Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) R47H Variant Causes Distinct Age- and Sex-Dependent Musculoskeletal Alterations in Mice

Previous studies proposed the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a receptor expressed in myeloid cells including microglia in brain and osteoclasts in bone, as a link between brain and bone disease. The TREM2 R47H variant is a known risk factor for Alzheimer's disease (AD), the most common form of dementia. To investigate whether altered TREM2 signaling could contribute to bone and skeletal muscle loss, independently of central nervous system defects, we used mice globally hemizygous for the TREM2 R47H variant (TREM2^R47H/+), which do not exhibit AD pathology, and wild-type (WT) littermate control mice. Dxa/Piximus showed bone loss in female TREM2^R47H/+ animals between 4 and 13 months of age and reduced cancellous and cortical bone (measured by micro-computed tomography [μCT]) at 13 months, which stalled out by 20 months of age. In addition, they exhibited decreased femoral biomechanical properties measured by three-point bending at 13 months of age, but not at 4 or 20 months. Male TREM2^R47H/+ animals had decreased trabecular bone geometry but increased ultimate strain and failure force at 20 months of age versus WT. Only male TREM2^R47H/+ osteoclasts differentiated more ex vivo after 7 days with receptor activator of nuclear factor κB ligand (RANKL)/macrophage colony-stimulating factor (M-CSF) compared to WT littermates. Yet, estrogen receptor alpha expression was higher in female and male TREM2^R47H/+ osteoclasts compared to WT mice. However, female TREM2^R47H/+ osteoclasts expressed less complement 3 (C3), an estrogen responsive element, and increased protein kinase B (Akt) activity, suggesting altered estrogen signaling in TREM2^R47H/+ cells. Despite lower bone volume/strength in TREM2^R47H/+ mice, skeletal muscle function measured by plantar flexion and muscle contractility was increased in 13-month-old female mutant mice. Overall, these data demonstrate that an AD-associated TREM2 variant can alter bone and skeletal muscle strength in a sex-dimorphic manner independent of central neuropathology, potentially mediated through changes in osteoclastic intracellular signaling. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Echocardiography in adult patients with PDA: A simplified approach

Patent ductus arteriosus is a common congenital heart anomaly in the newborn and children. It is often diagnosed and treated in childhood; however, there are a subset of patients who survive to adulthood undiagnosed, and it is present in adulthood with various clinical presentations. The clinical presentation, hemodynamics, and management of PDA presentation in adults depend on various factors, primarily the size of PDA, magnitude of shunting, and status of pulmonary vasculature. Echocardiography is often the primary imaging modality in the evaluation of adult patients with PDA and is an important tool that provides diagnostic and hemodynamic assessment for the initial evaluation and routine follow-up after PDA closure. In this review, we present a simplified approach of basic echocardiographic assessment of various types of PDA presentations in adults.     

Infratemporal fossa myoepithelial carcinoma—a rare case report

Introduction

Myoepithelial tumours are rare clinicopathological identity. It has been found in parotid glands and salivary glands but never reported in infratemporal fossa or other sites of lateral skull base region.

Discussion

Unlike its benign counterpart, myoepithelial carcinoma is biologically very aggressive and prone to recur even after adequate therapy.

Case report

Here, a rare case of myoepithelial carcinoma arising from infratemporal fossa has been described along with its treatment options and outcome.     

Buonocore memorial lecture. Adhesion to enamel and dentin: current status and future challenges

Bonding to tooth tissue can be achieved through an "etch&rinse," "self-etch" or "glass-ionomer" approach. In this paper, the basic bonding mechanism to enamel and dentin of these three approaches is demonstrated by means of ultramorphological and chemical characterization of tooth-biomaterial interfacial interactions. Furthermore, bond-strength testing and measurement of marginal-sealing effectiveness (the two most commonly employed methodologies to determine "bonding effectiveness" in the laboratory) are evaluated upon their value and relevance in predicting clinical performance. A new dynamic methodology to test biomaterial-tooth bonds in a fatigue mode is introduced with a recently developed micro-rotary fatigue-testing device. Eventually, today's adhesives will be critically weighted upon their performance in diverse laboratory studies and clinical trials. Special attention has been given to the benefits/drawbacks of an etch&rinse versus a self-etch approach and the long-term performance of these adhesives. Correlating data gathered in the laboratory with clinical results clearly showed that laboratory research CAN predict clinical effectiveness. Although there is a tendency to simplify bonding procedures, the data presented confirm that conventional three-step etch&rinse adhesives still perform most favorably and are most reliable in the long-term. Nevertheless, a self-etch approach may have the best future perspective. Clinically, when adhesives no longer require an "etch&rinse" step, the application time, and probably more importantly, the technique-sensitivity are substantially reduced. Especially "mild," two-step self-etch adhesives that bond through a combined micromechanical and chemical interaction with tooth tissue closely approach conventional three-step systems in bonding performance.     

Unique Doppler pattern of "obstruction alternans" of a St Jude prosthetic mitral valve.

We present a case of a patient who was pregnant and had symptomatic, intermittent obstruction of her St Jude mitral prosthesis showing a very unique Doppler flow pattern suggesting impaired disk movement with every other cardiac cycle. Mechanism of this "obstruction alternans" is discussed.     

Nutritional Status and Physical Fitness of Tribal Adolescents in Ahmednagar District of Maharashtra

We examined the influence of nutritional status, body fat, and anemia on the physical fitness (PFI) of tribal adolescents. Weight, height, skinfold thickness, PFI, and hemoglobin levels of 147 adolescents (11 to 16 years) were measured. The experience of cycling was recorded. Overall, 31.3% were mildly, 12.9% were moderately, and 10.9% were severely thin. The majority (81.6%) were nonanemic. All had “poor” PFI scores. Hemoglobin levels were significantly associated with PFI scores in boys and girls. Experience of cycling also predicted PFI in girls. Nutritional status, hemoglobin level, and physical activity were associated with the fitness levels of these adolescents.