Nevin Manimala

JMIR Hum Factors. 2024 Mar 12;11:e52048. doi: 10.2196/52048.

ABSTRACT

BACKGROUND: Young women in Lesotho face myriad sexual and reproductive health problems. There is little time to provide health education to women in low-resource settings with critical shortages of human resources for health.

OBJECTIVE: This study aims to determine the acceptability and usability of a conversational agent system, the Nthabi health promotion app, which was culturally adapted for use in Lesotho.

METHODS: We conducted a descriptive quantitative study, using a 22-item Likert scale survey to assess the perceptions of the usability and acceptability of 172 young women aged 18-28 years in rural districts of Lesotho, who used the system on either smartphones or tablets for up to 6 weeks. Descriptive statistics were used to calculate the averages and frequencies of the variables. χ² tests were used to determine any associations among variables.

RESULTS: A total of 138 participants were enrolled and completed the survey. The mean age was 22 years, most were unmarried, 56 (40.6%) participants had completed high school, 39 (28.3%) participants were unemployed, and 88 (63.8%) participants were students. Respondents believed the app was helpful, with 134 (97.1%) participants strongly agreeing or agreeing that the app was “effective in helping them make decisions” and “could quickly improve health education and counselling.” In addition, 136 (98.5%) participants strongly agreed or agreed that the app was “simple to use,” 130 (94.2 %) participants reported that Nthabi could “easily repeat words that were not well understood,” and 128 (92.7%) participants reported that the app “could quickly load the information on the screen.” Respondents were generally satisfied with the app, with 132 (95.6%) participants strongly agreeing or agreeing that the health education content delivered by the app was “well organised and delivered in a timely way,” while 133 (96.4%) participants “enjoyed using the interface.” They were satisfied with the cultural adaptation, with 133 (96.4%) participants strongly agreeing or agreeing that the app was “culturally appropriate and that it could be easily shared with a family or community members.” They also reported that Nthabi was worthwhile, with 127 (92%) participants reporting that they strongly agreed or agreed that they were “satisfied with the application and intended to continue using it,” while 135 (97.8%) participants would “encourage others to use it.” Participants aged 18-24 years (vs those aged 25-28 years) agreed that the “Nthabi app was simple to use” (106/106, 100% vs 30/32, 98.8%; P=.01), and agreed that “the educational content was well organised and delivered in a timely way” (104/106, 98.1% vs 28/32, 87.5%; P=.01).

CONCLUSIONS: These results support further study of conversational agent systems as alternatives to traditional face-to-face provision of health education services in Lesotho, where there are critical shortages of human resources for health.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04354168; https://www.clinicaltrials.gov/study/NCT04354168.

PMID:38470460 | DOI:10.2196/52048

Cancer. 2024 Mar 12. doi: 10.1002/cncr.35281. Online ahead of print.

ABSTRACT

BACKGROUND: Small-cell lung cancer (SCLC) is characterized by rapid proliferation and early dissemination. The objective of this study was to examine the demographic trends and outcomes in SCLC.

METHODS: The authors queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results database to assess the trends in incidence, demographics, staging, and survival for SCLC from 1975 to 2019. Trends were determined using joinpoint analysis according to the year of diagnosis.

RESULTS: Among the 530,198 patients with lung cancer, there were 73,362 (13.8%) with SCLC. The incidence per 100,000 population peaked at 15.3 in 1986 followed by a decline to 6.5 in 2019. The percentage of SCLC among all lung tumors increased from 13.3% in 1975 to a peak of 17.5% in 1986, declining to 11.1% by 2019. There was an increased median age at diagnosis from 63 to 69 years and an increased percentage of women from 31.4% to 51.2%. The percentage of stage IV increased from 58.6% in 1988 to 70.8% in 2010, without further increase. The most common sites of metastasis at diagnosis were mediastinal lymph nodes (75.3%) liver (31.6%), bone (23.7%), and brain (16.4%). The 1-year and 5-year overall survival rate increased from 23% and 3.6%, respectively, in 1975-1979 to 30.8% and 6.8%, respectively, in 2010-2019.

