Polychlorinated biphenyls in mountain pine (Pinus uncinata) needles from Central Pyrenean high mountains (Catalonia, Spain).
The polychlorobiphenyl (PCB) composition of pine needles of Pinus uncinata from the Pyrenean high mountains has been investigated. Samples from four altitudes (1750, 1950, 2150, and 2250 m above sea level) were collected in March 2002 and June 2002 in a central area near Lake Redon. The observed concentrations were similar to those found in pine trees from rural areas in Europe. A correlation between log-transformed PCB concentrations and reciprocal of absolute average air temperature was observed for all congeners studied except No. 28, the most volatile congener studied. The highest concentrations were found at the lowest temperatures. Phase-change enthalpies calculated from the slopes of the concentration-temperature dependencies showed a good agreement with the enthalpies of vaporization. The pine needle-atmosphere partition coefficients of the studied PCB congeners increased with higher degrees of compound chlorination and with lower average air temperatures. They exhibit a good linear relationship with log(K(oa)) but the temperature dependence was stronger for log(K(pa)) than log(K(oa)).


Nuclear binding of the estrogen receptor: heterogeneity of sites and uterotropic response.
Two kinds of estradiol binding sites are present in purified nuclei from the rat uterus following estradiol injection. One of these sites (type I) corresponds to the well-known estrogen receptor which undergoes translocation from the cytoplasm to the nucleus. The second site (type II) is not translocated from the cytoplasm to the nucleus, however, estradiol treatment does stimulate an increased number of these sites. Type II sites are observed in purified nuclei and chromatin isolated from the uterus but not from non-target tissues such as the spleen and diaphragm. Thus an elevation in the levels of type II sites appear to be a specific nuclear response of the rat uterus to estradiol. Saturation analysis over a wide range of [3H]-estradiol concentrations produces a binding curve for type II sites which is sigmoidal and hence no accurate estimation of the dissociation constant is possible. The binding of [3H]-estradiol to nuclear type II sites is inhibited by estradiol and diethylstilbestrol but not by progesterone, testosterone, or corticosterone. Extraction of nuclei isolated from estrogen treated rat uteri with KCl provides a complex picture. Direct labeling of nuclear estrogen receptors either by in vivo injection or in vitro incubation of intact uteri with [3H]-estradiol measures only a fraction of the specific estrogen binding sites associated with the nuclear pellet following 0.4 M KCl extraction. These sites are more accurately determined by performing saturation analysis over a wide range of [3H]-estradiol concentrations by exchange which measures specific estrogen binding sites, not [3H]-steroid. Saturation analysis of estradiol binding to KCl extracted nuclei when performed by exchange, with appropriate corrections for type II binding, reveals that approximately 1000--2000 receptors per nucleus are resistant to KCl extraction 1 hr after administration. The same numbers of type I sites display long-term nuclear retention. A single injection of estradiol results in long term (greater than 6 h) retention of type I sites, rapid and sustained elevations (1--72h) in type II sites and true uterine growth (uterine wet weight at 24--43 h). Estriol injections caused a rapid increase in nuclear type I sites which was not accompanied by an increase in type II sites and no true uterine growth occurred. Administration of estriol or estradiol as a pellet implant, which causes continuous occupancy of type I sites, increases the quantity of nuclear type II sites and stimulates true uterine growth. Therefore, we conclude that elevated levels of nuclear type II sites correlate with the long term uterotropic response to estrogenic hormones. Although we do not understand the function of this second class of binding sites it is possible that the type II sites represent a major component in the mechanism by which estrogens stimulate growth of the uterus.


Relationships between skin test, specific IgE and levels of cytokines in patients with penicillin allergy.
The aim of this study was to investigate the relationships between skin test, specific immunoglobulin (Ig) E and cytokines in penicillin allergy. We collected the sera of 259 patients with historical positive skin test to penicillins, with immediate positive skin test and with a negative skin test results. The positive rate of specific IgE antibodies in 259 patients was 62.2% (161) by using radioallergosorbent test (RAST). Of the eight kinds of antigenic determinants, the positive rates of specific IgE to major and minor determinants were 43.63% (113) and 52.51% (136), respectively (p < 0.05). In 122 patients with immediate positive skin test, when the degrees of skin test were +, 2+, 3+ and 4+, the positive rates of specific IgE were 45.7, 57.1, 85.2 and 100%, respectively. The levels of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma in the sera of patients with positive skin test were significantly increased with the degree of positive skin test (p < 0.05). The combined use of major and minor determinants in RAST offers the better test for the detection of penicillin-specific IgE antibodies. IL-4, IL-13 and IFN-gamma play important roles in penicillin allergy.


Cross bridge slippage induced by the ATP analogue AMP-PNP and stretch in glycerol-extracted fibrillar muscle fibres.
Glycerol-extracted insect fibillar muscle fibers in rigor exhibited both an elastic and a plastic phase in the length-tension diagram. The transition between these phases took place at a critical tension, the "yield point" or elastic limit. In the plastic phase the apparent static elastic modulus became zero, whereas the immediate elastic modulus (measured by rapid length changes completed within 4 ms) exhibited no abrupt change at the yield point. The tension value of the yield point (but not immediate stiffness) was lowered by addition of AMP-PNP and was partially restored by washing out AMP-PNP. The dependence of the critical tension at which plastic flow begins on cooperative cross bridge behaviour is discussed in terms of breaking and reforming acto-myosin linkages. Evidence is presented that addition of AMP-PNP induces slippage of cross bridges on the actin filament by affecting the interaction between myosin and actin.


Long-term consequences of live kidney donation follow-up in 93% of living kidney donors in a single transplant center.
Live kidney donation is increasing rapidly. Increases of blood pressure and proteinuria but no accelerated loss of renal function in kidney donors have been described. The credibility of this research is hampered by retrieval rates of only 50-70% of donors. We studied renal function, blood pressure, proteinuria, parathyroid hormone, 1,25(OH)2 cholecalciferol and calcium and phosphate excretion in a live kidney donor cohort with a 93% retrieval rate. A comprehensive physical and laboratory examination including 24-h urine collection was conducted. None of the 152 donors had renal failure. Mean time after uninephrectomy was 11 +/- 7 (range: 1-28) years. GFR had declined by 25%. Blood pressure had increased from 125 +/- 15/79 +/- 11 to 134 +/- 19/81 +/- 9 mmHg (p < 0.01) but remained significantly below normal. Fifty six percent of donors developed proteinuria (>150 mg/day), but only 10% had albuminuria. Nineteen percent had increased PTH, 30% had a decreased tubular reabsorption rate of phosphate. Regarding risk factors for a higher loss of GFR, greater increases in blood pressure or proteinuria no consistent picture emerged. Because of the high incidence of proteinuria and possible changes in bone metabolism inclusion of kidney donors in registries appears worthwhile.


Detection of malignant tumors: water-suppressed proton nuclear magnetic resonance spectroscopy of plasma.
Average linewidths of methyl and methylene proton resonances of plasma lipoproteins from healthy controls and untreated cancer patients were measured in water-suppressed proton spectra obtained at 400 MHz. In contrast to a previous report (E. T. Fossel, J. M. Carr, and J. McDonagh, N. Engl. J. Med. 315, 1369 (1986] no statistically significant difference (P greater than 0.5) was found between the average linewidths in plasma samples from 20 normal controls (36.0 +/- 6.4 Hz) and 17 untreated cancer patients (34.6 +/- 6.3 Hz). When the effect of lactate was removed by graphical extrapolation, a small but marginally significant (P = 0.08) difference was observed between the average linewidths of the normal controls (35.1 +/- 5.8 Hz) and untreated cancer patients (31.8 +/- 5.2 Hz). However, there was still a large overlap between the two groups. In addition, substantial day to day variations in the linewidths of samples from the same individuals were observed. We conclude that these measurements cannot be used to detect cancer.


Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.
To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout.


New methods for fast on-site measurement of odorous compounds.
New methods for measurement of odorous gases, especially for aerosol-bound chemical compounds, have been developed in the Department of Measurement Technology (Technical University of Hamburg Harburg--MT-TUHH). Odorous compounds in the waste gases produced by the food industry were analysed based on high-volume aerosol sampling techniques, enrichment on solid phase micro extraction (SPE) cartridges and analytical measurement techniques using thermal desorption gas chromatography-mass spectrometry. The analysis results were compared to classic analytical procedures using adsorbence materials (Tenax) for enrichment. In comparison to aerosol sampling, analysis of Tenax samples was found to be ineffective, especially for analyzing polar semi volatile compounds. In addition, sensor arrays were also used in the study to characterize odors of different waste gases emitted by food production facilities. Measuring the odor units of the waste gas of a fat producing factory, the results of sensor-array-measurements show good correlation with results obtained with olfactometric measurements.


Cartography of SARS-CoV-2 variants based on the susceptibility to therapeutic monoclonal antibodies.
A comprehensive picture of a phenotypic relationship among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has been poorly studied. Here, this study presents cartography showing how the wild-type strain of SARS-CoV-2 and 14 variants are alike or different from the perspective of the susceptibility to 12 therapeutic monoclonal antibodies. The Alpha variant is close to the wild-type strain, whereas the Beta, Gamma, and Delta variants diverge from the wild-type. The map highlights the very unique property of the Omicron variant. Interestingly, sublineages of the Omicron variants, BA.1, BA.2, and BA.4/5, differ substantially in the cartography.


Ballistics for neurosurgeons: Effects of firearms of customized cranioplasty implants.
There are about 33,000 deaths caused by gunshot wounds in the USA each year. Probably half of these deaths result from head wounds. Among US Army soldiers, 17% of all ballistic injuries are head wounds. This means that, even in those protected by ballistic helmets, gunshot injuries to the head represent a danger. The aim of this study was to examine the effects of shelling of computer-aided designed (CAD) cranioplasty implants made of two different materials. An experimental model was developed in an indoor gun range. CAD cranioplasties with a material thickness of 2-6 mm, made of titanium or PEEK-OPTIMA(®) were fixed in a watermelon and shot at with a .222 Remington rifle at a distance of 30 m distance, a .30-06 Springfield rifle at a distance of 30 m, a Luger 9 mm pistol at a distance of 8 m, or a .375 Magnum revolver at a distance of 8 m. The CAD cranioplasties were subsequently inspected for ballistic effects by a neurosurgeon. Titanium CAD cranioplasty implants resisted shots from the 9 mm Luger pistol and were penetrated by both the .222 Remington and the .30-06 Springfield rifle. Shooting with the .357 Magnum revolver resulted in the titanium implant bursting. PEEK-OPTIMA(®) implants did not resist bullets shot from any weapon. The implants burst on shooting with the 9 mm Luger pistol, the .222 Remington, the .30-06 Springfield rifle, and the .357 Magnum revolver. Titanium CAD cranioplasty implants may offer protection from ballistic injuries caused by small caliber weapons fired at short distances. This could provide a life-saving advantage in civilian as well as military combat situations.


