Cortical Bone Porosity in Rabbit Models of Osteoporosis

Cortical bone porosity is intimately linked with remodeling, is of growing clinical interest, and is increasingly accessible by imaging. Thus, the potential of animal models of osteoporosis (OP) to provide a platform for studying how porosity develops and responds to interventions is tremendous. To date, rabbit models of OP have largely focused on trabecular microarchitecture or bone density; some such as ovariectomy (OVX) have uncertain efficacy and cortical porosity has not been extensively reported. Our primary objective was to characterize tibial cortical porosity in rabbit-based models of OP, including OVX, glucocorticoids (GC), and OVX + GC relative to controls (SHAM). We sought to: (i) test the hypothesis that intracortical remodeling is elevated in these models; (ii) contrast cortical remodeling and porosity in these models with that induced by parathyroid hormone (1–34; PTH); and (iii) contrast trabecular morphology in the proximal tibia across all groups. Evidence that an increase in cortical porosity occurred in all groups was observed, although this was the least robust for GC. Histomorphometric measures supported the hypothesis that remodeling rate was elevated in all groups and also revealed evidence of uncoupling of bone resorption and formation in the GC and OVX + GC groups. For trabecular bone, a pattern of loss was observed for OVX, GC, and OVX + GC groups, whereas the opposite was observed for PTH. Change in trabecular number best explained these patterns. Taken together, the findings indicated rabbit models provide a viable and varied platform for the study of OP and associated changes in cortical remodeling and porosity. Intriguingly, the evidence revealed differing effects on the cortical and trabecular envelopes for the PTH model. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..     

New discoveries and directions for medical, dental and dental hygiene research: low temperature atmospheric pressure plasma

Abstract:  The study of plasma integrates physics, chemistry, biology, and engineering, and has recently engaged medicine and dental hygiene in research efforts. The study of plasma holds promise for a myriad of applications ranging from lasers and electronics, hazardous waste management, decontamination, sterilization and disinfection of foods, soil, water, instruments, to medical uses in wound healing and treating certain types of tumours and cancers. Plasma represents a new state-of-the-art sterilization and disinfection treatment for certain oral and enviornmental pathogens, heat-sensitive materials, contaminated medical waste, hard and soft surfaces, and ventilation systems may assist health care facilities in the management of various health concerns. The role that Low Temperature Atmospheric Pressure Plasma (LTAPP) could play in the inactivation of pathogenic microorganisms might prove to be a new, faster, noncorrosive, more economical alternative, as well as support green healthcare.     

Effects of a nurse-led heart failure clinic on hospital readmission and mortality in Hong Kong

Background Heart failure (HF) is a physically and socially debilitating disease that carries the burden of hospital re-admission and mortality. As an aging society, Hong Kong urgently needs to find ways to reduce the hospital readmission of HF patients. This study evaluates the effects of a nurse-led HF clinic on the hospital readmission and mortality rates among older HF patients in Hong Kong. Methods This study is a retrospective data analysis that compares HF patient in a nurse-led HF clinic in Hong Kong compared with HF patients who did not attend the clinic. The nurses of this clinic provide education on lifestyle modification and symptom monitoring, as well as titrate the medications and measure biochemical markers by following established protocols. This analysis used the socio-demographic and clinical data of HF patients who were aged ≥ 65 years old and stayed in the clinic over a six-month period. Results The data of a total of 78 HF patients were included in this data analysis. The mean age of the patients was 77.38 ± 6.80 years. Approximately half of the HF patients were male (51.3%), almost half were smokers (46.2%), and the majority received ≤ six years of formal education. Most of the HF patients (87.2%) belonged to classes II and III of the New York Heart Association Functional Classification, with a mean ejection fraction of 47.15 ± 20.31 mL. The HF patients who attended the clinic (n = 38, 75.13 ± 5.89 yrs) were significantly younger than those who did not attend the clinic (n = 40, 79.53 ± 6.96 yrs) (P = 0.04), and had lower recorded blood pressure. No other statistically significant difference existed between the socio-demographic and clinical characteristics of the two groups. The HF patients who did not attend the nurse-led HF clinic demonstrated a significantly higher risk of hospital readmission [odd ratio (OR): 7.40; P < 0.01] than those who attended after adjusting for the effect of age and blood pressure. In addition, HF patients who attended the clinic had lower mortality (n = 4) than those who did not attend (n = 14). However, such a difference did not reach statistical significance when the effects of age and blood pressure were adjusted. A significant reduction in systolic blood pressure [F (2, 94) = 3.39, P = 0.04] and diastolic blood pressure [F (2, 94) = 8.48, P < 0.01] was observed among the HF patients who attended the clinic during the six-month period. Conclusions The finding of this study suggests the important role of nurse-led HF clinics in reducing healthcare burden and improving patient outcomes among HF patients in Hong Kong.     

