Decoding information about cognitive health from the brainwaves of sleep.

Sleep electroencephalogram (EEG) signals likely encode brain health information that may identify individuals at high risk for age-related brain diseases. Here, we evaluate the correlation of a previously proposed brain age biomarker, the "brain age index" (BAI), with cognitive test scores and use machine learning to develop and validate a series of new sleep EEG-based indices, termed "sleep cognitive indices" (SCIs), that are directly optimized to correlate with specific cognitive scores. Three overarching cognitive processes were examined: total, fluid (a measure of cognitive processes involved in reasoning-based problem solving and susceptible to aging and neuropathology), and crystallized cognition (a measure of cognitive processes involved in applying acquired knowledge toward problem-solving). We show that SCI decoded information about total cognition (Pearson's r = 0.37) and fluid cognition (Pearson's r = 0.56), while BAI correlated only with crystallized cognition (Pearson's r = - 0.25). Overall, these sleep EEG-derived biomarkers may provide accessible and clinically meaningful indicators of neurocognitive health.

Review article: Accuracy of emergency physician performed point-of-care ultrasound of the thoracic aorta: A systematic review and narrative synthesis of the literature.

Point-of-care ultrasound (POCUS) is becoming ubiquitous in emergency medicine. POCUS for abdominal aortic aneurysm is well established in practice. The thoracic aorta can also be assessed by POCUS for dissection and aneurysm and transthoracic echocardiography is endorsed by international guidelines as an initial test for thoracic aortic pathologies. A systematic search of Ovid Medline, PubMed, EMBASE, SCOPUS and Web of Science from January 2000 to August 2022 identified four studies evaluating diagnostic accuracy of emergency physician POCUS for thoracic aortic dissection (TAD) and five studies for thoracic aortic aneurysm (TAA). Study designs were heterogeneous including differing diagnostic criteria for aortic pathology. Convenience recruitment was frequent in prospective studies. Sensitivity and specificity ranges for studies of TAD were 41-91% and 94-100%, respectively when an intimal flap was seen. Sensitivity and specificity ranges for studies of thoracic aorta dilation >40 mm were 50-100% and 93-100%, respectively; for >45 mm ranges were 64-65% and 95-99%. Literature review identified that POCUS is specific for TAD and TAA. POCUS reduces the time to diagnosis of thoracic aortic pathology; however, it remains insensitive and cannot be recommended as a stand-alone rule-out test. We suggest that detection of thoracic aorta dilation >40 mm by POCUS at any site increases the suspicion of serious aortic pathology. Studies incorporating algorithmic use of POCUS, Aortic Dissection Detection Risk Score and D-dimer as decision tools are promising and may improve current ED practices. Further research is warranted in this rapidly evolving field.

Perioperative Management of Extended-release Buprenorphine.

Perioperative management of buprenorphine is increasingly characterized by continuation of buprenorphine throughout the perioperative period while coadministering full agonist opioids for analgesia. Although this "simultaneous strategy" is commonly used for the shorter-acting sublingual buprenorphine formulations, there is little to guide management of the extended-release formulations of buprenorphine. Here we report the perioperative experience of an individual maintained on extended-release buprenorphine who successfully underwent major surgeries utilizing a strategy of performing the surgeries at the time of the next scheduled dose.

A Small Change With a Twist Ending: A Single Residue in EGF-CFC Drives Bilaterian Asymmetry.

Asymmetries are essential for proper organization and function of organ systems. Genetic studies in bilaterians have shown signaling through the Nodal/Smad2 pathway plays a key, conserved role in the establishment of body asymmetries. Although the main molecular players in the network for the establishment of left-right asymmetry (LRA) have been deeply described in deuterostomes, little is known about the regulation of Nodal signaling in spiralians. Here, we identified orthologs of the egf-cfc gene, a master regulator of the Nodal pathway in vertebrates, in several invertebrate species, which includes the first evidence of its presence in non-deuterostomes. Our functional experiments indicate that despite being present, egf-cfc does not play a role in the establishment of LRA in gastropods. However, experiments in zebrafish suggest that a single amino acid mutation in the egf-cfc gene in at least the common ancestor of chordates was the necessary step to induce a gain of function in LRA regulation. This study shows that the egf-cfc gene likely appeared in the ancestors of deuterostomes and "protostomes", before being adopted as a mechanism to regulate the Nodal pathway and the establishment of LRA in some lineages of deuterostomes.

