Subjective measures of workload and sleep in Australian Army recruits:Potential utility as monitoring tools

Introduction: Subjective measures may offer practitioners a relatively simple method to monitor recruit responses to basic military training (BMT). Yet, a lack of agreement between subjective and objective measures may presents a problem to practitioners wishing to implement subjective monitoring strategies. This study therefore aims to examine associations between subjective and objective measures of workload and sleep in Australian Army recruits. Materials and Methods: Thirty recruits provided daily rating of perceived exertion (RPE) and differential RPE (d-RPE) for breathlessness and leg muscle exertion each evening. Daily internal workloads determined via heart rate monitors were expressed as Edwards training impulse (TRIMP) and average heart rate. External workloads were determined via global positioning system (PlayerLoad™) and activity monitors (step count). Subjective sleep quality and duration was monitored in 29 different recruits via a customized questionnaire. Activity monitors assessed objective sleep measures. Linear mixed-models assessed associations between objective and subjective measures. Akaike Information Criterion assessed if the inclusion of d-RPE measures resulted in a more parsimonious model. Mean bias, typical error of the estimate (TEE) and withinsubject repeated measures correlations examined agreement between subjective and objective sleep duration. Results: Conditional R2 for associations between objective and subjective workloads ranged from 0.18 to 0.78, P \u3c 0.01, with strong associations between subjective measures of workload and TRIMP (0.65-0.78), average heart rate (0.57-0.73), and PlayerLoad™ (0.54-0.68). Including d-RPE lowered Akaike Information Criterion. The slope estimate between objective and subjective measures of sleep quality was not significant. A trivial relationship (r=0.12; CI -0.03, 0.27) was observed between objective and subjective sleep duration with subjective measures overestimating (mean bias 25 min) sleep duration (TEE 41 min). Conclusions: Daily RPE offers a proxy measure of internal workload in Australian Army recruits; however, the current subjective sleep questionnaire should not be considered a proxy measure of objective sleep measures

Impact of sequential surface-modification of graphene oxide on ice nucleation

Base-washed graphene-oxide which has been sequentially modified by thiol-epoxy chemistry, results in materials with ice nucleation activity. The role of hydro-philic/phobic grafts and polymers was evaluated with the most potent functioning at just 0.25 wt %. These 2-D hybrid materials may find use in cryopreservation and fundamental studies on ice formation

Single cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation

The human endometrium experiences repetitive cycles of tissue wounding characterised by piecemeal shedding of the surface epithelium and rapid restoration of tissue homeostasis. In this study, we used a mouse model of endometrial repair and three transgenic lines of mice to investigate whether epithelial cells that become incorporated into the newly formed luminal epithelium have their origins in one or more of the mesenchymal cell types present in the stromal compartment of the endometrium. Using scRNAseq, we identified a novel population of PDGFRb + mesenchymal stromal cells that developed a unique transcriptomic signature in response to endometrial breakdown/repair. These cells expressed genes usually considered specific to epithelial cells and in silico trajectory analysis suggested they were stromal fibroblasts in transition to becoming epithelial cells. To confirm our hypothesis we used a lineage tracing strategy to compare the fate of stromal fibroblasts (PDGFRa+) and stromal perivascular cells (NG2/CSPG4+). We demonstrated that stromal fibroblasts can undergo a mesenchyme to epithelial transformation and become incorporated into the re-epithelialised luminal surface of the repaired tissue. This study is the first to discover a novel population of wound-responsive, plastic endometrial stromal fibroblasts that contribute to the rapid restoration of an intact luminal epithelium during endometrial repair. These findings form a platform for comparisons both to endometrial pathologies which involve a fibrotic response (Asherman’s syndrome, endometriosis) as well as other mucosal tissues which have a variable response to wounding

NALCN Dysfunction as a Cause of Disordered Respiratory Rhythm With Central Apnea

The sodium leak channel nonselective protein (NALCN) is a regulator of the pacemaker neurons that are responsible for rhythmic behavior (including respiration), maintaining the resting membrane potential, and are required for action potential production. NALCN-null mice show early death associated with disrupted respiratory rhythms, characterized by frequent and profound apneas. We report 3 children (2 siblings) with compound heterozygous mutations in NALCN associated with developmental impairment, hypotonia, and central sleep-disordered breathing causing apneas. Supplemental oxygen normalized the respiratory rhythm. NALCN mutations have been previously reported to cause severe hypotonia, speech impairment, and cognitive delay as well as infantile neuroaxonal dystrophy and facial dysmorphism. Nonsynonymous changes in the 2 affected extracellular loops may be responsible for the deleterious effect on the stability of the respiratory rhythm. Although oxygen is known to be a stabilizer of respiratory rhythm in central apnea in children, its role in NALCN dysfunction requires further investigation.</jats:p

