The synergistic effect of beta-boswellic acid and Nurr1 overexpression on dopaminergic programming of antioxidant glutathione peroxidase-1-expressing murine embryonic stem cells.
Parkinson's disease (PD) is a neurodegenerative disorder in which the nigro-striatal dopaminergic (DAergic) neurons have been selectively lost. Due to side effects of levodopa, a dopamine precursor drug, recently cell replacement therapy for PD has been considered. Lack of sufficient amounts of, embryos and ethical problems regarding the use of dopamine-rich embryonic neural cells have limited the application of these cells for PD cell therapy. Therefore, many investigators have focused on using the pluripotent stem cells to generate DAergic neurons. This study is aimed first to establish a mouse embryonic stem (mES) cell line that can stably co-express Nurr1 (Nuclear receptor subfamily 4, group A, member 2) transcription factor in order to efficiently generate DAergic neurons, and glutathione peroxidase-1 (GPX-1) to protect the differentiated DAergic-like cells against oxidative stress. In addition to genetic engineering of ES cells, the effect of Beta-boswellic acid (BBA) on DAergic differentiation course of mES cells was sought in the present study. To that end, the feeder-independent CGR8 mouse embryonic stem cells were transduced by Nurr1- and GPX-1-harboring Lentiviruses and the generated Nurr1/GPX-1-expresssing ES clones were characterized and verified. Gene expression analyses demonstrated that BBA treatment and overexpression of Nurr1 has a synergistic effect on derivation of DAergic neurons from Nurr1/GPX-1-expressing ES cells. The differentiated cells could exclusively synthesize and secrete dopamine in response to stimuli. Overexpression of GPX-1 in genetically engineered Nurr1/GPX-1-ES cells increased the viability of these cells during their differentiation into CNS stem cells. In conclusion, the results demonstrated that Nurr1-overexpressing feeder-independent ES cells like the feeder-dependent ES cells, can be efficiently programmed into functional DAergic neurons and additional treatment of cells by BBA can even augment this efficiency. GPX-1 overexpression in Nurr1/GPX-1-ES cells increases the viability of differentiated CNS stem-like cells. The result of this study may have impact on future stem cell therapy of PD.


Nonoperative management with selective delayed surgery for large abdominal aortic aneurysms in patients at high risk.
An accepted fact is that abdominal aortic aneurysms (AAAs) larger than 5.5 cm should undergo elective repair. However, subsets of these patients have serious comorbid conditions, which greatly increase operative risk. This study evaluated the outcomes of periods of protracted nonoperative observational management with selective delayed surgery in patients at high risk with large infrarenal and pararenal AAAs. Among 226 patients with AAAs more than 5.5 cm, we selected 72 with AAAs from 5.6 to 12.0 cm (mean, 7.0 cm) for periods of nonoperative management because of their prohibitive surgical risks. Comorbid factors included a low ejection fraction of 15% to 34% (mean, 22%) in 18 patients, 1 second forced expiratory volume less than 50% (mean, 38%) in 25, prior laparotomy in 10, and morbid obesity in 22. Follow-up examination was complete in the 72 patients for the 6 to 76 months (mean, 23 months) that they underwent nonoperative treatment. Fifty-three patients ultimately underwent operation because of AAA enlargement or onset of symptoms after 6 to 72 months (mean, 19 months) of nonoperative treatment. Of the 72 selected patients, 54 (75%) are living and 18 (25%) are dead. Seven patients who underwent only nonoperative treatment presently survive after 28 to 76 months (mean, 48 months). Of the 18 deaths, AAA rupture occurred in only three patients (4%) who were observed for 12, 31, and 72 months before rupture. Nine other deaths (13%) occurred after 6 to 72 months from comorbidities unrelated to the AAA. Six of the 53 patients who underwent delayed operation died within 30 days of operation (11% mortality rate). The mortality rate for the 154 good-risk patients with an AAA who underwent prompt open or endovascular repair was 2.2%. These data indicate that some patients with large AAAs and serious comorbidities are acceptably managed for long periods (6 to 76 months) with nonoperative means. Substantial delays of 12 to 76 months resulted in an AAA rupture rate of only 4%, and 13% of these patients (nine of 72) died of comorbidities unrelated to AAA rupture or surgery. Mortality rate in this group of patients, when operated, was 11% (six of 53). These findings support the selective use of nonoperative management in some patients with large AAAs and serious comorbidities.


Intravenous fluid prescribing errors in children: Mixed methods analysis of critical incidents.
Recent National Institute for Health and Care Excellence (NICE) guidelines aim to improve intravenous (IV) fluid prescribing for children, but existing evidence about how and why fluid prescribing errors occur is limited. Studying this can lead to more effective implementation, through education and systems design. Identify types of IV fluid prescribing errors reported in practiceAnalyse factors that contribute to errorsProvide guidance to educators and those responsible for designing systems. Mixed methods observational study which analysed critical incident reports relating to IV fluid prescribing errors in children aged 0-16, occurring between 2011 and 2015 in UK secondary care. We quantified characteristics and types of errors, then qualitatively analysed narrative descriptions, identifying underlying contributing factors. In the 40 incidents analysed, principal types of errors were incorrect rate of fluids, inappropriate choice of solution, and incorrect completion of prescription charts. Prescribers had to negotiate complex patients, interactions with other practitioners and teams, and challenging work environments; errors resulted from these inter-related contributing factors. This study highlights the diverse range and complex nature of IV fluid prescribing errors reported in practice. While these findings have the inherent limitations of critical incident reports, they point to areas of potential improvement in education and systems design. Practising prescribing in context, inducting doctors within the many specialties who contribute to care of children, and educating them in joint working with nurses and pharmacists could help reduce errors.


Colonoscopy: Its principles and applications.
Fiberoptic colonoscopy has seen its early development in the past five years and in the last two to three years a rapidly expanding experience has developed. The use of this instrument has been documented abundantly both as a diagnostic tool and as a therapeutic tool, and its effectiveness in both areas is well established. The chief therapeutic use of the colonoscope is in the removal of polyps, and in this area the experience has been most gratifying in regard to the ability to remove most polyps and the low incidencs of complications.


Beta thalassemia major in a developing country: epidemiological, clinical and evolutionary aspects.
Beta-thalassemia major (TM) remains to be one of the major health problems particularly in developing countries. Tunisia is a part of the Mediterranean countries mostly affected by this disease which is highly concentrated in small towns in families with low-income earners. The main objectives of this study are to provide a description of the demographic, clinical features and transfusion-related complications in patients with TM living in Tunisia. A standardized questionnaire was sent to clinicians throughout 33 different medical institutions caring for thalassemic patients. 391 transfusion dependant thalassemic patients with a median age of 10.7 years (range 3 months- 31 years) were included in the study. The majority originated from the north west of the country. A moderate iron overload between 1501 and 2500 ng/ml was found in 61patients, while 81 patients (26.9%) had a ferritin level more than 2500 ng/ml and greater than 5000ng/ml in 21 patients (6.9%). 51 patients died from complications related to their disease. Heart failure was the main cause of death. The incidence of cardiac, endocrine, and infectious complications will be reviewed. Preventive measures such as health education, carrier screening and premarital screening remain the best ways for lowering the incidence of these diseases, which might be reflected in financial saving, social s and health benefits.


Material efficiency: rare and critical metals.
In the last few decades, progress in electronics, especially, has resulted in important new uses for a number of geologically rare metals, some of which were mere curiosities in the past. Most of them are not mined for their own sake (gold, the platinum group metals and the rare Earth elements are exceptions) but are found mainly in the ores of the major industrial metals, such as aluminium, copper, zinc and nickel. We call these major metals 'attractors' and the rare accompanying metals 'hitch-hikers'. The key implication is that rising prices do not necessarily call forth greater output because that would normally require greater output of the attractor metal. We trace the geological relationships and the functional uses of these metals. Some of these metals appear to be irreplaceable in the sense that there are no known substitutes for them in their current functional uses. Recycling is going to be increasingly important, notwithstanding a number of barriers.


Escherichia coli MltA: MAD phasing and refinement of a tetartohedrally twinned protein crystal structure.
Crystals were grown of a mutant form of the bacterial cell-wall maintenance protein MltA that diffracted to 2.15 A resolution. When phasing with molecular replacement using the native structure failed, selenium MAD was used to obtain initial phases. However, after MAD phasing the crystals were found to be tetartohedrally twinned, hampering correct space-group determination and refinement. A refinement protocol was designed to take tetartohedral twinning into account and was successfully applied to refine the structure. The refinement protocol is described and the reasons for the failure of molecular replacement and the success of MAD are discussed in terms of the effects of the tetartohedral twinning.


Contamination by respiratory viruses on outer surface of medical masks used by hospital healthcare workers.
Medical masks are commonly used in health care settings to protect healthcare workers (HCWs) from respiratory and other infections. Airborne respiratory pathogens may settle on the surface of used masks layers, resulting in contamination. The main aim of this study was to study the presence of viruses on the surface of medical masks. Two pilot studies in laboratory and clinical settings were carried out to determine the areas of masks likely to contain maximum viral particles. A laboratory study using a mannequin and fluorescent spray showed maximum particles concentrated on upper right, middle and left sections of the medical masks. These findings were confirmed through a small clinical study. The main study was then conducted in high-risk wards of three selected hospitals in Beijing China. Participants (n = 148) were asked to wear medical masks for a shift (6-8 h) or as long as they could tolerate. Used samples of medical masks were tested for presence of respiratory viruses in upper sections of the medical masks, in line with the pilot studies. Overall virus positivity rate was 10.1% (15/148). Commonly isolated viruses from masks samples were adenovirus (n = 7), bocavirus (n = 2), respiratory syncytial virus (n = 2) and influenza virus (n = 2). Virus positivity was significantly higher in masks samples worn for > 6 h (14.1%, 14/99 versus 1.2%, 1/49, OR 7.9, 95% CI 1.01-61.99) and in samples used by participants who examined > 25 patients per day (16.9%, 12/71 versus 3.9%, 3/77, OR 5.02, 95% CI 1.35-18.60). Most of the participants (83.8%, 124/148) reported at least one problem associated with mask use. Commonly reported problems were pressure on face (16.9%, 25/148), breathing difficulty (12.2%, 18/148), discomfort (9.5% 14/148), trouble communicating with the patient (7.4%, 11/148) and headache (6.1%, 9/148). Respiratory pathogens on the outer surface of the used medical masks may result in self-contamination. The risk is higher with longer duration of mask use (> 6 h) and with higher rates of clinical contact. Protocols on duration of mask use should specify a maximum time of continuous use, and should consider guidance in high contact settings. Viruses were isolated from the upper sections of around 10% samples, but other sections of masks may also be contaminated. HCWs should be aware of these risks in order to protect themselves and people around them.


