Species-area curves, spatial aggregation, and habitat specialization in tropical forests.
The relationship between species diversity and sampled area is fundamental to ecology. Traditionally, theories of the species-area relationship have been dominated by random-placement models. Such models were used to formulate the canonical theory of species-area curves and species abundances. In this paper, however, armed with a detailed data set from a moist tropical forest, we investigate the validity of random placement and suggest improved models based upon spatial aggregation. By accounting for intraspecific, small-scale aggregation, we develop a cluster model which reproduces empirical species-area curves with high fidelity. We find that inter-specific aggregation patterns, on the other hand, do not affect the species-area curves significantly. We demonstrate that the tendency for a tree species to aggregate, as well as its average clump size, is not significantly correlated with the species' abundance. In addition, we investigate hierarchical clumping and the extent to which aggregation is driven by topography. We conclude that small-scale phenomena such as dispersal and gap recruitment determine individual tree placement more than adaptation to larger-scale topography.


[The therapeutic efficacy and the effect of gidazepam and fenazepam on the psychophysiological status and on the performance of operators with mental disorders at a neurotic level].
The effect of placebo and gidazepam on the state, psychophysiological predictors of the quality of the operator's performance and its results in individuals with neurotic reactions was studied (test dose 20 mg 7-day course, 40 mg daily, 24 individuals), as well as the effect of gidazepam and phenazepam (42 individuals with neurotic and neurosis-like states; gidazepam test doses 20 and 50 mg, 14-day course, 40 and 100 mg daily; phenazepam test doses 0.5 and 1 mg, 14-day course, daily dose 2 mg). The generally accepted methods of clinical and psychophysiological examination were applied. Gidazepam in the doses under study did not yield to phenazepam in therapeutic activity. A single and a course administration of gidazepam improved the parameters of the psychophysiological state and the efficacy of the operator performance in patients with neurotic reactions and in those with neurotic and neurosis-like states. This makes it possible, whenever necessary, to recommend this drug for the treatment of the indicated disorders in the working operators.


Developmental aspects of mongolism.
To sum up, the testing of neurological responses in our series lends support to the view that whereas psychomotor retardation is a major factor in the development of mongol babies, hypotonia is at the same time of great importance. Our study is not yet complete nor ready for statistical analysis, but the results so far seem to show that mongol babies are particularly retarded in reactions calling for muscular tone, such as posture in ventral suspension and the traction response. It is hoped that as our study proceeds, comparison of neurological with psychological findings will provide another dimension to the interpretation of results. Also we hope to see by long-term follow-up whether the early neurological testing of mongols is of predictive value as regards later development.


Interaction of ganglioside GM1 with the B subunit of cholera toxin modulates growth and differentiation of neuroblastoma N18 cells.
The present study uses the B subunit of cholera toxin, a protein that binds specifically to ganglioside GM1, to examine the role of endogenous GM1 in the process of growth and differentiation of mouse neuroblastoma N18 cells. Binding of the B subunit to neuroblastoma N18 cells inhibited DNA synthesis with concomitant induction of differentiation. The B subunit induced pronounced morphological changes: an increase in neurite outgrowth with branched neurites and spinelike processes. The distinct morphological alterations and neuritogenesis in response to the B subunit were also revealed by immunofluorescence with fluorescein-labeled B subunit. The mechanism of the B subunit-induced differentiation is different than that of spontaneous differentiation. Thrombin, a serine protease present in normal serum, inhibits neurite outgrowth induced by the removal of serum from the medium. In contrast, thrombin did not cause retraction of the neurites induced by the B subunit. Thus, thrombin or a thrombin-like protease is not involved in the process of neurite outgrowth mediated through endogenous GM1. The biological effects of the B subunit are due to the binding of the B subunit to ganglioside GM1 and not due to changes in cAMP levels resulting from contaminating A subunit. We used highly purified cloned B subunit that cannot contain any A subunit because it was isolated from a Vibrio cholerae mutant that only expresses the B subunit. Neither the cloned nor commercial preparations of the B subunit induced increases of cAMP in these cells. There was a good correlation between the amount of B subunit bound to the cells and the biological effect. Finally, treatment with neuraminidase, which caused a fourfold increase in the level of membrane GM1 as determined by iodinated cholera toxin binding, enhanced the biological effect of the B subunit. However, neuraminidase treatment alone did not have significant effects, either on DNA synthesis or on morphology of the cells, indicating that elevations in the level of GM1 per se are not sufficient by themselves to cause significant changes in cell growth or differentiation. It seems most likely that the aggregation of endogenous GM1 on the cell surface by the B subunit is responsible for these effects on mouse neuroblastoma N18 cells.


Gut bacteria facilitate adaptation to crop rotation in the western corn rootworm.
Insects are constantly adapting to human-driven landscape changes; however, the roles of their gut microbiota in these processes remain largely unknown. The western corn rootworm (WCR, Diabrotica virgifera virgifera LeConte) (Coleoptera: Chrysomelidae) is a major corn pest that has been controlled via annual rotation between corn (Zea mays) and nonhost soybean (Glycine max) in the United States. This practice selected for a "rotation-resistant" variant (RR-WCR) with reduced ovipositional fidelity to cornfields. When in soybean fields, RR-WCRs also exhibit an elevated tolerance of antiherbivory defenses (i.e., cysteine protease inhibitors) expressed in soybean foliage. Here we show that gut bacterial microbiota is an important factor facilitating this corn specialist's (WCR's) physiological adaptation to brief soybean herbivory. Comparisons of gut microbiota between RR- and wild-type WCR (WT-WCR) revealed concomitant shifts in bacterial community structure with host adaptation to soybean diets. Antibiotic suppression of gut bacteria significantly reduced RR-WCR tolerance of soybean herbivory to the level of WT-WCR, whereas WT-WCR were unaffected. Our findings demonstrate that gut bacteria help to facilitate rapid adaptation of insects in managed ecosystems.


Influence of oxygen content immediately after graft reperfusion on occurrence of postoperative acute kidney injury in living donor liver transplantation.
Acute kidney injury (AKI) is a common complication after living donor liver transplantation (LDLT). In this study, we investigated perioperative factors, including oxygen content, related to the postoperative development of AKI after LDLT. The perioperative data of 334 patients were reviewed retrospectively. We identified the postoperative development of AKI based on the Acute Kidney Injury Network criteria. Perioperative variables, including oxygen content, were compared between patients with and without AKI. Potentially significant variables in a univariate analysis were evaluated by multivariate analysis. Postoperative AKI developed in 76 patients (22.7%). Univariate analysis revealed that preoperative factors (body mass index [BMI], diabetes mellitus, C-reactive protein) and intraoperative factors (severe postreperfusion syndrome, packed red blood cell transfusion, furosemide, and oxygen content at the anhepatic phase, 5 minutes and 1 hour after graft reperfusion, and at peritoneal closure) of recipients were significant. The multivariate analysis showed that oxygen content 5 minutes after graft reperfusion, BMI, and furosemide administration were independently associated with postoperative AKI. In conclusion, postoperative AKI was independently associated with oxygen content 5 minutes after graft reperfusion, BMI, and furosemide administration. Meticulous ventilator care and transfusion should be required to maintain sufficient oxygen content immediately after graft reperfusion in patients who undergo LDLT.


Characteristics of human metapneumovirus infection in adults hospitalized for community-acquired influenza-like illness in France, 2012-2018: a retrospective observational study.
To describe the prevalence, clinical features and complications of human metapneumovirus (hMPV) infections in a population of adults hospitalized with influenza-like illness (ILI). This was a retrospective, observational, multicenter cohort study using prospectively collected data from adult patients hospitalized during influenza virus circulation, for at least 24 h, for community-acquired ILI (with symptom onset <7 days). Data were collected from five French teaching hospitals over six consecutive winters (2012-2018). Respiratory viruses were identified by multiplex reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens. hMPV + patients were compared with hMPV- patients, influenza+ and respiratory syncytial virus (RSV)+ patients using multivariate logistic regressions. Primary outcome was the prevalence of hMPV in patients hospitalized for ILI. Among the 3148 patients included (1449 (46%) women, 1988 (63%) aged 65 and over; 2508 (80%) with chronic disease), at least one respiratory virus was detected in 1604 (51%, 95% confidence interval (CI) 49-53), including 100 cases of hMPV (100/3148, 3% 95% CI 3-4), of which 10 (10%) were viral co-infection. In the hMPV + patients, mean length of stay was 7 days, 62% (56/90) developed a complication, 21% (14/68) were admitted to intensive care unit and 4% (4/90) died during hospitalization. In comparison with influenza + patients, hMPV + patients were more frequently >65 years old (adjusted odds ratio (aOR) = 3.3, 95% CI 1.9-6.3) and presented more acute heart failure during hospitalization (aOR = 1.8, 95% CI 1.0-2.9). Compared with RSV + patients, hMPV + patients had less cancer (aOR = 0.4, 95% CI 0.2-0.9) and were less likely to smoke (aOR = 0.5, 95% CI 0.2-0.9) but had similar outcomes, especially high rates of respiratory and cardiovascular complications. Adult hMPV infections mainly affect the elderly and patients with chronic conditions and are responsible for frequent cardiac and pulmonary complications similar to those of RSV infections. At-risk populations would benefit from the development of antivirals and vaccines targeting hMPV.


Local active suppression and successful vaccination against spontaneous abortion in CBA/J mice.
We report here that vaccination of CBA/J female mice with DBA/2 X BALB/c recombinant line that decreases the spontaneous abortion rate increases local active decidua-associated suppressor cell activity. In contrast, vaccination with a recombinant line that increases the abortion rate decreases suppressor cell activity. No correlation was seen between the effect on the abortion rate and the ability of cells from the fetoplacental unit to inhibit cytolysis by NK cells. Successful vaccination against spontaneous abortion may act primarily by augmenting suppressor cell activity in the decidua at the implantation site.


