A controlled study of disruptive vocalizations among geriatric residents in nursing homes.
This paper reports the results of a controlled study comparing geriatric residents in nursing homes who displayed disruptive vocalizations with residents in a comparison group. Two 350-bed nursing homes were surveyed, and it was found that 11% of the residents engaged in disruptive vocalizations, at least once per week, of sufficient severity to require consideration in the resident's care plan. Results show that disruptive vocalizers were more functionally impaired and were more likely to receive a diagnosis of dementia. They were also more likely to display a higher activity level and to experience sleep disturbance and to be prescribed neuroleptic medications. Descriptive data are presented on typology of disruptive vocalizations, likely situations for their occurrence, and the utilization and perceived efficacy of common interventions. Suggestions are made regarding behavioral treatments for this vexing problem.


Detection of antibodies to myelin basic protein by solid-phase radioimmunoassay with [125I]protein A.
A solid phase radioimmunoassay (RIA) for the detection of antibodies to myelin basic protein (MBP) in sera has been developed employing MBP-coated flexible polyvinylchloride microtiter trays and [125I]protein-A as the radiolabel. [125I]Protein-A directly binds to the Fc region of serum IgG from several animal species and serves as an excellent reagent for detecting antibody. It can also be used to bind to a second antibody ligand, thereby making it useful even when it does not bind directly to the primary antibody Fc region. The use of one preparation of [125I]protein-A label allows sera from several species to be tested for antibodies to MBP simultaneously, thereby making this RIA technically simple, rapid and economical. This assay has been particularly useful in examining serum samples from animals with experimental autoimmune encephalomyelitis and hypomyelinogenisis congenita. In patients with multiple sclerosis low levels of antibody to MBP can be detected in cerebrospinal fluid (CSF) and acid-eluted extracts from brain plaque material; detection of low levels of antibody in human serum has not been possible due to non-specific binding of human serum Ig in this RIA.


Indicators for Medical Mistrust in Healthcare-A Review and Standpoint from Southeast Asia.
The relationship based on trust is exceptionally important in healthcare, where life or death and quality of health are major concerns. Relational crack jeopardises the provision of quality healthcare when trust is taken for granted. Trust is believed to be the vital key to minimise medical negligence, lawsuits and patient complaints towards healthcare providers while acting as an empowering agent to significant clinical outcomes. Trust is indispensable to healthcare. However, to identify its deterioration is not a simple feature. Moreover, lack of research and public dissemination complicate this topic further. Hence, understanding medical mistrust issues and their associated indicators is urgently needed to ensure the top-notch provision of healthcare. We employed narrative review methodology together with key terms matching for the selected electronic databases for this article. Our review concluded that an "Increasing number of medical litigations and complaints towards physicians", "Physicians' low mastery of interpersonal communication skill" and "Patients' demand, practice, and non-disclosure of alternative treatments" are the possible indicators to predict mistrust. Efforts to restore and strengthen trust can only be made when these indicators are well understood firsthand.


JSOM: Jointly-evolving self-organizing maps for alignment of biological datasets and identification of related clusters.
With the rapid advances of various single-cell technologies, an increasing number of single-cell datasets are being generated, and the computational tools for aligning the datasets which make subsequent integration or meta-analysis possible have become critical. Typically, single-cell datasets from different technologies cannot be directly combined or concatenated, due to the innate difference in the data, such as the number of measured parameters and the distributions. Even datasets generated by the same technology are often affected by the batch effect. A computational approach for aligning different datasets and hence identifying related clusters will be useful for data integration and interpretation in large scale single-cell experiments. Our proposed algorithm called JSOM, a variation of the Self-organizing map, aligns two related datasets that contain similar clusters, by constructing two maps-low-dimensional discretized representation of datasets-that jointly evolve according to both datasets. Here we applied the JSOM algorithm to flow cytometry, mass cytometry, and single-cell RNA sequencing datasets. The resulting JSOM maps not only align the related clusters in the two datasets but also preserve the topology of the datasets so that the maps could be used for further analysis, such as clustering.


Mast cell deficiency attenuates acupuncture analgesia for mechanical pain using c-kit gene mutant rats.
Acupuncture therapy plays a pivotal role in pain relief, and increasing evidence demonstrates that mast cells (MCs) may mediate acupuncture analgesia. The present study aims to investigate the role of MCs in acupuncture analgesia using c-kit gene mutant-induced MC-deficient rats. WsRC-Ws/Ws rats and their wild-type (WT) littermates (WsRC-+/+) were used. The number of MCs in skin of ST36 area was compared in two rats after immunofluorescence labeling. Mechanical withdrawal latency (MWL), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were measured on bilateral plantar for pain threshold evaluation before and after each stimulus. Acupuncture- and moxibustion-like stimuli (43°C, 46°C heat, 1 mA electroacupuncture [EA], 3 mA EA, and manual acupuncture [MA]) were applied randomly on different days. Fewer MCs were observed in the skin of ST36 in mutant rats compared to WT rats (P<0.001). For pain thresholds, MWL and MWT were higher in WsRC-Ws/Ws compared to WsRC-+/+ on bilateral paws (P<0.05), but TWL was not different between the two rats (P>0.05). Bilateral MWL and MWT in WsRC-+/+ rats increased significantly after each stimulus compared to baseline (P<0.01, P<0.001). In WsRC-Ws/Ws rats, only noxious stimuli could produce anti-nociceptive effects for mechanical pain (46°C, 3 mA EA, MA) (P<0.01, P<0.001). Additionally, the net increases in MWL and MWT induced by most stimuli were greater in WT than in mutant rats (P<0.05). For thermal nociception, either high- or low-intensity stimuli could significantly augment TWL in two rats (P<0.001), and the net increases of TWL evoked by most stimuli were to the same extent in two genetic variants. MCs influence the basic mechanical but not thermal pain threshold. MCs participate in acupuncture analgesia in mechanical but not in thermal nociception, in that MC deficiency may attenuate the mechanical analgesia evoked by high-intensity stimuli and eliminate analgesia provoked by low-intensity stimuli.


Dominant-negative effect of the c-fos family gene products on inducible NO synthase expression in macrophages.
Activation of murine peritoneal macrophages or the macrophage cell line RAW264 with IFN-gamma and bacterial lipopolysaccharide promotes a transient up-regulation of c-fos family gene expression following inducible NO synthase (iNOS) production. Since introduction of a double mutation into the two AP-1-binding sites in the iNOS promoter region reduced the promoter activity to 25% of the authentic one in activated RAW264 cells, the induced c-Fos/AP-1 may promote iNOS expression in activated macrophages. Surprisingly, overexpression of c-fos in activated macrophages completely suppressed the production of iNOS, but not that of IL-6 and IL-1beta. The regulatory effect was also observed by overexpression of c-fos, c-jun or fosB on the promoter activity as deduced from transfection experiments. However, the mutation of AP-1-binding sites in the promoter region did not abrogate the regulatory effect of c-fos and the effect of c-fos was diminished by co-transfection with c-jun, but not with fosB, suggesting no relation between the regulatory effect and a c-Fos/AP-1 complex. Expression of NF-IL6 (C/EBPbeta), whose gene product can make a non-functional heterodimer with c-Fos family proteins, was transiently induced in activated macrophages. Overexpression of NF-IL6 in activated RAW264 cells augmented iNOS promoter activity and reduced the regulatory effect of c-fos overexpression. Thus, overproduction of c-Fos family proteins acts as a dominant-negative-type regulator on iNOS expression in activated macrophages.


Autoregressive processes with anomalous scaling behavior: applications to high-frequency variations of a stock market index.
We employ autoregressive conditional heteroskedasticity processes to model the probability distribution function (PDF) of high-frequency relative variations of the Standard & Poors 500 market index data, obtained at the time horizon of 1 min. The model reproduces quantitatively the shape of the PDF, characterized by a Lévy-type power-law decay around its center, followed by a crossover to a faster decay at the tails. Furthermore, it is able to reproduce accurately the anomalous decay of the central part of the PDF at larger time horizons and, by the introduction of a short-range memory, also the crossover behavior of the corresponding standard deviations and the time scale of the exponentially decaying autocorrelation function of returns displayed by the empirical data.


Magnetic-field decay of three interlocked flux rings with zero linking number.
The resistive decay of chains of three interlocked magnetic flux rings is considered. Depending on the relative orientation of the magnetic field in the three rings, the late-time decay can be either fast or slow. Thus, the qualitative degree of tangledness is less important than the actual value of the linking number or, equivalently, the net magnetic helicity. Our results do not suggest that invariants of higher order than that of the magnetic helicity need to be considered to characterize the decay of the field.


New nursing: the road to freedom?
The consequences that recent developments in nursing have had for the nurse-patient relationship are the concern of this paper. It is argued that, by attempting to reduce the power differentials that exist between nurse and patient, 'new nursing' reforms encourage rational, rather than distorted, communication between lay and professional participants in health care encounters. The significance of these developments is underlined by framing them within the theoretical framework developed by Jürgen Habermas, who argues that, because symbolic communication is a defining feature of our essential humanity, distortion of communication by means of coercive power is a denial of that humanity. Conversely, rational communication is the stuff of truth, freedom and justice. Empirical evidence from in-depth interviews with nurses is used to demonstrate that there have been significant changes in the nurse-patient relationship, which have led to improvements in communication and to the empowerment of patients. Despite the fact that the reforms face significant obstacles, nurses can be proud of the fact that their efforts have contributed to the re-affirmation of the full humanity of people requiring health care.


Lower prevalence of IL-4 receptor alpha-chain gene G variant in very-low-birth-weight infants with necrotizing enterocolitis.
Altered production of immunoregulatory cytokines is associated with the development of necrotizing enterocolitis (NEC) in preterm very low-birth-weight (VLBW) infants. According to data obtained in adults, functional genetic polymorphisms influence cytokine production capacity. The aim of this study was to evaluate whether functional polymorphisms of interleukin (IL)-1beta, IL-4 receptor alpha-chain (IL-4ra), IL-6, and IL-10 genes might be associated with the risk of NEC in VLBW infants. Dried blood spot samples of 46 VLBW infants with NEC were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Samples from 90 VLBW infants without NEC were used as controls. Infants with NEC carried the mutant variant of IL-4ra less frequently than controls (0.125 v 0.224; P <.05) even after adjustment for risk factors of NEC. No significant differences were found in the allelic frequencies of IL-1beta, IL-6, and IL-10 genes between NEC and control infants. Carrier state of IL-4ra mutant allele might be associated with lower risk of NEC in VLBW infants. This genetic variant is associated with enhanced IL-4 effect. IL-4 is a major regulator of Th1-Th2 shift. The authors hypothesize that infants carrying the IL-4ra mutant allele might have Th2 skewness that might defend against the development of NEC.


