Comparative Effectiveness of Treatment Strategies for Bladder Cancer With Clinical Evidence of Regional Lymph Node Involvement.
Patients with bladder cancer with clinical lymph node involvement (cN+) are at high risk for distant metastases, but are potentially curable. Such patients are excluded from neoadjuvant chemotherapy trials and pooled with patients with distant metastases in first-line chemotherapy trials not suited to define the role of combined-modality therapy. To address this evidence void, we performed a comparative effectiveness analysis. We included cTanyN1-3M0 bladder cancer patients from the National Cancer Data Base (2003-2012) treated with chemotherapy and/or cystectomy. We used multistate survival analysis, allowing for delayed entry, to assess overall survival (OS) according to various treatment strategies. Effectiveness was estimated with multivariable adjustment for tumor-, patient-, and facility-level characteristics. Among 1,739 patients (cN1, 48%; cN2, 45%; cN3, 7%), 1,104 underwent cystectomy and 635 were treated with chemotherapy alone. Of the cystectomy patients, 363 received preoperative and 328 received adjuvant chemotherapy. The crude 5-year OS for chemotherapy alone, cystectomy alone, preoperative chemotherapy followed by cystectomy, and cystectomy followed by adjuvant chemotherapy was 14% (95% CI, 11% to 17%), 19% (95% CI, 15% to 24%), 31% (95% CI, 25% to 38%), and 26% (95% CI, 21% to 34%), respectively. Compared with cystectomy alone, preoperative chemotherapy was associated with a significant improvement in OS (hazard ratio, 0.80; 95% CI, 0.66 to 0.97). Adjuvant chemotherapy was also associated with a significant improvement in survival compared with cystectomy alone. The survival of patients treated with chemotherapy alone was worse than those treated with cystectomy alone. A subset of patients with cN+ bladder cancer achieves long-term survival. Combined-modality therapy, with chemotherapy and cystectomy, is associated with the best outcomes.


Isolation and characterization of native single-chain porcine pancreatic kallikrein, another possible precursor of urinary kallikrein.
Porcine pancreatic kallikrein B' was isolated from partially purified prokallikrein B activated "spontaneously" (most probably due to the action of some contaminating proteinase). Upon dodecyl sulfate electrophoresis after reduction, the enzyme migrated like the single-chain alpha-kallikreins A from submandibular glands and urine of the pig, indicating an apparent molecular weight of about 36,000. Evidently, porcine pancreatic kallikrein B' is also a single-chain alpha-kallikrein, in contrast to the two-chain beta-kallikrein obtained by the usual isolation procedure from autolyzed porcine pancreas. The amino acid composition of kallikrein B' is very similar to that of the other porcine glandular kallikreins and it too contains glucosamine. The specific activities of kallikrein B', as measured under various conditions, also resemble closely those of porcine urinary and submandibular kallikreins, as do the rates of the enzyme-catalyzed hydrolyses of various amino acid ester substrates. During the hydrolysis of Bz-LysOMe or low concentrations of Bz-ArgOEt, the same strange biphasic course of the reaction is seen, as observed previously in the case of the other single-chain porcine kallikreins. Consequently, the properties of native porcine pancreatic kallikrein are well consistent with the suggestion that urinary kallikrein represents filtered enzyme of pancreatic and submandibular origin. Further available evidence for this and the alternative hypothesis of synthesis of urinary kallikrein in the kidney is discussed.


Transient uniocular visual loss on deviation of the eye in association with intraorbital tumours.
Five patients with unilateral orbital tumours are described in whom transient loss of vision occurred on deviation of the affected eye from the primary position. Other presenting features were diplopia, proptosis, poor visual acuity, visual field defects, pupillary abnormalities, fundal changes and altered colour vision. Abnormalities on fluorescein angiography suggest that the visual loss is due to transient ischaemia. Temporary uniocular loss of vision on eye movement may be an early sign of an intra-orbital mass.


The association between periodontal disease parameters and severity of atherosclerosis.
Atherosclerosis is the most common cause for heart attack and stroke. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. The aim of this research was to determine the possible association between chronic periodontal disease and severity of atherosclerosis. Eighty-two subjects that were referred to Chamran Heart Hospital in Isfahan for angiography were involved in this study. Fifty-nine subjects had coronary artery obstruction (CAO) and 23 showed no obstruction after angiography. The severity of CAO was assessed. Periodontal parameters including pocket depth (PD), gingival recession (R), clinical attachment level (CAL), and bleeding on probing (BOP) of all subjects were recorded. The decayed-missing-filled (DMF) index of all subjects was also measured. For statistical analysis, Pearson correlation test, Chi-square, and independent t-test were used. There were significant positive correlation between variables R, PD, CAL, decayed (D), missing (M), DMF, BOP, and degree of CAO. However, there were no significant differences between filling variable degree of CAO (left anterior descending, left circumflex, and right coronary artery). Independent t-test showed that the mean of variables R, PD, AL, D, M, and DMF in patients with obstructed arteries were significantly higher than subjects without CAO. But there were no significant differences between variable F in two groups. The results of this cross-section analytical study showed an association between periodontal disease and dental parameters with the severity of CAO measured by angiography. However, this association must not interpret as a cause and effect relationship.


Diagnosis and management of Rosai-Dorfman disease involving the central nervous system.
Rosai-Dorfman disease is a benign non-neoplastic proliferative disorder of histiocytes originally described in the cervical lymph nodes. Extranodal sites were later recognized, and by 1990, they were shown to represent over 40% of cases; however, central nervous system involvement is still considered rare. We review the literature, which shows a steady increase in reports of Rosai-Dorfman disease involving the brain and/or spine. A literature search was performed for the period 1969-2008, using multiple search engines, with keywords Rosai-Dorfman disease, central nervous system Rosai-Dorfman disease and sinus histiocytosis with massive lymphadenopathy. By December 2008, 111 cases of Rosai-Dorfman disease involving the central nervous system had been reported in the literature, including our cases. In the central nervous system, Rosai-Dorfman disease is ubiquitous. Although it is characterized by unique, indeed pathognomonic, histopathological cytoarchitecture, it may be mistaken for many other neoplastic and inflammatory histioproliferative diseases. Surgical resection with post-operative corticosteroids remains the treatment of choice. Rosai-Dorfman disease involving the central nervous system appears to be more common than previously thought and may well assume a more prominent place in the differential diagnoses of dural-based lesions. Expert awareness of the characteristic histopathology and immunohistochemistry of the disease is required for accurate diagnosis.


Simultaneous Multiselective Spectroelectrochemical Fiber-Optic Sensor: Sensing with an Optically Transparent Electrode.
We present a spectroelectrochemical fiber-optic sensor with an optically transparent electrode. The sensor was fabricated by coating indium tin oxide (ITO) onto the surface of fiber-optic core chips using a polygonal barrel-sputtering method. The ITO-coated fiber-optic probe can be simply and cheaply mass-produced and used as a disposable probe. The sensing is based on changes in an attenuated total reflection signal accompanying the electrochemical oxidation-reduction of an analyte at the electrode. The properties of an ITO-coated fiber-optic probe as an optically transparent electrode were investigated for varying thicknesses of ITO. The sensor responses were successfully enhanced with an additional level of selectivity via an electrostatically adsorbed, self-assembled monolayer, which comprised a polyanion and polycation.


Failure in chymotrypsin enhancement of human rotavirus infectivity.
Effects of alpha-chymotrypsin on human rotavirus infectivity and hemagglutination activity were investigated using the KUN strain which was grown in the absence of trypsin and noninfectious. No activating effect of the enzyme on the virus infectivity was found, while HA titers of the virus rapidly decreased after exposure to the enzyme.


Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL.
Lacrimal gland benign lymphoepithelial lesion (LGBLEL) is an IgG4-related disease of unknown etiology with a risk for malignant transformation. Estrogen is considered to be related to LGBLEL onset. Seventy-eight LGBLEL and 13 control clinical samples were collected and studied to determine the relationship between estrogen and its receptors and LGBLEL development. The serological analysis revealed no significant differences in the levels of three estrogens be-tween the LGBLEL and control groups. However, immunohistochemical analyses indicated that the expression levels of ERβ and its downstream receptor RERG were relatively lower in LGBLEL samples than in control samples, with higher expression in the lacrimal gland and lower expression in the lymphocyte infiltration region. However, low expression of ERα was detected. The transcriptome sequence analysis revealed upregulated genes associated with LGBLEL enriched in lymphocyte proliferation and activation function; downregulated genes were enriched in epithelial and vascular proliferation functions. The key genes and gene networks were further analyzed. Interactions between B cells and epithelial cells were analyzed due to the identified involvement of leukocyte subsets and epithelial cells. B cell proliferation was found to potentially contribute to lacrimal gland apoptosis. Therefore, the tissue-heterogeneous expression pattern of ERβ is potentially related to the clinical manifestations and progression of LGBLEL, although further investigations are required to confirm this finding.


Approximating the DCJ distance of balanced genomes in linear time.
Rearrangements are large-scale mutations in genomes, responsible for complex changes and structural variations. Most rearrangements that modify the organization of a genome can be represented by the double cut and join (DCJ) operation. Given two balanced genomes, i.e., two genomes that have exactly the same number of occurrences of each gene in each genome, we are interested in the problem of computing the rearrangement distance between them, i.e., finding the minimum number of DCJ operations that transform one genome into the other. This problem is known to be NP-hard. We propose a linear time approximation algorithm with approximation factor O(k) for the DCJ distance problem, where k is the maximum number of occurrences of any gene in the input genomes. Our algorithm works for linear and circular unichromosomal balanced genomes and uses as an intermediate step an O(k)-approximation for the minimum common string partition problem, which is closely related to the DCJ distance problem. Experiments on simulated data sets show that our approximation algorithm is very competitive both in efficiency and in quality of the solutions.


A structural equation model to predict the social-cognitive determinants related to physical activity in Iranian women with diabetes mellitus.
Lifestyle-modification programs including physical activity are essential for both treatment and prevention of Type 2 Diabetes Mellitus (T2DM). However, factors associated with physical activity among patients are poorly understood. This study applied Social-Cognitive Theory (SCT) for predicting determinants of physical activity among women with T2DM in Iran, 2013. In this cross-sectional study, partial least square path modeling (PLS-PM) was used as an estimation technique for structural equation model. This model specified hypotheses between components of Social-cognitive Theory on physical activity behavior. A random sample of 300 women with T2DM was selected, and completed SCT constructs instrument. Data were analyzed using statistical software WarpPLS Ver. 4.0. The model explained 26% of the variance in physical activity. Self-regulation, task self-efficacy and barrier self-efficacy were significantly direct predictors of physical activity among women with T2DM. Task self-efficacy, social support and modeling had significantly indirect effects on physical activity behavior (P<0.001). Our findings showed evidence for adequacy of a theoretical framework that could be used to predict physical activity behavior among women with T2DM.


