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1.
Health SA ; 29: 2522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726064

RESUMO

Background: Much has been written about fathers, fatherhood and premature babies. However, in the South African context, studies about the experiences of fathers having a premature baby are lacking. Aim: This study aimed to explore how South African fathers (n = 10) experience having a premature baby using a descriptive phenomenological approach. Setting: This research study was conducted online using various social media platforms such as WhatsApp, Google Meet and through telephonic conversations. Methods: A descriptive phenomenological approach that allowed for the distillation and elucidation of common core experiences among fathers who had a premature baby. Results: The findings demonstrated that the participants experienced intense fears regarding the survival and well-being of their children. They reported experiencing financial difficulties related to hospital bills and experienced being alienated by hospital institutions. Despite these reported barriers, these fathers were adamant in their resolve to support their children and partners during this challenging time. Conclusion: The experiences of fathers were riddled with fear, uncertainty, ambiguity and alienation, which placed them in very precarious situations when trying to navigate their role in a more sensitive and enlightened way. Having a premature infant calls into question the systems that men are positioned within as these systems to a large extent shape these events and how they are experienced. Contribution: This study is original as no other published studies seem to exist in South Africa that speaks to fathers' lived experiences of having a premature baby.

2.
Nat Protoc ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413781

RESUMO

Engineered by nature, biological entities are exceptional building blocks for biomaterials. These entities can impart enhanced functionalities on the final material that are otherwise unattainable. However, preserving the bioactive functionalities of these building blocks during the material fabrication process remains a challenge. We describe a high-throughput protocol for the bottom-up self-assembly of highly concentrated phages into microgels while preserving and amplifying their inherent antimicrobial activity and biofunctionality. Each microgel is comprised of half a million cross-linked phages as the sole structural component, self-organized in aligned bundles. We discuss common pitfalls in the preparation procedure and describe optimization processes to ensure the preservation of the biofunctionality of the phage building blocks. This protocol enables the production of an antimicrobial spray containing the manufactured phage microgels, loaded with potent virulent phages that effectively reduced high loads of multidrug-resistant Escherichia coli O157:H7 on red meat and fresh produce. Compared with other microgel preparation methods, our protocol is particularly well suited to biological materials because it is free of organic solvents and heat. Bench-scale preparation of base materials, namely microporous films (the template for casting microgels) and pure concentrated phage suspension, requires 3.5 h and 5 d, respectively. A single production run, that yields over 1,750,000 microgels, ranges from 2 h to 2 d depending on the rate of cross-linking chemistry. We expect that this platform will address bottlenecks associated with shelf-stability, preservation and delivery of phage for antimicrobial applications, expanding the use of phage for prevention and control of bacterial infections and contaminants.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38302302

RESUMO

PURPOSE: The objective of this study is to assess factors that influence radiology residents' decision to pursue fellowship. Historically a large majority of Diagnostic Radiology (DR) residents have pursued fellowship, but with changes in the job market and the Covid-19 pandemic, this study analyzes the current trends associated with radiology fellowship choice. MATERIALS AND METHODS: An anonymous 28-question survey was constructed based on literature review and pilot feedback from university radiology residents. The survey was distributed through APDR and to all program coordinators to be distributed to residents. Demographic information and questions related to fellowship choice were assessed. The survey was conducted through RedCap and consisted of multiple choice and sliding scale questions. RESULTS: 214 radiology residents responded, representing 4.6 % of US DR residents across 199 programs. The top fellowship choices included neuroradiology (20.5 %), musculoskeletal imaging (17.3 %), body imaging (16.8 %), and breast imaging (16.4 %). Most influential factors for fellowship selection were strong personal interest, enjoyable rotation, work hours, job security, and compensation. Least influential factors were research opportunities and specific group practice. CONCLUSION: The decision to pursue fellowship remains almost unanimous among US DR residents. Strong personal interest, enjoyable rotations, and favorable work hours were rated as the most important factors in the decision to pursue fellowship. Neuroradiology, musculoskeletal, and body imaging remained the most popular specialties, with a notable increase in interest in breast radiology compared to literature. To attract prospective fellows, residency and fellowship programs should emphasize aforementioned factors and offer more early exposure to subspecialties during residency.

