Conectar
by Gerik W. Tushoski-Alemán, Kelly M. Herremans, Patrick W. Underwood, Ashwin Akki, Andrea N. Riner, Jose G. Trevino, Song Han, Steven J. Hughes
BackgroundPancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.
MethodsTissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.
ResultsOur findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.
ConclusionIn this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.
by Maryam N. Chaudhary, Voon-Ching Lim, Erwin Martinez Faller, Pramod Regmi, Nirmal Aryal, Siti Nursheena Mohd Zain, Adzzie Shazleen Azman, Norhidayu Sahimin
BackgroundGlobally, 390 million dengue virus infections occur per year. In Malaysia, migrant workers are particularly vulnerable to dengue fever (DF) due to mosquito breeding sites exposure and poor health literacy. Therefore, this study aimed to (i) assess the current DF knowledge, attitudes and practices (KAP), and (ii) identify strategies to promote DF awareness, among migrant workers in Klang Valley.
MethodA survey was conducted with 403 Nepali, Filipino and Indonesian migrant workers through phone interviews and online self-administered questionnaires. Piecewise structural equation modelling was applied to identify predictor variables for DF KAP.
ResultsMost respondents were male, working in the services industry, had completed high school, aged between 30–39 years and with less than ten years work experience in Malaysia. Overall, respondents’ knowledge was positively correlated with attitude but negatively with practices. Older respondents, who had completed higher education, obtained higher knowledge scores. Similarly, those with working experience of >20 years in Malaysia obtained higher attitude scores. Respondents with a previous history of DF strongly considered the removal of mosquito breeding sites as their own responsibility, hence tended to frequently practise DF preventive measures. Respondents’ knowledge was also positively correlated to their understanding of DF information sourced from social media platforms.
ConclusionThese findings highlighted: (i) the need for targeted DF educational intervention among younger and newly arrived workers with lower levels of education and (ii) maximising the usage of social media platforms to improve DF public awareness.
by Hannah Oh, Brittany N. Morey, Yuxi Shi, Sunmin Lee
BackgroundStudies suggest that distress is associated with various health conditions such as hypertension, asthma, diabetes, and coronary heart disease. However, only few studies focused on Asian Americans and little is known about the association with multiple comorbidity.
MethodsWe conducted a cross-sectional analysis among 400 Chinese and Korean American participants (aged 50–75 years) of the STOP CRC randomized controlled trial. Perceived distress was assessed using the distress thermometer scale (range 0–10). Disease diagnosis was self-reported by the participants. Multimorbidity (MM) was defined as having ≥2 chronic conditions. Complex multimorbidity (CMM) was defined as having ≥3 of the following body system disorders: circulation disorder, endocrine-metabolic disorder, cancer, anxiety or depression, breathing problem, and other health problems. We performed logistic regression for CMM and Poisson regression with robust error variance for MM to estimate associations with distress, adjusting for potential confounders.
ResultsThe mean age was 58.4 years and mean distress score was 3.65. One-unit increase in distress score was associated with a 1.22-fold increase in the odds of having CMM (95% CI: 1.04–1.42). The magnitude of association slightly increased after additional adjustment for socioeconomic factors and health insurance status (OR: 1.29; 95% CI: 1.10–1.52). Higher distress score was positively associated with MM but the association was only marginally significant (PR: 1.04; 95% CI: 0.99–1.10), adjusting for socioeconomic factors and health insurance status.
ConclusionOur data suggest that higher perceived distress may be associated with simultaneous dysfunction of multiple distinct body systems among Chinese and Korean American older adults.
by Karim S. Ladha, Jiwon Lee, Gabriella F. Mattina, Janneth Pazmino-Canizares, Duminda N. Wijeysundera, Fatemeh Gholamali Nezhad, Kaylyssa Philip, Vanessa K. Tassone, Fathima Adamsahib, Venkat Bhat, on behalf of the SMILE Study Investigators
BackgroundNitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.
MethodsIn this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score Discussion
This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression.
Trial registrationClinicalTrials.gov NCT04957368. Registered on July 12, 2021.
by Jake V. Hinton, Calvin M. Fletcher, Luke A. Perry, Noah Greifer, Jessica N. Hinton, Jenni Williams-Spence, Reny Segal, Julian A. Smith, Christopher M. Reid, Laurence Weinberg, Rinaldo Bellomo
BackgroundPlatelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown.
MethodsWe conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005–2021 across 58 sites were included. The primary outcome was operative mortality.
