Continuous chest compression during sustained inflation versus continuous compression with asynchronized ventilation in an infantile porcine model of severe bradycardia.

Background: Recently, the American Heart Association released a statement calling for research examining the appropriate age to transition from the neonatal to pediatric cardiopulmonary resuscitation approach to resuscitation. Aim: To compare neonatal and pediatric resuscitation approach by using either continuous chest compression with asynchronized ventilation (CCaV) or continuous chest compression superimposed with sustained inflation (CC + SI) during infant cardiopulmonary resuscitation. We hypothesized that CC + SI compared to CCaV would reduce time to return of spontaneous circulation (ROSC) in infantile piglets with asphyxia-induced bradycardic cardiac arrest. Methods: Twenty infantile piglets (5-10 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to CC + SI or CCaV for resuscitation (n = 10/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, intrathoracic pressure and respiratory parameters were continuously recorded throughout the experiment. Main results: The median (IQR) time to ROSC with CC + SI compared to CCaV was 179 (104-447) vs 660 (189-660), p = 0.05. The number of piglets achieving ROSC with CC + SI and CCaV were 8/10 and 6/10, p = 0.628. Piglets resuscitated with CC + SI required less epinephrine compared to CCaV (p = 0.039). CC + SI increased the intrathoracic pressure throughout resuscitation (p = 0.025) and increased minute ventilation (p < 0.001), compared to CCaV. There was no difference in hemodynamic parameters between groups. Conclusions: CC + SI improves resuscitative efforts of infantile piglets by increasing the intrathoracic pressure and minute ventilation, and thus reducing the duration of resuscitation, compared to CCaV.

Safety planning intervention and follow-up: A telehealth service model for suicidal individuals in emergency department settings: Study design and protocol.

BACKGROUND: The Safety Planning Intervention with follow-up services (SPI+) is a promising suicide prevention intervention, yet many Emergency Departments (EDs) lack the resources for adequate implementation. Comprehensive strategies addressing structural and organizational barriers are needed to optimize SPI+ implementation and scale-up. This protocol describes a test of one strategy in which ED staff connect at-risk patients to expert clinicians from a Suicide Prevention Consultation Center (SPCC) via telehealth. METHOD: This stepped wedge, cluster-randomized trial compares the effectiveness, implementation, cost, and cost offsets of SPI+ delivered by SPCC clinicians versus ED-based clinicians (enhanced usual care; EUC). Eight EDs will start with EUC and cross over to the SPCC phase. Blocks of two EDs will be randomly assigned to start dates 3 months apart. Approximately 13,320 adults discharged following a suicide-related ED visit will be included; EUC and SPCC samples will comprise patients from before and after SPCC crossover, respectively. Effectiveness data sources are electronic health records, administrative claims, and the National Death Index. Primary effectiveness outcomes are presence of suicidal behavior and number/type of mental healthcare visits and secondary outcomes include number/type of suicide-related acute services 6-months post-discharge. We will use the same data sources to assess cost offsets to gauge SPCC scalability and sustainability. We will examine preliminary implementation outcomes (reach, adoption, fidelity, acceptability, and feasibility) through patient, clinician, and health-system leader interviews and surveys. CONCLUSION: If the SPCC demonstrates clinical effectiveness and health system cost reduction, it may be a scalable model for evidence-based suicide prevention in the ED.

Cardiac Agents during Neonatal Cardiopulmonary Resuscitation.

BACKGROUND: Epinephrine (adrenaline) is currently the only cardiac agent recommended during neonatal resuscitation. The inability to predict which newborns are at risk of requiring resuscitative efforts at birth has prevented the collection of large, high-quality human data. SUMMARY: Information on the optimal dosage and route of epinephrine administration is extrapolated from neonatal animal studies and human adult and pediatric studies. Adult resuscitation guidelines have previously recommended vasopressin use; however, neonatal studies needed to create guidelines are lacking. A review of the literature demonstrates conflicting results regarding epinephrine efficacy through various routes of access as well as vasopressin during asystolic cardiac arrest in animal models. Vasopressin appears to improve hemodynamic and post-resuscitation outcomes compared to epinephrine in asystolic cardiac arrest animal models. KEY MESSAGES: The current neonatal resuscitation guidelines recommend epinephrine be primarily given via the intravenous or intraosseous route, with the endotracheal route as an alternative if these routes are not feasible or unsuccessful. The intravenous or intraosseous dose ranges between 0.01 and 0.03 mg/kg, which should be repeated every 3-5 min during chest compressions. However, the optimal dosing and route of administration of epinephrine remain unknown. There is evidence from adult and pediatric studies that vasopressin might be an alternative to epinephrine; however, the neonatal data are scarce.

