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1.
Artigo em Inglês | MEDLINE | ID: mdl-38639844

RESUMO

The escalating rates of rape and sexual assault cases underscore the essential need to analyze associative evidence of sexual assault to ensure justice. The condom, when used during the act of sexual assault/rape, leaves behind traces of lubricant that could be instrumental in establishing the link between the victim and perpetrator. This leading evidence is crucial especially when the traditional DNA analysis is challenging owing to the lack of biological evidence. The present study employs the use of ATR FTIR spectroscopy coupled with the chemometric, to discern the chemical discrimination of condom lubricants. The study also aimed to investigate simulated real-case scenarios by analysing the effect of different matrices such as vaginal fluid, menstrual blood, and undergarment substrates (cotton, polyester and nylon) on condom traces. The difference in the spectral profile of pre-coitus and post-coitus samples was also investigated. The results of the present study are noteworthy, unveiling the efficacy of discriminating the condom lubricants of different brands and other frequently used household lubricants with 100% sensitivity, specificity, and accuracy. Condom lubricants are detected despite the presence of contaminants such as menstrual blood, and vaginal fluid, across different substrates and, in post-coital conditions. In conclusion, this study presents a comprehensive approach to analysing condom lubricants, offering a potential breakthrough in the investigation of sexual assault cases, coupled with the ability to counter false accusations.

2.
Psychol Serv ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436647

RESUMO

Transgender and gender diverse (TGD) veterans in the Veterans Health Administration experience health and health care disparities, and research with this population is needed to improve gender-affirming care in Veterans Health Administration. However, TGD veterans may experience hesitancy to participate in research. We must address barriers to participation through feasible and acceptable methods. Opt-out letters are an effective tool used to recruit veterans in mental health research. The present study examined the feasibility and acceptability of opt-out letters modified for TGD veterans. Opt-out letters were sent to 54 potential TGD participants at three sites. The letters stated the research team would begin contacting veterans by phone in 2 weeks if they did not opt out of being contacted. Feasibility was measured through response rate. Acceptability was assessed through qualitative template analysis of interview data. Of the 54 potential participants, two opted out, three letters were undeliverable, and eight veterans called to opt in. Veterans reported that they found the letters to be clear and useful. The responses to the opt-out letters resulted in completing recruitment for two of the three sites. The research team then called the veterans who received the letter at the third site (three veterans) and recruited one additional veteran, for a total of nine TGD veterans. Opt-out letters may be a helpful tool to recruit TGD veterans to participate in research. Although these letters were designed to opt out, 89% of participants called the research team to opt in. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

3.
Forensic Sci Int ; 357: 111988, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38520829

RESUMO

In recent years, collection and analysis of condom evidence in sexual assault investigations are becoming more common in forensic caseworks. Condom analysis can provide investigative leads or establish potential contact between the suspect and victim in the absence of DNA evidence or supplement biological evidence. Recent forensic literature shows significant advancements in the analysis of condom lubricants, including casework samples. There is an increasing trend in the use of chemometric tools for the comparison and interpretation of the results. This review highlights the advances in common analytical techniques used for the analysis of condom lubricants with a particular focus on the developments occurring in recent years, including chemometric interpretation. The analysis of reference and casework samples (swab samples, samples on skin, clothing and fingermark) are discussed separately. For casework samples, the transfer and persistence of different lubricant formulations are discussed, along with their detection with various analytical approaches. The issues with the interpretation of lubricants are also discussed in another section, with particular emphasis on samples such as personal hygiene products which have similar formulations with sexual lubricants and the interpretation of negative profiles. The current challenges in the field and prospects for future research are also discussed.