The human trochlear and abducens nerves at different ages - a morphometric study.
The trochlear and abducens nerves (TN and AN) control the movement of the superior oblique and lateral rectus muscles of the eyeball, respectively. Despite their immense clinical and radiological importance no morphometric data was available from a wide spectrum of age groups for comparison with either pathological or other conditions involving these nerves. In the present study, morphometry of the TN and AN was performed on twenty post-mortem samples ranging from 12-90 years of age. The nerve samples were processed for resin embedding and toluidine blue stained thin (1µm) sections were used for estimating the total number of myelinated axons by fractionator and the cross sectional area of the nerve and the axons by point counting methods. We observed that the TN was covered by a well-defined epineurium and had ill-defined fascicles, whereas the AN had multiple fascicles with scanty epineurium. Both nerves contained myelinated and unmyelinated fibers of various sizes intermingled with each other. Out of the four age groups (12-20y, 21-40y, 41-60y and >61y) the younger groups revealed isolated bundles of small thinly myelinated axons. The total number of myelinated fibers in the TN and AN at various ages ranged from 1100-3000 and 1600-7000, respectively. There was no significant change in the cross-sectional area of the nerves or the axonal area of the myelinated nerves across the age groups. However, myelin thickness increased significantly in the AN with aging (one way ANOVA). The present study provides baseline morphometric data on the human TN and AN at various ages.


[Age-specific structural features of the nasal septum in children].
Hearing was studied in 20 and 34 patients with subclinical and initial renal failure (RF), respectively. RF was secondary to chronic glomerulonephritis, chronic pyelonephritis, renal polycystosis (29, 24 and 1 patients, respectively). Hearing function was assessed at tonal threshold, suprathreshold and speech audiometry, ultrasound investigations. It was found that one third of the patients had bilateral symmetric hearing disorder of neurosensory hypoacusis type. The affection was not severe but involved both peripheral and central compartments of the acoustic analyzer. High-frequency sound sensitivity suffered most of all. There was a rise in hearing thresholds by air and bone conductivity at frequencies 12-18 kHz. This rise was the only marker of affected acoustic analyzer in 39% of the examinees. 12% of the patients demonstrated elevated hearing thresholds combined with elevated ultrasound thresholds, low differential threshold of sound intensity and abnormal threshold adaptation.


Transpupillary thermotherapy-induced modification of angiogenesis- and coagulation-related gene expression in the rat posterior fundus.
To study gene expression changes in the rat retina and choroid following transpupillary thermotherapy (TTT) and to identify molecular mechanisms that may enhance treatment of choroidal neovascularization, complicating age-related macular degeneration. One fundus of Brown Norway rats was treated with an 810 nm diode laser while the contralateral fundus received no treatment. The mRNA was extracted and processed for cDNA microarray analysis. Genes with increased expression were validated by semiquantitative reverse transcription polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR). Of the 14,815 cDNA elements on the array, 12 genes were up-regulated in TTT treated eyes. Upregulation of eight of these 12 genes could be verified by semiquantitative RT-PCR. The eight verified genes were EPCR, IL-1beta, MCP-1, TSP-1, Fgl, Asns, MT-2, and NMDMC, which included 4 angiogenesis- and coagulation-related genes. This study demonstrates upregulation of angiogenesis- and coagulation-related genes following TTT. The response profile and its temporal relationships provide insight into the molecular mechanisms that lead to vascular occlusion and antiangiogenesis induced by TTT.


Relaxation stretching, fast dynamics, and activation energy: a comparison of molecular and ionic liquids as revealed by depolarized light scattering.
Depolarized light scattering (DLS) spectra of a series of 16 molecular and 6 room temperature ionic liquids are investigated by applying tandem-Fabry-Pérot interferometry, double monochromator, and photon correlation spectroscopy. Temperatures up to well above the melting point, in some cases, even up to the boiling point, are covered, and all liquids can be supercooled. The accessed time constants are between 1 ps and 10 ns; in some cases, even longer times are reached. The susceptibility spectra and likewise the corresponding reorientational correlation functions are characterized by stretching parameter β(CD) (0.32-0.80) for the long-time decay (α-process), strength of fast dynamics 1 - f, and time scale at shortest times expressed by k(B)T/I* with the apparent quantity I* reflecting essentially inertia effects. An additional (intermediate) power-law regime (or excess wing in the frequency domain) between fast dynamics and the α-process has to be taken into account. For a given system the spectral parameters are virtually temperature independent up to the boiling point, i.e., frequency-temperature superposition applies for the α-process. Among the liquids, the quantity I* correlates with molecular mass, and the larger 1 - f, the smaller the inertial quantity I*. No correlation among 1 - f and β(CD) is revealed. Testing for correlation of β(CD) or 1 - f with parameters describing the temperature dependence of the correlation time τ(α), namely, high-temperature activation energy E(∞), fragility m, or glass transition temperature T(g), no significant correlation is found. Regarding molecular vs ionic liquids, no relevant difference in the evolution of their DLS spectra is observed.


The HOME-21: A revised measure of the home environment for the 21st century tested in two independent samples.
For decades, the Home Observation for Measurement of the Environment (HOME) has been the most widely used measure of children's home environments. This report provides a revised version of the HOME-Short Form, the HOME-21, reflecting historical changes in family composition and caregiver roles, norms about the acceptability of different forms of discipline, and children's digital environments. Using data from two samples of parents of children ages 0-17 (Fast Track [FT], N = 553, age = 33.8, 49.2% female, 48.1% Black, 51.9% White/other; Great Smoky Mountains Study [GSMS], N = 722, age = 37.2, 54.7% female, 67.6% White, 6.6% Black, 25.8% American Indian), we assess the utility of the HOME-21 with descriptive statistics and correlations with a range of demographic, family context, parenting, and child adjustment measures. Higher HOME-21 scores were correlated with obtaining a high school diploma or equivalency diploma (in GSMS only), having 4 or more years of college, and household income. HOME-21 was also correlated with having a more favorable family context indexed by fewer stressful life events (in FT only), less household food insecurity, lower household chaos, and more perceived social support. Higher HOME-21 scores were correlated with better parenting in the form of parental acceptance, positive parenting, warm involvement, appropriate and consistent discipline, verbal discussion, less physical aggression, and greater parental self-efficacy. Higher HOME-21 scores were correlated with better child adjustment in terms of fewer emotional and conduct problems, less hyperactivity, and more prosocial behavior. The HOME-21 has utility for use in future studies of children's home environments in the 21st century. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Alpha-1-antitrypsin deficiency in a Southland family.
After diagnosis of an alpha-1-antitrypsin deficiency in a patient with emphysema, three complete generations of his family were screened for the defect. Half of the 42 subjects had a defective phenotype (18 were MZ, two were ZZ, and one SZ). Of this group, five had other avoidable risk factors predisposing to emphysema, and a further 10 were children. The four oldest subjects had radiological evidence of emphysema. Patients at risk were advised to stop smoking and avoid occupational exposure to lung irritants.


Band structure and Fermi surface of electron-doped C60 monolayers.
C60 fullerides are challenging systems because both the electron-phonon and electron-electron interactions are large on the energy scale of the expected narrow band width. We report angle-resolved photoemission data on the band dispersion for an alkali-doped C60 monolayer and a detailed comparison with theory. Compared to the maximum bare theoretical band width of 170 meV, the observed 100-meV dispersion is within the range of renormalization by electron-phonon coupling. This dispersion is only a fraction of the integrated peak width, revealing the importance of many-body effects. Additionally, measurements on the Fermi surface indicate the robustness of the Luttinger theorem even for materials with strong interactions.


Predictors of parent-reported quality of life of adolescents with cerebral palsy: A longitudinal study.
Parent-reporting is needed to examine Quality of Life (QoL) of children with cerebral palsy (CP) across all severities. This study examines whether QoL changes between childhood and adolescence, and what predicts adolescent QoL. SPARCLE is a European cohort study of children with CP, randomly sampled from population databases. Of 818 8-12-year-olds joining the study, 594 (73%) were revisited as 13-17-year-olds. The subject of this report is the 551 (316 boys, 235 girls) where the same parent reported QoL on both occasions using KIDSCREEN-52 (transformed Rasch scale, mean 50, SD 10 per domain). Associations were assessed using linear regression. Between childhood and adolescence, average QoL reduced in six domains (1.3-3.8 points, p<0.01) and was stable in three (Physical wellbeing, Autonomy, Social acceptance). Socio-demographic factors had little predictive value. Childhood QoL was a strong predictor of all domains of adolescent QoL. Severe impairments of motor function, IQ or communication predicted higher adolescent QoL on some domains; except that severe motor impairment predicted lower adolescent QoL on the Autonomy domain. More psychological problems and higher parenting stress in childhood and their worsening by adolescence predicted lower QoL in five and eight domains respectively; contemporaneous pain in seven domains. The final model explained 30%-40% of variance in QoL, depending on domain. In general, impairment severity and socio-demographic factors were not predictors of lower adolescent QoL. However, pain, psychological problems and parenting stress were predictors of lower adolescent QoL in most domains. These are modifiable factors and addressing them may improve adolescent QoL.