Once a pregnancy, always a cesarean? Rationale and feasibility of a randomized controlled trial.
Although vaginal delivery has long been assumed to be the preferred route of delivery in women who have not had a prior cesarean delivery, some have recently advocated that women be offered the option of elective, primary cesarean delivery in all pregnancies. Available outcome data, however, do not permit ready comparison of these alternate plans for delivery. Important maternal outcomes include short-term complications such as death, bleeding, infection, and damage to pelvic organs as well as long-term effects on future pregnancies, fecal and urinary incontinence, and pelvic organ prolapse. Important neonatal outcomes include asphyxic and traumatic birth injury, infection, respiratory complications, and stillbirth. To weigh the relative merits of elective primary cesarean delivery and a trial of labor, a randomized controlled trial is needed. Such a trial would be both ethical and feasible.


Comparative analysis of the effect of prostatic invasion patterns on cancer-specific mortality after radical cystectomy in pT4a urothelial carcinoma of the bladder.
To evaluate the prognostic relevance of different prostatic invasion patterns in pT4a urothelial carcinoma of the bladder (UCB) after radical cystectomy. Our study comprised a total of 358 men with pT4a UCB. Patients were divided in 2 groups-group A with stromal infiltration of the prostate via the prostatic urethra with additional muscle-invasive UCB (n = 121, 33.8%) and group B with continuous infiltration of the prostate through the entire bladder wall (n = 237, 66.2%). The effect of age, tumor grade, carcinoma in situ, lymphovascular invasion, soft tissue surgical margin, lymph node metastases, administration of adjuvant chemotherapy, and prostatic invasion patterns on cancer-specific mortality (CSM) was evaluated using competing-risk regression analysis. Decision curve analysis was used to evaluate the net benefit of including the variable invasion pattern within our model. The estimated 5-year CSM-rates for group A and B were 50.1% and 66.0%, respectively. In multivariable competing-risk analysis, lymph node metastases (hazard ratio [HR] = 1.73, P<0.001), lymphovascular invasion (HR = 1.62, P = 0.0023), soft tissue surgical margin (HR = 1.49, P = 0.026), absence of adjuvant chemotherapy (HR = 2.11, P<0.001), and tumor infiltration of the prostate by continuous infiltration of the entire bladder wall (HR = 1.37, P = 0.044) were significantly associated with a higher risk for CSM. Decision curve analysis showed a net benefit of our model including the variable invasion pattern. Continuous infiltration of the prostate through the entire bladder wall showed an adverse effect on CSM. Besides including these patients into clinical trials for an adjuvant therapy, we recommend including prostatic invasion patterns in predictive models in pT4a UCB in men.


Copolymers of starch, a sustainable template for biomedical applications: A review.
The outstanding versatility of starch offers a source of inspiration for the development of high-performance-value-added biomaterials for the biomedical field, including drug delivery, tissue engineering and diagnostic imaging. This is because starch-based materials can be tailored to specific applications via facile grafting or other chemistries, introducing specific substituents, with starch being effectively the "template" used in all the chemical transformations discussed in this review. A considerable effort has been carried out to obtain specific tailored starch-based grafted polymers, taking advantage of its biocompatibility and biodegradability with appealing sustainability considerations. The aim of this review is to critically explore the latest research that use grafting chemistries on starch for the synthesis of products for biomedical applications. An effort is made in reviewing the literature that proposes synthetic "greener" approaches, the use of enzymes and their immobilized analogues and alternative solvent systems, including water emulsions, ionic liquids and supercritical CO2.


Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity.
In vivo 31P-NMR was used to measure the effects of the anti-tumor drug adriamycin on the energy metabolism of rat heart. The exclusive acquisition of NMR signal from cardiac muscle was assured by positioning a solenoidal radio-frequency NMR coil around the heart. Appropriate control experiments verified that 31P-NMR spectra solely originated from this organ. Acute effects occurring shortly after adriamycin administration are expressed in 31P spectra as a dose-dependent decline in the cardiac levels of phosphocreatine, after which stabilization at a new steady-state level occurs. These acute effects of a single dose are complete in 30-60 min and no significant further changes take place within 150 min after drug introduction. Longer-term effects of single high doses and of multiple lower doses were measured up to a week after the initiation of treatment. It seemed that at a total dose of 20 mg/kg, drug-induced interference with cardiac energy metabolism was more pronounced than at the same dose in the acute phase. These 31P-NMR data demonstrate that adriamycin treatment is accompanied by a decrease of the cardiac phosphocreatine/ATP ratio which might be an expression of the well-established cardiotoxicity of the drug.


Non-invasive assessment of growth, gender and time of day related changes of respiratory pattern in healthy cats by use of barometric whole body plethysmography.
The objective of this study was to establish a reference base for respiratory variables (respiratory rate [R(R)], inspiratory and expiratory time [T(i) and T(e)], peak inspiratory and expiratory pseudoflow [PIF and PEF], tidal volume [V(T)], minute ventilation [V(E)] and enhanced pause [Penh]) of healthy cats by use of barometric whole body plethysmography (BWBP). Eighteen healthy European cats (10 male, 8 female) were studied from the age of 3 to 13 months in order to assess growth- and gender-related changes of BWBP variables. Chest radiographs and bronchoalveolar lavage cytology were performed to confirm pulmonary health status. Diurnal changes were investigated every 2 h over a period of 24 h when the cats were adult. V(T), V(E), PIF and PEF significantly increased during somatic growth and were higher in males than in females, whereas R(R), T(i), T(e), T(e)/T(i) ratio, PEF/PIF ratio and Penh remained unchanged and were not affected by gender. When measured over 24 h, Penh, T(e) and T(i) were significantly increased in the early morning hours (04:00 h), whereas R(R), PIF and PEF were decreased at that time. This study provides reference values of BWBP variables for healthy male and female cats and indicates when circadian changes might be observed.


Who benefits most from outpatient lifestyle intervention? An IMI-SOPHIA study on pediatric individuals living with overweight and obesity.
The first-line approach for childhood obesity is lifestyle intervention (LI); however, success varies. This study aimed first to identify distinct subgroups of response in children living with overweight and obesity and second to elucidate predictors for subclusters. Based on the obesity patient follow-up registry the APV (Adipositas-Patienten-Verlaufsdokumentation) initiative, a total of 12,453 children and adolescents (median age: 11.5 [IQR: 9.7-13.2] years; BMI z score [BMIz]: 2.06 [IQR: 1.79-2.34]; 52.6% girls) living with overweight/obesity and participating in outpatient LI were studied. Longitudinal k-means clustering was used to identify individual BMIz response curve for up to 2 years after treatment initiation. Multinomial logistic regression was used to elucidate predictors for cluster membership. A total of 36.3% of children and adolescents experienced "no BMIz loss." The largest subcluster (44.8%) achieved "moderate BMIz loss," with an average delta-BMIz of -0.23 (IQR: -0.33 to -0.14) at study end. A total of 18.9% had a "pronounced BMIz loss" up to -0.61 (IQR: -0.76 to -0.49). Younger age and lower BMIz at LI initiation, larger initial BMIz loss, and less social deprivation were linked with higher likelihood for moderate or pronounced BMIz loss compared with the no BMIz loss cluster (all p < 0.05). These results support the importance of patient-tailored intervention and earlier treatment escalation in high-risk individuals who have little chance of success.


Development and Progression of Shoulder Lesions and Their Influence on Sow Behavior.
Shoulder lesions can develop in sows during lactation and vary in severity, potentially leading to euthanasia of the sow. There are questions about how these lesions affect the sow's welfare. Here, sows that were loaded into farrowing pens were monitored prospectively to elucidate the risk for lesion development. To determine whether the presence of shoulder lesions affected behavior, 44 sows with shoulder lesions (LES) were matched to controls (CON) and observed during farrowing for postures and during nursing and gestation for posture and location. Lesions were measured daily. A low weaning body condition score (BCS) increased the possibility of lesion development (OR = 4.8 ± 2.8; p = 0.01). There was no difference in behavior between LES and CON with the exception of a higher frequency of postural changes in CON sows (p = 0.01). A larger maximum lesion size was associated with larger initial lesion (p < 0.01), higher weaning BCS (p < 0.001), low parity (p < 0.001), and lameness (p < 0.001). Median time to healing (24 ± 2.2 days) correlated with maximum lesion size. A low BCS during weaning increased the risk for lesion development and there were multiple factors found which influenced maximum lesion size; however, we did not find behavioral indications that lesions impacted welfare.


[Emergency treatment with a temporary balloon-floated pacemaker electrode (author's transl)].
The "blind" insertion of a balloon-tipped pacemaker electrode is a suitable method when emergency pacing at the bedside is needed. The disadvantage of placement of the electrode without fluoroscopic control is counter-balanced by the saving of time and the lesser stress and risk involved for the patient, who is not required to be moved to a fluoroscopic room.


Mexican-American cultural meanings, expressions, self-care and dependent-care actions associated with experiences of pain.
The experience of pain within specific cultural groups has not been well studied. The purpose of this ethnographic study was to discover Mexican-American meanings, expressions, and care associated with pain. Data were obtained from 20 key and 14 general informants and analyzed using thematic and pattern analysis. Themes identified included: pain as encompassing experience of suffering; the obligation to bear pain and to endure it stoically; and the primacy of caring for others. Based on study findings, a beginning description of the cultural context is provided from which pain as experienced by Mexican-Americans can be understood and from which culturally competent nursing care can be designed.


Identification of a novel HLA-G allele, HLA-G*010113, in a Korean individual.
In the present study, a novel human leucocyte antigen-G allele, G*010113, was identified via direct sequencing from donor gDNA in a Korean population. This allele differs from G*01010201 by a single nucleotide substitution, C to T, in codon 169 of exon 3 but did not result in any amino acid change.


