Prader-Willi syndrome: are there population differences?

A 15 1/2-year-old black female with features consistent with the Prader-Willi syndrome is reported. This is the second case report of a black individual and the first case of a black female with the Prader-Willi syndrome. There is an apparent paucity of blacks reported with this condition. Whether this difference is a true difference or represents under-reporting is not known. We urge reporting of individuals representing other racial groups with this disorder and suggest population studies to determine the incidence as well as the true population difference in the Prader-Willi syndrome

Muscle Glycogen Depletion Following 75-km of Cycling Is Not Linked to Increased Muscle IL-6, IL-8, and MCP-1 mRNA Expression and Protein Content

The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists (N=20) participated in a 75-km cycling time trial (168±26.0 min), with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2±17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5±2.8-, 45.3±7.8-, and 8.25±1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5±14.1%, 347±68.1%, and 148±21.3%, respectively (all, P<0.001). Serum myoglobin and cortisol increased 32.1±3.3 to 242±48.3 mg/mL, and 295±27.6 to 784±63.5 nmol/L, respectively (both P<0.001). Plasma IL-6, IL-8, and MCP-1 increased 0.42±0.07 to 18.5±3.8, 4.07±0.37 to 17.0±1.8, and 96.5±3.7 to 240±21.6 pg/mL, respectively (all P<0.001). Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 (r=0.462, P=0.040), with change in myoglobin related to plasma IL-8 (r=0.582, P=0.007) and plasma MCP-1 (r=0.457, P=0.043), and muscle MCP-1 protein (r=0.588, P=0.017); cortisol was related to plasma IL-8 (r=0.613, P=0.004), muscle IL-8 protein (r=0.681, P=0.004), and plasma MCP-1 (r=0.442, P=0.050). In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1

A commercialized dietary supplement alleviates joint pain in community adults: a double-blind, placebo-controlled community trial

BACKGROUND: The purpose of this study was to assess the effect of 8-weeks ingestion of a commercialized joint pain dietary supplement (InstaflexTM Joint Support, Direct Digital, Charlotte, NC) compared to placebo on joint pain, stiffness, and function in adults with self-reported joint pain. InstaflexTM is a joint pain supplement containing glucosamine sulfate, methylsufonlylmethane (MSM), white willow bark extract (15% salicin), ginger root concentrate, boswella serrata extract (65% boswellic acid), turmeric root extract, cayenne, and hyaluronic acid. METHODS: Subjects included 100 men and women, ages 50-75 years, with a history (>3 months) of joint pain, and were randomized to Instaflex™ or placebo (3 colored gel capsules per day for 8 weeks, double-blind administration). Subjects agreed to avoid the use of non-steroidal anti-inflammatory drugs (NSAID) and all other medications and supplements targeted for joint pain. Primary outcome measures were obtained pre- and post-study and included joint pain severity, stiffness, and function (Western Ontario and McMaster Universities [WOMAC]), and secondary outcome measures included health-related quality of life (Short Form 36 or SF-36), systemic inflammation (serum C-reactive protein and 9 plasma cytokines), and physical function (6-minute walk test). Joint pain symptom severity was assessed bi-weekly using a 12-point Likert visual scale (12-VS). RESULTS: Joint pain severity was significantly reduced in Instaflex™ compared to placebo (8-week WOMAC, ↓37% versus ↓16%, respectively, interaction effect P = 0.025), with group differences using the 12-VS emerging by week 4 of the study (interaction effect, P = 0.0125). Improvements in ability to perform daily activities and stiffness scores in Instaflex™ compared to placebo were most evident for the 74% of subjects reporting knee pain (8-week WOMAC function score, ↓39% versus ↓14%, respectively, interaction effect P = 0.027; stiffness score, ↓30% versus ↓12%, respectively, interaction effect P = 0.081). Patterns of change in SF-36, systemic inflammation biomarkers, and the 6-minute walk test did not differ significantly between groups during the 8-week study CONCLUSIONS: Results from this randomized, double blind, placebo-controlled community trial support the use of the Instaflex™ dietary supplement in alleviating joint pain severity in middle-aged and older adults, with mitigation of difficulty performing daily activities most apparent in subjects with knee pain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0195650

The ANZUS Treaty during the Cold War: a reinterpretation of U.S. diplomacy in the Southwest Pacific

