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Phase 1 trials are primarily conducted to evaluate the safety and feasibility of new interventions, usually without recruiting control patients. This retrospective study aims to characterize clinical and biological outcomes in historical and contemporary cases of neonates and infants undergoing two-ventricle repair to facilitate future secondary endpoint analyses for such trials. This retrospective study included neonates/infants (ages ≤ 6 months) who underwent two-ventricle repair between 2015 and 2021 using the same criteria as our phase 1 trial (n = 199). Patients were allocated into the ventricular septal defect (n = 61), the Tetralogy of Fallot (TOF, n = 88), and the transposition of the great arteries (n = 50) groups with an additional comparison between two eras (2015-2019 vs. 2020-2021). Patient characteristics and most variables assessed were different between the three diagnostic groups indicating the importance of diagnostic matching for secondary analyses. Although the era did not alter cerebral/somatic oxygenation, ventricular function, neuroimaging findings, and complication rates, we observed improvement of inotropic and/or vasoactive-inotropic scores in all groups during the more recent era. In 2020-2021, the age and the body weight at the operation were higher, and hospital stay was shorter in the TOF group, suggesting the possible impact of the pandemic. Results also indicated that matching altered characteristics such as age at operation that may limit the temporal effects and optimize secondary analyses. Using optimal contemporary cases and historical data based on this study will assist in developing a comprehensive study design for a future efficacy/effectiveness trial.
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BACKGROUND: Self-monitoring of glucose is important to the successful management of diabetes; however, existing monitoring methods require a degree of invasive measurement which can be unpleasant for users. This study investigates the accuracy of a noninvasive glucose monitoring system that analyses spectral variations in microwave signals. METHODS: An open-label, pilot design study was conducted with four cohorts (N = 5/cohort). In each session, a dial-resonating sensor (DRS) attached to the wrist automatically collected data every 60 seconds, with a novel artificial intelligence (AI) model converting signal resonance output to a glucose prediction. Plasma glucose was measured in venous blood samples every 5 minutes for Cohorts 1 to 3 and every 10 minutes for Cohort 4. Accuracy was evaluated by calculating the mean absolute relative difference (MARD) between the DRS and plasma glucose values. RESULTS: Accurate plasma glucose predictions were obtained across all four cohorts using a random sampling procedure applied to the full four-cohort data set, with an average MARD of 10.3%. A statistical analysis demonstrates the quality of these predictions, with a surveillance error grid (SEG) plot indicating no data pairs falling into the high-risk zones. CONCLUSIONS: These findings show that MARD values approaching accuracies comparable to current commercial alternatives can be obtained from a multiparticipant pilot study with the application of AI. Microwave biosensors and AI models show promise for improving the accuracy and convenience of glucose monitoring systems for people with diabetes.
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BACKGROUND: Congenital heart disease (CHD) is the most common birth defect, influenced by maternal health, environmental conditions, and genetics. Maternal health and nutrition, particularly maternal diabetes, is a modifiable risk factor for development of CHD in the fetus. However, the importance of food access during pregnancy on the development of CHD remains unknown. The objective of this study was to investigate the association between maternal neighborhood characteristics, particularly food access, and occurrence of prenatally diagnosed CHD. METHODS: A retrospective case series studied maternal-fetal dyads with prenatally diagnosed CHD between 2019 and 2021 in Washington, DC. Moran's I of maternal addresses evaluated geographic clustering of disease. Negative binomial regression assessed association between census tract demographics and population-adjusted CHD rate. RESULTS: A total of 307 dyads were analyzed. Global Moran's I showed significant CHD clustering (p-value = .004). However, degree of clustering was not clinically meaningful. After adjusting for neighborhood socioeconomic status, residing in food deserts was not a predictor for CHD. However, neighborhoods with a higher percentage of households receiving Supplemental Nutrition Assistance Program (SNAP) benefits were associated with higher rates of conotruncal heart defects (Incident Rate Ratio [IRR] = 1.04, CI = 1.01-1.08) and aggregate CHD (IRR = 1.03, CI = 1.01-1.05). CONCLUSIONS: Neighborhood location and food access were not associated with CHD. However, increased enrollment in SNAP was associated with higher rates of CHD. The association between CHD and SNAP benefits warrants further exploration. Understanding food access and maternal nutrition may illuminate disparities in the burden of CHD.
