Prevalence of stroke and coexistent conditions: disparities between indigenous and nonindigenous Western Australians.
Worldwide, the prevalence of stroke is poorly described in indigenous populations, despite high stroke burden. This paper reports the average point prevalence of hospitalized stroke and coexistent conditions (2007-2011) in indigenous and nonindigenous people in Western Australia, the largest and most sparsely populated Australian jurisdiction. Using state-wide linked hospital and mortality data, indigenous and nonindigenous prevalent stroke cases (aged 25-84 years) were identified after reviewing stroke admissions over a fixed 20-year look-back period. Prevalent cases were those alive at midyear of each study year. The 2007-2011 period prevalence was a weighted average of annual prevalence. Histories of 11 comorbidities were identified using the 20-year look-back period. Indigenous cases comprised 5% of the average 13 591 annual prevalent cases. Indigenous patients were more likely to be younger, female, and have unknown stroke type. Indigenous prevalence was higher at every age. The age-standardized prevalence in indigenous men (33·7 per 1000; 95% confidence interval 31·9-35·4) was 3.7 times greater than in nonindigenous men (9·1 per 1000; 95% confidence interval 9·0-9·2). The corresponding estimates for women were 27·1 per 1000 (25·7-28·4) and 6·1 per 1000 (6·0-6·2) (ratio = 4·4). The percentage with selected comorbid conditions was substantially higher for indigenous patients. The high stroke prevalence in indigenous Western Australians, coupled with clinical complexity from comorbid conditions, requires access to culturally appropriate medical, rehabilitation, and logistical support. Intensified primary and secondary prevention is needed to reduce the impact of stroke on indigenous people.


[Pharmacotherapeutic correction of gastric motility and emptying after gastric resection and vagotomy].
Motor-evacuational function of stomach, duodenum and its draining loop after gastric resection and vagotomy in 82 patients is studied up. Two variants of medicinal correction of the stomach and efferent intestinal loop motor disorders are elaborated.


Neurocysticercosis and epilepsy in Peru.
This study was carried out to determine the prevailing type of epilepsy in neurocysticercosis. We also evaluated if it could account for the predominance of generalized epilepsy in Peru. We studied the records and EEGs of 49 cases of neurocysticercosis, representing 5.9% of all hospital admissions. Cysticercosis was diagnosed using clinical, blood, CSF (complement fixation, ELISA, immunoblot) and CT scan criteria. We found 49 epileptic patients. Their type of epilepsy was as follows: 35 subjects had generalized epilepsy and 14 had partial epilepsy (5 motor partial, 5 complex partial, both with secondary generalization and 4 motor partial). All but 3 patients were over 25 years old (mean 33 years). We conclude that generalized epilepsy is frequent among cysticercosis patients and that it may account, partially, for the predominance of generalized seizures in Peru and in other areas of South America where cysticercosis is endemic.


Optimization of gene delivery methods in Xenopus laevis kidney (A6) and Chinese hamster ovary (CHO) cell lines for heterologous expression of Xenopus inner ear genes.
The Xenopus inner ear provides a useful model for studies of hearing and balance because it shares features with the mammalian inner ear, and because amphibians are capable of regenerating damaged mechanosensory hair cells. The structure and function of many proteins necessary for inner ear function have yet to be elucidated and require methods for analysis. To this end, we seek to characterize Xenopus inner ear genes outside of the animal model through heterologous expression in cell lines. As part of this effort, we aimed to optimize physical (electroporation), chemical (lipid-mediated; Lipofectamine™ 2000, Metafectene® Pro), and biological (viral-mediated; BacMam virus Cellular Lights™ Tubulin-RFP) gene delivery methods in amphibian (Xenopus; A6) cells and mammalian (Chinese hamster ovary (CHO)) cells. We successfully introduced the commercially available pEGFP-N3, pmCherry-N1, pEYFP-Tubulin, and Cellular Lights™ Tubulin-RFP fluorescent constructs to cells and evaluated their transfection or transduction efficiencies using the three gene delivery methods. In addition, we analyzed the transfection efficiency of a novel construct synthesized in our laboratory by cloning the Xenopus inner ear calcium-activated potassium channel β1 subunit, then subcloning the subunit into the pmCherry-N1 vector. Every gene delivery method was significantly more effective in CHO cells. Although results for the A6 cell line were not statistically significant, both cell lines illustrate a trend towards more efficient gene delivery using viral-mediated methods; however the cost of viral transduction is also much higher. Our findings demonstrate the need to improve gene delivery methods for amphibian cells and underscore the necessity for a greater understanding of amphibian cell biology.


Anemoside B4 ameliorates experimental autoimmune encephalomyelitis in mice by modulating inflammatory responses and the gut microbiota.
Anemoside B4 (AB4) is a representative component of Pulsatilla decoction that is used in traditional Chinese medicine for treating inflammatory conditions. It is not known whether AB4 has beneficial effects on multiple sclerosis (MS). In the present study, we examined the preventative and therapeutic effects of AB4, and the possible mechanism by which it protects female mice against experimental autoimmune encephalomyelitis (EAE). Preventative treatment with AB4 (given orally at 100 and 200 mg/kg for 18 days) reduced the clinical severity of EAE significantly (from 3.6 ± 1.3 to 1.8 ± 1.5 and 1.6 ± 0.6, respectively), and inhibited demyelination and inflammatory infiltration of the spinal cord. In the therapeutic protocol, oral administration of 200 mg/kg AB4 for 21 days after initiation of EAE significantly alleviated disease severity (from 2.6 ± 1.3 to 0.9 ± 0.6) and was as effective as the clinically used drug fingolimod (0.3 ± 0.6). Furthermore, both doses of AB4 significantly inhibited mRNA expression of TNF-α, IL-6, and IL-17, and STAT3 activation, in the spinal cord; and the ex vivo and iv vitro AB4 treatment markedly inhibited secretion of the three cytokines from lymphocytes of EAE mice upon in vitro restimulation. In addition, AB4 reversed the changes in the composition of the intestinal microbiome observed in EAE mice. We reveal for the first time that AB4 protects against EAE by modulating inflammatory responses and the gut microbiota, demonstrating that AB4 may have potential as a therapeutic agent for treating MS in humans.


The effects of short-term overfeeding on adipocyte metabolism in Pima Indians.
The effects on adipocyte metabolism of increasing daily caloric intake by approximately 60% for 14 days was studied in seven nondiabetic moderately obese southwestern Native American Indians. Mean body weight increased by 3.0 +/- 0.3 kg, without any change in average size of isolated abdominal adipocytes. Overfeeding resulted in a 58% increase (P less than 0.01) in mean fasting plasma insulin concentration, whereas fasting plasma glucose concentration remained constant. Basal and maximum (8 nmol/L) insulin-stimulated glucose transport rates by isolated adipocytes increased by 83% (P less than 0.02) and 110% (P less than 0.01), respectively, after overfeeding, associated with an increase of 118% (P less than 0.01) in the incremental response to maximal insulin stimulation. However, no differences in either the sensitivity (ED50 of insulin for the stimulation of glucose transport) or the responsiveness (percent stimulation by insulin) of glucose transport were seen in isolated adipocytes as a result of overfeeding. Maximum insulin-stimulated total glucose utilization rates by isolated adipocytes incubated at 5.5 mmol/L glucose were 63% greater after overfeeding, due to increases in lactate formation, triglyceride synthesis, and CO2 production. Mono125I-(Tyr A14)-insulin binding per cell and per cell surface area was similar before and after overfeeding. The lipolytic rate of isolated adipocytes, in the absence and presence of 25 nmol/L and 2 mumol/L isoproterenol, was decreased by 75% (P less than 0.02), 45% (P less than 0.05), and 27% (P less than 0.05), respectively, after overfeeding. However, overfeeding did not result in a significant difference in the sensitivity of antilipolysis to insulin.(ABSTRACT TRUNCATED AT 250 WORDS)


A new Igk-V gene family in the mouse.
We have identified and characterized a novel mouse Igk-V gene family, which we have designated Igk-V34. Southern hybridization and nucleotide sequence analysis indicate that this family is comprised of either one or two members in mice of different Igk haplotypes. The gene family members share between 95% and 98% sequence similarity, indicating that they diverged only recently during the evolution of the Igk locus. Sequence relationships between members of this family are discussed.


Tumor-induced lymphangiogenesis: a target for cancer therapy?
Recent advances in understanding the biology of lymphangiogenesis, the new growth of lymphatic vessels, have cast new light on the molecular basis of metastasis to regional lymph nodes. The receptor tyrosine kinase VEGFR-3 is virtually exclusively expressed on lymphatic but not blood endothelium in the adult, and activation of VEGFR-3 by its ligands VEGF-C and VEGF-D is sufficient to induce lymphangiogenesis. Correlative studies with human tumors and functional studies using animal tumor models show that increased levels of VEGF-C or VEGF-D in tumors lead to enhanced numbers of lymphatic vessels in the vicinity of tumors, which in turn promotes metastasis to regional lymph nodes by providing a greater number of entry sites into the lymphatic system for invading tumor cells. These findings have prompted studies to investigate whether inhibitors of VEGFR-3 activation might represent novel therapeutic agents for the suppression of metastasis. However, a number of points regarding the therapeutic potential of anti-lymphangiogenic treatments in the context of cancer remain to be addressed. The spectrum and relative importance of molecules that induce lymphangiogenesis and the regulation of their expression during tumor progression, the reversibility of tumor-induced lymphangiogenesis, and possible side-effects of anti-lymphangiogenesis-based therapies all need to be investigated. Most importantly, the extent to which lymph node metastases contribute to the formation of metastases in other organs remains to be elucidated. These aspects are the focus of this review, and their investigation should serve as a roadmap to possible translational application.


Identifying Gingival Pigmentation Patterns and Skin Color and Its Co-relation With Serum Ferritin Levels in Thalassemic Patients.
Patients with β-thalassemia major (β-TM), a genetic issue due to hemoglobin (Hb) synthesis disorder, require life-long erythrocyte transfusion. The purpose of this study is to evaluate and compare gingival pigmentation and skin color with serum ferritin levels of patients with β-TM, using the Dummett's oral pigmentation index (DOPI) and Fitzpatrick skin scale, respectively. A total of 100 patients were monitored at a thalassemia care center. Each patient's gingival pigmentation and skin color were matched with DOPI and the skin scale under natural light. Serum ferritin levels, the interval of blood transfusions, and iron chelation medications were studied. A gingival pigmentation score and skin color type were compared with the serum ferritin. A significant correlation was found between age, serum ferritin, pigmentation score, and skin color, which means as serum ferritin level increases, gingival pigmentation score increases, and skin color darkens. This study evaluated the correlation between gingival pigmentation and skin color with serum ferritin levels and established gingival pigmentation as a sign of iron deposition in β-TM patients. This is the simplest and least invasive method for evaluating serum ferritin level parameters in β-TM patients.