Therapeutic affordances of online support group use in women with endometriosis

Background: The Internet has provided women living with endometriosis new opportunities to seek support online. Online support groups may provide a range of therapeutic affordances which may benefit these women. Objective: To examine the presence of therapeutic affordances as perceived by women who use endometriosis online support groups. Methods: Sixty-nine women (aged 19 to 50 years; Mean = 34.2; 65.2% UK; 21.7% USA) participated in an online interview exploring online support group use. Participants had been using online support groups on average 2 years and 4 months (Range = 1 month to 14 years, 9 months). Responses were analysed using inductive thematic analysis. Results: The analysis revealed 4 therapeutic affordances related to online support group use; i) “connection” i.e. the ability to connect in order to support each other, exchange advice, and to try to overcome feelings of loneliness; ii) “exploration” i.e. the ability to look for information, learn and bolster their knowledge; iii) “narration” i.e. the ability to share their experiences, as well as read about the experiences of others; and iv) “self-presentation” i.e. the ability to manage how they present themselves online. The associated outcomes of use were predominantly positive, such as reassurance and improved coping. However, a number of negative aspects were revealed including: concerns about the accuracy of information, arguments between members, over-reliance on the group, becoming upset by negative experiences or good news items and confidentiality of personal information. Conclusions: Our findings support the SCENA model (Self-presentation, Connection, Exploration, Narration and Adaptation) proposed by Merolli et al., (2014) and reveal a range of positive aspects that may benefit members, particularly in relation to reassurance and coping. However, negative aspects need to be addressed in order to maximise the potential benefit of support groups. Some of these can be addressed relatively easily through making privacy policies clearer, including health professionals to moderate content and structuring forums to encourage the sharing of positive stories

Evaluation of changes in sleep breathing patterns after primary palatoplasty in cleft children

Introduction: There is a need to more clearly understand the characteristics of breathing patterns in children with cleft palate in the first year of life, as there is little data available to guide current practice. Pierre Robin patients are known to have a higher incidence, however we hypothesised sleep breathing disturbance is not confined to this sub-group of cleft patient. Methods: We conducted a prospective observational study of sleep disordered breathing patterns in a cohort of infants with oro-nasal clefts (cleft palate with or without cleft lip) to describe the spectrum of sleep breathing patterns both pre and post palate repair. Sleep breathing studies were performed pre- and post-operatively in sequential infants referred to a regional cleft lip and palate unit. Results of sleep breathing studies were analysed according to American Academy of Sleep Medicine scoring guidelines and correlated with clinical history and details of peri-operative respiratory compromise. The degree of sleep disordered breathing was characterised using desaturation indices (number of desaturations from baseline SpO2 of >=4%, per hour). Results: Thirty-nine infants were included in this study, twenty-five female and fourteen male. Twelve had isolated Cleft Palate as part of an associated syndrome. Patients were categorised into Isolated Cleft Palate, Isolated Cleft Palate in the context of Pierre Robin Sequence, and those with Cleft Lip and Palate. All groups demonstrated some degree of sleep breathing abnormality. Not unsurprisingly the eight infants with Pierre Robin Sequence had a significantly higher desaturation index before surgical intervention (p=0.043), and were more likely to require a pre-operative airway intervention (p=0.009). Palate repair in this group did not alter the relative distribution of patients in each severity category of sleep disorder breathing. Surgical repair of the secondary palate in the remaining children was associated with some improvement but by no means complete resolution of their sleep disordered breathing patterns. Conclusions: We conclude that sleep breathing disturbance is not confined to Pierre Robin patients alone and all cleft palate patients should undergo pre-operative and post-operative sleep breathing analysis

History, College of Medicine: 1959-1968. Chapter 2: College Administration

Prepared for the Centennial of The Ohio State University

Circulating Folate Concentrations and Risk of Peripheral Neuropathy and Mortality: A Retrospective Cohort Study in the U.K

