Fibromyalgia and Risk of Dementia—A Nationwide,Population-Based,Cohort Study

Background

Fibromyalgia is a syndrome of chronic pain and other symptoms and is associated with patient discomfort and other diseases. This nationwide matched-cohort population-based study aimed to investigate the association between fibromyalgia and the risk of developing dementia, and to clarify the association between fibromyalgia and dementia.

Local somatothermal stimulation inhibits motility of the internal anal sphincter through nitrergic neural release of nitric oxide

PURPOSE: A somatoanal reflex had been demonstrated in our previous work. Because nitric oxide plays an important role in mediating relaxation of the internal anal sphincter, our purpose was to examine whether and how local somatothermal stimulation inhibits the function of the internal anal sphincter by stimulating nitric oxide releasevia nitrergic neurons and to elucidate the possible mechanism. METHODS: The activity of the internal anal sphincter in anesthetized rabbits was measured by use of continuously perfused, open-tip manometric methods. Local somatothermal stimulation was achieved by applying an electroheating rod 1 cm away from the skin area at the right popliteal region. The responses were further manipulated by pretreating the rabbits with agonists or antagonists linked to nitric oxide synthesis. RESULTS: The motility of the internal anal sphincter before and during local somatothermal stimulation was significantly different (tonic pressure (mean ± standard error of the mean), 5.4 ± 0.3vs. 4.9 ± 0.3 mmHg,P=0.0195; phasic pressure, 3.9 ± 0.6vs. 2.9 ± 0.4 mmHg,P=0.0002; frequency distribution of the phasic contractions (peak-to-peak interval), 28.9 ± 3.7vs. 65.3 ± 10.4 seconds,P=0.0001). The response began at approximately one minute after local somatothermal stimulation when the skin temperature was 41 ± 0.3°C. No anal response was observed when local somatothermal stimulation was applied at the control area. The local somatothermal stimulation-induced internal anal sphincter relaxation was not inhibited by pretreatment with atropine, propranolol, or phentolamine (tonic pressure, 5.8 ± 1vs. 5.2 ± 0.8 mmHg,P=0.038; phasic pressure, 4.2 ± 0.9vs. 3.1 ± 0.6 mmHg,P=0.020; peak-to-peak interval, 27.2 ± 4.3vs. 52.9 ± 14.5 seconds,P=0.043) but was completely blocked by pretreatment with a nitric oxide synthesis inhibitor. The effect of the nitric oxide synthesis inhibitor could be reversed by pretreatment with L-arginine (tonic pressure, 6 ± 0.7vs. 5.6 ± 0.7 mmHg,P=0.047; phasic pressure, 4.7 ± 0.7vs. 3.9 ± 0.5 mmHg,P=0.048; peak-to-peak interval, 23.8 ± 3vs. 33 ± 3.7 seconds,P=0.048), but not by D-arginine. CONCUSION: Local somatothermal stimulation inhibits internal anal sphincter motility through the activation of nonadrenergic noncholinergic neural release of nitric oxide. This procedure may represent a simplified approach for the treatment of anorectal diseases with hypofunction of the L-arginine/nitric oxide pathway.Presented at the XVIIth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Malmö, Sweden, June 7 to 11, 1998.     

Inhibition of ultra-rapid delayed rectifier K+ current by verapamil in human atrial myocytes

Verapamil is a widely used Ca(2+) channel antagonist in the treatment of cardiovascular disorders including atrial arrhythmias. However, it is unknown whether the drug would inhibit the repolarization currents transient outward K(+) current (I(to1)) and ultra-rapid delayed rectifier K(+) current (I(Kur)) in human atrium. With whole-cell patch configuration, we evaluated effects of verapamil on I(to1) and I(Kur) in isolated human atrial myocytes. It was found that verapamil did not decrease I(to1) at 1-50 microM. However, verapamil reversibly inhibited I(Kur) in a concentration-dependent manner (IC(50) = 3.2 microM). At test potential of +50 mV, 5 microM verapamil decreased I(Kur) by 61.3 +/- 7.5%. Verapamil significantly accelerated inactivation of I(Kur), suggesting an open channel block mechanism. The results indicate that verapamil significantly blocks the repolarization K(+) current I(Kur), but not I(to1), in human atrial atrium, which may account at least in part for the atrial effect of the drug.     

