Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal.
Noxious stimuli have motivational power and can support associative learning, but the neural circuitry mediating such avoidance learning is poorly understood. The anterior cingulate cortex (ACC) is implicated in the affective response to noxious stimuli and the motivational properties of conditioned stimuli that predict noxious stimulation. Using conditioned place aversion (CPA) in rats, we found that excitatory amino acid microinjection into the ACC during conditioning produces avoidance learning in the absence of a peripheral noxious stimulus. Furthermore, microinjection of an excitatory amino acid antagonist into the ACC during conditioning blocked learning elicited by a noxious stimulus. ACC lesions made after conditioning did not impair expression of CPA. Thus, ACC neuronal activity is necessary and sufficient for noxious stimuli to produce an aversive teaching signal. Our results support the idea that a shared ACC pathway mediates both pain-induced negative affect and a nociceptor-driven aversive teaching signal.


Seizures.
Seizures can be a clinical presentation of acute stroke or complicate the clinical course of patients with stroke. Post-stroke seizures are significantly more common in patients with cortical involvement, severe and large size stroke and those with cortical hemorrhagic transformation of ischemic stroke. The influence of post-stroke seizures on functional outcome is controversial. The differences concerning the pathophysiology of and recurrence risk for early and late seizures suggests the need for a specific management. The choice of the antiepileptic drug will be influenced by the risk of drug interactions and possible side effects, especially in the elderly. Currently there is no evidence to support the use of antiepileptic drugs in patients with stroke in the absence of seizure even in the presence of risk factors for developing seizure.


Accuracy and precision of noninvasive temperature measurement in adult intensive care patients.
Research on the accuracy and precision of noninvasive methods of measuring body temperature is equivocal. To determine accuracy and precision of oral, ear-based, temporal artery, and axillary temperature measurements compared with pulmonary artery temperature. Repeated-measures design conducted for 6 months. Sequential temperature measurements on the same side of the body were obtained within 1 minute, with measurements repeated 3 times at 20-minute intervals. Accuracy, precision, and confidence limits were analyzed. In 60 adults with cardiopulmonary disease and a pulmonary artery catheter, mean pulmonary artery temperature was 37.1 degrees C (SD 0.6 degrees C, range 35.3 degrees C-39.4 degrees C). Mean (SD) offset from pulmonary artery temperature (with the mean reflecting accuracy and SD reflecting precision) and confidence limits were 0.09 degrees C (0.43 degrees C) and -0.75 degrees C to 0.93 degrees C for oral measurements, -0.36 degrees C (0.56 degrees C) and -1.46 degrees C to 0.74 degrees C for ear measurements, -0.02 degrees C (0.47 degrees C) and -0.92 degrees C to 0.88 degrees C for temporal artery measurements, and 0.23 degrees C (0.44 degrees C) and -0.64 degrees C to 1.12 degrees C for axillary measurements. Percentage of pairs with differences greater than +/-0.5 degrees C was 19% for oral, 49% for ear, 20% for temporal artery, and 27% for axillary measurements. Intubation increased oral measurements compared with pulmonary artery temperatures (mean difference 0.3 degrees C, SD 0.3 degrees C, P = .001). Oral and temporal artery measurements were most accurate and precise. Axillary measurements underestimated pulmonary artery temperature. Ear measurements were least accurate and precise. Intubation affected the accuracy of oral measurements; diaphoresis and airflow across the face may affect temporal artery measurements.


Detection of hemophilia by fluorescence spectroscopy: A photodiagnosis approach.
Hemophilia (HP), the deficiency of clotting factors such as VIII (FVIII) and IX, is an inherited blood disorder which is due to the lack of clotting protein. Conventional techniques for detecting hemophilia are based on clotting factor tests such as hemostasis assays to determine various types of hemophilia and its severity. In the current study, we propose a new approach involving a spectral technique to discriminate normal controls from hemophilia patients with an accuracy above 80 %. This accuracy is calculated on the normalized relative intensity based on the light measurement of blood components by analyzing a certain set of fluorescent bio molecules. Our results indicated that Red Blood Cells (RBCs) show lower porphyrin content and enzyme deficiencies in hemophilia patients than in normal controls. Therefore, the spectral features in hemophilia patients are different from those of normal controls. Thus, the proposed technique is a good alternative for the detection of hemophilia patients when compared with conventional detection techniques.


Capillary electrophoresis analysis of hydrolysis, isomerization and enantiomerization of aspartyl model tripeptides in acidic and alkaline solution.
In order to investigate the degradation of two aspartyl tripeptides, Gly-Asp-PheNH2 and Phe-Asp-GlyNH2 in solution capillary, electrophoresis methods were developed and validated. Separation of most degradation products including those arising from isomerization and enantiomerization of the Asp residues was achieved in a 50 mM sodium phosphate buffer, pH 3.0. Resolution of comigrating compounds could be achieved by addition of cyclodextrins to the background electrolyte. For tripeptide derivatives the assays were linear in the range of 0.015-3.0 mmol/l. Some dipeptides and amino acids exhibited a narrower linear range due to low UV absorbance. The limits of detection were in the range of 0.005-0.1 mmol/l. Incubation of the model peptides was carried out at pH 2 and 10. At pH 2, degradation of the peptides proceeded via C-terminal deamidation and peptide backbone hydrolysis. In contrast, isomerization and enantiomerization were observed in combination with deamidation at pH 10. Generally, degradation of Phe-Asp-GlyNH2 proceeded faster compared to Gly-Asp-PheNH2 due to steric hindrance by the phenyl side chain.


A quantitative study of glomerular basement membrane changes in IgA nephropathy.
A quantitative study of glomerular basement membrane (GBM) changes in 16 cases of IgA nephropathy was carried out on two whole glomeruli per case using a wide-field electron microscope. We found that GBM changes are observed more frequently than previously reported, although some changes are small and uneven in distribution. Changes include (a) attenuation, (b) lytic attenuation, (c) garland-shaped widening of the GBM, (d) dome-shaped widening of the GBM, and (e) disruption of the GBM. There was some correlation between the severity of light microscopic findings and the percentage of GBM affected by complicated changes ((b)-(e)). The percentage of complicated GBM changes correlated with the amount of proteinuria at biopsy. The frequent occurrence of GBM changes in IgA nephropathy suggests that they might be playing a role in the pathogenesis of IgA nephropathy.


Disease surveillance in England and Wales, July 2017.
Current and emerging issues: reminder of the notifiable status of porcine epidemic diarrhoeaHighlights from the scanning surveillance networkUpdate on international disease threatsReview of animal health threats by the Veterinary Risk Group These are among matters discussed in the Animal and Plant Health Agency's (APHA's) disease surveillance report for July 2017.


Deep learning-based metal artifact reduction using cycle-consistent adversarial network for intensity-modulated head and neck radiation therapy treatment planning.
To develop a deep learning-based metal artifact reduction (DL-MAR) method using unpaired data and to evaluate its dosimetric impact in head and neck intensity-modulated radiation therapy (IMRT) compared with the water density override method. The data set comprised the data of 107 patients who underwent radiotherapy. Fifteen patients with dental fillings were used as the test data set. The computed tomography (CT) images of the remaining 92 patients were divided into two domains: the metal artifact and artifact-free domains. CycleGAN was used for domain translation. The artifact index of the DL-MAR images was compared with that of the original uncorrected (UC) CT images. The dose distributions of the DL-MAR and UC plans were created by comparing the reference clinical plan with the water density override method (water plan) in each dataset. Dosimetric deviation in the oral cavity from the water plan was evaluated. The artifact index of the DL-MAR images was significantly smaller than that of the UC images in all patients (13.2 ± 4.3 vs. 267.3 ± 113.7). Compared with the reference water plan, dose differences of the UC plans were greater than those of the DL-MAR plans. DL-MAR images provided dosimetric results that were more similar to those of the water plan than the UC plan. We developed a fast DL-MAR method using CycleGAN for head and neck IMRT. The proposed method could provide consistent dose calculation against metal artifact and improve the efficiency of the planning process by eliminating manual delineation.


Epidemiological profile of tuberculosis patients in Delhi, India: A retrospective data analysis from the directly observed treatment short-course (DOTS) center.
Tuberculosis (TB) has been a public health menace for decades. India harbors its highest burden globally. The present study was conducted to study the epidemiological profile of patients taking treatment from a directly observed treatment short-course (DOTS) center in Delhi, India. Retrospective analysis of past 1-year treatment records of a total of 227 patients undergoing treatment in DOTS since June 2014-2015 was undertaken. Socio-demographic information, data related to disease status, and HIV testing were collected and analyzed. The majority of cases were new (77.1%) and pulmonary TB (69.2%). The highest disease burden was found in the 20-60 year age group (72.2%) and males (58.6%). Genitourinary TB was present only among females. None of the patients was HIV positive. A significant association was found between the age group of 20-60 years and relapse and loss to follow-up cases (P < 0.05). A higher proportion of adult males aged 20-60 years constituted the majority of patients treated in the DOTS center. Focussed interventions can be designed for this age group in future public health policies to reduce disease burden in the total population. Further research is required to be undertaken in exploring reasons for higher prevalence among males and productive age group and role of age, gender in disease causation.


