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.

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.

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.

Vertically coupled GaInAsP--InP microring resonators.

Vertically coupled microring resonator channel-dropping filters are demonstrated in the GaInAsP-InP material system. These devices were fabricated without regrowth. In this method, low-loss single-mode waveguides are removed from the growth substrate and bonded to a GaAs transfer substrate with benzocyclobutene. This permits fabrication of vertically coupled waveguides on both sides of the epilayer. Optical quality facets are obtained by cleaving through the transfer substrate. Operation of single-mode, single-ring optical channel-dropping filters is demonstrated.

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.

Directional, enhanced fluorescence from molecules near a periodic surface.

We extend the research of Holland and Hall on the use of waveguide modes to enhance the fluorescent signal from a layer of molecules [Opt. Lett. 10,414 (1985)] by incorporating a grating into the basic sample structure. Our measurements show that the combination of the directionality imposed by the grating and the previously reported enhancement mechanism has the effect of increasing the intensity of the signal detected over a narrow angular range from a layer of fluorescing molecules by a factor of ~ 1000 over that from a reference sample. Simultaneously our method allows for both polarization and wavelength discrimination of the emitted radiation because of the characteristic nature of the incorporated grating.

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.

Peak cerebrospinal fluid platinum levels in a patient with ependymoma: evaluation of two different methods of cisplatin administration.

Peak CSF and serum platinum levels were examined in a patient with ependymoma after each of four consecutive cisplatin doses of 100 mg/m2 administered by either 30-minute or 3-hour infusion. Both infusion lengths produced similar peak CSF platinum levels within 2 hours after the completion. Ultrafiltrate serum platinum levels correlated with the CSF platinum levels, whereas total plasma platinum did not. No differences in clinical toxicity or response were seen between the two methods of administration. Based on these preliminary results, similar peak CSF platinum concentrations are achieved by 30-minute or 3-hour infusions, and ultrafiltrate serum platinum concentrations can be used to predict these levels.

Neuro-ocular damage in pediatric oncology patients: predictor of long-term visual disability or tool for limiting toxicity?

We present a group of eight pediatric cancer patients with a spectrum of visual afferent pathway abnormalities. Changes include decreased visual acuity, visual field alterations, abnormal visual evoked potentials, changes in the optic disc and nerve fiber layer of the retina, radiation retinopathy, and CNS injury. These changes occur in long term survivors of pediatric malignancy (especially those with prolonged, multimodal, and multicourse therapy), but they may be minimally symptomatic. The changes appear to be analogous to the CNS changes (leukoencephalopathy) described in patients with leukemia and attributed to multimodal therapy. By taking advantage of opportunities to detect adverse effects earlier in the treatment course, the present excellent cure rate may be improved by refinements in therapy that also improve the quality of survival.

Ultrafiltrate and total platinum in plasma and cerebrospinal fluid in a patient with neuroblastoma.

Ultrafiltrate and total plasma and cerebrospinal fluid (CSF) platinum concentrations were examined in a patient with neuroblastoma following a 2-hour infusion of 120 mg/m2 of cisplatin. Total plasma platinum was 93.4% bound, while the ultrafiltrate of plasma accounted for the remaining 6.6%. The CSF ultrafiltrate resulted in equivalent concentrations of platinum to total CSF platinum. CSF concentrations were 2.9% of the total plasma platinum and 43.5% of the ultrafiltrate plasma platinum 2 hours after the end of the infusion.

Immunoreactive calcitonin in brain regions and pituitary of sheep.

In this study we have investigated the presence of immunoreactive calcitonin in the central nervous system and pituitary of sheep. The calcitonin concentrations were determined radioimmunologically by two different antibodies. We have demonstrated calcitonin in extracts of areas of the central nervous system, whole pituitary, thyroid gland and plasma of 21 sheep. The concentrations were (ng/g wet weight, mean values +/- SE): thyroid 16.0 +/- 4.4, pituitary 2.03 +/- 0.34, reticular formation 1.64 +/- 0.25, substantia nigra 1.53 +/- 0.46, dentate nucleus 1.11 +/- 0.27, putamen 1.05 +/- 0.35, hippocampus 0.97 +/- 0.17, fornix 0.96 +/- 0.15, anterior thalamus 0.92 +/- 0.28, mammillary body 0.88 +/- 0.12, cerebellum 0.86 +/- 0.09, caudate nucleus 0.84 +/- 0.11, posterior hypothalamus 0.83 +/- 0.19, epiphysis 0.75 +/- 0.25, thalamus centralis 0.71 +/- 0.10, almond nucleus 0.69 +/- 0.16, medulla oblongata 0.67 +/- 0.15, anterior hypothalamus 0.66 +/- 0.20, precentral gyrus 0.66 +/- 0.16, globus pallidus 0.63 +/- 0.31, postcentral gyrus 0.36 +/- 0.08 and plasma (ng/ml) 0.058 +/- 0.013. Our results demonstrate that immunoreactive calcitonin is present in the central nervous system (CNS) of sheep, compatible with a neurotransmitter function for this hormone.

Distribution and concentration of immunoreactive parathyroid hormone in brain and pituitary of sheep.

We have studied the presence of immunoreactive parathyroid hormone (PTH) in the central nervous system and pituitary of sheep. The PTH concentrations were measured radioimmunologically by two different region-specific antibodies. We could demonstrate PTH in various areas of the brain, whole pituitary, parathyroid glands and plasma of 21 sheep. Measurable concentrations of the two different parathyroid regions (35-84 and 44-68 amino acids fragments) were found in all samples.