Usual drinking patterns and non-fatal injury among patients seeking emergency care.
To explore the association between drinking patterns, irrespective of whether alcohol was consumed in the event of the injury or not, and different injury variables; and to identify settings and situations in which risky drinkers have an increased likelihood of injury. The study population consisted of all patients aged 18-70 years registered for an injury according to ICD-10 at a Swedish emergency department during an 18-month period. After informed consent, the injury patients were screened for drinking habits by the AUDIT-C questionnaire. The gender, age and drinking pattern of injury patients were compared with the general population. A total of 2782 patients aged 18-70 years were registered for an injury during the study period. The number of drop-outs was 631. Drop-outs include those who did not consent to participate, were severely injured, too intoxicated or did not fill out the questionnaire satisfactory. Thus, 77.3% of the target group were included for further analysis (1944 drinkers and 207 abstainers). The patients were categorized into three drinking categories: abstainers, non-risky and risky drinkers. Risky drinkers were defined according to usual weekly consumption of 80g or more of alcohol for women and 110g or more for men and/or heavy episodic drinking (i.e. having six glasses or more one glass=12g alcohol), or both, on one occasion at least once a month, valid for both women and men. To estimate the relationship between drinking patterns and the injury variables (environment, cause of injury, activity and diagnosis), odds ratios (OR) were calculated by logistic regression. Multiple logistic regression was used in order to control for age and sex differences between the various drinking and injury categories. The proportion of risky drinkers was higher in the study population compared with the general population in the same area. When controlling for age and sex, risky drinkers (OR 6.4(adj) Confidence interval CI 1.9-21.2) and non-risky drinkers (OR .4.5(adj) CI 1.4-14.5) displayed an increased risk for injury compared with abstainers, in amusement locations, parks, by or on lakes or seas, especially while engaged in play, hobby or other leisure activities (risky drinkers: OR 2.8(adj) CI 1.3-5.6; non-risky drinkers: OR 2.4(adj) CI 1.2-4.6). All differences between drinking patterns in external cause of injury disappeared when age and sex were considered. During rest, meals and attending to personal hygiene, the non-risky drinkers had a lower probability of injury compared with abstainers (OR 0.3(adj) CI 0.1-0.8). Non-risky drinkers had a higher probability than abstainers of suffering luxation (dislocation) or distortion (OR 1.6(adj) CI 1.1-2.5). Nine per cent of the study population reported that they believed that their injury was related to intake of alcohol. Half of this group were non-risky drinkers (CI for the 13.7% difference was 9.7-17.6). Few significant associations between drinking pattern and injury remained when age and sex were controlled for.


Cardiac function in end-stage renal disease.
To assess cardiac status in end-stage renal disease, we compared clinical, ECG, and echocardiographic data from 37 patients on maintenance hemodialysis with data from 42 patients with functioning renal transplants. Cardiovascular symptoms and abnormal cardiovascular findings were more common in dialysis-maintained patients than in those with transplants. Follow-up studies indicated that despite a high prevalence of cardiac symptoms, abnormal physical signs, and dilated left ventricles among patients with end-stage renal disease, systolic left ventricular function was generally well preserved irrespective of renal failure therapy. Compared with maintenance hemodialysis, however, successful renal transplantation is associated with an overall enhancement of cardiac status, the majority of which is probably secondary to transplant-associated improvement in hemoglobin level and control of intravascular volume.


SALMFamide2 and serotonin immunoreactivity in the nervous system of some acoels (Xenacoelomorpha).
Acoel worms are simple, often microscopic animals with direct development, a multiciliated epidermis, a statocyst, and a digestive parenchyma instead of a gut epithelium. Morphological characters of acoels have been notoriously difficult to interpret due to their relative scarcity. The nervous system is one of the most accessible and widely used comparative features in acoels, which have a so-called commissural brain without capsule and several major longitudinal neurite bundles. Here, we use the selective binding properties of a neuropeptide antibody raised in echinoderms (SALMFamide2, or S2), and a commercial antibody against serotonin (5-HT) to provide additional characters of the acoel nervous system. We have prepared whole-mount immunofluorescent stainings of three acoel species: Symsagittifera psammophila (Convolutidae), Aphanostoma pisae, and the model acoel Isodiametra pulchra (both Isodiametridae). The commissural brain of all three acoels is delimited anteriorly by the ventral anterior commissure, and posteriorly by the dorsal posterior commissure. The dorsal anterior commissure is situated between the ventral anterior commissure and the dorsal posterior commissure, while the statocyst lies between dorsal anterior and dorsal posterior commissure. S2 and serotonin do not co-localise, and they follow similar patterns to each other within an animal. In particular, S2, but not 5-HT, stains a prominent commissure posterior to the main (dorsal) posterior commissure. We have for the first time observed a closed posterior loop of the main neurite bundles in S. psammophila for both the amidergic and the serotonergic nervous system. In I. pulchra, the lateral neurite bundles also form a posterior loop in our serotonergic nervous system stainings.


Switchable deep eutectic solvent-based homogenous liquid-liquid microextraction combined with high-performance liquid chromatography-diode-array detection for the determination of the chiral fungicide mefentrifluconazole in water, fruit juice, and fermented liquor.
A switchable deep eutectic solvent-based homogeneous liquid-liquid microextraction (SDES-HLLME) technique was developed and combined with high-performance liquid chromatography-diode-array detection for the determination of the chiral fungicide mefentrifluconazole. A (green) SDES was synthesized from 4-methoxyphenyl and 3-amino-1-propanol and used as an extraction solvent (thus avoiding the use of toxic extraction solvents). To improve the efficiency of the extraction process, a hydrophobic extraction solvent was subsequently generated in situ by adjusting the pH. The detection process is linear in the range of 0.01 to 1 μg ml-1 . The limit of detection and limit of quantification were determined to be 0.003 and 0.01 μg ml-1 , respectively. Recovery rates of 79.2% to 104.6% were acquired with relative standard deviations of 0.6% to 2.5%. The method is fast, simple, and environmentally friendly. Moreover, it was successfully used to enantioselectively determine the concentrations of mefentrifluconazole residues in water, fruit juice, and fermented liquor samples.


Non-invasive Oscillometry-Based Estimation of Cardiac Output - Can We Use It in Clinical Practice?
While invasive thermodilution techniques remain the reference methods for cardiac output (CO) measurement, there is a currently unmet need for non-invasive techniques to simplify CO determination, reduce complications related to invasive procedures required for indicator dilution CO measurement, and expand the application field toward emergency room, non-intensive care, or outpatient settings. We evaluated the performance of a non-invasive oscillometry-based CO estimation method compared to transpulmonary thermodilution. To assess agreement between the devices, we used Bland-Altman analysis. Four-quadrant plot analysis was used to visualize the ability of Mobil-O-Graph (MG) to track CO changes after a fluid challenge. Trending analysis of CO trajectories was used to compare MG and PiCCO® calibrated pulse wave analysis over time (6 h). We included 40 patients from the medical intensive care unit at the Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin between November 2019 and June 2020. The median age was 73 years. Forty percent of the study population was male; 98% was ventilator-dependent and 75% vasopressor-dependent at study entry. The mean of the observed differences for the cardiac output index (COI) was 0.7 l∗min-1*m-2 and the lower, and upper 95% limits of agreement (LOA) were -1.9 and 3.3 l∗min-1*m-2, respectively. The 95% confidence interval for the LOA was ± 0.26 l∗min-1*m-2, the percentage error 83.6%. We observed concordant changes in CO with MG and PiCCO® in 50% of the measurements after a fluid challenge and over the course of 6 h. Cardiac output calculation with a novel oscillometry-based pulse wave analysis method is feasible and replicable in critically ill patients. However, we did not find clinically applicable agreement between MG and thermodilution or calibrated pulse wave analysis, respectively, assessed with established evaluation routine using the Bland-Altman approach and with trending analysis methods. In summary, we do not recommend the use of this method in critically ill patients at this time. As the basic approach is promising and the CO determination with MG very simple to perform, further studies should be undertaken both in hemodynamically stable patients, and in the critical care setting to allow additional adjustments of the underlying algorithm for CO estimation with MG.


Altered growth factor expression in the aging penis: the Brown-Norway rat model.
The objective of the present study was to evaluate age-related changes in the protein and gene expression of modulators of erectile function (nitric oxide [NO] and endothelin-1 [ET-1]) and growth factors such as transforming growth factor (TGF-beta1) and vascular endothelial growth factor (VEGF) in the penile tissue of Brown-Norway (BN) rats. Young and old BN male rats were euthanized, and the penile tissue was processed for immunohistochemical and molecular analyses. Total RNA was extracted, and an Access reverse transcription-polymerase chain reaction (RT-PCR) system was used for messenger RNA (mRNA) expression analysis. Immunohistochemical studies showed a decreased expression of endothelial nitric oxide synthase (eNOS) protein and an increased staining for ET-1. Quantitative analysis of PCR products revealed decreased levels of VEGF mRNA expression in the old population of rats. The most significant decrease was detected between bands corresponding to splice forms 164 (21%) and 120 (18%). The observed alterations in the gene expression of growth factors such as VEGF may contribute to the abnormal age-related morphological and physiological alterations in the erectile tissue.


Incidence of bla NDM-1 gene in Escherichia coli isolates at a tertiary care referral hospital in Northeast India.
Increasing reports on New Delhi metallo-β-lactamase-1 (NDM-1) producing Escherichia coli constitute a serious threat to global health since it is found to be highly resistant to most of the currently available antibiotics including carbapenems. This study has been performed to find out the incidence blaNDM-1 in E. coli isolates recovered from the various clinical samples at a tertiary care referral hospital in Northeast India. A total of 270 non-duplicated E. coli isolates were recovered from the various clinical samples at a tertiary care referral hospital in Northeast India. All isolates with reduced susceptibility to meropenem or ertapenem (diameter of zones of inhibition, ≤ 21 mm) were further phenotypically confirmed for carbapenemase production by modified Hodge test. All screened isolates were also subjected to the polymerase chain reaction detection of blaNDM-1 gene and additional bla genes coding for transmission electron microscopy, SHV, CTX-M, and AmpC. Out of 270 E. coli isolates, 14 were screened for carbapenemase production on the basis of their reduced susceptibility to meropenem or ertapenem. All screened isolates were found to be positive for blaNDM-1 . Each of the blaNDM-1 possessing isolate was also positive for two or more additional bla genes, such as blaTEM , blaCTX-M and blaAmpC . Phylogenetic analysis showed very less variation in blaNDM-1 gene with respect to blaNDM-1 possessing E. coli isolates from other parts of India and abroad. Our findings highlight the incidence of blaNDM-1 in E. coli isolates with a reduced susceptibility to meropenem or ertapenem.