ResultsOf 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P Conclusion
In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting.
by Magdi E. A. Zaki, Sami A. AL-Hussain, Aamal A. Al-Mutairi, Abdul Samad, Vijay H. Masand, Rahul G. Ingle, Vivek Digamber Rathod, Nikita Maruti Gaikwad, Summya Rashid, Pravin N. Khatale, Pramod V. Burakale, Rahul D. Jawarkar
Several studies have revealed that SARS-CoV-2 damages brain function and produces significant neurological disability. The SARS-CoV-2 coronavirus, which causes COVID-19, may infect the heart, kidneys, and brain. Recent research suggests that monoamine oxidase B (MAO-B) may be involved in metabolomics variations in delirium-prone individuals and severe SARS-CoV-2 infection. In light of this situation, we have employed a variety of computational to develop suitable QSAR model using PyDescriptor and genetic algorithm-multilinear regression (GA-MLR) models (R2 = 0.800–793, Q2LOO = 0.734–0.727, and so on) on the data set of 106 molecules whose anti-SARS-CoV-2 activity was empirically determined. QSAR models generated follow OECD standards and are predictive. QSAR model descriptors were also observed in x-ray-resolved structures. After developing a QSAR model, we did a QSAR-based virtual screening on an in-house database of 200 compounds and found a potential hit molecule. The new hit’s docking score (-8.208 kcal/mol) and PIC50 (7.85 M) demonstrated a significant affinity for SARS-CoV-2’s main protease. Based on post-covid neurodegenerative episodes in Alzheimer’s and Parkinson’s-like disorders and MAO-B’s role in neurodegeneration, the initially disclosed hit for the SARS-CoV-2 main protease was repurposed against the MAO-B receptor using receptor-based molecular docking, which yielded a docking score of -12.0 kcal/mol. This shows that the compound that inhibits SARS-CoV-2’s primary protease may bind allosterically to the MAO-B receptor. We then did molecular dynamic simulations and MMGBSA tests to confirm molecular docking analyses and quantify binding free energy. The drug-receptor complex was stable during the 150-ns MD simulation. The first computational effort to show in-silico inhibition of SARS-CoV-2 Mpro and allosteric interaction of novel inhibitors with MAO-B in post-covid neurodegenerative symptoms and other disorders. The current study seeks a novel compound that inhibits SAR’s COV-2 Mpro and perhaps binds MAO-B allosterically. Thus, this study will enable scientists design a new SARS-CoV-2 Mpro that inhibits the MAO-B receptor to treat post-covid neurological illness.by Ranya F. Elemam, Jamal M. El Swiah, Abduallah O. Durda, Nagwa N. Hegazy
During the COVID-19 pandemic, many educational institutions switched to e-learning educational platforms. This approach was essential but raised challenges, particularly in training practitioners for medical emergencies. This approach not only led to global challenges and a need for rapid adaptation, but also raised inequities across countries, with some facing far more technical challenges than others. In Libya, low investment in education technology and unpredictable internet connectivity limited its integration into schools and universities even before the pandemic. The current study reports feedback from an online continuing dental education (CDE) course for dental practitioners that was developed emergently during the pandemic and aimed to address the challenges posed by Libya’s internet environment. Participants were recruited through social media and received an 8-hour online CDE course consisting of three modules. Participants were invited to complete a pre-course demographic/informational survey on a Google form. After passing all modules, students were prompted to complete a post-course survey consisting of 23, five-point Likert scale questions. Respondents included 43 females (74.1%) and 15 males (25.9%). For ~50% of the cohort (n = 32), this was their first online clinical course. 87.9% of post-course participants rated the course as a positive learning experience, while 90.9% agreed their learning outcomes had been achieved. Most participants (97%) agreed the course instructor explained all concepts clearly. In total, 81.8% agreed that the technology effectively supported their learning. Most agreed that a clear demarcation between each course module existed and that the language and depth of the material were adequate. Some students reported technical difficulties, and 33.3% saw repetitions in the modules. However, all post-course respondents said they would recommend the online course to colleagues. Libyan dental practitioners showed high satisfaction levels towards the e-learning process, course content, instructors’ attitudes, and overall e-learning experience despite the inherent e-learning challenges posed in this country.by Alex Buga, David G. Harper, Teryn N. Sapper, Parker N. Hyde, Brandon Fell, Ryan Dickerson, Justen T. Stoner, Madison L. Kackley, Christopher D. Crabtree, Drew D. Decker, Bradley T. Robinson, Gerald Krystal, Katherine Binzel, Maryam B. Lustberg, Jeff S. Volek
PurposeKetogenic diets may positively influence cancer through pleiotropic mechanisms, but only a few small and short-term studies have addressed feasibility and efficacy in cancer patients. The primary goals of this study were to evaluate the feasibility and the sustained metabolic effects of a personalized well-formulated ketogenic diet (WFKD) designed to achieve consistent blood beta-hydroxybutyrate (βHB) >0.5 mM in women diagnosed with stage IV metastatic breast cancer (MBC) undergoing chemotherapy.