Genome-wide identification and characterization of ABC transporter superfamily in the legume Cajanus cajan.
Plant ATP-binding cassette (ABC) protein family is the largest multifunctional highly conserved protein superfamily that transports diverse substrates across biological membranes by the hydrolysis of ATP and is also the part of the several other biological processes like cellular detoxification, growth and development, stress biology, and signaling processes. In the agriculturally important legume crop Cajanus cajan, a genome-wide identification and characterization of the ABC gene family was carried out. A total of 159 ABC genes were identified that belong to eight canonical classes CcABCA to CcABCG and CcABCI based on the phylogenetic analysis. The number of genes was highest in CcABCG followed by CcABCC and CcABCB class. A total of 85 CcABC genes were found on 11 chromosomes and 74 were found on scaffold. Tandem duplication was the major driver of CcABC gene family expansion. The dN/dS ratio revealed the purifying selection. The phylogenetic analysis revealed class-specific eight superclades which reflect their functional importance. The largest clade was found to be CcABCG which reflects their functional significance. CcABC proteins were mainly basic in nature and found to be localized in the plasma membrane. The secondary structure prediction revealed the dominance of α-helix. The canonical transmembrane and nucleotide binding domain, signature motif LSSGQ, Walker A, Walker B region, and Q loop were also identified. A class-specific exon-intron pattern was also observed. In addition to core elements, different cis-acting regulatory elements like stress, hormone, and cellular responsive were also identified. Expression profiling of CcABC genes at various developmental stages of different anatomical tissues was performed and it was noticed that CcABCF3, CcABCF4, CcABCF5, CcABCG66, and CcABCI3 had the highest expression. The results of the current study endow us with the further functional analysis of Cajanus ABC in the future.


Biennial screening mammography: How many women ask for more? Estimate of the interval mammogram rate in an organised population-based screening programme.
To estimate the interval mammogram rate, i.e. the undertaking of an additional mammography between scheduled screening rounds, and identify factors influencing this phenomenon. Data from our screening programme for the year 2014, excluding prevalent rounds, were analysed. Information about the number of women who underwent interval mammograms was obtained reviewing the questionnaires and searching the department database. Data on age, breast density, family history of breast cancer, number of screening rounds, previous recalls, general practitioner, and city of residence (used as a proxy of local socio-economic differences) were evaluated using chi-square test. Of 2780 screened women (incident rounds), 2566 had complete data (92%). The interval mammogram rate was 384/2566 (15%, 95% confidence interval 14-17%). Women classified with American College of Radiology c or d breast density categories showed a higher interval mammography probability than those with a and b density (p < 0.001); women in their second round showed a higher probability of interval mammogram compared to women in their fifth, sixth, or seventh round (p ≤ 0.004). No significant differences were found between women with and without an interval mammogram when considering previous recalls for a negative work-up (p = 0.241), positive breast cancer family history (p = 0.538), and city of residence (p = 0.177). The interval mammogram rate was relatively low (15%). Higher breast density and first of years of adherence to the programme were associated with higher interval mammogram rate.


Interleukin 18 and cognitive impairment in first episode and drug naïve schizophrenia versus healthy controls.
Alterations in the inflammatory and immune systems have been documented to occur from the earliest stages of schizophrenia, and have been associated with neurodevelopmental changes. Cognitive impairment is a core feature in the pathology of schizophrenia, and recent studies showed a significant increase in serum IL-18 in schizophrenia, and a putative role of IL-18 in neuroprogression and thus neurocognitive defects. The purpose of this study was to examine the association of IL-18 with cognitive deficits in schizophrenia. We recruited 77 first episode and drug naïve schizophrenic patients and 75 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-18 in both groups. Schizophrenic symptoms were assessed using the positive and negative syndrome scale (PANSS). We found that IL-18 levels were non-significantly higher in patients than controls (206.0±92.9 pg/ml vs 193.2±41.8 pg/ml, p=0.28). Cognitive scores on the RBANS and nearly all of its five subscales (all p<0.05) except for the Visuospatial/Constructional index (p>0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, IL-18 was positively associated with the Visuospatial/Constructional domain of cognitive deficits in schizophrenia. Our findings suggest that cognitive deficits occur during the acute stage of a schizophrenic episode, and IL-18 may be involved in Visuospatial/Constructional deficits of these patients.


Smoking Reduces Plasma Bilirubin: Observational and Genetic Analyses in the Copenhagen General Population Study.
Observational studies have found lower concentrations of plasma bilirubin in current smokers compared with former and never smokers. However, whether there is a causal relationship between smoking and bilirubin is unknown. In a Mendelian randomization analysis, we tested the hypothesis that higher tobacco consumption is causally associated with lower concentrations of plasma bilirubin. We genotyped 103 557 individuals aged 20-100 years from the Copenhagen General Population Study for the CHRNA3 rs1051730 genotype, known to be associated with higher tobacco consumption. Tobacco consumption was defined as daily and cumulative tobacco consumption. In observational multivariable-adjusted analyses, a 10 g/day higher daily tobacco consumption was associated with a 0.28 µmol/L (95% confidence interval = 0.20 to 0.35) lower concentration of plasma bilirubin in current smokers, and a 10 pack-year higher cumulative tobacco consumption was associated with a 0.19 µmol/L (0.17 to 0.21) lower concentration of plasma bilirubin in former and current smokers. Using the CHRNA3 rs1051730 genotype as a proxy for daily and cumulative tobacco consumption, the difference in plasma bilirubin per T-allele was -0.12 µmol/L (-0.23 to -0.002) in current smokers and -0.09 µmol/L (-0.15 to -0.01) in current and former smokers combined. Furthermore, observationally bilirubin concentrations increased with time from smoking cessation in former smokers. Higher daily and cumulative tobacco consumption were associated with lower concentrations of plasma bilirubin in observational and genetic analyses, suggesting that the association is causal. Our results are compatible with two possible interpretations of previous observational studies, either that bilirubin is a mediator of smoking-induced respiratory disease or that the association between plasma bilirubin and respiratory disease stems from residual confounding because of smoking. Future studies should examine whether bilirubin is a causal risk factor for respiratory disease, or merely a marker of smoking status.


Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome.
Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease characterized by abnormalities in the left ventricle, associated valves, and ascending aorta. Studies have shown intrinsic myocardial defects but do not sufficiently explain developmental defects in the endocardial-derived cardiac valve, septum, and vasculature. Here, we identify a developmentally impaired endocardial population in HLHS through single-cell RNA profiling of hiPSC-derived endocardium and human fetal heart tissue with an underdeveloped left ventricle. Intrinsic endocardial defects contribute to abnormal endothelial-to-mesenchymal transition, NOTCH signaling, and extracellular matrix organization, key factors in valve formation. Endocardial abnormalities cause reduced cardiomyocyte proliferation and maturation by disrupting fibronectin-integrin signaling, consistent with recently described de novo HLHS mutations associated with abnormal endocardial gene and fibronectin regulation. Together, these results reveal a critical role for endocardium in HLHS etiology and provide a rationale for considering endocardial function in regenerative strategies.


Morphologic evidence of poxvirus in "tattoo" lesions from captive bottlenosed dolphins.
Skin lesions known as "tattoos", were observed in several captive Atlantic bottlenosed dolphins (tursiops truncatus) maintained at the Naval Ocean Systems Center, San Diego, California. Biopsy of typical lesions and subsequent ultrastructural examination revealed intracytoplasmic particles with poxvirus morphology.


Unique genetic alterations and clinicopathological features of hepatocellular adenoma in Chinese population.
Hepatocellular adenoma (HCA) is a benign hepatocyte-derived tumor commonly seen in reproductive-aged women with long-term use of oral contraceptives (OCs) in European and North American countries. Accordingly, HCA is currently classified into four molecular subtypes as adopted by the World Health Organization. The present study was firstly to characterize and determine the genetic alterations and clinicopathological features of the largest series of HCAs in China. We reviewed 189 patients with HCA who underwent hepatectomies at our liver center from January 1984 to January 2012, among which 36 HCAs were randomly selected for the sequencing of HNF1α, β-catenin and gp130 genes, and 60 HCAs were randomly selected for detecting microsatellite instability (MSI). Compared with Western studies, our data showed distinctive findings including male (69.8%) and overweight/obese (50.3%) predominance. Only 3.5% of female patients had a documented history of OCs use for 2-4 years. All 36 sequenced HCAs showed HNF1α mutations (72% missense, 28% synonymous), 2 hotspot polymorphisms of HNF1α (I27L: rs1169288 and S487N: rs2464196) were seen in 17 (47%) and 10 (27.8%) cases, respectively, and a novel single nucleotide polymorphism site (rs1169304) in intron 9 of HNF1α was detected in 32 (88%) cases, but no β-catenin or gp130 gene mutation was detected, and no nuclear β-catenin staining was detected by immunohistochemistry. The frequency of MSI was 75% for D12S1398 (HNF1α inactivated pathway) and 78.5% for D6S1064 (HIPPO signaling pathway) in 34 overweight/obese patients with HCA. Our results firstly indicate that patients with HCA in China frequently occur in male overweigh and obese adult population, lack an association with OCs use and exhibit unique genetic alterations. Taken together, these observations suggest that alternative pathogenetic pathways involve in HCA tumorigenesis in Chinese patients.


Transcranial magnetic stimulation and aging: Effects on spatial learning and memory after sleep deprivation in Octodon degus.
The benefits of neuromodulatory procedures as a possible therapeutic application for cognitive rehabilitation have increased with the progress made in non-invasive modes of brain stimulation in aged-related disorders. Transcranial magnetic stimulation (TMS) is a non-invasive method used to examine multiple facets of the human brain and to ameliorate the impairment in cognition caused by Alzheimer's disease (AD). The present study was designed to evaluate how a chronic TMS treatment could improve learning and memory functions after sleep deprivation (SD) in old Octodon degus. SD was executed by gently handling to keep the animals awake throughout the night. Thirty young and twenty-four old O. degus females were divided in six groups (control, acute and chronic TMS treatment). Behavioral tests included; Radial Arm Maze (RAM), Barnes Maze (BM) and Novel Object Recognition (NOR). Although learning and memory functions improved in young animals with only one session of TMS treatment, a significant improvement in cognitive performance was seen in old animals after 4 and 7days of TMS, depending on the task that was performed. No side effects were observed following, which showed therapeutic potential for improving age-related cognitive performance.