CONCLUSIONS: The incidence of SCLC peaked in 1988 followed by a gradual decline. Other notable changes include increased median age at diagnosis, the percentage of women, and the percentage of stage IV at diagnosis. The improvement in 5-year overall survival has been statistically significant but clinically modest.

PMID:38470453 | DOI:10.1002/cncr.35281

Dev Psychobiol. 2024 Apr;66(3):e22479. doi: 10.1002/dev.22479.

ABSTRACT

Maternal care during the early postnatal period of altricial mammals is a key factor in the survival and adaptation of offspring to environmental conditions. Natural variations in maternal care and experimental manipulations with maternal-child relationships modeling early-life adversity (ELA) in laboratory rats and mice have a strong long-term influence on the physiology and behavior of offspring in rats and mice. This literature review is devoted to the latest research on the role of epigenetic mechanisms in these effects of ELA and mother-infant relationship, with a focus on the regulation of hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor. An important part of this review is dedicated to pharmacological interventions and epigenetic editing as tools for studying the causal role of epigenetic mechanisms in the development of physiological and behavioral profiles. A special section of the manuscript will discuss the translational potential of the discussed research.

PMID:38470450 | DOI:10.1002/dev.22479

J Vet Dent. 2024 Mar 12:8987564241232862. doi: 10.1177/08987564241232862. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the effects of Coriandrum sativum L. (CSL) seed extract on gingival levels of antioxidant enzymes, pro-inflammatory cytokines and on alveolar bone and attachment levels after experimental periodontitis induction in rats and compare it with low-dose doxycycline (LDD). Forty adult male Wistar Albino rats were divided randomly into 5 groups as follows: 1 = periodontally healthy (control); 2 = periodontitis; 3 = periodontitis + CSL (32 mg/kg); 4 = periodontitis + CSL (200 mg/kg); and 5 = periodontitis + LDD (6 mg/kg). Gingival superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) levels were evaluated by enzyme-linked immunosorbent assay. The presence of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1βeta (IL-1β) immunoreactivity was detected immunohistochemically. Alveolar bone area in the furcation space (ABA), alveolar bone loss (ABL), and attachment loss (AL) were evaluated histomorphometrically. The SOD level was lower in group 5 than in groups 2, 3, and 4. The IL-1β level was highest in group 4. The TNF-α level was statistically higher in groups 2 and 4 than in groups 1, 3, and 5. The IL-6 level was highest in group 4. Its level was higher in groups 2 and 3 than in group 5. ABA was less in groups 2, 3, and 4 compared to groups 1 and 5. ABL was less in group 5 than in groups 2, 3, and 4. AL was greater in group 4 than in group 5. The use of 200 mg/kg CSL showed a pro-inflammatory effect and IL-1β and TNF-α levels decreased after 32 mg/kg CSL application in the treatment of periodontitis.

PMID:38470443 | DOI:10.1177/08987564241232862

JAMA Netw Open. 2024 Mar 4;7(3):e240555. doi: 10.1001/jamanetworkopen.2024.0555.

ABSTRACT

IMPORTANCE: High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives.

OBJECTIVE: To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children’s hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded.

EXPOSURE: Any opioid exposure and methadone treatment.

MAIN OUTCOMES AND MEASURES: Regional and institutional variations in opioid exposure.

RESULTS: Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

PMID:38470421 | DOI:10.1001/jamanetworkopen.2024.0555

JAMA Netw Open. 2024 Mar 4;7(3):e241958. doi: 10.1001/jamanetworkopen.2024.1958.

ABSTRACT

IMPORTANCE: COVID-19 prompted rapid development of scarce resource allocation (SRA) policies to be implemented if demand eclipsed health systems’ ability to provide critical care. While SRA policies follow general ethical frameworks, understanding priorities of those affected by policies and/or tasked with implementing them is critical.

