Influence of three BALB/c substrain backgrounds on the skin tumor induction efficacy to DMBA and TPA cotreatment.
Differences in responsiveness of BALB/c substrains have been investigated in various fields, including diabetes induction, corpus callosum deficiency, virus-induced demyelinating disease, aggressive behavior and osteonecrosis. However, induction efficacy of skin tumor remains untried. We therefore investigated the influence of BALB/c substrain backgrounds on the skin tumor induction efficacy in response to DMBA (7,12-Dimethylbenz[a]anthracene) and TPA (12-O-tetradecanoylphorbol-13-acetate) cotreatment. Alterations in the levels of tumor growth related factors, histopathological structure, and the expression to tumor related proteins were measured in three BALB/c substrains (BALB/cKorl, BALB/cA and BALB/cB) after exposure to DMBA (25 μg/kg) and three different doses of TPA (2, 4 and 8 μg/kg). The average number and induction efficacy of tumors in response to DMBA+TPA treatment were significantly greater in the BALB/cKorl substrain than in BALB/cA and BALB/cB. However, cotreatment with DMBA+TPA induced similar responses for body and organ weights of all three substrains. Few differences were detected in the serum analyzing factors, while similar responsiveness was observed for blood analyzing factors after DMBA+TPA treatment. Furthermore, the three BALB/c substrains exhibited similar patterns in their histopathological structure in DMBA+TPA-induced tumors. The expression levels of apoptotic proteins and tumor related proteins were constantly maintained in all three BALB/c substrains treated with DMBA+TPA. In addition, the responsiveness to cisplatin treatment was overall very similar in the three BALB/c substrains with DMBA+TPA-induced tumors. Taken together, these results indicate that genetic background of the three BALB/c substrains does not have a major effect on the DMBA+TPA-induced skin carcinogenesis and therapeutic responsiveness of cisplatin, except induction efficacy.


Diagnostic yield of the cytomegalovirus (CMV) antigenemia assay and clinical features in solid organ transplant recipients and hematopoietic stem cell transplant recipients with CMV pneumonia.
Data are limited on the value of non-invasive diagnostic methods, such as the cytomegalovirus (CMV) antigenemia assay, and the clinical features of CMV pneumonia in patients who have undergone solid organ transplant (SOT) compared with those who have had hematopoietic stem cell transplant (HSCT). All adult patients with suspected CMV pneumonia, who had received SOT or HSCT in a tertiary hospital during a 5-year period, were retrospectively enrolled. CMV pneumonia was defined as clinical and radiographic evidence of pneumonia in association with the isolation of CMV in viral cultures of bronchoalveolar lavage or lung tissue specimens, or with the identification of CMV in lung tissue. In total, 36 patients with CMV pneumonia were identified. Of these, 29 (80%) had received SOT and 7 (20%) had received HSCT. The incidence of CMV pneumonia in the patients with SOT (3.0 per 1000 person-years [95% confidence interval {CI} 0.6-8.7]) was lower than in those with HSCT (17.0 per 1000 person-years [95% CI 9.9-27.2], P = 0.003) and CMV-related mortality showed a tendency to have lower mortality in patients with SOT (10% [3/29]) than with HSCT (43% [3/7], P = 0.07). The overall sensitivity of the CMV assay (≥ 1/200,000 leukocytes) in patients with CMV pneumonia was 69% (95% CI 52-84%). The CMV antigenemia test is of limited value in diagnosing CMV pneumonia, given the high cost of false-negative diagnoses of CMV pneumonia.


Effect of aerobic fitness on capillary blood volume and diffusing membrane capacity responses to exercise.
Endurance trained athletes exhibit enhanced cardiovascular function compared to non-athletes, although it is considered that exercise training does not enhance lung structure and function. An increased pulmonary capillary blood volume at rest is associated with a higher V̇O2 max . In the present study, we compared the diffusion capacity, pulmonary capillary blood volume and diffusing membrane capacity responses to exercise in endurance-trained males compared to non-trained males. Exercise diffusion capacity was greater in athletes, secondary to an increased membrane diffusing capacity, and not pulmonary capillary blood volume. Endurance-trained athletes appear to have differences within the pulmonary membrane that facilitate the increased O2 demand needed for high-level exercise. Endurance-trained athletes exhibit enhanced cardiovascular function compared to non-athletes, allthough it is generally accepted that exercise training does not enhance lung structure and function. Recent work has shown that an increased resting pulmonary capillary blood volume (VC ) is associated with a higher maximum oxygen consumption (V̇O2 max ), although there have been no studies to date examining how aerobic fitness affects the VC response to exercise. Based on previous work, we hypothesized that endurance-trained athletes will have greater VC compared to non-athletes during cycling exercise. Fifteen endurance-trained athletes (HI: V̇O2 max 64.6 ± 1.8 ml kg(-1) min(-1) ) and 14 non-endurance trained males (LO: V̇O2 max 45.0 ± 1.2 ml kg(-1) min(-1) ) were matched for age and height. Haemoglobin-corrected diffusion capacity (DLCO), VC and diffusing membrane capacity (DM ) were determined using the Roughton and Forster () multiple fraction of inspired O2 (FI O2 )-DLCO method at baseline and during incremental cycle exercise up to 90% of peak O2 consumption. During exercise, both groups exhibited increases in DLCO, DM and VC with exercise intensity. Athletes had a greater DLCO and greater DM at 80 and 90% of V̇O2 max compared to non-athletes. However, VC was not different between groups during exercise. In contrast to our hypothesis, exercise VC was not greater in endurance-trained subjects compared to controls; rather, the increased DLCO in athletes at peak exercise was secondary to an enhanced DM . These findings suggest that endurance-trained athletes appear to have differences within the pulmonary membrane that facilitate the increased O2 demand needed for high-level exercise.


Ventilation-perfusion lung scans for pulmonary emboli. Accuracy of reporting.
Reports were made on combined ventilation-perfusion lung scans by three observers on three occasions and by another observer once. Reproducibility for each observer varied between 80 and 88%. There was complete agreement about the areas of scans reported as abnormal. Agreement between observes on whether or not the abnormality represented a pulmonary embolus averaged 77%. There was 86% agreement with the final clinical diagnosis. Our results show that reporting of ventilation perfusion lung scans by eye is reproducible. They support the claims that, under routine clinical conditions, the technique is 91% to 95% accurate for pulmonary emboli.


SRC homology 3 domains: multifaceted binding modules.
The assembly of complexes following the detection of extracellular signals is often controlled by signaling proteins comprising multiple peptide binding modules. The SRC homology (SH)3 family represents the archetypical modular protein interaction module, with ~300 annotated SH3 domains in humans that regulate an impressive array of signaling processes. We review recent findings regarding the allosteric contributions of SH3 domains host protein context, their phosphoregulation, and their roles in phase separation that challenge the simple model in which SH3s are considered to be portable domains binding to specific proline-rich peptide motifs.


Effect of ultrasound on a bilayer lipid membrane.
The effects of continuous wave ultrasound at a frequency of 1 MHz in the intensity range of 0-1.4 W/cm2 on an oxidized cholesterol bilayer lipid membrane (BLM) were observed. Ultrasound at 1.5 W/cm2 broke the membrane; in the range from 0.5 to 1.4 W/cm2, it accelerated the draining of the bulk lipid solution from the annulus to the Teflon support. At all intensities it has no effect on the conductance, the capacitance, or the dependence of each on the voltage applied across the membrane. Electrical parameters were measured in the presence of aqueous solutions of NaCl, KCl, and distilled water. The motivation and results of this project are explained in relation to an overall objective of determining the specific effects of ultrasound on biological membranes.


Lin28A and androgen receptor expression in ER-/Her2+ breast cancer.
The aim of this study was to examine the expression of Lin28A and androgen receptor (AR) in ER-/Her2+ breast cancer, and to research the association of Lin28A and AR co-expression status with patients' prognosis. The expression of Lin28A and AR in formalin-fixed and paraffin-embedded surgical sections from 305 patients with ER-/Her2+ breast cancer was analyzed by immunohistochemistry, and the co-expression patterns in breast cancer cells were investigated by immunofluorescent staining. The impact of the expression of Lin28A and AR in prognosis was also assessed by the Kaplan-Meier, univariate, and multivariate logistic regression models. This study included 305 cases ER-/Her2+ breast cancer patients. Lin28A and AR were expressed in 240 cases (78.7 %) and 220 cases (72.1 %), respectively. Lin28A tended to be higher in AR-positive patients (75.0 %). Lin28A and AR co-expression (Lin28+/AR+) was significantly associated with high tumor grade (G3) (p = 0.023) and high Ki67 index (p = 0.020). The mRNA and protein expression levels of Lin28A and AR were higher in MDA-MB-453 cells (ER-/Her2+) than in the MDA-MB-231 cells (ER-/Her2-). In univariate analysis, Lin28A+/AR+ was significant risk factors associated with unfavorable OS (p = 0.049) and RFS (p = 0.019). Kaplan-Meier analysis showed that Lin28A+/AR+ expression showed lower RFS rates compared with Lin28A-/AR+ (p = 0.043) and Lin28A-/AR- patients(p = 0.019). Multivariate cox model showed that Lin28A+/AR+ remained an independent negative prognostic factor for RFS. Our study showed that Lin28A and AR co-expressed in ER-/Her-2+ breast cancer and correlated with poor prognosis. The possibility that Lin28A may drive AR expression via a positive feedback mechanism remains to be tested.


Recall bias of the symptoms of nausea and vomiting of pregnancy.
Nausea and vomiting of pregnancy is the most common medical condition in pregnancy. Relatively little research has been conducted on this condition, and much of it is based on women's reports. Determinants that affect women's reports of their nausea and vomiting of pregnancy symptoms have not been elucidated. The purpose of this study was to assess the accuracy of recall by women of their symptoms of nausea and vomiting of pregnancy. Two hundred women who called the Motherisk nausea and vomiting of pregnancy counseling line in Toronto were asked about the severity of their nausea and vomiting of pregnancy symptoms with the use of the pregnancy unique quantification of emesis and nausea system (PUQE). The patients were asked the same questions again during a follow-up call, which took place up to 16 weeks later. There was a recall (or reporting) bias for nausea and vomiting, with women reporting significantly more severe symptoms during their follow-up call than they had reported originally. Multivariate analysis revealed that the severity of the symptoms affected the accuracy of recall positively, whereas the time that has elapsed affected it negatively. Retrospective evaluation of nausea and vomiting of pregnancy symptoms may produce a recall bias, which may distort the evaluation of the therapeutic effectiveness of antiemetics.