4.
Am J Transplant ; 24(4): 606-618, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38142955

RESUMO

Kidney transplantation from blood type A2/A2B donors to type B recipients (A2→B) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used data from the Scientific Registry of Transplant Recipients from December 2014 until June 2022 to evaluate the association between A2→B listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2→B recipients. Among 53 409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2→B offers ("A2-eligible"). The rates of DDKT at 1-, 3-, and 5-years were 32.1%, 61.4%, and 72.1% among A2-eligible candidates and 14.1%, 29.9%, and 44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted hazard ratio (wHR) = 2.192.332.47; P < .001). The 7-year adjusted mortality was comparable between A2→B and B-ABOc (type B/O donors to B recipients) recipients (wHR 0.780.941.13, P = .5). Moreover, there was no difference between A2→B vs B-ABOc DDKT recipients with regards to death-censored graft failure (wHR 0.771.001.29, P > .9) or all-cause graft loss (wHR 0.820.961.12, P = .6). Following its broader adoption since the implementation of the kidney allocation system, A2→B DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2→B listing for eligible type B candidates should be expanded.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Doadores Vivos , Transplantados , Sistema de Registros , Rim , Sobrevivência de Enxerto
5.
Artigo em Inglês | MEDLINE | ID: mdl-38059129

RESUMO

There is growing interest in the kinematic analysis of human functional upper extremity movement (FUEM) for applications such as health monitoring and rehabilitation. Deconstructing functional movements into activities, actions, and primitives is a necessary procedure for many of these kinematic analyses. Advances in machine learning have led to progress in human activity and action recognition. However, their utility for analyzing the FUEM primitives of reaching and targeting during reach-to-grasp and reach-to-point tasks remains limited. Domain experts use a variety of methods for segmenting the reaching and targeting motion primitives, such as kinematic thresholds, with no consensus on what methods are best to use. Additionally, current studies are small enough that segmentation results can be manually inspected for correctness. As interest in FUEM kinematic analysis expands, such as in the clinic, the amount of data needing segmentation will likely exceed the capacity of existing segmentation workflows used in research laboratories, requiring new methods and workflows for making segmentation less cumbersome. This paper investigates five reaching and targeting motion primitive segmentation methods in two different domains (haptics simulation and real world) and how to evaluate these methods. This work finds that most of the segmentation methods evaluated perform reasonably well given current limitations in our ability to evaluate segmentation results. Furthermore, we propose a method to automatically identify potentially incorrect segmentation results for further review by the human evaluator. Clinical impact: This work supports efforts to automate aspects of processing upper extremity kinematic data used to evaluate reaching and grasping, which will be necessary for more widespread usage in clinical settings.


Assuntos
Movimento , Extremidade Superior , Humanos , Movimento (Física) , Fenômenos Biomecânicos , Força da Mão
6.
Am J Transplant ; 23(12): 1980-1989, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37748554

RESUMO

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.


Assuntos
Transplante de Rim , Humanos , Idoso , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Adulto , Transplante de Rim/efeitos adversos , Doadores Vivos , Sobrevivência de Enxerto , Rejeição de Enxerto/etiologia , Antígenos HLA , Fatores de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-37689032

RESUMO

As cases of multidrug resistant bacterial infections increase, scientists and clinicians around the world are increasingly turning to bacteriophages as alternatives to antibiotics. Even though our understanding of phage has increased significantly since the early days of its discovery, over a century ago, the currently used tools and technologies for phage purification for therapeutic applications are severely limited. Bacteriophages are produced by bacterial cultures, and impurities such as endotoxins must therefore be removed before clinical use. We present an anion exchange bind-and-elute membrane chromatographic method for purifying T7 bacteriophage from Escherichia coli culture supernatant that removes undesirable impurities, while ensuring a high viable phage count in the purified product. Our method does not involve the use of chemicals such as organic solvents and caesium chloride that could typically leave residual toxicity in the final product. It also does not require expensive equipment, such as an ultracentrifuge. Using our method, that is based on an in-house designed membrane module, 65% of viable T7 phage was recovered, and up to 94% endotoxins could be removed. The method, which took approximately 15 min, is rapid and scalable, and produces quite pure bacteriophage samples in a single step. It therefore potentially represents a major improvement over the status quo, and shows the way ahead for streamlining phage manufacturing for therapeutic use.


