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1.
Reprod Health ; 19(1): 156, 2022 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-35804372

RESUMEN

BACKGROUND: Despite efforts to reduce the burden of female genital mutilation (FGM) in Guinea, the practice remains prevalent, and health care providers are increasingly being implicated in its medicalization. This formative study was conducted to understand the factors that facilitate or impede the health sector in providing FGM prevention and care services to inform the development of health sector-based interventions. METHODS: Between April and May 2018, a mixed methods formative study was carried out using a rapid assessment methodology in three regions of Guinea-Faranah, Labe and Conakry. A structured questionnaire was completed by one hundred and fifty health care providers of different cadres and 37 semi-structured interviews were conducted with health care providers, women seeking services at public health clinics and key stakeholders, including health systems managers, heads of professional associations and schools of nursing, midwifery, and medicine as well as representatives of the Ministry of Health. Eleven focus group discussions were conducted with female and male community members. RESULTS: This study revealed health systems factors, attitudinal factors held by health care providers, and other factors, that may not only promote FGM medicalization but also impede a comprehensive health sector response. Our findings confirm that there is currently no standardized pre-service training on how to assess, document and manage complications of FGM nor are there interventions to promote the prevention of the practice within the health sector. This research also demonstrates the deeply held beliefs of health care providers and community members that perpetuate this practice, and which need to be addressed as part of a health sector approach to FGM prevention. CONCLUSION: As integral members of FGM practicing communities, health care providers understand community beliefs and norms, making them potential change agents. The health sector can support them by incorporating FGM content into their clinical training, ensuring accountability to legal and policy standards, and promoting FGM abandonment as part of a multi-sectoral approach. The findings from this formative research have informed the development of a health sector intervention that is being field tested as part of a multi-country implementation research study in Guinea, Kenya, and Somalia.


Despite the implementation of various interventions to prevent female genital mutilation (FGM), it is still widely practiced in Guinea, and health care providers are increasingly being implicated in the practice. We conducted research in three regions of Guinea, namely, Faranah, Labe and Conakry, to understand factors that might be addressed to strengthen the role of the health sector in prevention and care of women and girls who have undergone FGM. Our findings highlight the need to strengthen the capacity of health care providers to be able to identify cases of FGM and manage complications. The study also highlights the importance of engaging health care providers in efforts to prevent FGM, which will require that any trainings include an opportunity to discuss their own values and beliefs around FGM so that they are better equipped to communicate with their clients and patients in a sensitive and non-judgmental manner, whether during consultation visits or community health outreach activities. The results of this research have informed the development of a health system strengthening intervention package for the prevention and care of FGM, which is being tested in Kenya, Somalia, and Guinea.


Asunto(s)
Circuncisión Femenina , Femenino , Grupos Focales , Guinea , Personal de Salud , Humanos , Masculino , Medicalización
2.
Qual Health Res ; 32(10): 1544-1556, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35549600

RESUMEN

Nodding Syndrome (NS) occurs within a wide spectrum of epilepsies seen in onchocerciasis endemic areas of sub-Saharan Africa. It has debilitating consequences on affected individuals and increases the socio-economic, physical and psychological burden on care-givers and their households, diminishing their standing within the community. Social science research on the disproportionate burden of the disease on females is limited. Based on ethnographic research over 3 years in northern Uganda, we explored the burden of being ill and care-giving for persons with NS from a gendered perspective. We found that NS-affected females were at greater risk of physical and psychological abuse, sexual violence, unwanted pregnancies, sexually transmitted infections and stigma, in a context of deteriorating socio-economic conditions. Primary care-givers of the NS-affected, mostly women, struggled to make ends meet and were subjected to stigma and abandonment. Targeted interventions, including legal protection for affected females, stigma reduction, and psycho-social and financial support are needed.