Focused and divided attention in Alzheimer's disease.
Visual search tasks were used to examine two aspects of selective attention (focused and divided attention) in normal young and older persons and in Alzheimer patients. Normal and demented subjects were equally efficient in using a color cue to selectively search only the relevant items in an array. Thus, focused attention abilities appear to be relatively unimpaired by Alzheimer's disease. By contrast, in comparison to normals, the search time of demented patients rose disproportionately as the number of items over which they had to distribute their attention was increased. This suggests that Alzheimer patients are less efficient than normals in dividing their attention.


Surface electromyography study on asymmetry in paravertebral muscle degeneration in patients with degenerative lumbar scoliosis.
The asymmetry of paravertebral muscle (PVM) degeneration in degenerative lumbar scoliosis (DLS) patients has been extensively studied by imaging and histological examination and has not yet been verified by surface electromyography (sEMG) techniques. To study the relationship between the surface electromyography (sEMG) and degenerative characteristics of paravertebral muscles (PVMs) in patients with degenerative lumbar scoliosis (DLS). In twenty DLS patients and fifteen healthy subjects, sEMG activity of the PVMs at the level of the upper end vertebra (UEV), apical vertebra (AV) and lower end vertebra (LEV) was measured during static standing and dynamic standing forward flexion and backward extension tasks. Action segmentation was achieved according to inertial measurement unit (IMU) data. The sEMG characteristics of the PVMs on the convex and concave sides were compared, and the relationship of these data with the Cobb angle and lumbar lordotic angle (LL) was analyzed. In the DLS group, there was no difference in sEMG activity between the convex and concave sides at the UEV or AV level, but in the motion and return phases of the standing forward flexion task (P = 0.000, P = 0.015) and the maintenance and return phases of the standing backward extension task (P = 0.001, P = 0.01), there was a significant difference in sEMG activity between the convex and concave sides at the LEV level. Asymmetrical sEMG activity at the LEV level was negatively correlated with the Cobb angle (F = 93.791, P < 0.001) and LL angle (F = 65.564, P < 0.001). In the DLS group, asymmetrical sEMG activity of the PVMs appeared at the LEV level, with the concave side being more active than the convex side. This sEMG characteristics were consistent with their imaging and histological degenerative features and correlated with bone structural parameters.


Managing cardiovascular risk in patients with chronic inflammatory diseases.
The role of traditional risk factors in the development of cardiovascular disease has been well studied. However, the relationship between chronic inflammatory conditions and cardiovascular risk has only recently been appreciated. Expression of numerous pro-inflammatory cytokines is common to the pathogenesis of both atherosclerosis and other chronic inflammatory diseases and may suggest that systemic inflammation independently contributes to elevated risk. This article examines the magnitude of cardiovascular risk in several of the most common chronic inflammatory diseases and summarizes currently available data to discern whether this risk is largely due to the presence of co-existing traditional risk factors for cardiovascular disease or the effect of increased systemic inflammation. Evidence is summarized to show which therapies may positively or negatively impact cardiovascular risk. Evidence is discussed in context of practical patient management tools, appropriate treatment based on risk, and treatment targets for high-risk patients. Overall, patients with chronic inflammatory diseases are at an often underestimated increase in cardiovascular risk and require individualized therapy and specific patient management strategies to address the disease process, cardiovascular risk factors, and comorbidities.


Precision spectroscopy of pionic 1s states of Sn nuclei and evidence for partial restoration of chiral symmetry in the nuclear medium.
Deeply bound 1s states of pi(-) in (115,119,123)Sn were preferentially observed using the Sn(d,3He) pion-transfer reaction under the recoil-free condition. The 1s binding energies and widths were precisely determined and were used to deduce the isovector parameter of the s-wave pion-nucleus potential to be b1=-(0.115+/-0.007)m(-1)(pi). The observed enhancement of |b(1)| over the free piN value (b(free)1/b1=0.78+/-0.05) indicates a reduction of the chiral order parameter, f*pi(rho)2/f2pi approximately 0.64, at the normal nuclear density, rho=rho(0).


Impact on quality of life after mastoid obliteration.
To understand the long-term impact on quality of life (QOL) in patients undergoing mastoid obliteration surgery for a chronically draining cavity, using the Glascow Benefit Inventory (GBI) QOL survey, and to correlate these findings to perceived changes in drainage and hearing. Retrospective chart review. Adult patients undergoing mastoid obliteration and restoration of the middle ear space with cartilage reconstruction of the tympanic membrane, with at least 3-year follow-up, were contacted by phone to solicit participation. Those who agreed to participate were mailed the GBI and consent documents with a prepaid self-addressed envelope. Of 80 patients meeting the inclusion criteria, 37 were successfully contacted and agreed to participate, yielding 23 returned questionnaires. The vast majority (19 of 23; 83%) reported improved QOL after surgery, with the most positive effects seen on confidence and social situations, and patients experiencing less inconvenience, self-consciousness, and embarrassment. Eighty-three percent reported a perceived improvement in hearing; 74% reported an improvement in drainage. Over 90% would recommend the procedure to a family member. The average score on the GBI was 28.9, and a two-tailed one-sample t test showed that mastoid obliteration significantly improved QOL in our patients (t = 4.65, P < .001). There was a fairly good correlation between the perceived improvement in QOL with improvement in hearing and/or drainage. The GBI is a valuable tool for evaluating patient satisfaction after revision surgery for a draining cavity. This information is helpful in understanding the impact of a draining cavity on an individual's life and may be beneficial in preoperative selection and counseling.


Relationship of PS2 with response to tamoxifen therapy in patients with recurrent breast cancer.
PS2, an oestrogen-inducible protein, was measured in the cytosol of 230 primary tumours from patients who were subjected to first-line tamoxifen therapy for advanced disease without prior adjuvant therapy with tamoxifen. PS2 correlated positively with oestrogen receptor (ER, P < 0.01) and progesterone receptor content (PgR, P < 0.001), and with the length of progression-free survival (PFS, P = 0.05). Although not statistically significant, higher levels of PS2 (> or = 10 ng mg-1 protein) were also associated with increased probability of response to tamoxifen treatment and a longer total post-relapse survival (PRS). ER, PgR, menopausal status, site of disease and prior adjuvant chemotherapy were all associated with response to tamoxifen therapy and with PFS. In multivariate analysis for PFS, low levels of ER and PgR, visceral metastasis, a disease-free interval of less than 1 year and prior adjuvant chemotherapy were all significantly associated with an increased probability of a rapid disease progression after start of tamoxifen therapy. In the subset of 83 tumours with intermediate levels of ER and PgR (both > or = 10, but not both > or = 75 fmol mg-1 protein), PS2 was positively related with the length of PFS (P < 0.01) and PRS (P < 0.05). PS2 remained the strongest factor in multivariate analysis for PFS (P < 0.01) in this ER/PgR intermediate subgroup, but was not of predictive value in univariate or multivariate analysis for both PFS and PRS in tumours classified as ER/PgR low or high (> or = 75 fmol mg-1 protein). It is concluded that PS2 status may be used as a parameter, additional to ER and PgR, for better refinement of prediction of response to tamoxifen treatment in advanced breast cancer patients especially with intermediate ER/PgR levels in their primary tumour.


Immunohistochemical localization of growth hormone-releasing hormone in human gonads.
Human gonads were examined for the presence of ir growth hormone-releasing-hormone. We demonstrated the presence of immunostainable cells both in ovarian and in testicular tissue using a non-crossreactive anti-GRH antiserum and the immunoperoxidase detection technique. In ovaries from ovulating women, GRH immunoreactivity was localized in the corpora lutea; granulosa cells, theca cells and cells of primary follicles did not stain. In premenopausal ovaries, staining was detectable in scattered luteinized stromal cells. In testes from post-puberal men GRH immunoreactivity was localized in the Leydig cells; cells of the germinal epithelium did not stain. These results demonstrate the presence of GRH in human gonads and suggest that this peptide may exert regulatory function at the testicular and ovarian levels.


Circulating chemoattractants RANTES, negatively related to endogenous androgens, and MCP-1 are differentially suppressed by hormone therapy and raloxifene.
The cardinal role of chronic inflammation in the development of atherosclerosis is increasingly being recognized. Estrogens may prevent the evolution of atherosclerosis by suppressing immune response. Furthermore, the conflicting reports on the cardiovascular effects of hormone therapy between observational and clinical trials have triggered interest on the effect of alternative therapies on the cardiovascular system. The aim of this study was to assess the effect of estrogen, estrogen-progestin, tibolone and raloxifene therapy on circulating markers of chemotaxis in healthy postmenopausal women. Eighty-eight postmenopausal women aged 44-62 years were randomly allocated to daily: (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and at 3 months. Endogenous testosterone and free androgen index (FAI) correlated negatively, while SHBG correlated positively with serum RANTES (testosterone: r=-0.27, p=0.033; FAI: r=-0.43, p=0.004: SHBG: r=0.34, p=0.026). Serum MCP-1 decreased significantly in the CEE group (baseline 125.3+/-51 pg/ml, 3 months 84.5+/-36.1 pg/ml, p=0.043), while no difference was detected between baseline and post-treatment levels in the other groups. Furthermore, a significant decrease in serum RANTES was observed at the end of 3 months only in the E2/NETA and the raloxifene group (E2/NETA baseline 8690.6+/-3880.0 pg/ml, 3 months 6894.0+/-1720.0 pg/ml, p=0.007; raloxifene baseline 9042.4+/-3765.6 pg/ml, 3 months 6718.1+/-2366.2 pg/ml, p=0.011). Endogenous androgens may suppress chemotactic response. Postmenopausal hormone therapy and raloxifene may inhibit the expression of chemoattractant molecules and thus attenuate inflammation. The relevance of these findings in terms of clinically established caridoprotection remains to be clarified.


[Coagulative and fibrinolytic properties of blood effused into the pleural cavity after lung surgery].
Coagulative properties of the blood and exudate accumulated in the pleural cavity following lung operations were studied. On the grounds of the studies of plasmin potential and active antiplasmin of the exudate a method of local fibrionolytic therapy of coagulated hemothorax with intrapleural injections of fibrinilysis activators was devised. Fibrinolytic therapy was applied in 106 patients, streptokinase preparations were injected to 28 of them.