Assuntos
Medicina Legal , Delitos Sexuais , Medicina Legal/métodos , Preservativos , Lubrificantes/análise , Pele/química
4.
Paediatr Int Child Health ; 44(1): 24-29, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38482867

RESUMO

INTRODUCTION: Raised serum bilirubin levels can cause kernicterus, and premature infants are at increased risk owing to metabolic immaturity. The standard treatment for neonatal jaundice is phototherapy, but probiotics alone can reduce the duration of phototherapy and hospitalisation. OBJECTIVES: To determine the effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates. PATIENTS AND METHODS: The open-labelled randomised controlled trial was conducted from January 2022 to January 2023 in the neonatal unit of the University of Lahore Teaching Hospital, Pakistan. A total of 76 preterm neonates who fulfilled the selection criteria were included and divided into two groups. Both groups received standard phototherapy. In Group B, a probiotic (Saccharomyces boulardii) 125 mg, twice daily, orally (in 5 cc of whichever milk the infant was receiving) was given until discharge from hospital. The primary outcome measurements were the duration of phototherapy and the length of hospitalisation. RESULTS: The mean (SD) duration of phototherapy was 36.55 (14.25) hours in Group A and 24.61 (9.25) hours in Group B (p <0.05). The mean (SD) duration of hospital stay was 47.36 (16.51) hours in Group A and 33.13 (8.93) hours in Group B (p <0.05). CONCLUSION: Oral probiotics (Saccharomyces boulardii) have a significant effect on the duration of phototherapy for neonatal hyperbilirubinaemia, and they decrease the chances of nosocomial infection. Exploration of clinical outcomes by investigating faecal flora and undertaking large randomised controlled trials of various probiotics are needed. ABBREVIATIONS: ABE: acute bilirubin encephalopathy; CNS: central nervous system; GA: gestational age; IVIG: intravenous immunoglobulin; KSD: kernicterus; NNU: neonatal unit; RCT: randomised controlled trial; S. boulardii: Saccharomyces boulardii.


Assuntos
Hiperbilirrubinemia Neonatal , Icterícia Neonatal , Kernicterus , Probióticos , Recém-Nascido , Lactente , Humanos , Hiperbilirrubinemia Neonatal/terapia , Icterícia Neonatal/terapia , Fototerapia , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Psychiatr Serv ; : appips20230277, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38444365

RESUMO

OBJECTIVE: In 2017, the Veterans Health Administration (VHA) implemented a national suicide prevention program, called Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH VET), that uses a predictive algorithm to identify, attempt to reach, assess, and care for patients at the highest risk for suicide. The authors aimed to evaluate whether facilitation enhanced implementation of REACH VET at VHA facilities not meeting target completion rates. METHODS: In this hybrid effectiveness-implementation type 2 program evaluation, a quasi-experimental pre-post design was used to assess changes in implementation outcome measures evaluated 6 months before and 6 months after onset of facilitation of REACH VET implementation at 23 VHA facilities. Measures included percentages of patients with documented coordinator and provider acknowledgment of receipt, care evaluation, and outreach attempt. Generalized estimating equations were used to compare differences in REACH VET outcome measures before and after facilitation. Qualitative interviews were conducted with personnel and were explored via template analysis. RESULTS: Time had a significant effect in all outcomes models (p<0.001). An effect of facilitation was significant only for the outcome of attempted outreach. Patients identified by REACH VET had significantly higher odds of having a documented outreach attempt after facilitation of REACH VET implementation, compared with before facilitation. Site personnel felt supported and reported that the external facilitators were helpful and responsive. CONCLUSIONS: Facilitation of REACH VET implementation was associated with an improvement in outreach attempts to veterans identified as being at increased risk for suicide. Outreach is critical for engaging veterans in care.

6.
J Med Chem ; 66(24): 17086-17104, 2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-38079537

RESUMO

A set of focused analogues have been generated around a lead indirect adenosine monophosphate-activated kinase (AMPK) activator to improve the rat clearance of the molecule. Analogues were focused on inhibiting amide hydrolysis by the strategic placement of substituents that increased the steric environment about the secondary amide bond between 4-aminopiperidine and pyridine-5-carboxylic acid. It was found that placing substituents at position 3 of the piperidine ring and position 4 of the pyridine could all improve clearance without significantly impacting on-target potency. Notably, trans-3-fluoropiperidine 32 reduced rat clearance from above liver blood flow to 19 mL/min/kg and improved the hERG profile by attenuating the basicity of the piperidine moiety. Oral dosing of 32 activated AMPK in mouse liver and after 2 weeks of dosing improved glucose handling in a db/db mouse model of Type II diabetes as well as lowering fasted glucose and insulin levels.


