Turbinal bones are still one of the last frontiers of the tetrapod skull: hypotheses, challenges and perspectives.

Turbinals are bony or cartilaginous structures that are present in the nasal cavity of most tetrapods. They are involved in key functions such as olfaction, heat, and moisture conservation, as well as protection of the respiratory tract. Despite recent studies that challenged long-standing hypotheses about their physiological and genomic correlation, turbinals remain largely unexplored, particularly for non-mammalian species. Herein, we review and synthesise the current knowledge of turbinals using an integrative approach that includes comparative anatomy, physiology, histology and genomics. In addition, we provide synonyms and correspondences of tetrapod turbinals from about 80 publications. This work represents a first step towards drawing hypotheses of homology for the whole clade, and provides a strong basis to develop new research avenues.

Functional microanatomy of the vomeronasal complex of bats.

Recently, Yohe and Krell (The Anatomical Record, vol. 306:2765-2780) lamented the incongruence between genetics and morphology in the vomeronasal system of bats. Here, we studied 105 bat species from 19 families using histology, iodine-enhanced computed tomography (CT), and/or micro-CT. We focused on structural elements that support a functional peripheral vomeronasal receptor organ (vomeronasal organ [VNO]), together comprising the "vomeronasal complex." Our results support prior studies that describe a functional VNO in most phyllostomid bats, miniopterids, and some mormoopids (most known Pteronotus spp.). All of these species (or congeners, at least) have vomeronasal nerves connecting the VNO with the brain and some intact genes related to a functional VNO. However, some bats have VNOs that lack a neuroepithelium and yet still possess elements that aid VNO function, such as a "capsular" morphology of the vomeronasal cartilages (VNCs), and even large venous sinuses, which together facilitate a vasomotor pump mechanism that can draw fluid into the VNO. We also show that ostensibly functionless VNOs of some bats are developmentally associated with ganglionic masses, perhaps involved in endocrine pathways. Finally, we demonstrate that the capsular VNC articulates with the premaxilla or maxilla, and that these bones bear visible grooves denoting the location of the VNC. Since these paraseptal grooves are absent in bats that have simpler (bar-shaped or curved) VNCs, this trait could be useful in fossil studies. Variable retention of some but not all "functional" elements of the vomeronasal complex suggests diverse mechanisms of VNO loss among some bat lineages.

Prevalence and risk factors for milk allergy overdiagnosis in the BEEP trial cohort.

BACKGROUND: Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual-level and primary care practice-level risk factors. METHODS: We analysed data from 1394 children born in England in 2014-2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent-reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low-allergy formula prescription. RESULTS: CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent-reported cow's milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low-allergy formula prescription. Symptoms attributed to cow's milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low-allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice-based low-allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low-allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto-injectors or anti-reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis. CONCLUSION: CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice-based low-allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.

From masks to muscles: Mapping facial structure of Nycticebus.

Facial musculature in mammals underlies mastication and nonverbal communicative facial displays. Our understanding of primate facial expression comes primarily from haplorrhines (monkeys and apes), while our understanding of strepsirrhine (lemurs and lorises) facial expression remains incomplete. We examined the facial muscles of six specimens from three Nycticebus species (Nycticebus coucang, Nycticebus javanicus, and Nycticebus menagensis) using traditional dissection methodology and novel three-dimensional facial scanning to produce a detailed facial muscle map, and compared these results to another nocturnal strepsirrhine genus, the greater bushbaby (Otolemur spp.). We observed 19 muscles with no differences among Nycticebus specimens. A total of 17 muscles were observed in both Nycticebus and Otolemur, with little difference in attachment and function but some difference in directionality of movement. In the oral region, we note the presence of the depressor anguli oris, which has been reported in other primate species but is absent in Otolemur. The remaining muscle is a previously undescribed constrictor nasalis muscle located on the lateral nasal alar region, likely responsible for constriction of the nares. We propose this newly described muscle may relate to vomeronasal organ functioning and the importance of the use of nasal musculature in olfactory communication. We discuss how this combined methodology enabled imaging of small complex muscles. We further discuss how the facial anatomy of Nycticebus spp. relates to their unique physiology and behavioral ecology.

Developmental milestones in captive Galago moholi.