Chest compressions superimposed with sustained inflations during cardiopulmonary resuscitation in asphyxiated pediatric piglets.

BACKGROUND: Pediatric resuscitation guidelines recommend continuous chest compression with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation. We recently described that providing a constant high distending pressure, or sustained inflation (SI) while performing continuous chest compressions (CC = CC + SI) reduces time to return of spontaneous circulation (ROSC) in neonatal and pediatric piglets with asphyxia-induced cardiac arrest. METHODS: To determine if CC + SI compared to CCaV will improve frequency of achieving ROSC and reduce time to ROSC in asphyxiated pediatric piglets. Twenty-eight pediatric piglets (21-24 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to CC + SI or CCaV for resuscitation (n = 14/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. RESULTS: The mean(SD) duration of resuscitation was significantly reduced with CC + SI compared to CCaV with 208(190) vs. 388(258)s, p = 0.045, respectively. The number of piglets achieving ROSC with CC + SI and CCaV were 12/14 vs. 6/14, p = 0.046. Minute ventilation, end-tidal carbon dioxide, ventilation rate, and positive end expiratory pressures were also significantly improved with CC + SI. CONCLUSIONS: CC + SI improves duration of resuscitation and increases number of piglets achieving ROSC secondary to improved minute ventilation. IMPACT: Chest compressions superimposed with sustained inflation resulted in shorter duration of resuscitation Chest compressions superimposed with sustained inflation resulted in higher number of piglets achieving return of spontaneous circulation Further animal studies are needed to examine chest compressions superimposed with sustained inflation.

Comparison of hemodynamic effects of chest compression delivered via machine or human in asphyxiated piglets.

BACKGROUND: High-quality chest compressions (CC) are an important factor of neonatal resuscitation. Mechanical CC devices may provide superior CC delivery and improve resuscitation outcomes. We aimed to compare the hemodynamic effects of CC delivered by machine and human using a neonatal piglet model. METHODS: Twelve asphyxiated piglets were randomized to receive CC during resuscitation using an automated mechanical CC device ("machine") or the two-thumb encircling technique ("human"). CC was superimposed with sustained inflations. RESULTS: Twelve newborn piglets (age 0-3 days, weight 2.12 ± 0.17 kg) were included in the study. Machine-delivered CC resulted in an increase in stroke volume, and minimum and maximum rate of left ventricle pressure change (dp/dtmin and dp/dtmax) compared to human-delivered CC. CONCLUSIONS: During machine-delivered CC, stroke volume and left ventricular contractility were significantly improved. Mechanical CC devices may provide improved cardiopulmonary resuscitation outcomes in neonatal cardiac arrest induced by asphyxia. IMPACT: Machine chest compression leads to changes in hemodynamic parameters during resuscitation of asphyxiated neonatal piglets, namely greater stroke volume and left ventricular contractility, compared with standard two-thumb compression technique. Mechanical chest compression devices may provide improved cardiopulmonary resuscitation outcomes in neonatal and pediatric asphyxia-induced cardiac arrest.

An exposure-based implementation strategy to decrease clinician anxiety about implementing suicide prevention evidence-based practices: protocol for development and pilot testing (Project CALMER).