Use of calculations to validate beam quality and relative dose measurements for a kilovoltage X-ray therapy unit.
Relative dosimetry measurements are required to fully commission kilovoltage X-ray units for superficial and orthovoltage X-ray therapy. Validation of these relative dosimetry measurements with Monte Carlo methods is advantageous being independent of the measurement process. In this study use is made of the X-ray spectrum generating program SpekPy along with the EGSnrc Monte Carlo code to calculate depth doses and explore the dosimetry effect of changes in backscatter. These calculations are compared with previously reported measurements for the Pantak SXT 150 X-ray therapy unit. SpekPy can also be used to generate half value layer (HVL) values and these are also compared to previously reported HVL measurements for the same X-ray therapy unit. It was found that agreements of the order of 5% in HVL, 3% in depth dose and 1% in backscatter doses were found between Monte Carlo calculations and the previously published measured data. Exit doses in conditions of lack of full backscatter were explored with Monte Carlo calculations demonstrating reduced exit dose up to 20% in these conditions. It is concluded that SpekPy with Monte Carlo codes such as EGSnrc provides a straightforward approach to validating various relative dosimetry measurements in kilovoltage X-ray dosimetry.


Effects of renal ischemia injury on brain in diabetic and non-diabetic rats: Role of angiotensin II type 2 receptor and angiotensin-converting enzyme 2.
Clinically, patients with diabetes mellitus (DM) are more susceptible to ischemic renal injury (IRI) than non-diabetic (ND) patients. Besides, IRI predisposes distant organ dysfunctions including, neurological dysfunction, in which the major contributor remains renin-angiotensin system (RAS). Interestingly, the role of depressor arm of RAS on IRI-associated neurological sequalae remains unclear. Hence, this study aimed to delineate the role of angiotensin II type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2) under the same. ND and Streptozotocin-induced DM rats with bilateral IRI were treated with AT2R agonist-Compound 21 (C21) (0.3 mg/kg/day, i.p.) or ACE2 activator-Diminazene Aceturate (Dize), (5 mg/kg/day, p.o.) either alone or as combination therapy. Effect of IRI on neurological functions were assessed by behavioural, biochemical, and histopathological analysis. Immunohistochemistry, ELISA and qRT-PCR experiments were conducted for evaluation of the molecular mechanisms. We found that in ND and DM rats, IRI causes increased hippocampal MDA and nitrite levels, augmented inflammatory cytokines (granulocyte-colony stimulating factor, glial fibrillary acidic protein), altered protein levels of Ang II, Ang-(1-7) and mRNA expressions of At1r, At2r and Masr. Treatment with C21 and Dize effectively normalised above-mentioned pathological alterations. Moreover, the protective effect of C21 and Dize combination therapy was better than respective monotherapies, and more likely, exerted via augmentation of protein and mRNA levels of depressor arm components. Thus, AT2R agonist and ACE2 activator therapy prevents the development of IRI-associated neurological dysfunction by attenuating oxidative stress and inflammation, upregulating depressor arm of RAS in brain under ND and DM conditions.


Can imagery become reality?
Previous studies showed that highly hypnotizable persons imagining a specific sensory context behave according to the corresponding real stimulation and perceive their behaviour as involuntary. The aim of the study was to confirm the hypothesis of a translation of sensory imagery into real perception and, thus, of a true involuntary response. We studied the imagery-induced modulation of the vestibulospinal (VS) reflex earlier component in highly (Highs) and low hypnotizable subjects (Lows), as it is not affected by voluntary control, its amplitude depends on the stimulus intensity, and the plane of body sway depends on the position of the head with respect to the trunk. Results showed that the effects of the "obstructive" imagery of anaesthesia are different from those elicited by the "constructive" imagery of head rotation. Indeed, both Highs and Lows having their face forward and reporting high vividness of imagery experienced anaesthesia and reduced their VS reflex amplitude in the frontal plane, while only Highs changed the plane of body sway according to the imagined head rotation that is from the frontal to the sagittal one. These effects cannot be voluntary and should be attributed to translation of sensory imagery into the corresponding real perception.


A fatal case of acute progression of generalized edema and simultaneous flash pulmonary edema in a patient with idiopathic systemic capillary leak syndrome: a case report.
Idiopathic systemic capillary leak syndrome is a rare and fatal disease due to the unexplained episodic attacks of capillary leakage of plasma from the intravascular into the interstitial space. The attack consists of three phases, a prodromal phase, peripheral leak phase and recruitment phase. During the peripheral leak phase, generalized edema, mainly in the trunk and extremities, with hemoconcentration and hypoalbuminemia occurs, while usually the visceral organs like lungs, brain, heart and kidneys seem not to be involved. Treatment of the acute phase is supportive, focusing on adequate but not overzealous fluid resuscitation, because pulmonary edema usually occurs in the recruitment phase. A 65-year-old Japanese woman was admitted to our hospital because of severe hypovolemic shock with metabolic acidosis and hemoconcentration and hypoalbuminemia. Although she was considered to be in the peripheral leak phase of idiopathic systemic capillary leak syndrome, which could not be diagnosed during the treatment, the generalized edema worsened further, severe flash pulmonary edema progressed rapidly after fluid resuscitation and she died. The autopsy showed generalized edema, especially alveolar pulmonary edema without endothelial apoptosis. Because hypovolemic shock and fatal pulmonary edema may progress rapidly together even in the peripheral leak phase of idiopathic systemic capillary leak syndrome, we should keep in mind this rare and fatal disease and recognize the pathophysiology to treat it effectively when the patient has hypovolemia with metabolic acidosis.


Liver involvement in human immunodeficiency virus infection.
The advances in management of patients with acquired immunodeficiency syndrome (AIDS) with highly effective anti-retroviral therapy (HAART) have resulted in increased longevity of patients with human immunodeficiency virus (HIV) infection. AIDS-related illnesses now account for less than 50 % of the deaths, and liver diseases have emerged as the leading cause of death in patients with HIV infection. Chronic viral hepatitis, drug-related hepatotoxicity, non-alcoholic fatty liver disease, and opportunistic infections are the common liver diseases that are seen in HIV-infected individuals. Because of the shared routes of transmission, co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are very common in HIV-infected persons. Hepatitis C is the most common viral hepatitis seen in HIV-infected patients. With the availability of directly acting agents, treatment outcome of HCV is comparable to that seen in non HIV-infected patients. Careful monitoring is required for drug interactions and drug-induced hepatotoxicity and modification of drugs should be done where necessary. The results of liver transplantation in select HIV-infected patients can be comparable with those of HIV-negative patients.


No significant elevation of translocator protein binding in the brains of recently abstinent methamphetamine users.
Radioligands for the translocator protein (TSPO) 18 kDa have been used with positron emission tomography (PET) to assess neuroinflammation and microglial activation in psychiatric disorders. One study using this approach showed substantial TSPO elevation throughout the brain in chronic methamphetamine users following long-term abstinence (0.5-4 years), but clients typically present for treatment earlier in abstinence. We used PET with [11C]DAA1106 to compare standardized uptake values (SUVs) as an index of TSPO binding in the brains of methamphetamine-dependent participants who were abstinent for < 6 months (n = 11) and healthy controls (n = 12). We also assayed other typical correlates of Methamphetamine Dependence (e.g., striatal D2-type dopamine receptor deficits, depressed mood, anxiety and impaired emotion regulation). Methamphetamine users exhibited depression (p < 0.0001), anxiety (p = 0.002), difficulties in emotional regulation (p = 0.01), and lower striatal dopamine D2-type receptor availability vs. controls (p = 0.02). SUVs for [11C]DAA1106 were larger in all brain regions of methamphetamine-dependent participants vs. controls, but the effect size was small to medium and not statistically significant. The discrepancy between the lack of significant difference in TSPO binding in early-abstinent methamphetamine users vs. controls in this study and a previous report of elevated binding in longer-abstinent methamphetamine users may reflect methodological differences or limitations of TSPO binding as an index of neuroinflammation. It also seems possible that gliosis increases over time during the first 6 months of abstinence; longitudinal studies could clarify this possibility.


Preparation of ceric oxide and cobalt sulfide-ceric oxide/cellulose-chitosan nanocomposites as a novel catalyst for efficient photocatalysis and antimicrobial study.
In this project, we have prepared a nanostructure of CeO2 nanorods, CoS2-CeO2, and CoS2-CeO2/cellulose-chitosan (CSCS) nanocomposites by ultrasonic method. This nanostructure was characterized using XRD, DLS, field emission scanning microscopy/EDS, DLS, UV-vis DRS, and PL spectrophotometer for determination of crystalline status, morphological, and bandgap data. Both the CeO2 and CoS2 show crystal structure with cubic and pyrite phase. It was found to be the crystal size of CeO2 nanorods, CoS2-CeO2 and CoS2-CeO2/CSCS were 56.19 nm, 62.11 nm, and 65.14 nm, respectively. The photocatalytic activity of CeO2 nanorods, CoS2-CeO2, and CoS2-CeO2/CSCS nanocomposites was evaluated with the photo-degradation of 4-nitrophenol (4NP) as a toxic organic pollutant under UV light irradiation. The 4NP photo-degradation amount reached 95.42% after 60 min UV light irradiation for CoS2-CeO2/CSCS nanocomposites due to the band gap data of CoS2-CeO2/CSCS was lower than other catalyst and photocatalytic modification process. The antimicrobial data indicated the significant properties of CoS2-CeO2/CSCS nanocomposites for this study.


Use of clinical disease activity index score for assessment of disease activity in rheumatoid arthritis patients: an Indian experience.
Introduction. Serial objective assessment of disease activity in Rheumatoid Arthritis (RA) is imperative to achieve remission. The CDAI score appears more practical than DAS-28 in routine assessment of disease activity in RA patients. Objective. To evaluate correlation and agreement of the DAS-28 with CDAI in RA patients. Methods. A total of 200 patients of RA were evaluated by DAS-28 and CDAI and divided into 4 categories of disease activity i.e. Group-I: Remission (DAS-28 < 2.6; CDAI < 2.8), Group II: Low disease activity (DAS-28 = 2.6-3.2; CDAI = 2.8-10), Group III: Moderate disease activity (DAS-28 = 3.2- 5.1; CDAI = 10-22), Group IV: High disease activity (DAS-28 > 5.1; CDAI > 22). DAS-28 was compared to CDAI in each group using spearman correlation coefficient and kappa statistics. Results. Group I shows mean DAS-28 of 1.99 ± 0.38; mean CDAI of 0.90 ± 0.65, (P = 0.0001). Group II shows mean DAS-28 of 3.04 ± 0.17; mean CDAI of 6.45 ± 02.35, (P = 0.0001). Group III shows mean DAS-28 of 4.25 ± 0.58; mean CDAI of 16.46 ± 3.31 (P < 0.0001). Group IV shows mean DAS-28 of 6.38 ± 0.87; mean CDAI of 38.56 ± 11.88 (P < 0.0001). Kappa statistics (κ) of the above comparison was 0.533. Conclusion. Our findings indicate that CDAI-a composite score that employs only clinical variables and omits assessment of Acute Phase Reactant (APR), has moderate to good correlation (Kappa value = 0.533) to DAS-28 for assessment of disease activity in RA patients.