Assuntos
Bacteriófagos , Cromatografia , Endotoxinas , Ânions , Solventes
8.
Gut Microbes ; 15(1): 2205425, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37131291

RESUMO

Emerging evidence implicates microbial proteolytic activity in ulcerative colitis (UC), but whether it also plays a role in Crohn's disease (CD) remains unclear. We investigated the effects of colonizing adult and neonatal germ-free C57BL/6 mice with CD microbiota, selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), or microbiota from healthy controls with LPA (HC-LPA) or HPA (HC-HPA). We then investigated colitogenic mechanisms in gnotobiotic C57BL/6, and in mice with impaired Nucleotide-binding Oligomerization Domain-2 (NOD2) and Protease-Activated Receptor 2 (PAR2) cleavage resistant mice (Nod2-/-; R38E-PAR2 respectively). At sacrifice, total fecal proteolytic, elastolytic, and mucolytic activity were analyzed. Microbial community and predicted function were assessed by 16S rRNA gene sequencing and PICRUSt2. Immune function and colonic injury were investigated by inflammatory gene expression (NanoString) and histology. Colonization with HC-LPA or CD-LPA lowered baseline fecal proteolytic activity in germ-free mice, which was paralleled by lower acute inflammatory cell infiltrate. CD-HPA further increased proteolytic activity compared with germ-free mice. CD-HPA mice had lower alpha diversity, distinct microbial profiles and higher fecal proteolytic activity compared with CD-LPA. C57BL/6 and Nod2-/- mice, but not R38E-PAR2, colonized with CD-HPA had higher colitis severity than those colonized with CD-LPA. Our results indicate that CD proteolytic microbiota is proinflammatory, increasing colitis severity through a PAR2 pathway.


Assuntos
Colite Ulcerativa , Colite , Doença de Crohn , Microbioma Gastrointestinal , Microbiota , Animais , Camundongos , Camundongos Endogâmicos C57BL , Receptor PAR-2/genética , RNA Ribossômico 16S/genética , Inflamação , Serina Proteases
9.
Front Rehabil Sci ; 4: 1130847, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37113748

RESUMO

The analysis of functional upper extremity (UE) movement kinematics has implications across domains such as rehabilitation and evaluating job-related skills. Using movement kinematics to quantify movement quality and skill is a promising area of research but is currently not being used widely due to issues associated with cost and the need for further methodological validation. Recent developments by computationally-oriented research communities have resulted in potentially useful methods for evaluating UE function that may make kinematic analyses easier to perform, generally more accessible, and provide more objective information about movement quality, the importance of which has been highlighted during the COVID-19 pandemic. This narrative review provides an interdisciplinary perspective on the current state of computer-assisted methods for analyzing UE kinematics with a specific focus on how to make kinematic analyses more accessible to domain experts. We find that a variety of methods exist to more easily measure and segment functional UE movement, with a subset of those methods being validated for specific applications. Future directions include developing more robust methods for measurement and segmentation, validating these methods in conjunction with proposed kinematic outcome measures, and studying how to integrate kinematic analyses into domain expert workflows in a way that improves outcomes.