MethodsWomen (n = 20) were enrolled in a six month, two-phase, single-arm WFKD intervention (NCT03535701). Phase I was a highly-supervised, ad libitum, personalized WFKD, where women were provided with ketogenic-appropriate food daily for three months. Phase II transitioned women to a self-administered WFKD with ongoing coaching for an additional three months. Fasting capillary βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three and six months.
ResultsCapillary βHB indicated women achieved nutritional ketosis (Phase I mean: 0.8 mM (n = 15); Phase II mean: 0.7 mM (n = 9)). Body weight decreased 10% after three months, primarily from body fat. Fasting plasma glucose, plasma insulin, and insulin resistance also decreased significantly after three months (p Conclusions
Women diagnosed with MBC undergoing chemotherapy can safely achieve and maintain nutritional ketosis, while improving body composition and insulin resistance, out to six months.
by Nandana D. Rao, Rozenn N. Lemaitre, Colleen M. Sitlani, Jason G. Umans, Karin Haack, Veronica Handeland, Ana Navas-Acien, Shelley A. Cole, Lyle G. Best, Amanda M. Fretts
ObjectivesTo examine the associations of dietary Mg intake with inflammatory biomarkers (C-reactive protein (CRP) and interleukin 6 (IL-6)), and the interaction of dietary Mg intake with single nucleotide polymorphism (SNP) rs3740393, a SNP related to Mg metabolism and transport, on CRP and IL-6 among American Indians (AIs).
MethodsThis cross-sectional study included AI participants (n = 1,924) from the Strong Heart Family Study (SHFS). Mg intake from foods and dietary supplements was ascertained using a 119-item Block food frequency questionnaire, CRP and IL-6 were measured from blood, and SNP rs3740393 was genotyped using MetaboChip. Generalized estimating equations were used to examine associations of Mg intake, and the interaction between rs3740393 and dietary Mg, with CRP and IL-6.
ResultsReported Mg intake was not associated with CRP or IL-6, irrespective of genotype. A significant interaction (p-interaction = 0.018) was observed between Mg intake and rs3740393 on IL-6. Among participants with the C/C genotype, for every 1 SD higher in log-Mg, log-IL-6 was 0.04 (95% CI: -0.10 to 0.17) pg/mL higher. Among participants with the C/G genotype, for every 1 SD higher in log-Mg, log-IL-6 was 0.08 (95% CI: -0.21 to 0.05) pg/mL lower, and among participants with the G/G genotype, for every 1 SD higher in log-Mg, log-IL-6 was 0.19 (95% CI: -0.38 to -0.01) pg/mL lower.
ConclusionsMg intake may be associated with lower IL-6 with increasing dosage of the G allele at rs3740393. Future research is necessary to replicate this finding and examine other Mg-related genes that influence associations of Mg intake with inflammation.
by Yingzhou Liu, Menggang Yu, Jamie N. LaMantia, Jennifer Mason Lobo, Justin J. Boutilier, Yao Liu, Meghan B. Brennan
ObjectiveSpecialty care may improve diabetic foot ulcer outcomes. Medically underserved populations receive less specialty care. We aimed to determine the association between specialty care and ulcer progression, major amputation, or death. If a beneficial association is found, increasing access to specialty care might help advance health equity.
Research design and methodsWe retrospectively analyzed a cohort of Wisconsin and Illinois Medicare patients with diabetic foot ulcers (n = 55,409), stratified by ulcer severity (i.e., early stage, osteomyelitis, or gangrene). Within each stratum, we constructed Kaplan-Meier curves for event-free survival, defining events as: ulcer progression, major amputation, or death. Patients were grouped based on whether they received specialty care from at least one of six disciplines: endocrinology, infectious disease, orthopedic surgery, plastic surgery, podiatry, and vascular surgery. Multivariate Cox proportional hazard models estimated the association between specialty care and event-free survival, adjusting for sociodemographic factors and comorbidities, and stratifying on ulcer severity.
