A massively multi-scale approach to characterizing tissue architecture by synchrotron micro-CT applied to the human placenta.

Multi-scale structural assessment of biological soft tissue is challenging but essential to gain insight into structure-function relationships of tissue/organ. Using the human placenta as an example, this study brings together sophisticated sample preparation protocols, advanced imaging and robust, validated machine-learning segmentation techniques to provide the first massively multi-scale and multi-domain information that enables detailed morphological and functional analyses of both maternal and fetal placental domains. Finally, we quantify the scale-dependent error in morphological metrics of heterogeneous placental tissue, estimating the minimal tissue scale needed in extracting meaningful biological data. The developed protocol is beneficial for high-throughput investigation of structure-function relationships in both normal and diseased placentas, allowing us to optimize therapeutic approaches for pathological pregnancies. In addition, the methodology presented is applicable in the characterization of tissue architecture and physiological behaviours of other complex organs with similarity to the placenta, where an exchange barrier possesses circulating vascular and avascular fluid spaces.

Reviewing COVID-19 Modelling amidst Recent United States Protests.

The unfortunate death of George Floyd in Minnesota, following police brutality, is deeply regrettable, and the ensuing protests in cities across the United States bring up issues on the potential impacts of the protests on the epidemiology of COVID-19 in the United States. Modelling scientists will need the best time-series estimates of the numbers of protesters in every city where protests took place; the length of time the protests were active, and what distance and routes were covered by the protesters; and the numbers and distribution of security personnel deployed to keep the protests safe, as well as curtail the chaotic exacerbations that were reported across many areas.

Lemierre syndrome leading to ankylosis of the temporomandibular joint.

Lemierre syndrome, also known as Lemierre's disease is a rare condition that was first described by Andre Lemierre in 1936. We present a case of a 3-year-old boy who presented with ankylosis of the right temporomandibular joint (TMJ) secondary to a mastoid infection as part of Lemierre syndrome. His ankylosis resulted in restricted mouth opening, which had a considerable impact on his speech and ability to eat. Surgical treatment comprising right coronoidectomy, gap arthroplasty of the TMJ, and interpositional fat grafting, enabled him to move his jaw and function has returned. This case report highlights the consequences of Lemierre syndrome and the need for clinicians to be aware of its features and the impact it may have on patients.

Case report of atypical osteonecrosis of the jaws: a clinical dilemma.

Osteonecrosis of the jaws is defined as exposed jawbone that persists for more than eight weeks. Treatment may be challenging and can adversely affect the patient's quality of life. We present a male patient who was referred to our department with areas of extensive osteonecrosis in the maxilla and mandible. He had no history of antiresorptive, antiangiogenic treatments, or radiotherapy to the head and neck. He had a history of renal transplantation, diabetes, glucocorticoids, and periodontal disease. This case highlights multiple aetiological factors that can contribute to osteonecrosis and the diagnostic dilemma that they may cause.

A universal biosensing platform based on optical micro-ring resonators.

The use of optical micro-ring resonators as a platform for quantitative and qualitative biosensing applications was explored. Vertically coupled, high refractive index micro-ring resonators, used as sensing elements, were fabricated on silicon chips by photolithographic techniques. An optical reader system consisting of a near-infrared broad band light source and an optical spectrum analyzer were employed for data acquisition. Micro-ring resonator surfaces were modified with specific target receptors, including antibodies and single-stranded DNA oligonucleotides. The system was successfully used for label-free, specific, and rapid detection of whole bacterial cells, proteins and nucleic acids.

Non-competitive cyclic peptides for targeting enzyme-substrate complexes.

Affinity reagents are of central importance for selectively identifying proteins and investigating their interactions. We report on the development and use of cyclic peptides, identified by mRNA display-based RaPID methodology, that are selective for, and tight binders of, the human hypoxia inducible factor prolyl hydroxylases (PHDs) - enzymes crucial in hypoxia sensing. Biophysical analyses reveal the cyclic peptides to bind in a distinct site, away from the enzyme active site pocket, enabling conservation of substrate binding and catalysis. A biotinylated cyclic peptide captures not only the PHDs, but also their primary substrate hypoxia inducible factor HIF1-α. Our work highlights the potential for tight, non-active site binding cyclic peptides to act as promising affinity reagents for studying protein-protein interactions.

The effect of air-abrasion on the susceptibility of sound enamel to acid challenge.

OBJECTIVE: To evaluate the effect of air-abrasion using three abrasive powders, on the susceptibility of sound enamel to an acid challenge. METHODS: 40 human enamel samples were flattened, polished and assigned to 4 experimental groups (n=10); a: alumina air-abrasion, b: sodium bicarbonate air-abrasion, c: bioactive glass (BAG) air-abrasion and d: no surface treatment (control). White light confocal profilometry was used to measure the step height enamel loss of the abraded area within each sample at three stages; after sample preparation (baseline), after air-abrasion and finally after exposing the samples to pH-cycling for 10 days. Data was analysed statistically using one-way ANOVA with Tukey's HSD post-hoc tests (p<0.05). Unique prismatic structures generated by abrasion and subsequent pH cycling were imaged using multiphoton excitation microscopy, exploiting strong autofluorescence properties of the enamel without labelling. Z-stacks of treated and equivalent control surfaces were used to generate non-destructively 3-dimensional surface profiles similar to those produced by scanning electron microscopy. RESULTS: There was no significant difference in the step height enamel loss after initial surface air-abrasion compared to the negative control group. However, a significant increase in the step height enamel loss was observed in the alumina air-abraded samples after pH-cycling compared to the negative control (p<0.05). Sodium bicarbonate as well as BAG air-abrasion exhibited similar enamel surface loss to that detected in the negative control group (p>0.05). Surface profile examination revealed a deposition effect across sodium bicarbonate and BAG-abraded groups. CONCLUSION: This study demonstrates the importance of powder selection when using air abrasion technology in clinical dentistry. Pre-treating the enamel surface with alumina air-abrasion significantly increased its susceptibility to acid challenge. Therefore, when using alumina air-abrasion clinically, clinicians must be aware that abrading sound enamel excessively renders that surface more susceptible to the effects of acid erosion. BAG and sodium bicarbonate powders were less invasive when compared to the alumina powder, supporting their use for controlled surface stain removal from enamel where indicated clinically.