Assuntos
Diabetes Mellitus Tipo 2 , Camundongos , Ratos , Animais , Proteínas Quinases Ativadas por AMP , Diamida , Glucose , Piridinas/farmacologia , Piperidinas , Amidas
7.
Physiol Mol Biol Plants ; 29(9): 1301-1318, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38024957

RESUMO

A refined SNP array containing 92,459 probes was developed and applied for chromosome scanning, construction of a high-density genetic linkage map and QTL analysis in a selfed Nigerian oil palm family (T128). Genotyping of the T128 mapping family generated 76,447 good quality SNPs for detailed scanning of aberration and homozygosity in the individual pseudo-chromosomes. Of them, 25,364 polymorphic SNPs were used for linkage analysis resulting in an 84.4% mapping rate. A total of 21,413 SNPs were mapped into 16 linkage groups (LGs), covering a total map length of 1364.5 cM. This genetic map is 16X denser than the previous version used to establish pseudo-chromosomes of the oil palm reference genome published in 2013. The QTLs associated with height, height increment and rachis length were identified in LGs TT05, 06, 08, 15 and 16. The present QTLs as well as those published previously were tagged to the reference genome to determine their chromosomal locations. Almost all the QTLs identified in this study were either close to or co-located with those reported in other populations. Determining the QTL position on chromosomes was also helpful in mining for the underlying candidate genes. In total, 55 putative genes and transcription factors involved in the biosynthesis, conjugation and signalling of the major phytohormones, especially for gibberellins and cell wall morphogenesis were found to be present in the identified genomic QTL regions, and their potential roles in plant dwarfism are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01360-2.

8.
Nano Lett ; 23(21): 9677-9682, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37902816

RESUMO

In recent years, molecularly imprinted polymer nanoparticles (nanoMIPs) have proven to be an attractive alternative to antibodies in diagnostic and therapeutic applications. However, several key questions remain: how suitable are intracellular epitopes as targets for nanoMIP binding? And to what extent can protein function be modulated via targeting specific epitopes? To investigate this, three extracellular and three intracellular epitopes of epidermal growth factor receptor (EGFR) were used as templates for the synthesis of nanoMIPs which were then used to treat cancer cells with different expression levels of EGFR. It was observed that nanoMIPs imprinted with epitopes from the intracellular kinase domain and the extracellular ligand binding domain of EGFR caused cells to form large foci of EGFR sequestered away from the cell surface, caused a reduction in autophosphorylation, and demonstrated effects on cell viability. Collectively, this suggests that intracellular domain-targeting nanoMIPs can be a potential new tool for cancer therapy.


Assuntos
Impressão Molecular , Nanopartículas , Polímeros Molecularmente Impressos , Epitopos , Polímeros/química , Nanopartículas/química , Receptores ErbB/metabolismo
9.
J Forensic Sci ; 68(6): 1982-1990, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37606297

RESUMO

Sealing wax is used for maintaining the integrity and authenticity of a document or physical evidence. Any tampering with the seal calls into question the overall integrity and authenticity of the tangible evidence or document. In these circumstances, determining the authenticity of the sealing material (physical and chemical) becomes imperative. In this study, ATR-FTIR spectroscopy supported by chemometrics has been used to differentiate sealing wax samples belonging to 12 different brands available across India. All the samples were first melted, cooled, and then analyzed using ATR-FTIR spectroscopy in the mid-infrared region (4000-600 cm-1 ). The obtained spectra were first examined visually for the presence of different functional groups. Principal component analysis (PCA) and principal component analysis-linear discriminant analysis (PCA-LDA) were employed to analyze the sample clustering patterns and to categorize them into their respective groups, respectively. For classification, a PCA-LDA training model was applied, and it demonstrated 95.83% accuracy. The validation test resulted in an accuracy of 83.33%. PCA-LDA model offered 100% accurate prediction for samples on various substrates, including cloth, cardboard, and paper. A blind study was also performed using five unknown samples, which were accurately classified into their respective groups. PCA-LDA model will be helpful in providing investigative leads by linking a questioned sealing wax sample with its respective group.

