RESUMEN
PURPOSE: Pathogenic variants of FIG4 generate enlarged lysosomes and neurological and developmental disorders. To identify additional genes regulating lysosomal volume, we carried out a genome-wide activation screen to detect suppression of enlarged lysosomes in FIG4-/- cells. METHODS: The CRISPR-a gene activation screen utilized sgRNAs from the promoters of protein-coding genes. Fluorescence-activated cell sorting separated cells with correction of the enlarged lysosomes from uncorrected cells. Patient variants of SLC12A9 were identified by exome or genome sequencing and studied by segregation analysis and clinical characterization. RESULTS: Overexpression of SLC12A9, a solute co-transporter, corrected lysosomal swelling in FIG4-/- cells. SLC12A9 (NP_064631.2) colocalized with LAMP2 at the lysosome membrane. Biallelic variants of SLC12A9 were identified in 3 unrelated probands with neurodevelopmental disorders. Common features included intellectual disability, skeletal and brain structural abnormalities, congenital heart defects, and hypopigmented hair. Patient 1 was homozygous for nonsense variant p.(Arg615∗), patient 2 was compound heterozygous for p.(Ser109Lysfs∗20) and a large deletion, and proband 3 was compound heterozygous for p.(Glu290Glyfs∗36) and p.(Asn552Lys). Fibroblasts from proband 1 contained enlarged lysosomes that were corrected by wild-type SLC12A9 cDNA. Patient variant p.(Asn552Lys) failed to correct the lysosomal defect. CONCLUSION: Impaired function of SLC12A9 results in enlarged lysosomes and a recessive disorder with a recognizable neurodevelopmental phenotype.
Asunto(s)
Lisosomas , Trastornos del Neurodesarrollo , Simportadores de Cloruro de Sodio-Potasio , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Alelos , Mutación con Pérdida de Función/genética , Lisosomas/genética , Lisosomas/metabolismo , Lisosomas/patología , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/patología , Linaje , Fenotipo , Simportadores de Cloruro de Sodio-Potasio/genéticaRESUMEN
Liver biopsies have consistently contributed to our understanding of the pathogenesis and aetiologies of acute liver disease. As other diagnostic modalities have been developed and refined, the role of biopsy in the management of patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute hepatitis, including acute liver injury (ALI), has changed. Liver biopsy remains particularly valuable when first-line diagnostic algorithms fail to determine aetiology. Despite not being identified as a mandatory diagnostic tool in recent clinical guidelines for the management of ALF or ACLF, many centres continue to undertake biopsies given the relative safety of transjugular biopsy in this setting. Several studies have demonstrated that liver biopsy can provide prognostic information, particularly in the context of so-called indeterminate hepatitis, and is extremely useful in excluding conditions such as metastatic tumours that would preclude transplantation. In addition, its widespread use of percutaneous biopsies in cases of less severe acute liver injury, for example in the establishment of a diagnosis of acute presentation of autoimmune hepatitis or confirmation of a probable or definite drug-induced liver injury (DILI), has meant that many centres have seen a shift in the ratio of specimens they are receiving from patients with chronic to acute liver disease. Histopathologists therefore need to be equipped to deal with these challenging specimens. This overview provides an insight into the contemporary role of biopsies (as well as explant and autopsy material) in diagnosing acute liver disease. It outlines up-to-date clinical definitions of liver injury and considers recent recommendations for the diagnosis of AIH and drug-induced, autoimmune-like hepatitis (DI-AIH).
RESUMEN
Recreational angling of nesting largemouth bass (Micropterus nigricans) and smallmouth bass (M. dolomieu) can greatly increase nest abandonment, and in the northern clines of their range, decrease recruitment. This is the case in eastern Ontario, where high levels of non-compliance and difficult to enforce regulations have impacted black bass (Micropterus spp.) conservation and management. Effective January 1, 2024 until December 31st, 2025, novel and experimental fishing sanctuaries were imposed on portions of Charleston Lake and Opinicon Lake that prohibit recreational fishing of all types from April 15th to the Friday before the first Saturday in July (encompassing the full bass reproductive season). As part of the formal process to institute these experimental regulations, public comments were collected on the Environmental Registry of Ontario. We examined those comments and identified supportive and non-supportive themes related to these experimental regulations. While a majority of stakeholders were in support of the new regulations, we also noted sub-themes that may hinder regulation acceptance. Those sub-themes include: a perceived lack of enforcement negating the potential benefits of the sanctuaries, under-estimation of the extent of non-compliance with existing regulations such that new regulations are unnecessary, misunderstanding and misinformation, as well as distrust of government and the academic research community. Understanding and addressing these stakeholder perspectives will help researchers studying the new sanctuary areas and managers understand any lack of compliance while informing future decisions about bass management in eastern Ontario and beyond.