Effect of guanosine 5'-diphosphate 3'-diphosphate and related nucleoside polyphosphates on induction of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli.
Exogenous addition of guanosine and adenosine 5'-(mono, di and tri) phosphate 3'-diphosphates (pppGpp, ppGpp, pGpp, pppApp, ppApp and pApp) stimulated the synthesis of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli. From the results obtained with ppGpp and pppApp, this effect appeared to be at a transcriptional level and depended greatly on the growth condition; the largest effect was observed in cells under shiftdown or grown on poor enrgy source. ppGpp and pppApp, unlike cyclic AMP, did not act to overcome the inhibition of enzyme induction by glucose, but in combination with cyclic AMP caused a synergistic stimulation effect. In the shiftdown cells, ppGpp and pppApp gave 30% or more stimulation effect on tryptophanase induction while cyclic AMP did not stimulate induction. There was therefore a pronounced difference between cyclic AMP and ppGpp or pppApp in stimulatory function.


A mouse ear reaction for assessment of human lymphocyte immunocompetence.
A mouse ear reaction for testing cell mediated immunity of human lymphocytes using the local graft-versus-host reaction assay is described. Five million human mononuclears were locally injected into the ears of immune suppressed NZW mice. The reaction mounted was quantitated by determining the 125I-Iodo-Deoxyuridine (125I-UdR) incorporation in both ears. The ratio of 125I-UdR incorporation, of the injected to that of the non-injected ear (GVHR index), 7 days after lymphocyte injection, served as an accurate measure for the extent of the reaction. Only normal human mononuclears and purified, separated normal human T lymphocytes mounted a local graft-versus-host reaction. Whereas normal human B lymphocytes, chronic lymphatic leukemia B lymphocytes, mononuclears from patients with transitional cell carcinoma of the bladder, irradiated normal human mononuclears, mouse syngeneic mononuclears, or human erythrocytes gave no positive reaction. These experiments demonstrate that this assay can be used to quantitate an in-vivo specific graft-versus-host reaction.


The interacting MYB75 and KNAT7 transcription factors modulate secondary cell wall deposition both in stems and seed coat in Arabidopsis.
The Arabidopsis thaliana KNAT7 (KNOX family) and MYB75 (MYB family) transcription factors were each shown earlier to interact in yeast two-hybrid assays, and to modulate secondary cell wall formation in inflorescence stems. We demonstrate here that their interaction also occurs in vivo, and that specific domains of each protein mediate this process. The participation of these interacting transcription factors in secondary cell wall formation was then extended to the developing seed coat through the use of targeted transcript analysis and SEM in single loss-of-function mutants. Novel genetic and protein-protein interactions of MYB75 and KNAT7 with other transcription factors known to be involved in seed coat regulation were also identified. We propose that a MYB75-associated protein complex is likely to be involved in modulating secondary cell wall biosynthesis in both the Arabidopsis inflorescence stem and seed coat, and that at least some parts of the transcriptional regulatory network in the two tissues are functionally conserved.


Integrated VASO and perfusion contrast: A new tool for laminar functional MRI.
Earlier research in cats has shown that both cerebral blood volume (CBV) and cerebral blood flow (CBF) can be used to identify layer-dependent fMRI activation with spatial specificity superior to gradient-echo blood-oxygen-level-dependent (BOLD) contrast (Jin and Kim, 2008a). CBF contrast of perfusion fMRI at ultra-high field has not been widely applied in humans to measure laminar activity due to its low sensitivity, while CBV contrast for fMRI using vascular space occupancy (VASO) has been successfully used. However, VASO can be compromised by interference of blood in-flow effects and a temporally limited acquisition window around the blood-nulling time point. Here, we proposed to use DANTE (Delay Alternating with Nutation for Tailored Excitation) pulse trains combined with 3D-EPI to acquire an integrated VASO and perfusion (VAPER) contrast. The signal origin of the VAPER contrast was theoretically evaluated with respect to its CBV and CBF contributions using a four-compartment simulation model. The feasibility of VAPER to measure layer-dependent activity was empirically investigated in human primary motor cortex at 7 T. We demonstrated this new tool, with its highly specified functional layer profile, robust reproducibility, and improved sensitivity, to allow investigation of layer-specific cortical functions.


Modelling the flowing behaviour of dika kernel powder and soup as affected by moisture content, physical and rheological properties.
Dika kernels are known for their mucilaginous consistency, but limited work has been reported about it. This study investigated the flowing characteristics (share stress and viscosity) of the dika kernel and its soup; and this was assessed at specific temperatures (30, 50, 70 and 90) °C by the use of a viscometer. All samples behaved as non-Newtonian fluids. The bulk, tapped and loose densities of the powdered samples were obtained to evaluate the Carr index, Hausner ratio and porosity. The viscosity and shear stress of the reconstituted powder and soup samples as a function of the shear rate were investigated (30-90 °C). Dika kernel at its natural moisture content has excellent flowing property (1.118 Hausner ratio, 10.566 Carr index and 20.300% porosity), but increase in moisture content decreased this ability. The viscosity of the soup (165.789-14,546.341 mPa s) was higher than the reconstituted dika (69.831-206.240 mPa s) at all temperature studied. Shear stress was temperature-dependent, and Bingham and Power-law models gave the best predictions of flow.


Cardiac and Skeletal Muscle Pathology in the D2/mdx Mouse Model and Caveats Associated with the Quantification of Utrophin.
Duchenne muscular dystrophy (DMD) (the most common form of muscular dystrophy) is caused by a lack of dystrophin protein. Currently, although many therapeutic strategies are under investigation, there is no cure for DMD and unfortunately, patients succumb to respiratory and/or cardiac failure in their second or third decade of life. Preclinical work has focused on the mouse model C57BL/10ScSn-Dmdmdx/J (BL10/mdx), which does not exhibit a robust pathophenotype. More recently, the D2.B10-Dmdmdx/J (D2/mdx) mouse has been utilized, which presents a more severe pathology and therefore more closely mimics the human pathophenotype, particularly in the heart. Here, we outline important considerations when utilizing the D2/mdx model by highlighting the differences between these models in addition to describing histological and immunohistochemical methods utilized in Kennedy et al. (Mol Ther Methods Clin Dev 11:92-105, 2018) for both cardiac and skeletal muscle, which can quantify these differences. These considerations are particularly important when investigating treatment strategies that may be affected by regeneration; such is the case for upregulation of the dystrophin paralogue, utrophin.


Deconstructing patient centred communication and uncovering shared decision making: an observational study.
Patient centred communication (PCC) has been described as a method for doctor-patient communication. The principles of shared decision making (SDM) have been proposed more recently. This study aimed to examine PCC and SDM empirically with respect to their mutual association, the variation in practitioners' working styles, and the associations with patient characteristics. Sixty general practitioners recruited 596 adult patients who gave written consent to have their consultations videotaped. The tapes were assessed by two researchers, using a standardised instrument for global communication. For the purpose of this exploratory study, scales for PCC and SDM were based on subsamples of items in the MAAS. The scales for PCC and SDM were weakly associated (Pearson correlation: 0.25). Physicians varied more on SDM than on PCC. The intracluster correlation of the PCC and SDM scales were, respectively, 0.34 and 0.19. However, hypotheses regarding associations with patient characteristics were not confirmed. Neither PCC nor SDM scores were related to patient gender, education, age, functional health status or existence of chronic conditions. The study provides evidence that PCC and SDM can be differentiated and comprise approaches to communication between clinicians and patients which may be more clearly distinguished by further focused research and training developments.


Identification, expression analysis and functional verification of two genes encoding small heat shock proteins in the western flower thrips, Frankliniella occidentalis (Pergande).
Small heat shock proteins (sHSPs) help prevent the irreversible aggregation of denatured proteins that occurs in response to organismal stress. In this study, we identified two intron-free genes encoding sHSPs from Frankliniella occidentalis; these were designated FoHSP11.6 and FoHSP28.0 and belonged to an atypical and typical sHSP family, respectively. Both FoHSPs were transcribed in all developmental stages of F. occidentalis with the highest expression levels in pupae and adults and greater expression in males than females. Although the FoHSPs had different temperature-induced expression profiles, they were generally induced by both low and high temperatures and reached maximal expression levels after 0.5-1 h of temperature stress. The FoHSPs expression levels in pupae were induced by drought and high humidity, and higher expression levels were correlated with lower survival rates. The thermotolerance of F. occidentalis decreased when theFoHSPs were silenced by RNA interference. Our results show that FoHSP11.6 and FoHSP28.0 are involved in the response to temperature and drought and may also function in growth and development of F. occidentalis.


Interplay between the Brassica napus phytoglobin (BnPgb1), folic acid, and antioxidant responses enhances plant tolerance to waterlogging.
Oxygen deprivation by waterlogging reduces the productivity of several crop species, including the oil-producing crop Brassica napus L., which is highly sensitive to excess moisture. Among factors induced by oxygen deficiency are phytoglobins (Pgbs), heme-containing proteins known to ameliorate the response of plants to the stress. This study examined the early responses to waterlogging in B. napus plants over-expressing or down-regulating the class 1 (BnPgb1) and class 2 (BnPgb2) Pgbs. The depression of gas exchange parameters and plant biomass was exacerbated by the suppression of BnPgb1, while suppression of BnPgb2 did not evoke any changes. This suggests that natural occurring levels of BnPgb1 (but not BnPg2) are required for the response of the plants to waterlogging. Typical waterlogging symptoms, including the accumulation of reactive oxygen species (ROS) and the deterioration of the root apical meristem (RAM) were attenuated by over-expression of BnPgb1. These effects were associated with the activation of antioxidant system and the transcriptional induction of folic acid (FA). Pharmacological treatments revealed that high levels of FA were sufficient to revert the inhibitory effect of waterlogging, suggesting that the interplay between BnPgb1, antioxidant responses and FA might contribute to plant tolerance to waterlogging stress.


Data on removal kinetics of pharmaceutical compounds, artificial sweeteners, and perfluoroalkyl substances from water using a passive treatment system containing zero-valent iron and biochar.
The data presented in this paper relate to the research paper "Removal of pharmaceutical compounds, artificial sweeteners, and perfluoroalkyl substances from water using a passive treatment system containing zero-valent iron and biochar" [1]. Four columns packed with different ratios of reactive media, including silica sand (SS), zero-valent iron (ZVI), and biochar (BC), were evaluated for simultaneous removal of 14 emerging contaminants from water. The target emerging contaminants included eight pharmaceuticals (carbamazepine, caffeine, sulfamethoxazole, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, ibuprofen, gemfibrozil, and naproxen), four artificial sweeteners (acesulfame-K, sucralose, saccharin, and cyclamate), and two perfluoroalkyl substances (perfluorooctanoic acid and perfluorooctane sulfonic acid). The samples for target contaminant analysis were collected from the influent, effluent, and profile (along the flow direction) ports of each column. The removal data (concentration vs. residence time) for each target contaminant were fitted to the first-order (exponential decay equation) or zero-order (linear equation) model using SigmaPlot. The removal rate, removal rate constant (k obs ), mass normalized rate constant (k M ), surface area normalized rate constant (k SA , specific reaction rate constant), and half-life (t 0.5 ) of target contaminants in Columns ZVI, BC, and (ZVI + BC) were calculated and summarized in this dataset.