Mesoscale networks and corresponding transitions from self-assembly of block copolymers

A series of cubic network phases was obtained from the self-assembly of a single-composition lamellae (L)-forming block copolymer (BCP) polystyrene-block-polydimethylsiloxane (PS-b-PDMS) through solution casting using a PS-selective solvent. An unusual network phase in diblock copolymers, double-primitive phase (DP) with space group of Im3¯m, can be observed. With the reduction of solvent evaporation rate for solution casting, a double-diamond phase (DD) with space group of Pn3¯m can be formed. By taking advantage of thermal annealing, order–order transitions from the DP and DD phases to a double-gyroid phase (DG) with space group of Ia3¯d can be identified. The order–order transitions from DP (hexapod network) to DD (tetrapod network), and finally to DG (trigonal planar network) are attributed to the reduction of the degree of packing frustration within the junction (node), different from the predicted Bonnet transformation from DD to DG, and finally to DP based on enthalpic consideration only. This discovery suggests a new methodology to acquire various network phases from a simple diblock system by kinetically controlling self-assembling process.

From constituted molecules to polymers, finally ordered hierarchical superstructures, self-assembled solids cover a vast area of nanostructures where the characters of building blocks direct the progress of self-assembly (1, 2). In nature, fascinating periodic network structures and morphologies from different species are appealing in nanoscience and nanotechnology due to their superior properties, especially for photonic crystal structures (3–7). For gyroid, trigonal planar network with chirality demonstrates its potential as chiropitc metamaterial (8–10). Beyond the splendid colors, networks either in macroscale or mesoscale mechanically strengthen their skeletons and protect those fragile but vital organs from impact (11, 12). Inspired by nature, biomimicking materials with mesoscale network may exceed the limitation of the intrinsic properties (13). The topology of networks could further improve their adaptability, allowing extreme deformation for energy dissipation (14). Moreover, network materials from hybridization of self-assembled block copolymers (BCPs) have been exploited to the design of mesoscale quantum metamaterials (15, 16). With the desire to acquire network textures for biomimicking nanomaterials, BCPs with immiscible constituted segments covalently joined together give the accessibility to the formation of nanonetwork morphologies via balancing enthalpic penalty from the repulsive interaction of constituted blocks and entropic penalty from the stretching of polymer chains (17–21). By taking advantage of precise synthesis procedures, it is feasible to obtain the aimed network phases from the self-assembly of BCPs such as Fddd (O⁷⁰) (22–24), gyroid (Q²¹⁴, Q²³⁰) (20, 21, 25–27), and diamond (Q²²⁴, Q²²⁷) (28–31) experimentally and theoretically. On the basis of theoretical prediction, the junction points (nodes) in the network phases could be coordinated with three, four, or six neighbors in three-dimensional space, resulting in the enhancement of packing frustration (31). Topologically, all these phases match the coordination number to neighbors (n = 3, 4, 6), showing no special case of quasicrystal. Accordingly, an order–order transition from double-diamond phase (DD, tetrapod) to double-gyroid phase (DG, trigonal planar network) has been observed (29). Yet, there is no DP phase being found in simple diblock systems except for liquid crystals (32, 33) or organic–inorganic nanocomposites from the mixtures of BCP with inorganic precursors (34, 35). Searching the rare occurrence of network phases and the corresponding phase transitions among phases will be essential to the demands for application by considering the deliberate structuring effects on aimed properties but the approaches remain challenging (8, 36–40). For instance, viewing the narrow window for network morphologies in diblock copolymer phase diagram, it demands harsh requirements for syntheses (2, 41). Recently, by taking advantage of using selective solvent for solution casting, it is feasible to acquire DG phase and even inverted DG phase from the self-assembly of lamellae (L)-forming polystyrene-block-polydimethylsiloxane (PS-b-PDMS) (42). Apart from that, a triclinic DG phase was recently discovered from the PS-b-PDMS which is commonly believed nonexisting in the conventional phase diagram (43). As a result, the phase diagram of BCPs with high interaction parameter is worthy of study for searching the metastable phases with unique network textures (44). Herein, we aim to acquire network phases from a simple diblock system by kinetically controlling the transformation mechanisms of self-assembly. As exemplified by using the PS-b-PDMS for solution casting, with the use of a PS-selective solvent (chloroform), a DP phase and a DD phase could be formed through controlled self-assembly, giving unique network phases simply from solution casting. Moreover, a DG phase can be also acquired from phase transformation. Consequently, a series of network phases with hexapod, tetrapod, and trigonal planar building units could be successfully obtained by using a single-composition L-forming PS-b-PDMS for self-assembly. The corresponding order–order transitions among these network phases examined by temperature-resolved in situ small-angle X-ray scattering (SAXS) combining with electron tomography results provide insights of network phase formation and the corresponding phase transformation mechanisms in the self-assembly of BCPs.     

