Correlates of compliance with measurement protocols in a Latino nutrition-intervention study.
It is well known that attrition and noncompliance in longitudinal health intervention studies contribute to bias in both internal and external validity. However, little is known about rates and correlates of compliance with measurement protocols among Latinos. This article investigates correlates of compliance with follow-up physical measurement protocols among Latino subjects in a nutrition-oriented cardiovascular disease prevention program targeting low-English literate adults. Correlates of compliance, measured at baseline, included four classes of variables: demographic characteristics, physical measures, health behaviors, and nutrition-related psychological variables. Subjects were categorized into one of three compliance groups: on-time compliers, late or "reluctant" compliers, and noncompliers. Approximately 36% of subjects complied on time, 25% complied late, and 39% did not comply. Analyses showed that, relative to on-time and late compliers, noncompliers tended to be male, younger, of lower income and Spanish-literacy level, to drink more alcohol, to be less physically active, and to have lower dietary fat avoidance scores. No significant differences were found for other factors considered (e.g., physical health measures). These results generally reflect those of non-Hispanics that indicate that individuals at greater "risk" are less likely to comply with study protocols. Such results may be useful for designing culturally appropriate cohort maintenance strategies for longitudinal studies with Latinos.


Barley DNA-binding methionine aminopeptidase, which changes the localization from the nucleus to the cytoplasm by low temperature, is involved in freezing tolerance.
The polymerase chain reaction-based Mirror Orientation Selection (MOS) method was used to isolate low temperature-induced genes from cold-treated winter barley (Hordeum vulgare L. cv. Dongbori). MOS screening identified a novel methionine (Met) aminopeptidase (MAP) designated as HvMAP. The deduced HvMAP protein was determined to possess an aminopeptidase domain and a nuclear localization signal. An in vitro enzyme assay using recombinant HvMAP protein demonstrated MAP activity. The expression of this gene was induced by low temperature and abscisic acid treatment, and overexpression of this gene conferred stronger freezing tolerance to Arabidopsis transgenic plants as compared to wild-type plants. Interestingly, low temperature treatment changed the localization of HvMAP from the nucleus to the cytoplasm. These findings suggest that HvMAP is a novel MAP that functions in freezing tolerance by facilitating protein maturation.


Incentive salience attribution under reward uncertainty: A Pavlovian model.
There is a vast literature on the behavioural effects of partial reinforcement in Pavlovian conditioning. Compared with animals receiving continuous reinforcement, partially rewarded animals typically show (a) a slower development of the conditioned response (CR) early in training and (b) a higher asymptotic level of the CR later in training. This phenomenon is known as the partial reinforcement acquisition effect (PRAE). Learning models of Pavlovian conditioning fail to account for it. In accordance with the incentive salience hypothesis, it is here argued that incentive motivation (or 'wanting') plays a more direct role in controlling behaviour than does learning, and reward uncertainty is shown to have an excitatory effect on incentive motivation. The psychological origin of that effect is discussed and a computational model integrating this new interpretation is developed. Many features of CRs under partial reinforcement emerge from this model.


Survival and development of a stored-product pest, Sitophilus zeamais (Coleoptera: Curculionidae), and its natural enemy, the parasitoid Lariophagus distinguendus (Hymenoptera: Pteromalidae), on transgenic Bt maize.
The effect of transgenic maize (Zea mays L.) containing a lepidopteran-specific Bt toxin on a stored-product pest, Sitophilus zeamais Motschulsky, and its parasitoid, Lariophagus distinguendus Förster, was examined in the laboratory to test the impact of transgenic maize on stored-product pests and their biological control. Weevils were not harmfully affected by transgenic Bt maize in their development characteristics (development time, body mass), and females emerging from transgenic maize kernels were larger. However, significantly fewer parasitoid females emerged from weevils that developed in transgenic kernels, although parasitoids did not develop more slowly and were not different in size or mass from their conspecifics emerging from hosts in non-transgenic maize kernels. The emergence of female parasitoids was reduced in transgenic Bt maize, and this effect cannot be explained by the known lepidopteran-specific toxicity of Bt Cry1Ab toxin.


Enhancing fatigue life by ductile-transformable multicomponent B2 precipitates in a high-entropy alloy.
Catastrophic accidents caused by fatigue failures often occur in engineering structures. Thus, a fundamental understanding of cyclic-deformation and fatigue-failure mechanisms is critical for the development of fatigue-resistant structural materials. Here we report a high-entropy alloy with enhanced fatigue life by ductile-transformable multicomponent B2 precipitates. Its cyclic-deformation mechanisms are revealed by real-time in-situ neutron diffraction, transmission-electron microscopy, crystal-plasticity modeling, and Monte-Carlo simulations. Multiple cyclic-deformation mechanisms, including dislocation slips, precipitation strengthening, deformation twinning, and reversible martensitic phase transformation, are observed in the studied high-entropy alloy. Its improved fatigue performance at low strain amplitudes, i.e., the high fatigue-crack-initiation resistance, is attributed to the high elasticity, plastic deformability, and martensitic transformation of the B2-strengthening phase. This study shows that fatigue-resistant alloys can be developed by incorporating strengthening ductile-transformable multicomponent intermetallic phases.


Atmospheric residence times and excess of unsupported 210Po in aerosol samples from the Kuwait bay-northern gulf.
The concentration of cosmogenic radionuclide 7Be and the naturally occurring radionuclide 222Rn and its progenies 210Pb, 210Po, and 214Pb were measured in the ground surface air in the urban area of the northern Arabian Gulf close to Kuwait Bay. A high-volume air sampler connected with a five-stage cascade impactor was used to collect approximately 1800 cubic meter weekly for a period of one year. The concentrations of 210Pb and 210Po varied from 0.35 to 1.65 mBq m-3 and from 0.23 to 3.2 mBq m-3, respectively; the 210Po/210Pb activity ratio was close to one. The average concentration of 7Be was 6.24 mBq m-3, ranging from 3 to 10 mBq m-3. The temporal variations of 210Pb, 210Po and 7Be showed maximum concentrations of 210Po and 7Be in occurred summer months. The observed excess of 210Po concentrations can be attributed to the local and long-range transport of suspended dust with 210Pb and 210Po in radioactive equilibrium state, oil industry emissions, local resuspended dust and the sea-salt-aerosols from the Arabian Gulf. The range of the residence time estimation using the 222Rn/210Pb and 214Pb/210Pb activity ratio methods ranged from three to five days. Moreover, the estimated residence time by the application of 7Be from the activity median aerodynamic diameter method was 4.2 days. The method of using the 210Po/210Pb activity ratio was invalid because of the excess 210Po sources of anthropogenic origin. Therefore, extensive accurate diurnal measurements of 214Pb and 222Rn can be applied in hot arid regions for better aerosols residence time estimation.


[Ambulatory minimally invasive hysterectomy: Limiting factors related to health professionals].
The feasibility of minimally invasive hysterectomy for ambulatory benign pathology has been demonstrated in many international studies. France has a considerable delay of multifactorial origin in this field. The objective of this study is to identify the limiting factors related to health professionals to the realization of minimally invasive ambulatory hysterectomy and to determine possible strategies to increase its rate. This is a cross-sectional survey conducted over 2 months using a self-administered questionnaire sent by email to 180 gynecological surgeons in 2 French regions (Grand Est and Bourgogne-Franche Comté). A total of 22% of health professionals responded to the survey. The vast majority of practitioners (60%) said they did not carry out ambulatory care by habit. The apprehension of the reaction of the patients (47.5%), the fear of delayed diagnosis of complications (12.5%), the management of pain in the postoperative period (42.5%) also participated in brake of the promotion of ambulatory care. Improvement of the organisation of city and hospital management allowing a better continuity of care (70%), the economic valuation (37.5%) and the increase in the hourly amplitude of the ambulatory surgery unit (5%) would improve the rate of ambulatory care of minimally invasive hysterectomies, according to the gynecologist surgeons surveyed. In addition, a prospective study evaluating the quality of life of patients after ambulatory care of minimally invasive hysterectomy would allow better adherence of health professionals and patients to the ambulatory care project in 70% of cases. The change of mentality of health professionals remains a priority for the promotion of ambulatory surgery in gynecology. Information and communication are therefore essential to the expansion of the ambulatory.


Biological responses and toxicopathic effects elicited in Solea senegalensis juveniles by waterborne exposure to benzo[a]pyrene.
Polycyclic aromatic hydrocarbons (PAHs) are priority contaminants in coastal and estuarine ecosystems under anthropogenic pressure. Although PAHs tend to accumulate in the sediment, toxicity for benthic flat fish such as soles may be caused by PAHs released from the sediment to the water column. Within this context, the present investigation aims at recognizing toxicopathic effects elicited after waterborne exposure to benzo[a]pyrene B[a]P, a model individual PAH compound, in juvenile Solea senegalensis. Sole juveniles were exposed to various concentrations of waterborne B[a]P for 3 and 7 days. Brain, liver, gills and gonad were the target tissues selected to determine biochemical and lysosomal biomarkers, and histopathology. Biological responses and toxicopathic effects were consistent with B[a]P concentration and exposure time. From day 3, hepatic catalase inhibition indicated potential oxidative effects of B[a]P. At day 7, contaminant exposure produced hepatic glutathione-S-transferase induction at low concentrations and inhibition at higher levels, evidencing a bell-shaped response. A clear gradient in lysosomal membrane destabilisation was observed in relation with B[a]P concentrations. Histopathological lesions were more frequent at day 7 and at higher contaminant levels. It seems that environmentally relevant waterborne concentrations of B[a]P (1000 ng/l) would suffice to cause toxicopathic effects on sole juveniles in relatively short exposure times. In agreement, the Integrative Biological Response index (IBR/n) indicated a dose-dependent decline in health condition upon exposure to B[a]P (IBR/nHighB[a]P > IBR/nMidB[a]P > IBR/nLowB[a]P > IBR/nDMSO > IBR/nControl). Overall, changes in antioxidant enzymes activity, lysosomal biomarkers and gill and liver histopathology are responsive early-warning signs of health disturbance in sole juveniles exposed to waterborne PAHs.


Heat penetration attributes of milkfish (Chanos chanos) thermal processed in flexible pouches: a comparative study between steam application and water immersion.
The difference in the heating penetration characteristics of product processed in retort by steam-air application and water immersion was studied. Fresh milkfish (Chanos chanos) packed in dry pack and in oil medium, both in flexible pouches, was thermal processed to minimum F0 value of 7.77 at 121.1°C. Heat penetration values were recorded for each minute of processing with the aid Ellab (TM 9608, Denmark) temperature recorder. Retort come up time to achieve 121.1°C was observed to be less in steam-air which invariably led to a lower Ball's process time (B) and the total process time (T) observed in steam-air as compared to water immersion. Obtained data were plotted on a semi-logarithmic paper with temperature deficit on x-axis against time on the y-axis.


