Substance use Attitudes, Beliefs, Experience, and Knowledge Among Nursing and Nursing Assistant Students.

Stigma is a public health concern. Stigmatizing attitudes toward persons with substance use disorders (SUDs) can adversely impact clinical care and outcomes. Beliefs about SUD, prior experience and familiarity to persons with SUD, and educational curricula drive attitudes among health-care workers. In 2019, nursing and nursing assistant students were recruited through an online survey platform. Participants completed an SUD knowledge test and a survey assessing education, beliefs, personal experience, and confidence in recognizing the signs and symptoms of SUD. One hundred and ten health-care students (nursing students, n = 67 and nursing assistant students, n = 43) completed the survey. Among nursing assistant students, endorsing a disease model of addiction (F(2, 40) = 5.83, p < .001, R2 = .23), and personal familiarity with SUD (F(2, 40) = 4.46, p < .001, R2 = .18), were significantly positively predictive of positive regard toward working with persons with SUD. For nursing students, endorsing a disease model of addiction, educational curricula involving persons with SUD, and personal familiarity were significantly positively predictive of positive regard toward working with persons with SUDs (F(2, 61) = 11.52, p < .001, R2 = .36). Interventions to mitigate drug-related stigma among health-care students should center students with personal familiarity, promote the disease concept of addiction, and incorporate contact-based training.

Trans-Ancestral Genetic Risk Factors for Treatment-Related Type 2 Diabetes Mellitus in Survivors of Childhood Cancer.

PURPOSE: Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D. PATIENTS AND METHODS: Leveraging whole-genome sequencing data from the St Jude Lifetime Cohort (N = 3,676, 304 clinically ascertained cases), we conducted ancestry-specific genome-wide association studies among survivors of African and European genetic ancestry (AFR and EUR, respectively) followed by trans-ancestry meta-analysis. Trans-/within-ancestry replication including data from the Childhood Cancer Survivor Study (N = 5,965) was required for prioritization. Three external general population T2D polygenic risk scores (PRSs) were assessed, including multiancestry PRSs. Treatment risk effect modification was evaluated for prioritized loci. RESULTS: Four novel T2D risk loci showing trans-/within-ancestry replication evidence were identified, with three loci achieving genome-wide significance (P < 5 × 10-8). Among these, common variants at 5p15.2 (LINC02112), 2p25.3 (MYT1L), and 19p12 (ZNF492) showed evidence of modifying alkylating agent-related T2D risk in both ancestral groups, but showed disproportionately greater risk in AFR survivors (AFR odds ratios [ORs], 3.95-17.81; EUR ORs, 2.37-3.32). In survivor-specific RNA-sequencing data (N = 207), the 19p12 locus variant was associated with greater ZNF492 expression dysregulation after exposures to alkylators. Elevated T2D risks across ancestry groups were only observed with increasing values for multiancestry T2D PRSs and were especially increased among survivors treated with alkylators (top v bottom quintiles: ORAFR, 20.18; P = .023; OREUR, 13.44; P = 1.3 × 10-9). CONCLUSION: Our findings suggest therapy-related genetic risks contribute to the increased T2D burden among non-Hispanic Black childhood cancer survivors. Additional study of how therapy-related genetic susceptibility contributes to this disparity is needed.

Perceptions of dengue risk and acceptability of a dengue vaccine in residents of Puerto Rico.

Dengvaxia is the first dengue vaccine recommended in the United States (U.S.). It is recommended for children aged 9-16 y with laboratory-confirmed previous dengue infection and living in areas where dengue is endemic. We conducted focus groups with parents and in-depth interviews with key informants (i.e. practicing pediatricians, physicians from immunization clinics, university researchers, and school officials) in Puerto Rico (P.R.) to examine acceptability, barriers, and motivators to vaccinate with Dengvaxia. We also carried out informal meetings and semi-structured interviews to evaluate key messages and educational materials with pediatricians and parents. Barriers to vaccination included lack of information, distrust toward new vaccines, vaccine side effects and risks, and high cost of/lack of insurance coverage for laboratory tests and vaccines. Motivators included clear information about the vaccine, a desire to prevent future dengue infections, the experience of a previous dengue infection or awareness of dengue fatality, vaccine and laboratory tests covered by health insurance, availability of rapid test results and vaccine appointments. School officials and parents agreed parents would pay a deductible of $5-20 for Dengvaxia. For vaccine information dissemination, parents preferred an educational campaign through traditional media and social media, and one-on-one counseling of parents by healthcare providers. Education about this vaccine to healthcare providers will help them answer parents' questions. Dengvaxia acceptability in P.R. will increase by addressing motivators and barriers to vaccination and by disseminating vaccine information in plain language through spokespersons from health institutions in P.R.