ResultsPatients who received specialty care had longer event-free survival compared to those who did not (log-rank p Conclusions
Specialty care was associated with longer event-free survivals for patients with diabetic foot ulcers. Increased, equitable access to specialty care might improve diabetic foot ulcer outcomes and disparities.
by Zaina A. Zayyad, John H. R. Maunsell, Jason N. MacLean
When multiple stimuli appear together in the receptive field of a visual cortical neuron, the response is typically close to the average of that neuron’s response to each individual stimulus. The departure from a linear sum of each individual response is referred to as normalization. In mammals, normalization has been best characterized in the visual cortex of macaques and cats. Here we study visually evoked normalization in the visual cortex of awake mice using imaging of calcium indicators in large populations of layer 2/3 (L2/3) V1 excitatory neurons and electrophysiological recordings across layers in V1. Regardless of recording method, mouse visual cortical neurons exhibit normalization to varying degrees. The distributions of normalization strength are similar to those described in cats and macaques, albeit slightly weaker on average.by Pedro A. R. Vanzele, Luiz Gustavo Sparvoli, Patricia P. de Camargo, Carla R. Tragante, Glenda P. N. S. Beozzo, Vera L. J. Krebs, Ramon V. Cortez, Carla R. Taddei
Very low birth weight (VLBW) infants, mostly preterm, have many barriers to feeding directly from the mother’s breast, and need to be fed alternatively. Feeding is a major influencer in oral microbial colonization, and this colonization in early life is crucial for the promotion of human health. Therefore, this research aimed to observe the establishment of oral microbiome in VLBW infants during their first month of life through hospitalization, and to verify the impact caused by the implementation of oral diet on the colonization of these newborns. We included 23 newborns followed during hospitalization and analyzed saliva samples collected weekly, using 16S rRNA gene sequencing. We observed a significant decrease in richness and diversity and an increase in dominance over time (q-value Streptococcus. Our results indicate that although time is related to significant changes in the oral microbial profile, oral feeding benefits genera that will remain colonizers throughout the host’s life.by Nelio N. Veiga-Junior, Caroline Eugeni, Beatriz D. Kajiura, Priscilla B. F. Dantas, Caroline B. Trabach, Aline A. Junqueira, Carina C. Nunes, Luiz F. Baccaro
BackgroundManagement of uterine evacuation is essential for increasing safe abortion care. Monitoring through surveillance systems tracks changes in clinical practice and provides information to improve equity in abortion care quality.
ObjectiveThis study aimed to evaluate the frequency of manual vacuum aspiration (MVA) and medical abortion (MA), and identify the factors associated with each uterine evacuation method after surveillance network installation at a Brazilian hospital.
MethodsThis cross-sectional study included women admitted for abortion or miscarriage to the University of Campinas Women’s Hospital, Brazil, between July 2017 and November 2020. The dependent variables were the use of MVA and MA with misoprostol. The independent variables were the patients’ clinical and sociodemographic data. The Cochran–Armitage, chi-square, and Mann–Whitney U tests, as well as multiple logistic regression analysis, were used to compare uterine evacuation methods.
ResultsWe enrolled 474 women in the study, 91.35% of whom underwent uterine evacuation via uterine curettage (78.75%), MVA (9.46%), or MA (11.54%). MVA use increased during the study period (Z = 9.85, p Conclusion
MVA use increased following the installation of a surveillance network for good clinical practice. Being part of a network that encourages the use of evidence-based methods provides an opportunity for healthcare facilities to increase access to safe abortions.
by Evan R. Polzer, Ryan Holliday, Carly M. Rohs, Suzanne M. Thomas, Christin N. Miller, Joseph A. Simonetti, Lisa A. Brenner, Lindsey L. Monteith
AimsFirearms have become an increasingly common method of suicide among women Veterans, yet this population has rarely been a focus in firearm suicide prevention research. Limited knowledge is available regarding the preferences, experiences, or needs of women Veterans with respect to firearm lethal means counseling (LMC), an evidence-based suicide prevention strategy. Understanding is necessary to optimize delivery for this population.
MethodOur sample included forty women Veterans with lifetime suicidal ideation or suicide attempt(s) and firearm access following military separation, all enrolled in the Veterans Health Administration. Participants were interviewed regarding their perspectives, experiences, and preferences for firearm LMC. Data were analyzed using a mixed inductive-deductive thematic analysis.