Partial transfection of cells using laminar flows in microchannels.
This manuscript describes a convenient method for partial transfection using a Y-shaped microchannel polydimethylsiloxane (PDMS)-glass chip and on-chip cationic lipid-mediated transfection. Enhanced green fluorescent protein genes (pEGFP-N2) were introduced into the COS-7 cells cultured in half of the channel, while red fluorescent protein genes (pDsRed-N1) were introduced into the cells cultured in another half of the channel. This on-chip partial transfection technique provides an avenue for the spatial control of transfection. It is possible to use this technique to perform parallel transfection on chips in order to study cell behaviors under two or more gene transfections in the same culture.


Zonal cultivars of field crops as a reserve for the phytoremediation of fluorides polluted soils.
To solve the problems of improving arable soils contaminated with fluorides of aluminum smelter, it is necessary to select plants that combine the ability to bioaccumulate pollutants without compromising the viability. It makes sense to carry out the search among field crops cultivated in the region, as they are most adapted to specific soil and climatic conditions. Indicators of productivity and bioaccumulation factors (Bf) were studied in Galega orientalis Lam., Melilótus officinális Lam., Heliánthus tuberósus L., Zéa máys L., Avena sativa L., Medicago sativa L., and Raphanus sativus var. oleifera Metzg which are zonal for agriculture of Baikal Siberia. In the field experiments on the gray forest soils uncontaminated and contaminated by aluminum technogenic exhaust, it was shown that zonal cultivars of M. officinális Lam. and R. sativus var. oleifera Metzg have the greatest potential for phytoextraction of fluorides from contaminated soils (Bf >1).


Incidence of acute mountain sickness in young adults at 3200 meters: comparison of the Lake Louise Scoring and Chinese Scoring Systems.
The purpose of this study was to compare two scoring systems used for the diagnosis of acute mountain sickness (AMS): the Lake Louise Scoring (AMS-LLS) and the Chinese Scoring Systems (AMS-CSS). In total, 339 healthy young adult volunteers residing at sea level ascended to 3200 m by train and bus over a total journey time of 48 h. All subjects ascended in the same manner and were divided into three groups that were assessed after one (N = 88), two (N = 91), and three (N = 160) nights, respectively, at altitude. The overall incidence of AMS was 17.11% (N = 58) and 29.79% (N = 101) according to the AMS-LLS and AMS-CSS, respectively. Two participants (0.59%) experienced high-altitude pulmonary edema. Both scoring systems showed the highest incidence of AMS after the second night at high altitude. The AMS-CSS and AMS-LLS scores were significantly correlated (Pearson's r = 0.820, P < 0.001). The AMS-CSS identified all AMS subjects diagnosed by the AMS-LLS, and an additional 43 subjects. The dominant symptoms were reduced exercise tolerance (61.7%), fatigue (49.0%), dizziness (28.9%), chest distress (28.3%), and headache (27.4%). Compared with the AMS-LLS, the sensitivity, specificity, and positive and negative predictive values of the AMS-CSS were 100, 84.7, 57.43, and 100%, respectively. There was no relationship between oxygen saturation levels and AMS scores at 3200 m. In summary, the AMS-CSS was similar to AMS-LLS, except that it resulted in more positive diagnoses, and headache did not play a large diagnostic role.


Accidental hypothermia.
Knowledge of the effects of hypothermia has increased greatly over the past 25 yr. Thousands of patients have been cooled intentionally in the operating room, and hundreds of thousands of living hearts have been temporarily stopped by cold cardioplegia and restarted without difficulty or apparent ill-effect. Yet in spite of the acquisition of this vast body of clinical experience an aura of mystery stills surrounds the patient who becomes hypothermic accidentally. The best treatment in any particular case is not always clear, and published accounts do not always give the impression that the hypothermic patient is treated with the same rational approach with which other sick and comatose patients are treated. In summarizing, therefore, conclusions that might be reached from reviewing past experience several important points emerge. The severely hypothermic patient should be treated in an intensive care unit where appropriate monitoring of temperature, cardiovascular function and respiratory function are available, and where full respiratory support including assisted ventilation can be given. The final outcome depends upon the etiology. The young healthy victim of exposure has a good chance of surviving. The patient poisoned by alcohol or barbiturates has a good chance of surviving provided the level of intoxication is not itself lethal. The elderly without severe underlying disease have a good chance of surviving. The patient with severe underlying disease of the endocrine, cardiovascular or neurologic system probably has, at best, a 50% chance of surviving and, at worst, a chance of only 10-20%, depending upon the associated disease. There is no statistical evidence that any one method of rewarming is significantly better than any other. But there is anecdotal evidence that in the absence of full monitoring and support systems slow rewarming is safer than over-energetic external rewarming. Internal rewarming, peritoneal dialysis, hemodialysis, inhalation of warmed oxygen and extracorporeal circulation are effective in severe cases and can be used with safety. The causes of, and triggering mechanism for, ventricular fibrillation are still largely unknown but the onset of ventricular fibrillation in a very cold patient may often be an irreversible complication. The place of modern anti-arrhythmic drugs in the prevention and management of this complication has yet to be elucidated. Cardiopulmonary resuscitation is difficult in profoundly hypothermic patients but should be maintained until a body temperature of 30 degrees C has been achieved.(ABSTRACT TRUNCATED AT 400 WORDS)


[Procoagulant activity of alveolar macrophages in bleomycin-induced lung fibrosis in rats].
Interstitial and intraalveolar fibrin deposition is a prominent feature in adult respiratory distress syndrome and is also observed in the inflammatory phase of interstitial lung disease (ILD). It is suggested that the coagulation abnormality in these disorders may be implicated in the pathogenesis of subsequent fibrosis of the lung. In this study, we examined the procoagulant activity (PCA) of alveolar macrophages during the development of bleomycin-induced lung fibrosis in rats. The PCA of alveolar macrophages was significantly increased at 2, 7 and 14 days after the intratracheal administration of bleomycin compared with that of control rats. The greatest PCA was observed at 7 days after the bleomycin injection, the inflammatory phase in the development of lung fibrosis. Increased PCA returned to the normal value at 21 days, while the fibrotic process advanced and the collagen content increased in the lung. Alveolar macrophages at 7 days after the administration of bleomycin or saline were separated into five density fractions on discontinuous Percoll gradients. The increase in the percentage of low-density macrophages was observed in bleomycin-injected rats. The greatest PCA was demonstrated in the lowest-density fraction (specific gravity less than 1.030), while reduced activities were observed in the higher-density fractions, in each group. The increased PCA of alveolar macrophages during lung injury was due in part to the increase of low-density subpopulation, which had greater PCA, although the fibrin deposition in the development of lung fibrosis remained to be defined, the increase of coagulation pathways may contribute to the progression of interstitial fibrotic lung diseases.


Isolated insulin-derived amyloidoma of the breast.
Isolated amyloidomas derived from insulin are extremely rare, and there is only one reported case to date of insulin-derived amyloidoma in the breast.We present the case of a 36-year-old woman reporting a lump in the right breast. It was clinically assessed as a probable fibroadenoma but was removed surgically given the size of the lesion. On histological analysis, the lesion had features consistent with amyloid. Further investigations showed the amyloid to be derived from insulin. The lump was removed in its entirety, and the patient made a full recovery.


Liver resection: 10-year experience from a single institution.
Liver resection constitutes the main treatment of most liver primary neoplasms and selected cases of metastatic tumors. However, this procedure is associated with significant morbidity and mortality rates. To analyze our experience with liver resections over a period of 10 years to determine the morbidity, mortality and risk factors of hepatectomy. Retrospective review of medical records of patients who underwent liver resection from January 1994 to March 2003. Eighty-three (41 women and 42 men) patients underwent liver resection during the study period, with a mean age of 52.7 years (range 13-82 years). Metastatic colorectal carcinoma and hepatocellular carcinoma were the main indications for hepatic resection, with 36 and 19 patients, respectively. Extended and major resections were performed in 20.4% and 40.9% of the patients, respectively. Blood transfusion was needed in 38.5% of the operations. Overall morbidity was 44.5%. Life-threatening complications occurred in 22.8% of cases and the most common were pneumonia, hepatic failure, intraabdominal collection and intraabdominal bleeding. Among minor complications (30%), the most common were biliary leakage and pleural effusion. Size of the tumor and blood transfusion were associated with major complications (P = 0.0185 and P = 0.0141, respectively). Operative mortality was 8.4% and risk factors related to mortality were increased age and use of vascular exclusion (P = 0.0395 and P = 0.0404, respectively). Median hospital stay was 6.7 days. Liver resections can be performed with low mortality and acceptable morbidity rates. Blood transfusion may be reduced by employing meticulous technique and, whenever indicated, vascular exclusion.


Comparison of thallium-201 and gallium-67 scintigraphy in the evaluation of non-Hodgkin's lymphoma.
Gallium-67 (Ga-67) is widely used in the assessment of patients with lymphoma. Although highly sensitive in Hodgkin's disease and high grade non-Hodgkin's lymphoma (NHL), its sensitivity is reported to be reduced in lower grades of NHL. Several series have suggested that thallium-201 (Tl-201) may be more useful than Ga-67 in the evaluation of low and possibly intermediate grade NHL. To compare the sensitivity and relative avidities (uptakes) of Tl-201 and Ga-67 in patients with NHL. A total of 36 pairs of studies were performed in 33 patients (14 male: 19 female; age range 16-84 years, mean 55 years). All had whole body Ga-67 (400 MBq) and Tl-201 (100-200 MBq) studies (interval 0-three days) which were read by two experienced nuclear medicine physicians blinded to clinical history and results of other investigations. Tl-201 had a higher sensitivity and avidity than Ga-67 in patients with low grade NHL. In contrast, Ga-67 was slightly more sensitive and had a higher avidity in patients with both intermediate and high grade NHL. We conclude that Tl-201 is more sensitive and avid for low grade NHL than Ga-67 and that consideration should be given to its use in this condition in conjunction with Ga-67 as it may provide complementary information. Routine use in intermediate grade NHL is less convincing as Ga-67 was superior in most cases. Ga-67 is more sensitive than Tl-201 in assessment of high grade NHL.