Systems of the body develop in a modular manner. For example, neural development in primates is generally rapid, whereas dental development varies much more. In the present study, we examined development of the skull, teeth, and postcrania in a highly specialized leaping primate, Galago moholi. Eighteen specimens ranging from birth to adult were studied. Bones, teeth, and the cranial cavity (i.e., endocast) were reconstructed with Amira software based on microCT cross-referenced to histology. Amira was also used to compute endocast volume (as a proxy for brain size). Reconstructions of the wrist and ankle show that ossification is complete at 1 month postnatally, consistent with the onset of leaping locomotion in this species. Endocranial volume is less than 50% of adult volume at birth, ~80% by 1 month, and has reached adult volume by 2 months postnatal age. Full deciduous dentition eruption occurs by 2 weeks, and the young are known to begin capturing and consuming arthropods on their own by 4 weeks, contemporaneous with the timing of bone and ankle ossification that accompanies successful hunting. The modular pattern of development of body systems in Galago moholi provides an interesting view of a "race" to adult morphology for some joints that are critical for specialized leaping and clinging, rapid crown mineralization to begin a transitional diet, but perhaps more prolonged reliance on nursing to support brain growth.

Space invaders: Reassessing the histology of hyperostosis frontalis interna.

Hyperostosis frontalis interna (HFI) is a human skeletal lesion characterized by nodules of hyperplastic bone and thickening of the frontal bone's inner surface. Despite its prevalence in the general population and its long history of observation-it is one of the most frequently observed pathologies in gross anatomy laboratories-HFI's etiology and pathogenesis remain poorly understood. This is largely due to the lack of a thorough survey of its histology across the various stages of its development. Our study has three major aims: (1) assess HFI histology from incipient to advanced lesions; (2) elucidate lamellar and trabecular structure in HFI; and (3) clarify impacts/roles of the dura mater in HFI. Sections of nondecalcified bone provide evidence for two different categories of lesions: (1) stratum lesions, characterized by lamellar-based overall thickening of the internal table, and (2) eruptive lesions, characterized by nodular formations of initially lamellar bone that appear to form the bulk of bone mass in advanced stages. Sections of nondecalcified bone also suggest that for both lesion types, HFI growths begin as deposits of lamellar bone, which are later remodeled into woven bone deposits; our data do not support the hypothesis that lesions begin as a "diploization" of cortical bone as suggested by prior studies. Trichrome-stained sections provide evidence that growing lesions erode through and engulf the dura mater, effectively destroying this tissue layer as they grow laterally and inwardly. Our results indicate possible avenues of research to better understand the root causes of this disorder.

Growth and microanatomy of the paranasal sinuses in two species of New World monkeys.

Paranasal sinuses of living apes and humans grow with positive allometry, suggesting a novel mechanism for bone enlargement. Here, we examine the paranasal sinuses of the owl monkey (Aotus spp.) and a tamarin (Saguinus midas) across postnatal development. The prediction that paranasal sinuses grow disproportionately faster than the main nasal chamber is tested. We used diffusible iodine-based contrast-enhanced computed tomography and histology to study sinuses in eight Aotus and three tamarins ranging from newborn to adult ages. Sinuses were segmented at the mucosa-air cavity interface and measured in volume. All sinuses were lined by a ciliated respiratory epithelium, except for the ethmoid air cells in Aotus, which are lined in part by olfactory epithelium. An age comparison indicates that only the maxillary sinus and ethmoid air cells are present in newborns, and two additional sinuses (invading the orbitosphenoid and the frontal bone), do not appear until late infancy or later. Comparing newborns and adults, the main nasal airway is 10 times larger in the adult Aotus and ~ 6.5 times larger in adult Saguinus. In contrast, the maxillary sinus far exceeds this magnitude of difference: 24 times larger in the adult Aotus and 46 times larger in adult Saguinus. The frontal sinuses add significantly to total paranasal space volume in both species, but this growth is likely delayed until juvenile age. Results suggest ethmoid air cells expand the least. These results support our prediction that most paranasal sinuses have a distinctly higher growth rate compared to the main nasal chamber.

Ecomorphology and sensory biology of bats.

This special issue of The Anatomical Record is inspired by and dedicated to Professor Kunwar P. Bhatnagar, whose lifelong interests in biology, and long career studying bats, inspired many and advanced our knowledge of the world's only flying mammals. The 15 articles included here represent a broad range of investigators, treading topics familiar to Prof. Bhatnagar, who was interested in seemingly every aspect of bat biology. Key topics include broad themes of bat development, sensory systems, and specializations related to flight and diet. These articles paint a complex picture of the fascinating adaptations of bats, such as rapid fore limb development, ear morphologies relating to echolocation, and other enhanced senses that allow bats to exploit niches in virtually every part of the world. In this introduction, we integrate and contextualize these articles within the broader story of bat ecomorphology, providing an overview of each of the key themes noted above. This special issue will serve as a springboard for future studies both in bat biology and in the broader world of mammalian comparative anatomy and ecomorphology.

