TSG101, a tumor susceptibility gene, bidirectionally modulates cell invasion through regulating MMP-9 mRNA expression.
Tumor susceptibility gene 101 (TSG101) was initially identified in fibroblasts as a tumor suppressor gene but subsequent studies show that TSG101 also functions as a tumor-enhancing gene in some epithelial tumor cells. Although previous studies have unraveled diverse biological functions of TSG101, the precise mechanism by which TSG101 is involved in carcinogenesis and tumor progression in a bidirectional and multifaceted manner remains unclear. To reveal the mechanism underlying bidirectional modulation of cell invasion by TSG101, we used RNA interference to examine whether TSG101 depletion bidirectionally modulated matrix metalloproteinase (MMP)-9 expression in different cell types. TSG101 depletion promoted cell invasion of HT1080 cells but contrarily reduced cell invasion of HeLaS3 cells. In HT1080 cells, TSG101 depletion increased both baseline and phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 secretion through enhancing MMP-9 mRNA expression, but did not affect the expression or activation of MMP-2. In contrast, TSG101 depletion decreased PMA-induced MMP-9 secretion through reducing MMP-9 mRNA expression in HeLaS3 cells. TSG101 depletion had little impact on the signaling pathways required for the activation of transcription of MMP-9 or MMP-9 mRNA stability in either cell line. TSG101 bidirectionally modulates cell invasion through regulating MMP-9 mRNA expression in different cell types. Our results provide a mechanistic context for the role of TSG101 in cell invasion as a multifaceted gene.


Daily defecation outputs of mountain gorillas (Gorilla beringei beringei) in the Volcanoes National Park, Rwanda.
Increasing population density can increase infectious disease risk and thus reduce population growth and size. Host-parasite interactions of threatened animals that remain in small protected forest fragments therefore need to be monitored carefully. Due to extreme conservation efforts, the mountain gorilla (Gorilla beringei beringei) population in the 450-km2 Virunga Massif has more than doubled since 1973, reaching 604 individuals in 2016. To better understand changes in the transmission risks of soil-borne and other enteric pathogens for mountain gorillas, we determined defecation outputs of different age-sex classes and the diurnal variation in feces deposition. We weighed 399 wet fecal samples deposited at nest sites and on trails between nest sites by gorillas of varying age and sex, determined by lobe diameter, from five social groups (n = 58 gorillas) that range in the Volcanoes National Park, Rwanda. We found increasing daily average defecation outputs with increasing age-sex class (infants, 435 g; juveniles, 1346 g; medium-sized gorillas, 2446 g; silverbacks, 3609 g). Gorillas deposited two- to threefold the amount of feces at nest sites compared to on trails, suggesting that nest sites may function as hotspots for enteric pathogen infections through direct contact or when gorillas ingest foods contaminated with infectious larvae during site revisits in intervals matching the maturation period of environmentally transmitted gastrointestinal parasites. In combination with ranging and demographic data, these findings will enable the modeling of spatiotemporal variation in soil contamination and infectious disease risk for Virunga gorillas as their population density continues to increase.


A toolbox for light control of Drosophila behaviors through Channelrhodopsin 2-mediated photoactivation of targeted neurons.
In order to study the function of specific neural circuits, we generated UAS-Channelrhodopsin2 (ChR2) transgenic Drosophila and established a ChR2-based system that enables specific activation of targeted neurons in larval and adult fruit flies with blue light illumination, under the control of a newly designed light source that provides fully programmable stimulation patterns. We showed that stimulating selectively the nociceptor of larvae expressing ChR2 elicited light-induced 'pain' response, confined freely behaving larvae in defined area and directed larva migration along a preset route. In freely behaving adult flies, rapid photoactivation of targeted gustatory sensory neurons, dopaminergic modulatory neurons and motor neurons triggered the proboscis extension response, escaping reflex and changes in the locomotion pattern, respectively, with precise temporal control. This non-invasive method for remote control of animal behaviors also provides a potential tool for conducting 'gain of function' studies toward understanding how animal behaviors are controlled by neural activity.


The modern Latin word rhabdus belongs to the feminine gender, inducing necessary corrections according to Rules 65(2), 12c(1) and 13b of the Bacteriological Code (1990 Revision).
The modern Latin word rhabdus does belong to the feminine gender. According to Rules 65(2), 12c(1) and 13b of the Bacteriological Code (1990 Revision), the gender of six generic names and the spelling of nine specific and subspecific epithets are proposed to be corrected.


The evolution of sports participation guidelines and the influence of genotype-phenotype correlation in long QT syndrome.
Congenital Long QT Syndrome (LQTS) results in abnormal ventricular repolarization in patients with otherwise structurally normal hearts. Following the initial clinical descriptions of LQTS, there has been a great deal of investigation into the genetic etiology and pathophysiology of these entities, with the goal of improved screening tools and understanding of associated risks. Through this work, heart rhythm experts continue to revise their recommendations regarding sports eligibility. We review the evolution of sports participation recommendations for LQTS.


Bicyclic Guanidine Catalyzed Asymmetric Tandem Isomerization Intramolecular-Diels-Alder Reaction: The First Catalytic Enantioselective Total Synthesis of (+)-alpha-Yohimbine.
Hydroisoquinoline derivatives were prepared in moderate to good enantioselectivities via a bicyclic guanidine-catalyzed tandem isomerization intramolecular-Diels-Alder (IMDA) reaction of alkynes. With this synthetic method, the first enantioselective synthesis of (+)-alpha-yohimbine was completed in 9 steps from the IMDA products.


Clinical utility of a standardized chronic hypersensitivity pneumonitis exposure questionnaire.
Identification of an exposure is integral to the diagnosis, management, and prognostication of chronic hypersensitivity pneumonitis (CHP). Standardized questionnaires may aid in the identification of exposures, however, there currently are no evidence-based patient-validated questionnaires available. Key qualifiers (including duration and frequency) which indicate exposure relevance are also poorly defined. This study assessed the use of a standardized CHP exposure questionnaire in the identification of exposures and diagnostic confidence of CHP. People with a multi-disciplinary meeting (MDM) diagnosis from five Australian interstitial lung disease (ILD) expert centres who provided informed consent were included. Participants completed a previously developed standardized CHP Exposure Questionnaire. Responses were collected with the participant's MDM data, including diagnosis, diagnostic confidence, and clinician-elicited exposures. One hundred thirty participants (IPF = 58, CHP = 24, CTD-ILD = 17, unclassifiable = 19, other = 12) were included. In 33% of CHP participants, a standardized questionnaire elicited an exposure where the clinician did not. 63% of these had provisional low confidence CHP; and an exposure history would have increased the diagnostic confidence in these cases. Using the standardized questionnaire, 96% of CHP participants reporting any exposure, compared with 75% of non-HP ILD participants. CHP participants were 3.5 times more likely (p = 0.004) to report their symptoms improved on avoidance, and 2.3 times more likely (p = 0.018) to report daily frequent exposure, compared with non-HP ILDs. A standardized questionnaire which elicits exposure characteristics in addition to presence or absence of relevant exposures can increase the diagnostic confidence of CHP and reduce the proportion of antigen-indeterminate CHP.


Peri-interventional coronary vasomotion.
A percutaneous coronary intervention (PCI) is a unique condition to study the effects of ischemia and reperfusion in patients with severe coronary atherosclerosis when coronary vasomotor function is compromised by loss of endothelial and autoregulatory vasodilation. We studied the effects of intracoronary non-selective α-, as well as selective α(1)- and α(2)-blockade in counteracting the observed vasoconstriction in patients with stable and unstable angina and in patients with acute myocardial infarction. Coronary vasoconstriction in our studies was a diffuse phenomenon and involved not only the culprit lesion but also vessels with angiographically not visible plaques. Post-PCI vasoconstriction was reflected by increased coronary vascular resistance and associated with decreased LV-function. α (1)-Blockade with urapidil dilated epicardial coronary arteries, improved coronary flow reserve and counteracted LV dysfunction. Non-selective α-blockade with phentolamine induced epicardial and microvascular dilation, while selective α(2)-blockade with yohimbine had only minor vasodilator and functional effects. Intracoronary α-blockade also attenuated the no-reflow phenomenon following primary PCI. This article is part of a Special Issue entitled "Coronary Blood Flow".


Multiplexed immunofluorescence identifies high stromal CD68+PD-L1+ macrophages as a predictor of improved survival in triple negative breast cancer.
Triple negative breast cancer (TNBC) comprises 10-15% of all breast cancers and has a poor prognosis with a high risk of recurrence within 5 years. PD-L1 is an important biomarker for patient selection for immunotherapy but its cellular expression and co-localization within the tumour immune microenvironment and associated prognostic value is not well defined. We aimed to characterise the phenotypes of immune cells expressing PD-L1 and determine their association with overall survival (OS) and breast cancer-specific survival (BCSS). Using tissue microarrays from a retrospective cohort of TNBC patients from St George Hospital, Sydney (n = 244), multiplexed immunofluorescence (mIF) was used to assess staining for CD3, CD8, CD20, CD68, PD-1, PD-L1, FOXP3 and pan-cytokeratin on the Vectra Polaris™ platform and analysed using QuPath. Cox multivariate analyses showed high CD68+PD-L1+ stromal cell counts were associated with improved prognosis for OS (HR 0.56, 95% CI 0.33-0.95, p = 0.030) and BCSS (HR 0.47, 95% CI 0.25-0.88, p = 0.018) in the whole cohort and in patients receiving chemotherapy, improving incrementally upon the predictive value of PD-L1+ alone for BCSS. These data suggest that CD68+PD-L1+ status can provide clinically useful prognostic information to identify sub-groups of patients with good or poor prognosis and guide treatment decisions in TNBC.


Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer.
KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate histone H3K23 and exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of KAT6A to achieve therapeutic benefit has been a challenge. Here we describe identification of a highly potent, selective, and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from a benzisoxazole series, which demonstrates anti-tumor activity in correlation with H3K23Ac inhibition in KAT6A over-expressing breast cancer. Transcriptional and epigenetic profiling studies show reduced RNA Pol II binding and downregulation of genes involved in estrogen signaling, cell cycle, Myc and stem cell pathways associated with CTx-648 anti-tumor activity in ER-positive (ER+) breast cancer. CTx-648 treatment leads to potent tumor growth inhibition in ER+ breast cancer in vivo models, including models refractory to endocrine therapy, highlighting the potential for targeting KAT6A in ER+ breast cancer.