Choosing appropriate pharmacotherapy for drug-resistant HIV.
Despite the potency of current antiretrovirals, some patients continue to struggle with the management of the treatment of HIV due to drug resistance-associated mutations. The underlying causes of these developments are usually drug adherence and drug availability as well as the economic affordability of those potent drugs in low to middle-income countries as well as in some industrialised countries. Viral replication, despite therapy, varies by region from 5 to 28. Non-adherence includes a variety of behaviours with different clinical implications. Addressing non-adherence and choosing new regimens based on a strategic vision may aid overall treatment strategies in the future. Areas covered: The authors review the literature derived from Embase, MEDLINE and the main international congresses on transmitted and selected drug resistance to HIV therapeutics. They also consider the pharmacological aspects of antiretroviral therapy including the genetic barrier, convenience, potency, drug-drug interactions and tolerability are discuss prospective randomized or observational clinical trials on salvage therapy. Expert opinion: Preventive intervention is the most efficient way to reduce the selection and transmission of drug-resistant mutations. While subjects with no current available options may benefit from new compounds (ibalizumab and fostemsavir), strategies should be implemented to spare as many patients as possible from drug resistance.


Macrophage activation syndrome in juvenile rheumatoid arthritis successfully treated with cyclosporine A: a case report.
Macrophage activation syndrome (MAS) is one of the serious complications of juvenile rheumatoid arthritis (JRA) and recently, cyclosporine A has been found to be effective in patients with corticosteroid-resistant MAS. A 29-yr-old male was admitted with high fever and jaundice for one month. He was diagnosed as juvenile arthritis 16 yr ago. Physical and laboratory results showed hepatosplenomegaly, high fever, pancytopenia and impaired liver and renal function tests, elevated triglyceride and serum ferritin levels. Bone marrow biopsy showed hyperplasia of histiocytes with active hemophagocytosis. He was diagnosed as MAS associated with juvenile rheumatoid arthritis and managed with high-dose corticosteroids initially, but clinical symptoms and laboratory findings did not improve immediately. Finally, he completely recovered after treatment with cyclosporine A (3 mg/kg/day).


Shifting the light emitting component from core to shell: an effective approach to improve the efficiency of light-emitting diodes based on multi-junction quantum materials.
Herein, using the light emitting component as the inner shell, we construct an advanced quantum-dot-quantum-well structure, ZnCdS/CdSe/CdZnSeS/ZnS, and use it for the fabrication of a light-emitting-diode. In comparison with the device containing conventional structured quantum dots, CdSe/CdZnSeS/ZnS, the advanced device possesses a superior performance in aspects of luminance, current efficiency, turn-on voltage and emitting wavelength tunability. Therefore, this paper indicates a promising strategy for the fabrication of light emitting devices based on quantum materials.


Effects of anions on ATP-activated nonselective cation current in NG108-15 cells.
Extracellular ATP induces a nonselective cation current and elevates intracellular Ca2+ concentration via P2Z receptors in NG108-15 cells. We found that the ATP-induced nonselective cation current became larger in methanesulfonic acid (MS-) than in Cl- external solution. We therefore examined the effects of various external anions on the ATP-induced cation current with the use of the whole cell patch-clamp technique. The concentration-response curves for ATP were obtained in different anionic external solutions. The maximum current density (Imax) and the concentration of agonist that gives 50% of maximum response (EC50) value of ATP were obtained by fitting the curves with the use of the Hill coefficient of 2. The apparent Imax decreased in the order of aspartic acid (Asp-) > MS- > F- > Cl- > Br- > or = I-. The apparent EC50 values for ATP were shifted to the right in the sequence of Asp- < F- < MS- < Br- < Cl- < I-. Thus both Imax and EC50 values were affected by anions, indicating that anions are mixed-type inhibitors of the ATP-induced current. The shift of the EC50 values of ATP indicates that anions interfere with ATP binding to the receptor. External Cl- was a noncompetitive inhibitor with respect to external Na+, a major cation carrying the ATP-induced current. We conclude that extracellular anions inhibit the ATP-induced nonselective cation current at least partly by interfering with ATP binding to the P2Z receptor, which is associated with the nonselective cation channels.


[Experimental study of HIF-1alpha antisense oligonucleotide on implanted human gastric cancer in nude mice].
To observe the effect of HIF-1alpha antisense oligonucleotide (HIF-1alpha ASOND) on implanted human gastric cancer in nude mice. BALB/c nude mice were subcutaneously transplanted with SCG-7901 tumor cells, then the mice were randomly divided into antisense oligonucleotide (ASOND) group, sense oligonucleotide (SOND) group and the control group. The HIF-1alpha ASOND complexed with cationic liposome, HIF-1alpha SOND complexed with cationic liposome and liposome were injected intra-tumorally in the above groups, respectively. Tumor growth curve in each group animals was observed. The tumor weight was measured and then the rate of inhibition was calculated. The morphological changes of tumor cells was observed under microscope. The expression of HIF-1alpha, VEGF and MVD in tumor tissue was determined by immunohistochemical methods. The growth of tumor of ASOND group was significantly inhibited. There was statistically significant difference (P < 0.05) in the weight of tumor between ASOND group and control group. The inhibitory rates of ASOND group and SOND group were 47.94% and 16.88% respectively, and both inhibitory rates were significantly different (P < 0.01). The tumor tissue expression of HIF-1alpha, VEGF and MVD in ASOND group was significantly lower than those of SOND and the control groups (P < 0.01). In tumor tissue, the injection of HIF-1alpha ASOND to treat gastric carcinoma transplanted subcutaneously in nude mice can reduce the expression of HIF-1alpha, consequently reduce the formation of VEGF and new blood vessels, so as to achieve inhibition of tumor growth.


Organization of the cortico-ponto-cerebellar pathway to the dorsal paraflocculus. An experimental study with anterograde and retrograde transport of WGA-HRP in the cat.
To reveal the organization and relative magnitude of connections from various parts of the cerebral cortex to the dorsal paraflocculus via the pontine nuclei, WGA-HRP was injected in the dorsal paraflocculus in conjunction with injection of the same tracer in various parts of the cerebral cortex in 17 cats. Termination areas of cortical fibres (anterogradely labelled) and pontine neurons projecting to the dorsal paraflocculus (retrogradely labelled) were carefully plotted in serial transverse sections. As an average of countings in ten cats, 90% of the labelled cells were found in the pontine nuclei contralateral to the injection, and the majority (70%) were located in the rostral half of the nuclei. The highest degree of overlap between anterograde and retrograde labelling was found after injections of the parietal association cortex (areas 5 and 7). In an experiment with double anterograde tracing, it was shown that both area 5 and 7 contribute substantially to the cerebral inputs to the dorsal paraflocculus. High degree of overlap also occurred after injections of several visual cortical areas (areas 17, 18, 19, 20 and the posteromedial lateral suprasylvian visual area, PMLS). Cases with injections restricted to individual visual areas indicate that they all contribute to the parafloccular input. Considerably less overlap occurred after injections of the primary sensorimotor region (SI, MI) and second somatosensory area (SII), while the supplementary motor area, the auditory cortex and gyrus cinguli probably have no or very restricted access to the dorsal paraflocculus. It is concluded that the dorsal paraflocculus has its major cortical input from the parietal association cortex and the visual cortical areas. Since all the various cortical regions studied project to largely different parts of the pontine nuclei, and overlap with neurons projecting to the dorsal paraflocculus takes place at numerous places, it follows that the pontine neurons projecting to the dorsal paraflocculus must consist of many subgroups differing with regard to their cortical input.


Total Synthesis of the Marine Natural Product Hemiasterlin by Organocatalyzed α-Hydrazination.
An efficient synthesis of the potently cytotoxic marine peptide hemiasterlin is presented. The tetramethyltryptophan moiety is assembled by tert-prenylation of indole, followed by the high-yielding organocatalyzed α-hydrazination of a sterically congested aldehyde with excellent enantioselectivity. 2-Bromo-N-ethylpyridinium tetrafluoroborate (BEP)-mediated peptide coupling completes the synthesis, being the first approach that does not employ chiral auxiliaries. A novel phenonium-type rearrangement of the indole system occurred when subjecting dihydroxylated 3-tert-prenylindole to Mitsunobu conditions.


Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity.
The potentially tridentate ligand 2-pyridinecarbaldehyde isonicotinoyl hydrazone (HPCIH) and its analogues are an emerging class of orally effective Fe chelators that show great promise for the treatment of Fe overload diseases. Herein, we present an extensive study of the Fe coordination chemistry of the HPCIH analogues including the first crystallographically characterised Fe(II) complex of these chelators. Unlike most other clinically effective Fe chelators, the HPCIH analogues bind Fe(II) and not Fe(III). In fact, these chelators form low-spin bis-ligand Fe(II) complexes, although NMR suggests that the complexes are close to the high-spin/low-spin crossover. All the Fe complexes show a high potential Fe(III/II) redox couple (> 500 mV vs. NHE) and cyclic voltammetry in aqueous or mixed aqueous/organic solvents is irreversible as a consequence of a rapid hydration reaction that occurs upon oxidation. A number of the HPCIH analogues show high activity at inducing Fe efflux from cells and also at preventing Fe uptake by cells from the serum Fe transport protein transferrin. As a class of ligands, these chelators are more effective at reducing Fe uptake from transferrin than inducing Fe mobilisation from cells. This may be related to their ability to intercept Fe(II) after its release from transferrin within the cell. Our studies indicate that their Fe chelation efficacy is due, at least in part, to the fact that these ligands and their Fe(II) complexes are neutral at physiological pH (7.4) and sufficiently lipophilic to permeate cell membranes.


