What the subjects have to say.
It is argued that if professional codes of ethics are to be effective in preventing unethical actions by psychologists, they should be partly based upon empirical research documenting how participants in our research feel about our research procedures. If, for instance, participants do not object to deception and if being deceived does not make them regard psychological research in a negative light, on what grounds would it be regarded as unethical to deceive them? In order to make informed decisions about the likely consequences of our research procedures upon participants, we need to rest such decisions upon research findings rather than upon professional prejudgements. An exploratory experiment is described which examines the effects of deception, physical discomfort (stress), and experimenter considerateness upon subjects' reactions both to the experiment in which they participated and upon their feelings about psychological research in general. Whilst the manipulations did affect subjects' reactions somewhat adversely, on the whole their reactions were positive. In addition, a direct comparison is made between the reactions of subjects in a passive role-playing condition (PRPs) and those who actually took part, to see if the reactions of the PRPs could be a useful guide to those of actual participants. If so, then investigators concerned about the possible adverse effects of their research upon participants could use the reactions of PRPs as one criterion by which to judge the ethicality of their proposed research. It was found that PRPs overestimate the degree of stress involved, but are otherwise reasonably accurate in predicting how actual participants feel. Implications of the results for our ethical codes are discussed.


Fault-Tolerant Control of Stochastic High-Order Fully Actuated Systems.
In recent years, high-order fully actuated (HOFA) systems, founded by Prof. GR Duan, have recorded rapid progress for deterministic systems. However, the control issue of stochastic fully actuated systems is still an open problem. This study develops a novel stochastic HOFA system model that complements the existing HOFA methodology. Notably, stochastic signals can be considered in the proposed model, different from the case in the deterministic model. By adopting a high-order operator, equivalent control and stabilization control laws are realized to guarantee the global asymptotic stability in probability of the closed-loop system. For the system with sensor gain faults, an observer-based fault-tolerant control law is designed. Finally, the simulation results validate the effectiveness of the proposed control schemes.


ER function in the adult male rat: short- and long-term effects of the antiestrogen ICI 182,780 on the testis and efferent ductules, without changes in testosterone.
Male rats, 30 d old, were treated with the antiestrogen ICI 182,780 (3-150 d) to determine sequences of events leading to testicular atrophy and infertility. Plasma testosterone and LH concentrations were unchanged. ICI 182,780 induced dilation of efferent ductules as early as 3 d post treatment, and the dilation increased over time, resulting in an overall increase of 200% in tubule diameter. A gradual reduction in height of the ductule epithelium was observed; however, the microvilli height increased up to d 73 but subsequently decreased. A transient increase in lysosomes in nonciliated cells was seen from d 15 to d 100. Testicular weight increased by d 45 and seminiferous tubules were dilated by d 52. These effects on testes persisted until d 100, but on d 150 the weight decreased and severe atrophy was observed. These testicular effects were probably owing to accumulation of fluid following inhibition of reabsorption in the efferent ductules, similar to the ER-alpha knockout mouse. In agreement with this conclusion, there was a decrease in Na+-H+ exchanger-3 mRNA and protein, which is consistent with previous studies showing that ER is required for expression of Na+-H+ exchanger-3 and ultimately fluid reabsorption in the efferent ductules.


[Combination therapy for severe sleep apnea syndrome].
We assessed the treatment of severe SAS (sleep apnea syndrome) patients who had an AHI (apnea hypopnea index) over 100. Eleven (3.3%) of the 374 patients who came to our hospital between May 2002 and December 2003 had an AHI over 100. They received CPAP (continuous positive airway pressure) therapy as initial therapy, and the AHI recovered within normal limit in the five patients who did not have tonsillar hypertrophy. The other six patients had tonsillar hypertrophy, and the effect of CPAP was poor. Two of the six patients with tonsillar hypertrophy, underwent UPPP (uvuropalatopharyngoplasty), and CPAP become effective postoperatively. These results indicate that combined treatment by CPAP and surgery is an effective means of treating severe SAS with tonsillar hypertrophy.


Myocardial energetics in cardiac hypertrophy.
1. This review is presented with the intent of illustrating the representative studies of functional and myocardial energetic consequences of hearts with postinfarction left ventricular (LV) remodelling or with concentric hypertrophy and diastolic LV dysfunction in porcine models. 2. Both eccentric and concentric cardiac hypertrophy are associated with the abnormal myocardial energetics that are most severe in hearts with congestive heart failure (CHF). Presently, these abnormalities cannot be satisfactorily explained to be the cause(s) of the dysfunction of failing hearts or cause the progress from compensated cardiac hypertrophy to CHF. 3. Mechanisms governing abnormal myocardial high-energy phosphate (HEP) metabolism in hearts with cardiac hypertrophy and CHF are unclear. Myocardial energy metabolism studies use both kinetic and thermodynamic models. The thermodynamic studies examine the myocardial steady state levels of high- and low-energy phosphate, which indicate myocardial energy state or phosphorylation potential that is defined by the ratio of [ATP]/([ADP][Pi]). The kinetics studies examine the reaction velocity that is regulated by: (i) quantity and activity of the key enzymes; (ii) the concentrations of all the substrates and products; and (iii) the Michaelis-Menten constants of each substrate of the reaction. 4. Significant alterations in myocardial concentrations of phosphocreatine (PCr), ATP and ADP, myocardial oxidative phosphorylation (OXPHOS) protein expression and substrate preference are found in hearts with postinfarction LV remodelling and CHF. However, to define a causal relationship is a different matter. 5. Future studies of animal models of LV hypertrophy or heart failure using gene manipulation may provide additional insights to answer the persisting question of whether limitations of ATP synthetic or transport capacities contribute to the pathogenesis of LV remodelling or failure.


Serum neutrophil gelatinase-associated lipocalin has an advantage over serum cystatin C and glomerular filtration rate in prediction of adverse cardiovascular outcome in patients with ST-segment elevation myocardial infarction.
The aim of this study was to assess significance of serum neutrophil gelatinase-associated lipocalin (sNGAL) and cystatin C (sCC) in prediction of adverse cardiovascular outcome after ST-segment elevation myocardial infarction (STEMI). We recruited 357 consecutive patients who were admitted to the hospital within 24 h after onset of STEMI. On the 1st and 12th-14th day after hospital admission, we measured levels of sNGAL and sCC. We also determined presence of renal dysfunction (RD), defined as glomerular filtration rate < 60 mL/min/1.73 m2. After 3 years of follow-up, we performed a logistic regression and assessed the value of RD, sNGAL, and sCC in prediction of combined endpoint, defined as cardiovascular death or any cardiovascular complication. RD, sCC level ≥ 1.9 mg/L, and sNGAL level ≥ 1.25 ng/mL on the 12th-14th day of hospitalization were associated with a 1.6-fold, 1.9-fold, and 2.9-fold higher risk of adverse cardiovascular outcome, respectively. Area under the ROC curve was the highest for the model based on sNGAL level compared to the models based on sCC level or RD presence. Measurement of sNGAL level in patients with STEMI on the 12th-14th day after hospital admission may improve prediction of adverse cardiovascular outcome.


Physiological and transcriptional characterization of Saccharomyces cerevisiae strains with modified expression of catabolic regulators.
A comparative physiological and transcriptional study is presented on wild-type Saccharomyces cerevisiae and mutants with altered levels of catabolic regulators: hxk2Delta lacking hexokinase2, HAP4 / overproducing hap4p and hxk2 Delta HAP4 upward arrow. Relative to the wild-type, HAP4 / showed the same growth rate with some increased yield on glucose, and hxk2Delta grew 28% slower but with a dramatically improved yield. Hxk2 Delta HAP4 / grew 14% slower but showed fully oxidative growth. A higher yield correlated with increased respiration. For both hxk2 Delta strains, glucose repression was suppressed (upregulation of high-affinity sugar transporters, invertase and oxidative phosphorylation). T-profiler analysis showed that genes under control of the hap2/3/4/5-binding motif were significantly altered in expression in all strains. HAP4 overexpression, directly or in hxk2 knockouts, led to repression of the genes containing the Zap1p motif including ZAP1 itself, indicating altered zinc metabolism. Whereas HAP4 overexpression resulted in a shift towards oxidative metabolism only, deletion of HXK2 resulted in a strain that, in addition to being oxidative, almost completely lacked the ability to sense glucose. As the double mutant had an energy efficiency close to the maximum even with excess glucose and was derepressed to a larger extent and over a broader range, the functioning of the two regulators is in general considered to be additive.


Low-molecular-weight heparin lowers the recurrence rate of preeclampsia and restores the physiological vascular changes in angiotensin-converting enzyme DD women.
Data from literature report that angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the recurrence of preeclampsia and that low-molecular-weight heparin (LMWH) prevents adverse outcomes in thrombophilic women. We investigated the effect of LMWH on the pregnancy outcome, on maternal blood pressure values, and on uteroplacental flow in ACE DD nonthrombophilic women with history of preeclampsia. Eighty nonthrombophilic ACE DD women were randomized in 2 groups: 41 treated with dalteparin 5000 IU/day and 39 untreated (control group). Women underwent 24-hour automated blood pressure monitoring in the preconceptional period and every 2 weeks from weeks 8 to 36 and transabdominal color flow/pulsed Doppler examination at weeks 16, 20, and 24. LMWH reduced the risk of clinical negative outcomes (74.1% reduction of preeclampsia and 77.5% reduction of fetal growth restriction) and the severity (88.3% reduction of early onset of preeclampsia and 86.4% reduction of early onset of fetal growth restriction). In treated women, the relative risk for preeclampsia was 0.26 (P=0.02), and the relative risk for fetal growth restriction was 0.14 (P<0.001). Systolic (P=0.002) and diastolic (P=0.002) blood pressures, as well as awake (P=0.04) and asleep (P=0.01) period values, and the resistance indexes of both uterine arteries (P=0.002) were lower in the treated group. LMWH reduces the recurrence of preeclampsia, of negative outcomes, and the resistance of uteroplacental flow, and also prevents maternal blood pressure increase in ACE DD homozygote women with a previous history of preeclampsia.