Asunto(s)
Epilepsia , Síndrome del Cabeceo , Oncocercosis , Femenino , Humanos , Masculino , Síndrome del Cabeceo/epidemiología , Síndrome del Cabeceo/psicología , Oncocercosis/epidemiología , Estigma Social , Uganda/epidemiología
3.
Anthropol Med ; 29(3): 237-254, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34842011

RESUMEN

Growing numbers of women are showing interest in clitoral reconstructive surgery after 'Female Genital Mutilation'. The safety and success of reconstructive surgery, however, has not clearly been established and due to lack of evidence the World Health Organization does not recommend it. Based on anthropological research among patients who requested surgery at the Brussels specialist clinic between 2017 and 2020, this paper looks at two cases of women who actually enjoy sex and experience pleasure but request the procedure to become 'whole again' after stigmatising experiences with health-care professionals, sexual partners or gossip among African migrant communities. An ethnographic approach was used including indepth interviews and participant observation during reception appointments, gynecological consultations, sexology and psychotherapy sessions. Despite limited evidence on the safety of the surgical intervention, surgery is often perceived as the ultimate remedy for the 'missing' clitoris. Such beliefs are nourished by predominant discourses of cut women as 'sexually mutilated'. Following Butler, this article elicits how discursive practices on the physiological sex of a woman can shape her gender identity as a complete or incomplete person. We also examine what it was that changed the patients' mind about the surgery in the process of re-building their confidence through sexology therapy and psychotherapy.


Asunto(s)
Circuncisión Femenina , Procedimientos de Cirugía Plástica , Antropología Médica , Bélgica , Femenino , Identidad de Género , Humanos , Masculino , Placer , Procedimientos de Cirugía Plástica/métodos
4.
Am J Med Genet A ; 185(9): 2829-2845, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34056834

RESUMEN

Mosaic KRAS variants and other RASopathy genes cause oculoectodermal, encephalo-cranio-cutaneous lipomatosis, and Schimmelpenning-Feuerstein-Mims syndromes, and a spectrum of vascular malformations, overgrowth and other associated anomalies, the latter of which are only recently being characterized. We describe eight individuals in total (six unreported cases and two previously reported cases) with somatic KRAS variants and variably associated features. Given the findings of somatic overgrowth (in seven individuals) and vascular or lymphatic malformations (in eight individuals), we suggest mosaic RASopathies (mosaic KRAS variants) be considered in the differential diagnosis for individuals presenting with asymmetric overgrowth and lymphatic or vascular anomalies. We expand the association with embryonal tumors, including the third report of embryonal rhabdomyosarcoma, as well as novel findings of Wilms tumor and nephroblastomatosis in two individuals. Rare or novel findings in our series include the presence of epilepsy, polycystic kidneys, and T-cell deficiency in one individual, and multifocal lytic bone lesions in two individuals. Finally, we describe the first use of targeted therapy with a MEK inhibitor for an individual with a mosaic KRAS variant. The purposes of this report are to expand the phenotypic spectrum of mosaic KRAS-related disorders, and to propose possible mechanisms of pathogenesis, and surveillance of its associated findings.


Asunto(s)
Anomalías Múltiples/patología , Neoplasias Renales/patología , Mosaicismo , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Malformaciones Vasculares/patología , Tumor de Wilms/patología , Anomalías Múltiples/genética , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Neoplasias Renales/genética , Masculino , Fenotipo , Malformaciones Vasculares/genética , Tumor de Wilms/genética
5.
Colorectal Dis ; 23(12): 3173-3179, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34731512

RESUMEN

AIM: Rectal neuroendocrine tumours (NETs) are the most common type of gastrointestinal NET. European Neuroendocrine Tumour Society guidelines suggest that rectal NETs measuring ≤10 mm are indolent with low risk of spread. In practice, many patients with lesions ≤1 cm do not undergo complete tumour staging. However, the size of the lesion may not be the only risk factor for nodal involvement/metastases. The aim of this study was to determine if MRI ± nuclear medicine imaging alters tumour stage in patients with rectal NETs ≤10 mm. METHODS: Patients referred to a tertiary NET centre between 2005 and 2020 who met the inclusion criteria of a rectal NET ≤10 mm, full cross-sectional imaging, primarily an MRI scan and, if abnormal findings were identified, a subsequent 68 Ga-DOTATATE positron emission tomography scan were included. All patients were followed up at our institution. RESULTS: In all, 32 patients with rectal NETs 10 mm or less were included in the study: 16 women; median age 58 years (range 33-71); 47% (n = 15) were referred from bowel cancer screening procedures. The median size of the lesions was 5 mm (range 2-10 mm). 81% (n = 26) were World Health Organization Grade 1 tumours with Ki67 <3%. Radiological staging confirmed nodal involvement in 25% (8/32); two cases had distant metastatic disease. Lymphovascular invasion was present in 3% (1/32) of patients but none demonstrated peri-neural invasion. CONCLUSION: This study demonstrates that small rectal NETs can develop nodal metastases; therefore it is important to stage these tumours accurately with MRI at baseline and, if there are concerns regarding potential lymph node metastases, to consider 68 Ga-DOTATATE positron emission tomography imaging.