Development and testing of a prototype reflex measurement system employing artificial neural networks.
This paper presents the development, testing and performance evaluation of a patellar tendon reflex measurement system to provide a quantitative reflex evaluation for use by medical practitioners and in a telemedicine or E-medicine environment. A prototype was developed that makes use of XSens MTx orientation sensors, force-sensitive resistors and an electromyogram to measure the reflex response. Suitable parameters from the sensors were identified for analysis, and clinical testing was performed on 20 subjects to collect data to evaluate the system's performance. Subjective reflex evaluations were conducted by three medical doctors according to a standard reflex grading scale using video recordings of the tests. Multi-layer feed-forward (MLFF) artificial neural networks (ANNs) were used to analyze the collected data with the aim of pattern identification and reflex grading prediction. It was found that the MLFF network delivered the corresponding reflex grading with an accuracy of 85%, which was of the same order as the rate of differences between the subjective reflex evaluations performed by the doctors (80%). The use of ANNs to analyze a reflex measurement offers a repeatable and concise representation of the reflex that is familiar to doctors and can be developed for use in a general clinical setting or for telemedicine purposes.


The respiratory syncytial virus polymerase can perform RNA synthesis with modified primers and nucleotide analogs.
Respiratory syncytial virus (RSV) is significant for public health, capable of causing respiratory tract disease in infants, the elderly and the immunocompromised. The RSV polymerase is an attractive target for antiviral drug development, but as yet, there is no high throughput assay for analyzing RSV polymerase activity, specifically. In this study, using a primer elongation assay as a basis, we analyzed the tolerance of the RSV polymerase for modifications at the 5' end of the primer, and nucleotide analogs. The RSV polymerase was found to accept primers containing 5' biotin or digoxygenin modifications, and nucleotide analogs that are reactive or fluorescent, including 5-ethynyl UTP, 8-azido ATP, 2-amino PTP, and thieno-GTP. These findings provide a menu of options for developing non-isotopic high throughput assays for RSV polymerase RNA synthesis activity, and yield insight regarding the molecular biology of the polymerase complex.


Cortico-subthalamic connection predicts individual differences in value-driven choice bias.
It has been suggested that a connection between the STN and value-sensitive areas of the prefrontal cortex might mediate value-based actions in perceptual decision making. In this study, we first seek to quantify a structural connection between the STN and a cortical region that was associated with mechanisms underlying bias in choice behavior (vmPFC). Next, we tested whether individual differences in the probabilistic tract-strength of this connection were predictive for individual differences in the magnitude of bias in a perceptual decision-making task. Probabilistic tractography was used to measure the tract-strength between the STN and the vmPFC. Bias was quantified using an accumulation-to-bound model where a shift in the starting point of the accumulation of sensory evidence causes faster and more choices for an alternative that is more likely or more valuable. Results show that vmPFC is structurally connected with the STN and that the strength of this connection is predictive for choice bias towards an alternative that is more valuable, but not for choice bias towards an alternative that is more likely. These findings confirm the involvement of the cortico-subthalamic circuit in mechanisms underlying value-based actions in perceptual decision making.


Regulatory responses of arginine deiminase in whole cells of Clostridium sporogenes.
Arginine deiminase (EC 18.104.22.168) has been shown to have regulatory properties. The activity was observed to be sigmoidal with respect to substrate concentrations. Addition of histidine to the system caused the abolition of sigmoidal responses. The regulatory properties of the enzyme as well as the desensitising action of histidine could also be demonstrated with whole cell suspensions. The pH of the system also seemed to influence modulations in the enzyme.


Two-Layer numerical model of soil moisture dynamics: Model assessment and Bayesian uncertainty estimation.
A two-layer model based on the integrated form of Richards' equation (RE) was recently developed to simulate the soil water movement in the roots layer and the vadose zone with a relatively shallow and dynamic water table. The model simulates thickness-averaged volumetric water content and matric suction as opposed to point values and was numerically verified for three soil textures using HYDRUS as a benchmark. However, the strengths and limitations of the two-layer model and its performance in stratified soils and under actual field conditions have not been tested. This study further examined the two-layer model using two numerical verification experiments and, most importantly, tested its performance at site-level under actual, highly variable hydroclimate conditions. Moreover, model parameters were estimated and uncertainty and sources of errors were quantified using a Bayesian framework. First, the two-layer model was evaluated for 231 soil textures under varying soil layer thicknesses with a uniform soil profile. Second, the two-layer model was assessed for stratified conditions where the top and bottom soil layers have contrasting hydraulic conductivities. The model was evaluated by comparing soil moisture and flux estimates to those from the HYDRUS model. Last, a case study of model application using data from a Soil Climate Analysis Network (SCAN) site was presented. Bayesian Monte Carlo (BMC) method was implemented for model calibration and quantifying sources of uncertainty under real hydroclimate and soil conditions. For a homogeneous soil profile, the two-layer model generally had excellent performance in estimating volumetric water content and fluxes, while the model performance slightly declined with increasing layer thickness and coarser textured soils. The model configurations regarding layer thicknesses and soil textures that generate accurate soil moisture and flux estimations were further suggested. With the two layers of contrasting permeability, model-simulated soil moisture contents and fluxes agreed well with those computed by HYDRUS, indicating that the two-layer model accurately handles the water flow dynamics around the layer interface. In the field application, given the highly variable hydroclimate conditions, the two-layer model combined with the BMC method showed good agreement with the observed average soil moisture of the root zone and the vadose zone below (RMSE <0.021 during calibration and <0.023 during validation periods). The contribution of parametric uncertainty to the total model uncertainty was too small compared to other sources. The numerical tests and the site level application showed that the two-layer model can reliably simulate thickness-averaged soil moisture and estimate fluxes in the vadose zone under various soil and hydroclimate conditions. Results also indicated that the BMC method could be a robust framework for vadose zone hydraulic parameters identification and model uncertainty estimation.


Detection of metronidazole resistance in Trichomonas vaginalis using uncultured vaginal swabs.
Trichomonas vaginalis (T. vaginalis) is the most prevalent sexually transmitted infection (STI) globally. Metronidazole is the drug of choice for treating T. vaginalis infections although metronidazole-resistant T. vaginalis has been reported in clinical isolates. The purpose of this study was to determine the presence of mutations in nitroreductase genes associated with metronidazole resistance in vaginal swabs testing positive for T. vaginalis. This study included 385 human immunodeficiency virus (HIV)-positive pregnant women. Vaginal swabs were collected from consenting pregnant women and used for the detection of T. vaginalis using the TaqMan assay. From the vaginal swabs, nitroreductase genes ntr4 and ntr6 containing mutations associated with metronidazole resistance were amplified using a quantitative polymerase chain reaction (PCR) assay. To validate the PCR assay, T. vaginalis cultured isolates with known metronidazole resistance profiles were used as controls in the mutation detection assays. The prevalence of T. vaginalis in the study population was 12.2% (47/385). Mutations associated with resistance to metronidazole were detected in more than 40% of the samples tested, i.e. 21/47 (45%) and 24/47 (51%) for ntr4 and ntr6, respectively. A total of 19 samples (40%) carried mutations for both ntr4 and ntr6 genes associated with metronidazole resistance. The validation assays showed a positive correlation between phenotypic and genotypic resistance profiles. This study found a high prevalence of mutations associated with metronidazole resistance. This is concerning since metronidazole is currently used in the syndromic management of STIs in South Africa. Molecular-based assays for monitoring metronidazole resistance profiles using nitroreductase genes may serve as a feasible method for antimicrobial surveillance studies for T. vaginalis.


What is the role of the physical medicine and rehabilitation unit after total knee arthroplasty? Clinical practice recommendations.
To develop clinical practice guidelines concerning the interest of post-operative rehabilitation in physical medicine and functional rehabilitation (PMR) ward after total knee arthroplasty (TKA). The SOFMER (French Physical Medicine and Rehabilitation Society) methodology, associating a systematic literature review, collection of everyday clinical practice, and external review by a multidisciplinary expert panel, was used. Main outcomes were impairment, disability, medico-economic implications and postoperative complications. Post-operative rehabilitation in a PMR ward after TKA is recommended for patients because of preoperative joint stiffness, and/or associated co-morbidities. The other parameters used by French physician for post-operative rehabilitation in a PMR ward after TKA are: the self-governing of the patient at home, the wishes of the patient and the opinion of the surgeon on the post-operative functional evolution of the patients. For patients in whom sustained rehabilitation is not necessary but who cannot return home, a stay in a non-specific (non-PMR) post-operative centre could be recommended. Post-operative rehabilitation in a PMR ward after TKA could reduce the length of stay in a surgical ward and increase the functional status of patients with co-morbidities. Studies with good methodological quality are needed to evaluate the cost/benefit ratio in the French health care system. This study suggests a value of rehabilitation in a PMR ward after TKA, but good methodological quality studies are needed to evaluate the cost/benefit ratio of rehabilitation in a PMR ward after TKA in the French health care system.


Treatment access for opioid use disorder in pregnancy among rural and American Indian communities.
Opioid use disorder (OUD) in pregnancy disproportionately impacts rural and American Indian (AI) communities. With limited data available about access to care for these populations, this study's objective was to assess clinic knowledge and new patient access for OUD treatment in three rural U.S. counties. The research team used unannounced standardized patients (USPs) to request new patient appointments by phone for white and AI pregnant individuals with OUD at primary care and OB/GYN clinics that provide prenatal care in three rural Utah counties. We assessed a) clinic familiarity with buprenorphine for OUD; b) appointment availability for buprenorphine treatment; c) appointment wait times; d) referral provision when care was unavailable; and e) availability of OUD care at referral locations. We compared outcomes for AI and white USP profiles using descriptive statistics. The USPs made 34 calls to 17 clinics, including 4 with publicly listed buprenorphine prescribers on the Substance Abuse and Mental Health Services Administration website. Among clinical staff answering calls, 16 (47%) were unfamiliar with buprenorphine. OUD treatment was offered when requested in 6 calls (17.6%), with a median appointment wait time of 2.5 days (IQR 1-5). Among clinics with a listed buprenorphine prescriber, 2 of 4 (50%) offered OUD treatment. Most clinics (n = 24/28, 85.7%) not offering OUD treatment provided a referral; however, a buprenorphine provider was unavailable/unreachable 67% of the time. The study observed no differences in appointment availability between AI and white individuals. Rural-dwelling AI and white pregnant individuals with OUD experience significant barriers to accessing care. Improving OUD knowledge and referral practices among rural clinics may increase access to care for this high-risk population.