Pendimethalin induces apoptotic cell death through activating ER stress-mediated mitochondrial dysfunction in human umbilical vein endothelial cells.
Pendimethalin is globally registered for control of a wide range of weeds in agriculture and home landscaping. Human exposure to pendimethalin can occur by the oral route through food and other sources. Endothelial function is vital to numerous biological processes, and endothelial dysfunction and poor vascular health is associated with increased atherosclerotic events; however, no study has yet investigated the potential effect of pendimethalin on endothelial function and vasculature formation. The objective of the current study is to investigate if pendimethalin may affect the viability and function of vascular endothelial cells. We observed that pendimethalin significantly repressed viability of human endothelial cells, inducing G1 cell cycle arrest and apoptotic/necrotic cell death. Pendimethalin treatment also activated ER stress and autophagy, leading to loss of mitochondrial membrane potential. In addition, pendimethalin impaired the tube forming and migratory abilities of endothelial cells. This study provides previously unrecognized adverse effects of pendimethalin in vascular endothelial cells, mediated by ER stress-induced mitochondrial dysfunction.


How Do Chemistry Faculty and Graduate Students Engage in Decision Making on Issues Related to Ethical and Responsible Conduct of Research Including Authorship?
In the United States National Science Foundation and the National Institutes of Health have mandated training STEM doctoral students in the ethical and responsible conduct of research to improve doctoral students' ethical decision-making skills; however, little is known about the process and factors that STEM faculty and graduate students use in their decision-making. This exploratory case study examined how four triads of chemistry faculty and their doctoral students recruited from three research universities in the eastern United States engaged in ethical decision-making on issues of authorship, assignment of credit, and plagiarism. A mixed-methods approach involving the administration of an online survey consisting of three open-ended case studies followed by a think-aloud interview was utilized. Participants were found to use analogical reasoning and base their decision-making on a common core set of considerations including fundamental principles, social contracts, consequences, and discussion with an advisor, often using prior personal experiences as sources. Co-authorship did not appear to impact the doctoral students' ethical decision-making. Gender may play a role in graduate students' decision-making; female doctoral students appeared to be less likely to consider prior experiences when evaluating the vignettes. Graduate students' lack of knowledge of the core issues in the responsible conduct of research, coupled with their lack of research experience, and inability to identify the core considerations may lead them to make bad judgments in specific situations. Our findings help explain the minimal impact that the current responsible conduct of research training methods has had on graduate students' ethical decision-making and should lead to the development of more effective approaches.


Prediction of infarction development after endovascular stroke therapy with dual-energy computed tomography.
After intraarterial recanalisation (IAR), the haemorrhage and the blood-brain barrier (BBB) disruption can be distinguished using dual-energy computed tomography (DECT). The aim of the present study was to investigate whether future infarction development can be predicted from DECT. DECT scans of 20 patients showing 45 BBB disrupted areas after IAR were assessed and compared with follow-up examinations. Receiver operator characteristic (ROC) analyses using densities from the iodine map (IM) and virtual non-contrast (VNC) were performed. Future infarction areas are denser than future non-infarction areas on IM series (23.44 ± 24.86 vs. 5.77 ± 2.77; p < 0.0001) and more hypodense on VNC series (29.71 ± 3.33 vs. 35.33 ± 3.50; p < 0.0001). ROC analyses for the IM series showed an area under the curve (AUC) of 0.99 (cut-off: <9.97 HU; p < 0.05; sensitivity 91.18 %; specificity 100.00 %; accuracy 0.93) for the prediction of future infarctions. The AUC for the prediction of haemorrhagic infarctions was 0.78 (cut-off >17.13 HU; p < 0.05; sensitivity 90.00 %; specificity 62.86 %; accuracy 0.69). The VNC series allowed prediction of infarction volume. Future infarction development after IAR can be reliably predicted with the IM series. The prediction of haemorrhages and of infarction size is less reliable. • The IM series (DECT) can predict future infarction development after IAR. • Later haemorrhages can be predicted using the IM and the BW series. • The volume of definable hypodense areas in VNC correlates with infarction volume.


Composite lipid polyelectrolyte capsules templated on red blood cells: fabrication and structural characterisation.
Charged phospholipids and mixtures of charged phospholipids with zwitterionic lipids were adsorbed onto polyelectrolyte capsules templated on erythrocytes. The assembly was proved by means of electrophoretic mobility measurements, confocal laser scanning microscopy and flow cytometry. Freeze-fracture electron microscopy proved that the phospholipids assemble as bilayers or multilayers. Single particle light scattering showed that bilayers composed of anionic lipids can be intercalated between subsequent polyelectrolyte inter-layers in a regular manner. Neutral lipids can form multilayers. A pronounced decrease in capsule permeability for small polar dyes upon lipid adsorption was followed by confocal laser scanning microscopy.


Gemcitabine and paclitaxel combination as second-line chemotherapy in patients with small-cell lung cancer: a phase II study.
Although small-cell lung cancer is a chemosensitive malignancy, most patients rapidly relapse. Results of second-line treatment are generally poor. We conducted a phase II study to evaluate the activity and toxicity of a combination of gemcitabine and paclitaxel as second-line chemotherapy. Eligible patients were refractory or relapsed small-cell lung cancer, with an Eastern Cooperative Oncology Group performance status of 0-2 and measurable disease. Paclitaxel was administered at 135 mg/m(2) days 1 and 8 immediately followed by gemcitabine at 1000 mg/m(2) every 3 weeks up to 6 courses. Restaging of disease was scheduled every 3 courses. Forty-one patients were enrolled. The median age was 65 years. Nineteen patients were considered refractory (progressive disease during or within 90 days from completion of first-line treatment), whereas 22 patients were chemotherapy sensitive. A total of 135 courses was administered (range, 1-6; median, 3). Nine patients achieved a partial remission (partial response, 22%), and 10 patients had stable disease (24%), with a disease control rate (partial response + stable disease) of 46%: in 12 (55%) of 22 patients who were sensitive and in 7 (37%) of 19 patients with refractory disease, respectively. All partial responses but one were observed in the sensitive group. The median duration of response was 5 months. The most-frequent severe toxicities were neutropenia grade 3-4 and neurologic grade 3 in 24% and 7% of delivered courses, respectively. The combination of gemcitabine and paclitaxel investigated in our study achieved a high disease control rate, but the schedule we adopted appeared to be quite toxic.


Treatment of primary hepatic neuroendocrine tumors with associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): A case report and literature review.
Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare and are difficult to diagnose preoperatively.We report a case of PHNET diagnosed preoperatively and successfully resected using associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). A 72-year-old woman was admitted to our hospital for a hepatic mass, which was incidentally identified during a routine health checkup. The patient has no other obvious symptoms of discomfort. Physical examination revealed a palpable mass in the right upper quadrant of her abdomen. Dynamic contrast-enhanced abdominal computed tomography (CT) showed a low-density mass measuring 13 × 7 × 6 cm in both, the right and left hepatic lobes. F-fluorodesoxyglucose positron emission tomography (F-FDG PET) and fused PET/CT showed increased uptake by the mass, which was indicative of a hepatic tumor. We use a novel ALPPS surgical procedure to safely and radically remove primary neuroendocrine tumors. No postoperative bleeding and bile leakage were reported, and the patient recovered uneventfully.The patient was followed-up for a year without recurrence. PHNETs are rare tumors, and confirming the diagnosis using the best possible preoperative examination is important. An optimal treatment plan is selected based on the patient's condition to ensure a favorable prognosis. Tumors too large to undergo surgical removal can be resected using the ALPPS procedure, as described in this case report.


Evaluation of the efficacy and safety of Griflow(®) Dual, a pre-set two-flow infusion device for intravenous immunoglobulin (Flebogamma(®) 5%) administration.
A single center, prospective study was performed to assess the efficacy and safety of Griflow(®) Dual a gravity-fed device for intravenous delivery of human immunoglobulin Flebogamma(®). A total of 2 infusions in 2 visits per patient were assessed using G2 and G3 Griflow(®) Dual models that provide different flow rates adjusted to the patient's weight. To follow the most common method of intravenous immunoglobulin administration, infusion through the two-way device commenced with the low flow rate capillary (clamp closed) for 30 minutes and continued with the high flow rate, opening both ways. Reliability of flow delivery (average flow rates), adverse events, as well as functionality in daily practice (questionnaire to nurses) were assessed. twenty-five valid infusions were evaluated on 13 subjects. Except for the G2 model with closed clamp in which 14.5% deviation was observed, actual average flow rate values fell well into the maximum 10% deviation permitted with respect to expected charted values (G2: 55 and 142 mL/h; G3: 76 and 189 mL/h). Discrepancies could be explained by patient's arm movements or posture change during infusion. No adverse events related to the study device occurred. In the functionality questionnaires, nurse's comfort and safety of infusion with Griflow(®) Dual were rated higher than without Griflow(®) Dual but lower than with infusion pumps. Although it may not be as precise as an infusion pump, Griflow(®) Dual proved to be a reliable and suitable device to administer Flebogamma(®) 5%. Correct safety should be confirmed in a larger sample.


Sensory Adapted Dental Environments to Enhance Oral Care for Children with Autism Spectrum Disorders: A Randomized Controlled Pilot Study.
This pilot and feasibility study examined the impact of a sensory adapted dental environment (SADE) to reduce distress, sensory discomfort, and perception of pain during oral prophylaxis for children with autism spectrum disorder (ASD). Participants were 44 children ages 6-12 (n = 22 typical, n = 22 ASD). In an experimental crossover design, each participant underwent two professional dental cleanings, one in a regular dental environment (RDE) and one in a SADE, administered in a randomized and counterbalanced order 3-4 months apart. Outcomes included measures of physiological anxiety, behavioral distress, pain intensity, and sensory discomfort. Both groups exhibited decreased physiological anxiety and reported lower pain and sensory discomfort in the SADE condition compared to RDE, indicating a beneficial effect of the SADE.


