The Role of NLRP3 Inflammasome in Lupus Nephritis.
Lupus nephritis (LN) is the most frequent and severe of systemic lupus erythematosus (SLE) clinical manifestations and contributes to the increase of morbidity and mortality of patients due to chronic kidney disease. The NLRP3 (NLR pyrin domain containing 3) is a member of the NLR (NOD-like receptors), and its activation results in the production of pro-inflammatory cytokines, which can contribute to the pathogenesis of LN. In this review manuscript, we approach the relation between the NLRP3 inflammasome, SLE, and LN, highlighting the influence of genetic susceptibility of NLRP3 polymorphisms in the disease; the main functional studies using cellular and animal models of NLRP3 activation; and finally, some mechanisms of NLRP3 inhibition for the development of possible therapeutic drugs for LN.


Epigenetic modification of miR-663 controls mitochondria-to-nucleus retrograde signaling and tumor progression.
The normal cellular function requires communication between mitochondria and the nucleus, termed mitochondria-to-nucleus retrograde signaling. Disruption of this mechanism has been implicated in the development of cancers. Many proteins are known modulators of retrograde signaling, but whether microRNAs (miRNAs) are also involved is unknown. We conducted an miRNA microarray analysis using RNA from a parental cell line, a Rho0 line lacking mitochondrial DNA (mtDNA) and a Rho0 line with restored mtDNA. We found that miR-663 was down-regulated in the mtDNA-depleted Rho0 line. mtDNA restoration reversed this miRNA to parental level, suggesting that miR-663 may be epigenetically regulated by retrograde signaling. By using methylation-specific PCR and bisulfite sequencing we demonstrate that miR-663 promoter is epigenetically regulated not only by genetic but also by pharmacological disruption of oxidative phosphorylation (OXPHOS). Restoration of OXPHOS Complex I inhibitor-induced miR-663 expression by N-acetylcysteine suggested that reactive oxygen species (ROS) play a key role in epigenetic regulation of miR-663. We determined that miR-663 regulates the expression of nuclear-encoded respiratory chain subunits involved in Complexes I, II, III, and IV. miR-663 also controlled the expression of the Complexes I (NDUFAF1), II (SDHAF2), III (UQCC2), and IV (SCO1) assembly factors and was required for stability of respiratory supercomplexes. Furthermore, using luciferase assays, we found that miR-663 directly regulates UQCC2. The anti-miR-663 reduced OXPHOS complex activity and increased in vitro cellular proliferation and promoted tumor development in vivo in mice. We also found that increased miR-663 expression in breast tumors consistently correlates with increased patient survival. We provide the first evidence for miRNA controlling retrograde signaling, demonstrating its epigenetic regulation and its role in breast tumorigenesis.


Molecular and immunological characterization of a Gq protein from ventral and lateral eye of the horseshoe crab Limulus polyphemus.
GTP binding proteins of the Gq family have been implicated in phototransduction in rhabdomeral photoreceptors. In this study we used molecular and immunochemical techniques to characterize a GTP-binding protein alpha subunit of the Gq family in ventral and lateral photoreceptors of the horseshoe crab, Limulus polyphemus. Both ventral photoreceptors and lateral eye retinular cells became strongly labeled with an antibody directed against the common carboxyl tail of two Gq family proteins, G alpha q and G alpha 11. This antibody also labeled a 42 kDa band on Western blots of proteins from ventral photoreceptor cell bodies, ventral photoreceptor axons, lateral eyes and lateral optic nerves. The reverse transcription-polymerase chain reaction (RT-PCR), along with degenerate oligonucleotide primers designed against conserved regions of known G alpha q and G alpha 11 proteins, was used to isolate a cDNA from ventral eye RNA which encodes a protein with high identity to known Gq proteins. Ribonuclease protection assays showed that the corresponding message was expressed in ventral eye, but these assays, as well as Northern blots, failed to detect expression in lateral eye. Therefore, while photoreceptors of both ventral and lateral eyes contain a Gq-like protein, the mRNA encoding the Gq protein in the ventral eye may differ in nucleotide sequence from its lateral eye counterpart.


A New Energy-Efficient Topology for Wireless Body Area Networks.
Wireless body area networks consist of several devices placed on the human body, sensing vital signs and providing remote recognition of health disorders. Low power consumption is crucial in these networks. A new energy-efficient topology is provided in this paper, considering relay and sensor nodes' energy consumption and network maintenance costs. In this topology design, relay nodes, placed on the cloth, are used to help the sensor nodes forwarding data to the sink. Relay nodes' situation is determined such that the relay nodes' energy consumption merges the uniform distribution. Simulation results show that the proposed method increases the lifetime of the network with nearly uniform distribution of the relay nodes' energy consumption. Furthermore, this technique simultaneously reduces network maintenance costs and continuous replacements of the designer clothing. The proposed method also determines the way by which the network traffic is split and multipath routed to the sink.


Silver-film subwavelength gratings for polarizers in the terahertz and mid-infrared regions.
Silver is proposed as a useful metal for thin metal-film subwavelength-grating polarizers in both the terahertz and mid-infrared regions. A triangular Ag-film grating for a terahertz-region polarizer fabricated on a resin substrate showed measured TE-wave losses of higher than 45 dB in the frequency range of 0.5-2.2 THz, while TM-wave losses were lower than 0.75 dB in the range of 0.5-3THz. A triangular double Ag-film grating structure on a thin silicon substrate with an anti-reflection layer on its reverse side was fabricated for the polarizer in the mid-infrared region. Measured TE-wave losses were higher than 27 dB in the wavelength range of 16-21 μm, while the minimum TM-wave loss was 3.5 dB at around the wavelength of 19 μm. Silver films are confirmed to be promising candidates for fabricating high-performance polarizers in the terahertz and mid-infrared regions.


Human p300 protein is a coactivator for the transcription factor MyoD.
Human p300 protein is a cellular target of adenoviral E1A oncoprotein and a potential transcriptional coactivator. Both p300 and Rb family protein-binding regions of E1A are required for the repression of muscle gene expression, which is regulated by MyoD family transactivators. This implies that p300 is involved in MyoD-dependent transactivation. We show that the repression of MyoD-mediated E box (MyoD consensus) reporter activity by E1A is correlated with its interaction with p300, indicating that p300 participates in MyoD-dependent transactivation. In addition, p300 is able to interact both in vivo and in vitro with MyoD through a portion at the carboxyl-terminal cysteine/histidine-rich domain and associates with the components of the basal transcriptional complex through its two separate transactivation domains at the amino and carboxyl termini. Consistent with its role as a coactivator, p300 potentiates MyoD-activated transcription.


Larval development of Brachidontes solisianus (Bivalvia, Mytilidae), with notes on differences between its hinge system and that of the mollusk Perna perna.
This work, which is part of a study program on meroplankton larvae, aims to gain more in-depth knowledge about planktonic larvae. This study began with the mollusk Brachidontes solisianus (Bivalvia-Mytilidae), which is abundant on the rocky shores of the Cabo Frio region (state of Rio de Janeiro, Brazil). Brachidontes solisianus larvae were grown under controlled conditions for a period of 26 days and were fed with Isochrysis galbana and Tetraselmis chui. The temperature was kept at 26 degrees C and the saltiness at 28. Images of the larvae were taken daily with a light camera and measured with a micrometric lens until settlement occurred. The average size of the first D-shaped veliger stage was 90 microm in length and 70 microm in height, while the size in the last stage before settlement (pediveliger) was 273 microm in length and 257 microm in height. The comparative study of the hinge system involved the most abundant intertidal species of the study area: Brachidontes solisianus and Perna perna. The B. solisianus species were found to have more visible denticles at the extremities of the provinculum, whereas the denticles of the P. perna species occur along the entire provinculum.


cDNA cloning and molecular characterization of human brain metalloprotease MP100: a beta-secretase candidate?
Metalloprotease MP100 was originally isolated as a beta-secretase candidate from human brain using a beta-amyloid precursor protein (beta-APP)-derived p-nitroanilide (pNA) peptide substrate. Peptide sequences from purified MP100 were now found to resemble sequences reported for a puromycin-sensitive aminopeptidase (PSA) highly enriched in brain, and cDNA cloning revealed nearly complete homology of MP100 to PSA, with only a single bp difference resulting in an amino acid change at position 184. Another MP100 cDNA encoded a protein with a 36-amino acid deletion (positions 180-217) and a two-amino acid insertion after Val533. Purified recombinant human MP100 cleaved the original pNA substrate as well as a free beta-site-spanning amyloid beta (A beta) peptide (A beta(-10/+10)), generating A beta(1-10). The latter substrate, however, remained uncleaved, if N- and C-terminally blocked, and also purified beta-APP was not cleaved. Double immunoimaging revealed partial, patchy, colocalization of beta-APP and MP100 in doubly transfected human embryonic kidney cells (HEK cells) and in normal neuroblastoma cells, and both proteins could be coimmunoprecipitated from rat brain extracts, suggesting their close vicinity in vivo. Coexpression of MP100 and beta-APP695, however, did not boost A beta levels in HEK cells, although active enzyme was produced. Thus, MP100 does not exert true beta-secretase-like function in cells, although it may well act as a secondary exoprotease in a complex beta-APP/A beta metabolism.


Significant impact of terminal room cleaning with bleach on reducing nosocomial Clostridium difficile.
We were alerted to increased rates of Clostridium difficile-positive tests at all 3 hospitals in our health care system by MedMined Data Mining Surveillance Service, CareFusion (San Diego, CA). In response, an intervention of terminal room cleaning with dilute bleach was instituted to decrease the amount of C difficile environmental spore contamination from patients with C difficile infection (CDI). The intervention consisted of replacing quaternary ammonium compound as a room cleaning agent with dilute bleach to disinfect rooms of patients with CDI upon discharge. All surfaces, floor to ceiling were wiped with dilute bleach applied with towels to thoroughly wet the surfaces. Daily room cleaning remained unchanged. Patients remained on C difficile contact isolation precautions until discharge. To determine the effectiveness of this program, rates of nosocomial CDI for all 3 hospitals were determined using the MedMined Virtual Surveillance Interface for 10 months prior to and 2 years after the cleaning intervention. Statistical significance was determined using Poisson regression analysis. There was a 48% reduction in the prevalence density of C difficile after the bleaching intervention (95% confidence interval: 36%-58%, P < .0001). The implementation of a thorough, all-surface terminal bleach cleaning program in the rooms of patients with CDI has made a sustained, significant impact on reducing the rate of nosocomial CDI in our health care system.