PHLDA1 is a P53 target gene involved in P53-mediated cell apoptosis.
Pleckstrin homeolike domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays diverse roles in A variety of biological processes, including cell death, and hence its altered expression has been found in different types of cancer. Although studies have shown a regulatory relationship between p53 and PHLDA1, the molecular mechanism is still unclear. Especially, the role of PHLDA1 in the process of apoptosis is still controversial. In this study, we found that the expression of PHLDA1 in human cervical cancer cell lines was correlated with the up-expression of p53 after treatment with apoptosis-inducing factors. Subsequently, the binding site and the binding effect of p53 on the promoter region of PHLDA1 were verified by our bioinformatics data analysis and luciferase reporter assay. Indeed, we used CRISPR-Cas9 to knockout the p53 gene in HeLa cells and further confirmed that p53 can bind to the promoter region of PHLDA1 gene, and then directly regulate the expression of PHLDA1 by recruiting P300 and CBP to change the acetylation and methylation levels in the promoter region. Finally, a series of gain-of-function experiments further confirmed that p53 re-expression in HeLap53-/- cell can up-regulate the reduction of PHLDA1 caused by p53 knockout, and affect cell apoptosis and proliferation. Our study is the first to explore the regulatory mechanism of p53 on PHLDA1 by using the p53 gene knockout cell model, which further proves that PHLDA1 is a target-gene in p53-mediated apoptosis, and reveals the important role of PHLDA1 in cell fate determination.


Coronin 2A (CRN5) expression is associated with colorectal adenoma-adenocarcinoma sequence and oncogenic signalling.
Coronin proteins are known as regulators of actin-based cellular processes, and some of them are associated with the malignant progression of human cancer. Here, we show that expression of coronin 2A is up-regulated in human colon carcinoma. This study included 26 human colon tumour specimens and 9 normal controls. Expression and localisation of coronin 2A was studied by immunohistochemistry, immunofluorescence imaging, cell fractionation, and immunoblotting. Functional roles of coronin 2A were analysed by over-expression and knock-down of the protein. Protein interactions were studied by co-immunoprecipitation and pull-down experiments, mass spectrometry analyses, and in vitro kinase and methylation assays. Histopathological investigation revealed that the expression of coronin 2A in colon tumour cells is up-regulated during the adenoma-adenocarcinoma progression. At the subcellular level, coronin 2A localised to multiple compartments, i.e. F-actin stress fibres, the front of lamellipodia, focal adhesions, and the nuclei. Over-expression of coronin 2A led to a reduction of F-actin stress fibres and elevated cell migration velocity. We identified two novel direct coronin 2A interaction partners. The interaction of coronin 2A with MAPK14 (mitogen activated protein kinase 14 or MAP kinase p38α) led to phosphorylation of coronin 2A and also to activation of the MAPK14 pathway. Moreover, coronin 2A interacted with PRMT5 (protein arginine N-methyltransferase 5), which modulates the sensitivity of tumour cells to TRAIL-induced cell death. We show that increased expression of coronin 2A is associated with the malignant phenotype of human colon carcinoma. Moreover, we linked coronin 2A to MAPK14 and PRMT5 signalling pathways involved in tumour progression.


A rare case of floating fifth metacarpal and review of literature.
Floating metacarpal is a rare concurrent bipolar dislocation of metacarpal at both ends. Isolated dislocations of Carpo-metacarpal (CMC) or Metacarpo-phalangeal (MCP) have been previously reported, simultaneous dislocations of both joints is scarcely reported in literature and bares high chance of diagnosis being missed on presentation. A 29-year-old male presented with pain, swelling in left hand and loss of movement in fifth and fourth finger following a motorcycle fall injury. Radiography showed floating metacarpal of fifth ray along with fracture dislocation of at base of fourth metacarpal. The patient was diagnosed with floating fifth metacarpal along with fracture dislocation at base of fourth metacarpal. Open reduction and K-wire fixation was performed across CMC for fifth and fourth metacarpal along with MCP fixation for fifth metacarpal joint. The patient had excellent outcome after one year with normal Range of motion and grip. Early recognition and prompt management of these injuries are considered as hallmark of prognosis. Ideal treatment for such dislocation is controversial. However, we have noted from earlier case reports that with acute dislocation and minimal swelling closed reduction and cast immobilization could be sufficient. In case of delayed presentation or swelling along with fracture, open reduction is favorable choice of treatment.


The impact of PLGA scaffold orientation on in vitro cartilage regeneration.
The success of in vitro cartilage regeneration provides a promising approach for cartilage repair. However, the currently engineered cartilage in vitro is unsatisfactory for clinical application due to non-homogeneous structure, inadequate thickness, and poor mechanical property. It has been widely reported that orientation of scaffolds can promote cell migration and thus probably contributes to improving tissue regeneration. This study explored the impact of microtubular oriented scaffold on in vitro cartilage regeneration. Porcine articular chondrocytes were seeded into microtubule-oriented PLGA scaffolds and non-oriented scaffolds respectively. A long-term in vitro culture followed by a long-term in vivo implantation was performed to evaluate the influence of scaffold orientation on cartilage regeneration. The current results showed that the oriented scaffolds could efficiently promote cell migration towards the inner region of the constructs. After 12 weeks of in vitro culture, the chondrocyte-scaffold constructs in the oriented group formed thicker cartilage with more homogeneous structure, stronger mechanical property, and higher cartilage matrix content compared to the non-oriented group. Furthermore, the in vitro engineered cartilage based on oriented scaffolds showed better cartilage formation in terms of size, wet weight, and homogeneity after 12-week in vivo implantation in nude mice. These results indicated that the longitudinal microtubular orientation of scaffolds can efficiently improve the structure and function of in vitro engineered cartilage.


Data assimilation and agent-based modelling: towards the incorporation of categorical agent parameters.
This paper explores the use of a particle filter-a data assimilation method-to incorporate real-time data into an agent-based model. We apply the method to a simulation of real pedestrians moving through the concourse of Grand Central Terminal in New York City (USA). The results show that the particle filter does not perform well due to (i) the unpredictable behaviour of some pedestrians and (ii) because the filter does not optimise the categorical agent parameters that are characteristic of this type of model. This problem only arises because the experiments use real-world pedestrian movement data, rather than simulated, hypothetical data, as is more common. We point to a potential solution that involves resampling some of the variables in a particle, such as the locations of the agents in space, but keeps other variables such as the agents' choice of destination. This research illustrates the importance of including real-world data and provides a proof of concept for the application of an improved particle filter to an agent-based model. The obstacles and solutions discussed have important implications for future work that is focused on building large-scale real-time agent-based models.


[Clinical research in hand surgery: the problem and value of retrospective studies].
Retrospective studies are still very important in clinical decision making although they present severe methodological deficiencies compared to controlled trials. Imprecise and incomplete data gathering, lack of homogeneity in the group studied, and lack of randomisation are the main drawbacks. Indications for retrospective studies and criteria for their execution are presented.


Restless legs syndrome in Parkinson's disease.
Recent clinical and functional imaging data suggest impaired central dopaminergic transmission in restless legs syndrome (RLS). As RLS responds to dopaminergic medications, an etiologic link between RLS and Parkinson's disease (PD) has been proposed. However, few studies have examined this association. To investigate the prevalence of RLS amongst PD outpatient population. The prevalence of RLS was determined by the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG). Consecutive PD patients (n=125) were prospectively evaluated in our clinic. There were 77 (61.6%) males and 48 (38.4%) females with a mean age of 65.1+/-9.3 (SD) years (range 34-83), and mean age of onset of disease at 59.6 years+/-10.7 (SD) years (range 30-81). Nineteen (15.2%) patients had motor restlessness. Of these, one (0.8%) patient had RLS-like symptoms closely correlated to wearing "off" effect of levodopa. None of the patients satisfied the IRLSSG diagnostic criteria of RLS. This was not significantly different compared to the 0.6% and 0.1% RLS prevalence in our general population and clinic population. Our study demonstrates that motor restlessness was present in 15.2% of our PD patients. However, prevalence of RLS in our PD patients was not significantly different from our general population or clinic population, suggesting that these two diseases may not share the same pathophysiologic mechanism.


Neurostimulation as a Putative Method for the Treatment of Drug-resistant Epilepsy in Patient and Animal Models of Epilepsy.
A patient with epilepsy was shown to have neurobiological, psychological, cognitive, and social issues as a result of recurring seizures, which is regarded as a chronic brain disease. However, despite numerous drug treatments, approximately, 30%-40% of all patients are resistant to antiepileptic drugs. Therefore, newer therapeutic modalities are introduced into clinical practice which involve neurostimulation and direct stimulation of the brain. Hence, we review published literature on vagus nerve stimulation, trigeminal nerve stimulation, applying responsive stimulation systems, and deep brain stimulation (DBS) in animals and epileptic patient with an emphasis on drug-resistant epilepsy.


Myoplasmic binding of fura-2 investigated by steady-state fluorescence and absorbance measurements.
Binding of the fluorescent Ca2+ indicator dye fura-2 by intracellular constituents has been investigated by steady-state optical measurements. Fura-2's (a) fluorescence intensity, (b) fluorescence emission anisotropy, (c) fluorescence emission spectrum, and (d) absorbance spectra were measured in glass capillary tubes containing solutions of purified myoplasmic proteins; properties b and c were also measured in frog skeletal muscle fibers microinjected with fura-2. The results indicate that more than half, and possibly as much as 85%, of fura-2 molecules in myoplasm are in a protein-bound form, and that the binding changes many properties of the dye. For example, in vitro characterization of the Ca2+-dye reaction indicates that when fura-2 is bound to aldolase (a large and abundant myoplasmic protein), the dissociation constant of the dye for Ca2+ is three- to fourfold larger than that measured in the absence of protein. The problems raised by intracellular binding of fura-2 to cytoplasmic proteins may well apply to cells other than skeletal muscle fibers.


