Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres.

Dynamic interaction between BRCA2 and telomeric G-quadruplexes (G4) is crucial for maintaining telomere replication homeostasis. Cells lacking BRCA2 display telomeric damage with a subset of these cells bypassing senescence to initiate break-induced replication (BIR) for telomere synthesis. Here we show that the abnormal stabilization of telomeric G4 following BRCA2 depletion leads to telomeric repeat-containing RNA (TERRA)-R-loop accumulation, triggering liquid-liquid phase separation (LLPS) and the assembly of Alternative Lengthening of Telomeres (ALT)-associated promyelocytic leukemia (PML) bodies (APBs). Disruption of R-loops abolishes LLPS and impairs telomere synthesis. Artificial engineering of telomeric LLPS restores telomere synthesis, underscoring the critical role of LLPS in ALT. TERRA-R-loops also recruit Polycomb Repressive Complex 2 (PRC2), leading to tri-methylation of Lys27 on histone H3 (H3K27me3) at telomeres. Half of paraffin-embedded tissue sections from human breast cancers exhibit APBs and telomere length heterogeneity, suggesting that BRCA2 mutations can predispose individuals to ALT-type tumorigenesis. Overall, BRCA2 abrogation disrupts the dynamicity of telomeric G4, producing TERRA-R-loops, finally leading to the assembly of telomeric liquid condensates crucial for ALT. We propose that modulating the dynamicity of telomeric G4 and targeting TERRA-R-loops in telomeric LLPS maintenance may represent effective therapeutic strategies for treating ALT-like cancers with APBs, including those with BRCA2 disruptions.

COVID-19 vaccination safety and associated health care utilization among adults with inflammatory bowel disease - a population-based self-controlled case series analysis.

BACKGROUND AND AIMS: There is an incomplete understanding of the full safety profiles of repeated COVID-19 vaccinations in patients with inflammatory bowel disease (IBD). Among individuals with IBD, we assessed whether COVID-19 vaccines were associated with serious adverse events of special interest (AESI) and health care utilization [all-cause hospitalizations, Emergency Department (ED) visits, gastroenterology visits, IBD-related visits]. METHODS: Using comprehensive administrative health data from Ontario, Canada, adults with IBD who received at least one COVID-19 vaccine from December 2020-January 2022 were included. Self-controlled case series analyses were conducted to evaluate the relative incidence rates of AESI and health care utilization outcomes across post-vaccination risk and control periods. RESULTS: Among 88,407 IBD patients, 99.7% received mRNA vaccines and 75.9% received ≥ 3 doses. Relative to control periods, we did not detect an increase in AESI. IBD patients had fewer all-cause hospitalizations during post-vaccination risk periods. Patients experienced more all-cause ED visits after dose 2 [Relative Incidence (RI):1.08(95%CI:1.04-1.12)] but fewer visits after doses 3 [RI:0.85 (95%CI:0.81-0.90)] and 4 [RI:0.73 (95%CI:0.57-0.92)]. There was no increase in gastroenterologist visits or IBD-related health care utilization post-vaccination. There were fewer IBD-related hospitalizations after dose 1 [RI:0.84 (95%CI:0.72-0.98)] and 3 [RI:0.63 (95%CI:0.52-0.76)], fewer IBD-related ED visits after dose 3 [RI:0.81 (95%CI:0.71-0.91)] and 4 [RI:0.55 (95%CI:0.32-0.96)], and fewer outpatient visits after dose 2 [RI:0.91 (95%CI:0.90-0.93)] and 3 [RI:0.87 (95%CI:0.86-0.89)]. CONCLUSION: This population-based study did not detect increased AESI, all-cause or IBD-related health care utilization following COVID-19 vaccination, suggesting a lack of association between vaccination and increased disease activity.

Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.

Addressing Suicide Risk Among Immigrant Women Survivors of Intimate Partner Violence.