AFP level and histologic differentiation predict the survival of patients with liver transplantation for hepatocellular carcinoma.
In liver transplantation or resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features. In patients with HCC, we performed a clinicopathological analysis of risk factors that affected survival after liver transplantation. In 389 liver transplantations performed from 2004 to 2010, 102 were for HCC patients. Data were collected retrospectively from the Organ Transplantation Center Database. Variables were as follows: age, gender, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, prognostic staging criteria (Milan and UCSF), etiology, number of tumors, the largest tumor size, total tumor size, multifocality, intrahepatic portal vein tumor thrombosis, bilobarity, and histological differentiation. One hundred and two patients were evaluated. The 5-year overall survival rate was 56.5%. According to the UCSF criteria, 63% of the patients were within and 37% were beyond UCSF (P=0.03). Ten patients were excluded (one with fibrolamellary HCC and 9 because of early postoperative death without HCC recurrence), and 92 patients were assessed. The mean age of the patients was 56.5+/-6.9 years. Sixty-two patients underwent living donor liver transplantations. The mean follow-up time was 29.4+/-22.6 months. Fifteen patients (16.3%) died in the follow-up period due to HCC recurrence. Univariate analysis showed that AFP level, intrahepatic portal vein tumor thrombosis, histologic differentiation and UCSF criteria were significant factors related to survival and tumor recurrence.The 5-year estimated overall survival rate was 62.2% in all patients. According to the UCSF criteria, and the 5-year overall survival rate was 66.7% within and 52.7% beyond the criteria (P=0.04). Multivariate analysis showed that AFP level and poor differentiation were independent factors. For proper patient selection in liver transplantation for HCC, prognostic criteria related to tumor biology (especially AFP level and histological differentiation) should be considered. Poor differentiation and higher AFP levels are indicators of poor prognosis after liver transplantation.


Echocontrast agent enhanced color flow imaging of the breast.
An ultrasound contrast agent which survives transit through the pulmonary circulation after injection into a peripheral vein can also be used for the demonstration of flow characteristics in the peripheral organs. Such a substance (SH U 508 A, Schering AG, Berlin) was tested in the Gynecological Department of the University of Marburg for its suitability for enhancing color-coded Doppler signals in mammary diagnosis in a group of ten women with breast tumors. The observations made are compared with the histologically confirmed diagnoses. The very distinct enhancement of the color-coded Doppler signals allows reliable demonstration of the vascularization characteristics, not only of the malignant, but also of all benign solid tumors examined. Color signals were even recorded from normal mammary tissue, which means that the demonstration of perfusion can no longer be used on its own as a diagnostic criterion. Observation of the characteristics of the blood supply to a tumor might, on the other hand, be an advantage, not only in respect of tumor typing, but also as regards the prognosis of a tumor. In this connection, the registration of the arrival, retention and wash-out phases specific to a contrast agent appears to furnish particularly interesting information about the growth dynamics of a tumor.


Infectious transmission of human T-cell leukemia virus to animals.
An human T-cell leukemia virus (HTLV)-producing cell line (Ra-1) was established from rabbit lymphocytes by co-cultivation with lethally irradiated MT-2 cells. Ra-1 cells were inoculated intravenously into a Japanese monkey and rabbits. All animals responded with the production of antibodies to HTLV. Lymphocytes from the seroconverted animals were grown in the presence of T-cell growth factor (TCGF) or co-cultured with lymphocytes from seronegative healthy persons. The TCGF-grown cells, which were chromosomally of the recipient type, expressed HTLV antigens and particles. The co-cultures gave rise to human T-cell lines which also harbored HTLV antigens and particles. Blood transfusion from the infected rabbits resulted in the seroconversion of the recipient rabbits. HTLV-producing lymphoid cell lines were established from some of the transfused rabbits. The recipient origin of these cell lines was determined by chromosome analysis. It was possible to serially transmit HTLV by blood transfusion in rabbits. Thus, these animals offer promise as a laboratory model for HTLV infection.


Deep learning-empowered crop breeding: intelligent, efficient and promising.
Crop breeding is one of the main approaches to increase crop yield and improve crop quality. However, the breeding process faces challenges such as complex data, difficulties in data acquisition, and low prediction accuracy, resulting in low breeding efficiency and long cycle. Deep learning-based crop breeding is a strategy that applies deep learning techniques to improve and optimize the breeding process, leading to accelerated crop improvement, enhanced breeding efficiency, and the development of higher-yielding, more adaptive, and disease-resistant varieties for agricultural production. This perspective briefly discusses the mechanisms, key applications, and impact of deep learning in crop breeding. We also highlight the current challenges associated with this topic and provide insights into its future application prospects.


Preoperative fasting: old habits die hard.
Prolonged preoperative fasting is a time-honored tradition. The typical order of "npo after midnight" (or no liquid or food after 12 am on the day of surgery) has been challenged in recent years-so much so that in 1999 the American Society of Anesthesiology (ASA) revised its practice guidelines for preoperative fasting in healthy patients undergoing elective procedures. The newer, more liberal recommendations, based on studies showing that pulmonary aspiration occurs only rarely as a complication of modern anesthesia, allow the consumption of clear liquids up to two hours before elective surgery, a light breakfast (tea and toast, for example) six hours before the procedure, and a heavier meal eight hours beforehand. There is a well-known lag between the dissemination and implementation of practice guidelines, so the authors sought to determine whether the publication of the revised ASA recommendations had changed preoperative fasting practices. They interviewed 155 patients in one hospital about their preoperative fasting, comparing instructed, actual, and ASA-recommended fasting durations for liquids and solids. Their findings demonstrate that the majority of patients continued to receive instructions of npo after midnight for both liquids and solids, whether they were scheduled for early or late surgery. On average, the patients fasted from liquids and solids for 12 and 14 hours, respectively, with some patients fasting as long as 20 hours from liquids and 37 hours from solids. These fasts were significantly longer than those recommended by the ASA, indicating that inappropriate preoperative fasting is an issue that demands attention. The authors conclude that more collaboration between nurses and physicians is needed to assure that fasting instructions are consistent with the ASA guidelines and that patients understand these directives.


Granulomatous mycoses of the central nervous system.
A clinical and pathological description of five cases of granulomatous mycoses of the C.N.S. is reported. Four had an intracranial and one a spinal localization. In all patients the clinical pattern was of tumoral type, while the disease evolution was favourable only in one case. From a histipatholic point of view the preliminary diagnosis was of granulomatous process. The fungi organisms were identified only by means of combined stain methods. Beside the pathogenetic problems the Authors outline some histological methods useful for diagnostic purposes when a culture procedure for fungi is lacking.


Employment of a promoter-swapping technique shows that PhoU modulates the activity of the PstSCAB2 ABC transporter in Escherichia coli.
Expression of the Pho regulon in Escherichia coli is induced in response to low levels of environmental phosphate (P(i)). Under these conditions, the high-affinity PstSCAB(2) protein (i.e., with two PstB proteins) is the primary P(i) transporter. Expression from the pstSCAB-phoU operon is regulated by the PhoB/PhoR two-component regulatory system. PhoU is a negative regulator of the Pho regulon; however, the mechanism by which PhoU accomplishes this is currently unknown. Genetic studies of phoU have proven to be difficult because deletion of the phoU gene leads to a severe growth defect and creates strong selection for compensatory mutations resulting in confounding data. To overcome the instability of phoU deletions, we employed a promoter-swapping technique that places expression of the phoBR two-component system under control of the P(tac) promoter and the lacO(ID) regulatory module. This technique may be generally applicable for controlling expression of other chromosomal genes in E. coli. Here we utilized P(phoB)::P(tac) and P(pstS)::P(tac) strains to characterize phenotypes resulting from various DeltaphoU mutations. Our results indicate that PhoU controls the activity of the PstSCAB(2) transporter, as well as its abundance within the cell. In addition, we used the P(phoB)::P(tac) DeltaphoU strain as a platform to begin characterizing new phoU mutations in plasmids.


Arsenic speciation in rice and soil containing related compounds of chemical warfare agents.
Diphenylarsinic acid, phenylarsonic acid, methylphenylarsinic acid (MPAA), dimethylphenylarsine oxide (DMPAO), and methyldiphenylarsine oxide (MDPAO) in soil and rice were extracted, separated by reversed-phase chromatography, and quantified by ICPMS with a membrane desolvating system. For the extraction of arsenicals from rice grain and straw, 68% HNO3 provided better extraction efficiency than water, 50% methanol, or 2.0 mol L(-1) trifluoroacetic acid. For the extraction from soil, 68% HNO3 provided better extraction efficiency than H2O, 1 mol L(-1) H3PO4, or 1 mol L(-1) NaOH. The contaminated soil contained all five aromatic arsenicals along with inorganic arsenicals as main species (5.86 +/- 0.19 microg of As kg(-1): 60.8 +/- 2.0% of total extracted As). After pot experiments, rice straw contained mainly DMPAO (7.71 +/- 0.48 microg of As kg(-1): 60.5 +/- 3.7%), MDPAO (0.91 +/- 0.07 microg of As kg(-1): 7.2 +/- 0.5%), and inorganic As (2.85 +/- 0.20 microg of As kg(-1): 22.3 +/- 1.6%). On the other hand, rice grain contained mainly MPAA (1.17 +/- 0.04 microg of As kg(-1): 86.7 +/- 2.7%). The root uptake of each species from the soil and transport from straw to grains were significantly related to the calculated log K(ow) values.


High glucose levels affect spermatogenesis: an in vitro approach.
Besides known factors that may cause male infertility, systemic diseases such as diabetes mellitus may further exacerbate a decline in male fertility. This metabolic disease, clinically characterised by a hyperglycaemic phenotype, has devastating consequences in terms of human health, with reproductive dysfunction being one of the associated clinical complications. Nonetheless, the mechanisms responsible for such alterations are still poorly understood due to the multiplicity of factors involved in the induced pathophysiological changes. With this in mind, we focused on the main mediator of diabetes-associated alterations and performed an in vitro approach to address the effects of high glucose conditions on spermatogenesis, avoiding other confounding in vivo factors. Mouse (5 days post partum) testis fragments were cultured on agar gel stands at a gas-liquid interface with either 5, 25 or 50mM D-glucose for 3 weeks. Stereological analysis revealed that high D-glucose levels increased Sertoli cell number (P<0.05) and decreased tubular luminal area (P<0.01), suggesting an impairment of this somatic cell type. Moreover, higher proliferative activity in a TM4 Sertoli cell line exposed to high D-glucose was found (P<0.05) without compromising cell viability (P>0.05), further suggesting altered Sertoli cell maturation. Overall, high D-glucose concentrations may lead to impairment of Sertoli cell function, which, given their significant role in spermatogenic control, may compromise male fertility.