Light Quality Affects Chloroplast Electron Transport Rates Estimated from Chl Fluorescence Measurements.
Chl fluorescence has been used widely to calculate photosynthetic electron transport rates. Portable photosynthesis instruments allow for combined measurements of gas exchange and Chl fluorescence. We analyzed the influence of spectral quality of actinic light on Chl fluorescence and the calculated electron transport rate, and compared this with photosynthetic rates measured by gas exchange in the absence of photorespiration. In blue actinic light, the electron transport rate calculated from Chl fluorescence overestimated the true rate by nearly a factor of two, whereas there was closer agreement under red light. This was consistent with the prediction made with a multilayer leaf model using profiles of light absorption and photosynthetic capacity. Caution is needed when interpreting combined measurements of Chl fluorescence and gas exchange, such as the calculation of CO2 partial pressure in leaf chloroplasts.


Treatment of protoscoleces with gamma radiation: Potential immunoprotective effect against experimental murine echinococcosis.
Cystic echinococcosis (CE) is one of the most important zoonotic diseases with a worldwide distribution. It is caused by the larval stage of the dog tapeworm "Echinococcus granulosussensu lato" and constitutes a major economic and public health problem in several countries. Protoscoleces are one component of this larval stage that can interact with both definitive and intermediate hosts. The aim of the present study was to investigate the potential role of using a radio-attenuated form of these protoscoleces for immunoprophylaxis against experimental murine echinococcosis. However, mice were immunized twice at 15-day intervals with gamma (γ) irradiated protoscoleces at doses of 0.4, 0.8, 1.2 and 1.4 kGy then challenged with the intact parasites. Macroscopic and histological analyses with cytokine measurements were performed in order to estimate the number and diameter of cysts, microscopic changes and cytokine profile. An improvement in protection against the challenge dose was observed with increasing dose, giving percentages of 47.7, 49, 55.23 and 70.6%, for the 0.4, 0.8, 1.2 and 1.4 kGy-groups respectively. These data suggest that immunization with radio-attenuated protoscoleces may induce satisfactory protective immunity by reducing successfully the formation of cysts, caused by challenge infection.


Differential responses to Smith D autoantigen by mice with HLA-DR and HLA-DQ transgenes: dominant responses by HLA-DR3 transgenic mice with diversification of autoantibodies to small nuclear ribonucleoprotein, double-stranded DNA, and nuclear antigens.
Anti-Smith (Sm) D autoantibodies are specific for systemic lupus erythematosus. In this investigation, the influence of HLA-D genes on immune responses to SmD was investigated. Mice with HLA-DR3, HLA-DR4, HLA-DQ0601, HLA-DQ0604, or HLA-DQ8 transgenes were immunized with recombinant SmD1, and their Ab responses were analyzed. Analysis by ELISA showed that all strains responded well to SmD. However, when synthetic SmD peptides were used as substrate, DR3 mice had the highest Ab response followed by DQ8, DQ0604, DQ0601, and DR4. A similar trend was observed in Western blot analysis using WEHI 7.1 cell lysate as the substrate, with the exception that DR4 mice did not generate detectable amounts of Abs. Only sera from DR3 and DQ0604 mice immunoprecipitated A-ribonucleoprotein (RNP), SmB, and SmD. Intermolecular epitope spreading to A-RNP and SmB was evident in DR3 and DQ0604 mice, as sera depleted of anti-SmD Abs were reactive with these proteins. DR3 mice also generated an immune response to C-RNP. Anti-nuclear Abs were detected in the majority of the DR3 mice, whereas moderate reactivities were seen in DQ0604 and DQ8 mice. Interestingly, only DR3 mice mounted an anti-dsDNA Ab response. Approximately half of the anti-dsDNA Abs were cross-reactive with SmD. Ab responses correlated with the strength of the T cell responses. Thus, HLA-DR3 appears to be the dominant HLA-D gene that determines the magnitude and quality of the anti-SmD immune response. In addition, our findings provide insights into the origin of the anti-dsDNA Abs often detected in patients with systemic lupus erythematosus.


Treatment of knee osteoarthritis by arthroscopic synovectomy and debridement of cartilage lesions--late results.
Osteoarthritis (OA) is accompanied by degeneration and destruction of the articular cartilage, development of inflammatory process in the synovial membrane and periarticular tissues. Despite the introduction of new modern medications, the articular inflammatory changes often progress and therapy gives only a transitory improvement. Arthroscopic synovectomy (AS) in knee OA combined with resection of the cartilage lesions is a mild operative procedure and is not associated with postoperative joint stiffness and necessity of continuous rehabilitation. The aim of our study was to assess the late results in primary OA of the knee joint after arthroscopic synovectomy with resection of the cartilage lesions and tidal lavage. AS was performed in 71 patients with primary knee OA and chronic synovitis. The diagnosis OA of the knee joint was made according the criteria of American College of Rheumatology (1986). All patients, included in the study, had OA resistant to the conventional treatment. The arthroscopy was performed with a 30 degrees oblique optical system under local anesthesia. The synovectomy was performed with rotative resectors. The toilet of the articular cartilage includes the removal of macroscopic non-vital cartilage and free intraarticular bodies followed by monitored tidal lavage. The patients were examined before the arthroscopy and followed-up in 1, 3 and 5 years after AS. For the clinical assessment the WOMAC test was used. The WOMAC functional index shows statistically significant improvement at 1 and 3 years (p < 0.0001), as well as at 5 years (p < 0.001) after AS. The WOMAC pain index was significantly reduced in the arthroscopic joint at 1 and 3 years (p < 0.0001). The good therapeutic result was maintained for 5 years (p < 0.001). The WOMAC joint stiffness index was improved to the greatest extent 1 and 3 years after AS (p < 0.0001). In the 5th year a favourable statistically significant improvement was preserved. The total WOMAC index showed a durable general functional improvement including 3 years after the AS. The AS was performed in advanced OA of the knee joint accompanied with a chronic synovitis, resistant to medical therapy and topical management. The functional therapeutic results from AS were very good and lasting even 5 years after the AS.


Nd:YAG Capsulotomy Rates With Two Trifocal Intraocular Lenses.
To compare Nd:YAG capsulotomy rates following implantation of two diffractive trifocal intraocular lenses (IOLs). This multi-center retrospective analysis included patients who underwent uncomplicated lens phacoemulsification and were implanted with a diffractive trifocal IOL: FineVision MicroF (PhysIOL, Liège, Belgium) or AT Lisa tri 839MP (Carl Zeiss Meditec, Jena, Germany). All surgeries were performed during the same period. The postoperative follow-up period was at least 1 year. Chi-square and Kaplan-Meier tests analyzed non-parametric estimates for survival/failure functions. The Wilcoxon (Breslow) test compared Nd:YAG capsulotomy rates between the two groups. Of 5,130 eyes included, 3,387 were implanted with the FineVision MicroF IOL and 1,743 with the AT Lisa tri 839MP IOL. There were no statistical differences in age, axial length, or IOL power between groups. Nd:YAG capsulotomies were necessary in 330 eyes (9%) in the FineVision group and 408 eyes (23%) in the AT Lisa tri group (P < .001). The probability of having Nd:YAG capsulotomy up to 9 months postoperatively was equal for both lenses. Beyond 9 months, the Nd:YAG capsulotomy rate increased significantly more in the AT Lisa tri group, reaching a probability of 35% for eyes with a follow-up of 34 to 44 months, whereas in the FineVision group the probability was 14% after a follow-up of 37 to 47 months. The differences in survival (without Nd:YAG capsulotomy)/failure (with Nd:YAG capsulotomy) functions were significant (P < .001). Eyes implanted with the FineVision MicroF IOL required significantly fewer Nd:YAG laser capsulotomies than those with the AT Lisa tri 839MP IOL during the first years after implantation. The design of the IOL platforms could account for these differences. [J Refract Surg. 2016;32(11):748-752.].


Disposition of [14C]ruboxistaurin in humans.
Ruboxistaurin is a potent and specific inhibitor of the beta isoforms of protein kinase C (PKC) that is being developed for the treatment of diabetic microvascular complications. The disposition of [(14)C]ruboxistaurin was determined in six healthy male subjects who received a single oral dose of 64 mg of [(14)C]ruboxistaurin in solution. There were no clinically significant adverse events during the study. Whole blood, urine, and feces were collected at frequent intervals after dosing. Metabolites were profiled by high performance liquid chromatography with radiometric detection. The total mean recovery of the radioactive dose was approximately 87%, with the majority of the radioactivity (82.6 +/- 1.1%) recovered in the feces. Urine was a minor pathway of elimination (4.1 +/- 0.3%). The major route of ruboxistaurin metabolism was to the N-desmethyl ruboxistaurin metabolite (LY338522), which has been shown to be active and equipotent to ruboxistaurin in the inhibition of PKC(beta). In addition, multiple hydroxylated metabolites were identified by liquid chromatography-mass spectrometry in all matrices. Pharmacokinetics were conducted for both ruboxistaurin and LY338522 (N-desmethyl ruboxistaurin, 1). These moieties together accounted for approximately 52% of the radiocarbon measured in the plasma. The excreted radioactivity was profiled using radiochromatography, and approximately 31% was structurally characterized as ruboxistaurin or N-desmethyl ruboxistaurin. These data demonstrate that ruboxistaurin is metabolized primarily to N-desmethyl ruboxistaurin (1) and multiple other oxidation products, and is excreted primarily in the feces.


Effect of passive jaw opening on the electromyographic activity of the temporalis, masseter, digastric, and infrahyoid muscles in healthy adults.
To investigate the surface electromyography (EMG) activity of the temporalis, masseter, digastric, and infrahyoid muscles during passive jaw opening in healthy adults. The EMG activity of the masseter, temporalis, digastric anterior belly, and infrahyoid muscles on the right side was recorded during the four jaw-opening tasks: active opening to 20 mm (AO20); active opening to 40 mm (AO40); passive opening to 40 mm with a rubber mouth prop on the right posterior teeth (POR40); and passive opening to 40 mm with a mouth prop on the left posterior teeth (POL40). The EMG amplitude of the digastric anterior belly and infrahyoid muscles in either POL40 or POR40 was significantly less than that in AO20 or AO40, respectively. Passive jaw opening reduces the EMG activity of the digastric and infrahyoid muscles significantly and could help reduce the load on these muscles during prolonged mouth-opening conditions.


