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1.
Int J Clin Pharm ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39368042

RESUMO

BACKGROUND: Medications form the basis of treatment for heart failure (HF) and adherence is crucial as untreated HF has a mortality of greater than 30%. As such, specialist HF pharmacists with expertise in prescribing and promoting adherence have become an integral part of the wider HF multidisciplinary team (MDT). AIM: To implement specialist HF pharmacist prescribing clinics and evaluate their impact. SETTING: An integrated HF team at a tertiary London hospital. DEVELOPMENT: The clinic was initially developed to facilitate the introduction of sacubitril-valsartan evolving to 6 dedicated clinics/week. IMPLEMENTATION: A dedicated electronic referral pathway was created to channel referrals to the specialist clinic, and referral criteria expanded to all patients requiring optimisation of medical therapy. EVALUATION: Data were retrospectively collected for patients with heart failure with reduced ejection fraction seen in the HF pharmacist clinic between September 2021 and July 2022. Overall, 114 patients were seen (mean age 66 years, 78 male). The mean time to medication optimisation was 3 months (averaging 1 appointment/month). The number on optimised doses of guideline-directed medical therapy, increased significantly from 8% at first appointment to 76% on discharge (p < 0.001). The HF pharmacists reviewed all medications and optimised non-HF medications for 17.5% (n = 20) of patients. CONCLUSION: HF pharmacists can optimise patients' HF and non-HF medical therapy typically within 3 months. By reviewing all prescribed medications, HF pharmacists provide a holistic review of all medications. They can play a vital role in addressing the underutilisation of HF medical therapy and thereby improving patient outcomes.

2.
Lancet Microbe ; : 100969, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39389079

RESUMO

Delivering large-scale routine pathogen genomics surveillance for public health is of considerable interest, although translational research models that promote national-level implementation are not well defined. We describe the development and deployment of the Australian Pathogen Genomics Program (AusPathoGen), a comprehensive national partnership between academia, public health laboratories, and public health agencies that commenced in January, 2021. Successfully establishing and delivering a national programme requires inclusive and transparent collaboration between stakeholders, defined and clear focus on public health priorities, and support for strengthening national genomics capacity. Major enablers for delivering such a programme include technical solutions for data integration and analysis, such as the genomics surveillance platform AusTrakka, standard bioinformatic analysis methods, and national ethics and data sharing agreements that promote nationally integrated surveillance systems. Training of public health officials to interpret and act on genomic data is crucial, and evaluation and cost-effectiveness programmes will provide a benchmark and evidence for sustainable investment in genomics nationally and globally.

3.
Am J Trop Med Hyg ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226893

RESUMO

Melioidosis is an emerging tropical infectious disease with a rising global burden caused by the environmental bacterium Burkholderia pseudomallei. It is endemic in Southeast and South Asia, including Bangladesh. A rare aminoglycoside-susceptible B. pseudomallei isolate (Y2019) has recently been reported from a melioidosis patient in Dhaka, Bangladesh. To understand the geographical origins of Y2019, we subjected it and 10 other isolates from Bangladesh to whole-genome sequencing. In a phylogenetic tree with a global set of B. pseudomallei genomes, most Bangladeshi genomes clustered tightly within the Asian clade. In contrast, Y2019 was closely related to ST881 isolates from Sarawak, Malaysian Borneo, a gentamicin-sensitive sequence type, suggesting infection in Borneo. Y2019 also contained the same gentamicin sensitivity conferring nonsynonymous mutation in the drug efflux pump encoding the amrB gene. In the absence of a full travel history, whole-genome sequencing and bioinformatics tools have revealed the likely origin of this rare isolate.