Cleaning symbioses are described for the first time between fresh water fishes in their natural habitat. The symbioses are only facultative and were observed intra-and intorspecifically between members of the species Rhodeus amarus, Alburnus alburnus, Tinca, tinca and juvenile Rutilus rutilus, Scardinius erythrophthalmus and Perca fluviatilis.When the motivation to become cleaned is transmitted within a school of fish, mutual cleaning and inviting each other is common. The first stage in cleaning behaviour is cessation of movement and maintenance of a rigid posture which in these species of fish-contrary to marine species-is accompanied by compensatory fin movements.The more vertical the motionless posture of a fish the more active is the cleaning response of the partner. The vertical position is attained by passive sliding down of the head part. This form of display may be learned individually by imitation and (or) by trial and error.Fish approaching an inviting partner very often assume the invitation posture themselves instead of starting with the cleaning activity. This may be explained by transmission of the mood of invitation or because the invitation display raises the expectation in the approaching fish to become cleaned. Occasionally the invitation display is enhanced by head jerks (in Alburnus) or by body wriggling (in Scardinius).Tests with dummies prove that all details of the invitation pattern have to be fulfilled in order to make it acceptable as such by the partner. This points towards a learned releasing mechanism. Juveniles of Perca fluviatilis, besides assuming a slightly oblique posture, also show an additional feature of the invitation display by slow "rubbing" motions in front of swimming partners. This "sslow motion rubbing" may have developed from the normal cleaning behaviour which consists in rubbing the body against the ground. Intermediate stages between these two functions of rubbing motions are shown by Rhodeus amarus ("apparent rubbing").The motionless posture of invitation is broken by a large beating of the tail, which may be a displacement activity. This exaggerated intention movement has, however, not yet evolved into a social signal, comparable, for example, to the body shaking of some marine fish by which these induce their cleaners to leave. There are no specialized cleaning fishes in fresh water which explains the dominance of invitation dispays over cleaning activities.


Work-related psychosocial challenges and coping strategies among nursing workforce during the COVID-19 pandemic: a scoping review.
Nurses and midwives have been stretched by the COVID-19 pandemic amidst the heroic roles they have played during the peak of the COVID-19 pandemic. Nurses stood tall among their peers in the healthcare industry saving lives. The pandemic has had a toll on nurses physically, psychologically, and socio-economically. The numerous deaths have traumatized nurses coupled with the fear of possible infection. Nurses have seen their colleagues and loved ones lose their lives to the pandemic, nevertheless, they still render care to patients no matter the circumstances. Due to that, it is imperative to ascertain the extent to which nurses who are much needed in healthcare delivery have been affected by this pandemic. This scoping review used Arksey and O'Malley's review methodology to investigate the nature of work-related psychosocial challenges nurses encountered during the peak of the pandemic, noting the major contributors to the challenges and the coping strategies used to address them. We performed a scoping review and searched for articles from five databases including PUBMED, CINAHL, SCOPUS, Google Scholar, and Grey literature from December 2019 to December 2021. A total of 7,334 articles were retrieved for the study but 45 met the inclusion criteria. Work-related psychosocial challenges identified included stress, burnout (emotional exhaustion and depersonalization), Post-Traumatic Stress Disorder, depression, sleeplessness, and anxiety. Factors that accounted for the challenges were inadequate personal protective equipment (PPEs), discomfort using the PPEs, extreme workload, and fatigue. Nurses experienced job insecurity, business closure, and separation from family and loved ones, and these contributed to their challenges. Strategies used to deal with the challenges centred on emotion-focused and problem-focused coping. The study recommends regular counselling and support for all nurses working at the frontline to help them better cope with the devastating effects of the pandemic so that they could build resilience towards future pandemics.


Drug activation by gamma irradiation: a new direction for molecular design. Part I: In vitro and in vivo studies of a substituted polyaminoaryl nitrile.
The disodium salt of 4-diethyl aminophenyl-4',4''-bis(3-sulfobenzyl ethyl aminophenyl)acetonitrile was made and studied. It was found to release cyanide lineraly with exposure to ionizing radiation. When administered ip to mice, it was absorbed in significant amounts and retained its ability to cleave upon irradiation. Based upon this, we gathered evidence and proposed that it is feasible to design a non-toxic compound which when exposed to ionizing radiation would yield predictable reactive end products that would remain localized and augment the effects of irradiation upon a neoplasm.


Measuring Phonon Mean Free Path Distributions by Probing Quasiballistic Phonon Transport in Grating Nanostructures.
Heat conduction in semiconductors and dielectrics depends upon their phonon mean free paths that describe the average travelling distance between two consecutive phonon scattering events. Nondiffusive phonon transport is being exploited to extract phonon mean free path distributions. Here, we describe an implementation of a nanoscale thermal conductivity spectroscopy technique that allows for the study of mean free path distributions in optically absorbing materials with relatively simple fabrication and a straightforward analysis scheme. We pattern 1D metallic grating of various line widths but fixed gap size on sample surfaces. The metal lines serve as both heaters and thermometers in time-domain thermoreflectance measurements and simultaneously act as wire-grid polarizers that protect the underlying substrate from direct optical excitation and heating. We demonstrate the viability of this technique by studying length-dependent thermal conductivities of silicon at various temperatures. The thermal conductivities measured with different metal line widths are analyzed using suppression functions calculated from the Boltzmann transport equation to extract the phonon mean free path distributions with no calibration required. This table-top ultrafast thermal transport spectroscopy technique enables the study of mean free path spectra in a wide range of technologically important materials.


Evaluation of three full-scale stormwater treatment systems with respect to water yield, pathogen removal efficacy and human health risk from faecal pathogens.
In this study, three full-scale, operational stormwater harvesting systems located in Melbourne, Australia were evaluated with respect to water yields; pathogen removal performance by analysis of native surrogate data (Escherichiacoli, somatic coliphages and Clostridium perfringens); and potential human health risk associated with exposures to faecal pathogens using Quantitative Microbial Risk Assessment (QMRA). The water yield assessment confirmed variation between design and measured yields. Faecal contamination of urban stormwater was site specific and variable. Different treatment removal performance was observed between each of the microbial surrogates and varied between event and baseline conditions, with negligible removal of viruses during event conditions. Open storages that provide a habitat for waterfowl may lead to elevated risk due to the potential for zoonotic transmission. Nevertheless, in the Australian urban setting studied, the potential for human faecal contamination of the separated stormwater system was a critical driver of risk. If the integrity of the sewerage system can be ensured, then predicted health risks are dramatically reduced.


30-year progress of membrane transport in plants.
In the past 30 years enormous progress was made in plant membrane biology and transport physiology, a fact reflected in the appearance of textbooks. The first book dedicated to 'Membrane Transport in Plants' was published on the occasion of the 'International Workshop on Membrane Transport in Plants' held at the Nuclear Research Center, Jülich, Germany [Zimmermann and Dainty (eds) 1974] and was followed in 1976 by a related volume 'Transport in plants II' in the 'Encyclopedia of plant physiology' [Lüttge and Pitman (eds) 1976]. A broad spectrum of topics including thermodynamics of transport processes, water relations, primary reactions of photosynthesis, as well as more conventional aspects of membrane transport was presented. The aim of the editors of the first book was to bring advanced thermodynamical concepts to the attention of biologists and to show physical chemists and biophysicist what the more complex biological systems were like. To bundle known data on membrane transport in plants and relevant fields for mutual understanding, interdisciplinary research and clarification of problems were considered highly important for further progress in this scientific area of plant physiology. The present review will critically evaluate the progress in research in membrane transport in plants that was achieved during the past. How did 'Membrane Transport in Plants' progress within the 30 years between the publication of the first book about this topic (Zimmermann and Dainty 1974), a recent one with the same title (Blatt 2004), and today?


The ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation.
Recognition of histones by epigenetic readers is a fundamental mechanism for the regulation of chromatin and transcription. Most reader modules target specific post-translational modifications on histones. Here, we report the identification of a reader of histone H3, the ZZ-type zinc finger (ZZ) domain of ZZZ3, a subunit of the Ada-two-A-containing (ATAC) histone acetyltransferase complex. The solution NMR structure of the ZZ in complex with the H3 peptide reveals a unique binding mechanism involving caging of the N-terminal Alanine 1 of histone H3 in an acidic cavity of the ZZ domain, indicating a specific recognition of H3 versus other histones. Depletion of ZZZ3 or disruption of the ZZ-H3 interaction dampens ATAC-dependent promoter histone H3K9 acetylation and target gene expression. Overall, our study identifies the ZZ domain of ZZZ3 as a histone H3 reader that is required for the ATAC complex-mediated maintenance of histone acetylation and gene activation.


Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501).
In 2004, level I evidence was established for the postoperative adjuvant treatment of patients with selected high-risk locally advanced head and neck cancers, with the publication of the results of two trials conducted in Europe (European Organization Research and Treatment of Cancer; EORTC) and the United States (Radiation Therapy Oncology Group; RTOG). Adjuvant chemotherapy-enhanced radiation therapy (CERT) was shown to be more efficacious than postoperative radiotherapy for these tumors in terms of locoregional control and disease-free survival. However, additional studies were needed to identify precisely which patients were most suitable for such intense treatment. Both studies compared the addition of concomitant relatively high doses of cisplatin (on days 1, 22, and 43) to radiotherapy vs radiotherapy alone given after surgery in patients with high-risk cancers of the oral cavity, oropharynx, larynx, or hypopharynx. A comparative analysis of the selection criteria, clinical and pathologic risk factors, and treatment outcomes was carried out using data pooled from these two trials. Extracapsular extension (ECE) and/or microscopically involved surgical margins were the only risk factors for which the impact of CERT was significant in both trials. There was also a trend in favor of CERT in the group of patients who had stage III-IV disease, perineural infiltration, vascular embolisms, and/or clinically enlarged level IV-V lymph nodes secondary to tumors arising in the oral cavity or oropharynx. Patients who had two or more histopathologically involved lymph nodes without ECE as their only risk factor did not seem to benefit from the addition of chemotherapy in this analysis. Subject to the usual caveats of retrospective subgroup analysis, our data suggest that in locally advanced head and neck cancer, microscopically involved resection margins and extracapsular spread of tumor from neck nodes are the most significant prognostic factors for poor outcome. The addition of concomitant cisplatin to postoperative radiotherapy improves outcome in patients with one or both of these risk factors who are medically fit to receive chemotherapy.


