Development and implementation of an interdisciplinary oncology program in a community hospital.
The development and implementation of an interdisciplinary oncology program in a community hospital are described. Before the program was established, clinical pharmacists responsible for order entry and verification did not have a defined structure and resource to effectively communicate with medical oncologists and nurses on patient care issues and oncology drug information. The practice model did not meet practice needs, departmental safety, quality, or cost-saving goals. An interdisciplinary team was established to determine where current processes and procedures were needed to decrease errors and improve efficiency associated with chemotherapy services. Three stages of practice development were planned, and an interdisciplinary oncology program involving nursing and pharmacy team members and medical oncologists was established. Standardized order forms, various pharmacy collaborative agreements, protocols, improved oncology nursing and pharmacy processes, and established standards in order writing, dispensing, administration, and monitoring were developed. An oncology pharmacist specialist position was requested, and this pharmacist played an essential role in helping the hospital realize significant cost savings and improve the quality of care provided to patients receiving chemotherapy services. Data were collected for 96 chemotherapy orders before program implementation and for 75 orders after program implementation, and a 45% reduction in total error related to chemotherapy drugs was observed (p < 0.0625). The most common cause of errors was missing information, typically an omitted duration or frequency, dose, route, or premedication (63% of all errors documented). The development and implementation of an interdisciplinary oncology program resulted in decreased medication-error rates, expanded pharmacy services, and cost savings.


Chain elongation of aldoses by indium-mediated coupling with 3-bromopropenyl esters.
[Chemical reaction: see text] A procedure is described for acyloxyallylation of unprotected aldoses with two functionalized reagents: 3-bromopropenyl acetate and 3-bromopropenyl benzoate. The reaction is performed in ethanol or a dioxane/water mixture in the presence of indium metal. The products are deesterified in the workup to afford unsaturated polyols, which are isolated as mixtures of two diastereomers. The major diastereomers are subjected to ozonolysis to afford new aldoses, which have been elongated by two carbon atoms compared to the starting materials. The new aldoses all have lyxo configuration at positions 2, 3, and 4.


A universal route with fine kinetic control to a family of penta-twinned gold nanocrystals.
Some of the major difficulties hindering the synthesis of different types of colloidal nanocrystals are their complex synthetic methods and the lack of a universal growth mechanism in one system. Herein, we propose a general strategy of kinetically controlled seed-mediated growth to synthesize a family of penta-twinned gold nanocrystals. Specifically, different kinds of penta-twinned nanocrystals (truncated penta-twinned decahedra, truncated bipyramids, bipyramids, truncated bipyramids with tips, star-like penta-twinned nanocrystals, decahedra with concave edges, and decahedra) with tunable sizes and high purity were readily achieved in one system solely by tailoring the deposition kinetics of adatoms on different sites of decahedral seeds. The controllable deposition kinetics can be realized by changing the ratio of reductant/gold precursors (R), which dictates whether horizontal or vertical features along the 5-fold axis direction of Au decahedral seeds are produced. Additionally, the selective growth of a second metal (silver) on penta-twinned gold seeds can be reached through minor modification of R, which opens a new avenue for mechanistic investigation by visualizing the seed localization within the final particles. The present work demonstrates a general paradigm for the kinetic growth of penta-twinned crystals and would be extended to the synthesis of other families of nanocrystals.


Assessment of XCMS Optimization Methods with Machine-Learning Performance.
The metabolomics field is under rapid development. In particular, biomarker identification and pathway analysis are growing, as untargeted metabolomics is usable for discovery research. Frequently, new processing and statistical strategies are proposed to accommodate the increasing demand for robust and standardized data. One such algorithm is XCMS, which processes raw data into integrated peaks. Multiple studies have tried to assess the effect of optimizing XCMS parameters, but it is challenging to quantify the quality of the XCMS output. In this study, we investigate the effect of two automated optimization tools (Autotuner and isotopologue parameter optimization (IPO)) using the prediction power of machine learning as a proxy for the quality of the data set. We show that optimized parameters outperform default XCMS settings and that manually chosen parameters by liquid chromatography-mass spectrometry (LC-MS) experts remain the best. Finally, the machine-learning approach of quality assessment is proposed for future evaluations of newly developed optimization methods because its performance directly measures the retained signal upon preprocessing.