Cellular and molecular profiles of larval and adult Xenopus corneal epithelia resolved at the single-cell level.

Corneal Epithelial Stem Cells (CESCs) and their proliferative progeny, the Transit Amplifying Cells (TACs), are responsible for homeostasis and maintaining corneal transparency. Owing to our limited knowledge of cell fates and gene activity within the cornea, the search for unique markers to identify and isolate these cells remains crucial for ocular surface reconstruction. We performed single-cell RNA sequencing of corneal cells from larval and adult stages of Xenopus. Our results indicate that as the cornea develops and matures, there is an increase in cellular diversity, which is accompanied by a substantial shift in transcriptional profile, gene regulatory network and cell-cell communication dynamics. Our data also reveals several novel genes expressed in corneal cells and changes in gene expression during corneal differentiation at both developmental time-points. Importantly, we identify specific basal cell clusters in both the larval and adult cornea that comprise a relatively undifferentiated cell type and express distinct stem cell markers, which we propose are the putative larval and adult CESCs, respectively. This study offers a detailed atlas of single-cell transcriptomes in the frog cornea. In the future, this work will be useful to elucidate the function of novel genes in corneal epithelial homeostasis, wound healing and regeneration.

Shared genetic background between SARS-CoV-2 infection and large artery stroke.

BACKGROUND AND AIMS: Increased risk of stroke, particularly large artery stroke (LAS), has been observed in patients with COVID-19. The biological processes underlying the observed higher risk are still unknown. We explored the association between stroke subtypes and COVID-19 susceptibility to understand whether biological mechanisms specific to SARS-CoV-2 uptake/infection could be leading to excess stroke risk in this population. PATIENTS AND METHODS: We constructed a polygenic risk score (PRS) of COVID-19 susceptibility and tested its association with stroke subtypes using individual- and summary-level genetic data (SiGN, MEGASTROKE). We generated co-expression networks of genes involved in SARS-CoV-2 uptake/infection (ACE2, TMPRSS2, BEST3, ISLR2 and ADAM17) based on existing tissue expression libraries. Gene-based association testing was performed using S-PrediXcan and VEGAS2. Permutation independence tests were performed to assess SARS-CoV-2-related gene enrichment in stroke and its subtypes. RESULTS: Our PRS demonstrated an association between COVID-19 susceptibility and LAS in SiGN (OR = 1.05 per SD increase, 95% CI: (1.00, 1.10), p = 0.04) and MEGASTROKE (ß = 0.510, 95% CI: (0.242, 0.779), FDR-p = 0.0019). The SARS-CoV-2 risk-related ISLR2 co-expression gene network was significantly associated with genetic risk of LAS in aorta, tibial arteries, and multiple brain regions (P < 0.05). CONCLUSION: Presence of genetic correlation and significant pathway enrichment suggest that increases in LAS risk reported in COVID-19 patients may be intrinsic to the viral infection, rather than a more generalized response to severe illness.

Long-Term Blood Pressure Variability and Major Adverse Cardiovascular and Cerebrovascular Events After Intracerebral Hemorrhage.