[Negative pressure pulmonary edema: report of case series and review of the literature].
Negative pressure pulmonary edema occurs by increased intrathoracic negative pressure following inspiration against obstructed upper airway. The pressure generated is transmitted to the pulmonary capillaries and exceeds the pressure of hydrostatic equilibrium, causing fluid extravasation into the pulmonary parenchyma and alveoli. In anesthesiology, common situations such as laryngospasm and upper airway obstruction can trigger this complication, which presents considerable morbidity and requires immediate diagnosis and propaedeutics. Upper airway patency, noninvasive ventilation with positive pressure, supplemental oxygen and, if necessary, reintubation with mechanical ventilation are the basis of therapy. Case 1: Male, 52 years old, undergoing appendectomy under general anesthesia with orotracheal intubation, non-depolarizing neuromuscular blocker, reversed with anticholinesterase, presented with laryngospasm after extubation, followed by pulmonary edema. Case 2: Female, 23 years old, undergoing breast reduction under general anesthesia with orotracheal intubation, non-depolarizing neuromuscular blocker, reversed with anticholinesterase, presented with inspiration against closed glottis after extubation, was treated with non-invasive ventilation with positive pressure; after 1 hour, she had pulmonary edema. Case 3: Male, 44 years old, undergoing ureterolithotripsy under general anesthesia, without neuromuscular blocker, presented with laryngospasm after laryngeal mask removal evolving with pulmonary edema. Case 4: Male, 7 years old, undergoing crude fracture reduction under general anesthesia with orotracheal intubation, non-depolarizing neuromuscular blocker, presented with laryngospasm reversed with non-invasive ventilation with positive pressure after extubation, followed by pulmonary edema. The anesthesiologists should prevent the patient from perform a forced inspiration against closed glottis, in addition to being able to recognize and treat cases of negative pressure pulmonary edema.


Chlorambucil-induced structural changes in the gpt gene of AS52 cells.
The bifunctional alkylating agent chlorambucil (CBC) is a chemotherapeutic agent that induces a high yield of mouse germ-line mutations, apparently due to multi-locus deletions or other chromosomal rearrangements. We investigated the mutagenicity of CBC in cultured mammalian cells by comparing its effect in the AS52/gpt and CHO/hprt gene mutation assays, which detect large and small effects, respectively. CBC significantly increased the mutant frequency in the AS52/gpt assay, but not in the CHO/hprt assay, while the cytotoxic responses to CBC were similar in the two cell lines. This indicates that CBC induced predominantly large deletions or other gross structural changes, and not point or other small mutations. The mutational responses to CBC were similar to the responses to mitomycin C comparing them based on the cytotoxic responses. Molecular analysis of the gpt gene in AS52 mutant cells by electrophoresis following PCR amplification revealed that 81% of CBC-induced mutants lost the entire gpt gene, which is caused by large deletions or interchromosomal recombinations. The loss frequency was lower in spontaneous mutants (42%) and ethylmethanesulfonate-induced mutants (29%). This supports cytogenetic data showing that CBC is a potent clastogen in cultured mammalian cells, inducing predominantly large deletions and/or other gross structural alterations.


A complex network of QTL for thousand-kernel weight in the rye genome.
Here, QTL mapping for thousand-kernel weight carried out within a 541 × Ot1-3 population of recombinant inbred lines using high-density DArT-based map and three methods (single-marker analysis with F parametric test, marker analysis with the Kruskal-Wallis K* nonparametric test, and the recently developed analysis named genes interaction assorting by divergent selection with χ2 test) revealed 28 QTL distributed over all seven rye chromosomes. The first two methods showed a high level of consistency in QTL detection. Each of 13 QTL revealed in the course of gene interaction assorting by divergent selection analysis coincided with those detected by the two other methods, confirming the reliability of the new approach to QTL mapping. Its unique feature of discriminating QTL classes might help in selecting positively acting QTL and alleles for marker-assisted selection. Also, interaction among seven QTL for thousand-kernel weight was analyzed using gene interaction assorting by the divergent selection method. Pairs of QTL showed a predominantly additive relationship, but epistatic and complementary types of two-loci interactions were also revealed.


Human males and females body thermoregulation: perfusion effect analysis.
Skin temperature is a common physiological parameter that reflects thermal responses. Blood perfusion is an important part of the physiological processes that the human body undergoes in order to maintain homeostasis. This study focuses on the effect of perfusion on the temperature distribution in human males and females body in different thermal environment. The study has been carried out for one dimensional steady cases using finite element method. The input parameter of the model is the blood perfusion or volumetric flow rate within the tissue. The appropriate physical and physiological parameters together with suitable boundary conditions that affect the heat regulations have been incorporated in the model. The study is to have a better understanding that how does thermoregulation change in human males and females skin layered due to perfusion.


The neuroprotective effects of NMDAR antagonist, ifenprodil and ASIC1a inhibitor, flurbiprofen on post-ischemic cerebral injury.
Owing to the complex and multifactorial pathology of cerebral stroke, multiple drug therapy had long been advocated by STAIR committee for stroke successful treatment. In this context, we analyzed the effect of Ifenprodil, an NR2b selective NMDAR antagonist and its combination at lower doses with flurbiprofen, a selective ASIC1a inhibitor on rat model of focal cerebral ischemia. We found that the combination produced significant neuroprotective effect as produced by ifenprodil at higher doses, which was evidenced by reduction in infarct volume, neurological deficit and MDA levels. Further, histopathological studies revealed that, the combination not only attenuated the cell damage in striatal regions of ischemic brain, but also significantly inhibited apoptotic cell death, which was more pronounced than monotherapy with ifenprodil or flurbiprofen. Thus, it appears that the combination therapy will be more efficacious in offering neuroprotection on one hand and also lower the risks associated by mono-therapy with ifenprodil at higher doses.


[Proximal interphalangeal (PIP) finger prosthesis - what have we learnt? Experiences over 10 years].
In the following article we evaluate the clinical and radiological results after PIP joint replacement to answer the question if the outcome improved over the last years. In a retrospective clinical study 53 patients with 66 PIP joint implants (SBI-Avanta, Small Bone Innovations, Inc.) were assessed on the basis of clinical and radiological parameters. We examined the patients' range of motion, their grip strength, the rate of radiological loosening, the development of pain and the patients' satisfaction. 2 groups were included in the study. Patients operated from 2001 to 2007 (group A) were compared with patients operated from 2008 to 2011 (group B). To facilitate a standardized examination, we developed a score providing a comprehensive representation of the outcome after PIP joint replacement. Group B showed significant improvement in the rate of loosening of the prosthesis (44-4%) in the last follow-up examination. Further improvement was demonstrated in pain reduction, range of motion (77°/67°), the patients' satisfaction and development of swan neck deformity (11%/18%). There was no significant improvement in the patients' grip strength and the rate of revision surgery. Overall, the results after PIP joint replacement are very good. All patients reported a marked improvement in pain reduction. In group B a significant reduction in the rate of loosening of the prosthesis was shown. Moreover, the rate of swan neck deformity, the range of motion, the reduction of pain and the patient's satisfaction improved over the last years. The application of a new PIP-joint-score for a standardized evaluation of the outcome indicated a good correlation with patient satisfaction over time. The experience of the past years enabled improvements in PIP joint replacement. We consider cementing the prosthesis, a large contact area between the prosthesis and the bone and an emphasis on easy intraoperative flexion/extension as factors which can improve the results after PIP joint replacement. However, some problems could not been solved to date. In this respect, prospective clinical and biomechanical studies are necessary.


Genetic diagnosis of multiple affected tissues in a patient with McCune-Albright syndrome.
McCune-Albright syndrome (MAS) is a sporadic disorder characterized by the classic triad of polyostotic fibrous dysplasia, café-au-lait' skin pigmentation, and hyperfunctional endocrinopathy. It is caused by embryonic somatic mutations leading to the substitution of His or Cys for Arg at amino acid 201 of the alpha-subunit of the signal transduction protein Gs (Gsalpha). A 32-year-old man was diagnosed as McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, café-au-lait' spots and acromegaly. An ultrasonic examination showed that he had left-pleural effusion, which disappeared after almost a year without special treatment. Genomic DNA was isolated from the peripheral blood, bone tissue, skin lesion and pleura samples of the patient. Then PCR and direct sequencing were performed. An activating mutation of the Gsalpha gene (Arg201Cys) was found in the genomic DNA isolated from the peripheral blood and the bone tissue, but not in genomic DNA isolated from the skin and pleura samples.


Detection of disturbances in pulmonary gas exchanges during exercise from arterialized earlobe PO2.
Blood sampling from the arterialized earlobe is widely used in clinical exercise testing but Fajac et al. (1998) (Eur. Respir. J. 11, 712-715) have shown that arterialized P(O2) Pc(CO2) is not a valid surrogate for Pa(O2). In the present study, in order to detect disturbances in pulmonary gas exchanges during clinical exercise testing from the alveolar-arterial gradient of P(O2) (P[Ai-a](O2)), a correction factor for Pc(O2) was validated from data on a large cohort (107 patients at one or two levels of exercise: 172 pairs of samples). Pulmonary gas exchanges and pH, P(O2), P(CO2), PA(iO2) and P(Ai-a)(O2) from arterial and arterialized blood were measured or computed. Arterial and arterialized pH and P(CO2) (and thus PA(iO2)) were similar but P(CO2) was lower than arterial P(O2) (Pa(O2)). However, when corrected for the systematic bias between Pa(O2) and Pc(O2), which increased with Pc(O2), Pc(O2) adequately detected disturbances in pulmonary gas exchanges with a very high sensibility and specificity (predictive values of a negative or positive test ∼95%).


Determination of methionine sulfoxide in proteins: comparison of a gas-chromatographic and electrophoretic method.
Two methods for the determination of methionine in proteins have been used to estimate the extent of methionine sulfoxide obtained upon exposure of proteins to oxidizing agents. Both methods are based on prior treatment with cyanogen bromide, which attacks methionines (but not the sulfoxide derivative) with the resultant formation of methyl thiocyanate and peptides. The amount of methyl thiocyanate is determined quantitatively by gas chromatography, while the number of peptides is ascertained by SDS-polyacrylamide gel electrophoresis. The gas chromatographic estimate of CH3SCN offers an accurate and precise method (down to nanogram values) for the quantitative determination of methionine sulfoxide in proteins. Due to its simplicity and the use of low-cost equipment, the electrophoretic method appears to be a valuable complement to the gas chromatographic method, and the two methods in conjunction provide novel results.