Endomyocardial biopsy to monitor anthracycline therapy in children.

Evaluation of the ultrastructure of material obtained by endomyocardial biopsy has been proposed as a means to evaluate patients for impending anthracycline cardiotoxicity. Eighteen biopsies obtained from 13 patients (age, 3-18 years) are reported. Twelve biopsy procedures were done to evaluate the cardiac status on reaching a cumulative dose of 400 mg/m2 and three patients had six subsequent biopsies after having received significantly more drug or receiving radiation therapy to the lungs or mediastinum. Scores were assigned to the tissue obtained and used to guide the decision to continue or stop anthracycline therapy. Three patients with abnormal cardiac studies at low cumulative doses, five of whom had received greater than 400 mg/m2 and three of whom had received considerably higher doses and thoracic irradiation were given more drug without incident. Two specimens were interpreted to indicate avoidance of further anthracycline and two patients were cautiously given more despite evidence of mild myocardial damage. These results indicate that endomyocardial biopsies can be performed on a pediatric population with a reasonable complication rate. Further studies should be undertaken to evaluate its usefulness as a means to predict and avoid anthracycline cardiomyopathy.

Diagnosis of neuroblastoma by electron microscopy of bone marrow aspirates.

Three patients are reported in whom the diagnosis of neuroblastoma was made following electron microscopy of a bone marrow aspirate. The ultrastructure of neuroblastoma cells is distinctive, and they can be distinguished by electron microscopy from cells of the other tumors with which neuroblastoma is often confused by light microscopy. The rapidity with which the diagnosis can be obtained through use of this procedure argues for its adoption in any patient in whom the diagnosis is suspected and who has tumor cells in bone marrow. Early initiation of appropriate therapy is made possible, and elaborate diagnostic procedures may be avoided.

The significance of elongation and angulation of the carotid artery: a negative view.

Many authors have postulated that angulation of the carotid artery is a cause of stroke and recommend corrective operation. Symptoms attributed to such lesions are often nebulous and unrelieved by the operation, and proof is lacking that unselected patients who have this condition have a risk of stroke exceeding operative risk. A review of 282 cerebral angiograms showed an incidence of elongation and potential angulation of 43 percent in children and 20 percent in adults. Acutal angulation was not found in children, however, and no child was suspected of having cerebral ischemia. Of 47 adults with potential angulation, 17 were suspected of having cerebral ischemia, the remainder having a variety of other lesions, such as tumors, aneurysm, and intracranial hemorrhage. Of the 17 having suspected cerebral ischemia, all had alternative explanations for their symptoms (hypertension, intracranial atherosclerosis), except one whose symptoms were completely inappropriate to the carotid distribution. A single patient had a completed stroke, demonstrable angulation, and only mild hypertension. Elongation and potential angulation of the carotid artery is common but usually coexists with other lesions. If the finding is postulated as the cause for neurologic morbidity the surgeon must be assured that symptoms are clearly neurologic, that no other cause exists, that angulation reduces the carotid lumen significantly and reproduces symptoms, and that the risk of operation is less than the expected risk of stroke in untreated patients.

Massive intracerebral hemorrhage following carotid endarterectomy.

To our knowledge, a particularly lethal complication of carotid endarterectomy, intracerebral hemorrhage, has not been given due consideration in the literature concerning carotid surgery. In the Atlanta area, massive intracranial hemorrhage developed in ten patients following routine carotid endarterectomies performed during a recent ten-year period. All ten of the patients in this series died despite a variety of therapeutic interventions. Risk factors may include the following: extreme arterial stenosis with resultant postoperative hyperperfusion, involvement of multiple extracranial cerebral vessels, postoperative systemic hypertension, and administration of anticoagulant or antiplatelet medications. Unfortunately, identification of the subset of patients potentially at risk for this complication is difficult, and, to date, therapy has been generally ineffective.

Spondylolysis.

Spondylolysis is a relatively common incidental radiographic finding that, most frequently, is asymptomatic. Isthmic spondylolysis with a lesion in the pars interarticularis may be a significant cause of pain in a given individual, particularly in adolescent athletes involved in sports with repetitive spinal motions. The pars lesion likely represents a stress fracture of the bone caused by the cumulative effect of repetitive stress imposed by physical activity. The lesion frequently presents as focal LBP and can often be identified on plain radiography. Advanced imaging with SPECT, CT, and MR imaging may be needed to ascertain the acuity of the lesion, assist in identifying a particular pars lesion as potentially symptomatic, and to exclude other spinal pathology that may be present. Conservative treatment is usually successful in controlling symptoms and restoring function; only a small percentage of patients require surgical intervention for pain or progressive spondylolisthesis. Based on current evidence, treatment requires activity restriction (i.e., temporary discontinuation of the aggravating sport or activity) and may require bracing to achieve treatment goals, although healing, pain relief or both may occur without brace application. A full understanding of spinal biomechanics and pathophysiology, the role of diagnostic imaging, and treatment options is needed to care for these patients.