ResultsWomen Veterans’ firearm and firearm LMC perspectives were shaped by their military service histories and identity, military sexual trauma, spouses/partners, children, rurality, and experiences with suicidal ideation and attempts. Half reported they had not engaged in firearm LMC previously. For those who had, positive aspects included a trusting, caring relationship, direct communication of rationale for questions, and discussion of exceptions to confidentiality. Negative aspects included conversations that felt impersonal, not sufficiently comprehensive, and Veterans’ fears regarding implications of disclosure, which impeded conversations. Women Veterans’ preferences for future firearm LMC encompassed providers communicating why such conversations are important, how they should be framed (e.g., around safety and genuine concern), what they should entail (e.g., discussing concerns regarding disclosure), whom should initiate (e.g., trusted caring provider) and where they should occur (e.g., safe spaces, women-specific groups comprised of peers).
DiscussionThis study is the first to examine women Veterans’ experiences with, and preferences for, firearm LMC. Detailed inquiry of the nuances of how, where, why, and by whom firearms are stored and used may help to facilitate firearm LMC with women Veterans.
by Joseph B. Kahan, Patrick Burroughs, Logan Petit, Christopher A. Schneble, Peter Joo, Jay Moran, Maxwell Modrak, William Mclaughlin, Adam Nasreddine, Jonathan N. Grauer, Michael J. Medvecky
ObjectivesThe purpose of this study was to compare the rates of secondary knee surgery for patients undergoing meniscus repair with or without concurrent anterior cruciate ligament reconstruction (ACLr).
MethodsUtilizing a large national database, patients with meniscal repair with or without concurrent arthroscopic ACLr were identified. The two cohorts were then queried for secondary surgical procedures of the knee within the following 2 years. Frequency, age distribution, rates of secondary surgery, and type of secondary procedures performed were compared.
ResultsIn total, 1,585 patients were identified: meniscus repair with ACLr was performed for 1,006 (63.5%) and isolated meniscal repair was performed for 579 (36.5%). Minimum of two year follow up was present for 487 (30.7% of the overall study population).Secondary surgery rates were not significantly different between meniscus repair with concurrent ACLr and isolated meniscus repairs with an overall mean follow up of 13 years (1.5–24 years) (10.6% vs. 13.6%, p = 0.126). For the 2 year follow up cohort, secondary surgery rates were not significantly different (19.3% vs. 25.6%, p = 0.1098). There were no differences in survivorship patterns between the two procedures, both in the larger cohort (p = 0.2016), and the cohort with minimum 2-year follow-up (p = 0.0586).
ConclusionThe current study assessed secondary surgery rates in patients undergoing meniscus repair with or without concurrent ACLr in a large patient database. Based on this data, no significant difference in rates of secondary knee surgery was identified.
by Matthias Bosman, Dustin N. Krüger, Kasper Favere, Guido R. Y. De Meyer, Constantijn Franssen, Emeline M. Van Craenenbroeck, Pieter-Jan Guns
Apart from cardiotoxicity, the chemotherapeutic agent doxorubicin (DOX) provokes acute and long-term vascular toxicity. Dexrazoxane (DEXRA) is an effective drug for treatment of DOX-induced cardiotoxicity, yet it remains currently unknown whether DEXRA prevents vascular toxicity associated with DOX. Accordingly, the present study aimed to evaluate the protective potential of DEXRA against DOX-related vascular toxicity in a previously-established in vivo and ex vivo model of vascular dysfunction induced by 16 hour (h) DOX exposure. Vascular function was evaluated in the thoracic aorta in organ baths, 16h after administration of DOX (4 mg/kg) or DOX with DEXRA (40 mg/kg) to male C57BL6/J mice. In parallel, vascular reactivity was evaluated after ex vivo incubation (16h) of murine aortic segments with DOX (1 μM) or DOX with DEXRA (10 μM). In both in vivo and ex vivo experiments, DOX impaired acetylcholine-stimulated endothelium-dependent vasodilation. In the ex vivo setting, DOX additionally attenuated phenylephrine-elicited vascular smooth muscle cell (VSMC) contraction. Importantly, DEXRA failed to prevent DOX-induced endothelial dysfunction and hypocontraction. Furthermore, RT-qPCR and Western blotting showed that DOX decreased the protein levels of topoisomerase-IIβ (TOP-IIβ), a key target of DEXRA, in the heart, but not in the aorta. Additionally, the effect of N-acetylcysteine (NAC, 10 μM), a reactive oxygen species (ROS) scavenger, was evaluated ex vivo. NAC did not prevent DOX-induced impairment of acetylcholine-stimulated vasodilation. In conclusion, our results show that DEXRA fails to prevent vascular toxicity resulting from 16h DOX treatment. This may relate to DOX provoking vascular toxicity in a ROS- and TOP-IIβ-independent way, at least in the evaluated acute setting. However, it is important to mention that these findings only apply to the acute (16h) treatment period, and further research is warranted to delineate the therapeutic potential of DEXRA against vascular toxicity associated with longer-term repetitive DOX dosing.by Samina Ali, Claudia Maki, Asa Rahimi, Keon Ma, Maryna Yaskina, Helen Wong, Antonia Stang, Tania Principi, Naveen Poonai, Serge Gouin, Sylvia Froese R. N., Paul Clerc, Redjana Carciumaru, Waleed Alqurashi, Manasi Rajagopal, Elise Kammerer, Julie Leung, Bruce Wright, Shannon D. Scott, on behalf of the Pediatric Emergency Research Canada Family Needs Study Group
ObjectivesTo describe the extent to which caregivers’ emotional and communication needs were met during pediatric emergency department (PED) visits. Secondary objectives included describing the association of caregiver emotional needs, satisfaction with care, and comfort in caring for their child’s illness at the time of discharge with demographic characteristics, caregiver experiences, and ED visit details.