Photodynamic killing of retinoblastoma cells with hematoporphyrin and light.
Hematoporphyrin and white light exerted a lethal effect on two cell lines of retinoblastoma cells. The lowest values of dye concentration and light exposure capable of killing an entire cell population were, respectively, 2 X 10(-5) M and 6 min exposure to an irradiance of 6.0 microwatts/sq mm. Cells exposed to light in the presence of the dye did not require lengthy incubation periods but were rapidly killed with increasing periods of light exposure. Cells washed free of the dye, however, required a minimum sensitizing period of 3.5 hr to achieve a value close to 100% cell death. An inhibitor of this photodynamic process was demonstrated in normal serum. When the concentration of either fetal calf serum, rabbit serum, or rabbit plasma was increased to 25% from a standard 10%, there was as much as a 100-fold greater requirement of hematoporphyrin concentration to produce the same lethal response. The suggested explanation for this phenomenon is a porphyrin-binding plasma factor, hemopexin, which is a natural beta-glycoprotein believed to be responsible for the transport of circulating porphyrins to the liver for their elimination. Retinoblastoma cells grow in suspension and thereby provide an excellent tool for study of photosensitive dyes, especially in the case of the rapidly growing Y79 cell line.


Anti-lymphokine antibody. II. Specificity of biological activity.
The present study was designed to explore the range of biologic activity of an anti-lymphokine antiserum (ALKS). This preparation, which was produced by a two-stage immunization procedure, was used to prepare Sepharose bead immunoadsorbent columns. Columns made with ALKS, but not with anti-control antiserum, could specifically remove MIF activity, but not LT, MF, or NCF activity from activated lymphocyte culture supernatants. MIF but not LT, MF, or NCF could be recovered from the beads by acid extraction. These findings, taken in conjunction with the previously described capacity of ALKS to remove MCF and SRF activity from supernatants, demonstrated that ALKS although prepared against a lymphokine preparation with multiple activities, has restricted specificity. Thus far, its traget appear to be those mediators that affect macrophages either in vitro or in vivo. The capacity of ALKS to suppress delayed hypersensitivity reactions in the guinea pig is consistent with these observations, since the macrophage is the predominant infiltrating cell in those reactions.


In vitro detection of porphyrin-producing wound bacteria with real-time fluorescence imaging.
Aim: Fluorescence imaging can visualize polymicrobial populations in chronic and acute wounds based on porphyrin fluorescence. We investigated the fluorescent properties of specific wound pathogens and the fluorescence detected from bacteria in biofilm. Methods: Utilizing Remel Porphyrin Test Agar, 32 bacterial and four yeast species were examined for red fluorescence under 405 nm violet light illumination. Polymicrobial biofilms, supplemented with δ-aminolevulinic acid, were investigated similarly. Results: A total of 28/32 bacteria, 1/4 yeast species and polymicrobial biofilms produced red fluorescence, in agreement with their known porphyrin production abilities. Conclusion: These results identify common wound pathogens capable of producing porphyrin-specific fluorescence and support clinical observations using fluorescence imaging to detect pathogenic bacteria in chronic wounds.


Matching study to registry data: maintaining data privacy in a study on family based colorectal cancer.
Confidentiality of patient data in the field of medical informatics is an important task. Leaked sensitive information within this data can be adverse to and being abused against a patient. Therefore, when working with medical data, appropriate and secure models which serve as guidelines for different applications are needed. Consequently, this work presents a model for performing a privacy preserving record linkage between study and registry data. The model takes into account seven requirements related to data privacy. Furthermore, this model is exemplified with a study on family based colorectal cancer in Germany. The model is very strict and excludes possible violations towards data privacy protection to a reasonable degree. It should be applicable to similar use cases which are in need of a mapping between medical data of a study and a registry database.


[Effect of cyclophosphamide on the bone marrow hematopoiesis in the mouse].
This paper reports the effect of cyclophosphamide on the bone marrow hematopoiesis in the mouse. Cyclophosphamide 0.12 mg/g body weight was injected into the mice once and the observation lasted for 2 weeks. After the injection, peripheral leukocytes were reduced to the lowest level on day 4 and then increased higher than the control on day 7 to 14. The number of nucleated cell in the bone marrow was the lowest at the 48th hour and gradually became normal within two weeks. The pluripotent hemopoietic stem cells--CFU-S (colony forming unit-spleen) were depleted abruptly in 24 hours, then reproliferated exponentially to a peak on day 3, followed by a second decrease and came back to normal level on day 11 to 14. The changes of granulocytic progenitor cell CFU-D (colony forming unit-diffusion chamber) and CFU-C (colony forming unit-culture) were quite similar to that of CFU-S but their proliferation peak was on day 4. The peripheral leukocyte drop was slower and the return to normal was earlier than the hemopoietic cells. So the recovery of leukocyte count does not mean a real reconstruction of hematopoiesis. The bone marrow stroma observed by CFU-F (colony forming unit-fibroblastoid) assay and marrow microcirculation were also damaged and did not recover to normal during the observation. The bone marrow stroma and microcirculation showed a more serious damage.


An Update from the Benchmark Survey of phactMI™ Member Companies on Providing Medical Information in the Digital Space.
The Pharma Collaboration for Transparent Medical Information (phactMI™) benchmarking survey of 32 pharmaceutical companies describes the use of technology by Medical Information Departments. A survey was distributed to phactMI™ member companies in June 2022 and included 79 closed and open-ended questions. The survey's six sections included demographics, chatbot, social media, instant messaging applications, websites, and technology. Most Medical Information Departments have implemented innovative technology since 2019 with the main driver of remaining up-to-date. A total of 94% have a Medical Information website. Of those with a Medical Information website for healthcare professionals (HCPs), 97% allow for self-authentication. Most HCP-based websites have webforms for inquiries and 1-800 numbers, while only few offer video chat, chatbot, and the ability to identify local representatives. These websites also link to clinicaltrials.gov, publications, posters, and congress materials. Only 30% have a website for patients/caregivers. Most websites are discoverable by Google™. Awareness of Medical Information Websites occurs in a variety of ways, with most using multiple strategies to reach HCPs. There is wide variation in the technology platform used for the core functions of Medical Information. As technology continues to advance and omnichannel content remains a key objective, Medical Information needs to remain agile and transformative in their strategic and tactical planning and execution. Based on this benchmarking survey, the authors recommend that Medical Information Departments focus on expanding services for patients/caregivers, leverage digital innovations, expanding awareness, building efficiencies in workflow through technology, and continually improving website functionalities with innovative technologies.


Near-infrared spectroscopic technique for detection of beef hamburger adulteration.
A near-infrared spectroscopic technique was developed to detect beef hamburgers adulterated with 5-25% mutton, pork, skim milk powder, or wheat flour with an accuracy up to 92.7%. The accuracy of detection increased with the increase of adulteration level. When an adulterant was detected, the adulteration level was further predicted by calibration equations. The established calibration equations for predicting adulteration levels with mutton, pork, skim milk powder, and wheat flour had standard errors of cross-validation of 3.33, 2.99, 0.92, and 0.57% and coefficients of variance of 0.87, 0.89, 0.99, and 1.00, respectively. The results of this study indicate that near-infrared spectroscopy is potentially useful in detection of beef hamburger adulteration.


Septic elbow in the setting of neuropathic joint as the initial presentation of a cervical syrinx.
Neuropathic arthropathy, or Charcot's joint, is a degenerative disorder resulting from abnormal sensory innervation that is associated with diabetes mellitus, tabes dorsalis, and syringomyelia. Patients may present with a painless instability of the affected joint, although a range of symptoms are seen. This article presents a case of a patient who presented with a swollen elbow, consistent with septic arthritis, and bilateral lower extremity weakness. Joint fluid cultures were positive for methicillin-resistant Staphylococcus aureus. Extensive joint destruction on radiographic imaging and a thorough neurologic examination revealing generalized weakness and upper motor neuron signs prompted magnetic resonance imaging (MRI) of the spine which revealed a cervical syrinx. Our patient was diagnosed with syringomyelia-associated neuropathic arthropathy that initially presented as a septic joint. In the setting of septic arthritis, substantial joint destruction (particularly in a patient with neurologic deficits) should prompt additional investigation, including MRI of the spine, for neurologic causes. Although surgery is generally not recommended for neuropathic arthropathy because of poor healing and high rates of complication, neuropathic arthropathy in the setting of a septic joint requires operative irrigation and debridement.


Optimization of Underbody Blast Energy-Attenuating Seat Mechanisms Using Modified MADYMO Human Body Models.
Though energy attenuating (EA) seats for air and spacecraft applications have existed for decades, they have not yet been fully characterized for their energy attenuation capability or resulting effect on occupant protection in vertical underbody blast. EA seats utilize stroking mechanisms to absorb energy and reduce the vertical forces imparted on the occupant's pelvis and lower spine. Using dynamic rigid-body modeling, a virtual tool to determine optimal force and deflection limits was developed to reduce pelvis and lower spine injuries in underbody blast events using a generic seat model. The tool consists of a mathematical dynamic model (MADYMO)-modified human body model (HBM), basic EA seat model, and an optimizing sequence using modefrontier software. This optimizing tool may be shared with EA seat manufacturers and applied to military seat development efforts for EA mechanisms for a given occupant and designated blast severity. To optimally tune the EA seat response, the MADYMO human body model was first updated to improve its fidelity in kinematic response data for high rate vertical accelerative loading relative to experimental data from laboratory simulated underbody blast tests using postmortem human surrogates (PMHS). Subsequently, using available injury criteria for underbody blast, the optimization tool demonstrated the ability to identify successful EA mechanism critical design value configurations to reduce forces and accelerations in the pelvis and lower spine HBM to presumed noninjurious levels. This tool could be tailored by varying input pulses, force and deflection limits, and occupant size to evaluate EA mechanism designs.


Historical note: Snow, Empson and the Barkers of Bath.
The identity of the artist who painted the well-known portrait of John Snow has been established. It has been discovered that the painting was exhibited at the Royal Academy of Arts, London in 1847.


