Chemokines and their receptors in Atherosclerosis.
Atherosclerosis, a chronic inflammatory disease of the medium- and large-sized arteries, is the main underlying cause of cardiovascular diseases (CVDs) most often leading to a myocardial infarction or stroke. However, atherosclerosis can also develop without this clinical manifestation. The pathophysiology of atherosclerosis is very complex and consists of many cells and molecules interacting with each other. Over the last years, chemokines (small 8-12 kDa cytokines with chemotactic properties) have been identified as key players in atherogenesis. However, this remains a very active and dynamic field of research. Here, we will give an overview of the current knowledge about the involvement of chemokines in all phases of atherosclerotic lesion development. Furthermore, we will focus on two chemokines that recently have been associated with atherogenesis, CXCL12, and macrophage migration inhibitory factor (MIF). Both chemokines play a crucial role in leukocyte recruitment and arrest, a critical step in atherosclerosis development. MIF has shown to be a more pro-inflammatory and thus pro-atherogenic chemokine, instead CXCL12 seems to have a more protective function. However, results about this protective role are still quite debatable. Future research will further elucidate the precise role of these chemokines in atherosclerosis and determine the potential of chemokine-based therapies.


The mediating role of self-efficacy in the development of entrepreneurial intentions.
The purpose of this study was to investigate the mediating role of self-efficacy in the development of students' intentions to become entrepreneurs. The authors used structural equation modeling with a sample of 265 master of business administration students across 5 universities to test their hypotheses. The results showed that the effects of perceived learning from entrepreneurship-related courses, previous entrepreneurial experience, and risk propensity on entrepreneurial intentions were fully mediated by entrepreneurial self-efficacy. Contrary to expectations, gender was not mediated by self-efficacy but had a direct effect such that women reported lower entrepreneurial career intentions. The authors discuss practical implications and directions for future research.


Chemotherapy-Induced Febrile Neutropenia in Solid Tumours.
Febrile neutropaenia (FN) is defined as an oral temperature of >38.3°C or two consecutive readings of >38.0°C for 2 hours and an absolute neutrophil count (ANC) of <0.5 × 109/l, or expected to fall below 0.5 × 109/l. Fever is one of the characteristic symptoms of FN and is usually associated with the presence of an infection caused by various microorganisms. The incidence and epidemiology of FN are variable based on different factors: (type of cancer, the age/sex of the patient, chemotherapy type /number of cycles). FN remains one of the most common and risky complications of chemotherapy which occurred within 6-8 days with standard chemotherapy and it is occurred as about 7-8/1000 patients receiving treatment with chemotherapeutic agents. There is a clear relationship between the severity of neutropaenia (which directly influences the incidence of FN) and the intensity of chemotherapy. Currently, the different regimens are classified as producing a high risk (>20%), an intermediate risk (10%-20%) or a low risk (<10%) of FN. The causative organisms including either bacteria, fungi or viruses. The bacteria Gram-positive (currently dominating) and Gram-negative (Dominant in the 1970s), are usually the main microorganisms responsible for FN and cause complicated infections. Although the morbidity and mortality rates of FN have decreased over the years due to use of proper antibiotic treatment, preventive measures and use the standardrisk management plan as per guidelines but it is still one of oncological emergency. FN is responsible for considerable morbidity as 20%-30% of patient's present complications that require in-hospital management, with an overall in-hospital mortality of ~10%.


Predictive value of D-dimer and analysis of risk factors in pregnant women with suspected pulmonary embolism after cesarean section.
Acute pulmonary embolism (PE) is one of the leading causes of maternal mortality, and cesarean section is an established independent risk factor for PE. The diagnostic utility of D-dimer for PE in non-pregnant women has been well-established, but its role in women with suspected PE after cesarean section is unclear. Furthermore, the optimal threshold level in this patient population is unknown. Traditional D-dimer levels have low diagnostic specificity, resulting in many pregnant women being exposed to potentially harmful radiation despite negative diagnostic imaging results. This research aimed to optimize the clinical threshold for D-dimer to improve specificity while ensuring high sensitivity and to identify risk factors for PE after cesarean section. This retrospective study of 289 women who underwent diagnostic imaging (ventilation/perfusion [V/Q] or computed tomographic pulmonary angiography [CTPA]) for suspected acute PE after cesarean delivery from 2010 to 2021 was conducted. Clinical data and laboratory indicators within 24 h postpartum including D-dimer levels were collected for analyses. The final analysis included 125 patients, among whom 33 were diagnosed with acute PE (incidence of 11.42%, 95% confidence interval 7.7-15.1). The receiver operating characteristic curve analysis suggested that a D-dimer cut-off value of 800 ng/mL had specificity of 25.26% and sensitivity of 100% for detecting PE. The cut-off value was adjusted to 1000 ng/mL with a specificity of 34.74% and a sensitivity of 96.67%. Using a D-dimer cut-off value of 800 ng/mL (instead of the conventional value of 500 ng/mL) increased the number of patients excluded from suspected PE from 9.6 to 18.4% without additional false-negative results. Of note, a history of known thrombophilia was significantly more common in patients with PE than in those without (P < 0.05). No other independent risk factors were noted in our study. The D-dimer cut-off value of 800 ng/mL ensures high sensitivity and increases specificity compared to the conventional threshold of 500 ng/mL. Utilizing this higher threshold can reduce the number of unnecessary CT and subsequently unnecessary radiation exposure, in women after cesarean delivery. Prospective studies should also be conducted to verify these results.


Clinical aspects of calcium pyrophosphate dihydrate crystal deposition.
CPPD deposition occurs in a wide variety of clinical settings, most commonly as an age-related phenomenon in the absence of other joint abnormality. Although our knowledge of CPPD and other intra-articular particles has increased in the last decade, the role of CPPD remains unclear. The paradox of asymptomatic deposition of phlogistic crystals, the wide spectrum of clinical presentation, and the lack of disease specificity, however, have challenged recognition of pyrophosphate arthropathy (PA) as a separate, distinct disease entity and led to reappraisal of earlier concepts of crystal deposition disease. In this article, clinical aspects of PA will first be presented; the validity of PA as a discrete arthropathy will then be discussed.


[Mycobacterium abscessus infection in insulin injection sites in a diabetic patient].
Insulin injection site abscesses have been attributed to pyogenic streptococci and Staphylococcus aureus. In this report, the authors describe a patient in whom Mycobacterium abscessus was isolated from one of multiple insulin injection sites. The article reviews six additional cases of rapidly growing Mycobacteria identified as the causative agent of skin infections at insulin injection sites. In most cases, precise identification of the source of infection was not successful. Possibly, inadequate skin preparation prior to injection or a contaminated insulin ampoule resulted in these infections.


Differentiation of the toxicities of silver nanoparticles and silver ions to the Japanese medaka (Oryzias latipes) and the cladoceran Daphnia magna.
Silver nanoparticles (AgNPs) are increasingly used in various fields. However, little is known about the environmental effects of widespread use of products containing AgNPs. The objective of this study was to determine the ecotoxicity caused by AgNPs. The 48-h effective concentration 50 (EC(50)) values for Daphnia magna of suspensions of 60 nm and 300 nm AgNPs were 1.0 (95% confidence interval [CI] = 0.1-1.3) and 1.4 (95% CI = 0.3-2.1) μg Ag/l, respectively. The 96 h LC(50) values for Oryzias latipes of 60 nm and 300 nm AgNP suspensions were 28 (95% CI = 23-34) and 67 (95% CI = 45-108) μg Ag/l, respectively. To show that toxicity is caused only by Ag(+) and not by AgNPs, Ag(+) was adsorbed onto the synthesized sorbents packed in a column and D. magna was exposed to the column-passed-300 nm AgNP suspensions. There was no acute toxicity with the AgNP suspensions not containing Ag(+).


Biokinetics of 90Sr in Male Nonhuman Primates.
The current study tests the hypothesis that the biokinetics of Sr can be represented by simplification of the ICRP publication 78 Sr model. Default and proposed models were evaluated by their ability to predict injected activity and more thoroughly define the activity residing in the skeleton of rhesus monkeys. The data obtained from studies done by Patricia Durbin and her colleagues at the Lawrence Berkley National Laboratory were used to create a profile of the activity residing in the skeleton at the time of sacrifice. Post mortem data along with periodic whole body count data were used to optimize the biokinetic parameters using the Integrated Modules for Bioassay Analysis (IMBA), Weighted Likelihood Monte-Carlo Sampling (WeLMoS) program to better predict the intake and fit of the bioassay data. Analysis of the default ICRP 78 parameters resulted in an overprediction of activity in the skeleton for a male cohort by as much as 180%. Using Monte Carlo sampling methods, three models were developed and optimized for a composite cohort of male monkeys. Of the three developed models, one model proved to have the best predictive capabilities. The optimized model C obtained for the male cohort was then tested on a validation cohort to test predictive capabilities. Using the optimized model C parameters, the ability to predict activity in the skeleton was improved in comparison to ICRP 78. Prediction of the intake from bioassay data was also improved by a factor of 2 in comparison to ICRP 78. The results suggest that the modified transfer rates of model C could be used as default parameters for biokinetic nonhuman primate modeling and potentially extrapolated to humans.


LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice.
The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell-extracellular matrix interaction and adhesion. Here, we report that deleting Pinch1 in limb mesenchymal stem cells (MSCs) and Pinch2 globally (double knockout; dKO) in mice causes severe chondrodysplasia, while single mutant mice do not display marked defects. Pinch deletion decreases chondrocyte proliferation, accelerates cell differentiation and disrupts column formation. Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone (PZ) chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone (HZ) chondrocytes. Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes, reduces bone formation, and increases bone resorption, leading to low bone mass. In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes. Through its C-terminal region, Pinch1 interacts with Smad2/3 proteins. Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells (BMSCs). Pinch loss reduces TGF-β-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs. Interestingly, compared to those from single mutant mice, BMSCs from dKO mice express dramatically lower protein levels of β-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity. Finally, ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening. Collectively, our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms.