White light requirements for stimulation of plant growth by malformin.
Over a 3-day period, the minimum white fluorescent light intensity required for malformin-induced growth stimulation of etiolated and green cuttings of Phaseolus aureus was approximately 2.6 x 10(3) and 0.4 x 10(3) ergs/cm(2) . sec, respectively. High light intensities were unable to inhibit the ability of malformin to stimulate growth. Over 3 days, the minimum photoperiod for malformin-induced growth stimulation using etiolated and green cuttings and a light intensity of 13.5 x 10(3) ergs/cm(2) . sec was 4 hours and 1 hour, respectively. Malformin must be present in the area of growth stimulation during the time of light treatment. Those changes induced by light and required for malformin-induced growth stimulation were estimated to undergo almost complete decay within 1 hour in the dark. By manipulating the experimental technique, it was possible to stimulate the growth of green cuttings with malformin with a 10-min light treatment (13.5 x 10(3) ergs/cm(2) . sec). Although low light intensities and short photoperiods did not allow growth stimulation by malformin using etiolated cuttings, they prevented or alleviated growth inhibition induced by malformin in the dark.


Surgical treatment of ulcerative colitis: ileorectal vs ileal pouch-anal anastomosis.
Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the current gold standard in the surgical treatment of ulcerative colitis (UC) refractory to medical management. A procedure of significant magnitude carries its own risks including anastomotic failure, pelvic sepsis and a low rate of neoplastic degeneration overtime. Recent studies have shown that total colectomy with ileorectal anastomosis (IRA) has been associated with good long-term functional results in a selected group of UC patients amenable to undergo a strict surveillance for the relatively high risk of cancer in the rectum. This manuscript will review and compare the most recent literature on IRA and IPAA as it pertains to postoperative morbidity and mortality, failure rates, functional outcomes and cancer risk.


Benign Traumatic Rib Fracture: A Potential Pitfall on 68Ga-Prostate-Specific Membrane Antigen PET/CT for Prostate Cancer.
Two, respectively, 72- and 76-year-old men with recently diagnosed high-risk prostate cancer were referred for primary staging with Ga-prostate-specific membrane antigen (PSMA) PET/CT. In both patients, the PET scans revealed increased Ga-PSMA uptake in, respectively, 3 and 4 rib fractures, characteristically placed as "pearls on a string." These cases illustrate important pitfalls when reporting PSMA PET.


Characteristics of persistent diaper dermatitis in children with food allergy.
Diaper dermatitis is often caused by irritant contact occurring beneath the diaper of an infant, and it is aggravated by factors such as dampness, friction, urea, and feces. Food-allergic patients are known to exhibit various skin lesions ranging from urticaria to eczema. This study aims to determine the relationship between persistent diaper dermatitis and food allergy. A retrospective chart review was conducted of pediatric patients with a diagnosis of persistent diaper dermatitis between August 2015 and November 2017. The study included 157 patients diagnosed with persistent diaper dermatitis (67 male, 72 female; median age: 13 months). Diaper dermatitis was more common and included the whole perineum in children who had multiple food allergies (P = 0.001). In children with multiple food allergies, the course of diaper dermatitis was more severe, and the condition did not respond to topical treatment (P = 0.025). A longer elimination diet was required for patients with Type I reactions and persistent diaper dermatitis (P = 0.018). In patients with Type II and mixed reactions, diaper dermatitis was more diffuse and covered the whole perineum (P = 0.025). In patients with Type II and mixed reactions, diaper dermatitis was more severe and did not respond to topical treatment (P = 0.025). Persistent diaper dermatitis lasting longer than a month may be associated with food allergy. The diaper rash may also be the only indicator of the food allergy. Elimination of the responsible food may allow these patients to recover from persistent diaper dermatitis.


A comparison of extended-release oxybutynin and tolterodine for treatment of overactive bladder in women.
Women with urge or mixed incontinence were randomized to a daily dose of 10 mg extended-release oxybutynin chloride (qd) or tolterodine tartrate 4 mg (2 mg bid) for 12 weeks. Subjects completed 7-day voiding diaries at baseline and at 12 weeks. A total of 315 women were treated. At the end of the study, extended-release oxybutynin chloride was more effective than twice-daily tolterodine tartrate as measured by urge and total incontinence episodes (p=0.038, p=0.030, respectively). Overall, the reduction in micturition frequency between groups was not significantly different. In women aged 64 years and younger (comprising 63% of the population) extended-release oxybutynin was more effective than tolterodine for urge (p=0.005) and total incontinence (p=0.005), and for micturition frequency (0.024). Adverse events were infrequent, mostly mild, and similar between treatment groups. We concluded that daily extended-release oxybutynin chloride (10 mg) was more effective than tolterodine tartrate (2 mg bid) in treating urge and total incontinence. The incidences of dry mouth, CNS events, and other adverse events were similar for both drugs.


Expression of OCTN2 and OCTN3 in the apical membrane of rat renal cortex and medulla.
Immunological assays and transport measurements in apical membrane vesicles revealed that the apical membrane of rat kidney cortex and medulla presents OCTN2 and OCTN3 proteins and transports L-[(3)H]-carnitine in a Na(+)-dependent and -independent manner. OCTN2 mediates the Na(+)/L-carnitine transport activity measured in medulla because (i) the transport showed the same characteristics as the cortical Na(+)/L-carnitine transporter and (ii) the medulla expressed OCTN2 mRNA and protein. The Na(+)-independent L-carnitine transport activity appears to be mediated by both OCTN2 and OCTN3 since: (i) Na(+)-independent L-carnitine uptake was inhibited by both, anti-OCTN2 and anti-OCTN3 antibodies, (ii) kinetics studies revealed the involvement of a high- and a low-affinity transport systems, and (iii) Western and immunohistochemistry studies revealed that OCTN3 protein is located at the apical membrane of the kidney epithelia. The Na(+)-independent L-carnitine uptake exhibited trans-stimulation by intravesicular L-carnitine or betaine. This trans-stimulation was inhibited by anti-OCTN3 antibody, but not by anti-OCTN2 antibody, indicating that OCTN3 can function as an L-carnitine/organic compound exchanger. This is the first report showing a functional apical OCTN2 in the renal medulla and a functional apical OCTN3 in both renal cortex and medulla.


[A study on the development of symptoms and their relationship to the total chain-saw operating time].
To investigate the dose-response relationship and the relationships among symptoms related to the vibration syndrome, 266 chain saw operators were examined. The subjects were classified into four groups according to total operating time (TOT): Group E1 (below 2,000 hrs, n = 39), Group E2 (2,000-5,000 hrs, n = 76), Group E3 (5,000-8,000 hrs, n = 51), and Group E4 (over 8,000 hrs, n = 100). The control group (Group O) consisted of 46 healthy subjects with very brief employment period as bush cleaners. The subjective symptoms and clinical findings were divided into four major symptom categories: circulatory disturbances, sensory disturbances, damage to muscles and joints, and general symptoms such as autonomic nerve disturbances. Each major symptom category was rated from 0 to 25 according to the severity of the symptoms observed (Table 2). The mean scores in the four major symptom categories were compared for the four TOT groups in order to study the dose-response relationship. The relationship among symptoms was investigated by cluster analysis for the four major symptom categories of all operators in each group and inferred from the significance of partial correlation coefficients between the two of the four major symptom categories calculated for each group. The mean scores in the four major categories showed a significant elevation with the increase in TOT. A dose-response relationship of the vibration syndrome was proved. Each major symptom category was aggravated, not independently, but in close correlation with the symptoms. The inter-symptom relationships of the vibration syndrome were confirmed. That is, very close correlations between circulatory disturbances and sensory disturbances and between sensory disturbances and damages to muscles and joints were demonstrated.


Postadmission function best predicts acute hospital outcomes after stroke.
This study was conducted to determine the relative value of selected variables for predicting three acute hospital outcomes (length of stay, charges, discharge destination) after stroke. Data were obtained prospectively from 92 patients admitted with ischemic stroke to an acute care hospital. The relationship between five independent variables (age, sex, National Institutes of Health Stroke Scale [NIHSS] scores, prestroke Barthel Index scores, and postadmission Barthel Index scores) and the three outcome variables (hospital length of stay, hospital charges, and hospital discharge destination) were examined. Significant bivariate correlations were found between two predictors (NIHSS scores and Barthel Index scores) and all three outcome variables. Regression analysis showed that once postadmission Barthel Index scores were accounted for, no other variable added to the prediction of hospital length of stay or discharge destination. The NIHSS score added to the explanation of hospital charges provided by postadmission Barthel Index scores. Postadmission Barthel Index scores were the best predictor of the three outcomes measured in this study.


Cyclic AMP-dependent protein kinase in subtypes of major depression and normal volunteers.
We have shown a reduction in beta adrenoceptor-linked, cyclic AMP-dependent protein kinase [protein kinase A (PKA)] activity in fibroblasts of patients with major depression with melancholic features relative to normal volunteers. We evaluated a group of 35 patients with major depression subtyped by DSM-IV criteria as melancholic, atypical, and those not meeting either subtype designation ('non-subtyped') and 21 normal volunteers to ascertain whether or not the PKA activity abnormality was specific to melancholia. The melancholics showed marked reduction in cyclic AMP-stimulated PKA activity relative to normal volunteers. Although the atypicals were statistically significantly lower, almost all fell into the range for the normals. The non-subtyped group fell between the atypicals and the melancholics. Basal activity was significantly lower in atypical and melancholic groups. The data suggest that reduced PKA activity is consistently found in melancholic major depression and may not be seen with other depressive subtypes.


Pyruvate enhances DNA single-strand break formation while abolishing cytotoxicity in U937 cells exposed to tert-butylhydroperoxide.
tert-Butylhydroperoxide (tB-OOH) induces killing and DNA single strand breaks (SSBs) in cultured U937 cells. Pyruvate while increasing the rate of oxygen consumption also increased the magnitude of the DNA scission produced by tB-OOH. Rotenone, an inhibitor of complex I, abolished both effects but did not, however, affect the DNA SSB-frequency observed after treatment with tB-OOH alone. These results collectively suggest that pyruvate potentiates the DNA-damaging activity of tB-OOH via stimulation of oxygen consumption. Importantly, under the same experimental conditions, pyruvate was found to abolish both the decline in nonprotein sulfhydryls (NPSH) and the cytotoxicity induced by tB-OOH. Thus, cells with energized mitochondria are more sensitive to the DNA-damaging effects of tB-OOH and display resistance against its cytotoxic effects. As a consequence, DNA SSBs promoted by tB-OOH do not appear to be toxic for the cell.