Antigen-specific T-cell immunity in multiple myeloma patients is restored following high-dose therapy: implications for timing of vaccination.
The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine induced specific immunity in multiple myeloma patients. Peripheral blood was collected from six multiple myeloma (MM) patients at serial time points in connection with treatment and during a follow-up period of 3 months. T-cell response to cytomegalovirus (CMV), varicella zoster virus (VZV) and tetanus toxoid (TT) was determined by flow cytometry analysis for CD69, TNFalpha, IFNgamma, IL-4 expression and cell proliferation. At diagnosis and prior to induction chemotherapy TNFalpha expressing T cells in 5/6 patients were found specific for CMV, 3/6 for VZV and 4/6 for TT. Serial analyses during treatment conclude impaired immune response, however, 3 months post-transplantation all but one patient had regained cytokine expressing CD8(+) T cells specific for CMV, VZV and TT. The highest percentages of cytokine responding T cells were observed after stimulation with CMV antigen. A striking observation was the low cytokine reactivity (close to zero) measured in G-CSF mobilized blood at the time of leukapheresis. In spite of a general reduction of the CD4/CD8 ratio following transplantation, recovery of antigen specific CD4(+) T cells reactivity generally occurred prior to CD8(+) recovery and often to a higher level. In conclusion, the study demonstrates that natural as well as vaccine induced specific immunity present prior to HD was regained after stem cell transplantation, hence identifying a possible window for future vaccination trials.


CD8+ T Cells in the Lymph Node Play a Key Role in Immunotherapy Response.
CD8+ T-cell populations in the lymph node (LN) modulate antitumor responses after immunotherapy.


Frequency of radiculopathies in motor vehicle accidents.
This retrospective study compared the frequency of electrodiagnostically confirmed cervical and lumbar radiculopathies in a motor vehicle accident (MVA) population to that of a non-MVA population in 24,651 consecutive initial electrodiagnostic reports. The frequency of cervical radiculopathy was slightly but significantly increased in 8% of the MVA compared to 6% of the non-MVA patients. The frequency of plexopathy was significantly increased in the MVA (3%) compared to the non-MVA patients (2%). The frequency of lumbar radiculopathy was not significantly increased (12% for both groups). Nineteen percent of the MVA patients and 18% of the non-MVA patients had cervical and/or lumbar radiculopathy. This shows that the frequency of cervical and lumbar radiculopathies is low after MVAs. MVA appears to cause a small but significant increase in the frequency of cervical radiculopathy and plexopathy.


Association of increased S100A8 serum protein with early pregnancy loss.
The contribution of systemic S100A8 protein in menstrual cycle, pregnancy, and early pregnancy loss (EPL) is not known. Altered expression of S100A8 in maternal decidua is associated with recurrent early pregnancy loss. The objective of this study was to investigate the systemic level of S100A8 in different phases of menstrual cycle, different trimester of pregnancy, and in EPL. Level of S100A8 was investigated in serum samples of the subjects through enzyme-linked immunosorbent assay (ELISA). S100A8 levels were elevated during proliferative phase of menstrual cycle. We found no statistical difference in S100A8 level in different trimester of pregnancy. S100A8 level was found to be significantly elevated in patients with EPL. This is the first study evaluating the systemic level of S100A8 predicting its role during menstrual cycle and pregnancy. It opens a new perspective in which S100A8 can be used as a prognostic marker for EPL.


Propagation of low calcium non-synaptic induced epileptiform activity to the contralateral hippocampus in vivo.
Recent experiments show that non-synaptic epileptiform activity can be induced by high K+ and low Ca2+ solution in vivo in the hippocampal CA1 region when synaptic transmission is blocked. However, the ability of this type of epileptiform activity to propagate to other brain areas is unknown. Presumably, this epileptiform activity should propagate and project along the axons to remote brain areas. This hypothesis was tested in vivo by inducing non-synaptic seizures in the left hippocampus and by recording spontaneous and evoked field potentials in both left and right hippocampi. The results show that one type of non-synaptic epileptiform activity, late bursts, observed in the left exposed CA1 and CA3 regions could propagate to the contralateral intact CA1 and induce seizures with onsets of high-frequency rhythm. A cut of the commissural fibers near the midline of the brain prevented this propagation. In addition, the measurement of time delays between the exposed left CA3 and contralateral right CA1, as well as between the two recording electrodes in the right CA1, showed that the burst activity propagated through the commissural pathways. Experimental data also showed that these late bursts in the left hippocampus were first generated in the Schaffer collaterals of the CA1 region, traveled to the ipsilateral CA3 region and then propagated through the commissural fibers to the other side. These results suggest that non-synaptic epileptiform activity can propagate along axon projections to intact brain area causing seizure activity. This non-synaptic activity propagating through axonal pathway provides a possible mechanism for the generation of high-frequency low-amplitude onset activity observed commonly in human epileptic EEGs.


Dictyostelium nucleomorphin is a member of the BRCT-domain family of cell cycle checkpoint proteins.
A search of the Dictyostelium genome project database (http://dictybase.org/db/cgi-bin/blast.pl) with nucleomorphin, a protein that regulates the nuclear number, predicted it to be encoded by a larger gene containing a putative breast cancer carboxy-terminus domain (BRCT). Using RT-PCR, Northern and Western blotting we have identified a differentially expressed, 2318 bp cDNA encoding a protein isoform of Dictyostelium NumA with an apparent molecular weight of 70 kDa that we have called NumB. It contains a single amino-terminal BRCT-domain spanning residues 125-201. Starvation of shaking cultures reduces NumA expression by approximately 88+/-5.6%, whereas NumB expression increases approximately 35+/-3.5% from vegetative levels. NumC, a third isoform that is also expressed during development but not growth, remains to be characterized. These findings suggest NumB may be a member of the BRCT-domain containing cell cycle checkpoint proteins.


Phenacyl azides as efficient intermediates: one-pot synthesis of pyrrolidines and imidazoles.
Phenacyl azides were decomposed in basic media to generate N-unsubstituted imines which were reacted with cyclic amino acids to give an azomethine ylide that underwent [3 + 2] cycloaddition with maleimides and N-unsubstituted imines to yield various diastereoselective pyrrolidines and imidazoles respectively in a one-pot three component manner with good to excellent yields.


Quantifying the parallel mediation influence of body mass index and depression on physical activity and cognitive function among 3,611 Chinese older adults.
Engagement in physically active lifestyles brings multidimensional health benefits including better cognitive function. While prior studies examined the link between physical activity and cognitive function, a remaining unanswered question is what modifiable factors channel such effects. This study investigates the extent to which subject's body mass index (BMI) and depression mediate the link between physical activity and cognitive function among older adults in China. This study builds a parallel structural equation model utilizing the 2013-2018 China Health and Retirement Longitudinal Study (CHARLS) dataset. We screened a total of 14,724 subjects, among which 3,611 subjects met the inclusion criteria. Physical activity, depression, and cognitive function are measured using the International Physical Activity Questionnaire (IPAQ), Center for Epidemiological Research Depression Scale (CES-D), and Mini-Mental State Examination (MMSE) instruments. Parallel mediation analyses indicate that depression significantly mediates the link between physical activity and cognitive function (std. β = 0.023, p-value = 0.010), while no significant mediation was observed via BMI (std. β = 0.005, p-value = 0.155). Findings also show that physical activity is positively associated with cognitive function (std. β = 0.104, p-value = 0.004), whereas physical activity is inversely associated with BMI (std. β = -0.072, p-value = 0.045). Both BMI (std. β = -0.071, p-value = 0.042) and depression (std. β = -0.199, p-value = 0.001) are negatively associated with cognitive function. This study quantifies the positive association between physical activity and cognitive function in older Chinese adults, and uncovers a significant mediation channel occurring through depression. From a clinical perspective, physical behavioral modifications can lead to linked improvements in both mental and cognitive wellbeing for older adults.


Surgical stabilisation of the spine.
It is important to assess spinal injuries, both in terms of cord damage and column damage, shortly after the trauma has occurred. A decision should then be made concerning the eventual stability of the bony vertebral column. If a lesion is unlikely to heal soundly by bone or if one is unable to obtain a reduction by conservative measures, one should consider surgical stabilisation of the damaged spine in the subacute phase. At the same time as one stabilISES THe spine with metallic fixation, bone grafts should be added for ultimate stability. If an unstable spine is encountered in the later stages of treatment, surgical stabilisation is again indicated. Metallic fixation can greatly aid in stabilising the spine until bone grafts can mature. Osteotomies of the spine through a combined transthoracic and posterior approach can be extremely valuable in correcting deformity. While there is no role for decompressive surgery after spinal cord injury, there is still a definite role for surgery in balancing and stabilising the vertebral column.


The effect of COVID-19 pandemic restrictions on neovascular AMD patients treated with treat-and-extend protocol.
To investigate the adherence rate of neovascular age-related macular degeneration (nAMD) patients in treat-and-extend (TAE) protocol to their anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection (IVI) appointments and to evaluate the functional and anatomical outcomes of the patients who attended and did not attend their IVI appointments during the coronavirus disease 2019 (COVID-19) restriction period (RP). The patients with nAMD having IVI appointments between March 16 and June 1, 2020 (RP in Turkey) were included in this retrospective study. For adherence analysis, the patients who attended (Group 1, n = 44) and who did not attend (Group 2, n = 60) their IVI appointment visits during the RP (VRP) were evaluated according to their last visit before the RP (V0). For outcome analysis, the patients who attend VRP and have follow-up (Group 1a, 46 eyes) and who did not attend VRP but later attended for follow-up (Group 2a, 33 eyes) were evaluated for functional (best-corrected visual acuity, BCVA [logMAR]) and anatomical (optical coherence tomography [OCT] disease activity) outcomes at the first visit after RP (V1) and last visit within six months after RP (V2). Patients received a complete ophthalmologic evaluation with anti-VEGF (Aflibercept) IVI administration at all visits. The adherence rate of the patients to VRP was 42.3% (44/104). The patients in Group 1 were significantly younger (mean ± SD years, 71.0 ± 8.1 vs. 74.7 ± 8.0, p = 0.024), had better median [IQR] BCVA at their first presentation (0.30 [0.54] vs. 0.61 [1.08], p = 0.023) and V0 (0.40 [0.48] vs. 0.52 [0.70], p = 0.031), and had less hypertension (36.4% vs. 58.3%, p = 0.044) than Group 2. The mean ± SD delay of planned IVI at VRP in Group 2a was 13.9 ± 6.2 weeks. Disease activity in OCT was significantly higher in Group 2a than Group 1a at V1 (60.6% vs. 32.6%, p = 0.025). In Group 2a, the median (IQR) BCVA was significantly worse at V1 (0.70 [0.58]) and V2 (0.70 [0.59]) than V0 (0.52 [0.40], p = 0.047 and p = 0.035, respectively). More than half of the scheduled nAMD patients in TAE protocol missed their IVI visits during the RP, which resulted in a delay of their treatments. The delay of IVI treatment in those patients resulted in an increase in OCT disease activity and a decrease in BCVA.


