In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health and highlight some recent developments in understanding and exploiting adipocyte biology. Adipose tissue plays critical roles in the regulation of systemic glucose and lipid metabolism and secretes bioactive molecules possessing endocrine, paracrine, and autocrine functions. Dysfunctional adipose tissue has a detrimental impact on metabolic health and is intimately involved in key aspects of metabolic diseases such as insulin resistance, lipid overload, inflammation, and organelle stress. Differences in the distribution of fat depots and adipose characteristics relate to divergent degrees of metabolic dysfunction found in metabolically healthy and unhealthy obese individuals. Thermogenic adipocytes increase energy expenditure via mitochondrial uncoupling or adenosine triphosphate-consuming futile substrate cycles, while functioning as a metabolic sink and participating in crosstalk with other metabolic organs. Manipulation of adipose tissue provides a wealth of opportunities to intervene and combat the progression of associated metabolic diseases. We discuss current treatment modalities for obesity including incretin hormone analogs and touch upon emerging strategies with therapeutic potential including exosome-based therapy, pharmacological activation of brown and beige adipocyte thermogenesis, and administration or inhibition of adipocyte-derived factors.

STUDY DESIGN: Retrospective comparative study. PURPOSE: To assess differences in computed tomography (CT) imaging parameters between patients with cervical myelopathy and controls. OVERVIEW OF LITERATURE: There is a lack of information regarding the best predictor of symptomatic stenosis based on osseous canal dimensions. We postulate that smaller osseous canal dimensions increase the risk of symptomatic central stenosis. METHODS: CT images and medical records of patients with cervical myelopathy (19 patients, 8 males; average age, 64.4+/-13.4 years) and controls (18 patients, 14 males; average age, 60.4+/-11.0 years) were collected. A new measure called the laminar roof pitch angle (=angle between the lamina) was conducted along with linear measures, ratios and surrogates of canal perimeter and area at each level C2-C7 (222 levels). Receiver-operator curves were used to assess the diagnostic value of each. Rater reliability was assessed for the measures. RESULTS: The medial-lateral (ML) diameter (at mid-pedicle level) and calculated canal area (=anterior-posterior. x ML diameters) were the most accurate and highly reliable. ML diameter below 23.5 mm and calculated canal area below 300 mm2 generated 82% to 84% sensitivity and 67% to 68% sensitivity. No significant correlations were identified between age, height, weight, body mass in dex and gender for each of the CT measures. CONCLUSIONS: CT measures including ML dimensions were most predictive. This study is the first to identify an important role for the ML dimension in cases of slowly progressive compressive myelopathy. A ML reserve may be protective when the canal is progressively compromised in the anterior-posterior dimension.
Body Weight ; Case-Control Studies* ; Constriction, Pathologic ; Humans ; Male ; Medical Records ; Retrospective Studies ; Spinal Cord Compression ; Spinal Cord Diseases* ; Spinal Stenosis*

BACKGROUND: We have recently shown that lipopolysaccharide (LPS), a major biologically active component of Gram-negative bacteria, mediate the activation of human keratinocytes by CD14 and Toll-like receptor (TLR 4). However, the mechanism of activation of keratinocytes by Gram-positive bacterial toxins remains unclear. OBJECTIVE: We investigated the mechanism of activation of human keratinocytes by lipoteichoic acid (LTA), a main stimulatory component of Gram-positive bacteria. METHODS: The effects of LTA on CD14, TLR2 and TLR4 mRNA expression were measured by quantitative RT-PCR in cultured human keratinocytes. To determine whether the effects of LTA on CD14, TLR2 and TLR4 expressions of the human keratinocytes were biologically functional, NF-kappaB nuclear translocation and IL-1alpha secretion were measured by immunofluorescence staining and ELISA, respectively. Furthermore, to determine whether these effects by LTA were specific for CD14, TLR2 and TLR4, some cells were pretreated with anti-CD14, anti-TLR2, or anti-TLR2 monoclonal antibodies prior to the addition of LTA. RESULTS: TLR4 mRNA expression on keratinocytes was augmented by exposure to LTA. LTA binding to keratinocytes resulted in NF-kappaB nuclear translocation and secretion of interleukin-1alpha. These responses by LTA were effectively abrogated by preincubating cells with anti-TLR4 monoclonal antibody, but not with anti-CD14 or anti- TLR2 monoclonal antibodies. CONCLUSION: These results indicate that, similar to LPS, LTA induces activation of human keratinocytes mainly through TLR4, however, in contrast to LPS signaling, LTA-induced keratinocyte activation is CD14-independent.
Antibodies, Monoclonal ; Bacterial Toxins ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Humans* ; Interleukin-1alpha ; Keratinocytes* ; NF-kappa B ; RNA, Messenger ; Toll-Like Receptor 4* ; Toll-Like Receptors*

It is controversial whether isolated lesions of mammillothalamic tract (MTT) produce significant amnesia. Since the MTT is small and adjacent to several important structures for memory, amnesia associated with isolated MTT infarction has been rarely reported. We report a patient who developed amnesia following an infarction of the left MTT that spared adjacent memory-related structures including the anterior thalamic nucleus. The patient s memory deficit was characterized by a severe anterograde encoding deficit and retrograde amnesia with a temporal gradient. In contrast, he did not show either frontal executive dysfunction or personality change that is frequently recognized in the anterior or medial thalamic lesion. We postulate that an amnesic syndrome can develop following discrete lesions of the MTT.
Aged ; Amnesia/*etiology ; Cerebral Infarction/*complications ; Humans ; Male ; Mamillary Bodies/*physiopathology ; Neuropsychological Tests ; Thalamus/*physiopathology

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.