St. Jude Survivorship Portal: sharing and analyzing large clinical and genomic datasets from pediatric cancer survivors.

Childhood cancer survivorship studies generate comprehensive datasets comprising demographic, diagnosis, treatment, outcome, and genomic data from survivors. To broadly share this data, we created the St. Jude Survivorship Portal (https://survivorship.stjude.cloud), the first data portal for sharing, analyzing, and visualizing pediatric cancer survivorship data. Over 1,600 phenotypic variables and 400 million genetic variants from over 7,700 childhood cancer survivors can be explored on this free, open-access portal. Summary statistics of variables are computed on-the-fly and visualized through interactive and customizable charts. Survivor cohorts can be customized and/or divided into groups for comparative analysis. Users can also seamlessly perform cumulative incidence and regression analyses on the stored survivorship data. Using the portal, we explored the ototoxic effects of platinum-based chemotherapy, uncovered a novel association between mental health, age, and limb amputation, and discovered a novel haplotype in MAGI3 strongly associated with cardiomyopathy specifically in survivors of African ancestry.

Physical and structural characterization of bis-acryl composite resin.

During the preparation of fixed prosthesis (including individual bridges and crowns) it is important to select the materials that have the best features and properties to predict a successful clinical treatment. The objective of this study was to determine if the chemical and structural characteristics could cause to increase the fracture resistance, we used four bis-acryl resins Luxatemp, Protemp, Structur and Telio. Three-points bending by Flexural test were performed in ten bars and they were carried out to compare with Anova test. In addition, the bis-acryl resins were analyzed by scanning electron microscopy, to analyze microstructure and morphology and the molecular structure were performed by Infrared Spectroscopy through Attenuated Total Reflectance. A higher flexural strength was found in Luxatemp and Structur with, no significant differences between this study groups. Regarding Protemp and Telio, these study groups showed a lower flexural strength when were compared with Luxatemp and Structur. These results corroborate SEM and ATR analysis because Luxatemp sample showed a regular size particle on the surface and chemically presents a long cross-linkage polymer chain. The presence of CO3, SiO2 and N-H groups as a fillers particle interacting with OH groups cause a higher flexural strength compared with another groups.

Surface modified copper foam with cobalt phthalocyanine carbon nanotube hybrids for tuning CO2 reduction reaction products.

The CO2 reduction reaction (CO2RR) is a feasible way to convert this greenhouse gas into molecules of industrial interest. Herein we present the modification of the Cu foam cathode using molecular catalyst hybrid from cobalt phthalocyanine (CoPc) to increase selectivity and stability towards CO2RR products in a flow cell setup.

Single-cell transcriptomics of the human parasite Schistosoma mansoni first intra-molluscan stage reveals tentative tegumental and stem-cell regulators.

Schistosomiasis is a major Neglected Tropical Disease, caused by the infection with blood flukes in the genus Schistosoma. To complete the life cycle, the parasite undergoes asexual and sexual reproduction within an intermediate snail host and a definitive mammalian host, respectively. The intra-molluscan phase provides a critical amplification step that ensures a successful transmission. However, the cellular and molecular mechanisms underlying the development of the intra-molluscan stages remain poorly understood. Here, single cell suspensions from S. mansoni mother sporocysts were produced and sequenced using the droplet-based 10X Genomics Chromium platform. Six cell clusters comprising two tegument, muscle, neuron, parenchyma and stem/germinal cell clusters were identified and validated by in situ hybridisation. Gene Ontology term analysis predicted key biological processes for each of the clusters, including three stem/germinal sub-clusters. Furthermore, putative transcription factors predicted for stem/germinal and tegument clusters may play key roles during parasite development and interaction with the intermediate host.

