Chronic fibrosing osteomyelitis of the jaws: an important cause of recalcitrant facial pain. A clinicopathologic study of 331 cases in 227 patients

Objective This was a retrospective and follow-up analysis of 331 cases of chronic fibrosing osteomyelitis of the jaws (CFOJ) in 227 patients. Study Design Demographic, clinical, surgical, and microscopic characteristics were tabulated for all patients. A follow-up mail survey was used to determine the degree of symptom relief experienced after surgery. Results The female to male ratio approached 7:1, and mean age of patients was 53 years. The most common sites were the mandibular posterior region, followed by the maxillary posterior region. Consistent clinical findings included intractable jaw pain mimicking that of odontogenic origin but unresponsive to usual therapies, minimal or undetectable radiographic abnormalities on plain films but dramatic radiolucencies detected on cone beam computed tomography, and large cavities that were either empty or filled with blood mixed with lipid globules encountered at surgery. The most common histomorphologic findings were vital lamellar bone, prominent resting and reversal lines, microshards and splaying of trabeculae, rounded trabeculae, marrow fibrosis, and pools of erythrocytes and lipid globules, often together. Moderate to complete relief of symptoms for periods up to 108 months after surgery were reported by 83% of the 70 patients who returned the survey. Conclusions On the basis of the findings of this study, CFOJ can be considered a unique entity with consistent clinicopathologic features. Its features suggest a pathogenesis based on bone marrow ischemia. CFOJ can be treated on a rational basis with a justifiable expectation of success and probable cure

Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents

Background & Aims: Remnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors. Methods: Adolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed. Results: NAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR. Conclusions: There is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk. Lay summary: Remnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease

Constitutively active Notch4 receptor elicits brain arteriovenous malformations through enlargement of capillary-like vessels

Arteriovenous (AV) malformation (AVM) is a devastating condition characterized by focal lesions of enlarged, tangled vessels that shunt blood from arteries directly to veins. AVMs can form anywhere in the body and can cause debilitating ischemia and life-threatening hemorrhagic stroke. The mechanisms that underlie AVM formation remain poorly understood. Here, we examined the cellular and hemodynamic changes at the earliest stages of brain AVM formation by time-lapse two-photon imaging through cranial windows of mice expressing constitutively active Notch4 (Notch4*). AVMs arose from enlargement of preexisting microvessels with capillary diameter and blood flow and no smooth muscle cell coverage. AV shunting began promptly after Notch4* expression in endothelial cells (ECs), accompanied by increased individual EC areas, rather than increased EC number or proliferation. Alterations in Notch signaling in ECs of all vessels, but not arteries alone, affected AVM formation, suggesting that Notch functions in the microvasculature and/or veins to induce AVM. Increased Notch signaling interfered with the normal biological control of hemodynamics, permitting a positive feedback loop of increasing blood flow and vessel diameter and driving focal AVM growth from AV connections with higher blood velocity at the expense of adjacent AV connections with lower velocity. Endothelial expression of constitutively active Notch1 also led to brain AVMs in mice. Our data shed light on cellular and hemodynamic mechanisms underlying AVM pathogenesis elicited by increased Notch signaling in the endothelium.American Heart Association (Grant 0715062Y)Tobacco-Related Disease Research Program (Predoctoral Fellowship 18DT-0009

Unstable superheavy relic particles as a source of neutrinos responsible for the ultrahigh-energy cosmic rays

Decays of superheavy relic particles may produce extremely energetic neutrinos. Their annihilations on the relic neutrinos can be the origin of the cosmic rays with energies beyond the Greisen-Zatsepin-Kuzmin cutoff. The red shift acts as a cosmological filter selecting the sources at some particular value z_e, for which the present neutrino energy is close to the Z pole of the annihilation cross section. We predict no directional correlation of the ultrahigh-energy cosmic rays with the galactic halo. At the same time, there can be some directional correlations in the data, reflecting the distribution of matter at red shift z=z_e. Both of these features are manifest in the existing data. Our scenario is consistent with the neutrino mass reported by Super-Kamiokande and requires no lepton asymmetry or clustering of the background neutrinos.Comment: 3 pages, revtex; references adde

Associations between prenatal exposure to phthalates and features of the metabolic syndrome in males from childhood into adulthood