Adaptation of a haptic robot in a 3T fMRI.
Functional magnetic resonance imaging (fMRI) provides excellent functional brain imaging via the BOLD signal with advantages including non-ionizing radiation, millimeter spatial accuracy of anatomical and functional data, and nearly real-time analyses. Haptic robots provide precise measurement and control of position and force of a cursor in a reasonably confined space. Here we combine these two technologies to allow precision experiments involving motor control with haptic/tactile environment interaction such as reaching or grasping. The basic idea is to attach an 8 foot end effecter supported in the center to the robot allowing the subject to use the robot, but shielding it and keeping it out of the most extreme part of the magnetic field from the fMRI machine (Figure 1). The Phantom Premium 3.0, 6DoF, high-force robot (SensAble Technologies, Inc.) is an excellent choice for providing force-feedback in virtual reality experiments, but it is inherently non-MR safe, introduces significant noise to the sensitive fMRI equipment, and its electric motors may be affected by the fMRI's strongly varying magnetic field. We have constructed a table and shielding system that allows the robot to be safely introduced into the fMRI environment and limits both the degradation of the fMRI signal by the electrically noisy motors and the degradation of the electric motor performance by the strongly varying magnetic field of the fMRI. With the shield, the signal to noise ratio (SNR: mean signal/noise standard deviation) of the fMRI goes from a baseline of ~380 to ~330, and ~250 without the shielding. The remaining noise appears to be uncorrelated and does not add artifacts to the fMRI of a test sphere (Figure 2). The long, stiff handle allows placement of the robot out of range of the most strongly varying parts of the magnetic field so there is no significant effect of the fMRI on the robot. The effect of the handle on the robot's kinematics is minimal since it is lightweight (~2.6 lbs) but extremely stiff 3/4" graphite and well balanced on the 3DoF joint in the middle. The end result is an fMRI compatible, haptic system with about 1 cubic foot of working space, and, when combined with virtual reality, it allows for a new set of experiments to be performed in the fMRI environment including naturalistic reaching, passive displacement of the limb and haptic perception, adaptation learning in varying force fields, or texture identification.


Energy dose and other variables possibly affecting ventricular defibrillation during cardiac surgery.
Previous studies have suggested that shocks of 5-10 J are required for direct ventricular defibrillation during open heart surgery. However, the efficacy of shocks of less than 5 J, the effects of thermal, biochemical, and temporal factors, and the influence of disease process on defibrillation have not been fully investigated, particularly with modern techniques of myocardial preservation. The purpose of this prospective study in 150 adult cardiac surgical patients was to evaluate the energy, current, and myocardial resistance with low energy DC shocks of 1, 2.5, and 5 J and to relate which biochemical, temporal, thermal, or other factors influence the outcome of a DC shock. Twenty-eight percent of shocks of 1 J and 55% of shocks of 2.5 J produced defibrillation. Above 2.5 J, the success rate reached a plateau at 55%. Other factors associated with the success of DC shocks were high normal serum potassium levels, high PaO2, high ionized calcium levels, and longer reperfusion times at mean arterial and coronary perfusion pressures above 50 mm Hg. Disease process may also play a role because patients with valvular heart disease were more difficult to defibrillate. Heart weight and thickness of ventricular myocardium, measured angiographically, appeared less important in direct defibrillation, except with 1 J shocks when thinner-walled ventricles defibrillated more easily.


Early innate and longer-term adaptive cutaneous immunoinflammatory responses during primary infestation with the sheep scab mite, Psoroptes ovis.
Clinical observation has indicated that Psoroptes ovis mites provoke cutaneous inflammation within hours of experimental infestation, but the nature of this reaction has not been described. After infestation of naive sheep with ovigerous P. ovis mites, significant influxes of eosinophils (P<0.004) and neutrophils (P<0.001) were detected within 24 h. A significant (P<0.001) increase in mast cell numbers was observed by 96 h post-infestation. In addition, marked degenerative and proliferative epidermal lesions were evident 24 and 96 h, respectively, after infestation. The influence of the later, adaptive response on the cellular infiltrate at the advancing margin of the lesion and the original site of infestation was also monitored. Mast cell numbers were greatest at 21 days while recruitment of eosinophils and neutrophils was maximal 63 days after infestation. Lesional severity was particularly pronounced from 42 to 63 days after infestation, but significant resolution had occurred by 84 days. Pathological changes at the advancing margin of the lesion were more severe than at the initial site of infestation, and this was reflected by the numbers of mites present. These data suggest that P. ovis elicits an early innate cutaneous response that is subsequently augmented by the development of an adaptive immune response, the intensity of which corresponds to the local population density of mites.


Advances in Multiple Sclerosis Research-Series I.
Designing immunotherapeutics, drugs, and anti-inflammatory reagents has been at the forefront of autoimmune research, in particular, multiple sclerosis, for over 20 years. Delivery methods that are used to modulate effective and long-lasting immune responses have been the major focus. This Special Issue, "Advances in Multiple Sclerosis Research-Series I", focused on delivery methods used for immunotherapeutic approaches, drug design, anti-inflammatories, identification of markers, methods for detection and monitoring MS and treatment modalities. The issue gained much attention with 20 publications, and, as a result, we launched Series II with the deadline for submission being 30 April 2021.


Suppression and enhancement of diffusion in disordered dynamical systems.
The impact of quenched disorder on deterministic diffusion in chaotic dynamical systems is studied. As a simple example, we consider piecewise linear maps on the line. In computer simulations we find a complex scenario of multiple suppression and enhancement of normal diffusion, under variation of the perturbation strength. These results are explained by a theoretical approximation, showing that the oscillations emerge as a direct consequence of the unperturbed diffusion coefficient, which is known to be a fractal function of a control parameter.


[A case of ischemic proctitis caused by impaired venous blood flow 11 months after surgery for sigmoid colon cancer].
A Japanese male in his 50s was presented to our hospital with the chief complaint of positive fecal immunochemical test. He had a history of hypertension. He underwent colonoscopy and was diagnosed with sigmoid colon cancer. He also underwent laparoscopic sigmoid colectomy with D3 lymph node dissection for sigmoid colon cancer. The inferior mesenteric artery and inferior mesenteric vein were amputated at the root of the vessels. The patient received adjuvant chemotherapy and was recurrence-free. Eleven months after the surgery, lower abdominal pain during defecation appeared. Contrast-enhanced computed tomography (CT) and colonoscopy showed marked rectal mucosal edema and increased fatty tissue density (dirty fat sign) around the anorectal side of the anastomosis. Intestinal blood flow was maintained. There were many fine blood vessels around the rectal wall, and the amputated distal part of the superior rectal artery was retrogradely contrasted. Amputated superior rectal artery and superior rectal vein were dilated than before. Colonoscopy revealed mucosal redness, edema, and easy bleeding on the anorectal side of the anastomosis. Abdominal contrast-enhanced 3D-CT showed increased arterial blood flow and increased fine blood vessels around the rectal wall. It suggested the presence of an arteriovenous fistula and venous congestion. Conservative treatment with total parenteral nutrition and prednisolone infusion did not improve the patient's condition, and a colostomy was performed. After colostomy, the pain improved, and the CT scan of the abdomen showed improvement in arterial blood flow and venous congestion. Colostomy was closed after 10 months. There has been no relapse since the closure of the colostomy. There are few reports on ischemic proctitis on the anorectal side of the anastomosis after colon cancer resection due to impaired venous blood flow.


Development and validation of the Family Motivational Climate Questionnaire (FMC-Q).
The goal of this study was to develop and validate the Family Motivational Climate Questionnaire (FMCQ). Parental involvement (PI) affects children's academic orientations. However, PI questionnaires had not considered parenting behaviours from the perspective of motivational theories. It was therefore decided to develop the FMCQ. 570 Secondary-School students formed the sample. To validate the FMCQ, confirmatory factor analyses, reliability analysis and correlation and regression analyses were conducted. Children's attribution to parents of perceived change in motivational variables affecting achievement, were used as external criteria. Results support most of the hypotheses either related to the FMCQ structure or to its moderating role as predictor of school achievement and of attribution to parents of changes in different motivational variables --interest, effort, perceived ability, success expectancies, resilience, and satisfaction. The results underline the importance of acting on FMC-components in order to improve Children's motivation and achievement.


Molecular phylogenetic studies of Brassica, rorippa, arabidopsis and allied genera based on the internal transcribed spacer region of 18S-25S rDNA.
The phylogenetic relationships of nine genera in four tribes of the family Brassicaceae were estimated from the sequences of the internal transcribed spacer region (ITS) of the 18S-25S nuclear ribosomal DNA. The entire ITS region of 16 accessions belonging to 10 species of seven genera was sequenced. Eight published sequences of Brassicaceae were also used. A total of 27 sequences were included in this study; four of them were found to be pseudogenes. Both the neighbor-joining and the parsimony trees suggest that the nine genera can be divided into three groups: (1) Arabidopsis, Cardaminopsis, Capsella, and Lepidium; (2) Rorippa and Cardamine; and (3) Brassica, Sinapis, and Raphanus. In contradiction to the proposal that Cardaminopsis and Arabidopsis be put into an expanded tribe Arabideae, our data show that these two genera are more closely related to Capsella and Lepidium (tribe Lepidieae) than to Rorippa and Cardamine (tribe Arabideae). Further, our data show that within the tribe Brassiceae, Raphanus is more closely related to B. nigra than to the B. oleracea/B. rapa clade. This result is in agreement with the nuclear data obtained in several studies, but is in conflict with the RFLP data of mitochondrial and chloroplast DNA. As pointed out by previous authors, it is possible that Raphanus is a hybrid between the B. nigra and B. oleracea/B. rapa lineages with the latter as the maternal parent.


Hydroxyethylamine isostere of an HIV-1 protease inhibitor prefers its amine to the hydroxy group in binding to catalytic aspartates. A synchrotron study of HIV-1 protease in complex with a peptidomimetic inhibitor.
A complex structure of HIV-1 protease with a hydroxyethylamine-containing inhibitor Boc-Phe-Psi[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2 has been determined by X-ray diffraction to 1.8 A resolution. The inhibitor is bound in the active site of the protease dimer with its hydroxyethylamine isostere participating in hydrogen bonds to the catalytic aspartates 25 and 25' and glycine 27' of the active site triads via five hydrogen bonds. The isostere amine interactions with the catalytic aspartates result in a displacement of the isostere hydroxy group in comparison with the common position known for analogous hydroxyethylamine containing inhibitors. A comparison with another inhibitor of this series shows that the change of one atom of the P2' side chain (Glu/Gln) leads to an altered ability of creating hydrogen bonds to the active site and within the inhibitor molecule. The diffraction data collected at a synchrotron radiation source enabled a detailed analysis of the complex solvation and of alternative conformations of protein side chains.