10.
BMC Pregnancy Childbirth ; 23(1): 168, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36922778

RESUMO

BACKGROUND: The experience of expectant parenthood is commensurate of relative angst and nervousness albeit one of overall excitement and joy. However, when the pregnancy is regarded as high-risk, this experience changes dramatically for both parents. While literature on high-risk pregnancies is gaining traction, the focus is predominantly on the mother's experiences and therefore, a paucity exists in exploring the father's experiences of a high-risk pregnancy. This study aimed to determine the current extent of literature focusing on father's experiences of a high-risk pregnancy using a scoping review methodology. METHOD: Nine databases were reviewed using the EBSCOHost metadatabase: Academic Search Complete; APA PsychArticles; CINAHL Plus with full-text; Health Source: Nursing/Academic Edition; MasterFILE Premier; MasterFILE Reference eBook Collection; MEDLINE; SocINDEX with full-text; and eBook Collection. Data was extracted according to the following headings: Authors (including the year of publication); aim of the study; research context; research design; sample characteristics; and key findings. RESULTS: Fifteen studies were included in this review. A narrative synthesis was applied within which 4 key themes emerged from the data: (1) The father versus the healthcare professional and the hospital environment; (2) The impact of high-risk pregnancies on fathers; (3) Redefining the role of 'father' after experiencing high-risk pregnancy and (4) Focus on fathers: Recommendations for support during high-risk pregnancies. CONCLUSION: The findings of this study highlights the importance of the inclusion of men and fathers in supporting both his partner and (un)born child. The findings further illustrated the long-lasting impact of trauma felt by men which constrained his ability to support his family. A family-centred approach is needed to further support the family and the impact of a high-risk pregnancy on all members within the family unit.


Assuntos
Pai , Gravidez de Alto Risco , Masculino , Gravidez , Feminino , Criança , Humanos , Emoções , Pais , Ansiedade
11.
Transplantation ; 107(5): e127-e138, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36928182

RESUMO

BACKGROUND: Biliary complications (BCs) continue to impact patient and graft survival after liver transplant (LT), despite improvements in organ preservation, surgical technique, and posttransplant care. Real-world evidence provides a national estimate of the incidence of BC after LT, implications for patient and graft outcomes, and attributable cost not available in transplant registry data. METHODS: An administrative health claims-based BC identification algorithm was validated using electronic health records (N = 128) and then applied to nationally linked Medicare and transplant registry claims. RESULTS: The real-world evidence algorithm identified 97% of BCs in the electronic health record review. Nationally, the incidence of BCs within 1 y of LT appears to have improved from 22.2% in 2002 to 20.8% in 2018. Factors associated with BCs include donor type (living versus deceased), recipient age, diagnosis, prior transplant, donor age, and donor cause of death. BCs increased the risk-adjusted hazard ratio (aHR) for posttransplant death (aHR, 1.43; P < 0.0001) and graft loss (aHR, 1.48; P < 0.0001). Nationally, BCs requiring intervention increased risk-adjusted first-year Medicare spending by $39 710 ( P < 0.0001). CONCLUSIONS: BCs remain an important cause of morbidity and expense after LT and would benefit from a systematic quality-improvement program.


Assuntos
Transplante de Fígado , Idoso , Humanos , Estados Unidos/epidemiologia , Transplante de Fígado/métodos , Fatores de Risco , Medicare , Doadores de Tecidos , Modelos de Riscos Proporcionais , Sobrevivência de Enxerto , Estudos Retrospectivos , Resultado do Tratamento
12.
Liver Transpl ; 29(3): 268-278, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36651194

RESUMO

Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.


Assuntos
Fígado Gorduroso , Processamento de Imagem Assistida por Computador , Transplante de Fígado , Humanos , Alanina Transaminase , Aspartato Aminotransferases , Bilirrubina , Biópsia , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Transplante de Fígado/métodos , Software , Processamento de Imagem Assistida por Computador/métodos
13.
Radiology ; 306(3): e212403, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36283115