Hidden Burden of Electronic Health Record-Identified Familial Hypercholesterolemia: Clinical Outcomes and Cost of Medical Care.
Background Familial hypercholesterolemia ( FH ), is a historically underdiagnosed, undertreated, high-risk condition that is associated with a high burden of cardiovascular morbidity and mortality. In this study, we use a population-based approach using electronic health record ( EHR )-based algorithms to identify FH . We report the major adverse cardiovascular events, mortality, and cost of medical care associated with this diagnosis. Methods and Results In our 1.18 million EHR- eligible cohort, International Classification of Diseases, Ninth Revision ( ICD -9) code-defined hyperlipidemia was categorized into FH and non- FH groups using an EHR algorithm designed using the modified Dutch Lipid Clinic Network criteria. Major adverse cardiovascular events, mortality, and cost of medical care were analyzed. A priori associated variables/confounders were used for multivariate analyses using binary logistic regression and linear regression with propensity score-based weighted methods as appropriate. EHR FH was identified in 32 613 individuals, which was 2.7% of the 1.18 million EHR cohort and 13.7% of 237 903 patients with hyperlipidemia. FH had higher rates of myocardial infarction (14.77% versus 8.33%; P<0.0001), heart failure (11.82% versus 10.50%; P<0.0001), and, after adjusting for traditional risk factors, significantly correlated to a composite major adverse cardiovascular events variable (odds ratio, 4.02; 95% CI, 3.88-4.16; P<0.0001), mortality (odds ratio, 1.20; CI, 1.15-1.26; P<0.0001), and higher total revenue per-year (incidence rate ratio, 1.30; 95% CI, 1.28-1.33; P<0.0001). Conclusions EHR -based algorithms discovered a disproportionately high prevalence of FH in our medical cohort, which was associated with worse outcomes and higher costs of medical care. This data-driven approach allows for a more precise method to identify traditionally high-risk groups within large populations allowing for targeted prevention and therapeutic strategies.


Identification of Anopheles aquasalis as a possible vector of malaria in Guyana, South America.
Adult female mosquitoes were collected in Mahdia, Guyana, to determine the incidence of malaria in Anopheles species found during the month of June 2000. Centers for Disease Control miniature white (incandescent) light traps, model 512, and miniature black (ultraviolet) light traps, model 912, were used to capture female mosquitoes. Numbers of mosquitoes collected were compared between white and black light traps and between traps set outside and inside of buildings. Adult female Anopheles mosquitoes were identified and an ELISA dipstick test for Plasmodium vivax and Plasmodium falciparum was performed on each mosquito. An aquasalis, An oswaldoi, and An braziliensis were attracted to white light traps. An triannulatus and An darlingi were collected from black light traps. Approximately the same numbers of all female Anopheles mosquitoes 28/45 (62%) were caught inside buildings as outside. Numbers of female non-anopheles mosquitoes captured in light traps varied between the traps set outside of buildings and inside of buildings with bright light traps collecting 91/122 (75%). A total of 45 Anopheles mosquitoes were captured and 122 non-anopheles species. Of the two known vectors of malaria in Guyana, An darlingi mosquitoes were not infected with P vivax but An aquasalis was found to be a carrier. The findings of this study suggest a need for further surveying and identification of current malaria vectors in Guyana.


Missed opportunities for family planning counselling among HIV-positive women receiving HIV Care in Uganda.
HIV-positive women who are still in the reproductive years need adequate sexual and reproductive health information to make informed reproductive health choices. However, many HIV-positive women who interface with the health system continue to miss out on this information. We sought to: a) determine the proportion of HIV-positive women enrolled in HIV care who missed family planning (FP) counselling; and b) assess if any association existed between receipt of FP counselling and current use of modern contraception to inform programming. Data were drawn from a quantitative national cross-sectional survey of 5198 HIV-positive women receiving HIV care at 245 HIV clinics in Uganda; conducted between August and November 2016. Family planning counselling was defined as provision of FP information (i.e. available FP methods and choices) to an HIV-positive woman by a health provider during ANC, at the time of delivery or at the PNC visit. Analyses on receipt of FP counselling were done on 2760 HIV-positive women aged 15-49 years who were not currently pregnant and did not intend to have children in the future. We used a modified Poisson regression model to determine the Prevalence Ratio (PR) as a measure of association between receipt of any FP counselling and current use of modern contraception, controlling for potential confounders. Analyses were performed using STATA statistical software, version 14.1. Overall, 2104 (76.2%) HIV-positive women reported that they received FP counselling at any of the three critical time-points. Of the 24% (n = 656) who did not, 37.9% missed FP counselling at ANC; 41% missed FP counselling during delivery; while 54% missed FP counselling at the post-natal care visit. HIV-positive women who received any FP counselling were significantly more likely to report current use of modern contraception than those who did not (adjusted PR [adj. PR] = 1.21; 95% Confidence Interval [CI]: 1.10, 1.33). Nearly one-quarter of HIV-positive women did not receive any form of FP counselling when they interfaced with the healthcare system. This presents a missed opportunity for prevention of unintended pregnancies, and suggests a need for the integration of FP counselling into HIV care at all critical time-points.


Peroperative irrigation of the vas deferens during vasectomy.
In 59 consecutive vasectomies for the purpose of sterilization, one-half, chosen by random numbers, received an irrigation of the vas deferens with 40 ml of sterile water on each side. Afterwards, the men sent in every fourth ejaculation, until two consecutive samples were without spermatozoa. The postoperative sperm samples were examined microscopically without knowing whether the man belonged to the treated group or the control group. The irrigation procedure did not shorten the time needed to reach azoospermia.


Intervention Effect of Traditional Chinese Medicine Hot Pressing Combined with Health Education on the Adolescent's Visual Fatigue.
To explore the intervention effect of traditional Chinese medicine hot pressing combined with health education in adolescents with asthenopia, 92 adolescents with asthenopia admitted to the outpatient department of Guangming Traditional Chinese Medicine Hospital in Pudong New Area from October 2019 to January 2021 were selected and randomly divided into two groups: the control group and the test group, each with 46 cases. Both received health education. The control group was given sodium hyaluronate eye drops, and the test group was given traditional Chinese medicine hot ironing technique intervention. After 2 courses of treatment, the scores of visual fatigue symptoms, clinical curative effect, and eye refractive power of the two groups were observed. The satisfaction of treatment was compared between the two groups. The scores of asthenopia of the two groups were compared at 6 months after intervention. After the intervention, the scores of visual fatigue symptoms in the control group and the test group were reduced after one or two courses of treatment (control group: t = 4.167, 6.318, and P=0.027, 0.010; test group: t = 4.820, 6.834, and P=0.013, <0.001). The scores of asthenopia symptoms of the trial group after the intervention for one and two courses were significantly lower than those of the control group (P < 0.05); the total clinical effective rate of the trial group was 93.48%, which was significantly higher than that of the control group (80.43%). The difference between the groups was statistically significant (P < 0.05); the left and right eyes of the control group did not change significantly before and after the intervention (P > 0.05). After the intervention, the left and right eyes of the paper group were significantly reduced (P < 0.05). After the intervention, the difference of the two groups in the refractive power of the left and right eyes was statistically significant (P < 0.05). After treatment, the satisfaction of the experimental group was significantly higher than that of the control group (P < 0.05). After 6 months, there was no significant change in the visual fatigue score of the experimental group, while the visual fatigue score of the control group increased significantly. The traditional Chinese medicine ironing combined with health education intervention can improve the symptoms of adolescents' asthenopia and improve the treatment efficiency. The method is safe, and the operation is convenient. It is worthy of clinical promotion.


An examination of discharge against medical advice from brain injury inpatient rehabilitation.
Discharges against medical advice (DAMA) have been considered predictors of adverse outcomes for patients in acute care and psychiatric hospitals. However, little is known about the profile of patients who discharge AMA admitted to rehabilitation hospitals. The aims of this study were to provide a profile of patients who received inpatient rehabilitation services following a traumatic brain injury (TBI) who discharged AMA and to compare this group with the regular discharge group. Retrospective cohort study. Hospital discharge data from two national administrative databases were reviewed for the years 2001-2006. The databases yielded 1559 cases of TBI (average length of stay = 51 days). Of these, 31 (2.0%) had recorded DAMA events: one in 50 patients left rehabilitation against medical advice. Compared to regular discharge (n = 1247), DAMA was significantly associated with unemployment, intentional injury, higher motor functions at admission and shorter length of stay. Known factors for DAMA in acute hospitals, such as male sex, young age and substance abuse history, were not significant. Careful screening and assessment of patients who discharge AMA could enable better prevention and management strategies, thus improving health outcomes and enhancing healthcare delivery.


Gas chromatography/tandem mass spectrometry analysis of alkylresorcinols in red blood cells.
Erythrocyte alkylresorcinols (5-alkyl-1,3-dihydroxybenzenes) are potential biomarkers of wholegrain wheat and rye intake. However, their high-throughput quantitative analysis by gas chromatography/mass spectrometry (GC/MS) is hindered by the time-consuming sample preparation and, more importantly, by interfering compounds that still remain after sample cleanup. In the present work we describe a gas chromatography/tandem mass spectrometry (GC/MS/MS) method for the rapid and reliable quantification of alkylresorcinols in erythrocyte samples. The performance of the GC/MS/MS method is compared with that of GC/MS. The main characteristics of the method are: lower limits of detection: 2-10 microg/L standard solution; lower limits of quantification: 6-30 microg/L standard solution; linearity coefficients: 0.9611-0.9888; linear ranges: 2-20 microg/L in erythrocytes; and intra-day precisions (n = 6): 4-13% at endogenous analyte levels in non-spiked erythrocytes. Tandem mass spectrometry showed greatly improved selectivity over single-stage mass spectrometry in the case of erythrocyte samples, eliminating all interferences detectable in single-stage MS and enabling simple peak integration for quantification. Moreover, increased selectivity resulted in GC separation speeded up by a factor of two, allowing the duplicate analysis of over 40 samples per day. This GC/MS/MS method is suggested as an improved alternative to GC/MS for the quantification of alkylresorcinols in erythrocytes for assessing wholegrain wheat and rye intake.


Increased numbers of CD8+CD11+, CD8+CD11- and CD8+Leu7+ cells in patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation.
Peripheral blood lymphocytes from 25 allogeneic bone marrow transplant recipients were studied serially using flow cytometry and two colour analysis. Fourteen patients were transplanted for haematologic malignancies, eight for aplastic anaemia, two for congenital immunodeficiencies and one for Morquio's disease. All patients were alive more than 100 days post-grafting; nine patients had chronic graft-versus-host disease (GVHD). Dual labelling with monoclonal antibodies, CD4/2H4, CD4/4B4, CD8/CD11, CD8/HLA-DR and CD8/Leu 7 was used to analyse the surface phenotypes of lymphocytes. The population of CD4+2H4+ cells was decreased, and CD8+CD11+, CD8+CD11- and CD8+Leu7+ cells were markedly increased in patients with chronic GVHD. The increase of CD8+CD11+, CD8+CD11- and CD8+Leu7+ cells closely correlated with clinical signs of chronic GVHD in each patient. These results suggest that CD8+ cells may play an important role in effector and/or suppressor mechanisms of chronic GVHD and could be used as an indicator of need for and response to treatment.