A panel data analysis of the probability of childbirth in a Japanese sample: New evidence of the two-child norm.
To reveal the conditions that could facilitate childbirth in modern humans, it is necessary to analyze not only cross-sectional surveys but also panel data that track the same person for a long period. In this study, we analyzed factors that would influence the probability of childbirth. We analyzed Japanese panel data with a Cox proportional hazard model. Subjects of our analysis were married women and their childbirth records from 2004 to 2009. Contrary to the predictions based on the theory of behavioral ecology, we found no positive relationship between good parental conditions for childcare, such as high income, increase in income, or coresidence with parents (i.e., grandparents of children), and the occurrence of childbirth. We found that the number of existing children had a significant impact on the probability of childbirth. The likelihood of further childbirth by couples with one child was nearly equal to that of childless ones. However, the corresponding likelihood of couples with two children was about five times lower than that of childless ones. The total fertility rates in modern developed societies are quite low and couples prefer having two children. This trend is known as the two-child norm, but it is a paradoxical phenomenon in terms of fitness maximization. Our result provided new quantitative evidence of this norm. This study revealed that the number of existing children being less than two was one of the factors associated with further childbearing in our Japanese sample.


Prediction of drug pro-arrhythmic cardiotoxicity using a semi-physiologically based pharmacokinetic model linked to cardiac ionic currents inhibition.
Drug-induced torsades de pointes (TdP) risks are responsible for the withdrawal of many drugs from the market. Nowadays, assessments of drug-induced TdP risks are mainly based on maximum effective free therapeutic plasma concentration (EFTPCmax) and cardiac ionic current inhibitions using the human ventricular myocytes model (Tor-ORd model). Myocytes are targets of drug-induced TdP. The TdP risks may be directly linked to myocyte drug concentrations. We aimed to develop a semi-physiologically based pharmacokinetic (Semi-PBPK) model linked to cardiac ionic current inhibition (pharmacodynamics, PD) (Semi-PBPK-PD) to simultaneously predict myocyte drug concentrations and their TdP risks in humans. Alterations in action potential duration (ΔAPD90) were simulated using the Tor-ORd model and ionic current inhibition parameters based on myocyte or plasma drug concentrations. The predicted ΔAPD90 values were translated into in vivo alterations in QT interval(ΔQTc) induced by moxifloxacin, dofetilide, or sotalol. Myocyte drug concentrations of moxifloxacin, dofetilide, and sotalol gave better predictions of ΔQTc than plasma. Following validating the developed semi-PBPK-PD model, TdP risks of 37 drugs were assessed using ΔAPD90 and early afterdepolarization occurrence, which were estimated based on 10 × EFTPCmax and 10 × EFTMCmax (maximum effective free therapeutic myocyte concentration). 10 × EFTMCmax gave more sensitive and accurate predictions of pro-arrhythmic cardiotoxicity and the predicted TdP risks were also closer to clinic practice than 10 × EFTPCmax. In conclusion, pharmacokinetics and TdP risks of 37 drugs were successfully predicted using the semi-PBPK-PD model. Myocyte drug concentrations gave better predictions of ΔQTc and TdP risks than plasma.


Control of beta 3-adrenergic receptor gene expression in brown adipocytes in culture.
Brown adipose tissue is a mammalian thermogenic tissue. Its ability to dissipate energy as heat is due to a unique mitochondrial protein, uncoupling protein (UCP). Activation and expression of UCP is under control of the sympathetic nervous system acting through beta -adrenergic receptors (AR). In this study we used Siberian hamster brown adipocytes differentiated in vitro to investigate the expression of the fat specific beta 3-AR. Binding studies using the new labelled beta 3 adrenergic ligand [3H]SB 206606 showed a density of beta 3-AR in brown adipocyte plasma membranes comparable to that measured in vivo. beta 3-AR mRNA expression was very high in mature brown adipocytes and was started to be expressed during differentiation before UCP mRNA. Its half-life was approximately 50 min. Treatment of cells with non-specific beta adrenergic agonists, specific beta 3-adrenergic agonists, and dibutyryl cyclic AMP resulted in a marked down regulation of beta 3-AR mRNA level within several hours.


Supporting Sustained STAR-VA Implementation: Evaluation of a Sustainment Coaching Program.
The Veterans Health Administration (VA) STAR-VA program is a person-centered, interdisciplinary intervention for managing distress behaviors in dementia in VA nursing homes, called Community Living Centers (CLCs). Teams often struggle to sustain STAR-VA after site-lead partner turnover. The STAR-VA Sustainment Coaching Program was developed to support a new local STAR-VA behavioral coordinator and/or nurse champion (ie, site-leads) and engage the team to implement sustainment strategies. The aims of this evaluation were to document sustainment needs, barriers and facilitators, and effective strategies used during a sustainment intervention. We describe qualitative and quantitative findings of a program evaluation of the STAR-VA Sustainment Coaching pilot program. Eight CLC teams participated in the pilot program, 5 training a new nurse champion, 2 a new behavioral coordinator, and 1 both new site-leads. CLC teams completed a needs assessment, developed sustainment goals and plans, tracked sustainment interventions implemented, and reported case outcomes. Outcome assessment and tracking reports were summarized and themes identified using a qualitative inductive approach. Common sustainment needs were to train a new nurse champion, promote staff understanding of dementia and distress behaviors, and promote a culture of person-centered dementia care. Most sites selected sustainment goals of implementing training procedures and behavioral rounds. Sustainment barriers included limited staff time, staff turnover, lack of supportive routines and tools, and limited awareness of STAR-VA. Facilitators included leadership support, staff interest, and training resources. Most sites reported successful implementation of STAR-VA behavior rounds, whereas strategies to achieve training-related goals had variable success. The STAR-VA Sustainment Coaching Program helped CLC teams identify and implement strategies to support sustained STAR-VA implementation. The results of this project are informing ongoing efforts to integrate STAR-VA components into usual care processes for CLC residents with dementia.


A SPECT Camera for Combined MRI and SPECT for Small Animals.
We describe an MR-compatible SPECT camera for small animals. The SPECT camera system can be inserted into the bore of a state-of-the-art MRI system and allows researchers to acquire tomographic images from a mouse in-vivo with the MRI and the SPECT acquiring simultaneously. The SPECT system provides functional information, while MRI provides anatomical information. Until today it was impossible to operate conventional SPECT inside the MRI because of mutual interference. The new SPECT technology is based on semiconductor radiation sensors (CZT, ASICs), and it fits into conventional high field MRI systems with a minimum 12-cm bore size. The SPECT camera has an MR-compatible multi-pinhole collimator for mice with a ø25-mm field-of-view. For the work reported here we assembled a prototype SPECT camera system and acquired SPECT and MRI data from radioactive sources and resolution phantoms using the camera outside and inside the MRI.


A short exposure to a semi-natural habitat alleviates the honey bee hive microbial imbalance caused by agricultural stress.
Honeybee health and the species' gut microbiota are interconnected. Also noteworthy are the multiple niches present within hives, each with distinct microbiotas and all coexisting, which we termed "apibiome". External stressors (e.g. anthropization) can compromise microbial balance and bee resilience. We hypothesised that (1) the bacterial communities of hives located in areas with different degrees of anthropization differ in composition, and (2) due to interactions between the multiple microbiomes within the apibiome, changes in the community of a niche would impact the bacteria present in other hive sections. We characterised the bacterial consortia of different niches (bee gut, bee bread, hive entrance and internal hive air) of 43 hives from 3 different environments (agricultural, semi-natural and natural) through 16S rRNA amplicon sequencing. Agricultural samples presented lower community evenness, depletion of beneficial bacteria, and increased recruitment of stress related pathways (predicted via PICRUSt2). The taxonomic and functional composition of gut and hive entrance followed an environmental gradient. Arsenophonus emerged as a possible indicator of anthropization, gradually decreasing in abundance from agriculture to the natural environment in multiple niches. Importantly, after 16 days of exposure to a semi-natural landscape hives showed intermediate profiles, suggesting alleviation of microbial dysbiosis through reduction of anthropization.


Modular Engineering to Enhance Keratinase Production for Biotransformation of Discarded Feathers.
Biotransformation of wasted feathers via feather-degrading enzyme has gained immense popularity, low conversion efficiency hinders its scale application, and the main purpose of this study is to improve feather-degrading enzyme production in Bacillus licheniformis. Firstly, keratinase from Bacillus amyloliquefaciens K11 was attained with the best performance for feather hydrolysis, via screening several extracellular proteases from Bacillus; also, feather powder was proven as the most suitable substrate for determination of feather-degrading enzyme activity. Then, expression elements, including signal peptides and promoters, were optimized, and the combination of signal peptide SPSacC with promoter Pdual3 owned the best performance, keratinase activity aggrandized by 6.21-fold. According to amino acid compositions of keratinase and feeding assays, Ala, Val, and Ser were proven as critical precursors, and strengthening these precursors' supplies via metabolic pathway optimization resulted in a 33.59% increase in the keratinase activity. Furthermore, keratinase activity reached 2210.66 U/mL, up to 56.74-fold from the original activity under the optimized fermentation condition in 3-L fermentor. Finally, the biotransformation process of discarded feathers by the fermented keratinase was optimized, and our results indicated that 90.94% of discarded feathers (16%, w/v) were decomposed in 12 h. Our results suggested that strengthening precursor amino acids' supplies was an efficient strategy for enhanced production of keratinase, and this research provided an efficient strain as well as the biotransformation process for discarded feather re-utilization.


The lack of a structured blood-brain barrier in the onychophoran Peripatus acacioi.
Onychophorans are 'living fossils' frequently purported to have evolved from the same ancestor as the arthropods and annelids. In the CNS of Peripatus acacioi, beneath an outer acellular neural lamella, glial cells ensheath the cerebral ganglion and the nerve cords. These glial cells are, however, attenuated and rather few in number and, although they interdigitate with one another, they seem to lack intercellular junctions. Exogenous tracers penetrate between them and into the underlying neuropile, suggesting that there is no structural blood-brain barrier. Throughout the nervous tissue, extracellular spaces occur which contain banded collagen fibrils embedded in a matrix material. Thin glial cell processes, characterized by dense filaments, surround these regions and frequently form hemi-desmosomes with the extracellular matrix. The peripheral nerve cell bodies have a range of diameters; some have the characteristics of neurosecretory neurons. Granules in such neurons are produced by the Golgi saccules and associated fenestrated membranes which also possess many coated vesicles. Comparable granules are also found in axonal tracts, but no distinct peripheral neurohaemal areas have been found. Lysosomes are common in the nerve cell bodies and are frequently in the form of multivesicular bodies or large phagocytic vacuoles. Beneath the outer nerve cells lie many tracheae, arranged as a ring around the central neuropile which consists of glial processes, extracellular matrix, axons and nerve terminals. These nerve terminals occur throughout the central neuropile and are characterized by dense pyramidal presynaptic specializations and postsynaptic subsurface cisternae. The nervous system of Peripatus is relatively simple in its organization, in the lack of glial intercellular junctions and in the ready accessibility of substances from the external milieu.