Intimate partner violence (IPV) is a significant public health problem contributing to multiple morbidities. Immigrant women who experience IPV may be disproportionately vulnerable to poor mental health outcomes, including self-harm and suicidal ideation, due to cultural experiences and contextual factors that prevent them from accessing services. While existing studies identify the risks for suicidal ideation amongst survivors of IPV, there is limited knowledge on how to tailor strategies to support immigrant women survivors of IPV who experience suicidal ideation. This study was conducted as part of the formative phase of a longitudinal research project designed to develop and evaluate a safety planning intervention for immigrant women survivors of IPV. Using qualitative in-depth interviews, we explored the perspectives of immigrant women survivors of IPV (n = 46) from various countries of origin, ages, and educational backgrounds on effective strategies for supporting immigrant women who disclose suicidal ideation. Study participants discussed various strategies for supporting survivors including building trust, providing encouragement, strengthening social support networks, and reminding survivors of parental responsibilities. Participants also pointed to the importance of the following services: domestic violence support, faith-based health resources, supportive immigration programs, mental health support, and emergency and medical treatment. These findings are informative for researchers and practitioners who work with immigrant women survivors of IPV, and they can be used to develop appropriate safety protocols and support strategies for survivors who are experiencing or have previously experienced suicidal ideation to mitigate the risk of self-harm.

Alternative paths to telomere elongation.

Overcoming cellular senescence that is induced by telomere shortening is critical in tumorigenesis. A majority of cancers achieve telomere maintenance through telomerase expression. However, a subset of cancers takes an alternate route for elongating telomeres: recombination-based alternative lengthening of telomeres (ALT). Current evidence suggests that break-induced replication (BIR), independent of RAD51, underlies ALT telomere synthesis. However, RAD51-dependent homologous recombination is required for homology search and inter-chromosomal telomere recombination in human ALT cancer cell maintenance. Accumulating evidence suggests that the breakdown of stalled replication forks, the replication stress, induces BIR at telomeres. Nevertheless, ALT research is still in its early stage and a comprehensive view is still unclear. Here, we review the current findings regarding the genesis of ALT, how this recombinant pathway is chosen, the epigenetic regulation of telomeres in ALT, and perspectives for clinical applications with the hope that this overview will generate new questions.

A decade of progress in juvenile idiopathic athritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

OBJECTIVE: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing a 2005-2010 and a 2017-2021 inception cohorts. METHODS: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan Meier survival analysis and multivariable Cox regression. RESULTS: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for Inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for a good health-related quality of life. CONCLUSION: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient reported outcomes were smaller than improvements in disease activity.

Evaluating the time-varying risk of hypertension, cardiac events, and mortality following Kawasaki disease diagnosis.

BACKGROUND: This study evaluated the risk of hypertension, major adverse cardiac events (MACE), and all-cause mortality in Kawasaki disease (KD) patients up to young adulthood. METHODS: An inception cohort of 1169 KD patients between 1991 and 2008 from a tertiary-level hospital in Ontario, Canada was linked with health administrative data to ascertain outcomes up to 28 years of follow-up. Their risk was compared with 11,690 matched population comparators. The primary outcome was hypertension and secondary outcomes were MACE and death. RESULTS: After a median follow-up of 20 years [IQR: 8.3], the cumulative incidence of hypertension and MACE in the KD group was 3.8% (95% CI: 2.5-5.5) and 1.2% (95% CI: 0.6-2.4%), respectively. The overall survival probability in the KD group was 98.6% (95% CI: 97.2-99.3%). Relative to comparators, KD patients were at an increased risk for hypertension [aHR: 2.2 (95% CI: 1.5-3.4)], death [aHR: 2.5 (95% CI: 1.3-5.0)], and MACE [aHR: 10.7 (95% CI: 6.4-17.9)]. For hypertension and MACE, the aHR was the highest following diagnosis and then the excess risk diminished after 16 and 13 years of follow-up, respectively. MACE occurred largely in KD patients with coronary aneurysms [cumulative incidence: 12.8%]. CONCLUSIONS: KD patients demonstrated a reassuring cardiac prognosis up to young adulthood with low events and excellent survival. KD patients were at increased risk for hypertension, but this excess risk occurred early and declined with time. IMPACT: With the current standard of care, KD patients demonstrated favorable cardiac prognosis, with low events of hypertension, MACE, and excellent survival. Hypertension and MACE risk appear to be highest around the time of KD diagnosis. MACE occurred primarily in KD patients with coronary aneurysms. Our findings are reassuring to KD patients, families, and their providers. Our study demonstrated an association between KD exposure and hypertension. This association is relatively novel. Previous studies have remained conflicting if KD contributes to long-term atherosclerotic risk.