4.
Cureus ; 16(7): e65630, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39205703

RESUMO

With echocardiography standing as the most widely used cardiac imaging modality, echocardiography report interpretation is a core responsibility of junior doctors. The literature, however, reveals a deficit in echocardiography education. The implications of this for patient care should not be ignored. To address this need, a hybrid teaching session was developed for junior (intern and resident grade) doctors, with the aim to increase understanding of echocardiography and increase confidence in report interpretation. Pre- and post-session data were analysed. Results revealed that the vast majority of respondents received less than an hour of echocardiography teaching at medical school, with over two-thirds receiving less than an hour in the postgraduate setting. A total of 80% of doctors interpreted echocardiography reports weekly, with almost all doctors perceiving this skill as important. Despite this, an overwhelming majority of doctors did not feel confident interpreting reports. The educational intervention achieved significant increases in perceived understanding of echocardiography and confidence with report interpretation. Participants were better able to identify cardiac pathology and understand report terminology. This intervention has the scope to improve patient safety through better management of cardiac patients and recognition of pathology from echocardiography. This work also identifies a need for more echocardiography education, having uncovered a concerning lack of confidence amongst junior doctors and an appetite for further teaching on this important topic.

5.
J Pharm Sci ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39182845

RESUMO

Charge variants are one of the most important quality attributes for protein therapeutics, including antibody drug conjugates (ADCs). ADCs are conjugation products between monoclonal antibodies (mAbs) and highly potent payloads. After attaching a payload, the charge profile of a mAb can be modified due to the change in net charge or surface charge. In this study, we present a unique challenge of charge assay development that arises from a desirable engineering of ADCs that incorporates the hydrolysis-prone succinimide-thioether conjugation chemistry. This engineered hydrolysis at conjugation sites is usually not complete during conjugation process and continuously progressing during mild stress. This hydrolysis also creates a carboxylic functional group, which manifests as acidic peaks in the ADC charge profiles. As a result, ion exchange chromatograms become sensitive measurements of this hydrolysis, which often masks the charge profile change due to other important post-translational modifications. In this study, two approaches were explored to address this unique challenge: to remove the hydrolysis heterogeneity by incubating ADCs under high pH conditions to drive complete hydrolysis; and to analyze charge variants at the subunit level after IdeS digestion. Acceptable charge profiles and quantitative integration results were successfully obtained by both approaches.

6.
Neuropsychiatr ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995527

RESUMO

PURPOSE: Social challenges are common in patients with eating disorders (ED). The presence of autistic characteristics often exacerbates social difficulties within this group, potentially affecting treatment outcomes. This study investigates the communication preferences, challenges, dislikes, and support needs of patients with ED, both with and without autistic traits, using a communication passport in a national inpatient ED service. METHODS: An explorative qualitative analysis of 38 completed communication passports was conducted to investigate patients' communication preferences, sensory needs, struggles and dislikes, and areas of support required, paying particular attention to the distinct needs of patients with high levels of autistic traits. RESULTS: The communication passport provided valuable insights into patients' communication preferences, sensory sensitivities, challenges, and support needed. Patients also used the passports to share information about their strengths, personal identity, and life beyond the hospital. CONCLUSION: The communication passport fosters a deeper understanding of patients' needs and may support clinicians in care planning and communication strategies tailored to each patient's needs. Regular evaluation and updates are warranted to ensure its usability and accessibility by the wider care team.

7.
Pediatrics ; 154(2)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39034828

RESUMO

Oral health is an essential component of overall health for all individuals. The oral health of children and youth with developmental disabilities (CYDD) involves unique characteristics and needs of which pediatricians and pediatric clinicians can be aware. Risk for oral disease in CYDD is multifactorial and includes underlying medical conditions, medications, and ability to participate in preventive oral health care and treatment, and lack of access to providers is common for this population despite being eligible for Medicaid. Pediatric clinicians are uniquely positioned to support the oral health needs of CYDD and their families through the medical home. This clinical report aims to inform pediatric clinicians about the unique oral health needs of CYDD. It provides guidance on assessing caries risk and periodontal status using structured screening instruments; understanding dental trauma, the role of diet and caries risk, trauma prevention, and malocclusion; and providing anticipatory guidance on oral hygiene that includes tooth brushing, use of fluoridated toothpaste, assessing community water fluoridation, advocating for a dental home by 1 year of age, and transition to adult dental care as part of adolescent health care. It also highlights special considerations for dental treatment rendered under sedation or general anesthesia that CYDD may need. Pediatric clinicians can help reduce risk of CYDD developing dental disease by understanding the unique needs of their patients and their barriers to accessing oral health care in their community, communicating with the child's dental home, and advocating for safe and accessible dental procedures.