Peripheral venous thrombosis in children and adolescents with adipsic hypernatremia secondary to hypothalamic tumors.
To determine the clinical presentation and laboratory follow-up in patients with the syndrome of adipsic hypernatremia complicated with a peripheral thrombosis event. Report of 3 patients (6-19 years old) with chronic hypernatremia with sustained difficulties to normalize their serum osmolality levels. During post-surgical management the 3 patients developed a peripheral venous thrombotic event as a complication of their chronic hyperosmolality. Chronic hypernatremia in patients with prolonged immobilization is associated with an increased risk for development of deep venous thrombosis.


Prognostic Role of Cell Cycle and Proliferative Markers in Clear Cell Renal Cell Carcinoma.
The cell cycle is one of the most important regulatory mechanisms of cellular growth and proliferation. Dysregulation of this pathway is thought to be the first step in carcinogenesis of renal cell carcinoma (RCC), important for tumor invasion and metastases. Multiple different parts and regulators of the cell cycle are detectable via assays like immunohistochemistry and have been studied extensively. This review aims to provide an overview of current data regarding individual cell cycle and proliferative markers and their association with clinicopathologic parameters and their impact on prognosis for patients with RCC. Furthermore, the value of marker combinations is discussed.


Deregulated DNA damage response network in Behcet's disease.
Behcet's disease (BD) is a chronic, relapsing systemic vasculitis of unknown etiology. Since the DNA repair enzyme NEIL1 has been identified as one of the two genetic risk factors for BD by whole exome study, we examined the potential involvement of the DNA damage response (DDR) network in BD. Peripheral blood mononuclear cells from 26 patients and 26 age-/sex-matched healthy controls were studied. Endogenous DNA damage levels were increased in active BD patients compared to controls or patients in remission. In parallel, BD patients had defective nucleotide excision repair capacity. RNA-sequencing revealed reduced expression of NEIL1 that negatively correlated with DNA damage accumulation. On the other hand, expression of genes involved in senescence and senescence-associated secretory phenotype positively correlated with individual endogenous DNA damage levels. We conclude that deregulated DDR contributes to the proinflammatory environment in BD.


A robust point-matching algorithm for autoradiograph alignment.
We present a novel method for the geometric alignment of autoradiographs of the brain. The method is based on finding the spatial mapping and the one-to-one correspondences (or homologies) between point features extracted from the images and rejecting non-homologies as outliers. In this way, we attempt to account for the local, natural and artifactual differences between the autoradiograph slices. We have used the resulting automated algorithm on a set of left prefrontal cortex autoradiograph slices, specifically demonstrated its ability to perform point outlier rejection, validated its robustness property using synthetically generated spatial mappings and provided an anecdotal visual comparison with the well-known iterated closest-point (ICP) algorithm. Visualization of a stack of aligned left prefrontal cortex autoradiograph slices is also provided.


Synthesis and physicochemical study of the laminin active sequence: SIKVAV.
The synthesis, physicochemical characterization, and interaction with membrane model systems of a peptide derived from the PA22-2 region of laminin are described. Surface activity studies indicate that this peptide is able to spread at the air-water interface being the maximal spreading pressure 20 mN/m at subphase concentrations around 10 micro M. Besides, these peptide molecules are also able to form stable monolayers. Physicochemical studies concerning the interaction of this peptide with lipids, organized in mono and bilayers, were carried out using Langmuir balance experiments and polarization fluorescence techniques. The peptide penetrates better in monolayers of DPPC than in those of PC and forms condensed mixed monolayers with DPPC. Energies of mixing are small thus indicating that deviations from ideality were almost negligible. Interactions with bilayers were studied through microviscosity changes (DPH and TMA-DPH probes), membrane permeability alterations (CF, NBD-PE/dithionite), and fusion promotion (NBD-PE/Rh-PE, resonance energy transfer). Results indicate that this sequence interacts very softly with bilayers without promoting changes in their organization. These data as well as the lack of interaction with erythrocytes suggest that coating liposomes with this peptide through chemical amide bonds can render stable inmunoliposomes for further biological applications.


An investigation of preclinical medical students' preference for summative or formative assessment for physiology learning.
Both summative and formative assessments are known to facilitate student learning and understanding and help students to identify areas of weakness. However, few studies have investigated students' preference for either summative or formative evaluations, particularly in the area of preclinical medicine. The current study addresses this deficit by surveying 137 first-year graduate entry to medicine (GEM) preclinical medical students from 2 consecutive years (2018-2019 and 2019-2020), for their thoughts on the 6 summative (i.e., for a small percentage of marks), proctored and the 5 informal, formative (i.e., no marks available) continuous assessments in physiology that they encountered in semesters 1 and 2, respectively. Our survey revealed that between 75 and 90% of students felt that both evaluation formats were roughly equally useful (i.e., selecting options, "agree" or "strongly agree") both for providing feedback about their understanding of physiology and for identifying deficits in their physiology knowledge. However, although a significantly larger number of students felt that summative evaluations motivated them to study more than the formative evaluations (P = 0.006), overall, more students favored formative over summative assessments. Notably, however, GEM students from nonbiomedical backgrounds were significantly more in favor of summative assessments than those from either biomedical backgrounds (P = 0.003) or the whole GEM survey cohort (P = 0.01). The implications of these findings will be discussed, with suggestions as to how the student views outlined here might be facilitated within an academic program to maximize both student learning as well as their motivation to study and keep up with taught material.NEW & NOTEWORTHY Although several studies have investigated the relative effectiveness of regular summative versus formative assessments as tools to facilitate student learning and understanding, ours is the first to explicitly solicit students' views on, and preferences for, either regular formative or summative assessment in preclinical medicine. We demonstrate that, overall, students preferred formative- to summative-type assessments, due to the immediacy of feedback, but also that summative tests incentivized them to study and keep up with material more.


Genetic neuromuscular disorders: living the era of a therapeutic revolution. Part 2: diseases of motor neuron and skeletal muscle.
This is the second part of a two-part document intended to discuss recent therapeutic progresses in genetic neuromuscular disorders. The present review is for diseases of motor neuron and skeletal muscle, some of which reached recently the most innovative therapeutic approaches. Nusinersen, an SMN2 mRNA splicing modifier, was approved as first-ever therapy of spinal muscular atrophy (SMA) by FDA in 2016 and by EMA in 2017. The orally administered small-molecule risdiplam, which increases SMN protein levels similarly but also in peripheral organs, is tested in ongoing phase 2 and 3 trials. After positive results with phase 1 treatment with AAV9-SMN, the first gene therapy for SMA, a phase 3 clinical trial is ongoing. Ataluren is the first approved drug for Duchenne muscular dystrophy (DMD) patients with premature stop codon mutations and its indication has been recently extended since the age of 2 years. Exon skipping technology was and is currently tested in many phase 3 trials, and eteplirsen received a conditional approval by FDA for patients amenable to exon 51 skipping, but not by EMA. Many other compounds with different mechanisms of action are now tested in DMD by phase 2 and 3 trials, including phase 1 gene therapy. Other innovative approaches are under investigation, i.e., gene therapy in X-linked myotubular myopathy and Pompe disease, and antisense oligonucleotides in myotonic dystrophy type 1. Positive evidences are discussed about lamotrigine and ranolazine in non-dystrophic myotonias, chaperons in Pompe disease, and nucleosides in mitochondrial DNA depletion induced by thymidine kinase 2 deficiency.


[Fluorometric determination of "activated" cyclophosphamide and ifosfamide in blood (author's transl)].
"Activated" N-(2-Chloroethyl)amido-oxazaphosphorines like 4-hydroxycyclophosphamide, 4-hydroperoxycyclophosphamide, 4-hydroxyifosfamide, and 4-hydroperoxyifosfamide can be determined fluorometrically by condensation of liberated acrolein with m-aminophenol yielding 7-hydroxychinolin. The method permits determination of 10(-10) mol and is specific for "activated" N-(2-Chloroethyl)amido-oxazaphosphorine metabolites which liberate acrolein under conditions of the test. Neither cyclophosphamide nor ifosfamide or other metabolites of this cytostatics interfere with the test. Blood levels of free 4-hydroxycyclophosphamide and 4-hydroxyifosfamide were determined after injection of cyclophosphamide and ifosfamide into mice.


Segregation of cortical head direction cell assemblies on alternating θ cycles.
High-level cortical systems for spatial navigation, including entorhinal grid cells, critically depend on input from the head direction system. We examined spiking rhythms and modes of synchrony between neurons participating in head direction networks for evidence of internal processing, independent of direct sensory drive, which may be important for grid cell function. We found that head direction networks of rats were segregated into at least two populations of neurons firing on alternate theta cycles (theta cycle skipping) with fixed synchronous or anti-synchronous relationships. Pairs of anti-synchronous theta cycle skipping neurons exhibited larger differences in head direction tuning, with a minimum difference of 40 degrees of head direction. Septal inactivation preserved the head direction signal, but eliminated theta cycle skipping of head direction cells and grid cell spatial periodicity. We propose that internal mechanisms underlying cycle skipping in head direction networks may be critical for downstream spatial computation by grid cells.


Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up.
Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population. The COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression. Duration of follow-up in patients alive was mean 23 (range 22-24) years. In total, 44 patients died (28%, SMR=0.80 [95% CI 0.59 to 1.06]); 20 of 75 COBRA patients (27%, SMR 0.75 [0.47 to 1.14]) and 24 of 79 SSZ patients (30%, SMR 0.85 [0.56 to 1.25]); p=0.61). In the reference sample of the general population, 55 people (36%) died. 5 factors were significantly associated with increased mortality hazard: damage progression at 28 weeks; high Health Assessment Questionnaire (HAQ) score and absence of HLA-DR 2 or 3; disease duration from start of complaints was also significant, but showed an uninterpretable pattern. This prospective trial cohort study of early RA is one of the first to show similar mortality compared with the general population after 23 years of follow-up. It confirms that early, intensive treatment of RA has long-term benefits and suggests that treating to target is especially important for patients with poor prognosis.