10.
Front Health Serv ; 3: 1124290, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560195

RESUMO

Introduction: Engaging service users or consumers in quality improvement or implementing a new service is important across settings and may reduce health inequities. Implementation strategies leveraging consumer engagement are neither commonly used nor robustly operationalized in implementation science. Implementers (e.g., middle managers, facilitators) want to involve consumers in implementation activities, but do not always feel confident in how to proceed. We developed a compendium of tools called Consumer Voice to guide others how to engage consumers in design/delivery of implementation strategies. Although generalizable to other settings, we developed Consumer Voice within the context of implementing suicide prevention treatments in healthcare to reach rural U.S. military veterans, as there are suicide inequities for people in rural areas. Methods: We developed Consumer Voice using a multistep process and human-centered design methods. In between steps, a design team met to generate insights from data, and decide which prototypes to create/refine. In preliminary work, we conducted a scan of examples in healthcare of patient engagement in implementation activities and interviewed two implementation experts about preferred learning styles. In Step 1, we interviewed 26 participants with experience in community engagement, implementation, or lived experience as a rural U.S. veteran with suicidal thoughts/behavior. In Step 2, 11 implementers beta tested prototypes then share feedback in focus groups. In Step 3, we reconvened participants from prior steps to review tools and, using nominal group technique, prioritized remaining recommendations. Results: Consumer Voice is online, modular, and nonlinear for self-guided learning tailored to beginner, intermediate, or advanced experience with consumer engagement. Tools consist of slides, audiovisual content with written text, and templates. Findings indicated there is not one "right" way to engage consumers in implementation activities, rather that implementers wanted tools showcasing core principles for consumer engagement and practical ideas. Discussion: Consumer Voice can be used by implementers to reflect and decide on how to apply consumer engagement implementation strategies to improve equitable dissemination and uptake of evidence-based practices. Most insights generated by user data were explicitly to build trust between consumers and professionals representing institutions, which may be one component to reducing healthcare inequities.

11.
J Forensic Leg Med ; 98: 102564, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37459705

RESUMO

Abrus precatorius is a poisonous plant known since ancient times. Accidental poisoning is more common due to the intake of plant seeds containing deadly abrin which is a highly toxic and a thermolabile plant toxalbumin. Abrin has also been reported to be a potential chemical agent that can be used as bioweapon in military or terrorism. Abrin is a ribosome inactivating protein that contains multiple isotoxic forms of protein subunits called chain A and B. The identification of this toxalbumin in the plant is important to determine cause of death in poisoning cases. Therefore, the present review focuses on the structure, mode of administration, tokicokinetics, extraction procedures and forensic analysis of abrin and other constituents. It is observed that most of the researchers have utilized immunological methods for the detection of plant components. This technique has proved to be more sensitive, reliable and accurate for the detection of extremely low concentrations of toxin.


Assuntos
Abrina , Humanos , Abrina/toxicidade , Plantas Tóxicas
12.
J Forensic Sci ; 68(6): 1972-1981, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37417337

RESUMO

Lip balm may be encountered as physical evidence in cases involving sexual assaults, homicides, and kidnappings. Lip balm can be used as corroborative evidence by providing a potential link between the victim, accused, and the crime scene. For lip balms to be used as evidence, it is important to understand the diversity and their aging process under different conditions. Therefore, in this study, ATR-FTIR spectroscopy in conjunction with chemometric tools such as principal component analysis (PCA) and linear discriminant analysis (LDA) has been used for the objective identification and differentiation of 20 brands of lip balms. Moreover, lip balms on different substrates and wearing effects over time were also investigated. The results show that the PCA-LDA training accuracy was 92.5%, whereas the validation accuracy comes out to be 83.33%. A blind study using pristine samples was also performed which resulted in 80% PCA-LDA accuracy. PCA-LDA prediction of samples on various substrates showed a higher chemometric prediction accuracy for nonporous substrates (glass, plastic, and steel), than for porous substrates (cotton cloth, cotton swab stick, dry tissue paper, and white paper) for samples kept in room temperature and under sunlight for 15 days. The substrate study showed that the samples from various substrates could effectively generate respective spectra which can help in brand-level identification even after several days. The present method demonstrates a potential for lip balm samples to be used in forensic casework applications.


