Loose-patch clamp analysis applied to voltage-gated ionic currents following pharmacological ryanodine receptor modulation in murine hippocampal cornu ammonis-1 pyramidal neurons.

Introduction: The loose-patch clamp technique was first developed and used in native amphibian skeletal muscle (SkM), offering useful features complementing conventional sharp micro-electrode, gap, or conventional patch voltage clamping. It demonstrated the feedback effects of pharmacological modification of ryanodine receptor (RyR)-mediated Ca2+ release on the Na+ channel (Nav1.4) currents, initiating excitation-contraction coupling in native murine SkM. The effects of the further RyR and Ca2+-ATPase (SERCA) antagonists, dantrolene and cyclopiazonic acid (CPA), additionally implicated background tubular-sarcoplasmic Ca2+ domains in these actions. Materials and methods: We extend the loose-patch clamp approach to ion current measurements in murine hippocampal brain slice cornu ammonis-1 (CA1) pyramidal neurons. We explored the effects on Na+ currents of pharmacologically manipulating RyR and SERCA-mediated intracellular store Ca2+ release and reuptake. We adopted protocols previously applied to native skeletal muscle. These demonstrated Ca2+-mediated feedback effects on the Na+ channel function. Results: Experiments applying depolarizing 15 ms duration loose-patch clamp steps to test voltages ranging from -40 to 120 mV positive to the resting membrane potential demonstrated that 0.5 mM caffeine decreased inward current amplitudes, agreeing with the previous SkM findings. It also decreased transient but not prolonged outward current amplitudes. However, 2 mM caffeine affected neither inward nor transient outward but increased prolonged outward currents, in contrast to its increasing inward currents in SkM. Furthermore, similarly and in contrast to previous SkM findings, both dantrolene (10 µM) and CPA (1 µM) pre-administration left both inward and outward currents unchanged. Nevertheless, dantrolene pretreatment still abrogated the effects of subsequent 0.5- and 2-mM caffeine challenges on both inward and outward currents. Finally, CPA abrogated the effects of 0.5 mM caffeine on both inward and outward currents, but with 2 mM caffeine, inward and transient outward currents were unchanged, but sustained outward currents increased. Conclusion: We, thus, extend loose-patch clamping to establish pharmacological properties of murine CA1 pyramidal neurons and their similarities and contrasts with SkM. Here, evoked though not background Ca2+-store release influenced Nav and Kv excitation, consistent with smaller contributions of background store Ca2+ release to resting [Ca2+]. This potential non-canonical mechanism could modulate neuronal membrane excitability or cellular firing rates.

Tests of evolutionary and genetic rescue using flour beetles, Tribolium castaneum, experimentally evolved to thermal conditions.

Small, isolated populations are often characterised by low levels of genetic diversity. This can result in inbreeding depression and reduced capacity to adapt to changes in the environment, and therefore higher risk of extinction. However, sometimes these populations can be rescued if allowed to increase in size or if migrants enter, bringing in new allelic variation and thus increasing genetic diversity. This study uses experimental manipulation of population size and migration to quantify their effects on fitness in a challenging environment to better understand genetic rescue. Using small, replicated populations of Tribolium castaneum experimentally evolved to different temperature regimes we tested genetic and demographic rescue, by performing large-scale manipulations of population size and migration and examining fitness consequences over multiple generations. We measured fitness in high temperature (38°C) thermal lines maintained at their usual 'small' population size of N = 100 individuals, and with 'large' scaled up duplicates containing N≈10,000 individuals. We compared these large lines with and without migration (m = 0.1) for 10 generations. Additionally, we assessed the effects of outcrossing at an individual level, by comparing fitness of hybrid (thermal line × stock) offspring with within-line crosses. We found that, at the population level, a rapid increase in the number of individuals in the population resulted in reduced fitness (represented by reproductive output and survival through heatwave conditions), regardless of migration. However, at an individual level, the hybrid offspring of migrants with native individuals generally demonstrated increased longevity in high temperature conditions compared with individuals from thermal selection lines. Overall, these populations showed no evidence that demographic manipulations led to genetic or evolutionary rescue. Following the effects of migration in individuals over several generations may be the next step in unravelling these conflicting results. We discuss these findings in the context of conservation intervention.

