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1.
Mol Ecol ; : e17277, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38279695

RESUMEN

Chromosomal inversions can play an important role in divergence and reproductive isolation by building and maintaining distinct allelic combinations between evolutionary lineages. Alternatively, they can take the form of balanced polymorphisms that segregate within populations until one arrangement becomes fixed. Many questions remain about how inversion polymorphisms arise, how they are maintained over the long term, and ultimately, whether and how they contribute to speciation. The long-snouted seahorse (Hippocampus guttulatus) is genetically subdivided into geographic lineages and marine-lagoon ecotypes, with shared structural variation underlying lineage and ecotype divergence. Here, we aim to characterize structural variants and to reconstruct their history and suspected role in ecotype formation. We generated a near chromosome-level genome assembly and described genome-wide patterns of diversity and divergence through the analysis of 112 whole-genome sequences from Atlantic, Mediterranean, and Black Sea populations. By also analysing linked-read sequencing data, we found evidence for two chromosomal inversions that were several megabases in length and showed contrasting allele frequency patterns between lineages and ecotypes across the species range. We reveal that these inversions represent ancient intraspecific polymorphisms, one likely being maintained by divergent selection and the other by pseudo-overdominance. A possible selective coupling between the two inversions was further supported by the absence of specific haplotype combinations and a putative functional interaction between the two inversions in reproduction. Lastly, we detected gene flux eroding divergence between inverted alleles at varying levels for the two inversions, with a likely impact on their dynamics and contribution to divergence and speciation.

2.
CA Cancer J Clin ; 67(2): 93-99, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28094848

RESUMEN

The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.


Asunto(s)
Estadificación de Neoplasias/métodos , Medicina de Precisión/métodos , Diagnóstico por Imagen , Humanos , Metástasis Linfática , Estadificación de Neoplasias/normas , Guías de Práctica Clínica como Asunto , Medicina de Precisión/normas , Terminología como Asunto , Estados Unidos
3.
J Fish Biol ; 100(2): 594-600, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34837218

RESUMEN

Reports of morphological differences between European anchovy (Engraulis cf. encrasicolus) from coastal and marine habitats have long existed in the ichthyologic literature and have given rise to a long-standing debate on their taxonomic status. More recently, molecular studies have confirmed the existence of genetic differentiation between the two anchovy ecotypes. Using ancestry-informative markers, we show that coastal anchovies throughout the Mediterranean share a common ancestry and that substantial genetic differentiation persists in different pairs of coastal/marine populations despite the presence of limited gene flow. On the basis of genetic and ecological arguments, we propose that coastal anchovies deserve a species status of their own (E. maeoticus) and argue that a unified taxonomical framework is critical for future research and management.


Asunto(s)
Peces , Alimentos Marinos , Animales , Ecosistema , Peces/genética , Flujo Génico , Flujo Genético
4.
Angew Chem Int Ed Engl ; 60(1): 290-296, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-32770641

RESUMEN

The hydrogenation of benzaldehyde to benzyl alcohol on carbon-supported metals in water, enabled by an external potential, is markedly promoted by polarization of the functional groups. The presence of polar co-adsorbates, such as substituted phenols, enhances the hydrogenation rate of the aldehyde by two effects, that is, polarizing the carbonyl group and increasing the probability of forming a transition state for H addition. These two effects enable a hydrogenation route, in which phenol acts as a conduit for proton addition, with a higher rate than the direct proton transfer from hydronium ions. The fast hydrogenation enabled by the presence of phenol and applied potential overcompensates for the decrease in coverage of benzaldehyde caused by competitive adsorption. A higher acid strength of the co-adsorbate increases the intensity of interactions and the rates of selective carbonyl reduction.

5.
J Gerontol Soc Work ; 63(5): 464-477, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32449479

RESUMEN

Supportive housing later in life tends to be a key concern for lesbian, gay, bisexual, and transgender (LGBT) elders. Most senior care providers are un(der)prepared to meet the needs of older LGBT adults. This study evaluated the efficacy of a 4 hours, face-to-face, research-based, LGBT-diversity training designed to improve senior housing facility staff's cultural competency regarding the needs of LGBT elders. Findings from this study found a significant increase in LGBT content knowledge between pre- and post-intervention assessments and a significant decrease in perceived preparedness when working with LGBT elders. These effects remained significant after controlling for staff designation, religion, educational attainment, and training session. Findings suggest that staff's cultural competence affected their perceived readiness to address LGBT elders' needs. Implications are related to the concept of cultural humility or the lifelong process of understanding others' experiences based on the recognition of lack of un(der)preparedness to create a culturally supportive residential environment.