Assuntos
Medicina Legal , Lábio , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Discriminante , Análise de Componente Principal , Homicídio
13.
Perit Dial Int ; : 8968608221149546, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36749175

RESUMO

BACKGROUND: In 2016, Peritoneal Dialysis Assist (PDA) was implemented in British Columbia, Canada, as a pilot program to allow patients with physical, cognitive and social impairments to access an independent dialysis modality. This is a presentation of the usage and 5-year clinical outcomes of our provincial assisted peritoneal dialysis (PD) program. METHODS: Patients who utilised long-term or respite PDA services in British Columbia, Canada, from 2016 to 2021 were included in this program evaluation. Incident and prevalent patient numbers were characterised annually as well as indications for PDA and patient demographics both annually and over time. Outcomes of interest included death, transfer to haemodialysis, transplantation and cessation of the PDA program but retention on PD. RESULTS: Three hundred twenty-two total patients received services through the PDA program. The percentage of PD patients supported by long-term PDA service has grown to 11.2% in the most recent year. Patients spend a median of 13.6 (95% CI: 11.0, 16.1) months on long-term PDA, prolonging overall patient duration on PD by a little over a year. Of the patients who exited the long-term PDA program, 73 (37.4%) were able to utilise the service until they died. CONCLUSION: PDA is an accessible, patient-centric service with clear and standardised referral criteria. Through the implementation of a local PDA program, patients have accessed PD and may have extended their PD life span, through avoidance of in-centre haemodialysis, by over 13 months during this 5-year study period. A significant proportion of patients on long-term PDA were able to use their preferred kidney replacement modality at home until they reached end of life.

14.
Perit Dial Int ; 43(2): 139-144, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35491897

RESUMO

The wave of kidney and heart outcome trials, showing multiple potential benefits for sodium-glucose co-transport 2 (SGLT2) inhibitors, have excluded patients with an estimated glomerular filtration rate below 25 ml/min/1.73 m2. However, dialysis patients are at the highest risk of cardiovascular disease and would benefit most from effective cardioprotective therapies. There is emerging evidence from experimental studies and post hoc analyses of randomised clinical trials that SGLT2 inhibitors are well tolerated and may also be effective in preventing cardiovascular and mortality outcomes in patients with severe chronic kidney disease, including patients receiving dialysis. As such, extending the usage of SGLT2 inhibitors to dialysis patients could provide a major advancement in their care. Peritoneal dialysis (PD) patients have an additional unmet need for effective pharmacotherapy to preserve their residual kidney function (RKF), with its associated mortality benefits, and for treatment options that help reduce the risk of transfer to haemodialysis. Experimental data suggest that SGLT2 inhibitors, via various mechanisms, may preserve RKF and protect the peritoneal membrane. There is sound physiological rationale and an urgent clinical need to execute robust randomised control trials to study the use of SGLT2 inhibitors in PD patients to answer important questions of relevance to patients and healthcare systems.


Assuntos
Diabetes Mellitus Tipo 2 , Diálise Peritoneal , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diálise Peritoneal/efeitos adversos , Glucose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Rim , Sódio , Diabetes Mellitus Tipo 2/tratamento farmacológico
15.
Comput Biol Chem ; 102: 107801, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36528019