BACKGROUND: Clinicians often report that their own anxiety and low self-efficacy inhibit their use of evidence-based suicide prevention practices, including gold-standard screening and brief interventions. Exposure therapy to reduce clinician maladaptive anxiety and bolster self-efficacy use is a compelling but untested approach to improving the implementation of suicide prevention evidence-based practices (EBPs). This project brings together an interdisciplinary team to leverage decades of research on behavior change from exposure theory to design and pilot test an exposure-based implementation strategy (EBIS) to target clinician anxiety to improve suicide prevention EBP implementation. METHODS: We will develop, iteratively refine, and pilot test an EBIS paired with implementation as usual (IAU; didactic training and consultation) in preparation for a larger study of the effect of this strategy on reducing clinician anxiety, improving self-efficacy, and increasing use of the Columbia Suicide Severity Rating Scale and the Safety Planning Intervention in outpatient mental health settings. Aim 1 of this study is to use participatory design methods to develop and refine the EBIS in collaboration with a stakeholder advisory board. Aim 2 is to iteratively refine the EBIS with up to 15 clinicians in a pilot field test using rapid cycle prototyping. Aim 3 is to test the refined EBIS in a pilot implementation trial. Forty community mental health clinicians will be randomized 1:1 to receive either IAU or IAU + EBIS for 12 weeks. Our primary outcomes are EBIS acceptability and feasibility, measured through questionnaires, interviews, and recruitment and retention statistics. Secondary outcomes are the engagement of target implementation mechanisms (clinician anxiety and self-efficacy related to implementation) and preliminary effectiveness of EBIS on implementation outcomes (adoption and fidelity) assessed via mixed methods (questionnaires, chart-stimulated recall, observer-coded role plays, and interviews). DISCUSSION: Outcomes from this study will yield insight into the feasibility and utility of directly targeting clinician anxiety and self-efficacy as mechanistic processes informing the implementation of suicide prevention EBPs. Results will inform a fully powered hybrid effectiveness-implementation trial to test EBIS' effect on implementation and patient outcomes. TRIAL REGISTRATION: Clinical Trials Registration Number: NCT05172609 . Registered on 12/29/2021.

Transition from stromatolite to thrombolite fabric: potential role for reticulopodial protists in lake microbialites of a Proterozoic ecosystem analog.

Prior observations suggest that foraminiferan protists use their reticulopodia (anastomosing pseudopodia) to alter sediment fabric by disrupting laminations of subtidal marine stromatolites, erasing the layered structures in an experimental setting. Because microbialites and foraminifera are found in non-marine settings, we hypothesized that foraminifera living in lakes could also disrupt layered microbialite fabric. With this aim and using a variety of multidisciplinary approaches, we conducted field surveys and an experiment on microbialites from Green Lake (GL; Fayetteville, New York State, United States), which has been studied as a Proterozoic ecosystem analog. The lake is meromictic and alkaline, receiving calcium sulfate-rich water in the monimolimnion; it supports a well-developed carbonate platform that provides access to living and relict microbialites. The living microbialites grow from early spring to autumn, forming a laminated mat at their surface (top ~5 mm), but a clotted or massive structure exists at depth (> ~ 1 cm). We observed a morphotype of "naked" foraminiferan-like protist in samples from GL microbialites and sediments; thus, considered the possibility of freshwater foraminiferan impact on microbialite fabric. Results of an experiment that seeded the cultured freshwater foraminifer Haplomyxa saranae onto the GL microbialite surface indicates via micro-CT scanning and anisotropy analysis that the introduced foraminifer impacted uppermost microbialite layering (n = 3 cores); those cores with an added inhibitor lacked changes in anisotropy for two of those three cores. Thus, it remains plausible that the much smaller, relatively common, native free-form reticulate protist, which we identified as Chlamydomyxa labyrinthuloides, can disrupt microbialite fabrics on sub-millimeter scales. Our observations do not exclude contributions of other possible causal factors.

Comparison of various vasopressin doses to epinephrine during cardiopulmonary resuscitation in asphyxiated neonatal piglets.

BACKGROUND: Current neonatal resuscitation guidelines recommend epinephrine for cardiac arrest. Vasopressin might be an alternative during asphyxial cardiac arrest. We aimed to compare vasopressin and epinephrine on incidence and time to return of spontaneous circulation (ROSC) in asphyxiated newborn piglets. DESIGN/METHODS: Newborn piglets (n = 8/group) were anesthetized, intubated, instrumented, and exposed to 30 min of normocapnic hypoxia, followed by asphyxia and asystolic cardiac arrest. Piglets were randomized to 0.2, 0.4, or 0.8IU/kg vasopressin, or 0.02 mg/kg epinephrine. Hemodynamic parameters were continuously measured. RESULTS: Median (IQR) time to ROSC was 172(103-418)s, 157(100-413)s, 122(93-289)s, and 276(117-480)s for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine groups, respectively (p = 0.59). The number of piglets that achieved ROSC was 6(75%), 6(75%), 7(88%), and 5(63%) for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine, respectively (p = 0.94). The epinephrine group had a 60% (3/5) rate of post-ROSC survival compared to 83% (5/6), 83% (5/6), and 57% (4/7) in the 0.2, 0.4, and 0.8IU/kg vasopressin groups, respectively (p = 0.61). CONCLUSION: Time to and incidence of ROSC were not different between all vasopressin dosages and epinephrine. However, non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin groups warrant further investigation. IMPACT: Time to and incidence of ROSC were not statistically different between all vasopressin dosages and epinephrine. Non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin-treated piglets. Overall poorer hemodynamic recovery following ROSC in epinephrine piglets compared to vasopressin groups. Human neonatal clinical trials examining the efficacy of vasopressin during asphyxial cardiac arrest will begin recruitment soon.