Factors related to fatalities and clinical progression of Crimean-Congo hemorrhagic fever patients and the effects of IL 28-B gene polymorphism.
Mortality rates of Crimean-Congo hemorrhagic fever (CCHF) vary from 5% to 80%. However, there is no clear information available about why this disease is fatal for some people while others recover. In this study, the factors related to fatalities and serious clinical progression of CCHF patients and the correlation between serious prognosis and IL 28-B gene polymorphism were investigated. The study included 107 patients with a preliminary diagnosis of CCHF, and the patients were found positive for CCHFV RNA based on polymerase chain reaction (PCR) analysis. The IL 28-B rs12979860 polymorphism was identified by PCR "restriction fragment length polymorphism" (PCR-RFLP) analysis using blood samples from the patients. In addition to the IL 28-B analysis results, a variety of data along with laboratory records obtained during the hospital stay were evaluated using statistical analysis. Of the 107 cases, nine were fatal (8.4%), while the other patients recovered and were discharged. Twenty-four patients had the CC genotype (22.43%), 64 had the CT genotype (59.81%), and 19 had the TT genotype (17.76%). Of the nine patients who died, three had the CC genotype (33.33%) and six had the CT genotype (66.67%). None of the patients who died had the TT genotype. Symptoms and findings of diarrhea, abdominal pain, hemorrhage, and rash were more common in fatal cases than in non-fatal cases. The IL 28-B rs12979860 polymorphism was not found to have a statistically significant correlation with fatality or symptoms indicating serious clinical progression in CCHF patients. As has been observed in previous studies, our study showed that leukocytosis, abdominal pain and diarrhea were more common in fatal cases.


Cervico-mediastinal goiter: is telescopic exploration of the mediastinum (video mediastinoscopy) useful?
Surgeons are aware that most mediastinal goiters can be excised through a Kocher transverse collar incision, but in rare circumstances a partial-complete median sternotomy or a thoracotomy are mandatory. During an operation to remove a large cervico-mediastinal goiter (CMG) a profound, not massive, bleeding in the anterior mediastinum developed. Bleeding was unsuccessfully treated with packing. Instead, to perform an urgent sternotomy we used telescopic imaging to identify the source of hemorrhage, and a metallic clip was used to stop the bleeding. Since then we have prospectively used the telescope in the case of large CMG causing compression of an adjacent structure. This report is a preliminary communication demonstrating the technique. Telescopic exploration of the mediastinum was performed in seven patients. The goiters were located in the middle mediastinum in five patients and in the anterior and middle mediastinum in one, respectively. The use of a telescope can help the surgeon during the removal of a large mediastinal goiter. It facilitates a) the visualization of the intrathoracic tributaries reducing the risk of hemorrhage, b) the research of ectopic thyroid gland, and finally c) minimizes the risk of complications of a median sternotomy.


Compartmental utilization of carboxyl-C-tripalmitin by tissue homogenate of pine seeds.
A tissue homogenate of megagemetophyte of germinating seeds of Jeffrey pine (Pinus Jefferii Grev. and Balf.) was incubated with sonication-dispersed and albumin-carried (14)C-tripalmitin in order to elucidate the sequential and quantitative role of cellular organelles in utilizing lipid reserve in seeds. After 5 minutes at 30 C, 25% of the tracer was localized in the fat body fraction, 9% in the pellet containing mitochondria and glyoxysomes, 14% in the supernatant, and 2% was found as CO(2). Radioactivity increased with time of incubation in the latter three fractions indicating the forward direction of utilization. Fat bodies contained mainly lipases and hydrolyzed the tracer to palmitate with diglyceride and monoglyceride as intermediates. About two-thirds of the palmitate had left the fat bodies in 5 minutes and entered the pellet fraction within which the tracer was distributed 1:2 in mitochondria and glyoxysomes, respectively. Longer incubation reduced the ratio to 1:3 while both organelles acquired more radioactive intermediates. Labeled acetyl-CoA and intermediate of beta-oxidation were found in both organelle-containing fractions. The supernatant fraction contained radioactive diglycerides, monoglycerides, palmitate, sterol esters, and phospholipids, indicating lipase activity and direct utilization of fatty acid for the synthesis of sterol esters and polar lipids.


Cephaloceles: treatment, outcome, and antenatal diagnosis.
A series of 74 cephaloceles (17 cranial meningoceles and 57 meningoencephaloceles) is reported. Infants born with large meningoencephaloceles containing recognizable cerebral tissue usually did badly despite endeavors to conserve brain function by expanding the cranial capacity (5 cases) or decompressing hydrocephalic ventricles (9 cases). Infants with cranial meningoceles almost all did well, even when there was associated hydrocephalus. The etiological diversity of cephaloceles is emphasized. Frontoethmoidal meningoencephaloceles, which occur with noteworthy frequency in South and Southeast Asia, require separate consideration in both genetic counseling and treatment; the associated facial deformities (hypertelorism and orbital dystopia) can be corrected with a one-stage craniofacial reconstruction. Antenatal diagnosis by ultrasound is now often possible and was achieved in 4 cases; we suggest that neurosurgeons should participate in such antenatal evaluations.


Investigation of an entropic stabilizer for the lattice-Boltzmann method.
The lattice-Boltzmann (LB) method is commonly used for the simulation of fluid flows at the hydrodynamic level of description. Due to its kinetic theory origins, the standard LB schemes carry more degrees of freedom than strictly needed, e.g., for the approximation of solutions to the Navier-stokes equation. In particular, there is freedom in the details of the so-called collision operator. This aspect was recently utilized when an entropic stabilizer, based on the principle of maximizing local entropy, was proposed for the LB method [I. V. Karlin, F. Bösch, and S. S. Chikatamarla, Phys. Rev. E 90, 031302(R) (2014)]. The proposed stabilizer can be considered as an add-on or extension to basic LB schemes. Here the entropic stabilizer is investigated numerically using the perturbed double periodic shear layer flow as a benchmark case. The investigation is carried out by comparing numerical results obtained with six distinct LB schemes. The main observation is that the unbounded, and not explicitly controllable, relaxation time for the higher-order moments will directly influence the leading-order error terms. As a consequence, the order of accuracy and, in general, the numerical behavior of LB schemes are substantially altered. Hence, in addition to systematic numerical validation, more detailed theoretical analysis of the entropic stabilizer is still required in order to properly understand its properties.


Evidence of a non-progressive course of alternating hemiplegia of childhood: study of a large cohort of children and adults.
Alternating hemiplegia of childhood is a neurological disorder characterized by episodes of hemiplegia, various non-epileptic paroxysmal events and global neurological impairment. Characterization of the evolution and outcome into adulthood has not been sufficiently investigated. The goal of this study was to elucidate the natural history of alternating hemiplegia within a large cohort of 157 patients, as part of the European Network for Research on Alternating Hemiplegia project. A questionnaire was formulated to determine the severity of both paroxysmal and global neurological impairment and address progression of the disorder by allocating data to specific age epochs up to and over 24 years of age. Patients in early age groups were consistently present in subsequent later age groups and for each patient, data were collected for each corresponding age epoch. The study was based on predominantly retrospective and, for a period of 2 years, prospective data. At inclusion, patients were aged from 9 months to 52 years. The median age at diagnosis was 20 months. All patients experienced hemiplegic attacks; 86.5% reported episodes of bilateral weakness, 88% dystonic attacks, 53% epileptic seizures, 72% developed chorea and/or dystonia and 92% mental retardation. When data over the course of the illness were examined for the whole cohort, the severity of symptoms did not appear to change, with the exception of abnormal ocular movements and hypotonia that regressed, but did not disappear into adulthood (from 86 to 36% and 76 to 36%, respectively). No statistically significant correlation between a history of severe paroxysmal hemiplegic/dystonic episodes and a worse neurological outcome was identified. Seven patients died, some of whom experienced severe plegic attacks or epileptic seizures at the time of death. History of severe plegic/dystonic attacks was not found to be an aggravating factor for deceased patients. Our results provide evidence that the natural history of alternating hemiplegia is highly variable and unpredictable for individual patients. However, we did not find evidence to support a steadily progressive and degenerative course of the disorder when patients were analysed as a group. For a minority of patients, a risk of sudden death was associated with more severe neurological impairment. The European Network for Research on Alternating Hemiplegia Registry, validated by our study, includes all major neurological signs and symptoms of alternating hemiplegia and may thus be used as a precedent for the progressive inclusion and follow-up of patients as well as a reference for genetic studies and treatment trials.


Race and Drug Toxicity: A Study of Three Cardiovascular Drugs with Strong Pharmacogenetic Recommendations.
The Clinical Pharmacogenetics Implementation Consortium (CPIC®) establishes evidence-based guidelines for utilizing pharmacogenetic information for certain priority drugs. Warfarin, clopidogrel and simvastatin are cardiovascular drugs that carry strong prescribing guidance by CPIC. The respective pharmacogenes for each of these drugs exhibit considerable variability amongst different ethnic/ancestral/racial populations. Race and ethnicity are commonly employed as surrogate biomarkers in clinical practice and can be found in many prescribing guidelines. This is controversial due to the large variability that exists amongst different racial/ethnic groups, lack of detailed ethnic information and the broad geographic categorization of racial groups. Using a retrospective analysis of electronic health records (EHR), we sought to determine the degree to which self-reported race/ethnicity contributed to the probability of adverse drug reactions for these drugs. All models used individuals self-reporting as White as the comparison group. The majority of apparent associations between different racial groups and drug toxicity observed in the "race only" model failed to remain significant when we corrected for covariates. We did observe self-identified Asian race as a significant predictor (p = 0.016) for warfarin hemorrhagic events in all models. In addition, patients identifying as either Black/African-American (p = 0.001) or Other/Multiple race (p = 0.019) had a lower probability of reporting an adverse reaction than White individuals while on simvastatin even after correcting for other covariates. In both instances where race/ethnicity was predictive of drug toxicity (i.e., warfarin, simvastatin), the findings are consistent with the known global variability in the pharmacogenes described in the CPIC guidelines for these medications. These results confirm that the reliability of using self-identified race/ethnic information extracted from EHRs as a predictor of adverse drug reactions is likely limited to situations where the genes influencing drug toxicity display large, distinct ethnogeographic variability.