RESUMO

A high-quality reference genome is an important resource that can help decipher the genetic basis of traits in combination with linkage or association analyses. The publicly available oil palm draft genome sequence of AVROS pisifera (EG5) accounts for 1.535 Gb of the 1.8 Gb oil palm genome. However, the assemblies are fragmented, and the earlier assembly only had 43% of the sequences placed on pseudo-chromosomes. By integrating a number of SNP and SSR-based genetic maps, a consensus map (AM_EG5.1), comprising of 828.243 Mb genomic scaffolds anchored to 16 pseudo-chromosomes, was generated. This accounted for 54% of the genome assembly, which is a significant improvement to the original assembly. The total length of N50 scaffolds anchored to the pseudo-chromosomes increased by ∼18% compared to the previous assembly. A total of 139 quantitative trait loci for agronomically important quantitative traits, sourced from literature, were successfully mapped on the new pseudo-chromosomes. The improved assembly could also be used as a reference to identify potential errors in placement of specific markers in the linkage groups of the genetic maps used to assemble the consensus map. The 3422 unique markers from five genetic maps, anchored to the pseudo-chromosomes of AM_EG5.1, are an important resource that can be used preferentially to either construct new maps or fill gaps in existing genetic maps. Synteny analysis further revealed that the AM_EG5.1 had high collinearity with the date palm genome cultivar 'Barhee BC4' and shared most of its segmental duplications. This improved chromosomal-level genome is a valuable resource for genetic research in oil palm.


Assuntos
Arecaceae , Locos de Características Quantitativas , Mapeamento Cromossômico , Consenso , Ligação Genética , Genômica , Arecaceae/genética , Genoma de Planta/genética , Repetições de Microssatélites
16.
Front Public Health ; 11: 1251565, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38352130

RESUMO

Background: In the United States Department of Veterans Affairs (VA), veterans who are lesbian, gay, bisexual, transgender, queer, and similar gender and sexual minoritized people (LGBTQ+) experience health disparities compared to cisgender, heterosexual veterans. VA's LGBTQ+ Health Program created two healthcare policies on providing LGBTQ+ affirming care (healthcare that is inclusive, validating, and understanding of the LGBTQ+ population). The current project examines providers' barriers and facilitators to providing LGBTQ+ affirming care and LGBTQ+ veterans' barriers and facilitators to receiving LGBTQ+ affirming care. Methods: Data collection and analysis were informed by the Consolidated Framework for Implementation Research, which was adapted to include three health equity domains. Data collection involved telephone interviews conducted with 11 VA providers and 12 LGBTQ+ veterans at one rural and one urban VA medical center, and one rural VA community clinic. Qualitative data were rapidly analyzed using template analysis, a data reduction technique. Results: Providers described limited education, limited time, lack of experience with the population, and a lack of awareness of resources as barriers. Providers discussed comfort with consulting trusted peers, interest in learning more about providing LGBTQ+ affirming care, and openness and acceptance of the LGBTQ+ community as facilitators. LGBTQ+ veterans described a lack of provider awareness of their needs, concerns related to safety and discrimination, and structural discrimination as barriers. LGBTQ+ veterans described positive relationships with providers, knowledge of their own healthcare needs, and ability to advocate for their healthcare needs as facilitators. Although VA's LGBTQ+ affirming care policies are in place, providers and veterans noted a lack of awareness regarding specific healthcare processes. Conclusion: Allowing more time and capacity for education and engaging LGBTQ+ veterans in determining how to improve their healthcare may be the path forward to increase adherence to LGBTQ+ affirming care policies. Engaging patients, especially those from marginalized backgrounds, in strategies focused on the uptake of policy may be a path to improve policy implementation. It is possible that creating truly collaborative structures in which patients, staff, providers, leadership, and policymakers can work together towards policy implementation may be a useful strategy. In turn, improved policy implementation would result in increased physical and mental health for LGBTQ+ veterans.


