Palatal rugae patterns in Australian Aborigines and Caucasians

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.The purpose of this study was to determine whether rugae patterns change with age and to compare the number and pattern of rugae in Australian Aborigines with those of Caucasians. For the longitudinal part of the study, serial dental casts of ten Aborigines, from 6 to 20 years of age, were examined and rugae patterns were recorded. To enable comparisons to be made between different ethnic groups an additional 100 dental casts of Australian Aborigines and 200 casts of Caucasians, ranging in age from 13 to 17 years, were examined. Characteristics observed were number, length, shape, direction and unification of rugae. The length of rugae increased significantly with age but the total number of rugae remained constant. Thirty-two per cent of rugae showed changes in shape, while 28 per cent displayed a change in orientation. In contrast to studies suggesting that rugae move forward with age, the majority of Aboriginal rugae that changed direction moved posteriorly. Changes in rugae patterns have been assumed to result from pala al growth but alterations in pattern were observed in the Aboriginal sample even after palatal growth had ceased. The mean number of primary rugae in Aborigines was higher than in Caucasians, although more primary rugae in Caucasians exceeded 10 mm in length than in Aborigines. The most common shapes in both ethnic groups were wavy and curved forms, whereas straight and circular types were least common. There was a statistically significant association between rugae forms and ethnicity, straight forms being more common in Caucasians whereas wavy forms were more common in Aborigines.Sunita Kapali, Grant Townsend, Lindsay Richards, Tracey Paris

Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells.

Many therapies using mesenchymal stem cells (MSC) rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR). We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1α and induce transwell migration of CD34(+) hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1α antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA, and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds

Recombinant canine single chain insulin analogues: Insulin receptor binding capacity and ability to stimulate glucose uptake

Virtually all diabetic dogs require exogenous insulin therapy to control their hyperglycaemia. In the UK, the only licensed insulin product currently available is a purified porcine insulin preparation. Recombinant insulin is somewhat problematic in terms of its manufacture, since the gene product (preproinsulin) undergoes substantial post-translational modification in pancreatic β cells before it becomes biologically active. The aim of the present study was to develop recombinant canine single chain insulin (SCI) analogues that could be produced in a prokaryotic expression system and which would require minimal processing. Three recombinant SCI constructs were developed in a prokaryotic expression vector, by replacing the insulin C-peptide sequence with one encoding a synthetic peptide (GGGPGKR), or with one of two insulin-like growth factor (IGF)-2 C-peptide coding sequences (human: SRVSRRSR; canine: SRVTRRSSR). Recombinant proteins were expressed in the periplasmic fraction of Escherichia coli and assessed for their ability to bind to the insulin and IGF-1 receptors, and to stimulate glucose uptake in 3T3-L1 adipocytes. All three recombinant SCI analogues demonstrated preferential binding to the insulin receptor compared to the IGF-1 receptor, with increased binding compared to recombinant canine proinsulin. The recombinant SCI analogues stimulated glucose uptake in 3T3-L1 adipocytes compared to negligible uptake using recombinant canine proinsulin, with the canine insulin/cIGF-2 chimaeric SCI analogue demonstrating the greatest effect. Thus, biologically-active recombinant canine SCI analogues can be produced relatively easily in bacteria, which could potentially be used for treatment of diabetic dogs

Detection of Catecholamines Produced in Planktonic P. aeruginosa and S. aureus Treated with Adult Bovine Serum

Bacterial biofilms play a critical role in inducing and sustaining chronic wounds that are serious health threats. Bacterial biofilms can also be found on medical prosthetics and implants that sustain infections in patients and cause life threatening situations. Bacteria self-produce these sticky extracellular substances termed a biofilm which help them to adhere to each other forming a community of microorganisms. One of the major issues is that biofilms have antimicrobial characteristics and provide protection from the immune system; biofilms are found in over 80% of human bacterial infections. Formation of a bacterial biofilm occurs when an individual (planktonic) bacterial cell attaches to a surface such as collagen exposed in a wound. The planktonic bacterial cell then converts into a biofilm phenotype which allows it to grow and divide on the surface thereby forming layers of microcolonies. After maturation, which is characterized by the production of an extracellular matrix, cells detach from the biofilm and disperse to re-enter the planktonic mode and repeat the biofilm cycle. Under conditions of stress, namely injury or disease, the human body releases adrenaline-like hormones called catecholamines such as epinephrine (adrenaline) and norepinephrine (noradrenaline). Many studies have indicated a close relationship between the presence of catecholamine hormones in a human host and the growth, formation, and virulence of bacterial biofilms. Furthermore, studies from Dr. Isseroff’s dermatology lab at UC Davis confirm that the presence of these catecholamines at dermal wound sites impair the healing process by generating a cellular response through activation of beta-adrenergic receptors. However, few species of bacterial biofilms have been shown to produce catecholamines independently, and none have been shown to produce epinephrine. We examined two species of bacteria commonly found in chronic wounds, Pseudomonas aeruginosa(Gram negative) and Staphylococcus aureus (Gram positive), to determine whether they can produce catecholamines in eukaryotic cell growth conditions. We examined the supernatants of the media after the bacteria were cultured with 0% and 10% concentrations of Adult Bovine Serum (ABS) and then detected for the presence of catecholamines by High Pressure Liquid Chromatography Electrochemical Detection (HPLC-ED)

Regeneration of blood vessels within diabetic wounds after treatment with mesenchymal stem cells