Asunto(s)
Competencia Cultural/educación , Personal de Salud/educación , Instituciones Residenciales , Minorías Sexuales y de Género , Anciano , Femenino , Humanos , Masculino , Ohio , Personas Transgénero
6.
J Bacteriol ; 200(13)2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29686138

RESUMEN

The DNA damage response ddrI gene encodes a transcription regulator belonging to the cAMP receptor protein (CRP) family. Cells devoid of the DdrI protein exhibit a pleiotropic phenotype, including growth defects and sensitivity to DNA-damaging agents and to oxidative stress. Here, we show that the absence of the DdrI protein also confers sensitivity to heat shock treatment, and several genes involved in heat shock response were shown to be upregulated in a DdrI-dependent manner. Interestingly, expression of the Escherichia coli CRP partially compensates for the absence of the DdrI protein. Microscopic observations of ΔddrI mutant cells revealed an increased proportion of two-tetrad and anucleated cells in the population compared to the wild-type strain, indicating that DdrI is crucial for the completion of cell division and/or chromosome segregation. We show that DdrI is also involved in the megaplasmid MP1 stability and in efficient plasmid transformation by facilitating the maintenance of the incoming plasmid in the cell. The in silico prediction of putative DdrI binding sites in the D. radiodurans genome suggests that hundreds of genes, belonging to several functional groups, may be regulated by DdrI. In addition, the DdrI protein absolutely requires cAMP for in vitro binding to specific target sequences, and it acts as a dimer. All these data underline the major role of DdrI in D. radiodurans physiology under normal and stress conditions by regulating, both directly and indirectly, a cohort of genes involved in various cellular processes, including central metabolism and specific responses to diverse harmful environments.IMPORTANCEDeinococcus radiodurans has been extensively studied to elucidate the molecular mechanisms responsible for its exceptional ability to withstand lethal effects of various DNA-damaging agents. A complex network, including efficient DNA repair, protein protection against oxidation, and diverse metabolic pathways, plays a crucial role for its radioresistance. The regulatory networks orchestrating these various pathways are still missing. Our data provide new insights into the crucial contribution of the transcription factor DdrI for the D. radiodurans ability to withstand harmful conditions, including UV radiation, mitomycin C treatment, heat shock, and oxidative stress. Finally, we highlight that DdrI is also required for accurate cell division, for maintenance of plasmid replicons, and for central metabolism processes responsible for the overall cell physiology.


Asunto(s)
Proteínas Bacterianas/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , Deinococcus/metabolismo , Regulación Bacteriana de la Expresión Génica , Adaptación Fisiológica , Proteínas Bacterianas/genética , Proteína Receptora de AMP Cíclico/genética , Deinococcus/genética , Deinococcus/efectos de la radiación , Rayos Ultravioleta
7.
Emerg Radiol ; 25(1): 41-49, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28948391

RESUMEN

INTRODUCTION: Using the study design from a prominent 2004 study, we aimed to reassess patient, provider, and radiologist awareness of CT radiation more than a decade later. METHODS: Adults presenting to the emergency department of a tertiary care center over a 2-week period with mild to moderate pain requiring an abdominopelvic CT scan were surveyed. Patients were asked if anyone had discussed the risks/benefits of the CT scan including radiation dose and were asked to estimate their dose compared to a chest X-ray. Emergency providers and radiologists were given similar surveys and were asked about potential obstacles to discussing CT radiation with patients. RESULTS: A total of 101 patients, 570 emergency providers, and 161 radiologists were surveyed. Twenty-three percent (14/61) of patients, 39% (219/568) of emergency providers, and 48% (77/161) of radiologists correctly selected the radiation dose range of an abdominopelvic CT. Seventy-eight percent (441/567) of emergency providers reported routinely discussing radiation dose with patients, while 20% (20/98) of patients reported that their emergency provider discussed radiation dose with them. Time limitation and concern of dissuading the patient from CT were the most commonly reported obstacles for discussing risks. CONCLUSIONS: Patients and providers in 2015 appear to be more aware of radiation dose from CT than they were in 2004. Discussion of CT scan radiation exposure and associated risks only occurs sometimes and may actually occur less frequently than perceived by emergency providers.