Cross-sectional comparisons of dietary indexes underlying nutrition labels: nutri-score, Canadian 'high in' labels and Diabetes Canada Clinical Practices (DCCP).

PURPOSE: To assess the cross-sectional association between dietary indexes (DI) that underlie, respectively, the Nutri-score (NS), the proposed Canadian 'High In' Symbol (CHIL) and the Diabetes Canada Clinical Practice Guidelines (DCCP) with food consumption, nutrient intakes and metabolic markers. METHODS: 1836 adults (18-74 years) participating in the representative ESTEBAN study, conducted in mainland France in 2014-2016, were included in the analysis. Food consumption was assessed with three repeated 24 h dietary recalls. Anthropometric measurements and biomarkers of metabolic risk (cholesterol-total, LDL (Low Density Lipoprotein), HDL (High Density Lipoprotein)-triglycerides, glucose) were obtained through a clinical examination and fasting blood draw. The DI were assessed for their association with food consumption, dietary intakes and metabolic biomarkers as quintiles and continuous variables using multi-adjusted linear regression. Heathier diets were assigned to lower scores. RESULTS: Correlations between scores ranged from + 0.62 between CHIL-DI and NS-DI to + 0.75 between NS-DI and DCCP-DI. All DIs discriminated individuals according to the nutritional quality of their diets through food consumption and nutrient intakes (healthier diets were associated with lower intakes of energy, added sugars and saturated fat; and with higher intakes of fiber, vitamins and minerals). NS-DI was associated with blood glucose (adjusted mean in Q1 = 5 vs. Q5 = 5.46 mmol/dl, ptrend = 0.001) and DCCP-DI was associated with BMI (Q1 = 24.8 kg/m2 vs. Q5 = 25.8 kg/m2, ptrend = 0.025), while CHIL showed no significant association with any anthropometric measures or biomarkers. CONCLUSIONS: This study provides elements supporting the validity of the nutrient profiling systems underlying front-of-package nutrition labellings (FOPLs) to characterize the healthiness of diets.

Promoting community institutional partnerships to improve the health of intimate partner violence survivors experiencing homelessness.

BACKGROUND: Disparities faced by individuals experiencing homelessness pose significant threats to the health and wellbeing of communities. Survivors of intimate partner violence are at heightened risk, with over 80% experiencing homelessness at some point in time. The intersection of homelessness and survivorship creates numerous barriers to care including safety concerns, stable housing, employment and childcare needs. The establishment of community institutional partnerships offers an opportunity to provide healthcare in transitional housing settings. AIMS: The aim of this paper is to discuss the need for community institutional partnerships in addressing the health needs of intimate partner violence survivors and provide a working example of an existing partnership. METHODS: A critical literature review of the literature was conducted. Multiple databases were searched to identify articles relating to health services, community institutional partnerships, intimate partner violence and sheltered housing. Articles were reviewed using The Johns Hopkins Nursing Evidence-Based Practice Quality Guide. FINDINGS: Three types of partnerships that can be leveraged to address the needs of individuals experiencing homelessness were identified: academic-community, hospital-community, and large-scale partnerships. Only one article was identified that focused on the health needs of survivors experiencing homelessness, pointing to the need for implementation of more community institutional partnerships to address the unique needs of homeless intimate partner violence survivors. We highlighted a current successful community institutional partnership that addresses the health needs of survivors living in an emergency shelter. IMPLICATIONS: Addressing the complex needs of this population is imperative to dismantle health inequities and structural barriers to healthcare. Holistic, nurse-led approaches to care are essential to address the health of intimate partner violence survivors experiencing homelessness. The example of a successful community institutional partnership provides a framework for delivering a wide range of healthcare services. Future nursing research is needed to evaluate programmes and provide foundational support for increased funding.