Associations of seven measures of biological age acceleration with frailty and all-cause mortality among adult survivors of childhood cancer in the St. Jude Lifetime Cohort.

Survivors of childhood cancer may experience accelerated biological aging, resulting in premature frailty and death. We used seven measures of biological age in the St. Jude Lifetime (SJLIFE) Cohort to compare biological age acceleration between the SJLIFE Cohort and the third United States National Health and Nutrition Examination Survey controls, explore trajectories of biological age according to cancer treatment and type, and test associations of biological age acceleration with frailty and death (mean follow-up of 26.5 years) among survivors. Survivors of cancer aged 5% faster per year and measured, on average, 0.6-6.44 years biologically older compared to controls and 5-16 years biologically older compared to age-matched individuals at the population level. Survivors treated with hematopoietic cell transplant and vinca alkaloid chemotherapy evidenced the fastest trajectories of biological aging. Biologically, older and faster-aging survivors consistently and robustly had a higher risk of frailty and died earlier than those with slower biological aging, suggesting a potential opportunity to intervene on excess aging.

Positive modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors differentially alters spatial learning and memory in juvenile rats younger and older than three weeks.

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.

Acceptability of emergent Aedes aegypti vector control methods in Ponce, Puerto Rico: A qualitative assessment.

Aedes aegypti control has been fraught with challenges in Puerto Rico. The government has implemented commonly used vector control methods, but arboviral epidemics still occur. It is necessary to explore new Ae. aegypti control methods. This study aimed to understand the perceptions of community members in Ponce, Puerto Rico about emergent and traditional Ae. aegypti vector control methods and determine their acceptability and support for these methods. We identified the type of information needed to increase support for emergent vector control methods, and the preferred strategies to disseminate this information. Four group discussions were conducted with a total of 32 participants representing eight of the 14 clusters participating in the Communities Organized for the Prevention of Arboviruses (COPA), a project designed to mobilize communities in Ponce, Puerto Rico to prevent diseases transmitted by mosquitoes. Group discussions began with an overview of different methods used for controlling Ae. aegypti mosquitoes. These overviews facilitated participant understanding of the mosquito control methods presented. Use of source reduction, autocidal gravid ovitraps (AGO), and manual application of larvicide for arboviral mosquito control received support from almost all participants. Vector control methods that use more familiar techniques in Puerto Rico such as truck-mounted larvicide spraying (TMLS) and insecticide residual spraying received support from most participants. More than half of participants supported the use of emergent mosquito control methods including Wolbachia suppression, Wolbachia replacement, or genetically modified mosquitoes (GMM). Participants preferred to receive vector control information through house-to-house visits with the distribution of written materials, followed by dissemination of information through traditional (i.e., radio, television) and social media. The detailed information resulting from this study was used to develop messages for a communications campaign to garner future community support. Community acceptance and support are critical for the success of vector control programs using emergent mosquito control methods.

Identical sequences, different behaviors: Protein diversity captured at the single-molecule level.

The classical "one sequence, one structure, one function" paradigm has shaped much of our intuition of how proteins work inside the cell. Partially due to the insight provided by bulk biochemical assays, individual biomolecules are often assumed to behave as identical entities, and their characterization relies on ensemble averages that flatten any conformational diversity into a unique phenotype. While the emergence of single-molecule techniques opened the gates to interrogating individual molecules, technical shortcomings typically limit the duration of these measurements, which precludes a complete characterization of an individual protein and, hence, capturing the heterogeneity among molecular populations. Here, we introduce an ultrastable magnetic tweezers design, which enables us to measure the folding dynamics of a single protein during several uninterrupted days with high temporal and spatial resolution. Thanks to this instrumental development, we fully characterize the nanomechanics of two proteins with a very distinct force response, the talin R3IVVI domain and protein L. Days-long recordings on the same protein individual accumulate thousands of folding transitions with submicrosecond resolution, allowing us to reconstruct their free energy landscapes and describe how they evolve with force. By mapping the nanomechanical identity of many different protein individuals, we directly capture their molecular diversity as a quantifiable dispersion on their force response and folding kinetics. By significantly expanding the measurable timescales, our instrumental development offers a tool for profiling individual molecules, opening the gates to directly characterizing biomolecular heterogeneity.