Best practice advice on pre-hospital emergency anaesthesia & advanced airway management.
Effective and timely airway management is a priority for sick and injured patients. The benefit and conduct of pre-hospital emergency anaesthesia (PHEA) and advanced airway management remains controversial but there are a proportion of critically ill and injured patients who require urgent advanced airway management prior to hospital arrival. This document provides current best practice advice for the provision of PHEA and advanced airway management. This best practice advice was developed from EHAC Medical Working Group enforced by pre-hospital critical care experts. The group used a nominal group technique to establish the current best practice for the provision of PHEA and advanced airway management. The group met on three separate occasions to discuss and develop the guideline. All members of the working party were able to access and edit the guideline online. This EHAC best practice advice covers all areas of PHEA and advanced airway management and provides up to date evidence of current best practice. PHEA and advanced airway management are complex interventions that should be delivered by appropriately trained personnel using a well-rehearsed approach and standardised equipment. Where advanced airway interventions cannot be delivered, careful attention should be given to applying basic airway interventions and ensuring their effectiveness at all times.


Prediction of diffusion coefficients of proteins.
A correlation for predicting the diffusion coefficients of proteins at standard conditions is proposed by adapting the Stokes-Einstein equation to a model for the equivalent hydrodynamic sphere. The radius of gyration, which accounts for the size and shape of protein molecules in solution, was used in deriving the new correlation. The correlation successfully predicted the diffusion coefficients of proteins, for which experimental data were available, with a higher degree of accuracy than achieved by previous correlation methods.


IgG and IgG subclass antibodies in patients with active cutaneous leishmaniasis.
This research was planned to detect IgG and IgG subclasses in sera of patients with active cutaneous leishmaniasis (CL). Sera from 30 patients with active CL aged between 10 and 50 years and from 30 healthy controls aged between 8 and 50 years were included in the study. Levels of IgG and its subclasses were measured by a nephelometer. Levels of IgG, IgG1 and IgG3 in the CL patients were higher than in the controls. In addition, IgG and IgG1, and IgG and IgG3 levels showed a significant positive correlation. These results showed that IgG subclasses could possibly be used as a helpful diagnostic marker in CL.


Hyperosmotic saline dextran for resuscitation from traumatic-hemorrhagic hypotension: effect on regional blood flow.
The macro- and microcirculatory effect of small-volume resuscitation with hyperosmotic-hyperoncotic solutions was analyzed in 21 anesthetized beagles subjected to standardized traumatic-hemorrhagic hypotension (laparotomy and exteriorization of the intestine; MAP 40 mmHg for 75 min). Primary resuscitation consisted of bolus infusion of 10% of the blood loss (approx. 4 ml/kg) of either hyperosmotic (7.2%) saline -HSS-, hyperoncotic (10%) dextran 60 -HDS-, or hyperosomotic-hyperoncotic saline dextran (10% dextran 60 in 7.2% saline; HHS). Within 5 min CO was restored and systemic pressure significantly increased. In the HHS-group nutritional blood flow (RBF, measured by radiolabeled microspheres phi 15 microns) in kidneys, gastric mucosa, small intestine, colon, and pancreas was completely restored, while RBF to the myocardium, brain, and skeletal muscles exceeded baseline values. Despite the identical response in central hemodynamics, RBF to gastric mucosa, intestine, pancreas, and kidneys was significantly lower in HSS-animals (P less than 0.05 vs. HHS). In contrast, in the HDS-group CO, splanchnic, myocardial, and renal blood flow remained significantly reduced (P less than 0.05 vs. HHS). Despite the normalization of cardiac output by small volumes of hypertonic solutions, 7.2% saline alone failed to fully restore RBF after protracted traumatic hemorrhage. For the concept of small-volume resuscitation, the hyperosomotic-hyperoncotic solution of 10% dextran 60 in 7.2% saline appears to be most effective to improve organ perfusion during the prehospital period of trauma patients.


Association of Conicity Index with Different Cardiovascular Disease Risk Factors among Rural Elderly Women of West Bengal, India.
In menopause, changes in body fat distribution lead to increasing risk of cardiovascular and metabolic diseases. Therefore, the prediction of cardiovascular disease (CVD) by the presence of risk factors is of importance in elderly women. To find out the conicity index (CI) and its association with different CVD risk factors among rural elderly women of West Bengal. The study was conducted among 236 rural elderly women, selected randomly from 30 villages of Amdanga block, West Bengal. Components of metabolic syndrome (MS), body fat percentage, different lipid profile fractions, CI, and body mass index (BMI) were measured. Statistical tests were calculated using SPSS software version 20.0. P ≤ 0.05 was considered statistically significant. High CI (median 1.25 and interquartile range 1.05-1.45) was found. The proportion of participants with high CI were significantly higher among those with MS (87.95%), waist circumference having 80 cm or more (99.09%), blood pressure having ≥ 130/85 mm of Hg (75.66%), body fat percentage ≥25% (80.14%), and BMI ≥23 (93.18%). High prevalence of CI existed among rural elderly women. Significant correlation existed between CI and different CVD risk factors as well as some of the components of MS indicating a possible coexistence of different CVD risks.


The Etiology of Pancreatic Manifestations in Patients with Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) is an idiopathic chronic and recurrent condition that comprises Crohn's disease and ulcerative colitis. A pancreatic lesion is one of the extraintestinal lesions in patients with IBD. Acute pancreatitis is the representative manifestation, and various causes of pancreatitis have been reported, including those involving adverse effects of drug therapies such as 5-aminosalicylic acid and thiopurines, gall stones, gastrointestinal lesions on the duodenum, iatrogenic harm accompanying endoscopic procedures such as balloon endoscopy, and autoimmunity. Of these potential causes, autoimmune pancreatitis (AIP) is a relatively newly recognized disease and is being increasingly diagnosed in IBD. AIP cases can be divided into type 1 cases involving lymphocytes and IgG4-positive plasma cells, and type 2 cases primarily involving neutrophils; the majority of AIP cases complicating IBD are type 2. The association between IBD and chronic pancreatitis, exocrine pancreatic insufficiency, pancreatic cancer, etc. has also been suggested; however, studies with high-quality level evidence are limited, and much remains unknown. In this review, we provide an overview of the etiology of pancreatic manifestation in patients with IBD.


Evaluation of the Diagnostic Potential of Liver Aminotransferases and Alkaline Phosphatase in Patients with Cardiovascular Diseases.
Background Cardiovascular diseases (CVDs) are the major cause of morbidity and mortality, particularly in developing countries. Early diagnosis with the best diagnostic marker is highly desired for the prevention and timely treatment of CVDs. However, there is still a dearth of an ideal marker for the detection of CVDs. Objective To explore the diagnostic potential of liver aminotransferases (AST and ALT), and alkaline phosphatase for the diagnosis of CVDs without liver involvement. Method This was a cross-sectional study conducted among 200 adult patients with CVDs, who visited the cardiology and emergency units of Manipal Teaching Hospital, Pokhara, Nepal. The study was conducted from January 2018 to December 2020. The baseline data on family history, anthropometry, baseline biochemical parameters, liver enzymes, and cardiac biomarkers were collected using standard and validated methods. The data were analyzed using SPSS version 21 and MedCalc software 2021. Result The diagnostic sensitivity of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were 53.7%, 52.6%, and 33.7% and specificity were 99%, 90%, and 90% respectively. The area under the curve (AUC) of AST, ALT, and ALP were 0.78, 0.73, and 0.52 respectively. ROC curve indicated that serum AST and ALT activity was a better reliable marker than the serum ALP activities. Conclusion Our study suggests that serum aspartate aminotransferase and alanine aminotransferase but not alkaline phosphatase could have some diagnostic potential to diagnose the risk of CVDs. However, they could not replace the currently adopted cardiac biomarkers such as cTnI and CK-MB.


Wingspan in-stent restenosis and thrombosis: incidence, clinical presentation, and management.
Wingspan (Boston Scientific, Fremont, CA) is a self-expanding stent designed specifically for the treatment of symptomatic intracranial atheromatous disease. The current series reports the observed incidence of in-stent restenosis (ISR) and thrombosis on angiographic follow-up. A prospective, intent-to-treat registry of patients in whom the Wingspan stent system was used to treat symptomatic intracranial atheromatous disease was maintained at five participating institutions. Clinical and angiographic follow-up results were recorded. ISR was defined as stenosis greater than 50% within or immediately adjacent (within 5 mm) to the implanted stents and absolute luminal loss greater than 20%. To date, follow-up imaging (average duration, 5.9 mo; range, 1.5-15.5 mo) is available for 84 lesions treated with the Wingspan stent (78 patients). Follow-up examinations consisted of 65 conventional angiograms, 17 computed tomographic angiograms, and two magnetic resonance angiograms. Of these lesions with follow-up, ISR was documented in 25 and complete thrombosis in four. Two of the 4 patients with stent thrombosis had lengthy lesions requiring more than one stent to bridge the diseased segment. ISR was more frequent (odds ratio, 4.7; 95% confidence intervals, 1.4-15.5) within the anterior circulation (42%) than the posterior circulation (13%). Of the 29 patients with ISR or thrombosis, eight were symptomatic (four with stroke, four with transient ischemic attack) and 15 were retreated. Of the retreatments, four were complicated by clinically silent in-stent dissections, two of which required the placement of a second stent. One was complicated by a postprocedural reperfusion hemorrhage. The ISR rate with the Wingspan stent is higher in our series than previously reported, occurring in 29.7% of patients. ISR was more frequent within the anterior circulation than the posterior circulation. Although typically asymptomatic (76% of patients in our series), ISR can cause neurological symptoms and may require target vessel revascularization.