Enhanced thermal conductivity in copolymerized polyimide.
From flexible electronics and multifunctional textiles to artificial tissues, polymers penetrate nearly every aspect of modern technology. High thermal conductivity of polymers is often required in their applications, where heat dissipation is crucial to maintain product reliability and functionality. However, the intrinsic thermal conductivity of bulk polymers is largely hindered by the randomly coiled and entangled chain conformation. Here, we report a copolymerization strategy that can simultaneously manipulate the intrachain and interchain hopping and increase the thermal conductivity of linear copolymerized polyimide (PI) to three times higher than that of pure PI at a low-level introduction of 2,4,5,7-tetraamino-1,8-dihydroxyanthracene-9,10-dione (10%). In addition, the large-scale copolymerized PI films display thermal stability after annealing. These remarkable results allow bulk PI to be a potential candidate for thermal management, and this copolymerization method may benefit future synthesis of interfacial thermal materials.


Ontogeny of 'macrophage' function. V. Differential effect of prostaglandin E2 on the activation of newborn and adult mouse macrophages.
Our previous papers indicate that peritoneal exudate macrophages (PM) of newborn mice are strongly suppressive for the tumor cell growth in comparison with those of adult mice. Neither newborn PM nor adult PM are cytolytic, but they both can be activated to be cytolytic by being cultured overnight either with a high concentration of bacterial lipopolysaccharide (LPS) or with a low concentration of LPS plus lymphokine. This paper shows that the activation of adult PM was inhibited by prostaglandin E2 (PGE2) added simultaneously with LPS, though that of newborn PM was not affected by PGE2. Adult PM, however, acquired the resistance to PGE2 by the preculture with LPS and/or lymphokine for 4 hr so as to be activated by LPS in the presence of PGE2. These results indicate that newborn PM are more activated than adult PM to a state which adult PM attain after moderate activation with LPS or lymphokine.


Origin of Open-Circuit Voltage Losses in Perovskite Solar Cells Investigated by Surface Photovoltage Measurement.
Increasing the open-circuit voltage (Voc) is one of the key strategies for further improvement of the efficiency of perovskite solar cells. It requires fundamental understanding of the complex optoelectronic processes related to charge carrier generation, transport, extraction, and their loss mechanisms inside a device upon illumination. Herein, we report the important origin of Voc losses in methylammonium lead iodide perovskite (MAPI)-based solar cells, which results from undesirable positive charge (hole) accumulation at the interface between the perovskite photoactive layer and the poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hole-transport layer. We show strong correlation between the thickness-dependent surface photovoltage and device performance, unraveling that the interfacial charge accumulation leads to charge carrier recombination and results in a large decrease in Voc for the PEDOT:PSS/MAPI inverted devices (180 mV reduction in 50 nm thick device compared to 230 nm thick one). In contrast, accumulated positive charges at the TiO2/MAPI interface modify interfacial energy band bending, which leads to an increase in Voc for the TiO2/MAPI conventional devices (70 mV increase in 50 nm thick device compared to 230 nm thick one). Our results provide an important guideline for better control of interfaces in perovskite solar cells to improve device performance further.


Study on multi-objective decision-making operation strategy of heat supply tower.
In northern China, the long-term operation of ground source heat pumps brings the problem of soil cold accumulation, which can be effectively solved by adopting the heat supply tower to recharge the ground in summer. In this paper, seven indexes affecting the performance of the heat supply tower, such as temperature difference between inlet and outlet water, heating approach, thermal efficiency, and exergy destruction, are studied experimentally, and the energy efficiency ratio of the heat supply tower is analyzed. Then, based on the experimental data, the decision of the operating conditions is made. The results show that it is impossible to judge the performance of the heat supply tower based on a single index, and multiple criteria need to be considered at the same time. The energy efficiency ratios of the heat supply tower range from 12.7 to 22.5 and the optimal operating conditions of the heat supply tower under the experimental conditions are derived based on the TOPSIS decision. This paper provides a theoretical basis for the performance analysis and operation condition study of the heat supply tower.


Repair of a delayed-union stress fracture of the dorsal cortex of a metacarpal bone in a horse.
A delayed union metacarpal stress fracture was repaired in a horse, using lag-screw fixation in conjunction with dc electrical stimulation. Twelve weeks after surgery, radiographic and scintigraphic evaluations revealed that the fracture line was not discernible and that there was a decrease in radiopharmaceutic uptake, as compared with that in previous bone imaging studies. In this horse, DC stimulation of a delayed union stress fracture in a bone resulted in a healing pattern similar to that in human beings with delayed union fractures when treated with electrical stimulation.


Pathopharmacology of excessive hemorrhage in mifepristone abortions.
To explain a pathopharmacologic mechanism that initiates an increase in hemorrhage following medical abortions with mifepristone. MEDLINE, PubMed, and Google Scholar databases were searched (1990-July 2007). Key search terms were mifepristone, RU486, medical abortion hemorrhage, bleeding, inflammation, innate immune system, phagocytes, macrocytes, cytokines, interleukins, and nitric oxide. All articles identified from the data sources were evaluated and all information deemed relevant was included for the information related to the development of the understanding of the pathopharmacology of mifepristone as the initiating cause of increased hemorrhage in medical abortions. Mifepristone's blockade of glucocorticoid receptors, prolonged generation of nitric oxide (NO), and postabortion vasodilatation of uterine vasculature by NO that favors excessive hemorrhage were the criteria used to determine whether information was relevant for inclusion. Inescapable bacterial contamination of the decidua accompanies spontaneous, surgical, and mifepristone abortions and is routinely overcome by activation of the innate immune system. The combination of the induction of NO synthase (NOS) and local production of NO is one of the key features of the activation of the innate immune system's phagocytes. NO is a potent vasodilator and is associated with menstrual menorrhagia. Glucocorticoids prevent the overproduction of NOS and NO and thereby contribute to the control of hemorrhage in the postabortion phase. Blockade of the glucocorticoid receptors by mifepristone can result in an excess of NO that is theorized to be the cause of excessive hemorrhage seen in mifepristone abortions.


Dual effect of hydrogen peroxide on store-mediated calcium entry in human platelets.
Redox regulation is important for the modulation of cytosolic Ca(2+) concentration. Hence, we have investigated the effect of H(2)O(2) on store-mediated Ca(2+) entry (SMCE). In fura-2-loaded human platelets treatment with H(2)O(2) resulted in a concentration-dependent increase in Ca(2+) release from intracellular stores, while the effect on Ca(2+) entry was biphasic. In addition, 1mM H(2)O(2) reduced SMCE induced by agonists. The inhibitory effect of 1mM H(2)O(2) was prevented by inhibition of actin polymerization with cytochalasin D. Consistent with this, we found that 10microM H(2)O(2) and store depletion by treatment with thapsigargin plus ionomycin induced a similar temporal sequence of actin reorganization, while exposure to 1mM H(2)O(2) shifted the dynamics between polymerization and depolymerization in favor of the former. One millimolar H(2)O(2)-induced polymerization was reduced by treatment with methyl 2,5-dihydroxycinnamate and farnesylthioacetic acid, inhibitors of tyrosine kinases and Ras superfamily proteins, respectively. Finally, exposure to 1mM H(2)O(2) significantly increased store depletion-induced p60(src) activation. We conclude that H(2)O(2) exerted a biphasic effect on SMCE. The inhibitory role of high H(2)O(2) concentrations is mediated by an abnormal actin reorganization pattern involving both Ras- and tyrosine kinases-dependent pathways.


Histological spectrum of cutaneous reactions to aspirin in chronic idiopathic urticaria.
During a clinical trial, we obtained 16 biopsies of skin eruptions induced by aspirin in patients with chronic idiopathic urticaria (CIU). In this setting, aspirin triggers skin eruptions through a well-established non-immunological mechanism involving the inhibition of cyclooxygenase type I. This presented the rare opportunity to evaluate histological features of a series of skin eruptions induced by a drug acting through a defined mechanism in a controlled experimental setting. Histological analysis of 16 biopsies of skin eruptions induced by oral aspirin challenge in patients with CIU. Microscopic analysis of tissue sections. 16 patients with CIU. Aspirin (up to 500 mg) induced a restricted range of histological responses with a classic pattern of urticarial tissue reaction occurring in the majority of (12 of 16) cases. Two biopsies showed an interstitial fibrohistiocytic (granuloma annulare-like) reaction pattern. One case showed only a sparse perivascular lymphocytic infiltrate, and paucicellular dermal mucinosis was observed in one case. Polymorphism of histological patterns induced by aspirin suggests that in addition to the drug-specific mechanisms triggering drug eruptions, individual factors also play a role in determining the ultimate histological phenotype of a drug response.


Evidence of three maternal lineages in Near Eastern sheep supporting multiple domestication events.
The variability of mtDNA was analysed in local sheep breeds reared throughout Turkey, for which a fragment of the D-loop region and the complete cytochrome b were sequenced. Phylogenetic analyses performed independently for the D-loop and the Cyt b gene revealed three clearly separated clusters indicating three major maternal lineages, two of which had been previously described as types B and A. The new type, C, was present in all the breeds analysed and showed considerable mtDNA variability. Divergence time was obtained on the basis of Cyt b gene and was estimated to be around 160,000-170,000 years ago for lineages B and A, whereas the divergence of lineage C proved to have occurred earlier (between 450,000 and 750,000 years ago). These times greatly predate domestication and suggest that the origin of modern sheep breeds was more complex than previously thought and that at least three independent sheep domestication events occurred. Our results, together with archaeological information and the current wild sheep populations in the Near East region support the high importance of this area in the sheep domestication process. Finally, the evidence of a third maternal lineage has important implications regarding the history of modern sheep.


Mammary carcinoma developing after radiotherapy and chemotherapy for Hodgkin's disease.
Two patients developed breast cancer after treatment of Hodgkin's disease. Both had received mediastinal irradiation 13 to 15 years, respectively, before the diagnosis of breast carcinoma. One patient had synchronous bilateral breast cancer when the diagnosis was made. Discussed is the risk of mammary carcinoma as a second malignant neoplasm in patients treated for Hodgkin's disease.