Background Survivors of intracranial hemorrhage (ICH) are at increased risk for major adverse cardiovascular and cerebrovascular events (MACCE), in the form of recurrent stroke and myocardial Infarction. We investigated whether long-term blood pressure (BP) variability represents a risk factor for MACCE after ICH, independent of average BP. Methods and Results We analyzed data from prospective ICH cohort studies at Massachusetts General Hospital and the University of Hong Kong. We captured long-term (ie, visit-to-visit) BP variability, quantified as individual participants' variation coefficient. We explored determinants of systolic and diastolic BP variability and generated survival analyses models to explore their association with MACCE. Among 1828 survivors of ICH followed for a median of 46.2 months we identified 166 with recurrent ICH, 68 with ischemic strokes, and 69 with myocardial infarction. Black (coefficient +3.8, SE 1.3) and Asian (coefficient +2.2, SE 0.4) participants displayed higher BP variability. Long-term systolic BP variability was independently associated with recurrent ICH (subhazard ratio [SHR], 1.82; 95% CI, 1.19-2.79), ischemic stroke (SHR, 1.62; 95% CI, 1.06-2.47), and myocardial infarction (SHR, 1.54; 95% CI, 1.05-2.24). Average BP during follow-up did not modify the association between long-term systolic BP variability and MACCE. Conclusions Long-term BP variability is a potent risk factor for recurrent hemorrhage, ischemic stroke, and myocardial infarction after ICH, even among survivors with well-controlled hypertension. Our findings support the hypothesis that combined control of average BP and its variability after ICH is required to minimize incidence of MACCE.

Slipper snail tales: How Crepidula fornicata and Crepidula atrasolea became model molluscs.

Despite the great abundance and diversity of molluscs, only a few have attained "model research organism" status. One of those species is the slipper snail Crepidula fornicata. Its embryos were first used for classical lineage tracing studies in the late 19th century, and over a 100 years later they were "re-discovered" by our labs and used for modern fate mapping, gene perturbation, in vivo imaging, transcriptomics, and the first application of CRISPR/Cas9-mediated genome editing among the Spiralia/Lophotrochozoa. Simultaneously, other labs made extensive examinations of taxonomy, phylogeny, ecology, life-history, mode of development, larval feeding behavior, and responses to the environment in members of the family Calyptraeidae, which includes the genus Crepidula. Recently, we developed tools, resources, and husbandry protocols for another, direct-developing species, Crepidula atrasolea. This species is an ideal "lab rat" among molluscs. Together these species will be valuable for probing the cellular and molecular mechanisms underlying molluscan biology and evolution.

Biological and Social Determinants of Hypertension Severity Before vs After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Although blood pressure (BP) control is considered the most effective measure to prevent functional decline after intracerebral hemorrhage (ICH), fewer than half of survivors achieve treatment goals. We hypothesized that long-term (i.e., prehemorrhage) hypertension severity may be a crucial factor in explaining poor BP control after ICH. We investigated changes in hypertension severity after vs before ICH using latent class analysis (LCA) and identified patient characteristics predictive of individuals' BP trajectories. METHODS: We analyzed data for ICH survivors enrolled in a study conducted at Massachusetts General Hospital (MGH) from 2002 to 2019 in Boston, a high-resource setting with near-universal medical insurance coverage. We captured BP measurements in the 12 months preceding and following the acute ICH hospitalization. Using LCA, we identified patient groups (classes) based on changes in hypertension severity over time in an unbiased manner. We then created multinomial logistic regression models to identify patient factors associated with these classes. RESULTS: Among 336 participants, the average age was 74.4 years, 166 (49%) were male, and 288 (86%) self-reported White race/ethnicity. LCA identified 3 patient classes, corresponding to minimal (n = 114, 34%), intermediate (n = 128, 38%), and substantial (n = 94, 28%) improvement in hypertension severity after vs before ICH. Survivors with undertreated (relative risk ratio [RRR] 0.05, 95% CI 0.01-0.23) or resistant (RRR 0.03, 95% CI 0.01-0.06) hypertension before ICH were less likely to experience substantial improvement afterwards. Residents of high-income neighborhoods were more likely to experience substantial improvement (RRR 1.14 per $10,000, 95% CI 1.02-1.28). Black, Hispanic, and Asian participants with uncontrolled hypertension before ICH were more likely to experience minimal improvement after hemorrhagic stroke (interaction p < 0.001). DISCUSSION: Most ICH survivors do not display consistent improvement in hypertension severity after hemorrhagic stroke. BP control after ICH is profoundly influenced by patient characteristics predating the hemorrhage, chiefly prestroke hypertension severity and socioeconomic status. Neighborhood income was associated with hypertension severity after ICH in a high-resource setting with near-universal health care coverage. These findings likely contribute to previously documented racial/ethnic disparities in BP control and clinical outcomes following ICH.