Asunto(s)
Lubina , Conservación de los Recursos Naturales , Explotaciones Pesqueras , Reproducción , Animales , Ontario , Conservación de los Recursos Naturales/legislación & jurisprudencia , Conservación de los Recursos Naturales/métodos , Explotaciones Pesqueras/legislación & jurisprudencia , Opinión PúblicaRESUMEN
Natural resource governance is inherently complex owing to the socio-ecological systems in which it is embedded. Working arrangements have been fundamentally transformed throughout the COVID-19 pandemic with potential negative impacts on trust-based social networks foundational to resource management and transboundary governance. To inform development of a post-pandemic new-normal in resource management, we examined trust relationships using the Laurentian Great Lakes of North America as a case study. 82.9% (n = 97/117) of Great Lakes fishery managers and scientists surveyed indicated that virtual engagement was effective for maintaining well-established relationships during the pandemic; however, 76.7% (n = 89/116) of respondents indicated in-person engagement to be more effective than virtual engagement for building and maintaining trust. Despite some shortcomings, virtual or remote engagement presents opportunities, such as: (1) care and nurturing of well-established long-term relationships; (2) short-term (1-3 years) trust maintenance; (3) peer-peer or mentor-mentee coordination; (4) supplemental communications; (5) producer-push knowledge dissemination; and, if done thoughtfully, (6) enhancing diversity, equity, and inclusion. Without change, pre-pandemic trust-based relationships foundational to cooperative, multinational, resource management are under threat.
Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Confianza , Recursos Naturales , Conservación de los Recursos NaturalesRESUMEN
BACKGROUND: Exposure to childhood adversities (CHAD) has been found to be strongly associated with individuals' mental health and social development. Recently, it has been suggested that certain CHAD patterns exist in the population, which are more closely related to individuals' later mental health than the simple summation of adversities. The current study aims 1) to establish CHAD patterns based on self-reported child abuse and family dysfunction and 2) to assess their associations with mental disorders and sociodemographic indicators reported in adulthood. METHODS: Data used in this cross-sectional study were derived from the representative CoLaus/PsyCoLaus population-based cohort (N = 5111, 35 to 88 years). Latent class analysis was conducted for the identification of CHAD patterns, while their associations with mental disorders and socioeconomic achievements (e. g. education and income) were investigated using correspondence analysis. RESULTS: Four CHAD patterns emerged. While the majority (70.7%) of the sample showed an overall low adversity pattern (c1), 13.6% had not been raised by both of their biological parents due to divorce or being placed in foster home (c2), 11.0% had been raised by conflictive / dysfunctional / abusive parents (c3), and 4.7% showed high overall adversities (c4). Patterns c3 and c4 were most strongly associated with various mental disorders, especially c3 with internalizing anxiety disorders, while c2 was closely related to lower educational achievement. CONCLUSIONS: Four CHAD patterns characterised by varying levels of child abuse and family dysfunction existed in this community sample. They yielded distinct associations with mental disorders and socioeconomic indicators.