Cryptosporidium sp. skunk genotype in wild raccoons (Procyon lotor) naturally infected with Baylisascaris procyonis from Central Germany.
Cryptosporidium spp. are apicomplexan parasites of public health concern. They are one of the main causes of intestinal diseases in humans and animals. Contaminated water is among the main sources of infection for humans and mammals. Raccoons are an introduced species in Germany. They are anthropogenic adapters with a natural affinity for water bodies. We collected samples from wild raccoons in the Federal States of Saxony and Thuringia, Central Germany. Through molecular genotyping, we found Cryptosporidium sp. skunk genotype in one raccoon from Saxony (1/24) and in one animal from Thuringia (1/27). Both raccoons were also infected with the zoonotic nematode Baylisascaris procyonis. This is the first report of co-infection with these two parasites in raccoons from Germany. Our study highlights the potential of these animals as carriers of zoonotic pathogens. Since raccoons can thrive in human settlements, this study provides data that can be used as a baseline for preventive programs.


Quantitative trait loci of stripe rust resistance in wheat.
Over thirty publications during the last 10 years have identified more than 140 QTLs for stripe rust resistance in wheat. It is likely that many of these QTLs are identical genes that have been spread through plant breeding into diverse backgrounds through phenotypic selection under stripe rust epidemics. Allelism testing can be used to differentiate genes in similar locations but in different genetic backgrounds; however, this is problematic for QTL studies where multiple loci segregate from any one parent. This review utilizes consensus maps to illustrate important genomic regions that have had effects against stripe rust in wheat, and although this methodology cannot distinguish alleles from closely linked genes, it does highlight the extent of genetic diversity for this trait and identifies the most valuable loci and the parents possessing them for utilization in breeding programs. With the advent of cheaper, high throughput genotyping technologies, it is envisioned that there will be many more publications in the near future describing ever more QTLs. This review sets the scene for the coming influx of data and will quickly enable researchers to identify new loci in their given populations.


Novel isomerically pure tetrasubstituted allylboronates: stereocontrolled synthesis of alpha-exomethylene gamma-lactones as aldol-like adducts with a stereogenic quaternary carbon center.
In spite of their inherent isomerization tendency and low reactivity, 1-alkoxycarbonyl vinylcopper(I) intermediates from the conjugate addition of organocuprates onto acetylenic esters were trapped with very high cis-addition selectivity with iodomethylboronic esters in the presence of HMPA. The resulting isomerically pure 3,3-disubstituted allylboronates react with aldehydes in a highly diastereo- and enantioselective manner, providing alpha-exomethylene gamma-lactones with a stereogenic quaternary beta-carbon center.


Linking signalling pathways, thymic stroma integrity and autoimmunity.
Medullary thymic epithelial cells (mTECs) are indispensable for self-tolerance to peripheral organs by virtue of their expression of a host of tissue-restricted self-antigens. The full extent of this promiscuous gene expression is confined to functionally mature mTECs. Consequently, any interference with signalling pathways directing the differentiation and/or proliferation of this mature subset will affect the scope of central tolerance and potentially predispose to autoimmunity. In a recent study, tumour necrosis factor receptor-associated factor 6 (TRAF6) has been identified as an essential component of a new signalling pathway directing mTEC development.


Cytogenetics of spermatocytic tumors with a discussion of gain of chromosome 12p in anaplastic variants.
Most spermatocytic tumors (STs) have an excellent prognosis. In rare instances, metastatic disease has been documented. However, it is unclear if aggressive tumors have specific molecular alterations. Herein, we have studied primary STs with (n = 4) and without (n = 3) anaplastic features, including single-nucleotide polymorphism microarrays for 5 ST (nonanaplastic: 3; anaplastic: 2). The mean age at orchiectomy and tumor size was 49 years and 6.5 cm, respectively. Lymphovascular invasion and necrosis were identified in 3 (of 4, 75%) anaplastic STs, including one with clinically metastatic disease and one with locally aggressive disease. None of the cases in this study exhibited sarcomatoid change. The mean mitotic count was higher in anaplastic tumors (59/10 versus 10/10 high-power fields). All STs in this study were positive for SALL4 and CD117 and negative for OCT3/4 and CD30 (7/7, 100%). SSX-C positivity was identified in all but the locally aggressive anaplastic ST (5 of 6, 83%). All STs showed a consistent gain of chromosome 9 including the locus for the DMRT1 gene (5 of 5 cases, 100%), while gains of chromosome 12p were only seen in 2 (of 2) anaplastic variants. Gains of 12p in anaplastic STs may represent a biomarker of transformation into more aggressive tumors. Alternatively, STs with gain of 12p may represent an intermediate state between type II and type III germ cell tumors. Future studies are needed to validate whether gain of 12p is a consistent feature of STs with anaplastic morphology and its association with aggressive clinical behavior.


The CUSUM Slope Equals Observed Minus Expected Mortality and Can Be Visualized by a "Slope-Meter".
We present an additional advantage of the Risk-Adjusted CUSUM (RA-CUSUM), namely, that its slope can be quantified and is in fact equivalent to Observed (O) minus Expected (E) mortality. That is, the height of the RA-CUSUM is the O minus E deaths, which measures performance since the start of the series, and the slope of the RA-CUSUM is the O minus E mortality which measures performance during a chosen interval. We present a useful graphical tool (Slope-Meter) to allow approximation of this mortality difference by the viewer.


The sensitizing capacity of naturally occurring quinones. Experimental studies in guinea pigs. II. Benzoquinones.
Experimental studies on the sensitizing capacity of naturally occurring benzoquinones, isolated from plants and woods have been carried out in guinea pigs of the Pirbright white strain. Seven compounds were available: primin, three dalbergiones, mansonia quinone (mansonone A), 2,6-dimethoxybenzoquinone and rapanone. With five of these substances (primin, mansonone A, three dalbergiones) guinea pigs could be sensitized. Primin, the allergen of Primula obconica Hance (primrose) proved to be the most effective one of all quinones tested in this and the preceding studies. As a similar but weaker sensitizer R-3, 4-dimethoxydalbergione from Machaerium scleroxylon Tul. (Pao ferro, Caviuna vermelha) could be identified. The results obtained with mansonone A, a sesquiterpenoid quinone from Mansonia altissima A. Chev. demonstrate that even naturally occurring orthoquinones are capable of inducing contact allergy. Allergic cross reactions could be obtained between all chemically related mansonones A-F. The results are in good accordance with the view that the sensitizing capacity of naturally occurring quinones depends on the fundamental quinoid structure and the length, position and configuration of the aliphatic side-chain.


Preservation of red blood cells: studies of erythrocyte adenine nucleotides using luminescence analysis.
The levels of ATP and total adenine nucleotides (ATP + ADP + AMP) were determined by firefly luciferase assay in red blood cells during storage for 5 weeks at 4 degrees C. With few exceptions, no significant differences in nucleotide levels were found between whole blood stored in CPD-adenine and various preparations of red blood cells in CPD-adenine or CPD with saline-adenine-glucose (SAG) as additive. The levels of ATP and total adenine nucleotides during storage are discussed in relation to glucose levels, extracellular pH and shelf life of the red blood cells.


Preventing hospital admissions by reviewing medication (PHARM) in primary care: an open controlled study in an elderly population.
Limited and conflicting evidence exists on the effect of a multicomponent pharmaceutical care intervention (i.e. medication review, involving collaboration between general practitioners (GPs), pharmacists and patients) on medication-related hospitalizations, survival, adverse drug events (ADEs) and quality of life. We aimed to investigate the effect of a multicomponent pharmaceutical care intervention on these outcomes. An open controlled multicentre study was conducted within primary care settings. Patients with a high risk on medication-related hospitalizations based on old age, use of five or more medicines, non-adherence and type of medication used were included. The intervention consisted of a patient interview, a review of the pharmacotherapy and the execution and follow-up evaluation of a pharmaceutical care plan. The patient's own pharmacist and GP carried out the intervention. The control group received usual care and was cared for by a GP other than the intervention GP. The primary outcome of the study was the frequency of hospital admissions related to medication within the study period of 12 months for each patient. Secondary outcomes were survival, quality of life and ADEs. 364 intervention and 310 control patients were included. Less medication-related hospital admissions were found in the intervention group (n = 6; 1·6%) than in the control group (n = 10; 3·2%) but the overall effect was not statistically significant (hazard ratio (HR) 0·50, 95% confidence interval (CI) 0·12-1·59). The secondary outcomes were not statistically significantly different either. The study was underpowered, which may explain the negative results. A post hoc analysis showed that the effect of the intervention was statistically significant for patients with five diseases or more: five diseases, HR 0·28 (95% bootstrap CI: 0·056-0·73) and eight diseases, HR 0·11 (95% CI: 0·013-0·34). A multicomponent pharmaceutical care intervention does not prevent medication-related hospital admissions. Whether this is true for such interventions in general is unknown, because the PHARM study was underpowered. The intervention may significantly reduce medication-related hospitalizations in patients with five or more comorbidities, but this is only based on a post hoc analysis and thus needs confirmation in large controlled trials.


Isoflurane in a circle system with low gas flow.
Isoflurane was administered from a Goldman vaporizer to a circle breathing system with low fresh gas flows. The uptake and vapour concentration of isoflurane were compared in two groups of spontaneously breathing patients receiving oxygen alone (n = 19), or nitrous oxide and oxygen (n = 30). Anaesthesia was maintained successfully in all patients. The authors believe this to be a safe and economical way of delivering isoflurane.