Effect of dietary vitamin A or N-acetylcysteine on ethylnitrosourea-induced rat gliomas.
It is our hypothesis that low grade gliomas are the glial counterparts of other precancerous lesions such as colon polyps and, therefore, suitable targets for chemoprevention. Steps in the molecular progression of gliomas have been described, indicating that an accumulation of abnormalities is required for progression to a high grade and interruption of this progression might be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the offspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Animals exposed to ENU and receiving a control diet developed brain tumors and had a shortened life expectancy compared with rats unexposed to ENU. The animals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Animals receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no reduction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the putative mechanism of action of these agents. These data indicate that glioma chemoprevention is possible and deserves further exploration.


Stimulation of platelet-derived growth factor-induced DNA synthesis by angiotensin II in rabbit vascular smooth muscle cells.
In cultured rabbit vascular smooth muscle cells (VSMCs), angiotensin II by itself had little mitogenic effect even in the presence of cell-free plasma-derived serum (PDS), but markedly stimulated the platelet-derived growth factor (PDGF)-induced DNA synthesis in the presence of PDS. The maximal extent of DNA synthesis induced by PDGF plus angiotensin II was about twice that induced by PDGF alone. The stimulatory effect of angiotensin II was dose-dependent with the maximal response seen at 1 microM and was inhibited by the specific angiotensin II receptor antagonist, [Sar1, Ile8]angiotensin II. In VSMCs, both PDGF and angiotensin II induced expression of the c-fos gene in dose-dependent manners. In contrast to the synergistic effect of angiotensin II and PDGF on DNA synthesis, they induced expression of the c-fos gene in an additive manner. These results suggest that angiotensin II may act as a growth regulator for VSMCs in addition to acting as a vasoconstrictor.


Caesarean section under continuous spinal anaesthesia in a parturient with pulmonary hypertension: A case report.
Women with pulmonary hypertension have high morbidity and mortality during pregnancy. The inability to increase cardiac output can lead to heart failure, while hypercoagulability and reduced systemic vascular resistance also lead to other risks. This paper report the case of a parturient admitted for caesarean section under continuous spinal anaesthesia scheduled at 34 weeks of amenorrhea following severe pulmonary arterial hypertension. She had a history of significant mitral insufficiency. The procedure was performed without incident. The catheter was removed immediately postoperatively. The baby was female and in good health. She was transferred to the resuscitation service with restoration of oral nutrition. Loco-regional anaesthesia is to be preferred in pulmonary hypertension associated to pregnancy. In order to reduce the risk of mortality due to general anaesthesia for this type of patient, it is possible to practice the continuous spinal anaesthesia for caesarean section without having hemodynamic consequences.


6-deoxyerythronolide B production through chromosomal localization of the deoxyerythronolide B synthase genes in E. coli.
Chromosomal engineering was used to localize the deoxyerythronolide B synthase (DEBS) genes and propionyl-CoA carboxylase (PCC) genes to the BAP1 Escherichia coli chromosome creating the new strain YW9. YW9 then featured a plasmid-free heterologous pathway for the production of the polyketide product 6-deoxyerythronolide B (6dEB, a precursor to the antibiotic erythromycin) highlighted by the successful chromosomal integration of five genes total and three DEBS genes each approximately 10 kb in length. The new strain was tested for small-scale 6dEB biosynthesis and compared to 6dEB production from plasmid-derived gene expression at 22, 30, and 37 degrees C. YW9 produced 6dEB at each temperature tested; whereas, the current plasmid-based system could only produce 6dEB at 22 and 30 degrees C. As determined by MS analysis, average production levels for YW9 were 0.47 (22 degrees C), 0.52 (30 degrees C), and 0.11 (37 degrees C)mg/L.


Commentary: why don't plant leaves get fat?
Recent pressures to obtain energy from plant biomass have encouraged new metabolic engineering strategies that focus on accumulating lipids in vegetative tissues at the expense of lignin, cellulose and/or carbohydrates. There are at least three important factors that support this rationale. (i) Lipids are more reduced than carbohydrates and so they have more energy per unit of mass. (ii) Lipids are hydrophobic and thus take up less volume than hydrated carbohydrates on a mass basis for storage in tissues. (iii) Lipids are more easily extracted and converted into useable biofuels than cellulosic-derived fuels, which require extensive fractionation, degradation of lignocellulose and fermentation of plant tissues. However, while vegetative organs such as leaves are the majority of harvestable biomass and would be ideal for accumulation of lipids, they have evolved as "source" tissues that are highly specialized for carbohydrate synthesis and export and do not have a propensity to accumulate lipid. Metabolism in leaves is directed mostly toward the synthesis and export of sucrose, and engineering strategies have been devised to divert the flow of photosynthetic carbon from sucrose, starch, lignocellulose, etc. toward the accumulation of triacylglycerols in non-seed, vegetative tissues for bioenergy applications.


Management and outcome in prenatally diagnosed sacrococcygeal teratomas.
The aim of the present study was to retrospectively determine the clinical factors affecting the outcome after birth in prenatally diagnosed sacrococcygeal teratomas (SCT). Six cases of prenatal SCT were identified from January 1985 until August 2005. A retrospective review of case-notes and pathological reports was carried out. Clinical data during the perinatal period, operative findings, postoperative complications and follow up were evaluated in the patients with prenatally diagnosed SCT. SCT presented as type I in two neonates and type III in four between 22 and 33 weeks' gestation. Fetal intervention was not performed for any fetus. Five of six were delivered by cesarean section and the other was delivered vaginally due to small tumor size. Patients were born at between 29 and 39 weeks' gestation and weighed from 1840 to 3500 g. All patients with type III SCT presented with related diseases, including bilateral hydronephrosis, neurological deficit of the communicating peroneal nerve such as paralytic talipes equines, bladder or bowel dysfunction, high-output cardiac failure, or fetal hydrops in one of a set of fraternal twins. A baby with high-output cardiac failure and fetal hydrops underwent urgent cesarean section at 29 weeks' gestation and died 8 days after birth despite intensive care due to multi-organ failure. In five cases, surgery was successful with good outcomes maintained at follow-up of between 8 months and 14 years. Detailed ultrasound should be performed to rule out associated anomalies, and determine the presence or absence of hydrops in prenatally diagnosed SCT. Fetal hydrops, orthopedic impairment such as lower extremity weakness and swelling, and urinary incontinence are important clinical factors affecting the outcome after birth in prenatally diagnosed SCT. In particular, the present study indicated that the association of a fraternal twin and fetal hydrops makes it very difficult to treat SCT perinatally.


Management of complications of wrist fractures.
This article reviews the most common complications associated with the management of carpal fractures. Discussion focuses on the recognition of commonly "missed" fractures and fracture patterns and the negative sequelae that can result from these delayed diagnoses. The pitfalls of conservative treatment of specific carpal fractures are reviewed, and the most common complications resulting from the operative management of carpal injuries are described.


[Effect of steroid hormones on the rate of NADPH and NADH oxidation by rat liver microsomes].
Sex hormones heighten the rate of the NADP-H oxidation. A relation between the oxidation rate of steroids and the polarity of their molecule has been found. Both androgens and estogens inhibit the transport of electrons in the NAD-H-dependent chain. The capability of steroids to hydrooxylate depends upon the chemical structure and not the affiliation to androgens or estrogens.


Effect of sialidase on blood group specificity of hog submaxillary glycoproteins.
Hogs can be divided into three phenotypes A, H and In, depending on the ability of extracts of their submaxillary glands to inhibit the agglutination of human A cells with human anti-A, and human O cells with eel-anti-H serum. Evidence is here provided that the inactive glycoprotein, In, represents H active glycoprotein containing additional N-glycolyl neuraminic acid, which stereospecifically masks the H determinant, alpha (1 --> 2)-L-fucosyl residue.


Carboxylic acid-tethered polyaniline as a generic immobilization matrix for electrochemical bioassays.
Polyaniline (PANI) was functionalized by thiol-ene click chemistry to obtain carboxylic acid-tethered polyaniline (PCOOH). The versatility of PCOOH as an immobilization matrix was demonstrated by constructing four different biosensors for detection of metabolites and cancer biomarker. Immobilization efficiency of PCOOH was investigated by surface plasmon resonance and fluorescence microscopic analysis which revealed dense immobilization of biomolecules on PCOOH as compared to conventional PANI. A sandwich electrochemical biosensor was constructed using PCOOH for detection of liver cancer biomarker, α-fetoprotein (AFP). The sensor displayed sensitivity of 15.24 µA (ng mL-1)-1 cm-2, with good specificity, reproducibility (RSD 3.4%), wide linear range (0.25-40 ng mL-1) at - 0.1 V (vs. Ag/AgCl), and a low detection limit of 2 pg mL-1. The sensor was validated by estimating AFP in human blood serum samples where the AFP concentrations obtained are consistent with the values estimated using ELISA. Furthermore, utilization of PCOOH for construction of enzymatic biosensor was demonstrated by covalent immobilization of glucose oxidase, uricase, and horseradish peroxidase (HRP) for detection of glucose, uric acid, and H2O2, respectively. The biosensors displayed reasonable sensitivity (50, 148, 127 µA mM-1 cm-2), and linear ranges (0.1-5, 0.1-6, 0.1-7 mM) with a detection limit of 10, 1, and 8 µM for glucose, uric acid, and H2O2, respectively. The present study demonstrates the capability of PCOOH to support and enable oxidation of H2O2 generated by oxidase enzymes as well as HRP enzyme catalyzed reduction of H2O2. Thus, PCOOH offers a great promise as an immobilization matrix for development of high-performance biosensors to quantify a variety of other disease biomarkers. Carboxylic acid-tethered polyaniline synthesized by thiol-ene click chemistry was used as matrix to construct four different electrochemical biosensors for detection of cancer biomarker α-fetoprotein, glucose, uric acid, and H2O2.