Spatiotemporal heterogeneity of ecosystem service interactions and their drivers at different spatial scales in the Yellow River Basin.
Accurately understanding ecosystem service (ES) interactions and an analysis of the complex, multiscale driving mechanisms are foundational prerequisites for implementing effective multiscale ES management. This study dives into the spatial and temporal variations of ES interactions in the Yellow River Basin across four spatial scales. The eXtreme Gradient Boosting (XGBoost) model is later deployed to pinpoint the key drivers of ecosystem services and their indirect pathways to ESs are illuminated utilizing Partial Least Squares-Structural Equation Modeling (PLS-SEM). The results indicate that (1) The synergistic effect between ES pairs in the Yellow River Basin surpasses that of trade-offs. Various types of ecosystem service bundles have transformed into each other from 2000 to 2020, and the spatial patterns of ES interactions bear resemblances at different scales. (2) The factors driving habitat quality (HQ), carbon sequestration (CS), and landscape aesthetics (LA) are mainly the landscape configuration and biophysical conditions. The factor driving food production (FP) is mainly the level of urbanization, whereas soil conservation (SC) and water yield (WY) are mainly subject to climate. (3) When biophysical conditions and level of urbanization serve as mediating variables in pathways, driving factors invariably have negative indirect effects on ESs. When landscape configuration serves as a mediating variable, biophysical conditions positively influence HQ and CS, and negatively impact FP, WY, and LA. Conversely, the level of urbanization negatively affects all ESs. (4) The combination of XGBoost and PLS-SEM offers a comprehensive and innovative lens for analyzing ESs driving mechanisms. Based on our findings, scientific management of ESs should account not only for the direct impacts of driving elements but also for their scale and indirect effects.


Kinetic and stereochemical comparison of wild-type and active-site K145Q mutant enzyme of bacterial D-amino acid transaminase.
D-Amino acid transaminase (EC 188.8.131.52), from Bacillus sp. YM-1, a thermostable enzyme with pyridoxal 5'-phosphate as coenzyme and a target for the design of novel antimicrobial agents, catalyzes the reversible transfer of an amino group between D-alanine and alpha-ketoglutarate to form pyruvate and D-glutamate, respectively. To explore the catalytic role of Lys-145, which binds the coenzyme, a site-specific mutant enzyme, K145Q (in which Lys-145 had been mutated to glutamine) constructed earlier (Futaki, S., Ueno, H., Martinez del Pozo, A., Pospischil, M. A., Manning, J. M., Ringe, D., Stoddard, B., Tanizawa, K., Yoshimura, T., and Soda, K. (1990) J. Biol. Chem. 265, 22306-22312) was compared to the wild-type enzyme for its kinetic parameters. Initial velocity studies and partial reaction isotope exchange experiments showed that the low activity of the mutant enzyme (about 1.5% the activity of the wild-type enzyme with saturating substrates) is an intrinsic property, confirming that contaminating enzymes do not account for the low activity of the K145Q mutant enzyme. The rates of the forward reaction for both wild-type and mutant enzymes were 30-40 times higher than the rates of the reverse reaction. KM values for the four substrates were 10 to 100 higher for the mutant compared to the wild-type enzyme. Whereas D-alanine is preferred over L-alanine by the wild-type enzyme (10(3) higher kcat/KM for D- over L-alanine), the K145Q enzyme does not efficiently discriminate between L- and D-alanine. Both wild-type and mutant enzymes also catalyze the slow racemization of L- and D-alanine. Proton NMR studies showed that wild-type enzyme catalyzed a time-dependent exchange of the C alpha proton of D-alanine with solvent D2O and a slow exchange of the alpha proton of L-alanine; the latter slow exchange rate is the same for the C alpha proton of both L- and D-alanine with the K145Q mutant enzyme. Thus, in addition to binding pyridoxal 5'-phosphate, the active-site Lys-145 of D-amino acid transaminase is involved in several other important functions, i.e. it optimizes catalytic efficiency and it maintains stereochemical fidelity. The steady-state kinetic results on the K145Q mutant enzyme together with the findings on the relative racemization rates and the NMR protein exchange data suggest that an alternate base catalyzes abstraction of the alpha proton of substrate in this mutant D-amino acid transaminase.


Employment outcomes following successful renal transplantation.
Data on employment outcomes after successful renal transplantation are few. We conducted this study to identify favorable factors for employment after transplantation. Adult patients <65 yr of age who underwent renal transplantation between January 1, 2002 and December 31, 2007 were surveyed. Patients with graft survival <1 yr were excluded. We also tested their knowledge of Medicare coverage after transplantation. Data were analyzed using chi-squared and Fisher's exact tests. p-Value <0.05 was considered statistically significant. A 55% response rate was obtained where 56% of respondents were employed after transplantation. Race, marital status, previous transplant, and complicated post-operative course did not influence employment. Favorable factors include male gender (p=0.04), younger age (<40 [p=0.0003] or <50 yr [p<0.0001]), having ≥1 dependent (p=0.04), higher education (minimum high school degree [p=0.003] or some college [p=0.002]), live donor recipient (p=0.004), wait time <2 yr (p=0.03), dialysis <2 yr (p<0.0001) or pre-dialysis (p=0.04), and pre-transplantation employment (p<0.0001). Mean time for employment was 4.9±6.3 months (median three months). Common reasons for unemployment were disability (59%) and retirement (27%). Finally, 7% correctly responded that Medicare benefits end 36 months following transplantation. Potentially modifiable factors to improve employment are earlier referral and better education regarding Medicare eligibility.


Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage.
Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups (n = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4+COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α. The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.


Physical and chemical properties of nabak (Zizyphus spina-christi) seed kernel and sweet pepper (Capsicum annuum L.) seed oils.
Nabak seed kernels and sweet pepper seeds, which are separated from the fruits and discarded as waste after processing or consumption, contain high levels of oils (30.19% and 19.57%, respectively). The chemical and thermal characteristics of nabak seed kernel oil (NSO) and sweet pepper seed oil (PSO) were investigated in this study. The NSO and PSO contained high levels of unsaturated fatty acids (84.1% and 86.5%, respectively), and the major fatty acid was oleic acid (57.3%) in NSO, but it was linoleic acid (69.4%) in PSO. The triacylglycerol (TAG) profiles show that NSO contained ten TAG species, three of which represented 87.1%, namely C54:3, C52:2 and C54:4, and triolein was the dominant (OOO, 47.0%). Pepper seed oil contained nine TAG molecular species, four of which represented 93.6%, namely C54:6, C52:4, C54:4 and C52:5, and trilinolein was dominant (LLL, 44.0%). The differential scanning calorimetry (DSC) analysis of NSO revealed that three exothermal peaks were detected during cooling, two endothermal peaks were detected during melting, and the major peak occurred at a low temperature. For PSO, three exothermal peaks were detected during cooling, three peaks were detected (one of them was exothermal) during melting, and the major peaks were observed at low temperatures. Fourier transform infrared (FTIR) spectra indicated that NSO and PSO did not contain peroxides or trans fatty acids, but they did contain low concentrations of free fatty acids. This study offers a scientific basis for the use of NSO and PSO as new sources of edible oils for food applications. © 2021 Society of Chemical Industry.


Effect of nitrogen and phosphorus deficiency on transcriptional regulation of genes encoding key enzymes of starch metabolism in duckweed (Landoltia punctata).
The production of starch by plants influences their use as biofuels. Nitrogen (N) and phosphorus (P) regulate starch gene expression during plant growth and development, yet the role of key enzymes such as ADP-glucose pyrophosphorylase (E.C. 220.127.116.11 AGPase) in starch metabolism during N- and P-deficiency remains unknown. We investigated the effect of N- and P-deficiency on the expression of large (LeAPL1, LeAPL2, and LeAPL3) and small (LeAPS) subunits of AGPase in duckweed (Landoltia punctata) and their correlation with starch content. We first isolated the full-length cDNA encoding LeAPL1 (GenBank Accession No. KJ603244) and LeAPS (GenBank Accession No. KJ603243); they contained open reading frames of 1554 bp (57.7-kDa polypeptide of 517 amino acids) and 1578 bp (57.0 kDa polypeptide of 525 amino acids), respectively. Real-time PCR analysis revealed that LeAPL1 and LeAPL3 were highly expressed during early stages of N-deficiency, while LeAPL2 was only expressed during late stage. However, in response to P-deficiency, LeAPL1 and LeAPL2 were upregulated during early stages and LeAPL3 was primarily expressed in the late stage. Interestingly, LeAPS was highly expressed following N-deficiency during both stages, but was only upregulated in the early stage after P-deficiency. The activities of AGPase and soluble starch synthesis enzyme (SSS EC 126.96.36.199) were positively correlated with changes in starch content. Furthermore, LeAPL3 and LeSSS (SSS gene) were positively correlated with changes in starch content during N-deficiency, while LeAPS and LeSSS were correlated with starch content in response to P-deficiency. These results elevate current knowledge of the molecular mechanisms underlying starch synthesis.