Does Cd36 gene play a key role in disturbed glucose and fatty acid metabolism in Prague hypertensive hypertriglyceridemic rats?
Close links between hypertension, hypertriglyceridemia, insulin resistance and other symptoms of metabolic syndrome was demonstrated in humans and experimental animals. Quantitative trait loci for defects in glucose and fatty acid metabolism, hypertriglyceridemia and hypertension were mapped in spontaneously hypertensive rats (SHR) on chromosome 4 and defective Cd36 gene was identified in this region. Here we investigated the polymorphism of Cd36 gene in Prague hereditary hypertriglyceridemic (HTG) rats, which represent another model of genetic hypertension and metabolic syndrome. These animals were compared with NIH-derived SHR and two different normotensive control strains (WKY, LEW). In spite of the fact that HTG and SHR rats had similar metabolic disturbances, genotype analysis of PCR products has shown that Cd36 mutation was not present in HTG rats. In conclusion, we have revealed that defective Cd36 is probably a candidate gene for disorded fatty-acid metabolism, glucose intolerance and insulin resistance in NIH-derived SHR, but other genes might play a role in pathogenesis of metabolic syndrome in Prague hereditary hypertriglyceridemic rats. This is in accordance with the absence of defective Cd36 gene in original SHR from Japan.


Histologic, serologic, and molecular analysis of persistent ehrlichiosis in a murine model.
Human monocytotropic ehrlichiosis caused by Ehrlichia chaffeensis was reported in 1987. An animal model to study acute fatal ehrlichiosis in mice that has been developed closely resembles the fatal form of human monocytotropic ehrlichiosis. However, animal models for persistent infection in the genus Ehrlichia in immunocompetent mice have not been characterized. We report the histopathological progression of Ehrlichia muris infection in immunocompetent mice (AKR and C57BL/6 strains) correlated with their antibody response determined by indirect immunofluorescence and Western immunoblotting, and the distribution and quantity of the ehrlichial load by immunohistochemistry, polymerase chain reaction (PCR), and real-time PCR in lungs, liver, and spleen. Mild to moderate correlation was observed between histopathological grading in these organs and relative ehrlichial loads. The highest ehrlichial loads were present between days 4 and 14 after infection. E. muris was detected in tissues examined up to 150 days after infection by real-time PCR. Analysis of the serological response revealed several immunodominant antigens, including 200-, 180-, 100-, 73/75-, 45-, and 28-kd proteins. In conclusion, we have provided for the first time a complete histopathological, serological, immunohistochemical, and quantitative analysis of an animal model for the study of persistent ehrlichial infection.


The effect of the screw pull-out rate on cortical screw purchase in unreamed and reamed synthetic long bones.
Orthopaedic fracture fixation constructs are typically mounted on to human long bones using cortical screws. Biomechanical studies are increasingly employing commercially available synthetic bones. The aim of this investigation was to examine the effect of the screw pull-out rate and canal reaming on the cortical bone screw purchase strength in synthetic bone. Cylinders made of synthetic material were used to simulate unreamed (foam-filled) and reamed (hollow) human long bone with an outer diameter of 35 mm and a cortex wall thickness of 4 mm. The unreamed and reamed cylinders each had 56 sites along their lengths into which orthopaedic cortical bone screws (major diameter, 3.5 mm) were inserted to engage both cortices. The 16 test groups (n = 7 screw sites per group) had screws extracted at rates of 1 mm/ min, 5 mm/min, 10 mm/min, 20 mm/min, 30 mm/min, 40 mm/min, 50 mm/min, and 60 mm/ min. The failure force and failure stress increased and were highly linearly correlated with pull-out rate for reamed (R2 = 0.60 and 0.60), but not for unreamed (R2 = 0.00 and 0.00) specimens. The failure displacement and failure energy were relatively unchanged with pull-out rate, yielding low coefficients for unreamed (R2 = 0.25 and 0.00) and reamed (R2 = 0.27 and 0.00) groups. Unreamed versus reamed specimens were statistically different for failure force (p = 0.000) and stress (p = 0.000), but not for failure displacement (p = 0.297) and energy (0.054 < p < 1.000). This is the first study to perform an extensive investigation of the screw pull-out rate in unreamed and reamed synthetic long bone.


Latent membrane protein-1 oncogene deletions in nasopharyngeal carcinoma in Caucasian patients.
The latent membrane protein-1 (LMP-1) is an Epstein-Barr virus (EBV)-transforming protein expressed in nasopharyngeal carcinoma (NPC). A 30-bp deletion in the LMP-1 oncogene has been described in NPC patients from Asia. The purpose of this study was to evaluate the association between NPC and such an EBV deletion in Caucasian patients. Twenty-seven patients with a diagnosis of NPC were selected. Most of the NPCs were classified as Stages III and IV using the International Union Against Cancer system. Formalin-fixed, paraffin-embedded NPC specimens were found for these cases. Hematoxylin-eosin slides were reviewed and survival analysis was done using the log-rank method. In situ hybridization for EBV-encoded non-polyadenylated RNAs and expression of LMP-1 by means of immunohistochemistry was also performed. Polymerase chain reaction for LMP-1 oncogene analysis was performed to detect the presence of a 30-bp deletion in NPC specimens and EBV-related controls The 30-bp deletion was identified in 67% of NPC cases and in 30% of controls, a statistically significant difference (p = 0.01, chi2 test). LMP-1 deletion was not statistically associated with a worse prognosis in NPC patients (5-year survival: 33% in wild-LMP-1 strains vs 24% in deleted-LMP-1 strains; p = 0.053, log-rank test). A 30-bp deletion in the LMP-1 oncogene is present in more than half of Caucasian NPC cases EBV carrying partial deletions in the LMP-1 oncogene may play a role in the pathogenesis of NPC in Caucasian patients.


Indole-3-acetic acid and auxin herbicides up-regulate 9-cis-epoxycarotenoid dioxygenase gene expression and abscisic acid accumulation in cleavers (Galium aparine): interaction with ethylene.
Interaction between auxin and auxin-induced ethylene was suggested in previous work to up-regulate abscisic acid (ABA) biosynthesis in cleavers (Galium aparine) through stimulated cleavage of xanthophylls to xanthoxin, catalysed by 9-cis-epoxycarotenoid dioxygenase (NCED). Here, the effects of auxin on NCED gene expression were studied in relation to changes in ethylene synthesis and ABA levels. A gene from G. aparine shoot tissue was cloned based on sequence similarity to cloned NCED genes from tomato (LeNCED1), potato, Phaseolus, and Arabidopsis. When the roots of G. aparine plants were treated with 0.5 mM indole-3-acetic acid (IAA), IAA concentrations increased from 0.2 microM to 65 microM IAA in the shoot tissue after 3 h. Transient increases in GaNCED1 mRNA levels were detectable as early as 1 h after treatment and reached maximum values of 40-fold, relative to the control, after 3 h. Increases in GaNCED1 mRNA preceded increases in 1-aminocyclopropane-1-carboxylic acid and ethylene. Levels of ABA began to increase more slowly and, significantly, with a lag phase of 2 h, and reached levels 24-fold higher than those in controls after 24 h. GaNCED1 gene expression was also stimulated by auxin herbicides. The ethylene-releasing compound ethephon induced GaNCED1 transcript levels only moderately. In accordance with this, aminoethoxyvinylglycine and cobalt ions, which inhibit ethylene synthesis, only slightly affected the increase in GaNCED1 transcript levels by IAA. However, both ethylene inhibitors decreased IAA-induced ABA accumulation by up to 70%. This suggests that auxin and auxin-induced ethylene are involved in ABA accumulation. While auxin is the primary trigger for NCED gene expression, ethylene appears to enhance ABA biosynthesis, possibly by up-regulation of NCED activity post-transcriptionally.


Inducible nitric oxide synthase inhibition delays death of rabies virus-infected mice.
A pathophysiological mechanism of cerebral damage and impairment of neuronal function during rabies virus infection was examined. Synthesis of nitric oxide (NO) and expression of the inducible nitric oxide synthase (iNOS) gene are strongly upregulated during rabies virus infection. Treatment of rabies virus-infected mice with a selective inhibitor of iNOS, aminoguanidine (AG), significantly delayed their death. Prolonged survival was not due to suppression of an inflammatory response in the central nervous system. One effect of iNOS inhibition was at the level of viral replication. Treatment with AG delayed rabies virus replication by 2 days. Moreover, iNOS inhibition also suppressed an early phase of expression of an apoptotic gene, Caspase-1, which resulted in slow progression of infected cells into apoptotic death. iNOS inhibition had no effect on expression of the anti-apoptotic gene, bcl-2. In conclusion, iNOS inhibition delayed the death of rabies virus-infected mice by affecting viral replication and apoptotic death of infected cells.


Molecular cloning of a unique human T-cell leukemia virus (HTLV-IIMo).
Human T-cell leukemia virus IIMo (HTLV-IIMo) is a human retrovirus isolated from a patient with a T-cell hairy cell leukemia. This virus has been shown to have core protein (gag) antigens similar to, but distinct from, those of all known isolates of the prototype human T-cell leukemia virus (HTLV-I). We have used a subgenomic clone of the HTLV-I env-pX region to detect and characterize HTLV-IIMo proviral sequences by performing Southern blot hybridization under conditions of low stringency. Using the HTLV-I probe, we cloned a partial integrated HTLV-IIMo provirus from a genomic library of the producer Mo cell line. These sequences could be characterized by low stringency hybridization with different subgenomic clones of HTLV-I. An HTLV-IIMo-specific subclone was made by isolating a 3.6-kilobase BamHI fragment of the partial provirus. This was used to clone two full-length integrated viral genomes. Using the HTLV-IIMo viral probe, we also showed by hybridization under stringent conditions to DNA and RNA of various infected and uninfected cell lines that these HTLV-IIMo sequences are unique.