The alpha-smooth muscle actin-positive cells in healing human myocardial scars.
Interstitial cells in the scars of human myocardial infarctions of different postinfarction times (6 hours to 17 years old) were characterized by antibodies to alpha-smooth muscle actin (ASMA), vimentin, and desmin. Basal lamina deposition was studied with antibodies to the basal lamina protein type IV collagen. Nonvascular spindle-shaped cells expressing ASMA were present within 4 to 6 days after infarction. These cells co-expressed vimentin but no desmin and showed discontinuous basal lamina deposition. In electron microscopy these cells showed features characteristic of myofibroblasts. The spindle-shaped cells persisted for a long period of time and could even be identified 17 years postinfarction. In transmural infarctions they were orientated parallel to the endocardium and epicardium. In nontransmural patchy infarctions they showed an orientation adjacent to the cardiomyocytes and appeared to be less dense than in the transmural infarctions. In conclusion, myofibroblasts expressing ASMA persist within human myocardial scars and show a preferential alignment that may be the result of the continuous mechanical stress caused by the ongoing contraction and relaxation of the surrounding viable myocardium.


The "Little AVM": A New Entity in High-flow versus Low-flow Vascular Malformations.
Arteriovenous malformations (AVMs) are high-flow lesions with abnormal connections between arteries and veins without an intervening capillary bed. Infrequently, the radiographic diagnosis of a vascular lesion will not support the clinical diagnosis of an AVM. These "discrepant" lesions are not adequately captured within the current classification system and represent a treatment dilemma. The purpose of this study is to review our center's experience with vascular malformations where incongruity in a patient's clinical and radiographic presentation produces a diagnostic and therapeutic challenge. A retrospective chart review of patients with atypical AVM pre sen ta tions was performed. Parameters reviewed included patient history and demogra phics, clinical presentation, radiological imaging, and treatment modalities. Over a 15-year period, we identified 7 cases of vascular malformations with discrepant clinical and radiological findings concerning flow characteristics. All patients were treated based on their radiological diagnosis and most were managed with sclerotherapy. No lesions evolved into a high-flow process, and there was no recurrence at a minimum of 24 months of follow-up. We have identified and described a unique subcategory of vascular malformations that have clinical features of high-flow malformations but radiological features of low-flow malformations. These lesions behave like low-flow malformations and should be treated as such. We propose that complex vascular malformations are best evaluated by both clinical and specialized diagnostic radiological means; the radiologic diagnoses should supplant what is found clinically, and ultimately treatment should be preferentially based on a radiological diagnosis.


Rapid and sensitive nonradioactive detection of mutant K-ras genes via 'enriched' PCR amplification.
We have developed a rapid and highly sensitive nonradioactive method for the detection of a mutant codon 12 human c-K-ras allele in the presence of as many as 10(4) copies of the wild type codon 12 allele. This sensitivity is achieved by selective polymerase chain reaction (PCR) amplification of mutant K-ras gene sequences employing a two stage procedure. The first stage entails the amplification of both K-ras mutant and wild type codon 12 sequences, followed by a selective restriction enzyme digestion of only wild type sequences. The second stage involves a subsequent amplification of undigested amplified fragments, enriched in mutant codon 12 sequences. These products are subject to restriction length polymorphism analysis for the detection of point mutations at codon 12. This technique is rapid, nonradioactive, and eliminates the need for either oligonucleotide hybridization or DNA sequencing. Variations of this selective amplification procedure may prove promising for the detection of specific point mutations in heterogenous cell populations.


Effects of novel beta-adrenoceptor agonists on carbohydrate metabolism: relevance for the treatment of non-insulin-dependent diabetes.
BRL 26830A, (R*, R*)-(+/-)-methyl 4-[2-[(2-hydroxy-2-phenylethyl) amino] propyl]-benzoate, (E)-2-butenedioate (2:1) salt, is a new antihyperglycemic agent orally active in obese-hyperglycemic animal models. In C57Bl/6 ob/ob mice, BRL 26830A (1 mg/kg) given daily for periods of 14 d-6 weeks produced a marked improvement in glucose tolerance and a reduction in the fasting plasma insulin concentration. Adipocytes prepared from treated mice showed improved insulin responsiveness. In Zucker fa/fa rats, treatment with BRL 26830A (2.9 mg/kg/d for 23 d) produced improvements in both glucose tolerance and whole animal insulin sensitivity, as assessed by rate of fall of blood glucose in response to an intravenous dose of insulin. In C57Bl/KSJ db/db mice, BRL 26830A (admixed with food at 50 mg/kg diet) decreased blood glucose to values similar to those in lean mice. At the end of a 10-week treatment, BRL 26830A-treated mice had a higher plasma and pancreatic insulin content than the untreated db/db mice. In normoglycaemic rats and mice, BRL 26830A increases the plasma insulin concentration and increases glucose disposal. However, in most circumstances, there is a counteracting increase in endogenous glucose synthesis and, therefore, no change in blood glucose occurs. Improvements in glucose tolerance occur in 24-h fasted rats and mice. BRL 26830A has thermogenic activity and it is suggested that this might be linked to increased glucose utilization. Brown adipose tissue (BAT) of C57Bl/KSJ db/db mice has a reduced maximum glycolytic capacity relative to lean littermates. Treatment with BRL 26830A increased the glycolytic capacity 10-fold.


COX16 promotes COX2 metallation and assembly during respiratory complex IV biogenesis.
Cytochrome c oxidase of the mitochondrial oxidative phosphorylation system reduces molecular oxygen with redox equivalent-derived electrons. The conserved mitochondrial-encoded COX1- and COX2-subunits are the heme- and copper-center containing core subunits that catalyze water formation. COX1 and COX2 initially follow independent biogenesis pathways creating assembly modules with subunit-specific, chaperone-like assembly factors that assist in redox centers formation. Here, we find that COX16, a protein required for cytochrome c oxidase assembly, interacts specifically with newly synthesized COX2 and its copper center-forming metallochaperones SCO1, SCO2, and COA6. The recruitment of SCO1 to the COX2-module is COX16- dependent and patient-mimicking mutations in SCO1 affect interaction with COX16. These findings implicate COX16 in CuA-site formation. Surprisingly, COX16 is also found in COX1-containing assembly intermediates and COX2 recruitment to COX1. We conclude that COX16 participates in merging the COX1 and COX2 assembly lines.


rs10263935 and rs6045676 identified by genome-wide association study were associated with aortic dissection in a Chinese population.
Aortic dissection (AD) is a disease characterized by a tear in the aortic intimal layer and separation of the arterial wall. Some risk factors, such as hypertension and Marfan syndrome, are well known in AD, but the role of genetic factor is largely unknown. In this study, we investigated the relation between two single nucleotide polymorphisms (SNPs) identified by genome-wide association study and AD. Approximately 177 patients diagnosed with AD through clinical evaluation and imaging techniques and 183 age- and sex-matched control subjects who were suffering from chest pain but without AD were included in the study. Genotyping of rs10263935 and rs6045676 was performed in both patients and control subjects using the TaqMan(®) method [Life Technologies (AB & Invitrogen), Carlsbad, CA]. The frequency of the AA and AG genotype in rs10263935 was significantly higher in the AD patients (0.085 and 0.435, respectively) than in the control subjects (0.033 and 0.355, respectively). The rs10263935 A allele frequency in the AD patients was higher than that in the control subjects [0.302 vs 0.210, odds ratio (OR) = 1.62, 95% confidence interval (CI): 1.26-2.28, P = 0.005]. Similarly, the frequency of the GG genotype in rs6045676 was significantly higher in the AD patients than in the control subjects (0.107 vs 0.038, P = 0.015). The rs6045676 G allele frequency in the AD patients was higher than that in the control subjects (0.282 vs 0.191, OR = 1.67, 95% CI: 1.18-2.50, P = 0.004). After adjustment of the confounding factors, such as smoking, sex, and age, the differences remain significant in several models (rs10263935: GG vs AA: OR = 3.13, 95% CI: 1.15-8.33, P = 0.025; GG vs AG: OR = 1.57, 95% CI: 1.01-2.44, P = 0.045; rs6045676: GG vs CC: OR = 3.30, 95% CI: 1.32-8.25, P = 0.011). rs10263935 on chromosome 7 and rs6045676 on chromosome 20 are associated with AD. Further studies are warranted to elucidate the functional role of these two variants.


Bioleaching of zinc and iron from steel plant waste using Acidithiobacillus ferrooxidans.
The bacterial leaching of zinc and iron from solid wastes at the Isdemir iron and steel plant has been investigated using Acidithiobacillus ferrooxidans as the bacterial agent. The effects of a range of operational parameters, including particle size, solids concentration and pH, on the efficiency of the bioleaching process were investigated. In each test, several variables were determined to assess the efficiency of leaching, including slurry pH and redox potential, temperature, bacteria population and concentrations of zinc and iron in solution. Experimental results demonstrated that pulp solids concentration, slurry pH and solids particle size were all important parameters in the bacterial leaching process. Maximum extraction was achieved at pH values around 1.3 and a solids concentration of 1% w/v, with 35% of the Zn content and 37% of the Fe being dissolved.


Inhibitory effect of oleanolic acid from the rhizomes of Cyperus rotundus on transient receptor potential vanilloid 1 channel.
Cyperus rotundus is used as an analgesic and sedative in oriental medicine and has been reported to exhibit antinociceptive and anti-inflammatory effects. On the other hand, the transient receptor potential vanilloid 1 channel is a nonselective cation channel that senses various noxious chemical and thermal stimuli. However, it has recently been reported that the epidermally expressed transient receptor potential vanilloid 1 channel is involved in heat- and UV-induced skin aging. The aim of this study was to evaluate whether C. rotundus extract and its constituents can inhibit this channel. Ethylacetate and hexane fractions of the methanol extract were found to partially inhibit transient receptor potential vanilloid 1 channel activity, and at a concentration of 90 µM, oleanolic acid, which was one of three constituents isolated from the ethylacetate fraction, inhibited this activity by 61.4 ± 8.0 %. This is first electrophysiological study to be conducted on the effects of C. rotundus extract and its constituents on the transient receptor potential vanilloid 1 channel. The results obtained provide insight of the potential therapeutic effects of C. rotundus in the contexts of analgesia and UV-induced photoaging.