Chronic Osteoporotic Pain in Mice: Cutaneous and Deep Musculoskeletal Pain Are Partially Independent of Bone Resorption and Differentially Sensitive to Pharmacological Interventions.
Although the pathological changes in osteoporotic bones are well established, the characterization of the osteoporotic pain and its appropriate treatment are not fully elucidated. We investigated the behavioral signs of cutaneous and deep musculoskeletal pain and physical function; time-dependent changes in bone mineral density (BMD) and the emergence of the behavioral phenotype; and the effects of pharmacological interventions having different mechanisms of action (chronic intraperitoneal administration of pamidronate [0.25 mg/kg, 5x/week for 5 weeks] versus acute treatment with intraperitoneal morphine [10 mg/kg] and pregabalin [100 mg/kg]) in a mouse model of ovariectomized or sham-operated mice 6 months following surgery. We observed reduced BMD associated with weight gain, referred cutaneous hypersensitivity, and deep musculoskeletal pain that persisted for 6 months. Chronic bisphosphonate treatment, 6 months after ovariectomy, reversed bone loss and hypersensitivity to cold, but other behavioral indices of osteoporotic pain were unchanged. While the efficacy of acute morphine on cutaneous pain was weak, pregabalin was highly effective; deep musculoskeletal pain was intractable. In conclusion, the reversal of bone loss alone is insufficient to manage pain in chronic osteoporosis. Additional treatments, both pharmacological and nonpharmacological, should be implemented to improve quality of life for osteoporosis patients.


[Can we influence the negative drug attitude? Interpretation of the rejection of COVID-19 vaccine in the light of results of a pilot study].
Vaccination refusal is a serious obstacle to minimizing the spread of COVID-19. Nevertheless, the rejection of vaccine can be considered the result of a negative attitude towards medical treatment, and according to our previously published data, it can be influenced by the underlying affective state. Increased incidence of affective disorders and anxiety could be observed globally during the pandemic, which may have a significant impact on vaccination acceptance. The aim of our pilot study was to determine the association between clinical improvement of affective and neurocognitive symptoms and change of drug attitude and health control beliefs in a sample of psychiatric patients. A data set of 85 patients with psychiatric disorder has been analysed with the use of Patient's Health Belief Questionnaire on Psychiatric Treatment (PHBQPT) with 5 subscales (Negative Aspect of Medication - NA; Positive Aspect of Medication - PA; Doctor health locus of control- Doctor HLOC; Internal HLOC; Psychological Reactance - PR); Hospital Anxiety Depression Scale (HADS-Anx; HADS-Dep) and neurocognitive tests, such as the Stroop test and the Trail Making Tests. All the tests were performed before and after a 14 days treatment. Paired t-tests and generalized linear models were performed to assess the associations between the variables. The baseline scores of NA and HADS-Anx correlated significantly (p=0.001) and after two weeks of treatment NA decreased (p=0.001), while Doctor HLOC and Internal HLOC increased (p=0.001 and p=0.006). The patients performance of the neurocognitive tests improved (all p<0.05). The reduction of HADS-Anx (p=0.002) and HADS-Dep (p=0.006) scores showed significant associations with the decrease of NA. Increase of the PA score was associated with reduction of HADS-Dep (p=0.028). Improvement of neurocognitive functions had no effect on PHBQPT scores. Important conclusions can be drawn regarding the rejection of the COVID-19 vaccine based on the associations found between the intensity of affective and anxiety symptoms and the attitude towards treatment. Our findings suggest that affective symptoms have a negative influence on the attitude towards treatment and that the improvement of these symptoms can facilitate the acceptance of the therapy, regardless of diagnosis. The modest effect of the improvement of neurocognitive functioning on the attitude towards drugs and the significant role of affective-emotional factors suggest that the accep-tance of vaccination probably cannot be facilitated solely with the aid of educational programs. Considering the increasing incidence of affective disorders during the COVID-19 pandemic, the screening of affective and anxiety symptoms and treatment of these disorders could be an important step towards the acceptance of the vaccine. Although psychiatry is not considered as a frontline care unit of the COVID cases, more attention is needed to pay on the availability of mental health services because refuse of vaccine can develop due to affective disorders too.


Miliary osteoma of the face: a report of 4 cases and review of the literature.
Osteoma cutis (OC) is a rare disorder characterized by compact bone formation in the dermis and subcutaneous tissue. It is classified in primary and secondary forms according to the presence or absence of previous cutaneous lesions. Miliary osteoma of the face (MOF) is a form of primary OC that generally occurs in middle-aged and older adult women. We report 3 cases of typical MOF and one additional case in a black patient, which to our knowledge has not been described previously.


Endothelial Glycocalyx Damage and Renal Dysfunction in HIV Patients Receiving Combined Antiretroviral Therapy.
Widespread use of combined antiretroviral therapy (cART) increased HIV patients' life expectancy, however, favored the development of kidney and cardiovascular diseases. The aim of this study was to investigate endothelial glycocalyx (eGC) damage and its association with renal function in HIV patients receiving cART. This is a cross-sectional study with HIV-infected patients with no renal and cardiovascular disease, recruited in public health centers in Brazil. Clinical and laboratory parameters of HIV patients were compared according to cART use and with a healthy control group. Blood ICAM-1 and syndecan-1 levels were quantified by ELISA kit. Estimated glomerular filtration rate (eGFR) was evaluated. A total of 69 HIV patients were included, with mean age of 33.4 ± 8.9 years, and 77.3% were male. Serum urea, creatinine, and eGFR were similar in all groups. No HIV patient had decreased GFR <60 ml/min. All HIV patients had higher systemic syndecan-1 compared with healthy controls (71.8 ± 25.4 ng/ml vs. 36.5 ± 14.3 ng/ml, p < .001). Syndecan-1 showed a significant positive correlation with serum creatinine (r = 0.437, p = .001), serum urea levels (r = 0.352, p = .006), and a negative correlation with eGFR (r = -0.315, p = .015) in HIV patients. Syndecan-1 remained independently associated with serum creatinine and reduced GFR even after we forced variables related with HIV infection status, tenofovir use, treatment time, dyslipidemia, and others in a multivariate analysis. HIV patients using cART with no clinical renal and cardiovascular disease presented eGC damage and it is associated with clinical markers of kidney dysfunction. Syndecan-1 may be a useful early biomarker to monitoring renal dysfunction in HIV patients in chronic use of cART. Further research is needed to evaluate this applicability.


Airway response to emotional stimuli in asthma: the role of the cholinergic pathway.
In asthma, airways constrict in response to emotion and stress, but underlying mechanisms, potential extrathoracic contributions, and associations with airway pathophysiology have not been elucidated. We therefore investigated the role of the cholinergic pathway in emotion-induced airway responses in patients with asthma and the association of these responses with airway pathophysiology. Patients with asthma (n=54) and healthy participants (n=25) received either 40 microg ipratropium bromide or a placebo in a double-blind double-dummy cross-over design in two laboratory sessions with experimental emotion induction. Stimuli were preevaluated films and pictures of pleasant, unpleasant, and neutral quality. Respiratory resistance and reactance at 5 and 20 Hz were measured continuously before and during presentations, together with respiration by impedance plethysmography and end-tidal PCO2 by capnometry. In addition, measures of airway inflammation (fraction of exhaled nitric oxide), airway hyperreactivity (methacholine challenge), and reversibility of obstruction were obtained. Respiratory resistance at 5 and 20 Hz increased during unpleasant stimuli in asthma patients. This response was blocked by ipratropium bromide and was not substantially associated with asthma severity, airway inflammation, hyperreactivity and reversibility, or pattern of ventilation and PCO2. Under the placebo condition, changes in resistance during unpleasant films were positively correlated with patients' reports of psychological asthma triggers. In conclusion, airway constriction to unpleasant stimuli in asthma depends on an intact cholinergic pathway, is largely due to the central airways, and is not substantially associated with other indicators of airway pathology. Its link to the perceived psychological triggers in patients' daily lives suggests a physiological basis for emotion-induced asthma.


The "deroofing" of Schlemm's canal in patients with open-angle glaucoma through placement of a collagen drainage device.
A preliminary study was conducted to examine a new surgical approach for the management of patients with open-angle glaucoma in which Schlemm's canal is opened to restore drainage in a nonpenetrating fashion. The authors compared the results of the surgical procedure including the new glaucoma drainage device with the results of standard trabeculectomy. The authors performed a new type of surgical procedure on 58 consecutive patients with open-angle glaucoma. The procedure entails "deroofing" Schlemm's canal to facilitate the drainage of aqueous without penetrating the eye. This is done by exposing the canal after a partial-thickness sclerectomy and keratectomy along a 5-mm arc. After the canal was deroofed, a new type of collagen glaucoma drainage device was placed in the surgical site to maintain drainage postoperatively. Patient data, including intraocular pressure (IOP), complications, and the number of medications required to maintain adequate pressures, were analyzed for 1 year postoperatively. Within 1 to 2 months postoperatively, 80.9% of the patients achieved an IOP lower than 21 mm Hg. This improved to 88.9% at 3 to 6 months postoperatively and 87.5% at 6 to 12 months postoperatively. The only major complications were microperforations (8.6%) related to surgical technique and a few cases of high IOP that required repeat operations (10.3%). The nonpenetrating technique for deroofing the canal effectively allows the drainage of aqueous to acceptable levels (in the range of 15 to 17 mm Hg) without the complications associated with penetrating trabeculectomy. Complications are rare, and the collagen drainage device appears to be effective for allowing the drainage site to remain patent after its dissolution.


Hemophagocytic lymphohistiocytosis associated with HBV-HCV coinfection in adult: Case report.
The case reported is the first case in Morocco to our knowledge. The reason for sharing this case is to facilitate knowledge transfer between physicians, caring for adult patients with HLH, with the aim to improve the outcome of these patients.