Retinoids promote penis development in sequentially hermaphroditic snails.

Sexual systems are surprisingly diverse, considering the ubiquity of sexual reproduction. Sequential hermaphroditism, the ability of an individual to change sex, has emerged multiple times independently across the animal kingdom. In molluscs, repeated shifts between ancestrally separate sexes and hermaphroditism are generally found at the level of family and above, suggesting recruitment of deeply conserved mechanisms. Despite this, molecular mechanisms of sexual development are poorly known. In molluscs with separate sexes, endocrine disrupting toxins bind the retinoid X receptor (RXR), activating ectopic male development in females, suggesting the retinoid pathway as a candidate controlling sexual transitions in sequential hermaphrodites. We therefore tested the role of retinoic acid signaling in sequentially hermaphroditic Crepidula snails, which develop first into males, then change sex, maturing into females. We show that retinoid agonists induce precocious penis growth in juveniles and superimposition of male development in females. Combining RXR antagonists with retinoid agonists significantly reduces penis length in induced juveniles, while similar treatments using retinoic acid receptor (RAR) antagonists increase penis length. Transcripts of both receptors are expressed in the induced penis. Our findings therefore show that retinoid signaling can initiate molluscan male genital development, and regulate penis length. Further, we show that retinoids induce ectopic male development in multiple Crepidula species. Species-specific influence of conspecific induction of sexual transitions correlates with responsiveness to retinoids. We propose that retinoid signaling plays a conserved role in molluscan male development, and that shifts in the timing of retinoid signaling may have been important for the origins of sequential hermaphroditism within molluscs.

Rare Missense Functional Variants at COL4A1 and COL4A2 in Sporadic Intracerebral Hemorrhage.

ObjectiveTo test the genetic contribution of rare missense variants in COL4A1 and COL4A2 in which common variants are genetically associated with sporadic intracerebral hemorrhage (ICH), we performed rare variant analysis in multiple sequencing data for the risk for sporadic ICH.MethodsWe performed sequencing across 559Kbp at 13q34 including COL4A1 and COL4A2 among 2,133 individuals (1,055 ICH cases; 1,078 controls) in US-based and 1,492 individuals (192 ICH cases; 1,189 controls) from Scotland-based cohorts, followed by sequence annotation, functional impact prediction, genetic association testing, and in silico thermodynamic modeling.ResultsWe identified 107 rare nonsynonymous variants in sporadic ICH, of which two missense variants, rs138269346 (COL4A1I110T) and rs201716258 (COL4A2H203L), were predicted to be highly functional and occurred in multiple ICH cases but not in controls from the US-based cohort. The minor allele of rs201716258 was also present in Scottish ICH patients, and rs138269346 was observed in two ICH-free controls with a history of hypertension and myocardial infarction. Rs138269346 was nominally associated with non-lobar ICH risk (P=0.05), but not with lobar ICH (P=0.08), while associations between rs201716258 and ICH subtypes were non-significant (P>0.12). Both variants were considered pathogenic based on minor allele frequency (<0.00035 in EUR), predicted functional impact (deleterious or probably damaging), and in silico modeling studies (substantially altered physical length and thermal stability of collagen).ConclusionsWe identified rare missense variants in COL4A1/A2 in association with sporadic ICH. Our annotation and simulation studies suggest that these variants are highly functional and may represent targets for translational follow-up.