Modic Changes in the Lumbar Spine: Exploring Their Association with Abdominal Aortic Calcification as a Potential Indicator of Systemic Atherosclerosis.

BACKGROUND: This was a cross-sectional study on the correlation between abdominal aortic calcification (AAC) and Modic changes (MC). Little is known regarding the etiology of MC in the lumbar spine. Currently, insufficient vascularization of the endplate has been proposed to contribute to the appearance of MC. Our objective was to investigate whether AAC, a marker for a poor vascular status, is associated with MC in patients suffering from degenerative disc disease. METHODS: Radiologic images of patients (n = 130) suffering from degenerative lumbar disc disease were reviewed. Type and severity of MC were assessed using magnetic resonance images, and severity of AAC was evaluated using computed tomography images or fluoroscopy. Both items were dichotomized into minimal and relevant grades. The correlation between them was studied using Spearman's correlation test, with age as a covariate. RESULTS: Of the patients, 113 (87%) demonstrated MC (31% type I, 63% type II, and 6% type III) (55% relevant grade), and 68% had AAC (44% relevant grade). Spearman statistical analysis revealed that AAC was correlated with age (P < 0.001), whereas MC were not (P = 0.142). AAC severity was significantly correlated with MC, remaining so after age adjustment (P < 0.05). While MC type I lacked correlation with AAC, MC type II were significantly correlated with AAC (0.288, P = 0.015); however, this association lost significance after adjusting for age (P = 0.057). CONCLUSIONS: AAC and MC (mainly MC type II) are associated, indicating that reduced blood supply or even a poor systemic vascularization status due to atherosclerotic disease may play a role in the formation of MC. Future studies focusing on the etiology of MC should pay more attention to patients' vascular status and determinants of abdominal aorta calcification.

Quantitative computed tomography analysis of body composition changes in paediatric patients with acute lymphoblastic leukaemia.

Children with acute lymphoblastic leukaemia (ALL) are at risk for obesity and cardiometabolic diseases. To gain insight into body composition changes among children with ALL, we assessed quantitative computed tomography (QCT) data for specific body compartments (subcutaneous adipose tissue [SAT], visceral adipose tissue [VAT], total adipose tissue [TAT], lean tissue [LT], LT/TAT and VAT/SAT at lumbar vertebrae L1 and L2) at diagnosis and at off-therapy for 189 children with ALL and evaluated associations between body mass index (BMI) Z-score and clinical characteristics. BMI Z-score correlated positively with SAT, VAT and TAT and negatively with LT/TAT and VAT/SAT. At off-therapy, BMI Z-score, SAT, VAT and TAT values were higher than at diagnosis, but LT, LT/TAT and VAT/SAT were lower. Patients aged ≥10 years at diagnosis had higher SAT, VAT and TAT and lower LT and LT/TAT than patients aged 2.0-9.9 years. Female patients had lower LT and LT/TAT than male patients. Black patients had less VAT than White patients. QCT analysis showed increases in adipose tissue and decreases in LT during ALL therapy when BMI Z-scores increased. Early dietary and physical therapy interventions should be considered, particularly for patients at risk for obesity.

Pneumococcal serotypes and risk factors in adult community-acquired pneumonia 2018-20; a multicentre UK cohort study.

Background: Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic. Methods: We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis. Findings: Of 1921 adults hospitalised with CAP, 781 (40.7%, 95% confidence intervals (CI) 38.5-42.9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31.0%, 95% CI 27.8-34.3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70.7%, 95% CI 64.5-76.0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2.8-5.6%), and PCV20-non13-serotypes in 192 (24.6%), with serotype 8 most prevalent (123/192, 64.1%, 95% CI 57.1-70.5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p < 0.001) and less likely to be male (44% versus 61%, p = 0.01). PPV23-non13-serotypes were found in 252 (32.3%, 95% CI 29.1-35.6%) pneumococcal CAP patients. Interpretation: Despite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors. Funding: Unrestricted investigator-initiated research grant from Pfizer, United Kingdom; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.