Asunto(s)
Experiencias Adversas de la Infancia , Maltrato a los Niños , Trastornos Mentales , Adulto , Niño , Estudios Transversales , Humanos , Trastornos Mentales/epidemiología , Factores de Riesgo , Factores Socioeconómicos , Suiza/epidemiologíaRESUMEN
OBJECTIVES: The COVID-19 pandemic highlighted the importance of routine syndromic surveillance of respiratory infections, specifically new cases of severe acute respiratory infection (SARI). This surveillance often relies on questionnaires carried out by research nurses or transcriptions of doctor's notes, but existing, routinely collected electronic healthcare data sets are increasingly being used for such surveillance. We investigated how patient diagnosis codes, recorded within such data sets, could be used to capture SARI trends in Scotland. STUDY DESIGN: We conducted a retrospective observational study using electronic healthcare data sets between 2017 and 2022. METHODS: Sensitive, specific and timely case definition (CDs) based on patient diagnosis codes contained within national registers in Scotland were proposed to identify SARI cases. Representativeness and sensitivity analyses were performed to assess how well SARI cases captured by each definition matched trends in historic influenza and SARS-CoV-2 data. RESULTS: All CDs accurately captured the peaks seen in laboratory-confirmed positive influenza and SARS-CoV-2 data, although the completeness of patient diagnosis records was discovered to vary widely. The timely CD provided the earliest detection of changes in SARI activity, whilst the sensitive CD provided insight into the burden and severity of SARI infections. CONCLUSIONS: A universal SARI surveillance system has been developed and demonstrated to accurately capture seasonal SARI trends. It can be used as an indicator of emerging secondary care burden of emerging SARI outbreaks. The system further strengthens Scotland's existing strategies for respiratory surveillance, and the methods described here can be applied within any country with suitable electronic patient records.
Asunto(s)
COVID-19 , Gripe Humana , Humanos , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , SARS-CoV-2 , COVID-19/epidemiología , Pandemias , HospitalesRESUMEN
Sessile plants have evolved distinct mechanisms to respond and adapt to adverse environmental conditions through diverse mechanisms including RNA processing. While the role of RNA processing in the stress response is well understood for Arabidopsis thaliana, limited information is available for rice (Oryza sativa). Here, we show that OsFKBP20-1b, belonging to the immunophilin family, interacts with the splicing factor OsSR45 in both nuclear speckles and cytoplasmic foci, and plays an essential role in post-transcriptional regulation of abiotic stress response. The expression of OsFKBP20-1b was highly upregulated under various abiotic stresses. Moreover genetic analysis revealed that OsFKBP20-1b positively affected transcription and pre-mRNA splicing of stress-responsive genes under abiotic stress conditions. In osfkbp20-1b loss-of-function mutants, the expression of stress-responsive genes was downregulated, while that of their splicing variants was increased. Conversely, in plants overexpressing OsFKBP20-1b, the expression of the same stress-responsive genes was strikingly upregulated under abiotic stress. In vivo experiments demonstrated that OsFKBP20-1b directly maintains protein stability of OsSR45 splicing factor. Furthermore, we found that the plant-specific OsFKBP20-1b gene has uniquely evolved as a paralogue only in some Poaceae species. Together, our findings suggest that OsFKBP20-1b-mediated RNA processing contributes to stress adaptation in rice.
Asunto(s)
Oryza/metabolismo , Proteínas de Plantas/metabolismo , Factores de Empalme de ARN/metabolismo , Empalme Alternativo/genética , Empalme Alternativo/fisiología , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Oryza/genética , Proteínas de Plantas/genética , Unión Proteica , Procesamiento Postranscripcional del ARN/genética , Procesamiento Postranscripcional del ARN/fisiología , Factores de Empalme de ARN/genética , Estrés Fisiológico/genética , Estrés Fisiológico/fisiologíaRESUMEN
BACKGROUND AND AIMS: Differences in combined hepatocellular-cholangiocarcinomas (cHCC-CCAs) arising in high-risk patients with or without liver cirrhosis have not been elucidated. This study aimed to compare the clinicopathologic and imaging characteristics of cHCC-CCAs in patients with or without cirrhosis and to determine the prognostic factors for recurrence-free survival (RFS) after curative resections of single cHCC-CCAs. METHODS: This retrospective study included 113 patients with surgically resected single cHCC-CCAs who underwent preoperative magnetic resonance imaging from January 2008 to December 2019 at two tertiary referral centres. Clinical, pathologic and imaging features of tumours were compared in high-risk patients with or without cirrhosis. Imaging features were assessed using the Liver Imaging Reporting and Data System (LI-RADS) version 2018. RFS and associated factors were evaluated using Cox proportional hazards regression analysis, Kaplan-Meier analysis and log-rank test. RESULTS: cHCC-CCAs arising from cirrhotic livers had a smaller mean tumour size (2.9 cm vs. 4.5 cm; P < .001) and were more frequently categorized as LR-5 or 4 (41.2% vs. 20.0%; P = .024) than those arising from non-cirrhotic livers. In multivariable analysis, a tumour size of > 3 cm (hazard ratio [HR], 2.081; 95% confidence interval [CI], 1.180-3.668; P = .011) and the LR-M category (HR, 2.302; 95% CI, 1.198-4.424; P = .012) were independent predictors associated with worse RFS. CONCLUSIONS: The tumour size and distribution of LI-RADS categories of cHCC-CCAs differed in high-risk patients with or without cirrhosis. And LR-M category was a worse prognosis predictor after curative resections than LR-5 or 4 category.
Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos , Carcinoma Hepatocelular/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Medios de Contraste , Humanos , Cirrosis Hepática/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
BACKGROUND & AIMS: Noncoding RNAs (ncRNAs) play critical roles in hepatocellular carcinoma (HCC) progression. Here, by performing RNA-sequencing (RNA-Seq) profiling, we sought to identify novel ncRNAs that potentially drive the heterogeneous progression of liver cancers. METHODS: RNA-Seq profiles were obtained from 68 HCC specimens and 10 samples of adjacent non-tumour liver tissues. The functional significance of the potential driver ncRNAs was evaluated by cell experiments. RESULTS: TPRG1-AS1 was identified as a potential driver noncoding RNA that promotes heterogeneous liver cancer progression. TPRG1-AS1 induced tumour suppressor RNA-binding motif protein 24 (RBM24), suppressing tumour growth by activating apoptotic tumour cell death. In addition, we report that TPRG1-AS1 acts as a competing endogenous RNA (ceRNA) for RBM24, sponging miR-4691-5p and miR-3659 to interfere with their binding to RBM24. CONCLUSIONS: We suggest that TPRG1-AS1 is a novel ceRNA sponging miR-4691-5p and miR-3659, resulting in RBM24 expression and suppression of liver cancer growth. Our results provide new insights into the functions of ncRNAs in heterogeneous HCC progression.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN sin Sentido/genética , Proteínas de Unión al ARN , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , MicroARNs/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
A control theory perspective on determination of optimal dynamic treatment regimes is considered. The aim is to adapt statistical methodology that has been developed for medical or other biostatistical applications to incorporate powerful control techniques that have been designed for engineering or other technological problems. Data tend to be sparse and noisy in the biostatistical area and interest has tended to be in statistical inference for treatment effects. In engineering fields, experimental data can be more easily obtained and reproduced and interest is more often in performance and stability of proposed controllers rather than modeling and inference per se. We propose that modeling and estimation should be based on standard statistical techniques but subsequent treatment policy should be obtained from robust control. To bring focus, we concentrate on A-learning methodology as developed in the biostatistical literature and H∞ -synthesis from control theory. Simulations and two applications demonstrate robustness of the H∞ strategy compared to standard A-learning in the presence of model misspecification or measurement error.
Asunto(s)
Modelos EstadísticosRESUMEN
The plant cell wall is an important factor for determining cell shape, function and response to the environment. Secondary cell walls, such as those found in xylem, are composed of cellulose, hemicelluloses and lignin and account for the bulk of plant biomass. The coordination between transcriptional regulation of synthesis for each polymer is complex and vital to cell function. A regulatory hierarchy of developmental switches has been proposed, although the full complement of regulators remains unknown. Here we present a protein-DNA network between Arabidopsis thaliana transcription factors and secondary cell wall metabolic genes with gene expression regulated by a series of feed-forward loops. This model allowed us to develop and validate new hypotheses about secondary wall gene regulation under abiotic stress. Distinct stresses are able to perturb targeted genes to potentially promote functional adaptation. These interactions will serve as a foundation for understanding the regulation of a complex, integral plant component.