GRade, Age, Nodes, and Tumor (GRANT) compared with Leibovich score to predict survival in localized renal cell carcinoma: A nationwide study.
To examine the performance of Leibovich score versus GRade, Age, Nodes, and Tumor score in predicting disease recurrence in renal cell carcinoma. In total, 7653 patients diagnosed with renal cell carcinoma from 2010 to 2018 were captured in the nationwide DaRenCa database; 2652 underwent radical or partial nephrectomy and had full datasets regarding the GRade, Age, Nodes, and Tumor score and Leibovich score. Discrimination was assessed with a Cox regression model. The results were evaluated with concordance index analysis. Median follow-up was 40 months (interquartile range 24-56). Recurrence occurred in 17%, and 15% died. A significant proportion of patients (36%) had missing data for the calculation of the Leibovich score. Among 1957 clear cell renal cell carcinoma patients the distribution of GRade, Age, Nodes, and Tumor score of 0, 1, 2, or 3/4 was 21%, 56%, 21% and 1.4%, respectively, and for Leibovich score of low/intermediate/high this was 47%, 36% and 18%, respectively. A similar distribution was seen in 655 non-clear cell patients. Both Leibovich and GRade, Age, Nodes, and Tumor scores performed well in predicting outcomes for the favorable patient risk groups. The Leibovich score was better at predicting recurrence-free survival (concordance index 0.736 versus 0.643), but not overall survival (concordance index 0.657 versus 0.648). Similar results were obtained in non-clear cell renal cell carcinoma. GRade, Age, Nodes, and Tumor and Leibovich scores were validated in clear cell and non-clear cell renal cell carcinoma. Leibovich score outperformed the GRade, Age, Nodes, and Tumor score in predicting recurrence-free survival and should remain the standard approach to risk stratify patients during follow-up when all data are available.


New insights into bacterial type II polyketide biosynthesis.
Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures and biological activities and are usually biosynthesized by type II polyketide synthases (PKSs). Since the starting point of biosynthesis and combinatorial biosynthesis in 1984-1985, there has been a continuous effort to investigate the biosynthetic logic of aromatic polyketides owing to the urgent need of developing promising therapeutic candidates from these compounds. Recently, significant advances in the structural and mechanistic identification of enzymes involved in aromatic polyketide biosynthesis have been made on the basis of novel genetic, biochemical, and chemical technologies. This review highlights the progress in bacterial type II PKSs in the past three years (2013-2016). Moreover, novel compounds discovered or created by genome mining and biosynthetic engineering are also included.


The protective effects of Zhen-Wu-Tang against cisplatin-induced acute kidney injury in rats.
Acute kidney injury (AKI) is a common clinical condition that confers a risk of progression of chronic kidney disease and a high risk of death. The purpose of the current study is to investigate the anti-apoptotic and anti-fibrotic effects of Zhen-Wu-Tang (ZWT) on cisplatin (CIS)-induced renal injury and elucidate the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the PI3K/Akt signaling pathway, transforming growth factor (TGF)-β and the Wnt/β-catenin signaling pathway in the positive effects of Zhen-Wu-Tang on the kidneys. Wistar rats were randomly assigned into six groups of 6 rats each as follows: normal control 1; normal control 2; CIS 1 and CIS 2, which received single intraperitoneal injections of CIS (6 mg/kg); CIS+ZWT 4 and CIS+ZWT 10, which received ZWT (1 ml/100 g/day, ig) starting days after the CIS injection for 4 and 10 days, respectively. Hematoxylin-eosin (H&E) staining was performed to identify the amelioration of histopathological changes in the kidneys and apoptosis of the renal proximal tubular cells. Picrosirius red staining was used to evaluate renal fibrosis after ZWT treatment. The relationship between ZWT and the upregulation of Nrf2, phosphorylation of Akt, and the downregulation of TGF-β and WNT/β-catenin were determined by Western blotting. At the end of the experiment, serum was isolated from the orbital blood of rats, and blood urea nitrogen (BUN) and creatinine (Cr) levels were measured. The results showed that ZWT restored the histological alterations, aberrant collagen deposition in the kidneys and the BUN and Cr levels that were increased by CIS. Treatment with ZWT reduced the expression levels of TGF-β and Wnt and increased the expression levels of Nrf2, PI3K and Akt in the CIS-exposed kidney tissues. Furthermore, ZWT downregulated apoptosis and fibrosis by modulating the expression levels of caspase-3, Bax and alpha-smooth muscle actin (α-SMA). In conclusion, this study provides evidence for the anti-fibrotic and anti-apoptotic roles of ZWT in CIS-induced experimental kidney injury.


12 hour shifts the Nambour Hospital experience.
Union members have a lengthy history of campaigning for fair working hours and conditions. The success of such campaigns has led to the implementation of the eight hour working day and the 40 hour and then 38 hour week as industrial standards. More recently though, calls for greater flexibility in their shift arrangements by nurses at Nambour Hospital have led to a voluntary 12 hour shift being implemented in their Intensive Care Unit. While union members are protective of their hard won gains in achieving reduced working hours through the 8 hour day--ICU nurses at Nambour Hospital say the voluntary 12 hour shift initiative goes a way in addressing their work/life balance issues.


Lipid Target in Very High-Risk Cardiovascular Patients: Lesson from PCSK9 Monoclonal Antibodies.
The role of low-density lipoproteins (LDLs) as a major risk factor for cardiovascular disease has been demonstrated by several epidemiological studies. The molecular basis for LDLs in atherosclerotic plaque formation and progression is not completely unraveled yet. Pharmacological modulation of plasma LDL-C concentrations and randomized clinical trials addressing the impact of lipid-lowering interventions on cardiovascular outcome have clearly shown that reducing plasma LDL-C concentrations results in a significant decrease in major cardiovascular events. For many years, statins have represented the most powerful pharmacological agents available to lower plasma LDL-C concentrations. In clinical trials, it has been shown that the greater the reduction in plasma LDL-C concentrations, the lower the rate of major cardiovascular events, especially in high-risk patients, because of multiple risk factors and recurrent events. However, in a substantial number of patients, the recommended LDL target is difficult to achieve because of different factors: genetic background (familial hypercholesterolemia), side effects (statin intolerance), or high baseline plasma LDL-C concentrations. In the last decade, our understanding of the molecular mechanisms involved in LDL metabolism has progressed significantly and the key role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged. This protein is an enzyme able to bind the LDL receptors (LDL-R) on hepatocytes, favoring their degradation. Blocking PCSK9 represents an intriguing new therapeutic approach to decrease plasma LDL-C concentrations, which in recent studies has been demonstrated to also result in a significant reduction in major cardiovascular events.


Suprofen. An overview of long-term safety.
Suprofen, a new oral peripherally acting analgesic agent, has been shown to be effective in the relief of acute and chronic pain. This paper reviews data relative to long-term safety from more than 800 patients who received suprofen. Some of these patients were followed up to 2 years. Suprofen was generally found to be at least as safe and as well tolerated as reference drugs of aspirin, propoxyphene and propoxyphene combination. The discontinuance rate because of side effects was 17.7% for patients receiving suprofen and 23.9% for patients receiving reference drugs. Gastrointestinal side effects were the most frequently reported reasons for all patient dropout in all treatment groups. Fewer patients receiving suprofen discontinued due to gastrointestinal side effects (10.9%) than with reference drugs (17.2%).


A retrospective, descriptive, exploratory study evaluating incidence of postoperative urinary retention after spinal anesthesia and its effect on PACU discharge.
Postoperative urinary retention (POUR) is a common problem that occurs at rates ranging from 7% to 52%. It is uncertain exactly what patient-related or surgery factors may influence POUR. This retrospective, descriptive, exploratory study of 102 patients examined the incidence of POUR, its impact on length-of-stay, and the patient/procedural characteristics that are associated with POUR. The incidence of POUR in our facility was found to be 44.1%. Length-of-stay in the PACU was 26 minutes longer for patients with POUR; although not statistically significant, this was clinically significant. Mean bladder volume on admission to the PACU was 467.6 mL (range, 0 to 1000 mL) with >500 mL associated with POUR, chi(2) = .00. A protocol for draining the patient's bladder at the end of the surgical procedure or immediately upon admission to the PACU could be beneficial to both patients and PACU nursing staff by reducing patient discomfort and length-of-stay.


Tranexamic acid in bleeding reduction and operative time of nasal surgeries: systematic review and meta-analysis.
Our study goal is to review the efficacy of tranexamic acid in reducing blood loss and operative time in nasal surgeries. We included randomized clinical trials using oral or intravenous tranexamic acid, excluded non-randomized studies, topic administration, coagulopathy, and using other drugs interfering in the coagulation cascade. Online databases, National Library of Medicine (MEDLINE-PubMED), Latin American and Caribbean Literature on Health Sciences (Lilacs), Cochrane Library, Embase and Google Scholar were used to perform the search. The review was registered in PROSPERO by no CRD42022310977. Two authors, independently, selected the articles meeting the inclusion criteria. They extracted the data and used RevMan 5 software to perform the meta-analysis. Our search resulted in 16 RCTs that were included in the meta-analysis totalizing 1108 patients. Studies were evaluated resulting in a low risk of bias for the five domains. The use of tranexamic acid resulted in significant reduction in duration of surgery (DOS) and intraoperative blood loss (IBL) had significant reduction. The level of evidence according to GRADE System was high in all studies and variables. Tranexamic acid has an important role in reducing intraoperative blood loss and duration of surgery. Our study has some limitations due to the low number of RCTs available in the literature.


Suppression of SMOC2 alleviates myocardial fibrosis via the ILK/p38 pathway.
Fibrosis of the myocardium is one of the main pathological changes of adverse cardiac remodeling, which is associated with unsatisfactory outcomes in patients with heart disease. Further investigations into the precise molecular mechanisms of cardiac fibrosis are urgently required to seek alternative therapeutic strategies for individuals suffering from heart failure. SMOC2 has been shown to be essential to exert key pathophysiological roles in various physiological processes in vivo, possibly contributing to the pathogenesis of fibrosis. A study investigating the relationship between SMOC2 and myocardial fibrosis has yet to be conducted. Mice received a continuous ISO injection subcutaneously to induce cardiac fibrosis, and down-regulation of SMOC2 was achieved by adeno-associated virus-9 (AAV9)-mediated shRNA knockdown. Neonatal fibroblasts were separated and cultured in vitro with TGFβ to trigger fibrosis and infected with either sh-SMOC2 or sh-RNA as a control. The role and mechanisms of SMOC2 in myocardial fibrosis were further examined and analyzed. SMOC2 knockdown partially reversed cardiac functional impairment and cardiac fibrosis in vivo after 21 consecutive days of ISO injection. We further demonstrated that targeting SMOC2 expression effectively slowed down the trans-differentiation and collagen deposition of cardiac fibroblasts stimulated by TGFβ. Mechanistically, targeting SMOC2 expression inhibited the induction of ILK and p38 in vivo and in vitro, and ILK overexpression increased p38 phosphorylation activity and compromised the protective effects of sh-SMOC2-mediated cardiac fibrosis. Therapeutic SMOC2 silencing alleviated cardiac fibrosis through inhibition of the ILK/p38 signaling, providing a preventative and control strategy for cardiac remodeling management in clinical practice.