Intrafamilial phenotypic variability in Friedreich ataxia associated with a G130V mutation in the FRDA gene.
Most patients with Friedreich ataxia (FA) have a GAA trinucleotide repeat expansion in intron 1 of the FA gene (FRDA) on both arms of chromosome 9. However, some patients are compound heterozygotes and harbor a GAA expansion on one allele and a point mutation on the other. Compound heterozygous patients with FA who have a GAA expansion and a G130V mutation have been reported to have an atypical phenotype with a slow disease progression, minimal or no ataxia, or gait spasticity. To describe intrafamilial phenotypic variability in a GAA expansion/G130V mutation compound heterozygous family with FA. Tertiary referral university hospital setting. A 34-year-old man presented to our hospital with a 24-year history of stiff legs and mild unsteadiness of gait. Clinical examination showed a spastic paraparesis with normal to pathologically brisk deep tendon reflexes and mild left upper limb ataxia. His 27-year-old sister presented with a slowly progressive early-onset ataxic syndrome. She had ataxia of gait, mild to severe limb ataxia, and reduced or absent deep tendon reflexes, but no evidence of spasticity on examination. Neurophysiologic investigations showed evidence of a sensory axonal neuropathy, and molecular genetic analysis showed that both siblings were compound heterozygotes with a GAA expansion and a G130V mutation. This report confirms that compound heterozygous patients with FA who have a GAA expansion and a G130V mutation may present with an ataxic phenotype and that intrafamilial phenotypic variability in these pedigrees can occur. It also emphasizes the importance of performing molecular genetic analysis for the GAA trinucleotide expansion in patients presenting with a spastic paraparesis of undetermined etiology, especially when there is neurophysiologic evidence of a sensory axonal neuropathy.


Complete Genome Sequence of Arthrobacter Phage GantcherGoblin Exhibits Both Conservation with Subcluster AU6 Phages and Genetic Novelty.
GantcherGoblin is a lytic siphovirus that was isolated on Arthrobacter globiformis B-2979 from soil collected in Massachusetts. The 55,368-bp genome has a GC content of 50.1% and 91 predicted protein-coding genes. Based on gene content similarity to phages in the Actinobacteriophage Database, GantcherGoblin was assigned to phage subcluster AU6.


Enhanced liver functions of hepatocytes cocultured with NIH 3T3 in the alginate/galactosylated chitosan scaffold.
Formation of primary hepatocyte spheroids in the hydrogel scaffold is a promising approach for enhancing liver-specific functions in liver tissue engineering as well as for developing bioartificial liver (BAL) devices. In the present study, a highly porous hydrogel scaffold composed of alginate (AL) and galactosylated chitosan (GC) as a synthetic extracellular matrix (ECM) for hepatocytes was fabricated with 150-200 microm pore size in diameter. Cell adhesion onto AL/GC and AL/chitosan film was 72.7 and 45% at 1 wt% of GC (or chitosan) to AL content whereas cell adhesion onto AL film was 28.5%. The optimal concentration of GC in AL/GC sponge was 1 wt% to AL content by the measurement of albumin secretion. Cell viabilities performed on AL and AL/GC sponges were 72.2+/-3.6 and 81.3+/-3.5% of control, respectively, after 10 days incubation. Hepatocytes were aggregated to form multicellular spheroids in AL/GC sponge with diameter enlarged up to about 100 microm, 36 h postseeding, whereas most of them in the AL sponge remained as single cells and only a few cells began to form aggregates. Intercellular molecules such as connexin32 and E-cadherin genes related with cell-cell contact were expressed in hepatocytes within AL/GC sponge at 36 h after incubation, but not in AL sponge. Treatment with a gap junctional intercellular communication (GJIC) inhibitor, 18beta-glycyrrhetinic acid, resulted in a 1.5-fold marked decrease in albumin secretion levels in AL/GC sponge. Specially, coculture of hepatocytes in AL and AL/GC sponges with NIH3T3 in a transwell insert resulted in enhanced increase of liver-specific functions, such as albumin secretion rates, ammonia elimination rates, and ethoxyresorufin-O-deethylase activity by cytochrome P4501A1, compared to those in hepatocyte monoculture. The results suggest that formation of hepatocyte spheroids in coculture system enhances liver-specific functions for the AL/GC sponge as a new synthetic ECM to design developed BAL devices.


High-quality TEM specimen preparation for lithium-ion conducting solid electrolytes by low-energy ion milling.
Focused ion beam (FIB) is a widely used method to prepare transmission electron microscopy (TEM) specimen from bulk materials. However, the surface amorphous layer induced by ion beam is an obstacle to obtain high-quality atomic-scale images for quantitative analysis, especially for the analysis of light elements such as lithium in lithium-ion conducting solid electrolytes. Here, taking lithium-ion conducting solid electrolyte materials as an example, the advantages and disadvantages of applying low-energy Ar+ ion for fine milling after FIB are investigated. Combining Monte-Carlo simulations with ion milling experiments, the milling parameters are evaluated and discussed in detail. With optimized parameters, TEM specimens with less beam damage and thinner amorphous layer were prepared, enabling the acquisition of high-quality atomic-scale images. Furthermore, low-energy Ar+ ion milling is also able to remove hydrocarbon contamination formed during the electron beam illumination inside the microscope, making the contaminated TEM specimens reusable.


Urological complications after 134 pediatric kidney transplants: a single-center study.
The incidence of surgical complications after kidney transplantation has been reported to range from 1% to 33%. The aim of this work was to report surgical urological complications among our cohort of 134 pediatric kidney transplantations. Epidemiological and clinical data of all patients younger than 18 years transplanted between January 1984 and May 2012 were collected from our prospective database. Urologic complications and management are reported herein. One hundred twenty-four patients, including 44% females underwent 134 renal transplants. Median age at the time of the surgery was 13 years. Mean time of end-stage renal disease was 25 months. We identified 10 subjects (7.5%) with urological complications: 5 ureterovesical stenoses, 2 lymphoceles, and 3 lower ureteral fistulas. All of the renal allografts were obtained from cadaveric donors. Mean age of these patients at the time of transplantation was 13 years. Mean cold ischemia time was 1613 minutes. All the patients required surgical management. All patients with ureterovesical stenoses underwent ureteral reimplantation using a Boari flap; those with lymphoceles underwent open marsupialization; 2 with ureteral fistulas underwent reimplantation of the ureter, and the other patient's case required placement of a nephrostomy tube and an antegrade ureteral catheter. All patients were treated successfully. Mean follow-up time of cases with urological complications was 9.5 years. Currently, 60% has nonfunctioning allografts; the mean current glomerular filtration rate of the functioning renal allografts is 55 mL/min. Despite requiring surgical management, all patients were treated successfully. Prompt identification and treatment of any complication are critical for graft and patient survival.


Scientific yoga module for hypothyroidism: A study protocol for tele-yoga RCT.
Management of thyroid dysfunction has a direct effect on the quality of life and studies have recognized that hypothyroidism has become a public health challenge. Although conventional medicine is widely used, its long-term side effects are elucidated. This study aims to conduct a randomized controlled trial (RCT) through tele-mode to assess the effectiveness of the newly developed and validated "Scientific Yoga Module" as a telehealth concept for improving the quality of life in patients with hypothyroidism along with management of other symptoms as compared to the standard of care. This is a single-blinded, two-arm, parallel-group RCT in which at least a total of 120 primary hypothyroid subjects both male and female between the age group 18 to 60 will be recruited from the database of Swami Vivekananda Yoga Anusandhana Samsthana (SVYASA). Participants will be randomly divided into a yoga intervention group (n = 60) and a waitlist control group (n = 60) as per the inclusion and exclusion criteria of the study. A tele-yoga intervention for six months will be administered and pre-interim-post data will be recorded for both groups. This protocol is designed to study the effect of Scientific Yoga Module intervention on primary assessments of SF-36 scale [health-related quality of life (HRQOL) that includes physical, mental, emotional, and social states] along with secondary assessments on the biochemical test of thyroid profile-{Triiodothyronine (T3), Thyroxine (T4), Thyroid Stimulating Hormones (TSH)}, Body Mass Index (BMI), Blood Pressure (BP), Fatigue Assessment Scale (FAS), Perceived Stress Scale (PSS), Gita Inventory of personality scale (GIP). To the best of our knowledge, this tele-yoga RCT for hypothyroidism will be the first clinical trial to analyze the effectiveness of a "Scientific Yoga Module" imparted through tele-mode.


Dietary induction of cholesterol gallstones in hamsters from three different sources.
Cholesterol gallstones were produced in young male, golden Syrian hamsters, obtained from three different suppliers, by administering a nutritionally adequate, semipurified diet for periods of either 5 or 10 weeks. The major components of the lithogenic diet were casein, cornstarch, butterfat, corn oil and 0.3% cholesterol. The hamsters were obtained from Sesco, Harlan Sprague-Dawley (Engle hamster) and Charles River (Lakeview hamster). There were profound differences among the three groups with respect to gallstone formation and cholesterol metabolism: The highest incidence of gallstones occurred in Sesco hamsters, 44.4% and 63.6% after 5 and 10 weeks on the lithogenic diet, respectively. In the Engle hamster, after a 5-week feeding, cholesterol crystals and gallstones were absent. When the feeding period was extended to 10 weeks, cholesterol gallstones were present in 45.5% of the animals. In the Lakeview hamsters, neither gallstones nor cholesterol crystals were found in the gallbladder after a 5-week period. After 10 weeks, cholesterol gallstones were found in only a single hamster. In all groups, the lithogenic diet produced large increases of liver, serum and biliary cholesterol concentrations and increased liver weights. When the animals were fed for 5 weeks, only the bile of Sesco hamsters became supersaturated. Supersaturated bile was induced in all groups after a 10-week feeding of the lithogenic diet with cholesterol saturation ranging from 1.47 to 1.97. These data indicate that it is possible to induce cholesterol gallstones in hamsters by means of a nutritionally adequate, semipurified diet of moderate cholesterol content.(ABSTRACT TRUNCATED AT 250 WORDS)


Chronic mucocutaneous candidiasis and congenital susceptibility to Candida.
To give an overview on the clinical spectrum and the molecular background of host defence against Candida. For many decades the molecular causes and the pathogenesis for an increased susceptibility to Candida - and fungal infections in general - have been elusive. In 2009 and 2010 interesting reports on the genetic background and the pathomechanisms involved in chronic mucocutaneous candidiasis (CMC) have been published. The susceptibility to recurrent Candida infections can be a monogenetic Mendelian trait. The sensing of Candida cell wall components and the consecutive intracellular signalling in myeloid cells via CARD9, but also the role of Th17 cells and their cytokines take centre stage in the human host defence against Candida.


Is cattle veterinary practice fit for the future?
This question was examined during a debate at this year's congress of the British Cattle Veterinary Association, Suzanne Jarvis reports.