Asunto(s)
Toma de Decisiones , Pautas de la Práctica en Medicina/estadística & datos numéricos , Dosis de Radiación , Tomografía Computarizada por Rayos X/efectos adversos , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Adulto , Servicio de Urgencia en Hospital , Femenino , Humanos , Consentimiento Informado , Masculino , Persona de Mediana Edad , Riesgo
8.
Pediatr Radiol ; 47(6): 665-673, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28283728

RESUMEN

BACKGROUND: Gadolinium-based contrast agents (GBCAs) have been used for magnetic resonance (MR) imaging over the last three decades. Recent reports demonstrated gadolinium retention in patients' brains following intravenous administration. Since gadolinium is a highly toxic heavy metal, there is a potential for adverse effects from prolonged retention or deposition, particularly in children. For this reason, the Society (SPR) for Pediatric Radiology Quality and Safety committee conducted a survey to evaluate the current status of GBCAs usage among pediatric radiologists. OBJECTIVE: To assess the usage of GBCAs among SPR members. MATERIALS AND METHODS: An online 15-question survey was distributed to SPR members. Survey questions pertained to the type of GBCAs used, protocoling workflow, requirement of renal function or pregnancy tests, and various clinical indications for contrast-enhanced MRI examinations. RESULTS: A total of 163 survey responses were compiled (11.1% of survey invitations), the majority of these from academic institutions in the United States. Ninety-four percent reported that MR studies are always or usually protocoled by pediatric radiologists. The most common GBCA utilized by survey respondents were Eovist (60.7%), Ablavar (45.4%), Gadovist (38.7%), Magnevist (34.4%) and Dotarem (32.5%). For several clinical indications, survey responses regarding GBCA administration were concordant with American College of Radiology (ACR) Appropriateness Criteria, including seizures, headache and osteomyelitis. For other indications, including growth hormone deficiency and suspected vascular ring, survey responses revealed potential overutilization of GBCAs when compared to ACR recommendations. CONCLUSION: Survey results demonstrate that GBCAs are administered judiciously in children, yet there is an opportunity to improve their utilization with the goal of reducing potential future adverse effects.


Asunto(s)
Medios de Contraste/administración & dosificación , Gadolinio/administración & dosificación , Imagen por Resonancia Magnética , Pautas de la Práctica en Medicina/estadística & datos numéricos , Encéfalo/metabolismo , Niño , Medios de Contraste/farmacocinética , Gadolinio/farmacocinética , Humanos , Internacionalidad , Sociedades Médicas , Encuestas y Cuestionarios , Flujo de Trabajo
9.
Pain Med ; 17(3): 530-538, 2016 03.
Artículo en Inglés | MEDLINE | ID: mdl-26332796

RESUMEN

OBJECTIVES: The perception of being a burden or self-perceived burden (SPB) is associated with suicide ideation in chronic pain patients (CPPs). The objective of this study was to determine if SPB is associated with five types of suicidality (wish to die, active suicide ideation, presence of suicide plan, history of suicide attempts, and preference for death over being disabled) in CPPs and acute pain patients (APPs). METHODS: Affirmation of SPB was statistically compared between community nonpatients without pain (CNPWP), APPs, and CPPs. APPs and CPPs who had affirmed any of the five types of suicidality were compared statistically for affirmation of SPB. Hierarchical regression analysis was utilized to determine the significance of SPB in predicting each of the five types of suicidality in APPs and CPPs controlling for age, gender, race, education status, and two types of measures of depression (current depression and vegetative depression). RESULTS: APPs and CPPs were statistically more likely to affirm SPB than CNPWPs and CPPs were more likely than APPs to do so. There were no differences between APPs and CPPs in affirming SPB in APPs and CPPs who had affirmed any of the five types of suicidality. In CPPs, SPB predicted each type of suicidality in a significant fashion utilizing both types of depression measures. For APPs, SPB predicted each type of suicidality in a significant fashion except for history of suicide attempt controlling for vegetative depression. CONCLUSIONS: SPB is associated with the vast majority of different types of suicidality in APPs and CPPs.