Interaction between carotid and cardiopulmonary baroreflexes in control of plasma ADH.
The purpose of this study was to determine if there is an interaction between carotid baroreceptors (CBR) and cardiopulmonary receptors with vagal afferents (CPVA) in the control of plasma vasopressin (ADH). Changes in ADH (radioimmunoassay) in the superior vena cava were determined in 13 chloralose-anesthetized dogs with aortic nerves sectioned during concomitantly induced changes in CBR and CPVA input. CBR input was changed by altering pressure (CSP) in the isolated perfused sinuses. Carotid sinus pressure (CSP) was initially set at 50 mmHg. The CPVA input was reversibly interrupted by cooling the vagi to 0 degrees C while CSP was concomitantly increased to 135 or 200 mmHg or was held constant at 50 mmHg. Vagal cold block (VCB) with CSP held constant at 50 mmHg resulted in large increases in arterial pressure and plasma vasopressin. Increases in CSP to 200 mmHg resulted in significant decreases in arterial pressure and in plasma vasopressin despite concomitant VCB. VCB and concomitant increase in CSP to 135 mmHg resulted in a significant fall in arterial pressure, whereas plasma vasopressin tended to increase. Thus, the influence on arterial pressure of raising CSP to 135 mmHg exceeds that of VCB. In contrast, the influence of VCB on ADH equals or exceeds that of raising CSP to 135 mmHg. These differential responses of arterial pressure and plasma ADH suggest an interaction between CBR and CPVA in the control of ADH and arterial pressure.


[Nosocomial infection with methicillin-resistant Staphylococcus aureus].
Methicillin-resistant Staphylococcus aureus (MRSA) isolated in our hospital between 1986 and 1989 were mainly examined for their susceptibility to various antibiotics and coagulase types. The isolation frequency of MRSA among S. aureus isolated from clinical specimens has been steadily increasing; 37.8% in 1986, 49.8% in 1987, 60.6% in 1988 and 63.2% in 1989. This trend was particularly noticeable in the specimens associated with the respiratory tracts. The isolation rate of MRSA in the surgery and pediatrics wards was higher than that in the internal medicine ward. More than 80% of MRSA were coagulase type II, which were multi-resistant to penicillins, cephems, aminoglycosides and macrolides, and sensitive to MINO, new quinolones and VCM. These epidemic strains were also isolated from the nose of medical staff and from air samples in the wards. These findings suggest that the hospital environment including the patients and hospital personnel is extensively contaminated with multi-resistant MRSA of coagulase type II. Measures should be taken for prevention and control of nosocomial infection with MRSA in the whole hospital.


Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.
Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. These results provide valuable information supporting the current cell-based serum-free EV71 vaccine candidate going into human Phase I clinical trials.


[Regular medical check-ups of industrial workers in the city of Kazan].
The organization of preliminary medical check-ups (PMC) and regular medical check-ups (RMC) of industrial workers is discussed under the conditions of the reform of the medical preventive care in the city of Kazan (at the stabilization stage). Data are presented on advancing and enhancing the efficiency of PMC and RMC in the major industrial city of the Tatar Republic.