Asunto(s)
Neoplasias Intestinales , Tumores Neuroendocrinos , Compuestos Organometálicos , Neoplasias Pancreáticas , Adulto , Anciano , Femenino , Humanos , Neoplasias Intestinales/diagnóstico por imagen , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Tomografía de Emisión de Positrones , Cintigrafía , Radiofármacos
6.
Qual Health Res ; 31(9): 1738-1750, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098783

RESUMEN

The health consequences of female genital mutilation (FGM) have been described previously; however, evidence of the social consequences is more intangible. To date, few systematic reviews have addressed the impact of the practice on psycho-social well-being, and there is limited understanding of what these consequences might consist. To complement knowledge on the known health consequences, this article systematically reviewed qualitative evidence of the psycho-social impact of FGM in countries where it is originally practiced (Africa, the Middle East, and Asia) and in countries of the diaspora. Twenty-three qualitative studies describing the psycho-social impact of FGM on women's lives were selected after screening. This review provides a framework for understanding the less visible ways in which women and girls with FGM experience adverse effects that may affect their sense of identity, their self-esteem, and well-being as well as their participation in society.


Asunto(s)
Circuncisión Femenina , África , Circuncisión Femenina/efectos adversos , Femenino , Humanos , Investigación Cualitativa
7.
J Pediatr Psychol ; 45(7): 793-802, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32679586

RESUMEN

OBJECTIVE: This longitudinal study examined whether preschool attention deficit hyperactivity disorder (ADHD) symptoms and neuropsychological functioning predicted trajectories of children's social functioning from age 3 to 4 through 12 years. METHODS: Three- and four-year-old children (N = 208; 72.6% boys) were evaluated annually through age 12. Parent and teacher Attention Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition responses during the initial evaluation were used to categorize preschoolers as "High" or "Low" risk for ADHD. Children's neuropsychological functioning was assessed using the NEPSY. Teachers' reports of children's social functioning were obtained annually from preschool through age 12 years using the Adaptability, Functional Communication, and Social Skills subscales of the Behavioral Assessment System for Children, Second Edition. Hierarchical linear modeling was used to assess the trajectories of social functioning and determine whether preschoolers' neuropsychological functioning and ADHD risk status predicted social functioning at age 12 years, and/or change in social functioning throughout childhood. All models controlled for baseline socioeconomic status. RESULTS: High Risk children had significantly lower teacher-rated Adaptability and Social Skills at age 12 years. High Risk children and those with lower Verbal neuropsychological functioning in preschool had lower teacher-rated Functional Communication at 12 years old. Lower preschool Verbal neuropsychological functioning predicted greater positive change in teacher-rated Functional Communication across childhood. CONCLUSIONS: Early identification of and intervention for children exhibiting ADHD behaviors is critical given the enduring negative impact of these behaviors on social functioning. Screening preschoolers for verbal difficulties is encouraged given their long-term impact on children's ability to clearly express thoughts and feelings and obtain and provide information.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/psicología , Pruebas Neuropsicológicas/estadística & datos numéricos , Interacción Social , Habilidades Sociales , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Niño , Preescolar , Cognición , Femenino , Humanos , Recién Nacido , Estudios Longitudinales , Masculino
8.
Int J Mol Sci ; 21(24)2020 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-33352749

RESUMEN

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0-2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.


Asunto(s)
Plaquetas/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Nanopartículas/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Plasma Rico en Plaquetas/efectos de los fármacos , Polietilenglicoles/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Plaquetas/fisiología , Portadores de Fármacos/química , Humanos , Nanopartículas/química , Agregación Plaquetaria/fisiología , Plasma Rico en Plaquetas/fisiología
9.
Molecules ; 25(23)2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33255230

RESUMEN

Herein, we report the design and characterization of guanosine-containing self-assembling nucleopeptides that form nanosheets and nanofibers. Through spectroscopy and microscopy analysis, we propose that the peptide component of the nucleopeptide drives the assembly into ß-sheet structures with hydrogen-bonded guanosine forming additional secondary structures cooperatively within the peptide framework. Interestingly, the distinct supramolecular morphologies are driven not by metal cation responsiveness common to guanine-based materials, but by the C-terminal peptide chemistry. This work highlights the structural diversity of self-assembling nucleopeptides and will help advance the development of applications for these supramolecular guanosine-containing nucleopeptides.