Genotypic variation in C and N isotope discrimination suggests local adaptation of heart-leaved willow.
Plants acquire multiple resources from the environment and may need to adjust and/or balance their respective resource-use efficiencies to maximize grow and survival, in a locally adaptive manner. In this study, tissue and whole-plant carbon (C) isotopic composition (δ13C) and carbon/nitrogen (C/N) ratios provided long-term measures of use efficiencies for water (WUE) and nitrogen (NUE), and a nitrogen (N) isotopic composition (δ15N)-based mass balance model was used to estimate traits related to N uptake and assimilation in heart-leaved willow (Salix eriocephala Michx.). In an initial common garden experiment consisting of 34 populations, we found population-level variation in δ13C, C/N ratio and δ15N, indicating different patterns in WUE, NUE and N uptake and assimilation. Although there was no relationship between foliar δ13C and C/N ratios among populations, there was a significant negative correlation between these measures across all individuals, implying a genetic and/or plastic trade-off between WUE and NUE not associated with local adaptation. To eliminate any environmental effect, we grew a subset of 21 genotypes hydroponically with nitrate as the sole N source and detected significant variation in δ13C, δ15N and C/N ratios. Variation in δ15N was mainly due to genotypic differences in the nitrate efflux/influx ratio (E/I) at the root. Both experiments suggested clinal variation in δ15N (and thus N uptake efficiency) with latitude of origin, which may relate to water availability and could contribute to global patterns in ecosystem δ15N. There was a tendency for genotypes with higher WUE to come from more water-replete sites with shorter and cooler growing seasons. We found that δ13C, C/N ratio and E/I were not inter-correlated, suggesting that the selection of growth, WUE, NUE and N uptake efficiency can occur without trade-off.


Cultural Competency and Surgical Decision Making in Otolaryngology.
Given the high prevalence of otolaryngology infections such as tonsillitis, otitis, and pharyngitis in low and middle income countries, the field of global otolaryngology continues to grow to accommodate patients around the world. This commentary focuses on best practices in transcultural communications between US doctors and foreign patients with an emphasis on cultural competency. We use alternative medicine as an exemplar for how to collaborate with patients to develop treatment plans that respect their cultural beliefs and lifestyles. Rather than assigning value to the patient's alternative medicine practices, we believe that instructing and counseling a patient on how to incorporate follow-up visits and rehabilitation after allopathic medical procedures such as surgical tonsillectomy should be done in a way that respects the patient's preexisting health regimen. By doing so, these new aspects of their health care will take a discrete place in their wellness practices and engender more trust and better health outcomes.


Identification of New ATG8s-Binding Proteins with Canonical LC3-Interacting Region in Autophagosomes of Barley Callus.
Autophagy is essential to maintain cellular homeostasis for normal cell growth and development. In selective autophagy, ATG8 plays a crucial role in cargo target recognition by binding to various adaptors and receptors with the ATG8-interacting motif, also known as the LC3-interacting region (LIR). However, the process of autophagy in the callus, as a proliferating cell type, is largely unknown. In this study, we overexpressed green fluorescent protein (GFP)-ATG8a and GFP-ATG8b transgenic barley callus and checked their autophagic activities. We identified five new ATG8 candidate interactors containing the canonical LIR motif by using immunoprecipitation coupled with mass spectrometry: RPP3, COPE, NCLN, RAE1, and CTSL. The binding activities between these candidate interactors and ATG8 were further demonstrated in the punctate structure. Notably, RPP3 was colocalized in ATG8-labeled autophagosomes under tunicamycin-induced ER stress. GST pull-down assays showed that the interaction between RPP3 and ATG8 could be prevented by mutating the LIRs region of RPP3 or the LIR docking site (LDS) of ATG8, suggesting that RPP3 directly interacted with ATG8 in an LIR-dependent manner via the LDS. Our findings would provide the basis for further investigations on novel receptors and functions of autophagy in plants, especially in the physiological state of cell de-differentiation.


Emergence of Transdiagnostic Treatments for PTSD and Posttraumatic Distress.
Both theoretical and empirical findings have demonstrated similarities across diagnoses, leading to a growing interest in transdiagnostic interventions. Most of the evidence supporting transdiagnostic treatment has accumulated for depression, anxiety, and eating disorders, with minimal attention given to posttraumatic stress disorder and other reactions to traumatic stressors. Although single-diagnosis protocols are effective for posttraumatic stress disorder (PTSD) and other trauma-related disorders, in principle, transdiagnostic approaches may have beneficial applications within a traumatized population. This paper defines different types of transdiagnostic treatments, reviews transdiagnostic approaches used in related disorders, and discusses their applicability to PTSD. Examples are drawn from existing transdiagnostic treatments in order to provide a framework for the application of such interventions to the field of traumatic stress. Implications for implementation and dissemination are also discussed.


Developing a planning model to estimate future cash flows.
Financial managers are discovering that net income and other traditional measures of cash flow may not provide them with the flexibility needed for comprehensive internal planning and control. By using a discretionary cash flow model, financial managers have a forecasting tool that can help them measure anticipated cash flows, and make better decisions concerning financing alternatives, capital expansion, and performance appraisal.


Generating predictions: lesion evidence on the role of left inferior frontal cortex in rapid syntactic analysis.
A well-documented phenomenon in event-related electroencephalography (EEG) and magnetoencephalography (MEG) studies on language processing is that syntactic violations of different types elicit negativities as early as 100 msec after the violation point. Recently, these responses have been associated with activations in or very close to sensory cortices, suggesting the involvement of basic sensory mechanisms in the detection of syntactic violations. The present study investigated whether intact auditory cortices and adjacent temporal regions are sufficient to generate early syntactic negativities in the auditory event-related potential (ERP). We tested ten clinically non-aphasic patients with left inferior frontal lesions, but intact temporal cortices in a passive auditory ERP paradigm that had reliably elicited early negativities in response to violations of subject-verb agreement and word category in the past. Subject-verb agreement violations failed to elicit early grammaticality effects in these patients, whereas a group of ten age-matched controls showed a reliable early negativity. This finding supports the idea that sensory aspects of syntactic analysis as reflected in early syntactic negativities critically depend on top-down predictions generated by the left inferior frontal cortex. In contrast, word category violations elicited a small, marginally significant early negativity both in controls and patients, suggesting an additional involvement of temporal regions in early phrase structure processing. In an additional auditory oddball experiment patients showed a regular P300, but no N2b component in response to deviant tones, indicating that their deficit in generating sensory predictions extends beyond the language domain.


Engineering Trojan-horse bacteria to fight cancer.
In this issue of Blood, Massa et al demonstrated that tumor-tropic bacteria engineered to express specific cancer-related antibodies can recognize and specifically destroy the malignant cells by infecting them with toxic cargo. The findings provide an essential step in establishing the novel approach of enlisting engineered bacteria that speak cancer's language to outsmart and defeat cancer


Morphology, in vivo distribution and antitumor activity of bexarotene nanocrystals in lung cancer.
The objective of this study was to develop and evaluate the morphology, biodistribution and antitumor activity of bexarotene nanocrystals delivery system. The morphology was investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscope and bexarotene nanocrystals exhibited the advantages of making the efficacy more steady and durable compared with control group in lung with less cardiac accumulation as shown by biodistribution studies in vivo. In addition, MTT assay, flow cytometry analysis, observation of morphological changes and apoptotic body demonstrated that bexarotene nanocrystals could significantly enhance the in vitro cytotoxicity and induced G1 cycle arrest and apoptosis against A549 cells. Also, bexarotene nanocrystals had significant antitumor activity in mice bearing A549 cell line. This finding was correlated with both in vitro and in vivo. Thereby, the overall results suggest that the bexarotene nanocrystals represent a potential source of medicine, which made bexarotene nanocrystals a promising candidate for the treatment of lung cancer.


Pentachlorophenol degradation by Janibacter sp., a new actinobacterium isolated from saline sediment of arid land.
Many pentachlorophenol- (PCP-) contaminated environments are characterized by low or elevated temperatures, acidic or alkaline pH, and high salt concentrations. PCP-degrading microorganisms, adapted to grow and prosper in these environments, play an important role in the biological treatment of polluted extreme habitats. A PCP-degrading bacterium was isolated and characterized from arid and saline soil in southern Tunisia and was enriched in mineral salts medium supplemented with PCP as source of carbon and energy. Based on 16S rRNA coding gene sequence analysis, the strain FAS23 was identified as Janibacter sp. As revealed by high performance liquid chromatography (HPLC) analysis, FAS23 strain was found to be efficient for PCP removal in the presence of 1% of glucose. The conditions of growth and PCP removal by FAS23 strain were found to be optimal in neutral pH and at a temperature of 30 °C. Moreover, this strain was found to be halotolerant at a range of 1-10% of NaCl and able to degrade PCP at a concentration up to 300 mg/L, while the addition of nonionic surfactant (Tween 80) enhanced the PCP removal capacity.


Approaches to the treatment of depression.
Depression has a biological basis and patients should not be stigmatized by societal misperceptions. Depression is a recurrent disease that often requires long-term therapy. Combining antidepressant medications with cognitive behavior therapy or psychotherapy is the optimal approach. New antidepressants with improved potency and tolerability are under development.


The Validity and Reliability of Retrospective Measures of Childhood Socioeconomic Status in the Health and Retirement Study: Evidence From the 1940 U.S. Census.
Retrospective measures of childhood socioeconomic status (SES) in cohort studies of aging that first observe people late in life-such as the Health and Retirement Study (HRS)-are widely used. However, their measurement validity and reliability are unknown. We assess the reliability and validity of the HRS's retrospective measures of parental education and childhood family finances. We use records for 6,343 HRS sample members who were children in 1940 that have been linked to records from the complete-count 1940 U.S. Census. We assess interrater reliability by comparing (a) retrospective reports of childhood SES collected from sample members in the 1992-2018 HRS to (b) prospective measures of parallel concepts collected from HRS sample members' parents in the 1940 Census. We assess predictive validity by comparing the results of analyses that model later-life outcomes as a function of childhood SES as measured both prospectively and retrospectively. Interrater reliabilities of retrospective measures of parental education are high; however, the same is not true of the retrospective measure of childhood family finances. Both retrospective and prospective measures of childhood SES are predictive of later-life outcomes, and with similar strengths and directions of associations for most outcomes. Researchers who rely on retrospective indicators of childhood SES from the HRS should be aware of their measurement properties. They are measured with error, and that error modestly attenuates estimates of their associations with later-life outcomes. However, prospective and retrospective measures of childhood SES have similar predictive validity. These findings should reassure researchers who rely on retrospective measures of childhood SES in the HRS and similarly designed surveys.