Genomic and phenotypic insight into Xanthomonas vesicatoria strains with different aggressiveness on tomato.
Xanthomonas vesicatoria is one of the causal agents of bacterial spot, a disease that seriously affects the production of tomato (Solanum lycopersicum) and pepper (Capsicum annum) worldwide. In Argentina, bacterial spot is found in all tomato producing areas, with X. vesicatoria being one of the main species detected in the fields. Previously, we isolated three X. vesicatoria strains BNM 208, BNM 214, and BNM 216 from tomato plants with bacterial spot, and found they differed in their ability to form biofilm and in their degree of aggressiveness. Here, the likely causes of those differences were explored through genotypic and phenotypic studies. The genomes of the three strains were sequenced and assembled, and then compared with each other and also with 12 other publicly available X. vesicatoria genomes. Phenotypic characteristics (mainly linked to biofilm formation and virulence) were studied in vitro. Our results show that the differences observed earlier between BNM 208, BNM 214, and BNM 216 may be related to the structural characteristics of the xanthan gum produced by each strain, their repertoire of type III effectors (T3Es), the presence of certain genes associated with c-di-GMP metabolism and type IV pili (T4P). These findings on the pathogenicity mechanisms of X. vesicatoria could be useful for developing bacterial spot control strategies aimed at interfering with the infection processes.


Contextualizing Genetics for Regional Heart Failure Care.
Congestive heart failure (CHF) is a chronic and often devastating cardiovascular disorder with no cure. There has been much advancement in the last two decades that has seen improvements in morbidity and mortality. Clinicians have also noted variations in the responses to therapies. More detailed observations also point to clusters of diseases, phenotypic groupings, unusual severity and the rates at which CHF occurs. Medical genetics is playing an increasingly important role in answering some of these observations. This developing field in many respects provides more information than is currently clinically applicable. This includes making sense of the established single gene mutations or uncommon private mutations. In this thematic series which discusses the many factors that could be relevant for CHF care, once established treatments are available in the communities; this section addresses a contextual role for medical genetics.


Regeneration and rewiring of rodent olfactory sensory neurons.
The olfactory sensory neurons are the only neurons in the mammalian nervous system that not only regenerate naturally and in response to injury, but also project to specific targets in the brain. The stem cells in the olfactory epithelium commit to both neuronal and non-neuronal lineages depending on the environmental conditions. They provide a continuous supply of new neurons. A newly generated neuron must express a specific odorant receptor gene and project to a central target consist of axons expressing the same receptor type. Recent studies have provided insights into this highly regulated, complex process. However, the molecular mechanisms that determine the regenerative capacity of stem cells, and the ability of newly generated neurons in directing their axons toward specific targets, remain elusive. Here we review progresses and controversies in the field and offer testable models.


Incidence and prognosis of pacemaker lead-associated masses: a study of 1,569 transesophageal echocardiograms.
Endovascular lead infection is an uncommon but serious problem. Transesophageal echocardiography (TEE) is a useful tool for identification of pacemaker lead vegetations. Additionally, incidental echogenic masses are occasionally identified by TEE. The prognosis and optimal treatment of either suspected lead infection or an incidental mass is poorly understood. The purpose of this study was to examine the incidence and clinical course of pacemaker lead masses. A total of 1,569 sequential TEE examinations performed from January 2002 to January 2005 were reviewed. Retrospective chart analysis of patients with a pacing lead-associated mass was performed to review the indication for TEE as well as clinical management. Telephone follow up was also performed. During 125 TEE examinations, pacemaker leads were visualized in the right-sided chambers. Fifteen studies demonstrated an echogenic mass associated with the lead. In 9 of these studies, endocarditis was suspected, and the mass was felt to be a vegetation: 6 were treated with antibiotics alone, with 1 death attributed to a complication of endocarditis (autopsy proven massive pulmonary embolus); 3 patients were treated with lead extraction, both were alive at follow up; 1 patient was lost to follow up after the TEE. Six patients (5%) were found incidentally to have a mass on the pacing lead during TEE: 3 were treated with warfarin; 2 received no specific therapy; and 1 underwent surgical debridement of the lead during valve surgery. All of the patients in this group were alive at follow up, and no significant clinical events attributable to the lead-associated mass were observed. TEE identified an echogenic mass on 12% of the leads imaged, with 60% having suspected endocarditis. The mortality rate of lead vegetation was 11%. An incidental mass was noted on 5% of the leads, with no significant associated morbidity or mortality observed.


Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy.
Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD. We introduce two Dystrophin Expressing Chimeric (DEC) cell lines created by ex vivo fusion of human myoblasts (MB) derived from two normal donors (MBN1/MBN2), and normal and DMD donors (MBN/MBDMD). The efficacy of fusion was confirmed by flow cytometry and confocal microscopy based on donor cell fluorescent labeling (PKH26/PKH67). In vitro, DEC displayed phenotype and genotype of donor parent cells, expressed dystrophin, and maintained proliferation and myogenic differentiation. In vivo, local delivery of both DEC lines (0.5 × 106) restored dystrophin expression (17.27%±8.05-MBN1/MBN2 and 23.79%±3.82-MBN/MBDMD) which correlated with significant improvement of muscle force, contraction and tolerance to fatigue at 90 days after DEC transplant to the gastrocnemius muscles (GM) of dystrophin-deficient mdx/scid mice. This study establishes DEC as a potential therapy for DMD and other types of muscular dystrophies.


Anaesthetic potencies of primary alkanols: implications for the molecular dimensions of the anaesthetic site.
1. We have redetermined the anaesthetic potencies (EC50S) for a series of primary alkanols, to resolve uncertainties about the molecular dimensions of the anaesthetic site resulting from the use of data from different laboratories. 2. For each alkanol, concentration-response relationships for loss of righting reflex (LRR) were plotted for over one hundred tadpoles, and the median effective concentrations determined. Aqueous concentrations present during potency assays were determined independently, and for alkanols with chain length greater than nonanol, correction was made for depletion from the aqueous phase. 3. The EC50S were found to decrease logarithmically with increasing number of carbon atoms in the hydrocarbon chain of the alkanol (CN), such that, on average, each additional methylene group was associated with an approximately four fold increase in potency. 4. The relationship between log EC50 and CN was best described by the quadratic equation, log EC50 = 0.022 (+/- 0.0038) CN2 + 0.76 (+/- 0.051) CN + 3.7 (+/- 0.14) (r2 = 0.9951). 5. A previously described correlation between the apparent changes in the free energy of binding of an additional methylene group both to luciferase and to the sites for LRR in tadpoles was not confirmed. 6. A cut-off in potency beyond dodecanol was established in experiments where tadpoles were maintained in supersaturated solutions of tridecanol for 20 h without demonstrable LRR. 7. These findings indicate that the soluble enzyme firefly luciferase does not adequately model the anaesthetic site. Specifically, there are discrepancies in the position of cut-off, and the apparent changes in the free energy of binding, per methylene group, of an alkanol to luciferase do not parallel that for tadpoles.


Hemiballism in multiple sclerosis.
Hemiballism has rarely been reported in the setting of multiple sclerosis. Review of clinical descriptions cast some doubt on the accuracy of the diagnosis of the movement disorder in several previous cases. We report a patient with definite multiple sclerosis, with videotape documentation of hemiballism, and demonstration of a plaque in the contralateral subthalamic nucleus on a magnetic resonance image.


Inhibition of VEGF-C modulates distal lymphatic remodeling and secondary metastasis.
Tumor-associated lymphatics are postulated to provide a transit route for disseminating metastatic cells. This notion is supported by preclinical findings that inhibition of pro-lymphangiogenic signaling during tumor development reduces cell spread to sentinel lymph nodes (SLNs). However, it is unclear how lymphatics downstream of SLNs contribute to metastatic spread into distal organs, or if modulating distal lymph transport impacts disease progression. Utilizing murine models of metastasis, longitudinal in vivo imaging of lymph transport, and function blocking antibodies against two VEGF family members, we provide evidence that distal lymphatics undergo disease course-dependent up-regulation of lymph transport coincidental with structural remodeling. Inhibition of VEGF-C activity with antibodies against VEGF-C or NRP2 prevented these disease-associated changes. Furthermore, utilizing a novel model of adjuvant treatment, we demonstrate that antagonism of VEGF-C or NRP2 decreases post SLN metastasis. These data support a potential therapeutic strategy for inhibiting distant metastatic dissemination via targeting tumor-associated lymphatic remodeling.


[Introduction and the current status of unrelated peripheral blood stem cells transplantation in Japan].
In other countries, unrelated donor peripheral blood stem cell transplantation (PBSCT) is more prevalent than bone marrow transplantation; however, in Japan, it was introduced in 2010 after confirming the safety of donors. PBSCT does not require blood donation, general anesthesia, or frequent bone marrow aspiration of the donor. After PBSCT, numerous hematopoietic cells can prompt blood recovery and engraftment, which has enabled reduced intensity transplantation in elderly patients and patients with concurrent diseases, such as infection. In addition, GVL effect by a large number of donor lymphocytes is expected, however, chronic GVHD is a major concern. When introducing PBSCT in Japan, manuals were drafted considering the short-term safety of donors, and data were collected on the occurrence of long- and short-term adverse events. A randomized trial reported no difference in the survival rate between bone marrow transplantation and PBSCT at 5 years; however, it revealed that QOL was better in the former. PB is a essential transplant source option, and attempts are being made to overcome chronic GVHD. PBSC contains abundant stem cells, progenitor cells, and immunocompetent cells and is indispensable for the development of cell therapy for blood diseases in the future.


Diversity indices for ecological networks: a unifying framework using Hill numbers.
Describing how ecological interactions change over space and time and how they are shaped by environmental conditions is crucial to understand and predict ecosystem trajectories. However, it requires having an appropriate framework to measure network diversity locally, regionally and between samples (α-, γ- and β-diversity). Here, we propose a unifying framework that builds on Hill numbers and accounts both for the probabilistic nature of biotic interactions and the abundances of species or groups. We emphasise the importance of analysing network diversity across different species aggregation levels (e.g. from species to trophic groups) to get a better understanding of network structure. We illustrate our framework with a simulation experiment and an empirical analysis using a global food-web database. We discuss further usages of the framework and show how it responds to recent calls on comparing ecological networks and analysing their variation across environmental gradients and time.


[Renovascular hypertension and Takayasu disease].
We present three cases of Takayasu disease which were peculiar because all three of them first manifested as vasculorenal hypertension. The pathogenic mechanisms of hypertension in this disease are reviewed, being renal arteries stenosis the most important mechanism. The great prognostic and therapeutic implications of hypertension in these patients made us suggest the performance of arteriographies of supraaortic trunks in all cases of vasculorenal arterial hypertension associated to certain clinical, analytical and/or arteriographic criteria which are mentioned.