Asunto(s)
Guanosina/química , Ácidos Nucleicos de Péptidos/química , Péptidos/química , Técnicas de Química Sintética , Estructura Molecular , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X
10.
Dev World Bioeth ; 18(4): 406-419, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-28816023

RESUMEN

BACKGROUND: Ensuring individual free and informed decision-making for research participation is challenging. It is thought that preliminarily informing communities through 'community sensitization' procedures may improve individual decision-making. This study set out to assess the relevance of community sensitization for individual decision-making in research participation in rural Gambia. METHODS: This anthropological mixed-methods study triangulated qualitative methods and quantitative survey methods in the context of an observational study and a clinical trial on malaria carried out by the Medical Research Council Unit Gambia. RESULTS/DISCUSSION: Although 38.7% of the respondents were present during sensitization sessions, 91.1% of the respondents were inclined to participate in the trial when surveyed after the sensitization and prior to the informed consent process. This difference can be explained by the informal transmission of information within the community after the community sensitization, expectations such as the benefits of participation based on previous research experiences, and the positive reputation of the research institute. Commonly mentioned barriers to participation were blood sampling and the potential disapproval of the household head. CONCLUSION: Community sensitization is effective in providing first-hand, reliable information to communities as the information is cascaded to those who could not attend the sessions. However, further research is needed to assess how the informal spread of information further shapes people's expectations, how the process engages with existing social relations and hierarchies (e.g. local political power structures; permissions of heads of households) and how this influences or changes individual consent.


Asunto(s)
Investigación Biomédica/ética , Toma de Decisiones , Educación en Salud , Difusión de la Información , Consentimiento Informado , Malaria , Características de la Residencia , Adolescente , Adulto , Anciano , Ética en Investigación , Composición Familiar , Femenino , Gambia , Humanos , Malaria/terapia , Masculino , Investigación Cualitativa , Encuestas y Cuestionarios
11.
Curr Psychiatry Rep ; 19(12): 95, 2017 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-29082443

RESUMEN

PURPOSE OF REVIEW: This paper summarizes key, recently published research examining longitudinal outcomes for preschoolers with high levels of inattention and/or hyperactivity/impulsivity. RECENT FINDINGS: Symptom trajectories show that hyperactivity/impulsivity declines across childhood. At the group level, the course of inattention appears more variable. However, identification of subgroups of children showing stable, rising, and falling inattention over time is promising. Early ADHD-like symptoms portend risk for academic and social difficulties, as well as comorbid emotional and behavioral problems in childhood and adolescence. Several early risk factors appear to moderate these relations, including comorbid symptoms, parental psychopathology, socioeconomic disadvantage, and perhaps neuropsychological dysfunction. Furthermore, high levels of inattention and/or hyperactivity/impulsivity during the preschool period appear to compromise development of regulatory and neuropsychological functions, which in turn increases risk for negative outcomes later in childhood. Identified risk factors are targets for novel interventions, which ideally would be delivered early to at-risk children.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Intervención Educativa Precoz , Problema de Conducta/psicología , Medición de Riesgo , Adolescente , Edad de Inicio , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Preescolar , Humanos , Conducta Impulsiva , Pronóstico , Psicopatología
12.
Malar J ; 15: 195, 2016 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-27068760

RESUMEN

BACKGROUND: Despite declining prevalence of malaria in The Gambia, non-adherence to anti-malarial treatment still remains a challenge to control efforts. There is limited evidence on the socio-cultural factors that influence adherence to anti-malarial treatment in pregnancy. This study explored perceptions of malaria in pregnancy and their influence on adherence to anti-malarial treatment in a rural area of The Gambia. METHODS: An exploratory ethnographic study was conducted ancillary to a cluster-randomized trial on scheduled screening and treatment of malaria in pregnancy at village level in the Upper River Region of The Gambia from June to August 2014. Qualitative data were collected through interviewing and participant observation. Analysis was concurrent to data collection and carried out using NVivo 10. RESULTS: Although women had good bio-medical knowledge of malaria in pregnancy, adherence to anti-malarial treatment was generally perceived to be low. Pregnant women were perceived to discontinue the provided anti-malarial treatment after one or 2 days mainly due to non-recognition of symptoms, perceived ineffectiveness of the anti-malarial treatment, the perceived risks of medication and advice received from mothers-in-law. CONCLUSION: Improving women's knowledge of malaria in pregnancy is not sufficient to assure adherence to anti-malarial treatment. Addressing structural barriers such as unclear health workers' messages about medication dosage, illness recognition, side effects of the medication and the integration of relatives, especially the mothers-in-law, in community-based programmes are additionally required.