Trousseau's syndrome in a patient with advanced stage gastric cancer

Patients with cancer are at high risk for thrombotic events,which are known collectively as Trousseau's syndrome. Herein,we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery,the left common iliac artery,the posterior tibial artery,and the peroneal artery,which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events,which may correlate with gastric adenocarcinoma. In summary,we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered.     

Therapeutic monitoring of the immuno-modulating drugs in systemic lupus erythematosus

Introduction: Despite the emergence of newer immunomodulating agents for systemic lupus erythematosus (SLE), a substantial proportion of patients still do not respond optimally. While the mechanisms for the differential responses to drug therapy are unclear, variation in drug exposure with the same dosing protocol related to pharmacogenetic and pharmacokinetic factors may contribute. This article discusses the use of therapeutic drug monitoring (TDM) to optimize therapies in SLE patients.

Areas covered: Evidence on the relationship between blood levels and efficacy/toxicity of immuno-modulating drugs such as hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) and the calcineurin inhibitors that are often used in SLE.

Expert commentary: Current data suggest a correlation between exposure and efficacy of HCQ and MMF in SLE. The relationship between HCQ or MMF blood concentrations and their adverse effects requires further elucidation. The serum trough level of tacrolimus does not appear to correlate with clinical response in lupus nephritis but is associated with toxic effects. Owing to the paucity of data, the ‘optimal’ blood levels of these agents in SLE have yet to be determined by large population pharmacokinetic studies. Nevertheless, TDM enables early identification of non-adherence and over-exposure to these SLE medications so that dosing adjustment can be performed to minimize toxicities and wastage.     

Assessing Bone Type of Implant Recipient Sites by Stereomicroscopic Observation of Bone Core Specimens: A Comparison With the Assessment Using Dental Radiography

Background: The aim of the study is to determine if bone quality evaluation of surgically obtained bone core specimens using a stereomicroscope is reliable for determining bone quality at implant recipient sites. Methods: Bone quality was presurgically assessed in 122 edentulous ridges obtained from 62 patients using periapical radiographs and categorized according to the Lekholm and Zarb classification. During surgery, bone specimens were trephined, and bone types were immediately classified using a stereomicroscope. Microarchitectural characteristics of bone cores were evaluated after being scanned using microcomputed tomography (micro‐CT). Results: Bone types of implant sites categorized from radiography and stereomicroscope had statistically similar distribution but poor interrater agreement. Using micro‐CT, maxillae and mandibles showed significant differences in microarchitectural characteristics of bone cores. Bone volume (BV), total volume (TV), and trabecular thickness (Tb.Th) increased, whereas bone surface density (BS/BV) and open porosity (Po.[Op]) decreased in mandibular bone cores compared with those in maxillary bone cores. Moreover, micro‐CT values of BV/TV and Po.(Op) statistically correlated with bone types assessed by stereomicroscopy, particularly in mandibles (adjusted means of BV/TV of Type 2 to 4 versus Type 1 decreasing from ?9.88%, ?15.09%, ?29.31%; those of Po.(Op) ranged from 9.77%, 15.06%, 29.52% in an upward trend). However, such correlations were not found in maxillae or when bone types were classified using periapical radiographs. Conclusions: Caution is needed when using presurgical periapical radiographs to predict bone quality at implant recipient sites. Surgically preserved bone core specimens, whenever obtainable, might offer additional information to accurately assess bone quality, particularly at mandibular implant sites.     

Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling

Glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are highly susceptible to viral infection. This study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes—tumor necrosis factor alpha (TNF-α) and GTPase myxovirus resistance 1 (MX1)—in G6PD-knockdown cells upon human coronavirus 229E (HCoV-229E) and enterovirus 71 (EV71) infection. Molecular analysis revealed that the promoter activities of TNF-α and MX1 were downregulated in G6PD-knockdown cells, and that the IκB degradation and DNA binding activity of NF-κB were decreased. The HSCARG protein, a nicotinamide adenine dinucleotide phosphate (NADPH) sensor and negative regulator of NF-κB, was upregulated in G6PD-knockdown cells with decreased NADPH/NADP⁺ ratio. Treatment of G6PD-knockdown cells with siRNA against HSCARG enhanced the DNA binding activity of NF-κB and the expression of TNF-α and MX1, but suppressed the expression of viral genes; however, the overexpression of HSCARG inhibited the antiviral response. Exogenous G6PD or IDH1 expression inhibited the expression of HSCARG, resulting in increased expression of TNF-α and MX1 and reduced viral gene expression upon virus infection. Our findings suggest that the increased susceptibility of the G6PD-knockdown cells to viral infection was due to impaired NF-κB signaling and antiviral response mediated by HSCARG.