Specific Features of the Coagulopathy Signature in Severe COVID-19 Pneumonia.
Rationale: COVID-19 displays distinct characteristics that suggest a unique pathogenesis. The objective of this study was to compare biomarkers of coagulopathy and outcomes in COVID-19 and non-COVID-19 patients with severe pneumonia. Methods: Thirty-six non-COVID-19 and 27 COVID-19 non-immunocompromised patients with severe pneumonia were prospectively enrolled, most requiring intensive care. Clinical and biological characteristics (including plasma biomarkers of coagulopathy) were compared. Results: At similar baseline severity, COVID-19 patients required mechanical ventilation (MV) for significantly longer than non-COVID-19 patients (p = 0.0049) and more frequently developed venous thrombotic complications (p = 0.031). COVID-19 patients had significantly higher plasma concentrations of soluble VCAM1 (sVCAM1) (5,739 ± 3,293 vs. 3,700 ± 2,124 ng/ml; p = 0.009), but lower levels of D-dimers, vWF-A2, sICAM1, sTREM1, VEGF, and P-selectin, compared to non-COVID-19 patients. Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariable regression analysis confirmed that sVCAM1 rising levels were independently associated with a longer duration of MV. Finally, we identified close correlations between sVCAM1 and some features of COVID-19 immune dysregulation (ie. CXCL10, GM-CSF, and IL-10). Conclusion: We identified specific features of the coagulopathy signature in severe COVID-19 patients, with higher plasma sVCAM1 levels, that were independently associated with the longer duration of mechanical ventilation. Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03505281.


Allergic Fungal Sinusitis: Ophthalmic Complications Due to the COVID-19 Pandemic and the Potential of Telemedicine.
We report a case of a 26-year-old female who initially presented to an outside optometrist with complaints of proptosis and decreased visual acuity. Magnetic resonance imaging (MRI) obtained at that time was concerning for allergic fungal sinusitis. Unfortunately, the patient's referral to ophthalmology was delayed due to the coronavirus disease 2019 (COVID-19) pandemic. On presentation to ophthalmology one year later, the patient had clinically deteriorated with significant visual and olfactory loss. She underwent emergent endoscopic sinus surgery by otolaryngology with histological analysis of the sinus debris confirming allergic fungal sinusitis. This is a unique case demonstrating the devastating impact that the COVID-19 pandemic had on patient care for an otherwise treatable condition. We propose the utilization of telemedicine networks as a way to prevent similar complications.


Effect of HEMA-containing dentin desensitizers on shear bond strength of a resin cement.
To determine whether the use of two HEMA-containing dentin desensitizing agents [Health-Dent Desensitizer with fluoride (H) or Gluma Desensitizer (G)], when applied at simulated "cavity preparation" and "cementation" appointments, affects the bond strength of lab processed resin composite restorations cemented to dentin. The occlusal surfaces of 70 teeth were ground flat to expose dentin and polished to 600 grit. Teeth were randomly assigned to seven groups (n = 10). The treatments were applied in two sessions in order to simulate cavity preparation and cementation appointments. Water (W) was applied as a control instead of a desensitizing agent. H or G were applied for 30 seconds with a rubbing motion (1) at preparation appointment (HW and GW), or (2) at cementation appointment, after etching (WH and WG), or (3) at both sessions (HH and GG). In the control group, water was applied at both sessions (WW). All-Bond 2 and Dual Cement were used according to manufacturers' instructions to cement pre-polymerized resin composite cylinders (4 mm diameter) to the dentin surfaces using a force of 1.0 MPa. Specimens were thermocycled 300x and tested in shear until failure. Data was analyzed using one-way ANOVA and Tukey's HSD test at alpha = 0.05. Mean bond strength and standard deviations are reported in MPa: GW = 7.4 +/- 6.0; WW = 7.7 +/- 5.8; HW = 8.2 +/- 4.3; WH = 10.8 +/- 6.2; GG = 13.5 +/- 6.0; HH = 13.8 +/- 7.1; WG = 19.9 +/- 8.8. There were no significant differences in bond strengths for GW, WW, HW, WH and GG. Shear bond strength for WG and HH was significantly higher than all groups except for GG. Results of this in vitro study indicate that the use of desensitizers at the preparation and/or cementation appointment does not interfere with bond strengths of resin cement to dentin.


Staff support groups: helping nurses to help themselves.
When the goals of staff development programming include increased introspection, problem-solving skills, or team effort, nursing administration may find that nurses are their own best resources. A nursing staff support group, run by a qualified leader, can offer nurses mutual help in reducing stress and managing conflict.


Xinshuaining preparation protects H9c2 cells from H2O2-induced oxidative damage through the PI3K/Akt/Nrf-2 signaling pathway.
Cardiovascular disease (CVD) is the leading cause of death. Oxidative stress is an important pathological process of a variety of CVDs. Xinshuaining preparation has a therapeutic effect on the heart failure. However, the anti-oxidative stress role of Xinshuaining preparation in H9c2 cells is still unclear. The medicated serum of Xinshuaining preparation was acquired and utilized to hatch with H2O2-induced H9c2 cells. Main components in the Xinshuaining preparation were analyzed by liquid chromatography-mass spectrometry (LC/MS). The effect of medicated serum on the cell viability, apoptosis rate, the oxidative stress indicators (SOD, GSH-Px, and MDA), mitochondrial membrane potential (MMP), and ROS level was evaluated by CCK-8, flow cytometry, commercial biochemical detection kits, and JC-1 staining. Additionally, the associated mechanism was determined by the detection of the protein levels (PI3K, phosphorylated PI3K, Akt, phosphorylated Akt, and Nrf-2) through western blot assays, which was also further assessed with the application of LY294002. The medicated serum of Xinshuaining preparation notably increased the H2O2-reduced, the cell viability, the concentration of SOD and GSH-Px, MMP level and the relative protein expression level of phosphorylated PI3K and Akt and Nrf-2, while dampened the H2O2-elevated the level of the cell apoptosis rate, MDA, and ROS. However, Xinshuaining preparation on the cell viability, apoptosis, and oxidative stress was notably antagonized by LY294002 pre-treatment. The medicated serum of Xinshuaining preparation increased the cell viability and suppressed apoptosis and oxidative stress via the PI3K/Akt/Nrf-2 signaling pathway.


Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome-Based Verification Study.
The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC). This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2), tetraspanin-6 (TSPAN6), bone marrow stromal antigen 2 (BST2), and tumor necrosis factor receptor superfamily member 16 (NGFR)) as potential plasma CRC biomarkers. The study population comprises 152 CRC patients and 152 controls. Target protein levels in plasma and tissue samples were assessed by ELISA and immunohistochemistry, respectively. Among the four candidate proteins examined by ELISA in a small sample set, only BST2 showed significantly elevated plasma levels in CRC patients versus controls. Immunohistochemical analysis revealed the overexpression of BST2 in CRC tissues, and higher BST2 expression levels correlated with poorer 5-year survival (46.47% versus 65.57%; p = 0.044). Further verification confirmed the elevated plasma BST2 levels in CRC patients (2.35 ± 0.13 ng/mL) versus controls (1.04 ± 0.03 ng/mL) (p < 0.01), with an area under the ROC curve (AUC) being 0.858 comparable to that of CEA (0.867). BST2, a membrane protein selectively detected in CRC cell secretome, may be a novel plasma biomarker and prognosticator for CRC.


Culture-Specific Pathogenicity of Dhat (Semen Loss) Syndrome in an Arab/Islamic Society, Oman.
A number of reports from different parts of the world have challenged the assumption that Dhat syndrome is confined to populations in and around the Indian subcontinent. This single case study reports an Omani with features typical of Dhat syndrome. Psychometric measures showed elevated scores on indices of hypochondriasis, psychasthenia, and gender role development as defined in the Minnesota Multiphasic Personality Inventory. He rated adequately in measures assessing cognitive and executive functioning. Implementation of cognitive behavioral therapy, concurrent with a successful marriage proposal, resulted in a gradual resolution of the symptoms. This report concludes with a discussion on whether his Dhat syndrome should be viewed as a culture-reactive or culture-specific syndrome.


Recombinant modified vaccinia virus Ankara generating excess early double-stranded RNA transiently activates protein kinase R and triggers enhanced innate immune responses.
Double-stranded RNA (dsRNA) is an important molecular pattern associated with viral infection and is detected by various extra- and intracellular recognition molecules. Poxviruses have evolved to avoid producing dsRNA early in infection but generate significant amounts of dsRNA late in infection due to convergent transcription of late genes. Protein kinase R (PKR) is activated by dsRNA and triggers major cellular defenses against viral infection, including protein synthesis shutdown, apoptosis, and type I interferon (IFN-I) production. The poxviral E3 protein binds and sequesters viral dsRNA and is a major antagonist of the PKR pathway. We found that the highly replication-restricted modified vaccinia virus Ankara (MVA) engineered to produce excess amounts of dsRNA early in infection showed enhanced induction of IFN-β in murine and human cells in the presence of an intact E3L gene. IFN-β induction required a minimum overlap length of 300 bp between early complementary transcripts and was strongly PKR dependent. Excess early dsRNA produced by MVA activated PKR early but transiently in murine cells and induced enhanced systemic levels of IFN-α, IFN-γ, and other cytokines and chemokines in mice in a largely PKR-dependent manner. Replication-competent chorioallantois vaccinia virus Ankara (CVA) generating excess early dsRNA also enhanced IFN-I production and was apathogenic in mice even at very high doses but showed no in vitro host range defect. Thus, genetically adjuvanting MVA and CVA to generate excess early dsRNA is an effective method to enhance innate immune stimulation by orthopoxvirus vectors and to attenuate replicating vaccinia virus in vivo. Efficient cellular sensing of pathogen-specific components, including double-stranded RNA (dsRNA), is an important prerequisite of an effective antiviral immune response. The prototype poxvirus vaccinia virus (VACV) and its derivative modified vaccinia virus Ankara (MVA) produce dsRNA as a by-product of viral transcription. We found that inhibition of cellular dsRNA recognition established by the virus-encoded proteins E3 and K3 can be overcome by directing viral overexpression of dsRNA early in infection without compromising replication of MVA in permissive cells. Early dsRNA induced transient activation of the cellular dsRNA sensor protein kinase R (PKR), resulting in enhanced production of interferons and cytokines in cells and mice. Enhancing the capacity of MVA to activate the innate immune system is an important approach to further improve the immunogenicity of this promising vaccine vector.