Loose patch clamp membrane current measurements in cornus ammonis 1 neurons in murine hippocampal slices.

Hippocampal pyramidal neuronal activity has been previously studied using conventional patch clamp in isolated cells and brain slices. We here introduce the loose patch clamping study of voltage-activated currents from in situ pyramidal neurons in murine cornus ammonis 1 hippocampal coronal slices. Depolarizing pulses of 15-ms duration elicited early transient inward, followed by transient and prolonged outward currents in the readily identifiable junctional region between the stratum pyramidalis (SP) and oriens (SO) containing pyramidal cell somas and initial segments. These resembled pyramidal cell currents previously recorded using conventional patch clamp. Shortening the depolarizing pulses to >1-2 ms continued to evoke transient currents; hyperpolarizing pulses to varying voltages evoked decays whose time constants could be shortened to <1 ms, clarifying the speed of clamping in this experimental system. The inward and outward currents had distinct pharmacological characteristics and voltage-dependent inactivation and recovery from inactivation. Comparative recordings from the SP, known to contain pyramidal cell somas, demonstrated similar current properties. Recordings from the SO and stratum radiatum demonstrated smaller inward and outward current magnitudes and reduced transient outward currents, consistent with previous conventional patch clamp results from their different interneuron types. The loose patch clamp method is thus useful for in situ studies of neurons in hippocampal brain slices.

Greater Protein Intake Emphasizing Lean Beef Does Not Affect Resistance Training-Induced Adaptations in Skeletal Muscle and Tendon of Older Women: A Randomized Controlled Feeding Trial.

BACKGROUND: Although experimental research supports that resistance training (RT), especially with greater dietary protein intake, improves muscle mass and strength in older adults, comparable research on tendons is needed. OBJECTIVES: We assessed the effects of a protein-rich diet emphasizing lean beef, compared with 2 control diets, on RT-induced changes in skeletal muscle and tendon size and strength in older women. METHODS: We randomly assigned women [age: 66 ± 1 y, body mass index (BMI): 28 ± 1] to groups that consumed 1) 0.8 g total protein/kg body weight/day from mixed food sources (normal protein control, n = 16); 2) 1.4 g/kg/d protein from mixed food sources (high protein control, n = 17); or 3) 1.4 g/kg/d protein emphasizing unprocessed lean beef (high protein experimental group, n = 16). Participants were provided with all foods and performed RT 3 times/wk, 70% of 1-repetition maximum for 12 wk. We measured quadriceps muscle volume via magnetic resonance imaging (MRI). We estimated patellar tendon biomechanical properties and cross-sectional area (CSA) using ultrasound and MRI. RESULTS: Dietary intake did not influence RT-induced increases in quadriceps strength (P < 0.0001) or muscle volume (P < 0.05). We noted a trend for an RT effect on mean tendon CSA (P = 0.07), with no differences among diets (P > 0.05). Proximal tendon CSA increased with RT (P < 0.05) with no difference between dietary groups (P > 0.05). Among all participants, midtendon CSA increased with RT (P ≤ 0.05). We found a decrease in distal CSA in the 0.8 g group (P < 0.05) but no change in the 1.4 g group (P > 0.05). Patellar tendon MRI signal or biomechanical properties were unchanged. CONCLUSIONS: Our findings indicated that greater daily protein intake, emphasizing beef, did not influence RT-induced changes in quadriceps muscle strength or muscle volume of older women. Although we noted trends in tendon CSA, we did not find a statistically significant impact of greater daily protein intake from beef on tendon outcomes. This trial was registered at clinicaltrials.gov as NCT04347447.

Consistency in Verreaux's sifaka home range and core area size despite seasonal variation in resource availability as assessed by Enhanced Vegetation Index (EVI).