Neuronal scaling in the olfactory system of bats.

Comparative studies are a common way to address large-scale questions in sensory biology. For studies that investigate olfactory abilities, the most commonly used metric is olfactory bulb size. However, recent work has called into question the broad-scale use of olfactory bulb size. In this paper, we use three neuroanatomical measures with a more mechanistic link to olfactory function (number of olfactory sensory neurons (OSNs), number of mitral cells (MCs), and number of glomeruli) to ask how species with different diets may differ with respect to olfactory ability. We use phyllostomid bats as our study system because behavioral and physiological work has shown that fruit- and nectar-feeding phyllostomids rely on odors for detecting, localizing, and assessing potential foods, while insect-eating species do not. Therefore, we predicted that fruit- and nectar-feeding bats would have larger numbers of these three neuroanatomical measures than insect-eating species. In general, our results supported the predictions. We found that fruit-eaters had greater numbers of OSNs and glomeruli than insect-eaters, but we found no difference between groups in number of MCs. We also examined the allometric relationship between the three neuroanatomical variables and olfactory bulb volume, and we found isometry in all cases. These findings lend support to the notion that neuroanatomical measures can offer valuable insights into comparative olfactory abilities, and suggest that the size of the olfactory bulb may be an informative parameter to use at the whole-organism level.

Prognostic significance of haemodynamic parameters in patients with cardiogenic shock.

AIMS: Invasive haemodynamic assessment with a pulmonary artery catheter is often used to guide the management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting haemodynamic parameters in CS. METHODS AND RESULTS: The Critical Care Cardiology Trials Network is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018-2022) who underwent invasive haemodynamic assessment within 24 h of CICU admission were included. Associations of haemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score. Among the 3603 admissions with CS, 1473 had haemodynamic data collected within 24 h of CICU admission. The median cardiac index was 1.9 (25th-75th percentile, 1.6-2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66-86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for the intensity of background pharmacologic and mechanical haemodynamic support. These parameters were also associated with higher presenting serum lactate. CONCLUSION: In a contemporary CS population, presenting haemodynamic parameters reflecting decreased systemic arterial tone and right ventricular dysfunction are associated with adverse outcomes and systemic hypoperfusion.

Renal impairment and mortality in patients with STEMI and cardiogenic shock/cardiac arrest.

OBJECTIVES: We sought to study the association of renal impairment (RI) with mortality in ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock and/or cardiac arrest (CS/CA). METHODS: Patients with RI (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) were identified from the Midwest STEMI consortium, a prospective registry of four large regional programs comprising consecutive patients over 17 years. Primary outcome was in-hospital and 1-year mortality stratified by RI status and presence of CS/CA among patients with STEMI referred for coronary angiography. RESULTS: In a cohort of 13,463 STEMI patients, 13% (n = 1754) had CS/CA, 30% (n = 4085) had RI. Overall, in-hospital mortality was 5% (12% RI vs. 2% no-RI, p < 0.001) and 1-year mortality 9% (21% RI vs. 4% no-RI, p < 0.001). Among uncomplicated STEMI, in-hospital mortality was 2% (4% RI vs. 1% no-RI, p < 0.001) and 1-year mortality 6% (13% RI vs. 3% no-RI, p < 0.001). In STEMI with CS/CA, in-hospital mortality was 29% (43% RI vs. 15% no-RI, p < 0.001) and 1-year mortality 33% (50% RI vs. 16% no-RI, p < 0.001). Using Cox proportional hazards, RI was an independent predictor of in-hospital mortality in STEMI with CS/CA (odds ratio [OR]: 3.86; confidence interval [CI]: 2.6, 5.8). CONCLUSIONS: The association of RI with in-hospital and 1-year mortality is disproportionately greater in those with CS/CA compared to uncomplicated STEMI presentations. Factors predisposing RI patients to higher risk STEMI presentations and pathways to promote earlier recognition in the chain of survival need further investigation.

Mechanical Circulatory Support in COVID-19.

Despite aggressive care, patients with cardiopulmonary failure and COVID-19 experience unacceptably high mortality rates. The use of mechanical circulatory support devices in this population offers potential benefits but confers significant morbidity and novel challenges for the clinician. Thoughtful application of this complex technology is of the utmost importance and should be done in a multidisciplinary fashion by teams familiar with mechanical support devices and aware of the particular challenges provided by this complex patient population.

How to make a vampire.