Evaluation of focal thyroid lesions incidentally detected in fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography images.
Background and Purpose: Increased uptake in the thyroid gland (TG) is often identified as an incidental finding on the whole body fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in non-thyroid cancer patients. Currently, there is no consensus on the appropriate approach for the management of these cases. Thyroid ultrasound, scintigraphy and fine-needle aspiration biopsy (FNAB) are suggested to exclude malignant thyroid lesions. Our aim is to determine the importance of increased F-18-FDG uptake in the TG on positron emission tomography/computed tomography (PET/CT) scans in patients who are being screened for various forms of non-thyroid cancer. Materials and Methods: We evaluated 2000 cases undergoing whole body PET/CT scanning between April 2011 and October 2012. The age, sex, type of primary cancer, maximum standardized uptake value (SUV max ), size of the thyroid nodules and cervical lymph nodes (CLNs) on 18 F-FDG PET/CT images and if available, the biopsy results were evaluated. Results: In total, 57 patients (23 men, 34 women, mean age ± standard deviation (SD), 60.89 ± 14 years) showed an increased fluorine-18-fluorodeoxyglucose ( 18 F-FDG) uptake by the TG (average SUV max : 4.07 ± 3.7). The CLNs were detected in 19/57 patients (33%). Only 20 cases (35%) received FNAB. The final histopathological diagnosis was papillary thyroid carcinoma in seven patients (mean SUV max ± SD: 6.0 ± 5.43) and benign thyroid disease in seven patients (mean SUV max ± SD: 2.36 ± 0.63). The FNAB results were undetermined for six patients. Conclusion: Focal high 18 F-FDG uptake in the TG may be associated with an increased risk of malignancy, but the clinical significance is unclear. More data are needed to elucidate the role of the SUV in the differentiation of benign and malign thyroid lesions. If a focal increase in 18 F-FDG uptake in the TG on PET/CT is present, a prompt histopathological evaluation should be suggested to clinicians for definitive diagnosis.


Age changes in the neuronal microenvironment.
The extracellular space of the rat brain was visualized by electron roscopy in sections of cerebral cortex fixed by freeze-substitution. The volume tissue occupied by the extracellular space was estimated stereomnetrically, and found to decrease from 20.8 percent in 3-month-old rats to 9.6 percent in escent animals, 26 months of age. This decrease in extracellular space indicates age-associated change in the microenvironment of nerve cells.


Evaluating the antibody response to SARS-COV-2 vaccination amongst kidney transplant recipients at a single nephrology centre.
Kidney transplant recipients are highly vulnerable to the serious complications of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infections and thus stand to benefit from vaccination. Therefore, it is necessary to establish the effectiveness of available vaccines as this group of patients was not represented in the randomized trials. A total of 707 consecutive adult kidney transplant recipients in a single center in the United Kingdom were evaluated. 373 were confirmed to have received two doses of either the BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford-AstraZeneca) and subsequently had SARS-COV-2 antibody testing were included in the final analysis. Participants were excluded from the analysis if they had a previous history of SARS-COV-2 infection or were seropositive for SARS-COV-2 antibody pre-vaccination. Multivariate and propensity score analyses were performed to identify the predictors of antibody response to SARS-COV-2 vaccines. The primary outcome was seroconversion rates following two vaccine doses. Antibody responders were 56.8% (212/373) and non-responders 43.2% (161/373). Antibody response was associated with greater estimated glomerular filtration (eGFR) rate [odds ratio (OR), for every 10 ml/min/1.73m2 = 1.40 (1.19-1.66), P<0.001] whereas, non-response was associated with mycophenolic acid immunosuppression [OR, 0.02(0.01-0.11), p<0.001] and increasing age [OR per 10year increase, 0.61(0.48-0.78), p<0.001]. In the propensity-score analysis of four treatment variables (vaccine type, mycophenolic acid, corticosteroid, and triple immunosuppression), only mycophenolic acid was significantly associated with vaccine response [adjusted OR by PSA 0.17 (0.07-0.41): p<0.001]. 22 SARS-COV-2 infections were recorded in our cohort following vaccination. 17(77%) infections, with 3 deaths, occurred in the non-responder group. No death occurred in the responder group. Vaccine response in allograft recipients after two doses of SARS-COV-2 vaccine is poor compared to the general population. Maintenance with mycophenolic acid appears to have the strongest negative impact on vaccine response.


Exploring the Use of Complementary and Alternative Medicine in Cancer Patients.
In Australia, it is estimated that around 17% to 87% of cancer patients have used one form of complementary therapy during their cancer treatment. There are numerous reasons and contributing factors for cancer patients to consider using complementary and alternative medicine (CAM). CAM information and products are readily available. However, the level of evidence to support the benefits of use in the cancer setting is limited, and the associated adverse effects and interactions with conventional medicine may not be fully studied. Besides, not all health professionals favor the concept of integrative health approaches, or have the confidence in dealing with CAM due to a lack of knowledge and standardization of practices. A thematic review of the literature was performed on the main contributing factors to cancer patients' use of CAM, as well as the current issues that may be encountered by the patients and health professionals.