RESUMO

Background Pre-liver transplant (LT) sarcopenia is associated with poor survival. Methods exist for measuring body composition with use of CT scans; however, it is unclear which components best predict post-LT outcomes. Purpose To quantify the association between abdominal CT-based body composition measurements and post-LT mortality in a large North American cohort. Materials and Methods This was a retrospective cohort of adult first-time deceased-donor LT recipients from 2009 to 2018 who underwent pre-LT abdominal CT scans, including at the L3 vertebral level, at Johns Hopkins Hospital. Measurements included sarcopenia (skeletal muscle index [SMI] <50 in men and <39 in women), sarcopenic obesity, myosteatosis (skeletal muscle CT attenuation <41 mean HU for body mass index [BMI] <25 and <33 mean HU for BMI ≥25), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio. Covariates in the adjusted models were selected with use of least absolute shrinkage and selection operator regression with lambda chosen by means of 10-fold cross-validation. Cox proportional hazards models were used to quantify associations with post-LT mortality. Model discrimination was quantified using the Harrell C-statistic. Results A total of 454 recipients (median age, 57 years [IQR, 50-62 years]; 294 men) were evaluated. In the adjusted model, pre-LT sarcopenia was associated with a higher hazard ratio (HR) of post-LT mortality (HR, 1.6 [95% CI: 1.1, 2.4]; C-statistic, 0.64; P = .02). SMI was significantly negatively associated with survival after adjustment for covariates. There was no evidence that myosteatosis was associated with mortality (HR, 1.3 [95% CI: 0.86, 2.1]; C-statistic, 0.64; P = .21). There was no evidence that BMI (HR, 1.2 [95% CI: 0.95, 1.4]), VAT (HR, 1.0 [95% CI: 0.98, 1.1]), SAT (HR, 1.0 [95% CI: 0.97, 1.0]), and VAT/SAT ratio (HR, 1.1 [95% CI: 0.90, 1.4]) were associated with mortality (P = .15-.77). Conclusions Sarcopenia, as assessed on routine pre-liver transplant (LT) abdominal CT scans, was the only factor significantly associated with post-LT mortality. © RSNA, 2022 See also the editorial by Ruehm in this issue.


Assuntos
Transplante de Fígado , Sarcopenia , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Estudos Retrospectivos , Doadores Vivos , Composição Corporal , Músculo Esquelético , Tomografia Computadorizada por Raios X/métodos
15.
Nat Commun ; 13(1): 7158, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470891

RESUMO

Nanofilamentous bacteriophages (bacterial viruses) are biofunctional, self-propagating, and monodisperse natural building blocks for virus-built materials. Minifying phage-built materials to microscale offers the promise of expanding the range function for these biomaterials to sprays and colloidal bioassays/biosensors. Here, we crosslink half a million self-organized phages as the sole structural component to construct each soft microgel. Through an in-house developed, biologics-friendly, high-throughput template method, over 35,000 phage-built microgels are produced from every square centimetre of a peelable microporous film template, constituting a 13-billion phage community. The phage-exclusive microgels exhibit a self-organized, highly-aligned nanofibrous texture and tunable auto-fluorescence. Further preservation of antimicrobial activity was achieved by making hybrid protein-phage microgels. When loaded with potent virulent phages, these microgels effectively reduce heavy loads of multidrug-resistant Escherichia coli O157:H7 on food products, leading to up to 6 logs reduction in 9 hours and rendering food contaminant free.


Assuntos
Anti-Infecciosos , Bacteriófagos , Escherichia coli O157 , Microgéis , Nanofibras , Anti-Infecciosos/farmacologia
16.
Transplant Direct ; 8(11): e1388, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36284928

RESUMO

ABO type B and O kidney transplant candidates have increased difficulty identifying a compatible donor for living donor kidney transplantation (LDKT) and are harder to match in kidney paired donation registries. A2-incompatible (A2i) LDKT increases access to LDKT for these patients. To better inform living donor selection, we evaluated the association between A2i LDKT and patient and graft survival. Methods: We used weighted Cox regression to compare mortality, death-censored graft failure, and all-cause graft loss in A2i versus ABO-compatible (ABOc) recipients. Results: Using Scientific Registry of Transplant Recipients data 2000-2019, we identified 345 A2i LDKT recipients. Mortality was comparable among A2i and ABOc recipients; weighted 1-/5-/10-y mortality was 0.9%/6.5%/24.2%, respectively, among A2i LDKT recipients versus 1.4%/7.7%/22.2%, respectively, among ABOc LDKT recipients (weighted hazard ratio [wHR], 0.811.041.33; P = 0.8). However, A2i recipients faced higher risk of death-censored graft failure; weighted 1-/5-/10-y graft failure was 5.7%/11.6%/22.4% for A2i versus 1.7%/7.5%/17.2% for ABOc recipients (wHR in year 1 = 2.243.565.66; through year 5 = 1.251.782.53; through year 10 = 1.151.552.07). By comparison, 1-/5-/10-y wHRs for A1-incompatible recipients were 0.631.966.08/0.390.942.27/0.390.831.74. Conclusions: A2i LDKT is generally safe, but A2i donor/recipient pairs should be counseled about the increased risk of graft failure and be monitored as closely as their A1-incompatible counterparts posttransplant.