Herein, we compared the developmental maturity of the cranium, limbs, and feeding apparatus in a perinatal common vampire bat relative to its mother. In addition, we introduce a method for combining two computed tomographic imaging techniques to three-dimensionally reconstruct endocasts in poorly ossified crania. The Desmodus specimens were scanned using microcomputed tomography (microCT) and diffusible iodine-based contrast-enhanced CT to image bone and soft tissues. Muscles of the jaw and limbs, and the endocranial cavity were segmented using imaging software. Endocranial volume (ECV) of the perinatal Desmodus is 74% of adult ECV. The facial skeletal is less developed (e.g., palatal length 60% of adult length), but volumes for alveolar crypts/sockets of permanent teeth are nearly identical. The forelimb skeleton is uniformly less ossified than the distal hind limb, with no secondary centers ossified and an entirely cartilaginous carpus. All epiphyseal growth zones are active in the brachium and antebrachium, with the distal radius exhibiting the greatest number of proliferating chondrocytes arranged in columns. The hind limb skeleton is precociously ossified from the knee distally. The musculature of the fore limb, temporalis, and masseter muscles appear weakly developed (6-11% of the adult volume). In contrast, the leg and foot musculature is better developed (23-25% of adult volume), possibly enhancing the newborn's capability to grip the mother's fur. Desmodus is born relatively large, and our results suggest they are born neurally and dentally precocious, with generally underdeveloped limbs, especially the fore limb.

Ontogenetic transformation of the cartilaginous nasal capsule in mammals, a review with new observations on bats.

The nasal capsule, as the most rostral part of the chondrocranium, is a critical point of connection with the facial skeleton. Its fate may influence facial form, and the varied fates of cartilage may be a vehicle contributing to morphological diversity. Here, we review ontogenetic changes in the cartilaginous nasal capsule of mammals, and make new observations on perinatal specimens of two chiropteran species of different suborders. Our observations reveal some commonalities between Rousettus leschenaultii and Desmodus rotundus, such as perinatal ossification of the first ethmoturbinal. However, in Rousettus, ossification of turbinals is demonstrated as either perichondrial or endochondral. In Desmodus, perichondrial and endochondral ossification of the posterior nasal cupula is observed at birth, a part of the nasal capsule previously shown to persist as cartilage into infancy in Rousettus. Combined with prior findings on cranial cartilages we identify several diverse transformational mechanisms by which cartilage as a tissue type may contribute to morphological diversity of the cranium. First, cartilage differentiates in an iterative fashion to increase nasal complexity, but still retains the capacity for later elaboration via de novo bone emanating outward before or after cartilage ossifies. Second, cartilage acts as a driver of growth at growth centers, or via interstitial growth (e.g., septal cartilage). Finally, cartilage as a tissue may influence the timing of ossification and union of the facial and basicranial skeleton. In particular, cartilage at certain points of ontogeny may "model" via selective resorption, showing some similarity to bone.

Intravascular Lithotripsy for Treatment of Calcified Coronary Artery Disease.

Intravascular lithotripsy (IVL) uses acoustic shock waves in a balloon-based delivery system to modify severely calcified atherosclerotic coronary vascular lesions in preparation for stent implantation. IVL results in circumferential and longitudinal calcium fracture, which improves transmural vessel compliance and facilitates subsequent stent expansion without requiring high-pressure balloon dilation. Clinical trials have demonstrated IVL to be safe (low rates of major adverse cardiac events in hospital and to 1 year; low rates of severe angiographic complications), effective (high rates of procedural success), and easy to use (little or no learning curve) when applied in the treatment of severely calcified coronary arteries.

Critical Care Cardiology Trials Network (CCCTN): a cohort profile.

AIMS: The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicentre research network to conduct randomised clinical trials (RCTs) in patients with cardiac critical illness. METHODS AND RESULTS: The CCCTN was founded in 2017 with 16 centres and has grown to a research network of over 40 academic and clinical centres in the United States and Canada. Each centre enters data for consecutive cardiac intensive care unit (CICU) admissions for at least 2 months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterised utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicentre collaboration, the CCCTN has established a robust research network to facilitate multicentre registry-based randomised trials in patients with cardiac critical illness. CONCLUSION: The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomised controlled trials in this important patient population.

Mechanical Circulatory Support in COVID-19.

Despite aggressive care, patients with cardiopulmonary failure and COVID-19 experience unacceptably high mortality rates. The use of mechanical circulatory support devices in this population offers potential benefits but confers significant morbidity and novel challenges for the clinician. Thoughtful application of this complex technology is of the utmost importance and should be done in a multidisciplinary fashion by teams familiar with mechanical support devices and aware of the particular challenges provided by this complex patient population.