Flibanserin for the treatment of hypoactive sexual desire disorder in premenopausal women.
Hypoactive sexual desire disorder (HSDD) is the most common form of female sexual dysfunction (FSD). Some theories suggest that HSDD has a neurobiological component linked to neurotransmitter imbalances. Flibanserin is the only FDA-approved treatment of HSDD; before its approval, the disorder was often left untreated or interventions were made using evidence-based psychological methods or 'off-label' use of bupropion, testosterone and other dopaminergic agents. Flibanserin, a multifunctional serotonin agonist/antagonist, is approved as a nonhormonal option designed specifically for the treatment of HSDD. Flibanserin has been shown to cause statistically significant increases in the number of satisfying sexual events and in sexual desire scores on standardized/validated measures while reducing FSD-related distress of premenopausal women diagnosed with HSDD. Similar efficacy has been demonstrated in a smaller group of postmenopausal women also affected by HSDD. The side effects of flibanserin include dizziness, somnolence, nausea and (rarely) syncope, and are comparable to other CNS drugs. While there has been debate over the approval of flibanserin for treatment of HSDD, it is evident that flibanserin provides meaningful relief to women suffering from a common sexual dysfunction and is an important addition to the field of women's health.


Fisher-Tippett region-merging approach to transrectal ultrasound prostate lesion segmentation.
In this paper, a computerized approach to segmenting prostate lesions in transrectal ultrasound (TRUS) images is presented. The segmentation of prostate lesions from TRUS images is very challenging due to issues, such as poor contrast, low SNRs, and irregular shape variations. To address these issues, a novel approach is employed to segment the lesions from the surrounding prostate, where region merging is performed via a region-merging likelihood function based on regional statistics, as well as Fisher-Tippett statistics. Experimental results using TRUS prostate images demonstrate that the proposed Fisher-Tippett region-merging approach achieves more accurate segmentation of prostate lesions when compared to other segmentation methods.


Exceptions to Cajal's neuron theory: communicating synapses.
Ultrastructural images of some neurons and their synaptic connections, belonging to the nucleus of the periaqueductal grey substance in the domestic cat mesencephalon, are shown. The finding that some axosomatic synapses showed an open communication between the pre- and postsynaptic portion attracted our attention. In this way a continuity is made between the presynaptic bouton of one neuron (axon) and the postsynaptic portion of the other (neuronal soma). Synapses having these interneuronal communications could be denominated communicating synapses. Accepting Cajal's neuron theory and his law of neuronal independence, it is very difficult to interpret these images. We wonder if this type of communicating synapses could be the exception that proves the rule of the neuron independence.


The dynamic motor imagery of locomotion is task-dependent in patients with stroke.
Recently, Motor Imagery (MI) has been associated with the execution of movements miming in part the mentally represented action (dynamic MI, dMI). Preliminary studies have reported as dMI may improve trainings in sport, with imagery timing close to the physical execution one. This study was aimed to investigate time and spatial parameters of dMI with actual locomotion in people with stroke. Twelve patients (stroke group, SG) were compared with twelve healthy elderly (elderly group, EG) and twenty young adults (young group, YG). Subjects performed mental representations of different walking (forward, FW; lateral, LW, backward, BW), accompanied or not by movements imitating walking (dMI and static MI, sMI). Then, they performed actual locomotion (AL). Outcome measures were related to the time and the number of steps spent for completing the tasks for all the given locomotor conditions. Significant differences were found in patients with respect to healthy subjects, with time in sMI significantly shorter than in dMI (p < 0.004) and AL (p < 0.002), but not between dMI and AL in FW (p = 0.806). In patients, times obtained in sMI and dMI was significantly shorter with respect to those of AL in LW and BW. Patients performed imagery tasks with similar times in all locomotion. Healthy groups did not reveal differences among tasks in BW, while significant differences were found in LW. Analogous results were found in terms of number of performed steps. In patients with stroke, a spatiotemporal functional equivalence with AL was found only for dMI, and not for sMI, in forward walking. This could be due to familiarity with this task. These results might have implications for the rehabilitative techniques based on MI.