Modulation of thiol-disulfide oxidoreductases for increased production of disulfide-bond-containing proteins in Bacillus subtilis.
Disulfide bonds are important for the correct folding, structural integrity, and activity of many biotechnologically relevant proteins. For synthesis and subsequent secretion of these proteins in bacteria, such as the well-known "cell factory" Bacillus subtilis, it is often the correct formation of disulfide bonds that is the greatest bottleneck. Degradation of inefficiently or incorrectly oxidized proteins and the requirement for costly and time-consuming reduction and oxidation steps in the downstream processing of the proteins still are major limitations for full exploitation of B. subtilis for biopharmaceutical production. Therefore, the present study was aimed at developing a novel in vivo strategy for improved production of secreted disulfide-bond-containing proteins. Three approaches were tested: depletion of the major cytoplasmic reductase TrxA; introduction of the heterologous oxidase DsbA from Staphylococcus carnosus; and addition of redox-active compounds to the growth medium. As shown using the disulfide-bond-containing molecule Escherichia coli PhoA as a model protein, combined use of these three approaches resulted in secretion of amounts of active PhoA that were approximately 3.5-fold larger than the amounts secreted by the parental strain B. subtilis 168. Our findings indicate that Bacillus strains with improved oxidizing properties can be engineered for biotechnological production of heterologous high-value proteins containing disulfide bonds.


A clinical trial of aminoglutethimide in advanced postmenopausal breast carcinoma: low response in patients previously treated with medroxyprogesterone.
In an attempt to define the influence of prior hormonal treatments upon aminoglutethimide activity in advanced cancer of the breast, 42 heavily pretreated postmenopausal patients received aminoglutethimide, 4 X 250 mg daily, with hydrocortisone or cortisone. Twenty-six received high doses of medroxyprogesterone before entering this study. There was no significant difference in patients' characteristics with or without medroxyprogesterone pretreatment. A comparison of patients with and without prior medroxyprogesterone shows a significant difference in the response rate to aminoglutethimide-hydrocortisone (4 vs 32%, P = 0.02). In patients pretreated with tamoxifen but not with medroxyprogesterone the response rate to aminoglutethimide was 36%. These results suggest that aminoglutethimide has a low activity in breast cancer patients previously exposed to medroxyprogesterone, an agent with glucocorticoid-like activity inducing adrenal suppression.


The 2012 International Union against Sexually Transmitted Infections European Collaborative Clinical Group report on the diagnosis and management of Neisseria gonorrhoeae infections in Europe.
The European Collaborative Clinical Group (ECCG) was inaugurated at the 26th International Union against Sexually Transmitted Infections (IUSTI) Congress in Riga, Latvia 2011. The ECCG is a network of over 100 sexually transmitted infection specialists who have come together to conduct questionnaire-based research across the European region. It is expected that this work will focus and direct guideline development. A central core group of the ECCG has also been established who are responsible for identifying suitable survey questions that will be carried out but only after approval by the full ECCG Board. The ECCG aims to conduct a maximum of two projects per year which will be presented at the annual regional congresses and published as appropriate.


Host-associated differences in fitness within and between populations of a seed beetle (Bruchidae): effects of plant variability.
Experiments were conducted with the sexually reproducing seed beetle Stator limbatus and its hosts in north-central Arizona to determine if it was substructured into units, each specialized for higher fitness on a specific host species. Unlike many studies, we incorporated scale, i.e., conducting experiments between and within beetle populations on seeds from within and between plant species. Of particular interest was whether intraspecific plant variability prevented beetle specialization within beetle populations. Results suggest that S. limbatus is specialized to certain hosts. On the palo verde Cercidium floridum, beetles originally reared from this host had significantly higher emergence compared to beetles transferred from other hosts. We did not test directly for a genetic basis for this. Alternative hypotheses of variation in symbiotic microorganisms in larval guts and maternal effects were assessed. Essentially no bacteria, yeast or protozoa were found, and maternal effects as expressed by varying egg weights were not detected; however, other microorganisms might have been present and maternal effects through inducible enzymes was possible. Caution, then, is needed in any genetic interpretations of our results. The differences on C. floridum were detected from tests between and within beetle populations. Evidence for specialization was not detected on the other hosts, Cercidium microphyllum and Acacia greggii. On the other hosts, beetles performed well regardless of their source. Significant differences were detected among individual plants of C. floridum as to the suitability of their seeds for deveoopment of S. limbatus. No such differences were detected among the other host plants. These patterns of conspecific plant variability are opposite of what is expected if plant variability prevents specialization of beetles to particular species of hosts. Thus, the data suggest seed variability among plants does not prevent specialization to host species in this system. We discuss how the patterns of host use in this study relate to the hypothesis of sympatric host race formation.


The histopathology of naturally-occurring cutaneous leishmaniasis in the reservoir host, Psammomys obesus.
Ears from infected Psammomys obesus, the gerbil reservoir host of Leishmania major, were histopathologically studied. The histopathology was a chronic localized infection consisting of an epithelioid granuloma with greatly increased populations of mast cells, melanocytes and melanophores; ulceration was present and parasites were always very few and inside parasitophorus vacuoles.


The determinants of marital fertility in the United States, 1968-1970: inferences from a dynamic model.
Criticizing the static assumptions of previous socioeconomic and microeconomic models of marital fertility, particularly regarding the sequential and stochastic facets of family building, this paper advocates a dynamic perspective. Of particular concern is the assumption of equilibrium family size made by those who employ the static perspective. The equilibrium family size assumption implies that the parameters relating social and economic variables to fertility will be similar for all births, regardless of order. To test this assumption of constancy, a two-equation model of fertility and female employment is introduced. Contrary to the static perspective's implication of constant effects, substantial parity differences in the estimates of parameters for both equations are reported, as are several differences between blacks and whites. On the basis of this evidence, I conclude that the static decision-making framework should be replaced by a dynamic approach to marital fertility.


Interleukin 1 and tumor necrosis factor signal transduction mechanisms: potential targets for pharmacological control of inflammation.
Interleukin 1 and tumor necrosis factor activate serine/threonine kinase activity in cells within minutes of receptor interaction. Kinases increasing phosphorylation of the small heat shock protein (HSP 27) and epidermal growth factor receptor have been identified and shown to be activated independent of protein kinase A or C. Such kinases are also implicated in activation of the transcription factor nuclear factor kappa B. The cytokines have novel signal transduction pathways that could offer potential therapeutic targets.


Central dopamine-synthesis regulation by the calcium-calmodulin-dependent system.
The effects of the intraventricular (IVT) administration of calcium on the amount of dopamine (DA) in various regions of the mouse brain were analyzed immunohistochemically by using a microphotometry system. The DA levels in the nucleus accumbens and the lateral part of the neostriatum were increased by approximately 45% (p less than 0.01) and 25-35% (p less than 0.01), respectively, by the IVT administration of CaCl2 (10 mumol/kg). It was also found that this effect was abolished by the calmodulin antagonist, W-7 (4.2 micrograms/mouse, IVT). The brain regions in which the amount of DA was increased by calcium were areas where high levels of calmodulin and tyrosine hydroxylase are distributed. These findings suggest that the synthesis of central DA is regulated by calcium through a calmodulin-dependent system.


Investigation role of ondansetron on long QT interval among non-cardiac patients.
Ondansetron is one of the commonly prescribed anti-emetic in emergency department however, high dose of the drug is associated with prolonged QT interval. This study was designed to evaluate the effect of ondansetron on prolongation of QT interval among patients referred to our emergency department. In this cross-sectional study patients referred to the emergency department of Imam Reza hospital from June 2019 to December 2019 were included. Before the administration of ondansetron 12-lead electrocardiography was performed in all the patients. 4 mg of i.v. ondansetron was administered to these patients and ECG was obtained again. QT interval was calculated automatically from the system from these electrocardiographs. Demographic data of these patients along with QT interval findings was recorded in the questionnaire and analyzed statistically using SPSS software. A total of 55 patients were included with the mean age of 58 ± 13 years, where 36 were females (65.5%) and 19 were males (34.5%). The mean QT interval before and after injection of 4 mg intravenous ondansetron was not statistically significant, p-value = 0.073. Similarly, QT interval before and after the administration of the drugs was also not significantly different among females and males, p = 0.479 and p = 0.078, respectively. The age of the patients was also not associated with prolonged QT interval, p = 0.948. The findings of our study indicated that 4 mg i.v. administration of ondansetron among non-cardiac patients referred to emergency department is not associated with QT interval prolongation.


Impact of whole-body electromyostimulation on body composition in elderly women at risk for sarcopenia: the Training and ElectroStimulation Trial (TEST-III).
Most studies have confirmed the positive impact of resistance training on muscle mass and functional capacity in aging adults. However, due to physical limitation or a simple aversion against regular exercise, the majority of elderly subjects do not reach the exercise doses recommended for impacting strength or muscle mass. This led us to evaluate the effect of whole-body electromyostimulation (WB-EMS), a novel, time-efficient and smooth training technology, on body composition with special regard to sarcopenia. Seventy-six lean, non-sportive women (75 ± 4 years) were randomly assigned to either a WB-EMS group (WB-EMS, n = 38) that performed 18 min of WB-EMS (bipolar, 85 Hz) 3 sessions in 14 days (1.5 sessions/week) or a semi-active control group (aCG, n = 38). Body composition was assessed by dual-energy X-ray absorptiometry and maximum strength was evaluated using isometric techniques for trunk and legs. After 54 weeks of intervention, significant inter-group differences were determined for appendicular skeletal muscle mass (WB-EMS, 0.4 ± 2.2 % vs. aCG, -1.5 ± 3.1 %; p = 0.009), lean body mass (WB-EMS, 0.8 ± 1.8 % vs. aCG, -0.8 ± 2.7 %; p = 0.008) and maximum isometric strength (leg extensors, 9.8 ± 12.9 % vs. 0.2 ± 10.4 %; p = 0.003; trunk extensors, 10.1 ± 12.7 vs. -1.6 ± 8.6 %; p = 0.001). Although borderline significant for abdominal fat mass (WB-EMS, -2.9 ± 8.3 vs. aCG, 1.5 ± 10.7 %; p = 0.069), differences did not reach statistically significant levels for body fat parameters. Considering the clinical effectiveness for impacting sarcopenia and the good acceptance of this technology by this non-sportive cohort of elderly women, we conclude that for elderly subjects unable or unwilling to perform dynamic strength exercises, electromyostimulation may be a less off-putting alternative to maintain lean body mass and strength.