Chest compression rates of 60/min versus 90/min during neonatal cardiopulmonary resuscitation: a randomized controlled animal trial.

Background: To compare chest compression (CC) rates of 60/min with 90/min and their effect on the time to return of spontaneous circulation (ROSC), survival, hemodynamic, and respiratory parameters. We hypothesized that asphyxiated newborn piglets that received CC at 60/min vs. 90/min during cardiopulmonary resuscitation would have a shorter time to ROSC. Methods: Newborn piglets (n = 7/group) were anesthetized, tracheotomized and intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to a CC rate of 60/min or 90/min. CC was performed using an automated CC machine using CC superimposed with sustained inflation. Hemodynamic parameters, respiratory parameters, and applied compression force were continuously measured. Results: The mean (IQR) time to ROSC was 97 (65-149) s and 136 (88-395) s for CC rates of 60/min and 90/min, respectively (p = 0.31). The number of piglets that achieved ROSC was 5 (71%) and 5 (71%) with 60/min and 90/min CC rates, respectively (p = 1.00). Hemodynamic parameters (i.e., diastolic and mean blood pressure, carotid blood flow, stroke volume, end-diastolic volume, left ventricular contractile function) and respiratory parameters (i.e., minute ventilation, peak inflation and peak expiration flow) were all similar with a CC rate of 60/min compared to 90/min. Conclusion: Time to ROSC, hemodynamic, and respiratory parameters were not significantly different between CC rates of 60/min vs. 90/min. Different CC rates during neonatal resuscitation warrant further investigation.

Vasopressin versus epinephrine during neonatal cardiopulmonary resuscitation of asphyxiated post-transitional piglets.

Background: Epinephrine is currently the only recommended cardio-resuscitative medication for use in neonatal cardiopulmonary resuscitation (CPR), as per the consensus of science and treatment recommendations. An alternative medication, vasopressin, might be beneficial in neonatal CPR due to its combined pulmonary vasodilation and systemic vasoconstriction properties. Aim: We aimed to compare the time to return of spontaneous circulation (ROSC) with administration of vasopressin or epinephrine during CPR of asphyxiated post-transitional piglets. Methods: Newborn piglets (n = 8/group) were anesthetized, tracheotomized and intubated, instrumented, and exposed to 50 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to receive vasopressin (Vaso, 0.4 U/kg) or epinephrine (Epi, 0.02 mg/kg) during CPR. Piglets were resuscitated with chest compressions superimposed with sustained inflations, and were administered either Vaso or Epi intravenously every 3 min until ROSC (max. 3 doses). Hemodynamic and cardiac function parameters were collected. Main Results: The median (IQR) time to ROSC was 106 (93-140) s with Vaso and 128 (100-198) s with Epi (p = 0.28). The number of piglets that achieved ROSC was 8 (100%) with Vaso and 7 (88%) with Epi (p = 1.00). Vaso-treated piglets had a significantly longer post-resuscitation survival time (240 (240-240) min) than Epi-treated piglets (65 (30-240) min, p = 0.02). Vaso-treated piglets had significantly improved carotid blood flow immediately after ROSC (p < 0.05), had longer duration of post-resuscitation hypertension (p = 0.05), and had significantly improved heart rate, arterial pressure, and cerebral blood oxygen saturation 4 h after ROSC (p < 0.05). Conclusions: Vasopressin improved post-resuscitation survival and hemodynamics, and might be an alternative cardio-resuscitative medication during neonatal CPR, but further studies are warranted.

Sphere-Based Expansion of Myogenic Progenitors from Human Pluripotent Stem Cells.

