Special Issue "Bone Ontogeny, Embryology, and Homeostasis".

The intention of this Special Issue is to provide the reader with an in-depth understanding of the ontogeny, embryology, and homeostasis of bone, with an emphasis on recent research that has contributed to our understanding of the skeletal system at the molecular level [...].

A Rare Case of Simultaneous Pheochromocytoma Accompanied with an Ileocecal Neuroendocrine Tumor.

The detection rates of neuroendocrine tumors (NETs) are rising, which has led to a better understanding of their histopathologic characteristics. We present a case of adrenal pheochromocytoma with an incidental finding of a concurrent ileocecal NET detected on early post-adrenalectomy imaging. A 59-year-old male was noted to have microscopic hematuria on a routine workup. Further imaging identified a right adrenal lesion suggestive of pheochromocytoma. He was reporting intermittent headaches, and his urinary normetanephrine and norepinephrine levels were elevated. He underwent a right retroperitoneal adrenalectomy, and pathology confirmed a pheochromocytoma with no malignancy. Postoperatively, he developed a hematoma at the surgical bed that was identified on CT scan. An incidental lesion at the level of the ileocecal valve was noted on the CT scan as well. This was further investigated by colonoscopy and biopsy that confirmed a carcinoid tumor. He had no gastrointestinal symptoms, chromogranin A was normal, and 24-h urinary 5-hydroxyindolacetic acid levels were slightly elevated. He subsequently underwent a laparoscopic right hemicolectomy 3 months from his initial adrenalectomy. Final pathology confirmed a grade 2 NET with metastatic involvement of 4 regional lymph nodes. We report an extremely rare case of simultaneous pheochromocytoma accompanied with an ileocecal NET. Genetic testing for multiple endocrine neoplasia was undertaken and was found negative for 9 tested genes.

Why Measure Patient Experience in Physical Therapy?

BACKGROUND: Patient experience is an important component of quality and patient centered health care not fully explored in physical therapy. MAIN BODY: This article addresses (1) concept of patient experience, (2) importance of capturing the patient experience, (3) measures to capture patient experience and whether these measures exhibit psychometrically sound measurement properties, (4) relationship between patient experience and clinical effectiveness outcomes, and (5) clinical applications of patient experience measures in the outpatient physical therapy setting, including suggestions for future studies. SHORT CONCLUSION: Employing patient experience measures into physical therapy practice may be an important key to improve clinical effectiveness outcomes and provide excellent patient-centered care delivery. An area of continued research should be focused on demonstrating the generalizability and measurement properties of patient reported experience measures for the musculoskeletal outpatient physical therapy population focusing first on the most common musculoskeletal conditions such as cervical, low back, and shoulder pain.

Frontal Plane Rotation of the First Ray in Hallux Valgus using Standing Computerized Tomography (CT).

The purpose of the present study was to analyze the difference in frontal plane rotation of the entire first ray in patients with and without hallux valgus using standing weightbearing computed tomography (CT). Ten feet of 10 patients with hallux valgus and 36 feet of 36 patients without hallux valgus were examined. Standing weightbearing CT scans and radiographs were taken for all subjects. Frontal plane measurements of the sesamoid apparatus, first metatarsal head, first metatarsal base, and medial cuneiform were performed. Frontal plane rotation of the first tarsometatarsal joint and intrinsic first metatarsal torsion was calculated. An independent 2 sample t test was used to compare means of outcomes of interest across control and treatment groups. Statistical significance was set at an alpha level of 0.05. There was a significant increase in pronation of the sesamoid apparatus (23.49° vs 6.60°) and first metatarsal head (17.79° vs 9.81°) in patients with hallux valgus. There was a significant increase in first metatarsal torsion toward pronation in patients with hallux valgus (22.28° vs 13.52°). No significant difference was detected in the rotation at the first tarsometatarsal joint or the frontal plane orientations of the first metatarsal base and medial cuneiform. By examining the frontal plane position of the entire first ray during weightbearing using standing CT in patients with and without hallux valgus, we determined the level at which pronation originates to be within the first metatarsal bone rather than the first tarsometatarsal joint.