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Cardiopatías Congénitas , Femenino , Embarazo , Humanos , Estudios Retrospectivos , Factores de Riesgo , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/etiología , Cardiopatías Congénitas/diagnóstico , Características de la Residencia , FetoRESUMEN
BACKGROUND: Contraceptive choice is central to reproductive autonomy. The internet, including social networking sites like Reddit, is an important resource for people seeking contraceptive information and support. A subreddit dedicated to contraception, r/birthcontrol, provides a platform for people to post about contraception. OBJECTIVE: This study explored the use of r/birthcontrol, from the inception of the subreddit through the end of 2020. We describe the web-based community, identify distinctive interests and themes based upon the textual content of posts, and explore the content of posts with the most user engagement (ie, "popular" posts). METHODS: Data were obtained from the PushShift Reddit application programming interface from the establishment of r/birthcontrol to the start date of analysis (July 21, 2011, to December 31, 2020). User interactions within the subreddit were analyzed to describe community use over time, specifically the commonality of use based on the volume of posts, the length of posts (character count), and the proportion of posts with any and each flair applied. "Popular" posts on r/birthcontrol were determined based on the number of comments and "scores," or upvotes minus downvotes; popular posts had 9 comments and a score of ≥3. Term Frequency-Inverse Document Frequency (TF-IDF) analyses were run on all posts with flairs applied, posts within each flair group, and popular posts within each flair group to characterize and compare the distinctive language used in each group. RESULTS: There were 105,485 posts to r/birthcontrol during the study period, with the volume of posts increasing over time. Within the time frame for which flairs were available on r/birthcontrol (after February 4, 2016), users applied flairs to 78% (n=73,426) of posts. Most posts contained exclusively textual content (n=66,071, 96%), had comments (n=59,189, 86%), and had a score (n=66,071, 96%). Posts averaged 731 characters in length (median 555). "SideEffects!?" was the most frequently used flair overall (n=27,530, 40%), while "Experience" (n=719, 31%) and "SideEffects!?" (n=672, 29%) were most common among popular posts. TF-IDF analyses of all posts showed interest in contraceptive methods, menstrual experiences, timing, feelings, and unprotected sex. While TF-IDF results for posts with each flair varied, the contraceptive pill, menstrual experiences, and timing were discussed across flair groups. Among popular posts, intrauterine devices and contraceptive use experiences were often discussed. CONCLUSIONS: People commonly wrote about contraceptive side effects and experiences using methods, highlighting the value of r/birthcontrol as a space to post about aspects of contraceptive use that are not well addressed by clinical contraceptive counseling. The value of real-time, open-access data on contraceptive users' interests is especially high given the shifting landscape of and increasing constraints on reproductive health care in the United States.