Gut modulator effects of Conyza bonariensis explain its traditional use in constipation and diarrhea.
The current investigation was carried out to explore the pharmacological basis of the crude extract of Conyza bonariensis (Cb.Cr) for its use in constipation and diarrhea. The plant extract of Conyza bonariensis (C. bonariensis) was prepared, isolated guinea-pig ileum and rabbit jejunum preparations were used to evaluate its gut modulator effects. The Cb.Cr (0.3-10 mg/mL) exhibited spasmogenic effect in isolated guinea-pig ileum preparation, which was about 19-84% of the acetylcholine maximum. Pretreatment of the tissues with atropine (0.1 µM) abolished the contractile effect, similar to acetylcholine. Among the fractions, only the butanol fraction exhibited atropine sensitive contractile effect. In isolated rabbit jejunum preparations, Cb.Cr produced appreciable atropine-sensitive spasmogenic effect at lower concentrations (0.03-0.3 mg/mL) followed by spasmolytic effect at next higher concentration (1.0 and 3.0 mg/mL). Cb.Cr caused an inhibition of the high K+ induced contraction in isolated rabbit jejunum preparation with EC50 value of 0.62 mg/mL. Similarly, verapamil, a standard calcium blocker, inhibited high K+ induced contraction in isolated rabbit jejunum preparations. Cb.Cr caused a right ward shift in the Ca++ concentration response curve, similar to verapamil. Among various fractions of C. bonariensis, only hexane and ethylacetate fractions showed spasmolytic effects. The crude extract of C. bonariensis contains spasmogenic and spasmolytic constituents, which explains its medicinal use in constipation and diarrhea.


Theoretical detection limits of magnetic biobarcode sensors and the phase space of nanobiosensing.
A scaling theory of the sub atto-molar (aM) detection limits of magnetic particle (MP) based biosensors (e.g., bio-barcode assays) is developed and discussed. Despite the dramatic differences of sensing protocols and detection limits, the MP-based sensors can be interpreted within the same theoretical framework as any other classical biosensor (e.g., nanowire sensors), except that these sensors are differentiated by the geometry of diffusion and the probe (ρ(MP))/target (ρ(T)) density ratio. Our model predicts two regimes for biomolecule detection: For classical biosensors with ρ(MP) ≤ ρ(T), the response time t(s) proportional to 1/ρ(T); while for MP-based biosensors with ρ(MP) > ρ(T), t(s) proportional to 1/ρ(MP). The theory (i) explains the performance improvement of MP-sensors by ρ(MP)/ρ(T) (order of 10(3)-10(6)), broadly validating the sub-aM detection limits reported in literature, (ii) offers intuitive interpretation for the counter-intuitive ρ(T)-independence of detection time in MP-sensors, (iii) shows that statistical fluctuations should reduce with ρ(T) for MP sensors, and (iv) offers obvious routes to sensitivity improvement of classical sensors.


Functional change in the pattern of swallowing through the performance of orofacial exercises.
The objective was to determine if there was functional improvement of swallowing pattern in subjects identified with risk of oropharyngeal dysphagia after four weeks of specific oropharyngeal exercises. These exercises have pre-determined intensity and duration. It is a longitudinal study of functional effect, determined by initial and final comparative measures. Participants were adults and elderly, selected in a period of 24 months. A total of 68 participants were included. All subjects had a clinical evaluation of swallowing, and an initial measure in a functional scale. The individuals were split into two groups, according to the initial levelling of ASHA NOMS scale. In Group 1 (G1) - ASHA NOMS, initial of levels 1 and 2; Group 2 (G2) - ASHA NOMS, initial of levels 3, 4 and 5. All subjects executed an exercise protocol performed for four weeks. The protocol includes sessions with a speech therapist, and continuity of activities in home environment. Finally, new measurement of swallowing performance was held. For G2 group there was statistically significant improvement. For G1, the relation was insignificant, despite the intense change in ASHA NOMS scale, however, in this group there was a reduced number of individuals due to the profile severity. The program was effective because after four exercise sessions, there was significant improvement in swallowing pattern, demonstrated by functional scale.


Plastination of macroparasites: An eco-friendly method of long-term preservation.
Preservation of macroparasites by infiltrating the polymer in the tissues can defy the inherited shortcoming of classical wet preservation method. Preservation was done by infiltrating the melamine alone or with xylene (MX)/chloroform (MC)/turpentine oil (MT) in 1:1 and hardener (MH) in 9:1 ratio in the tissues of the gross specimen of the animal parasites. The plastinated models withstand the process of microbial decomposition, and remain intact in the environmental conditions. The polymer mixture resists the entry of the water molecule, and model dried just after taking out it from the water tank. Overall, the plastinated parasites were dry, non-sticky, glossy, odorless, chemical free, and harmless, to some extent flexible, with detectable morphological structure, and retain their natural form but lost their natural color. Full marks were assigned to the degree of dryness, non-stickiness, and odorlessness to the model plastinated in different solutions on a five-point scale. For flexibility, the score was 1.2, 2.2, and 2.4 for the plastinated model in melamine/MH, MX/MC, and MT solutions, respectively. The average score of glossiness was 4.6 and 5 for the specimen plastinated in melamine/MH and MX/MC/MT solutions, respectively. The degree of dryness, glossiness, stickiness, and flexibility varies non-significantly, with the polymer mixtures used. The prepared model can be used to educate the students/general mass population.


Nanocellulose Paper Semiconductor with a 3D Network Structure and Its Nano-Micro-Macro Trans-Scale Design.
Semiconducting nanomaterials with 3D network structures exhibit various fascinating properties such as electrical conduction, high permeability, and large surface areas, which are beneficial for adsorption, separation, and sensing applications. However, research on these materials is substantially restricted by the limited trans-scalability of their structural design and tunability of electrical conductivity. To overcome this challenge, a pyrolyzed cellulose nanofiber paper (CNP) semiconductor with a 3D network structure is proposed. Its nano-micro-macro trans-scale structural design is achieved by a combination of iodine-mediated morphology-retaining pyrolysis with spatially controlled drying of a cellulose nanofiber dispersion and paper-crafting techniques, such as microembossing, origami, and kirigami. The electrical conduction of this semiconductor is widely and systematically tuned, via the temperature-controlled progressive pyrolysis of CNP, from insulating (1012 Ω cm) to quasimetallic (10-2 Ω cm), which considerably exceeds that attained in other previously reported nanomaterials with 3D networks. The pyrolyzed CNP semiconductor provides not only the tailorable functionality for applications ranging from water-vapor-selective sensors to enzymatic biofuel cell electrodes but also the designability of macroscopic device configurations for stretchable and wearable applications. This study provides a pathway to realize structurally and functionally designable semiconducting nanomaterials and all-nanocellulose semiconducting technology for diverse electronics.


Applications of community detection techniques to brain graphs: Algorithmic considerations and implications for neural function.
The human brain can be represented as a graph in which neural units such as cells or small volumes of tissue are heterogeneously connected to one another through structural or functional links. Brain graphs are parsimonious representations of neural systems that have begun to offer fundamental insights into healthy human cognition, as well as its alteration in disease. A critical open question in network neuroscience lies in how neural units cluster into densely interconnected groups that can provide the coordinated activity that is characteristic of perception, action, and adaptive behaviors. Tools that have proven particularly useful for addressing this question are community detection approaches, which can identify communities or modules: groups of neural units that are densely interconnected with other units in their own group but sparsely interconnected with units in other groups. In this paper, we describe a common community detection algorithm known as modularity maximization, and we detail its applications to brain graphs constructed from neuroimaging data. We pay particular attention to important algorithmic considerations, especially in recent extensions of these techniques to graphs that evolve in time. After recounting a few fundamental insights that these techniques have provided into brain function, we highlight potential avenues of methodological advancements for future studies seeking to better characterize the patterns of coordinated activity in the brain that accompany human behavior. This tutorial provides a naive reader with an introduction to theoretical considerations pertinent to the generation of brain graphs, an understanding of modularity maximization for community detection, a resource of statistical measures that can be used to characterize community structure, and an appreciation of the usefulness of these approaches in uncovering behaviorally-relevant network dynamics in neuroimaging data.


The Cellular basis of loss of smell in 2019-nCoV-infected individuals.
A prominent clinical symptom of 2019-novel coronavirus (nCoV) infection is hyposmia/anosmia (decrease or loss of sense of smell), along with general symptoms such as fatigue, shortness of breath, fever and cough. The identity of the cell lineages that underpin the infection-associated loss of olfaction could be critical for the clinical management of 2019-nCoV-infected individuals. Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2, TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. We studied if anosmia in 2019-nCoV-infected individuals can be explained by the expression patterns associated with these host-specific moieties across the known olfactory epithelial cell types, identified from a recently published single-cell expression study. Our findings underscore selective expression of these viral entry-associated genes in a subset of sustentacular cells (SUSs), Bowman's gland cells (BGCs) and stem cells of the olfactory epithelium. Co-expression analysis of ACE2 and TMPRSS2 and protein-protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium. Furthermore, expression, structural and docking analyses of ACE2 revealed the potential risk of olfactory dysfunction in four additional mammalian species, revealing an evolutionarily conserved infection susceptibility. In summary, our findings provide a plausible cellular basis for the loss of smell in 2019-nCoV-infected patients.


Impact of a Novel Social Work Program on Access to Tertiary Care.
In the movement for global health equity, increased research and funding have not yet addressed a shortage of evidence on effectively implementing context-specific interventions; one unmet need is facilitating access to specialty care within the public health sector in Mexico. Compañeros en Salud has been piloting a novel program, called Right to Healthcare (RTHC), to increase access to specialty care for the rural poor in Chiapas, Mexico. The RTHC program incorporates social work, patient navigation, referrals, direct economic support, and accompaniment for patients. This study evaluates the effectiveness of the RTHC program. Primary outcomes analyzed included acceptance of any referral and attendance of any appointment. Secondary outcomes included acceptance of the first referral and rate of appointment attendance for patients with an accepted referral. Using referral process data for the years 2014 to 2019 from a public tertiary care hospital in Chiapas, 91 RTHC patients were matched using 2:1 optimal pair matching with a control cohort balancing covariates of patient age, sex, specialty referred to, level of referring hospital, and municipality. RTHC patients were more likely to have had an accepted referral (OR 17.42, 95% CI 3.68 to 414.16) and to have attended an appointment (OR 5.49, 95% CI 2.93 to 11.60) compared to the matched control group. RTHC patients were also more likely to have had their first referral accepted (OR 2.78, 95% CI 1.29 to 6.73). Among patients with an accepted referral, RTHC patients were more likely to have attended an appointment (OR 3.86, 95% CI 1.90 to 8.57). The results demonstrate that the RTHC model is successful in increasing access to specialty care by both increasing referral acceptance and appointment attendance.