Asunto(s)
Arabidopsis/genética , Arabidopsis/metabolismo , Pared Celular/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Redes Reguladoras de Genes/genética , Factores de Transcripción/metabolismo , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , ADN de Plantas/genética , ADN de Plantas/metabolismo , Factores de Transcripción E2F/metabolismo , Retroalimentación , Regulación del Desarrollo de la Expresión Génica/genética , Deficiencias de Hierro , Especificidad de Órganos , Regiones Promotoras Genéticas/genética , Reproducibilidad de los Resultados , Salinidad , Factores de Tiempo , Xilema/genética , Xilema/crecimiento & desarrollo , Xilema/metabolismoRESUMEN
Pro-environmental behaviours (PEBs) are important for mitigation and restoration efforts in the Anthropocene. As recreationists are motivated to engage in leisure activities to increase their own personal wellbeing, we submit that threats to wellbeing (an egocentric motivator) predict engagement in PEBs amongst recreationists. We also predict that differences in experiences across groups of recreationists leads to differences in PEB engagement. Using an online survey, we test our two hypotheses (if recreationists perceive there is a threat to their wellbeing and that their behaviours can yield environmental successes, then they will be more likely to engage in PEBs, and if recreationists differ in recreational experiences then they will demonstrate differences in PEB engagement) amongst outdoor recreationists, specifically Canadian rainbow trout and steelhead anglers in British Columbia (n = 894 respondents). We define 'threat to wellbeing' as the interaction of environmental threat-perceptions of used environments for fishing, and level of centrality fishing has to one's lifestyle. To test our first hypothesis, we conducted three linear regressions corresponding to three different PEBs related to catch-and-release (C&R) fishing. Our egocentric predictor 'threat to wellbeing' was only significant for one out of the three PEBs tested, showing mixed support for our first hypothesis. It is of note that 'environmental threat perceptions' and one's belief in successes resulting from PEB engagement were found to be significant predictors for all three PEBs tested. These results suggest that predictors of PEB may not always be transferable across PEBs relating to recreational activities, and environmental threat perception and one's belief in successes resulting from PEB engagement are strong predictors of PEBs amongst recreationists. To test our second hypothesis, we conducted a Kruskal Wallis test to determine if there were significant differences across angler groups in PEB predictor scores and PEB engagement and conducted pairwise population Z-tests to determine proportional participation rates across angler groups for the three PEBs and PEB predictors investigated. Experiences were found to shape predictors of PEBs, as well as likelihood to engage in PEBs, as different angler groups targeting different fish (i.e., rainbow trout vs steelhead) and using different aquatic habitats (i.e., rivers vs. lakes) demonstrated significantly different scores for PEB predictors, as well as significantly different likelihood to engage in two of the three PEBs tested. These findings support the notion that recreationists are not a homogenous group, and that their beliefs and resulting behaviours during recreational activities are determined by their experiences in nature and can be influenced by the species with which they interact, and the habitats they use for recreation.
Asunto(s)
Explotaciones Pesqueras , Recreación , Animales , Colombia Británica , Conservación de los Recursos Naturales , Ecosistema , LagosRESUMEN
The COVID-19 pandemic and corresponding public health mitigation strategies have altered many facets of human life. And yet, little is known about how public health measures have impacted complex socio-ecological systems such as recreational fisheries. Using an online snowball survey, we targeted resident anglers in Ontario, Canada, to obtain preliminary insights on how the pandemic has impacted recreational fishing and related activity. We also explored angler perspectives on pandemic-related restrictions and other aspects of fisheries management. Our results point to the value of recreational fisheries for the mental and physical well-being of participants, as well as the value and popularity of outdoor recreation during a pandemic. Although angling effort and fish consumption appeared to decline during the early phases of the pandemic, approximately 21 % of the anglers who responded to our survey self-identified as new entrants who had begun or resumed fishing in that time. Self-reported motivations to fish during the pandemic suggest that free time, importance to mental and physical health, and desires for self-sufficiency caused some anglers to fish more, whereas a lack of free time, poor or uncertain accessibility, and perceived risks caused some anglers to fish less. Respondents also expressed their desires for more clear and consistent communication about COVID-19 fishing restrictions from governments, and viewed angling as a safe pandemic activity. Information on recreational angler behaviours, motivations, and perspectives during the pandemic may prove valuable to fisheries managers and policy makers looking to optimize their strategies for confronting this and other similar crises.