Both age and experience are important for successful problem solving in juvenile fawn-footed mosaic-tailed rats Melomys cervinipes.
Problem solving ability is affected by many factors, including physiology, personality, and cognition. However, how age and experience influence problem-solving ability during development is harder to untangle. We tested how age and experience affected problem solving in a native Australian rodent, the fawn-footed mosaic-tailed rat Melomys cervinipes. Juveniles were divided into two groups (different ages at start of testing) and then received a food-baited cardboard matchbox every 10 days for a total of three tests. We compared the problem-solving ability of individuals from both groups, which allowed us to separate the effects of age and experience. Juveniles with more experience solved the task faster than juveniles with less experience. Furthermore, inexperienced older juveniles interacted with the problems more than inexperienced younger juveniles. Previous solving experience may be important for short-term solving success, while age, in the absence of experience, might be associated with increased exploration, leading to increased investigation of novel problems. Previous experience at manipulating objects generally may also be important for problem-solving success, which likely provides an advantage as resources and habitats change seasonally and annually.


Physical activity participation among adolescents with autism spectrum disorder.
Adolescents with autism spectrum disorder are less likely to be physically active compared to their age-related peers. Despite the lower levels of physical activity observed among adolescents with autism spectrum disorder, it is unknown why they are predominantly inactive. Much of the research so far has focused on understanding how biological aspects influence physical activity participation. But there is little research that has examined how social and cultural components influence their physical activity participation. There is also little research that has sought the perspectives and experiences of adolescents with autism spectrum disorder. In this study, 10 adolescent boys with autism spectrum disorder created a digital story, and also participated in two face-to-face interviews. The purpose of the study was to examine how individual, social, and cultural forces influenced physical activity participation. Analysis of the data highlight that bullying, challenges in community programs, and the prioritization of therapeutic interventions limited participation. On the contrary, participants were more likely to be active when physical activity generated meaning, purpose, a sense of identity, and affective pleasures. The findings add new knowledge suggesting that adolescents with autism spectrum disorder are not simply unmotivated. Rather, physical activity participation was shaped by wider social experiences, norms, values, and practices in which they were immersed. The findings suggest a need for directed efforts to create policies and practices which are individualized and reflective of the needs and abilities of adolescents with autism spectrum disorder to promote physical activity participation and potentially enhance physical health and wellbeing.


The perimetric boycott: a tool for tobacco control advocacy.
To propose criteria to help advocates: (1) determine when tobacco related boycotts may be useful; (2) select appropriate targets; and (3) predict and measure boycott success. Analysis of tobacco focused boycotts retrieved from internal tobacco industry documents websites and other scholarship on boycotts. Tobacco related boycotts may be characterised by boycott target and reason undertaken. Most boycotts targeted the industry itself and were called for political or economic reasons unrelated to tobacco disease, often resulting in settlements that gave the industry marketing and public relations advantages. Even a lengthy health focused boycott of tobacco industry food subsidiaries accomplished little, making demands the industry was unlikely to meet. In contrast, a perimetric boycott (targeting institutions at the perimeter of the core target) of an organisation that was taking tobacco money mobilised its constituency and convinced the organisation to end the practice. Direct boycotts of the industry have rarely advanced tobacco control. Perimetric boycotts of industry allies offer advocates a promising tool for further marginalising the industry. Successful boycotts include a focus on the public health consequences of tobacco use; an accessible point of pressure; a mutual interest between the target and the boycotters; realistic goals; and clear and measurable demands.


Recovery of a Sendai virus variant with temperature-sensitive hemolytic activity from persistently infected cells from mouse brain.
A persistently infected cell line designated MB/Senas was established by cultivation of mouse brain cells from four-day-old C3H mice infected intracerebrally at birth with 10(6) PFU of Sendai virus, strain 52. After 5 passages, 0.16 per cent of Sendai52 antiserum (containing two 50 per cent plaque reducing doses/ml of serum) was introduced into the culture medium. The addition of antiserum was accompanied by a rise in cell-associated viral antigen from a level of 5 per cent antigen positive cells to 100 per cent demonstrable by both intracellular and membrane immunofluorescence. A variant of Sendai52 virus, designated Sendaias, was recovered from MB/Senas by inoculation of supernatant medium into chick embryos. Infection of chick embryos at 37 degrees C was abortive. Fifty per cent or less of chick embryos infected at dilutions 10(-1) to 10(-9) yielded detectable virus. Hemagglutination (HA) was weak but could be improved by trypsinization of allantoic fluids. Neuraminidase (NA) activity was barely detectable. Hemolysis (HE) was absent. Propagation of Sendaias virus at 33 degrees C showed no change from weak HA and NA activities but HE activity was now apparent which was temperature sensitive. Mortality of infected chick embryos increased to 100 per cent. HE activity and lethality for chick embryos was thermolabile at 45 degrees C.


The contrast-enhanced CT scan in the diagnosis of isodense subdural hematoma.
The authors review 29 cases of surgically-proven isodense subdural hematomas examined by non-contrast and contrast-enhanced computerized tomography scans. Three types of isodense collections were noted: homogeneous isodense collections, mixed-density collections, and gravitational layering within subdural collections. Contrast enhancement within the cerebral cortex, cortical vessels, and subdural membranes led to the correct diagnosis in each case. Contrast-enhanced scans are essential for the evaluation of isodense subdural hematomas.


Continuous Flow Synthesis and Purification of Aryldiazomethanes through Hydrazone Fragmentation.
Electron-rich diazo compounds, such as aryldiazomethanes, are powerful reagents for the synthesis of complex structures, but the risks associated with their toxicity and instability often limit their use. Flow chemistry techniques make these issues avoidable, as the hazardous intermediate can be used as it is produced, avoiding accumulation and handling. Unfortunately, the produced stream is often contaminated with other reagents and by-products, making it incompatible with many applications, especially in catalysis. Herein is reported a metal-free continuous flow method for the production of aryldiazomethane solutions in a non-coordinating solvent from easily prepared, bench-stable sulfonylhydrazones. All by-products are removed by an in-line aqueous wash, leaving a clean, base-free diazo stream. Three successful sensitive metal-catalyzed transformations demonstrated the value of the method.


Mercury in hair and in fish consumed by Riparian women of the Rio Negro, Amazon, Brazil.
This work puts the risks and benefits of a mercury acquisition through a fish-dominated diet in the context of the other endemic health problems in the Amazon. Fish consumption rate was assessed after determining mercury concentrations in the most consumed fish and in hair of women at fertile age (15 to 45 years of age), living in remote localities of the Rio Negro basin (not impacted by gold mining). Fish-meals were consumed once a day (7.1%) but in most cases (78.6 %) at least twice a day with an estimated mean fish consumption rate of 170.5 g (range 23 to 293 g). The fish-species most preferred were Tucunarés (Cichla spp), Pacus (Mylossoma aureum and Myleus micans), Piranhas (Sarrasalmus spp), Cará (Satanoperca jurupari), Jaraquí (Semaprochilodus taeniurus). The mean Hg concentration in these species varies widely (38 to 592 ng g(- 1)) but 27% of samples had Hg concentrations above 500 ng g(- 1), and only 7% were above 1000 ng g(- 1). The hair-Hg concentrations ranged from 6.5 to 32.6 microg g(- 1) with 82% of them having concentrations above 10 microg g(- 1) (w.w.) hair. Hair-Hg concentrations were positively correlated with women's age (r=0.4500; P=0.0111). Clinical evaluation did not detected symptoms (paraparesis, tremor, numbness of limbs, sensory disturbances) compatible with Minamata disease, but there was a high (71%) incidence of clinical history of malaria. Fish is an abundant natural resource, rich in essential nutrients and important to the diet of 'ribeirinhos' of Brazilian Amazonia. We hypothesize that lack of basic medical care in these communities outweighs risk of naturally occurring fish-MMHg. Therefore food habits based on fish consumption is part of a successful strategy for survival and should be considered as a health asset.


The amplitude of coagulation curves from thrombin time tests allows dysfibrinogenemia caused by the common mutation FGG-Arg301 to be distinguished from hypofibrinogenemia.
Thrombin time (TT) tests are useful for diagnosing coagulation disorders involving abnormal fibrinogen but do not allow us to distinguish between qualitative and quantitative defects. However, with the widening availability of optical coagulation automates, more information about the coagulation process is becoming increasingly accessible. In this study, we compared the coagulation curves of TT tests carried out with plasma from healthy donors with those from patients with acquired low Clauss fibrinogen levels or with dysfibrinogenemia caused by a heterozygous point mutation in the fibrinogen γ-chain that results in a p.Arg301(275)Cys substitution. The functional fibrinogen levels of these three groups of samples were also measured with the Clauss method, and their fibrinogen protein levels were determined by ELISA. Our data indicate that the amplitude and maximal velocity of coagulation curves from plasma samples from FGG p.Arg301(275)Cys dysfibrinogenemic patients were comparable to those from plasma samples with fibrinogen in the normal range, whereas the amplitude of coagulation curves from patients with acquired low fibrinogen levels was lower. Examination of the amplitude of coagulation curves generated during TT tests may provide additional information to enable the differential diagnoses of diseases following a low fibrinogen measurement by the Clauss method.


Arthropod-borne arthritides.
Infections with several types of viral and bacterial pathogens are able to cause arthritic disease. Arthropod vectors such as ticks and mosquitoes transmit a number of these arthritis-causing pathogens, and as these vectors increase their global distribution, so too do the diseases they spread. The typical clinical manifestations of infectious arthritis are often similar in presentation to rheumatoid arthritis. Hence, care needs to be taken in the diagnoses and management of these conditions. Additionally, clinical reports suggest that prolonged arthropathies may result from infection, highlighting the need for careful clinical management and further research into underlying disease mechanisms.


Detection of reverse transcriptase activity in association with the non-A, non-B hepatitis agent(s).
Particle-associated reverse transcriptase activity was detected in four human serum specimens and in two plasma-derived products, all of which had been shown to transmit non-A, non-B hepatitis (NANBH) to other human beings and/or chimpanzees. Reverse transcriptase activity was also detected in all twelve sera from patients with acute or chronic NANBH. In contrast, reverse transcriptase activity was found in only 2 of 49 serum specimens from healthy plasma donors and laboratory workers. Sucrose density gradient fractions of two of the infectious human sera (peak reverse transcriptase activity at 1.14 g/ml) transmitted NANBH to chimpanzees. Biochemical and enzymatic data indicate that the NANBH agent(s) is a retrovirus or is retrovirus-like.