Assuntos
Deficiências do Desenvolvimento , Saúde Bucal , Humanos , Deficiências do Desenvolvimento/terapia , Adolescente , Criança , Assistência Odontológica para a Pessoa com Deficiência , Assistência Odontológica para Crianças , Cárie Dentária/prevenção & controle , Cárie Dentária/terapia
8.
PLoS Negl Trop Dis ; 18(5): e0012195, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38805481

RESUMO

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, that is common in tropical and subtropical countries including Southeast Asia and Northern Australia. The magnitude of undiagnosed and untreated melioidosis across the country remains unclear. Given its proximity to regions with high infection rates, Riau Province on Sumatera Island is anticipated to have endemic melioidosis. This study reports retrospectively collected data on 68 culture-confirmed melioidosis cases from two hospitals in Riau Province between January 1, 2009, and December 31, 2021, with full clinical data available on 41 cases. We also describe whole genome sequencing and genotypic analysis of six isolates of B. pseudomallei. The mean age of the melioidosis patients was 49.1 (SD 11.5) years, 85% were male and the most common risk factor was diabetes mellitus (78%). Pulmonary infection was the most common presentation (39%), and overall mortality was 41%. Lung as a focal infection (aOR: 6.43; 95% CI: 1.13-36.59, p = 0.036) and bacteremia (aOR: 15.21; 95% CI: 2.59-89.31, p = 0.003) were significantly associated with death. Multilocus sequence typing analysis conducted on six B.pseudomallei genomes identified three sequence types (STs), namely novel ST1794 (n = 3), ST46 (n = 2), and ST289 (n = 1). A phylogenetic tree of Riau B. pseudomallei whole genome sequences with a global dataset of genomes clearly distinguished the genomes of B. pseudomallei in Indonesia from the ancestral Australian clade and classified them within the Asian clade. This study expands the known presence of B. pseudomallei within Indonesia and confirms that Indonesian B. pseudomallei are genetically linked to those in the rest of Southeast Asia. It is anticipated that melioidosis will be found in other locations across Indonesia as laboratory capacities improve and standardized protocols for detecting and confirming suspected cases of melioidosis are more widely implemented.


Assuntos
Burkholderia pseudomallei , Variação Genética , Melioidose , Sequenciamento Completo do Genoma , Humanos , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/classificação , Burkholderia pseudomallei/isolamento & purificação , Melioidose/epidemiologia , Melioidose/microbiologia , Masculino , Pessoa de Meia-Idade , Feminino , Indonésia/epidemiologia , Adulto , Estudos Retrospectivos , Filogenia , Genótipo , Idoso , Fatores de Risco
9.
Echo Res Pract ; 11(1): 10, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627858

RESUMO

BACKGROUND: The burden of screening for inherited cardiac conditions on health services grows ever larger, with each new diagnosis necessitating screening of additional family members. Screening these usually asymptomatic, low-risk individuals is currently performed by consultant cardiologists, consuming vital clinic resources that could otherwise be diverted to sicker patients requiring specialist consultant input. Clinical scientists now constitute a highly skilled and often underutilised group of individuals with training in areas such as clinical evaluation, 12-lead electrocardiography (ECG) interpretation, and echocardiography. These skills place them in a unique position to offer a full screening evaluation in a single consultation. The aim of this study was to implement and evaluate a novel clinical scientist-led screening clinic for first-degree relatives of patients with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The clinical scientist-led screening clinic was established at a London tertiary centre to allow review of asymptomatic, first-degree relatives of patients with a confirmed diagnosis of HCM or DCM, independent of a cardiology consultant. Patients were evaluated with history, examination, ECG, and echocardiography, with further investigations if deemed necessary. A retrospective review was performed of the first 200 patients seen in the clinic. RESULTS: Of the 200 individuals reviewed between September 2019 and July 2022, 99 had a proband with HCM and 101 a proband with DCM. Overall, 169 individuals (85%) revealed normal screenings and were discharged. Thirty-one individuals (15.5%), all asymptomatic, revealed ECG changes and/or significant echocardiographic findings. Of these, 21 individuals (10.5% of the total cohort) were subsequently diagnosed with a cardiomyopathy or early phenotypic changes consistent with a cardiomyopathy (11 with HCM and 10 with DCM). These individuals were referred on to an inherited cardiac conditions consultant clinic for regular follow-up. Overall, 179 consultant clinic appointments were saved which could instead be allocated to patients requiring specialist consultant input. CONCLUSIONS: This is the first description of a clinical scientist-led screening clinic for first-degree relatives of patients with HCM and DCM. The findings demonstrate that implementation of such a service into routine clinical practice is feasible, effective, safe, and can free up capacity in consultant clinics for patients requiring specialist input.