Atomic beam spectrometer using a LiF analyzer crystal.
An energy analyzer has been constructed and operated in UHV for the purpose of analyzing the energy of neutral atoms scattered from solid surfaces. The analyzer consists of a LiF single crystal located at an angle close to the normal to the sample crystal so that the diffraction pattern obtained by scanning the LiF crystal yields the energy of the scattered atoms. Two designs which have been used are described. The temperature of both sample and analyzer crystal is near 20 K and once cleaned they can be maintained in the state of initial preparation for many weeks. The sample was a (001) Cu surface in this case. Such an energy analyzer can only be used, in most cases, for He atom scattering although Ne atoms could be used if the scattered intensities were adequate. The detector developed in this study is able to detect about 2x10(5) atoms/s. The resolution of the spectrometer depends on the incident energy of the atom and is about 1 meV at an incident energy of 23 meV. This resolution can be improved by a factor of 3 to 4 by cooling the nozzle to a temperature lower than 77 K and using variable size slits which can be inserted into the beam path.


Assessment of legacy mine metal contamination using ants as indicators of contamination.
Most legacy mines contributed to contamination of the environment before and after cessation of mining. Contamination from waste rock, slag and tailings can introduce large concentrations of metals and metalloids to the surface soil and downstream sediments. Since ants are able to accumulate metals in their bodies, we investigated the possibility of using the elemental compositions of ants as indicators of metals at legacy mines developed on ores rich in copper (Cu), zinc (Zn), arsenic (As), silver (Ag) and lead (Pb). Our results showed the concentrations of manganese (Mn) and Cu in ants were not significantly different between mine and reference samples and only Zn was significantly different between contaminated and reference areas. Crematogaster spp. and Notoncus spp. from reference areas accumulated larger concentrations of metals in their bodies compared to ants from the mine. Ants accumulated metals in different parts of their bodies. The abdomen was the main site for accumulation of Mn, iron (Fe) and Zn. Mandibles were only associated with accumulation of Zn. Copper and Pb showed no area of preferential accumulation and traces were detected in the whole body of the ants. Ants from five genera had similar regions for metal accumulation. The exoskeleton did not contribute to accumulation of metals; instead all metals were stored in internal organs. Not all genera were suitable for use as indicators; only Iridomyrmex spp. and Ochetellus spp. accumulated larger amount of metals in mine samples compared to reference samples.


Targeting Macrophage for the Treatment of Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that specifically affects motor neurons in the brain and in the spinal cord. Patients with amyotrophic lateral sclerosis usually die from respiratory failure within 3 to 5 years from when the symptoms first appear. Currently, there is no cure for amyotrophic lateral sclerosis. Accumulating evidence suggests that dismantling of neuromuscular junction is an early event in the pathogenesis of amyotrophic lateral sclerosis. It is starting to realized that macrophage malfunction contributes to the disruption of neuromuscular junction. Modulation of macrophage activation states may stabilize neuromuscular junction and provide protection against motor neuron degeneration in amyotrophic lateral sclerosis.


Components of light scattered by eye lens.
Using the angular dependence of intensities of light scattered on sections of bovine lenses, we have determined correlation lengths related to the scattering samples. The correlations were calculated on the basis of random density and orientation fluctuation theory. The lenses were classified by means of an instrument for the measurement of transmission and the unscattered component of light. The correlation lengths are compared with dimensions of aggregates.


Development and Evaluation of a Cetuximab-based Humanized Single Chain Antibody Against EGFR-overexpressing Tumors.
Production of humanized single chain antibodies (hscFv) can potentially be a powerful solution to limitations imposed by large size and murine nature of cetuximab. The present study describes generation of a cetuximab-based hscFv using CDR-grafting method. Cetuximab CDRs were grafted on frameworks selected from human germline antibody sequence repertoire. The strategy employed in selecting human sequences was the highest sequence similarity of variable domains between human and parental antibodies as well as similarity in the CDRs canonical structures. To maintain the binding affinity, the parental vernier zone residues were retained murine in hscFv. Recombinant hscFv was expressed in E. coli and affinity purified by Ni-NTA column. The potency of hscFv in targeting EGFR was evaluated using A431, a cell line over-expressing EGFR. Dot blot and ELISA tests were used to assess the reactivity and MTT assay to evaluate the growth inhibition of hscFv on A431 cell line. The humanization of cetuximab variable regions resulted in 22.2% increase in humanness of hscFv. Reactivity analyses of hscFv on A431 cells showed better binding affinity and higher growth inhibition effect (2.6 times) comparing to murine counterpart. In conclusion, hscFv produced in this study displayed reduced potential immunogenicity as well as enhanced cytotoxic effect on EGFR- overexpressing tumor cells.


Inferring hidden states in Langevin dynamics on large networks: Average case performance.
We present average performance results for dynamical inference problems in large networks, where a set of nodes is hidden while the time trajectories of the others are observed. Examples of this scenario can occur in signal transduction and gene regulation networks. We focus on the linear stochastic dynamics of continuous variables interacting via random Gaussian couplings of generic symmetry. We analyze the inference error, given by the variance of the posterior distribution over hidden paths, in the thermodynamic limit and as a function of the system parameters and the ratio α between the number of hidden and observed nodes. By applying Kalman filter recursions we find that the posterior dynamics is governed by an "effective" drift that incorporates the effect of the observations. We present two approaches for characterizing the posterior variance that allow us to tackle, respectively, equilibrium and nonequilibrium dynamics. The first appeals to Random Matrix Theory and reveals average spectral properties of the inference error and typical posterior relaxation times; the second is based on dynamical functionals and yields the inference error as the solution of an algebraic equation.


Does the opioid-sparing effect of rectal diclofenac following total abdominal hysterectomy benefit the patient?
The aim of this prospective, double-blind, randomized, placebo-controlled clinical trial was to investigate the opioid-sparing effects of rectal diclofenac following total abdominal hysterectomy. Forty ASA I-II patients, aged 20-60 yr, were randomized to receive identical-looking suppositories of either diclofenac 75 mg or placebo, twice daily. All patients were given a standardized anaesthetic, with intravenous morphine via a patient-controlled analgesia device and either diclofenac or placebo for postoperative analgesia. The median 24 h morphine consumption (interquartile range) was significantly higher (P=0.02) in the placebo group [59 (45-85) mg] than in the diclofenac group [31 (14-65) mg]. In comparison with the placebo group, there were significant reductions in total pain score in the diclofenac group at rest (P=0.04) and on movement (P<0.01). Total (SD) sedation score was significantly lower (P=0.04) in the diclofenac group [90 (73) mm] than in the placebo group [148 (89) mm]. Total (interquartile range) nausea score was significantly lower (P<0.01) in the diclofenac group [14 (0-53) mm] than in the placebo group [64 (30-109) mm]. There was no significant difference between the two groups of patients in episodes of vomiting or number of rescue antiemetics. Rectal diclofenac reduces morphine consumption, improves postoperative analgesia, and reduces the incidence of adverse effects such as sedation and nausea.


Initial forces experienced by the anterior and posterior teeth during dental-anchored or skeletal-anchored en masse retraction in vitro.
To investigate initial forces acting on teeth around the arch during en masse retraction using an in vitro Orthodontic SIMulator (OSIM). The OSIM was used to represent the full maxillary arch in a case wherein both first premolars had been extracted. Dental and skeletal anchorage to a posted archwire and skeletal anchorage to a 10-mm power arm were all simulated. A 0.019 × 0.025-inch stainless steel archwire was used in all cases, and 15-mm light nickel-titanium springs were activated to approximately 150 g on both sides of the arch. A sample size of n = 40 springs were tested for each of the three groups. Multivariate analysis of variance (α = 0.05) was used to determine differences between treatment groups. In the anterior segment, it was found that skeletal anchorage with power arms generated the largest retraction force (P < .001). The largest vertical forces on the unit were generated using skeletal anchorage, followed by skeletal anchorage with power arms, and finally dental anchorage. Power arms were found to generate larger intrusive forces on the lateral incisors and extrusive forces on the canines than on other groups. For the posterior anchorage unit, dental anchorage generated the largest protraction and palatal forces. Negligible forces were measured for both skeletal anchorage groups. Vertical forces on the posterior unit were minimal in all cases (<0.1 N). All retraction methods produced sufficient forces to retract the anterior teeth during en masse retraction. Skeletal anchorage reduced forces on the posterior teeth but introduced greater vertical forces on the anterior teeth.


Rearrangements of immunoglobulin- and BCR-genes in chronic myeloid leukemia.
Clonal rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes have been demonstrated in malignant lymphoid tumors of B and T cell origin. In Philadelphia chromosome (Ph1) positive chronic myeloid leukemia (CML) the bcr and c-abl genes are reorganized and a new transcript, composed of both genes is expressed. Immunoglobulin gene rearrangements were also detected in lymphoid blast crisis but not in myeloid blast crisis of CML. We analyzed in Southern blot experiments whether Ig and TCR rearrangements could also occur in the chronic or accelerated phase of the disease. Our results indicate that immunoglobulin but not TCR delta or TCR gamma gene rearrangements also occurred in some patients with CML in chronic and accelerated phase but not in myeloid blast crisis, together with rearrangements of the bcr gene.