Exposure to Tobacco Advertising, Promotion Among the Adult Population in Vietnam and Its Implications for Public Health.
The Law on Tobacco Control and the Law on Advertisement prohibit the advertising of any tobacco product in Vietnam. Tobacco promotion and marketing are alsostrictly prohibited. However, the violation of tobacco adverting and promotion is still common in Vietnam. This article aims at describing the exposure to tobacco advertising and promotion among the population aged 15+ years in Vietnam based on the data from the Global Adult Tobacco Survey 2015 from the view of the community, identifying any possible associations between the exposure to tobacco advertising and promotion and other individual factors, and discussing its possible public health implications. A cross-sectional study with the nationwide scale. Secondary data from the Global Adult Tobacco Survey 2015 was explored and analyzed. Chi-square test and multivariate logistic regressions were applied in the data analysis. The most common type of adults' exposure to tobacco advertising and promotion was points of sale (8.6%); 9.8% adults exposure to one source of tobacco advertising and 4.0% of them exposed to one source of tobacco promotion. Around 13.3% of Vietnamese adults were exposed to tobacco advertisement, while 2.0% were exposed to tobacco promotion, 5.3% were exposed to both tobacco advertising and promotion, and 16.6% were exposed to tobacco advertising or promotion. Gender, educational level, age, occupation, marital status, socioeconomic status, location (urban, rural), and current smoking status were associated with the exposure to tobacco advertising, tobacco promotion, tobacco advertising and promotion, and tobacco advertising or promotion. Although there are comprehensive bans on tobacco advertising and promotion in Vietnam, adults aged 15+ years still reported their exposure to tobacco advertising and promotion. There should be a strict enforcement of the ban on tobacco advertising and promotion in Vietnam.


Vitamin B12 Deficiency: A Rare Cause of Excessive Daytime Sleepiness.
Excessive daytime sleepiness (EDS) is one of the leading reasons that patients present to sleep clinics. Approximately 10% to 14% of the adults report that excessive sleepiness interferes with their daily lives. Common causes of EDS include obstructive sleep apnea, sleep deprivation, circadian rhythm disorders, medication effects, psychiatric conditions especially depression, and primary hypersomnia such as narcolepsy or central idiopathic hypersomnia. Vitamin B12 deficiency is a rare cause of EDS. We are presenting a case of severe vitamin B12 deficiency as an unusual and rare cause of hypersomnia. Khawaja I, Yingling K, Bukamur H, Abusnina W. Vitamin B12 deficiency: a rare cause of excessive daytime sleepiness. J Clin Sleep Med. 2019;15(9):1365-1367.


Effect of Ag alloying and trace precipitation on corrosion resistance of Ti-Ta-Ag ternary alloy.
This work systematically analysed the electrochemical and corrosion behaviour of Ti-Ta-Ag ternary alloy samples in Hank's solution. For the samples with 1.5% and 3% Ag content, the sintering temperature increased from 750 to 950°C, and the corresponding corrosion resistance increased by 100 times due to the increased alloying of Ag; meanwhile for the sample with 4.5% Ag content, the sintering temperature increased from 750 to 950°C, and the corresponding corrosion resistance decreased by six times due to the increased precipitation of Ag. These tests prove that the Ag alloying is beneficial to the enhancement of the corrosion resistance of Ti-Ta-Ag ternary alloy, but the Ag trace precipitation has the opposite effect. A series of electrochemical characterizations and density functional theory calculations explain the mechanism of the above phenomenon. Ag alloying can promote the formation of uniform, complete, dense, stable and thick passivation layer on the surface of Ti-Ta-Ag ternary alloy, which makes Ti-Ta-Ag ternary alloy uniformly corroded without pitting. In addition, Ag alloying can effectively reduce the contact resistance of the solid-liquid interface. However, the trace precipitation of Ag plays the opposite role to the above effect.


Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.
Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.


Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.
T cells targeting self-proteins are important mediators in autoimmune diseases. T cells express unique cell-surface receptors (TCRs) that recognize peptides presented by major histocompatibility molecules. TCRs have been identified from blood and pancreatic islets of individuals with type 1 diabetes (T1D). Here, we tracked ~1700 known antigen-specific TCR sequences, islet antigen or viral reactive, in bulk TCRβ sequencing from longitudinal blood DNA samples in at-risk cases who progressed to T1D, age/sex/human leukocyte antigen-matched controls, and a new-onset T1D cohort. Shared and frequent antigen-specific TCRβ sequences were identified in all three cohorts, and viral sequences were present across all ages. Islet sequences had different patterns of accumulation based upon antigen specificity in the at-risk cases. Furthermore, 73 islet-antigen TCRβ sequences were present in higher frequencies and numbers in T1D samples relative to controls. The total number of these disease-associated TCRβ sequences inversely correlated with age at clinical diagnosis, indicating the potential to use disease-relevant TCR sequences as biomarkers in autoimmune disorders.


Discrimination experienced by Asian Canadian and Asian American health care workers during the COVID-19 pandemic: a qualitative study.
Asian Canadians and Asian Americans face COVID-19-related discrimination. The objective of this qualitative study was to explore the experiences of Asian health care workers dealing with discrimination, with a focus on racial micro-agressions, in Canada and the United States during the COVID-19 pandemic. We adopted a qualitative descriptive approach. We used convenience and snowball sampling strategies to recruit participants. We conducted individual, in-depth semistructured interviews with Asian health care workers in Canada and the US via videoconferencing between May and September 2020. Eligible participants had to self-identify as Asian and be currently employed as a health care worker with at least 1 year of full-time employment. We used an inductive thematic approach to analyze the data. Thirty participants were recruited. Fifteen (50%) were Canadians and 15 (50%) were Americans; there were 18 women (60%), 11 men (37%) and 1 nonbinary person. Most of the participants were aged 25-29 years (n = 16, 53%). More than half were nurses (n = 16, 53%); the other participants were attending physicians (n = 5), physiotherapists (n = 3), resident physicians (n = 2), a midwife, a paramedic, a pharmacist and a physician assistant. Two themes emerged from the data: a surge of racial microaggressions related to COVID-19 and a lack of institutional and public acknowledgement. Participants noted that they have experienced an increase in racial microaggressions during the COVID-19 pandemic. They have also experienced threats of violence and actual violence. The largely silent organizational response to the challenges being faced by people of Asian descent and the use of disparaging terms such as "China virus" in the early stages of the pandemic were a substantial source of frustration. Asian health care workers have experienced challenges in dealing with racial microaggressions related to COVID-19 in the US and Canada. More research should be done on the experiences of Asian Americans and Asian Canadians, both during and after the pandemic, and supportive measures should be put in place to protect Asian health care workers.


Gene transfer by polyoma-like particles assembled in a cell-free system.
Empty capsids of polyoma virus interact with DNA in a cell-free system to form polyoma-like particles (PLP). The DNA in these particles is protected from the action of pancreatic deoxyribonuclease. Transfer of genetic information by PLP has been accomplished by using a restriction fragment containing the transforming sequences of polyoma DNA as a model gene. Infection of rat F111 cells by PLP containing these sequences results in DNA-mediated cellular transformation. Gene transfer by PLP is 50 to 150 times more efficient than by the calcium phosphate precipitation method.


Bounding the bias of unmeasured factors with confounding and effect-modifying potentials.
Confounding is a major concern in observational studies. To adjust for confounding bias, the potential confounder(s) for a study must first be identified and measured. But this is not always possible. The unmeasured factors may also exhibit effect modification, and this further complicates the situation. In this paper, the author derives bounding formulas for the bias of unmeasured factors with confounding and effect-modifying potentials. Based on these formulas, the author derives two conditions (for the unmeasured factors) to explain away an observed positive finding: the low-threshold (for the minimum of two parameters related to the unmeasured factors) and the high-threshold (for the maximum) conditions. All these should help researchers make more prudent interpretations of their (potentially biased) results.


Climate variability and spruce beetle (Dendroctonus rufipennis) outbreaks in south-central and southwest Alaska.
We used tree ring data (AD 1601-2007) to examine the occurrence of and climatic influences on spruce beetle (Dendroctonus rufipennis) outbreaks in south-central and southwest Alaska and found evidence of regional-scale outbreaks dating from the mid-1700s, related to climate variability at multiple temporal scales. Over interannual time scales (approximately 1-3 years), El Niño years, combined with severe late-summer drought, appeared to contribute significantly to spruce beetle outbreaks in the study area. Over multidecadal time scales (up to approximately 40 years), cool-phase Pacific Decadal Oscillation (PDO) conditions tended to precede beetle outbreaks, regardless of the phase of El Niño-Southern Oscillation (ENSO). All sites showed low-severity disturbances attributed to spruce beetle damage, most notably during the 1810s. During other major periods of disturbance (i.e., 1870s, 1910s, 1970s), the effects of spruce beetle outbreaks were of moderate or higher severity. The highly synchronized timing of spruce beetle outbreaks at interannual to multidecadal scales, and particularly the association between cool-phase PDO conditions and beetle disturbance, suggests that climate (i.e., temperature, precipitation) is a primary driver of outbreaks in the study area. Our disturbance chronologies (mid-1700s to present) suggest that recent irruptions (1990s to present) in south-central and southwest Alaska are within the historical geographic range, but that outbreaks since the 1990s show greater spatiotemporal synchrony (i.e., more sites record high-severity infestations) than at any other time in the past approximatly 250 years.


Establishment of exotic parasites: the origins and characteristics of an avian malaria community in an isolated island avifauna.
Knowledge of the processes favouring the establishment of exotic parasites is poor. Herein, we test the characteristics of successful exotic parasites that have co-established in the remote island archipelago of New Zealand, due to the introduction of numerous avian host species. Our results show that avian malaria parasites (AM; parasites of the genus Plasmodium) that successfully invaded are more globally generalist (both geographically widespread and with a broad taxonomic range of hosts) than AM parasites not co-introduced to New Zealand. Furthermore, the successful AM parasites are presently more prevalent in their native range than AM parasites found in the same native range but not co-introduced to New Zealand. This has resulted in an increased number and greater taxonomic diversity of AM parasites now in New Zealand.