A statewide analysis of SARS-CoV-2 transmission in New York

New York State, in particular the New York City metropolitan area, was the early epicenter of the SARS-CoV-2 pandemic in the United States. Similar to initial pandemic dynamics in many metropolitan areas, multiple introductions from various locations appear to have contributed to the swell of positive cases. However, representation and analysis of samples from New York regions outside the greater New York City area were lacking, as were SARS-CoV-2 genomes from the earliest cases associated with the Westchester County outbreak, which represents the first outbreak recorded in New York State. The Wadsworth Center, the public health laboratory of New York State, sought to characterize the transmission dynamics of SARS-CoV-2 across the entire state of New York from March to September with the addition of over 600 genomes from under-sampled and previously unsampled New York counties and to more fully understand the breadth of the initial outbreak in Westchester County. Additional sequencing confirmed the dominance of B.1 and descendant lineages (collectively referred to as B.1.X) in New York State. Community structure, phylogenetic, and phylogeographic analyses suggested that the Westchester outbreak was associated with continued transmission of the virus throughout the state, even after travel restrictions and the on-pause measures of March, contributing to a substantial proportion of the B.1 transmission clusters as of September 30th, 2020.

Exercise as an Adjuvant to Cartilage Regeneration Therapy.

This article provides a brief review of the pathophysiology of osteoarthritis and the ontogeny of chondrocytes and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of autologous chondrocyte implants, matrix-induced autologous chondrocyte implants, and mesenchymal stem cell implants for the successful treatment of damaged articular cartilage and subchondral bone. In response to exercise, articular chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins, and anti-inflammatory cytokines and decrease their production of proinflammatory cytokines and matrix-degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise enhances joint recruitment of bone marrow-derived mesenchymal stem cells and upregulates their expression of osteogenic and chondrogenic genes, osteogenic microRNAs, and osteogenic growth factors. Rodent experiments demonstrate that exercise enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin-1ß, tumor necrosis factor-α, and interferon-γ, while increasing their production of antiosteoclastogenic cytokines interleukin-10 and transforming growth factor-ß. In conclusion, physical exercise done both by bone marrow-derived mesenchymal stem cell donors and recipients and by autologous chondrocyte donor recipients may improve the outcome of osteochondral regeneration therapy and improve skeletal health by downregulating osteoclastogenic cytokine production and upregulating antiosteoclastogenic cytokine production by circulating immune cells.

Osteoclasts and Microgravity.

Astronauts are at risk of losing 1.0% to 1.5% of their bone mass for every month they spend in space despite their adherence to diets and exercise regimens designed to protect their musculoskeletal systems. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells and the contributions macrophage colony stimulating factor, receptor activator of the nuclear factor-kappa B ligand, and the calcineurin pathways make in osteoclast differentiation and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in space, and under conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

The Evolution of Tissue Engineered Vascular Graft Technologies: From Preclinical Trials to Advancing Patient Care.

Currently available synthetic grafts have contributed to improved outcomes in cardiovascular surgery. However, the implementation of these graft materials at small diameters have demonstrated poor patency, inhibiting their use for coronary artery bypass surgery in adults. Additionally, when applied to a pediatric patient population, they are handicapped by their lack of growth ability. Tissue engineered alternatives could possibly address these limitations by producing biocompatible implants with the ability to repair, remodel, grow, and regenerate. A tissue engineered vascular graft (TEVG) generally consists of a scaffold, seeded cells, and the appropriate environmental cues (i.e., growth factors, physical stimulation) to induce tissue formation. This review critically appraises current state-of-the-art techniques for vascular graft production. We additionally examine current graft shortcomings and future prospects, as they relate to cardiovascular surgery, from two major clinical trials.