Measurement of retinal blood flow in the rat by combining Doppler Fourier-domain optical coherence tomography with fundus imaging.
A wide variety of ocular diseases are associated with abnormalities in ocular circulation. As such, there is considerable interest in techniques for quantifying retinal blood flow, among which Doppler optical coherence tomography (OCT) may be the most promising. We present an approach to measure retinal blood flow in the rat using a new optical system that combines the measurement of blood flow velocities via Doppler Fourier-domain optical coherence tomography and the measurement of vessel diameters using a fundus camera-based technique. Relying on fundus images for extraction of retinal vessel diameters instead of OCT images improves the reliability of the technique. The system was operated with an 841-nm superluminescent diode and a charge-coupled device camera that could be operated at a line rate of 20 kHz. We show that the system is capable of quantifying the response of 100% oxygen breathing on the retinal blood flow. In six rats, we observed a decrease in retinal vessel diameters of 13.2% and a decrease in retinal blood velocity of 42.6%, leading to a decrease in retinal blood flow of 56.7%. Furthermore, in four rats, the response of retinal blood flow during stimulation with diffuse flicker light was assessed. Retinal vessel diameter and blood velocity increased by 3.4% and 28.1%, respectively, leading to a relative increase in blood flow of 36.2%. The presented technique shows much promise to quantify early changes in retinal blood flow during provocation with various stimuli in rodent models of ocular diseases in rats.


Cutting edge: genetic characterization of IFN-producing killer dendritic cells.
The combined phenotypic expression of CD11c(low)B220(+)CD122(+)DX5(+) has been used to define a novel cell type termed IFN-producing killer dendritic cells (IKDC). IKDC readily produce IFN-gamma and demonstrate spontaneous cytotoxic activity toward tumors, suggesting that a modulation of IKDC number may be beneficial in cancer treatment. We examined various mouse strains and found that IKDC number was highly variable between the different strains. A linkage analysis associated the distal arm of chromosome 7 with variations in IKDC number. The genetic contribution of chromosome 7 to the regulation of IKDC number was confirmed through the use of congenic mice. We further demonstrate that IKDC proportion is regulated by intrinsic hematopoietic factors. We discuss the role of various candidate genes in the regulation of this newly described cell type and its implication in therapy.


[Dermatological particularities and pathologies of premature infants].
In contrast with the full-term infant, the skin of the preterm neonate is structurally and functionally immature, especially birth occurred before 30 weeks gestation. The inefficiency of the epidermal barrier may result in dehydration, thermal instability and toxic reactions from percutaneous absorption of topically applied agents. An increased risk for bacteremia and sepsis exist because of the easily injured skin, combined with compromised immunity. The present article summarizes the consequences of this skin immaturity and the different means to avoid them. We shall also describe 2 pathologies more frequent in premature infants: sclerema neonatorum and acquired zinc deficiency.


GutBalance: a server for the human gut microbiome-based disease prediction and biomarker discovery with compositionality addressed.
The compositionality of the microbiome data is well-known but often neglected. The compositional transformation pertains to the supervised learning of microbiome data and is a critical step that decides the performance and reliability of the disease classifiers. We value the excellent performance of the distal discriminative balance analysis (DBA) method, which selects distal balances of pairs and trios of bacteria, in addressing the classification of high-dimensional microbiome data. By applying this method to the species-level abundances of all the disease phenotypes in the GMrepo database, we build a balance-based model repository for the classification of human gut microbiome-related diseases. The model repository supports the prediction of disease risks for new sample(s). More importantly, we highlight the concept of balance-disease associations rather than the conventional microbe-disease associations and develop the human Gut Balance-Disease Association Database (GBDAD). Each predictable balance for each disease model indicates a potential biomarker-disease relationship and can be interpreted as a bacteria ratio positively or negatively correlated with the disease. Furthermore, by linking the balance-disease associations to the evidenced microbe-disease associations in MicroPhenoDB, we surprisingly found that most species-disease associations inferred from the shotgun metagenomic datasets can be validated by external evidence beyond MicroPhenoDB. The balance-based species-disease association inference will accelerate the generation of new microbe-disease association hypotheses in gastrointestinal microecology research and clinical trials. The model repository and the GBDAD database are deployed on the GutBalance server, which supports interactive visualization and systematic interrogation of the disease models, disease-related balances and disease-related species of interest.


Pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: clinical strategies.
Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder of childhood that can result in significant functional impairment, and if not adequately treated can lead to impaired quality of life. Pharmacotherapy is considered the first-line treatment for ADHD in children and adolescents. We review both recent literature and seminal studies regarding the pharmacological treatment of ADHD in children and adolescents. There is ample evidence for the efficacy and safety of both stimulants and non-stimulants in the treatment of ADHD. We review important aspects of evaluation and assessment and discuss first-line pharmacological treatments and as well as when to consider using alternative pharmacological agents. Treatment approaches to manage frequently seen comorbid disorders with ADHD are also covered.


Fluorescence characteristics of chromophoric dissolved organic matter in shallow water along the Zhejiang coasts, southeast China.
Twenty-eight surface water samples from rivers, muddy intertidal flats, sand shores, and bedrock coasts were collected along the Zhejiang coastline in southeast China. In addition, three samples from the Changjiang (Yangtze River) were collected for comparison. CDOM (chromophoric dissolved organic matter) absorption and fluorescence excitation-emission matrix (EEM) spectroscopy, as well as nutrients and DOC were measured in these samples. According to salinity, nutrient, and DOC constituents, the 28 Zhejiang samples were categorized into four groups, i.e. highly-polluted, river derived, muddy-flat derived, and saltwater dominated ones. Among the six parameters (two humic-like and two protein-like peak intensities in fluorescence EEM contours, absorption at 300 nm, and DOC concentration) for the Zhejiang samples, any two of them were positively correlated. The submarine groundwater discharge, rather than local rivers, might have provided most of the freshwater that interacted with the saltwater during the mixing process. The high protein-like EEM peaks in samples from muddy salt marshes and rivers were probably caused by terrestrial inputs, land-based pollution, and local biological activities in combination.


Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis.
Vitamin K-dependent protein C is an important regulator of blood coagulation. After its activation on the endothelial cell surface by thrombin bound to thrombomodulin, it cleaves and inactivates procoagulant cofactors Va and VIIIa, protein S and intact factor V working as cofactors. Until recently, genetic defects of protein C or protein S were, together with antithrombin III deficiency, the established major causes of familial venous thromboembolism, but they were found in fewer than 5-10% of patients with thrombosis. In 1993, inherited resistance to activated protein C (APC) was described as a major risk factor for venous thrombosis. It is found in up to 60% of patients with venous thrombosis. In more than 90% of cases, the molecular background for the APC resistance is a single point mutation in the factor V gene, which predicts substitution of an arginine (R) at position 506 by a glutamine (Q). Mutated factor V (FV:Q506) is activated by thrombin or factor Xa in normal way, but impaired inactivation of mutated factor Va by APC results in life-long hypercoagulability. The prevalence of the FV:Q506 allele in the general population of Western countries varies between 2 and 15%, whereas it is not found in several other populations with different ethnic backgrounds. Owing to the high prevalence of FV:Q506 in Western populations, it occasionally occurs in patients with deficiency of protein S, protein C, or antithrombin III. Individuals with combined defects suffer more severely from thrombosis, and often at a younger age, than those with single defects, suggesting severe thrombophilia to be a multigenetic disease.


Spider venom peptides for gene therapy of Chlamydia infection.
Spider venoms are vast natural pharmacopoeias selected by evolution. The venom of the ant spider Lachesana tarabaevi contains a wide variety of antimicrobial peptides. We tested six of them (latarcins 1, 2a, 3a, 4b, 5, and cytoinsectotoxin 1a) for their ability to suppress Chlamydia trachomatis infection. HEK293 cells were transfected with plasmid vectors harboring the genes of the selected peptides. Controlled expression of the transgenes led to a significant decrease of C. trachomatis viability inside the infected cells.


Case report of flipper anatomic anomaly of Sotalia guianensis from Sepetiba Bay, Rio de Janeiro.
The cetacean flipper consists of a soft tissue that encases most of the forelimb containing humerus, radius, ulna, carpals, metacarpals, and phalanges. Several studies have documented the typical cetacean's flipper anatomy, but only a few described digital anomalies and the most common are fusions and supernumerary such as polydactily and polyphalangy. The flippers of the Guiana dolphin, Sotalia guianensis have a falciform general aspect showing individual differences and marks produced by individual contact in social interactions that mainly occur on the posterior border. Here, we report for the first time a case of flippers with anatomical anomalies of loss of digits and deviation of radius of an adult S. guianensis from Baía de Sepetiba (22°54'-23°04', 43°36'-44°02'W), Rio de Janeiro, Southeastern Brazil.


Cardiovascular Response to Posture Changes: Multiscale Modeling and in vivo Validation During Head-Up Tilt.
In spite of cardiovascular system (CVS) response to posture changes have been widely studied, a number of mechanisms and their interplay in regulating central blood pressure and organs perfusion upon orthostatic stress are not yet clear. We propose a novel multiscale 1D-0D mathematical model of the human CVS to investigate the effects of passive (i.e., through head-up tilt without muscular intervention) posture changes. The model includes the main short-term regulation mechanisms and is carefully validated against literature data and in vivo measures here carried out. The model is used to study the transient and steady-state response of the CVS to tilting, the effects of the tilting rate, and the differences between tilt-up and tilt-down. Passive upright tilt led to an increase of mean arterial pressure and heart rate, and a decrease of stroke volume and cardiac output, in agreement with literature data and present in vivo experiments. Pressure and flow rate waveform analysis along the arterial tree together with mechano-energetic and oxygen consumption parameters highlighted that the whole system approaches a less stressed condition at passive upright posture than supine, with a slight unbalance of the energy supply-demand ratio. The transient dynamics is not symmetric in tilt-up and tilt-down testing, and is non-linearly affected by the tilting rate, with stronger under- and overshoots of the hemodynamic parameters as the duration of tilt is reduced. By enriching the CVS response to posture changes, the present modeling approach shows promise in a number of applications, ranging from autonomic system disorders to spaceflight deconditioning.