Three phase II cytokine working group trials of gp100 (210M) peptide plus high-dose interleukin-2 in patients with HLA-A2-positive advanced melanoma.
High-dose interleukin-2 (IL-2) induces responses in 15% to 20% of patients with advanced melanoma; 5% to 8% are durable complete responses (CRs). The HLA-A2-restricted, modified gp100 peptide (210M) induces T-cell immunity in vivo and has little antitumor activity but, combined with high-dose IL-2, reportedly has a 42% (13 of 31 patients) response rate (RR). We evaluated 210M with one of three different IL-2 schedules to determine whether a basis exists for a phase III trial. In three separate phase II trials, patients with melanoma received 210M subcutaneously during weeks 1, 4, 7, and 10 and standard high-dose IL-2 during weeks 1 and 3 (trial 1), weeks 7 and 9 (trial 2), or weeks 1, 4, 7, and 10 (trial 3). Immune assays were performed on peripheral-blood mononuclear cells collected before and after treatment. From 1998 to 2003, 131 patients with HLA-A2-positive were enrolled. With 60-month median follow-up time, the overall RR for 121 assessable patients was 16.5% (95% CI, 10% to 26%); the RRs were 23.8% in trial 1 (42 patients), 12.5% in trial 2 (40 patients), and 12.8% in trial 3 (39 patients). There were 11 CRs (9%) and nine partial responses (7%), with 11 patients (9%) progression free at >or= 30 months. Immune studies including assays of CD3-zeta expression and numbers of CD4(+)/CD25(+)/FoxP3(+) regulatory T cells, CD15(+)/CD11b(+)/CD14(-) immature myeloid-derived cells, and CD8(+)gp100 tetramer-positive cells in the blood did not correlate with clinical benefit. The results again demonstrate efficacy of high-dose IL-2 in advanced melanoma but did not demonstrate the promising clinical activity reported with vaccine and high-dose IL-2 in any of three phase II trials.


Spectrofluorometric study of iron removal from bovine lactoferrin by ethylenediamminetetraacetic acid.
The kinetics of iron removal from the two metal binding sites of the bovine lactoferrin by ethylenediaminetetraacetic acid (EDTA) was investigated at pH 7.5 and 33°C. Solutions were buffered at pH 7.5 by 0.15 M Tris-HCl. Pseudo first-order rate constants as a function of ligand concentration were measured for iron removal from diferric lactoferrin and from N- and C-terminal monoferric lactoferrin. Diferric lactoferrin showed simple saturation behavior while both the monoferric forms showed a two-term dependence of kobs on ligand concentration that signifies two pathways for iron removal under the conditions applied. Moreover, the results show that the N-terminal site is more labile towards iron removal by EDTA than the C-terminal site.


Sleep disorder symptoms among nurses and nursing aides.
Nurses and nursing aides (n = 418) currently working on a regular evening or day schedule were compared in terms of sleep disorder symptoms. The relationship between past nightwork and sleep disorder symptoms was also assessed. The prevalence of individual symptoms varied from 6 to 53%. Evening workers showed a pattern of sleep disorder compatible with sleep deprivation, whereas the pattern for day workers was more compatible with insomnia. Past nightwork was significantly associated with symptoms of day tiredness and the quantity of sleep obtained was influenced by past nightwork. The prevalence of a combination of four insomnia symptoms (initial, intermittent, and terminal insomnia and fatigue during the day) was 5.4% among current day workers but no cases were identified among evening workers. Among day workers, the trend for insomnia across levels of duration of past nightwork fell slightly short of conventional statistical significance (P = 0.09). The relationship between a combination of four symptoms was neither modified nor confounded by variables such as age, chronotype, intensity of past nightwork, and latency. In conclusion, although some sleep symptoms were associated with nightwork, a clear residual effect on a combination of symptoms could not be shown.


Optimal Criteria Survey for Preresuscitation Delivery Room Checklists.
To investigate the optimal format and content of delivery room reminder tools, such as checklists. Voluntary, anonymous web-based surveys on checklists and reminder tools for neonatal resuscitation were sent to clinicians at participating hospitals. Summary statistics including the mean and standard deviation of the survey items were calculated. Several key comparisons between groups were completed using Student t-test. Fifteen hospitals were surveyed and 299 responses were collected. Almost all (96%) respondents favored some form of a reminder tool. Specific reminders such as "check and prepare all equipment" (mean 3.69, SD 0.81) were ranked higher than general reminders and personnel reminders such as "introduction and assigning roles" (mean 3.23, SD 1.08). Rankings varied by profession, institution, and deliveries attended per month. Clinicians perceive a benefit of a checklist for neonatal resuscitation in the delivery room. Preparation of equipment was perceived as the most important use for checklists.


Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa.
The outer membrane of Gram-negative bacteria functions as an impermeable barrier to foreign compounds. Thus, modulating membrane transport can contribute to improving susceptibility to antibiotics and efficiency of bioproduction reactions. In this study, the cellular uptake of hydrophobic and large-scaffold antibiotics and other compounds in Gram-negative bacteria was investigated by modulating the homolog expression of bamB encoding an outer membrane lipoprotein and tolC encoding an outer membrane efflux protein via gene deletion and gene silencing. The potential of deletion mutants for biotechnological applications, such as drug screening and bioproduction, was also demonstrated. Instead of being subjected to gene deletion, wild-type bacterial cells were treated with cell-penetrating peptide conjugates of a peptide nucleic acid (CPP-PNA) against bamB and tolC homologs as antisense agents. Results revealed that the single deletion of bamB and tolC in Escherichia coli increased the uptake of large- and small-scaffold hydrophobic compounds, respectively. A bamB-and-tolC double deletion mutant had a higher uptake efficiency for certain antibiotics and other compounds with high hydrophobicity than each single deletion mutant. The CPP-PNA treated E. coli and Pseudomonas aeruginosa cells showed high sensitivity to various antibiotics. Therefore, these gene deletion and silencing approaches can be utilized in therapeutic and biotechnological fields.


Slowly exchanging calcium binding sites unique to cardiac/slow muscle troponin C.
Evidence is presented for the existence of slowly exchanging Ca2(+)-binding sites in troponin C (CTNC) of cardiac and slow twitch skeletal muscles. These sites were revealed in the course of experiments aimed at measuring the Ca2(+)-binding properties of TNC in the myofilament lattice. 45Ca bound to chemically skinned muscle fibers or myofibrils of cardiac and soleus muscles was eluted by EGTA in a two-exponential timecourse with a slow phase of a rate constant of about 2 x 10(-4)/s. The slow phase was not found in skinned fiber or myofibrils of psoas, a fast skeletal muscle. However, skinned psoas fibers in which the native TNC was replaced by CTNC exhibited the slow 45Ca elution characteristic of soleus and cardiac preparations, indicating that the slowly-exchanging sites are located in CTNC. These sites are tentatively identified as the Ca2(+)-Mg2+ sites of CTNC on the basis that the slow phase was observed under conditions known to restrict Ca2+ binding to the Ca2(+)-Mg2+ sites.


Neural representations of honesty predict future trust behavior.
Theoretical accounts propose honesty as a central determinant of trustworthiness impressions and trusting behavior. However, behavioral and neural evidence on the relationships between honesty and trust is missing. Here, combining a novel paradigm that successfully induces trustworthiness impressions with functional MRI and multivariate analyses, we demonstrate that honesty-based trustworthiness is represented in the posterior cingulate cortex, dorsolateral prefrontal cortex and intraparietal sulcus. Crucially, brain signals in these regions predict individual trust in a subsequent social interaction with the same partner. Honesty recruited the ventromedial prefrontal cortex (VMPFC), and stronger functional connectivity between the VMPFC and temporoparietal junction during honesty encoding was associated with higher trust in the subsequent interaction. These results suggest that honesty signals in the VMPFC are integrated into trustworthiness beliefs to inform present and future social behaviors. These findings improve our understanding of the neural representations of an individual's social character that guide behaviors during interpersonal interactions.


Organizational framework for health information technology.
We do not yet know how best to design, implement, and use health information technology (IT). A comprehensive framework that captures knowledge on the implementation, use, and optimization of health IT will help guide more effective approaches in the future. The authors conducted a targeted review of existing literature on health IT implementation and use, including health IT-related theories and models. By crosswalking elements of current theories and models, the authors identified five major facets of an organizational framework that provides a structure to organize and capture information on the implementation and use of health IT. The authors propose a novel organizational framework for health IT implementation and use with five major facets: technology, use, environment, outcomes, and temporality. Each major facet is described in detail along with associated categories and measures. The proposed framework is an essential first step toward ensuring a more consistent and comprehensive understanding of health IT implementation and use and a more rigorous approach to data collection, measurement development, and theory building.


Crystal Structure of the Catalytic Domain of a Botulinum Neurotoxin Homologue from Enterococcus faecium: Potential Insights into Substrate Recognition.
Clostridium botulinum neurotoxins (BoNTs) are the most potent toxins known, causing the deadly disease botulism. They function through Zn2+-dependent endopeptidase cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, preventing vesicular fusion and subsequent neurotransmitter release from motor neurons. Several serotypes of BoNTs produced by Clostridium botulinum (BoNT/A-/G and/X) have been well-characterised over the years. However, a BoNT-like gene (homologue of BoNT) was recently identified in the non-clostridial species, Enterococcus faecium, which is the leading cause of hospital-acquired multi-drug resistant infections. Here, we report the crystal structure of the catalytic domain of a BoNT homologue from Enterococcus faecium (LC/En) at 2.0 Å resolution. Detailed structural analysis in comparison with the full-length BoNT/En AlphaFold2-predicted structure, LC/A (from BoNT/A), and LC/F (from BoNT/F) revealed putative subsites and exosites (including loops 1-5) involved in recognition of LC/En substrates. LC/En also appears to possess a conserved autoproteolytic cleavage site whose function is yet to be established.


Thrombotic complications and anticoagulation in COVID-19 pneumonia: a New York City hospital experience.
Infection with SARS-CoV-2 (COVID-19) can cause prothrombotic complications. We aim to study the frequency of thrombotic complications and impact of anticoagulation on outcomes in hospitalized patients. We conducted a retrospective chart review of 921 consecutive patients admitted to our hospital with COVID-19. Patients were divided into four groups depending on whether they were on anticoagulation prior to admission, started anticoagulation during the admission, received prophylactic anticoagulation, or did not receive any anticoagulation. At the time of analysis, 325 patients (35.3%) had died, while 544 patients (59%) had been discharged resulting in inpatient mortality of 37.3%. Male sex, age > 65 years, and high D-dimer at admission were associated with higher mortality. Sixteen patients (1.7%) had venous thromboembolism confirmed with imaging, 11 patients had a stroke, and 2 patients developed limb ischemia. Treatment with therapeutic anticoagulation was associated with improved inpatient mortality compared with prophylactic anticoagulation alone (63% vs 86.2%, p < 0.0001) in patients requiring mechanical ventilation. Other outcomes such as rates of liberation from mechanical ventilation and duration of mechanical ventilation were not significantly impacted by the type of anticoagulation.