The protocol presented here is to derive, maintain, and differentiate human pluripotent stem cells into skeletal muscle progenitor/stem cells (myogenic progenitors) using a sphere-based culture approach. This sphere-based culture is an attractive method for maintaining progenitor cells due to their longevity and the presence of cell-cell interactions and molecules. Large numbers of cells can be expanded in culture using this method, which represents a valuable source for cell-based tissue modeling and regenerative medicine.

Four Different Finger Positions and Their Effects on Hemodynamic Changes during Chest Compression in Asphyxiated Neonatal Piglets.

Background: The Neonatal Life Support Consensus on Science With Treatment Recommendations states that chest compressions (CC) be performed preferably with the 2-thumb encircling technique. The aim of this study was to compare the hemodynamic effects of four different finger positions during CC in a piglet model of neonatal asphyxia. Methods: Seven asphyxiated post-transitional piglets were randomized to CC with 2-thumb-, 2-finger-, knocking-fingers-, and over-the-head 2-thumb-techniques for one minute at each technique. CC superimposed with sustained inflations were performed manually. Results: Seven newborn piglets (age 0-4 days, weight 2.0-2.1 kg) were included in the study. The mean (SD) slope rise of carotid blood flow was significantly higher with the 2-thumb-technique and over-the-head 2-thumb-technique (118 (45) mL/min/s and 121 (46) mL/min/s, respectively) compared to the 2-finger-technique and knocking-finger-technique (75 (48) mL/min/s and 71 (67) mL/min/s, respectively) (p < 0.001). The mean (SD) dp/dtmin (as an expression of left ventricular function) was significantly lower with the 2-thumb-technique, with -1052 (369) mmHg/s, compared to -568 (229) mmHg/s and -578(180) mmHg/s (both p = 0.012) with the 2-finger-technique and knocking-finger-technique, respectively. Conclusion: The 2-thumb-technique and the over-the-head 2-thumb-technique resulted in improved slope rises of carotid blood flow and dp/dtmin during chest compression.

Haemodynamic changes with varying chest compression rates in asphyxiated piglets.

BACKGROUND: Current neonatal resuscitation guidelines recommend that chest compressions (CCs) be delivered at a rate of 90/min. The aim of the study was to investigate the haemodynamic effects of different CC rates in a neonatal piglet model. METHODS: Six asphyxiated piglets were randomised to CC with rates of 60/min, 90/min, 120/min, 150/min and 180/min for 1 min at each rate. CCs superimposed with sustained inflations were performed with an automated CC machine. RESULTS: Six newborn piglets (age 0-3 days, weight 2.0-2.3 kg) were included in the study. Overall, there was a gradual increase in stroke volume, minimum and maximum rate of left ventricle pressure change (dp/dtmin and dp/dtmax), and carotid blood flow until CC rate of 150/min, with a level-off effect at a CC rate of 180/min. However, cardiac output continued to increase with the highest being at a CC rate of 180/min. CONCLUSION: Rate of CC was associated with changes in haemodynamic parameters during cardiopulmonary resuscitation. CC rate of 150-180/min during CC resulted in the highest cardiac output and arterial blood pressure. TRIAL REGISTRATION NUMBER: Preclincialtrials.eu PCTE0000249.

Chest Compression Rates of 90/min versus 180/min during Neonatal Cardiopulmonary Resuscitation: A Randomized Controlled Animal Trial.

BACKGROUND: To compare chest compression (CC) rates of 90/min with 180/min and their effect on the time to return of spontaneous circulation (ROSC), survival, hemodynamic, and respiratory parameters. We hypothesized that asphyxiated newborn piglets that received CC at 180/min vs. 90/min during cardiopulmonary resuscitation would have a shorter time to ROSC. METHODS: Newborn piglets (n = 7/group) were anesthetized, intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to a CC rate of 180/min or 90/min. CC was performed using an automated chest compression machine using CC superimposed with sustained inflation. Hemodynamic and respiratory parameters and applied compression force were continuously measured. RESULTS: The mean (SD) time to ROSC was 91 (34) and 256 (97) s for CC rates of 180/min and 90/min, respectively (p = 0.08). The number of piglets that achieved ROSC was 7 (100%) and 5 (71%) with 180/min and 90/min CC rates, respectively (p = 0.46). Hemodynamic parameters (i.e., diastolic and mean blood pressure, carotid blood flow, stroke volume, end-diastolic volume, left ventricular contractile function) and respiratory parameters (i.e., minute ventilation, peak inflation and peak expiration flow) were all improved with a CC rate of 180/min. CONCLUSION: Time to ROSC and hemodynamic and respiratory parameters were not statistical significant different between CC rates of 90/min and 180/min. Higher CC rates during neonatal resuscitation warrant further investigation.