Takotsubo Cardiomyopathy after Spinal Anesthesia for a Minimally Invasive Urologic Procedure.
We present the case of a patient who suffered from Takotsubo cardiomyopathy (TCM) immediately after the initiation of subarachnoid anesthesia for a minimally invasive urologic procedure (tension-free vaginal tape (TVT) surgery for stress urine incontinence). TCM mimics acute coronary syndrome and is caused by an exaggerated sympathetic reaction to significant emotional or physical stress. Our patient suffered from chest pain, palpitations, dyspnea, and hemodynamic instability immediately following subarachnoid anesthesia and later in the postanesthesia care unit. Blood troponin was elevated and new electrocardiographic changes appeared indicative of cardiac ischemia. Cardiac ultrasound indicated left ventricular apical akinesia and ballooning with severely affected contractility. The patient was admitted to coronary intensive care for the proper care and finally was discharged. TCM was attributed to high emotional preoperative stress for which no premedication had been administered to the patient. In conclusion, adequate premedication and anxiety management are not only a measure to alleviate psychological stress of surgical patients, but, more importantly, an imperative mean to suppress sympathetic nerve system response and its cardiovascular consequences.


Chronic lymphocytic leukemia presenting as unilateral extraocular muscle enlargement and proptosis.
Orbital involvement in chronic lymphocytic leukemia (CLL) is rare with very few published cases. We describe a case of unilateral isolated extraocular muscle enlargement in a patient with CLL. An incisional biopsy was performed from the left medial rectus muscle and histology revealed a lymphocytic infiltrate suggestive of CLL. Complete resolution of signs and symptoms was subsequently achieved with chemotherapy. We would suggest that in patients presenting with atypical clinical features, it is important to consider nonthyroid-related causes of extraocular muscle enlargement and a muscle biopsy should be considered to exclude neoplastic causes.


[Vision quality of intraocular refraction surgery].
Intraocular refractive surgery is one of challenges since it is undertaken mostly for high myopia patient with healthy transparent crystalline lens. The improved vision quality is the premise for conducting this kind of surgery. Vision quality is one of comprehensive factors which are connected to the surgery techniques, ocular optics, ocular physical biometry, intraocular lens power calculation and psycho-physical perception of patient.


EOS calculations for hydrothermal diamond anvil cell operation.
The hydrothermal diamond anvil cell (HDAC) is an excellent tool for high-temperature, high-pressure (hydrothermal) experiments. For an accurate determination of pressure induced by a certain temperature in an isochoric sample chamber volume, an equation of state (EOS) of water can be used instead of direct measurement. This paper reviews the theoretic background and provides all needed equations for the application of EOS of water to HDAC experiments summarizing state-of-the-art knowledge and incorporating up-to-date thermodynamic data. The p-T conditions determined using the IAPWS-95 formulation for the thermodynamic properties of ordinary water are in agreement with values obtained from direct methods or other established EOS formulations. In particular, (1) the calculation of density through the (a) melting point or (b) homogenization method along with determining (2) pressure as a function of density and temperature or (3) density as a function of pressure and temperature is explained. As a new aspect in the context of HDAC operations, the critical influence of nucleation and a strategy to overcome this problem are discussed. Furthermore, we have derived new polynomial equations, which allow the direct calculation of the fluid phase's density from the melting temperature. These are implemented in a spreadsheet program, which is freely available for interested users.


Implementation of safety checklists in surgery: a realist synthesis of evidence.
The aim of this review is to present a realist synthesis of the evidence of implementation interventions to improve adherence to the use of safety checklists in surgery. Surgical safety checklists have been shown to improve teamwork and patient safety in the operating room. Yet, despite the benefits associated with their use, universal implementation of and compliance with these checklists has been inconsistent. An overview of the literature from 2008 is examined in relation to checklist implementation, compliance, and sustainability. Pawson's and Rycroft-Malone's realist synthesis methodology was used to explain the interaction between context, mechanism, and outcome. This approach incorporated the following: defining the scope of the review, searching and appraising the evidence, extracting and synthesising the findings, and disseminating, implementing, and evaluating the evidence. We identified two theories a priori that explained contextual nuances associated with implementation and evaluation of checklists in surgery: the Normalisation Process Theory and Responsive Regulation Theory. We identified four a priori propositions: (1) Checklist protocols that are prospectively tailored to the context are more likely to be used and sustained in practice, (2) Fidelity and sustainability is increased when checklist protocols can be seamlessly integrated into daily professional practice, (3) Routine embedding of checklist protocols in practice is influenced by factors that promote or inhibit clinicians' participation, and (4) Regulation reinforcement mechanisms that are more contextually responsive should lead to greater compliance in using checklist protocols. The final explanatory model suggests that the sustained use of surgical checklists is discipline-specific and is more likely to occur when medical staff are actively engaged and leading the process of implementation. Involving clinicians in tailoring the checklist to better fit their context of practice and giving them the opportunity to reflect and evaluate the implementation intervention enables greater participation and ownership of the process. A major limitation in the surgical checklist literature is the lack of robust descriptions of intervention methods and implementation strategies. Despite this, two consequential findings have emerged through this realist synthesis: First, the sustained use of surgical checklists is discipline-specific and is more successful when physicians are actively engaged and leading implementation. Second, involving clinicians in tailoring the checklist to their context and encouraging them to reflect on and evaluate the implementation process enables greater participation and ownership.


Effect of 4 wk of deep water run training on running performance.
The purpose of this study was to determine whether trained competitive runners could maintain on-land running performance using 4 wk of deep water run training instead of on-land training. Eleven well-trained competitive runners (10 males, 1 female; ages, 32.5 +/- 5.4 yr; height, 179.8 +/- 9.3 cm; weight, 70.4 +/- 6.7 kg (mean +/- SD)) trained exclusively using deep water run training for 4 wk. Subjects trained 5-6 d.wk-1 for a total of 20-24 sessions (mean +/- SD, 22 +/- 1.5 sessions). Instruction and practice sessions were conducted prior to the training period. Before and after the deep water run training, subjects completed a 5-km race on the treadmill using a computer based system, a submaximal run at the same absolute workload to assess running economy, and a combined lactate threshold and maximal oxygen consumption test. No significant differences were found for (mean +/- SEM): 5-km run time (pre, 1142.7 +/- 39.5 s; post, 1149.8 +/- 36.9 s; P = 0.28), submaximal oxygen consumption (pre 44.8 +/- 1.2 mL.kg-1.min-1; post, 45.3 +/- 1.5 mL.kg-1.min-1; P = 0.47), lactate threshold running velocity (pre, 249.1 +/- 0.9 m.min-1; post, 253.6 +/- 6.3 m.min-1; P = 0.44), or maximal oxygen consumption (pre, 63.4 +/- 1.3 mL.kg-1.min-1; post, 62.2 +/- 1.3 mL.kg-1.min-1; P = 0.11). Also no differences were found among Global Mood State pre-training, each week during training, and post-training. Competitive distance runners maintained running performance using 4 wk of deep water run training as a replacement for on-land training.


Nanocellulose-stabilized Pickering emulsions and their applications.
Pickering emulsion, which is an emulsion stabilized by solid particles, offers a wide range of potential applications because it generally provides a more stable system than surfactant-stabilized emulsion. Among various solid stabilizers, nanocellulose may open up new opportunities for future Pickering emulsions owing to its unique nanosizes, amphiphilicity, and other favorable properties (e.g. chemical stability, biodegradability, biocompatibility, and renewability). In this review, the preparation and properties of nanocellulose-stabilized Pickering emulsions are summarized. We also provide future perspectives on their applications, such as drug delivery, food, and composite materials.


Language Differences at 12 Months in Infants Who Develop Autism Spectrum Disorder.
Little is known about early language development in infants who later develop autism spectrum disorder (ASD). We analyzed prospective data from 346 infants, some of whom were at high risk for developing ASD, to determine if language differences could be detected at 12 months of age in the infants who later were diagnosed with ASD. Analyses revealed lower receptive and expressive language scores in infants who later were diagnosed with ASD. Controlling for overall ability to understand and produce single words, a Rasch analysis indicated that infants who later developed ASD had a higher degree of statistically unexpected word understanding and production. At 12 months of age, quantitative and qualitative language patterns distinguished infants who later developed ASD from those who did not.


Simultaneous determination of quinoxaline-1,4-dioxides in feeds using molecularly imprinted solid-phase extraction coupled with HPLC.
A simple, selective, and reproducible molecularly imprinted SPE coupled with HPLC method was developed for monitoring quinoxaline-1,4-dioxides in feeds. Molecularly imprinted polymers were synthesized in methanol using mequindox (MEQ) as template molecule and acrylamide as functional monomer by bulk polymerization. Under the optimum SPE conditions, the novel polymer sorbents can selectively extract and enrich carbadox, MEQ, quinocetone, and cyadox from a variety of feeds. The molecularly imprinted SPE cartridge was better than nonimprinted, C(18) , and HLB cartridges in terms of both recovery and precision. Mean recoveries of four quinoxaline-1,4-dioxides from six kinds of feeds spiked at 1.0, 10, and 100 mg/kg ranged between 75.2 and 94.7% with RSDs of less than 10%. The decision limits (CCαs) and the detection capabilities (CCβs) of four analytes were 0.15-0.20 mg/kg and 0.44-0.56 mg/kg, respectively. The class selectivity of the polymers was evaluated by checking three drugs with different molecular structures to that of MEQ.


Clonal origin, restricted natural distribution, and conservation of virulence factors in isolates of enterotoxigenic Escherichia coli serogroup O126.
Enterotoxigenic Escherichia coli serogroup O126 isolates have been isolated in Hong Kong since 1982 from sporadic cases of infantile diarrhea and from one outbreak in a neonatal ward. A 64-megadalton plasmid encoding colonization factor antigen I and heat-stable enterotoxin was identified in all 23 isolates. Enterotoxigenic E. coli strains producing heat-stable enterotoxin from different regions of Southeast Asia were collected and compared by biotyping, antibiotic resistance patterns, and plasmid profiles. Restriction endonuclease digestion of plasmids and subsequent Southern blot analysis with the heat-stable enterotoxin gene probe of representative strains showed a unique plasmid was harbored by all heat-stable enterotoxin-producing O126 strains tested. These results are consistent with conservative inheritance of enterotoxin plasmids within enterotoxigenic E. coli strains over a 2-year period in Hong Kong.


Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.
To the authors' knowledge, outcomes and prognostic tools have yet to be clearly defined in patients with metastatic renal cell carcinoma (mRCC) who are treated with immuno-oncology (IO) checkpoint inhibitors (programmed death-ligand 1 [PD-L1] inhibitors). In the current study, the authors aimed to establish IO efficacy benchmarks in patients with mRCC and update patient outcomes in each International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class. A retrospective analysis was performed using the IMDC database with data from 38 centers. It included patients with mRCC who were treated with ≥1 line of IO. Overall response rates (ORRs), duration of treatment (DOT), and overall survival (OS) were calculated. Patients were stratified using IMDC prognostic factors. A total of 687 patients (90% with clear cell and 10% with non-clear cell) were included. The ORR was 27% in evaluable patients (461 patients). In patients treated with first-line nivolumab and ipilimumab (49 patients), the combination of PD-L1 inhibitor and vascular endothelial growth factor inhibitor (72 patients), and PD-L1 inhibitor (51 patients), the ORR was 31%, 39%, and 40%, respectively, and the median DOT was 8.3 months, 14.7 months, and 8.3 months, respectively. The ORR for second-line, third-line, and fourth-line nivolumab was 22%, 24%, and 26%, respectively. The median DOT was 5.7 months, 6.2 months, and 8.3 months, respectively, in the second-line, third-line, and fourth-line settings. When segregated into IMDC favorable-risk, intermediate-risk, and poor-risk groups, the median OS rates for the first-line, second-line, third-line, and fourth-line treatment settings were not reached (NR), NR, and NR, respectively (P = .163); NR, 26.7 months, and 7.4 months, respectively (P < 0. 0001); 36.1 months, 28.2 months, and 11.1 months, respectively (P = .016); and NR, NR, and 6.7 months, respectively (P = .047). The ORR was not found to deteriorate from the first-line to the fourth-line of IO therapy. In the second line through fourth line, the IMDC criteria appropriately stratified patients into favorable-risk, intermediate-risk, and poor-risk groups for OS.


Interpretable inference on the mixed effect model with the Box-Cox transformation.
We derived results for inference on parameters of the marginal model of the mixed effect model with the Box-Cox transformation based on the asymptotic theory approach. We also provided a robust variance estimator of the maximum likelihood estimator of the parameters of this model in consideration of the model misspecifications. Using these results, we developed an inference procedure for the difference of the model median between treatment groups at the specified occasion in the context of mixed effects models for repeated measures analysis for randomized clinical trials, which provided interpretable estimates of the treatment effect. From simulation studies, it was shown that our proposed method controlled type I error of the statistical test for the model median difference in almost all the situations and had moderate or high performance for power compared with the existing methods. We illustrated our method with cluster of differentiation 4 (CD4) data in an AIDS clinical trial, where the interpretability of the analysis results based on our proposed method is demonstrated. Copyright © 2017 John Wiley & Sons, Ltd.


Kinetic Studies of Acetyl Group Migration between the Saccharide Units in an Oligomannoside Trisaccharide Model Compound and a Native Galactoglucomannan Polysaccharide.
Acyl group migration is a fundamental phenomenon in carbohydrate chemistry, recently shown to take place also between two non-adjacent hydroxyl groups, across the glycosidic bond, in a β-(1→4)-linked mannan trisaccharide model compound. With the central mannoside unit containing acetyl groups at the O2 and O3 positions, the O2-acetyl was in the earlier study shown to migrate to O6 of the reducing end. Potential implications of the general acyl migration process on cell signaling events and plant growth in nature are intriguing open questions. In the present work, migration kinetics in this original trisaccharide model system were studied in more detail together with potential interactions of the model compound and the migration products with DC-SIGN lectin. Furthermore, we demonstrate here for the first time that similar migration may also take place in native polysaccharides, here represented by galactoglucomannan from Norway spruce.


Copper-Catalyzed Aerobic Oxidative Reaction of C60 with Aliphatic Primary Amines and CS2.
A novel type of fullerene derivatives, [60]fullerothiazolidinethiones (2), were obtained from the copper-catalyzed aerobic oxidative reaction of C60 with aliphatic primary amines and CS2 in 4:1 v/v DMF and o-DCB. The obtained products were fully characterized with the X-ray single-crystal diffraction and spectroscopic methods. Control experiment with maleic anhydride, an analogue to C60, also afforded thiazolidinethione product, but via a mechanism different from that of C60 judging from the structure difference between the two types of thiazolidinethione compounds, demonstrating the unique reactivity of C60.


Preconcentration and determination of trace elements with 2,6-diacetylpyridine functionalized Amberlite XAD-4 by flow injection and atomic spectroscopy.
An on-line flow injection method for the direct determination of trace elements in environmental samples is described. A mini-column packed with 2,6-diacetylpyridine functionalized Amberlite XAD-4 was used to preconcentrate and separate 8 trace metals (Cd, Co, Cu, Mn, Ni, Pb, U and Zn) from water and extracts from solid samples. The metals were eluted with 0.1 M HNO(3) directly to the detection system (either inductively coupled plasma-mass spectrometry (ICP-MS) or flame atomic absorption spectrometry (FAAS)). As well as demonstrating that the resin could be used to preconcentrate ultra-trace analytes from natural waters, it was also shown to work well at a pH of 5.5. Therefore, after treatment of sample digests with sodium fluoride, samples that contain extremely large concentrations of iron may be analysed for trace analytes without the excess iron overloading the capacity of the resin. To this end, the analytes Cd, Co, Cu and Ni were preconcentrated from acid extracts of certified soil/sediment samples and then eluted with nitric acid to be determined on-line. Limits of detection (3sigma) of Cd = 0.33 microg l(-1), Co = 0.094 microg l(-1), Cu = 0.34 microg l(-1), Mn = 0.32 microg l(-1), Ni = 0.30 microg l(-1), Pb = 0.43 microg l(-1), U = 0.067 microg l(-1) and Zn = 0.20 microg l(-1) for the FI-ICP-MS system and Cd = 22 microg l(-1), Co = 60 microg l(-1), Cu = 10 microg l(-1) and Ni = 4.8 microg l(-1) for the FI-FAAS system were obtained. Analysis of certified reference materials showed good agreement with the certified values using the two methods.


Assessment of the road safety performance of four roundabouts in Kumasi, Ghana.
Upgrade of the Ejisu-Kumasi section of the N6 saw the construction of roundabouts at selected intersections. Their use appears challenging particularly for vehicles with elevated Centre-of-Gravity. The objective of this study was to establish the relative risk of traffic accident deaths or hospitalized injuries at the roundabouts. Five-year crash data covering a 100 m stretch upstream and downstream of the roundabouts were analysed. A total of 119 crashes occurred with 18% casualty hospitalization and 12%fatalities. Compared with the Ejisu roundabout, fatal or hospitalized injuries were significantly higher at the Boadi (OR = 25.6, p = 0.0021) and Kwame Nkrumah University of Science and Technology Police Station Junctions (OR = 48.2, p < 0.001). Occupants of buses, heavy goods vehicles and riders of two wheelers were at elevated risk of deaths or serious injuries. Crash severity at the round abouts was aggravated by night-time, steep gradients and adverse cambers. It is recommended that, signalization and grade separation should be used in the current arrangement where appropriate.


Elevated fruit nitrogen impairs oil biosynthesis in olive (Olea europaea L.).
Oil in fruits and seeds is an important source of calories and essential fatty acids for humans. This specifically holds true for olive oil, which is appreciated for its superior nutritional value. Most olive orchards are cultivated to produce oil, which are the outcome of fruit yield and oil content. Little information is available on the effect of nitrogen (N) on olive fruit oil content. The response of olive trees to different rates of N was therefore studied in soilless culture (3 years) and commercial field (6 years) experiments. In both experiments, fruit N level and oil biosynthesis were negatively associated. Fruit N increased in response to N fertilization level and was inversely related to fruit load. The negative correlation between fruit N and oil content was more pronounced under high fruit load, indicating sink limitation for carbon. These results agree with those reported for oilseed crops for which a trade-off between oil and protein was proposed as the governing mechanism for the negative response to elevated N levels. Our results suggest that the protein/oil trade-off paradigm cannot explain the noticeable decrease in oil biosynthesis in olives, indicating that additional mechanisms are involved in N-induced inhibition of oil production. This inhibition was not related to the soluble carbohydrate levels in the fruit, which were comparable regardless of N level. These results emphasize the importance of balanced N nutrition in oil-olive cultivation to optimize production with oil content.


Rare cases of vesicouterine fistula.
Vesicouterine fistula (VUF) is the rarest form of genitourinary fistulas. As lower-segment cesarean section becomes a more common mode of delivery, they have become the leading cause of VUF formation. We present four VUF patients with varied symptoms such as menouria, amenorrhea, with or without urinary incontinence. We diagnosed all of our cases through cystoscopy in conjunction with methylene blue dye test or hysteroscopy. We successfully repaired VUF in three open surgery instances and one laparoscopic case. To diagnose VUF, cystoscopy and hysteroscopy are still the gold standard. An expert surgeon's open or laparoscopic repair is effective and safe. The patients no longer experienced incontinence, cyclical hematuria (menouria), discomfort, or sexual dysfunction. Cystoscopy and hysteroscopy remain the gold standard tool in diagnosing VUF. Open or laparoscopic repair performed by an experienced surgeon is an effective and safe technique with a successful outcome.


[Early Diagnosis of Chorea-Acanthocytosis: Orofacial Dyskinesia, Epileptic Seizures, and HyperCKemia].
Chorea-acanthocytosis is an uncommon neurodegenerative disorder. Early diagnosis is often challenging. The triad of orofacial dyskinesia, epileptic seizures, and hyperCKemia should alert neurologists of a neuroacanthocytosis syndrome. The diagnosis can be confirmed by detection of chorein deficiency or through molecular genetics (VPS13A mutation).