Asunto(s)
Antimaláricos/administración & dosificación , Malaria/tratamiento farmacológico , Cumplimiento de la Medicación/psicología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Gambia , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Embarazo , Población Rural , Adulto Joven
13.
J Child Psychol Psychiatry ; 56(9): 958-65, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26053870

RESUMEN

BACKGROUND: Hyperactive/Inattentive preschool children show clear evidence of neuropsychological dysfunction. We examined whether patterns and severity of test scores could reliably identify subgroups of preschoolers with differential risk for ADHD during school-age. METHOD: Typically developing (TD: n = 76) and Hyperactive/Inattentive (HI: n = 138) 3-4 year olds were assessed annually for 6 years (T1-T6). Latent profile analysis (LPA) was used to form subgroups among the HI group based on objective/neuropsychological measures (NEPSY, Actigraph and Continuous Performance Test). Logistic regression assessed the predictive validity of empirically formed subgroups at risk for ADHD diagnosis relative to the TD group and to each other from T2 to T6. RESULTS: Latent profile analysis yielded two subgroups of HI preschoolers: (a) selectively weak Attention/Executive functions, and (b) pervasive neuropsychological dysfunction across all measures. Both subgroups were more likely to have ADHD at all follow-up time-points relative to the TD group (OR range: 11.29-86.32), but there were no significant differences between the LPA-formed subgroups of HI children at any time-point. CONCLUSIONS: Objective/neuropsychological measures distinguish HI preschoolers from their TD peers, but patterns and severity of neuropsychological dysfunction do not predict risk for ADHD during school-age. We hypothesize that trajectories in at-risk children are influenced by subsequent environmental and neurodevelopmental factors, raising the possibility that they are amenable to early intervention.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Pruebas Neuropsicológicas , Trastorno por Déficit de Atención con Hiperactividad/clasificación , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Niño , Preescolar , Susceptibilidad a Enfermedades , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Riesgo
14.
Malar J ; 14: 167, 2015 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-25908392

RESUMEN

BACKGROUND: As the disease burden in the Gambia has reduced considerably over the last decade, heterogeneity in malaria transmission has become more marked, with infected but asymptomatic individuals maintaining the reservoir. The identification, timely diagnosis and treatment of malaria-infected individuals are crucial to further reduce or eliminate the human parasite reservoir. This ethnographic study focused on the relationship between local beliefs of the cause of malaria and treatment itineraries of suspected cases. METHODS: An ethnographic qualitative study was conducted in twelve rural communities in the Upper River Region and the Central River Region in the Gambia. The data collection methods included in-depth interviews, participant observation, informal conversations, and focus group discussions. RESULTS: While at first glance, the majority of people seek biomedical treatment for 'malaria', there are several constraints to seeking treatment at health centres. Certain folk illnesses, such as Jontinooje and Kajeje, translated and interpreted as 'malaria' by healthcare professionals, are often not considered to be malaria by local populations but rather as self-limiting febrile illnesses--consequently not leading to seeking care in the biomedical sector. Furthermore, respondents reported delaying treatment at a health centre while seeking financial resources, and consequently relying on herbal treatments. In addition, when malaria cases present symptoms, such as convulsions, hallucinations and/or loss of consciousness, the illness is often interpreted as having a supernatural aetiology, leading to diagnosis and treatment by traditional healers. CONCLUSION: Although malaria diagnostics and treatment-seeking in the biomedical sector has been reported to be relatively high in the Gambia compared to other sub-Saharan African countries, local symptom interpretation and illness conceptions can delay or stop people from seeking timely biomedical treatment, which may contribute to maintaining a parasite reservoir of undiagnosed and untreated malaria patients.