Addressing health disparities of individuals experiencing homelessness in the U.S. with community institutional partnerships: An integrative review.

AIMS: To examine existing community-institutional partnerships providing health care services to people experiencing homelessness by addressing social determinants of health (SDOH) at multiple socioecological levels. DESIGN: Integrative review. DATA SOURCES: PubMed (Public/Publisher MEDLINE), CINAHL (The Cumulative Index of Nursing and Allied Health Literature database), and EMBASE (Excerpta Medica database) were searched to identify articles on health care services, partnerships, and transitional housing. REVIEW METHODS: Database search used the following keywords: Public-private sector partnerships, community-institutional relation, community-academic, academic community, community university, university community, housing, emergency shelter, homeless persons, shelter, and transitional housing. Articles published until November 2021 were eligible for inclusion. The Johns Hopkins Nursing Evidence-Based Practice Quality Guide was used to appraise the quality of articles included in the review by two researchers. RESULTS: Seventeen total articles were included in the review. The types of partnerships discussed in the articles included academic-community partnerships (n = 12) and hospital-community partnerships (n = 5). Health services were also provided by different kinds of health care providers, including nursing and medical students, nurses, physicians, social workers, psychiatrists, nutritionists, and pharmacists. Health care services spanning from preventative care services to acute and specialized care services and health education were also made possible through community-institutional partnerships. CONCLUSION: There is a need for more studies on partnerships that aim to improve the health of homeless populations by addressing social determinants of health at multiple socioecological levels of individuals who experience homelessness. Existing studies do not utilize elaborate evaluation methods to determine partnership efficacy. IMPACT: Findings from this review highlight gaps in the current understanding of partnerships that seek to increase access to care services for people who experience homelessness. NO PATIENT OR PUBLIC CONTRIBUTION: The results of the systematic review were solely from the articles reviewed and do not include information from patients, service users, caregivers, or members of the public.

Evaluating the potential implications of canadian front-of-pack labelling regulations in generic and branded food composition databases.

BACKGROUND: Canada proposed the implementation of mandatory front-of-pack (FOP) labelling regulations, whereby foods meeting or exceeding thresholds for nutrients-of-concern (i.e., total sugars, saturated fat, sodium) must display a 'high-in' FOP symbol (FOP). The objective of the study was to evaluate the potential implications of the proposed regulations using Canadian generic and branded food composition databases. METHODS: A generic food composition database of products consumed by Canadians, Canadian Nutrient File (CNF) 2015 (n = 3,677), and a branded food composition database of packaged foods and beverages, Food Label Information Program (FLIP) 2017 (n = 17,521), were used to evaluate the number and proportion of foods that would display a FOP symbol based on the details of the proposed FOP labelling regulations published in 2018. RESULTS: Overall, 35.5% (n = 1,306) of products in CNF 2015 and 63.9% (n = 11,193) of products in FLIP 2017 would display a FOP symbol for at least one nutrient-of-concern exceeding proposed thresholds. Soups, Combination Dishes, and Desserts categories in CNF 2015 and Combination dishes, Soups, and Meats categories in FLIP 2017 would have the highest proportion of products that would display a FOP symbol. Although displaying a FOP symbol for one nutrient was most common in both CNF 2015 (n = 992; 27.0%) and FLIP 2017 (n = 7,296, 41.6%), the number (i.e., 0-3) and type (i.e., saturated fat, sodium, total sugar) of nutrients displayed varied by food category. CONCLUSION: While the generic database, containing both packaged and unpackaged foods, revealed a low prevalence of foods that would display a FOP symbol, the branded database showed that the proposed FOP labelling regulations would identify over 60% of packaged foods with excess contents of nutrients-of-concern. Considering the high prevalence of packaged foods in Canada that would meet or exceed the thresholds of nutrients-of-concern, the proposed FOP labelling regulations should be implemented in a timely manner to help consumers easily identify foods high in nutrients-of-concern and encourage manufacturer-driven product reformulations.

Ultrasound Evaluation of Gastric Emptying Time in Healthy Term Neonates after Formula Feeding.