10.
Alzheimers Dement ; 20(5): 3270-3280, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38506627

RESUMO

INTRODUCTION: People with Down syndrome (DS) have high risk of developing Alzheimer's disease (AD). This study examined mean ages of AD diagnosis and associations with co-occurring conditions among adults with DS from five European countries. METHODS: Data from 1335 people with DS from the Horizon 21 European DS Consortium were used for the analysis. RESULTS: Mean ages of AD diagnosis ranged between 51.4 (SD 7.0) years (United Kingdom) and 55.6 (SD 6.8) years (France). Sleep-related and mental health problems were associated with earlier age of AD diagnosis. The higher number of co-occurring conditions the more likely the person with DS is diagnosed with AD at an earlier age. DISCUSSION: Mean age of AD diagnosis in DS was relatively consistent across countries. However, co-occurring conditions varied and impacted on age of diagnosis, suggesting that improvements can be made in diagnosing and managing these conditions to delay onset of AD in DS. HIGHLIGHTS: Mean age of AD diagnosis was relatively consistent between countries Sleep problems and mental health problems were associated with earlier age of AD diagnosis APOE ε4 carriers were diagnosed with AD at an earlier age compared to non-carriers Number of co-occurring conditions was associated with earlier age of AD diagnosis No differences between level of intellectual disability and mean age of AD diagnosis.


Assuntos
Doença de Alzheimer , Síndrome de Down , Humanos , Síndrome de Down/epidemiologia , Síndrome de Down/diagnóstico , Síndrome de Down/complicações , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Europa (Continente)/epidemiologia , Adulto , Reino Unido/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/diagnóstico , Fatores Etários , Idade de Início , França/epidemiologia , Idoso , Comorbidade , Apolipoproteína E4/genética
11.
Front Aging ; 4: 1180939, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593678

RESUMO

Introduction: Exercise "snacking" and Tai-chi 'snacking' protocols are designed to overcome typical barriers to older adults' participation in muscle strength and balance exercise, using short bouts of home-based exercise. This study aimed to investigate the acceptability of homebred exercise- and Tai-chi snacking in British and Taiwanese older adults of high and low physical function. Methods: Thirty-three British and Thirty Taiwanese older adults took part in semi-structured interviews, after trying 1-week of exercise- and Tai-chi snacking. The interview schedule and deductive framework analysis was based on the seven components of the Theoretical Framework of Acceptability (TFA). Differences between the Taiwanese and United Kingdom participants and those considered high versus low physical function were also analysed. Results: Both snacking regimes were found to be convenient and easy to implement. Participants reported that no activity had to be given up, and considered the programmes would be beneficial to their physical and mental health. Interestingly, more UK-based participants preferred the elegant and relaxing movements of Tai-chi snacking, yet participants with low physical function experienced difficulties when mastering Tai-chi movements. A few high physical function participants perceived exercise snacking to be tedious. Discussion: Overall, the snacking exercise was found to be acceptable and useful. Personal affective attitude and different cultural backgrounds may affect exercise participation. Nevertheless, it is important to consider individuals' physical function when designing exercise regime. The findings indicate that making Tai-chi snacking easier to master initially, building in progression and adding some upper body movements in the exercise snacking may further enhance acceptability.