Serine phosphorylation of biosynthetic pro-urokinase from human tumor cells.
Phosphorylation is a potent mechanism regulating the activity of many intracellular enzymes. We have discovered that the product of the human urokinase plasminogen activator gene, pro-uPA, is phosphorylated in serine in at least two human cell lines. Phosphorylation occurs within the cell during biosynthesis, and phosphorylated intracellular pro-uPA is secreted into the medium. Of the secreted pro-uPA molecules, 20-50% are phosphorylated in serine, thus representing a meaningful fraction of the total biosynthetic pro-uPA. Although the sites of phosphorylation have not yet been determined, at least two such sites must exist; in fact plasmin cleavage of phosphorylated single chain pro-uPA yields a two chain uPA in which both chains are phosphorylated. A specific function for pro-uPA phosphorylation has not yet been identified; however, it is tempting to speculate that, as in many other cases, phosphorylation may affect the activity of the enzyme, its response to inhibitors or the conversion of pro-uPA zymogen to active two-chain uPA. This would represent an additional way of regulating extracellular proteolysis, an important pathway involved in both intra- and extravascular phenomena like fibrinolysis, cell migration and invasiveness.


Right ventricular wall dissection complicating myocardial infarction.
Right ventricular wall dissection is extremely rare and can result in dismal clinical outcomes. We report a 68-year-old patient who presented with acute myocardial infarction and was found to have right ventricular wall dissection by ventriculography. At surgery, the infarcted myocardium was excised, and a two-patch technique was used to repair the ventricular septal defect.


Ultrastructure and morphometry of the alveolar lung of guinea pigs chronically exposed to diesel engine exhaust: six month's experience.
The impact of chronic inhalation of diesel exhaust (DE) on alveolar lung was studied in 24 Hartley guinea pigs. Groups were sacrificed sequentially at 2 weeks, 3 months and 6 months of exposure to either 750 micrograms or 1500 micrograms DE particles (DEP) per m3 along with age-matched concurrent controls. Although qualitative ultrastructural changes were noticed during this time interval and dosage schedule, there was no evidence of pathologic changes such as fibrosis or emphysema. The cellular uptake of DEP was striking. By 2 weeks three alveolar cell types (alveolar macrophages, epithelial type 1 cells and interstitial macrophages) plus one type of granulocytic leukocyte (eosinophils) confined DEP within phagosomes without evidence of cytotoxicity. A certain phagosomal DEP population had a bull's eye appearance and diameters of 0.0727 +/- 0.01 micron. Morphometric analysis applied to electron micrographs demonstrated that arithmetic mean tissue thickness of the air-blood barrier was generally increased (p less than 0.05) during DE exposure. For the 750 micrograms DE sets, the increase over control (1.56 micron) was 41% at 2 weeks, 46% at 3 months and 77% at 6 months while the 1500 micrograms DE set at 6 months exceeded control by 130%. Increases in absolute tissue volumes of interstitium and epithelial type 2 cells largely accounted for the increased tissue thickness. Harmonic mean tissue thickness for controls remained near 0.537 +/- 0.03 micron for the study interval, contrasting with values for 3 and 6 months 750 micrograms DE and 6 months 1500 micrograms DE sets which increased. However, the diffusion capacity of the lung determined morphometrically was not decreased in DE exposed sets. Although cellular uptake of DEP and increased prominence of secretory epithelium were dose/duration related, absence of linearity suggests adaptative responses.


Highly efficient charge transfer from small-sized cadmium sulfide nanosheets to large-scale nitrogen-doped carbon for visible-light dominated hydrogen evolution.
Slow charge transfer and carrier recombination are key issues in photocatalytic reactions. The current solution is to load small-sized cocatalysts onto large-sized photocatalysts. Here a new strategy is proposed. Small-sized photocatalysts of cadmium sulfide (CdS) nanosheets are grown onto large-sized cocatalysts of N-doped amorphous carbon (a-CN) to construct CdS @ a-CN photocatalysts. Photoluminescence spectra and transient photocurrent demonstrate that optimized CdS @ a-CN shows effective charge separation compared with CdS. The corresponding photocatalytic H2 yield of optimized CdS @ a-CN is ∼244 μmol, which is 3.6 times higher than that of CdS. Besides, the hydrogen yield for CdS under visible-light irradiation is significantly improved from ∼44 μmol to ∼217 μmol for the optimized CdS @ a-CN. Our design strategy provides an effective way to construct photocatalytic systems with outstanding photocatalytic performance.


Binding of estradiol receptor complexes to isolated human breast chromatin.
The interaction of estradiol-receptor complexes and isolated human breast tumor chromatin was studied under equilibrium conditions. The estradiol-receptor complexes bound specifically to the chromatin of hormone dependent tumors and showed a single class of binding sites with a Ka of 0.96 X 10(10) M-1 and a binding capacity of 1.5 pmoles/mg DNA. The binding was a temperature-dependent process and involved a "transformation" of the receptor protein. The heat-activated hormone-receptor complex was more active than the 8S form in the binding phenomenon. The specific interaction of estradiol-receptor complex with isolated chromatin was saturable and sensitive to conditions of temperature and ionic strength. Furthermore under optimal conditions no acceptor sites were detected in chromatin of hormone independent tumors.


Anthropogenic noise influences on marine soundscape variability across coastal areas.
Acoustic data was collected across 15 sites distributed through the coastal area of Rio de Janeiro, Brazil, encompassing regions of different natural characteristics. Noise levels and the acoustic complexity index were calculated. Quantity and composition of anthropogenic sound sources varied across recording sites, with at least one type of sound source being registered in each location. A cluster analysis using third-octave levels from eight frequency bands divided recording sites into two groups, one considered as impacted by anthropogenic noise and the other as less-impacted. The noisiest recording locations were those with higher numbers of anthropogenic sound sources, specifically large ships. It was evidenced that anthropogenic noise affects not only noise levels, but also low-frequency acoustic complexity, which decreased in the presence of vessel traffic. The constant noise input of human activities tended to mask natural variability in the soundscape at lower frequencies.


Extracellular lipid metabolism influences the survival of ovarian cancer cells.
Lysophosphatidic acid (LPA) is an extracellular lipid mediator consisting of a fatty acid and a phosphate group linked to the glycerol backbone. Here, we show that 1-oleoyl- and 1-palmitoyl-LPA, but not 1-stearoyl- or alkyl-LPA, enhance HNOA ovarian cancer cell survival. Other lysophospholipids with oleic or lauric acid, but not stearic acid, also induce the survival effects. HNOA cells have the lipase activities that cleave LPA to generate fatty acid. Oleic acid stimulates HNOA cell survival via increased glucose utilization. Our findings suggest that extracellular lysolipid metabolism might play an important role in HNOA cell growth.


Plant-based production of biopharmaceuticals.
Plants are now gaining widespread acceptance as a general platform for the large-scale production of recombinant proteins. The first plant-derived recombinant pharmaceutical proteins are reaching the final stages of clinical evaluation, and many more are in the development pipeline. Over the past two years, there have been some notable technological advances in this flourishing area of applied biotechnology, as shown by the continuing commercial development of novel plant-based expression platforms. There has also been significant success in tackling some of the limitations of plant bioreactors, such as low yields and inconsistent product quality, that have limited the approval of plant-derived pharmaceuticals.


Publisher Correction: Discovery of novel biomarkers for atherosclerotic aortic aneurysm through proteomics-based assessment of disease progression.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


The inadvertent administration of anticoagulants to ED patients ultimately diagnosed with thoracic aortic dissection.
Aortic dissection (AD) may present similarly to acute coronary syndrome or pulmonary embolus; however, anticoagulation may be detrimental to patients with AD. Clinical data were abstracted from medical records of emergency department (ED) patients with nontraumatic AD. Patients administered with anticoagulants were compared with non-anticoagulated patients with regard to presenting symptoms, chest radiograph and electrocardiogram (ECG) findings, and outcome. A total of 44 ED patients with nontraumatic AD was identified over a 4-year period; anticoagulants were administered to 9 (21%). Anticoagulated patients had a higher incidence of chest pain without back pain (78% vs 23%; P = .002) and ST elevations or depressions on ECG (89% vs 6%; P < .001) and were less likely to have a widened mediastinum on chest radiograph (0% vs 67%; P < .001). Two ED anticoagulated patients died, one required a second surgery for bleeding complications, and another suffered a stroke after reversal of anticoagulation. There is a clinically significant incidence of anticoagulation administration to ED patients ultimately diagnosed with AD, especially in the presence of ambiguous ECG and radiographic findings.


Neisseria meningitidis Infecting a Prosthetic Knee Joint: A New Case of an Unusual Disease.
Primary meningococcal meningitis is an infrequent but known disease. However, the infection of a prosthetic joint with Neisseria meningitidis is rare. We hereby describe the second case of an arthroplasty infected with Neisseria meningitidis that responded favourably to prosthesis retention with surgical debridement, in combination with antibiotics treatment.


Targeting brain metastases in breast cancer.
Brain metastases (BMs) are an important source of morbidity and mortality in patients with metastatic breast cancer (BC). As survival of patients with advanced BC considerably improved thanks to research advancements and new therapeutic approaches, the apparent incidence of BMs is increasing. Local interventions, in the form of either surgical resection or radiation therapy, remain the mainstay in the management of BMs. Systemic treatments are typically used to complement local strategies to further improve and maintain control of central nervous system (CNS) disease. Although high-level evidence data about the impact of the blood-brain barrier (BBB), as well as the efficacy of anti-cancer agents on BMs and differentials between the systemic compartment and CNS are still scant, our understanding of the activity of systemic treatments with impact on BMs is rapidly evolving. Novel anti-HER2 agents, such as tucatinib, ado-trastuzumab emtansine, trastuzumab deruxtecan and neratinib, have shown intracranial efficacy. Current research efforts are ongoing not only to clarify the activity of existing treatments on the CNS, as well as to develop new drugs and innovative multi-modality approaches. This review will encompass the current treatment landscape of BMs arising from BC, with a focus on recent advancements in the field and investigational approaches.


Chromosome aberrations as a predictor of clinical outcome for smoking associated lung cancer.
The ability to identify individuals at greatest risk of developing lung cancer can significantly enhance the efficacy of intervention modalities. One strategy for identifying these individuals is through biomarkers that reflect the severity of their cancer. In the present study, we evaluated 22 lung cancer patients and 35 controls to determine whether the frequency of chromosome aberrations was significantly associated with specific clinical variables such as the histological type, grade and stage of the tumors. Chromosome aberrations (expressed as total breaks) were investigated on chromosome 1 in interphase nuclei obtained from blood lymphocytes of the study participants using the fluorescence in situ hybridization (FISH) chromosome aberration assay. Our results indicate a significant linear increase (P=0.01) in the level of breaks with respect to the grade of the carcinoma. The poorly differentiated tumors had a significantly higher level of chromosome breaks mean+/-SD (1.7+/-0.46) as compared to the well differentiated tumors (0.98+/-0.23, P<0.05). These results indicate that chromosome aberrations, as determined by the FISH assay, can be used as a biomarker for identifying individuals with aggressive types of lung cancer and potentially, as a predictor for prognostic outcome of the disease.