[Association of RAS mutations in circulating cell-free DNA in the plasma with clinicopathological features of colorectal cancer].
To detect RAS mutations in the circulating cell-free DNA (cfDNA) in the plasma and explore the their correlation with the clinicopathological features in patients with colorectal cancer. Real-time PCR was used to detect RAS mutations in plasma cfDNA and matched tumor tissue DNA samples from 71 colorectal cancer patients. The correlation of RAS mutations with the clinicopathological features of the patients were analyzed. Of the 71 patients with colorectal cancer, 23 (32.39%) showed RAS mutations in the cfDNA and 36 (50.7%) showed RAS mutations in tumor tissue DNA, with a concordance rate of 76.06% in the results between the two samples (Kappa=0.523). RAS mutations in the cfDNA were not related to the patients' age (P=0.072), gender (P=0.320), tumor stage (IVa and IVb, P=0.450), primary tumor position (P=0.324), lung metastasis (P=0.237), CEA level (P=0.284) or CA199 level (P=0.427). The positivity rate of RAS mutations in plasma cfDNA was significantly higher in patients with liver metastasis than those without liver metastasis (P=0.045). Plasma cfDNA can be a reliable source of diagnostic DNA to replace the tumor tissue DNA for diagnosis of RAS mutations. RAS mutations in plasma cfDNA occur more frequently in colorectal cancer patients with liver metastasis.


Adenosine monophosphate-activated protein kinase activation enhances embryonic neural stem cell apoptosis in a mouse model of amyotrophic lateral sclerosis.
Alterations in embryonic neural stem cells play crucial roles in the pathogenesis of amyotrophic lateral sclerosis. We hypothesized that embryonic neural stem cells from SOD1(G93A) individuals might be more susceptible to oxidative injury, resulting in a propensity for neurodegeneration at later stages. In this study, embryonic neural stem cells obtained from human superoxide dismutase 1 mutant (SOD1(G93A)) and wild-type (SOD1(WT)) mouse models were exposed to H2O2. We assayed cell viability with mitochondrial succinic dehydrogenase colorimetric reagent, and measured cell apoptosis by flow cytometry. Moreover, we evaluated the expression of the adenosine monophosphate-activated protein kinase (AMPK) α-subunit, paired box 3 (Pax3) protein, and p53 in western blot analyses. Compared with SOD1(WT) cells, SOD1(G93A) embryonic neural stem cells were more likely to undergo H2O2-induced apoptosis. Phosphorylation of AMPKα in SOD1(G93A) cells was higher than that in SOD1(WT) cells. Pax3 expression was inversely correlated with the phosphorylation levels of AMPKα. p53 protein levels were also correlated with AMPKα phosphorylation levels. Compound C, an inhibitor of AMPKα, attenuated the effects of H2O2. These results suggest that embryonic neural stem cells from SOD1(G93A) mice are more susceptible to apoptosis in the presence of oxidative stress compared with those from wild-type controls, and the effects are mainly mediated by Pax3 and p53 in the AMPKα pathway.


Coupled Kinetics Model for Microbially Mediated Arsenic Reduction and Adsorption/Desorption on Iron Oxides: Role of Arsenic Desorption Induced by Microbes.
The dynamic behavior of arsenic (As) species is closely associated with iron mineral dissolution/transformation in the environment. Bacterially induced As(V) desorption from iron oxides may be another important process that facilitates As(V) release from iron oxides without significant reductive dissolution of iron oxides. Under the impact of bacterially induced desorption, As kinetic behavior is controlled by both the microbial reduction of As(V) and the As(III)&As(V) reactions on iron oxide surfaces. However, there is still a lack of quantitative understanding on the coupled kinetics of these processes in complex systems. We developed a quantitative model that integrated the time-dependent microbial reduction of As(V) with nonlinear As(III)&As(V) adsorption/desorption kinetics on iron oxides under the impact of bacterially induced As(V) desorption. We collected and modeled literature data from 11 representative studies, in which microbial reduction reactions occurred with minimal iron oxide dissolution/transformation. Our model highlighted the significance of microbially induced As(V) desorption and time-dependent changes of microbial reduction rates. The model can quantitatively assess the roles and the coupling of individual reactions in controlling the overall reaction rates. It provided a basis for developing comprehensive models for As cycling in the environment by coupling with other chemical, physical, and microbial processes.


Induction of long-term graft acceptance by a combination treatment of donor splenocytes and CTLA4Ig in a high responder rat liver transplantation model.
The CTLA4Ig has led to an improved survival rate in various allograft transplantation models. We investigated in a high responder rat model (Dark Agouti to Lewis) of orthotopic liver transplantation (ORLT), whether an additional adoptive cell transfer can enhance the effect of CTLA4Ig. After transplantation, recipients (n = 13/group) were treated with donor or third-party splenocytes alone or in combination with CTLA4Ig. Administration of splenocytes alone had no significant effect on survival (median 13 days, range 9-14) compared with untreated controls (median 10 days, range 8-12). CTLA4Ig monotherapy prolonged survival to a median of 30 days (range 11-150) but resulted in long-term graft rejection. The additional administration of third-party splenocytes showed no significant improvement over CTLA4Ig monotherapy. Only the combination of donor splenocytes with CTLA4Ig led to long-term graft acceptance (>150 days) without clinical and/or histological signs of rejection. A higher rate of apoptosis could be detected in livers at early time-points in long-term survivors receiving CTLA4Ig and donor splenocytes. Analysis of cytokine mRNA expression revealed a decrease of interleukin-2 at early time-points in all groups receiving CTLA4Ig; whereas, interferon-gamma was increased in long-term survivors receiving CTLA4Ig and donor cells or donor cells alone. The combination of CTLA4Ig and donor derived splenocytes is potent to induce long-term survival and graft acceptance. The mechanisms appear to involve the induction of an early inflammatory impulse and apoptosis.


Evaluation of Oral Tiazinidine Effects on [intraoperative] Hemodynamic Responses During Direct Laryngoscopy Under General Anesthesia.
Direct laryngoscopy and tracheal intubation can result in blood pressure and heart rate increase which in turn may lead to myocardial ischemia, cerebral hemorrhage, and even death in susceptible patients. Tizanidine is α2-receptor agonists that suppresses central sympathetic system. This study evaluates the effects of oral Tizanidine on hemodynamic responses during operations and aims to determine the appropriate Propofol dosage to maintain anesthesia under BIS monitoring. A double-blind clinical trial has been performed on 70 candidates for elective abdominal surgery undergoing general anesthesia in Educational Hospital of Ghaem, Mashhad, Iran. 35 randomly selected patients (the case group) were given 4 mg of oral Tizanidine 90 minutes before the induction of anesthesia whereas the remaining subjects (the control group) were given placebo. Blood pressure and heart rate before and after induction of anesthesia, and after intubation and extubation, existence of postoperative shivering, and the needed Propofol dosage were measured and recorded. Data analysis was done with T-test and Chi-squared test, using SPSS software version 16. Variations of blood pressure and heart rate after anesthesia induction, intubation and extubation were less in Tizanidine group generally. Postoperative shivering was reported in 28.6% and 11.4% of patients in control and case group respectively. Average propofol needed dose for anesthesia maintenance in case group was 25% less than the needed amount in the control group. Using oral Tizanidine as a premedication, yielded stability in blood pressure and heart rate during surgery and decreased required Propofol. Considering its short duration of action, Tizanidine use as a premedication is recommended for sedation and stabilization of hemodynamic responses during the operations.


Simulation of impedance changes with a FEM model of a myelinated nerve fibre.
Fast neural electrical impedance tomography (EIT) is a method which permits imaging of neuronal activity in nerves by measuring the associated impedance changes (dZ). Due to the small magnitudes of dZ signals, EIT parameters require optimization, which can be done using in silico modelling: apart from predicting the best parameters for imaging, it can also help to validate experimental data and explain the nature of the observed dZ. This has previously been completed for unmyelinated fibres, but an extension to myelinated fibres is required for the development of a full nerve model which could aid imaging neuronal traffic at the fascicular level and optimise neuromodulation of the supplied internal organs to treat various diseases. An active finite element method (FEM) model of a myelinated fibre coupled with external space was developed. A spatial dimension was added to the experimentally validated space-clamped model of a human sensory fibre using the double cable paradigm. Electrical parameters of the model were changed so that nodal and internodal membrane potential as well as propagation velocity agreed with experimental values. Impedance changes were simulated during activity under various conditions and the optimal parameters for imaging were determined. When using AC, dZ could be recorded only at frequencies above 4 kHz, which is supported by experimental data. Optimal bandwidths for dZ measurement were found to increase with AC frequency. The novel fully bi-directionally coupled FEM model of a myelinated fibre was able to optimize EIT for myelinated fibres and explain the biophysical basis of the measured signals.


[Early diagnosis and treatment of acute mesentric ischemia for 42 cases in single center].
To investigate the early diagnosis and treatment of acute mesenteric ischemia. Forty-two patients with acute mesenteric ischemia from June 2007 to November 2011 were reviewed retrospectively. All patients were diagnosed with DSA and (or) CT and (or) surgery. In this group, there were 32 cases of acute occlusion of meseteric ischemia (AOMI), 9 cases of superior mesenteric venous thrombosis (SMVT) and 1 case of non-occlusive mesenteric ischemia. The patients were treated using comprehensive treatment including early intervention treatment and application of the principle of damage control. The survival of all patients was followed up for 6 months or more in outpatient. (1) Of the 32 AOMI cases, 4 cases healing by systemic anticoagulation; The 19 cases received interventional treatment, including 10 cases received simply interventional treatment, surgery after the failure of intervention in 5 cases, 3 patients died without surgery and postoperative interventional treatment one cases were cured; Eight cases received surgery treatment; One case gave up. (2) Of the 9 SMVT cases, 2 cases healing by systemic anticoagulation; The 6 cases received interventional treatment, including 1 cases received simply interventional treatment, surgery after the failure of intervention in 1 cases, 4 cases to consider intestinal necrosis received interventional treatment again after surgery; One patient died without treatment. (3) Eight cases received delay abdomen close treatment with the principle of damage control surgery. The overall mortality rate of 23.8% (10/42). Interventional treatment of 26 cases, 4 deaths, a mortality rate of 15.3%; The abdomen delayed close of 8 cases, 1 death. The results show that early diagnosis and treatment is critical to reduce AMI mortality. Comprehensive treatment of early intervention treatment and application of the principle of damage control can significantly reduce the mortality of AMI.