12.
Front Psychol ; 14: 1234928, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37645066

RESUMO

Background: Social isolation, loneliness and difficulties in relationships are often described as a core feature of eating disorders. Based on the experimental research, we have designed one-off workshops for patients in inpatients and day care services and evaluated its acceptability and effectiveness using feedback questionnaires. Methods: This naturalistic project is an evaluation of multiple positive communication workshops. Forty-one participants completed workshop questionnaires, which were provided immediately at the beginning and end of the workshop, including feedback on these one-off groups. The workshops consisted of educational and experiential components. The questionnaire outcomes were evaluated by independent researchers. Results: All participants were female adults with a mean age of 33 (12.2) and a diagnosis of Anorexia Nervosa (AN; either restrictive or binge-purge subtype). Post-workshop questionnaires showed large effect sizes in the improvement of understanding the importance and confidence in using positive communication strategies. Discussion: Addressing social communication difficulties in eating disorder treatment programmes adds valuable dimensions to these symptom-based treatments in both inpatient settings and day services, and may provide broader benefits in overall social functioning in patients with AN. Conclusion: Brief one-off workshops targeting social functioning for patients with eating disorders might be useful complementary input for treatment programmes.

13.
Open Forum Infect Dis ; 10(8): ofad405, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37577114

RESUMO

Burkholderia pseudomallei, the causative agent of melioidosis, has not yet been reported in Timor-Leste, a sovereign state northwest of Australia. In the context of improved access to diagnostic resources and expanding clinical networks in the Australasian region, we report the first 3 cases of culture-confirmed melioidosis in Timor-Leste. These cases describe a broad range of typical presentations, including sepsis, pneumonia, multifocal abscesses, and cutaneous infection. Phylogenetic analysis revealed that the Timor-Leste isolates belong to the Australasian clade of B. pseudomallei, rather than the Asian clade, consistent with the phylogeographic separation across the Wallace Line. This study underscores an urgent need to increase awareness of this pathogen in Timor-Leste and establish diagnostic laboratories with improved culture capacity in regional hospitals. Clinical suspicion should prompt appropriate sampling and communication with laboratory staff to target diagnostic testing. Local antimicrobial guidelines have recently been revised to include recommendations for empiric treatment of severe sepsis.

14.
J Eat Disord ; 11(1): 117, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443135

RESUMO

BACKGROUND: A one-off sensory wellbeing workshop has been developed to help patients with eating disorders (ED) manage sensory sensitivities. The aim of this study was to evaluate and compare the outcomes of the workshop in online versus face-to-face (F2F) formats among a sample of patients with ED. METHODS: Cumulative link models were applied to the outcome measures (awareness of sensory wellbeing, awareness of strategies to enhance sensory wellbeing, and confidence in managing sensory wellbeing) to test the differences between online and F2F workshops. Participants' ratings of usefulness of the workshop were also compared between online and F2F workshops. RESULTS: A total of 14 workshops (4 online and 10 F2F) were run from 2020 to 2023. All participants reported significant and substantial improvements in all outcome measures. There was no significant difference in outcomes between online and F2F workshops. The majority of patients rated the workshops as useful. CONCLUSIONS: Both online and face-to-face formats of the sensory workshop led to improvement in sensory wellbeing management for patients with ED. Future studies are warranted to test the impact of the workshop on ED treatment outcomes.


People with eating disorders often have sensory issues, which can include being too sensitive to some senses (hearing, smell or taste, for example) or not sensitive enough. Explaining how the sensory system works and developing helpful strategies to manage sensory difficulties could be beneficial in the process of therapy. To try and support this, clinicians and researchers designed a sensory wellbeing workshop to help people become more aware of their sensory wellbeing and teach them strategies to manage their sensory wellbeing. The workshop can be delivered online or face-to-face. This study examined the feedback for online and face-to-face workshops. We found that both formats were helpful for people with eating disorders. We also discuss possible ways to develop and test the workshop further in order to better support patients with sensory difficulties.