Asunto(s)
Dolor Agudo/psicología , Dolor Crónico/psicología , Costo de Enfermedad , Autoimagen , Ideación Suicida , Encuestas y Cuestionarios , Dolor Agudo/diagnóstico , Adolescente , Adulto , Dolor Crónico/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
10.
Pain Med ; 16(1): 37-50, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25138039

RESUMEN

OBJECTIVES: Somatic/psychiatric symptoms are frequently found in chronic pain patients (CPPs). The objectives of this study were to determine 1) which somatic/psychiatric symptoms are more commonly found in acute pain patients (APPs) and CPPs vs community nonpatients without pain (CNPWPs) and 2) if somatic/psychiatric symptom prevalence differs between APPs and CPPs. DESIGN: The above groups were compared statistically for endorsement of 15 symptoms: fatigue, numbness/tingling, dizziness, difficulty opening/closing mouth, muscle weakness, difficulty staying asleep, depression, muscle tightness, nervousness, irritability, memory, falling, nausea, concentration, and headaches. RESULTS: After controlling for age, gender, and level of pain, APPs and CPPs had a statistically significantly greater prevalence (at a P < 0.01 level) for 11 and 13 symptoms, respectively, vs CNPWPs. After controlling for age, gender, and level of pain, CPPs had a statistically significantly greater prevalence (at a P < 0.01 level) for eight symptoms vs APPs. Symptoms were highly correlated in both APPs and CPPs. CONCLUSIONS: CPPs are characterized to a significantly greater extent than comparison groups by somatic/psychiatric symptoms that are highly intercorrelated. This has implications for clinical practice and future research.


Asunto(s)
Dolor Agudo/psicología , Dolor Crónico/psicología , Trastornos Somatomorfos/epidemiología , Femenino , Humanos , Masculino , Prevalencia
11.
Pain Pract ; 15(6): 518-29, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24766733

RESUMEN

OBJECTIVES: The belief in medical care entitlement has recently resulted in major changes in the medical system in the United States. The objectives of this study were the following: to compare endorsement of three medical entitlement beliefs (I deserve the best medical care no matter what the cost [BMC], I am entitled to all of the medical care I want at no charge [NC], I shouldn't have to wait to see my doctors [W]) in community nonpatients without pain (CNPWP), acute pain patients (APPs), and chronic pain patients (CPPs) and to develop predictor models for these beliefs in APPs and CPPs. DESIGN: CNPWP, APPs, and CPPs were compared statistically for frequency of endorsement of each belief. All available variables were utilized in logistic regression models to predict each belief in APPs and CPPs. Those affirming/nonaffirming each belief were compared by t-test for affirmation of narcissism, dependency, and antisocial practices on three scales from established inventories. RESULTS: CPPs were significantly more likely than APPs to endorse BMC. No other comparisons were significant. The logistic regression models identified variables that related to narcissism, anger, doctor dissatisfaction, depression, and anxiety, which entered the models for both APPs and CPPs for some beliefs. Those APPs and CPPs who affirmed the beliefs of NC and W were more likely than their counterparts to affirm antisocial practices, but not narcissism or dependency. CONCLUSIONS: Patient medical entitlement beliefs may be related to some psychiatric/psychological issues.


Asunto(s)
Dolor Agudo/psicología , Dolor Crónico/psicología , Conocimientos, Actitudes y Práctica en Salud , Asistencia Médica , Personalidad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Características de la Residencia , Estados Unidos
12.
Pain Pract ; 14(6): 515-25, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23834362

RESUMEN

OBJECTIVES: To further explore the controversy as to whether childhood molestation is associated with chronic pain in adulthood. DESIGN: Community nonpatients without pain (CNPWP), community patients with pain (CPWP), acute pain patients (APPs), and chronic pain patients (CPPs) were compared for endorsement of affirmation of childhood molestation by chi-square. Logistic regression was utilized to predict affirmation in male and female CPPs. RESULTS: A significantly higher percentage of male APPs affirmed molestation versus CNPWP and CPWP. No other comparisons were statistically significant for males. For females, no comparisons were significant. For male CPPs, the behavior health inventory-2 (BHI-2) survivor of violence scale and 1 item from this scale predicted affirmation. The following BHI-2 scales and items predicted affirmation for female CPPs: muscular bracing and survivor of violence scales; the item "I have been a victim of many sexual attacks"; and the item "My father was kind and loving to me when I was growing up" (scored opposite direction). CONCLUSIONS: In female PWCP, the prevalence of childhood molestation is not greater than in a number of unique comparison groups. Unique predictors of childhood molestation are yet to be identified.