Relationship between the Metabolic Associated Fatty Liver Disease and Endometrial Thickness in Postmenopausal Women: A Cross-sectional Study in China.
Objectives: To determine the relationship between the endometrial thickness (ET) and metabolic associated fatty liver disease (MAFLD) in the postmenopausal women who have a comprehensive health examination. Methods: This was a population-based, retrospective observational study of the prevalence of MAFLD in 8594 postmenopausal women with different ET in the Quality Control Center of Health Examination in Chongqing, China. Binary and multivariable logistic regression analyses were used to obtain odds ratios and 95% confidence intervals for patients of different ET with MAFLD after adjusting for age. Results: The incidences of MAFLD were 28.6% (1352), 30.3% (1058), 34.9% (133) in postmenopausal women with ET of < 3 mm, 3 mm ≤ & < 5 mm, and ≥ 5 mm, respectively. Compared with a baseline ET of less than 5.0 mm, the risk of MAFLD in patients with ET of ≥5.0 mm is higher (OR=1.291, 95% CI: 1.041-1.603, P<0.05). After adjustment for age, a statistically significant positive correlation was still observed. The increased prevalence of MAFLD in patients with ET of 3 mm ≤ &<5 mm (OR=1.110, 95% CI: 1.008-1.223) and ≥5 mm (OR=1.383, 95% CI: 1.109-1.724) achieved statistical significance, respectively. In addition, multiple logistic analyses controlling for age also confirmed the finding of positive correlation among body mass index (BMI) and ET. Conclusion: Our results suggest that there is a positive correlation between MAFLD and ET in postmenopausal women. In addition, increased BMI is also associated with an increased risk of thickened endometrium.


Solubility enhancement of a bisnaphthalimide tumoricidal agent, DMP 840, through complexation.
The purpose of this research was to enhance the aqueous solubility of DMP 840 by complexation with water-soluble and nontoxic agents, and to understand the nature of the interactions involved in complex formation using nuclear magnetic resonance (1H-NMR). The solubility of DMP 840 in water, saline, acetate buffers, and cosolvent mixtures was determined by high-performance liquid chromatography, and the effect of nicotinamide and pyridoxine concentrations on the solubility of DMP 840 was examined by the phase solubility method. 1H-NMR spectra were acquired in deuterated acetate buffer at 400 MHz on a Varian Unity-400 spectrometer. The aqueous solubility of DMP 840 was sensitive to the presence of chloride and acetate anions in solution, and did not improve in the presence of cosolvents. The use of the nontoxic and water-soluble complex-forming agents nicotinamide and pyridoxine, however, resulted in a linear increase in the aqueous solubility of DMP 840 with both ligands. The solubilization appears to be due to formation of 1:1 complexes between DMP 840 and the bioorganic ligands. The complexation constants were 15.57 M-1 for the DMP 840:nicotinamide complex and 13.36 M-1 for the DMP 840:pyridoxine complex. The NMR results indicate that the interaction is a result of vertical or plane-to-plane stacking and the complexation constants were in agreement with that obtained by phase solubility. The results suggest that the aqueous solubility of a poorly water soluble drug substance such as DMP 840 can be significantly enhanced by its complexation with water-soluble and nontoxic agents.


Apophallus microsoma N. SP. from chicks infected with metacercariae from coho salmon (Oncorhynchus kisutch) and review of the taxonomy and pathology of the genus Apophallus (Heterophyidae).
Metacercariae of an unidentified species of Apophallus Lühe, 1909 are associated with overwinter mortality in coho salmon, Oncorhynchus kisutch (Walbaum, 1792), in the West Fork Smith River, Oregon. We infected chicks with these metacercariae in order to identify the species. The average size of adult worms was 197 × 57 μm, which was 2 to 11 times smaller than other described Apophallus species. Eggs were also smaller, but larger in proportion to body size, than in other species of Apophallus. Based on these morphological differences, we describe Apophallus microsoma n. sp. In addition, sequences from the cytochrome c oxidase 1 gene from Apophallus sp. cercariae collected in the study area, which are likely conspecific with experimentally cultivated A. microsoma, differ by >12% from those we obtained from Apophallus donicus ( Skrjabin and Lindtrop, 1919 ) and from Apophallus brevis Ransom, 1920 . The taxonomy and pathology of Apophallus species is reviewed.


Coarse-grained molecular dynamics study of permeability enhancement in DPPC bilayers by incorporation of lysolipid.
The enhanced permeability of flat lipid bilayer membranes at their gel to liquid-crystalline (LC) phase transition has been explored using coarse-grained molecular dynamics. The phase transition temperature, T(m), is deduced by monitoring the area per lipid, the lipid lateral diffusion constant, and the lipid-lipid radial distribution function. We find that a peak in the permeability coincides with the phase transition from the gel to LC state when lysolipid is present. This peak in permeability correlates with a jump in the area per lipid near the same temperature as well as increased fluctuations in the lipid bilayer free volume. At temperatures above T(m), the permeability is only slightly dependent on the amount of lysolipid present. The increased free volume due to the "missing tail" of the lysolipid is partially compensated for by a decrease in area per lipid as the amount of lysolipid increases. We also found that in the coarse-grained model a small amount (< or = 15 mol %) of lysolipid stabilizes the gel phase and increases the phase transition temperature, while a larger amount of lysolipid (20 mol %) reduces T(m) back to that for pure DPPC, and bilayers consisting of > or = 30 mol % lysolipid did not form a gel phase but still exhibited a peak in permeability near T(m) for pure DPPC.


Effects of Early Postoperative Intraocular Pressure after Ahmed Glaucoma Valve Implantation on Long-term Surgical Outcomes.
To evaluate the long-term effects of early postoperative intraocular pressure (IOP) after Ahmed glaucoma valve (AGV) implantation on long-term surgical outcomes. This retrospective, non-randomized study included 100 eyes of 100 patients who underwent AGV surgery. We divided the enrolled patients into four groups according to the presence of transient hypotony within the first postoperative week or the presence of a hypertensive phase during the first three postoperative months. Postoperative IOP, the number of glaucoma medications, and cumulative success rate were compared among the groups. There was significantly better IOP control and a better success rate in the non-hypertensive phase group 2 years postoperatively. However, no significant difference was found in the IOP or success rate at 2 years postoperatively between the transient hypotony and non-hypotony groups. Further subgroup analysis showed that the non-hypotony, non-hypertensive phase group had a significantly higher success rate (100%) at 2 years postoperatively. We can predict the long-term prognosis after AGV implantation by considering the early postoperative IOP state and the presence of a hypertensive phase.


A review of the nematode assemblage of the Australian bandicoot, Isoodon macrourus (Peramelidae), from material held in the South Australian Museum with the description of Sprattellus cassonei n. sp. (Mackerrastrongylidae).
A total of 235 vials of nematodes held in the Australian Helminthological Collection of the South Australian Museum from 125 individuals of Isoodon macrourus were examined. The nematode assemblage of I. macrourus, comprising 12 families, including 16 genera and 23 identified species, was compared with the sympatric bandicoot species Perameles nasuta, 20 identified species (Sorensen's index of similarity 0.56) and P. pallescens, 12 identified species (Sorensen's index 0.51). Sprattellus cassonei n. sp. is distinguished from its congeners by having a synlophe with 7-8 ridges with the anterior ventral ridges interrupted, the morphology of the dorsal ray and the branching of the spicule tips. A single male specimen identified as Linstowinema sp. 1. is characterised by seven circles of body hooks, the oesophagus terminating at the level of the seventh circle and robust scale-like spines on the posterior ventral body. A complete description of the species will require additional material, including females. Difficulties in identifying individuals of the genus Mackerrastrongylus to species level are discussed. Overall similarities in the nematode assemblages of the three bandicoot hosts are likely due to shared relationships and similar behaviours.


Omani Frankincense nanoemulsion formulation efficacy and its latent effects on biological aspects of the spiny bollworm Earias insulana (Boisd.).
Our research shed light on the perspective of formulation technology regarding its responsibility to provide phyto-insecticides that are worthy of research into potential novel applications. There has been an increase in interest in using nanoemulsion as a new formulation in a variety of sectors during the last several decades. Boswellia sacra essential oil (Fam: Burseraceae) from the resin of frankincense trees has been recently proposed as a promising ingredient in a new generation of botanical insecticides. Frankincense nanoemulsion was formulated in 5% ratios comprising frankincense oil, surfactants, and water. A frankincense nanoemulsion was prepared using a high-energy ultra-sonication process and characterized by dynamic light scattering transmission electron microscopy surface tension, viscosity, and zeta potential value. Gas chromatography/mass spectrometry (GC/MS) was used to identify the chemical profiles of frankincense essential oil. Furthermore, insecticidal effects against second instar larvae of the spiny bollworm, Earias insulana, as well as their latent effects on the larvae were studied. In the present study, the formulation was a good nanoemulsion. The surface tension was 53.69, the viscosity was 4.76 cPs, the zeta potential was-10 mV, and the size distribution was 41.30 nm. The polydispersity index (PDI) of the nanoemulsion was found to be 0.26, and the morphology of the frankincense nanoemulsion was visualized in a spherical shape. The main constituents identified in frankincense oil were α-pinene (15.52%); monolinolenin (12.92%); and geranylgeranyl acetate (9.99%). The results showed significant insecticidal activity against the larval stage and considerably decreased the pupation percentage with increasing the volume of the frankincense nanoemulsion. On the other hand, the latent effects of the frankincense nanoemulsion on E. insulana resulted in a higher prolongation of larval and pupal durations as well as a significant reduction in the weight of larvae and pupae of E. insulana. Additionally, frankincense nanoemulsion dramatically influenced the adult emergence percentage. It also caused a significantly lower hatchability percentage compared to the untreated control. The concentrations used and the types of mating combination have a significant effect on the fecundity of E. insulana. This novel frankincense nanoemulsion formulation could be used in strategies to control the spiny bollworm on cotton plants.