RESUMEN
BACKGROUND: Comorbidity patterns of childhood infections, atopic diseases, and adverse childhood experiences (ACE) are related to immune system programming conditions. The aim of this study was to make a step beyond the hygiene hypothesis and to comprehensively classify these patterns with latent class analysis (LCA). A second aim was to characterize the classes by associations with immunological, clinical, and sociodemographic variables. METHODS: LCA was applied to data from the CoLaus|PsyCoLaus study (N = 4874, age range 35-82 years) separately for men and women. It was based on survey information on chickenpox, measles, mumps, rubella, herpes simplex, pertussis, scarlet fever, hay fever, asthma, eczema, urticaria, drug allergy, interparental violence, parental maltreatment, and trauma in early childhood. Subsequently, we examined how immune-mediated classes were reflected in leukocyte counts, inflammatory markers (IL-1ß, IL-6, TNF-α, hsCRP), chronic inflammatory diseases, and mental disorders, and how they differed across social classes and birth cohorts. RESULTS: LCA results with five classes were selected for further analysis. Latent classes were similar in both sexes and were labeled according to their associations as neutral, resilient, atopic, mixed (comprising infectious and atopic diseases), and ACE class. They came across with specific differences in biomarker levels. Mental disorders typically displayed increased lifetime prevalence rates in the atopic, the mixed, and the ACE classes, and decreased rates in the resilient class. The same patterns were apparent in chronic inflammatory diseases, except that the ACE class was relevant specifically in women but not in men. CONCLUSIONS: This is the first study to systematically determine immune-mediated classes that evolve early in life. They display characteristic associations with biomarker levels and somatic and psychiatric diseases occurring later in life. Moreover, they show different distributions across social classes and allow to better understand the mechanisms beyond the changes in the prevalence of chronic somatic and psychiatric diseases.
Asunto(s)
Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/inmunología , Hipótesis de la Higiene , Fenómenos del Sistema Inmunológico/fisiología , Análisis de Clases Latentes , Adulto , Anciano , Anciano de 80 o más Años , Asma/epidemiología , Asma/inmunología , Niño , Comorbilidad , Femenino , Humanos , Inflamación/complicaciones , Inflamación/epidemiología , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Afecciones Crónicas Múltiples/epidemiología , Prevalencia , Encuestas y CuestionariosRESUMEN
BACKGROUND: Despite WHO advocating for an integrated approach to antenatal care (ANC), testing coverage for conditions other than HIV remains low and women are referred to distant laboratories for testing. Using point-of-care tests (POCTs) at peripheral dispensaries could improve access to testing and timely treatment. However, the effect of providing additional services on nurse workload and client wait times are unknown. We use discrete-event simulation (DES) modelling to understand the effect of providing four point-of-care tests for ANC on nurse utilization and wait times for women seeking maternal and child health (MCH) services. METHODS: We collected detailed time-motion data over 20 days from one high volume dispensary in western Kenya during the 8-month implementation period (2014-2015) of the intervention. We constructed a simulation model using empirical arrival distributions, activity durations and client pathways of women seeking MCH services. We removed the intervention from the model to obtain wait times, length-of-stay and nurse utilization rates for the baseline scenario where only HIV testing was offered for ANC. Additionally, we modelled a scenario where nurse consultations were set to have minimum durations for sufficient delivery of all WHO-recommended services. RESULTS: A total of 183 women visited the dispensary for MCH services and 14 of these women received point-of-care testing (POCT). The mean difference in total waiting time was 2 min (95%CI: < 1-4 min, p = 0.026) for MCH women when integrated POCT was given, and 9 min (95%CI: 4-14 min, p < 0.001) when integrated POCT with adequate ANC consult times was given compared to the baseline scenario. Mean length-of-stay increased by 2 min (95%CI: < 1-4 min, p = 0.015) with integrated POCT and by 16 min (95%CI: 10-21 min, p < 0.001) with integrated POCT and adequate consult times compared to the baseline scenario. The two nurses' overall daily utilization in the scenario with sufficient minimum consult durations were 72 and 75%. CONCLUSION: The intervention had a modest overall impact on wait times and length-of-stay for women seeking MCH services while ensuring pregnant women received essential diagnostic testing. Nurse utilization rates fluctuated among days: nurses experienced spikes in workload on some days but were under-utilized on the majority of days. Overall, our model suggests there was sufficient time to deliver all WHO's required ANC activities and offer integrated testing for ANC first and re-visits with the current number of healthcare staff. Further investigations on improving healthcare worker, availability, performance and quality of care are needed. Delivering four point-of-care tests together for ANC at dispensary level would be a low burden strategy to improve ANC.