Isolation, characterization and in vitro cultivation of subfractions of neonatal mouse keratinocytes: effects of phorbol esters.
Using discontinuous Percoll density gradient centrifugation, keratinocytes from neonatal mouse skin were separated into four fractions. The fractions were characterized by light microscopy, by indirect immunofluorescence using lectins (Bandeira simplicifolia and Ulex europaeus) or an antibody against bullous pemphigoid antigen, and by electrophoretic analysis of the keratin polypeptide patterns. Two fractions, F1 and F2, were identified as being derived from suprabasal layers and two fractions, F3 and F4, as originating from the basal cell layer. F3 and F4 cells could be cultivated on plastic substratum in the presence of 4 X minimum essential medium, 10% fetal calf serum at 34 degrees C with plating efficiencies of 80-85%. DNA labeling of cultures of F3 and F4 cells indicated that basal cells in fractions F3 and F4 exhibited different growth behaviour in culture. Confluent cultures of F3 and F4 cells responded to phorbol esters by increased DNA synthesis. This result contradicts the in vivo situation where neonatal mouse skin is resistant to the irritant and mitogenic effects of phorbol esters. The mitogenic effect of 12-O-tetradecanoylphorbol-13-acetate on F3 cells is not mediated by endogenous prostaglandin formation.


ST-Segment Elevation Myocardial Infarction with Acute Stent Thrombosis Presenting as Intractable Hiccups: An Unusual Case.
BACKGROUND Acute coronary syndrome (ACS) can present with atypical chest pain or symptoms not attributed to heart disease, such as indigestion. Hiccups, a benign and self-limited condition, can become persistent or intractable with overlooked underlying etiology. There are various causes of protracted hiccups, including metabolic abnormalities, psychogenic disorders, malignancy, central nervous system pathology, medications, pulmonary disorders, or gastrointestinal etiologies. It is rarely attributed to cardiac disease. CASE REPORT We report a case of intractable hiccups in a 51-year-old male with cocaine related myocardial infarction (MI) before and after stent placement. Coronary angiogram showed in-stent thrombosis of the initial intervention. Following thrombectomy, balloon angioplasty, and stent, the patient recovered well without additional episodes of hiccups. Although hiccups are not known to present with a predilection for a particular cause of myocardial ischemia, this case may additionally be explained by the sympathomimetic effects of cocaine, which lead to vasoconstriction of coronary arteries. CONCLUSIONS Hiccups associated with cardiac enzyme elevation and EKG ST-segment elevation before and after percutaneous coronary intervention (PCI) maybe a manifestation of acute MI with or without stent. The fact that this patient was a cocaine user may have contributed to the unique presentation.


Classification of Autism Spectrum Disorder From EEG-Based Functional Brain Connectivity Analysis.
Autism is a psychiatric condition that is typically diagnosed with behavioral assessment methods. Recent years have seen a rise in the number of children with autism. Since this could have serious health and socioeconomic consequences, it is imperative to investigate how to develop strategies for an early diagnosis that might pave the way to an adequate intervention. In this study, the phase-based functional brain connectivity derived from electroencephalogram (EEG) in a machine learning framework was used to classify the children with autism and typical children in an experimentally obtained data set of 12 autism spectrum disorder (ASD) and 12 typical children. Specifically, the functional brain connectivity networks have quantitatively been characterized by graph-theoretic parameters computed from three proposed approaches based on a standard phase-locking value, which were used as the features in a machine learning environment. Our study was successfully classified between two groups with approximately 95.8% accuracy, 100% sensitivity, and 92% specificity through the trial-averaged phase-locking value (PLV) approach and cubic support vector machine (SVM). This work has also shown that significant changes in functional brain connectivity in ASD children have been revealed at theta band using the aggregated graph-theoretic features. Therefore, the findings from this study offer insight into the potential use of functional brain connectivity as a tool for classifying ASD children.


Strategies for Implementing Group Mental Health Interventions in a VA Community Living Center.
Objectives: Group mental health interventions are difficult to implement into rehabilitation facilities, but no one has studied the specific barriers. This mixed-methods project systematically examined the implementation of a mental health (MH) group intervention in a VA community living center (CLC) for residents on subacute rehabilitation units, using the Promoting Action on Research Implementation in Health Services (PARIHS) implementation framework.Methods: We implemented a group MH intervention, tracking team referrals, attendance rates, and reasons for declining to participate. We conducted qualitative interviews with attendees.Results: Individual barriers to attendance included acute illness (n = 67, 20%), attitudes toward MH (n = 50; 15%), and perceived busyness (n = 19; 6%). Facility barriers included competing appointments (n = 69; 21%). Interviews demonstrated challenges to implementation, including stigma toward mental health (Theme: Challenges and Supports to Implementation). Attendees found the group relatable, and noted that both positive and negative group dynamics contributed to their experience (Themes: Content Relevance and Group Dynamics).Conclusions: The results provide insight into implementing a group MH treatment into the CLC setting, with implications for the MH care of older adults residing in CLCs.Clinical Implications: 1) Group leaders should consider matching attendees for ability levels (physical or cognitive). 2) At the facility level, leaders may take steps to address stigma toward MH by adopting approaches (e.g., music) or framing MH issues (e.g., use of language) in a way that is approachable. 3) Modifiable barriers at the individual and facility level could be addressed to encourage ease of implementation.


[Genetic effects of the decay of tritium incorporated into Saccharomyces cerevisiae yeast cells. I. Lethal effect of 3H-alanine on cells of different ploidy and radiosensitivity].
Lethal effect of 3H-alanine on cells of different ploidy (1n-4n) and radiosensitivity wild type haploid and diploid strains; xrs2 mutant and diploid strains homozygous for this mutation is studied. It is shown that the efficiency of the inactivation per tritium decay depends on ploidy, radiosensitivity and geometric dimension of cells and nuclei. Do for all the studied strains is slightly higher than Do for these strains in case of external beta-irradiation. RBE of beta-ray tritium with respect to beta-ray of 32P is 1.5.


Sensing error for a mobile robot using line navigation.
The use of a contrasting line for the visual navigation of autonomous mobile robots in a factory environment is developed. Minimum and maximum linewidths are determined analytically by considering sensor geometry, field of view, and error conditions present in the system. The effects of these error conditions on the width of the line, as seen in the image plane, determines the optimal linewidth. Numerical examples using typical sensor parameters are given.


Characterization of a calmodulin-dependent high-affinity cyclic AMP and cyclic GMP phosphodiesterase from male mouse germ cells.
Two cyclic nucleotide phosphodiesterase activities were separated by ion-exchange chromatography of cytosol from male mouse germ cells. A form eluted at low salt concentration showed high affinity (Km congruent to 2 microM) and low affinity (Km congruent to 20 microM) for cyclic AMP, and high affinity (Km congruent to 3.5 microM) for cyclic GMP. A second form, eluted at high salt concentration, showed high affinity (Km congruent to 5 microM) for cyclic AMP and was similar to a phosphodiesterase activity described in rat germ cells. The present study was performed to characterize the first form, which represents most of the phosphodiesterase activity in mouse germ cells. The enzyme was sensitive to Ca2+ and calmodulin stimulation, which increased its activity 3-4-fold. Calmodulin stimulation depended on direct interaction of the activator with the enzyme, as indicated by the reversible changes in the chromatographic elution pattern in the presence of Ca2+, as well as by the increase in the sedimentation coefficient in the presence of calmodulin. Reciprocal inhibition kinetics between cyclic AMP and cyclic GMP for the calmodulin-dependent form demonstrated a non-competitive inhibition between the two substrates, suggesting the presence of separate catalytic sites. This is in agreement with kinetic parameters and different thermal stabilities of cyclic AMP- and cyclic GMP-hydrolysing activities. Furthermore, the relevant change in s value, depending on the absence or presence of Ca2+ and calmodulin, suggested that the enzyme is composed of subunits, which aggregate in the presence of the activator. A model for catalytic site composition and reciprocal interaction is also proposed.


The complete mitochondrial genome of the pygmy squid, Idiosepius (Cephalopoda: Decapodiformes): the first representative from the family Idiosepiidae.
We report the first complete mitochondrial genome of the pygmy squid, Idiosepius, (Idiosepiidae). The mtDNA genome is 16,183 bp long with an AT content of 75.4%. All conserved metazoan mitochondrial genes are identified with the addition of a 1018 bp non-coding region. Idiosepius gene order most closely resembles that of the bobtail squid Semirossia (Sepiolidae).


Accurate models for P-gp drug recognition induced from a cancer cell line cytotoxicity screen.
P-glycoprotein (P-gp, MDR1) is a promiscuous drug efflux pump of substantial pharmacological importance. Taking advantage of large-scale cytotoxicity screening data involving 60 cancer cell lines, we correlated the differential biological activities of ∼13,000 compounds against cellular P-gp levels. We created a large set of 934 high-confidence P-gp substrates or nonsubstrates by enforcing agreement with an orthogonal criterion involving P-gp overexpressing ADR-RES cells. A support vector machine (SVM) was 86.7% accurate in discriminating P-gp substrates on independent test data, exceeding previous models. Two molecular features had an overarching influence: nearly all P-gp substrates were large (>35 atoms including H) and dense (specific volume of <7.3 Å(3)/atom) molecules. Seven other descriptors and 24 molecular fragments ("effluxophores") were found enriched in the (non)substrates and incorporated into interpretable rule-based models. Biological experiments on an independent P-gp overexpressing cell line, the vincristine-resistant VK2, allowed us to reclassify six compounds previously annotated as substrates, validating our method's predictive ability. Models are freely available at http://pgp.biozyne.com .


Anthropogenic noise predicts sea turtle behavioural responses.
Anthropogenic noise is a pollutant of global concern. While the effects of underwater noise pollution have been frequently studied in fish and mammals, our understanding of how this anthropogenic stressor affects marine reptiles is scant. Using a multichannel data logger equipped with a camera and hydrophone, we quantified behavioural responses of a free-ranging green turtle (Chelonia mydas) to vessel noise in the Galapagos Archipelago, an important nesting site in the eastern Pacific. We found that while travelling the turtle increased its vigilance with increasing vessel noise. However, when on the seabed the turtle did not increase its vigilance with increasing noise levels. Our findings illustrate that noise pollution has the potential to alter overall time budgets of animals. Identifying real-time responses of wild animals illustrate how in situ approaches allow to assess the effects of human activities on marine systems.