Impact of Uncontrolled Hypertension at 3 Months After Intracerebral Hemorrhage.

Background Survivors of intracerebral hemorrhage (ICH) are at high risk for recurrent stroke, which is associated with blood pressure control. Because most recurrent stroke events occur within 12 to 18 months of the index ICH, rapid blood pressure control is likely to be crucial. We investigated the frequency and prognostic impact of uncontrolled short-term hypertension after ICH. Methods and Results We analyzed data from Massachusetts General Hospital (n=1305) and the University of Hong Kong (n=523). We classified hypertension as controlled, undertreated, or treatment resistant at 3 months after ICH and determined the following: (1) the risk factors for uncontrolled hypertension and (2) whether hypertension control at 3 months is associated with stroke recurrence and mortality. We followed 1828 survivors of ICH for a median of 46.2 months. Only 9 of 234 (4%) recurrent strokes occurred before 3 months after ICH. At 3 months, 713 participants (39%) had controlled hypertension, 755 (41%) had undertreated hypertension, and 360 (20%) had treatment-resistant hypertension. Black, Hispanic, and Asian race/ethnicity and higher blood pressure at time of ICH increased the risk of uncontrolled hypertension at 3 months (all P<0.05). Uncontrolled hypertension at 3 months was associated with recurrent stroke and mortality during long-term follow-up (all P<0.05). Conclusions Among survivors of ICH, >60% had uncontrolled hypertension at 3 months, with undertreatment accounting for the majority of cases. The 3-month blood pressure measurements were associated with higher recurrent stroke risk and mortality. Black, Hispanic, and Asian survivors of ICH and those presenting with severe acute hypertensive response were at highest risk for uncontrolled hypertension.

Understanding cornea epithelial stem cells and stem cell deficiency: Lessons learned using vertebrate model systems.

Animal models have contributed greatly to our understanding of human diseases. Here, we focus on cornea epithelial stem cell (CESC) deficiency (commonly called limbal stem cell deficiency, LSCD). Corneal development, homeostasis and wound healing are supported by specific stem cells, that include the CESCs. Damage to or loss of these cells results in blindness and other debilitating ocular conditions. Here we describe the contributions from several vertebrate models toward understanding CESCs and LSCD treatments. These include both mammalian models, as well as two aquatic models, Zebrafish and the amphibian, Xenopus. Pioneering developments have been made using stem cell transplants to restore normal vision in patients with LSCD, but questions still remain about the basic biology of CESCs, including their precise cell lineages and behavior in the cornea. We describe various cell lineage tracing studies to follow their patterns of division, and the fates of their progeny during development, homeostasis, and wound healing. In addition, we present some preliminary results using the Xenopus model system. Ultimately, a more thorough understanding of these cornea cells will advance our knowledge of stem cell biology and lead to better cornea disease therapeutics.

Single-session Mentalization-based Treatment Group for Law Enforcement Officers.

Law enforcement violence has emerged as a leading public health concern, and law enforcement officers are themselves at greater risk for a range of psychiatric disorders. Drawing on the significant empirical support for mentalization-based treatment (MBT), this paper explores the use of MBT as a transdiagnostic psychotherapy for law enforcement professionals. By helping patients to mentalize-that is, to "read," access, and reflect on mental states in oneself and other people-MBT could be useful as a dual-focus treatment, able to simultaneously impact psychiatric illness among law enforcement officers while also indirectly impacting the problem of law enforcement violence in the broader society. The core psychotherapeutic principles of MBT are reviewed, along with common vulnerabilities in mentalizing likely to arise for law enforcement professionals in the context of high emotional and interpersonal intensity. The authors outline a novel application of MBT which has implications for psychiatric treatment as well as police training: the single-session psychoeducation and psychotherapy group, where law enforcement officers practice both self-reflection and empathy in situations of relational conflict. Utilizing group process from a residential treatment program for first responders with mental health and substance use disorders, a case example is offered to illustrate this intervention.