BACKGROUND: The current American Society of Anesthesiologists fasting guideline for formula-fed infants in the periprocedural setting is 6 h. Prolonged fasting in very young infants is associated with an increased risk for hypoglycemia and dehydration as well as patient discomfort and patient/parental dissatisfaction. This study aimed to determine the time to gastric emptying in healthy neonates after formula feeding by serially evaluating the gastric antrum with ultrasound. The authors hypothesized that gastric emptying times in formula-fed neonates are significantly shorter than the current 6 h fasting recommendation. METHODS: After institutional review board approval and written informed parental consent, ultrasound examination was performed in healthy full-term neonates before and after formula feeding at 15-min intervals until return to baseline. Ultrasound images of the gastric antrum were measured to obtain cross-sectional areas, which were then used to estimate gastric antral volumes. RESULTS: Forty-six of 48 recruited neonates were included in the final analysis. Gastric emptying times ranged from 45 to 150 min and averaged 92.9 min (95% CI, 80.2 to 105.7 min; 99% CI, 76.0 to 109.8 min) in the overall study group. No significant differences were found in times to gastric emptying between male and female neonates (male: mean, 93.3 [95% CI, 82.4 to 104.2 min]; female: mean, 92.6 [95% CI, 82.0 to 103.2 min]; P = 0.930) or those delivered by vaginal versus cesarean routes (vaginal: mean, 93.9 [95% CI, 81.7 to 106.1 min]; cesarean: mean, 92.2 [95% CI, 82.5 to 101.9 min]; P = 0.819). CONCLUSIONS: These results demonstrate that gastric emptying times are substantially less than the current fasting guideline of 6 h for formula-fed, healthy term neonates.

Executive functions in children with heart disease: a systematic review and meta-analysis.

CONTEXT: People with CHD are at increased risk for executive functioning deficits. Meta-analyses of these measures in CHD patients compared to healthy controls have not been reported. OBJECTIVE: To examine differences in executive functions in individuals with CHD compared to healthy controls. DATA SOURCES: We performed a systematic review of publications from 1 January, 1986 to 15 June, 2020 indexed in PubMed, CINAHL, EMBASE, PsycInfo, Web of Science, and the Cochrane Library. STUDY SELECTION: Inclusion criteria were (1) studies containing at least one executive function measure; (2) participants were over the age of three. DATA EXTRACTION: Data extraction and quality assessment were performed independently by two authors. We used a shifting unit-of-analysis approach and pooled data using a random effects model. RESULTS: The search yielded 61,217 results. Twenty-eight studies met criteria. A total of 7789 people with CHD were compared with 8187 healthy controls. We found the following standardised mean differences: -0.628 (-0.726, -0.531) for cognitive flexibility and set shifting, -0.469 (-0.606, -0.333) for inhibition, -0.369 (-0.466, -0.273) for working memory, -0.334 (-0.546, -0.121) for planning/problem solving, -0.361 (-0.576, -0.147) for summary measures, and -0.444 (-0.614, -0.274) for reporter-based measures (p < 0.001). LIMITATIONS: Our analysis consisted of cross-sectional and observational studies. We could not quantify the effect of collinearity. CONCLUSIONS: Individuals with CHD appear to have at least moderate deficits in executive functions. Given the growing population of people with CHD, more attention should be devoted to identifying executive dysfunction in this vulnerable group.

Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer.

RAS (rat sarcoma virus) mutant cancers remain difficult to treat despite the advances in targeted therapy and immunotherapy. Targeted therapies against the components of mitogen-activated protein kinase (MAPK) pathways, including RAS, RAF, MEK, and ERK, have demonstrated activity in BRAF mutant and, in limited cases, RAS mutant cancer. RAS mutant cancers have been found to activate adaptive resistance mechanisms such as autophagy during MAPK inhibition. Here, we review the recent clinically relevant advances in the development of the MAPK pathway and autophagy inhibitors and focus on their application to RAS mutant cancers. We provide analysis of the preclinical rationale for combining the MAPK pathway and autophagy and highlight the most recent clinical trials that have been launched to capitalize on this potentially synthetic lethal approach to cancer therapy.