Fluorinated antimony(v) derivatives: strong Lewis acidic properties and application to the complexation of formaldehyde in aqueous solutions.
As part of our ongoing studies of water tolerant Lewis acids, we have synthesized and investigated the properties of Sb(C6F5)3(O2C6Cl4), a fluorinated stiborane whose Lewis acidity approaches that of B(C6F5)3. While chloroform solutions of this Lewis acid can be kept open to air or exposed to water for extended periods of time, this new Lewis acid reacts with P t Bu3 and paraformaldehyde to form the corresponding formaldehyde adduct t Bu3P-CH2-O-Sb(C6F5)3(O2C6Cl4). To test if this reactivity can also be observed with systems that combine the phosphine and the stiborane within the same molecule, we have also prepared o-C6H4(PPh2)(SbAr2(O2C6Cl4)) (Ar = Ph, C6F5). These yellow compounds, which possess an intramolecular P→Sb interaction, are remarkably inert to water but do, nonetheless, react with and accomodate formaldehyde into the P/Sb pocket. In the case of the fluorinated derivative o-C6H4(PPh2)(Sb(C6F5)2(O2C6Cl4)), formaldehyde complexation, which occurs in water/dichloromethane biphasic mixtures, is accompanied by a colourimetric turn-off response thus highlighting the potential that this chemistry holds in the domain of molecular sensing.


[Management of hemoptysis in children].
Hemoptysis in children are infrequent and often self-limiting. They are a manifestation of the broader spectrum of pulmonary haemorrhage. Diffuse pulmonary haemorrhages are often associated with diseases of other organs (cardiopathies, systemic diseases). Focal haemorrhages have multiple aetiologies, dominated by bronchopulmonary infections and cystic fibrosis. Fiberoptic bronchoscopy allows one to localise the bleeding, look for local causes and diagnose pulmonary hemosiderosis by BAL. For local lesions and if the medical management fails, bronchial arteriography is indicated to perform the embolisation of the bleeding vessels.


Functionalized core-shell hydrogel microsprings by anisotropic gelation with bevel-tip capillary.
This study describes a novel microfluidic-based method for the synthesis of hydrogel microsprings that are capable of encapsulating various functional materials. A continuous flow of alginate pre-gel solution can spontaneously form a hydrogel microspring by anisotropic gelation around the bevel-tip of the capillary. This technique allows fabrication of hydrogel microsprings using only simple capillaries and syringe pumps, while their complex compartmentalization characterized by a laminar flow inside the capillary can contribute to the optimization of the microspring internal structure and functionality. Encapsulation of several functional materials including magnetic-responsive nanoparticles or cell dispersed collagen for tissue scaffold was demonstrated to functionalize the microsprings. Our core-shell hydrogel microsprings have immense potential for application in a number of fields, including biological/chemical microsensors, biocompatible soft robots/microactuators, drug release, self-assembly of 3D structures and tissue engineering.


The Role of Transient Target Stimuli in a Steady-State Somatosensory Evoked Potential-Based Brain-Computer Interface Setup.
In earlier literature, so-called twitches were used to support a user in a steady-state somatosensory evoked potential (SSSEP) based brain-computer interface (BCI) to focus attention on the requested targets. Within this work, we investigate the impact of these transient target stimuli on SSSEPs in a real-life BCI setup. A hybrid BCI was designed which combines SSSEPs and P300 potentials evoked by twitches randomly embedded into the streams of tactile stimuli. The EEG of fourteen healthy subjects was recorded, while their left and right index fingers were simultaneously stimulated using frequencies selected in a screening procedure. The subjects were randomly instructed by a cue on a screen to focus attention on one or none of the fingers. Feature for SSSEPs and P300 potentials were extracted and classified using separately trained multi-class shrinkage LDA classifiers. Three-class classification accuracies significantly better than random could be reached by nine subjects using SSSEP features and by 12 subjects using P300 features respectively. The average classification accuracies were 48.6% using SSSEP and 50.7% using P300 features. By means of a Monte Carlo permutation test it could be shown that twitches have an attenuation effect on the SSSEP. Significant SSSEP blocking effects time-locked to twitch positions were found in seven subjects. Our findings suggest that the attempt to combine different types of stimulation signals like repetitive signals and twitches has a mutual influence on each other, which may be the main reason for the rather moderate BCI performance. This influence is originated at the level of stimulus generation but becomes apparent as physiological effect in the SSSEP. When designing a hybrid BCI based on SSSEPs and P300 potentials, one has to find an optimal tradeoff depending on the overall design goals or individual subjects' performance. Our results give therefore some new insights that may be useful for the successful design of hybrid BCIs.


Variant arteriovenous fistula of the superior sagittal sinus--case report.
A 57-year-old male presented with a rare variant of dural arteriovenous fistula, located in the wall of an unobstructed superior sagittal sinus. Drainage occurred through a cortical vein no longer connected to its parent sinus, which filled up a cluster of transmedullary running veins, one of which was the presumed site of hemorrhage. Arterial blood was supplied via the external carotid artery branches. This type of fistula seriously increases the risk of hemorrhage in the patient and therefore requires complete obliteration. Attempts to embolize the fistula failed. The draining vein was isolated and coagulated resulting in permanent occlusion of the fistula. The fistula probably developed through a process of thrombophlebitis and revascularization via arterioles of the vein rather than previous occlusion of the sinus.


Coronary multidetector computed tomographic angiography to evaluate coronary artery disease in liver transplant candidates: methods, feasibility and initial experience.
In patients undergoing orthotopic liver transplantation (OLT), coronary artery disease (CAD), obstructive and nonobstructive, is associated with high morbidity and mortality. In OLT candidates, stress testing for detecting ischemia is often inaccurate, and this patient population often has relative contraindications for cardiac catheterization. The objective of this study was to describe the methods, assess the feasibility and determine the extent and severity of CAD in OLT candidates without a prior history of CAD using coronary multidetector computer tomographic angiography (MDCTA). Sixty-five OLT candidates without known CAD underwent coronary MDCTA with dual source cardiac computed tomography (Siemens Definition). Coronary arteries were divided into 17 segments based on American Heart Association guidelines and evaluated independently by two blinded reviewers. Image quality of coronary MDCTA was assessed on a four-point Likert scale (0 = poor, 1 = fair, 2 = good, and 3 = excellent). Atherosclerotic lesions were evaluated for severity [mild (0-50%), moderate (51-70%), and severe (71-100%)], morphology, extent, location and consistency. Image quality was graded as good or excellent in 73.8%. In this cohort of OLT candidates without known CAD, 9% had normal coronary arteries, 58% had mild CAD and 34% had moderate to severe CAD. Plaque severity and burden scores were high. The prevalence of asymptomatic CAD is high in OLT candidates. Coronary MDCTA is feasible in OLT candidates and appears to be a useful technique to diagnose occult CAD in this patient population.


Development and validation of the Children's Competence in Decision-Making Scale.
Measuring competence in children's ability to make decisions about their care is laden with conceptual problems. Although there are a variety of tools to measure competence, no scales have been identified that measured competence in children. To develop, test and validate a scale that measured competence in the decision-making process of children aged 8-12 years with long-term conditions, called the Children's Competence in Decision-Making (CCD-M) Scale. A convergent, sequential, mixed-methods validation design was used. Four stages of scale development were used following recommended procedures. The qualitative arm explored the experiences of being involved in decision-making and these insights were used to develop the scale which was then subject to psychometric testing. Cronbach's α of the overall scale was 0.86, which shows good internal validity. Additionally, the α analysis when items were deleted showed no considerable variation and had no value below 0.7, showing excellent internal validity throughout. No substantial increase in α could be achieved. The CCD-M Scale offers practitioners the ability to test the competence levels of children to decide the extent to which they may want to be involved in the decision-making process. This, in turn, may help to plan care in a more effective way and may have an effect on adherence levels in self-management of illness.


Increased intake of fruits and vegetables in overweight subjects: effects on body weight, body composition, metabolic risk factors and dietary intake.
A diet rich in fruits and vegetables has been associated with several health benefits. However, the effects on body weight (BW) and metabolic markers are not fully known. The present study investigated the effects of increased intake of fruits and vegetables in overweight and obese men and women on dietary habits, anthropometry and metabolic control. In a 16-week controlled intervention, thirty-four men and thirty-four women aged 35-65 years (BMI>27 kg/m2) were randomised to an intervention (IN) or a reference (RG) group. All participants received general dietary advice, and subjects in the IN group received fruits and vegetables for free, of which ≥500 g had to be eaten daily. BW, waist circumference (WC), sagittal abdominal diameter (SAD), plasma insulin, blood glucose, glycated Hb (HbA1c), serum lipids, blood pressure, plasminogen activator inhibitor-1 activity, urinary isoprostane (iso-8-PGF 2α) and serum carotenoids were measured. Diet was assessed using 3-d weighed food records. In all, thirty subjects in the IN group and thirty-two in the RG group completed the intervention. Intake of fruits and vegetables doubled in the IN group, whereas intake of fruits increased in the RG group. Serum α- and β-carotene concentrations and intakes of folate and vitamin C increased significantly in the IN group. Energy intake, BW, WC and SAD decreased significantly in both groups. Supine systolic blood pressure decreased significantly in the IN group, with no between-group differences. No significant changes were observed for other metabolic markers. Provision of fruits and vegetables led to substantially increased intakes, with subsequent favourable changes in anthropometry and insulin levels, which tended to be more pronounced in the IN group. The observed improvements may, in combination with improved nutritional markers, have health benefits in the long term.