[Primary intestinal localisation of Hodgkin's disease. One case initially diagnosed as a benign eosinophilic granuloma of the small intestine (author's transl)].
Intestinal lesions in Hodgkin's disease remain relatively rare. Even rarer are forms in which intestinal lesions or mesenteric nodes remain the only manifestations of the disease for a number of years. In these cases, histological findings are usually less typical than in more usual sites and this explains the diagnostic hesitancy which sometimes occurs. In the case reported here, the diagnosis made and adhered to for four years and despite three successive operations was that of an eosinophilic granuloma of the small intestine.


Patent foramen ovale in liver transplant recipients does not negatively impact short-term outcomes.
Patent foramen ovale (PFO) is a common atrial septal defect that is largely asymptomatic and often undiagnosed. The impact of a PFO in patients undergoing liver transplantation (LT) is unknown. Assess the impact of PFO and physiologic intrapulmonary shunt (IPS) on the perioperative outcomes of patients who underwent LT. We performed a retrospective, intention-to-treat analysis of patients with PFO and controls without PFO who underwent LT at Mayo Clinic in Florida between 2008 and 2013. Patients with physiologic IPS were also analyzed. The cohorts were compared for baseline characteristics, length of stay in the intensive care unit (ICU), postoperative oxygen requirements, 30-d cerebrovascular accidents, and mortality. Of the 935 patients who underwent LT, 10.4% had proven PFO by pre-LT echocardiogram. Control patients (n = 101) were statistically older than PFO and IPS (n = 56) patients, but similar in sex, BMI, Model for End-stage Liver Disease score, American Society of Anesthesiologist score, and left ventricular ejection fraction. PFO and IPS patients had similar length of stay in the ICU, mechanical ventilation times, post-LT oxygen requirements, and 30-d mortality compared to controls. Subgroup analysis showed similar outcomes for large PFO and IPS patients to controls. The presence of PFO did not have a negative impact on perioperative LT outcomes.


Urine and kidney epidermal growth factor: ontogeny and sex difference in the mouse.
We have explored the physiology of urinary epidermal growth factor (EGF) in the mouse by studying its ontogeny, and the effects of testosterone therapy on immunoreactive EGF (IR-EGF) concentrations in urine, kidney, serum and submandibular gland (SMG). Urine IR-EGF (U-EGF) increased about 100-fold relative to urea concentration and about 1000-fold relative to urine volume from the 1st day of life to adulthood. Most of this increase occurred between days 6 and 18, which is the known period of steep rise in plasma thyroid hormone concentration in the mouse. A small F greater than M sex difference was present in the adult. This difference was opposite in direction to the large M greater than F sex difference in adult SMG-EGF concentration. On day 26 (age of appearance of morphological sex difference in SMG) the sex difference was not yet present in urine, although in SMG it was even larger than in the adult. Kidney EGF concentration was low relative to U-EGF: 1 ml of adult urine contained approximately as much IR-EGF as 100 pairs of adult kidneys. In the adult, but not on day 26, there was a sex difference in kidney EGF concentration parallel to the sex difference in urine: female levels were about 30% higher than male levels. Ten days of testosterone treatment of adult female mice evoked an increase in IR-EGF concentration which was 1.7-fold for serum and 5-fold for SMG. In contrast, this treatment did not increase kidney or urine IR-EGF concentrations although kidney weight increased 1.3-fold.(ABSTRACT TRUNCATED AT 250 WORDS)


Improving forensic science integration: A Director's perspective.
In testimony before the Presidential Commission on Law Enforcement and the Administration of Justice on April 14, 2020, the author was able to make recommendations for how Forensic Science Service Providers (FSSPs) and law enforcement can work more collaboratively and effectively on domestic abuse and sexual assault investigations. This Perspectives article focuses on four key areas of those recommendations: resources, sexual assault response collaboration, forensic criminal intelligence sharing, and quality assurance.


Immunoarchitecture of the bone marrow in neutropenia: increased HNK-1 + cells define a subset of neutropenic patients.
An immunoperoxidase technique was used to examine the distribution of lymphocyte subsets in bone marrow biopsies of 15 patients with neutropenia and seven non-neutropenic controls. The bone marrow of most patients and controls had similar distributions of immune effector cells characterized by a diffuse array of predominantly cytotoxic/suppressor T-cells and occasional nodular aggregates of helper T-cells. Cells displaying the natural killer cell marker HNK-1 were sparse in controls and most neutropenic patients. However, marked increases in marrow HNK-1 + cells were identified in four of the 15 patients. Three of these patients had diffuse HNK-1 + infiltrates associated with increased Leu 4+ (OKT-3+) T-cells while one had a nodular HNK-1+ infiltrate associated with small B-cell follicles. Each of these patients had clinical features similar to those described in the large granular lymphocyte (LGL) lymphocytosis (leukemia) syndrome, but only one of four demonstrated persistently increased numbers of LGLs in the peripheral blood. Thus, this study extends the association of neutropenia and increased numbers of cells with a T/NK phenotype to include patients whose bone marrow is the only demonstrable site of involvement. Since morphologic examination of the bone marrow could not identify the bone marrows with increased HNK-1+ cells, immunologic techniques are required to detect these cases.


Chaotropic resolution of high molecular weight (type I) NADH dehydrogenase, and reassociation of flavin-rich (type II) and flavin-poor subunits.
1. Type-I NADH dehydrogenase (Complex I) was solubilized and dissociated into subunits by NaClO4. NADH slows the dissociation. On subsequent stepwise addition of (NH4)2SO4 the dissociation is partly reversed, as is to be expected from the opposing effects of ClO-4 and SO-24, which are on the salting-in and salting-out sides, respectively, of the lyotropic series. 2. In consequence, the aggregates of subunits that are separated by (NH4)2-SO4 fractionation consist of randomly associated subunits as well as fragments of Type I enzyme. The fraction precipitating at 27% satd. (NH4)2SO4 is flavin-poor, that remaining soluble at 55% satd. (NH4)2SO4 flavin-rich and those separating between 27 and 55% satd. (NH4)2SO4 intermediate in composition. 3. The fraction remaining soluble at 55% satd. (NH4)2SO4 contains the purified low-molecular-weight iron-sulphur flavoprotein (Type-II dehydrogenase). It is a dimer consisting of one molecule of FMN, one 28-kilodalton and one 56-kilodalton subunit per protomer. Work of others indicates that it contains 4 Fe and 4 acid-labile S atoms per molecule of FMN. Sometimes the fraction remaining soluble at 55% satd. (NH4)2SO4 contained an additional small subunit (12 kilodaltons) and four additional Fe and acid labile S atoms per protomer. The sedimentation coefficients (s020,w) of the two preparations were 5.3 and 6.6 S, respectively, with calculated frictional ratios of 1.5 and 1.24, respectively. 4. The intermediate fractions are mixtures of the various subunits present in Complex I. Specifically a fraction separating at 55% satd. (NH4)2SO4 was found to be a mixture of two fragments, the pure iron-sulphur flavoprotein and a 26-S fragment that contained per protomer four subunits of 12 kilodaltons, one each of 28, 32, 56 and 77 kilodaltons, one molecule of FMN and 20 Fe and acid-labile S atoms. It was probably tetrameric or even larger. 5. The oxidoreductase activity of the intermediate fractions is dependent on the protein concentration, the activity with ferricyanide increasing and that with ferricytochrome c decreasing with increasing protein concentration. This is interpreted as an increased association of subunits present in the intermediate fractions. Similar results are obtained when flavin-rich and flavin-poor fractions are mixed. The association is cooperative. NADH favours the association of the subunits. 6. Association of the subunits is accompanied by a 10-fold increase in k2 (rate constant for intramolecular electron flow), a 10-fold decrease of the accessibility of ferricyanide to the reduced enzyme and a 10(4)-fold decrease of the accessibility of ferricytochrome c. The Ks (NADH) is also decreased. Although the changes are in the direction to be expected from a conversion of Type II enzyme to Type I, the value of k2 is still much less than in the latter enzyme.


CYP2C19*2 and prognosis after an acute coronary syndrome: Insights from a Portuguese center.
Clopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized. To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population. We performed a prospective, longitudinal study of 95 patients admitted for an ACS between March and October 2009 to a single coronary care unit. Patients aged under 75 who survived hospital stay and for whom clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped using a commercially available kit. Patients were divided into two groups: Group A (non-carriers, normal metabolizers, CYP2C19*1/*1), n=69; and Group B (carriers, slow metabolizers, CYP2C19*2/*1 or *2/*2), n=26. The primary endpoint was a combined outcome of cardiovascular death, non-fatal myocardial infarction or re-admission for unstable angina; median follow-up was 136.0 (79.0-188.0) days. The median age of the population was 62.0 (51.0-68.0) years, and 83.2% were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no differences between the groups with respect to demographic data or history of cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and renal function were also similar. The groups were also homogenous with respect to GRACE risk score (118.0 (95.0-136.5) vs. 115.0 (96.0-133.0), p=0.68), medical treatment and percutaneous revascularization during hospital stay. Event-free survival was higher for Group A (94.0% vs. 75.0%, log-rank p=0.010). Three readmissions for MI were documented, all in the slow metabolizers group. In our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker.