Asunto(s)
Dolor Agudo/epidemiología , Maltrato a los Niños , Dolor Crónico/epidemiología , Dolor/epidemiología , Delitos Sexuales , Niño , Femenino , Humanos , Modelos Logísticos , Masculino , Prevalencia , Factores Sexuales
13.
Pain Med ; 14(3): 403-16, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23279699

RESUMEN

OBJECTIVES.: The objectives of this study were to (1) compare the prevalence of smoking within chronic pain patients (CPPs) to community non-patients without pain (CNPWP), community patients with pain (CPWP), and acute pain patients (APPs); and (2) compare smokers to nonsmokers within CPPs, APPs, and CPWP for highest pain level. DESIGN.: CNPWP, CPWP, APPs, and CPPs were compared to each other for smoking status (nonsmoker, less than one pack per day, one pack/day or more, any amount per day). Within CPWP, APPs, and CPPs, smokers were also compared to nonsmokers by t-test for highest reported pain level. For both analyses, sub-analyses were performed controlling for age or gender, or race or education. RESULTS.: Utilizing all available patients, the prevalence of smokers within CPPs was significantly greater vs each of the comparison groups (CNPWP, CPWP, APPs). In the sub-analyses, only CPPs who were 38 or younger or male or White, or had some college or above were at greater risk than CPWP for smoking one pack or greater per day. CPP smokers were not significantly more likely than nonsmokers to have higher pain, and this was confirmed in the sub-analyses. CONCLUSIONS.: The prevalence of smokers could be significantly greater within CPPs vs CPWP. CPPs who smoke do not have higher levels of pain than nonsmoking CPPs.


Asunto(s)
Dolor Crónico/epidemiología , Fumar/epidemiología , Dolor Agudo/epidemiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Prevalencia , Índice de Severidad de la Enfermedad , Estados Unidos , Adulto Joven
14.
MicroPubl Biol ; 20232023.
Artículo en Inglés | MEDLINE | ID: mdl-37746059

RESUMEN

mRNA degradation is one of the main steps of gene expression, and a key player is the 5'-3' exonuclease Xrn1. In Saccharomyces cerevisiae , it was previously shown, by a microscopy approach, that Xrn1 is located to different cellular compartments, depending on physiological state. During exponential growth, Xrn1 is distributed in the cytoplasm, while it co-localizes with eisosomes after the post-diauxic shift (PDS). Here, we biochemically characterize the Xrn1-associated complexes in different cellular states. We demonstrate that, after PDS, Xrn1 but not the decapping nor Lsm1-7/Pat1 complexes associates with eisosomal proteins, strengthening the model that sequestration of Xrn1 in eisosomes preserves mRNAs from degradation during PDS.

15.
PLoS One ; 18(11): e0293228, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38011112

RESUMEN

Translation initiation is a complex and highly regulated process that represents an important mechanism, controlling gene expression. eIF2A was proposed as an alternative initiation factor, however, its role and biological targets remain to be discovered. To further gain insight into the function of eIF2A in Saccharomyces cerevisiae, we identified mRNAs associated with the eIF2A complex and showed that 24% of the most enriched mRNAs encode proteins related to cell wall biogenesis and maintenance. In agreement with this result, we showed that an eIF2A deletion sensitized cells to cell wall damage induced by calcofluor white. eIF2A overexpression led to a growth defect, correlated with decreased synthesis of several cell wall proteins. In contrast, no changes were observed in the transcriptome, suggesting that eIF2A controls the expression of cell wall-related proteins at a translational level. The biochemical characterization of the eIF2A complex revealed that it strongly interacts with the RNA binding protein, Ssd1, which is a negative translational regulator, controlling the expression of cell wall-related genes. Interestingly, eIF2A and Ssd1 bind several common mRNA targets and we found that the binding of eIF2A to some targets was mediated by Ssd1. Surprisingly, we further showed that eIF2A is physically and functionally associated with the exonuclease Xrn1 and other mRNA degradation factors, suggesting an additional level of regulation. Altogether, our results highlight new aspects of this complex and redundant fine-tuned regulation of proteins expression related to the cell wall, a structure required to maintain cell shape and rigidity, providing protection against harmful environmental stress.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , ARN Mensajero/metabolismo , Pared Celular/genética , Pared Celular/metabolismo , Expresión Génica , Regulación Fúngica de la Expresión Génica
16.
Glob Health Sci Pract ; 11(4)2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37640484