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Anticoncepción , Procesamiento de Lenguaje Natural , Humanos , Anticonceptivos , Dispositivos Anticonceptivos , Análisis de DocumentosRESUMEN
OBJECTIVES: To review outcomes after a uniform strategy of transventricular repair of tetralogy of Fallot. METHODS: A total of 244 consecutive patients underwent transventricular primary repair of tetralogy of Fallot from 2004 to 2019. Median age at operation was 71 days; 57 (23%) patients were premature; 57 (23%) patients had low birth weight (<2.5 kg), and 40 (16%) had genetic syndromes. The diameter of pulmonary valve annulus, right pulmonary artery (PA), and left PA were 6.0 ± 1.8 mm (z score, -1.7 ± 1.3), 4.3 ± 1.4 mm (z score, -0.9 ± 1.2) and 4.1 ± 1.5 mm (z score, -0.5 ± 1.3). RESULTS: Three (1.2%) operative deaths were recorded. Ninety patients (37%) underwent transannular patching. Postoperative echocardiographic peak right ventricular outflow tract gradient decreased from 72 ± 27 mm Hg to 21 ± 16 mm Hg. Median intensive care unit and hospital stay were 3 and 7 days. The survival rate at 10 years was 94.6% ± 1.8%. Reintervention was required 86 times (55 catheter interventions) in 56 patients following tetralogy of Fallot repair. The freedom from all-cause reintervention rate at 10 years was 70.5% ± 3.6%. Cyanotic spells (hazard ratio, 2.14; 95% CI, 1.22-3.90; P < .01) and smaller pulmonary valve annulus z score (hazard ratio, 1.26; 95% CI, 1.01-1.59; P = .04) were associated with increasing risk of all reinterventions. Freedom from redo surgery for right ventricular outflow tract obstruction and right ventricular dilatation at 10 years were, respectively, 85.0% ± 3.1% and 98.7% ± 0.9%. Freedom from valve implantation was 96.7% ± 1.5% at 10 years. CONCLUSIONS: A uniform strategy of primary repair of tetralogy of Fallot through a transventricular approach resulted in low reoperation rate in the first decade. The need of pulmonary valve implantation was limited to <4% at 10 years.
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Válvula Pulmonar , Tetralogía de Fallot , Humanos , Lactante , Tetralogía de Fallot/diagnóstico por imagen , Tetralogía de Fallot/cirugía , Tetralogía de Fallot/complicaciones , Reoperación/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/cirugíaRESUMEN
A fluorescence turn-on probe, an azide-masked and trehalose-derivatized carbazole (Tre-Cz), was developed to image mycobacteria. The fluorescence turn-on is achieved by photoactivation of the azide, which generates a fluorescent product through an efficient intramolecular C-H insertion reaction. The probe is highly specific for mycobacteria and could image mycobacteria in the presence of other Gram-positive and Gram-negative bacteria. Both the photoactivation and detection can be accomplished using a handheld UV lamp, giving a limit of detection of 103 CFU/mL, which can be visualized by the naked eye. The probe was also able to image mycobacteria spiked in sputum samples, although the detection sensitivity was lower. Studies using heat-killed, stationary-phase, and isoniazid-treated mycobacteria showed that metabolically active bacteria are required for the uptake of Tre-Cz. The uptake decreased in the presence of trehalose in a concentration-dependent manner, indicating that Tre-Cz hijacked the trehalose uptake pathway. Mechanistic studies demonstrated that the trehalose transporter LpqY-SugABC was the primary pathway for the uptake of Tre-Cz. The uptake decreased in the LpqY-SugABC deletion mutants ΔlpqY, ΔsugA, ΔsugB, and ΔsugC and fully recovered in the complemented strain of ΔsugC. For the mycolyl transferase antigen 85 complex (Ag85), however, only a slight reduction of uptake was observed in the Ag85 deletion mutant ΔAg85C, and no incorporation of Tre-Cz into the outer membrane was observed. The unique intracellular incorporation mechanism of Tre-Cz through the LpqY-SugABC transporter, which differs from other trehalose-based fluorescence probes, unlocks potential opportunities to bring molecular cargoes to mycobacteria for both fundamental studies and theranostic applications.
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Despite anxiety being a prevalent mental health problem in children, little data exist on the pervasiveness and levels of anxiety symptoms in kindergarteners. Data from the Early Development Instrument, a teacher-completed, population-level measure of child development, were collected across Canada from 2004 to 2015. The final analytic sample consisted of 974,319 children of whom 2.6% were classified as "highly anxious". Compared to children who exhibited "few to none" anxious behaviors, highly anxious children were more likely to be male, have English/French as a second language, and have a special needs designation. Furthermore, compared with their less anxious peers, highly anxious children had between 3.5 and 6.1 higher odds of scoring below the 10th percentile cut-off in physical, social, language/cognitive and communication domains. Our findings suggest that anxious behaviors are related to children's overall health and illustrate the consistency and extensiveness of anxiety at a very young age among Canadian children.