Capillary electrophoresis in analysis of veterinary drugs.
Antibiotics are extensively applied in veterinary medicine for the treatment of various bacterial infections. Because of their use in food producing animals, the risk of occurrence of unwanted residues in edible products exists. To ensure human food safety, The European Union has defined maximum residue limits (MRLs) for veterinary drug residues in food products. Analytical methods need to be developed to confirm the presence of antibiotics at the MRL level. A capillary electrophoresis (CE) method with UV detection is proposed for the quantitative determination of residues from poultry and porcine tissues. Eight of the most frequently used antibiotics and nifursol, which routinely used as poultry coccidiostat, were analysed. CE technique permitted analysing substances to be separated from muscle, liver, kidney and skin with fat after a simple extraction with acetonitrile or ethyl acetate under basic conditions. Proposed method is capable to identify drug residues in tissues at level below 20 microg/kg.


Exploring the therapeutic mechanism of Banxia Xiexin Decoction in mild cognitive impairment and diabetes mellitus: a network pharmacology approach.
The incidence of mild cognitive impairment (MCI) and diabetes mellitus (DM) is increasing year by year. Clinical findings show that Banxia Xiexin Decoction (BXD) can be combined to treat MCI and DM. However, the principle and mechanism of BXD in treating MCI and DM remain unclear. In this study, to explore the common mechanism of BXD in treating MCI and DM by using the method of network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was used to screen the main active components of BXD, as well as to predict and screen its potential targets. Using Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), DisGeNET, GeneCards to select the target proteins of two diseases, and intersecting the drug target and the disease target to obtain the common target of drug diseases, which is imported into cytoscape software to draw the network diagram of "drug components-target diseases" and the interaction network diagram between the common target proteins. According to the Database for Annotation, Visualization and Integrated Discovery (DAVID) database, we analyzed the common targets using two methods, gene ontology Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway enrichment analysis and Gene Ontology (GO) function enrichment analysis, as well as studied the interaction mechanism of the two diseases, with the results validated using molecular docking. A total of 267 main active components of BXD were screened, together with the two diseases shared 233 common targets. The top five key targets identified by the topological analysis were TP53, AKT1, STAT3, TNF, and MAPK3. Go enrichment results indicated that it was primarily related to response to drug, extracellular space, enzyme binding, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding. t KEGG enrichment pathway analysis identified 20 significant pathways, the majority of which are AGE-RAGE signaling pathways in diabetic complications, lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, TNF signaling pathway, and so on. The results of molecular docking revealed that the key components of BXD, baicalein, licochalcone a, quercetin, and naringenin, had strong binding ability with core targets TP53, AKT1, STAT3, TNF, MAPK3. BXD can treat MCI and DM by multi-targets and multi-channels,and plays a role of "homotherapy for heteropathy" mainly through response to drug, positive regulation of gene expression, extracellular space and enzyme binding and other ways.


Validity and reliability of the Turkish version of the neurogenic bladder symptom score.
The neurogenic bladder symptom score (NBSS) represents the effect of disease-specific symptoms on the quality of life in patients with neurogenic bladder (NB). The purpose of this study was to assess the psychometric properties of the Turkish version of the NBSS in spinal cord injury (SCI) and multiple sclerosis (MS) patients. The cross cultural adaptation was achieved through forward and back translation of the items of the original version by an expert committee. Face and content validity were evaluated in a prepatient group. Internal consistency and test-retest reliability were used for reliability assessment in 102 patients. Validity was examined using Short Form-12 and King's Health Questionnaire. Eighty-four patients with SCI and 18 with MS were included in the study. Cronbach's alpha values for the total score and the incontinence, storage/voiding, and consequences domains were 0.90, 0.91, 0.81, and 0.63, respectively. The intraclass correlation coefficients were >0.80 for all subdomains and the overall score. The correlation analyses indicated that the Turkish version has good construct validity. Our results showed that the Turkish version of the NBSS has good reliability and validity in patients with SCI and MS and can be used to evaluate NB symptoms. NCT03964077.Implications for rehabilitationThe Turkish version of the neurogenic bladder symptom score (NBSS) is a valid and reliable instrument to measure symptom specific quality of life (QOL) in both patients with spinal cord injury and multiple sclerosis.The Turkish version of the NBSS can be used in the Turkish population to measure neurogenic bladder related QOL for clinical and research purposes.


A sequential aerated electrocoagulation and peroxicoagulation process for the treatment of municipal stabilized landfill leachate by iron and graphite electrodes.
Electrochemical treatment has emerged as a viable technology for the treatment of leachate due to its efficient removal of ammonaical nitrogen and other recalcitrant organics. The main technical issues that prevent its practical deployment are restricted performance of a single electrochemical process and the lengthy tertiary treatment time required to achieve the disposal quality standards. This study demonstrates the performance of electrochemical treatments such as peroxicoagulation (PC) and aerated electrocoagulation (A-EC) separately and also sequentially for the treatment of stabilized leachate. In aerated electro coagulation iron is used as both anode and cathode, whereas in peroxicoagulation, iron is used as anode and graphite as cathode. The area of electrode used for treatments was fixed as 12.5 cm2. The initial concentration of NH4-N, TN, COD, and TOC of the leachate was found to be 480 mg/L, 997 mg/L, 40,200 mg/L, and 9850 mg/L respectively. Removal efficiency of aerated electrocoagulation for NH4-N, TN, COD and TOC were 25.6%, 23.67%, 25.6% and 28.7% respectively, current density of 30 mAcm-2, electrolysis time of 60 min and pH 7.3. Meanwhile for peroxicoagulation, the removal efficiency was found to be 37.2%, 43%, 37.3%, and 45.6% for NH4-N, TN, COD, and TOC respectively, at an current density of 30 mAcm-2, electrolysis time of 120 min and a pH of 3. The sequential aerated electrocoagulation - peroxicoagulation process achieves a maximum removal efficiency of 63%, 68%, 78%, and 75% for NH4-N, total nitrogen, COD, and TOC respectively for a reaction time of 180 min. Removal of NH4-N, total nitrogen, COD and TOC from stabilized landfill leachate with a BOD/COD ratio less than 0.1 was very much effective with the sequential aerated electrocoagulation - peroxicoagulaton treatment. The results also indicate that for the treatment of leachate, a significant synergistic index of 1.22 exists between aerated electrocoagulation and peroxicoagulation.


Answering the connectionist challenge: a symbolic model of learning the past tenses of English verbs.
Supporters of eliminative connectionism have argued for a pattern association-based explanation of language learning and language processing. They deny that explicit rules and symbolic representations play any role in language processing and cognition in general. Their argument is based to a large extent on two artificial neural network (ANN) models that are claimed to be able to learn the past tenses of English verbs (Rumelhart & McClelland, 1986, Parallel distributed processing, Vol. 2, Cambridge, MA: MIT Press; MacWhinney & Leinbach, 1991, Cognition, 40, 121-157). In this article we critically review Rumelhart and McClelland's as well as MacWhinney and Leinbach's ANN models and conclude that they do not succeed in the assigned task of learning the past tenses of English verbs. In order to answer their challenge to the symbolic processing approach, we present our symbolic pattern associator (SPA)-a general-purpose pattern associator that can learn to associate arbitrary discrete patterns. We carried out several experiments with the SPA using the same set of verbs that was used in MacWhinney and Leinbach's simulation with more realistic training and testing procedures. The SPA outperformed the connectionist models by a wide margin in the accuracy of learning, and successful inductive generalizations to unseen verbs. Our SPA has very natural and psychologically realistic explanations to many psychological effects such as U-shaped learning curve, and is much closer to human subjects in predicting past tense of the pseudo-verbs. In contrast to ANNs, whose internal representations are entirely opaque, the SPA can represent the acquired knowledge in the form of production rules that allow for further higher-level processing and integration, resulting in linguistically realistic associative templates for irregular verbs and production rules for regular verbs. In the light of these findings, we conclude that eliminative connectionists' vision of cognition as simple pattern association and pattern recognition without symbolic representation is inadequate. Pattern association as such does not imply rule-less or cue-based models of language acquisition or of human learning in general.


[Neurologic complications of vaccination against rabies. Magnetic resonance imaging in 1 case].
On the basis of case well documented by CT and NMR, the authors describe the nature, course, pathology and pathogenesis of neurological disorder consecutive to the use of rabies vaccines prepared from animal brains. The new vaccines obtained by the tissue cultures have completely suppressed the neurological risk.


Phase II clinical trial of pegylated liposomal doxorubicin (JNS002) in Japanese patients with mullerian carcinoma (epithelial ovarian carcinoma, primary carcinoma of fallopian tube, peritoneal carcinoma) having a therapeutic history of platinum-based chemotherapy: a Phase II Study of the Japanese Gynecologic Oncology Group.
This study was conducted to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in Japanese patients with Müllerian carcinoma having a therapeutic history of platinum-based chemotherapy. Patients who were diagnosed with Müllerian carcinoma (epithelial ovarian carcinoma, primary carcinoma of fallopian tube and peritoneal carcinoma) by histological examination and had received the initial platinum-based chemotherapy were included in the study. The study drug was administered to the patients at 50 mg/m(2) every 4 weeks. Seventy-four patients were enrolled in the study. All patients had received platinum-based chemotherapy as first-line regimen and more than 90% of patients had also received taxanes. The overall response rate was 21.9% (95% confidence interval, 13.1-33.1%) and 38.4% of patients had stable disease. The median time to progression was 166 days. The major non-haematological toxicities were hand-foot syndrome (Grade 3; 16.2%) and stomatitis (Grade 3; 8.1%). Myelosuppression such as leukopenia (Grade 3; 52.7%, Grade 4; 6.8%), neutropenia (Grade 3; 31.1%, Grade 4; 36.5%) and decreased haemoglobin (Grade 3; 14.9%, Grade 4; 2.7%) were the most common haematological toxicities. We confirmed that a 50 mg/m(2) every 4 weeks regimen of PLD was active in Japanese patients with Müllerian carcinoma having a therapeutic history of platinum-based chemotherapy and toxicity was manageable by dose modification of PLD or supportive care.