Asunto(s)
Enfermeras y Enfermeros/estadística & datos numéricos , Pruebas en el Punto de Atención/estadística & datos numéricos , Complicaciones del Embarazo/diagnóstico , Atención Prenatal/estadística & datos numéricos , Diagnóstico Prenatal/estadística & datos numéricos , Adulto , Anemia/diagnóstico , Femenino , Infecciones por VIH/diagnóstico , Humanos , Kenia , Malaria/diagnóstico , Embarazo , Atención Prenatal/métodos , Diagnóstico Prenatal/métodos , Derivación y Consulta , Sífilis/diagnóstico , Factores de Tiempo , Estudios de Tiempo y Movimiento , Carga de Trabajo/estadística & datos numéricosRESUMEN
Optimal patient management benefits from comprehensive and accurate pathology reports that contribute to cancer staging and prognostication. Proforma reports are used in many countries, but these vary in their structure and implementation. The International Collaboration on Cancer Reporting (ICCR) is an alliance formed by the Royal College of Pathologists of Australasia, the Royal College of Pathologists of the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer the European Society of Pathology and the American Society of Clinical Pathology (ASCP), with the aim of developing an evidence-based reporting data set for each cancer site. It is argued that this should reduce the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish and maintain standardised cancer reporting data sets. The resultant standardisation of cancer reporting will benefit not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. We describe the development of a cancer data set by the ICCR expert panel for the reporting of the main malignant liver tumours: intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma and present the 'required' and 'recommended' elements to be included in the report with an explanatory commentary. This data set incorporates definitions and classifications in the most recent World Health Organisation (WHO) publication on hepatic malignancies (4th edition) and the recently published tumour-node-metastasis (TNM)8 staging system. Widespread adoption and implementation of this data set will enable consistent and accurate data collection, comparison of epidemiological and pathological parameters between different populations, facilitate research and ultimately result in better patient outcomes.
Asunto(s)
Conjuntos de Datos como Asunto , Oncología Médica/normas , Patología Clínica/normas , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/patología , Colangiocarcinoma/patología , Humanos , Tumor de Klatskin/patología , Neoplasias Hepáticas/patología , Proyectos de Investigación/normasRESUMEN
INTRODUCTION: Jamaica has an estimated 200 persons with haemophilia (PWH), who face significant constraints in access to specialized haemophilia care, including access to clotting factor concentrates. AIM: The aim of this paper is to establish the current burden of disease in PWH in Jamaica. METHODS: PWH were enrolled through the University Hospital of the West Indies, Jamaica. The impact of haemophilia was assessed using a comprehensive battery of heath outcome measures that included the following: laboratory, clinical information and validated outcome measures of joint structure and function, activity, and health-related quality of life (HRQoL) to provide a health profile of the Jamaican haemophilia population. RESULTS: In all, 45 PWH were registered (mean age: 29, range: 0.17-69 years), including 13 children (<18 years of age) and 32 adults. In this sample, 41 had haemophilia A (30 severe) and 4 had haemophilia B (3 severe); 10 patients with haemophilia A were inhibitor positive. The results indicate that adults with haemophilia in Jamaica have significant joint damage: mean Haemophilia Joint Health Score (HJHS) = 42.1 (SD = 17.3); moderate activity levels - mean Haemophilia Activities List (HAL) score = 64.8 (SD = 17.8); and low HRQoL scores - mean Haemo-QoL-A score = 62.3 (SD = 19.4). Results for children are also reported but should be interpreted with caution due to the small sample size. CONCLUSIONS: There is a very high burden of disease in PWH in Jamaica. The health profiles reported in this paper are an essential first step in advocating for a multidisciplinary Comprehensive Care Program for assessment and care of PWH in Jamaica.