Effects of White Potatoes Consumed With Eggs on Satiety, Food Intake, and Glycemic Response in Children and Adolescents.

Objective: Short-term studies in adults have shown that white potatoes increase satiety and suppress food intake (FI) compared with several other carbohydrate-containing foods; however, studies are limited in children. The objective was to compare the effects of white potatoes in mixed meals on satiety, FI, and glycemic response in 9-14-year-old children and adolescents.Methods: Using a within-subject, repeated-measures design, 21 children completed five counter-balanced test sessions. After an overnight fast, children consumed one of four isocaloric treatment meals (450 kcal) of French fries, mashed potatoes, or white beans served with a fixed portion of egg omelet (30 g of protein), a control meal with cereal, milk, and bread, or continued to fast (i.e., meal skipping). Subjective appetite was measured using visual analogue scales. FI at an ad libitum pizza meal at 180 min and rest of day diet record were used to measure lunch FI and rest of day energy intake, respectively. Total daily energy intake was calculated by adding the energy intake from the treatment meal, the ad libitum pizza lunch, and rest of day food record. Capillary blood samples were collected to assess glycemic response over 180 min.Results: Change from baseline subjective average appetite scores were lower after mashed potatoes compared with all other treatment conditions (p < 0.001), and higher after French fries compared with white beans (p = 0.04). Lunch FI (kcal) was significantly lower (p < 0.001) after French fries (1010±73) and mashed potatoes (1039±74) compared with the control meal (1257±92) and meal skipping (1235±74). Total daily energy intake (kcal) was lower after French fries compared with the control meal (2228±141 vs. 2624±137; p = 0.04). Change from baseline blood glucose was lower after white beans and French fries compared with mashed potatoes (p < 0.05) and the control meal (p < 0.001).Conclusion: In conclusion, white potatoes with eggs increased satiety, decreased short-term FI, and resulted in similar energy intakes compared with meal skipping.

Standards for preclinical research and publications in developmental anaesthetic neurotoxicity: expert opinion statement from the SmartTots preclinical working group.

In March 2019, SmartTots, a public-private partnership between the US Food and Drug Administration and the International Anesthesia Research Society, hosted a meeting attended by research experts, anaesthesia journal editors, and government agency representatives to discuss the continued need for rigorous preclinical research and the importance of establishing reporting standards for the field of anaesthetic perinatal neurotoxicity. This group affirmed the importance of preclinical research in the field, and welcomed novel and mechanistic approaches to answer some of the field's largest questions. The attendees concluded that summarising the benefits and disadvantages of specific model systems, and providing guidance for reporting results, would be helpful for designing new experiments and interpreting results across laboratories. This expert opinion report is a summary of these discussions, and includes a focused review of current animal models and reporting standards for the field of perinatal anaesthetic neurotoxicity. This will serve as a practical guide and road map for novel and rigorous experimental work.

Unconventional delivery of inhaled nitric oxide during endoscopic laryngeal tracheal reconstruction in a child with pulmonary arterial hypertension: A case report.

Endoscopic laryngeal tracheal reconstruction was performed on a child with glottic stenosis and pulmonary arterial hypertension. The surgical repair was performed while delivering inhaled nitric oxide via the ventilating port of a suspension laryngoscope with the patient maintaining spontaneous respirations. The surgery was accomplished without complications.

A hot spot for systemic lupus erythematosus, but not for psoriatic arthritis, identified by spatial analysis suggests an interaction between ethnicity and place of residence.