Primates are adept at dealing with fluctuating availability of resources and display a range of responses to minimize the effects of food scarcity. An important component of primate conservation is to understand how primates adapt their foraging and ranging patterns in response to fluctuating food resources. Animals optimize resource acquisition within the home range through the selection of resource-bearing patches and choose between contrasting foraging strategies (resource-maximizing vs. area-minimizing). Our study aimed to characterize the foraging strategy of a folivorous primate, Verreaux's sifaka (Propithecus verreauxi), by evaluating whether group home range size varied between peak and lean leaf seasons within a seasonally dry tropical forest in Madagascar. We hypothesized that Verreaux's sifaka used the resource maximization strategy to select high-value resource patches so that during periods of resource depression, the home range area did not significantly change in size. We characterized resource availability (i.e., primary productivity) by season at Kirindy Mitea National Park using remotely-sensed Enhanced Vegetation Index data. We calculated group home ranges using 10 years of focal animal sampling data collected on eight groups using both 95% and 50% kernel density estimation. We used area accumulation curves to ensure each group had an adequate number of locations to reach seasonal home range asymptotes. Neither 95% home ranges nor 50% core areas differed across peak and lean leaf resource seasons, supporting the hypothesis that Verreaux's sifaka use a resource maximization strategy. With a better understanding of animal space use strategies, managers can model anticipated changes under environmental and/or anthropogenic resource depression scenarios. These findings demonstrate the value of long-term data for characterizing and understanding foraging and ranging patterns. We also illustrate the benefits of using satellite data for characterizing food resources for folivorous primates.

Dielectric properties of human macrophages are altered by Mycobacterium tuberculosis infection.

The analysis of cell electrophysiology for pathogenic samples at BSL3 can be problematic. It is virtually impossible to isolate infected from uninfected without a label, for example green fluorescent protein, which can potentially alter the cell electrical properties. Furthermore, the measurement of highly pathogenic organisms often requires equipment dedicated only for use with these organisms due to safety considerations. To address this, we have used dielectrophoresis to study the electrical properties of the human THP-1 cell line and monocyte-derived macrophages before and after infection with non-labelled Mycobacterium tuberculosis. Infection with these highly pathogenic bacilli resulted in changes including a raised surface conductance (associated with reduced zeta potential) and increased capacitance, suggesting an increase in surface roughness. We have also investigated the effect of fixation on THP-1 cells as a means to enable study on fixed samples in BSL1 or 2 laboratories, which suggests that the properties of these cells are largely unaffected by the fixation process. This advance results in a novel technique enabling the isolation of infected and non-infected cells in a sample without labelling.

Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.POUT was a phase III, randomized, open-label trial, including 261 patients with muscle-invasive or lymph node-positive, nonmetastatic upper tract urothelial cancer (UTUC) randomly assigned after radical nephroureterectomy to platinum-based chemotherapy (132) or surveillance (129). Primary outcome analysis demonstrated that chemotherapy improved disease-free survival (DFS). At that time, the planned secondary outcome analysis of overall survival (OS) was immature. By February 2022, 50 and 67 DFS events had occurred in the chemotherapy and surveillance groups, respectively, at a median follow-up of 65 months. The 5-year DFS was 62% versus 45%, univariable hazard ratio (HR), 0.55 (95% CI, 0.38 to 0.80, P = .001). The restricted mean survival time (RMST) was 18 months longer (95% CI, 6 to 30) in the chemotherapy arm. There were 46 and 60 deaths in the chemotherapy and control arms, respectively. The 5-year OS was 66% versus 57%, with univariable HR, 0.68 (95% CI, 0.46 to 1.00, P = .049) and RMST difference 11 months (95% CI, 1 to 21). Treatment effects were consistent across chemotherapy regimens (carboplatin or cisplatin) and disease stage. Toxicities were similar to those previously reported, and there were no clinically relevant differences in quality of life between arms. In summary, although OS was not the primary outcome measure, the updated results add further support for the use of adjuvant chemotherapy in patients with UTUC, suggesting long-term benefits.