Asunto(s)
Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Malaria/etnología , Malaria/terapia , Medicinas Tradicionales Africanas , Hechicería , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Gambia , Humanos , Masculino , Medicinas Tradicionales Africanas/estadística & datos numéricos , Persona de Mediana Edad , Salud Rural , Población Rural , Adulto Joven
16.
BJU Int ; 113 Suppl 2: 57-63, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24053545

RESUMEN

OBJECTIVE: To determine whether patients from regional areas undergoing surgery for kidney cancer present with more advanced disease as a result of geographic isolation. PATIENTS AND METHODS: Retrospective analysis of 221 patients undergoing surgery for renal cell carcinoma (RCC) from January 2004 to June 2012, from both a metropolitan centre and a large inner regional hospital. Data was collected on age, gender, presentation (incidental or symptomatic), clinical stage and pathological features. The Australian Standard Geographical Classification-Remoteness Area (ASGC-RA) is a system developed to allow quantitative comparisons between metropolitan and rural Australia. A score was assigned to each patient based on their location of residence at the time of surgery: metropolitan, RA1; inner regional, RA2; outer regional, RA3. Statistical significance was specified as P < 0.05 on Pearson's chi-square tests. RESULTS: Patients in each ASGC-RA group did not differ significantly in age, sex or mode of presentation. Pathological T stage on presentation increased with increasing ASGC-RA and thus distance from tertiary centres (P = 0.004). The proportion of patients with ≥T3 disease rose from 30% of RA1 to 73% of RA3 patients (P = 0.016) treated at our tertiary centre. Similarly, our regional centre had a larger proportion of patients presenting with ≥T3 disease from RA3 (31% vs 5%, P = 0.003). When the 221 patients with RCC were analysed as a group, clinical T stage was significantly associated with ASGC-RA (P < 0.001), symptomatic presentation (P < 0.001), N stage (P < 0.001), M stage (P < 0.001) and Fuhrman grade (P < 0.001). CONCLUSIONS: Our data quantifies the detrimental effect of physical distance on the health outcomes of regional Australians with kidney cancer. Australia's unique geography and rural culture may preclude any attempts to centralise cancer care to specialised metropolitan units, as has occurred in other countries.


Asunto(s)
Carcinoma de Células Renales/diagnóstico , Accesibilidad a los Servicios de Salud/organización & administración , Neoplasias Renales/diagnóstico , Servicios de Salud Rural/organización & administración , Población Rural , Factores de Edad , Australia/epidemiología , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/patología , Diagnóstico Tardío , Femenino , Necesidades y Demandas de Servicios de Salud , Humanos , Neoplasias Renales/epidemiología , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Población Rural/estadística & datos numéricos , Resultado del Tratamiento
17.
ACS Synth Biol ; 13(4): 1246-1258, 2024 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-38483353

RESUMEN

Saccharomyces cerevisiae is an attractive host for the expression of secreted proteins in a biotechnology context. Unfortunately, many heterologous proteins fail to enter, or efficiently progress through, the secretory pathway, resulting in poor yields. Similarly, yeast surface display has become a widely used technique in protein engineering but achieving sufficient levels of surface expression of recombinant proteins is often challenging. Signal peptides (SPs) and translational fusion partners (TFPs) can be used to direct heterologous proteins through the yeast secretory pathway, however, selection of the optimal secretion promoting sequence is largely a process of trial and error. The yeast modular cloning (MoClo) toolkit utilizes type IIS restriction enzymes to facilitate an efficient assembly of expression vectors from standardized parts. We have expanded this toolkit to enable the efficient incorporation of a panel of 16 well-characterized SPs and TFPs and five surface display anchor proteins into S. cerevisiae expression cassettes. The secretion promoting signals are validated by using five different proteins of interest. Comparison of intracellular and secreted protein levels reveals the optimal secretion promoting sequence for each individual protein. Large, protein of interest-specific variations in secretion efficiency are observed. SP sequences are also used with the five surface display anchors, and the combination of SP and anchor protein proves critical for efficient surface display. These observations highlight the value of the described panel of MoClo compatible parts to allow facile screening of SPs and TFPs and anchor proteins for optimal secretion and/or surface display of a given protein of interest in S. cerevisiae.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Transporte de Proteínas , Señales de Clasificación de Proteína/genética , Clonación Molecular
18.
bioRxiv ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38915627