RESUMEN

BACKGROUND: Limited information is available about the approaches used and lessons learned from low- and middle-income countries that have implemented inpatient services for small and sick newborns. We developed descriptive case studies to compare the journeys to establish inpatient newborn care across Ethiopia, India, Malawi, and Rwanda. METHODS: A total of 57 interviews with stakeholders in Ethiopia (n=12), India (n=12), Malawi (n=16), and Rwanda (n=17) informed the case studies. Our heuristic data analysis followed a deductive organizing framework approach. We informed our data analysis via targeted literature searches to uncover details related to key events. We used the NEST360 Theory of Change for facility-based care, which reflects the World Health Organization (WHO) Health Systems Framework as a starting point and added, as necessary, in an edit processing format until data saturation was achieved. FINDINGS: Results highlight the strategies and innovation used to establish small and sick newborn care by health system building block and by country. We conducted a gap analysis of implementation of WHO Standards for Improving Facility-Based Care. The journeys to establish inpatient newborn care across the 4 countries are similar in terms of trajectory yet unique in their implementation. Unifying themes include leadership and governance at national level to consolidate and coordinate action to improve newborn quality of care, investment to build staff skills on data collection and use, and institutionalization of regular neonatal data reviews to identify gaps and propose relevant strategies. CONCLUSION: Efforts to establish and scale inpatient care for small and sick newborns in Ethiopia, India, Malawi, and Rwanda over the last decade have led to remarkable success. These country examples can inspire more nascent initiatives that other low- and middle-income countries may undertake. Documentation should give voice to lived country experience, not all of which is fully captured in existing, peer-reviewed published literature.


Asunto(s)
Pacientes Internos , Recién Nacido , Humanos , Etiopía , Malaui , Rwanda , India
17.
Autophagy ; 19(11): 2982-2996, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37439113

RESUMEN

The selective autophagic degradation of mitochondria via mitophagy is essential for preserving mitochondrial homeostasis and, thereby, disease maintenance and progression in acute myeloid leukemia (AML). Mitophagy is orchestrated by a variety of mitophagy receptors whose interplay is not well understood. Here, we established a pairwise multiplexed CRISPR screen targeting mitophagy receptors to elucidate redundancies and gain a deeper understanding of the functional interactome governing mitophagy in AML. We identified OPTN (optineurin) as sole non-redundant mitophagy receptor and characterized its unique role in AML. Knockdown and overexpression experiments demonstrated that OPTN expression is rate-limiting for AML cell proliferation. In a MN1-driven murine transplantation model, loss of OPTN prolonged overall median survival by 7 days (+21%). Mechanistically, we found broadly impaired mitochondrial respiration and function with increased mitochondrial ROS, that most likely caused the proliferation defect. Our results decipher the intertwined network of mitophagy receptors in AML for both ubiquitin-dependent and receptor-mediated mitophagy, identify OPTN as a non-redundant tool to study mitophagy in the context of leukemia and suggest OPTN inhibition as an attractive therapeutic strategy.Abbreviations: AML: acute myeloid leukemia; CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats; CTRL: control; DFP: deferiprone; GI: genetic interaction; KD: knockdown; KO: knockout; ldMBM, lineage-depleted murine bone marrow; LFC: log2 fold change; LIR: LC3-interacting region; LSC: leukemic stem cell; MAGeCK: Model-based Analysis of Genome-wide CRISPR-Cas9 Knockout; MDIVI-1: mitochondrial division inhibitor 1; MOI: multiplicity of infection; MOM: mitochondrial outer membrane; NAC: N-acetyl-L-cysteine; OA: oligomycin-antimycin A; OCR: oxygen consumption rate; OE: overexpression; OPTN: optineurin; PINK1: PTEN induced putative kinase 1; ROS: reactive oxygen species; SEM: standard error of the mean; TCGA: The Cancer Genome Atlas; TEM: transmission electron microscopy; UBD: ubiquitin-binding domain; WT: wild type.