The evaluation of maternal health in rural western China.
The double burden of undernutrition and overnutrition is recognized as a global devastating problem. However, few studies have investigated the maternal nutritional status among different ethnicities and the socio-demographic characteristics in rural areas of western China. This study attempted to fill this gap. Data on 10,495 women with children under three years old were collected using a three-stage probability proportion to size sampling from 45 counties of 10 provinces in western China. Generalized Estimating Equation (GEE) was used to assess the maternal nutrition conditions, including chronic energy deficiency (CED) and overweight/obesity. According to the WHO BMI standard, the prevalences of CED and overweight/obesity were 12.3% (BMI≤18.5 kg/m2) and 12.4% (BMI≥25 kg/m2), respectively, while overweight/obesity rate was 18.5% (BMI≥24 kg/m2) based on the Chinese standard. A significant difference in malnutrition between Han and Minority was not observed. The relationship between breastfeeding and CED was inverse (OR 0.64, 95%CI: 0.48, 0.87), but higher parity were positively correlated with CED (OR 1.57, 95%CI: 1.36, 1.82). The highest odds of CED were observed in the group with 1-5 years of education (OR 1.21, 95%CI: 1.03, 1.43). Higher parity was also associated with overweight/obesity (OR 0.78, 95%CI: 0.67, 0.91), and rural women aged 30-39 years old were more likely to be overweight/obese (OR 2.21, 95%CI: 1.47, 3.32). In addition, higher socioeconomic status was positively related to overweight women (OR 1.19, 95%CI: 1.01, 1.43), and inversely associated with CED (OR 0.83, 95%CI: 0.72, 0.97). The coexistence of undernutrition and overweight among women of reproductive age are determined in rural western China. It appears that socio-demographic factors considerably influence maternal nutritional status in the study. These findings have important policy implications for recommendations on maternal health intervention in China.


Novel affinity ligands for chromatography using combinatorial chemistry.
Spatially addressable combinatorial libraries were synthesized by solution phase chemistry and screened for binding to human serum albumin. Members of arylidene diamide libraries were among the best hits found, having submicromolar binding affinities. The results were analyzed by the frequency with which particular substituents appeared among the most potent compounds. After immobilization of the ligands either through the oxazolone or the amine substituent, characterization by surface plasmon resonance showed that ibuprofen affected the binding kinetics, but phenylbutazone did not. It is therefore likely that these compounds bind to Site 2 in sub domain IIIA of human serum albumin (HSA).


Cost-effectiveness of disease-modifying therapies in the management of multiple sclerosis for the Medicare population.
To evaluate the cost-effectiveness of disease-modifying therapies (DMTs) for the management of multiple sclerosis (MS) compared to best supportive care in the United States. Cost-effectiveness analysis was undertaken using a state transition model of disease natural history and the impact of DMTs for the representative Medicare beneficiary with MS. Costs and outcomes were evaluated from the health-care payer perspective using a 50-year time horizon. Natural history data were drawn from a longitudinal cohort study. The effectiveness of the DMTs was evaluated through a systematic review. Utility data were taken from a study of patients with clinically definite MS in Nova Scotia. Resource use and cost data were derived from the Sonya Slifka database and associated literature. When based on placebo-controlled evidence, the marginal cost-effectiveness of interferon beta (IFNβ) and glatiramer acetate compared to best supportive care is expected to be in excess of $100,000 per quality-adjusted life-year gained. When evidence from head-to-head trials is incorporated into the model, the cost-effectiveness of 6 MIU IFNβ-1a is expected to be considerably less favorable. Treatment discontinuation upon progression to Expanded Disability Status Scale 7.0 is expected to improve the cost-effectiveness of all DMTs. Further research is required to examine the long-term clinical effectiveness and cost-effectiveness of these therapies. There is no definitive guidance in the United States concerning discontinuation of DMTs; this study suggests that the prudent use of a treatment discontinuation rule may considerably improve the cost-effectiveness of DMTs.


The Future of Dental Care: The Manipulation of Dental Instruments & Preparation Towards Automated Tooth Cleaning.
Dentistry is an essential practice to maintain the health of the oral cavity. Recent advances in digitization and technology for oral examinations have improved the speed and ease of disease diagnosis and dental treatment. Dental robotics has emerged as a new field of dentistry and offers numerous benefits to dental professionals and society. This paper proposes an innovative design of a dental robot setup with a preliminary study on a head model for the preparation of automated dental exploration in MATLAB and discusses further considerations for automation.


Application of total body bioimpedance to the critically ill patient. Brazilian Group for Bioimpedance Study.
In the past several years, considerable interest has developed in the study of total body bioimpedance analysis (TBBIA) and body composition in healthy subjects. This simple and noninvasive technique uses derived and regression equations to validate data comparative to the gold standards of total body water determination and body composition. However, this approach has not proved to be of value in the critically ill patient with distorted body composition under the effects of multiple drugs and interventions. Notwithstanding, in recent years several authors have demonstrated the usefulness of this technique, apart from derived equations, relying solely in the judicious interpretation of the primary impedance parameters: resistance (R, ohms [omega], reactance (Xc, omega) and the derived phase angle (phi, degrees). The principles of bioelectrical impedance postulate that R is the opposition of total body water and electrolytes to the flow of an alternating current of low amplitude and high frequency, typically 800 microA and 50 kHz, and Xc is the capacitance produced by tissue interface and cell membranes. The phase shift is quantified geometrically as the angular transformation of the ratio Xc/R and is designated as phi. Altered cellular membrane function is a common feature of the septic patient and it has been systematically associated with a significant low Xc and phi. On the other hand, the fluid balance can be precisely monitored by the changes in R, and the serial measurements of the relation Xc/R (or the phi) has been utilized to discriminate between normal subjects and patients, and between septic and nonseptic critically ill patient. Some authors have demonstrated that this relation Xc/R is highly correlated with mortality and could be used for the staging of critically ill patients throughout their stay in the ICU. The role of TBBIA as a simple and noninvasive technique, and its implications for the management of critically ill patients are presented and discussed. Areas for future investigations, with single and multiple frequency, have the potential to clarify many aspects of this emergent technology at the bedside.


Pain-reducing anesthesia prevents oxidative stress in human term placenta.
Anesthesia is sometimes used for the reduction of maternal pain in normal human term labor, but whether the drugs affect oxidative stress remains unclear. The placenta serves as an interface between the maternal and fetal vasculature. In this study, we immunohistochemically analyzed two markers for oxidative stress, namely 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal-modified proteins (HNE), using placentas from 21 cases of normal tansvaginal delivery (V group), 20 Caesarean sections (C group), and 17 normal transvaginal deliveries with epidural anesthesia (E group). 8-OHdG staining in the nuclei of trophoblasts lining the chorionic villi was significantly stronger in the V group either compared with the C or E group (p<0.001), without significant differences in the C and E groups (p = 0.792). Moderate to intense staining by HNE of the intravascular serum of chorionic villi vasculature was frequently observed in the placentas from the V group, but less frequently of those in either C or E groups (p<0.001), nor the p value comparing the C and E groups was significant (p = 0.128) for HNE staining. Our results suggest that although the role of oxidative stress and its influences on fetal state in the placenta in labor remains unclear, it seems to be lessened by epidural anesthesia.


Resource utilization and outcomes from percutaneous drainage and interval appendectomy for perforated appendicitis with abscess.
Given the perceived technical demands of laparoscopic appendectomy and the expected postoperative morbidity in patients with a well-defined abscess, initial percutaneous drainage has become an attractive option in this patient population. This strategy allows for a laparoscopic appendectomy to be performed in an elective manner at the convenience of the surgeon. However, the medical burden on the patient and on the quality of patient outcomes has not been described in the literature. Therefore, we audited our experience with initial percutaneous drainage followed by laparoscopic interval appendectomy to evaluate the need for a prospective trial. After institutional review board approval, a retrospective chart review was performed on all children who presented with perforated appendicitis and a well-defined abscess and were treated by initial percutaneous aspiration/drainage followed by interval appendectomy between January 2000 and September 2006. Continuous variables are listed with standard deviation. There were 52 patients with a mean age of 9.0 +/- 3.9 years and weight of 34.4 +/- 18.8 kg. The mean duration of symptoms at presentation was 8.4 +/- 7.6 days. Percutaneous aspiration only was performed in 2 patients. The mean volume of fluid on initial aspiration/drain placement was 76.3 +/- 81.1 mL. The mean time to appendectomy was 61.9 +/- 25.2 days. The laparoscopic approach was used in 49 patients (94.2%), of which one was converted to an open operation. The mean length of hospitalization after interval appendectomy was 1.4 +/- 1.4 days. A recurrent abscess developed in 17.3% of the patients. Six patients (11.5%) required another drainage procedure. The mean total charge to the patients was $40,414.02. There were 4 significant drain complications (ileal perforation, colon perforation, bladder perforation, and buttock/thigh necrotizing abscess). The child with the ileal perforation after drain placement is the only patient who failed initial nonoperative therapy. The use of initial percutaneous aspiration/drainage of periappendiceal abscess followed by interval appendectomy is an effective approach. However, this management poses complication risks and uses considerable resources. Therefore, this strategy should be compared with early operation in a prospective trial.


Amgen v. Sanofi: The U.S. Supreme Court Reviews Patent Enablement.
On June 18, 2023, the U.S. Supreme Court in the matter of Amgen, Inc. et al. v. Sanofi, et al.1 unanimously upheld the 2021 decision of the U.S. Court of Appeals for the Federal Circuit,2 striking down as overbroad Amgen's patent claim to an entire functional genus of monoclonal antibodies. Amgen's patent claims were not limited to antibody structure or antibody amino acid sequences. This is significant because Amgen's patent claims did have amino acid sequences, but they were directed to the epitope.


Altered expression profiles of circular RNA in colorectal cancer tissues from patients with lung metastasis.
The lung is the most common extra-abdominal site of metastasis in colorectal cancer (CRC), in which circular RNA (circRNA) may have a crucial role. Therefore, the present study detected circRNA expression to identify novel targets to further study lung metastasis in CRC. In the present study, total RNA was extracted from CRC tissues of patients with and without lung metastasis to perform high-throughput microarray assay in order to detect differentially expressed circRNA. Following this, gene ontology (GO) and pathway analyses of the genes producing differentially expressed circRNA were performed to predict the function of circRNA using standard enrichment computational methods. Additionally, the circRNA/microRNA (miRNA) interactions were constructed with bioinformatics methods to predict the binding of miRNA with circRNA. In the CRC tissues from patients with lung metastasis, 431 circRNA were detected to be differentially expressed, including 192 upregulated and 239 downregulated over 2-fold compared with the CRC tissues without metastasis. Furthermore, GO analysis revealed that the genes producing upregulated circRNA were involved in DNA repair, while the genes producing downregulated circRNA were enriched in signal transduction. By pathway analysis, it was identified that the genes producing downregulated circRNA were involved in the nuclear factor-κB and Wnt signaling pathway in the CRC tissues from patients with lung metastasis compared with the CRC tissues without metastasis. In addition, it was demonstrated that hsa_circRNA_105055, hsa_circRNA_086376 and hsa_circRNA_102761 could commonly bind with miR-7 regulating target genes PRKCB, EPHA3, BRCA1 and ABCC1. The findings of the present study may provide a novel perspective on circRNA and lay a foundation for future research of potential roles of circRNA in CRC with lung metastasis.