Altered excitatory-inhibitory balance within somatosensory cortex is associated with enhanced plasticity and pain sensitivity in a mouse model of multiple sclerosis.
Chronic neuropathic pain is a common symptom of multiple sclerosis (MS). MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) has been used as an animal model to investigate the mechanisms of pain in MS. Previous studies have implicated sensitization of spinal nociceptive networks in the pathogenesis of pain in EAE. However, the involvement of supraspinal sites of nociceptive integration, such as the primary somatosensory cortex (S1), has not been defined. We therefore examined functional, structural, and immunological alterations in S1 during the early stages of EAE, when pain behaviors first appear. We also assessed the effects of the antidepressant phenelzine (PLZ) on S1 alterations and nociceptive (mechanical) sensitivity in early EAE. PLZ has been shown to restore central nervous system (CNS) tissue concentrations of GABA and the monoamines (5-HT, NA) in EAE. We hypothesized that PLZ treatment would also normalize nociceptive sensitivity in EAE by restoring the balance of excitation and inhibition (E-I) in the CNS. We used in vivo flavoprotein autofluorescence imaging (FAI) to assess neural ensemble responses in S1 to vibrotactile stimulation of the limbs in early EAE. We also used immunohistochemistry (IHC), and Golgi-Cox staining, to examine synaptic changes and neuroinflammation in S1. Mechanical sensitivity was assessed at the clinical onset of EAE with Von Frey hairs. Mice with early EAE exhibited significantly intensified and expanded FAI responses in S1 compared to controls. IHC revealed increased vesicular glutamate transporter (VGLUT1) expression and disrupted parvalbumin+ (PV+) interneuron connectivity in S1 of EAE mice. Furthermore, peri-neuronal nets (PNNs) were significantly reduced in S1. Morphological analysis of excitatory neurons in S1 revealed increased dendritic spine densities. Iba-1+ cortical microglia were significantly elevated early in the disease. Chronic PLZ treatment was found to normalize mechanical thresholds in EAE. PLZ also normalized S1 FAI responses, neuronal morphologies, and cortical microglia numbers and attenuated VGLUT1 reactivity-but did not significantly attenuate the loss of PNNs. These findings implicate a pro-excitatory shift in the E-I balance of the somatosensory CNS, arising early in the pathogenesis EAE and leading to large-scale functional and structural plasticity in S1. They also suggest a novel antinociceptive effect of PLZ treatment.


[Densification of autotrophic bacteria sludge and its characteristics for wastewater treatment].
Autotrophic granular sludge was developed in an SBR reactor using inorganic carbonal substrate. The variation of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) during the densification process and their effects on granulation have been evaluated. It was found that the autotrophic bacteria granular sludge was compact with the density reached up to 1.06 g/mL, and the rod-like bacteria predominated in granules on the evidence of scanning electron microscopic (SEM) results. Ammonia, nitrite and nitrate in the effluent were 4.5-15.2 mg/L, 10.2-20.3 mg/L and 17.9-30.1 mg/L, respectively, and the ammonia removal efficiency was 78% -92%. By evaluating the profile of various types of nitrogen and their conversion rates, it was found that short settling time was the main factor that enriched the AOB at the beginning of this experiment, and the granulation did not correlate with AOB. On the contrary, nitrification rate well correlated with granulation, and evidence demonstrated that the formation of granulation was in favorate of immoblization of NOB and the metabolite of NOB stabilized granules, therefore granules and NOB mutually enhanced. Additionally, it was found that the autotrophic denitrification was gradually increased with the process of granulation.


Autophagy extends lifespan via vacuolar acidification.
Methionine restriction (MetR) is one of the rare regimes that prolongs lifespan across species barriers. Using a yeast model, we recently demonstrated that this lifespan extension is promoted by autophagy, which in turn requires vacuolar acidification. Our study is the first to place autophagy as one of the major players required for MetR-mediated longevity. In addition, our work identifies vacuolar acidification as a key downstream element of autophagy induction under MetR, and possibly after rapamycin treatment. Unlike other amino acids, methionine plays pleiotropic roles in many metabolism-relevant pathways. For instance, methionine (i) is the N-terminal amino acid of every newly translated protein; (ii) acts as the central donor of methyl groups through S-adenosyl methionine (SAM) during methylation reactions of proteins, DNA or RNA; and (iii) provides the sulfhydryl groups for FeS-cluster formation and redox detoxification via transsulfuration to cysteine. Intriguingly, MetR causes lifespan extension, both in yeast and in rodents. We could show that in Saccharomyces cerevisiae, chronological lifespan (CLS) is increased in two specific methionine-auxotrophic strains (namely Δmet2 and Δmet15).


Chemical Composition and Cytotoxic and Antibacterial Activities of the Essential Oil of Aloysia citriodora Palau Grown in Morocco.
The aim of this work is to investigate the in vitro cytotoxic and antibacterial effects of the essential oils of Aloysia citriodora Palau, harvested in different regions of Morocco. The chemical profile was established using gas chromatography-mass spectrometry analysis. The cytotoxic activity against P815, MCF7, and VERO cell lines as well as the normal human peripheral blood mononuclear cells (PBMCs) was evaluated using the MTT assay. Standard, ATCC, strains of bacteria (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) were cultivated in Muller Hinton media. Then, agar disc diffusion, minimum inhibitory concentrations (MICs), and minimal bactericidal concentrations (MBCs) were determined using microdilution method. The essential oils obtained were predominantly composed of β-spathulenol (15.61%), Ar-curcumene (14.15%), trans-caryophyllene oxide (14.14%), and neral (10.02%). The results of the assays showed that the cytotoxic effect of the essential oil of A. citriodora was high on P815 and moderate on MCF7 and on VERO cell lines. However, no cytotoxic effect was observed on PBMCs. On the other hand, essential oils showed a significant antimicrobial activity against both Gram-negative and Gram-positive bacteria. MICs ranged between 2.84 and 8.37 mg/ml. Essential oil of A. citriodora leaves possesses significant antibacterial effect and cytotoxic activity against tumor cell lines.


Recurrent facilitation of spinal reflexes.
Antidromic volleys in muscle nerves may facilitate monosynaptic reflexes originating from neighboring motoneurons. This facilitation has been studied in spinal cats. It is at its peak with a conditioning-test interval of 20 to 30 msec., and can last 50 to 100 msec. The threshold of facilitation is about the same as that of recurrent inhibition. Both phenomena appear to be activated by stimulation of the large motor axons. The latency of facilitation seems to be longer than that of recurrent inhibition by approximately 1 msec., suggesting the presence of at least one more synaptic delay. Facilitation often follows an inhibition of variable depth and duration. Frequently, however, the facilitation is not preceded by inhibition, and therefore it cannot be a rebound effect. The pharmacological properties of facilitation resemble those of recurrent inhibition. Dihydro-beta-erythroidine(1) partially blocks facilitation; the peak is decreased and occurs earlier, and the duration is shortened. Eserine increases the duration of facilitation and inhibition and sometimes enhances their magnitude. It is concluded that recurrent facilitation is mediated by the cholinergic axon collaterals, and that at least two interneurons are located between collateral and motoneuron. Possible mechanisms of facilitation are discussed.


CRISPR/Cas9-mediated deletion of the Wiskott-Aldrich syndrome locus causes actin cytoskeleton disorganization in murine erythroleukemia cells.
Wiskott-Aldrich syndrome (WAS) is a recessive X-linked inmmunodeficiency caused by loss-of-function mutations in the gene encoding the WAS protein (WASp). WASp plays an important role in the polymerization of the actin cytoskeleton in hematopoietic cells through activation of the Arp2/3 complex. In a previous study, we found that actin cytoskeleton proteins, including WASp, were silenced in murine erythroleukemia cells defective in differentiation. Here, we designed a CRISPR/Cas9 strategy to delete a 9.5-kb genomic region encompassing the Was gene in the X chromosome of murine erythroleukemia (MEL) cells. We show that Was-deficient MEL cells have a poor organization of the actin cytoskeleton that can be recovered by restoring Was expression. We found that whereas the total amount of actin protein was similar between wild-type and Was knockout MEL cells, the latter exhibited an altered ratio of monomeric G-actin to polymeric F-actin. We also demonstrate that Was overexpression can mediate the activation of Bruton's tyrosine kinase. Overall, these findings support the role of WASp as a key regulator of F-actin in erythroid cells.


Treatment of mucocutaneous presentations of herpes simplex virus infections.
Infections by herpes simplex virus (HSV) types I and II are diverse and quite frequent. After primary infection, the virus establishes a life-long latency in the sensory ganglia and recrudescences may occur at an unpredictable rate. Recurrent labial and genital herpes infections represent the majority of clinical manifestations of HSV infections. Their management is currently well established using evidence-based medicine data. Primary labial herpes is generally not treated with antivirals in otherwise healthy children, although intravenous aciclovir may be offered in severe primary infections, particularly in the immunocompromised patient. The decision whether or not to treat recurrent labial herpes should be evaluated individually and depends on the frequency and severity of relapses, the impairment of the quality of life, and the cost of therapy. Patients with mild disease may benefit from topical therapy, and those with severe and frequent recurrences may be considered for intermittent or long-term oral antiviral therapy. Primary genital herpes is treated with oral or intravenous antivirals, depending on the severity of the infection and associated symptoms. Recurrent genital herpes can be managed with episodic short courses of oral antivirals in patients whose recurrences are moderate to severe and rare, and have a clear prodrome. Patients with >5 episodes/year, severe recurrences or unrecognisable prodromes may be best managed with long-term suppressive antiviral prophylaxis. HSV is also responsible for a variety of other clinical manifestations, including herpetic whitlow, neonatal infection, disseminated and atypical cutaneous infections, traumatic herpes, eczema herpeticum, and HSV-associated erythema multiforme. HSV infection may also represent a complication following cosmetic procedures of the oro-facial region, surgical and dental interventions, sun exposure and burns. Precise treatment guidelines for these HSV infections are not firmly established.


Right heart morphology and function in heart transplantation recipients.
The right heart is a major determinant of prognosis in cardiac transplant recipient patients. To investigate right ventricular morphology and function and their relationship with exercise capacity in cardiac transplant recipient patients using standard tranthoracic echocardiography and a new three-dimensional echocardiographic software adapted for right ventricular analysis. One hundred fifteen relatively stable cardiac transplant recipient patients (71 men; 58.3 ± 5.8 years; 7.8 ± 4.5 years after transplantation) and 80 healthy age-comparable and sex-comparable controls underwent standard echocardiography, tissue Doppler imaging (TDI), and three-dimensional echocardiography, focused on the right ventricular analysis. Along with left heart parameters, right ventricular measurements included end-diastolic diameters at basal and mid-cavity level; base-to-apex length; tricuspid annulus plane systolic excursion (TAPSE); TDI right ventricular systolic peak velocity (Sm); and three-dimensional ejection fraction. Using the peak systolic tricuspid regurgitation velocity (TRV) and the end-diastolic pulmonary regurgitation velocity, the modified Bernoulli equation was used to calculate the pulmonary artery systolic (PASP) and diastolic pressures. Pulmonary artery vascular conductance (PAVC) was estimated by left ventricular stroke volume/4 × (TRV - pulmonary regurgitation velocity). Left ventricular diameters and ejection fraction did not significantly differ between the two groups, whereas mass index was increased in cardiac transplant recipient patients (P < 0.01). Right ventricular diameters were significantly increased (P < 0.001), whereas TAPSE and right ventricular Sm were significantly lower in cardiac transplant recipient patients. Conversely, in cardiac transplant recipient patients, three-dimensional right ventricular ejection fraction (RVEF) was not significantly reduced (P < 0.001), whereas both PASP and PAVC were impaired. By multivariable analysis, age at transplantation (P < 0.01) and pulmonary artery mean pressure (P < 0.001) were the only independent determinants of right ventricular diameters and RVEF in cardiac transplant. Furthermore, RVEF measured by real-time three-dimensional echocardiography was a powerful independent determinant of functional capacity in cardiac transplant recipient patients. Despite the reduction of right ventricular performance along the long axis suggested by TAPSE and right ventricular Sm, the increased right ventricular diameters along with absence of a decrease in three-dimensional RVEF support the hypothesis of geometrical rather than functional changes of the right ventricle in cardiac transplant recipient patients.