Neurological presentation of Ehlers-Danlos syndrome type IV in a family with parental mosaicism

Ehlers-Danlos syndrome type IV (EDS-IV) is an autosomal-dominant disorder caused by a defect of type III collagen which leads to ruptures of arteries and hollow organs. Neurological presentation with muscle involvement and flexion contractures of the finger joints is uncommon. We clinically characterized seven members of a family with EDS-IV. The index patient, a young woman with an acrogeric face, suffered chronic muscle pain and cramps, Achilles tendon retraction, finger flexion contractures and seizures. The mother had similar features and had experienced an ischemic stroke. Biochemical study in cultured fibroblasts and molecular analysis of the COL3A1 gene led to the diagnosis of EDS-IV. A glycine substitution, p.G883V, within the triple helix of the alpha 1(III) chain, was found in the index patient and in the mother. The maternal grandfather and an aunt each had an abdominal aortic aneurysm, the rupture of which was the cause of death in the latter, at 40 years of age. Surprisingly, we found the mutation, as a mosaic, in the asymptomatic maternal grandmother. This expands the clinical spectrum of EDS type IV and confirms that in some families mosaicism can be identified as the source of the mutation.     

Progress in the autosomal segmental aneusomy syndromes (SASs): single or multi-locus disorders?

Based on cytogenetic observations, several syndromes have been previously identified as microdeletion-based disorders. In this review, recent progress is presented regarding whether one or multiple genes can be implicated in the pathogenesis of these segmentally aneusomic syndromes. The syndromes discussed include Angelman, Alagille, Williams, Langer-Giedeon, Prader-Willi, Smith-Magenis, Miller-Dieker, and DiGeorge/velocardiofacial or the 22q11 deletion syndromes. For Angelman and Alagille syndromes, single genes have been identified, whereas for Williams and Langer-Giedion syndromes, more than one gene can be implicated. Although there has been significant progress in dissecting the molecular basis for the other disorders, the ultimate answer regarding one versus several genes remains to be determined.      

ASRI2005-88 Comparable levels of CD4+CD25+ CTLA4+ Treg cells in peripheral blood of pre-eclampsia and normal pregnant patients

The acceptance of the semiallogeneic fetus within the maternal environment requires tolerance mechanisms not fully characterized yet. Normal pregnancy is known to be associated with a Th2 profile. Furthermore, T-regulatory cells were proposed to regulate the Th2/Th1 balance at early stages of pregnancy. Treg may avoid the shift to a Th1 profile preventing miscarriage. Accordingly, spontaneous abortion is characterized by a Th1 dominance and diminished levels of Tregulatory cells (Treg). The major aim of the present work was to investigate if pre-eclampsia, a late immunological complication of pregnancy, is characterized by similar hallmarks. Therefore, we measured the surface antigens CD4, CD25, CD8, CTLA4 (as well as the secretion of IL-10) in peripheral blood from patients suffering from pre-eclampsia (n = 8) and age-matched patients undergoing normal pregnancies (n = 9) by 4-colour flow-cytometry. We were not able to find any significant differences in the levels of CD4⁺, CD25⁺, CD8⁺, CTLA4, CD4⁺/CD25⁺, CD4⁺/CD25^bright, CD4⁺/CTLA4, CD25⁺/CTLA4, CD4⁺/CD25⁺/CTLA4, CD8⁺/CD25⁺, CD8⁺/CTLA4 or CD8⁺/CD25⁺/CTLA4 cell subsets. Our data suggest that Treg may not participate in the onset of pre-eclampsia and suggest other regulatory mechanisms during late pregnancy.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.