Cytotoxic T lymphocytes from HLA-A2.1 transgenic mice define a potential human epitope from simian virus 40 large T antigen.
Recent reports have documented the presence of SV40 large T antigen (T ag) sequences in a number of human tumors and raised the question of whether cellular immunity to T ag is elicited in such individuals. We used HLA-A2.1 transgenic C57BL/6 mice to identify an epitope from T ag recognized by CD8+ CTLs when presented by this human MHC class I molecule. Immunization of HLA-A2.1 transgenic mice with syngeneic T ag-transformed cells resulted in the induction of HLA-A2.1-restricted, T ag-specific CTLs. The target epitope, residues 281-289 (KCDDVLLLL) of T ag, was identified using both cell lines expressing T ag variants and synthetic T ag peptides. Peptide 281-289 bound stably to HLA-A2.1 molecules, effectively sensitized target cells for CTL lysis, and was efficiently processed from endogenous T ag in cells of both mouse and human origin. CTLs were not cross-reactive on the human BK or JC virus T ags. Thus, SV40 T ag 281-289 represents a potential specific CTL recognition epitope for humans.


DIVI: Dynamically Interactive Visualization.
Dynamically Interactive Visualization (DIVI) is a novel approach for orchestrating interactions within and across static visualizations. DIVI deconstructs Scalable Vector Graphics charts at runtime to infer content and coordinate user input, decoupling interaction from specification logic. This decoupling allows interactions to extend and compose freely across different tools, chart types, and analysis goals. DIVI exploits positional relations of marks to detect chart components such as axes and legends, reconstruct scales and view encodings, and infer data fields. DIVI then enumerates candidate transformations across inferred data to perform linking between views. To support dynamic interaction without prior specification, we introduce a taxonomy that formalizes the space of standard interactions by chart element, interaction type, and input event. We demonstrate DIVI's usefulness for rapid data exploration and analysis through a usability study with 13 participants and a diverse gallery of dynamically interactive visualizations, including single chart, multi-view, and cross-tool configurations.


Extracellular Matrix Bioscaffolds as Immunomodulatory Biomaterials<sup/>.
Suppression of the recipient immune response is a common component of tissue and organ transplantation strategies and has also been used as a method of mitigating the inflammatory and scar tissue response to many biomaterials. It is now recognized, however, that long-term functional tissue replacement not only benefits from an intact host immune response but also depends upon such a response. The present article reviews the limitations associated with the traditionally held view of avoiding the immune response, the ability of acellular biologic scaffold materials to modulate the host immune response and promote a functional tissue replacement outcome, and current strategies within the fields of tissue engineering and biomaterials to develop immune-responsive and immunoregulatory biomaterials.


Theoretical analysis for integral imaging performance based on microscanning of a microlens array.
An integral imaging method based on microscanning of a microlens array is proposed. The effects of microscanning on the depth resolution and the product of depth of focus and lateral resolution squared (PDLRS) of an integral imaging system are quantitatively analyzed. Calculation results show that microscanning can improve not only the depth resolution, but the PDLRS can be increased. The amount of improvement of different microscanning modes to the performance of integral imaging is closely related to the fill factor of the detector and the diffraction factor of the microlens.


Patient-level indirect treatment comparison of lanadelumab versus pdC1-INH i.v. in hereditary angioedema patients: PATCH study.
Hereditary angioedema (HAE) is an autosomal dominant inherited disease in which patients suffer from local attacks primarily affecting skin and gastrointestinal tract, and sometimes even the upper respiratory tract leading to asphyxiation. Since head-to-head trials between authorized treatments are lacking, this study compares efficacy and safety of lanadelumab and intravenous plasma-derived C1-esterase inhibitor (pdC1-INH i.v.) in HAE patients on long-term prophylaxis by means of an indirect treatment comparison. Efficacy and safety of lanadelumab against pdC1-INH i.v. were analyzed in a fully prespecified indirect comparison based on individual patient data (n = 231) from the HELP and CHANGE clinical trials. Primary and secondary efficacy endpoints were compared using a generalized linear model for count data. Confounding variables were identified a priori via systematic literature research and validated by clinical experts. Adjustment of confounders was implemented using a conditional regression model. Lanadelumab showed a statistically significant improvement in reduction of HAE attack rates compared to pdC1-INH i.v. across multiple endpoints: Monthly attack rate of patients treated with lanadelumab was less than half compared to pdC1-INH i.v. (Rate ratio: 0.486; 95% CI: 0.253, 0.932). Monthly rate of laryngeal attacks was found to be five times lower for lanadelumab (Rate ratio: 0.2; 95% CI: 0.044, 0.915) and monthly rate of acute treated HAE attacks among lanadelumab patients was about one third of the attack rate of pdC1-INH i.v. patients (Rate ratio: 0.366; 95% CI: 0.185, 0.727). This study contributes to current knowledge in the treatment of HAE by indicating a statistically significant reduction of HAE attacks under lanadelumab compared to pdC1-INH i.v.


Ultraviolet radiation accelerates NRas-mutant melanomagenesis: A cooperative effect blocked by sunscreen.
To mitigate melanoma risk, sunscreen use is widely advocated; yet, the ability of sunscreens to prevent melanoma remains controversial. Here, we test the tenet that sunscreens limit melanoma risk by blocking ultraviolet radiation (UV)-induced DNA damage using murine models that recapitulate the genetics and spontaneous evolution of human melanoma. We find that a single, non-erythematous dose of UV dramatically accelerates melanoma onset and increases tumor multiplicity in mice carrying an endogenous, melanocyte-specific NRas61R allele. By contrast, transient UV exposure does not alter tumor onset in mice lacking p16INK4a or harboring an NRas12D allele. To block the rapid onset of melanoma cooperatively caused by UV and NRas61R , we employed a variety of aerosol sunscreens. While all sunscreens delayed melanoma formation and blocked UV-induced DNA damage, differences in aerosol output (i.e., amount applied/cm2 ) caused variability in the cancer preventative efficacy of products with identical sunburn protection factor (SPF) ratings.


Assessing PAH removal from clayey soil by means of electro-osmosis and electrodialysis.
Polycyclic aromatic hydrocarbons (PAH) are persistent and toxic contaminants which are difficult to remove from fine porous material like clayey soils. The present work aims at studying two electroremediation techniques for the removal of PAHs from a spiked natural silt soil from Saudi Arabia and a silty loam soil from The Netherlands which has been exposed to tar contamination for over 100 years. The two techniques at focus are electro-osmosis and electrodialysis. The latter is applied for the first time for the removal of PAH. The efficiency of the techniques is studied using these two soils, having been subjected to different PAH contact times. Two surfactants were used: the non-ionic surfactant Tween 80 and anionic surfactant sodium dodecyl sulphate (SDS) to aid desorption of PAHs from the soil. Results show a large discrepancy in the removal rates between spiked soil and long-term field contaminated soil, as expected. In spiked soil, electro-osmosis achieves up to 85% while electrodialysis accomplishes 68% PAH removal. In field contaminated soil, electro-osmosis results in 35% PAH removal whereas electrodialysis results in 79%. Short recommendations are derived for the up-scale of the two techniques.


Altered expression of genes for Kir ion channels in dilated cardiomyopathy.
Dilated cardiomyopathy (DCM) is a multifactorial disease characterized by left ventricular dilation that is associated with systolic dysfunction and increased action potential duration. The Kir2.x K⁺ channels (encoded by KCNJ genes) regulate the inward rectifier current (IK1) contributing to the final repolarization in cardiac muscle. Here, we describe the transitions in the gene expression profiles of 4 KCNJ genes from healthy or dilated cardiomyopathic human hearts. In the healthy adult ventricles, KCNJ2, KCNJ12, and KCNJ4 (Kir2.1-2.3, respectively) genes were expressed at high levels, while expression of the KCNJ14 (Kir2.4) gene was low. In DCM ventricles, the levels of Kir2.1 and Kir2.3 were upregulated, but those of Kir2.2 channels were downregulated. Additionally, the expression of the DLG1 gene coding for the synapse-associated protein 97 (SAP97) anchoring molecule exhibited a 2-fold decline with increasing age in normal hearts, and it was robustly downregulated in young DCM patients. These adaptations could offer a new aspect for the explanation of the generally observed physiological and molecular alterations found in DCM.


Unipedal balance is affected by lower extremity joint arthroplasty procedure 1 year following surgery.
Lower Extremity Joint Arthroplasty (LEJA) surgery is an effective way to alleviate painful osteoarthritis. Unfortunately, these surgeries do not normalize the loading asymmetry during the single leg stance phase of gait. Therefore, we examined single leg balance in 234 TJA patients (75 hips, 65 knees, 94 ankles) approximately 12 months following surgery. Patients passed if they maintained single leg balance for 10s with their eyes open. Patients one year following total hip arthroplasty (THA-63%) and total knee arthroplasty (TKA-69%) had similar pass rates compared to a total ankle arthroplasty (TAA-9%). Patients following THA and TKA exhibit better unilateral balance in comparison with TAA patients. It may be beneficial to include a rigorous proprioception and balance training program in TAA patients to optimize functional outcomes.


Inter-rater reliability data of classroom observation: Fidelity in large-scale randomized research in education.
This dataset belongs to a large-scale randomized controlled trial (RCT) in educational research targeting English learning students and their teachers' instructional capacity. The dataset includes ratings conducted through classroom observations of 45-minute English as a Second language (ESL) blocks. Each coder rated 60 recorded video segments collected from each teacher. During the 20-second segment, ratings of six domains of teachers' instruction (i.e., ESL Strategies, Group, Activity Structure, Mode, Language Content, Language of Teacher, Language of Student) were collected. The dataset is organized by teacher, by coder, and by domain, for researchers to analyze inter-rater reliability among coders by domain and/or cross-domain. This data article is related to the research article Tong et al. [3] on "The determination of appropriate coefficient indices for inter-rater reliability: using classroom observation instruments as fidelity measures in large-scale randomized research".