Second-harmonic generation enhancement in the presence of Tamm plasmon-polaritons.
Resonant enhancement of second-harmonic generation (SHG) intensity from a thin metal film is demonstrated in a Tamm plasmon-polariton mode excited at a metal/photonic crystal interface using nonlinear spectroscopy. Nonlinear effects enhancement in proposed structures exhibit strong polarization dependence (1:200 for the orthogonal fundamental polarizations). SHG enhancement factor evinces considerable angular dependence, rising from 50 for the 45° angle of incidence to 170 for the 10° angle of incidence. The results are analyzed numerically using a nonlinear transfer matrix technique. The findings elucidate the potential of Tamm plasmon-polaritons in the nonlinear optical applications.


Use of carbonate extraction in analyzing moderately hydrophobic transmembrane proteins in the mitochondrial inner membrane.
Resistance to sodium carbonate extraction is regarded as a canonical way to distinguish integral membrane proteins (MPs) from other membrane-associated proteins. However, it has been observed that carbonate extraction releases some mitochondrial integral MPs. Here, by analyzing both artificially designed and native mitochondrial inner MPs containing transmembrane domains (TMDs) of different hydrophobicities, we show that carbonate treatment can release moderately hydrophobic TMDs from the mitochondrial inner membrane. These results suggest that resistance and sensitivity to carbonate extraction may be interpreted with caution when analyzing the nature of mitochondrial inner MPs.


Ethiopian women's sexual experiences and coping strategies for sexual problems after gynaecological cancer treatment: a qualitative study.
This study explored women's sexual experiences and coping strategies for sexual problems after gynaecological treatment. The research was carried out at Tikur Anbessa Specialized Hospital, one of the two cancer centre hospitals in the country. A phenomenological qualitative study design was employed in this study. Participants were recruited using purposeful sampling. Thirteen eligible study participants were interviewed face to face. Data were collected from 2 February to 15 March 2019 and analysed at the same time. For data analysis, thematic analysis was used, which comprises three stages: data reduction, data display and data conclusion. Four themes resulted from the analysis of individual interview data, including treatment side effects, sexual issues following radiation therapy, lack of awareness regarding cancer treatment and sexual dysfunction, and coping strategies for sexual dysfunction following gynaecological cancer treatment. Three subthemes emerged as coping mechanisms for managing sexual issues and dysfunction among Ethiopian women with gynaecological cancer: avoiding sexual intercourse, praying for healing and seeking professional help. These themes were identified as the rich and detailed account of the experiences of sexually active women who have received treatment for their cervical cancer. This study has broadened the perspectives on sexuality in the setting of gynaecological cancer and challenged certain commonly held beliefs about sexuality after treatment. Researchers should look into how inclusive sexuality education and training may be better integrated into the training programmes of healthcare workers. More research is needed to learn how partners of women with gynaecological cancer cope with sexual changes after treatment, how the couple as a partnership negotiates changes after treatment, and the facilitators and barriers that healthcare providers face when discussing sexuality issues with patients.


A new species of short-fingered geckos Stenodactylus (Squamata, Geckonidae) from South Iran with taxonomic notes on validity of the genus Trigonodactylus Hass, 1957.
In the present study we provide evidence for the validity of the genus Trigonodactylus Hass, 1957, improve the diagnosis for this genus and describe a new species that belongs to it-Trigonodactylus persicus sp. nov., from the sand dunes in Khuzestan Province, southwestern Iran. The new species is closely related to Trigonodactylus [Stenodactylus] arabicus sensu Hass, and can be distinguished by the following morphological characteristics: small size, maximum SVL 34 mm; SVL/TailL-approximately 1:1; ventral scales roundish, weakly keeled, 54-61 longitudinal rows at midbody and 190-25 along midbody. No enlarged postmentals. Fingers and toes slightly flattened dorso-ventrally. Lateral edge of digits fringed by series of projecting triangular scales. No web between digits. No preanal and femoral pores. Dorsal color pattern formed by thin, dark, irregular vermicular patches and spots. Sometimes these dark dorsal patterns blend with each other and form transverse bands. There is a narrow, dark, longitudinal line between forelimbs and hindlimbs on lateral sides. Dark, well developed ʌ-shaped marking on snout, which continues behind orbit on tympanum region, approaches the upper ear opening and ends on the pectoral arch. Labial scales white, in some cases with grey-brown dots. Dorsal surfaces of limbs and digits with irregular dark bands. Dorsal surface of tail with 8-10 wide, dark brown bands with irregular margins, same size as alternating light bands. Ventral surface of body and limbs white, tail with dark spots that become more distinct posteriorly.


Influence of biomechanical and biochemical stimulation on the proliferation and differentiation of bone marrow stromal cells seeded on polyurethane scaffolds.
The aim of the present investigation was to compare the effects of cyclic compression, perfusion, dexamethasone (DEX) and bone morphogenetic protein-7 (BMP-7) on the proliferation and differentiation of human bone marrow stromal cells (hBMSCs) in polyurethane scaffolds in a perfusion bioreactor. Polyurethane scaffolds seeded with hBMSCs were cultured under six different conditions, as follows: 10% Cyclic compression at 0.5 and 5 Hz; 10 ml/min perfusion; 100 nM DEX; 100 ng/ml BMP-7; and 1 ml/min perfusion without mechanical and biochemical stimulation (control). On days 7 and 14, samples were tested for the following data: Cell proliferation; mRNA expression of Runx2, COL1A1 and osteocalcin; osteocalcin content; calcium deposition; and the equilibrium modulus of the tissue specimen. The results indicated that BMP-7 and 10 ml/min perfusion promoted cell proliferation, which was inhibited by 5 Hz cyclic compression and DEX. On day 7, the 5 Hz cyclic compression inhibited Runx2 expression, whereas the 0.5 Hz cyclic compression and BMP-7 upregulated the COL1A1 mRNA levels on day 7 and enhanced the osteocalcin expression on day 14. The DEX-treated hBMSCs exhibited downregulated osteocalcin expression. After 14 days, the BMP-7 group exhibited the highest calcium deposition, followed by the 0.5 Hz cyclic compression and the DEX groups. The equilibrium modulus of the engineered constructs significantly increased in the BMP-7, 0.5 Hz cyclic compression and DEX groups. In conclusion, the present results suggest that BMP-7 and perfusion enhance cell proliferation, whereas high frequency cyclic compression inhibits the proliferation and osteogenic differentiation of hBMSCs. Low frequency cyclic compression is more effective than DEX, but less effective compared with BMP-7 on the osteogenic differentiation of hBMSCs seeded on polyurethane scaffolds.


Catheter-based interventions for acute ischaemic stroke.
Catheter-based interventions for acute ischaemic stroke currently include clot removal (usually from the medial cerebral artery) with modern stent-retrievers and in one of five patients (who have simultaneous or stand-alone internal carotid occlusion) also extracranial carotid intervention. Several recently published randomized trials clearly demonstrated superiority of catheter-based interventions (with or without bridging thrombolysis) over best medical therapy alone. The healthcare systems should adopt the new strategies for acute stroke treatment (including fast track to interventional lab) to offer the benefits to all suitable acute stroke patients.


[Infant and childhood mortality in some ancient populations from Abruzzo: paleodemographic and paleopathological implications].
The paleopathologic and paleodemographic study of skeletal samples of ancient populations from Abruzzo, Central Italy, yields data on the trends of infant mortality through the ages from the 7th century B.C. to the modern age. These data integrate the informations deriving from historic sources.


[A fundus flavimaculatus associated with preretinal new vessels (author's transl)].
Case report of a Fundus flavimaculatus associated with preretinal new vessels in a patient without family history. The problem discussed is the outcome of the retinal vascularization during the progressive atrophy of retinal cells.


FDA final guidance on software validation.
The United States Food and Drug Administration (FDA) places considerable importance on the validation of software contained in and used to design, develop, or manufacture medical devices. This article discusses a recently published final FDA guidance document on software validation and the reasons for its importance.


Phase Locking of Auditory Nerve Fibers: The Role of Lowpass Filtering by Hair Cells.
Phase locking of auditory-nerve-fiber (ANF) responses to the temporal fine structure of acoustic stimuli, a hallmark of the auditory system's temporal precision, is important for many aspects of hearing. Previous work has shown that phase-locked period histograms are often well described by exponential transfer functions relating instantaneous stimulus pressure to instantaneous spike rate, with no observed clipping of the histograms. The operating points and slopes of these functions change with stimulus level. The mechanism underlying this apparent gain control is unclear but is distinct from mechanical compression, is independent of refractoriness and spike-rate adaptation, and is apparently instantaneous. Here we show that these findings can be accounted for by a model consisting of a static Boltzmann transducer function yielding a clipped output, followed by a lowpass filter and a static exponential transfer function. Using responses to tones of ANFs from cats of both sexes, we show that, for a given ANF, the period histograms obtained at all stimulus levels for a given stimulus frequency can be described using one set of level-independent model parameters. The model also accounts for changes in the maximum and minimum instantaneous spike rates with changes in stimulus level. Notably, the estimated cutoff frequency is lower for low- than for high-spontaneous-rate ANFs, implying a synapse-specific contribution to lowpass filtering. These findings advance our understanding of ANF phase locking by highlighting the role of peripheral filtering mechanisms in shaping responses of individual ANFs.SIGNIFICANCE STATEMENT Phase locking of auditory-nerve-fiber responses to the temporal fine structure of acoustic stimuli is important for many aspects of hearing. Period histograms typically retain an approximately sinusoidal shape across stimulus levels, with the peripheral auditory system operating as though its overall transfer function is an exponential function whose slope decreases with increasing stimulus level. This apparent gain control can be accounted for by a static saturating transducer function followed by a lowpass filter. In addition to attenuating the AC component, the filter approximately recovers the sinusoidal waveform of the stimulus. The estimated cutoff frequency varies with spontaneous rate, revealing a synaptic contribution to lowpass filtering. These findings highlight the significant impact of peripheral filtering mechanisms on phase locking.