A Randomized, Controlled Animal Study: 21% or 100% Oxygen during Cardiopulmonary Resuscitation in Asphyxiated Infant Piglets.

Background: During pediatric cardiopulmonary resuscitation (CPR), resuscitation guidelines recommend 100% oxygen (O2); however, the most effective O2 concentration for infants unknown. Aim: We aimed to determine if 21% O2 during CPR with either chest compression (CC) during sustained inflation (SI) (CC + SI) or continuous chest compression with asynchronized ventilation (CCaV) will reduce time to return of spontaneous circulation (ROSC) compared to 100% O2 in infant piglets with asphyxia-induced cardiac arrest. Methods: Piglets (20−23 days of age, weighing 6.2−10.2 kg) were anesthetized, intubated, instrumented, and exposed to asphyxia. Cardiac arrest was defined as mean arterial blood pressure < 25 mmHg with bradycardia. After cardiac arrest, piglets were randomized to CC + SI or CCaV with either 21% or 100% O2 or the sham. Heart rate, arterial blood pressure, carotid blood flow, and respiratory parameters were continuously recorded. Main results: Baseline parameters, duration, and degree of asphyxiation were not different. Median (interquartile range) time to ROSC was 107 (90−440) and 140 (105−200) s with CC + SI 21% and 100% O2, and 600 (50−600) and 600 (95−600) s with CCaV 21% and 100% O2 (p = 0.27). Overall, six (86%) and six (86%) piglets with CC + SI 21% and 100% O2, and three (43%) and three (43%) piglets achieved ROSC with CCaV 21% and 100% O2 (p = 0.13). Conclusions: In infant piglets resuscitated with CC + SI, time to ROSC reduced and survival improved compared to CCaV. The use of 21% O2 had similar time to ROSC, short-term survival, and hemodynamic recovery compared to 100% oxygen. Clinical studies comparing 21% with 100% O2 during infant CPR are warranted.

Obesity and patient-reported sexual health outcomes in gynecologic cancer survivors: A systematic review.

As obesity prevalence among gynecologic cancer (GC) survivors is expected to increase, the role of obesity in sexual health needs to be understood. This systematic review examined the impact of obesity on patient-reported sexual health outcomes (SHOs) in this population. PubMed, Embase, Web of Science, CINAHL, and PsycINFO were searched for original studies published between 2015 and 2020 following the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. We performed a narrative synthesis of findings via cancer type, cancer treatment, sexual health measures, and countries. Eleven observational studies were included. Most were conducted in European countries (n = 7), reported on endometrial cancer survivors (n = 7), and defined obesity as body mass index ≥30 kg/m2 (n = 10). Studies about cervical cancer survivors reported negative effects of obesity on sexual activity and body image while studies about endometrial cancer survivors reported positive effects of obesity on vaginal/sexual symptoms. Findings suggested interaction effects of radiotherapy and obesity on SHOs. Sexual functioning measured by the Female Sexual Function Index was less likely to be associated with obesity than other SHOs. A positive effect of obesity on SHOs was only found in studies conducted in European countries. Current evidence on the association between obesity and sexual health in GC survivors lacks in both quantity and quality. To better understand the effect of obesity on SHOs in the population, more studies are needed with critical evaluations of obesity and sexual health measures, careful considerations of cancer type and treatment, and a focus on the cultural context of obesity.

A whole blood microsampling furosemide assay: development, validation and use in a pediatric pharmacokinetic study.

Background: Furosemide is a commonly used diuretic for the treatment of edema. The pharmacokinetics of furosemide in neonates as they mature remains poorly understood. Microsampling assays facilitate research in pediatric populations. Results: We developed and validated a liquid chromatography-tandem mass spectrometry method for the quantitation of furosemide in human whole blood with volumetric absorptive microsampling (VAMS) devices (10 µl). Furosemide was stable in human whole blood VAMS under the study's assay conditions. This work established stability for furosemide for 161 days when stored as dried microsamples at -78°C. Conclusion: This method is being applied for the quantitation of furosemide in whole blood VAMS in an ongoing prospective pediatric clinical study. Representative clinical data are reported.