IL-6 and the dysregulation of immune, bone, muscle, and metabolic homeostasis during spaceflight.

We have previously reported that exercise-related secretion of IL-6 by peripheral blood mononuclear cells is proportionate to body weight, suggesting that IL-6 is gravisensitive and that suboptimal production of this key cytokine may contribute to homeostatic dysregulations that occur during spaceflight. This review details what is known about the role of this key cytokine in innate and adaptive immunity, hematopoiesis, and in bone, muscle and metabolic homeostasis on Earth and in the microgravity of space and suggests an experimental approach to confirm or disavow the role of IL-6 in space-related dysregulations.

Thermoregulatory performance and habitat selection of the eastern box turtle (Terrapene carolina carolina).

Environmental conditions may affect individual physiological processes that influence short-term performance and ultimately growth, survival and reproduction. As such, habitats selected by animals must provide suitable and adequate resources. Ectothermic species are highly dependent on climatic conditions and ambient temperatures that dictate body temperature regulation and in turn physiological processes. We investigated the thermoregulatory performance, habitat selection, and movements of an ectothermic vertebrate, the Eastern box turtle (Terrapene carolina carolina) to assess the importance of thermoregulatory physiology in habitat selection. We evaluated the relationship between habitat selection and thermoregulatory performance in Southwest Ohio over two active seasons from May until October. We found that T. carolina selected shaded habitats, including evergreen and deciduous forests, as well as herbaceous grasslands, conformed to the ambient temperatures throughout the active season, although these habitats had temperatures below those expected based on thermal optima of box turtles. Further, we found that movement was not correlated with internal body temperature. Our study shows that thermal conditions are not paramount in habitat selection of box turtles, but that cooler temperatures do not have an effect on the extent of their locomotion.

Yasuní--a hotspot for jaguars Panthera onca (Carnivora: Felidae)? Camera-traps and jaguar activity at Tiputini Biodiversity Station, Ecuador.

Jaguars (Panthera onca) are the largest predator in lowland forests of Amazonia but there have been few studies on their occurrence and activity in such forests. Here, we used camera traps to document the occurrence and activity of jaguars within a local area (-650ha) of lowland forest of Eastern Ecuador, over two sample periods (2005-2008, 7 222 trap days; 2010-2012, 6 199 trap days). We accumulated 151 independent photos of jaguars (189 total photographs) that represented 21 different individuals, including 11 males (114 photographs), seven females (32 photographs), and three that could not be assigned to a sex. Individual jaguars varied in the number of months they were recorded in the area; ten were photographed in only one month; five were photographed over periods of 8 to 22 months; and five from 45 to 81 months. Capture rates across all camera stations averaged 10.6/1 000 trap days; capture rates did not differ between the two sample periods. Male jaguars were more active during the day (06:00am-18:00pm; 71% of photographs), whereas females were equally active during the day and night. Monthly activity was variable but showed no consistent pattern. Although the study area is much smaller than typical home ranges of jaguars, the area is clearly visited by a large number of different individuals, some of whom repeatedly visit the area, indicating that it forms part of their home range. Other individuals likely were simply passing through the area. Based on the number of jaguars recorded during this study, it is clear that the region is an important area for conservation. Continued protection will be needed to ensure that populations ofjaguars and other species remain viable.

Cardiovascular disease and bridging the diagnostic gap.