OBJECTIVE: To evaluate whether community members and health care profesionals (HCP) agree with SRA protocols at the University of California (UC).

DESIGN, SETTING, AND PARTICIPANTS: This survey study used social media and community-partnered engagement to recruit participants to a web-based survey open to all participants aged older than 18 years who wished to enroll. This study was fielded between May and September 2020 and queried participants’ values and preferences on draft SRA policy tenets. Participants were also encouraged to forward the survey to their networks for snowball sampling. Data were analyzed from July 2020 to January 2024.

MAIN OUTCOMES AND MEASURES: Survey items assessed values and preferences, graded on Likert scales. Agreement was tabulated as difference in Likert points between expressed opinion and policy tenets. Descriptive statistics were tested for significance by HCP status. Free text responses were analyzed using applied rapid qualitative analysis.

RESULTS: A total of 1545 participants aged older than 18 years (mean [SD] age 49 [16] years; 1149 female participants [74%], 478 health care practitioners [30%]) provided data on SRA values and preferences. Agreement with UC SRA policy as drafted was moderately high among respondents, ranging from 67% to 83% across domains. Higher agreement with the interim policy was observed for laypersons across all domains except health-related factors. HCPs agreed more strongly on average that resources should not be allocated to those less likely to survive (HCP mean, 3.70; 95% CI, 3.16-3.59; vs layperson mean, 3.38; 95% CI, 3.17-3.59; P = .002), and were more in favor of reallocating life support from patients less likely to those more likely to survive (HCP mean, 6.41; 95% CI, 6.15-6.67; vs layperson mean, 5.40; 95% CI, 5.23-5.58; P < .001). Transparency and trust building themes were common in free text responses and highly rated on scaled items.

CONCLUSIONS AND RELEVANCE: This survey of SRA policy values found moderate agreement with fundamental principles of such policies. Engagement with communities affected by SRA policy should continue in iterative refinement in preparation for future crises.

PMID:38470416 | DOI:10.1001/jamanetworkopen.2024.1958

J Chem Theory Comput. 2024 Mar 12. doi: 10.1021/acs.jctc.3c01381. Online ahead of print.

ABSTRACT

The determination of the solvation free energy of ions and molecules holds profound importance across a spectrum of applications spanning chemistry, biology, energy storage, and the environment. Molecular dynamics simulations are powerful tools for computing this critical parameter. Nevertheless, the accurate and efficient calculation of the solvation free energy becomes a formidable endeavor when dealing with complex systems characterized by potent Coulombic interactions and sluggish ion dynamics and, consequently, slow transition across various metastable states. In the present study, we expose limitations stemming from the conventional calculation of the statistical inefficiency g in the thermodynamic integration method, a factor that can hinder the determination of convergence of the solvation free energy and its associated uncertainty. Instead, we propose a robust scheme based on Gelman-Rubin convergence diagnostics. We leverage this improved estimation of uncertainties to introduce an innovative accelerated thermodynamic integration method based on the Gaussian Process regression. This methodology is applied to the calculation of the solvation free energy of trivalent rare-earth elements immersed in ionic liquids, a scenario in which the aforementioned challenges render standard approaches ineffective. The proposed method proves to be effective in computing solvation free energy in situations where traditional thermodynamic integration methods fall short.

PMID:38470415 | DOI:10.1021/acs.jctc.3c01381

Cancer. 2024 Mar 12. doi: 10.1002/cncr.35276. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to estimate the event-free survival (EFS) of children and young adults with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) treated in nonrandomized phase 2 studies conducted by the Children’s Oncology Group (COG) and predecessor groups to establish a benchmark EFS for future phase 2 NRSTS trials evaluating the activity of novel agents.

METHODS: A retrospective analysis of patients with recurrent or refractory NRSTS prospectively enrolled in nonrandomized phase 2 COG and predecessor group trials between 1994 and 2015 was conducted. EFS was defined as disease progression/relapse or death and calculated via the Kaplan-Meier method. The log-rank test and relative risk regression were used to compare EFS distribution by age at enrollment, sex, race, NRSTS histology, prior lines of therapy, calendar year of trial, and type of radiographic response.