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Ansiedad , Desarrollo Infantil , Humanos , Masculino , Niño , Femenino , Canadá , Ansiedad/diagnóstico , Ansiedad/psicología , Trastornos de Ansiedad , Salud InfantilRESUMEN
We examined men's influence on women's interest in biomedical HIV prevention during pregnancy and breastfeeding through structured questionnaires and focus group discussions with currently or recently pregnant and breastfeeding (P/BF) women (n = 65), men with P/BF partners (n = 63) and mothers/mothers-in-law of P/BF women (n = 68) in eastern and southern Africa. Data were transcribed, coded and summarised into analytical memos. Men were depicted by most participants as joint decision-makers and influencers of women's use of HIV prevention. Cultural and religious norms depicting men as heads, breadwinners and protectors of the family were cited to legitimise their involvement in decision-making. Male partner education and engagement were recommended to garner their support in women's HIV prevention. This study elucidates how P/BF women's ability to prevent HIV is shaped by traditional and contemporary gender norms in social settings and locations where the study was conducted. Findings may aid intervention design to engage men for P/BF women's effective use of microbicide and oral PrEP.
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Dispositivos Anticonceptivos Femeninos , Infecciones por VIH , Embarazo , Humanos , Masculino , Femenino , Parejas Sexuales , Lactancia Materna , Infecciones por VIH/prevención & control , Identidad de GéneroRESUMEN
HIV acquisition among pregnant and breastfeeding women in sub-Saharan Africa and vertical transmission rates remain high despite established strategies for HIV prevention. During the MTN-041/MAMMA study, we explored the influence of grandmothers (mothers and mothers-in-law of pregnant and breastfeeding women) in eastern and southern Africa on the health-related decisions of pregnant and breastfeeding women and their potential to support use of HIV prevention products. To do this we used structured questionnaires and focus group discussions with three stakeholder groups: 1) grandmothers, 2) HIV-uninfected currently or recently pregnant or breastfeeding women and 3) male partners of currently or recently pregnant or breastfeeding women. A total of 23 focus group discussions comprising 68 grandmothers, 65 pregnant or breastfeeding women and 63 male partners were completed across four study sites. Grandmothers were described as important sources of information during pregnancy and breastfeeding playing both supportive and influencer roles due to personal maternal experience and generational knowledge. While pregnant and breastfeeding women were not keen to involve grandmothers in HIV prevention decision making, they were accepting of grandmothers' involvement in a supportive role. Grandmothers expressed willingness to support pre-exposure prophylaxis use and agreed with the other two stakeholder groups that this decision should be made by women themselves or together with partners. These novel data indicate potential for grandmothers' health related supportive roles to be extended to support decision-making and adherence to biomedical HIV prevention options, and possibly contribute to the decline in HIV acquisition among pregnant and breastfeeding women in these communities.