Psychometric testing of Ibadan low back pain disability questionnaire.
The Ibadan Low Back Pain Disability Questionnaire (ILBPDQ) was developed to meet the need for a LBP treatment outcome measure that was appropriate for the Nigerian culture and environment. The objective of this study was to determine the psychometric properties of ILBPDQ. This study used the validation design. One hundred and forty-two participants with LBP (LBPPs) and 142 age and sex-matched participants without LBP (NLBPPs) were included. The LBPPs were recruited consecutively from Physiotherapy clinics of selected tertiary hospitals in the six geopolitical zones of Nigeria. Both LBPPs and NLBPPs completed the ILBPDQ - the LBPPs completed the Numerical Pain Rating Scale (NPRS). The ILBPDQ was completed by 113 LBPPs two days after initial assessment. Sixty-four of the LBPPs received physiotherapy for 5-weeks, after which they were reassessed using ILBPDQ and NPRS. ILBPDQ score of LBPPs was significantly higher than that of NLBPPs (construct validity) and LBPPs NPRS score correlated significantly with their ILBPDQ score (r = 0.50) at baseline and post intervention (r =0.35) (divergent validity). ILBPDQ scores at baseline and 48 hours later for LBPPs correlated significantly (Intra Class Correlation =0.80) (test re -test reliability). Cronbach's α for ILBPDQ was 0.84 (internal consistency). The postintervention ILBPDQ and NPRS scores for LBPPs were significantly lower than their pre-intervention ILBPDQ scores (responsiveness) and NPRS scores. The changes in ILBPDQ and NPRS scores of the LBPPs correlated significantly (r =0.62) (responsiveness). The ILBPDQ demonstrated evidence of validity, reliability and responsiveness. University of Ibadan Senate Research Grant.


Outcomes of transplantation using kidneys from donors meeting expanded criteria in Australia and New Zealand, 1991 to 2005.
Kidneys from expanded criteria donors (ECD) are reported to have inferior transplant outcomes. Using the Australia and New Zealand Dialysis and Transplant Registry, we reviewed deceased donor kidneys transplanted from 1991 to 2005 in Australia and New Zealand, followed until December 2006. ECD was defined using United Network for Organ Sharing criteria. Graft and patient outcomes, estimated glomerular filtration rates (eGFR), acute rejection, and delayed graft function were analyzed by donor-age and ECD status, with adjustment for important covariates. There were 3248 recipients of non-ECD kidneys and 781 recipients of ECD kidneys. Compared with donors aged less than 50 years, adjusted hazard ratios for graft failure (GF) at 0 to 1 and 1 to 5 years for ECD kidneys from donors aged 60 years or above were 1.92 (1.48-2.49; P<0.001) and 2.52 (1.97-3.23; P<0.001). The hazard ratios for GF were 1.87 (1.31-2.70; P<0.05) for ECD kidneys from donors aged 50 to 59 years in the first year but were not increased subsequently. Mean eGFR at 1 year decreased with increasing donor age and ECD status (56.4 [53.8-58.9] mL/min for kidneys from donors aged <50, 46.6 [45.0-48.3] and 43.5 [41.1-45.9] for non-ECD and ECD donors aged 50 to 59 years, respectively, and 38.6 [36.9-40.4] for donors > or =60; P<0.001) but subsequent eGFR loss was similar except for donors aged 60 years or above (P=0.021). Acute rejection and delayed graft function were more frequent in ECD kidney recipients, but the associations between GF and donor age/ECD status were independent of these factors. For recipients of ECD kidneys, donor age 60 years or above is the most significant determinant of poor outcome; donor age 50 to 59 years represents a category of intermediate risk.


Herpes simplex virus infection in a hyper-IgE patient: appearance of unusual mass lesions.
A 7-year-old girl presented with large soft masses rising from the nostril and from behind the ear. She had previously been diagnosed as suffering from hyper-IgE syndrome. The presence of herpes simplex virus infection within these lesions was confirmed by biopsy and immunohistochemical studies. The mass lesions did not respond to antibacterial therapy with cefazolin, but improved promptly under antiviral therapy with acyclovir. Immunological studies revealed a mild decrease in the CD4 cell population. Based on our results and on the relevant literature we propose an immunological mechanism for this unique manifestation of herpes simplex virus infection in hyper-IgE syndrome.


Human cytomegalovirus TRS1 protein is required for efficient assembly of DNA-containing capsids.
The human cytomegalovirus tegument protein, pTRS1, appears to function at several discrete stages of the virus replication cycle. We previously demonstrated that pTRS1 acts during the late phase of infection to facilitate the production of infectious virions. We now have more precisely identified the late pTRS1 function by further study of a mutant virus lacking the TRS1 region, ADsubTRS1. We observed a significant reduction in the production of capsids, especially DNA-containing C-capsids, in mutant virus-infected cells. ADsubTRS1 exhibited normal cleavage of DNA concatemers, so the defect in C-capsid production must occur after DNA cleavage and before DNA is stably inserted into a capsid. Further, the normal virus-induced morphological reorganization of the nucleus did not occur after infection with the pTRS1-deficient mutant.


Occurrence of a cytochrome P-450-containing mixed-function oxidase system in the pond snail, Lymnaea stagnalis.
1. The occurrence of an as yet unidentified cytochrome P-450 in the microsomal fraction of the digestive gland of the snail, Lymnaea stagnalis was studied. 2. Studies in vivo and in vitro (digestive gland homogenates or the 170,000g fraction) of the cytochrome P-450-mediated metabolism of substrates such as biphenyl, pentoxy- and ethoxy-resorufin and aminopyrine have been made. 3. Cytochrome P-450 concentration in the digestive gland calculated from CO-difference spectra was 0.30 +/- 0.05 nmol/g tissue. This amount was not increased either by phenobarbital or by 3-methylcholanthrene. 4. Aniline binding spectra resembled normal type II spectra, while type I model substrates such as hexobarbital and 2,2'-dichlorobiphenyl showed type II- or reversed type I-like spectra. 5. O-Deethylation of 7-ethoxyresorufin did not occur, but 7-pentoxyresorufin O-depentylation activity (80.4 +/- 28.6 pmol resorufin/g per hour) and aminopyrine N-demethylation activity (375 +/- 96 pmol formaldehyde/g per minute) were demonstrated. 6. 4-Hydroxybiphenyl was the major metabolite of biphenyl, while minor amounts of 2-hydroxybiphenyl were formed (in vivo: 63.7 nmol 4-hydroxybiphenyl and 3.33 nmol 2-hydroxybiphenyl per snail per 24 h, after an oral dose of 778.2 nmol biphenyl; in vitro 118 +/- 21 pmol and 21 +/- 9 nmol, respectively (digestive gland homogenate/mg protein, per hour). 7. The results indicate that the isoenzymes involved in the observed MFO activities resemble isoenzymes P-450b/e.


Microsurgical techniques for lymphedema treatment: derivative lymphatic-venous microsurgery.
We analyzed clinicopathologic and imaging features of chronic peripheral lymphedema to identify imaging findings indicative of its exact etiopathogenesis and to establish the optimal treatment strategy. One of the main problems of microsurgery for lymphedema is the discrepancy between the excellent technical possibilities and the subsequently insufficient reduction of the lymphedematous tissue fibrosis and sclerosis. Appropriate treatment based on pathologic studies and surgical outcome have not been adequately documented. Over the past 25 years, 676 patients with peripheral lymphedema have been treated with microsurgical lymphatic-venous anastomoses. Of these patients, 447 (66%) were available for long-term follow-up study. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Objectively, volume changes showed a significant improvement in 561 patients (83%), with an average reduction of 67% of the excess volume. Of the 447 patients followed, 380 (85%) have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was an 87% reduction in the incidence of cellulitis after microsurgery. Microsurgical lymphatic-venous anastomoses have a place in the treatment of peripheral lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. Improved results can be expected with operations performed early, during the first stages of lymphedema.


Complementary and alternative medicine for chronic prostatitis/chronic pelvic pain syndrome.
To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990-2005 using the PubMed, Medline databases. Data from the articles were abstracted and pooled by subject. Keywords cross-searched with CP/CPPS included: complementary, alternative, integrative, therapies, interventions, nutrition, antioxidants, herbs, supplements, biofeedback and acupuncture. Listed articles with no abstracts were not included. Various CAM therapies for CP/CPPS exist including biofeedback, acupuncture, hyperthermia and electrostimulation. Additionally, a variety of in vitro and in vivo studies testing herbal and nutritional supplements were found. Saw palmetto, cernilton and quercetin were the most frequently tested supplements for CP/CPPS. Although many CAM therapies demonstrate positive preliminary observations as prospective treatments for CP/CPPS, further exploratory studies including more randomized, controlled trials are necessary for significant validation as treatment options for this complex disorder.


Clinical usefulness of binocular multifocal electroretinography in patients with monocular macular disease.
To evaluate the clinical usefulness of binocular multifocal electroretinography (mfERG) by comparing results with conventional monocular mfERG in patients with monocular macular disease. mfERG testing was conducted on 32 patients with monocular macular disease and 30 normal subjects. An initial mfERG was simultaneously recorded from both eyes with two recording electrodes under binocular stimulation. A second mfERG was subsequently recorded with conventional monocular stimulation. Amplitudes and implicit times of each ring response of the binocular and monocular recordings were compared. Ring ratios of the binocular and monocular recording were also compared. In the macular disease group, there were no statistical differences in amplitude or implicit time for each of the five concentric rings between the monocular and binocular recordings. However, with binocular simulation, the ring ratios (ring 1 / ring 4, ring 1 / ring 5) were significantly reduced in the affected eye. In the normal control group, there were no statistical differences in any parameters between the monocular and binocular recordings. Binocular mfERG could be a good alternative to the conventional monocular test. In addition, given that the test needs stable fixation of the affected eye during the binocular test, the reliability of the test results could be improved, especially for patients with monocular macular disease.