Neo-cartilage engineered from primary chondrocytes is epigenetically similar to autologous cartilage, in contrast to using mesenchymal stem cells.
To compare the epigenetic landscape of 3D cell models of human primary articular chondrocytes (hPACs) and human bone-marrow derived mesenchymal stem cells (hBMSCs) and their respective autologous articular cartilage. Using Illumina Infinium HumanMethylation450 BeadChip arrays, the DNA methylation landscape of the different cell sources and autologous cartilage was determined. Pathway enrichment was analyzed using DAVID. Principal Component Analysis (PCA) of methylation data revealed separate clustering of hBMSC samples. Between hBMSCs and autologous cartilage 86,881 cytosine-phosphate-guanine dinucleotides (CpGs) (20.2%), comprising 3,034 differentially methylated regions (DMRs; Δβ > 0.1; with the same direction of effect), were significantly differentially methylated. In contrast, between hPACs and autologous cartilage only 5,706 CpGs (1.33%) were differentially methylated. Of interest was the finding of the transcriptionally active, hyper-methylation of a Cartilage Intermediate Layer Protein (CILP) annotated DMR (Δβ = 0.16) in PAC-cartilage, corresponding to a profound decrease in CILP expression after in vitro culturing of hPACs as compared to autologous cartilage. In vitro engineered neo-cartilage tissue from primary chondrocytes, hPACs, exhibits a DNA methylation landscape that is almost identical (99% similarity) to autologous cartilage, in contrast to neo-cartilage engineered from bone marrow-derived mesenchymal stem cells (MSCs). Although hBMSCs are widely used for cartilage engineering purposes the effects of these vast differences on cartilage regeneration and long term consequences of implantation, are not known. The use of hBMSCs or hPACs for future cartilage tissue regeneration purposes should therefore be investigated in more depth in future endeavors to better understand the consequences of the differential methylome on neo-cartilage.


Prospective study of amphotericin B formulations in immunocompromised patients in 4 European countries.
Amphotericin B is a widely used broad-spectrum antifungal agent, despite being associated with significant adverse events, including nephrotoxicity. The present prospective study collected data on outcomes for 418 adult patients treated consecutively with polyenes in hematology and oncology wards in 20 hospitals in Europe. Patients initially received amphotericin B deoxycholate (62% of patients), liposomal amphotericin B (27%), or other lipid formulations of amphotericin B (11%). Of the patients initially treated with amphotericin B deoxycholate, 36% had therapy switched to lipid formulations of amphotericin B, primarily because of increased serum creatinine levels (in 45.7% of patients) or other amphotericin B-attributable adverse events (in 41.3% of patients). Nephrotoxicity, which was defined as a > or = 50% increase in the serum creatinine level, developed in 57% of patients with normal kidney function at baseline. Predictors of nephrotoxicity included formulation type and duration of treatment. Compared with patients without nephrotoxicity, patients with nephrotoxicity had a higher mortality rate (24%), and their mean length of stay in the hospital was prolonged by 8.6 days. Slight increases in the serum creatinine level (i.e., > or = 50%) were associated with a significantly longer stay in the hospital. Severe nephrotoxicity (i.e., a > or = 200% increase in the serum creatinine level) was a significant predictor of death, as were severe underlying medical conditions and documented fungal infection. This prospective study confirmed that, in European hospitals, amphotericin B formulations have a major influence on the length of stay in the hospital and nephrotoxicity-associated mortality.


Removal of steroid hormones and biocides from rural wastewater by an integrated constructed wetland.
Steroid hormones and biocides are regarded as emerging contaminants in rural wastewater in China, owing to their widespread occurrence and adverse effects on both aquatic organisms and humans. Constructed wetlands (CWs) are an alternative technology for cost-effective and efficient decentralized rural sewage treatment. In this study, an integrated constructed wetland (ICW) system was built and used to treat a typical rural wastewater mixture composed of domestic sewage and livestock wastewater from a small village. As expected, five steroid hormones (ADD, AED, 19-NTD, T, and P) and four biocides (DEET, TCS, CBD, and MP) were detected in the influent in concentrations ranging from 30.5 ± 1.25 ng/L to 105 ± 5.14 ng/L and from 63.4 ± 2.85 ng/L to 515 ± 19.7 ng/L, respectively. The ICW system effectively removed the detected steroid hormones (97.4 ± 0.09%) and biocides (92.4 ± 0.54%). Based on the measured concentrations, the total pollution loadings of the detected steroid hormones and biocides in the influent were calculated to be 2330 ± 26.5 μg/day and 5710 ± 196 μg/day, which decreased to 60.8 ± 1.44 μg/day and 433 ± 25.6 μg/day in the final effluent. The risk quotients for these steroid hormones and biocides in the effluent from the ICW system were lower than those from reported wastewater treatment plants, indicating that CWs are a promising technology for removing contaminants including steroid hormones and biocides in rural wastewater, although additional efforts are required to optimize and improve the design of CWs before the steroid hormones and biocides present in the effluent can be safely and directly discharged into the environment.


Comorbid anxiety disorder and the functioning and well-being of chronically ill patients of general medical providers.
The comorbidity of psychiatric disorders with chronic health conditions has emerged as a topic of considerable clinical and policy interest, in part owing to the evidence that anxiety disorders themselves are associated with morbidity. However, the implications for health-related quality of life that result from anxiety disorders, which are comorbid to chronic medical or psychiatric illness, are not well understood, especially in primary care samples. A 2-year observational study of 875 adult patients with hypertension, diabetes, heart disease, and current depressive disorder or subthreshold depression receiving care from general medical providers was conducted. The unique effect of any comorbid anxiety disorder on functioning and well-being (determined with the use of the 36-Item Short-Form Health Survey [SF-36]) was estimated, as well as the differential impact at baseline, 2-year follow-up, and change over time, of any comorbid anxiety disorder for patients with chronic medical conditions or depression. Patients with comorbid anxiety who received general medical care had lower levels of functioning and well-being than those without comorbid anxiety. These differences were most pronounced in mental health-related quality-of-life measures and when anxiety was comorbid with chronic medical conditions rather than with depression. Hypertensive and diabetic patients with comorbid anxiety were as debilitated as patients with depression or heart disease, and this low health-related quality of life persisted over time. Comorbid anxiety had less of an effect on patients with heart disease who already had a low health-related quality of life. The finding of substantial differences in the quality of life between hypertensive and diabetic patients with and without comorbid anxiety disorder highlights the clinical and societal importance of identifying comorbid anxiety in these patients.


[Distance education in the Discipline of Legislation, Ethics and Practice Nursing].
Report of experience whose aim is to describe the integration of the discipline of Legislation, Ethics and Practice of Nursing online in the Nursing Course at the University of Estácio Sá, Rio de Janeiro, Brazil. The construction of interactivity in distance education was critical to the continued planning of virtual environment through the development of students' feasible abilities and skills for the theching strategy of Course Political Educational Project combining with the current legislation needs of nursing profession. The development of education articulated by avaliable tools in the virtual environment aims at promoting the critical-relexive development of the future nurse.


In situ cross-linking of stimuli-responsive hemicellulose microgels during spray drying.
Chemical cross-linking during spray drying offers the potential for green fabrication of microgels with a rapid stimuli response and good blood compatibility and provides a platform for stimuli-responsive hemicellulose microgels (SRHMGs). The cross-linking reaction occurs rapidly in situ at elevated temperature during spray drying, enabling the production of microgels in a large scale within a few minutes. The SRHMGs with an average size range of ∼ 1-4 μm contain O-acetyl-galactoglucomannan as a matrix and poly(acrylic acid), aniline pentamer (AP), and iron as functional additives, which are responsive to external changes in pH, electrochemical stimuli, magnetic field, or dual-stimuli. The surface morphologies, chemical compositions, charge, pH, and mechanical properties of these smart microgels were evaluated using scanning electron microscopy, IR, zeta potential measurements, pH evaluation, and quantitative nanomechanical mapping, respectively. Different oxidation states were observed when AP was introduced, as confirmed by UV spectroscopy and cyclic voltammetry. Systematic blood compatibility evaluations revealed that the SRHMGs have good blood compatibility. This bottom-up strategy to synthesize SRHMGs enables a new route to the production of smart microgels for biomedical applications.


Profound negative regulatory effects by resveratrol on vascular smooth muscle cells: a role of p53-p21(WAF1/CIP1) pathway.
We investigated the role of resveratrol, a polyphenol rich in red wine, in cell cycle progression and apoptosis of vascular smooth muscle cells (VSMCs). Resveratrol inhibited the growth of human aortic VSMCs at concentrations as low as 1 microM. This was due to the profound dose-dependent inhibition of DNA synthesis by resveratrol. DNA synthesis was more effectively inhibited when cells were pretreated with resveratrol. Resveratrol caused a dose-dependent increase in intracellular p53 and p21(WAF1/CIP1) levels. At lower concentrations (6.25-12.5 microM), resveratrol effectively blocked cell cycle progression of serum-stimulated VSMCs without inducing apoptosis, while the higher concentration of resveratrol (25 microM) selectively induced apoptosis in the same VSMCs. Intriguingly, however, the same high concentration of resveratrol could not induce apoptosis in quiescent VSMCs. These differential biological effects of resveratrol on quiescent and proliferating VSMCs suggest that resveratrol may be capable of selectively eliminating abnormally proliferating VSMCs of the arterial walls in vivo.