Berberine-loaded albumin nanoparticles reverse aflatoxin B1-induced liver hyperplasia.
Hepatocellular carcinoma (HCC) can be produced from aflatoxin B1 (AFB1) administration. Although berberine (BER) acts as an anticancer agent and can counteract the AFB1 effect, it has low bioavailability. Nanotechnology can overcome this problem. This research aimed to synthesize berberine nanoparticles (NPs) and then estimate their therapeutic effect compared to that of berberine against aflatoxin-induced hepatotoxicity. The desolvation method was used to prepare BER-NPs. Aflatoxicosis was induced by 5 consecutive intraperitoneal injections (IP) of 200 µg/kg/day AFB dissolved in dimethylsulfoxide (DMSO). After the induction period, two treatments were performed: the first with 100 mg/kg BER and the second with 10 mg/kg BER-NPs. Liver, kidney, and diabetic profiles were estimated by using standardized methods. Hepatic oxidative stress, inflammatory, cancer cell proliferation, and invasion markers were used by ELISA and qPCR techniques. The TEM image shows that both BSA NPs and BER-BSA NPs had spherical, regular, and uniform shapes. The BER encapsulation efficiency % was 78.5. The formed-BER-BSA NPs showed a loading capacity % of 7.71 and the synthesis yield % of 92.6. AFB1 increases pro-oxidant markers, decreases antioxidant systems, stimulates inflammatory enzymes, inhibits anti-inflammatory markers, decreases tumor suppressor enzymes, increases oncogenes, increases glycolytic activity, prevents cell death, and promotes cell growth. Most of the biochemical markers and hepatic architecture were normalized in the BER-BSA NP-treated group but not in the BER-treated group. Altogether, the obtained data proved that treatment with BER-NPs was more efficient than treatment with berberine against aflatoxicoses induced in rats.


High throughput analysis and capture of benzo[a]pyrene using supermacroporous poly(4-vinyl pyridine-co-divinyl benzene) cryogel matrix.
A novel supermacroporous cryogel matrix, poly(4-vinyl pyridine-co-divinyl benzene) has been synthesized by free radical polymerization using 4-vinyl pyridine and divinyl benzene as monomers and poly(ethylene glycol) diacrylate as crosslinker. Hydrophobic property of such synthesized matrix allows capture of polyaromatic hydrocarbons like benzo[a]pyrene. The cryogel matrix produced is highly porous (porosity more than 80%) having large and interconnected pores in the range of 10-100 μm that allows easy passage of particulate matter and viscous liquids. The newly synthesized cryogel minicolumns (0.5 ml; 0.9 cm dia.× 1.2 cm height) were used to develop a high throughput analysis system in a miniaturized platform (open ended 96-well microtitre plate). The performance of the cryogel columns in 96-well microtitre plate was reproducible in different wells having approximately 72% binding. This system is drainage- and leakage- protected and can be used for the easy, fast and parallel analysis of many samples. The 96-well format also allows efficient analysis of benzo[a]pyrene in the spiked sample. The cryogel matrix was then used for column chromatography, which showed that the matrix has a binding capacity of 2 μg per ml of matrix for benzo[a]pyrene, thus providing a system for remediation/separation of benzo[a]pyrene. The chromatographic column could bind and partially separate the spiked mixture of benzo[a]pyrene and anthracene.


Morphometric and molecular characterisation of Tenuiproboscis keralensis n. sp. infecting marine and brackish water fishes from the south-west coast of India with a note on morphological plasticity.
A new species of acanthocephalan infecting marine and brackish water fishes from the south-west coast of India is described. The parasite belongs to the genus Tenuiproboscis, and the fish hosts include Lutjanus argentimaculatus, L. ehrenbergii, Siganus javus, Epinephelus malabaricus, E. coioides, Scatophagus argus, Parascolopsis aspinosa, Caranx ignobilis, Gerres filamentosus and Lates calcarifer. The parasite inhabits mid- and hindgut regions and is characterised by an elongated, cylindrical, bulbous and posteriorly tapering metasoma and a claviform proboscis having 14-15 rows of 14-15 hooks each. Females larger than males, measured 3898.16-10,318.00 μm (6430.00 ± 1417.30) in length and 458.93-1435.68 μm (929.81 ± 250.39) in width. Males measured 3234.89-8644.20 μm (5729.50 ± 1176.60) in length and 388.30-1584.61 μm (795.88 ± 184.12) in width. Parasites recovered from different host species showed morphological/morphometric variations. However, principal component analysis (PCA) revealed significant overlapping of characters indicating their similarities. Proboscis profiling based on variations in size and position of hooks also yielded similar results. Further, in molecular phylogenetic analysis, parasites from different fish hosts formed a monophyletic clade with strong bootstrap support, again indicating their conspecific nature. These morphological/morphometric variations can be ascribed to differences in host species. Morphology and morphometrics in combination with PCA, proboscis profiling and molecular analysis suggest the present acanthocephalan parasite is different from other described species of Tenuiproboscis. Hence, it is considered as a new species and named T. keralensis n. sp. Prevalence, intensity and abundance of the parasite in different hosts are also discussed.


Advanced Oxygen Therapy for the Small Animal Patient - High-Flow Oxygen Therapy and Mechanical Ventilation.
High-flow nasal oxygen therapy (HFNT) and positive pressure ventilation (PPV) are interventions used in the management of animals with respiratory failure. The indications for the use of these modalities, clinical application, prognosis, and a review of the current veterinary evidence are provided.


Releasing the peri-neuronal net to patch-clamp neurons in adult CNS.
The extracellular matrix of adult neural tissue contains chondroitin sulphated proteogylcans that form a dense peri-neuronal net surrounding the cell body and proximal dendrites of many neuronal classes. Development of the peri-neuronal net beyond approximately postnatal day 17 obscures visualization and often access by patch electrodes to neuronal membranes with the result that patch clamp recordings are most readily obtained from early postnatal animals. We describe a technique in which the surface tension of a sucrose-based medium promotes partial dissociation of thin tissue slices from adult tissue. Surface tension spreads the tissue and loosens the peri-neuronal net from neuronal membranes within minutes and in the absence of proteolytic enzymes. Furthermore, the extent of dissociation can be controlled so as to maintain the overall slice structure and allow identification of specific cell classes. Excellent structural preservation of neurons and dendrites can be obtained and full access by patch electrodes made possible for current- or voltage-clamp recordings in tissue well beyond the development of peri-neuronal nets. We demonstrate the feasibility of using this approach through patch recordings from neurons in the brainstem and cerebellum of adult gymnotiform fish and in deep cerebellar nuclei of rats as old as 6 months.


Influence of ruthenium doping on UV- and visible-light photoelectrocatalytic color removal from dye solutions using a TiO2 nanotube array photoanode.
The photocatalytic activity of TiO2 anodes was enhanced by synthesizing Ru-doped Ti|TiO2 nanotube arrays. Such photoanodes were fabricated via Ti anodization followed by Ru impregnation and annealing. The X-ray diffractograms revealed that anatase was the main TiO2 phase, while rutile was slightly present in all samples. Scanning electron microscopy evidenced a uniform morphology in all samples, with nanotube diameter ranging from 60 to 120 nm. The bias potential for the photoelectrochemical (PEC) treatment was selected from the electrochemical characterization of each electrode, made via linear sweep voltammetry. All the Ru-doped TiO2 nanotube array photoanodes showed a peak photocurrent (PP) and a saturation photocurrent (SP) upon their illumination with UV or visible light. In contrast, the undoped TiO2 nanotubes only showed the SP, which was higher than that reached with the Ru-doped photoanodes using UV light. An exception was the Ru(0.15 wt%)-doped TiO2, whose SP was comparable under visible light. Using that anode, the activity enhancement during the PEC treatment of a Terasil Blue dye solution at Ebias(PP) was much higher than that attained at Ebias(SP). The percentage of color removal at 120 min with the Ru(0.15 wt%)-doped TiO2 was 98% and 55% in PEC with UV and visible light, respectively, being much greater than 82% and 28% achieved in photocatalysis. The moderate visible-light photoactivity of the Ru-doped TiO2 nanotube arrays suggests their convenience to work under solar PEC conditions, aiming at using a large portion of the solar spectrum.


A new method of imaging the right ventricle using peripheral vein infusion of xenon 127.
We report the development of a new method for obtaining right ventriculograms using the peripheral intravenous infusion of a new tracer, 127Xe dissolved in saline. This tracer has a half life of 36 days, emits 172 keV and 203 keV photons, and is completely cleared by the lungs during pulmonary transit. The right ventricle can therefore be imaged free from interfering activity in the systemic circulation. The technique was used in 11 normal subjects and the results compared with those obtained using first pass and gated equilibrium blood pool angiography with 99mTc. Excellent images of the right ventricle were obtained and the tricuspid and pulmonary valve planes could be easily identified. This imaging technique has significant advantages over existing methods for the noninvasive assessment of right ventricular function.


Calcium-induced interaction of phospholipid vesicles and bilayer lipid membranes.
The interaction of unilamellar phospholipid vesicles with bilayer lipid membranes has been studied by observing the electrical conductance of the planar membrane. The presence of phosphatidylcholine vesicles as well as phosphatidylcholine/phosphatidylserine (1 : 1) vesicles on one side compartment of the bilayer membrane, but not phosphatidylserine vesicles, causes discrete fluctuations in the phosphatidylserine membrane conductance, which is also increased by at least an order of magnitude. These events are dependent on vesicle concentration as well as the presence of Ca2+. The results are interpreted in terms of the incorporation of domains of phosphatidylcholine into the membrane, which confer a higher conductance state.


A qualitative assessment of personal and social responsibility for kidney disease: the Increasing Kidney Disease Awareness Network Transplant Project.
Limited qualitative research has explored opinions of kidney disease health care providers regarding racial and ethnic disparities in access to and receipt of kidney transplantation. Key informant interviews were conducted among transplant nephrologists, nephrologists, transplant social workers, and transplant coordinators to determine barriers to transplantation among African Americans compared to whites with end-stage renal disease (ESRD). Thirty-eight interviews were audio recorded and transcribed to hardcopy for content analysis. Grounded theory was used to determine dominant themes within the interviews. Reliability and validity were ensured by several coinvestigators independently sorting verbatim responses used for generating themes and subsequent explanations. Several major categories arose from analysis of the transcripts. Under the category of personal and social responsibility for kidney transplantation, interviews revealed 4 major themes: negative personal behaviors, acquisition of and lack of self-treatment of comorbid conditions, lack of individual responsibility, and the need for more social responsibility. Many providers perceived patients as being largely responsible for the development of ESRD, while some providers expressed the idea that more social responsibility was needed to improve poor health status and disparities in kidney transplantation rates. Kidney disease health providers seemed torn between notions of patients' accountability and social responsibility for racial disparities in chronic kidney disease and ESRD. Further research is needed to clarify which aspects contribute most to disparities in access to transplantation.