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Abuelos , Infecciones por VIH , Profilaxis Pre-Exposición , África del Sur del Sahara/epidemiología , Lactancia Materna , Toma de Decisiones , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Madres , EmbarazoRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies used to activate the immune system against tumor cells. Despite therapeutic benefits, ICIs have the potential to cause immune-related adverse events such as myocarditis, a rare but serious side effect with up to 50% mortality in affected patients. Histologically, patients with ICI myocarditis have lymphocytic infiltrates in the heart, implicating T cell-mediated mechanisms. However, the precise pathological immune subsets and molecular changes in ICI myocarditis are unknown. METHODS: To identify immune subset(s) associated with ICI myocarditis, we performed time-of-flight mass cytometry on peripheral blood mononuclear cells from 52 individuals: 29 patients with autoimmune adverse events (immune-related adverse events) on ICI, including 8 patients with ICI myocarditis, and 23 healthy control subjects. We also used multiomics single-cell technology to immunophenotype 30 patients/control subjects using single-cell RNA sequencing, single-cell T-cell receptor sequencing, and cellular indexing of transcriptomes and epitopes by sequencing with feature barcoding for surface marker expression confirmation. To correlate between the blood and the heart, we performed single-cell RNA sequencing/T-cell receptor sequencing/cellular indexing of transcriptomes and epitopes by sequencing on MRL/Pdcd1-/- (Murphy Roths large/programmed death-1-deficient) mice with spontaneous myocarditis. RESULTS: Using these complementary approaches, we found an expansion of cytotoxic CD8+ T effector cells re-expressing CD45RA (Temra CD8+ cells) in patients with ICI myocarditis compared with control subjects. T-cell receptor sequencing demonstrated that these CD8+ Temra cells were clonally expanded in patients with myocarditis compared with control subjects. Transcriptomic analysis of these Temra CD8+ clones confirmed a highly activated and cytotoxic phenotype. Longitudinal study demonstrated progression of these Temra CD8+ cells into an exhausted phenotype 2 months after treatment with glucocorticoids. Differential expression analysis demonstrated elevated expression levels of proinflammatory chemokines (CCL5/CCL4/CCL4L2) in the clonally expanded Temra CD8+ cells, and ligand receptor analysis demonstrated their interactions with innate immune cells, including monocytes/macrophages, dendritic cells, and neutrophils, as well as the absence of key anti-inflammatory signals. To complement the human study, we performed single-cell RNA sequencing/T-cell receptor sequencing/cellular indexing of transcriptomes and epitopes by sequencing in Pdcd1-/- mice with spontaneous myocarditis and found analogous expansions of cytotoxic clonal effector CD8+ cells in both blood and hearts of such mice compared with controls. CONCLUSIONS: Clonal cytotoxic Temra CD8+ cells are significantly increased in the blood of patients with ICI myocarditis, corresponding to an analogous increase in effector cytotoxic CD8+ cells in the blood/hearts of Pdcd1-/- mice with myocarditis. These expanded effector CD8+ cells have unique transcriptional changes, including upregulation of chemokines CCL5/CCL4/CCL4L2, which may serve as attractive diagnostic/therapeutic targets for reducing life-threatening cardiac immune-related adverse events in ICI-treated patients with cancer.
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Antineoplásicos Inmunológicos , Antineoplásicos , Miocarditis , Animales , Antineoplásicos/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Epítopos/efectos adversos , Humanos , Leucocitos Mononucleares/metabolismo , Estudios Longitudinales , Ratones , Miocarditis/metabolismoRESUMEN
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has received empirical support as a viable treatment alternative for treatment-resistant major depressive disorder. Nevertheless, patients and the public-at-large may be hesitant to adopt rTMS. In three studies, we sought to (1) assess and (2) improve public perceptions of rTMS as a treatment for depression. METHODS: In Study 1 (N = 107), we administered questionnaires on Amazon's Mechanical Turk (MTurk) to individuals from the US and Canada in a cross-sectional design to assess perceptions of rTMS compared to psychopharmacology, electroconvulsive therapy (ECT), and talk therapy. In Study 2 (N = 106), we again used an MTurk sample and a cross-sectional design to assess perceptions of rTMS after providing participants with a relatively long description of rTMS. In Study 3 (N = 308), we conducted an experiment in undergraduate students. Participants were randomized to one of four experimental conditions manipulating participants' understanding of the causal mechanisms of depression prior to assessing their perceptions of rTMS. RESULTS: Public perceptions of rTMS were more negative than pharmacotherapy and talk therapy but not ECT (Study 1). rTMS perceptions were notably better when participants were given thorough information about rTMS procedures, pain, and side-effects (Study 2), compared to the previous study when they were given a very brief description of rTMS. Finally, perceptions of rTMS were significantly better when participants were given a brain circuitry-based causal explanation of depression compared to when they were given a psychological explanation of the causes of depression (Study 3). CONCLUSIONS: Public perceptions of rTMS are relatively poor. To improve rTMS acceptability, practitioners should carefully consider patients' prior attitudes and beliefs when explaining rTMS as a treatment alternative. Given that beliefs can have powerful effects on treatment outcome (e.g., placebo, nocebo), future research should explore whether rTMS effects on depression can be improved by facilitating less negative perceptions of rTMS.