This article explains the origins of the Australia–New Zealand–United States (ANZUS) Treaty by highlighting U.S. ambitions in the Pacific region after World War II. Three clarifications to the historiography merit attention. First, an alliance with Australia and New Zealand reflected the pursuit of U.S. interests rather than the skill of antipodean diplomacy. Despite initial reservations in Washington, geostrategic anxiety and economic ambition ultimately spurred cooperation. The U.S. government's eventual recourse to coercive diplomacy against the other ANZUS members, and the exclusion of Britain from the alliance, substantiate claims of self-interest. Second, the historiography neglects the economic rationale underlying the U.S. commitment to Pacific security. Regional cooperation ensured the revival of Japan, the avoidance of discriminatory trade policies, and the stability of the Bretton Woods monetary system. Third, scholars have unduly played down and misunderstood the concept of race. U.S. foreign policy elites invoked ideas about a “White Man's Club” in Asia to obscure the pursuit of U.S. interests in the region and to ensure British exclusion from the treaty

Metacarpophalangeal pattern profile analysis in diastrophic dysplasia

We analyzed the metacarpophalangeal pattern profile (MCPP) on 16 individuals with diastrophic dysplasia and calculated a mean syndrome profile. Correlation studies confirm clinical homogeneity of the hand profile in diastrophic dysplasia. Discriminant analysis of individuals with diastrophic dysplasia compared with a sample of normal individuals produced a function of 3 MCPP variables plus age that appears to be a useful diagnostic tool

Flexibility of in vitro cortical circuits influences resilience from microtrauma

BackgroundSmall clusters comprising hundreds to thousands of neurons are an important level of brain architecture that correlates single neuronal properties to fulfill brain function, but the specific mechanisms through which this scaling occurs are not well understood. In this study, we developed an in vitro experimental platform of small neuronal circuits (islands) to probe the importance of structural properties for their development, physiology, and response to microtrauma.MethodsPrimary cortical neurons were plated on a substrate patterned to promote attachment in clusters of hundreds of cells (islands), transduced with GCaMP6f, allowed to mature until 10–13 days in vitro (DIV), and monitored with Ca2+ as a non-invasive proxy for electrical activity. We adjusted two structural factors–island size and cellular density–to evaluate their role in guiding spontaneous activity and network formation in neuronal islands.ResultsWe found cellular density, but not island size, regulates of circuit activity and network function in this system. Low cellular density islands can achieve many states of activity, while high cellular density biases islands towards a limited regime characterized by low rates of activity and high synchronization, a property we summarized as “flexibility.” The injury severity required for an island to lose activity in 50% of its population was significantly higher in low-density, high flexibility islands.ConclusionTogether, these studies demonstrate flexible living cortical circuits are more resilient to microtrauma, providing the first evidence that initial circuit state may be a key factor to consider when evaluating the consequences of trauma to the cortex

A Novel Anthropomorphic Flow Phantom for the Quantitative Evaluation of Prostate DCE-MRI Acquisition Techniques

A novel anthropomorphic flow phantom device has been developed which can be used for quantitatively assessing the ability of MRI scanners to accurately measure signal / concentration time-intensity curves (CTCs) associated with dynamic contrast-enhanced (DCE) MRI. Modelling of the complex pharmacokinetics of contrast agents as they perfuse through the tumour capillary network has shown great promise for cancer diagnosis and therapy monitoring. However, clinical adoption has been hindered by methodological problems, resulting in a lack of consensus regarding the most appropriate acquisition and modelling methodology to use and a consequent wide discrepancy in published data. A heretofore overlooked source of such discrepancy may arise from measurement errors of tumour CTCs deriving from the imaging pulse sequence itself, while the effects on the fidelity of CTC measurement of using rapidly-accelerated sequences such as parallel imaging and compressed sensing remain unknown. The present work aimed to investigate these features by developing a test device in which „ground truth‟ CTCs were generated and presented to the MRI scanner for measurement, thereby allowing for an assessment of the DCE-MRI protocol to accurately measure this curve-shape. The device comprised of a 4-pump flow system wherein CTCs derived from prior patient prostate data were produced in measurement chambers placed within the imaged volume. The ground truth was determined as the mean of repeat measurements using an MRI-independent, custom-built optical imaging system. In DCE-MRI experiments, significant discrepancies between the ground truth and measured CTCs were found for both tumorous and healthy tissue-mimicking curve shapes. Pharmacokinetic modelling revealed errors in measured Ktrans, ve and kep values of up to 42%, 31%, and 50% respectively, following a simple variation of the parallel imaging factor and number of signal averages in the acquisition protocol The device allows for the quantitative assessment and standardisation of DCE-MRI protocols (both existing and emerging)

Absorbance based light emitting diode optical sensors and sensing devices

The ever increasing demand for in situ monitoring of health, environment and security has created a need for reliable, miniaturised sensing devices. To achieve this, appropriate analytical devices are required that possess operating characteristics of reliability, low power consumption, low cost, autonomous operation capability and compatibility with wireless communications systems. The use of light emitting diodes (LEDs) as light sources is one strategy, which has been successfully applied in chemical sensing. This paper summarises the development and advancement of LED based chemical sensors and sensing devices in terms of their configuration and application, with the focus on transmittance and reflectance absorptiometric measurements