RESULTS: In total, 137 patients were enrolled in 13 phase 2 trials. All trials used radiographic response rate as a primary outcome, and none of the agents used were considered active on the basis of trial-specified thresholds. The estimated median EFS and 6-month EFS of the entire study cohort was 1.5 months (95% confidence interval [CI], 1.3-1.8 months) and 19.4% (95% CI, 12.7%-26%), respectively. No difference in EFS was observed by age at enrollment, sex, race, NRSTS histology subtype, prior lines of therapies, and trial initiation year. EFS significantly differed by radiographic response.

CONCLUSIONS: The EFS for children and young adults with relapsed or refractory NRSTS remains suboptimal. Established EFS can be referenced as a benchmark for future single-agent phase 2 trials incorporating potentially active novel agents in this population.

PMID:38470405 | DOI:10.1002/cncr.35276

Rom J Intern Med. 2024 Mar 12. doi: 10.2478/rjim-2024-0010. Online ahead of print.

ABSTRACT

INTRODUCTION: Accidental hypothermia (AH) presents a significant mortality risk, even in individuals with good health. Early recognition of the parameters associated with negative prognosis could save more lives.

METHODS: This was a pilot, retrospective observational study, conducted in the largest Emergency Hospital in North Eastern Romania, which included all patients with AH (defined as body temperature below 35°C), hospitalized and treated in our hospital between 2019 and 2022.

RESULTS: A total of 104 patients with AH were included in our study, 90 of whom had data collected and statistically analyzed. The clinical, biological, and therapeutic parameters associated with negative outcomes were represented by a reduced GCS score (p=0.024), diminished systolic and diastolic blood pressure (p=0.007 respectively, 0.013), decreased bicarbonate (p=0.043) and hemoglobin levels (p=0.002), the presence of coagulation disorders (p=0.007), as well as the need for administration of inotropic or vasopressor medications (p=0.04).

CONCLUSION: In this pilot, retrospective, observational study, the negative outcomes observed in patients with AH hospitalized in the largest Emergency Hospital in North-Eastern Romania were associated with several clinical, biochemical, and therapeutic factors, which are easy to identify in clinical practice. Recognizing the significance of these associated factors empowers healthcare practitioners to intervene at an early stage to save more lives.

PMID:38470364 | DOI:10.2478/rjim-2024-0010

J Phys Chem A. 2024 Mar 12. doi: 10.1021/acs.jpca.3c07416. Online ahead of print.

ABSTRACT

Recent developments in light-emitting carbon nanodots and molecular organic semiconductors have seen renewed interest in the properties of polycyclic aromatic hydrocarbons (PAHs) as a family. The networks of delocalized π electrons in sp²-hybridized carbon grant PAHs light-emissive properties right across the visible spectrum. However, the mechanistic understanding of their emission energy has been limited due to the ground state-focused methods of determination. This computational chemistry work, therefore, seeks to validate existing rules and elucidate new features and characteristics of PAHs that influence their emissions. Predictions based on (time-dependent) density functional theory account for the full 3-dimensional electronic structure of ground and excited states and reveal that twisting and near-degeneracies strongly influence emission spectra and may therefore be used to tune the color of PAHs and, hence, carbon nanodots. We particularly note that the influence of twisting goes beyond torsional destabilization of the ground-state and geometric relaxation of the excited state, with a third contribution associated with the electric transition dipole. Symmetries and peri-condensation may also have an effect, but this could not be statistically confirmed. In pursuing this goal, we demonstrate that with minimal changes to molecular size, the entire visible spectrum may be spanned by geometric modification alone; we have also provided a first estimate of emission energy for 35 molecules currently lacking published emission spectra as well as clear guidelines for when more sophisticated computational techniques are required to predict the properties of PAHs accurately.

PMID:38470339 | DOI:10.1021/acs.jpca.3c07416