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Trastorno Depresivo Mayor , Terapia Electroconvulsiva , Alfabetización en Salud , Estudios Transversales , Trastorno Depresivo Mayor/terapia , Terapia Electroconvulsiva/métodos , Humanos , Estimulación Magnética Transcraneal/métodos , Resultado del TratamientoRESUMEN
Women who acquire HIV during the pregnancy and breastfeeding periods have a higher risk of transmitting the virus to their child than women who become infected with HIV before pregnancy. We explore the context of sexual beliefs and practices that may shape both HIV risk and willingness to use HIV prevention products during pregnancy and postpartum in Malawi, South Africa, Uganda and Zimbabwe. Twenty-three single sex focus group discussions and 36 in-depth interviews took place between May and November 2018 with recently pregnant or breastfeeding women, men, mothers and mothers-in-law of pregnant or breastfeeding women, and key informants. Participants across study groups and sites (N = 232) reported various perceived benefits and harms of sex during pregnancy and postpartum. Participants discussed reasons why men might seek sex outside of the relationship. There is a critical need for alternative prevention options to protect pregnant and breastfeeding women from HIV.
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Infecciones por VIH , Conocimientos, Actitudes y Práctica en Salud , Actitud , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Humanos , Malaui/epidemiología , Masculino , Madres , Embarazo , Sudáfrica/epidemiología , Uganda/epidemiología , Zimbabwe/epidemiologíaRESUMEN
Oral Pre-Exposure Prophylaxis (PrEP) is an established option, and the dapivirine vaginal ring is emerging as a promising strategy for HIV prevention option for women. Because of this, understanding the contextual and cultural factors that will support the increased uptake of these products is crucial. In sub-Saharan Africa, religious leaders may be important stakeholders to involve in product information, education and roll-out. We conducted a sub-analysis of data from 232 participants taking part in the MTN-041/MAMMA study to explore religious leaders' involvement in pregnant and breastfeeding women's health. Study participants viewed biomedicine and spirituality as interlinked and believed that women could seek health-related care from medical experts and turn to faith-based organisations for religious or spiritual needs. Religious leaders were invested in the health of their congregations, endorsed a variety of sexual health strategies, and were eager to learn more about emerging HIV prevention technologies. These data signal the role of religious leaders in supporting their communities, and the importance of involving religious leaders in efforts to roll out new HIV prevention products to facilitate uptake.