Trajectory of Serum Bilirubin Predicts Spontaneous Recovery in a Real-World Cohort of Patients With Alcoholic Hepatitis.
Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments. We analysed the trajectory of serum bilirubin concentration over the course of hospital admissions in patients with AH to predict spontaneous survival and the need for treatment. data from 426 patients were analysed. Based on bilirubin trajectory, patients were categorized into three groups: 'fast fallers' (bilirubin <0.8 x admission value at day 7), 'static' (bilirubin of >0.9 - <1.2 x admission value) and 'rapid risers' (bilirubin of ≥1.2 x admission bilirubin). Fast fallers had significantly better 90-day survival compared to other groups (log rank p < .001), and showed no benefit of corticosteroid therapy (OR for survival at 28 days of treatment, 0.94, 95% CI 0.06 - 8.41). These findings remained even amongst patients with severe disease based on initial DF, GAHS or MELD scores. We present an intuitive method of classifying patients with AH based on the trajectory of bilirubin over the first week of admission. It is complimentary to existing scores that identify candidates for corticosteroid treatment or assess response to treatment. This method identifies a group of patients with AH who recover spontaneously and can avoid corticosteroid therapy.


Ovarian torsion in a 23-year-old female with pelvic pain.
Ovarian torsion is infrequently seen in the emergency department, however, a delay in diagnosis and treatment can lead to necrosis and loss of the ovary (E. D. Shraga & M. Blanda, 2008). A patient with pelvic pain diagnosed with ovarian torsion is presented in this article. The diagnosis and treatment of ovarian torsion is discussed to help the advanced practice nurse gain a better understanding of this frequently missed problem.


Monokines in growth and development.
Stimulation of the immune system results in a series of metabolic changes that are antagonistic toward growth. Monokines, including interleukin-1, tumor necrosis factor, and interleukin-6, are released from cells of the monocyte-macrophage lineage after recognition of immunogens. They appear to mediate homeorhetic response, which alters the partitioning of dietary nutrients away from growth and skeletal muscle accretion in favor of metabolic processes which support the immune response and disease resistance. These alterations include 1) decreased skeletal muscle accretion due to increased rates of protein degradation and decreased protein synthesis; 2) increased basal metabolic rate resulting in increased energy utilization; 3) use of dietary amino acids for gluconeogenesis and as an energy source instead of for muscle protein accretion; 4) synthesis by the liver of acute phase proteins; 5) redistribution of iron, zinc, and copper within the body due to the hepatic synthesis of metallothionein, ferritin, and ceruloplasmin; (6) impaired accretion of cartilage and bone; and 7) release of hormones such as insulin, glucagon, and corticosterone. These monokines also influence the differentiation of cells. Tumor necrosis factor suppresses the differentiation of myoblasts and adipocytes whereas the chicken monokine myelomonocytic growth factor induces the differentiation of granulocytes.


Cerebral toxoplasmosis in striped dolphins (Stenella coeruleoalba) stranded along the Ligurian Sea coast of Italy.
This article reports the results of necropsy, parasitologic, microbiologic, histopathologic, immunohistochemical, indirect immunofluorescence, biomolecular, and serologic investigations on 8 striped dolphins (Stenella coeruleoalba) found stranded from August to December 2007 on the Ligurian Sea coast of Italy. Severe, nonsuppurative meningoencephalitis was found in 4 animals, as characterized by prominent perivascular mononuclear cell cuffing and macrophage accumulations in neuropil. These lesions were associated with mild lymphocytic-plasmacytic infiltration of choroid plexuses in 1 dolphin. Toxoplasma gondii cysts and zoites, confirmed by immunohistochemical labeling, were scattered throughout the brain parenchyma of 2 of the 4 dolphins. No viral inclusions were seen in the brain of any animal. Other findings included severe bronchointerstitial pneumonia and pulmonary atelectasis, consolidation, and emphysema. Parasites were identified in a variety of organs, including lung (Halocerchus lagenorhynchi). Microbiologic and serologic examinations for Brucella spp were negative on all 8 dolphins. The 4 animals with meningoencephalitis had serum antibodies against T gondii (titers ranging from 1:80 to 1:320) but not against morbillivirus. In contrast, the other 4 dolphins were seropositive for morbillivirus (with titers ranging from 1:10 to 1:40) but seronegative for T gondii. No morbillivirus antigen or nucleic acid was detected in the tissues of any dolphin. It is concluded that the severe lung and brain lesions were the cause of death and that T gondii was the likely etiologic agent of the cerebral lesions. Morbillivirus infection was not considered to have contributed to death of these animals.


Two Powerful Tests for Parent-of-Origin Effects at Quantitative Trait Loci on the X Chromosome.
Parent-of-origin effects, which describe an occurrence where the expression of a gene depends on its parental origin, are an important phenomenon in epigenetics. Statistical methods for detecting parent-of-origin effects on autosomes have been investigated for 20 years, but the development of statistical methods for detecting parent-of-origin effects on the X chromosome is relatively new. In the literature, a class of Q-XPAT-type tests are the only tests for the parent-of-origin effects for quantitative traits on the X chromosome. In this paper, we propose two simple and powerful classes of tests to detect parent-of-origin effects for quantitative trait values on the X chromosome. The proposed tests can accommodate complete and incomplete nuclear families with any number of daughters. The simulation study shows that our proposed tests produce empirical type I error rates that are close to their respective nominal levels, as well as powers that are larger than those of the Q-XPAT-type tests. The proposed tests are applied to a real data set on Turner's syndrome, and the proposed tests give a more significant finding than the Q-C-XPAT test.


The effect of colcemid and aluminum on the ultrastructure of human metaphase chromosomes.
Recently, we have reported new basic information on the ultrastructure of human metaphase chromosomes using both scanning and transmission electron microscopy. This includes the observation of a bipartite chromatid structure (BCS) for some metaphase chromatids, a "zipper-like" configuration (ZC) between chromatids that likely resulted from chromatin coiling, and a "brush-like" border (BB) that was observed primarily on chromosomes that were not exposed to colcemid. Now we have examined the effects of colcemid and several metals on the occurrence of the BCS, the ZC, and the BB. Although we do not as yet know the function of the zipper-like and bipartite chromatid configurations, we have found that colcemid clearly caused a significant increase in the occurrence of chromosomes with a BCS or ZC. We also have confirmed our original observation of increased occurrence of the BB on chromosomes not exposed to colcemid and finally, have shown that aluminum and other metals had some effect on the frequencies of the BCS, the ZC, and the BB with and without exposure to colcemid.


[Allergen challenge used to diagnose food allergy--oral allergy syndrome].
Food allergy is an immune mediated unwanted side effect to food. All types of hypersensitivity can be involved; the most prevalent is IgE mediated one. The diagnosis is based on the history, skin tests with allergens and detection of specific IgE. These procedures are not highly predictive for clinical reactivity to food allergens, true clinical reactivity can be confirmed by allergen challenge. Oral allergy syndrome is represented by mostly subjective symptoms in oral cavity, usually triggered by fruit or vegetable allergens, cross-reacting with pollen allergens. This cross-reactivity is based on protein homology and immunologic similarity. To confirm the diagnosis of food allergy, the ,,golden standard" is the double blind placebo controlled food challenge. The basic features of this test are discussed, particularly in the diagnosis of the oral allergy syndrome. Controlled food challenge is a useful test for patient's diagnosis confirmation, evaluation of other diagnostic tests or evaluation of food allergenicity.


Carpal tunnel syndrome despite negative neurophysiological studies.
The purpose of the present study was to compare the results of conservative and operative treatment for patients with carpal tunnel syndrome having normal neurophysiological studies. We studied 125 patients with normal neurophysiological studies and analysed eight symptoms and signs as "prognostic factors". Ninety-six patients were treated conservatively (splintage, steroid injection, antiinflammatory medications, activity modification) and 29 were treated surgically (open decompression). One year after initiation of treatment we assessed the outcome and statistically analysed (chi-square test) the differences between the two groups. We did not find any statistically significant correlation between "prognostic factors" and outcome. Twenty four percent of the group treated non-operatively had a good or excellent outcome, whereas 90% of the group treated operatively had a good or excellent outcome. This difference was statistically significant (p < 0.0001). Our study supports the view that the diagnosis of carpal tunnel syndrome is clinical and not neurophysiological. We now recommend operative treatment for these patients.


A nomogram to predict prognosis of patients with unresected hepatocellular carcinoma undergoing radiotherapy: a population-based study.
Background: Radiotherapy is a primary treatment strategy for patients with unresectable hepatocellular carcinoma (HCC); however, the prognostic factors among HCC patients who have received radiotherapy but not undergone surgery have not been systematically studied. Thus, the prognostic factors were investigated in this study based on the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Methods: A screening process was used for select cases from the SEER database. Survival was analyzed using the Kaplan-Meier method and log-rank test, the Cox proportional hazards regression model, and a competing risk model. A nomogram was established for predicting 1- and 3-year overall survival (OS) of patients. Results: A total of 1305 HCC patients who received radiotherapy but had not undergone surgery were included in this study and divided into training (n = 1175) and validation cohorts (n = 130). Patients in the training cohort had a 1-year OS rate of 30.9±1.3%, a 3-year OS rate of 10.0±1.0%, and a median survival rate of 6.0 months (range, 5.4-6.6 months). Race (p = 0.025), T stage (p < 0.001), N stage (p < 0.001), M stage (p < 0.001), and chemotherapy (p < 0.001) were identified as independent risk factors by multivariate analyses in the training cohort, while sex, age, grade, marital status, and insurance status were not independent factors. Survival in patients who received radiotherapy was worse with respect to the following characteristics: black race; higher T, N, or M stage; and no chemotherapy. A nomogram was established based on the results of the multivariate analysis, which was internally validated by a concordance index (C-index) of 0.731±0.016 and a group of calibration plots. External validation was carried out and the C-index was 0.738±0.049, which demonstrated the effectiveness of the nomogram we constructed. Conclusions: Race, T stage, N stage, M stage, and chemotherapy were independent risk factors for survival of HCC patients who received radiotherapy but had not undergone surgery. A validated nomogram was formulated to predict 1- and 3-year OS in these patients based on individual clinical characteristics.


Identifying non-reference sites to guide stream restoration and long-term monitoring.
The reference condition paradigm has served as the standard for assessing the outcomes of restoration projects, particularly their success in meeting project objectives. One limitation of relying solely on the reference condition in designing and monitoring restoration projects is that reference conditions do not necessarily elucidate impairments to effective restoration, especially diagnosing the causal mechanisms behind unsuccessful outcomes. We provide a spatial framework to select both reference and non-reference streams to guide restoration planning and long-term monitoring through reliance on anthropogenically altered ecosystems to understand processes that govern ecosystem biophysical properties and ecosystem responses to restoration practices. We then applied the spatial framework to East Fork Poplar Creek (EFPC), Tennessee (USA), a system receiving 30years of remediation and pollution abatement actions from industrialization, pollution, and urbanization. Out of >13,000 stream reaches, we identified anywhere from 4 to 48 reaches, depending on the scenario, that could be used in restoration planning and monitoring for specific sites. Preliminary comparison of fish species composition at these sites compared to EFPC sites were used to identify potential mechanisms limiting the ecological recovery following remediation. We suggest that understanding the relative role of anthropogenic pressures in governing ecosystem responses is required to successful, process-driven restoration.