BACKGROUND: Folate deficiency may increase the risk of peripheral neuropathy but there is a paucity of data from large prospective studies examining this association. METHODS: Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a U.K. primary care database including 594,338 patients aged 18-70 years with a folate measurement and without a history of peripheral neuropathy. RESULTS: After a mean follow-up of 3.71 (standard deviation (SD) = 3.14) years, 1949 patients were diagnosed with peripheral neuropathy and 20,679 patients died. In those <40 years, compared to patients with folate ≥13.6 nmol/L, those with folate <6.8 (deficient) and 6.8-13.5 nmol/L (insufficient) had a hazard ratio (HR) for peripheral neuropathy of 1.83 (95% confidence intervals (CI) = 1.16-2.91) and 1.48 (95% CI = 1.04-2.08), respectively. There was no significant association between folate and peripheral neuropathy among those aged 41-70 years. Compared to patients with folate ≥ 13.6 nmol/L, folate <6.8 nmol/L was associated with a greater risk of death among all ages. CONCLUSION: Folate deficiency and insufficiency was associated with a greater risk of peripheral neuropathy among younger patients. This investigation should be replicated in other large datasets and it may be important to monitor peripheral neuropathy incidence after the introduction of mandatory folic acid fortification of flour in the U.K

Single-cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium

The endometrium is a dynamic tissue that exhibits remarkable resilience to repeated episodes of differentiation, breakdown, regeneration, and remodeling. Endometrial physiology relies on a complex interplay between the stromal and epithelial compartments with the former containing a mixture of fibroblasts, vascular, and immune cells. There is evidence for rare populations of putative mesenchymal progenitor cells located in the perivascular niche of human endometrium, but the existence of an equivalent cell population in mouse is unclear. We used the Pdgfrb‐BAC‐eGFP transgenic reporter mouse in combination with bulk and single‐cell RNA sequencing to redefine the endometrial mesenchyme. In contrast to previous reports we show that CD146 is expressed in both PDGFRβ + perivascular cells and CD31 + endothelial cells. Bulk RNAseq revealed cells in the perivascular niche which express the high levels of Pdgfrb as well as genes previously identified in pericytes and/or vascular smooth muscle cells (Acta2, Myh11, Olfr78, Cspg4, Rgs4, Rgs5, Kcnj8, and Abcc9). scRNA‐seq identified five subpopulations of cells including closely related pericytes/vascular smooth muscle cells and three subpopulations of fibroblasts. All three fibroblast populations were PDGFRα+/CD34 + but were distinct in their expression of Ngfr/Spon2/Angptl7 (F1), Cxcl14/Smoc2/Rgs2 (F2), and Clec3b/Col14a1/Mmp3 (F3), with potential functions in the regulation of immune responses, response to wounding, and organization of extracellular matrix, respectively. Immunohistochemistry was used to investigate the spatial distribution of these populations revealing F1/NGFR + cells in most abundance beside epithelial cells. We provide the first definitive analysis of mesenchymal cells in the adult mouse endometrium identifying five subpopulations providing a platform for comparisons between mesenchymal cells in endometrium and other adult tissues which are prone to fibrosis

Timing of reproduction modifies transgenerational effects of chronic exposure to stressors in an annual vertebrate

Stressful environmental conditions can shape both an individual's phenotype and that of its offspring. However, little is known about transgenerational effects of chronic (as opposed to acute) stressors, nor whether these vary across the breeding lifespan of the parent. We exposed adult female (F0 generation) three-spined sticklebacks (Gasterosteus aculeatus) to chronic environmental stressors and compared their reproductive allocation with that of non-exposed controls across early, middle and late clutches produced within the single breeding season of this annual population. There was a seasonal trend (but no treatment difference) in F0 reproductive allocation, with increases in egg mass and fry size in late clutches. We then tested for transgenerational effects in the non-exposed F1 and F2 generations. Exposure of F0 females to stressors resulted in phenotypic change in their offspring and grandoffspring that were produced late in their breeding lifespan: F1 offspring produced from the late-season clutches of stressor-exposed F0 females had higher early life survival, and subsequently produced heavier eggs and F2 fry that were larger at hatching. Changed maternal allocation due to a combination of seasonal factors and environmental stressors can thus have a transgenerational effect by influencing the reproductive allocation of daughters, especially those born late in life