared IV vs intra-arterial (IA) injection into the carotid artery, finding that IA combined-targeting LNPs achieve 35% of the injected dose per gram (%ID/g) in the first-pass organ, the brain, among the highest reported. Thus, combining the affinity moiety and physicochemical strategies provides benefits that neither targeting method achieves alone.

18.
Epilepsy Behav ; 155: 109801, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38669973

ABSTRACT

INTRODUCTION: Epilepsy is a common neurological disorder associated with comorbidities and a reduced quality of life (QoL). Internalized stigma is negatively correlatedwiththe QoL, whereas high levels of resilience are associated with increased QoL. Although the stigma towards people with epilepsy (PWE) is expected to be higher in low-income settings than in high-income settings, further research is needed. This study aimed to examine the extent to which resilience and internalized stigma correlatewith the QoL in PWE from a low-income population. MATERIAL AND METHODS: A cross-sectional, observational, descriptive study was conducted on 60 PWE who visited the Neurology Department of the Hospital de Clinicas (Buenos Aires, Argentina) between May and September 2022. Demographic and clinical data were collected. Participants completed the Quality of Life, Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), the Chronic Illness Anticipated Stigma Scale (CIASS), and the Resilience Scale (RS). Variables that showed a significant association with the QoL in the univariate analysis were included in a multiple regression model. RESULTS: Participants had a low overall QoL score, with a median of 59 (95 %CI: 57.2-61.8). They had an average level of education and a high rate of unemployment. Perceived stigma was higher in the workplace than in the medical or family settings. Univariate analysis revealed that the QoL was associated with internalized stigma score, resilience score, seizure frequency, seizure etiology, work status, and educational level. The multiple regressionrevealed a significant decrease in the QoL when perceived stigma increased (p = 0.0016) or when the cause of epilepsy was structural (p = 0,006) and a significant increase in the QoL when the resilience score was higher (p = 0.0004). CONCLUSION: The QoL of PWE in a low-income context is strongly associated with their levels of resilience and internalized stigma. When addressing the social burden of epilepsy, resilience support should be increased in the care of PWE to reduce internalized stigma and improve the QoL.


Subject(s)
Epilepsy , Poverty , Quality of Life , Resilience, Psychological , Social Stigma , Humans , Quality of Life/psychology , Female , Male , Epilepsy/psychology , Epilepsy/epidemiology , Cross-Sectional Studies , Adult , Middle Aged , Poverty/psychology , Young Adult , Surveys and Questionnaires , Argentina/epidemiology , Aged
19.
Sci Rep ; 14(1): 8511, 2024 04 12.
Article in English | MEDLINE | ID: mdl-38609476

ABSTRACT

Health equity and accessing Spanish kidney transplant information continues being a substantial challenge facing the Hispanic community. This study evaluated ChatGPT's capabilities in translating 54 English kidney transplant frequently asked questions (FAQs) into Spanish using two versions of the AI model, GPT-3.5 and GPT-4.0. The FAQs included 19 from Organ Procurement and Transplantation Network (OPTN), 15 from National Health Service (NHS), and 20 from National Kidney Foundation (NKF). Two native Spanish-speaking nephrologists, both of whom are of Mexican heritage, scored the translations for linguistic accuracy and cultural sensitivity tailored to Hispanics using a 1-5 rubric. The inter-rater reliability of the evaluators, measured by Cohen's Kappa, was 0.85. Overall linguistic accuracy was 4.89 ± 0.31 for GPT-3.5 versus 4.94 ± 0.23 for GPT-4.0 (non-significant p = 0.23). Both versions scored 4.96 ± 0.19 in cultural sensitivity (p = 1.00). By source, GPT-3.5 linguistic accuracy was 4.84 ± 0.37 (OPTN), 4.93 ± 0.26 (NHS), 4.90 ± 0.31 (NKF). GPT-4.0 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 4.95 ± 0.22 (NKF). For cultural sensitivity, GPT-3.5 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 5.00 ± 0.00 (NKF), while GPT-4.0 scored 5.00 ± 0.00 (OPTN), 5.00 ± 0.00 (NHS), 4.90 ± 0.31 (NKF). These high linguistic and cultural sensitivity scores demonstrate Chat GPT effectively translated the English FAQs into Spanish across systems. The findings suggest Chat GPT's potential to promote health equity by improving Spanish access to essential kidney transplant information. Additional research should evaluate its medical translation capabilities across diverse contexts/languages. These English-to-Spanish translations may increase access to vital transplant information for underserved Spanish-speaking Hispanic patients.


Subject(s)
Kidney Transplantation , Humans , Alanine Transaminase , Artificial Intelligence , Choline O-Acetyltransferase , Health Promotion , Hispanic or Latino , Reproducibility of Results , State Medicine , Mexican Americans
20.
Article in English | MEDLINE | ID: mdl-38608872

ABSTRACT

BACKGROUND: The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established. OBJECTIVES: To assess the impact of MDR colonization on SOTR's mortality, infection, or graft loss. METHODS AND DATA SOURCES: Data from PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS were systematically reviewed, spanning from inception until 20 March 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, INTERVENTIONS, AND ASSESSMENT OF RISK OF BIAS: Cohorts and case-control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum ß-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae. (CRE), or MDR-pseudomonas, and compared to noncolonized, were included. Two reviewers assessed eligibility, conducted a risk of bias evaluation using the Newcastle-Ottawa Scale, and rated certainty of evidence using the GRADE approach. METHODS OF DATA SYNTHESIS: We employed RevMan for a meta-analysis, using random-effects models to compute pooled odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was determined using the I2 statistic. RESULTS: 15,202 SOTR (33 cohort, six case-control studies) were included, where liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased posttransplant 1-year mortality (OR, 2.35; 95% CI, 1.63-3.38) and mixed infections (OR, 10.74; 95% CI, 7.56-12.26) across transplant types (p < 0.001 and I2 = 58%), but no detected impact on graft loss (p 0.41, I2 = 0). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR, 3.94; mixed infections OR, 24.8; ESBL: mixed infections OR, 10.3; no mortality data) compared to MRSA (Death: OR, 2.25; mixed infection: OR, 7.75) or VRE colonization (Death: p 0.20, mixed infections: OR, 5.71). CONCLUSIONS: MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of the evidence, actions to prevent MDR colonization in transplant candidates are warranted.

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