An automated aquatic rack system for rearing marine invertebrates.

BACKGROUND: One hundred years ago, marine organisms were the dominant systems for the study of developmental biology. The challenges in rearing these organisms outside of a marine setting ultimately contributed to a shift towards work on a smaller number of so-called model systems. Those animals are typically non-marine organisms with advantages afforded by short life cycles, high fecundity, and relative ease in laboratory culture. However, a full understanding of biodiversity, evolution, and anthropogenic effects on biological systems requires a broader survey of development in the animal kingdom. To this day, marine organisms remain relatively understudied, particularly the members of the Lophotrochozoa (Spiralia), which include well over one third of the metazoan phyla (such as the annelids, mollusks, flatworms) and exhibit a tremendous diversity of body plans and developmental modes. To facilitate studies of this group, we have previously described the development and culture of one lophotrochozoan representative, the slipper snail Crepidula atrasolea, which is easy to rear in recirculating marine aquaria. Lab-based culture and rearing of larger populations of animals remain a general challenge for many marine organisms, particularly for inland laboratories. RESULTS: Here, we describe the development of an automated marine aquatic rack system for the high-density culture of marine species, which is particularly well suited for rearing filter-feeding animals. Based on existing freshwater recirculating aquatic rack systems, our system is specific to the needs of marine organisms and incorporates robust filtration measures to eliminate wastes, reducing the need for regular water changes. In addition, this system incorporates sensors and associated equipment for automated assessment and adjustment of water quality. An automated feeding system permits precise delivery of liquid food (e.g., phytoplankton) throughout the day, mimicking real-life feeding conditions that contribute to increased growth rates and fecundity. CONCLUSION: This automated system makes laboratory culture of marine animals feasible for both large and small research groups, significantly reducing the time, labor, and overall costs needed to rear these organisms.

BMP signaling plays a role in anterior-neural/head development, but not organizer activity, in the gastropod Crepidula fornicata.

BMP signaling is involved in many aspects of metazoan development, with two of the most conserved functions being to pattern the dorsal-ventral axis and to specify neural versus epidermal fates. An active area of research within developmental biology asks how BMP signaling was modified over evolution to build disparate body plans. Animals belonging to the superclade Spiralia/Lophotrochozoa are excellent experimental subjects for studying the evolution of BMP signaling because a highly conserved, stereotyped early cleavage program precedes the emergence of distinct body plans. In this study we examine the role of BMP signaling in one representative, the slipper snail Crepidula fornicata. We find that mRNAs encoding BMP pathway components (including the BMP ligand decapentaplegic, and BMP antagonists chordin and noggin-like proteins) are not asymmetrically localized along the dorsal-ventral axis in the early embryo, as they are in other species. Furthermore, when BMP signaling is perturbed by adding ectopic recombinant BMP4 protein, or by treating embryos with the selective Activin receptor-like kinase-2 (ALK-2) inhibitor Dorsomorphin Homolog 1 (DMH1), we observe no obvious effects on dorsal-ventral patterning within the posterior (post-trochal) region of the embryo. Instead, we see effects on head development and the balance between neural and epidermal fates specifically within the anterior, pre-trochal tissue derived from the 1q1 lineage. Our experiments define a window of BMP signaling sensitivity that ends at approximately 44-48 â€‹hours post fertilization, which occurs well after organizer activity has ended and after the dorsal-ventral axis has been determined. When embryos were exposed to BMP4 protein during this window, we observed morphogenetic defects leading to the separation of the anterior, 1q lineage from the rest of the embryo. The 1q-derived organoid remained largely undifferentiated and was radialized, while the post-trochal portion of the embryo developed relatively normally and exhibited clear signs of dorsal-ventral patterning. When embryos were exposed to DMH1 during the same time interval, we observed defects in the head, including protrusion of the apical plate, enlarged cerebral ganglia and ectopic ocelli, but otherwise the larvae appeared normal. No defects in shell development were noted following DMH1 treatments. The varied roles of BMP signaling in the development of several other spiralians have recently been examined. We discuss our results in this context, and highlight the diversity of developmental mechanisms within spiral-cleaving animals.