Trends in the management of traumatic vertebral artery injuries.
From 1975 to 1988, 25 patients with a vertebral artery (VA) injury were treated. Admission neurologic status was intact in 14 patients (56 percent). Eight patients had deficits due to direct nerve or spinal cord injury, two patients had symptoms referable to vertebrobasilar ischemia, and one patient had a contralateral deficit due to an associated carotid artery injury. Twenty-two of 25 patients (88 percent) underwent diagnostic arteriography. Twelve patients (48 percent) with 9 occlusive and 3 minimal injuries were observed. Seven patients (28 percent), three with exsanguinating hemorrhage, were treated by operative exploration and VA ligation. Six patients (24 percent), two with a VA pseudoaneurysm and four with an arteriovenous fistula, were managed by percutaneous transcatheter embolization. The neurologic status was unchanged or improved in 22 patients (88 percent) at discharge. Two patients developed Horner's syndrome after VA ligation. Transient posterior circulation ischemia occurred in a single patient after percutaneous transcatheter embolization. There was no mortality. The majority of VA injuries are best managed by nonoperative methods. Untoward neurologic sequelae are rare. Operative intervention and VA ligation should be reserved for patients with active hemorrhage or large pseudoaneurysms and arteriovenous fistulas which cannot be embolized.


Corticosteroid-free immunosuppression with daclizumab in HCV(+) liver transplant recipients: 1-year interim results of the HCV-3 study.
This work is a 1-yr interim analysis of a prospective, randomized, multicenter trial evaluating the effect of corticosteroid-free immunosuppression on hepatitis C virus-positive (HCV(+)) liver transplant recipients following liver transplantation (LT). Patients received tacrolimus and corticosteroids (Arm 1; n = 80); tacrolimus, corticosteroids, and mycophenolate mofetil (MMF) (Arm 2; n = 79); or daclizumab induction, tacrolimus, and MMF (Arm 3; n = 153). At 1 yr, 64.1%, 63.4%, and 69.4% of patients achieved the composite primary endpoint of freedom from rejection, freedom from HCV recurrence, and freedom from treatment failure, respectively. Excellent patient and graft survival did not differ significantly among treatment arms. Freedom from HCV recurrence at 1 yr was 61.8 +/- 6.2%, 60.1 +/- 6.1%, and 67.0 +/- 4.3% in Arms 1, 2, and 3, respectively (P = not significant). Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 (93.0 +/- 2.2% vs. 81.9 +/- 4.4%; P = 0.011). Multivariate analysis identified acute rejection (hazard ratio = 2.692; P = 0.001) and donor age (hazard ratio = 1.015; P = 0.001) as significant risk factors for HCV recurrence. HCV recurrence was not influenced by recipient demographics, HCV genotype, or immunosuppression. In conclusion, these results suggest that a corticosteroid-free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV(+) liver transplant recipients.


HLA-Clus: HLA class I clustering based on 3D structure.
In a previous paper, we classified populated HLA class I alleles into supertypes and subtypes based on the similarity of 3D landscape of peptide binding grooves, using newly defined structure distance metric and hierarchical clustering approach. Compared to other approaches, our method achieves higher correlation with peptide binding specificity, intra-cluster similarity (cohesion), and robustness. Here we introduce HLA-Clus, a Python package for clustering HLA Class I alleles using the method we developed recently and describe additional features including a new nearest neighbor clustering method that facilitates clustering based on user-defined criteria. The HLA-Clus pipeline includes three stages: First, HLA Class I structural models are coarse grained and transformed into clouds of labeled points. Second, similarities between alleles are determined using a newly defined structure distance metric that accounts for spatial and physicochemical similarities. Finally, alleles are clustered via hierarchical or nearest-neighbor approaches. We also interfaced HLA-Clus with the peptide:HLA affinity predictor MHCnuggets. By using the nearest neighbor clustering method to select optimal allele-specific deep learning models in MHCnuggets, the average accuracy of peptide binding prediction of rare alleles was improved. The HLA-Clus package offers a solution for characterizing the peptide binding specificities of a large number of HLA alleles. This method can be applied in HLA functional studies, such as the development of peptide affinity predictors, disease association studies, and HLA matching for grafting. HLA-Clus is freely available at our GitHub repository ( https://github.com/yshen25/HLA-Clus ).


Protocol from a randomized clinical trial of multiple pharmacotherapy adaptations based on treatment response in African Americans who smoke.
The standard of care in tobacco treatment is to continue individuals who smoke on the same cessation medication, even when they do not stop smoking. An alternative strategy is to adapt pharmacotherapy based on non-response. A handful of studies have examined this approach, but they have adapted pharmacotherapy only once and/or focused on adaptation distal rather than proximal to a failed quit attempt. Few studies have included racial/ethnic minorities who have less success in quitting and bear a disproportionate share of tobacco-related morbidity and mortality. The current study is comparing the efficacy of optimized (OPT) versus enhanced usual care (UC) for smoking cessation in African Americans (AA) who smoke cigarettes. AAs who smoke (n = 392) are randomized 1:1 to OPT or UC. Participants in both groups receive 7 sessions of smoking cessation counseling and18-weeks of pharmacotherapy with long-term follow-up through Week 26. OPT participants receive nicotine patch and up to two pharmacotherapy adaptations to varenicline and bupropion plus patch based on carbon monoxide verified smoking status (≥6 ppm) at Weeks 2 and 6. UC participants receive patch throughout the duration of treatment. We hypothesize that OPT will be more effective than UC on the primary outcome of biochemically verified abstinence at Week 12. If effective, findings could broaden the scope of tobacco dependence treatment and move the field toward optimization strategies that impro ve abstinence for AA who smoke. NCT03897439.


Branched chain amino acid metabolism in the retina of diabetic rats.
Diabetes is known to produce increased levels of the branched chain amino acids in plasma, heart and muscle as well as increased oxidation of [14C]-leucine by nerves and muscles from rats. Plasma and retinas from streptozotocin diabetic rats had significant elevations in branched chain amino acid levels compared to control. Retinas from diabetic rats have been found to oxidize significantly more of the branched chain amino acids, leucine, isoleucine and valine than did control retinas when incubated in media containing 16.5 mmol/l glucose. Neither the extracellular space nor the tissue pool of leucine was significantly different in the two groups. The addition of 19 amino acids, at normal plasma concentrations, to the incubation media resulted in 80 percent suppression of leucine oxidation without significant change in incorporation of [14C] into protein. These results suggest that the major role for the branched chain amino acids in the rat retina is in protein synthesis which is not affected by short-term diabetes.


Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model.
A randomised, blinded, prospective animal study with 296 male C57BL/6N mice was performed to evaluate the biomechanical, biomolecular, biochemical, and histological impact of anti-inflammatory medications on fracture healing. A reproducible closed tibia fracture was created and stabilised with an intramedullary pin. Animals were randomised to placebo, ketorolac, ibuprofen, celecoxib, or rofecoxib treatment groups with biomechanical and biochemical testing at 4, 8, and 12 weeks. A second arm of the study was conducted in which animals were randomised to indomethacin or placebo treatment with biomechanical testing at 12 weeks. Histological and biomolecular studies were performed at 2 weeks on all groups in the first arm of the study. Biomechanical testing consisted of three-point bending evaluating maximum load, energy absorbed to maximum load, and stiffness. Safranin O-Fast Green stain was performed for histology. Biochemical quantifications of chondroitin and dermatan sulphate, hydroxyproline, total protein, and DNA content were performed. Osteocalcin and collagen types II and X were evaluated by in situ hybridisation. Some mechanical differences were seen between ketorolac and placebo at 4 weeks with respect to energy absorbed, but there were no differences in maximum load or stiffness seen between any treatment group and placebo at any time point. Indomethacin, celecoxib, rofecoxib, ibuprofen, and ketorolac did not significantly affect fracture healing in this young murine model.


Effects of Broflanilide on Oxidative Stress and Expression of Apoptotic Genes in Zebrafish (Danio rerio) Gill.
Broflanilide exerted negative impacts on the gill of zebrafish. Thus, in this study, zebrafish gill was used to assess the apoptosis toxicity of broflanilide by determining the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) and apoptosis-related genes. The results found that the minimum threshold for the content and time of broflanilide affecting enzyme content and gene expression was 0.26 mg/L after 24 h exposure. After 96 h exposure, broflanilide could cause apoptosis and exerted significantly increased contents of ROS and MDA, while inhibiting the activities of SOD, CAT, and GPx at 0.26 and 0.57 mg/L. Broflanilide also had adverse effects on apoptosis-related genes, such as tumor protein p53 (p53), associated × (Bax), B-cell lymphama-2 (Bcl-2), caspase-3, caspase-9, and apoptotic protease activating factor-1(apaf-1), at 0.26 mg/L and 0.57 mg/L after 96 h exposure, respectively. These results provide new insight into the potential toxicity mechanisms of broflanilide in zebrafish gills.


Humoral factors released during trauma of Aplysia body wall. I. Body wall contraction, cardiac modulation, and central reflex suppression.
1. Mechanical or electrical stimulation of isolated sections of body wall produced contractions that were graded with the intensity of the stimulus. Injury of body wall with shallow incisions produced extremely persistent contractions. 2. Long-lasting contraction of isolated body wall was also produced by brief application of "stimulated body wall wash" (SBW), sea water which was first washed through another section of body wall subjected to intense mechanical or electrical stimulation. Contractions were produced by SBW diluted to concentrations as low as 1% of the initial concentration. Contractions produced by prolonged application of SBW showed little fatigue, tachyphylaxis, or desensitization. 3. SBW caused contraction of isolated sections of body wall from all regions of the body, including tail, parapodia, siphon, purple gland, rhinophores, and anterior tentacles. SBW also caused contraction of isolated lateral columellar muscle and of the gill. 4. 30 mM CoCl2 blocked the release of contractile factors into electrically stimulated body wall and reduced but did not abolish contractile responses of unstimulated body wall to perfused SBW. SBW contractions were unchanged by disconnection of the perfused tissue to the CNS. 5. Hemolymph collected from the neck of an intact donor following strong electrical stimulation of the tail or excision of a parapodium ('stimulated hemolymphh, SHL) caused long-lasting contractions which were larger than those produced by control hemolymph (CHL) collected prior to stimulation of the donor. 6. Similarities between body wall contractions produced by SHL and by SBW, including their occurrence in 30 mM CoCl2, suggest that some of the contractile activity in SHL may be directly released from traumatized body wall. 7. SHL caused significantly greater cardioacceleration of the isolated heart than did CHL. Similarities between the cardioacceleration produced by SHL and by SBW suggest that a source of cardiac activity in SHL may be traumatized body wall. 8. SBW suppressed the gill-withdrawal reflex when applied selectively to the sheathed or desheathed abdominal ganglion. SBW-induced suppression was associated with significant reduction of evoked spike activity in identified gill motor neurons. SHL collected 1-2 h after noxious stimulation caused weak but significant suppression of the gill-withdrawal reflex when applied to the fully sheathed abdominal ganglion.