Antagonism of 5-methoxy-N,N-dimethyltryptamine-induced changes in postdecapitation convulsions in rats by repeated treatment with drugs enhancing 5-hydroxytryptamine neurotransmission.
Repeated administration of drugs that increase tryptaminergic neurotransmission antagonized the increase in latency to onset and the duration of postdecapitation convulsions (PDCs) induced by an acute 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) injection; Zimelidine (2 X 5 mg kg-1), fluoxetine (2 X 5 mg kg-1), amiflamine (2 X 2.5 mg kg-1) and alpha-ethyltryptamine (2 X 2.5 mg kg-1) administered orally over 10 days caused a substantial blockade of the increase in latency to onset and duration of PDCs following 5-MeODMT, whereas alaproclate (2 X 5 mg kg-1), clorgyline (1 X 1 mg kg-1) and pargyline (2 X 2.5 mg kg-1) caused a lesser blockade. Repeated 5-MeODMT (3 X 2 mg kg-1) administration blocked the acute effects of 5-MeODMT (2 and 4 mg kg-1) upon PDCs completely. These findings indicate down-regulation of the 5-hydroxytryptamine receptors which mediate the action of 5-MeODMT on the PDCs and offer a simple model system for studying 5-HT receptor sensitivity changes at the spinal level.


Involvement of Calcium in the Photoperiodic Flower Induction Process of Pharbitis nil.
EGTA, a specific Ca(2+) chelator, inhibited the flowering response of Pharbitis nil when applied to the cotyledons immediately before the inductive dark period. Calcium sprayed 30 minutes after the EGTA blocked the effect of EGTA. The length of the critical dark period was increased both by EGTA and by LaCl(3). The calmodulin antagonists W-7 and chlorpromazine also reduced the flowering response. On the other hand, A23187, a calcium ionophore, increased the flowering response. Both EGTA and A23187 were effective at certain times of the photoperiod but had almost no effect when applied at other times. The results indicate that the level of endogenous Ca(2+) may be limiting for floral induction in Ph. nil. Ca(2+) seems to play a role during the early stages of the inductive dark period.


Electrochemical and Laser Deposition of Silver for Use in Metal-Enhanced Fluorescence.
We describe two reagentless methods of silver deposition for metal-enhanced fluorescence. Silver was deposited on glass positioned between two silver electrodes with a constant current in pure water. Illumination of the glass between the electrodes resulted in localized silver deposition. Alternatively, silver was deposited on an Indium Tin Oxide cathode, with a silver electrode as the anode. Both types of deposited silver produced a 5-18-fold increase in the fluorescence intensity of a nearby fluorophore, indocyanine green (ICG). Additionally, the photostability of ICG was dramatically increased by proximity to the deposited silver. These results suggest the use of silver deposited from pure water for surface-enhanced fluorescence, with potential applications in surface assays and lab-on-a-chip-based technologies, which ideally require highly fluorescent photostable systems.


Heme-dependent radical generation: possible involvement in antimalarial action of non-peroxide microbial metabolites, nanaomycin A and radicicol.
Antimalarial screening was performed for microbial metabolites that simulate artemisinin in their mode of action, a potent antimalarial component of an herbal remedy with a characteristic peroxide structure. Nanaomycin A was identified in this screen as an antimalarial compound, together with radicicol and several other compounds already reported (J. Antibiotics 51: 153 approximately 160, 1998). Nanaomycin A inhibited in vitro growth of the human malaria parasite Plasmodium falciparum with an IC80 value of 33.1 nM. It was as potent as radicicol and about 1/10 as potent as artemisinin. Studies on the mode of action suggested that the antimalarial action of the two non-peroxides, nanaomycin A and radicicol, involved heme-dependent radical generation, as is for the peroxide artemisinin. Namely, the inhibition of in vitro growth of malaria parasite by nanaomycin A or radicicol was reversed by tocopherol, a radical scavenger added to the assay mixture. Secondly, in a reaction system established for radical detection, in which a test radical donor and beta-alanylhistidine as a radical recipient were incubated with and without hemin, the two compounds caused heme-dependent decreases of beta-alanylhistidine, as did artemisinin. Among the 14 microbial metabolites identified during this screening, a correlation was observed between antimalarial activity and heme-dependent radical generating activity.


Jafrac2 is an IAP antagonist that promotes cell death by liberating Dronc from DIAP1.
Members of the Inhibitor of Apoptosis Protein (IAP) family are essential for cell survival in Drosophila and appear to neutralize the cell death machinery by binding to and ubiquitylating pro-apoptotic caspases. Cell death is triggered when "Reaper-like" proteins bind to IAPs and liberate caspases from IAPs. We have identified the thioredoxin peroxidase Jafrac2 as an IAP-interacting protein in Drosophila cells that harbours a conserved N-terminal IAP-binding motif. In healthy cells, Jafrac2 resides in the endoplasmic reticulum but is rapidly released into the cytosol following induction of apoptosis. Mature Jafrac2 interacts genetically and biochemically with DIAP1 and promotes cell death in tissue culture cells and the Drosophila developing eye. In common with Rpr, Jafrac2-mediated cell death is contingent on DIAP1 binding because mutations that abolish the Jafrac2-DIAP1 interaction suppress the eye phenotype caused by Jafrac2 expression. We show that Jafrac2 displaces Dronc from DIAP1 by competing with Dronc for the binding of DIAP1, consistent with the idea that Jafrac2 triggers cell death by liberating Dronc from DIAP1-mediated inhibition.


Facilitators and Barriers to Implementing Clinical Governance: A Qualitative Study among Senior Managers in Iran.
Health care systems should assign quality improvement as their main mission. Clinical governance (CG) is a key strategy to improve quality of health care services. The Iranian Ministry of Health and Medical Education (MOHME) has promoted CG as a framework for safeguarding quality and safety in all hospitals since 2009. The purpose of this study was to explore perceived facilitators and barriers to implementing CG by deputies for curative affairs of Iranian medical universities. A qualitative study was conducted using face to face interviews with a purposeful sample of 43 deputies for curative affairs of Iranian Medical Universities and documents review. Thematic analysis was used to analyze the data. Five themes were explored including: knowledge and attitude toward CG, culture, organizational factors, managerial factors and barriers. The main perceived facilitating factors were adequate knowledge and positive attitude toward CG, supporting culture, managers' commitment, effective communication and well designed incentives. Pe rceived barriers were the reverse of facilitators noted above in addition to insufficient resources, legal challenges, workload and parallel quality programs. Successful implementation of CG in Iran will require identifying barriers and challenges existing in the way of CG implementation and try to mitigate them by using appropriate facilitators.


Clinical Role of Adjuvant Chemotherapy after Radical Hysterectomy for FIGO Stage IB-IIA Cervical Cancer: Comparison with Adjuvant RT/CCRT Using Inverse-Probability-of-Treatment Weighting.
To evaluate the clinical role of adjuvant chemotherapy (AC) in FIGO stage IB-IIA cervical cancer patients. A cohort of 262 patients with cervical cancer who received radical hysterectomy (RH) and adjuvant therapy at Asan Medical Center between 1992 and 2012 was enrolled. In this cohort, 85 patients received adjuvant chemotherapy (AC), and 177 received adjuvant radiotherapy or concurrent chemoradiation therapy (AR). Oncologic outcomes and adverse events in both treatment arms were compared using weighted Cox proportional hazards regression models with inverse-probability-of-treatment weighting (IPTW) to reduce the impact of treatment selection bias and potential confounding factors. During a 46.8-month median follow-up duration, 39 patients (14.9%) had recurrences, and 18 patients (6.9%) died of disease. In multivariate analysis, the hazard ratio (HR) for recurrence and death was not significantly different in patients in either treatment arm (p=0.62 and 0.12, respectively). Also, after IPTW matching, the HR for recurrence did not significantly differ between the arms (HR 1.57, 95% CI 0.68-3.62, p=0.29). Similarly, disease-free survival and overall survival were not significantly different between the arms (p=0.47 and 0.13, respectively). In addition, patients with AC had a much lower prevalence of long-term complications (lymphedema: n=8 (9.4%) vs. 46 (26.0%), p=0.03; ureteral stricture: n=0 vs. 9 (6.2%), p=0.05). Patients with FIGO stage IB-IIA cervical cancer can benefit from AC after RH with fewer long-term complications and non-inferior therapeutic effect to AR. Chemotherapy may therefore be an alternative adjuvant treatment option for cervical cancer, particularly in younger patients.


The Trithorax protein Ash1L promotes myoblast fusion by activating Cdon expression.
Myoblast fusion (MF) is required for muscle growth and repair, and its alteration contributes to muscle diseases. The mechanisms governing this process are incompletely understood, and no epigenetic regulator has been previously described. Ash1L is an epigenetic activator belonging to the Trithorax group of proteins and is involved in FSHD muscular dystrophy, autism and cancer. Its physiological role in skeletal muscle is unknown. Here we report that Ash1L expression is positively correlated with MF and reduced in Duchenne muscular dystrophy. In vivo, ex vivo and in vitro experiments support a selective and evolutionary conserved requirement for Ash1L in MF. RNA- and ChIP-sequencing indicate that Ash1L is required to counteract Polycomb repressive activity to allow activation of selected myogenesis genes, in particular the key MF gene Cdon. Our results promote Ash1L as an important epigenetic regulator of MF and suggest that its activity could be targeted to improve cell therapy for muscle diseases.


DLC1 as a regulator of proliferation, invasion, cell cycle, and apoptosis in cutaneous squamous cell carcinoma.
Increasing evidence has demonstrated that the tumor suppressor gene deleted in liver cancer-1 (DLC1) is tightly implicated in the development and progression of tumors and is verified to be downregulated in a variety of tumors. However, the roles and precise molecular mechanisms of DLC1 in cutaneous squamous cell carcinoma (cutaneous SCC) remain to be elucidated. In the present study, we confirmed the reduced level in cutaneous SCC tissues and cells, and DLC1 mRNA relative level in cutaneous SCC tissues with lymph node metastasis (0.801 ± 0.079) was markedly lower than those without lymph node metastasis (1.245 ± 0.071) (P < 0.0001). Importantly, the survival rates of patients with low DLC1 level were lower than those with high DLC1 level (P = 0.0051). Further investigation revealed that DLC1 overexpression inhibited proliferation and arrested cell cycle at G0/G1 phase in A431 cells, which may be tightly associated with upregulation of p21 protein and downregulation of cyclin D1 and cdk2 proteins. Moreover, the decreases of FAK and p-FAK as well as the increase of E-cadherin level mediated by elevated DLC1 level suppressed invasion in A431 cells. Additionally, DLC1 overexpression induced apoptosis coupled with elevations of Bax level and caspase-3 activity and decrease of Bcl-2 level in A431 cells. Taken altogether, our data presented herein suggest that DLC1 plays a pivotal role in the development and progression of cutaneous SCC, which may be in part achieved by regulating the signaling pathway related to proliferation, invasion, cell cycle, and apoptosis in cutaneous SCC cells.