[Kinematic alignment-management of deformities and flexion contractures].
Kinematic alignment (KA) total knee arthroplasty (TKA) has proven to be a viable alternative to mechanical alignment (MA) TKA. Like any technique, its validity has to encounter challenges. Two of these are flexion contracture and large deformities of the knee. Flexion contracture is commonly treated with posterior capsular release. Often, however, this technique is not sufficient. Many surgeons accustomed to MA techniques and guided by traditional femoral instruments manage the problem by proximalizing the distal femoral cut. However, this has proven to be a surgical mistake that often leads to mid-flex knee instability. KA rules limit this mistake but leave the problem of flexion contracture. In these cases, the surgeon acts on the tibia distalizing the cut and, so as not to create instability in flexion, decreasing the slope. The technique is effective to obtain full extension but often leaves instability at 90° of knee flexion. To avoid this, it is useful to use the so-called "virtuous mistake" strategy, which strictly follows the KA guidelines but undercuts the posterior femoral condyles by 2 mm. Another problem that often limits the use of KA is large deformities. It is necessary to distinguish whether they are intra or extra-articular. In the first case, it is possible to decide whether to use the pure KA technique or to restrict the indication at the level of the tibial cut. In the latter, extraarticular osteotomies or combined procedures (osteotomy plus KA) have to be performed.


Investigation of the risk factors of anorectal malformations.
To investigate the factors that influence the occurrence of anorectal malformations (ARMs). From December 2018 to December 2019, 136 children treated for ARMs at the Children's Hospital of Chongqing Medical University were included in the case group. The control group consisted of children with intussusception or perianal abscesses. A uniform questionnaire was filled by the parents of the enrolled children. The birth weight of the cases was significantly lower than that of the controls (p < .01), and children with ARMs were more likely to be complicated with single umbilical artery (SUA) (p < .001). Maternal upper respiratory tract infection (adjusted odds ratio [ORadj ], 2.44; 95% confidence interval [CI], 1.29-4.63) and urogenital infection (ORadj , 2.67; 95% CI 1.11-6.38) during the first trimester of pregnancy, anemia during pregnancy (ORadj , 5.69; 95% CI, 1.01-32.07), and exposure to hazardous substances 6 months before pregnancy and during the first trimester of pregnancy (ORadj , 13.82; 95% CI, 3.86-49.35) are associated with increased risk of ARMs. Folic acid supplements (ORadj , 0.31; 95% CI, 0.14-0.65) and multivitamin (ORadj , 0.34; 95% CI, 0.15-0.79) had a protective effect on ARMs. Paternal drug use (ORadj , 9.17; 95% CI, 2.19-38.49) 6 months before their wives' conception increased the risk of ARMs. Maternal infection, anemia during pregnancy, and maternal hazardous substances exposure are possible risk factors for ARMs. Folic acid supplements and multivitamin can reduce the occurrence of ARMs. Meanwhile, paternal drug use may also be a risk factor for ARMs.


Long-term outcomes of upper tract urothelial carcinoma: A retrospective evaluation of single-center experience in 275 patients.
We aimed to report our 25-year experience on upper tract urothelial carcinoma (UTUC) on a larger number of patients with long-term follow-up at a single tertiary urology institute. A retrospective study was conducted on 275 patients from 1990 to 2015. Basic patient demographic data with the laboratory and radiologic investigations were collected. We used 1997 TNM classification and the three-tiered WHO grading system. Data were collected using an SPSS® version 21 spreadsheet. The mean age was 59±11 years, and 88% of all the patients were male. Previous and concurrent bladder tumors were found in 16% and 26%, respectively. Computed tomography gave an overall accuracy of 96%. Open nephroureterectomy and bladder cuff excision was performed for 85%, and the remaining by laparoscopy and nephron-sparing surgeries. Tumor was pelvicalyceal, ureteric, and both in 40%, 40%, and 20% respectively. In 97% of the patients, the tumor was transitional cell carcinoma. Nearly two-thirds of the patients were of low grade and non-invasive in stage. Nearly half of the patients (46%) had bladder tumor recurrence after NU. Bladder, urethral, and contralateral recurrence, distant, local metastasis occurred in 46%, 2%, 1%, 7.5%, and 6%, respectively. UTUC is a unique disease with synchronous and metachronous urothelial tumor recurrence that requires long-term surveillance. The majority (two-thirds) of the patients are non-invasive in stage of grade II. Tumor stage is of paramount prognostic significance for survival; the five-year survival rate of T1 and T4 is 80% and 0%, respectively.


Structural determinants of regulated proteolysis in pathogenic bacteria by ClpP and the proteasome.
Bacteria use gated proteolytic machines for routine protein quality control and regulated responses to environmental conditions. This review discusses recent advances in understanding the structure and regulation of ClpP proteases, nanomachines widely distributed across bacteria, and the bacterial proteasome, a protease found in relatively few species. For both machines, activators confer substrate specificity. We highlight new data from organisms encoding two ClpP isoforms and the central role of activators as platforms for integrating regulatory signals. Because proteolytic systems contribute to survival and virulence of many bacterial pathogens, understanding their forms and functions enables new approaches to design targeted therapeutics.


Less is More: A Shortcut for Anionocages Design Based on (RPO3 2- )-Monourea Coordination.
Anionocages have been developed as a unique family of hydrogen bonded cages. However, strategies for constructing anionocages are mainly limited to that based on (PO4 3- )-bisurea coordination, neither the ligands nor the anions lack the simplicity and diversity of the maturely developed analogues based on metal coordination (i.e. metallocage). We report herein a more simple strategy for anionocages design based on (RPO3 2- )-monourea coordination, utilizing monourea rather than bisurea as the hydrogen binding donor, and RPO3 2- rather than PO4 3- as the acceptor. Two fluorescent, quadruple helicate anionocages were constructed by a bis-monourea ligand, and dianions PhOPO3 2- (H1 ) or HOPO3 2- (H1A ), respectively, which were capable of encapsulating a series of cation guests. As revealed by molecular modeling, H1 features remarkable guest-adaptive cavity breathing without change of the quadruple helicate topology, which allowed the encapsulation of different sized guests in an "induced fit" manner.


The impairment of the deep vascular complex in prolonged type 2 diabetes patients without clinical diabetic retinopathy.
To identify the effects of prolonged type 2 diabetes (T2DM) on the retinal microvasculature of each retinal capillary plexus in patients without clinical diabetic retinopathy (DR). Subjects were divided into three groups: the control group (98 eyes), patients with T2DM < 10 years (DM group 1, 84 eyes), and patients with T2DM ≥ 10 years (DM group 2, 55 eyes). The vessel densities (VD) of the superficial and deep capillary plexus (SCP and DCP) were compared. Linear regression analyses were performed to identify factors associated with the VD. The mean VDs of the SCP in the control group, DM group 1, and DM group 2 were 35.9 ± 4.2, 34.9 ± 3.9, and 34.6 ± 5.1, respectively (P = 0.042). The mean VDs of the DCP in the three groups were 36.1 ± 3.1, 35.9 ± 3.0, and 34.0 ± 3.3, respectively (P < 0.001). In multivariate analyses, the BCVA was a significant factor associated with both the superficial VD (B = -7.10, P = 0.019) and deep VD (B = -5.70, P = 0.039). Hypertension (B = -1.22, P = 0.021) and DM duration (B = -0.20, P < 0.001) were significant factors associated with deep VD. T2DM patients without DR showed decreased VD in the SCP and DCP. The microvascular impairment of the DCP in patients with T2DM ≥ 10 years was in particular, more severe. Additionally, ischemia caused by hypertension and accumulated impairment of microvasculature due to prolonged T2DM would affect the DCP.


Induction of allergic neuritis in rhesus monkeys.
Experimental allergic neuritis (EAN) was induced in rhesus monkey (Macaca mulatta) following sensitization with rabbit nerve (PNS) myelin in complete Freund's adjuvant (CFA) or with bovine P2 protein complexed with phosphatidyl serine (P2-lipid) in CFA. The response of monkeys receiving PNS myelin in CFA differed from the previous studies where monkeys developed clinical signs of fatal EAN within 15-20 days following sensitization. The monkeys in this study (6) showed a much longer delay (40-114 days) before the appearance of severe clinical signs, and 4 of the 6 animals survived without further attack (1 year). Monkeys (4) injected with P2-lipid (2:1 ratio; w/w) developed severe clinical signs of EAN which was fetal in 3 cases. Peripheral lymphocytes from monkeys sensitized to the P2-lipid showed a much stronger mitogeneic response to P2 protein than those from the PNS myelin-sensitized monkeys. on quantitation of the circulating anti-P2 antibodies, the P2-sensitized monkeys generally had much titers than those sensitized with PNS myelin.


Intrapartum electrocardiogram alteration in fetuses with congenital heart disease: a case-control study.
To assess if the fetal electrocardiogram especially ST segment is modified by congenital heart diseases: modifications in frequencies of the different ST events and modifications in signal quality. A retrospective case-control study, comparing frequencies of the different ST events and the quality of the signal between fetuses with congenital heart diseases and fetuses without congenital heart disease. From 2000 to 2011, fifty-eight fetuses with congenital heart disease had their heart rate recording using a STAN device during labor. Control group was fetuses who were born just before a case and had a STAN as a second line for intrapartum surveillance. Cases and controls were matched on parity, gestational age at birth, presence of growth restriction and umbilical artery pH. Frequencies of the different ST event and quality of the signal were first analyzed for the global labor recording, and then separately for the first and the second phase of labor. No statistically significant difference in ST event frequencies between fetuses with congenital heart disease and the control group was found. Regarding the quality of the signal, 11.49% (±18.82) of recording time is a signal loss for fetus with congenital heart disease whereas only 5.18% (±10.67) for the control group (p=0.028). This is the first study investigating for intrapartum electrocardiogram modification in fetus with congenital heart disease. Congenital heart diseases do not modify frequencies of ST events.