Human serum albumin. Spectroscopic studies of binding and proximity relationships for fatty acids and bilirubin.
Binding and proximity relationships of hydrophobic ligands on human serum albumin have been studied using absorption, fluorescence, circular dichroism, and electron paramagnetic resonance spectroscopy. The ligands studied were bilirubin, two conjugated linear polyene fatty acids, cis-parinaric acid and cis-eleostearic acid, and three nitroxide derivatives of stearic acid with doxyl groups at positions 5, 10, and 12, respectively. Binding of polyene fatty acids was monitored by absorption peak shifts, induced circular dichroism, enhancement of fluorescence, and energy transfer between albumin's single tryptophanyl residue and the polyene chromophore. Induced circular dichroism studies indicate excitonic ligand-ligand interaction between bound fatty acids. Fluorescence enhancement of cis-parinaric acid was analyzed using a stepwise multiple equilibrium model, and six binding constants in the range 10(8) to 10(6) M-1 were obtained, in agreement with previous measurements for other fatty acids. The temperature dependence of the equilibrium constants indicates that the binding enthalpy is nearly zero. Fluorescence energy transfer was similarly used to quantitate bilirubin binding to albumin. Energy transfer, nitroxide quenching of fluorescence, and electron paramagnetic resonance spectroscopy were used to elucidate binding geometries which support and extend proposed structural models for albumin. It is suggested that the first two fatty acids bind side-by-side in an antiparallel fashion in domain III of human serum albumin.


Age-related changes in endocrine and renal function in patients with essential hypertension.
Endocrine and renal functions were studied in 149 patients with essential hypertension by measuring plasma electrolytes, renin activity, creatinine and aldoserone, as well as the urinary excretion of creatinine and sodium chloride, before and during treatment for hypertension. Half of the patients responded to trichlormethiazide (thiazide-responsive group) but the other half did not (thiazide-unresponsive group). Systolic and diastolic blood pressures increased progressively uith age in the thiazide-unresponsive group, but were lower and did not progress with age in the thiazide-responsive group. There was no consistent difference in plasma renin activity between the thiazide-responsive and the thiazide-unresponsive groups. The fluctuation of plasma renin activity in response to an excess of sodium chloride or to thiazide treatment was reduced progressively with age. Creatinine clearance decreased and the blood urea nitrogen level increased with age. The age-related decrease of plasma renin activity is discussed on the light of the age-related impairment in the ability of the kidney to excrete sodium and water.


Follow-up of prostaglandin plasma levels after acute myocardial infarction.
Prostaglandin plasma levels are elevated in patients with transient myocardial ischemia. We measured 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (B2(TXB2) in venous blood of 32 patients with myocardial infarction on the first, third, and seventh days. TXB2 and 6-keto-PGF1 alpha levels in these patients (up to 117 +/- 237 pg/ml and 96 +/- 105 pg/ml mean +/- SD, respectively) differed significantly from levels in normal control subjects (10 +/- 12 pg/ml and 4 +/- 7 pg/ml mean +/- SD, respectively) (p less than 0.01). Prostaglandin values remained elevated from day 1 through day 7. In most patients, 6-keto-PGF1 alpha levels prevailed over those of TXB2. In a subgroup suffering from cardiac arrhythmias, the ratio of 6-keto-PGF1 alpha/TXB2 was inverse. It is concluded that prostaglandin generation is increased for at least 7 days after myocardial infarction. A disturbed ratio of 6-keto-PGF1 alpha/TXB2 in favor of the latter might be associated with cardiac arrhythmias in myocardial infarction.


The autistic spectrum.
The autistic spectrum currently encompasses common precocious behaviourally identified constellations of social and communication atypicalities associated with restricted interests and repetitive behavior, together with uneven ability profiles. It is associated with multiple but heterogeneous genetic, functional, and structural variations whose established links with an autistic behavioral phenotype are as yet minimal. Strong evidence of high heritability contrasts with limited determination of genes and modes of transmission involved. Adaptation and outcomes vary widely according to opportunities, accommodation, and co-occurring conditions. With current diagnostic practices, multiple genetic conditions overlap with the autistic spectrum, with potential for confusion arising from phenocopies. Recent advances question the often presumed association between autism and intellectual disability and/or epilepsy. Autism is currently understood as a final common phenotypical pathway resulting from an indefinite number of genetic variations, possibly involving the same information processing pathways, and producing a variant in the way humans perceive, memorize, manipulate, and attribute emotional value to available information. Findings plausibly converge on more optional, rather than typically mandatory, hierarchies of information processing as fundamental to autism. Adaptation of education and employment according to individual strengths and needs, as well as attention to co-occurring conditions as necessary, remains today the best way to assist autistic individuals.


Preparation, characterization and stability of curcumin-loaded zein-shellac composite colloidal particles.
Curcumin-loaded zein-shellac composite particles were prepared by the antisolvent co-precipitation method. The encapsulation efficiency of curcumin was significantly improved from 82.7% in zein particles to 93.2% in zein-shellac complex particles. The result of differential scanning calorimetry suggested that curcumin in the polymeric matrix was in an amorphous state. Fourier transform infrared spectroscopy analysis revealed that curcumin had non-covalently interacted with zein and shellac, mainly through hydrogen bonding and hydrophobic interaction. Aggregates in irregular shapes, with large sizes, were found by atomic force microscopy, and conglutination, integration or fusion of different entities into network structures occurred at a high level of shellac. At the mass ratio of zein to shellac of 1:1, curcumin in the complex particles exhibited improved photochemical and thermal stability. Curcumin-loaded zein-shellac complex particles allowed the controlled release of curcumin in both PBS medium and simulated gastrointestinal fluids.


[The effects of naloxone on oxygen uptake, pulmonary ventilation and cardiac performance in adult non-anaesthetised persons (author's transl)].
10 normal persons were given 0.4 milligrams of Naloxone intravenously, and the following measurements were taken: oxygen uptake, CO2 production, respiratory quotient, respiratory minute volume, tidal air, dead space, effective dead space, specific ventilation, alveolar O2 partial pressure, end-expiratory CO2 partial pressure, heart rate, systolic and diastolic blood pressure and the Burger Index. Analysis of the results established that administration of Naloxone was followed by a statistically significant, but clinically not relevant, reduction in O2 uptake and CO2 production. Higher doses produced the same results. The findings appear to contradict those observed in anaesthetised patients who are given Naloxone during the postoperative stage. However, closer examination of the results suggests that the so-called tachytrophic effect of Naloxone is attributable to its antagonistic action on the analgesic and sedative effects of opiates rather than to a specific pharmacodynamic property of Naloxone.


Convalescent plasma therapy against the emerging SARS-CoV-2 variants: Delineation of the potentialities and risks.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a catastrophic pandemic and severely impacted people's livelihoods worldwide. In addition, the emergence of SARS-CoV-2 variants has posed a severe threat to humankind. Due to the dearth of therapeutic options during the commencement of the pandemic, convalescent plasma therapy (CPT) played a significant part in the management of patients with severe form of COVID-19. Several recent studies have proposed various protective effects of CPT, such as antiviral, anti-inflammatory, anti-thrombotic, and immunomodulatory actions, curtailing the devastating consequences of the SARS-CoV-2 infection. On the contrary, several clinical studies have raised some serious concerns about the effectiveness and reliability of CPT in the management of patients with COVID-19. The protective effects of CPT in severely ill patients are yet to be proved. Moreover, the emergence of SARS-CoV-2 variants has raised concerns about the effectiveness of CPT against COVID-19. Therefore, to establish concrete evidence of the efficacy of CPT and adjudicate its inclusion in the management of COVID-19, an updated review of present literature is required, which could help in the development of an efficient therapeutic regimen to treat COVID-19 amid the emergence of new viral variants.


The enzymatic cleavage of beta-carotene: still controversial.
The enzyme beta-carotene-15,15'-dioxygenase from guinea pig intestinal mucosa was found to cleave beta-carotene and produce 2 mol of retinal for 1 mol of beta-carotene. However, extensive evidence exists also for random (excentric) cleavage, resulting in retinoic acid and retinal, with a preponderance of apocarotenals formed as intermediates.


Enhancement of tolerance of abiotic stress by metabolic engineering of betaines and other compatible solutes.
The accumulation of compatible solutes, such as betaines, proline and sugar alcohols, is a widespread response that may protect plants against environmental stress. It is not yet fully understood how these compounds are involved in the stress tolerance of whole plants. Some plants have been genetically engineered to express enzymes that catalyze the synthesis of various compatible solutes. Some interventions have increased the tolerance of some crop plants to abiotic stress. Furthermore, analysis of such transgenic plants has begun to clarify the roles of compatible solutes in stress tolerance.


Effect of an aqueous extract of Portulaca oleracea leaves on smooth muscle and rat blood pressure.
An aqueous extract of Portulaca oleracea leaves and stems produced a dose-dependent relaxation of guinea pig fundus, taenia coli and rabbit jejunum and a dose-dependent contraction of the rabbit aorta. On spontaneously-beating rabbit right atria and electrically-paced left atria, the extract produced a dose-dependent negative inotropic and chronotropic effects. On rat blood pressure, the extract produced dose-dependent pressor responses. Phentolamine reduced the relaxant effect of the extract on gut smooth muscle and abolished the contractile response on the aorta as well as the pressor response on blood pressure. Guanethidine and tetrodotoxin had no effect on extract-induced relaxant or contractile responses. On rat blood pressure atropine and cyproheptadine had no effect on extract-induced pressor response, whereas propranolol slightly reduced the pressor response. An increase in extracellular calcium reversed the inhibitory effect of the extract on the rabbit atria. The extract may, therefore, act in part on postsynaptic alpha-adrenoceptors and by interference with transmembrane calcium influx.


Utilization of agro-wastes to inhibit aflatoxins synthesis by Aspergillus parasiticus: A biotreatment of three cereals for safe long-term storage.
The growth of Aspergillus parasiticus and aflatoxins production were inhibited during storage of three important cereals (wheat, maize and rice) using leaves of neem (Azadirachta indica) and kikar (Acacia nilotica). Cereals were inoculated with mould spores and stabilized by neem and kikar leaves-powder. Test samples with moisture levels of 21% were stored at 30°C for a period of 9months. Aflatoxins were quantified at different time intervals in stored cereals. Neem leaves fully inhibited all types of aflatoxins synthesis for 4months in wheat and for 2months in maize while in rice inhibited synthesis of only B2, G1 and G2 aflatoxin for 3months. Kikar leaves fully inhibited aflatoxin B2, G1 and G2 for 3months in wheat, and for 2months in maize. Among two investigated plants, neem leaves were found more effective for preventing the production of all types of aflatoxins in cereals' long-term storage.