Asunto(s)
Costo de Enfermedad , Hemofilia A/economía , Hemofilia A/epidemiología , Hemofilia B/economía , Hemofilia B/epidemiología , Sistema de Registros , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Jamaica/epidemiología , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION: The treatment of haemophilia varies across countries and across regions within some countries. Similar variation has been observed in health-related quality of life (HR-QoL). Relatively little is known about the HR-QoL of boys with haemophilia in China. AIM: The aim of this study was to describe the HR-QoL of boys with haemophilia in China using the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT). METHODS: Boys (4-18 years of age) with haemophilia and their parents were enroled in a cross-sectional study. All parents/guardians of study subjects were requested to complete a CHO-KLAT questionnaire during a clinic visit, and report on several other clinical and socioeconomic factors in the past year. Boys who were > 7 years also completed the CHO-KLAT. RESULTS: A total of 269 parents of boys with haemophilia, from 13 hospitals in 12 provinces, were enroled during 2014. The boys ranged from 4.0 to 17.9 years of age; 91% had haemophilia A, most had moderate (52%) or severe (36%) disease, and most were receiving sub-optimal on-demand therapy or low-dose prophylactic therapy. Child self-report CHO-KLAT scores were available for 171 boys ≥7 years of age and ranged from 24.2 to 85.3 with a mean of 57.6 (n = 171). Parent proxy-reported CHO-KLAT scores ranged from 25.0 to 88.7 with a mean of 55.1 (n = 269). CONCLUSION: HR-QoL scores in boys with haemophilia in China were substantially lower than reported from Canadian and European boys with haemophilia. Longer term prospective studies are required to examine the factors impacting the HR-QoL for boys with haemophilia in China.
Asunto(s)
Hemofilia A/psicología , Hemofilia B/psicología , Calidad de Vida , Adolescente , Niño , Preescolar , China , Estudios Transversales , Factor IX/uso terapéutico , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/patología , Hemofilia B/tratamiento farmacológico , Hemofilia B/patología , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud/métodos , Padres/psicología , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Although there has been abundant research on chronic low-grade inflammation as a potential mechanism underlying the link between mood disorders and cardiovascular risk, less is known about the role of inflammatory factors and anxiety disorders. The aim of this paper is to evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP) with anxiety disorders and its subgroups. METHODS: The sample consisted of 3,113 participants (53.7% women; mean age: 51.0, S.D. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, S.D. 0.6). Anxiety disorders were assessed with semistructured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. RESULTS: After adjustment for potential confounders, current anxiety disorders (ß = 0.09, 95% CI 0.00-0.17) and agoraphobia (ß = 0.25, 95% CI: 0.07-0.43) at baseline were associated with a steeper increase of hsCRP levels over the follow-up period. Current posttraumatic stress disorder (PTSD) was associated with a lower increase of IL-6 levels over the follow-up period (ß = -0.52, 95% CI: -1.00/-0.04). There was no evidence for an association between inflammation markers at baseline and anxiety disorders at follow-up. CONCLUSIONS: The prospective association between agoraphobia at baseline and hsCRP levels over the follow-up period suggests that chronic low-grade inflammation may be a consequence of this condition. The decrease in IL-6 in PTSD also requires further investigation. No evidence was found for chronic low-grade inflammation as a predictor of future anxiety disorders.
Asunto(s)
Agorafobia/sangre , Trastornos de Ansiedad/sangre , Proteína C-Reactiva , Inflamación/sangre , Interleucina-6/sangre , Trastornos por Estrés Postraumático/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Within recent years it has become apparent that protein glycosylation is not limited to eukaryotes. Indeed, in Campylobacter jejuni, a Gram-negative bacterium, more than 60 of its proteins are known to be glycosylated. One of the sugars found in such glycosylated proteins is 2,4-diacetamido-2,4,6-trideoxy-α-d-glucopyranose, hereafter referred to as QuiNAc4NAc. The pathway for its biosynthesis, initiating with UDP-GlcNAc, requires three enzymes referred to as PglF, PglE, and PlgD. The focus of this investigation is on PglF, an NAD+-dependent sugar 4,6-dehydratase known to belong to the short chain dehydrogenase/reductase (SDR) superfamily. Specifically, PglF catalyzes the first step in the pathway, namely, the dehydration of UDP-GlcNAc to UDP-2-acetamido-2,6-dideoxy-α-d-xylo-hexos-4-ulose. Most members of the SDR superfamily contain a characteristic signature sequence of YXXXK where the conserved tyrosine functions as a catalytic acid or a base. Strikingly, in PglF, this residue is a methionine. Here we describe a detailed structural and functional investigation of PglF from C. jejuni. For this investigation five X-ray structures were determined to resolutions of 2.0 Å or better. In addition, kinetic analyses of the wild-type and site-directed variants were performed. On the basis of the data reported herein, a new catalytic mechanism for a SDR superfamily member is proposed that does not require the typically conserved tyrosine residue.