17.
PNAS Nexus ; 1(3): pgac124, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36003074

RESUMO

Human leukocyte antigen class I (HLA-I) molecules bind and present peptides at the cell surface to facilitate the induction of appropriate CD8+ T cell-mediated immune responses to pathogen- and self-derived proteins. The HLA-I peptide-binding cleft contains dominant anchor sites in the B and F pockets that interact primarily with amino acids at peptide position 2 and the C-terminus, respectively. Nonpocket peptide-HLA interactions also contribute to peptide binding and stability, but these secondary interactions are thought to be unique to individual HLA allotypes or to specific peptide antigens. Here, we show that two positively charged residues located near the top of peptide-binding cleft facilitate interactions with negatively charged residues at position 4 of presented peptides, which occur at elevated frequencies across most HLA-I allotypes. Loss of these interactions was shown to impair HLA-I/peptide binding and complex stability, as demonstrated by both in vitro and in silico experiments. Furthermore, mutation of these Arginine-65 (R65) and/or Lysine-66 (K66) residues in HLA-A*02:01 and A*24:02 significantly reduced HLA-I cell surface expression while also reducing the diversity of the presented peptide repertoire by up to 5-fold. The impact of the R65 mutation demonstrates that nonpocket HLA-I/peptide interactions can constitute anchor motifs that exert an unexpectedly broad influence on HLA-I-mediated antigen presentation. These findings provide fundamental insights into peptide antigen binding that could broadly inform epitope discovery in the context of viral vaccine development and cancer immunotherapy.

18.
Inquiry ; 59: 469580221110520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35906761

RESUMO

The current study examines the potential mediating role of professional identification of school teachers in the relationship between psychological distress and teaching satisfaction. Professional identification is the extent to which an individual identifies with a professional group, including the values, beliefs, and commitment the individual has in relation to the professional group. Professional identification has been linked to negative work outcomes, such as job performance and turnover intentions, as well as to adverse mental health outcomes. In the context of education, professional identification is the extent to which teachers identify with the teaching profession. Participants (N = 355) were school teachers in South Africa who completed the Center for Epidemiological Depression Scale, the Beck Hopelessness Scale, the Professional Identification Scale, and the Teaching Satisfaction Scale. Structural equation analysis showed that professional identification plays a fully mediational role in the relationship between psychological distress and teaching satisfaction. Interventions that strengthen teachers' identification with the teaching profession should be considered a priority.


Assuntos
COVID-19 , Angústia Psicológica , Humanos , Satisfação no Emprego , Satisfação Pessoal
20.
Behav Sci (Basel) ; 12(6)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35735370

RESUMO

Teachers' work roles and responsibilities have changed dramatically because of the COVID-19 pandemic. These unprecedented changes have the potential to generate role stress and burnout and reduce teachers' job satisfaction. This study investigated the serial relationship between perceived vulnerability to disease, role stress, burnout, and teaching satisfaction. It was hypothesised that individuals who perceive themselves to be at high risk of contracting COVID-19 would report high role conflict and ambiguity in the workplace, which would in turn lead to high levels of burnout and low satisfaction with teaching. Participants were schoolteachers (N = 355) who completed the Perceived Vulnerability to Disease Questionnaire, the Role Orientation Questionnaire, the Maslach Burnout Inventory, and the Teaching Satisfaction Scale. Path analysis confirmed that perceived vulnerability to disease was associated with role conflict and ambiguity, which was in turn associated with emotional exhaustion, depersonalisation, and low teaching satisfaction. Teachers who appraised themselves as being more vulnerable to contracting COVID-19 experienced greater role stress, which was associated with high levels of burnout and low teaching satisfaction. This study highlights that threat appraisals related to contracting COVID-19 represent an additional job demand and this needs to be matched by job resources that can facilitate coping.

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