Phthalate metabolites are detectable within the majority of the population. Evidence suggests that a prenatal exposure to phthalates may be associated with the subsequent risks of obesity and elevated blood pressure. We hypothesised that a prenatal exposure to phthalates would lead to an increase in adverse cardiometabolic parameters through childhood and adulthood. The maternal serum phthalate measurements from the stored samples taken from Gen1 mothers at 18 and 34 weeks gestation were examined in relation to the cardiometabolic measures in 387 male offspring from the Raine Study. Data from the Gen2 follow-ups between 3 and 27 years were used. The primary outcomes were analysed longitudinally using linear mixed models for the repeated measures. Non-alcoholic fatty liver disease (NAFLD) was assessed at 17 years using logistic regression. A consistent positive relationship was observed between a prenatal exposure to mono-carboxy-iso-octyl phthalate (MCiOP) through adolescence into adulthood with systolic blood pressure. There were no other consistent cardiovascular associations. Mid-levels of prenatal exposures to Mono-n-butyl phthalate (MnBP) were associated with a greater incidence of NAFLD. Detectable Mono-3-carboxypropyl phthalate (MCPP) was associated with a lower serum HDL-C through late childhood into adulthood, while a higher prenatal exposure to mono-iso-butyl phthalate (MiBP), was associated with a higher LDL-C at 22 years of age. A mid-level prenatal exposure to mono-2-ethylhexyl phthalate (MEHP) metabolites was associated with higher insulin in adulthood, while a higher prenatal exposure to the sum of the Di-(2-ethyl-hexyl) phthalate (DEHP) and Di-iso-nonyl phthalate (DiNP) metabolites was associated with higher fasting serum glucose in adulthood. In conclusion, our study demonstrated that higher prenatal phthalate exposures to some phthalate metabolites was associated with some adverse metabolic profiles through adolescence into adulthood, although the consistent themes were limited to a few metabolites and the outcomes of systolic blood pressure, fasting insulin and glucose

Challenges for String Cosmology

We critically assess the twin prospects of describing the observed universe in string theory, and using cosmological experiments to probe string theory. For the purposes of this short review, we focus on the limitations imposed by our incomplete understanding of string theory. After presenting an array of significant obstacles, we indicate a few areas that may admit theoretical progress in the near future.Comment: 18 pages; contribution to a focus issue on string cosmology for Classical and Quantum Gravit

Natural Theories of Ultra-Low Mass PNGB's: Axions and Quintessence

We consider the Wilson Line PNGB which arises in a U(1)^N gauge theory, abstracted from a latticized, periodically compactified extra dimension U(1). Planck scale breaking of the PNGB's global symmetry is suppressed, providing natural candidates for the axion and quintessence. We construct an explicit model in which the axion may be viewed as the 5th component of the U(1)_Y gauge field in a 1+4 latticized periodically compactified extra dimension. We also construct a quintessence PNGB model where the ultra-low mass arises from Planck-scale suppressed physics itself.Comment: 20 pages, fixed typo and reference

Holographic and Wilsonian Renormalization Groups

We develop parallels between the holographic renormalization group in the bulk and the Wilsonian renormalization group in the dual field theory. Our philosophy differs from most previous work on the holographic RG; the most notable feature is the key role of multi-trace operators. We work out the forms of various single- and double-trace flows. The key question, `what cutoff on the field theory corresponds to a radial cutoff in the bulk?' is left unanswered, but by sharpening the analogy between the two sides we identify possible directions.Comment: 31 pages, 3 figures. v2: Minor clarifications. Added reference

Scientists as Midwives to Cluster Emergence: An Institutional Work Framework

The question of how embedded actors can create institutions that support cluster emergence remains unsolved in the cluster and national innovation systems literature. The present paper extends the recent literature on institutional entrepreneurship and institutional work to solve this paradox of embedded agency in the context of science-based clusters. Building on a longitudinal single case study of a functional foods cluster in Finland, we present an institutional work framework for cluster formation. We argue that, in addition to ideational, material and bridging work, authentic leadership work is critical for cluster emergence. The results of the study highlight the opportunities that scientists have to act as midwives to cluster formation, but they also show that well-functioning clusters need a broader support base.Peer reviewe