Clinician confidence about conversations at the end of life is strengthened using the four habits approach.
Can attending a communication skills workshop focused on advance care planning, shifting focus to palliative care, personal grief, managing anger, and culture and communication result in changes in attitudes and knowledge? One hundred and three clinicians completed surveys prior to and following the workshop resulting in significant changes in knowledge, attitudes and intent to change that persisted for at least 3 months. As most clinicians are not routinely exposed to learning communication skills for end-of-life conversations, opportunities to practice these skills in a safe supportive environment should be made available in medical schools, residency programs, and in the practice community.


An Effective Method of Isolating Honey Proteins.
Honey is a natural sweetener composed mostly of sugars, but it contains also pollen grains, proteins, free amino acids, and minerals. The amounts and proportions of these components depend on the honey type and bee species. Despite the low content of honey protein, they are becoming a popular study object, and have recently been used as markers of the authenticity and quality of honey. Currently, the most popular methods of protein isolation from honey are dialysis against distilled water, lyophilization of dialysate, or various precipitation protocols. In this work, we propose a new method based on saturated phenol. We tested it on three popular polish honey types and we proved its compatibility with both 1D and 2D polyacrylamide gel electrophoresis (PAGE) and MS (mass spectrometry) techniques. The elaborated technique is also potentially less expensive and less time-consuming than other previously described methods, while being equally effective.


The threat of vaccine associated poliomyelitis in India: medicolegal issues involved.
India is among the world's large reservoirs of wild poliovirus (WPV) with 559 confirmed cases of poliomyelitis (wild virus) being reported in 2008. The World Health Organization's program for the eradication of poliomyelitis in third world countries like India is associated with major ethical and medico-legal implications. Two vaccines are available in India for poliomyelitis i.e. oral polio vaccine (OPV) and inactivated polio vaccine (IPV), of which OPV is used in the eradication campaign, the case count for 2009 being 36 out of a total of 384 reported cases globally, the case count for mid 2010 being 19 cases out of 84 reported globally. There are widespread reports of vaccine derived poliomyelitis as well as vaccine associated poliomyelitis (VAP) from different parts of the country, which can be linked to resurgence of polio in several states or to the failure of the polio drive (Polio Sundays). Though an extended comprehensive polio campaign is on and both money and manpower are being dumped for achieving the goal of polio eradication, the ground reality is entirely different. The argument that wild polio strains have surfaced to hamper the drive cannot account for all post vaccination cases. The Indian Academy of Paediatrics has forcefully suggested replacement of OPV by IPV, as the effectiveness of IPV far exceeds the cost benefit of OPV. IPV has by and large replaced OPV in many parts of the world. The second issue is the threat of litigation on the health department once the post vaccination cases rise even further. There are certain other socio-ethical issues discussed in this paper on a subject which has an important bearing on the health statistics of this country.


Nano-graphene oxide composite for in vivo imaging.
Positron emission tomography (PET) tracers has the potential to revolutionize cancer imaging and diagnosis. PET tracers offer non-invasive quantitative imaging in biotechnology and biomedical applications, but it requires radioisotopes as radioactive imaging tracers or radiopharmaceuticals. This paper reports the synthesis of 18F-nGO-PEG by covalently functionalizing PEG with nano-graphene oxide, and its excellent stability in physiological solutions. Using a green synthesis route, nGO is then functionalized with a biocompatible PEG polymer to acquire high stability in PBS and DMEM. The radiochemical safety of 18F-nGO-PEG was measured by a reactive oxygen species and cell viability test. The biodistribution of 18F-nGO-PEG could be observed easily by PET, which suggested the significantly high sensitivity tumor uptake of 18F-nGO-PEG and in a tumor bearing CT-26 mouse compared to the control. 18F-nGO-PEG was applied successfully as an efficient radiotracer or drug agent in vivo using PET imaging. This article is expected to assist many researchers in the fabrication of 18F-labeled graphene-based bio-conjugates with high reproducibility for applications in the biomedicine field.


Influenza A virus nucleoprotein is acetylated by histone acetyltransferases PCAF and GCN5.
Histone acetylation plays crucial roles in transcriptional regulation and chromatin organization. Viral RNA of the influenza virus interacts with its nucleoprotein (NP), whose function corresponds to that of eukaryotic histones. NP regulates viral replication and has been shown to undergo acetylation by the cAMP-response element (CRE)-binding protein (CBP) from the host. However, whether NP is the target of other host acetyltransferases is unknown. Here, we show that influenza virus NP undergoes acetylation by the two host acetyltransferases GCN5 and P300/CBP-associated factor (PCAF) and that this modification affects viral polymerase activities. Western blot analysis with anti-acetyl-lysine antibody on cultured A549 human lung adenocarcinoma epithelial cells infected with different influenza virus strains indicated acetylation of the viral NP. A series of biochemical analyses disclosed that the host lysine acetyltransferases GCN5 and PCAF acetylate NP in vitro MS experiments identified three lysine residues as acetylation targets in the host cells and suggested that Lys-31 and Lys-90 are acetylated by PCAF and GCN5, respectively. RNAi-mediated silencing of GCN5 and PCAF did not change acetylation levels of NP. However, interestingly, viral polymerase activities were increased by the PCAF silencing and were decreased by the GCN5 silencing, suggesting that acetylation of the Lys-31 and Lys-90 residues has opposing effects on viral replication. Our findings suggest that epigenetic control of NP via acetylation by host acetyltransferases contributes to regulation of polymerase activity in the influenza A virus.


Complete mitochondrial DNA sequence of Tupaia belangeri yaoshanensis (Wang, 1987) from Dayao Mountains in China.
The tree shrew (Tupaia belangeri) is currently placed in the order Scandentia. Owing to their unique characteristics, such as small body size, high brain-to-body mass ratio, short reproductive cycle and life span, and low maintenance costs in laboratory conditions, tree shrews have been proposed as alternative experimental animals to primates in biomedical research. In this study, we determined the complete mitochondrial genome of the subspecies Tupaia belangeri yaoshanensis (T.b. yaoshanensis). The mitochondrial DNA (mtDNA) is 16,777 bp long and contains 13 protein-coding genes (PCGs), two ribosomal RNA genes (12S and 16S), and 22 transfer RNA (tRNA) genes. The base composition of the mitogenome was A (32.28%), T (26.82%), G (14.79%), and C (26.11%). For the 13 PCGs, 1405 variable sites were found between T.b. yaoshanensis and T.b. chinensis (JN800724), of which 916 were synonymous and 489 were nonsynonymous. The frequency of mutations significantly varied among the different genes, with the highest value in the mt-NAD5 gene of tree shrews. Phylogenetic analysis based on the amino acid sequences of 13 PCGs revealed a closer relationship between the species of Scandentia and Lagomorpha. To the best of our knowledge, this is the first study to report the complete mitochondrial genome sequence of T.b. yaoshanensis.


Stability and function of RCL1 are dependent on interaction with BMS1.
During ribosome biogenesis, the small subunit (SSU) processome is responsible for 40S assembly. The BMS1/RCL1 complex is a core component of SSU processome that plays an important role in 18S rRNA processing and maturation. Genetic studies using zebrafish mutants indicate that both Bms1l (Bms1-like) and Rcl1 are essential for digestive organs development. In spite of the vital functions of this complex, the mutual dependence for the stability and function of these two nucleolar proteins remains elusive. In this study, we identified an RCL1-interacting domain in BMS1 conserved in zebrafish and human. Moreover, both protein stability and nucleolar entry of RCL1 depend on BMS1, otherwise leading to RCL1 degradation through the ubiquitination-proteasome pathway. Functional studies reveal that overexpression of RCL1 in BMS1 knockdown cells can partially rescue the defects of 18S rRNA processing and cell proliferation, and hepatocyte-specific overexpression of Rcl1 can resume zebrafish liver development in the bms1l substitution mutant bms1lsq163/sq163but not the knockout mutant bms1lzju1/zju1, attributed to the nucleolar entry of Rcl1 in the former. Our data demonstrate that BMS1 and RCL1 interaction is essential not only for pre-rRNA processing but also for the communication between ribosome biogenesis and cell cycle regulation.


Precision measurement of electron-electron scattering in GaAs/AlGaAs using transverse magnetic focusing.
Electron-electron (e-e) interactions assume a cardinal role in solid-state physics. Quantifying the e-e scattering length is hence critical. In this paper we show that the mesoscopic phenomenon of transverse magnetic focusing (TMF) in two-dimensional electron systems forms a precise and sensitive technique to measure this length scale. Conversely we quantitatively demonstrate that e-e scattering is the predominant effect limiting TMF amplitudes in high-mobility materials. Using high-resolution kinetic simulations, we show that the TMF amplitude at a maximum decays exponentially as a function of the e-e scattering length, which leads to a ready approach to extract this length from the measured TMF amplitudes. The approach is applied to measure the temperature-dependent e-e scattering length in high-mobility GaAs/AlGaAs heterostructures. The simulations further reveal current vortices that accompany the cyclotron orbits - a collective phenomenon counterintuitive to the ballistic transport underlying a TMF setting.


The identification of ligand features essential for PXR activation by pharmacophore modeling.
Drug metabolizing enzymes and transporters are often involved in clinically relevant drug-drug interactions. These functional proteins can be induced by a wide range of xenobiotics. The induction is mediated by a group of receptors known as orphan nuclear receptors. The pregnane X receptor (PXR) is a member of this receptor family and regulates the expression of multiple Cytochrome P450 enzyme families (e.g. CYP 3A and 2B), phase II enzymes (e.g. UDP glucuronosyl transferases), and transporters (e.g. multidrug resistance protein 1). The software package Catalyst was employed to derive pharmacophore models for PXR activation. A structure based pharmacophore hypothesis and several ligand based ones were compared in order to identify ligand receptor interactions essential for receptor activation. The results suggest that hydrogen bonding to Gln285 is indispensable for PXR activation. Most ligands were found to form a second hydrogen bond to His407. Hydrophobic interactions are not essential for receptor activation but contribute to ligand affinity. Highly active compounds share up to five hydrophobic features that allow the ligand to occupy large areas of the predominantly hydrophobic binding pocket.