15.
Psychiatry Res ; 326: 115272, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37276647

RESUMO

This study used cluster analysis to explore clinically relevant subgroups of adult patients with anorexia nervosa (AN). Patients were clustered based on their body mass index (BMI), eating disorder symptomatology, anxiety and depression symptoms and autistic characteristics. The difference between clusters in work and social functioning, duration of illness, bingeing and purging behaviour, previous hospitalisations and number of comorbidities was also investigated. Two meaningful clusters emerged: a higher symptoms cluster with more severe eating pathology, anxiety, depression, and more autistic traits, and a second cluster with lower symptoms. BMI did not make major contributions to cluster formation. The higher symptoms cluster also reported lower self-efficacy to change, more previous hospitalisations, comorbid diagnoses, binge eating and purging behaviours and use of psychotropic medication. Our findings suggest that weight alone may not be a significant severity indicator amongst inpatients with AN, and targeted treatment of AN should consider a broader range of symptom severity indicators.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia , Transtornos da Alimentação e da Ingestão de Alimentos , Adulto , Humanos , Anorexia Nervosa/complicações , Anorexia Nervosa/epidemiologia , Anorexia Nervosa/diagnóstico , Síndrome , Bulimia/diagnóstico , Transtorno da Compulsão Alimentar/diagnóstico
16.
Antimicrob Agents Chemother ; 67(6): e0017123, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37133377

RESUMO

Cefiderocol is a siderophore cephalosporin designed mainly for treatment of infections caused by ß-lactam and multidrug-resistant Gram-negative bacteria. Burkholderia pseudomallei clinical isolates are usually highly cefiderocol susceptible, with in vitro resistance found in a few isolates. Resistance in clinical B. pseudomallei isolates from Australia is caused by a hitherto uncharacterized mechanism. We show that, like in other Gram-negatives, the PiuA outer membrane receptor plays a major role in cefiderocol nonsusceptibility in isolates from Malaysia.


Assuntos
Antibacterianos , Burkholderia pseudomallei , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Cefiderocol
17.
Biochemistry ; 62(5): 1012-1025, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36820504

RESUMO

The MID1 TRIM protein is important for ventral midline development in vertebrates, and mutations of its B-box1 domain result in several birth defects. The B-box1 domain of the human MID1 protein binds two zinc atoms and adopt a similar ßßα-RING structure. This domain is required for the efficient ubiquitination of protein phosphatase 2A, alpha4, and fused kinase. Considering the structural similarity, the MID1 B-box1 domain exhibits mono-autoubiquitination activity, in contrast to poly-autoubiquitination observed for RING E3 ligases. To understand its mechanism of action, the interaction of the B-box1 domain with Ube2D1 (UbcH5a, E2), a preferred E2 ligase, is investigated. Using isothermal titration calorimetry, the MID1 RING and B-box1 domains were observed to have similar binding affinities with the Ube2D1 protein. However, NMR 15N-1H Heteronuclear Single Quantum Coherence titration, 15N relaxation data, and High Ambiguity Driven protein-protein DOCKing (HADDOCK) calculations show the B-box1 domain binding on a surface distinct from where RING domains bind. The novel binding interaction shows the B-box1 domain partially overlapping the noncovalent Ube2D1 and a ubiquitin binding site that is necessary for poly-autoubiquitination activity. The B-box1 domain also displaces the ubiquitin from the Ube2D1 protein. These studies reveal a novel binding interaction between the zinc-binding ßßα-fold B-box1 domain and the Ube2D enzyme family and that this difference in binding, compared to RING E3 ligases, provides a rationale for its auto-monoubiquitination E3 ligase activity.


Assuntos
Proteínas dos Microtúbulos , Fatores de Transcrição , Enzimas de Conjugação de Ubiquitina , Ubiquitina-Proteína Ligases , Humanos , Sequência de Aminoácidos , Proteínas dos Microtúbulos/química , Modelos Moleculares , Estrutura Terciária de Proteína , Fatores de Transcrição/química , Ubiquitina/química , Enzimas de Conjugação de Ubiquitina/química , Ubiquitina-Proteína Ligases/química , Ubiquitinação , Zinco/química
18.
Int J Antimicrob Agents ; 61(3): 106714, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36640845