Preferences and barriers to the utilization of primary health care by sick physicians: a nationwide survey.
Physicians are often dissatisfied with their own medical care. Self-prescribing is common despite established guidelines that discourage this practice. From a pilot study, we know primary care physicians' (PCP) preferences, but we lack information regarding other specialties and work places. The goal of this study was to examine whether physicians are satisfied with their personal primary care and how this could be improved. We distributed an electronic survey to all physicians registered with the Israeli Medical Association. The questionnaire examined satisfaction with medical care, preferences for using formal care versus informal care, self-prescribing and barriers to using formal care. Two thousand three hundred and five out of 24 360 invited physicians responded. Fifty-six per cent of the respondents were satisfied with their personal primary care. Fifty-two per cent reported initiating self-treatment with a medication during the last year. Five and four per cent initiated treatment with a benzodiazepine and an antidepressant, respectively, during the last year. This was despite the fact that most physicians did not feel competent to treat themselves. Having a personal PCP was correlated with both a desire to use formal care and self-referral to formal care in practice. Regression analysis showed that the highest odds ratio (OR) for experiencing a large gap between desired and actual care were for physicians who had no personal PCP (OR = 1.92). Physicians frequently engage in self-treatment and in informal medical care. Whether the root cause is the health care system structure that does not meet their needs or the convenience of self-treatment is not known.


The Prevalence and Clinical Implications of Rectal SARS-CoV-2 Shedding in Danish COVID-19 Patients and the General Population.
Background: SARS-CoV-2 has resulted in a global pandemic since its outbreak in Wuhan, 2019. Virus transmission primarily occurs through close contact, respiratory droplets, and aerosol particles. However, since SARS-CoV-2 has been detected in fecal and rectal samples from infected individuals, the fecal-oral route has been suggested as another potential route of transmission. This study aimed to investigate the prevalence and clinical implications of rectal SARS-CoV-2 shedding in Danish COVID-19 patients. Methods: Hospitalized and non-hospitalized adults and children who were recently tested with a pharyngeal COVID-19 test, were included in the study. A rectal swab was collected from all participants. Hospitalized adults and COVID-19 positive children were followed with both pharyngeal and rectal swabs until two consecutive negative results were obtained. RT-qPCR targeting the envelope gene was used to detect SARS-CoV-2 in the samples. Demographic, medical, and biochemical information was obtained through questionnaires and medical records. Results: Twenty-eight of 52 (53.8%) COVID-19 positive adults and children were positive for SARS-CoV-2 in rectal swabs. Seven of the rectal positive participants were followed for more than 6 days. Two of these (28.6%) continued to test positive in their rectal swabs for up to 29 days after the pharyngeal swabs had turned negative. Hospitalized rectal positive and rectal negative adults were comparable regarding demographic, medical, and biochemical information. Furthermore, no difference was observed in the severity of the disease among the two groups. Conclusions: We provided evidence of rectal SARS-CoV-2 shedding in Danish COVID-19 patients. The clinical importance of rectal SARS-CoV-2 shedding appears to be minimal.


Tuning biomimetic membrane barrier properties by hydrocarbon, cholesterol and polymeric additives.
The barrier properties of cellular membranes are increasingly attracting attention as a source of inspiration for designing biomimetic membranes. The broad range of potential technological applications makes the use of lipid and lately also polymeric materials a popular choice for constructing biomimetic membranes, where the barrier properties can be controlled by the composition of the membrane constituent elements. Here we investigate the membrane properties reported by the light-induced proton pumping activity of bacteriorhodopsin (bR) reconstituted in three vesicle systems of different membrane composition. Specifically we quantify how the resulting proton influx and efflux rates are influenced by the membrane composition using a variety of membrane modulators. We demonstrate that by adding hydrocarbons to vesicles with reconstituted bR formed from asolectin lipids the resulting transmembrane proton fluxes changes proportional to the carbon chain length when compared against control. We observe a similar proportionality in single-component 1,2-Dioleoyl-sn-glycero-3-phosphocholine model membranes when using cholesterol. Lastly we investigate the effects of adding the amphiphilic di-block co-polymer polybutadiene-polyethyleneoxide (PB12-PEO10) to phospholipid membranes formed from 1,2-Dioleoyl-sn-glycero-3-phosphocholine, 1,2-Dioleoyl-sn-glycero-3-phosphatidylethanolamine, and 1,2-Dioleoyl-sn-glycero-3-phosphatidylserine. The proton pumping activity of bR (measured as a change in extra-vesicular pH) in mixed lipid/PB12-PEO10 lipid systems is up to six-fold higher compared to that observed for bR containing vesicles made from PB12-PEO10 alone. Interestingly, bR inserts with apparent opposite orientation in pure PB12-PEO10 vesicles as compared to pure lipid vesicles. Addition of equimolar amounts of lipids to PB12-PEO10 results in bR orientation similar to that observed for pure lipids. In conclusion our results show how the barrier properties of the membranes can be controlled by the composition of the membrane. In particular the use of mixed lipid-polymer systems may pave the way for constructing biomimetic membranes tailored for optimal properties in various applications including drug delivery systems, biosensors and energy conservation technology.


Variational principles for stochastic soliton dynamics.
We develop a variational method of deriving stochastic partial differential equations whose solutions follow the flow of a stochastic vector field. As an example in one spatial dimension, we numerically simulate singular solutions (peakons) of the stochastically perturbed Camassa-Holm (CH) equation derived using this method. These numerical simulations show that peakon soliton solutions of the stochastically perturbed CH equation persist and provide an interesting laboratory for investigating the sensitivity and accuracy of adding stochasticity to finite dimensional solutions of stochastic partial differential equations. In particular, some choices of stochastic perturbations of the peakon dynamics by Wiener noise (canonical Hamiltonian stochastic deformations, CH-SD) allow peakons to interpenetrate and exchange order on the real line in overtaking collisions, although this behaviour does not occur for other choices of stochastic perturbations which preserve the Euler-Poincaré structure of the CH equation (parametric stochastic deformations, P-SD), and it also does not occur for peakon solutions of the unperturbed deterministic CH equation. The discussion raises issues about the science of stochastic deformations of finite-dimensional approximations of evolutionary partial differential equation and the sensitivity of the resulting solutions to the choices made in stochastic modelling.


Characterization of a Saccharomyces cerevisiae fermentation process for production of a therapeutic recombinant protein using a multivariate Bayesian approach.
The principle of quality by design (QbD) has been widely applied to biopharmaceutical manufacturing processes. Process characterization is an essential step to implement the QbD concept to establish the design space and to define the proven acceptable ranges (PAR) for critical process parameters (CPPs). In this study, we present characterization of a Saccharomyces cerevisiae fermentation process using risk assessment analysis, statistical design of experiments (DoE), and the multivariate Bayesian predictive approach. The critical quality attributes (CQAs) and CPPs were identified with a risk assessment. The statistical model for each attribute was established using the results from the DoE study with consideration given to interactions between CPPs. Both the conventional overlapping contour plot and the multivariate Bayesian predictive approaches were used to establish the region of process operating conditions where all attributes met their specifications simultaneously. The quantitative Bayesian predictive approach was chosen to define the PARs for the CPPs, which apply to the manufacturing control strategy. Experience from the 10,000 L manufacturing scale process validation, including 64 continued process verification batches, indicates that the CPPs remain under a state of control and within the established PARs. The end product quality attributes were within their drug substance specifications. The probability generated with the Bayesian approach was also used as a tool to assess CPP deviations. This approach can be extended to develop other production process characterization and quantify a reliable operating region. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:799-812, 2016.


A rapid improved multiplex ligation detection reaction method for the identification of gene mutations in hereditary hearing loss.
Hearing loss (HL) is a common sensory disorder. More than half of HL cases can be attributed to genetic causes. There is no effective therapy for genetic HL at present, early diagnosis to reduce the incidence of genetic HL is important for clinical intervention in genetic HL. Previous studies have identified 111 nonsyndromic hearing loss genes. The most frequently mutated genes identified in NSHL patients in China include GJB2, SLC26A4, and the mitochondrial gene MT-RNR1. It is important to develop HL gene panels in Chinese population, which allow for etiologic diagnosis of both SHL and NSHL. In this study, a total of 220 unrelated Han Chinese patients with bilateral progressive SNHL and 50 unrelated healthy controls were performed Single nucleotide polymorphism (SNP) genotyping using an improved multiplex ligation detection reaction (iMLDR) technique, is to simultaneously detect a total of 32 mutations in ten HL genes, covering all currently characterized mutations involved in the etiology of nonsyndromic or syndromic hearing loss in the Chinese population. The 49 positive samples with known mutations were successfully detected using the iMLDR Technique. For 171 SNHL patients, gene variants were found in 57 cases (33.33%), among which, 30 patients carried mutations in GJB2, 14 patients carried mutations in SLC26A4, seven patients carried mutations in GJB3, and six patients carried mutations in MT-RNR1. The molecular etiology of deafness was confirmed in 12.9% (22/171) of patients carried homozygous variants. These results were verified by Sanger sequencing, indicating that the sensitivity and specificity of the iMLDR technique was 100%. We believe that the implementation of this population-specific technology at an efficient clinical level would have great value in HL diagnosis and treatment.


Targeted therapy of multiple myeloma.
Multiple myeloma (MM) is a malignant proliferative disease of monoclonal plasma cells (PCs) and is characterized by uncontrolled proliferation of PCs and excessive production of specific types of immunoglobulins. Since PCs are terminally differentiated B cells, the World Health Organization (WHO) classifies MM as lymphoproliferative B-cell disease. The incidence of MM is 6-7 cases per 100,000 people in the world every year and the second most common cancer in the blood system. Due to the effects of drug resistance and malignant regeneration of MM cells in the microenvironment, all current treatment methods can prolong both overall and symptom-free survival rates of patients with MM but cannot cure MM. Both basic and clinical studies have proven that targeted therapy leads to a clear and significant prolongation of the survival of patients with MM, but when the disease recurs again, resistance to the previous treatment will occur. Therefore, the discovery of new targets and treatment methods plays a vital role in the treatment of MM. This article introduces and summarizes targeted MM therapy, potential new targets, and future precision medicine in MM.