Neuropathology of sporadic amyotrophic lateral sclerosis of long duration.
We performed post-mortem examinations of three patients with progressive neurogenic amyotrophy of long duration. One patient had been clinically diagnosed as having sporadic amyotrophic lateral sclerosis (ALS) and two had been diagnosed with progressive spinal muscular atrophy (PSMA). The disease durations were 10, 17 and 20 years, respectively, and all of the patients died of respiratory failure with no artificial respiratory support. In all of the patients, both the upper and lower motor neuron systems were affected; degeneration of the former was definite, but was milder than that usually encountered in sporadic ALS patients, and the histopathology of the latter was identical to that of sporadic ALS. Light microscopy revealed Bunina bodies, which are characteristic of sporadic ALS, in the remaining anterior horn cells of each patient. In addition, ubiquitin-positive skein-like inclusions were also identified, immunohistochemically, in the remaining anterior horn cells of each patient. Neuron counts indicated that the number of neurons was preserved in Clarke's column in these patients, but was significantly reduced in the intermediolateral nucleus, compared with control subjects. Based on these findings, we think that these three patients, with long disease durations, were affected by essentially the same underlying disease process as that of sporadic, classical ALS. Moreover, we question the neuropathological occurrence of sporadic ALS without involvement of the upper motor neuron system, namely, pure PSMA or lower motor neuron disease.


Retzius-sparing technique independently predicts early recovery of urinary continence after robot-assisted radical prostatectomy.
Robot-assisted radical prostatectomy (RARP) is the conventional surgical treatment option for localised prostate cancer. We investigated factors which may be associated with recovery of early urinary continence (EUC), including the use of the Retzius-sparing technique (RS-RARP). From March 2018 to December 2018, 501 consecutive patients underwent RARP at our high-volume institution. Four hundred and thirty-one patients had complete follow-up data and were included in our analyses. EUC was defined as zero pad use and social urinary continence (SUC) was defined as ≤ 1 pad/24-h period at 3 months following surgery. Patient demographics and clinical factors such as age, body mass index (BMI), neurovascular bundle (NVB) sparing, RS-RARP operative technique and operating surgeon (consultant, trainee) were recorded. Median age was 64.0 years (IQR 57.0-69.0 years) with a median BMI of 27.0 (IQR 25.0-29.9). RS-RARP accounted for 59 of the 431 (13.7%) patients. 196 (45.5%), 142 (32.9%) and 86 (20.0%) received a bilateral, unilateral and nil NVB sparing, respectively. EUC was achieved by 241 patients (55.9%) and SUC was achieved in 339 (78.7%) patients. Multivariable logistic regression analysis suggests younger age (HR 1.04, 95% CI 1.01-1.07, p = 0.014) and RS-RARP technique (HR 2.19, 95% CI 1.15-4.16, p = 0.017) were independently associated with EUC at 3 months even after adjusting for BMI, external membranous urethral length and NVB sparing. Our results suggest that RS-RARP technique is independently predictive of EUC even after accounting for confounding factors. These findings should be further validated in a prospective or randomised trial.


Carlinoside reduces hepatic bilirubin accumulation by stimulating bilirubin-UGT activity through Nrf2 gene expression.
Accumulation of bilirubin, primarily because of its insolubility, has been found to be associated with liver diseases including jaundice. Free bilirubin is insoluble; its glucuronidation by bilirubin-UGT enzyme (UGT1A1) makes it soluble and eliminates it through urine and faeces. Taking CCl(4) induced rat liver dysfunction model, we demonstrated that suppression of UGT1A1 activity in rat liver increased serum bilirubin level which could be reversed by carlinoside (Cln), a flavone glycoside. Although Cln is a flavone compound, it escaped self-glucuronidation in the intestine and readily absorbed. Kinetic study of microsomal UGT1A1 from HepG2 cells suggested that Cln enhanced enzyme activity by increasing V(max) without altering K(m). This altered V(max) was found to be due to UGT1A1 overexpression by Cln which was observed in both HepG2 and rat primary hepatocytes. Since Nrf2 is the transcription factor of UGT1A1, we examined whether Cln effect on UGT1A1 overexpression is mediated through Nrf2. In Nrf2 knock-out cells, Cln could not elevate UGT1A1 activity indicating Nrf2 to be its target. Cln significantly increased Nrf2 gene expression in HepG2 cells which was subsequently localized in nuclear region. Results from ChIP assay showed that Cln markedly augmented Nrf2 binding to UGT1A1 promoter that consequently enhanced reporter activity. Our findings therefore show that Cln upregulated Nrf2 gene expression, increased its nuclear translocation and stimulated UGT1A1 promoter activity. Total outcome of these events brought about a significant increase of bilirubin glucuronidation. Cln therefore could be a worthy choice to intervene hyperbilirubinemia due to liver dysfunction.


Anxiety as a developmental disorder.
There is increasing recognition that many psychiatric disorders including anxiety disorders are neurodevelopmental in their origins. Here, we review and integrate data from human studies and from animal models that point to a critical period during which neural circuits that mediate anxiety develop. We then postulate that this highly plastic critical period is a time of heightened responsiveness that is particularly susceptible to adverse events. We discuss these concepts in the context the current heightened interest in gene by environment interactions in psychiatric illness emphasizing the importance of the temporal relationship between gene action and environmental milieu.


Steady-state fluorescence study on release of camptothecin from agar hydrogel.
The slow drug release processes from agar hydrogel were studied by steady-state fluorescence (SSF) measurement. An anticancer drug, camptothecin (CPT), was used as the release drug and the fluorescence probe for the real-time monitoring of the release processes by measuring the fluorescence intensity of the probe. The release kinetics of CPT at different temperatures was investigated. The Fickian diffusion model was adopted to fit the results and a good linear relationship could be observed between the logarithmic release fraction and the releasing time. The diffusion coefficients (D) at these conditions were thus obtained from the slopes of the fitting curves. By plotting D against temperature, the diffusion coefficient of CPT was found to obey the Arrhenius relation and the activation energy was then obtained to be 70.6 kJ mol(-1).


Lactobacillus paracasei-derived extracellular vesicles alleviate neutrophilic asthma by inhibiting the JNK pathway in airway epithelium.
Lactobacillus paracasei has been known to reduce airway resistance and inflammation in asthma. However, the therapeutic effect of its extracellular vesicles (EVs) in patients with asthma remains unclear. To validate the clinical relevance of L. paracasei-derived EVs (LpEV) in asthma, the composition of gut microbial EVs was verified by metagenomics in LPS-induced C57BL/6 mice. The components of proteins and metabolites in LpEV were identified by peptide mass fingerprinting and metabolomic analysis. The serum levels of specific IgG1 or IgG4 antibodies to LpEV were compared by ELISA between patients with eosinophilic asthma (EA, n = 10) and those with neutrophilic asthma (NA, n = 10) as well as with healthy controls (HCs, n = 10). Finally, therapeutic effects of LpEV and their metabolites in asthma were validated in vivo/in vitro. Significantly lower proportions of EVs derived from Lactobacillus at the genus level were noted in mice with NA than in control mice. Moreover, the serum levels of LpEV-specific IgG4, but not IgG1, were lower in patients with NA than in those with EA or in HCs and positively correlated with FEV1 (%) values. In addition, oral administration of LpEV reduced airway resistance and inflammation in mice with NA. Finally, LpEV and their 3 metabolites (dodecanoic acid, palmitoleic acid, and D-(-)-tagatose) significantly inhibited JNK phosphorylation/IL-8 production in airway epithelium in vitro. These findings suggest that LpEV may have a therapeutic potential targeting NA by suppressing the JNK pathway and proinflammatory cytokine production in airway epithelium.


Practice of radiation therapy for anal cancer in Austria-a survey on behalf of the Austrian radiation oncology society gastrointestinal tumor group (ÖGRO-GIT).
We conducted a patterns-of-care survey on chemoradiation for locoregionally confined anal cancer in Austria to evaluate areas of disagreement and to identify possible targets for further standardization. An anonymous questionnaire comprising 38 questions was sent to all Austrian radiation oncology departments. Results were analyzed descriptively and compared to two international guidelines. The response rate was 93%. Work-up generally includes DRE, endoscopy, and cross-sectional imaging of chest/abdomen and pelvis. PET-CT is used by 38%. Screening for HIV and biopsies of suspicious lymph nodes are infrequently used. All centers perform IMRT, mainly with daily IGRT. Median doses to the primary are 54.7 Gy (T1-2) and 59.4 Gy (T3-4). Suspicious nodes receive a boost (median dose 54 Gy), while elective nodal areas are mainly treated with 45-50.4 Gy. Target delineation of elective nodal areas seems generally uniform, although disagreement exists regarding inclusion of the common iliac nodes. No agreement was found for OAR-delineation and dose constraints. Concurrent chemotherapy is mitomycin and 5‑FU/capecitabine. Supportive care beyond skin care is infrequently offered. Intensive follow-up is performed for at least 5 years. Treatment of T1N0 shows considerable disagreement. We found a high rate of agreement between the centers and concordance with major guidelines. PET-CT, routine HIV testing, and biopsies of suspicious LN seem underrepresented. The largest controversy regarding target volumes concerns inclusion of the common iliac nodes. Prescribed doses are generally in line with the recommendations or higher. OAR delineation, dose constraints, supportive care, and treatment of early anal cancer represent areas for further standardization.


High and Low WWOX Gene Expression Levels in Acute Myeloid Leukemia - a Real Time RT-PCR Study.
Although expression of WWOX was extensively studied in different tumors, WWOX gene expression in acute myeloid leukemia is not well-known or recognized. Fifty control donors and fifty acute myeloid leukemia patients were enrolled in this research. The levels of WWOX gene in all participants were detected by RT-qPCR. Levels of WWOX gene in the AML group were significantly lower as compared to the control group (0.27205 ± 1.19812 vs. 10.501 ± 9.0338, respectively, p < 0.001**). Decreased expression of WWOX gene ran parallel with acute myeloid leukemia regression.


Barriers to PTSD treatment-seeking by women veterans who experienced military sexual trauma decades ago: The role of institutional betrayal.
While some barriers to PTSD treatment engagement among veterans are well-identified, e.g., stigma, little is known about the barriers to VA PTSD treatment-seeking among women veterans who experienced military sexual trauma (MST) decades ago. To explore the barriers to PTSD treatment-seeking of women veterans with PTSD related to MST experienced prior to 2000. Data were collected from women veterans (n = 14) who had experienced MST and sought VA PTSD treatment. Data analyses utilized a constructivist grounded theory approach. The context of the MST experience, including the military environment at the time, the era in which they experienced MST and the response of others to their reporting or disclosure of MST created decades-long barriers to PTSD treatment-seeking. Understanding institutional betrayal as a barrier to PTSD treatment-seeking among women veterans who experienced MST decades ago is necessary to develop effective targeted outreach and programs for this population.