OBJECTIVE: To describe the spatial distribution of incident cases of systemic lupus erythematosus (SLE) using geographic information systems (GIS). METHODS: Spatial analyses were carried out on 890 SLE patients and 541 psoriatic arthritis (PsA) patients (controls). Age- and sex-adjusted rates for SLE/PsA for each census tract were calculated using denominator population values from the Canadian census. Spatial variations in relative risk were estimated by modeling risk as the product of a time effect, an age effect, and a spatially autocorrelated risk surface to identify hot spots. Patients within the detected hot spot were compared to those outside the hot spot to identify explanatory factors. RESULTS: SLE patients were predominantly female (87.75%) and the incidence rate was highest among those 15-19 years of age (2.4 cases/100,000 person-years). In an SLE hot spot containing 59 patients, 100% of the patients were female and 49.1% (n = 29) were Caucasian, while outside of the hot spot, 86.9% (n = 722) of the patients were female and 68.4% (n = 568) were Caucasian. The proportion of cases of Chinese ethnicity was significantly greater within the hot spot. An interaction was found between Chinese ethnicity and residence within the hot spot, with the risk of SLE to the Chinese population found to be twice the risk to the non-Chinese population. CONCLUSION: GIS was used to map SLE cases and a hot spot was identified after adjustment for age and sex. Ethnicity by itself did not confer an increased risk of SLE, but the interaction of ethnicity with location of residence significantly increased the risk of SLE.

Does obesity prolong anesthesia in children undergoing common ENT surgery?

OBJECTIVES: To report the epidemiology of obesity in a pediatric surgical population and determine whether obesity is a risk factor for longer anesthesia duration. BACKGROUND: Childhood obesity is a significant public health problem in the United States. Epidemiologic studies on pediatric surgical populations have been limited to states with very high prevalence of adult obesity (Michigan, Texas). Data from other states and more recent data since 2006 are unavailable. METHODS: We examined anesthesia records for surgical patients age 2-18 years at Columbia University Medical Center from January 2009 to December 2010. Patients undergoing bariatric surgery or those with records missing preoperative height or weight data were excluded. Body mass index (BMI) was calculated as weight (kg)/height (m(2) ). BMI ≥95th percentile according to national growth charts were considered obese. RESULTS: We reviewed 9522 patients of which 1639 were obese (17.2%). The sex-age category interaction on obesity was not significant using logistic regression (P = 0.11). Among surgical groups, the otolaryngology (ENT) cohort had the highest obesity rate (21.7%, 360/1656). Obese children who had tonsillectomy, adenoidectomy, or both did not have a prolonged anesthetic (P = 0.33) or surgical duration (P = 0.61) compared with nonobese children, adjusting for surgeon, season, surgical procedure code, and ASA status. CONCLUSION: Children presenting for surgery, particularly the ENT cohort, have a high prevalence of obesity. Obese and nonobese children who had tonsillectomy, adenoidectomy, or both had comparable durations of anesthesia. Therefore, obesity did not lead to longer anesthetic duration.

Rosacea in Older Adults and Pharmacologic Treatments.

Rosacea is a chronic inflammatory skin condition that is often more severe in older patients. The main clinical features are erythema, telangiectasia, and inflammatory lesions of the face. The pathogenesis of this condition is not fully understood but certainly multifaceted. Immune and inflammatory dysregulation, genetics, neurogenic dysregulation, microbiome dysbiosis, and systemic disease have all been implicated in rosacea pathogenesis. As we better understand the various pathways that lead to rosacea, we acknowledge that the different symptoms may have unique underlying triggers and mechanisms. Aging also impacts rosacea diagnosis and treatment. Older adults have more severe rosacea symptoms while also having more sensitive and fragile skin than younger patients; therefore, rosacea treatments for older patients require a balance between delivering adequate potency while also minimizing skin irritation and other adverse effects. Until recently, rosacea diagnoses were based on concrete subtypes that did not necessarily capture each patient's manifestation of rosacea. There is now an emphasis on more personalized phenotype-based diagnoses and treatments, which allows for more emphasis on treating individual symptoms and accounting for the unique characteristics of older patients. Centrofacial erythema is best treated with brimonidine and oxymetazoline, while phymatous change and telangiectasia are best treated with surgery and laser ablation. Treatment for rosacea papules and pustules ranges from topicals, such as azelaic acid, ivermectin, metronidazole, minocycline, and encapsulated benzoyl peroxide, to systemics, such as doxycycline and isotretinoin. It is important to understand these treatments in relation to adverse effects and drug interactions that may specifically arise in older populations to provide optimal care. As we advance in understanding rosacea's pathogenesis and adopt personalized phenotype-based approaches, optimizing care for older patients becomes crucial. Continued research into novel treatments is essential to address their unique needs.