On the low-frequency dispersion observed in dielectrophoresis spectra.

The foundation of dielectrophoresis (DEP) as a tool for biological investigation is the use of the Clausius-Mossotti (C-M) factor to model the observed behaviour of cells experiencing DEP across a frequency range. Nevertheless, it is also the case that at lower frequencies, the DEP spectrum deviates from predictions; there exists a rise in DEP polarisability, which varies in frequency and magnitude with different cell types and medium conductivities. In order to evaluate the origin of this effect, we have studied DEP spectra from five cell types (erythrocytes, platelets, neurons, HeLa cancer cells and monocytes) in several conditions including medium conductivity and cell treatment. Our results suggest the effect manifests as a low-pass dispersion whose cut-off frequency varies with membrane conductance and capacitance as determined using the DEP spectrum; the effect also varies as a logarithm of medium conductivity and Debye length. These together suggest that the values of membrane capacitance and conductance depend not only on the impedance of the membrane itself, but also of the surrounding double layer. The amplitude of the effect in different cell types compared to the C-M factor was found to correlate with the depolarisation factors for the cells' shapes, suggesting that this ratio may be useful as an indicator of cell shape for DEP modelling.

Evolutionary Patterns of Intersexual Power.

Dominance and leverage are both possible causes of social inequality. If sexual dimorphism influences patterns of intersexual dominance, we predicted that highly dimorphic species are constrained to exhibit male-biased power (MP), but species with low sexual dimorphism are free to demonstrate a broader range of intersexual power relationships. If market effects influence intersexual leverage, we predicted that females have more power when group composition is more male-biased and estrus is asynchronous. We analyzed data on intersexual power, sexual dimorphism, expected estrous overlap, and sex ratio for 79 extant primate species using phylogenetic logistic regression and ancestral state reconstructions. Although MP is more common, every major primate clade includes non-MP species. MP was associated with greater body mass and canine length dimorphism and with female-biased sex-ratios. Low estrous overlap was associated with non-MP. Although MP was reconstructed as likely ancestral for anthropoids, the last common ancestor of this clade probably did not exhibit high sexual dimorphism. The last common ancestor of catarrhines was probably highly dimorphic, potentially constraining intersexual power relationships. Non-MP probably evolved multiple times in primates and may be less common because multiple traits are linked to MP while fewer traits are associated with female-biased power or equality.

Equality, diversity, and inclusion in oncology clinical trials: an audit of essential documents and data collection against INCLUDE under-served groups in a UK academic trial setting.

BACKGROUND: Clinical trials should be as inclusive as possible to facilitate equitable access to research and better reflect the population towards which any intervention is aimed. Informed by the UK's National Institute for Health and Care Research (NIHR) Innovations in Clinical Trial Design and Delivery for the Under-served (INCLUDE) guidance, we audited oncology trials conducted by the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London (ICR-CTSU) to identify whether essential documents were overtly excluding any groups and whether sufficient data were collected to assess diversity of trial participants from groups suggested by INCLUDE as under-served by research in the UK. METHODS: Thirty cancer clinical trials managed by ICR-CTSU and approved between 2011-2021 were audited. The first ethics approved version of each trial's protocol, patient information sheet, and patient completed questionnaire, together with the first case report forms (CRFs) version were reviewed. A range of items aligned with the INCLUDE under-served groups were assessed, including age, sex and gender, socio-economic and health factors. The scope did not cover trial processes in participating hospitals. RESULTS: Data relating to participants' age, ethnic group and health status were well collected and no upper age limit was specified in any trials' eligibility criteria. 23/30 (77%) information sheets used at least one gendered term to address patients. Most CRFs did not specify whether they were collecting sex or gender and only included male or female categories. The median reading age for information sheets was 15-16 years (IQR: 14-15 - 16-17). Socio-economic factors were not routinely collected and not commonly mentioned in trial protocols. CONCLUSIONS: No systemic issues were identified in protocols which would explicitly prevent any under-served group from participating. Areas for improvement include reducing use of gendered words and improving readability of patient information. The challenge of fully assessing adequate inclusion of under-served populations remains, as socio-economic factors are not routinely collected because they fall beyond the data generally required for protocol-specified trial endpoint assessments. This audit has highlighted the need to agree and standardise demographic data collection to permit adequate monitoring of the under-served groups identified by the NIHR.