[Specificity of functional changes of visual system at the early stage of involutional central chorioretinal dystrophy].
Involutional central chorioretinal dystrophy (ICCD) represents a disease of central zone of the retina in the persons of elderly and senile age that is characterized by bilateral affection and is one of the most widespread reasons for sight inability all over the world. The purpose of our research was to reveal specific symptoms of functional disturbance of the visual system at the early stage of ICCD. Clinical studies were based on the analysis of results 75 patients (142 eyes), at the age from 50 to 70 years with visual acuity 0.7-1.0., with "firm" drusen in 44 eyes, "soft" drusen in 51 eyes, "soft confluent" drusen in 47 eyes. Along with the routine ophtalmological methods of investigation, the psychophysical methods were used in order to study spatial contrast sensitivity (SCS) and color contrast sensitivity ("ON-OFF"). Specific functional changes of visual system at an early stage of ICCD are characterized by a reduction of spatial localization, infringement of topography of color and on-off contrast sensitivity. Possible explanation of the given fact is disturbance of fine exchange processes in a complex of photoreceptor-pigmentary epithelium, leading to the disturbance of the function of the retina's central cones. Thus, disturbance of spatial contrast, color and contrast sensitivity is a reliable diagnostic criterion allowing revealing the change of function of the retina's cone apparatus already at the early of ICCD.


Co3 O4 Supported on β-Mo2 C with Different Interfaces for Electrocatalytic Oxygen Evolution Reaction.
Interface engineering is an effective strategy for improving the activity of catalysts in electrocatalytic oxygen evolution reaction (OER). Herein, Co3 O4 supported on β-Mo2 C with different interfaces were investigated for electrocatalytic OER. The morphological diversity of β-Mo2 C supports allowed different Co3 O4 -Mo2 C interactions. Various techniques characterized the composition and microstructure of the interface in the composites. Due to the strong interaction between Co3 O4 nanoparticles and β-Mo2 C nanobelts with opposing surface potentials, compact interface was observed between Co3 O4 active species and β-Mo2 C nanobelt support. The compact interface enhanced the conductivity of the material and also regulated the interfacial electron redistribution of Mo and Co atoms, promoting the charge transfer process during OER. In addition, the surface loading of Co3 O4 can effectively improve the hydrophilicity of the surface. β-Mo2 C has the capability in dissociating H2 O molecules. Thus, an example has been carefully demonstrated for interface engineering in electrocatalytic OER.


Up-Regulation of Activating Transcription Factor 3 in Human Fibroblasts Inhibits Melanoma Cell Growth and Migration Through a Paracrine Pathway.
The treatment of melanoma has remained a difficult challenge. Targeting the tumor stroma has recently attracted attention for developing novel strategies for melanoma therapy. Activating transcription factor 3 (ATF3) plays a crucial role in regulating tumorigenesis and development, but whether the expression of ATF3 in human dermal fibroblasts (HDFs) can affect melanoma development hasn't been studied. Our results show that ATF3 expression is downregulated in stromal cells of human melanoma. HDFs expressing high levels of ATF3 suppressed the growth and migration of melanoma cells in association with downregulation of different cytokines including IL-6 in vitro. In vivo, HDFs with high ATF3 expression reduced tumor formation. Adding recombinant IL-6 to melanoma cells reversed those in vitro and in vivo effects, suggesting that ATF3 expression by HDFs regulates melanoma progression through the IL-6/STAT3 pathway. More importantly, HDFs pretreated with cyclosporine A or phenformin to induce ATF3 expression inhibited melanoma cell growth in vitro and in vivo. In summary, our study reveals that ATF3 suppresses human melanoma growth and that inducing the expression of ATF3 in HDFs can inhibit melanoma growth, a new potential melanoma therapeutic approach.


Cartilage in hemophilic arthropathy. Ultrastructural and microanalytical studies.
The presence of iron in articular cartilage was investigated in five human and two canine cases of factor VIII-deficiency hemophilic arthropathy. The lesions were mild in three cases. Advanced destruction of the cartilage was present in four cases, in one of which sufficient cartilage was preserved to permit recognition of hemosiderin in chondrocytes. The Fe was present in the form of siderosomes and ferritin granules free in the cytoplasm. Iron and phosphorus were demonstrated in the siderosomes by energy dispersion analysis of x-rays; but no Fe was identified by this means or by light or transmission electron microscopy in chondrocytes from the three subjects in an early stage of the disease or in the matrix from any of the seven subjects. The findings lend no support to the hypothesis that salt formation or chelation of Fe ions by matrix proteoglycans is responsible for destruction of cartilage in hemophilic or other chronic hemarthroses. A second, nonferruginous, bilirubin-like pigment (hematoidin) was present in the matrix at the surface of the cartilage in two specimens.


Rapid macular hole formation and closure in a vitrectomized eye following rhegmatogenous retinal detachment repair.
The development of a full-thickness macular hole (FTMH) after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) repair is a rare occurrence. We report the first case of rapid MH formation with internal limiting membrane (ILM)-like hyper-reflective bridging membrane under silicone oil (SO) meniscus, noted on the first postoperative day (POD) postvitrectomy for RRD. A 57-year-old man presented with best-corrected visual acuity (BCVA) of perception of light with immature cataract and total RRD in the left eye. He underwent cataract extraction with intraocular lens implantation with uneventful PPV, endolaser to primary break, and 360° periphery followed by injection of 1000 Cst SO. On the first POD, retina was attached in all quadrants with SO in situ. However, a dark red spot was noted at macula which was confirmed as FTMH with a bridging linear hyper-reflectivity under SO meniscus on optical coherence tomography (OCT). Repeat OCT, at 2 weeks and 3 months, revealed closed MH under the SO meniscus with BCVA improving to 6/60. This is the first reported case of very rapid FTMH formation with an ILM-like linear hyper-reflectivity following vitrectomy for RRD and highlights the possible contributory role of multiple nonconventional factors for rapid FTMH development and fibrinous membrane-assisted closure under SO tamponade.


Vocal Features of Song and Speech: Insights from Schoenberg's Pierrot Lunaire.
Similarities and differences between speech and song are often examined. However, the perceptual definition of these two types of vocalization is challenging. Indeed, the prototypical characteristics of speech or song support top-down processes, which influence listeners' perception of acoustic information. In order to examine vocal features associated with speaking and singing, we propose an innovative approach designed to facilitate bottom-up mechanisms in perceiving vocalizations by using material situated between speech and song: Speechsong. 25 participants were asked to evaluate 20 performances of a speechsong composition by Arnold Schoenberg, "Pierrot lunaire" op. 21 from 1912, evaluating 20 features of vocal-articulatory expression. Raters provided reliable judgments concerning the vocal features used by the performers and did not show strong appeal or specific expectations in reference to Schoenberg's piece. By examining the relationship between the vocal features and the impression of song or speech, the results confirm the importance of pitch (height, contour, range), but also point to the relevance of register, timbre, tension and faucal distance. Besides highlighting vocal features associated with speech and song, this study supports the relevance of the present approach of focusing on a theoretical middle category in order to better understand vocal expression in song and speech.


HIV-1 binding to CD4 T cells does not induce a Ca2+ influx or lead to activation of protein kinases.
The penetration of CD4+ cells by human immunodeficiency virus (HIV) involves a high affinity interaction between the viral attachment protein, gp120, and the cellular receptor, CD4. The mechanism by which the virus penetrates the host cell subsequent to viral binding is unknown. We have investigated the possibility that HIV penetration induces changes in the metabolic state of the infected cell similar to those seen with the perturbation of CD4 cells by monoclonal antibodies (MAb) directed against the CD4 molecule, or with specific antigen-mediated activation. The activation of cellular protein kinases was examined. The basal level of activity was not altered in the presence of HIV. Kinase activity was markedly increased in cells stimulated with phytohemagglutinin (PHA), and was qualitatively and quantitatively changed by a brief exposure to the phorbol ester TPA (12-o-tetradecanoyl phorbol-13-acetate). The phosphorylation state of the CD4 molecule was examined by radioimmunoprecipitation and found to be unaltered by the binding of HIV under conditions in which TPA induced rapid CD4 phosphorylation. The activity of the CD4-associated protein tyrosine kinase p56lck was measured by in vitro assays of 32PO4 incorporation in CD4 immunoprecipitates from HIV-incubated cells. TPA incubation resulted in a rapid loss of CD4-associated p56lck activity, presumably due to dissociation of the enzyme from CD4. Concanavalin A stimulation resulted in a similar change but with a slower time course. However, no change in CD4-associated activity was detected in HIV-incubated cells. We found that Ca2+ influx was not induced by the binding of HIV to CD4+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Cost and Capability Compromises in STEM Instrumentation for Low-Voltage Imaging.
Low-voltage transmission electron microscopy (≤80 kV) has many applications in imaging beam-sensitive samples, such as metallic nanoparticles, which may become damaged at higher voltages. To improve resolution, spherical aberration can be corrected for in a scanning transmission electron microscope (STEM); however, chromatic aberration may then dominate, limiting the ultimate resolution of the microscope. Using image simulations, we examine how a chromatic aberration corrector, different objective lenses, and different beam energy spreads each affect the image quality of a gold nanoparticle imaged at low voltages in a spherical aberration-corrected STEM. A quantitative analysis of the simulated examples can inform the choice of instrumentation for low-voltage imaging. We here demonstrate a methodology whereby the optimum energy spread to operate a specific STEM can be deduced. This methodology can then be adapted to the specific sample and instrument of the reader, enabling them to make an informed economical choice as to what would be most beneficial for their STEM in the cost-conscious landscape of scientific infrastructure.


A Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing Surgical versus Conservative Treatments for Acute Undisplaced or Minimally-Displaced Scaphoid Fractures.
Surgical and conservative methods have been reported by various studies for high rates of fracture union and subsequent regain of function among patients with undisplaced or minimally-displaced scaphoid fractures. Hence, this study aims to analyze the best available evidence to comprehend the relative benefits and risks of these therapeutic options. A systematic search of the literature from different databases and search engines was performed with strict eligibility criteria to obtain the highest quality of evidence. All randomized controlled trials delineating the outcomes of surgical versus conservative treatments for acute undisplaced or minimally-displaced scaphoid fractures were included and then evaluated using scoring tools: Cochrane risk of bias tool and PEDro scale. Data were pooled using random-effects models with standard mean differences for continuous outcomes and risk ratios for dichotomous variables. The search yielded 339 potentially related articles, further trimmed down to eight studies based on the eligibility criteria. The meta-analysis revealed that surgical treatment resulted in significantly better functional outcomes than conservative treatment. Furthermore, surgery resulted in the prevention of delayed union of fractures and reduction of time needed to return to work. While four studies reported advantages of surgical treatment, evidence was insufficient to provide a definitive conclusion that surgery is a better option. Due to the significant limitations with respect to certain variables, the superiority of one method to the other could not be established.