Study designElectronic surveys with medical record review were deployed at ten Canadian PEDs from October 2018 –March 2020. A convenience sample of families with children Results
This study recruited 2005 caregivers who self-identified as mothers (74.3%, 1462/1969); mean age was 37.8 years (SD 7.7). 71.7% (1081/1507) of caregivers felt their emotional needs were met. 86.4% (1293/1496) identified communication with the doctor as good/very good and 83.4% (1249/1498) with their child’s nurse. Caregiver involvement in their child’s care was reported as good/very good 85.6% (1271/1485) of the time. 81.8% (1074/1313) of caregivers felt comfortable in caring for their child at home at the time of discharge. Lower caregiver anxiety scores, caregiver involvement in their child’s care, satisfactory updates, and having questions adequately addressed positively impacted caregiver emotional needs and increased caregiver comfort in caring for their child’s illness at home.
ConclusionApproximately 30% of caregivers presenting to PEDs have unmet emotional needs, over 15% had unmet communication needs, and 15% felt inadequately involved in their child’s care. Family caregiver involvement in care and good communication from PED staff are key elements in improving overall patient experience and satisfaction.
by Kelsey McOwat, Snehal M. Pinto Pereira, Manjula D. Nugawela, Shamez N. Ladhani, Fiona Newlands, Terence Stephenson, Ruth Simmons, Malcolm G. Semple, Terry Segal, Marta Buszewicz, Isobel Heyman, Trudie Chalder, Tamsin Ford, Emma Dalrymple, Consortium , Roz Shafran
BackgroundDuring the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness.
Methods and findingsParticipants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness “Often/Always” and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28–3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3–4 siblings and lived in more deprived areas.
ConclusionsWe demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time.
by Rita L. Grunberg, Fletcher W. Halliday, Robert W. Heckman, Brooklynn N. Joyner, Kayleigh R. O’Keeffe, Charles E. Mitchell
Disease may drive variation in host community structure by modifying the interplay of deterministic and stochastic processes that shape communities. For instance, deterministic processes like ecological selection can benefit species less impacted by disease. When communities have higher levels of disease and disease consistently selects for certain host species, this can reduce variation in host community composition. On the other hand, when host communities are less impacted by disease and selection is weaker, stochastic processes (e.g., drift, dispersal) may play a bigger role in host community structure, which can increase variation among communities. While effects of disease on host community structure have been quantified in field experiments, few have addressed the role of disease in modulating variation in structure among host communities. To address this, we conducted a field experiment spanning three years, using a tractable system: foliar fungal pathogens in an old-field grassland community dominated by the grass Lolium arundinaceum, tall fescue. We reduced foliar fungal disease burden in replicate host communities (experimental plots in intact vegetation) in three fungicide regimens that varied in the seasonal duration of fungicide treatment and included a fungicide-free control. We measured host diversity, biomass, and variation in community structure among replicate communities. Disease reduction generally decreased plant richness and increased aboveground biomass relative to communities experiencing ambient levels of disease. These changes in richness and aboveground biomass were consistent across years despite changes in structure of the plant communities over the experiment’s three years. Importantly, disease reduction amplified host community variation, suggesting that disease diminished the degree to which host communities were structured by stochastic processes. These results of experimental disease reduction both highlight the potential importance of stochastic processes in plant communities and reveal the potential for disease to regulate variation in host community structure.
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