Comparison of monkey and human retrosplenial neurocytology.
Retrosplenial cortex (RSC) has unique problems for human neuroimaging studies as its divisions are small, at the lower end of functional scanner spatial resolution, and it is buried in the callosal sulcus. The present study sought to define the cytoarchitecture of RSC in human and monkey brains along its entire anteroposterior extent. The results show anterior extensions, a newly defined dichotomy of area 30, a new area p30, and an area p29v in monkey that differentiates into three divisions in human. Accordingly, anterior (a), intermediate (i), and posterior (p) divisions of areas 29l, 29m, 30l, and 30m were identified. Posterior area 29 has higher neuron packing in the granular layer than anterior and intermediate divisions of area 29. A newly detected dysgranular area p30 has larger neurons in layers II-IIIab than a30 and i30 and with substantially higher NFP expression in layer IIIab of posterior areas than areas a30 and i30. Medial area 30 has larger pyramids and higher NFP expression in all layers than area 30l. The new area p30 was seen between areas p29m and p30I in both species. Finally, a ventral area p29v is present in monkeys. This latter area appears to differentiate into three divisions in human with the most extensive granular layer adjacent to layer I in p29vm and p29vl. Functional imaging has identified pRSC as part of a cognitive map which is engaged in spatial navigation and localization of personally relevant objects.


cORF and RcRE, the Rev/Rex and RRE/RxRE homologues of the human endogenous retrovirus family HTDV/HERV-K.
cORF, a protein encoded by the human endogenous retrovirus family HTDV/HERV-K, contains amino acid motifs which resemble the nuclear import and export signals of the viral regulatory proteins Rev (human immunodeficiency virus) and Rex (human T-cell leukemia virus [HTLV]). In this study, we demonstrated that cORF indeed has a Rev-like function and mapped the cORF-responsive RNA element to a sequence in the 3' long terminal repeat, a localization similar to RxRE, the responsive element in HTLV type 1. Accordingly, we have given the element the designation RcRE. cORF and RcRE stabilize unspliced and incompletely spliced viral transcripts and enhance their nuclear export via the CRM1 export pathway. So far, HTDV/HERV-K is the only endogenous retrovirus family with a complex regulation at the posttranscriptional level. It may be regarded as an intermediate in the evolution from simple to complex retroviruses.


Antimicrobial resistance in typhoidal and nontyphoidal salmonellae.
Increasing occurrence of antimicrobial resistance in both typhoidal and nontyphoidal salmonellae is a major public health problem. Recent studies documenting the occurrence and types of resistance, with particular reference to quinolones and extended spectrum cephalosporins, and new approaches to treatment are reviewed. Community and hospital-based studies in different Asian and African countries show widely variable rates of resistance in Salmonella enterica serovars Typhi and Paratyphi A. Occurrence of multidrug resistance has declined in some areas, but the incidence of decreased ciprofloxacin susceptibility has reached high levels, particularly in the Indian subcontinent, and isolates with full resistance to this antimicrobial are increasingly reported. Similar variability in resistance rates occurs among nontyphoidal salmonellae, with variation between serovars and by region. There are reports of plasmid-mediated qnr genes and a variety of extended spectrum cephalosporin resistance genes in nontyphoidal serovars. Two randomized controlled trials report gatifloxacin as a potential treatment option in enteric fever caused by multidrug-resistant isolates with decreased ciprofloxacin susceptibility. Patterns of resistance in Salmonella are constantly changing. Continual surveillance of resistance levels is critical for clinicians to keep abreast of treatment options, but it is often lacking in resource-poor regions of the world with the highest disease burden.


Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy.
Immunotherapy with checkpoint inhibitors has shown impressive results in patients with melanoma, but still many do not benefit from this line of treatment. A lack of tumor-infiltrating T cells is a common reason for therapy failure but also a loss of intratumoral dendritic cells (DCs) has been described. We used the transgenic tg(Grm1)EPv melanoma mouse strain that develops spontaneous, slow-growing tumors to perform immunological analysis during tumor progression. With flow cytometry, the frequencies of DCs and T cells at different tumor stages and the expression of the inhibitory molecules programmed cell death protein-1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells were analyzed. This was complemented with RNA-sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR) analysis to investigate the immune status of the tumors. To boost DC numbers and function, we administered Fms-related tyrosine 3 ligand (Flt3L) plus an adjuvant mix of polyI:C and anti-CD40. To enhance T cell function, we tested several checkpoint blockade antibodies. Immunological alterations were characterized in tumor and tumor-draining lymph nodes (LNs) by flow cytometry, CyTOF, microarray and RT-qPCR to understand how immune cells can control tumor growth. The specific role of migratory skin DCs was investigated by coculture of sorted DC subsets with melanoma-specific CD8+ T cells. Our study revealed that tumor progression is characterized by upregulation of checkpoint molecules and a gradual loss of the dermal conventional DC (cDC) 2 subset. Monotherapy with checkpoint blockade could not restore antitumor immunity, whereas boosting DC numbers and activation increased tumor immunogenicity. This was reflected by higher numbers of activated cDC1 and cDC2 as well as CD4+ and CD8+ T cells in treated tumors. At the same time, the DC boost approach reinforced migratory dermal DC subsets to prime gp100-specific CD8+ T cells in tumor-draining LNs that expressed PD-1/TIM-3 and produced interferon γ (IFNγ)/tumor necrosis factor α (TNFα). As a consequence, the combination of the DC boost with antibodies against PD-1 and TIM-3 released the brake from T cells, leading to improved function within the tumors and delayed tumor growth. Our results set forth the importance of skin DC in cancer immunotherapy, and demonstrates that restoring DC function is key to enhancing tumor immunogenicity and subsequently responsiveness to checkpoint blockade therapy.


[Enterosorbent-induced halting of inverse inhibition of pancreatic enzyme secretion from the duodenum].
Three series of acute experiments were carried out on dogs. In the first series pancreatic enzyme secretion (PES) was stimulated by intravenous injection of secretin and pancreozymin and selectively inhibited by intraduodenal injection of amylase; in the second series PES was induced by intraduodenal injection of acidified hydrolysin and nonselectively inhibited by intraduodenal injection of PES from the same dog; in the third series of experiments PES was stimulated by intraduodenal injection of hydrolysin, and selectively inhibited by intraduodenal injection of amylase. Activated carbon and gastric mucus were used as enterosorbents of enzymes. Their administration into the duodenum simultaneously with pancreatic amylase or pancreatic secretion eliminated or diminished their selective and nonselective inhibitory effects on pancreatic secretion of enzymes. A conclusion has been made that enterosorbents of duodenal enzymes reduce or eliminate the inhibitory action of pancreatic enzymes from the duodenal chyme on pancreatic secretion of enzymes.


Intraperitoneal carboplatin with or without interferon-alpha in advanced ovarian cancer patients with minimal residual disease at second look: a prospective randomized trial of 111 patients. G.O.N.O. Gruppo Oncologic Nord Ovest.
From June 1990 to October 1994, 111 advanced ovarian cancer patients with minimal (less than 2 cm) residual disease after platinum-based front-line chemotherapy and second-look laparotomy entered a cooperative randomized study aimed at evaluating the effectiveness and the toxicity of the addition of interferon-alpha2 to carboplatin, both intraperitoneally (ip) administered. Patients were randomized to receive either 3 courses of ip Carboplatin 400 mg/m2 Day 1 q 28 days (54 pts) (CBDCA) or ip interferon-alpha 25 x 10(6) U Day 1 + ip carboplatin 400 mg/m2 Day 2 q 28 days (57 pts) (CBDCA + IFN). Patients treated with interferon experienced more severe (WHO grade 3-4) leukopenia (28% vs 17.1%) and anemia (14% vs 4.2%). Fever (P = 0.000) and flu-like syndrome (P = 0.02) were significantly more frequent in the combination arm. No difference in gastroenteric, neurologic, or renal toxicity was observed. At a median follow-up time of 13 months (range 1-72) 71 patients showed a disease progression (31 CBDCA, 40 CBDCA + IFN) and 44 patients died (21 CBDCA, 23 CBDCA + IFN). Median progression-free survival was 11 months in the CBDCA group and 10 months in the CBDCA + IFN arm. Median survival was 22 and 29 months in CBDCA and CBDCA + IFN arm, respectively. In conclusion, intraperitoneal interferon-alpha does not seem to improve the results achievable with intraperitoneal carboplatin in this subset of patients, while the toxicity and the costs of the combination are consistently higher than with chemotherapy alone.


Phase III, placebo-controlled trial of three doses of citalopram for the treatment of hot flashes: NCCTG trial N05C9.
Up to 75% of women experience hot flashes, which can negatively impact quality of life. As hot flash physiology is not definitively understood, it cannot be assumed that effective agents represent class effects. Therefore, there is a continued need for rigorous evaluation to identify effective nonhormonal options for hot flash relief. A randomized, double-blind trial evaluated citalopram at target doses of 10, 20, or 30 mg/d versus placebo for 6 weeks. Postmenopausal women with at least 14 bothersome hot flashes per week recorded hot flashes for 7 days before starting treatment and were then titrated to their target doses. The primary end point was the change from baseline to 6 weeks in hot flash score. Two hundred fifty-four women were randomly assigned onto this study. Data for hot flash scores and frequencies showed significant improvement in hot flashes with citalopram over placebo, with no significant differences among doses. Reductions in mean hot flash scores were 2.0 (23%), 7.0 (49%), 7.7 (50%), and 10.7 (55%) for placebo and 10, 20, and 30 mg of citalopram, respectively (P <or= .002). Improvement in secondary outcomes, such as the Hot Flash Related Daily Interference Scale, was statistically superior in the 20-mg arm. Citalopram was well-tolerated, with no significant negative adverse effects. Citalopram is an effective, well-tolerated agent in managing hot flashes. There does not appear to be a significant dose response above 10 mg/d, but broader helpful effects of the agent appear to be more evident at 20 mg/d.


[Nobel prize in Medicine and Physiology 1998 for the discovery of the role of nitric oxide as a signalling molecule].
The Nobel Prize for Medicine and Physiology 1998 was awarded to three American pharmacologists: Robert F.Furchgott, Louis J. Ignarro and Ferrid Murad for their work on nitric oxide as a signalling molecule in the cardiovascular system. This discovery is a classical case of serendipity. NO is an endothelium-derived factor which mediates local vasodilation. It protects the vascular system against atherosclerosis by various effects on leukocytes and vascular permeability. NO appears to be a universal signalling molecule in the body, involved in the inflammatory response, apoptosis and neurotransmission. Its biochemistry is closely linked to that of oxygen radicals.