Corrigendum: Somatic Experiencing: using interoception and proprioception as core elements of trauma therapy.
[This corrects the article on p. 93 in vol. 6, PMID: 25699005.].


Toxicogenomic analysis of the gene expression changes in rat liver after a 28-day oral Tripterygium wilfordii multiglycoside exposure.
Tripterygium wilfordii multiglycoside (GTW), which is an extract derived from Tripterygium wilfordii Hook.f., has been used for the treatment of rheumatoid arthritis and other immune diseases in China. However, its potential hepatotoxicity has not been completely investigated. The aim of the study was to determine the hepatotoxicity of GTW in Wistar rats and to investigate the underlying cellular mechanism further by microarray analysis. Doses of GTW at 60, 100 and 120mg/kg/day were administered by oral gavage for subchronic toxicity in Wistar rats. Changes in the hepatic gene expression were identified with oligonucleotide microarrays at the 100-mg/kg/day dose level to study the hepatotoxic mechanism of GTW. A number of changes in the body weight and food consumption, absolute and relative liver weight, biochemical analysis and histopathology were observed after the subacute exposure to GTW, and a dose-dependent hepatotoxicity was observed. A total of 1312 genes were found to be significantly altered (2-fold, P<0.05), including 582 up-regulated genes and 730 down-regulated genes. According to our biological pathway analysis, the GTW resulted in aberrant gene expression in metabolic pathways and the peroxisome proliferator-activated receptor (PPAR) signaling pathway and cellular stress. Real-time PCR analyses of several genes verified these results. Consequently, our gene expression microarray study will be useful for future GTW hepatotoxicity studies.


Coexistence of ventricular parasystole and ventricular couplets: mechanism and clinical significance.
In 78 consecutive patients with uniform ventricular ectopic complexes and without heart disease, ventricular couplets were present significantly more often when the coupling interval of ventricular ectopic complexes was variable than when it was fixed (P less than 0.04). In 69 consecutive patients with couplets, the prevalence of a variable coupling interval was significantly greater than that of (55 versus 14 cases; P less than 0.001). Among 55 patients with a variable coupling interval, ventricular parasystole was probable in 38 and possible in 17 patients. These results suggest that the association between ventricular couplets and parasystole is not coincidental. Of several possible mechanisms responsible for this association reentry within the parasystolic focus or its vicinity is the most probable. This may explain the observation that the couplets are seldom followed by consecutive ventricular ectopic complexes or ventricular tachycardia. If this hypothesis is correct, the clinical significance of ventricular couplets in the presence of ventricular parasystole may be similar to that of single reentrant ventricular ectopic complexes.


cNF-Skindex in Adults Living with Neurofibromatosis 1: Severity Strata in France and Validation in United States Adults.
Cutaneous neurofibromas (cNF) contribute to the impairment of QOL in individuals with neurofibromatosis 1. The cNF-Skindex, validated in a French population, specifically assesses the cNF-related QOL. In this study, we first defined severity strata using an anchoring approach on the basis of patient's burden. In total, 209 patients answered the anchor question and the cNF-Skindex. We tested the agreement among the three strata, generated by all potential couples of cut-off values of the cNF-Skindex and the three strata defined in the anchor question. The cut-off values 12 and 49 provided the highest Kappa value (κ = 0.685, 95% confidence interval = 0.604-0.765). Second, we validated the score and the strata in a United States population using the answers provided by 220 French and 148 United States adults. In the multivariable linear regression analysis, the country of origin was not a factor associated with the score (P = 0.297). The number of cNF along the different severity strata was similar between the French and the United States populations. In conclusion, stratification constitutes a powerful tool to better interpret the cNF-Skindex in daily practice and in clinical trials. This study validates its use in two populations that together constitute a large cohort of patients willing to participate in clinical research.


Age and Sex Influence Mitochondria and Cardiac Health in Offspring Exposed to Maternal Glucolipotoxicity.
Infants of diabetic mothers are at risk of cardiomyopathy at birth and myocardial infarction in adulthood, but prevention is hindered because mechanisms remain unknown. We previously showed that maternal glucolipotoxicity increases the risk of cardiomyopathy and mortality in newborn rats through fuel-mediated mitochondrial dysfunction. Here we demonstrate ongoing cardiometabolic consequences by cross-fostering and following echocardiography, cardiomyocyte bioenergetics, mitochondria-mediated turnover, and cell death following metabolic stress in aged adults. Like humans, cardiac function improves by weaning with no apparent differences in early adulthood but declines again in aged diabetes-exposed offspring. This is preceded by impaired oxidative phosphorylation, exaggerated age-related increase in mitochondrial number, and higher oxygen consumption. Prenatally exposed male cardiomyocytes have more mitolysosomes indicating high baseline turnover; when exposed to metabolic stress, mitophagy cannot increase and cardiomyocytes have faster mitochondrial membrane potential loss and mitochondria-mediated cell death. Details highlight age- and sex-specific roles of mitochondria in developmentally programmed adult heart disease.


Alcohol consumption in a community sample of older people.
To examine the prevalence and pattern of alcohol use among community-living elderly Australians. A survey was conducted of randomly selected non-institutionalised people aged 75 years and older living in the inner western suburbs of Sydney. Personal interviews by trained interviewers covered background demographic information and self-reported alcohol use. 72% of men and 54% of women drank alcohol. The median usual daily volume of ethanol consumed by drinkers was 10 grams for men and 1.3 grams for women. However 11% of male drinkers and 6% of female drinkers consumed at defined hazardous or harmful levels. Although a sizeable majority of these older people were either non-drinkers or very light drinkers, a small but important proportion drank in the hazardous to harmful range. Despite increasing evidence of the health benefits of alcohol consumption it remains important to be alert for potentially harmful alcohol use among older people.


[Isolation of vital human sperm from seminal plasma following cryopreservation].
In the present paper the conditions of separation of cryopreserved spermatozoa from seminal plasma were varied. The optimum seems to be at 300 g and 5 to 7 min of centrifugation. The effect of separation was approximately estimated by means of determination of concentration, motility, morphology, and supravital staining of spermatozoa. The concentration of seminal plasma was reduced to less than one per cent (use of a radioactive marker). After the separation the activity of free acrosin reached 64 p.c. of the total acrosin. The process of cryopreservation and separation reduced the ouabain-sensitive netto-uptake of K+ of spermatozoa by nearly 50 p.c.


Evolutionary epidemiology of Streptococcus iniae: Linking mutation rate dynamics with adaptation to novel immunological landscapes.
Pathogens continuously adapt to changing host environments where variation in their virulence and antigenicity is critical to their long-term evolutionary success. The emergence of novel variants is accelerated in microbial mutator strains (mutators) deficient in DNA repair genes, most often from mismatch repair and oxidized-guanine repair systems (MMR and OG respectively). Bacterial MMR/OG mutants are abundant in clinical samples and show increased adaptive potential in experimental infection models, yet the role of mutators in the epidemiology and evolution of infectious disease is not well understood. Here we investigated the role of mutation rate dynamics in the evolution of a broad host range pathogen, Streptococcus iniae, using a set of 80 strains isolated globally over 40 years. We have resolved phylogenetic relationships using non-recombinant core genome variants, measured in vivo mutation rates by fluctuation analysis, identified variation in major MMR/OG genes and their regulatory regions, and phenotyped the major traits determining virulence in streptococci. We found that both mutation rate and MMR/OG genotype are remarkably conserved within phylogenetic clades but significantly differ between major phylogenetic lineages. Further, variation in MMR/OG loci correlates with occurrence of atypical virulence-associated phenotypes, infection in atypical hosts (mammals), and atypical (osseous) tissue of a vaccinated primary host. These findings suggest that mutators are likely to facilitate adaptations preceding major diversification events and may promote emergence of variation permitting colonization of a novel host tissue, novel host taxa (host jumps), and immune-escape in the vaccinated host.


Deep learning enables super-resolution hydrodynamic flooding process modeling under spatiotemporally varying rainstorms.
Real-time information on flooding extent, severity, and duration is necessary for effective metropolitan flood emergency management. Existing pluvial flood analysis methods are unable to simulate real-time regional flooding processes under spatiotemporally varying rainstorms. This paper presents a deep learning-enabled super-resolution hydrodynamic flood analysis method to simulate the real-time pluvial flooding process over a large area under spatiotemporally varying rainstorms. Compared with existing flood downscaling techniques, which are limited to flow depth, the proposed method produces high-resolution flow depth and velocity predictions, providing more comprehensive information for flood emergency management. The proposed method adopts a coarse-grid hydrodynamic model to generate a low-resolution flood map time series, which is subsequently converted to high-resolution flood maps by a deep learning model. The deep learning model can be trained using a limited number of assumed rainfall scenarios, which greatly reduces data preparation effort. The proposed method is applied to a complex terrain of 352 km2 in Hong Kong that covers both mountainous and urban areas. Results show that the proposed method simulates the spatiotemporal variations of flood depth and velocity with root mean square errors as low as 0.082 m and 0.088 m/s, respectively, and correlation coefficients of 0.962 and 0.921, respectively. The computation time for a 48-h rainfall event in the study area is less than 30 s, which is 2690 times faster than the direct fine-grid hydrodynamic analysis. The deep learning-enabled super-resolution hydrodynamic flood analysis method provides a promising computational tool for emergency flood risk management.