Epidemiology of drug overdose in children.
Childhood drug overdoses are a continuing important public health problem. Although drug overdoses are no longer the important cause of childhood mortality they once were, such poisonings account for highly frequent and unacceptable instances of childhood injuries. These poisonings exact a high cost from society. They result in many emergency department visits and hospitalisations, with the attendant indirect costs of suffering, parental anxiety, and lost days of work or school. Childhood drug overdoses are preventable; those children and families at highest risk show identifiable characteristics, and the medications which pose the greatest hazard to children have already been identified. These injuries divert expensive and scarce medical resources from society's other health problems. Thus, clinicians must do more to prevent childhood drug overdoses whenever possible.


Hypopigmentary effects of ethyl P-methoxycinnamate isolated from Kaempferia galanga.
We isolated crystals from the chloroform fraction of an ethanol extract of Kaempferia galanga and identified it as ethyl p-methoxycinnamate through nuclear magnetic resonance analysis. In the present study, we found that ethyl p-methoxycinnamate significantly decreased melanin synthesis in B16F10 murine melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH). In a cell-free system, however, ethyl p-methoxycinnamate did not directly inhibit tyrosinase, the rate-limiting enzyme of melanogenesis. Instead, it inhibited tyrosinase activity in B16F10 cells in a dose-dependent manner. Furthermore, Western blot analysis showed that ethyl p-methoxycinnamate decreased microphthalmia-associated transcription factor and tyrosinase levels in α-MSH-stimulated B16F10 cells. These results indicate that the pigment-inhibitory effect of ethyl p-methoxycinnamate results from downregulation of tyrosinase. Ethyl p-methoxycinnamate isolated from K. galanga could be developed as a skin whitening agent to treat hyperpigmentary disorders.


Cervical non-invasive vagus nerve stimulation (nVNS) for preventive and acute treatment of episodic and chronic migraine and migraine-associated sleep disturbance: a prospective observational cohort study.
The debilitating nature of migraine and challenges associated with treatment-refractory migraine have a profound impact on patients. With the need for alternatives to pharmacologic agents, vagus nerve stimulation has demonstrated efficacy in treatment-refractory primary headache disorders. We investigated the use of cervical non-invasive vagus nerve stimulation (nVNS) for the acute treatment and prevention of migraine attacks in treatment-refractory episodic and chronic migraine (EM and CM) and evaluated the impact of nVNS on migraine-associated sleep disturbance, disability, and depressive symptoms. Twenty patients with treatment-refractory migraine were enrolled in this 3-month, open-label, prospective observational study. Patients administered nVNS prophylactically twice daily at prespecified times and acutely as adjunctive therapy for migraine attacks. Pain intensity (visual analogue scale [VAS]); number of headache days per month and number of migraine attacks per month; number of acutely treated attacks and time to achieve pain relief; sleep quality (Pittsburgh Sleep Quality Index [PSQI]); migraine disability assessment (MIDAS); depressive symptoms (Beck Depression Inventory(®) [BDI]); and adverse events (AEs) were evaluated. Of the 20 enrolled patients, 10 patients each had been diagnosed with EM and CM. Prophylaxis with nVNS was associated with significant overall reductions in patient-perceived pain intensity (mean VAS scores at baseline vs 3 months: 7.75 ± 0.64 vs 4.05 ± 0.76; 95 % CI: 3.3, 4.1; p < 0.0001), mean number of headache days per month (baseline vs 3 months: 14.7 ± 4.1 vs 8.9 ± 3.66; 95 % CI: 3.3, 8.3; p < 0.0001), and mean number of migraine attacks per month (baseline vs 3 months: 7.3 ± 3.85 vs 4.45 ± 2.48; 95 % CI: 0.8, 4.9; p < 0.01). For acutely treated migraine attacks, a reduction in mean time (minutes) to achieve pain relief (baseline vs 3 months: 84.5 ± 39.1 vs 52.75 ± 16.42; 95 % CI: 12.6, 51.0; p < 0.002) was noted. Significant improvements, more evident in patients with EM, were noted in MIDAS and BDI scores along with a trend toward improvement in PSQI daytime dysfunction subscore (p = 0.07). No severe or serious AEs occurred. In this study, treatment with nVNS was safe and provided clinically meaningful decreases in the frequency, intensity, and duration of migraine attacks in patients with treatment-refractory migraine. Improvements in migraine-associated disability, depression, and sleep quality were also noted.


A prospective analysis of pinch grafting of chronic leg ulcers in a series of elderly patients in rural Cameroon.
Chronic leg ulcers (CLUs) pose serious public health concerns worldwide. They mainly affect the elderly population. Pinch grafting (PG) could be used to treat a variety of CLUs. However, in Cameroon, there is scarce data on the outcome of PG of CLUs in elderly patients in rural hospitals where most of these patients seek for medical attention and where clinicians rely on unconventional wound dressing methods to treat CLUs. Our objective was to describe the outcome of PG of CLUs in elderly patients in rural Cameroon. This was a prospective study conducted in a rural hospital of North West Cameroon. From February 2015 to January 2016, comprehensive historical and clinical data were collected per elderly patient who presented with a chronic leg ulcer necessitating PG. PG was done using a simple procedure and each patient followed up for 8 months. Outcome was described in terms of ulcer healing and pain and donor site complications. Our series included 13 patients: 8 males (61.54%; 95% CI: 31.58-86.14) and 5 females (38.46%; 95% CI: 13.86-68.42) aged from 69 to 88 years (mean: 77.54 ± 5.70 years). Three patients (23.08%; 95% CI: 5.04-53.81) had associated co-morbidities. All the ulcers were unilateral with durations ranging from 7 to 41 months (mean: 19.46 ± 11.03 months). The ulcers ranged in size from 9.0 to 38.1 cm2 (mean: 17.66 ± 8.35 cm 2). We registered one (7.69%; 95% CI: 0.19-36.03) graft rejection. Concerning the other ulcers, ten (83.33%; 95% CI: 51.59-97.91) had healed after 12 postoperative weeks while 2 (16.67%; 95% CI: 2.09%-48.41) had healed after 14 postoperative weeks and the mean healing time was 12.33 ± 0.78 weeks. Patients with healed ulcers had reduced ulcer site pain from the immediate postoperative period but there was no significant difference in the mean pain scores before and after graft (6.77 against 4.23, p = 0.13). These ulcers remained healed after 8 postoperative months. Each donor site had healed 2 weeks after PG. Donor site problems were minimal and included hypopigmentation. The outcome of PG of CLUs in our series of older patients was satisfactory. This finding does not discount the role of conservative therapy, but we encourage clinicians in rural Cameroon to consider PG over long-term unconventional conservative therapy in the elderly.


Explore potential disease related metabolites based on latent factor model.
In biological systems, metabolomics can not only contribute to the discovery of metabolic signatures for disease diagnosis, but is very helpful to illustrate the underlying molecular disease-causing mechanism. Therefore, identification of disease-related metabolites is of great significance for comprehensively understanding the pathogenesis of diseases and improving clinical medicine. In the paper, we propose a disease and literature driven metabolism prediction model (DLMPM) to identify the potential associations between metabolites and diseases based on latent factor model. We build the disease glossary with disease terms from different databases and an association matrix based on the mapping between diseases and metabolites. The similarity of diseases and metabolites is used to complete the association matrix. Finally, we predict potential associations between metabolites and diseases based on the matrix decomposition method. In total, 1,406 direct associations between diseases and metabolites are found. There are 119,206 unknown associations between diseases and metabolites predicted with a coverage rate of 80.88%. Subsequently, we extract training sets and testing sets based on data increment from the database of disease-related metabolites and assess the performance of DLMPM on 19 diseases. As a result, DLMPM is proven to be successful in predicting potential metabolic signatures for human diseases with an average AUC value of 82.33%. In this paper, a computational model is proposed for exploring metabolite-disease pairs and has good performance in predicting potential metabolites related to diseases through adequate validation. The results show that DLMPM has a better performance in prioritizing candidate diseases-related metabolites compared with the previous methods and would be helpful for researchers to reveal more information about human diseases.


Evidence of microglial activation following exposure to serum from first-onset drug-naïve schizophrenia patients.
Abnormal activation of brain microglial cells is widely implicated in the pathogenesis of schizophrenia. Previously the pathophysiology of microglial activation was considered to be intrinsic to the central nervous system. We hypothesised that due to their perivascular localization, microglia can also be activated by factors present in circulating blood. Through application of high-content functional screening, we show that peripheral blood serum from first-onset drug-naïve schizophrenia patients is sufficient to provoke microglial cell signalling network responses in vitro which are indicative of proinflammatory activation. We further explore the composition of the serum for the presence of analytes, with the potential to activate microglia, and the utility of the resultant microglial cellular phenotype for novel drug discovery.


Race biology.
The founders of Hereditas envisioned that race biology would be a major subject that had social applications with utmost importance in the near future. Anthropometrics was in this context understood to be the pure and eugenics the applied science. Sweden had a long tradition in physical anthropometry. Herman Lundborg, member of the advisory board of Hereditas, united the anthropometric and eugenic approaches in a synthesis. He was the first head of the Institute for Race Biology in Sweden. The contents of Hereditas reflect the development of race biology in the Nordic countries. The initial enthusiasm for applied race biology did not last long. In the 1920's Hereditas carried papers on both physical anthropology and eugenics. Most paper dealt, however, with human genetics without eugenic content. Two papers, published in 1921 and 1939 show how the intellectual climate had changed from positive to negative. Finally only human genetics prevailed as the legitimate study of the human race or humankind. A belated defense of eugenics published in 1951 did not help; geneticists had abandoned anthropometrics for good around the year 1940 and eugenics about a decade later. In spite of that, eugenic legislation was amended astonishingly late, in the 1970's. The development was essentially similar in all Nordic countries.