Undergraduate cancer education in Spain: The debate, the opportunities and the initiatives of the University Forum of the Spanish Society of Radiation Oncology (SEOR).
Most medical schools in Spain (80%) offer undergraduate training in oncology. This education is highly variable in terms of content (theory and practical training), number of credits, and the medical specialty and departmental affiliation of the professors. Much of this variability is due to university traditions in the configuration of credits and programmes, and also to the structure of the hospital-based practical training. Undergraduate medical students deserve a more coherent and modern approach to education with a strong emphasis on clinical practice. Oncology is an interdisciplinary science that requires the input of professors from multiple specialties to provide the primary body of knowledge and skills needed to obtain both a theoretical and clinical understanding of cancer. Clinical skills should be a key focus due to their importance in the current model of integrated medical management and care. Clinical radiation oncology is a traditional and comprehensive hospital-based platform for undergraduate education in oncology. In Spain, a significant number (n = 80) of radiation oncology specialists have a contractual relationship to teach university courses. Most Spanish universities (80%) have a radiation oncologist on staff, some of whom are department chairs and many others are full professors who have been hired and promoted under competitive conditions of evaluation as established by the National Agency for Quality Evaluation. The Spanish Society of Radiation Oncology (SEOR) has identified new opportunities to improve undergraduate education in oncology. In this article, we discuss proposals related to theoretical (20 items) and practical clinical training (9 items). We also describe the SEOR University Forum, which is an initiative to develop a strategic plan to implement and organize cancer education at the undergraduate level in an interdisciplinary teaching spirit and with a strong contribution from radiation oncologists.


An update on clinical and basic aspects of the protein C anticoagulant pathway.
The protein C anticoagulant pathway provides a mechanism for regulating the coagulation process through the selective inactivation of factors Va and VIIIa. Recent studies have suggested that factor V may facilitate this process and that a mutation at one of the inactivation sites can contribute to resistance to activated protein C (APC) inactivation of factor Va. This appears to be a common cause of familial thrombophilia. The control mechanisms involved in factor Va inactivation have also begun to become more clear. Membrane surfaces seem to be critical to complete factor Va inactivation, and the membrane composition requirements for optimal anticoagulant activity are distinct from those of procoagulant reactions. Specifically, the APC anticoagulant activity requires phosphatidylethanolamine, whereas the prothrombin activation complex does not. These observations may partially explain thrombotic complications with antiphospholipid antibodies in which the some antibodies have been shown to react preferentially with phosphatidylethanolamine and could, therefore, selectively block APC function. Clinically, more complete studies on partial protein C deficiency indicate that, at least within families, the deficiency is a significant risk factor for thrombosis. The impact of deficiencies on thrombotic risk suggests that protein C or other components of the pathway may be useful therapeutic agents. The limited clinical experience in treating meningococcemia, warfarin-induced skin necrosis, and homozygous protein C deficiency with protein C concentrates suggests that this approach is safe and effective.


DCD Liver Grafts Can Safely Be Used for Recipients With Grade I-II Portal Vein Thrombosis: A Multicenter Analysis.
With donation after circulatory death (DCD) liver transplantation (LT), the goal of the recipient implantation procedure is to minimize surgical complexity to avoid a tenuous environment for an already marginal graft. The presence of portal vein thrombosis (PVT) at the time of LT adds surgical complexity, yet' to date, no studies have investigated the utilization of DCD liver grafts for patients with PVT. All DCD LT performed at Mayo Clinic-Florida, Mayo Clinic-Arizona, and Mayo Clinic-Rochester from 2006 to 2020 were reviewed (N = 771). Patients with PVT at the time of transplant were graded using Yerdel classification. A 1:3 propensity match between patients with PVT and those without PVT was performed. A total of 91 (11.8%) patients with PVT undergoing DCD LT were identified. Grade I PVT was present in 62.6% of patients, grade II PVT in 27.5%, grade III in 8.8%, and grade 4 in 1.1%. At the time of LT, thromboendovenectomy was performed in 89 cases (97.8%). There was no difference in the rates of early allograft dysfunction (43.2% versus 52.4%; P = 0.13) or primary nonfunction (1.1% versus 1.1%; P = 0.41) between the DCD PVT and DCD without PVT groups, respectively. The rate of ischemic cholangiopathy was not significantly different between the DCD PVT (11.0%) and DCD without PVT groups (10.6%; P = 0.92). Graft (P = 0.58) and patient survival (P = 0.08) were similar between the 2 groups. Graft survival at 1-, 3-, and 5-y was 89.9%, 84.5%, and 79.3% in the DCD PVT group. In appropriately selected recipients with grades I-II PVT, DCD liver grafts can be utilized safely with excellent outcomes.


Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction.
Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Phenotyping patients into pathophysiologically homogeneous groups may enable better targeting of treatment. Obesity is common in HFpEF and has many cardiovascular effects, suggesting that it may be a viable candidate for phenotyping. We compared cardiovascular structure, function, and reserve capacity in subjects with obese HFpEF, those with nonobese HFpEF, and control subjects. Subjects with obese HFpEF (body mass index ≥35 kg/m2; n=99), nonobese HFpEF (body mass index <30 kg/m2; n=96), and nonobese control subjects free of HF (n=71) underwent detailed clinical assessment, echocardiography, and invasive hemodynamic exercise testing. Compared with both subjects with nonobese HFpEF and control subjects, subjects with obese HFpEF displayed increased plasma volume (3907 mL [3563-4333 mL] versus 2772 mL [2555-3133 mL], and 2680 mL [2380-3006 mL]; P<0.0001), more concentric left ventricular remodeling, greater right ventricular dilatation (base, 34±7 versus 31±6 and 30±6 mm, P=0.0005; length, 66±7 versus 61±7 and 61±7 mm, P<0.0001), more right ventricular dysfunction, increased epicardial fat thickness (10±2 versus 7±2 and 6±2 mm; P<0.0001), and greater total epicardial heart volume (945 mL [831-1105 mL] versus 797 mL [643-979 mL] and 632 mL [517-768 mL]; P<0.0001), despite lower N-terminal pro-B-type natriuretic peptide levels. Pulmonary capillary wedge pressure was correlated with body mass and plasma volume in obese HFpEF (r=0.22 and 0.27, both P<0.05) but not in nonobese HFpEF (P≥0.3). The increase in heart volumes in obese HFpEF was associated with greater pericardial restraint and heightened ventricular interdependence, reflected by increased ratio of right- to left-sided heart filling pressures (0.64±0.17 versus 0.56±0.19 and 0.53±0.20; P=0.0004), higher pulmonary venous pressure relative to left ventricular transmural pressure, and greater left ventricular eccentricity index (1.10±0.19 versus 0.99±0.06 and 0.97±0.12; P<0.0001). Interdependence was enhanced as pulmonary artery pressure load increased (P for interaction <0.05). Compared with those with nonobese HFpEF and control subjects, obese patients with HFpEF displayed worse exercise capacity (peak oxygen consumption, 7.7±2.3 versus 10.0±3.4 and12.9±4.0 mL/min·kg; P<0.0001), higher biventricular filling pressures with exercise, and depressed pulmonary artery vasodilator reserve. Obesity-related HFpEF is a genuine form of cardiac failure and a clinically relevant phenotype that may require specific treatments.


Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes.
Zika virus (ZIKV) is an emergent arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnant women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24 h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-α, IL-6, IL-10 and VEGF levels were measured at 6 h and 24 h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings suggest that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to be a major contributor in the spread of the virus in cases of vertical transmission.


Quantitative retardance imaging of biological samples using quadriwave lateral shearing interferometry.
We describe a new technique based on the use of a high-resolution quadri-wave lateral shearing interferometer to perform quantitative linear retardance and birefringence measurements on biological samples. The system combines quantitative phase images with varying polarization excitation to create retardance images. This technique is compatible with living samples and gives information about the local retardance and structure of their anisotropic components. We applied our approach to collagen fibers leading to a birefringence value of (3.4 ± 0.3) · 10(-3) and to living cells, showing that cytoskeleton can be imaged label-free.


A case of primary chylous ascites resolved within 4 months by exclusive breast-feeding.
Chylous ascites is a rare disease in infancy. A two-month-old male infant was admitted to the Department of Pediatrics with chylous ascites. No cause was found throughout the investigation period. The baby recovered spontaneously through breast-feeding without any specific treatment and chylous ascites disappeared at the age of six months.


[Can cisplatin renal toxicity be prevented?].
Cis diamminedichloroplatinum (CDDP) is a widely used anticancer agent particularly effective in the treatment of solid tumors. Dose limiting toxicity of CDDP was shown to be renal. Numerous methods to reduce this nephrotoxicity have been proposed. Hydration remains the best protection against acute CDDP nephrotoxicity in both the clinical and experimental setting. In man, no controlled studies have demonstrated the efficacy of furosemide and mannitol in the reduction of the CDDP renal toxicity. Studies have shown, however, that sodium thiosulfate offers some nephroprotection. To date, no controlled studies have demonstrated any benefit in the use of calcium channel blockers on CDDP renal toxicity in man. New drugs such as carboplatin have recently been introduced that theoretically have less renal toxicity, but evidence to support these claims are lacking. CDDP nephro protection remains a problem of current clinical interest and has yet not to be totally resolved.