Phase 2 study of sodium phenylbutyrate in ALS.
The objective of the study was to establish the safety and pharmacodynamics of escalating dosages of sodium phenylbutyrate (NaPB) in participants with ALS. Transcription dysregulation may play a role in the pathogenesis of ALS. Sodium phenylbutyrate, a histone deacetylase inhibitor, improves transcription and post-transcriptional pathways, promoting cell survival in a mouse model of motor neuron disease. Forty research participants at eight sites enrolled in an open-label study. Study medication was increased from 9 to 21 g/day. The primary outcome measure was tolerability. Secondary outcome measures included adverse events, blood histone acetylation levels, and NaPB blood levels at each dosage. Twenty-six participants completed the 20-week treatment phase. NaPB was safe and tolerable. No study deaths or clinically relevant laboratory changes occurred with NaPB treatment. Histone acetylation was decreased by approximately 50% in blood buffy-coat specimens at screening and was significantly increased after NaPB administration. Blood levels of NaPB and the primary metabolite, phenylacetate, increased with dosage. While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels.


A case of double gallbladder with adenocarcinoma arising from the left hepatic duct: a case report and review of the literature.
Double gallbladder is a rare congenital biliary anomaly, but an accessory gallbladder arising from the left hepatic duct is a more remarkably rare congenital anomaly. We report a case of double gallbladder with adenocarcinoma and gallstones, which was preoperatively diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) and then confirmed by open laparotomy. A review of the literature is presented.


The dynamics of health and its determinants among the elderly in developing countries.
This paper examines the persistence of bad health among the elderly, and attempts to identify its determinants. We are particularly interested in the role of recent past bad health. Using a panel data set from Indonesia Family Life Survey (IFLS), several health measures such as poor general health status (poor GHS), hypertension, and low body mass index (low BMI) are examined. We find that for all health measures, recent past bad health has a small impact on current bad health once conditioning on individual fixed effects. For instance, in the case of poor GHS, the elderly with poor GHS in the recent past are only 4% points more likely to have poor GHS in the subsequent period compared to their counterparts.


The immune cell profile of the developing rat brain.
Little is known about the peripheral immune cell (PIC) profile of the developing brain despite growing appreciation for these cells in the mature nervous system. To address this gap, the PIC profile, defined as which cells are present, where they are located, and for how long, was examined in the developing rat using spectral flow cytometry. Select regions of the rat brain (cerebellum, hippocampus, and hypothalamus) were examined at embryonic day 20, and postnatal days 0, 7 and 16. At their peak (E20), PICs were most abundant in the cerebellum, then the hippocampus and hypothalamus. Within the PIC pool, monocytes were most prevalent in all regions and time points, and shifted from being majority classical at E20 to non-classical by PN7. T cells increased over time, and shifted from majority cytotoxic to T-helper cells by PN7. This suggests the PIC profile transitions from reactive to adaptive and surveilling in the second postnatal week. NK cells and mast cells increased temporarily, and mast cells were restricted to the hippocampus and hypothalamus, suggesting they may play a specific role in the development of those regions. Mimicking a viral infection by administration of Poly I:C increased the influx of PICs into the neonatal brain, particularly of NK cells and in the case of males only, non-classical monocytes. This work provides a map for researchers as they study immune cell contributions to healthy and pathological brain development.


Short-Term Plyometric Jump Training Improves Repeated-Sprint Ability in Prepuberal Male Soccer Players.
Negra, Y, Chaabene, H, Fernandez-Fernandez, J, Sammoud, S, Bouguezzi, R, Prieske, O, and Granacher, U. Short-term plyometric jump training improves repeated-sprint ability in prepuberal male soccer players. J Strength Cond Res 34(11): 3241-3249, 2020-This study examined the effects of a short-term (i.e., 8 weeks) combined horizontal and vertical plyometric jump training (PJT) program in combination with regular soccer-specific training as compared with soccer-specific training only on jump and change of direction (CoD) performances, speed, and repeated-sprint ability (RSA) in prepuberal male soccer players. Twenty-four players were recruited and randomly assigned to either a PJT group (PJTG; n = 13; 12.7 ± 0.2 years) or an active control group (CONG; n = 11; 12.7 ± 0.2 years). The outcome measures included tests for the assessment of jump performance (drop jump from 20- to 40-cm height [DJ20 and DJ40] and 3-hop test [THT]), speed (20-m sprint), CoD (T-test), and RSA (20-m repeated shuttle sprint). Data were analyzed using magnitude-based inferences. Within-group analyses revealed large performance improvements in the T-test (d = -1.2), DJ20 (d = 3.7), DJ40 (d = 3.6), THT (d = 0.6), and the RSAtotal (d = -1.6) in the PJTG. Between-group analyses showed greater performance improvements in the T-test (d = -2.9), 20-m sprint time (d = -2.0), DJ20 (d = 2.4), DJ40 (d = 2.0), THT (d = 1.9), RSAbest (d = -1.9), and the RSAtotal (d = -1.9) in the PJTG compared with CONG. Eight weeks of an in-season PJT in addition to regular soccer-specific training induced larger increases in measures of physical fitness in prepuberal male soccer players compared with regular soccer-specific training only. More specifically, PJT was effective in improving RSA performance.


Mechanisms that contribute to the development of lymphoid malignancies: roles for genetic alterations and cytokine production.
Recent studies have defined genetic alterations commonly associated with transformed lymphocytes. This review suggests roles for these alterations in the development of lymphoid neoplasms. Damage to the genes encoding proteins that function in intracellular signaling, transcription, or regulation of the cell cycle has been identified and linked at varying degrees to the progression of certain lymphoid malignancies. An understanding of the mechanistic consequences following such genetic alterations is essential to an understanding of the development of these lymphoid neoplasms. In contrast, it is also becoming clear that the dysregulated expression of proteins that are not genetically altered can also contribute to the progression of lymphoid malignancies. One such example is the excessive expression of "normal" lymphokines of cytokines which accompanies many lymphoproliferative diseases. The dysregulated expression of cytokines during malignancy can result in the augmentation of growth of transformed lymphocytes, as well as an alteration of the anti-tumor immune response. The latter mechanism is especially important because evasion of the impending immune response is a prerequisite for the progression of lymphoproliferative diseases. Taken together, this review supports the notion that the development of lymphoid malignancies is multifactorial, involving genetic alterations as well as dysregulated cytokine expression.


Selenium: a quest for better understanding.
Selenium is an essential trace element in nutrition for the prevention of disease in humans. Epidemiological studies indicate an association between low nutritional selenium status and increased risks of cardiomyopathy, cardiovascular disease, and carcinogenesis in various sites of the body. The role of selenium supplementation in the prevention and treatment of AIDS-related pathology has been considered. Selenoproteins discovered in mammalian cells may account for the essentiality of selenium in the body's antioxidant defense; thyroid hormone function; immune system function, particularly the cellular immunity; formation of sperm; and functioning of the prostate gland. The seleno-organic compounds, primarily L-(+)-selenomethionine, generally are recognized as safe and effective forms of selenium supplementation. The nutritionally recommended dose of elemental selenium is estimated at 50 to 200 micrograms [corrected] per day. There is, however, increased discussion of a pharmacological dose of selenium, significantly higher than the nutritional dose of the microelement, to treat active conditions. One way of increasing the tissue levels of selenium is to combine its ingestible form with a nutrient bioavailability enhancing compound.


The zebrafish dyrk1b gene is important for endoderm formation.
Nodal-signaling is required for specification of mesoderm, endoderm, establishing left-right asymmetry, and craniofacial development. Wdr68 is a WD40-repeat domain-containing protein recently shown to be required for endothelin-1 (edn1) expression and subsequent lower jaw development. Previous reports detected the Wdr68 protein in multiprotein complexes containing mammalian members of the dual-specificity tyrosine-regulated kinase (dyrk) family. Here we describe the characterization of the zebrafish dyrk1b homolog. We report the detection of a physical interaction between Dyrk1b and Wdr68. We also found perturbations of nodal signaling in dyrk1b antisense morpholino knockdown (dyrk1b-MO) animals. Specifically, we found reduced expression of lft1 and lft2 (lft1/2) during gastrulation and a near complete loss of the later asymmetric lft1/2 expression domains. Although wdr68-MO animals did not display lft1/2 expression defects during gastrulation, they displayed a near complete loss of the later asymmetric lft1/2 expression domains. While expression of ndr1 was not substantially effected during gastrulation, ndr2 expression was moderately reduced in dyrk1b-MO animals. Analysis of additional downstream components of the nodal signaling pathway in dyrk1b-MO animals revealed modestly expanded expression of the dorsal axial mesoderm marker gsc while the pan-mesodermal marker bik was largely unaffected. The endodermal markers cas and sox17 were also moderately reduced in dyrk1b-MO animals. Notably, and similar to defects previously reported for wdr68 mutant animals, we also found reduced expression of the pharyngeal pouch marker edn1 in dyrk1b-MO animals. Taken together, these data reveal a role for dyrk1b in endoderm formation and craniofacial patterning in the zebrafish.


A Versatile Plant Rhabdovirus-Based Vector for Gene Silencing, miRNA Expression and Depletion, and Antibody Production.
Plant virus vectors are ideal tools for delivery of genetic cargo into host cells for functional genomics studies and protein overexpression. Although a vast number of plant virus vectors have been developed for different purposes, the utility of a particular virus vector is generally limited. Here, we report a multipurpose plant rhabdovirus-based vector system suitable for a wide range of applications in Nicotiana benthamiana. We engineered sonchus yellow net rhabdovirus (SYNV)-based gene silencing vectors through expressing a sense, antisense, or double-stranded RNAs of target genes. Robust target gene silencing was also achieved with an SYNV vector expressing a designed artificial microRNA. In addition, ectopic expression of a short tandem target mimic RNA using the SYNV vector led to a significant depletion of the target miR165/166 and caused abnormal leaf development. More importantly, SYNV was able to harbor two expression cassettes that permitted simultaneous RNA silencing and overexpression of large reporter gene. This dual capacity vector also enabled systemic expression of a whole-molecule monoclonal antibody consisting of light and heavy chains. These results highlight the utility of the SYNV vector system in gene function studies and agricultural biotechnology and provide a technical template for developing similar vectors of other economically important plant rhabdoviruses.