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Dispositivos Anticonceptivos Femeninos , Infecciones por VIH , Profilaxis Pre-Exposición , Lactancia Materna , Toma de Decisiones , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , EmbarazoRESUMEN
BACKGROUND: Event perception provides a promising, novel approach for investigating underlying cognitive mechanisms of the social impairment associated with symptoms of ADHD. AIMS: The goal of this study was to establish the relationship among event perception, symptoms of ADHD, and social skills. METHODOLOGY: Eighty-three undergraduates were recruited from the University of Ottawa first year psychology courses (38 with ADHD, 45 without ADHD). They performed an event perception task and completed self-report questionnaires assessing social functioning and symptoms of ADHD (The Social Skills-Improvement System and the Conner's CBRS-SR). RESULTS: Bootstrapping mediation analyses revealed that symptoms of inattention and hyperactivity mediated the relationship between event perception and social skills. A model with predictor and mediator reversed was also tested, and was not significant, providing strength to the directionality of the relationships. Results highlight the applicability of event perception to understanding the association between social impairment and symptoms of ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Habilidades Sociales , Trastorno por Déficit de Atención con Hiperactividad/psicología , Cognición , Humanos , Percepción , EstudiantesRESUMEN
Event segmentation is the automatic cognitive process of chunking ongoing information into meaningful events. Event segmentation theory (EST) proposes that event segmentation is a grouping process fundamental to normal, everyday perceptual processing, taking a central role in attention and action control. The neurocognitive deficits observed among individuals with ADHD overlap those involved in event segmentation, but to date no research has examined event segmentation in the context of ADHD. Objective: The goal of this study was to document the event segmentation deficits of individuals with ADHD. Method: Seventy-five undergraduates with ADHD and seventy-nine without ADHD performed an event segmentation task. Results: Results revealed that undergraduates with ADHD identify significantly more large events. Conclusion: These findingssuggest explicit disturbances in the event model and updating system among those with ADHD. Future research directions include further elucidating these deficits with more varied stimuli and establishing associations with functional impairments.
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Trastorno por Déficit de Atención con Hiperactividad , Atención , Humanos , MemoriaRESUMEN
Female-initiated HIV prevention methods, such as oral pre-exposure prophylaxis (PrEP) and the vaginal ring, may be important risk reduction strategies for breastfeeding women. Given their novelty, information about the sociocultural context and how it influences perceptions of and support for their use during breastfeeding is lacking. To address this gap, we conducted 23 focus group discussions separately with pregnant and breastfeeding women, male partners and grandmothers (N = 196) and 36 in-depth interviews with key informants in Malawi, South Africa, Uganda and Zimbabwe. We analysed the data using a framework analysis method. Overall, breastfeeding was the norm, and participants described the transference of health (e.g., nutrition) and disease (e.g., HIV) to children through breast milk. Participants considered the early breastfeeding period as one of high HIV transmission risk for women. They explained that male partners tend to seek outside sexual partners during this period because women need time to recover from delivery, women focus their attention on the child, and some men are disgusted by breast milk. Participants highlighted concerns about the drugs in oral PrEP transferring to the child through breast milk, but fewer worried about the effects of the vaginal ring because the drug is localized. Women, grandmothers and key informants were supportive of women using these HIV prevention methods during breastfeeding, while male partners had mixed opinions. These findings can be used to tailor messages for promoting the use of PrEP or the vaginal ring during breastfeeding in sub-Saharan Africa.
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Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/uso terapéutico , Lactancia Materna , Niño , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Malaui/epidemiología , Masculino , Percepción , Embarazo , Sudáfrica/epidemiología , Esposos , Uganda/epidemiología , ZimbabweRESUMEN
The metalloenzyme acireductone dioxygenase (ARD) shows metal-dependent physical and enzymatic activities depending upon the metal bound in the active site. The Fe(II)-bound enzyme catalyzes the penultimate step of the methionine salvage pathway, converting 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one (acireductone) into formate and the ketoacid precursor of methionine, 2-keto-4-thiomethyl-2-oxobutanoate, using O2 as the oxidant. If Ni(II) is bound, an off-pathway shunt occurs, producing 3-methylthiopropionate, formate, and carbon monoxide from the same acireductone substrate. The solution structure of the Fe(II)-bound human enzyme, HsARD, is described and compared with the structures of Ni-bound forms of the closely related mouse enzyme, MmARD. Potential rationales for the different reactivities of the two isoforms are discussed. The human enzyme has been found to regulate the activity of matrix metalloproteinase I (MMP-I), which is involved in tumor metastasis, by binding the cytoplasmic transmembrane tail peptide of MMP-I. Nuclear magnetic resonance titration of HsARD with the MMP-I tail peptide permits identification of the peptide binding site on HsARD, a cleft anterior to the metal binding site adjacent to a dynamic proline-rich loop.