Progesterone receptor membrane component 1 reduces cardiac steatosis and lipotoxicity via activation of fatty acid oxidation and mitochondrial respiration.
Obesity is implicated in cardiovascular disease and heart failure. When fatty acids are transported to and not adequately oxidized in cardiac cells, they accumulate, causing lipotoxicity in the heart. Since hepatic progesterone receptor membrane component 1 (Pgrmc1) suppressed de novo lipogenesis in a previous study, it was questioned whether cardiac Pgrmc1 protects against lipotoxicity. Hence, we focused on the role of cardiac Pgrmc1 in basal (Resting), glucose-dominant (Refed) and lipid-dominant high-fat diet (HFD) conditions. Pgrmc1 KO mice showed high FFA levels and low glucose levels compared to wild-type (WT) mice. Pgrmc1 KO mice presented low number of mitochondrial DNA copies in heart, and it was concomitantly observed with low expression of TCA cycle genes and oxidative phosphorylation genes. Pgrmc1 absence in heart presented low fatty acid oxidation activity in all conditions, but the production of acetyl-CoA and ATP was in pronounced suppression only in HFD condition. Furthermore, HFD Pgrmc1 KO mice resulted in high cardiac fatty acyl-CoA levels and TG level. Accordingly, HFD Pgrmc1 KO mice were prone to cardiac lipotoxicity, featuring high levels in markers of inflammation, endoplasmic reticulum stress, oxidative stress, fibrosis, and heart failure. In vitro study, it was also confirmed that Pgrmc1 enhances rates of mitochondrial respiration and fatty acid oxidation. This study is clinically important because mitochondrial defects in Pgrmc1 KO mice hearts represent the late phase of cardiac failure.


Epithelial-mesenchymal transition induced by GRO-α-CXCR2 promotes bladder cancer recurrence after intravesical chemotherapy.
Non-muscle invasive bladder cancers (NMIBC) are typically treated by transurethral resection with intravesical chemotherapy. However, the post-therapeutic incidence of tumor recurrence and progression to muscle invasive disease is high, and the underlying mechanism(s) remains unknown. In this study, we observed that recurrent bladder cancer cells exhibit a mesenchymal phenotype, which is initiated by the autocrine GRO-α signaling. Mechanically, the chemotherapeutic drug epidoxorubicin induces GRO-α expression in primary bladder cancer cells at G1/S phase via p38-dependent activation of NF-κB. GRO-α phosphorylation of Snail on Ser246 supports Snail's accumulation in the nucleus, and thereby promotes transcription repression activity of Snail from E-cadherin promoters. In accordance, disrupting the GRO-α-Snail axis in NMIBC represents a promising alternative to prevent post-therapeutic tumor progression and recurrence.


Vagus nerve stimulation in children with intractable epilepsy: indications, complications and outcome.
To analyze the indication, complications and outcome of vagus nerve stimulation in intractable childhood epilepsy. We retrospectively reviewed the data of 69 children who had insertion of vagal nerve stimulator (VNS) between June 1995 and August 2006 for medically intractable epilepsy. Outcome was based on the Engel's classification. Statistical analysis of the data was also done to see if any of the parameters significantly influenced the outcome. Thirty-eight patients (55.08 %) had a satisfactory outcome (Engel class I, II or III), and in 31 patients (44.92 %), there was no worthwhile improvement of seizures (Engel class IV). There was no statistical significance between the type of seizure and outcome (Fisher's exact test, p = 0.351). Statistical analysis also showed that the following parameters did not significantly influence the outcome (p > 0.05): age at insertion of VNS, age of first fit, duration between first fit and insertion of VNS and the length of follow-up. Complications included infection, lead fracture, fluid collection around the stimulator, neck pain and difficulty swallowing. Vagus nerve stimulation is a relatively safe and potentially effective treatment for children with medically intractable epilepsy.


Relationship of patent ductus arteriosus management with neonatal AKI.
Investigate relationship between management of patent ductus arteriosus (PDA) and acute kidney injury (AKI) in very low birthweight neonates. Retrospective cohort study of neonates, <1500 g, admitted to 24 NICUs, 1/1/14 - 3/31/14. AKI diagnosed using the neonatal modified KDIGO definition; diagnosis and treatment of PDA extracted from the medical record. Demographics, clinical characteristics, and AKI stage compared using chi-square and analysis of variance. A general estimating equation logistic regression used to estimate adjusted odds ratios. Of 526 neonates with sufficient data to diagnose AKI, 157 (30%) had PDA (61 conservative management, 62 pharmacologic treatment only, 34 surgical ligation). In analyses adjusted for sex, birthweight, gestational age, caffeine, nephrotoxin exposure, vasopressor and mechanical ventilation use, with conservative management as reference, there were no differences among treatment cohorts in the odds of AKI. The underlying physiology of PDA, not management strategy, may determine the likelihood of AKI in neonates <1500 g.


Cell wall damage increases macromolecular crowding effects in the Escherichia coli cytoplasm.
The intracellular milieu is crowded with biomacromolecules. Macromolecular crowding changes the interactions, diffusion, and conformations of biomacromolecules. Changes in intracellular crowding have been mostly ascribed to differences in biomacromolecule concentration. However, spatial organization of these molecules should play a significant role in crowding effects. Here, we find that cell wall damage causes increased crowding effects in the Escherichia coli cytoplasm. Using a genetically encoded macromolecular crowding sensor, we see that crowding effects in spheroplasts and penicillin-treated cells well surpass crowding effects obtained using hyperosmotic stress. The crowding increase is not because of osmotic pressure, cell shape, or volume changes and therefore not crowder concentration. Instead, a genetically encoded nucleic acid stain and a DNA stain show cytoplasmic mixing and nucleoid expansion, which could cause these increased crowding effects. Our data demonstrate that cell wall damage alters the biochemical organization in the cytoplasm and induces significant conformational changes in a probe protein.


Evaluation of prognostic classifications for patients with syncope.
To evaluate two published sets of prognostic classifications for patients with syncope, 176 consecutive patients who presented to an emergency room with syncope were studied. Although relatively few patients had cardiac syncope, these data confirmed their high one-year mortality. At the other extreme, it was also confirmed that patients who were 30 years of age or less or 70 years of age or less and had vasovagal/psychogenic syncope or syncope of unknown cause had a benign prognosis, with only two deaths in 225 patients in pooled data. However, these data did not confirm the previously reported prognoses for "medium-risk patients" or for patients with diagnosable noncardiovascular causes of syncope, largely because of differences in criteria for patient eligibility. It is concluded that available data allow over 70 percent of patients with syncope to be placed into either very-high or very-low-risk groups. However, further investigation, taking into account differences in patient selection criteria, will be required before accurate prognostic classifications can be derived for the nearly 30 percent of patients who do not fall into one of these extreme prognostic categories.


Efficient sequential synthesis of PET Probes of the COX-2 inhibitor [11C]celecoxib and its major metabolite [11C]SC-62807 and in vivo PET evaluation.
Synthesis of [(11)C]celecoxib, a selective COX-2 inhibitor, and [(11)C]SC-62807, a major metabolite of celecoxib, were achieved and the potential of these PET probes for assessing the function of drug transporter in biliary excretion was evaluated. The synthesis of [(11)C]celecoxib was achieved in one-pot by reacting [(11)C]methyl iodide with an excess of the corresponding pinacol borate precursor using Pd(2)(dba)(3), P(o-tolyl)(3), and K(2)CO(3) (1:4:9) in DMF. The radiochemical yield of [(11)C]celecoxib was 63±23% (decay-corrected, based on [(11)C]CH(3)I) (n=7) with a specific radioactivity of 83±23GBq/μmol (n=7). The average time of synthesis from end of bombardment including formulation was 30min with >99% radiochemical purity. [(11)C]SC-62807 was synthesized from [(11)C]celecoxib by further rapid oxidation in the presence of excess KMnO(4) with microwave irradiation. The radiochemical yield of [(11)C]SC-62807 was 55±9% (n=3) (decay-corrected, based on [(11)C]celecoxib) with a specific radioactivity of 39±4GBq/μmol (n=3). The average time of synthesis from [(11)C]celecoxib including formulation was 20min and the radiochemical purity was >99%. PET studies in rats and the metabolite analyzes of [(11)C]celecoxib and [(11)C]SC-62807 showed largely different excretion processes, and consequently, [(11)C]SC-62807 was rapidly excreted via hepatobiliary excretion without further metabolism. [(11)C]SC-62807 was shown to have a high potential as a PET probe for evaluating drug transporter function in biliary excretion.


Meridional flows in the disk around a young star.
Protoplanetary disks are known to possess a variety of substructures in the distribution of their millimetre-sized grains, predominantly seen as rings and gaps1, which are frequently interpreted as arising from the shepherding of large grains by either hidden, still-forming planets within the disk2 or (magneto-)hydrodynamic instabilities3. The velocity structure of the gas offers a unique probe of both the underlying mechanisms driving the evolution of the disk-such as movement of planet-building material from volatile-rich regions to the chemically inert midplane-and the details of the required removal of angular momentum. Here we report radial profiles of the three velocity components of gas in the upper layers of the disk of the young star HD 163296, as traced by emission from 12CO molecules. These velocities reveal substantial flows from the surface of the disk towards its midplane at the radial locations of gaps that have been argued to be opened by embedded planets4-7: these flows bear a striking resemblance to meridional flows, long predicted to occur during the early stages of planet formation8-12. In addition, a persistent radial outflow is seen at the outer edge of the disk that is potentially the base of a wind associated with previously detected extended emission12.


P2X purinoceptor subtypes on paraventricular nucleus neurones projecting to the rostral ventrolateral medulla in the rat.
The rostral ventrolateral medulla (RVLM) is essential for the generation of sympathetic nerve activity. The RVLM receives a substantial innervation from the hypothalamic paraventricular nucleus (PVN). Activation of P2X purinoceptors via ATP has been shown to mediate fast excitatory synaptic neurotransmission. There is mounting evidence to suggest the presence of P2X purinoceptors in hypothalamic nuclei, including the PVN. In this study, we determined whether P2X1-P2X6 purinoceptor subtypes were present on PVN neurones that projected to the RVLM. Injection of the retrogradely transported tracer, rhodamine-tagged microspheres, into the pressor region of the RVLM was used to identify the neurones in the PVN that innervated the RVLM. P2X1-P2X6 purinoceptors were detected by immunohistochemistry. Double-labelled neurones were quantified and expressed as a proportion of the retrogradely labelled neurones. The proportions of double-labelled neurones for each of the P2X purinoceptor subtypes varied, on average, from 14 to 29%. The P2X3 purinoceptor subtype was found to be the dominant purinoceptor subtype present on PVN neurones projecting to the RVLM. Additionally it was apparent that more than one P2X purinoceptor subtype was present on the PVN neurones projecting to the RVLM, since the sum of the average percentages of double-labelled neurones for each P2X purinoceptor subtype exceeded 100%. These findings highlight the presence of the P2X1-P2X6 purinoceptors on PVN neurones projecting to the RVLM. The results suggest a potential role for ATP in the PVN in the regulation of sympathetic nerve activity.