Assuntos
Minorias Sexuais e de Gênero , Saúde dos Veteranos , Feminino , Humanos , Estados Unidos , Atenção à Saúde , Comportamento Sexual , Políticas
18.
Artigo em Inglês | MEDLINE | ID: mdl-36521445

RESUMO

INTRODUCTION: Detection of atrial fibrillation (AF) is challenging in patients after ischemic stroke due to its paroxysmal nature. We aim to determine the utility of a combined clinical, electrocardiographic and genetic variables model to predict AF in a post-stroke population. MATERIALS AND METHODS: We performed a cohort study at a single comprehensive stroke centre from 09/11/2009 to 31/10/2017. All patients recruited were diagnosed with acute ischemic stroke or transient ischemic attacks. Electrocardiographic variables including p-wave terminal force (PWTF), corrected QT interval (QTc) and genetic variables including single nucleotide polymorphisms (SNP) at the 4q25 (rs2200733) were evaluated. Clinical, electrocardiographic and genetic variables of patients without AF and those who developed AF were compared. Multiple logistic regression analysis and receiver operating characteristics were performed to identify parameters and determine their ability to predict the occurrence of AF. RESULTS: Out of 709 patients (median age of 59 years, IQR 52-67) recruited, sixty (8.5%) were found to develop AF on follow-up. Age (odds ratio (OR): 3.49, 95% confidence interval (CI): 2.03-5.98, p<0.0001), hypertension (OR: 2.76, 95% CI: 1.36-5.63, p=0.0052) and valvular heart disease (OR: 8.49, 95% CI: 2.62-27.6, p<0.004 were the strongest predictors of AF, with area under receiver operating value of 0.76 (95% CI: 0.70-0.82), and 0.82 (95% CI: 0.77-0.87) when electrocardiographic variables (PWTF and QTc) were added. SNP did not improve prediction modelling. CONCLUSION: We demonstrated that a model combining clinical and electrocardiographic variables provided robust prediction of AF in our post-stroke population. Role of SNP in prediction of AF was limited.

19.
ACS Med Chem Lett ; 13(11): 1805-1811, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36385926

RESUMO

Janus kinases (JAK) play a critical role in JAK/signal transducer and activator of transcription (STAT) signaling pathways that mediate immune response and cell growth. From high-throughput screening (HTS) hit to lead optimization, a series of pyrimidine compounds has been discovered as potent JAK1 inhibitors with selectivity over JAK2. Cell-based assays were used as primary screening methods for evaluating potency and selectivity, the results were further assessed and confirmed by biochemical and additional cellular assays for lead molecules. Also discussed is the unique correlation between a trifluomethyl group and CYP3A4 inhibition in the presence of NADPH, the activity of which was successfully decreased with the reduction of fluoro-atoms, increasing IC50 from 0.5 µM to >10 µM. The development of novel and scalable synthetic routes for amino-phenyl intermediates was essential for the discovery of late-stage lead molecules, including clinical candidate R507 (33). In preclinical studies, 33 exhibited great efficacy in mouse studies by inhibiting IFNγ expression induced by IL-2 and in a rat collagen-induced arthritis disease model.

20.
BMC Geriatr ; 22(1): 826, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36303107

RESUMO

BACKGROUND: Kidney transplantation is the definitive treatment for end stage renal disease (ESRD), offering improved quality of life and survival benefit over remaining on dialysis. There is, however, a prevailing significant mismatch between patients awaiting transplantation and available donor kidneys. Over time, initial stringent donor criteria have broadened and organs from extended criteria donors (ECDs) and older donors are now being accepted for transplantation. The spectrum of living donors has also undergone a change from close family members to an increasingly non-related, non-directed altruistic donors, newly classified as 'unspecified' donors. Unspecified elderly donors could be a potential untapped resource to expanding the kidney donor pool globally. CASE PRESENTATION: We present a case of an 85 year and 8 months old individual, who donated to an unrelated non-directed matched recipient in the national deceased donor transplant waiting list with excellent donor and recipient outcomes at 7 years. CONCLUSION: To our knowledge she is one of the oldest reported unspecified living kidney donors in the world to date. This case illustrates that elderly donors in good health can come forward to donate, knowing that it is safe and valuable. Once the immediate perioperative challenges after kidney donation are managed, elderly donors rarely encounter long term sequelae. We therefore report this case to increase awareness and refocus attention of transplant teams on elderly donors as a potential untapped group to help address the organ shortage problem in renal transplantation.


Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Doadores Vivos , Altruísmo
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