A Case of Meningitis in an Infant Due to Hypervirulent Klebsiella pneumoniae Transmission Within a Family.
Hypervirulent Klebsiella pneumoniae (hvKP), an emerging pathotype derived from K. pneumoniae, frequently causes invasive infections of multiple organs and is associated with both high disability and fatality rates. In this study, a case of meningitis in a young infant caused by hvKP is presented. Cytological and biochemical examinations of the cerebrospinal fluid (CSF) revealed purulent meningitis, a diagnosis that was confirmed by a positive CSF culture result. The pathogen was identified as hvKP through analysis of positive virulence-associated genes. Meanwhile, hvKP was also isolated from stool samples of both the infant and her father. Antimicrobial susceptibility, capsular typing, and multilocus sequence typing (MLST) of three isolates from the infant's CSF and stool and her father's stool samples were analyzed. The three K. pneumoniae isolates were susceptible to all antibiotics except ampicillin and were identified as capsular serotype K2 and sequence type 86. These genetic relatedness analyses indicated that the strain isolated from the infant's CSF might have originated from her father's stool via familial transmission. This case is the first report of meningitis in an infant due to hvKP transmitted within a family.


Hepatitis C and renal transplantation: a review on historical aspects and current issues.
Chronic liver disease has a significant impact on the survival of renal transplant recipients with an incidence rate of 4-38%. Approximately, 8-28% of renal transplant recipients die due to chronic liver disease. Hepatitis C seems to be the leading cause of chronic liver disease in kidney recipients. Hepatitis C virus (HCV) infection has a wide range of prevalence (2.6-66%) among renal transplant recipients living in different countries with great genotype diversity in different parts of the world. Nowadays, antiviral drugs are used for the management of hepatitis C. Because of graft-threatening effects of some antiviral drugs used in HCV-infected renal transplant recipients, we specifically focused on HCV treatment after renal transplantation. Treatment of post-renal transplantation chronic liver disease with INF and ribavirin remains controversial. Anecdotal reports on post-renal transplantation hepatitis C demonstrate encouraging findings. This review summarises the most current information on diagnosis, treatment, prognosis, complications as well as the new aspects of treatment in HCV-infected renal transplant recipients. HCV belongs to the family of Flaviviridae, genus Hepacivirus.


Unravelling the development of the visual cortex: implications for plasticity and repair.
The visual cortex comprises over 50 areas in the human, each with a specified role and distinct physiology, connectivity and cellular morphology. How these individual areas emerge during development still remains something of a mystery and, although much attention has been paid to the initial stages of the development of the visual cortex, especially its lamination, very little is known about the mechanisms responsible for the arealization and functional organization of this region of the brain. In recent years we have started to discover that it is the interplay of intrinsic (molecular) and extrinsic (afferent connections) cues that are responsible for the maturation of individual areas, and that there is a spatiotemporal sequence in the maturation of the primary visual cortex (striate cortex, V1) and the multiple extrastriate/association areas. Studies in both humans and non-human primates have started to highlight the specific neural underpinnings responsible for the maturation of the visual cortex, and how experience-dependent plasticity and perturbations to the visual system can impact upon its normal development. Furthermore, damage to specific nuclei of the visual cortex, such as the primary visual cortex (V1), is a common occurrence as a result of a stroke, neurotrauma, disease or hypoxia in both neonates and adults alike. However, the consequences of a focal injury differ between the immature and adult brain, with the immature brain demonstrating a higher level of functional resilience. With better techniques for examining specific molecular and connectional changes, we are now starting to uncover the mechanisms responsible for the increased neural plasticity that leads to significant recovery following injury during this early phase of life. Further advances in our understanding of postnatal development/maturation and plasticity observed during early life could offer new strategies to improve outcomes by recapitulating aspects of the developmental program in the adult brain.


Assessment of cardiac inflammation and remodeling during the development of streptozotocin-induced diabetic cardiomyopathy in vivo: a time course analysis.
In this study, we examined cardiac inflammation, fibrosis and left ventricular (LV) function during the development of streptozotocin (STZ)-induced diabetic cardiomyopathy using an animal model of diabetes mellitus (DM). Diabetes was induced in 22 Sprague‑Dawley rats by an intraperitoneal single injection of STZ (70 mg/kg). Non-diabetic animals served as the controls (n=6). LV function was documented using the conductance catheter technique 2 and 6 weeks after the induction of diabetes. Cardiac tissue was analyzed for cardiac immune cell infiltration, oxidative stress and remodeling in rats with STZ-induced diabetes at 2 different time points by immunohistochemistry. Cardiac function was significantly impaired in the diabetic animals. After 2 weeks, the induction of diabetes resulted in impaired cardiac function indexed by a decrease in systolic and diastolic LV function. This impairment of LV performance continued for up to 6 weeks after the STZ injection. This was associated with an increase in cardiac CD3+ and CD8a+ immune cell invasion and fibrosis, indexed by an increase in collagen content (p<0.05). Furthermore, oxidative stress response and matrix remodeling were increased after 2 weeks and this continued for up to 6 weeks after the induction of diabetes. In conclusion, cardiac dysfunction is associated with cardiac inflammation and adverse remodeling in experimental diabetic cardiomyopathy. Our results suggest that the model of STZ-induced diabetic cardiomyopathy is a robust model for investigating cardiac immune response and LV remodeling processes under diabetic conditions.


Effects of Cytokinin and Nitrogen on Drought Tolerance of Creeping Bentgrass.
Cytokinin (CK) is a vital plant hormone that controls many aspects of growth and development in plants. Nitrogen (N) is the indispensable macronutrient needed in plants and also one of the most important limiting factors for plant growth. This study was designed to investigate the simultaneous effects of CK and N on the visual turf quality and antioxidant metabolism of drought-stressed creeping bentgrass (Agrostis stolonifera L.). 'PennA-4' creeping bentgrass treated with trans-zeatin riboside at three rates of CK concentrations of 0, 10 and 100 μM (designated by CK0, 10, and 100) and two nitrogen rates with 2.5 and 7.5 kg N·ha-1 every 15 days (designated by low and high N) in a complete factorial arrangement was grown under two soil moisture regimes: well-watered and drought stress. Exogenous CK improved turf quality and delayed leaf wilting under drought stress, especially under high N. The grasses treated with CK10 and CK100 had lower O2- production and H2O2 concentration than those without CK treatment. The CK100 treatment enhanced the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and guaiacol peroxidase (POD) by 25%, 22%, 17% and 24%, respectively, relative to CK0. Moreover, the activity changes of the antioxidant enzyme isoforms were more significant under high N condition relative to low N condition. Our results demonstrated the beneficial impacts of CK and N on physiological reactions, especially antioxidant metabolism, and foliar application of CK at 10 or 100 μM plus 7.5 kg ha-1 N biweekly may improve drought stress resistance of creeping bentgrass.


First Report of Powdery Mildew Caused by Podosphaera xanthii on Cucurbita ficifolia in Korea.
Cucurbita ficifolia Bouché, called fig-leaf gourd, is a cucurbitaceous climbing plant native to the Americas. During summer and autumn of 2020, almost all of fig-leaf gourds planted in an experimental plot in Jeonju (35°50'54″N, 127°07'46″E), Korea, were found to be infected by a powdery mildew with a 100% disease severity. Symptoms first appeared as white, small, irregular colonies, later coalesced into abundant hyphal growth on both sides of the leaves and young stems. Subsequently premature senescence and poor growth of affected leaves was observed. A voucher specimen was housed in the Korea University herbarium (KUS-F32173). For morphological characterization of the fungus, fresh materials were used for microscopy. Conidiophores (n = 30) were straight, 90 to 190 × 10 to 12 μm and produced three to six immature conidia in chains with a crenate outline. Conidia (n = 30) were ellipsoid-ovoid to barrel-shaped, measured 28 to 38 × 18 to 24 μm with a length/width ratio of 1.3 to 2.0, and contained distinct fibrosin bodies. No chasmothecia were found over the course of the season. The morphological feature of the fungus and the host genus were compatible with those of Podosphaera xanthii (Castagne) U. Braun & Shishkoff (Braun and Cook 2012), a well-known cucurbitaceous powdery mildew. For further confirmation, DNA was extracted from mycelium taken from above mentioned specimen. Internal transcribed spacers (ITS1 and ITS2) and large subunit (LSU) gene of the rDNA were amplified using primer pairs ITS1F/PM6 and PM3/TW14, respectively (Takamatsu and Kano 2001). Newly obtained sequences were registered to the GenBank under the accession numbers OL677355 for ITS and OL677356 for LSU. Our sequences shared 99.54~99.77% identity for ITS (MW559231 and MT250855) and 99.58% for LSU with sequences of P. xanthii (MK357445 and MK357438) in BLAST'n search. Pathogenicity tests were performed twice by pressing method of mycelial patches of the infected leaf onto the young leaves of five healthy fig-leaf gourd plants. Five non-inoculated plants were used as controls. Inoculated leaves started to develop powdery mildew signs after 5 days treatment, whereas the control plants remained symptomless. The fungus on the inoculated plants was morphologically identical to that originally observed on diseased plants, fulfilling Koch's postulates. To date three powdery mildew species have been reported on C. ficifolia (Farr and Rossman 2021). Among these reports, Golovinomyces orontii sensu lato was known from Chile, Mexico, United Kingdom, and Germany, Leveillula taurica from Korea and Podosphaera fuliginea (currently P. xanthii) was recorded Australia and India. To our knowledge, this is the first report of P. xanthii on C. ficifolia in Korea. Since this plant is used as grafting rootstock for preventing soil-borne gummy stem blight of cucumber caused by Didymella bryoniae in Korea (Choi et al. 2009), economic importance of the powdery mildew occurring on leaves of this plant is currently limited. Nevertheless, presence of a powdery mildew could be informative to breeding program of Cucurbita spp. and safe production of C. ficifolia fruits globally.


[Traumatic retropharyngeal hematoma].
To accurate the diagnosis and treatment of retropharyngeal hematoma. The authors show a case of retropharyngeal hematoma that appears just after a difficult and urgent orotracheal intubation. The retropharyngeal hematomas use to be spontaneously uptaken so that treatment may be observation. Sometimes, a surgical drainage is needed. Etiology, clinical signs, diagnosis and surgical indications are reviewed.