Feasibility of endovascular cooling as an adjunct to primary percutaneous coronary intervention (results of the LOWTEMP pilot study).
In a nonrandomized feasibility study of therapeutic hypothermia in acute myocardial infarction, 18 patients were treated with endovascular cooling (Alsius, Irvine, California) as adjunctive therapy to primary percutaneous coronary intervention to assess measures of infarct size (area under the curve creatinine kinase-MB and technetium-99m single-photon emission computed tomography sestamibi) and the quality of myocardial perfusion (continuous ST-segment monitoring). Periprocedural endovascular cooling successfully decreased core body temperature (median 33.5 degrees C) and was well tolerated, which supports the evaluation of adjunctive hypothermia in pivotal trials to limit infarct size and decrease reperfusion injury.


[Proteomic study of total protein of Pinellia pedatisecta Schott effect on human ovarian cancer SKOV3 cells].
To study the proteomics of Pinellia pedatisecta Schott total protein on human ovarian cancer SKOV3 cells. SKOV3 cells were in vitro cultured. The growth inhibition of SKOV3 cells in the logarithmic phase with different concentrations of Pinellia pedatisecta Schott (0, 0.05, 0.10, 0.20, 0.30, 0.40, and 0.50 mg/mL) at different time points (24, 48, 72, and 96 h) was analyzed by CCK-8 colorimetry. The total protein was extracted after adding 0.296 mg/mL Pinellia pedatisecta Schott protein for 48 h. The protein with differential expressions was screened out using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The protein of Pinellia pedatisecta Schott (at 0.10 - 0.50 mg/mL) could significantly inhibit the growth of SKOV3 cells in a time- and dose-dependent manner (P < 0.05, P < 0.01). After analyzed by 2-DE and MALDI-TOF-MS, 43 differential protein dots were successfully identified (21 up-regulated and 22 down-regulated), including alpha-enolase 1, eukaryotic initiation factor 3alpha, cyclophilin B, and so on. Protein of Pinellia pedatisecta Schott could significantly inhibit the growth of SKOV3 cells, and lead to the proteomics changes of SKOV3 cell strain. They might be correlated with its anti-tumor mechanisms.


Construction of 2D heterojunction system with enhanced photocatalytic performance: Plasmonic Bi and reduced graphene oxide co-modified Bi5O7I with high-speed charge transfer channels.
The efficient electron-hole charge pair separation, ultra-fast electron migration and excellent light harvest capacity are essential for semiconductor photocatalyst with superior photocatalytic performance. In this study, we constructed layered 2D/2D heterojunction composite of Bi@Bi5O7I/rGO (BiBGOI) through a facile surface charge mediated self-assembly strategy. The unique 2D/2D heterostructure with face to face contact can increase the contact area and generate a large amount of charge transfer nanochannels in the interfacial heterojunction, resulting in the enhancement of photocatalytic activity. Addition of semimetal Bi can enhance light absorption, and the local electromagnetic field dominated by SPR effect is favorable for photoinduced charge pair separation. The novel composite showed superior photocatalytic performance for decomposing levofloxacin (LVFX), which was attributed to the unique 2D/2D structure and SPR effect. The enhanced mineralization ability of the novel composite was ascribed to the strong oxidization ability of photoinduced holes, further evaluating high charge pair separation efficiency. In addition, the strong adsorption capacity of rGO for LVFX molecules can enable active radicals transfer into the surface to decompose it. This work will shed light on constructing 2D/2D heterojunction system assisted with SPR effect for the practical application in removal of organic pollutants.


Study of light scattering using C-Quant® in patients with Fuchs' endothelial dystrophy: A pilot study.
The purpose of this study was to determine the light scattering in patients with Fuchs' endothelial dystrophy without clinically significant corneal oedema, and evaluate its relationship with endothelial cell count, corneal thickness, and corneal biomechanical parameters. The values of light scattering were measured by C-Quant® (Oculus Optikgeräte GmbH, Germany) in 32 eyes of 17 patients diagnosed with Fuchs' endothelial dystrophy without clinically significant corneal oedema. Corneal biomechanical properties were determined using ORA (ocular response) and Corvis ST® (tonometry). A light scattering value outside the normal range was observed in 93.8% of eyes studied. No statistically significant association (P>.05) was found between the values of the measured light scattering by C-Quant® and endothelial count, pachymetry, or corneal biomechanical properties. In this study, changes were found in the values of light scattering values of patients with corneal Fuchs' endothelial dystrophy. This change does not appear to correlate significantly with disease severity.


Cytogenetic effects of sildenafil citrate (Viagra) on SWR/J mouse bone marrow cells.
The present study was conducted to investigate the cytogenetic effects of sildenafil citrate in SWR/J mouse bone marrow cells. Thirty-six males and 36 females were used and divided into four groups. Each group contained 18 animals (9 males and 9 females), weighing 30-35 g. These animals were orally administered with a single dose of 13, 26 or 40 mg/kg sildenafil citrate solution. A control group received normal saline in an identical condition. The animals were sacrificed at 12, 24 or 48 h, after the treatment. Chromosome aberrations were investigated in 50 metaphases per animal. No significant differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between treated male and female mice at any doses or at any time intervals used, therefore, data from the two sexes were pooled when analyzed statistically. No significant (p < 0.05) differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between sildenafil citrate-treated groups and the control group at any doses or at any time intervals used. However, the percentages of centromeric adhesions increased significantly (p < 0.01) in treated groups as compared with the control group at all doses and at all time intervals used. In conclusion, the results of the present study suggest that sildenafil citrate does not have cytogenetic effects on mouse bone marrow cells, but the centromeric adhesions induced by this drug need further studies to confirm them and to investigate the possible mechanism(s) responsible for such effect.


Hypotension during transsphenoidal pituitary surgery associated with increase in plasma levels of brain injury markers.
Patients undergoing pituitary surgery may experience short- and long-term postoperative morbidity. Intraoperative factors such as hypotension might be a contributing factor. Our aim was to investigate the association between intraoperative hypotension and postoperative plasma levels of tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as markers of perioperative brain injury. Between June 2016 and October 2017, 35 patients from the Gothenburg Pituitary Tumor Study were included. For tau, NfL, and GFAP, concentrations were measured in plasma samples collected before and immediately following surgery, and on postoperative days 1 and 5. The difference between the highest postoperative value and the value before surgery was used for analysis (∆taupeak , ∆NfLpeak , ∆GFAPpeak ). Intraoperative hypotension was defined as the area under the curve of an absolute threshold below 70 mmHg (AUC70) and a relative threshold below 20% (AUC20%) of the baseline mean arterial blood pressure. Plasma tau and GFAP were highest immediately following surgery and on day 1, while NfL was highest on day 5. There was a positive correlation between AUC20% and both ∆taupeak (r2 = .20, p < .001) and ∆NfLpeak (r2 = .26, p < .001). No association was found between AUC20% and GFAP or between AUC70 and ∆taupeak , ∆NfLpeak or ∆GFAPpeak . Intraoperative relative, but not absolute, hypotension was associated with increased postoperative plasma tau and NfL concentrations. Patients undergoing pituitary surgery may be vulnerable to relative hypotension, but this needs to be validated in future prospective studies.


Infection and the evaluation of biomarkers in obstetrics and gynecology patients with infectious disease: a retrospective observational study from clinical pharmacists' consultation experience.
The use of empirical anti-infective medication calls for the identification of common pathogens and accurate infectious biomarkers. However, clinical pharmacists' anti-infective experience in the field of obstetrics and gynaecology is rare in the literature. This study aimed to retrospectively analyze the correlation between the anti-infective effectiveness after 7 days of antibiotic treatment and infectious biomarkers, according to clinical pharmacists' consultation cases of gynecological and obstetric infections. In this retrospective study, clinical pharmacists' anti-infective consultation experiences applied by physicians from January 1, 2018, to December 31, 2020, were included. The exclusion criteria were as follows: (1) the patient died or left the hospital before undergoing an effectiveness evaluation after the consultation; (2) treatment was discontinued due to adverse reactions related to antibiotics; (3) the patient did not undergo an effectiveness evaluation within 3 or 7 days after application of the clinical pharmacist's treatment plan; and (4) the physician did not adopt the clinical pharmacist's suggestions. The registered information included patient characteristics, pathological bacteria, anti-infective medication and changes in infection indices before and after treatment. Statistical analysis of temperature, white blood cells (WBCs), C-reactive protein (CRP), procalcitonin (PCT) and WBCs in urine after 3 days and 7 days of anti-infective treatment, compared with before anti-infective treatment, was performed by the chi-square test. A t test was conducted to further study WBC count and CRP. A receiver operating characteristic curve verified the sensitivity and specificity of WBC count, CRP and PCT. A total of 265 cases were included. The CRP levels of patients 3 d and 7 d after antibiotic treatment were significantly lower than before antibiotic treatment (P < 0.05, P < 0.01), while the WBC count showed a downward trend after 3 days and a significant decrease after 7 days (P < 0.01). The areas under the curve (AUCs) for prognosis on the 7th day for WBC count, CRP and PCT were 0.90, 0.75 and 0.522, respectively. The AUC for WBC count combined with CRP was 0.90, which was higher than that for the biomarkers tested separately, especially compared to PCT. The most common gynecological infections were surgical site infection (SSI), urinary tract infection and fever of unknown origin, and the most common pathogens were E. coli and E. faecalis in Gram-negative and Gram-positive samples, respectively. Pharmacists' recommended treatment plans included carbapenems and β-lactam antibiotics. Our dual-center study indicates that the combination of WBC count and CRP can improve diagnostic accuracy and treatment efficiency, and PCT alone is insensitive to gynecological infections, according to clinical pharmacists' experience.


Energy expenditure during flight in relation to body mass: effects of natural increases in mass and artificial load in Rose Coloured Starlings.
Rose Coloured Starlings (Sturnus roseus) flew repeatedly for several hours in a wind tunnel while undergoing spontaneous variation in body mass. The treatments were as follows: flying unrestrained (U), with a control harness of 1.2% of their body mass (C), or with a harness of 7.4% of their body mass, which was either applied immediately before the flight (LS) or at least 9 days in advance (LL). Energy expenditure during flight (ef in W) was measured with the Doubly Labelled Water method. Flight costs in L(S) and LL were not significantly different and therefore were pooled (L). The harness itself did not affect ef, i.e. U and C flights were not different. ef was allometrically related with body mass m (in g). The slopes were not significantly different between the treatments, but ef was increased by 5.4% in L compared to C flights (log10(ef) = 0.050 + 0.47 x log10(m) for C, and log10(ef) = 0.073 + 0.47 x log10(m) for L). The difference in ef between C, LS and LL was best explained by taking the transported mass m transp (in g) instead of m into account (log10(ef) = -0.08 + 0.54 x log10(m transp)). Flight costs increased to a lesser extent than expected from interspecific allometric comparison or aerodynamic theory, regardless of whether the increase in mass occurred naturally or artificially. We did not observe an effect of treatment on breast muscle size and wingbeat frequency. We propose that the relatively low costs at a high mass are rather a consequence of immediate adjustments in physiology and/or flight behaviour than of long-term adaptations.