The Ketogenic Diet but not Hydroxycitric Acid Keeps Brain Mitochondria Quality Control and mtDNA Integrity Under Focal Stroke.
Mitochondrial dysfunction in the ischemic brain is one of the hallmarks of stroke. Dietary interventions such as the ketogenic diet and hydroxycitric acid supplementation (a caloric restriction mimetic) may potentially protect neurons from mitochondrial damage induced by focal stroke in mice. We showed that in control mice, the ketogenic diet and the hydroxycitric acid did not impact significantly on the mtDNA integrity and expression of genes involved in the maintenance of mitochondrial quality control in the brain, liver, and kidney. The ketogenic diet changed the bacterial composition of the gut microbiome, which via the gut-brain axis may affect the increase in anxiety behavior and reduce mice mobility. The hydroxycitric acid causes mortality and suppresses mitochondrial biogenesis in the liver. Focal stroke modelling caused a significant decrease in the mtDNA copy number in both ipsilateral and contralateral brain cortex and increased the levels of mtDNA damage in the ipsilateral hemisphere. These alterations were accompanied by a decrease in the expression of some of the genes involved in maintaining mitochondrial quality control. The ketogenic diet consumption before stroke protects mtDNA in the ipsilateral cortex, probably via activation of the Nrf2 signaling. The hydroxycitric acid, on the contrary, increased stroke-induced injury. Thus, the ketogenic diet is the most preferred variant of dietetic intervention for stroke protection compared with the hydroxycitric acid supplementation. Our data confirm some reports about hydroxycitric acid toxicity, not only for the liver but also for the brain under stroke condition.


Unusual behaviour of the spin-phonon coupling in the quasi-one-dimensional antiferromagnet RbCoCl3.
We present an experimental and theoretical study for the lattice vibrational (phonon) modes in the quasi-one-dimensional (or chain-like) antiferromagnet RbCoCl3 at low temperatures both above and below the two different magnetic phase transitions. Clear evidence is found for the role of spin-phonon interactions in providing a temperature-dependent contribution for the frequencies of the E1g and E2g symmetry phonons that occur with frequencies comparable to those of the spin wave excitations (magnons) in this compound. The behaviour in RbCoCl3, as studied here by Raman scattering experiments, is quite different from that typically observed in rutile-structure antiferromagnets where the spin-phonon coupling has been well characterized. The theory is modified to take account of the strong Ising-like component in the spin Hamiltonian. This enables the spin-phonon coupling parameters to be deduced, with the analysis also revealing the onset of an extra frequency shift for the phonons below the transition temperature TN1 = 28 K associated with magnetic ordering along the Co chains.


ATG16L1 protects from interferon-γ-induced cell death in the small intestinal crypt.
The breakdown of the intestinal mucosal barrier is thought to underlie the progression to Crohn disease (CD), whereby numerous risk factors contribute. For example, a genetic polymorphism of the autophagy gene ATG16L1, associated with an increased risk of developing CD, contributes to the perturbation of the intestinal epithelium. We examined the role of Atg16l1 in protecting the murine small intestinal epithelium from T-cell-mediated damage using the anti-CD3 model of enteropathy. Our work showed that mice specifically deleted for Atg16l1 in intestinal epithelial cells (IECs) (Atg16l1ΔIEC) had exacerbated intestinal damage, characterized by crypt epithelial cell death, heightened inflammation, and decreased survival. Moreover, Atg16l1 deficiency delayed the recovery of the intestinal epithelium, and Atg16l1-deficient IECs were impaired in their proliferative response. Pathology was largely driven by interferon (IFN)-γ signaling in Atg16l1ΔIEC mice. Mechanistically, although survival was rescued by blocking tumor necrosis factor or IFN-γ independently, only anti-IFN-γ treatment abrogated IEC death in Atg16l1ΔIEC mice, thereby decoupling IEC death and survival. In summary, our findings suggest differential roles for IFN-γ and tumor necrosis factor in acute enteropathy and IEC death in the context of autophagy deficiency and suggest that IFN-γ-targeted therapy may be appropriate for patients with CD with variants in ATG16L1.


Peptic ulceration in general practice in England and Wales 1994-98: period prevalence and drug management.
Little is known about the burden of peptic ulcer in the community. To examine recent time trends in the period prevalence of peptic ulceration and its drug management, in England and Wales. For each year between 1994 and 1998, information on patients with a diagnosis of peptic ulceration was extracted from the General Practice Research Database. The annual age-standardized period prevalence of peptic ulceration decreased from 3.3/1000 in 1994 to 1.5/1000 in 1998 for men, and from 1.8/1000 to 0.9/1000 for women. This decline was more evident among younger people, and among males registered with practices located in the most deprived electoral wards compared to those located in the least deprived. The proportion of patients receiving H2 receptor antagonists declined from 68% in 1994 to 41% in 1998. In contrast, the proportion prescribed proton pump inhibitors rose from 46% to 66%. Over a 5-year period, the period prevalence of peptic ulceration has decreased markedly, especially among younger people and those from more deprived areas.


Tungiasis in the urban area of Popayán, Colombia: A case report
Tungiasis is an endemic ectoparasitosis in Latin America associated with risk factors such as rurality, poverty, and living with animals. In Popayán, a city in southwest Colombia, the disease was highly prevalent in the past, to such degree that its inhabitants were given the nickname of patojo, a word that describes the way of walking of people infested by the flea. However, it was believed eradicated at present. We present the case of a 12-year-old boy living in the urban area of Popayán, who presented with a one-month history of papular lesions with circular edges, blackish center, and hyperkeratotic halo on both feet. Tungiasis was suspected based on the clinical findings and ivermectin was administered. The lesions were surgically removed and sent for parasitological analysis, which confirmed the presence of Tunga penetrans. The patient evolved satisfactorily. The Secretaría de Salud Municipal de Popayán carried out an inspection of the patient's home where migrant dogs from the Colombian Pacific were found in the surroundings, some with suspicious lesions of tungiasis. We document here the resurgence of this pathology in urban areas, probably secondary to the migration of animals from rural areas. It is important to recognize the existence of the flea in rural and urban areas, make a medical diagnosis, and report cases to the surveillance entities to enable appropriate management and sanitary control of this neglected ectoparasitosis in humans and animals.


State medical malpractice laws and utilization of surgical treatment for rotator cuff tear and proximal humerus fracture: an observational cohort study.
How much does the medical malpractice system affect treatment decisions in orthopaedics? To further this inquiry, we sought to assess whether malpractice liability is associated with differences in surgery rates among elderly orthopaedic patients. Medicare data were obtained for patients with a rotator cuff tear or proximal humerus fracture in 2011. Multivariate regressions were used to assess whether the probability of surgery is associated with various state-level rules that increase or decrease malpractice liability risks. Study results indicate that lower liability is associated with higher surgery rates. States with joint and several liability, caps on punitive damages, and punitive evidence rule had surgery rates that were respectively 5%-, 1%-, and 1%-point higher for rotator cuff tears, and 2%-, 2%- and 1%-point higher for proximal humerus fractures. Conversely, greater liability is associated with lower surgery rates, respectively 6%- and 9%-points lower for rotator cuff patients in states with comparative negligence and pure comparative negligence. Medical malpractice liability is associated with orthopaedic treatment choices. Future research should investigate whether treatment differences result in health outcome changes to assess the costs and benefits of the medical liability system.


ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.
Cancer expression of PD-L1 suppresses anti-tumor immunity. PD-L1 has emerged as a remarkable therapeutic target. However, the regulation of PD-L1 degradation is not understood. Here, we identify several compounds as inducers of PD-L1 degradation using a high-throughput drug screen. We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. Overexpression of ARIH1 suppresses tumor growth and promotes cytotoxic T cell activation in wild-type, but not in immunocompromised mice, highlighting the role of ARIH1 in anti-tumor immunity. Moreover, combining EGFR inhibitor ES-072 with anti-CTLA4 immunotherapy results in an additive effect on both tumor growth and cytotoxic T cell activation. Our results delineate a mechanism of PD-L1 degradation and cancer escape from immunity via EGFR-GSK3α-ARIH1 signaling and suggest GSK3α and ARIH1 might be potential drug targets to boost anti-tumor immunity and enhance immunotherapies.


A test to determine the nature and presence of the memory effect columns packed with the amylose tris(3,5-dimethylphenylcarbamate) stationary phase.
Acid/base mobile phase modifiers affect enantioseparations in ways that are not fully understood yet, for the lack of systematic studies. This makes chiral analysis of some pharmaceuticals difficult to reproduce. Once a column has been exposed to a modifier, the selectivity of certain pairs of enantiomers may change, for the better or the worse. We study the behavior of five enantiomeric pairs, three which are highly sensitive to the addition of certain modifiers and two that have little sensitivity to these modifiers. Their use permits the determination of the extent of the memory effect response on individual columns. The selectivity of 4-chlorophenylalanine methyl and ethyl ester, and of ketoprofen improve as a solution of ethanesulfonic acid is percolated through the column. As a result, these pairs are most useful for the determination of the extent of acid memory effect on a column. The selectivity of propranolol HCl and, to a lesser degree, Tröger's base increases as a solution of diisopropylethylamine is percolated through the column. The separation of each one of these five pairs is inversely affected by the percolation of the opposite acid/base solution. We used trans-stilbene oxide (TSO) as a 'standard' to determine the column stability because no memory effect is observed for it (its retention, enantioselectivity, and resolution remain constant). Understanding whether a column is under the influence of the memory effect is critical to both the analysis of pharmaceutical ingredients and to the development of preparative purification techniques for racemic mixtures. Thus, columns that were unreliable for method development and method transfer, due to the memory effect and a lack of proper solvent exposure records, can now be used.