Hepatobiliary elimination of temafloxacin.
The biliary excretion of temafloxacin and temafloxacin glucuronide was characterised in this study after administration of a single oral temafloxacin 600mg dose to 8 patients with T-tube drainage of the common bile duct inserted after cholecystectomy or choledochotomy. High performance liquid chromatographic analyses of plasma, urine and bile samples collected during the 72h after temafloxacin administration showed that biliary concentrations of unchanged temafloxacin followed a time-course parallel to plasma concentrations but were 5- to 10-fold higher. Biliary temafloxacin peak concentrations ranged from 18.74 to 64.35 mg/L and time to peak concentrations from 0.71 to 10.23h. Mean hepatobiliary clearance of temafloxacin was 3.10 ml/min (0.19 L/h) when calculated for the unchanged drug and 1.43 ml/min (0.09 L/h) when calculated for its biliary excretion as glucuronic acid conjugates. Patients with higher bile production had markedly higher clearance of both temafloxacin and temafloxacin glucuronide. The elimination time-course of the conjugate in bile generally paralleled those of temafloxacin in bile and plasma, although there was a lag in the rate of appearance of the conjugate in bile. Biliary excretion of unchanged temafloxacin and temafloxacin glucuronide accounted for approximately 2.2 and 1% of the administered dose, respectively. Thus, it appears that hepatobiliary elimination of temafloxacin and its glucuronide acid accounts for only a small fraction of total temafloxacin clearance. Nonetheless, concentrations attained in the bile are far above the minimum inhibitory concentration values of pathogens relevant in biliary tract infections.


Enzymatic versus autolytic debridement of chronic leg ulcers: a prospective randomised trial.
A randomised clinical trial (n = 42) compared the effectiveness of two approaches to debriding chronic leg ulcers: TenderWet 24, which is designed to support the autolytic degradation process, and Iruxol N (Santyl), an enzymatic treatment claimed to enhance the degradation process. Patients were randomly assigned to one of the two treatment groups for three weeks. Wounds were evaluated weekly for the amount of eschar/slough, the area of healthy granulation and the re-epithelialised area. During days 1-14 slough within the groups was reduced by almost 19% for TenderWet 24 and by 9% for Iruxol N, followed by an increase of 26% and 10% respectively in granulation tissue. These effects were less accentuated during days 7-21. There was a further 11% improvement in tissue debridement for the TenderWet 24 group and a relapse (+9.1%) in the Iruxol N group. Although TenderWet 24 appeared to be more efficient in a few cases, the general efficacy of the two products appeared to be almost the same as no statistically significant superiority of either product was found.


Alterations of small-molecular-weight antioxidants in the blood of smokers.
Plasma alpha-tocopherol, ascorbate, retinol, uric acid, and lipid peroxides were investigated in 39 male smokers and 64 male non-smokers. The average level of plasma alpha-tocopherol of 35-45-year-old smokers (1.74+/-0.49 microg/mg total lipid) was significantly lower than that of age-matched non-smokers (2.55+/-0.88 microg/mg total lipid, P = 0.032). Similarly, the plasma alpha-tocopherol of smokers aged above 45 (1.66+/-0.29 microg/mg total lipid) was lower than that of the age-matched non-smokers (2.38+/-1.26 microg/mg total lipid, P = 0.014). However, no difference in plasma level of alpha-tocopherol was found between smokers and non-smokers below the age of 35. The average concentration of ascorbate in plasma was significantly decreased only in those smokers older than 45 (0.33+/-0.16 mg/dl vs non-smokers 0.53+/-0.19 mg/dl, P = 0.003). The average level of lipid peroxides (measured as malondialdehyde,MDA) in the plasma of smokers (2.77+/-0.51 nmol/ml) was higher than that of non-smokers (2.35+/-0.21 nmol/ml) aged above 45 (P = 0.034). No differences in the plasma levels of uric acid and retinol were noted between smokers and non-smokers in all age groups. Using partial correlation analysis under age control, we found that the plasma level of alpha-tocopherol was negatively correlated with the plasma level of MDA (r = -0.523, P = 0.038). In contrast, the plasma level of ascorbate was only weakly correlated with the plasma level of MDA (r = -0.341, P = 0.094). Moreover, we found a negative correlation between the plasma level of alpha-tocopherol and smoking index (r = -0.414, P = 0.006) under age control, but there was no correlation between plasma level of ascorbate and smoking index (r=0.221, P = 0.193). These results indicate that adequate levels of alpha-tocopherol and ascorbate may protect the plasma from oxidative damage elicited by smoking-mediated reactive oxygen species (ROS) and free radicals in young smokers. However, the antioxidant activities of alpha-tocopherol and ascorbate may be overwhelmed by the long-standing oxidative stress elicited by cigarette smoking in elderly subjects.


Alteration of the nucleus basalis of Meynert afferents to vibrissae-related sensory cortex in de-whiskered adolescent congenital hypothyroid rats.
Thyroid hypofunction during early development results in anatomical alterations in the cerebellum, cerebrum, hippocampus and other brain structures. The plastic organization of the nucleus basalis of Meynert (nBM) projections to the whiskers-related somatosensory (wS1) cortex in adolescent pups with maternal thyroid hypofunction and sensory deprivation was assessed through retrograde WGA-HRP labeling. Congenital hypothyroidism induced by adding PTU (25 ppm) to the drinking water from embryonic day 16 to postnatal day (PND) 60. Pregnant rats were divided to intact and congenital hypothyroid groups. In each group, the total whiskers of pups (4 of 8) were trimmed continuously from PND 0 to PND 60. Following separately WGA-HRP injections into wS1, retrogradely labeled neurons were observed in nBM. The number of labeled neurons in nBM were higher in the congenital hypothyroid and whisker deprived groups compared to their controls (P < 0.05). Based on our results both congenital hypothyroidism and sensory deprivation may disturb normal development of cortical circuits in of nBM afferents to the wS1 cortex.


Juvenile chronic arthritis.
The nomenclature and classification criteria for arthritis in children should be dealt with initially as separate issues, although they are undoubtedly intertwined. The classification criteria should aim to delineate homogeneous patient populations, yet should be flexible enough to incorporate advances in disease knowledge. It should be recognized that arriving at an international consensus for classification criteria will merely provide a set of operational definitions to facilitate research, and not a set of diagnostic criteria. Indeed the only point to obtaining consensus is to begin a process of systematic ongoing review of the criteria. The labels attached to any of these diseases should facilitate accurate communication. In view of the heterogeneous nature of childhood arthritis, consideration should be given to using a broad umbrella term such as juvenile or childhood arthritis only for communicating with the lay public. Medical nomenclature should be formulated to reflect accurately homogeneous subgroups of arthritis, and should not artificially proscribe a relationship between paediatric and adult disease.


"Follicular HCG endometrium priming for IVF patients experiencing resisting thin endometrium. A proof of concept study".
A thin endometrium is one of the most difficult problems encountered in assisted reproduction every day practice. Whether a daily dose of 150 IU HCG for 7 days concomitant with estrogen administration in estrogen replacement cycles can increase the endometrial thickness and improve pregnancy outcome, was the objective of the current study. Seventeen infertile patients with successive implantation failures and resisting thin endometrium, being recipients of fresh donor or frozen embryos were recruited. This was a prospective cohort, proof of concept study, NCT01768247. On day-8 or 9 of the estrogen administration, and continuing 8 mg estrogen per day, subcutaneous injections of 150 IU HCG were initiated daily for 7 days. After a week on HCG priming, (day-14 or 15) endometrial thickness was controlled with ultrasound, and progesterone was initiated. Mean endometrial thickness was increased from 5.2 mm to 6 mm (p = 0.008). 35.3 % of the patients had more than 20 % improvement of their endometrial thickness after HCG priming. 17 % achieved an endometrial thickness more than 7 mm, and 29.4 % did not improve their thickness at all. Interestingly, from the later two became pregnant. Overall, 41 % of them (7/17) finally delivered. One hundred fifty IU HCG endometrial priming for 7 days in the proliferative phase of estrogen substituted cycles for frozen embryos is highly promising, as not only the thickness of the endometrium improves but also eventually the receptivity appears normalized.


Susceptibility of domestic animals to a pseudotype virus bearing RD-114 virus envelope protein.
Retroviral vectors are used for gene transduction into cells and have been applied to gene therapy. Retroviral vectors using envelope protein (Env) of RD-114 virus, a feline endogenous retrovirus, have been used for gene transduction. In this study, we investigated the susceptibility to RD-114 Env-pseudotyped virus in twelve domestic animals including cattle, sheep, horse, pig, dog, cat, ferret, mink, rabbit, rat, mouse, and quail. Comparison of nucleotide sequences of ASCT2 (SLC1A5), a receptor of RD-114 virus, in 10 mammalian and 2 avian species revealed that insertion and deletion events at the region C of ASCT2 where RD-114 viral Env interacts occurred independently in the mouse and rat lineage and in the chicken and quail lineage. By the pseudotype virus infection assay, we found that RD-114 Env-pseudotyped virus could efficiently infect all cell lines except those from mouse and rat. Furthermore, we confirmed that bovine ASCT2 (bASCT2) functions as a receptor for RD-114 virus infection. We also investigated bASCT2 mRNA expression in cattle tissues and found that it is expressed in various tissues including lung, spleen and kidney. These results indicate that retrovirus vectors with RD-114 virus Env can be used for gene therapy in large domestic animals in addition to companion animals such as cat and dog.


Chemoproteomic profiling of protein modifications by lipid-derived electrophiles.
Lipid-derived electrophiles (LDEs) are a group of endogenous reactive metabolites generated as products of lipid peroxidation when cells are under oxidative stress. LDEs are able to covalently modify nucleophilic residues in proteins to alter their structures and activities, either resulting in irreversible functional damage or triggering aberrant signaling pathways. Traditional biochemical methods have revealed individual protein targets modified by LDEs, however, deciphering the toxicity and/or signaling roles of LDEs requires systematic studies of these modifications in a high-throughput fashion. Here we survey recent progress in developing chemical proteomic strategies to globally profile protein-LDE interactions directly from complex proteomes. These powerful chemoproteomic methods have yielded a rich inventory of proteins and residue sites that are sensitive to LDE modification, serving as valuable resources to investigate mechanisms of their cellular toxicity at the molecular level.


Reversible association of ox liver glutamate dehydrogenase with the inner mitochondrial membrane.
A comparative study on the catalytic and allosteric properties of particulate and soluble forms of ox liver glutamate dehydrogenase has been carried out. The response of the bound enzyme to release by various effectors was investigated. The particulate enzyme was found to have catalytic activities similar to the free enzyme in contrast to its behaviour when bound to pure anionic phospholipids. Possible reasons for such outstanding differences are discussed.


Current challenges and trends in the discovery of agrochemicals.
Crop protection chemistry has come a long way from its "alchemic" beginnings in the late 19th century to a high-tech science that supports the sustainable production of food, feed, and fiber for a rapidly growing population. Cutting-edge developments in the design and synthesis of agrochemicals help to tackle today's challenges of weed and pest resistance, higher regulatory safety margins, and higher cost of goods with the invention of selective, environmentally benign, low use rate, and cost-effective active ingredients.