The unfolding process of apo-human serum transferrin in the presence of cetylpyridinium chloride: an isothermal titration calorimetry study.
Isothermal titration calorimetry (ITC) was utilized at conditions close to physiological (50 mM HEPES buffer, pH 7.4 and 160 mM NaCl) and at various temperatures of 25, 30, 35 and 40 °C to evaluate the thermodynamic parameters, enthalpy and heat capacity changes, and subsequently the unfolding process of apo-human serum tarnsferrin (apo-hTf) in the presence of cetylpyridinium chloride (CPC) as a cationic surfactant. The precise thermograms and heat capacity curves obtained and interpreted in terms of molecular events such as specific and non-specific binding and the unfolding process. The analysis of obtained enthalpograms and heat capacity changes profile showed a distinct extreme region close to [CPC]/[apo-hTf] mole ratio of 20 indicated that predominant cooperative unfolding occurs at this mole ratio via a two states mechanism.


Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.
Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.


Children's cognitive ability from 4 to 9 years old as a function of prenatal cocaine exposure, environmental risk, and maternal verbal intelligence.
This study examined the effects of prenatal cocaine exposure, environmental risk, and maternal verbal intelligence on children's cognitive ability. Gender and age were examined as moderators of potential cocaine exposure effects. The Stanford-Binet IV intelligence test was administered to 231 children (91 cocaine exposed, 140 unexposed) at ages 4, 6, and 9 years. Neonatal medical risk and other prenatal exposures (alcohol, cigarettes, and marijuana) were also examined for their unique effects on child IQ. Mixed models analysis indicated that prenatal cocaine exposure interacted with gender, as cocaine-exposed boys had lower composite IQ scores. Age at assessment did not moderate this relation, indicating that cocaine-exposed boys had lower IQs across this age period. A stimulating home environment and high maternal verbal IQ also predicted higher composite IQ scores. Cocaine-exposed boys had lower scores on the Abstract/Visual Reasoning subscale, with trends for lower scores on the Short-Term Memory and Verbal Reasoning subscales, as exposure effects were observed across domains. The findings indicate that cocaine exposure continues to place children at risk for mild cognitive deficits into preadolescence. Possible mechanisms for the Exposure x Gender interaction are discussed.


Variations of direct fluorescent antibody test and serum bile acids levels following praziquantel treatment in Schistosoma mansoni experimentally infected mice.
This study was performed to evaluate the efficiency and use of an immunopathological test viz "Direct Fluorescent Antibody Test (DFAT) for detection of IgG and IgM deposits in liver and kidney biopsies" and a biochemical test viz "estimation of serum bile acids by enzymatic colorimetric technique" for follow up Schistosoma mansoni infection using Swiss albino mice. Test were done during infection and after Praziquantel (PZQ) treatment. Mice were classified according to the duration of infection and post-therapy periods. It was found that both tests should be used together to provide good parameters to demonstrate S. mansoni infection and to test the regression of the disease after treatment.


Recent advances in metal-catalysed asymmetric sigmatropic rearrangements.
Asymmetric sigmatropic rearrangement is a powerful organic transformation via substrate-reorganization to efficiently increase molecular complexity from readily accessible starting materials. In particular, a high level of diastereo- and enantioselectivity can be readily accessed through well-defined and predictable transition states in [3,3], [2,3]-sigmatropic rearrangements, which have been widely applied in the synthesis of various chiral building blocks, natural products, and pharmaceuticals. In recent years, catalytic asymmetric sigmatropic rearrangements involving chiral metal complexes to induce stereocontrol have been intensively studied. This review presents an overview of metal-catalysed enantioselective versions of sigmatropic rearrangements in the past two decades, mainly focusing on [3,3], [2,3], and [1,3]-rearrangements, to show the development of substrate design, new catalyst exploitation, and novel cascade processes. In addition, their application in the asymmetric synthesis of complex natural products is also exemplified.


Dereplication of Fungal Metabolites by NMR-Based Compound Networking Using MADByTE.
Strategies for natural product dereplication are continually evolving, essentially in lock step with advances in MS and NMR techniques. MADByTE is a new platform designed to identify common structural features between samples in complex extract libraries using two-dimensional NMR spectra. This study evaluated the performance of MADByTE for compound dereplication by examining two classes of fungal metabolites, the resorcylic acid lactones (RALs) and spirobisnaphthalenes. First, a pure compound database was created using the HSQC and TOCSY data from 19 RALs and 10 spirobisnaphthalenes. Second, this database was used to assess the accuracy of compound class clustering through the generation of a spin system feature network. Seven fungal extracts were dereplicated using this approach, leading to the correct prediction of members of both families from the extract set. Finally, NMR-guided isolation led to the discovery of three new palmarumycins (20-22). Together these results demonstrate that MADByTE is effective for the detection of specific compound classes in complex mixtures and that this detection is possible for both known and new natural products.


Twin Boundaries merely as Intrinsically Kinematic Barriers for Screw Dislocation Motion in FCC Metals.
Metals with nanoscale twins have shown ultrahigh strength and excellent ductility, attributed to the role of twin boundaries (TBs) as strong barriers for the motion of lattice dislocations. Though observed in both experiments and simulations, the barrier effect of TBs is rarely studied quantitatively. Here, with atomistic simulations and continuum based anisotropic bicrystal models, we find that the long-range interaction force between coherent TBs and screw dislocations is negligible. Further simulations of the pileup behavior of screw dislocations in front of TBs suggest that screw dislocations can be blocked kinematically by TBs due to the change of slip plane, leading to the pileup of subsequent dislocations with the elastic repulsion actually from the pinned dislocation in front of the TB. Our results well explain the experimental observations that the variation of yield strength with twin thickness for ultrafine-grained copper follows the Hall-Petch relationship.


Comparison of patients undergoing enhanced external counterpulsation and percutaneous coronary intervention for stable angina pectoris.
Enhanced external counterpulsation (EECP) has recently emerged as a treatment option for angina in selected patients suitable for revascularization with percutaneous coronary intervention (PCI). We compared baseline characteristics and 1-year outcome in 2 cohorts of PCI candidates presenting with stable symptoms: 323 patients treated with EECP in the International EECP Patient Registry (IEPR), and 448 NHLBI Dynamic Registry patients treated with elective PCI. Compared with patients receiving PCI, IEPR patients had a higher prevalence of many risk factors including prior PCI (53.0% vs 33.3%, p <0.001), prior coronary artery bypass grafting (42.1% vs 18.6%, p <0.001), prior myocardial infarction (56.4% vs 27.8%, p <0.001), history of congestive heart failure (16.8% vs 9.2%, p <0.01), and history of diabetes (37.9% vs 23.5%, p <0.001). Left ventricular ejection fraction was lower among IEPR patients (mean 50.3% vs 59.2%, p <0.001). At 1 year, survival was comparable in the 2 cohorts (98.7% IEPR vs 96.8% PCI, p = NS), as were rates of coronary artery bypass grafting during follow-up (4.5% IEPR vs 5.7% PCI, p = NS). At 1 year, 43.7% of IEPR patients reported no anginal symptoms compared with 73.4% of Dynamic Registry patients (p <0.001). Rates of severe symptoms (Canadian Cardiovascular Society class III, IV, or unstable) at 1 year were 15.5% among IEPR patients and 9.5% in the Dynamic Registry (p = 0.02). PCI candidates suitable for and treated with EECP had 1-year major event rates comparable to patients receiving elective PCI. Although PCI was associated with substantially lower rates of 1-year symptoms, EECP may be a safe treatment option for selected patients with obstructive coronary disease.


Clinician attitudes towards prescribing and implications for interventions in a multi-specialty group practice.
Prescribing decisions are subject to a myriad of external forces, including patient requests for advertised medications. Although numerous factors influence prescribing, resources to support unbiased evidence-based prescribing are not widely available. To guide future interventions, we surveyed clinicians about influences on prescribing, awareness of pharmaceutical costs and attitudes towards computerized decision support. A 21-item survey was sent to 604 prescribing clinicians in a large multi-specialty group practice that employs a robust electronic medical record. Surveys were returned from 405 clinicians (67%). Most respondents (87%) felt that direct-to-consumer (DTC) advertising prompts patients to request inappropriate medications, and more than one in five clinicians (22%) reported difficulty declining patients' requests for advertised medications. Providers with more clinical sessions per week reported greater difficulty. Although 93% of clinicians felt they have access to the information needed to guide prescribing, only about half (54%) reported they are aware of how much patients pay for prescription medications. Clinicians' awareness of medication costs varied considerably by specialty, with behavioural health clinicians being the most aware. The majority of providers (79%) stated that computerized prescribing alerts are a clinically useful source of information. Although the majority of clinicians reported that DTC advertising leads many patients to request medications that are inappropriate for their condition, a sizable proportion of clinicians reported difficulty declining these requests, and many are unaware of medication costs. Interventions to support prescribing decisions should provide the busiest clinicians with up-to-date, specialty-specific evidence and cost information.


Depressive Symptoms, Pain, and Quality of Life among Patients with Nonalcohol-Related Chronic Pancreatitis.
Objective. The present study was conducted to determine if depressive symptoms were associated with variability in pain perception and quality of life among patients with nonalcohol-related chronic pancreatitis. Methods. The research design was cross-sectional, and self-report data was collected from 692 patients with nonalcohol-related, intractable pancreatitis. The mean age of the sample was 52.6 (SD = 14.7); 41% of the sample were male. Participants completed the MOS SF12 Quality of Life Measure, the Center for Epidemiological Studies 10-item Depression Scale (CESD), and a numeric rating scale measure of "pain on average" from the Brief Pain Inventory. Results. Depressive symptoms were significantly related to participants' reports of increased pain and decreased quality of life. The mean CESD score of the sample was 10.6 (SD = 6.5) and 52% of the sample scored above the clinical cutoff for the presence of significant depressive symptomology. Patients scoring above the clinical cutoff on the depression screening measure rated their pain as significantly higher than those below the cutoff (P < 0.0001) and had significantly lower physical quality of life (P < 0.0001) and lower mental quality of life (P < 0.0001). Conclusion. Although causality cannot be determined based on cross-sectional, correlational data, findings suggest that among patients with nonalcoholic pancreatitis, the presence of depressive symptoms is common and may be a risk factor associated with increased pain and decreased quality of life. Thus, routine screening for depressive symptomology among patients with nonalcoholic pancreatitis may be warranted.