A Nuanced Examination of Primate Capture and Consumption and Human Socio-Economic Well-Being in Kirindy Mitea National Park, Madagascar.

The futures of human and nonhuman primates are closely tied in protected areas. Understanding this interconnectedness is especially urgent in Madagascar, one of the world's most impoverished biodiversity hotspots. Yet, no study has evaluated the relationship between poverty and lemur hunting and consumption using a composite poverty metric that includes health, education, and living standards. To address this gap, and to inform primate conservation practice and policy, we administered annual surveys to 81 households over six consecutive months (September 2018 to March 2019) in a village on the border of Kirindy Mitea National Park, Madagascar. We observed extreme deprivation scores across multiple dimensions of poverty and identified ninety-five percent of households as 'impoverished'. Of these, three-quarters (77%) of households were identified as being in 'severe poverty'. One-fifth (19%) of all households hunted lemurs and half (49%) of households consumed lemurs. While poverty eradication is an urgent need in communities around Kirindy Mitea National Park, our findings show no relationship between poverty and lemur hunting and consumption, perhaps due to the lack of variance in poverty. Our results highlight the need to investigate other contributory factors to lemur hunting and consumption locally. Because food insecurity is a known driver of lemur hunting and consumption among the study community, and because domestic meats can be preferred over protected species, we recommend testing the efficacy of livestock interventions near Kirindy Mitea National Park.

Study within a trial of electronic versus paper-based Patient-Reported oUtcomes CollEction (SPRUCE): study protocol for a partially randomised patient preference study.

INTRODUCTION: Patient-reported outcomes (PRO) are currently collected from trial participants using paper questionnaires by the Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU). Streamlining PRO collection using electronic questionnaires (ePRO) may improve data collection and patient experience. Here, we outline our protocol for a Study within a trial of electronic versus paper-based Patient-Reported oUtcomes CollEction (SPRUCE), which investigates the acceptability of ePRO in oncology clinical trials. METHODS AND ANALYSIS: SPRUCE was developed alongside patient and public contributors. SPRUCE runs in multiple host trials with a partially randomised patient preference design, allowing participants to be randomised or choose their preference of electronic or paper questionnaires. Questionnaires are scheduled in accordance with host trial follow-up. The primary objective will assess differences in return rates (compliance) between ePRO and paper PROs at the first timepoint post-host trial intervention in the randomised group. Paper PRO compliance is expected to be 90%. 244 randomised participants are required to exclude ≤80% compliance rates with ePRO (10% non-inferiority margin, with 80% power and one-sided alpha=0.05). SPRUCE aims to assess acceptability of ePRO in oncology clinical trials, establish whether ePRO is acceptable to ICR-CTSU trial participants and can capture complete PRO data, consistent with paper PROs. ETHICS AND DISSEMINATION: The SPRUCE protocol (ICR-CTSU/2021/10074) was approved by the Coventry and Warwick Central Research Ethics Committee (21/WM/0223) on 21 October 2021. Results will be disseminated via presentations, publications and lay summaries. No participant identifiable data will be included. TRIAL REGISTRATION: SWAT169.

Photodynamic Diagnosis-guided Transurethral Resection of Bladder Tumour in Participants with a First Suspected Diagnosis of Intermediate- or High-risk Non-muscle-invasive Bladder Cancer: Cost-effectiveness Analysis Alongside a Randomised Controlled Trial.