Research Alliance for Veterinary Science and Biodefense BSL-3 Network (RAV3N): Report on network origin and phase I activities.
Recent disease events have heightened awareness for the need for collaboration between the nation's public health and veterinary infectious disease communities to improve preparedness for current and future biological threats. To address this need, the U.S. Department of Agriculture's National Bio- and Agro-Defense Facility (USDA NBAF) has partnered with Texas A&M University through its Global Health Research Complex (TAMGHRC) to establish the Research Alliance for Veterinary Science and Biodefense BSL-3 Network (RAV3N). As a collaborative network of U.S. university and federal BSL-3Ag/BSL-3/BSL-4 laboratory research facilities, the objective of RAV3N is to establish strategic and coordinated approaches for harnessing collective large-animal biocontainment infrastructure and research capacity to improve bio-surveillance, diagnostics, and countermeasure development against high-consequence pathogens of veterinary and zoonotic importance. Here, we describe the origin and development of RAV3N, detail phase I activities, and summarize the proceedings of its first membership meeting held in August 2022.


Evaluating a standardized measure of healthcare personnel influenza vaccination.
Methods of measuring influenza vaccination of healthcare personnel (HCP) vary substantially, as do the groups of HCP that are included in any given set of measurements. Thus, comparison of vaccination rates across healthcare facilities is difficult. The goal of the study was to determine the feasibility of implementing a standardized measure for reporting HCP influenza vaccination data in various types of healthcare facilities. A total of 318 facilities recruited in four U.S. jurisdictions agreed to participate in the evaluation, including hospitals, long-term care facilities, dialysis clinics, ambulatory surgery centers, and physician practices. HCP in participating facilities were categorized as employees, credentialed non-employees, or other non-employees using standard definitions. Data were gathered using cross-sectional web-based surveys completed at three intervals between October 2010 and May 2011; data were analyzed in February 2012. 234 facilities (74%) completed all three surveys. Most facilities could report on-site employee vaccination; almost one third could not provide complete data on HCP vaccinated outside the facility, contraindications, or declinations, primarily due to missing non-employee data. Inability to determine vaccination status of credentialed and other non-employees was cited as a major barrier to measure implementation by 24% and 27% of respondents, respectively. Using the measure to report employee vaccination status was feasible for most facilities; tracking non-employee HCP was more challenging. Based on evaluation findings, the measure was revised to limit the types of non-employees included. Although the revised measure is less comprehensive, it is more likely to produce valid vaccination coverage estimates. Use of this standardized measure can inform quality improvement efforts and facilitate comparison of HCP influenza vaccination among facilities.


BCR-ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells.
Pre-B lymphoblastic leukemia cells carrying a BCR-ABL1 gene rearrangement exhibit an undifferentiated phenotype. Comparing the genome-wide gene expression profiles of normal B-cell subsets and BCR-ABL1+ pre-B lymphoblastic leukemia cells by SAGE, the leukemia cells show loss of B lymphoid identity and aberrant expression of myeloid lineage-specific molecules. Consistent with this, BCR-ABL1+ pre-B lymphoblastic leukemia cells exhibit defective expression of IKAROS, a transcription factor needed for early lymphoid lineage commitment. As shown by inducible expression of BCR-ABL1 in human and murine B-cell precursor cell lines, BCR-ABL1 induces the expression of a dominant-negative IKAROS splice variant, termed IK6. Comparing matched leukemia sample pairs from patients before and during therapy with the BCR-ABL1 kinase inhibitor STI571 (Imatinib), inhibition of BCR-ABL1 partially corrected aberrant expression of IK6 and lineage infidelity of the leukemia cells. To elucidate the contribution of IK6 to lineage infidelity in BCR-ABL1+ cell lines, IK6 expression was silenced by RNA interference. Upon inhibition of IK6, BCR-ABL1+ leukemia cells partially restored B lymphoid lineage commitment. Therefore, we propose that BCR-ABL1 induces aberrant splicing of IKAROS, which interferes with lineage identity and differentiation of pre-B lymphoblastic leukemia cells.


Anxiolytic-like effects of an mGluR 5 antagonist and a mGluR 2/3 agonist, and antidepressant-like effects of an mGluR 7 agonist in the chick social separation stress test, a dual-drug screening model of treatment-resistant depression.
Modulation of glutamate receptors has demonstrated anxiolytic and/or antidepressant effects in rodent stress models. The chick social-separation stress paradigm exposes socially raised aves to an isolation stressor which elicits distress vocalizations (DVocs) in an attempt to re-establish contact. The model presents a state of panic during the first 5 min followed by a state of behavioral despair during the last 60 to 90 min. Making it useful as a dual anxiolytic/antidepressant screening assay. Further research has identified the Black Australorp strain as a stress-vulnerable, treatment-resistant, and ketamine-sensitive genetic line. Utilizing this genetic line, we sought to evaluate modulation of glutamatergic receptors for potential anxiolytic and/or antidepressant effects. Separate dose-response studies were conducted for the following drugs: the AMPA PAM LY392098, the mGluR 5 antagonist MPEP, the mGluR 2/3 agonist LY404039, the mGluR 2/3 antagonist LY341495, and the mGluR 7 agonist AMN082. The norepinephrine α2 agonist clonidine and the NMDA antagonist ketamine were included as comparison for anxiolytic (anti-panic) and antidepressant effects, respectively. As in previous studies, clonidine reduced DVoc rates during the first 5 min (attenuation of panic) and ketamine elevated DVoc rates (attenuation of behavioral despair) during the last 60 min of isolation. The mGluR 2/3 agonist LY404039 and the mGluR 5 antagonist MPEP decreased DVoc rates during the first 5 min of isolation indicative of anxiolytic effects like that of clonidine while the mGluR 7 agonist AMN082 elevated DVoc rates in the later hour of isolation, representative of antidepressant effects like that of ketamine. Collectively, these findings suggest that certain glutamate targets may be clinically useful in treating panic disorder and/or treatment-resistant depression.


Epidemiology of irritable bowel syndrome among African Americans as compared with whites: a population-based study.
We studied the prevalence as well as the sociodemographic characteristics and quality of life of African American patients with irritable bowel syndrome (IBS) among the population at large and compared them with those of whites. A total of 990 adults from 9 different sites in the Jackson, Mississippi metropolitan area (670 African Americans and 320 whites) completed self-administered questionnaires providing sociodemographic information and details regarding bowel habits and associated symptoms for diagnosing IBS on the basis of Rome II criteria. Quality of life was assessed by the SF-12 questionnaire. Ninety-five of the 990 participants had IBS, giving a total sample prevalence of 9.6% (African Americans, 7.9%; whites, 13.1%). Adjusting for other risk factors in a reduced logistic regression model, we found race (P = .0004) and education (P = .0049) to be important correlates of IBS prevalence. The household income showed a trend toward statistical significance (P = .0845). With the adjusted odds ratio as an estimate of relative risk, whites were 2.5 (95% confidence interval, 1.5-4.0) more likely than African Americans to have IBS. In terms of an index for quality of life (possible score, 1-44), the adjusted mean score was lower for adults with IBS compared with non-IBS adults (IBS mean, 29.8; no IBS, 34.2; P < .0001), but the racial difference was not significant. IBS occurs less frequently among African Americans. Although IBS affects quality of life among both ethnicities, the degree of impairment is similar.


Challenges of the Nano-Bio Interface in Lateral Flow and Dipstick Immunoassays.
Lateral flow assays (LFAs) are highly attractive for point-of-care (POC) diagnostics for infectious disease, food safety, and many other medical uses. The unique optical, electronic, and chemical properties that arise from the nanostructured and material characteristics of nanoparticles provide an opportunity to increase LFA sensitivity and impart novel capabilities. However, interfacing to nanomaterials in complex biological environments is challenging and can result in undesirable side effects such as non-specific adsorption, protein denaturation, and steric hindrance. These issues are even more acute in LFAs where there are many different types of inorganic-biological interfaces, often of a complex nature. Therefore, the unique properties of nanomaterials for LFAs must be exploited in a way that addresses these interface challenges.


Inactivity of the bicyclic pyrimidine nucleoside analogues against simian varicella virus (SVV) does not correlate with their substrate activity for SVV-encoded thymidine kinase.
Simian varicella virus (SVV) and human varicella-zoster virus (VZV) are closely related viruses that share many structural and functional properties. 5-Substituted 2'-deoxyuridine derivatives (e.g., BVDU, BVaraU) and acyclic guanine nucleoside derivatives (i.e., ACV and GCV) show comparable antiviral efficacy against VZV and SVV in cell culture. In contrast, the novel bicyclic nucleoside analogues (BCNAs) are exquisitely inhibitory to VZV (EC50 in the lower nanomolar range) but completely inactive against SVV. The VZV-encoded thymidine kinase (TK) appeared to be essential for BCNA activation (phosphorylation) and anti-VZV activity. Also SVV TK is able to recognize the BCNAs as substrate, although with a different structure-affinity relationship. Thus, viral TK-catalyzed phosphorylation is necessary but not sufficient for the BCNAs to display antiviral activity. Our data suggest that the eventual target of the BCNAs against VZV is either absent in SVV or, alternatively, is insensitive for the (phosphorylated) BCNAs.


Auto-immune hemolytic anemia caused by anti-K13.
A case of auto-immune hemolytic anemia caused by auto anti-K13 is described. Direct antiglobulin tests using monospecific reagents showed that IgG and the C3 component of complement were present on the patient's red cells. Eluted auto-antibody did not react with Ko or with K:--13 cells. Kell blood group antigenicity of the patient's red cells did not appear to be reduced.


Theory of tip structure-dependent microtubule catastrophes and damage-induced microtubule rescues.
Microtubules are essential cytoskeletal polymers that exhibit stochastic switches between tubulin assembly and disassembly. Here, we examine possible mechanisms for these switches, called catastrophes and rescues. We formulate a four-state Monte Carlo model, explicitly considering two biochemical and two conformational states of tubulin, based on a recently conceived view of microtubule assembly with flared ends. The model predicts that high activation energy barriers for lateral tubulin interactions can cause lagging of curled protofilaments, leading to a ragged appearance of the growing tip. Changes in the extent of tip raggedness explain some important but poorly understood features of microtubule catastrophe: weak dependence on tubulin concentration and an increase in its probability over time, known as aging. The model predicts a vanishingly rare frequency of spontaneous rescue unless patches of guanosine triphosphate tubulin are artificially embedded into microtubule lattice. To test our model, we used in vitro reconstitution, designed to minimize artifacts induced by microtubule interaction with nearby surfaces. Microtubules were assembled from seeds overhanging from microfabricated pedestals and thus well separated from the coverslip. This geometry reduced the rescue frequency and the incorporation of tubulins into the microtubule shaft compared with the conventional assay, producing data consistent with the model. Moreover, the rescue positions of microtubules nucleated from coverslip-immobilized seeds displayed a nonexponential distribution, confirming that coverslips can affect microtubule dynamics. Overall, our study establishes a unified theory accounting for microtubule assembly with flared ends, a tip structure-dependent catastrophe frequency, and a microtubule rescue frequency dependent on lattice damage and repair.