Genetic overlap and causal inferences between kidney function and cerebrovascular disease.

OBJECTIVE: Leveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes. METHODS: We used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease diagnosis, estimated glomerular filtration rate [eGFR], and urinary albumin-to-creatinine ratio [UACR]) and cerebrovascular disease phenotypes (ischemic stroke and its subtypes, intracerebral hemorrhage [ICH], and white matter hyperintensities [WMH] on brain MRI). We (1) tested the genetic overlap between them with polygenic risk scores (PRS), (2) searched for common pleiotropic loci with pairwise GWAS analyses, and (3) explored causal associations by employing 2-sample Mendelian randomization. RESULTS: A PRS for lower eGFR was associated with higher large artery stroke (LAS) risk (p = 1 × 10-4). Multiple pleiotropic loci were identified between kidney function traits and cerebrovascular disease phenotypes, with 12q24 associated with eGFR and both LAS and small vessel stroke (SVS), and 2q33 associated with UACR and both SVS and WMH. Mendelian randomization revealed associations of both lower eGFR (odds ratio [OR] per 1-log decrement, 2.10; 95% confidence interval [CI], 1.38-3.21) and higher UACR (OR per 1-log increment, 2.35; 95% CI, 1.12-4.94) with a higher risk of LAS, as well as between higher UACR and higher risk of ICH. CONCLUSIONS: Impaired kidney function, as assessed by decreased eGFR and increased UACR, may be causally involved in the pathogenesis of LAS. Increased UACR, previously proposed as a marker of systemic small vessel disease, is involved in ICH risk and shares a genetic risk factor at 2q33 with manifestations of cerebral small vessel disease.

Paediatric point-of-care ultrasound in a resource-limited Melanesian setting: A case series.

Point-of-care ultrasound (POCUS) is an imaging modality with high potential impact on the practice of paediatric emergency medicine in resource-limited settings. Aside from the obvious diagnostic utility, it facilitates safe procedural guidance at the bedside and provides haemodynamic information to guide resuscitation of shocked states. This five-patient paediatric case series illustrates the range of POCUS modalities used while working in emergency medicine at a regional referral hospital in Vanuatu. Cases described include a teenager with meningococcaemia, femoral central line insertion in an infant, ventricular septal defect in an infant, a child with a leg abscess, and a child with rheumatic heart disease.

Sex Determination, Sexual Development, and Sex Change in Slipper Snails.

Sex determination and sexual development are highly diverse and controlled by mechanisms that are extremely labile. While dioecy (separate male and female functions) is the norm for most animals, hermaphroditism (both male and female functions within a single body) is phylogenetically widespread. Much of our current understanding of sexual development comes from a small number of model systems, limiting our ability to make broader conclusions about the evolution of sexual diversity. We present the calyptraeid gastropods as a model for the study of the evolution of sex determination in a sequentially hermaphroditic system. Calyptraeid gastropods, a group of sedentary, filter-feeding marine snails, are sequential hermaphrodites that change sex from male to female during their life span (protandry). This transition includes resorption of the penis and the elaboration of female genitalia, in addition to shifting from production of spermatocytes to oocytes. This transition is typically under environmental control and frequently mediated by social interactions. Males in contact with females delay sex change to transition at larger sizes, while isolated males transition more rapidly and at smaller sizes. This phenomenon has been known for over a century; however, the mechanisms that control the switch from male to female are poorly understood. We review here our current understanding of sexual development and sex determination in the calyptraeid gastropods and other molluscs, highlighting our current understanding of factors implicated in the timing of sex change and the potential mechanisms. We also consider the embryonic origins and earliest expression of the germ line and the effects of environmental contaminants on sexual development.