Background: Recurrence of non-muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumour (TURBT). Photodynamic diagnosis (PDD) may reduce recurrence. PDD uses a photosensitiser in the bladder that causes the tumour to fluoresce to guide resection. PDD provides better diagnostic accuracy and allows more complete tumour resection. Objective: To estimate the economic efficiency of PDD-guided TURBT (PDD-TURBT) in comparison to white light-guided TURNT (WL-TURBT) in individuals with a suspected first diagnosis of NMIBC at intermediate or high risk of recurrence on the basis of routine visual assessment before being scheduled for TURBT. Design setting and participants: This is a health economic evaluation alongside a pragmatic, open-label, parallel-group randomised trial from a societal perspective. A total of 493 participants (aged ≥16 yr) were randomly allocated to PDD-TURBT (n = 244) or WL-TURBT (n = 249) in 22 UK National Health Service hospitals. Outcome measurements and statistical analysis: Cost effectiveness ratios were based on the use of health care resources associated with PDD-TURBT and WL-TURBT and quality-adjusted life years (QALYs) gained within the trial. Uncertainties in key parameters were assessed using sensitivity analyses. Results and limitations: On the basis of the use of resources driven by the trial protocol, the incremental cost effectiveness of PDD-TURBT in comparison to WL-TURBT was not cost saving. At 3 yr, the total cost was £12 881 for PDD-TURBT and £12 005 for WL-TURBT. QALYs at three years were 2.087 for PDD-TURBT and 2.094 for WL-TURBT. The probability that PDD-TURBT is cost effective was never >30% above the range of societal cost-effectiveness thresholds. Conclusions: There was no evidence of a difference in either costs or QALYs over 3-yr follow-up between PDD-TURBT and WL-TURBT in individuals with suspected intermediate- or high-risk NMIBC. PDD-TURBT is not supported for the management of primary intermediate- or high-risk NMIBC. Patient summary: We assessed overall costs for two approaches for removal of bladder tumours in noninvasive cancer and measured quality-adjusted life years gained for each. We found that use of a photosensitiser in the bladder was not more cost effective than use of white light only during tumour removal.

Clinic reported facilitators and barriers to pediatric cancer survivor care delivery among survivorship clinics: A fishbone analysis.

BACKGROUND: Childhood cancer survivors need regular, long-term survivor care. The Children's Oncology Group (COG) recommends that pediatric patients receive ongoing, evidence-based surveillance for late effects, beginning 2 years after the completion of cancer therapy. However, at least a third of survivors are not engaging in long-term survivorship care. This study assessed facilitators and barriers to follow-up survivorship care through the perspectives of pediatric cancer survivor clinic representatives. METHODS: As part of a hybrid implementation-effectiveness trial, a representative from 12 participating pediatric cancer survivor clinics completed a survey about site characteristics and a semi-structured interview on facilitators and barriers to survivor care delivery at their institution. Interviews were grounded in the socio-ecological model (SEM) framework and utilized a fishbone diagram to understand what facilitates and impedes survivor care. We ran descriptive statistics and conducted thematic analyses of the interview transcripts to create two meta-fishbone diagrams. RESULTS: All participating clinics (N = 12) have existed for at least 5 years (mean = 15, median = 13, range = 3-31), and half (n = 6, 50%) reported seeing more than 300 survivors annually. In the fishbone diagram, the top facilitators were in the SEM domain of organization, specifically with familiar staff (n = 12, 100%), resource utilization (n = 11, 92%), dedicated survivorship staff (n = 10, 83%), and clinic processes (n = 10, 83%). Common barriers were across the domains of organization, community, and policy, which included distance/transportation to the clinic (n = 12, 100%), technology limits (n = 11, 92%), scheduling issues (n = 11, 92%), and insufficient funding/insurance (n = 11, 92%). CONCLUSION: Clinic staff and provider perceptions are instrumental in understanding multilevel contextual issues related to survivor care delivery for pediatric cancer survivor clinics. Future research can aid in developing education, processes, and services to promote cancer survivor follow-up care.

Diminished ovarian reserve in adolescent cancer survivors treated with heavy metal chemotherapy.