Cardiovascular disease (CVD) is now the leading cause of death worldwide. It continues to be on the rise and has become a true pandemic that has no respect to borders.' Coronary artery disease (CAD) is the most common type of CVD. It continues to be the leading cause of mortality both in men and women in the U.S.' Approximately every 25 seconds, an American will suffer an acute coronary syndrome, and approximately every minute someone will die of one. Risk stratification and early disease detection continue to be the bedrock of most preventative strategies. Risk assessment tools like Framingham Heart Score (FHS used in the U.S.), prospective cardiovascular monster (PROCAM used in Germany), or systemic coronary risk evaluation (SCORE used in Europe) are among the common and widely available estimators of a multi-factorial absolute risk of developing CVD.6 Recently, coronary artery calcium (CAC) has emerged as a non-invasive modality that might improve prediction of future cardiovascular events. We have conducted a comprehensive review of CVD risk factors, risk assessment and screening tools being applied to aid in early detection of CVD. As we work on bridging the diagnostic gap of the leading cause of mortality across the globe, utility of accurate and sensitive risk assessment and screening tools for early CVD detection is vital. This will aid in our goal of early detection, modifying risk factors and prevention of CVD incidence.

Doxycycline-induced pancreatitis: a rare finding.

BACKGROUND: Drug-induced pancreatitis (DIP) is a rare problem in medicine. A retrospective study from 45 German centers of gastroenterology concluded that only 22 of 1613 (1.4 percent) cases of acute pancreatitis in 1993 were DIP. Though DIP is a rare etiology of acute pancreatitis compared to other common etiologies like alcohol, gallstones, hypercalcemia, hypertriglyceridemia, infection, trauma or medical procedures like endoscopic retrograde cholangiopancreatography (ERCP), its incidence continues to rise. We report a case of a 21-year-old female with DIP following doxycycline treatment for an upper respiratory infection. CASE: A 21-year-old, otherwise healthy female presented with severe abdominal discomfort associated with nausea and vomiting. She was hemodynamically stable with normal vital signs. Physical exam revealed a soft but tender to palpation epigastric area. Peritoneal signs were negative. Urinalysis was negative for acute infection. Urine human chorionic gonadotrophin was negative for pregnancy. Laboratory findings revealed a mildly elevated lipase level at 128 U/L (normal 13-60) but was otherwise normal. A computed tomography of abdomen and pelvis revealed evidence of fat stranding consistent with acute pancreatitis. A right upper quadrant ultrasound ruled out gallstones. A serum triglyceride was within normal limit at 80mg/dl. She denied any alcohol use. On further questioning, the patient admitted to previously being diagnosed with an upper respiratory infection two weeks earlier. She had consequently finished a 10-day course of doxycycline therapy, with her last dose five days before presentation. After a literature review of drugs implicated in DIP and ruling out other causes of acute pancreatitis, we concluded that our patient had doxycycline-induced pancreatitis. Follow-up visit three weeks post discharge revealed complete resolution of previous symptoms. CONCLUSION: In our vastly evolving pharmacotherapy world, DIP should be entertained as a possible etiology of idiopathic pancreatitis, especially after other common causes have been ruled out.

Ketosis-resistant diabetes: a rare case in unlikely territory.