Diabetes is a chronic disease that affects more than 30 million Americans. This disorder leads to a variety of acute and chronic complications, including diabetic ulcers (chronic wounds). Chronic wounds often persist due to poor regeneration of the blood supply which is essential to bring nutrients for healing. Particularly, diabetic individuals are prone to damage in their peripheral tissues which leads to a high prevalence of ulcers in their extremities, often leading to limb amputations. The aim of this study is to improve healing outcomes for diabetics through the use of mesenchymal stem cells (MSCs) to stimulate healing, in which vasculogenesis is an important aspect. Catecholamines such as epinephrine (adrenaline) are prevalent in diabetic foot ulcer tissue and have been shown to inhibit wound healing. In this study, healing rates of type II diabetic mice wounds were evaluated when human MSCs were delivered within a collagen scaffold (IntegraTM) and treated with Timolol, a beta blocker that inhibits the effects of epinephrine. We examined wounded mice after 7 days that had received either no MSCs (control), MSCs, or MSCs treated with timolol for blood vessel development using immunohistochemical staining and confocal fluorescence microscopy. Blood vessel biomarkers GSL-I Isolectin B4 and CD31 were used to stain the wound tissue and fluorescent imaging data was quantified using software. Our results indicate that wound tissue treated with MSCs and timolol had the highest blood vessel regeneration and it was statistically significant when compared to control levels. Additionally, a Fluorescent in situ Hybridization (FISH) protocol to identify human chromosomes was successfully implemented using positive and negative control slides so that human MSCs can be identified when delivered to mouse wound tissue. Future experiments will examine how long the MSCs persist and whether they migrate outside the wound tissue bed

Acute Wounding Alters the Beta2-Adrenergic Signaling and Catecholamine Synthetic Pathways in Keratinocytes

Keratinocyte migration is critical for wound re-epithelialization. Previous studies showed that epinephrine activates the beta2-adrenergic receptor (B2AR), impairing keratinocyte migration. Here, we investigated the keratinocyte catecholamine synthetic pathway in response to acute trauma. Cultured keratinocytes were scratch wounded and expression levels of the B2AR and catecholamine synthetic enzymes tyrosine hydroxylase and phenylethanolamine-N-methyltransferase were assayed. The binding affinity of the B2AR was measured. Wounding downregulated B2AR, tyrosine hydroxylase, and phenylethanolamine-N-methyltransferase expression, but pre-exposure to timolol, a beta-adrenergic receptor antagonist, delayed this effect. In wounded keratinocytes, B2AR-binding affinity remained depressed even after its expression returned to prewounding levels. Keratinocyte-derived norepinephrine increased after wounding. Norepinephrine impaired keratinocyte migration; this effect was abrogated with B2AR-selective antagonist ICI-118,551 but not with B1AR-selective antagonist bisoprolol. Finally, for clinical relevance, we determined that norepinephrine was present in freshly wounded skin, thus providing a potential mechanism for impaired healing by local B2AR activation in wound-edge keratinocytes. Taken together, the data show that keratinocytes modulate catecholamine synthetic enzymes and release norepinephrine after scratch wounding. Norepinephrine appears to be a stress-related mediator that impairs keratinocyte migration through activation of the B2AR. Future therapeutic strategies evaluating modulation of norepinephrine-related effects in the wound are warranted

World allergy organization anaphylaxis guidance 2020

Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions. The occurrence of anaphylaxis has increased in recent years, and subsequently, there is a need to continue disseminating knowledge on the diagnosis and management, so every healthcare professional is prepared to deal with such emergencies. The rationale of this updated position document is the need to keep guidance aligned with the current state of the art of knowledge in anaphylaxis management. The World Allergy Organization (WAO) anaphylaxis guidelines were published in 2011, and the current guidance adopts their major indications, incorporating some novel changes. Intramuscular epinephrine (adrenaline) continues to be the first-line treatment for anaphylaxis. Nevertheless, its use remains suboptimal. After an anaphylaxis occurrence, patients should be referred to a specialist to assess the potential cause and to be educated on prevention of recurrences and self-management. The limited availability of epinephrine auto-injectors remains a major problem in many countries, as well as their affordability for some patients

Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study

The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy

A gravity and magnetic interpretation of the Bay St. George Carboniferous Subbasin in western Newfoundland

Gravity and magnetic data were used to model and interpret the subsurface structure of the Bay St. George Carboniferous Subbasin in western Newfoundland. -- A total of 236 gravity stations with an average spacing of 4.0 km were used. Magnetic data were digitized on a 0.8 km grid from existing 1:63360 scale aeromagnetic maps. Regional and residual anomaly maps for a 5th-order polynomial were obtained for both gravity and magnetic maps using a trend analysis program. -- Densities and magnetic susceptibilities from 242 samples of evaporites, representative sedimentary rocks, and anothositic samples of inferred basement type were determined. -- Program for 2-D and 2.5-D gravity inversion, 2.5-D forward gravity modelling, and 3-D gravity and magnetic modelling were written in FORTRAN and tested. These were used to determine the basement topography, and to delineate faults, obtain thickness estimates of the sedimentary infill, and locate possible new evaporite deposits. -- Results from the 2.5-D inversion compared favorably to the final 3-D gravity model, showing that the 2.5-D process can be used to estimate basement topography. 3-D magnetic modelling confirmed that the basement shape defined by gravity modelling was correct geometrically. -- The results of the modelling were combined with a qualitative interpretation of the gravity and magnetic maps to yield a model of the subsurface geology. Several new faults were located in the subbasin, and several of the old faults were extended. Three possible new evaporite deposits were also located. The maximum thicknesses of the sediments in the basin were discovered to be~6 km in the St. Davids Syncline and 4 to 5 km in the Barachois Synclinorium. The throws of the Crabbes Brook and Shoal Point faults were found to be between 0.5 and 3 km, and 4.5 km, respectively

Vampires: From Bad to Good

Vampires: From Bad to Good: a podcast created and performed by Michael Peavy, Anthony Alvarez, Thomas Roark, Carter McCormack