The extent to which heavy metal chemotherapy results in treatment-related ovarian damage is controversial. Anti-Mullerian hormone (AMH) levels measured more than 1 year after cancer therapy completion were abstracted from the medical records of 39 female survivors of childhood cancer aged 11 years and older, whose only gonadotoxic exposure was heavy metal chemotherapy. One-fifth of survivors who received cisplatin had AMH levels indicative of diminished ovarian reserve at last measurement. There was an observed clustering of low AMH in patients diagnosed in the peripubertal age range (i.e., 10-12 years). These findings may support a small, but present, risk of gonadal damage after heavy metal chemotherapy.

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review.

Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the proliferation, differentiation, and migration of musculoskeletal progenitor cells. Calcium- and voltage-activated potassium (KCa) channels are key players in cell physiology in cells of the musculoskeletal system. This review article focused on the big conductance (BK) KCa channels. The regulatory function of BK channels requires interactions with diverse sets of proteins that have different functions in tissue-resident stem cells. In this narrative review article, we discuss the main ion channels of musculoskeletal stem cells, with a focus on calcium-dependent potassium channels, especially on the large conductance BK channel. We review their expression and function in progenitor cell proliferation, differentiation, and migration and highlight gaps in current knowledge on their involvement in musculoskeletal diseases.

Breakfast Quality of Preschool-aged Canadian Children.

Purpose: To investigate the breakfast quality of preschool-aged children through a comparison of their energy and nutrient intakes at breakfast to published benchmarks for a balanced breakfast.Methods: Dietary data were collected for 163 children aged 3-5 years enrolled in the Guelph Family Health Study using one parent-reported online 24-hour recall and analyzed for energy and nutrient intakes. Breakfast quality was assessed by tallying the frequency of participants whose nutrient and energy intakes at their breakfast meal met the recommendations for a balanced breakfast established by the International Breakfast Research Initiative (IRBI).Results: Almost all participants (98%) consumed breakfast, and most participants (82.5%) met the energy IRBI recommendation. However, the majority of participants did not meet the IRBI recommendations for breakfast intakes of most macronutrients and micronutrients. In particular, fewer than 25% of participants met the IRBI recommendations for breakfast intakes of dietary fibre, niacin, folate, vitamin C, calcium, potassium and zinc.Conclusions: Almost all preschool-aged children in this study consumed breakfast, but the nutritional quality of their breakfast did not meet recommendations for most nutrients. These results can inform nutrition education and intervention programs for children that aim to improve the nutritional quality of breakfast.

Interest in fertility status assessment among young adult survivors of childhood cancer.

BACKGROUND: Cancer survivors who received gonadotoxic treatment are at-risk for future infertility and may desire a fertility status assessment (FSA), defined as semen analysis for males and consultation with a reproductive specialist for females. The purpose of this study was to describe the proportion of, and factors associated with, interest in FSA among young adult survivors of childhood cancer. METHODS: This retrospective single-institution review included patients with prior gonadotoxic treatment, aged 18-25 years and >1 year from cancer treatment completion, who received a fertility-focused discussion during survivorship. Documentation of interest in and completion of FSA, worry about infertility, sociodemographic, and clinical characteristics were abstracted from medical records. Multivariable logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with interest in FSA. RESULTS: Survivors (N = 259) were on average 19.2 ± 1.2 years at their fertility discussion; 55.6% were male and 57.9% non-Hispanic white. Interest in FSA was reported by 50.7% of males and 46.1% of females. Factors related to interest in FSA for males and females respectively, included worry about infertility (OR 2.40, 95%CI 1.11-5.27, p = 0.026 and OR 4.37, 95%CI 1.71-12.43, p = 0.003) and ≥2 fertility discussions (OR 3.78, 95%CI 1.70-8.75, p = 0.001 and 2.45, 95%CI 1.08-5.67, p = 0.033). Among males, fertility preservation consult/procedure at diagnosis (OR 3.02, 95%CI 1.09-9.04, p = 0.039) and high-risk for infertility (OR 2.47, 95%CI 1.07-5.87, p = 0.036) were also associated with interest in FSA. CONCLUSIONS: Cancer survivors are interested in FSA, particularly those who have had repeated fertility-focused discussions during survivorship care and who report worry about infertility.