Asunto(s)
Leucemia Mieloide Aguda , Mitofagia , Animales , Ratones , Autofagia , Mitofagia/genética , Especies Reactivas de Oxígeno/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas , Humanos
18.
J Clin Med ; 12(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37176611

RESUMEN

BACKGROUND: Childhood myelodysplastic neoplasm (cMDS) often raises concerns about an underlying germline predisposition, and its verification is necessary to guide therapeutic choice and allow family counseling. Here, we report a novel constitutional t(3;8)(p26;q21) in a child with MDS, inherited from the father, the ANKRD26 and SRP72 variants from the maternal origin, and the acquisition of molecular alterations during MDS evolution. CASE PRESENTATION: A 4-year-old girl showed repeated infections and severe neutropenia. Bone marrow presented hypocellularity with dysplastic features. The patient had a t(3;8)(p26;q21)c identified by G-banding and FISH analysis. The family nucleus investigation identified the paternal origin of the chromosomal translocation. The NGS study identified ANKRD26 and SRP72 variants of maternal origin. CGH-array analysis detected alterations in PRSS3P2 and KANSL genes. Immunohistochemistry showed abnormal p53 expression during the MDS evolution. CONCLUSION: This study shows for the first time, cytogenetic and genomic abnormalities inherited from the father and mother, respectively, and their clinical implications. It also shows the importance of investigating patients with constitutional cytogenetic alterations and/or germline variants to provide information to their family nucleus for genetic counseling and understanding of the pathogenesis of childhood MDS.

19.
Pain Med ; 13(4): 552-61, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22487542

RESUMEN

HYPOTHESIS: Passive, active, and historical suicidality are associated with preference for death over disability. DESIGN: Community nonpatients without pain, community patients with pain, and patients with acute and chronic pain were compared for endorsement of disability perception and preference for death over disability. Phi correlations and chi-square analyses were calculated between preference for death over disability and six suicidality items representing passive, active, and historical suicidality. Logistic regression was used to predict preference for death over disability in patients with acute and chronic pain. RESULTS: For patients with acute and chronic pain, endorsement of preference for death over disability correlated significantly with all six suicidality items. The logistic regression models identified the following variables as predictors for preference for death over disability in patients with acute pain: the Behavior Health Inventory (BHI 2) family dysfunction scale, history of wanting to die, and disability perception. For patients with chronic pain, predictors were the BHI 2 Borderline scale, history of wanting to die, treated fairly by family item, frequent suicide ideation, people I trust turn on me item, and disability perception. Preference for death over disability was a statistically significant predictor in patients with chronic pain for disability perception, recent suicide ideation, having a suicidal plan, and a history of wanting to die but was not a significant predictor for any suicide items in patients with acute pain. CONCLUSION: Preference for death over disability is associated with passive and active suicide ideation and historical suicidality in patients with chronic pain.


Asunto(s)
Dolor Agudo/psicología , Dolor Crónico/psicología , Muerte , Trastorno Depresivo/psicología , Conducta de Enfermedad , Ideación Suicida , Dolor Agudo/epidemiología , Adaptación Psicológica , Adulto , Dolor Crónico/epidemiología , Comorbilidad/tendencias , Trastorno Depresivo/epidemiología , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Percepción , Medición de Riesgo , Adulto Joven
20.
Prog Community Health Partnersh ; 16(2): 235-247, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35662150

RESUMEN

BACKGROUND: Community collaboration is a founding principle of the Early Success Coalition (ESC), a collaborative of over 74 agencies, engaging over 200 participants. The ESC aims to develop a comprehensive neighborhood young-child-wellness system model to better foster cognitive, physical, and social-emotional development of young children. The Wilder Collaborative Factors Inventory (WCFI) was used, as part of a participatory mixed-methods evaluation, to collect annual measures of collaboration. OBJECTIVE: To reflect on lessons learned, resulting from 4 years of ESC WCFI data. METHODS: ESC members completed the WCFI standardized survey tool, encompassing 40 questions grouped into 20 factors associated with successful collaboration, annually. LESSONS LEARNED: Community collaborations are naturally slow to establish, with funding/staffing concerns standing out as primary fears within the membership. CONCLUSIONS: Participation in the ESC provided leadership, structure, and concrete goals, which bolstered local collaborative efforts. Overall, the WCFI is proposed as an insightful tool for evaluating community collaboratives.


Asunto(s)
Investigación Participativa Basada en la Comunidad , Liderazgo , Preescolar , Investigación Participativa Basada en la Comunidad/métodos , Humanos , Características de la Residencia , Encuestas y Cuestionarios
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