2-deoxyglucose sensitizes melanoma cells to TRAIL-induced apoptosis which is reduced by mannose.
While melanoma cell lines use aerobic glycolysis, addition of a competitive inhibitor such as 2-deoxyglucose (2DG) by itself achieved only modest killing. To overcome high levels of pro-survival proteins in melanoma cells, 2DG or glucose deprivation (GD) was combined with tumor necrosis factor-related apoptosis inducing-ligand (TRAIL). TRAIL treatment by itself also only induced modest killing, but combining TRAIL with 2DG or GD triggered a synergistic pro-apoptotic response in melanoma lines but not melanocytes. In melanoma cells, there was cleavage of caspases 3, 8 and Bid. Killing by combination treatments was completely blocked by a pan-caspase inhibitor, z-VAD. Mechanistically, 2DG and GD enhanced surface levels for both death receptors (DR4 and DR5); which was accompanied by reductions in levels of Mcl-1, Bcl-2 and survivin. Mannose pre-treatment reduced enhanced killing by combination treatments, accompanied by reduced DR5 levels. These results indicate melanoma cells in which there is altered glucose-related metabolomics can be exploited by interfering with glucose metabolism in combination with TRAIL; thereby overcoming the notorious death resistance of melanoma. Thus, a new therapeutic window is open for future clinical trials using agents targeting the glucose-related metabolome, in combination with agents triggering death receptors in patients with melanoma.


Verapamil reverses calcium cardiotoxicity.
High circulating concentrations of calcium are toxic to the heart and may cause cardiac arrhythmias and arrest. To investigate the therapeutic use of calcium antagonists in hypercalcemia, we evaluated the efficacy of verapamil hydrochloride and magnesium chloride in the treatment of experimental calcium-induced cardiac arrest in laboratory rats. Verapamil rapidly reversed the experimental calcium-induced arrest and improved survival (83% survival versus 0% in controls). Magnesium failed to reverse this toxic event. We conclude from these experimental studies that verapamil may be useful in the treatment of hypercalcemic cardiac toxicity.


Molecular cloning and genomic organization of chicken syndecan-4.
We have cloned and determined the genomic organization of the core protein of the chicken transmembrane proteoglycan, syndecan-4. Identification of the initial cDNA was accomplished using polyclonal antibodies directed against the cytoplasmic domain of murine syndecan-1 core protein. The cDNA for chicken syndecan-4 encodes a putative core protein of 197 amino acids which consists of a 19-amino acid signal peptide, a 125-amino acid ectodomain, a 25-amino acid transmembrane domain, and a 28-amino acid cytoplasmic domain. The predicted molecular mass of the mature core protein is 19,639 daltons. The ectodomain of chicken syndecan-4 core protein contains three potential sites for glycosaminoglycan attachment, two sites for N-glycosylation, and lacks a dibasic protease cleavage site proximal to the membrane-spanning region found in other syndecan family members. Comparison of the complete amino acid sequence with human syndecan-4 (amphlican (David, G., van der Schueren, B., Marynen, P., Cassiman, J. J., and van den Berghe, H. (1992) J. Cell Biol. 118, 961-969)) and rat syndecan-4 (ryudocan (Kojima, T., Shworak, N. W., and Rosenberg, R. D. (1992) J. Biol. Chem. 267, 4870-4877)) indicates an overall identity of 58 and 56%, respectively, with a 91 and 92% identity in the highly conserved transmembrane and cytoplasmic domains. The core protein of chicken syndecan-4 synthesized by chicken cells is modified with heparan sulfate side chains yielding a proteoglycan with a molecular mass of > 200 kDa in LMH cells (immortalized male leghorn LM strain hepatocytes) and primary skin fibroblasts. Syndecan-4 isolated from chondrocyte cultures runs as a diffuse band between 100 and 200 kDa. Northern analysis of chicken syndecan-4 indicates three messages with distinct sizes of 0.9, 1.3, and 2.9 kb and a wide mRNA tissue distribution. The chicken syndecan-4 gene is divided into 5 exons encoding distinct regions which contain the signal peptide, the glycosaminoglycan attachment sites, a small spacer of unknown function, the glycosylation sites and the transmembrane and cytoplasmic domains.


Cytotoxicity and enzyme inhibition studies of polyoxometalates and their chitosan nanoassemblies.
Polyoxometalates (POMs) have become very significant in biomedical research for their structural diversity which renders them highly active against bacterial, viral and cancer diseases. In this study three different POMs were synthesized and nanoassemblies were made with chitosan (CTS), a natural biodegradable polymer with excellent drug carrier properties. The compounds were tested on two isoenzymes of alkaline phosphatases including tissue specific calf intestine alkaline phosphatase (CIAP) and tissue non-specific alkaline phosphatase (TNAP). Compound [TeW6O24]6- (TeW6) showed the highest activity (45.4 ± 11.3 nM) among tested compounds against TNAP. Similarly, chitosan-[TeW6O24]6- (CTS-TeW6) was proved to be a potent inhibitor of CIAP with Ki value of 22 ± 7 nM. A comparative study was made to evaluate their cytotoxic potential against HeLa cells. Among all tested compounds, Chitosan-[NaP5W30O110]14- (CTS-P5W30) has showed higher percent cytotoxicity (88 ± 10%) at 10 μM when compared with the standard anticancer drug vincristine (72 ± 7%). The study revealed that selected POMs proved excellent anticancer potential and were equally effective against alkaline phosphatase enzyme, an increased level of which may indicate cancer metastasis.


Changes in DNA Content and Cellular Death during a Starvation-Survival Process of Escherichia coli in River Water.
Abstract Four nucleoid staining procedures were compared during the starvation-survival process of Escherichia coli in river water. Only the method performed as a modification of the standard acridine orange direct procedure allowed us to visualize nucleoids during the 95 days of experimentation. Moreover, with this method the total number of cells and nucleoid-containing cells can be simultaneously enumerated. The decrease of the chromosomal DNA content of population and of the nucleoid-containing cells indicates that ghosts form and cellular death occurs throughout the starvation-survival process. A long time (<30 days) is needed for non-nucleoid-containing cells to appear in river water; plasmid DNA is also negatively affected by environmental stress. After 4 days of storage in river water, the need to increase the volume of lysed cells used for the plasmid band visualization as well as the decrease in the plasmid band intensity would indicate a decrease in the plasmid DNA content during the starvation-survival process. According to our results, both chromosomal and plasmid DNA content decrease during the starvation-survival process of E. coli in river water.


Enhance Safety in Aneurysm Surgery: Strategies for Prevention of Intraoperative Vascular Complications.
Complications during surgery for intracranial aneurysms can be devastating. Notorious pitfalls include premature rupture, parent vessel occlusion, local cerebral injury and brain contusion, and incomplete neck obliteration. These unfavorable intraoperative events can result in major neurological deficits with permanent morbidity and even mortality. Herein, the author highlights the relevant surgical strategies used in his daily practice of aneurysm surgery (e.g., aneurysm clipping with adenosine-induced temporary cardiac arrest), application of which may help prevent vascular complications and enhance surgical safety through reduction of the associated risks, thus allowing improvement of postoperative outcomes. Overall, all described methods and techniques should be considered as small pieces in the complex puzzle of prevention of vascular complications during aneurysm surgery.


Synovial cysts of the lumbar spine: diagnosis, surgical management, and pathogenesis. Report of eight cases.
Synovial cysts are uncommon extradural degenerative lesions associated with symptoms of lower back pain and radiculopathy. Most of these lesions occur in the lumbar spine at the L4-5 level and to a lesser extent at the L5-S1 and L3-4 levels. A retrospective study involving eight patients seen by the neurosurgery service from January 1, 1989, to May 30, 1994, was analyzed. The type, duration, and distribution of symptoms were evaluated, along with the patient's age and sex. All patients had lumbosacral spine x rays and magnetic resonance imaging. Four had a computed tomography-myelogram of the lumbar spine. All patients underwent a laminectomy or hemilaminectomy and cyst excision, and all were followed for a minimum of 1 year. The presence of a synovial cyst was confirmed by histopathology. Of the eight patients, seven had dramatic pain relief with five having complete resolution of pain. The single care of persistent pain was found to be due to scar tissue at the operative site. All five cases of preoperative lower extremity weakness showed complete resolution. Dysesthesia was either unchanged or decreased. Surgery is a safe, effective treatment for patients with lumbar synovial cysts and is the treatment of choice for these lesions.


Thick brain slices model the ischemic penumbra.
Hypothalamic brain slices, varying in thickness from 400 mu to 1,000 mu, were assessed by studying 2-deoxyglucose (2DG) metabolism, lactate accumulation, inulin spaces, and morphology at the light and ultrastructural levels. Evidence of increased glycolytic flux due to anaerobic metabolism is found at thickness greater than 600 mu in association with a progressive increase in the inulin-exclusion space. The metabolic profiles, as a function of depth into the slices, reveal that 700-mu slices function in a manner similar to 540-mu slices at the surfaces, but with a core of increased 2DG phosphorylation at the slice center. In contrast, the 1,000-mu slices show significant reduction of 2DG and increases in 2DG6P relative to the 540-mu slices at the slice surface as well as in the slice interior, suggesting impaired transport of 2DG into cells and spread of ischemic injury from the slice interior to the slice surface. Despite these metabolic changes, only minor morphologic changes of ischemic injury were found at the center of thicker slices, and in vitro glucose utilization of 1000-mu slices remained constant for up to 15 h. These three slice thicknesses should provide a useful model for studying the neurochemistry and neuropharmacology of the ischemic penumbra.


Recombinant chromosome as a result of pericentric inversion of X chromosome.
A structural X chromosome abnormality was found in the karyotype of a tall patient with gonadal dysgenesis and with no extragenital anomalies. Based on her mother's karyotype, which showed a pericentric inversion of the X chromosome: 46,X,inv(X)(p22q24), as well as from G and R banding, we concluded that the abnormal X chromosome of our patient was a recombinant chromosome that had originated as a result of one crossing over in the inversion loop during gametogenesis in her mother. The recombinant X chromosome had a partial delection of Xq and a partial duplication of Xp: 46,X,rec(S),dup p,inv(X)(p22q24). After BUDR incorporation, the abnormal X chromosome of the patient and that of her mother showed a late replication. The karyotype-phenotype correlation and the nonrandom inactivation of the inverted X chromosome in the mother are discussed.