Prediction of outcomes for patients with brain parenchymal metastases from breast cancer (BC): a new BC-specific prognostic model and a nomogram.
The purpose of this study is to validate the recently published Breast-Graded Prognostic Assessment (GPA) and propose a new prognostic model and nomogram for patients with brain parenchymal metastases (BM) from breast cancer (BC). We retrospectively investigated 171 consecutive patients who received a diagnosis of BM from BC during 2000-2008. We appraised the recently proposed Sperduto's BC-specific GPA in training cohort through Kaplan-Meier survival curve using log-rank test and area under the curve for the BC-GPA predicting overall survival at 1 year and developed a new nomogram to predict outcomes using multivariate Cox-regression analysis. By putting the Sperduto's Breast-GPA together with our nomogram, we developed a new prognostic model. We validated our new prognostic model with an independent external patient cohort from 2 institutes for the same period. On the basis of our Cox-regression analysis, therapeutic effect of trastuzumab and status of extracranial systemic disease control were incorporated into our new prognostic model in addition to Karnofsky performance status, age, and hormonal status. Our new prognostic model showed significant discrimination in median survival time, with 3.7 months for class I (n = 15), 7.8 months for class II (n = 82), 10.7 months for class III (n = 42), and 19.2 months for class IV (n = 32; P < .0001). The new prognostic model accurately predicted survival among patients with BC from BM in an external validation cohort (P < .0001). We propose a new prognostic model and a nomogram reflecting the different biological features of BC, including treatment effect and status of extracranial disease control, which was excellently validated in an independent external cohort.


Serotonergic modulation of appetitive and ingestive behavior in crayfish.
Serotonin is an important modulator of feeding behavior across animal species. In invertebrates, much is known about the regulation of feeding in several model organisms, but comparative data are limited. We examined the modulation of feeding behavior in crayfish by administering serotonin and two serotonin receptor ligands, mianserin and 5-carboxamidotryptamine. We found that, compared to control injections, exogenous serotonin significantly reduced appetitive behaviors in response to a chemical food stimulant and reduced consumption when food was present. The two ligands also significantly reduced the amount of food consumed. However, they had no significant effects on appetitive feeding movements, suggesting that appetitive and consummatory feeding phases may be regulated by different serotonergic mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


PB1-F2 Protein Does Not Impact the Virulence of Triple-Reassortant H3N2 Swine Influenza Virus in Pigs but Alters Pathogenicity and Transmission in Turkeys.
PB1-F2 protein, the 11th influenza A virus (IAV) protein, is considered to play an important role in primary influenza virus infection and postinfluenza secondary bacterial pneumonia in mice. The functional role of PB1-F2 has been reported to be a strain-specific and host-specific phenomenon. Its precise contribution to the pathogenicity and transmission of influenza virus in mammalian host, such as swine, and avian hosts, such as turkeys, remain largely unknown. In this study, we explored the role of PB1-F2 protein of triple-reassortant (TR) H3N2 swine influenza virus (SIV) in pigs and turkeys. Using the eight-plasmid reverse genetics system, we rescued wild-type SIV A/swine/Minnesota/1145/2007 (H3N2) (SIV 1145-WT), a PB1-F2 knockout mutant (SIV 1145-KO), and its N66S variant (SIV 1145-N66S). The ablation of PB1-F2 in SIV 1145 modulated early-stage apoptosis but did not affect the viral replication in swine alveolar macrophage cells. In pigs, PB1-F2 expression did not affect nasal shedding, lung viral load, immunophenotypes, and lung pathology. On the other hand, in turkeys, SIV 1145-KO infected poults, and its in-contacts developed clinical signs earlier than SIV 1145-WT groups and also displayed more extensive histopathological changes in intestine. Further, turkeys infected with SIV 1145-N66S displayed poor infectivity and transmissibility. The more extensive histopathologic changes in intestine and relative transmission advantage observed in turkeys infected with SIV 1145-KO need to be further explored. Taken together, these results emphasize the host-specific roles of PB1-F2 in the pathogenicity and transmission of IAV. Novel triple-reassortant H3N2 swine influenza virus emerged in 1998 and spread rapidly among the North American swine population. Subsequently, it showed an increased propensity to reassort, generating a range of reassortants. Unlike classical swine influenza virus, TR SIV produces a full-length PB1-F2 protein, which is considered an important virulence marker of IAV pathogenicity. Our study demonstrated that the expression of PB1-F2 does not impact the pathogenicity of TR H3N2 SIV in pigs. On the other hand, deletion of PB1-F2 caused TR H3N2 SIV to induce clinical disease early and resulted in effective transmission among the turkey poults. Our study emphasizes the continuing need to better understand the virulence determinants for IAV in intermediate hosts, such as swine and turkeys, and highlights the host-specific role of PB1-F2 protein.


Quantitating the relative abundance of isoaspartyl residues in deamidated proteins by electron capture dissociation.
Relative quantitation of aspartyl and isoaspartyl residue mixtures from asparagine deamidation is demonstrated using electron capture dissociation without prior HPLC separation. The method utilizes the linear relationship found between the relative abundance of the isoaspartyl diagnostic ion, z(n)-57, and % isoaspartyl content based on the ECD spectra of known isoaspartyl/aspartyl mixtures of synthetic peptides. The observed linearity appears to be sequence independent because the relationship exists despite sequence variations and changes in backbone fragment abundances when isoaspartyl and aspartyl residues are interchanged. Furthermore, a new method to calculate the relative abundances of isomer from protein deamidation without synthetic peptides is proposed and tested using a linear peptide released by protein digestion that contains the deamidation site. The proteolytic peptide can be rapidly aged to the expected 3:1 (isoaspartyl:aspartyl) mixture to generate a two-point calibration standard for ECD analysis. The procedure can then be used to determine the relative abundance of deamidation products from in vivo or in vitro protein aging experiments.


High-precision cavity spectroscopy using high-frequency squeezed light.
In this article, we present a novel spectroscopy technique that improves the signal-to-shot-noise ratio without the need to increase the laser power. Detrimental effects by technical noise sources are avoided by frequency-modulation techniques (frequency up-shifting). Superimposing the signal on non-classical states of light leads to a reduced quantum noise floor. Our method reveals in a proof-of-concept experiment small signals at Hz to kHz frequencies even below the shot noise limit. Our theoretical calculations fully support our experimental findings. The proposed technique is interesting for applications such as high-precision cavity spectroscopy, e.g., for explosive trace gas detection where the specific gas might set an upper limit for the laser power employed.


Inhibitory effect of the DA uptake blocker GBR 12909 on sodium channels of hippocampal neurons.
The effect of the selective dopamine uptake inhibitor GBR 12909 on TTX-sensitive sodium channels of cultured hippocampal neurons was investigated using whole cell patch-clamp technique. GBR 12909 dose-dependently inhibited sodium currents evoked by trains of depolarizing pulses with an IC50 of 6.3 microM. A weaker inhibition (IC50 = 17-35 microM) could be observed when currents were evoked by either single pulse depolarization or from hyperpolarized holding membrane potential. These data indicate that the extent of inhibition caused by GBR 12909 depends on the physiological activity pattern of neurons. Our results suggest that caution is needed for the interpretation of data when GBR 12909 is used for the inhibition of dopamine uptake at concentrations above the submicromolar range.


Heterodimeric deoxyguanosine kinase/deoxyadenosine kinase of Lactobacillus acidophilus R-26: heterotropic activation of deoxyadenosine kinase subunit implicated by limited proteolysis and affinity labeling.
The deoxyguanosine (dGuo) kinase/deoxyadenosine (dAdo) kinase complex of Lactobacillus has been purified to homogeneity by using a newly constructed dATP-Sepharose column as a final step (2700-fold purification). A heterodimeric structure for the complex has recently been established [Ikeda et al. (1994) Biochemistry 33, 5328-5334]. On the basis of the kinetic and structural data accumulated so far, a model for the heterotropic activation of the dAdo kinase subunit by dGuo or dGTP is proposed: (1) there is an intrinsic difference in the enzyme conformation of the two subunits, with the dAdo kinase subunit being in a constrained (closed) state and the counterpart dGuo kinase subunit being in a relaxed (open) state, as reflected in their relative Vmax values and in the presence or absence of heterotropic activation, and (2) the conformational change induced by the binding of dGuo or dGTP to the active site of the dGuo kinase subunit causes the activation of the dAdo kinase subunit through subunit--subunit interactions. These proposed mechanisms are strongly supported by the following new findings made in this work: (1) low concentrations of chaotropic agents such as guanidine--HCl were found to increase the Vmax of dAdo kinase up to 2-fold--in the same kinetic fashion, apparently, as the activation by dGuo--while showing no effect on dGuo kinase; (2) the proteolytic inactivation of dAdo kinase by trypsin is significantly slower than that of dGuo kinase, but its rate of inactivation is stimulated by dGTP to the same level as for dGuo kinase; (3) the activating effect of dGuo on dAdo kinase was abolished in the course of differential proteolytic inactivation of the dGuo kinase by trypsin in the presence of dATP; and (4) photoaffinity labeling with [8-14C]-8-azido-Ade produces a new species of kinase heterodimer in which the dAdo kinase subunit is permanently activated as a result of specific labeling of the dGuo kinase active site.