An Event-Based Digital Time Difference Encoder Model Implementation for Neuromorphic Systems.
Neuromorphic systems are a viable alternative to conventional systems for real-time tasks with constrained resources. Their low power consumption, compact hardware realization, and low-latency response characteristics are the key ingredients of such systems. Furthermore, the event-based signal processing approach can be exploited for reducing the computational load and avoiding data loss due to its inherently sparse representation of sensed data and adaptive sampling time. In event-based systems, the information is commonly coded by the number of spikes within a specific temporal window. However, the temporal information of event-based signals can be difficult to extract when using rate coding. In this work, we present a novel digital implementation of the model, called time difference encoder (TDE), for temporal encoding on event-based signals, which translates the time difference between two consecutive input events into a burst of output events. The number of output events along with the time between them encodes the temporal information. The proposed model has been implemented as a digital circuit with a configurable time constant, allowing it to be used in a wide range of sensing tasks that require the encoding of the time difference between events, such as optical flow-based obstacle avoidance, sound source localization, and gas source localization. This proposed bioinspired model offers an alternative to the Jeffress model for the interaural time difference estimation, which is validated in this work with a sound source lateralization proof-of-concept system. The model was simulated and implemented on a field-programmable gate array (FPGA), requiring 122 slice registers of hardware resources and less than 1 mW of power consumption.


Ultrasound of gynecologic pathologies.
Since the introduction of vaginal transducers and color Doppler ultrasound, there has been renewed interest in evaluating the female pelvis. Several recently published manuscripts presented convincing material that suggests benign and malignant ovarian and uterine pathologies can be distinguished from each other on the basis of their vascularity. Duplex Doppler signals obtained from malignant tumors tend to demonstrate a low resistance pattern with continuous blood flow throughout the cardiac cycle. Benign lesions, in contrast, tend to display a more resistive pattern. The role of ultrasound in pediatric gynecologic conditions has also been nicely summarized in several recent papers. These are also discussed.


Executive Function in Adolescence: Associations with Child and Family Risk Factors and Self-Regulation in Early Childhood.
Executive functions are important higher-order cognitive skills for goal-directed thought and action. These capacities contribute to successful school achievement and lifelong wellbeing. The importance of executive functions to children's education begins in early childhood and continues throughout development. This study explores contributions of child and family factors in early childhood to the development of executive function in adolescence. Analyses draw on data from the nationally representative study, Growing up in Australia: The Longitudinal Study of Australian Children. Participants are 4819 children in the Kindergarten Cohort who were recruited at age 4-5 years. Path analyses were employed to examine contributions of early childhood factors, including family socio-economic position (SEP), parenting behaviors, maternal mental health, and a child behavioral risk index, to the development of executive function in adolescence. The influence of children's early self-regulatory behaviors (attentional regulation at 4-5 years and approaches to learning at 6-7 years) were also taken into account. A composite score for the outcome measure of executive function was constructed from scores on three Cogstate computerized tasks for assessing cognition and measured visual attention, visual working memory, and spatial problem-solving. Covariates included child gender, age at assessment of executive function, Aboriginal and Torres Strait Islander status, speaking a language other than English at home, and child's receptive vocabulary skills. There were significant indirect effects involving child and family risk factors measured at 4-5 years on executive function at age 14-15 years, mediated by measures of self-regulatory behavior. Child behavioral risk, family SEP and parenting behaviors (anger, warmth, and consistency) were associated with attentional regulation at 4-5 years which, in turn, was significantly associated with approaches to learning at 6-7 years. Both attentional regulation and approaches to learning were directly associated with executive functioning at 14-15 years. These findings suggest that children's early self-regulatory capacities are the basis for later development of executive function in adolescence when capabilities for planning and problem-solving are important to achieving educational goals.