Comprehensive Ion Mobility Calibration: Poly(ethylene oxide) Polymer Calibrants and General Strategies.
Ion mobility (IM) is now a well-established and fast analytical technique. The IM hardware is constantly being improved, especially in terms of the resolving power. The Drift Tube (DTIMS), the Traveling Wave (TWIMS), and the Trapped Ion Mobility Spectrometry (TIMS) coupled to mass spectrometry are used to determine the Collision Cross-Sections (CCS) of ions. In analytical chemistry, the CCS is approached as a descriptor for ion identification and it is also used in physical chemistry for 3D structure elucidation with computational chemistry support. The CCS is a physical descriptor extracted from the reduced mobility (K0) measurements obtainable only from the DTIMS. TWIMS and TIMS routinely require a calibration procedure to convert measured physical quantities (drift time for TWIMS and elution voltage for TIMS) into CCS values. This calibration is a critical step to allow interinstrument comparisons. The previous calibrating substances lead to large prediction bands and introduced rather large uncertainties during the CCS determination. In this paper, we introduce a new IM calibrant (CCS and K0) using singly charged sodium adducts of poly(ethylene oxide) monomethyl ether (CH3O-PEO-H) for positive ionization in both helium and nitrogen as drift gas. These singly charged calibrating ions make it possible to determine the CCS/K0 of ions having higher charge states. The fitted calibration plots exhibit larger coverage with less data scattering and significantly improved prediction bands and uncertainties. The reasons for the improved CCS/K0 accuracy, advantages, and limitations of the calibration procedures are also discussed. A generalized IM calibration strategy is suggested.


A contemporary baseline record of the world's coral reefs.
Addressing the global decline of coral reefs requires effective actions from managers, policymakers and society as a whole. Coral reef scientists are therefore challenged with the task of providing prompt and relevant inputs for science-based decision-making. Here, we provide a baseline dataset, covering 1300 km of tropical coral reef habitats globally, and comprised of over one million geo-referenced, high-resolution photo-quadrats analysed using artificial intelligence to automatically estimate the proportional cover of benthic components. The dataset contains information on five major reef regions, and spans 2012-2018, including surveys before and after the 2016 global bleaching event. The taxonomic resolution attained by image analysis, as well as the spatially explicit nature of the images, allow for multi-scale spatial analyses, temporal assessments (decline and recovery), and serve for supporting image recognition developments. This standardised dataset across broad geographies offers a significant contribution towards a sound baseline for advancing our understanding of coral reef ecology and thereby taking collective and informed actions to mitigate catastrophic losses in coral reefs worldwide.


Identification and characterization of RAPD markers inferring genetic relationships among Pine species.
Total genomic DNAs were extracted from several populations of pine species and amplified using oligonucleotides of random sequences. Polymorphism in random amplified polymorphic DNA (RAPD) markers was high and sufficient in distinguishing each of the species. Genetic relationships among eight pine species (Pinus sylvestris, Pinus strobus, Pinus rigida, Pinus resinosa, Pinus nigra, Pinus contorta, Pinus monticola, and Pinus banksiana) from different provenances were analyzed. The degree of band sharing was used to evaluate genetic distance between species and to construct a phylogenetic tree. In general, the dendrogram corroborated the description of relationships based on morphological characteristics and crossability, but also provided new insights into pine taxonomy. RAPD markers specific to some pine species were cloned and sequenced. PCR amplifications using pairs of designed specific primers revealed that all the cloned sequences were likely genus specific because they were not found in spruce or larch. True species-specific sequences were identified using designed primers flanking cloned RAPD fragments. The analysis of RAPD fragment sequences confirmed the genetic relationships among species. A 2281-bp RAPD band called PI-Mt-Stb-23 from P. strobus was used as a probe in restriction fragment length polymorphism (RFLP) analysis and produced distinct banding patterns for each species examined, consistent with the highly polymorphic character of DNA-fingerprinting probes.


How common is heart failure? Evidence from PACT (prescribing analysis and cost) data in Nottingham.
The aim of the study was to determine the prevalence of heart failure in Nottinghamshire by an analysis of prescriptions for loop diuretics. An observational study was carried out in the Nottingham Health District, on the basis of Prescribing Analysis and Cost (PACT) data relating to nearly 400,000 kg of frusemide prescribed in the year 1991-1992 and general practitioner (GP) records on two groups of patients (total 903) prescribed frusemide. The total amount of frusemide prescribed on a daily basis in Nottinghamshire in 1,048,566 mg. The mean daily dose of frusemide per patient is 60 mg and the median dose 40 mg. There are between 13,107 and 26,214 patients taking frusemide in Nottinghamshire. Fifty-six per cent of patients prescribed loop diuretics by their GP fulfil diagnostic criteria for heart failure. The prevalence of heart failure in Nottinghamshire estimated from loop diuretic prescribing increases from 0.1 per cent in the age-group 30-39 years to 5.45 percent in patients aged over 90 years.


Geographic distribution of dentists in Japan: 1980-2000.
In the late 1950s and 1960s, Japan recognized that it had a shortage of dentists and that they were unevenly distributed. To solve these problems, four national and eight private dental schools were established, leading to a significant increase in the number of dental students in the 1970s and 1980s. The purpose of this study was to investigate the effects of this increased supply on the geographic distribution of dentists in Japan. We determined the number of dentists and the population in each of Japan's 3252 municipalities. The ratio of the number of dentists to the population of an area was assessed using Gini coefficients calculated from Lorenz curves. From 1980 to 2000, the average number of dentists per 100,000 persons in Japan increased from 44 to 70. The Lorenz curve plotted for 1980-1990 appeared as a nearly diagonal line, with the Gini coefficient decreasing from 0.310 to 0.263. The Gini coefficient in the year 2000 was 0.255, indicating only a slight improvement in 10 years from 1990 to 2000. The results suggest that the geographical distribution of dentists in Japan is influenced by municipalities' population size. While the number of dentists in municipalities with populations of less than 5000 increased during the years from 1980 to 2000, 25.9 percent of these municipalities still had no dentists at the end of this period. This is an important issue that warrants prompt corrective action.


Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells.
Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 ± 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 ± 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p < 0.05), without correlation with time from injury until surgery. The OPC markers Olig2, A2B5, NG2, and PDGFR-α were used. In contrast to the number of single-labeled Olig2, A2B5, NG2, and PDGFR-α-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p < 0.05); this was inversely correlated with time from injury to surgery (r = -0.8, p < 0.05). These results indicate that severe focal human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI.


Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue.
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are the hepatic manifestation of metabolic syndrome. However, its therapeutic strategy has not been established. Recently, an angiotensin II type 1 receptor blocker, telmisartan (Tel), has received a great deal of attention as a therapeutic tool for metabolic syndrome. The aim of this study was to investigate the efficacy and mechanisms of Tel on a murine NASH model. C57BL/6 mice were fed a methionine- and choline-deficient high-fat diet (MCDHF) or a standard diet with/without the administration of Tel (10 mg/kg/day) for 8 weeks. MCDHF feeding induced marked steatohepatitis with macrophage infiltration. Tel attenuated liver steatosis with decreased hepatic triglycerides (P<0.05) and fibrogenesis with decreased type I collagen and transforming growth factor-beta1 mRNA expressions (P<0.05). Tel also suppressed the infiltration of macrophages into the liver and decreased hepatic monocyte chemoattractant protein-1 and its receptor (CC-chemokine receptor 2; CCR2) mRNA expressions, especially CCR2. In vitro, Tel suppressed CCR2 expression, which was induced by low-density lipoprotein. The size of adipocyte in visceral fat tissue was reduced with an increased serum adiponectin concentration in the Tel group. In this study, we revealed that Tel attenuated steatohepatitis progression by suppressing the macrophage infiltration into the liver. Tel also affected the reduction of adipocyte size and elevation of serum adiponectin. Tel might serve as a new therapeutic strategy for NASH.


Pathogenesis of Cheyne-Stokes respiration in patients with congestive heart failure. Relationship to arterial PCO2.
In order to determine which patients with congestive heart failure (CHF) develop Cheyne-Stokes respiration (CSR) during sleep, we compared the cardiorespiratory profiles of CHF patients with CSR to those of CHF patients without CSR. Overnight polysomnography and continuous transcutaneous PCO2 (tc PCO2) monitoring, estimation of left ventricular ejection fraction (LVEF), pulmonary function tests, and chest radiograph were performed on 16 consecutive patients with chronic, stable CHF. The tc PCO2 monitor (Kontron 7640) was calibrated so that measurements reflected arterial PCO2 values. A mean value was calculated for wakefulness (W) and total sleep time (TST). Circulation time (CT) from the lung to the carotid body was estimated from the end of an apnea or voluntary breath-hold to the nadir of oxygen desaturation recorded on an ear oximeter. The duration of CSR was expressed as a percent of TST. Nine patients developed CSR during sleep (52.5 +/- 31.6 percent TST) (group 1) and 7 did not (group 2). All patients were male and both groups were a similar age (64 +/- 8 vs 63 +/- 4 years) and weight (body mass index, 28.1 +/- 3.5 vs 25.4 +/- 3.4 kg/m2). There were no significant intergroup differences between LVEF (22 +/- 5.2 vs 24.1 +/- 5.2 percent), CT (19.1 +/- 3.6 vs 15.9 +/- 6.7 s), SaO2 (W) (94 +/- 1.2 vs 92.4 +/- 2.1 percent), and SaO2 (TST) (90.8 +/- 2.7 vs 92.4 +/- 2.1 percent). The tc PCO2 (W) was lower in group 1 (34.4 +/- 3.5 vs 38.1 +/- 1.9 mm Hg), increased during sleep by a similar amount in both groups (1.6 +/- 1.5 vs 2.1 +/- 2.2 mm Hg), and was significantly lower during sleep in group 1 (36.1 +/- 3.4 vs 40.2 +/- 2.2 mm Hg). We conclude that CHF patients with CSR hyperventilate during sleep and wakefulness and that CHF patients with awake hypocapnia are more likely to develop CSR during sleep. These findings indicate that arterial PCO2 is important in determining which CHF patients develop CSR.