Synergistic anti-tumor effect of paclitaxel with CRM197, an inhibitor of HB-EGF, in ovarian cancer.
Heparin-binding EGF-like growth factor (HB-EGF) plays a pivotal role in tumor growth and clinical outcomes in patients with ovarian cancer, leading to the validation of HB-EGF as a target for ovarian cancer therapy. In this study, we investigated the anti-tumor effects of paclitaxel, as an anti-cancer agent, and CRM197, as a specific inhibitor off HB-EGF, in ovarian cancer. Paclitaxel induced transient ERK activation and sustained activation of JNK and p38 MAPK through the ectodomain shedding of HB-EGF in SKOV3 cells. In addition, the overexpression of HB-EGF in paclitaxel-treated SKOV3 cells resulted in modulation of paclitaxel-evoked MAPK signaling, including marked activation of ERK and Akt, and minimized activation of JNK and p38 MAPK, indicating that HB-EGF is involved in drug sensitivity through the balance of anti-apoptotic and pro-apoptotic signals induced by paclitaxel. The combination of paclitaxel with CRM197 had an inhibitory effect on cell proliferation and enhanced apoptosis via the inhibition of ERK and Akt activation and the stimulation of p38 and JNK activation. More prominently, the administration of paclitaxel with CRM197 resulted in synergistic anti-tumor effects in SKOV3 cells and in SKOV3 cells overexpressing HB-EGF in xenografted mice. Accordingly, inhibitory agents against HB-EGF, such as CRM197, represent possible chemotherapeutic and chemosensitizing agents for ovarian cancer.


Lymphocyte subsets in patients with acute myopericarditis, arrhythmias and dilated cardiomyopathy.
To investigate the role of immunoregulatory function in determining the clinical course of acute myopericarditis, lymphocyte subsets were analysed by laser flow cytometry in 20 patients with acute myopericarditis, 30 with various arrhythmias or atrio-ventricular block and 31 with dilated cardiomyopathy. During the healing stage of acute myopericarditis, patients with residual electrocardiographic or left ventricular wall motion abnormalities presented altered frequencies of lymphocyte subsets, increased B 1 and reduced OKT 8 positive cells with an elevated OKT 4/8 ratio. The abnormal pattern was not evident in patients with acute pericarditis nor in those with acute myocarditis who recovered completely without residual abnormalities. This observation suggested that an imbalance of helper/suppressor T cells could modulate the clinical course of acute myopericarditis, either by producing extensive and irreversible myocardial damage during acute illness or by inducing chronic smoulding myocardial inflammation. Patients with ventricular arrhythmias and left ventricular wall motion abnormalities also presented reduced suppressor/cytotoxic T cells, implying that they had been suffering from chronic smoulding myocarditis mediated by immunoregulatory dysfunction. However, we could not determine whether the imbalance of helper/suppressor T cells could mediate the progression from myocarditis to dilated cardiomyopathy, since no association was demonstrated between the abnormal lymphocyte subsets and mononuclear cell infiltration in endomyocardial biopsy sample from patients with dilated cardiomyopathy.


Auditory agnosia associated with bilateral putaminal hemorrhage: A case report of clinical course of recovery.
A 45-year-old right-handed man with a past history (10 years) of putaminal hemorrage presented with auditory agnosia associated with left putaminal hemorrhage. It was suspected that the auditory agnosia was due to bilateral damage in the acoustic radiations. Generalized auditory agnosia, verbal and non-verbal (music and environmental), was diagnosed by neuropsychological examinations. It improved 4 months after the onset. However, the clinical assessment of attention remained poor. The cognition for speech sounds improved slowly, but once it started to improve, the progress of improvement was rapid. Subsequently, the cognition for music sounds also improved, while the recovery of the cognition for environmental sounds remained delayed. There was a dissociation in recovery between these cognitions. He was able to return to work a year after the onset. We also reviewed the literature for cases with auditory agnosia and discuss their course of recovery in this report.


Factors influencing cognitive function in patients with Huntington's disease from China: A cross-sectional clinical study.
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG repeats expansion. Cognitive decline contributes to the loss of daily activity in manifest HD. We aimed to examine the cognition status in a Chinese HD cohort and explore factors influencing the diverse cognitive domains. A total of 205 participants were recruited in the study with the assessment by neuropsychological batteries, including the mini-mental state examination (MMSE), Stroop test, symbol digit modalities test (SDMT), trail making test (TMT), verbal fluency test (VFT), and Hopkins verbal learning test-revised, as well as motor and psychiatric assessment. Pearson correlation and multiple linear regression models were applied to investigate the correlation. Only 41.46% of patients had normal global function first come to our center. There was a significantly difference in MMSE, Stroop test, SDMT, TMT, and VFT across each stage of HD patients (p < .05). Apathy of PBA-s was correlated to MMSE, animal VFT and Stroop-interference tests performance. Severity of motor symptoms, functional capacity, age, and age of motor symptom onset were correlated to all neuropsychological scores, whereas education attainment and diagnostic delay were correlated to most neuropsychological scores except TMT. Severity of motor symptoms, functional capacity, and education attainment showed independent predicting effect (p < .05) in diverse cognitive domains. Cognitive impairment was very common in Chinese HD patients at the first visit and worse in the patients in advanced phase. The severity of motor symptoms and functional capacity were correlated to the diverse cognitive domains.


[Immunotherapy of cancer using cytokinins. Use and perspectives in lung oncology].
Progress in genetics now enables the synthesis of molecules acting on the regulation of the immune system which are called cytokines. Currently there are several cytokines, Interferon (IFN), Interleukin 2 (IL2), tumour necrosis factor (TNF) as well as haematopoietic growth factors and these are the object of study in clinical trials. Interferon has already been used in the therapy of hairy cell leukaemia, Kaposi sarcoma associated with AIDS(SIDA) and metastasis of malignant melanoma. Interleukin 2 allows for an increase in the cytotoxic activity of NK cells in producing LAK cells, the lymphocyte infiltrating the tumour (TIL). Therapeutic combinations combining IL2 associated with LAK or of TIL have been evaluated in some private studies. These treatments have shown some interesting response levels on those tumours which are usually resistant, such as malignant melanoma or carcinoma of the kidney. TNF is active in vitro on human tumours; its potential toxicity is important; it is the object of a phase 1 clinical trial. Haematopoietic growth factors, G-CSF and GM-CSF, stimulate the production of leucocytes which will be valuable to correct toxic affects on the marrow during chemotherapy. This will enable chemotherapy to be given at a high dose.


The interaction of calcitonin gene-related peptide with angiotensin II on blood pressure and renin release.
Calcitonin gene-related peptide (CGRP) has been shown to be a potent vasorelaxant. We tested the interaction of CGRP with angiotensin II (Ang II) in conscious, unrestrained Wistar rats. Rat CGRP (rCGRP, 0.1 and 1.0 nmol/kg per min) dose-dependently lowered mean arterial blood pressure and increased the heart rate. The effects continued throughout the infusion period of 30 min. Moreover, rCGRP significantly attenuated the pressor responses to Ang II (100 ng/kg per min). High-dose rCGRP (1.0 nmol/kg per min) almost abolished the pressor action of Ang II, and a much higher dose of Ang II (1000 ng/kg per min) was needed to restore the pre-infusion pressure. Plasma renin activity was dose-dependently increased by rCGRP, but was attenuated by simultaneous Ang II infusion. Rat CGRP also increased the plasma aldosterone concentration, as did Ang II. These results suggest that CGRP may have a neuromodulatory role in cardiovascular regulation.


The prevention paradox, traffic safety, and driving-while-intoxicated treatment.
In San Juan County, New Mexico, a 28-day jail/treatment program for first-time driving-while-intoxicated (DWI) offenders was established in 1994 to reduce both DWI recidivism and alcohol-related crashes. This paper assesses the impact of the program on both outcomes. The data are composed of driving records of all people arrested for DWI in San Juan County from August 1994 through December 2001. Subsequent re-arrests and crashes were analyzed to compare people who had been sentenced to the jail/treatment program and those who had not. Kaplan-Meier survival curves and Cox proportional hazards regression analyses were used. Covariates included age, gender, blood alcohol content (BAC), number of prior arrests, and ethnicity (Native American, non-Hispanic white, and Hispanic). Re-arrest rates were significantly lower for the treatment than the nontreatment group. Each of the three major ethnic groups showed similar effects. This was not observed for subsequent alcohol-related crashes, possibly as a result of insufficient numbers. BAC and number of previous arrests were, however, significant risk factors for subsequent crashes. Finally, although BAC and previous arrests were important risk factors for subsequent crashes, the vast majority of subsequent alcohol-related crashes occurred among people in the intermediate risk ranges. The jail/treatment program is effective in reducing the probability of DWI re-arrests. The evidence with respect to crashes is equivocal. That most crashes occur to people in the intermediate risk range exemplifies the prevention paradox, and means that the courts, which deal most severely with high-risk individuals, cannot be expected to have a major impact on alcohol-related crashes.


Bodies in relation--bodies in transition: lesbian partners of trans men and body image.
Presenting published narratives of transgender and transsexual men (henceforth "trans men"), along with case study interview narratives from five lesbian-identified partners of trans men, I consider how body image issues may surface both individually and interpersonally in relation to the body dysphoria of a trans partner. In addition to self-reports of negatively shifting body image among some interviewees, I also discuss how negative body image may adversely affect these relationships in terms of sexual and non-sexual intimacy, bodily self-expression, and self-confidence. I term these processes and effects relational body image in order to trouble dominant conceptualizations of negative body image as primarily an individual issue arising from external, macro-sociological forces and pressures. I present these cases as a starting point for future sociological theorizing and empirical work with this under-studied population.


Management of atherosclerosis risk factors for patients at high cardiovascular risk in real-world practice: a multicentre study.
Atherosclerotic cardiovascular disease is a global health burden. However, there are heterogeneities among countries or regions in the risk factors and clinical manifestations of atherosclerotic diseases as well as management patterns. We collected data from 25 centres in Thailand. Patients with documented coronary artery disease, cerebrovascular disease or peripheral arterial disease, or with at least three atherosclerosis risk factors were enrolled between April 2011 and March 2014. Data on demographics, atherosclerosis risk factors and the management pattern of risk factors, including laboratory findings, were recorded. In total, 9,390 patients, including 4,861 patients with established atherosclerotic disease and 4,529 patients with multiple risk factors, were enrolled. The modifiable risk factors, other than current smoking habit (5.3%), were common: hypertension (83.8%), dyslipidaemia (85.9%) and diabetes mellitus (57.4%). A majority of patients with hypertension (96.3%), dyslipidaemia (93.8%) and diabetes mellitus (78.5%) received medications for their conditions. Antiplatelet agents were given to 73.9% of patients. The undertreatment rate of cardiovascular risk factors, such as blood pressure, low-density lipoprotein cholesterol, haemoglobin A1c and smoking status, was 35.8%, 59.0%, 45.3% and 5.3%, respectively. Conventional atherosclerosis risk factors were common among Thai patients with established atherosclerotic disease. Even though most of the patients received recommended treatments according to established guidelines, a significant proportion of them were undertreated for atherosclerosis risk factors.