Transition From Pediatric to Adult Rheumatology Care: An Exploratory Study From Latin America.

BACKGROUND/PURPOSE: Adequate transition from pediatric to adult care is associated with better adherence to treatment and better outcomes in pediatric patients with chronic diseases. There are little data on transition programs, outcomes, use of transition guidelines, and available tools in pediatric rheumatology centers from Latin America (LATAM). In this study, we described the characteristics of transition programs from 3 pediatric rheumatology centers. We also introduced results of the first survey examining the transition experience in countries from LATAM. METHODS: The experience and implementation process of transition programs from 3 pediatric rheumatology centers were described. A survey based on a questionnaire created by Chira et al (J Rheumatol. 2014;41:768-779) from the Childhood Arthritis and Rheumatology Research Alliance was also administrated to pediatric rheumatology centers from LATAM. RESULTS: A total of 49 (68%) pediatric rheumatologists answered the survey. Most centers do not have an official and written transition program and reported a need for more tools and resources in their services to facilitate the transition experience. CONCLUSIONS: Transition guidelines culturally tailored to developing countries are needed in LATAM.

Application of short-wave pocket-sized near-infrared spectrophotometer to predict milk quality traits.

Portable-hand-held devices based on near-infrared (NIR) technology have improved and are gaining popularity, even if their implementation in milk has been barely evaluated. Thus, the aim of the present study was to assess short-wave pocket-sized NIR devices' feasibility to predict milk quality. A total of 331 individual milk samples from different cow breeds and herds were collected in 2 consecutive days for chemical determination and spectral collection by using 2 pocket-sized NIR spectrophotometers working in the range of 740-1070 nm. The reference data was matched with the corresponding spectrum and modified-partial least-squares regression models were developed. A 5-fold cross-validation was applied to evaluate individual devices' performance and an external-validation with 25% of the data set as the validation set was applied for the final models. Results revealed that both devices' absorbance was highly correlated but greater for instrument A than B. Thus, the final models were built by averaging the spectra from both devices for each sample. The fat content prediction model was adequate for quality control with a coefficient of determination (R2ExV) and a residual predictive deviation (RPDExV) in external validation of 0.93 and 3.73, respectively. Protein and casein content as well as fat-to-protein ratio prediction models might be used for a rough screening (R2ExV > 0.70; RPDExV > 1.73). However, poor prediction models were obtained for all the other traits with an R2ExV between 0.43 (urea) and 0.03 (somatic cell count), and a RPDExV between 1.18 (urea) and 0.22 (somatic cell count). In conclusion, short-wave portable-hand-held NIR devices accurately predicted milk fat content, and protein, casein, and fat-to-protein ratio might be applied for rough screening. It seems that there is not enough information in this NIR region to develop adequate prediction models for lactose, somatic cell count, urea, and freezing point.

Differential Proteins Expression Distinguished Between Patients With Infectious and Noninfectious Uveitis.

PURPOSE: We investigated the aqueous humor proteome and associated plasma proteome in patients with infectious or noninfectious uveitis. METHODS: AH and plasma were obtained from 28 patients with infectious uveitis (IU), 29 patients with noninfectious uveitis (NIU) and 35 healthy controls undergoing cataract surgery. The proteins profile was analyzed by SomaScan technology. RESULTS: We found 1844 and 2484 proteins up-regulated and 124 and 161 proteins down-regulated in the AH from IU and NIU groups, respectively. In the plasma, three proteins were up-regulated in NIU patients, and one and five proteins were down-regulated in the IU and NIU patients, respectively. The results of pathway enrichment analysis for both IU and NIU groups were related mostly to inflammatory and regulatory processes. CONCLUSION: SomaScan was able to detect novel AH and plasma protein biomarkers in IU and NIU patients. Also, the unique proteins found in both AH and plasma suggest a protein signature that could distinguish between infectious and noninfectious uveitis.

Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.