RESUMEN

Lipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading DNA would provide additional advantages such as long-term expression and availability of promoter sequences. However, here we show that plasmid DNA (pDNA) delivery via LNPs (pDNA-LNPs) induces acute inflammation in naïve mice which we find is primarily driven by the cGAS-STING pathway. Inspired by DNA viruses that inhibit this pathway for replication, we co-loaded endogenous lipids that inhibit STING into pDNA-LNPs. Specifically, loading nitro-oleic acid (NOA) into pDNA-LNPs (NOA-pDNA-LNPs) ameliorates serious inflammatory responses in vivo enabling prolonged transgene expression (at least 1 month). Additionally, we demonstrate the ability to iteratively optimize NOA-pDNA-LNPs' expression by performing a small LNP formulation screen, driving up expression 50-fold in vitro. Thus, NOA-pDNA-LNPs, and pDNA-LNPs co-loaded with other bioactive molecules, will provide a major new tool in the genetic medicine toolbox, leveraging the power of DNA's long-term and promoter-controlled expression.

19.
Law Hum Behav ; 37(5): 354-65, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24079847

RESUMEN

This study investigated whether preinterview interventions could help to facilitate children's accuracy under cross-examination-style questioning. Five- and 6-year-olds (n = 77; mean [SD] age = 5.84 [0.48] years; 57% boys) and 9- and 10-year-olds (n = 87; mean [SD] age = 10.30 [0.54] years; 56% boys) took part in a staged event and were then interviewed with analogues of direct examination and cross-examination. In a pilot study, we ascertained that a brief verbal warning about the nature of cross-examination-given immediately prior to the cross-examination interview-did not influence children's cross-examination accuracy, regardless of whether it was delivered by an unfamiliar interviewer or the cross-examining interviewer. In the main experiment, some children participated in a brief intervention involving practice and feedback with cross-examination questions. Relative to control children, those who underwent this preparation intervention made fewer changes to their direct-examination responses under cross-examination, changed a smaller proportion of their correct responses, and obtained higher ultimate accuracy levels. These findings provide some support for the notion that pretrial interventions, if sufficiently comprehensive, could help children to maintain accuracy during cross-examination.


Asunto(s)
Comunicación , Derecho Penal , Recuerdo Mental , Comunicación Persuasiva , Niño , Intervalos de Confianza , Femenino , Humanos , Masculino , Nueva Zelanda , Proyectos Piloto , Revelación de la Verdad
20.
Res Child Adolesc Psychopathol ; 51(9): 1257-1271, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37067623

RESUMEN

The in utero environment influences fetal development and may predispose to disease later in life. This study examines whether maternal suicidal ideation during pregnancy is associated with children's behavioral trajectories across early childhood, and whether prenatal maternal traumatic stress accelerates the trajectories. The study included mother-child dyads (N = 331, 51.1% boys) from the longitudinal Stress In Pregnancy study; 31.1% (n = 103) mothers were Exposed to Superstorm Sandy. During their second trimester, 12.4% (n = 41) women reported suicidal ideation during pregnancy. Mothers completed the Behavior Assessment Scale for Children-2 annually from ages 2- to 6-years-old to assess multiple behavioral domains. Hierarchical linear modeling estimated within-person longitudinal trajectories of clinical behaviors, and between-person effects of maternal suicidal ideation and disaster-related stress in utero on changes in child behavior. For children exposed to both risks, Atypical behaviors (i.e., unusual behaviors, social disconnection) increased linearly across early childhood. Exposure to Superstorm Sandy and maternal suicidal ideation were independently associated with non-linear increases in Anxiety severity and maternal suicidal ideation during pregnancy was associated with a linear increase in Attention problems across early childhood. Maternal suicidal ideation during pregnancy is associated with increased risk for a range of behavioral and emotional difficulties in early childhood and the trajectory of atypical behaviors was amplified by disaster-related traumatic stress. Findings highlight the need for health professionals to screen for suicidal ideation among their pregnant patients. Pregnant women who experience severe stress may require additional monitoring and support to reduce risk for poorer early childhood outcomes.


Asunto(s)
Problema de Conducta , Ideación Suicida , Masculino , Niño , Humanos , Femenino , Preescolar , Embarazo , Mujeres Embarazadas/psicología , Madres/psicología , Conducta Infantil
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