Dll1-Mediated Notch Signaling Drives Tumor Cell Cross-talk with Cancer-Associated Fibroblasts to Promote Radioresistance in Breast Cancer.

SIGNIFICANCE: Dll1+ breast cancer cells activate Notch signaling in cancer-associated fibroblasts that increases Wnt ligand secretion and leads to ß-catenin-driven radioresistance and metastasis, opening new therapeutic avenues for breast cancer.

Cell Surface Proteins for Enrichment and In Vitro Characterization of Human Pluripotent Stem Cell-Derived Myogenic Progenitors.

Human myogenic progenitors can be derived from pluripotent stem cells (PSCs) for use in modeling natural and pathological myogenesis, as well as treating muscle diseases. Transgene-free methods of deriving myogenic progenitors from different PSC lines often produce mixed populations that are heterogeneous in myogenic differentiation potential, yet detailed and accurate characterization of human PSC-derived myogenic progenitors remains elusive in the field. The isolation and purification of human PSC-derived myogenic progenitors is thus an important methodological consideration when we investigate the properties and behaviors of these cells in culture. We previously reported a transgene-free, serum-free floating sphere culture method for the derivation of myogenic progenitors from human PSCs. In this study, we first performed comprehensive cell surface protein profiling of the sphere culture cells through the screening of 255 antibodies. Next, we used magnetic activated cell sorting and enriched the cells according to the expression of specific surface markers. The ability of muscle differentiation in the resulting cells was characterized by immunofluorescent labeling and quantification of positively stained cells. Our results revealed that myotube-forming cells resided in the differentiated cultures of CD29+, CD56+, CD271+, and CD15- fractions, while thick and multinucleated myotubes were identified in the differentiated cultures from CD9+ and CD146+ fractions. We found that PAX7 localization to the nucleus correlates with myotube-forming ability in these sorted populations. We also demonstrated that cells in unsorted, CD271+, and CD15- fractions responded differently to cryopreservation and prolonged culture expansion. Lastly, we showed that CD271 expression is essential for terminal differentiation of human PSC-derived myogenic progenitors. Taken together, these cell surface proteins are not only useful markers to identify unique cellular populations in human PSC-derived myogenic progenitors but also functionally important molecules that can provide valuable insight into human myogenesis.

Pulmonary and Neurologic Effects of Mesenchymal Stromal Cell Extracellular Vesicles in a Multifactorial Lung Injury Model.

Rationale: Bronchopulmonary dysplasia, a chronic respiratory condition originating from preterm birth, is associated with abnormal neurodevelopment. Currently, there is an absence of effective therapies for bronchopulmonary dysplasia and its associated brain injury. In preclinical trials, mesenchymal stromal cell therapies demonstrate promise as a therapeutic alternative for bronchopulmonary dysplasia. Objectives: To investigate whether a multifactorial neonatal mouse model of lung injury perturbs neural progenitor cell function and to assess the ability of human umbilical cord-derived mesenchymal stromal cell extracellular vesicles to mitigate pulmonary and neurologic injury. Methods: Mice at Postnatal Day 7 or 8 were injected intraperitoneally with LPS and ventilated with 40% oxygen at Postnatal Day 9 or 10 for 8 hours. Treated animals received umbilical cord-mesenchymal stromal cell-derived extracellular vesicles intratracheally preceding ventilation. Lung morphology, vascularity, and inflammation were quantified. Neural progenitor cells were isolated from the subventricular zone and hippocampus and assessed for self-renewal, in vitro differentiation ability, and transcriptional profiles. Measurements and Main Results: The multifactorial lung injury model produced alveolar and vascular rarefaction mimicking bronchopulmonary dysplasia. Neural progenitor cells from lung injury mice showed reduced neurosphere and oligodendrocyte formation, as well as inflammatory transcriptional signatures. Mice treated with mesenchymal stromal cell extracellular vesicles showed significant improvement in lung architecture, vessel formation, and inflammatory modulation. In addition, we observed significantly increased in vitro neurosphere formation and altered neural progenitor cell transcriptional signatures. Conclusions: Our multifactorial lung injury model impairs neural progenitor cell function. Observed pulmonary and neurologic alterations are mitigated by intratracheal treatment with mesenchymal stromal cell-derived extracellular vesicles.