Density-dependent effects of prey defenses and predator offenses.
Defenses protect prey, while offenses arm predators. Some defenses and offenses are constitutive (e.g. tortoise shells), while others are phenotypically plastic and not always expressed (e.g. neckteeth in water fleas). All of them are costly and only adaptive at certain prey densities. Here, I analyse such density-dependent effects, applying a functional response model to categorize defenses and offenses and qualitatively predict at which prey densities each category should evolve (if it is constitutive) or be expressed (if it is phenotypically plastic). The categories refer to the step of the predation cycle that a defense or offense affects: (1) search, (2) encounter, (3) detection, (4) attack, or (5) meal. For example, prey warning signals such as red coloration prevent predator attacks and are hence step 4 defenses, while sharp predator eyes enhance detection and are step 3 offenses. My theoretical analyses predict that step 1 defenses, which prevent predators from searching for their next meal (e.g. toxic substances), evolve or are expressed at intermediate prey densities. Other defenses, however, should be most beneficial at low prey densities. Regarding predators, step 1 offenses (e.g. immunity against prey toxins) are predicted to evolve or be expressed at high prey densities, other offenses at intermediate densities. I provide evidence from the literature that supports these predictions.


Acute tolerance and metabolic responses of Chinese mitten crab (Eriocheir sinensis) juveniles to ambient nitrite.
The lethal concentration of nitrite to the Chinese mitten crab Eriocheir sinensis was tested by exposing the animals to 17.78, 23.71, 31.62, 42.17, and 56.23 mg NaNO2 L(-1) at 20 degrees C for 24, 48, 72, and 96 h. The corresponding LC50 value for each time exposure was 43.87 (38.70-51.70), 40.24 (34.88-46.01), 38.87 (33.72-46.01) and 38.87 (33.72-46.01) mg NaNO2 L(-1) or 29.25 (25.80-34.47), 26.83 (23.25-30.67), 25.91(22.48-30.67), 25.91(22.48-30.67) mg NO2-N L(-1), respectively. The physiological response of the crab to nitrite toxicity was further investigated by exposing the crab to 0, 10, 20, 30 and 40 mg NaNO2 L(-1) for 2 d. The changes of nitrogenous compounds in haemolymph, oxyhemocyanin and metabolism were measured at 3, 6, 24 and 48 h upon exposure. Haemolymph nitrite was significantly enhanced by the increase of nitrite from 10 to 40 mg NaNO2 L(-1) during the 2-day exposure. The concentrations of nitrate, urea and glutamate in haemolymph increased concomitantly with the exposing time and ambient nitrite levels, suggesting that the formation of nitrate, urea and glutamine may be the possible end products of nitrite detoxification in crabs. The diffusion of nitrite caused a reduction of oxyhemocyanin, resulting to hypoxia in tissues. Under a hypoxia condition, crabs increased energy demand for metabolism as indicated by the elevated levels of glucose and lactate in haemolymph. Our data showed that ambient nitrite could affect oxygen carrying capacity through oxyhemocyanin reduction and the increase of energy catabolism in crabs. This study suggests that nitrite could be detoxified through the pathway of nitrate, urea and glutamine formation in crabs.


The use of a three-dimensional imaging model to optimize the operative separation of pygopagus conjoined twins.
The surgical management of conjoined twins has evolved to the point that elective operative separation can safely be performed in the majority. Cross-sectional imaging is invaluable to accurately delineate the site of union and configuration of shared organ systems prior to surgery. The use of three-dimensional modeling also dramatically improves the planning process and assists in intraoperative decision-making. We present a case of pygopagus conjoined twins who underwent successful operative separation at 19 months of age with the aid of such technology. A three-dimensional computer animation was created by Medical Modeling LLC (Golden, CO, USA) from representative cross-sectional CT and MR images. The complete animation is available at http//www.medicalmodeling.com/ahmed. A plasticized bony pelvic model, accurate to 1mm, was also created using similar technology. The three-dimensional animation and pelvic model were utilized during both the planning and operative phases of the separation. The shared pelvic soft-tissue anatomy consisted of a conjoined penis with four corporal bodies, and a posteriorly conjoined urethra subtending two separate bladders and outlets. The rectum was conjoined approximately 2 cm proximal to the single anus. A blind-ending hindgut remnant was also documented by the animation. Following operative separation, both twins recovered uneventfully. Three-dimensional computer animation technology was extremely accurate intraoperatively and predicted exactly which shared organs would sequentially be encountered as the dissection commenced. It significantly reduced the overall operative time and provided critical intraoperative anatomic information. We recommend that this readily available technology be utilized for any patient requiring extensive reconstructive surgery.


Nanopatterned Human iPSC-based Model of a Dystrophin-Null Cardiomyopathic Phenotype.
Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer unprecedented opportunities to study inherited heart conditions in vitro, but are phenotypically immature, limiting their ability to effectively model adult-onset diseases. Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but the pathogenesis of this disease phenotype is not fully understood. Therefore, we aimed to test whether biomimetic nanotopography could further stratify the disease phenotype of DMD hiPSC-CMs to create more translationally relevant cardiomyocytes for disease modeling applications. We found that anisotropic nanotopography was necessary to distinguish structural differences between normal and DMD hiPSC-CMs, as these differences were masked on conventional flat substrates. DMD hiPSC-CMs exhibited a diminished structural and functional response to the underlying nanotopography compared to normal cardiomyocytes at both the macroscopic and subcellular levels. This blunted response may be due to a lower level of actin cytoskeleton turnover as measured by fluorescence recovery after photobleaching. Taken together these data suggest that DMD hiPSC-CMs are less adaptable to changes in their extracellular environment, and highlight the utility of nanotopographic substrates for effectively stratifying normal and structural cardiac disease phenotypes in vitro.


Evaluation of Seattle's sweetened beverage tax on tax support and perceived economic and health impacts.
It is important to understand whether the publics' attitudes towards sugary beverage taxes (SBT) change after tax implementation to ensure the long-term success of tax policies. Seattle's SBT went into effect on January 1, 2018. We administered a mixed-mode survey to adults in Seattle and comparison areas, pre- and 2-years post-tax, to evaluate the impact of the SBT on 1) tax support and 2) perceived tax impacts (N = 2,933). Using a difference-in-differences approach, we employed adjusted income-stratified modified Poisson models to test the impacts of the tax on net changes in attitudes in Seattle versus the comparison areas, pre- to post-tax. Among lower-income individuals in Seattle, support for the tax increased by 14% (PRDD: 1.14; 95% CI: 1.08, 1.21) and there was a 20% net-increase in the perception that the SBT would positively affect the economy (PRDD: 1.20; 95% CI: 1.05, 1.39), compared to changes in the comparison areas. Among higher-income individuals in Seattle, support for the tax was not different (PRDD: 0.93; 95% CI: 0.70, 1.22) pre- to post-tax, but there was a net-increase in the perception that the tax would have negative effects on small businesses (PRDD: 1.44; 95% CI: 1.03, 2.00) and family finances (PRDD: 1.86; 95% CI: 1.09, 3.19). After living with the tax for 2-years, support for the tax increased among lower-income individuals in Seattle. Tax support was high and unchanged among higher-income individuals, but overall attitudes became more negative. Policy makers should consider investing in ongoing campaigns that explain the benefits of SSB taxes and revenues.


Translocation yield from the mouse spermatogonial stem cell following fractionated X-ray treatments: influence of unequal fraction size and of increasing fractionation interval.
(1) The genetic response of the mouse spermatogonial stem cell to a high dose of X-rays given in two unequal fractions 24 h apart can be dependent upon the order in which the two fractions are given. When 1000 R was administered as 100 R followed by 900 R the recovered translocation yield (22%) was similar to that which can be obtained by extrapolation from lower doses and also to that of a 500 + 500 R 24 h fractionation. By contrast, when the 900 R preceded the 100 R the response was much lower (7.4%), yet still greater than that produced by a single 1000 R treatment (4.5%). The same order of effectiveness was observed for length of sterile period. (2) The sub-additive translocation yields previously obtained with 800 R treatments given in fractions of 500 R and 300 R at intervals of 3-12 days were found to be maintained with intervals up to at least 15 days but additivity was regained by the end of the third week. Sterile period data indicated that with these intervals the germinal epithelium had recovered sufficiently from the first fraction for spermatogenesis to restart before the second fraction was given. (3) It is concluded from the two experiments that (a) 24 h after a radiation exposure the surviving stem cells are more sensitive than formerly both to killing and genetic damage, (b) at this time they are no longer heterogeneous in their radiosensitivities, so that increasing yields of genetic damage may be obtained with increasing dose i.e. there is no fall in yield at higher doses, (c) the change in sensitivity could be a consequence of a synchronization to a sensitive stage in a cell cycle, or to a transitional phase preparatory to entering a different cell cycle. (d) to achieve rapid repopulation of the germinal epithelium the surviving stem cells are stimulated to enter a shorter cell cycle and this is the cause of the sub-additive translocation yields with fractionation intervals of 3-15 days, (e) the recommencement of spermatogenesis is associated with the reestablishment of the heterogeneity in radiosensitivity among the stem cells. At this time additive translocation yields can again be recovered.


Efficacy and reliability of active robotic-assisted total knee arthroplasty compared with conventional total knee arthroplasty: a systematic review and meta-analysis.
In the field of prosthetics, the ultimate goal is to improve the clinical outcome by using a technique that prolongs the longevity of prosthesis. Active robotic-assisted total knee arthroplasty (TKA) is one such technique that is capable of providing accurate implant position and restoring mechanical alignment. Although relevant studies have been carried out, the differences in the efficacy and reliability between active robotic-assisted TKA and conventional arthroplasty have not yet been adequately discussed. We referenced articles, including randomised controlled trials and comparative retrospective research, from PubMed, Embase, Cochrane Library and Web of Science, in order to compare active robotic-assisted TKA with the conventional technique. Data extraction and quality assessment were conducted for each study. Statistical analysis was performed using Revman V. 5.3. Seven studies with a total of 517 knees undergoing TKA were included. Compared with conventional surgery, active robotic TKA showed better outcomes in precise mechanical alignment (mean difference, MD: - 0.82, 95% CI: -1.15 to - 0.49, p < 0.05) and implant position, with lower outliers (p < 0.05), better functional score (Western Ontario and McMaster University, Knee Society Score functional score) and less drainage (MD: - 293.28, 95% CI: - 417.77 to - 168.79, p < 0.05). No significant differences were observed when comparing the operation time, range of motion and complication rates. The current research demonstrates that active robotic-assisted TKA surgeries are more capable of improving mechanical alignment and prosthesis implantation when compared with conventional surgery. Further studies are required to investigate the potential benefits and long-term clinical outcomes of active robotic-assisted TKA.