Stereoselective formation and hydration of benzo[c]phenanthrene 3,4- and 5,6-epoxide enantiomers by rat liver microsomal enzymes.
The K-region 5,6-epoxides, formed in the metabolism of benzo[c]phenanthrene (BcPh) in the presence of an epoxide hydrolase inhibitor 3,3,3-trichloropropylene 1,2-oxide (TCPO) by liver microsomes from untreated, phenobarbital-treated, 3-methylcholanthrene-treated, and polychlorinated biphenyls (Aroclor 1254)-treated rats of the Sprague-Dawley and the Long-Evans strains, were found by chiral stationary phase high-performance liquid chromatography analyses to be enriched (58-72%) in the 5S, 6R enantiomer. In the absence of TCPO, the metabolically formed BcPh trans-5,6-dihydrodiol was enriched (78-86%) in the 5S,6S enantiomer. The major enantiomer of the BcPh 3,4-epoxide metabolite was found to be enriched in the 3S,4R enantiomer which undergoes racemization under the experimental conditions. The major enantiomer of the 5,6-dihydrodiol metabolite was elucidated by the exciton chirality circular dichroism (CD) method to have a 5S,6S absolute stereochemistry. Absolute configurations of enantiomeric methoxylation products derived from each of the two BcPh 5,6-epoxide enantiomers. Optically pure BcPh 5S,6R-epoxide was enzymatically hydrated exclusively at the C6 position to form an optically pure BcPh 5S,6S-dihydrodiol. However, optically pure BcPh 5R,6S-epoxide was hydrated at both C5 and C6 positions to form a BcPh trans-5,6-dihydrodiol with a (5S,6S):(5R,6R) enantiomer ratio of 32:68.


Neuritis of the cauda equina, a chronic idiopathic polyradiculoneuritis in the horse.
Four cases of neuritis of the cauda equina (NCE) were studied by light and electron microscopy. Examination of sacral intradural rootlets revealed inflammatory cell infiltrates and an array of myelinated fiber changes which included myelin stripping by invading mononuclear cells and macrophages, as well as splitting and vesiculation of myelin lamellae without obvious participation by leukocytes. More distally in the extradural roots, there was marked granulomatous inflammation, and demyelinative changes were overshadowed by widespread evidence of irreversible axon damage. In all cases, unusual crystalline inclusions appeared in the endoneurium and sheaths of the rootlets and fascicles. The changes in NCE were compared and contrasted with those observed in acute and chronic inflammatory demyelinative neuropathies.


Impaired Cardiac Reserve and Abnormal Vascular Load Limit Exercise Capacity in Chronic Thromboembolic Disease.
This study was a comprehensive evaluation of cardiopulmonary function in patients with chronic thromboembolic (pulmonary vascular) disease (CTED) during exercise. Exertional dyspnea is frequent following pulmonary embolism, but only a minority of patients eventually develops chronic thromboembolic pulmonary hypertension (CTEPH). Better understanding of the factors that limit exercise capacity in patients with persistent pulmonary artery obstruction could help to further define the entity of CTED. Fifty-two subjects (13 healthy control subjects, 14 CTED patients, and 25 CTEPH patients) underwent cardiopulmonary exercise testing and exercise cardiac magnetic resonance with simultaneous invasive pressure registration. Pulmonary vascular function and right ventricular contractile reserve were assessed through combined invasive pressure measurements and magnetic resonance imaging volume measures. Exercise capacity was reduced by 29% and 57% in patients with CTED and CTEPH respectively, compared with control subjects. Both CTED (3.48 [interquartile range: 2.24 to 4.36] mm Hg × l-1 × min-1) and CTEPH patients (8.85 [interquartile range: 7.18 to 10.4] mm Hg × l-1 × min-1) had abnormal total pulmonary vascular resistance. Right ventricular contractile reserve was reduced in CTED patients compared with control subjects (2.23 ± 0.55 vs. 3.72 ± 0.94), but was still higher than that in CTEPH patients (1.34 ± 0.24; p < 0.001). As opposed to patients with CTEPH in whom right ventricular ejection fraction declined with exercise, right ventricular ejection fraction still increased in patients with CTED, albeit to a lesser extent than in healthy control subjects (interaction p < 0.001), which illustrated the distinct patterns of ventricular-arterial coupling. CTED represents an intermediate clinical phenotype. Exercise imaging unmasks cardiovascular dysfunction not evident at rest and identifies hemodynamically significant disease that results from reduced contractile reserve or increased vascular load.


Characterizing temporal variability in streams supports nutrient indicator development using diatom and bacterial DNA metabarcoding.
Interest in developing periphytic diatom and bacterial indicators of nutrient effects continues to grow in support of the assessment and management of stream ecosystems and their watersheds. However, temporal variability could confound relationships between indicators and nutrients, subsequently affecting assessment outcomes. To document how temporal variability affects measures of diatom and bacterial assemblages obtained from DNA metabarcoding, we conducted weekly periphyton and nutrient sampling from July to October 2016 in 25 streams in a 1293 km2 mixed land use watershed. Measures of both diatom and bacterial assemblages were strongly associated with the percent agriculture in upstream watersheds and total phosphorus (TP) and total nitrogen (TN) concentrations. Temporal variability in TP and TN concentrations increased with greater amounts of agriculture in watersheds, but overall diatom and bacterial assemblage variability within sites-measured as mean distance among samples to corresponding site centroids in ordination space-remained consistent. This consistency was due in part to offsets between decreasing variability in relative abundances of taxa typical of low nutrient conditions and increasing variability in those typical of high nutrient conditions as mean concentrations of TP and TN increased within sites. Weekly low and high nutrient diatom and bacterial metrics were more strongly correlated with site mean nutrient concentrations over the sampling period than with same day measurements and more strongly correlated with TP than with TN. Correlations with TP concentrations were consistently strong throughout the study except briefly following two major precipitation events. Following these events, biotic relationships with TP reestablished within one to three weeks. Collectively, these results can strengthen interpretations of survey results and inform monitoring strategies and decision making. These findings have direct applications for improving the use of diatoms and bacteria, and the use of DNA metabarcoding, in monitoring programs and stream site assessments.


Touching motion: rTMS on the human middle temporal complex interferes with tactile speed perception.
Brain functional and psychophysical studies have clearly demonstrated that visual motion perception relies on the activity of the middle temporal complex (hMT+). However, recent studies have shown that hMT+ seems to be also activated during tactile motion perception, suggesting that this visual extrastriate area is involved in the processing and integration of motion, irrespective of the sensorial modality. In the present study, we used repetitive transcranial magnetic stimulation (rTMS) to assess whether hMT+ plays a causal role in tactile motion processing. Blindfolded participants detected changes in the speed of a grid of tactile moving points with their finger (i.e. tactile modality). The experiment included three different conditions: a control condition with no TMS and two TMS conditions, i.e. hMT+-rTMS and posterior parietal cortex (PPC)-rTMS. Accuracies were significantly impaired during hMT+-rTMS but not in the other two conditions (No-rTMS or PPC-rTMS), moreover, thresholds for detecting speed changes were significantly higher in the hMT+-rTMS with respect to the control TMS conditions. These findings provide stronger evidence that the activity of the hMT+ area is involved in tactile speed processing, which may be consistent with the hypothesis of a supramodal role for that cortical region in motion processing.


Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese.
To determine whether mutations in the WD repeat domain 36 gene (WDR36) are associated with primary open-angle glaucoma (POAG) in Japanese. Subjects with high tension glaucoma (HTG) and normal tension glaucoma (NTG) were analyzed separately. One hundred and thirty-six unrelated Japanese patients with HTG and 103 unrelated patients with NTG were studied. Genomic DNA was extracted from peripheral blood leukocytes, and all 23 exons were amplified by polymerase chain reaction (PCR) and directly sequenced bidirectionally. Twenty sequence alterations were identified: 10 have already been reported (p.I264V, c.1494+90C>T, c.1494+143A>G, c.1609+89G>A, c.1775+89C>A, c.1965-30A>G, p.V714V, c.2170+217C>T, p.V727V, and c.2518+60G>C) and 10 were novel (p.D179D, p.Q270Q, p.M283R, c.898+63C>G, c.1074+20C>T, p.G459G, c.1884+26C>G, p.S664L, p.S664S, and p.P744P). One nonsynonymous amino acid change in exon 17, p.S664L, was identified in a patient with HTG. The frequency of the p.I264V variant was significantly higher in the HTG group than in the control group (p=0.01), but the frequency in the NTG group was not significantly different from the control group (p=0.12). The frequency of the c.1965-30A>G variant was also significantly higher in the HTG group than in the control group (p=0.03), but the frequency in the NTG group was not significantly different from the control group (p=0.06). One nonsynonymous variant, p.S664L, and the association of the allelic variants (p.I264V and c.1965-30A>G) in WDR36 and their prevalence in unrelated Japanese patients with HTG suggest that they are probably involved in the pathogenesis of HTG.


Optimizing adherence to pharmaceutical care plans.
Adherence to pharmacotherapy is essential to optimal therapeutic outcomes. The pivotal role of the pharmacist in optimizing adherence encompasses many actions: assessing the adherence problem, identifying predisposing factors, providing comprehensive counseling, and recommending specific adherence strategies targeted to the patient's needs. Patients who have chronic conditions, physical or cognitive impairments, or cultural backgrounds outside the mainstream may have special needs that should be addressed in the adherence plan. Pharmaceutical care plans also should take into account the patient's age, stage of life, and literacy level. Although a wide range of adherence aids and strategies are available, the key to success is to tailor the intervention to the individual patient and, when necessary, to combine interventions to optimize adherence.


The application of antidepressant drugs in cancer treatment.
Antidepressants refer to psychotropic drugs which are used to treat mental illness with prominent emotional depression symptoms. It was reported that antidepressants had associated with anti-carcinogenic function which was associated with various signaling pathways and changing of microenvironment. Its mechanism includes cell apoptosis, antiproliferative effects, mitochondria-mediated oxidative stress, DNA damaging, changing of immune response and inflammatory conditions, and acting by inhibiting multidrug resistance of cancer cells. Accumulated studies showed that antidepressants influenced the metabolic pathway of tumor cells. This review summarized recent developments with the impacts and mechanisms of 10 kinds of antidepressants in carcinostasis. Antidepressants are also used in combination therapy with typical anti-tumor drugs which shows a synergic effect in anti-tumor. By contrast, the promotion roles of antidepressants in increasing cancer recurrence risk, mortality, and morbidity are also included. Further clinical experiments and mechanism analyses needed to be achieved. A full understanding of the underlying mechanisms of antidepressants-mediated anticarcinogenic effects may provide new clues for cancer prevention and clinical treatment.