RESUMO

Burkholderia pseudomallei is a soil- and water-dwelling Gram-negative bacterium that causes melioidosis in humans and animals. Amoxicillin-clavulanic acid (AMC) susceptibility has been hailed as an integral part of the screening algorithm for identification of B. pseudomallei, but the molecular basis for the inherent AMC susceptibility of this bacterium remains undefined. This study showed that B. pseudomallei (and the closely-related B. mallei) wild-type strains are the only Burkholderia spp. that contain a 70STSK73 PenA Ambler motif. This motif was present in >99.5% of 1820 analysed B. pseudomallei strains and 100% of 83 analysed B. mallei strains, and is proposed as the likely cause for their inherent AMC sensitivity. The authors developed a polymerase chain reaction (PCR) assay that specifically amplifies the penA70ST(S/F)K73-containing region from B. pseudomallei and B. mallei, but not from the remaining B. pseudomallei complex species or the 70STFK73 region from the closely-related penB of B. cepacia complex species. The abundance and purity of the 193-bp PCR fragment from putative B. pseudomallei isolates from clinical and environmental samples is likely sufficient for reliable confirmation of the presence of B. pseudomallei. The PCR assay is designed to be especially suited for use in resource-constrained areas. While not further explored in this study, the assay may allow diagnosis of putative B. mallei in culture isolates from animal and human samples.


Assuntos
Burkholderia mallei , Burkholderia pseudomallei , Melioidose , Animais , Humanos , Burkholderia mallei/genética , Burkholderia pseudomallei/genética , Melioidose/diagnóstico , Melioidose/microbiologia , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , beta-Lactamases , Domínio Catalítico , Reação em Cadeia da Polimerase
19.
Eur J Hosp Pharm ; 30(e1): e14-e18, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34315773

RESUMO

OBJECTIVE: Pharmacists attending general medical post-admission ward rounds is established good practice. However, there is a lack of evidence on the impact of specialist heart failure (HF) prescribing pharmacists on consultant HF ward rounds. The aim of this study was to evaluate the impact on prescribing when a specialist HF prescribing pharmacist attended inpatient HF ward rounds. METHODS: A prospective service evaluation completed at a tertiary hospital between September and December 2020. The same HF prescribing pharmacist attended the HF consultant-led ward round once a week on 15 occasions. For each medicine change, the pharmacist documented: who suggested the intervention, the medicine, prescribing action, reason for review and the primary reason for change. Medicines were categorised into four groups (heart failure, cardiovascular, anticoagulation and other) for analysis. RESULTS: A total of 158 patients were reviewed and 226 individual changes suggested; 48% of these were consultant led (n=108) and 52% (n=118) due to pharmacist recommendations. All medicines interventions were prescribed on the round by the pharmacist. For consultants, the primary reason for medicine change was to ensure efficacy of HF medicines, 80% (n=73), followed by safety (HF medicines), 20% (n=18). For the pharmacist, the primary reason was safety across all the medicine groups, 36% (n=42), followed by efficacy relating to missing drug history items, 24% (n=28). CONCLUSIONS: HF consultants focused on ensuring patients have the most effective combination of HF medications. The addition of a specialist HF prescribing pharmacist ensured a wider range of medicines were reviewed for safety and optimisation, helping to deliver a holistic review of all medications.


Assuntos
Insuficiência Cardíaca , Erros de Medicação , Humanos , Farmacêuticos , Consultores , Centros de Atenção Terciária , Estudos Prospectivos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico
20.
Health (London) ; 27(1): 147-166, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-33947266

RESUMO

Physical activity can be a conduit for improving men's social connectedness as well as physical gains for well-being. However, marginalised men, and fathers in particular, can be challenged to engage in leisure time physical activity. This qualitative study reports how fathers, who experience complex and significant social and health inequities, conceptualise and experience barriers to physical activity. Drawing from focus groups with 17 fathers, and semi-structured interviews with seven service providers about their perspectives on men's physical activity in Vancouver's Downtown Eastside (DTES), a highly marginalised neighbourhood. A masculinities framework was used to describe and contextualise physical activity in fathers' lives. Three themes were inductively derived through the analyses: (1) 'they're busy surviving' a finding referencing the work and limits invoked by poverty wherein survival was triaged ahead of leisure time physical activity; (2) 'there is no activity centre' chronicling the lack of physical activity spaces, programmes and resources available to fathers; and (3) 'lifestyle affects our capability to exercise' a theme detailing how social isolation amplified by factors including housing and opioid crises, and being a father in a resource poor setting imposed significant barriers to physical activity. The findings support reconceptualising physical activity programmes with men who are living in marginalising conditions to address behavioural and structural health inequities in tailoring father-centred programmes and resources.


Assuntos
Exercício Físico , Isolamento Social , Humanos , Pesquisa Qualitativa
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