Activated partial thromboplastin time (aPTT) monitoring to achieve therapeutic anticoagulation before and after introducing a nomogram for adjunctive heparin treatment with thrombolytic therapy for acute myocardial infarction.
In patients with acute myocardial infarction (AMI) receiving thrombolytic therapy and i.v. unfractionated heparin, anticoagulant levels are frequently outside the target range. We evaluated the effects on anticoagulant levels before (group A) and after (group B) the introduction of a heparin nomogram in consecutive AMI-patients, receiving thrombolytic therapy and adjunctive heparin treatment. The target activated partial thromboplastin time (aPTT) was defined as 60-90 s. During the first 72 h after admission, the total number of aPTTs within the target range and the time taken to achieve the range were compared. The incidence of bleeding complications was assessed. Group A consisted of 56 and group B of 55 patients. The number of patients within the target range at 72 h (44 versus 51; chi2=4.51; P=0.034) was significantly higher in group B. No difference was found between total aPTTs within the target range (26% in group A versus 30% in group B; P=ns). Bleeding complications were slightly less in group B (7 versus in group A versus 2 patients in group B; P=ns). We concluded that the introduction of a nomogram resulted in significantly more patients with aPTTs within the target range. However, a substantial number of aPTTs before and after introduction of the nomogram were outside the target range. Moreover, this retrospective study shows that previously acquired prospective data (which showed a marked improvement of anticoagulation using a heparin nomogram) are not necessarily reproduced in the real life clinical setting.


Brainstem projections to the facial nucleus of the opossum. A study using axonal transport techniques.
The horseradish peroxidase and autoradiographic techniques have been used to determine the origin and intranuclear termination of brainstem axons projecting to the facial nucleus of the opossum and to define networks which could be utilized in some oral-facial behaviors. Two regions of the midbrain have dense projections to the facial nucleus. One region is the ventral periaqueductal gray and adjacent interstitial nucleus of the medial longitudinal fasciculus which project bilaterally to those areas of the facial nucleus supplying auricular and cervical musculature. A second is the paralemniscal zone of the caudolateral midbrain which innervates the same areas of the contralateral facial nucleus. The red nucleus and/or the adjacent tegmentum send a less dense projection to those regions of the contralateral facial nucleus which innervate buccolabial and zygomatic muscles. The dorsolateral pons (the parabrachial complex, the nucleus locus coeruleus, pars alpha, and the nucleus sensorius n. trigemini, pars dorsalis) projects densely to those areas of the ipsilateral facial nucleus which innervate buccolabial and zygomatic musculature. In contrast, the nucleus reticularis pontis, pars ventralis, projects bilaterally to parts of the facial nucleus supplying auricular and cervical muscles. There was evidence of some rostral to caudal organization in the latter projection. Neurons in medial parts of the lateral reticular formation project bilaterally to the facial nucleus. Those within the nucleus reticularis parvocellularis and the rostral nucleus reticularis medullae oblongatae ventralis innervate areas supplying buccolabial and zygomatic muscles. Neurons in the nucleus reticularis medullae oblongatae ventralis located caudal to the obex favor regions of the facial nuclei which supply auricular and cervical muscles. Neurons in the nucleus reticularis medullae oblongatae dorsalis and lamina V of the medullary and spinal dorsal horns project ipsilaterally to the facial nucleus in a manner suggesting that information from specific cutaneous areas reaches neurons supplying the muscles deep to them. The brainstem-facial connections are discussed in relation to the functionally diverse roles served by the facial nucleus in oral-facial behavior.


Dependence of cerebral capillary hematocrit on red cell flow separation at bifurcations: a computer simulation study.
The influence of preferential red cell entry into microvascular branches with higher flow on microvessel hematocrit distribution was studied by mathematical modeling in a reconstructed cerebrocortical microvascular network. More heterogeneous hematocrit distribution was obtained at stronger cell partitioning. Small variations in the cell separation parameter resulted in significantly different hematocrit distributions. The significance of these findings in vivo should be further evaluated.


In situ monitoring of IncF plasmid transfer on semi-solid agar surfaces reveals a limited invasion of plasmids in recipient colonies.
Most natural conjugative IncF plasmids encode a fertility inhibition system that represses transfer gene expression in the majority of plasmid-carrying cells. The successful spread of these plasmids in clinically relevant bacteria has been suggested to be supported by a transitory derepression of transfer gene expression in newly formed transconjugants. In this study, we aimed to monitor the extent of transitory derepression during agar surface matings in situ by comparing plasmid spread of the IncF plasmid R1 and its derepressed mutant R1drd19 at low initial cell densities. A zygotic induction strategy was used to visualize the spatial distribution of fluorescent transconjugants within the heterogeneous environment. Epifluorescence and confocal microscopy revealed different transfer patterns for both plasmids, however, spread beyond the first five recipient cell layers adjacent to the donor cells was not observed. Similar results were observed for other prototypical conjugative plasmids. These results cannot rule out that transitory derepression contributes to the limited R1 plasmid invasion, but other factors like nutrient availability or spatial structure seem to limit plasmid spread.


HWGMWSY, an unanticipated polystyrene binding peptide from random phage display libraries.
Phage display is a powerful technique for the discovery of peptide ligands that bind to various targets; however, ambiguous results often appear. Peptide HWGMWSY has been isolated repeatedly in our laboratory and by other research groups dealing with different protein and nonprotein targets, which led to a hypothesis that it may be a target-unrelated peptide interacting with polystyrene plastic surfaces. We compared binding properties and amplification rate of phage clone displaying the peptide HWGMWSY, a previously confirmed plastic binding clone WHWRLPS, and a control phage clone ASVQERK. An enzyme-linked immunosorbent assay and a phage elution assay confirmed that phage clone HWGMWSY binds to polystyrene. Surface plasmon resonance measurements on the other hand excluded the possibility of binding to bovine serum albumin, a common blocking agent in phage display experiments. Amplification rates of the above-noted phage clones were not statistically different. We therefore conclude that phage clone HWGMWSY was isolated in different selection procedures as a result of its affinity to polystyrene.


Identifying key factors in homeowner's adoption of water quality best management practices.
The recognition of the significance of the residential environment in contributing to non-point source (NPS) pollution and the inherently dispersed nature of NPS pollution itself that presents significant challenges to effective regulation has led to the creation and dissemination of best management practices (BMPs) that can reduce the impacts of NPS pollution (Environmental Protection Agency US, Protecting water quality from urban runoff, http://www.epa.gov/npdes/pubs/nps_urban-facts_final.pdf , 2003). However, very few studies have examined the factors that influence the adoption of BMPs by residential homeowners, despite the fact that residential environments have been identified as one of the most significant contributors to NPS pollution. Given this need, the purpose of this project was to explore how demographic and knowledge-based factors predict adoption of residential BMPs in an urbanizing watershed in Northern Illinois using statistical analyses of survey data collected as part of a watershed planning process. The findings indicate that broad knowledge of BMPs is the strongest predictor of use for a specific BMP. Knowledge of BMPs is strongly correlated with their use, which reinforces the need for educational programs, even among those assumed to be knowledgeable about BMPs.


Surgical management of cerebral metastases.
Important issues related to surgery for patient with cerebral metastases, including surgical anatomy and techniques, patient selection criteria, surgery for multiple and recurrent metastases, and the roles of adjunctive whole brain radiation, and stereotactic radiosurgery. A practical algorithm for decision making and survival statistics for the common metastatic tumors have been developed.


Early administration of tissue-plasminogen activator improves the long-term clinical outcome at 5years after onset.
Data on long-term outcomes after tissue-plasminogen activator (tPA) therapy are limited. We evaluated the rate of favorable outcomes and mortality at 5years after tPA therapy and investigated factors related to long-term clinical outcomes. Telephone interviews or interview letters were used to assess the modified Rankin Scale (mRS) scores at 3months, 6months, 1year, 2years, 3years, 4years, and 5years after tPA therapy. Favorable outcome was defined as mRS 0-2. Multivariate logistic regression analysis was conducted to investigate factors associated with favorable outcomes and mortality at 5years after tPA therapy. From 2005 to 2013, 256 (median age, 77 [interquartile range, 68-84] years; 157 [61%] males; median National Institutes of Health Stroke Scale score, 11 [5-18]) patients were enrolled. Kaplan-Meier curve showed that favorable outcomes after 5years after tPA therapy occurred in 45% of the patients and that the mortality rate was 40%. Univariate analysis showed that onset-to-treatment time (OTT) was 121 (107-172) minutes in patients with favorable outcomes and 156 (126-171) minutes in patients with unfavorable outcomes (p=0.016). In addition, OTT was 157 (133-172) minutes in the death group and 123 (106-169) minutes in the survival group (p=0.001). Multivariate regression analysis indicated that OTT was an independent factor related to favorable outcomes (odds ratio 0.96, 95% confidence interval 0.93-0.99, p=0.004) and mortality (odds ratio 1.04, 95% confidence interval 1.02-1.06, p=0.001). Early tPA administration can improve long-term clinical outcomes.


New host and locality records for the Ixodes auritulus (Acari: Ixodidae) species group, with a review of host relationships and distribution in the Neotropical Zoogeographic Region.
New Neotropical records are presented for ticks belonging to the Ixodes auritulus Neumann, 1904, species group, together with a review of hosts and localities from which members of this complex have previously been collected. The range of the I. auritulus species group is now understood to include Colombia, and 15 bird species are listed as new hosts. From Guatemala to southern Argentina and Chile, specimens of the I. auritulus group have been found on birds belonging to the orders Ciconiiformes, Columbiformes, Falconiformes, Galliformes, Passeriformes, Piciformes, Procellariiformes and Tinamiformes. Passeriform birds are probably the principal hosts, sustaining tick populations throughout the Neotropics. Collection data have yielded four areas--southern South America (from 56 degrees S to 51 degrees S), southern Brazil (25 degrees S-22 degrees S), south-central Peru (14 degrees S-10 degrees S) and Central America (10 degrees N-15 degrees N)--where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species.