West of Ireland facial injury study. Part 1.
The pattern, presentation, and volume of facial injury in the west of Ireland are subjectively different from that in the United Kingdom. We know of no prospective regional study of facial injury in Ireland to date, and nationally there is no system in place to collect data on injury. The epidemiology of facial trauma has important implications for the development of health services, the education and training of clinicians, workforce planning, prevention of injury, and promotion of health. Over one week we did a multicentre prospective data collection study involving all emergency departments in the west of Ireland. All patients who attended with facial injuries were included, and those with injuries solely of the scalp and neck were excluded. The proforma recorded patients' characteristics, details of injury and presentation, treatment and follow-up. It also included relation with sport, alcohol, assault, and animals. During the study period 325 patients were injured (5% of attendances at emergency departments in the region). The mean was 29.8%, and 68% were male. Falls caused 39% of injuries, sport 27%, and assault 14%. Sixteen percent of patients were treated in oral and maxillofacial surgery departments, and 16% in plastics, and ear, nose and throat (ENT) departments combined. There were 166 serious injuries. The busiest 24h were from Saturday at 09:00. Forty-five percent presented between 1 and 2h after injury. Different approaches and methods may be needed to prevent injury because of differences in aetiology, and staff in emergency departments will need training in this area, given the large proportion of facial injuries in the region.


Long-term potentiation of human visual evoked responses.
Long-term potentiation (LTP) is a candidate synaptic mechanism underlying learning and memory that has been studied extensively at the cellular and molecular level in laboratory animals. To date, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non-human preparations. Inquiry into the functional significance of LTP has been hindered by the absence of a human model. Here we give the first demonstration that the rapid repetitive presentation of a visual checkerboard (a photic 'tetanus') leads to a persistent enhancement of one of the early components of the visual evoked potential in normal humans. The potentiated response is largest in the hemisphere contralateral to the tetanized visual hemifield and is limited to one component of the visual evoked response (the N1b). The selective potentiation of only the N1b component makes overall brain excitability changes unlikely and suggests that the effect is due instead to an LTP process. While LTP is known to exist in the human brain, the ability to elicit LTP from non-surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders.


Interactions between cognition, compression, and listening conditions: effects on speech-in-noise performance in a two-channel hearing aid.
This study which included 23 experienced hearing aid users replicated several of the experiments reported in Gatehouse et al (2003, 2006) with new speech test material, language, and test procedure. The performance measure used was SNR required for 80% correct words in a sentence test. Consistent with Gatehouse et al, this study indicated that subjects showing a low score in a cognitive test (visual letter monitoring) performed better in the speech recognition test with slow time constants than with fast time constants, and performed better in unmodulated noise than in modulated noise, while subjects with high scores on the cognitive test showed the opposite pattern. Furthermore, cognitive test scores were significantly correlated with the differential advantage of fast-acting versus slow-acting compression in conditions of modulated noise. The pure tone average threshold explained 30% of the variance in aided speech recognition in noise under relatively simple listening conditions, while cognitive test scores explained about 40% of the variance under more complex, fluctuating listening conditions, where the pure tone average explained less than 5% of the variance. This suggests that speech recognition under steady-state noise conditions may underestimate the role of cognition in real-life listening.


Valosin-containing protein is a key mediator between autophagic cell death and apoptosis in adult hippocampal neural stem cells following insulin withdrawal.
Programmed cell death (PCD) plays essential roles in the regulation of survival and function of neural stem cells (NSCs). Abnormal regulation of this process is associated with developmental and degenerative neuronal disorders. However, the mechanisms underlying the PCD of NSCs remain largely unknown. Understanding the mechanisms of PCD in NSCs is crucial for exploring therapeutic strategies for the treatment of neurodegenerative diseases. We have previously reported that adult rat hippocampal neural stem (HCN) cells undergo autophagic cell death (ACD) following insulin withdrawal without apoptotic signs despite their normal apoptotic capabilities. It is unknown how interconnection between ACD and apoptosis is mediated in HCN cells. Valosin-containing protein (VCP) is known to be essential for autophagosome maturation in mammalian cells. VCP is abundantly expressed in HCN cells compared to hippocampal tissue and neurons. Pharmacological and genetic inhibition of VCP at basal state in the presence of insulin modestly impaired autophagic flux, consistent with its known role in autophagosome maturation. Of note, VCP inaction in insulin-deprived HCN cells significantly decreased ACD and down-regulated autophagy initiation signals with robust induction of apoptosis. Overall autophagy level was also substantially reduced, suggesting the novel roles of VCP at initial step of autophagy. Taken together, these data demonstrate that VCP may play an essential role in the initiation of autophagy and mediation of crosstalk between ACD and apoptosis in HCN cells when autophagy level is high upon insulin withdrawal. This is the first report on the role of VCP in regulation of NSC cell death. Elucidating the mechanism by which VCP regulates the crosstalk of ACD and apoptosis will contribute to understanding the molecular mechanism of PCD in NSCs.


Biofilm models for the food industry: hot spots for plasmid transfer?
Biofilms represent a substantial problem in the food industry, with food spoilage, equipment failure, and public health aspects to consider. Besides, biofilms may be a hot spot for plasmid transfer, by which antibiotic resistance can be disseminated to potential foodborne pathogens. This study investigated biomass and plasmid transfer in dual-species (Pseudomonas putida and Escherichia coli) biofilm models relevant to the food industry. Two different configurations (flow-through and drip-flow) and two different inoculation procedures (donor-recipient and recipient-donor) were tested. The drip-flow configuration integrated stainless steel coupons in the setup while the flow-through configuration included a glass flow cell and silicone tubing. The highest biomass density [10 log (cells cm-²)] was obtained in the silicone tubing when first the recipient strain was inoculated. High plasmid transfer ratios, up to 1/10 (transconjugants/total bacteria), were found. Depending on the order of inoculation, a difference in transfer efficiency between the biofilm models could be found. The ease by which the multiresistance plasmid was transferred highlights the importance of biofilms in the food industry as hot spots for the acquisition of multiresistance plasmids. This can impede the treatment of foodborne illnesses if pathogens acquire this multiresistance in or from the biofilm.


Familial Monkeypox Virus Infection Involving 2 Young Children.
We report intrafamilial transmission of monkeypox virus to all members of a family (father, mother, and 2 children). Case reports in young children have been extremely rare during the 2022 mpox outbreak. Their clinical signs were mild, and clinical diagnosis would be difficult without knowledge of the father's monkeypox virus infection.


Lactation performance and feeding behavior of dairy cows supplemented via automatic feeders with soy hulls or barley based pellets.
The potential of soy hulls to replace barley grain in pellets supplemented to lactating cows was measured in automatic concentrate feeders (ACF). Thirty-six cows were divided into 2 equal groups and fed 1 of the 2 experimental pellet supplements individually for 7 wk. All cows were group-fed a basic mixture along the feeding lane (~64% of dietary DM) plus a pelleted additive containing 50% barley or soy hulls as barley replacer, fed individually to each cow via the ACF in 6 feeding windows. Extent and rate of in vitro DM digestibility were similar for both types of pellets; however, NDF content and digestibility were higher in the soy hulls pellets. Average number of rewarded cow visits at the ACF, pellets intake per meal, and accumulated intake of pellets (8.64 kg/d DM) were similar in the 2 experimental groups. Most pellets were consumed during day and night in the first 2 h after feeding windows were opened. Total visits per day in the ACF and the maximal interval between visits were similar for the 2 pellets, indicating similar attractiveness to the cow. Predicted intake of the basic mixture was similar in both groups (14.8 to 15.1 kg of DM/d). Higher milk fat content was observed in the soy hulls-fed cows, whereas higher milk protein content was found in the barley-fed cows. Milk yield was similar in both groups. Data suggest that replacement of barley pellets with soy hulls pellets may slightly enhance milk fat while reducing milk protein production for dairy herds using automatic milking systems.


Role of the DECAF Score in Predicting In-hospital Mortality in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Introduction Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) can be fatal. In 2012, a comprehensive score was developed to predict the risk of in-hospital mortality in AECOPD called the dyspnoea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score. We conducted this study to assess the value of the DECAF score as a clinical prediction tool that claims to stratify all patients with AECOPD by risk accurately. Methods We conducted a prospective study of patients admitted to the intensive care unit (ICU) of the Department of Pulmonology in Civil Hospital, Jamshoro, from January 2016 to December 2018. Our inclusion criteria were that the patient must be age 35 years or older, have a primary clinical diagnosis of AECOPD, spirometry consistent with airflow obstruction, and have a smoking history of ≥10 cigarette pack per year. We excluded patients who had domiciliary ventilation, survival-limiting comorbidities (such as metastatic malignancy), and a primary reason for admission other than AECOPD. All sociodemographic data were collected at the time of admission, including age, gender, co-morbidities, housebound status, and number of previous AECOPD. Clinical data collected included plain chest x-ray, spirometry, electrocardiogram, arterial blood gases analysis, complete blood count, kidney function test, liver function test, and serum electrolytes. A DECAF score was applied to each patient. We noted in-hospital mortality and compared the characteristics of survivors and non-survivors. Data were analyzed using IBM SPSS for Windows, version 19.0 (IBM Corp, Armonk, NY). Results A total of 162 patients were included in the study. The mortality rate was 13% (n=21). More survivors had a DECAF score from zero to three than non-survivors. The difference in the number of survivors vs. non-survivors was statistically significant for DECAF scores zero and one. For DECAF scores four and five, there were more patients in the "non-survivors" group, and the differences were statistically significant. None of the patients scored six on DECAF. Conclusion Patients with a DECAF score of four or higher have a significant risk of mortality. DECAF is a simple tool that predicts mortality that incorporates routinely available indices to stratify AECOPD patients into mortality risk categories.


A Public Health Perspective on School Dropout and Adult Outcomes: A Prospective Study of Risk and Protective Factors From Age 5 to 27 Years.
This study aimed to advance a public health perspective on links between education and health by examining risk and protective factors that might alter the relation between dropping out of high school and subsequent negative outcomes. A community sample (N = 585) was followed from age 5 to 27 years. Data included self and parent reports, peer sociometric nominations, and observed mother-teen interactions. High school dropouts were up to four times more likely to experience individual negative outcomes (being arrested, fired, or on government assistance, using illicit substances, having poor health) by age 27 years and 24 times more likely compared to graduates to experience as many as four or more negative outcomes. Links between dropout and negative outcomes were more pronounced for individuals who were in low socioeconomic status families at age 5 years, rejected by elementary school peers, and became parents at a younger age; the dropout effect was decreased for individuals who had been treated for a behavioral, emotional, or drug problem by age 24 years. Addressing school dropout as a public health problem has the potential to improve the lives of dropouts and reduce societal costs of dropping out.