BACKGROUND: Ketosis-resistant diabetes is a syndrome that has undergone numerous classification schemes in the past. In 1979, the National Diabetes Data Group (NDDG) introduced an association of malnutrition and diabetes. In 1985, the World Health Organization (WHO) created a new diabetes category called malnutrition-related diabetes mellitus (MRDM). MRDM consisted of two subclasses: fibrocalculous pancreatic diabetes (FCPD) and protein-deficient pancreatic diabetes (PDPD). Ketosis-resistant diabetes of the young (KRDY) was included in the subclass of PDPD. We report a rare case of a 37-year-old Sudanese immigrant with ketosis-resistant diabetes. CASE: A previously healthy 37-year-old male presented with increased lethargy, polydipsia, polyuria and weight loss for the last seven to eight months. The patient had immigrated to the U.S. from his native country of Sudan about seven years earlier. He was hemodynamically stable. Physical exam was unremarkable with no evidence of retinopathy or neuropathy. Initial laboratory findings revealed a random blood sugar of 1,409 mg/dl and hemoglobin A1C of 17.8 percent. Urinalysis showed negative proteinuria, positive glycosuria, but only trace ketones were detected. Interestingly, the patient's serum ketones were negative. Arterial blood gas revealed PH 7.37, PCO2 47, P02 108 and HCO3 27. Further diagnostic workup revealed C-peptide 0.36, insulin antibodies less than 2, glutamic acid decarboxylase (GAD) antibodies less than 0.5, ICA 512 antibodies 2.9 and negative anti-islet cell antibodies. An abdominal ultrasound did not show any evidence of pancreatic calcifications or any pathology. Aggressive fluid resuscitation and intravenous insulin was initiated. The patient's hospital course was uncomplicated. He responded well to intravenous insulin drip and hydration. He was eventually transitioned to subcutaneous insulin. He was discharged three days later on a home regimen that included Lantus 28 units SQ at night, Novolog 8 units SQ with meals and a sliding scale with Novolog as needed. The patient's recent follow-up appointment revealed adequate glycemic control with HbA1C level of 7 percent. CONCLUSION: Our patient did not meet criteria for either type 1 or type 2 diabetes mellitus. After a literature review of atypical etiologies of diabetes and comparing them to our patient, we concluded that the most likely diagnosis was KRDY. In light of a high influx of refugees and immigrants to the U.S., we should entertain. KRDY and other rare causes of diabetes mellitus in patients not satisfying criteria of either type 1 or type 2 diabetes.

Simulation of a balloon expandable stent in a realistic coronary artery-Determination of the optimum modelling strategy.

Computational models of stent deployment in arteries have been widely used to shed light on various aspects of stent design and optimisation. In this context, modelling of balloon expandable stents has proved challenging due to the complex mechanics of balloon-stent interaction and the difficulties involved in creating folded balloon geometries. In this study, a method to create a folded balloon model is presented and utilised to numerically model the accurate deployment of a stent in a realistic geometry of an atherosclerotic human coronary artery. Stent deployment is, however, commonly modelled by applying an increasing pressure to the stent, thereby neglecting the balloon. This method is compared to the realistic balloon expansion simulation to fully elucidate the limitations of this procedure. The results illustrate that inclusion of a realistic balloon model is essential for accurate modelling of stent deformation and stent stresses. An alternative balloon simulation procedure is presented however, which overcomes many of the limitations of the applied pressure approach by using elements which restrain the stent as the desired diameter is achieved. This study shows that direct application of pressure to the stent inner surface may be used as an optimal modelling strategy to estimate the stresses in the vessel wall using these restraining elements and hence offer a very efficient alternative approach to numerically modelling stent deployment within complex arterial geometries. The method is limited however, in that it can only predict final stresses in the stented vessel and not those occurring during stent expansion, in which case the balloon expansion model is required.

Regulation and dysregulation of immunoglobulin E: a molecular and clinical perspective.

BACKGROUND: Altered levels of Immunoglobulin E (IgE) represent a dysregulation of IgE synthesis and may be seen in a variety of immunological disorders. The object of this review is to summarize the historical and molecular aspects of IgE synthesis and the disorders associated with dysregulation of IgE production. METHODS: Articles published in Medline/PubMed were searched with the keyword Immunoglobulin E and specific terms such as class switch recombination, deficiency and/or specific disease conditions (atopy, neoplasia, renal disease, myeloma, etc.). The selected papers included reviews, case reports, retrospective reviews and molecular mechanisms. Studies involving both sexes and all ages were included in the analysis. RESULTS: Both very low and elevated levels of IgE may be seen in clinical practice. Major advancements have been made in our understanding of the molecular basis of IgE class switching including roles for T cells, cytokines and T regulatory (or Treg) cells in this process. Dysregulation of this process may result in either elevated IgE levels or IgE deficiency. CONCLUSION: Evaluation of a patient with elevated IgE must involve a detailed differential diagnosis and consideration of various immunological and non-immunological disorders. The use of appropriate tests will allow the correct diagnosis to be made. This can often assist in the development of tailored treatments.