Examining Trends in Emergency Medicine Journals' Publications about Racism.
In recent years, the academic medicine community has produced numerous statements and calls to action condemning racism. Though health equity work examining health disparities has expanded, few studies specifically name racism as an operational construct. As emergency departments serve a high proportion of patients with social and economic disadvantage rooted in structural racism, it is critically important that racism be a focus of our academic discourse. This study examines the frequency at which four prominent Emergency Medicine journals, Annals of Emergency Medicine, Academic Emergency Medicine, the American Journal of Emergency Medicine, and the Western Journal of Emergency Medicine, publish on health disparities and racism. This is a descriptive analysis measuring the frequency of publications on health disparities and racism in US-based Emergency Medicine Journals from 2014 to 2021. The search strategies for the concepts of "racism" and "health disparities" used a combination of MeSH and keywords. These search strategies were developed based on prior literature and the MEDLINE®/PubMed® Health Disparities and Minority Health Search Strategy. Articles identified through the PubMed search were then reviewed by two authors for final inclusion. Since 2014, 6,248 articles were published by the four emergency medicine journals over the eight-year study period. Of those, 82 research papers that focused on health disparities were identified and only 16 that focused on racism. Most Emergency Medicine publications on racism and health disparities were in 2021. Our findings suggest that the national discourse on racism and calls to action within emergency medicine were followed by an increase in publications on health disparities and racism. Continued investigation is needed to evaluate these trends moving forward.


Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA): Early diagnosis, treatment and outcomes.
To describe and summarize the early diagnosis, treatment and outcomes of obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). Data from patients with OHVIRA treated at the study centre over the last decade were analysed retrospectively, including demographic characteristics, symptoms, diagnosis, treatment and outcomes. Relevant published literature was also reviewed in this study. In total, 11 cases were diagnosed with OHVIRA over the study period, ranging in age from 3 to 14 years (median 11 years). Four cases were asymptomatic, four had abdominal pain and three had urinary symptoms. All 11 cases underwent vaginoplasty. Ureteral bladder re-implantation (n = 1), dysplastic nephrectomy (n = 1), separation of labia minora adhesions (n = 1), perineoplasty (n = 1) and urethroplasty (n = 1) were performed. Cases were followed up for 2 months to 8 years (median 5 years) with good follow-up outcomes. Based on the cases in this study and the relevant literature, ultrasound appears to be an effective method for the diagnosis of OHVIRA. Experienced ultrasonographers are able to achieve a high corrected diagnosis rate. The differential diagnosis of OHVIRA should be considered by paediatric surgeons, urologists, emergency physicians and gynaecologists when they identify patients with didelphys uterus or renal agenesis. Early surgery can reduce the risk of potential genital tract infection and gynaecological complications.


Recovery of purified lactonic sophorolipids by spontaneous crystallization during the fermentation of sugarcane molasses with Candida albicans O-13-1.
Numerous studies have focused on how to obtain high yield of sophorolipids using low-cost materials as substrates, and there has been various work on the experimental methods for purifying lactonic sophorolipids. These studies have not yet obtained satisfied results in combining a low-cost fermentation process and the purification of lactonic sophorolipids. This study establishes a fed-batch fermentation process of purifying sophorolipids from Candida albicans O-13-1 using low-cost sugarcane molasses as the substrate. In the optimized conditions of this research, using sugarcane molasses as a substrate and product synthesis based on the temperature stage-controlled fermentation, our result indicates that sophorolipids production could reach 108.7 g/L. More importantly, lactonic sophorolipids can crystallize and precipitate during our established fermentation process. The structures and content of sophorolipids separated from the fermentation broth and sophorolipids crystallized in the fermentation broth were analyzed by a scanning electron microscope (SEM) and liquid chromatography-mass spectrometry (LC-MS). The fermentation process produced 90.5 g/L crystallized lactonic sophorolipids with 90.51% purity. This is an energy-saving and low-cost method to obtain such pure lactonic sophorolipids.


Efficacy of Nivolumab and AVD in Early-Stage Unfavorable Classic Hodgkin Lymphoma: The Randomized Phase 2 German Hodgkin Study Group NIVAHL Trial.
In early-stage unfavorable classic Hodgkin lymphoma (cHL), conventional therapy induces high cure rates but also relevant acute and long-term toxic effects. Nivolumab is well tolerated and highly effective in relapsed/refractory cHL but has not been adequately studied in first-line treatment of early-stage cHL. The NIVAHL trial evaluated nivolumab in this setting with the aim to develop a highly effective yet tolerable systemic therapy to ultimately mitigate morbidity in patients who survive cHL. To evaluate efficacy of 2 experimental nivolumab-based first-line treatment strategies in patients with early-stage unfavorable cHL. This was an open-label, multicenter, phase 2 randomized clinical trial, open between April 2017 and October 2018. The trial took place at 35 trial centers across Germany, ranging from academic centers to private offices. Eligibility was defined by age 18 to 60 years, cHL confirmed by expert pathology review, early-stage unfavorable disease by German Hodgkin Study Group criteria (stage I to II with risk factor[s]), and absence of serious concomitant disease or organ dysfunction. Among 110 enrolled patients, 109 were eligible. Systemic therapy, per random assignment (1:1) to either concomitant treatment with 4 cycles of nivolumab and doxorubicin, vinblastine, and dacarbazine (N-AVD) or sequential treatment with 4 doses of nivolumab, 2 cycles of N-AVD, and 2 cycles of AVD at standard doses, followed by 30-Gy involved-site radiotherapy. Complete remission (CR) rate after study treatment, aiming at excluding a CR rate of 80% or lower via a 2-sided 95% CI for each treatment group. Of 109 patients included in this study, 65 (59.6%) were women, and the median (range) age was 27 (18-60) years. At interim staging after 2 cycles of N-AVD or 4 doses of nivolumab monotherapy, 54 of 54 (100%) and 49 of 51 (96%) response-eligible patients, respectively, achieved an objective response, with CR in 47 (87%) and 26 (51%) patients, respectively. Among 101 patients eligible for primary end point analysis, 46 of 51 (90%; 95% CI, 79%-97%) patients receiving concomitant therapy and 47 of 50 (94%; 95% CI, 84%-99%) patients receiving sequential therapy achieved CR after study treatment. With a median follow-up of 13 months, 12-month progression-free survival was 100% for patients receiving concomitant treatment and 98% (95% CI, 95%-100%) for patients receiving sequential therapy. Both strategies combining nivolumab and AVD are feasible and resulted in high remission rates. Despite narrowly missing the efficacy benchmark in the concomitant group, the excellent 12-month progression-free survival and the unexpectedly high CR rate after 4 doses of nivolumab monotherapy warrant further evaluation of this approach in the first-line treatment of patients with early-stage cHL. ClinicalTrials.gov Identifier: NCT03004833.


Indigenous artifacts from remote areas, used to design a lesson plan for preservice math teachers regarding sustainable education.
In the context of sustainable education, remote areas require special treatment. However, teachers are not evenly distributed in terms of quantity and quality. Adaptable, creative, and innovative teachers are needed in remote areas. Therefore, universities must prepare preservice teachers to teach in these places. This study explores indigenous artifacts from local communities related to mathematical content that preservice teachers can adopt to design lesson plans using available resources. Data were collected through the artifacts of indigenous people in a mountainous region on the border of Yogyakarta and Central Java, Indonesia, and the math curriculum content was examined. The relational ideas of the artifacts and the math curriculum content were analyzed. Based on the results, this study shows that artifacts can be incorporated into math learning materials. Elaborating on the artifacts can potentially relate culture and math in the classroom. The artifacts contain mathematical value and are close to students' thoughts. Hence, preservice math teachers can use them to design lesson plans, particularly for math learning. By understanding artifacts in remote areas, preservice teachers will have a particular capability for preparing lesson plans relevant to students' environment for sustainable education.


Enhancing the electrical conductivity of a hybrid POSS-PCL/graphene nanocomposite polymer.
An electrically conductive polymer using polyhedral oligomeric silsesquioxane (POSS) nanocage incorporated into a modified poly [caprolactone based urea-urethane] (PCL)/graphene hybrid nanocomposite is described. Multilayer graphene flakes (8nm) were homogeneously dispersed into POSS-PCL at 0.1, 2, 5, and 10wt.% concentrations. This dispersion process of the graphene flakes was achieved by the use of stable dimethylacetamide (DMAc), via solution intercalation with POSS-PCL nanocomposites. The impedance spectroscopy of 5.0wt.% and higher concentration of graphene in POSS-PCL represented major improvement in conductivity over pristine POSS-PCL. The percolation threshold occurred at 5.0wt.% graphene concentration, converting the insulator POSS-PCL into a conductive POSS-PCL/graphene hybrid nanocomposite. The structures of the obtained hybrid materials were characterized with atomic force microscopy (AFM), Fourier transform infra-red (FT-IR), and Raman spectroscopy. The conductivity of the resultant nanocomposite polymer was investigated with electrochemical impedance spectroscopy (EIS). Herein, for the first time, we demonstrate a facile method of synthesizing, and describe the electrical properties of a conductive POSS-PCL/graphene nanocomposite polymer.


Use of 7-ethoxycoumarin to monitor multiple enzymes in the human CYP1, CYP2, and CYP3 families.
7-Ethoxycoumarin is metabolized by many cytochrome P450 enzymes active in foreign compound metabolism and has been used as a prototypic substrate to monitor P450 (P450) activity in both hepatic and extrahepatic tissues. A spectrofluorometric method is described for determination of P450-catalyzed 7-ethoxycoumarin O-deethylation. Following acidification of the incubation mixture, the enzymatic product, 7-hydroxycoumarin, is recovered by a double-extraction procedure and measured at an excitation wavelength of 370 nm and an emission wavelength of 450 nm. This method is applicable to enzymatic studies to determine the catalytic activity of cDNA-expressed human enzymes in the CYP1, CYP2, and CYP3 families, and 7-ethoxycoumarin O-deethylation activity in microsomes isolated from liver and other tissues.


Diazepam and discriminative motor control: acute, chronic and withdrawal effects.
Rats were trained to hold a force transducer operated with a paw so that it remained between upper and lower limits of a force band for a continuous 1.5-sec period to deliver each food pellet. Acute doses of diazepam impaired measures of this performance. Separate groups received chronic diazepam injections (6 mg/kg, IP) either presession (Before Group) or postsession (After Group), or presession vehicle (Vehicle Group). The After and Vehicle Groups demonstrated that neither chronic postsession diazepam, nor time alone, altered motor performance. The performance of the Before Group was affected by the daily diazepam, and although tolerance to the impairment developed, it was incomplete. Late in the chronic-administration phase (after 75 days) a toxic effect of the suspending agent became evident in all groups as a decrease in work rate, although the other performance indices were not affected. The withdrawal of diazepam from the Before Group led to improved performance which returned to the original baseline level.