Caregiving burden and healthcare utilization in family caregivers of people with dementia: Long term impact of the public family caregiver intervention.
Despite community-based interventions to decrease the caregiving burden on family caregivers of people with dementia (PwD), long-term assessment of community-based public programs is lacking. Therefore, the study aims to identify the long-term effects of community-based dementia caregiver intervention on the caregiving burden and healthcare utilization among family caregivers for PwD. Additionally, we investigated the predictors of caregiving burden and healthcare utilization. Of the participants, 32 (76%) intervention and 15 (38%) control groups responded to the one-year follow-up. We assessed caregiver burden using the short-form Zarit Burden Interview (sZBI) and collected healthcare utilization data using questionnaire at baseline and 12 months. Compared with the control group, the intervention group did not experience a reduction in caregiving burden and healthcare utilization. Predictors of caregivers' perceived burden were spouses as the primary caregiver and having multiple comorbidities. The predictors identified in this study should be considered when implementing public family support programs.


Optimism and precautionary measures during the COVID-19 outbreak in China.
The current study uses the unique setting created by the coronavirus crisis in China during the peak period of the pandemic to examine the behavioral factors affecting the decision of the Chinese people to adopt the precautionary actions recommended by the government. Using the social app WeChat, we conducted a cross sectional study of the Chinese people in mid-February 2020. Our results show that higher levels of dispositional optimism and support for the government's actions for managing the epidemic were positively correlated with the compliance level. In addition, women and married participants were more likely to comply with the recommendations. Optimism and support for government actions should be considered when promoting policies related to health behavior such as social distancing.


First-episode psychosis and substance use in Nelson Mandela Bay: Findings from an acute mental health unit.
Use of psychoactive substances is a common finding in studies on first-episode psychosis (FEP), and this has prognostic implications. We know very little about psychoactive substance use (SU) among patients with FEP in the Eastern Cape province (EC) of South Africa (SA). The study seeks to determine SU prevalence and associated features among inpatients with non-affective FEP in an acute mental health unit (MHU) in Nelson Mandela Bay, EC. Researchers conducted a retrospective clinical file review of a 12-month admission cohort of patients with FEP, without a concurrent mood episode, to the Dora Nginza Hospital MHU. Information collected included SU history, psychiatric diagnoses, and demographics. Data were then subjected to statistical analysis. Researchers conducted a retrospective clinical file review of a 12-month admission cohort of patients with FEP, without a concurrent mood episode, to the Dora Nginza Hospital MHU. Information collected included SU history, psychiatric diagnoses and demographics. Data were then subjected to statistical analysis. A total of 117 patients (86 [73.5%] males; 31 [26.5%] females) aged 18-60 years (mean 29 years) met the inclusion criteria. After controlling for missing information, 95 of 117 (81.2%) patients had a history of active or previous SU, 82 of 90 (91.1%) were single and 61 of 92 (66.3%) were unemployed. A significant association was found between SU and unemployment (p < 0.001), as well as male sex (p < 0.001). The most common substances used were cannabis (59.8%), followed by alcohol (57.3%) and stimulants (46.4%). In keeping with national and international literature, the results of this study showed a high prevalence of substance use in South African patients with first-episode psychosis. The high prevalence of lifetime substance use in this cohort compared to previous studies in South Africa requires further investigation and highlights the urgent need for dual diagnosis services in the Eastern Cape province.


Amoxicillin-induced aseptic meningitis: clinical features, diagnosis and management.
The clinical features of aseptic meningitis associated with amoxicillin are unknown. The main objective of this study was to investigate the clinical characteristics of amoxicillin-induced aseptic meningitis (AIAM) and provide a reference for clinical diagnosis and treatment. AIAM-related studies were collected by searching the relevant databases from inception to October 31, 2022. AIAM usually occurred 3 h to 7 days after amoxicillin administration in 13 males and 9 females. Twenty-one patients (95.5%) had recurrent AIAM with a total of 62 episodes. Fever (19 cases, 86.4%) and headache (18 cases, 81.8%) were the most common symptoms. Typical cerebrospinal fluid (CSF) findings were leukocytosis (100%) with lymphocytic predominance (14 cases, 63.6%), elevated protein (20 cases, 90.1%), normal glucose (21 cases, 95.5%) and negative culture (21 cases, 100%). Brain magnetic resonance imaging showed mild meningeal enhancement in one patient. The symptoms resolved mainly within 1-4 days after drug discontinuation in all patients. Clinical attention should be given to the adverse effects of AIAM. The medication history of patients with suspected meningitis should be investigated to avoid unnecessary examination and antibiotic treatment.


Quality of life, health, eating habits and physical development of middle school adolescents in the Świetokrzyskie.
Measurement of the health-related quality of life is currently one of the significant methods of self-evaluation of heath, enabling the detection of disorders in the biopsychosocial functioning of children and adolescents. The aim of the study was to establish significant relationships between the subjective sense of the health-related quality of life, eating habits and objective parameters of physical development among a group of adolescents. The study applied a diagnostic survey methodology with the use of the KIDSCREEN-52 questionnaire, the Health Behaviour in School-aged Children (HBSC) questionnaire, anthropometric measures of choice, and a self-constructed questionnaire. The significance level was set at p<0.05. The collected data was gathered and analyzed using Statistica 10.0 PL. Three distinct groups of adolescents with a varying subjective sense of the quality of life were identified. The frequency of basic meal consumption among participants showed some abnormalities. This concerned breakfast in particular, which was consumed before going to school by over half of the participants (63.61%), with boys (70.07%) eating it significantly more frequently than girls (57.83%). Indices based on weight-to-height ratios, such as: BMI, Rohrer's Index and Slender Index were significantly greater in value among boys compared with girls. Adolescents from the Świętokrzyskie region, for the most part exhibited a high subjective sense of the quality of life. The physical development of the participants, as far as basic anthropometric characteristics are concerned, was mostly appropriate and consistent with a high subjective sense of the quality of life and exhibited eating habits.


Pannexin1 channels regulate mechanically stimulated but not spontaneous adenosine release.
Fast-scan cyclic voltammetry (FSCV) is a rapid technique to measure neuromodulators, and using FSCV, two modes of rapid adenosine have been discovered. Spontaneous transients occur randomly in the brain, while mechanical stimulation also causes a rapid adenosine event. Pannexin1 channels are membrane channels that transport ions, including ATP, out of the cell where it is rapidly broken down into adenosine. Pannexin 1 channels (Panx1) have a flickering mode of rapid opening and are also mechanically stimulated. Here, we test the extent to which pannexin channels, specifically pannexin1 (Panx1) channels, are responsible for rapid adenosine events. Spontaneous adenosine release or mechanosensitive adenosine release were measured using fast-scan cyclic voltammetry in hippocampal (CA1) brain slices. In global Panx1KO mice, there is no significant difference in the frequency or concentration of spontaneous adenosine release, indicating Panx1 is not a release mechanism for spontaneous adenosine. Spontaneous adenosine frequency decreased slightly after administration of a large (100 µM) dose of carbenoxolone, a nonspecific inhibitor of many pannexin and connexin channels, suggesting other hemichannels only play a small role at most. For mechanically stimulated adenosine release, the concentration of each adenosine event significantly decreased 30% in Panx1KO mice and the frequency of stimulations that evoked adenosine also decreased. The response was similar in WT mice with carbenoxolone. Thus, Panx1 is a release mechanism for mechanically stimulated adenosine release, but not the only mechanism. These results demonstrate that pannexin channels differentially regulate rapid adenosine release and could be targeted to differentially affect mechanically stimulated adenosine due to brain damage.


Bioengineering solutions for ureteric disorders: clinical need, challenges and opportunities.
To summarise the causes of ureteric damage and the current standard of care, discussing the risks and benefits of available therapeutic options. We then focus on the current and future solutions that can be provided by ureteric bioengineering and provide a description of the ideal characteristics of a bioengineered product. We performed a literature search in February 2021 in: Google Scholar, Medline, and Web of Science. Three searches were conducted, investigating: (a) the epidemiology of ureteric pathology, (b) the current standard of care, and (c) the state of the art in ureteric bioengineering. The most-common causes of ureteric damage are iatrogenic injury and external trauma. Current approaches to treatment include stent placement or surgical reconstruction. Reconstruction can be done using either urological tissue or segments of the gastrointestinal tract. Limitations include scarring, strictures, and infections. Several bioengineered alternatives have been explored in animal studies, with variations in the choice of scaffold material, cellular seeding populations, and pre-implantation processing. Natural grafts and hybrid material appear to be associated with superior outcomes. Furthermore, seeding of the scaffold material with stem cells or differentiated urothelial cells allows for better function compared to acellular scaffolds. Some studies have attempted to pre-implant the graft in the omentum prior to reconstruction, but this has yet to prove any definitive benefits. There is an unmet clinical need for safer and more effective treatment for ureteric injuries. Urological bioengineering is a promising solution in preclinical studies. However, substantial scientific, logistic, and economic challenges must be addressed to harness its transformative potential in improving outcomes.


Race, ethnicity and urolithiasis: a critical review.
Using combinations of the key words urolithiasis, kidney stones, race, ethnicity, population group in Google Scholar and Pubmed, a literature search identified 40 articles. Of these, 33 satisfied the principal inclusion criterion of studies involving comparison of at least two groups in which there is a perceived difference in stone occurrence. Studies were classified as "weak" (no attempt to account for inter-racial or inter-ethnic group differences in stone occurrence), "soft" (speculative explanations reached by default) or "hard" (explanations based on empirically measured lithogenic risk factors). Only 12 studies (36 %) fell into the latter category. Among these, a wide diversity of lithogenic factors was invoked to explain inter-group differences in stone rates. Traditional urinary physicochemical risk factors do not convincingly account for these differences. Studies have failed to yield a consolidated and unifying theory which compellingly explains racial and ethnic differences in urolithiasis.