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Dioxigenasas/química , Dioxigenasas/metabolismo , Hierro/metabolismo , Metaloproteinasa 1 de la Matriz/química , Metaloproteinasa 1 de la Matriz/metabolismo , Dominio Catalítico , Humanos , Modelos Moleculares , SolucionesRESUMEN
INTRODUCTION: Women in sub-Saharan Africa spend a substantial portion of their reproductive lives pregnant and/or breastfeeding (P/BF), yet they have limited options to prevent HIV during these maternal stages. In preparation for phase 3b prevention trials in P/BF women, we explored attitudes about using a vaginal ring or oral pills for pre-exposure prophylaxis (PrEP), perceptions of HIV risk during P/BF and key influences on future PrEP use. METHODS: In 2018, we conducted 16 single-sex focus group discussions (FGDs) with community- and clinic-recruited HIV-uninfected women, currently or recently P/BF, aged 18 to 40, and men with (currently or recently) P/BF partners, aged 18+. Participants completed a behavioural questionnaire, viewed an educational video and handled prototype placebo products. FGDs were conducted in local languages and transcribed, coded and analysed, using a socio-ecological framework, for key influences on willingness to use products, HIV risk perceptions and opinions on product attributes. RESULTS: Of the 128 participants (65 women, 63 men) 75% lived with their partner and 84% had a child. Women reported the most important influencers when P/BF were partners, and all stated that health decisions when P/BF are typically made jointly (e.g. medication use; ante/postnatal and baby care). There was consensus that P/BF women are at high risk for HIV, primarily because of their partner's infidelities, and new prevention options were welcomed. Participants valued multiple options and stated that woman's personal preference would be key to product choice. Anticipated concerns about products included risk of miscarriage, impact on infant development, complications during delivery and adequate production or taste of breastmilk. Specific perceived disadvantages emerged for the ring (e.g. vaginal discomfort, difficulty inserting/removing) and for pills (e.g. nausea/vomiting) that may be exacerbated during pregnancy. Health care providers' (HCPs) knowledge and approval of product use during P/BF was needed to mitigate anticipated fears. CONCLUSIONS: Participants perceived pregnancy and breastfeeding as high HIV risk periods and valued new prevention options. HIV protection of the mother-child dyad, safety of the baby, and ultimately, health of the family were paramount. Endorsement by HCPs and support from partners were key to future product acceptance. Participants recommended involving partners and HCPs in sensitization efforts for future trials.
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Fármacos Anti-VIH/administración & dosificación , Lactancia Materna , Dispositivos Anticonceptivos Femeninos , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición/métodos , Complicaciones Infecciosas del Embarazo/prevención & control , Administración Oral , Adolescente , Adulto , África , Fármacos Anti-VIH/uso terapéutico , Femenino , Grupos Focales , Humanos , Masculino , Embarazo , Adulto JovenRESUMEN
BACKGROUND: There are many barriers to parental skin-to-skin contact for critically ill neonates. Our aims were to decrease median time to first parental hold of neonates requiring respiratory support from 6.4 to 3 days, and to increase the percentage of neonates held within the first 24 h after birth from 6 to 75%. METHODS: Lean Six Sigma methodology was used to identify barriers to holding and opportunities for improvement. INTERVENTION: A multifactorial improvement bundle was implemented to reduce the time to first parental hold of critically ill neonates. RESULTS: Median time to first parental hold was reduced from 6.4 to 1.2 days (p < 0.01). Infants held within the first 24 h after birth increased from 6 to 35%. There was no increase in adverse events associated with parental holding. CONCLUSIONS: Implementation of an improvement bundle resulted in a significant reduction in time to first parental hold of infants requiring respiratory support.