The Complex Quorum Sensing Circuitry of Burkholderia thailandensis Is Both Hierarchically and Homeostatically Organized.
The genome of the bacterium Burkholderia thailandensis encodes three complete LuxI/LuxR-type quorum sensing (QS) systems: BtaI1/BtaR1 (QS-1), BtaI2/BtaR2 (QS-2), and BtaI3/BtaR3 (QS-3). The LuxR-type transcriptional regulators BtaR1, BtaR2, and BtaR3 modulate the expression of target genes in association with various N-acyl-l-homoserine lactones (AHLs) as signaling molecules produced by the LuxI-type synthases BtaI1, BtaI2, and BtaI3. We have systematically dissected the complex QS circuitry of B. thailandensis strain E264. Direct quantification of N-octanoyl-homoserine lactone (C8-HSL), N-3-hydroxy-decanoyl-homoserine lactone (3OHC10-HSL), and N-3-hydroxy-octanoyl-homoserine lactone (3OHC8-HSL), the primary AHLs produced by this bacterium, was performed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the wild-type strain and in QS deletion mutants. This was compared to the transcription of btaI1, btaI2, and btaI3 using chromosomal mini-CTX-lux transcriptional reporters. Furthermore, the levels of expression of btaR1, btaR2, and btaR3 were monitored by quantitative reverse transcription-PCR (qRT-PCR). We observed that C8-HSL, 3OHC10-HSL, and 3OHC8-HSL are differentially produced over time during bacterial growth and correlate with the btaI1, btaI2, and btaI3 gene expression profiles, revealing a successive activation of the corresponding QS systems. Moreover, the transcription of the btaR1, btaR2, and btaR3 genes is modulated by cognate and noncognate AHLs, showing that their regulation depends on themselves and on other QS systems. We conclude that the three QS systems in B. thailandensis are interdependent, suggesting that they cooperate dynamically and function in a concerted manner in modulating the expression of QS target genes through a successive regulatory network.IMPORTANCE Quorum sensing (QS) is a widespread bacterial communication system coordinating the expression of specific genes in a cell density-dependent manner and allowing bacteria to synchronize their activities and to function as multicellular communities. QS plays a crucial role in bacterial pathogenicity by regulating the expression of a wide spectrum of virulence/survival factors and is essential to environmental adaptation. The results presented here demonstrate that the multiple QS systems coexisting in the bacterium Burkholderia thailandensis, which is considered the avirulent version of the human pathogen Burkholderia pseudomallei and thus commonly used as an alternative study model, are hierarchically and homeostatically organized. We found these QS systems to be finely integrated into a complex regulatory network, including transcriptional and posttranscriptional interactions, and further incorporating growth stages and temporal expression. These results provide a unique, comprehensive illustration of a sophisticated QS network and will contribute to a better comprehension of the regulatory mechanisms that can be involved in the expression of QS-controlled genes, in particular those associated with the establishment of host-pathogen interactions and acclimatization to the environment.


Transglutaminase type 2 plays a key role in the pathogenesis of Mycobacterium tuberculosis infection.
Mycobacterium tuberculosis (MTB), the aetiological agent of tuberculosis (TB), is capable of interfering with the phagosome maturation pathway, by inhibiting phagosome-lysosome fusion and the autophagic process to ensure survival and replication in macrophages. Thus, it has been proposed that the modulation of autophagy may represent a therapeutic approach to reduce MTB viability by enhancing its clearance. The aim of this study was to investigate whether transglutaminase type 2 (TG2) is involved in the pathogenesis of MTB. We have shown that either genetic or pharmacological inhibition of TG2 leads to a marked reduction in MTB replicative capacity. Infection of TG2 knockout mice demonstrated that TG2 is required for MTB intracellular survival in macrophages and host tissues. The same inhibitory effect can be reproduced in vitro using Z-DON, a specific inhibitor of the transamidating activity of TG2. Massive cell death observed in macrophages that properly express TG2 is hampered by the absence of the enzyme and can be largely reduced by the treatment of wild-type macrophages with the TG2 inhibitor. Our data suggest that reduced MTB replication in cells lacking TG2 is due to the impairment of LC3/autophagy homeostasis. Finally, we have shown that treatment of MTB-infected murine and human primary macrophages with cystamine, a TG2 inhibitor already tested in clinical studies, causes a reduction in intracellular colony-forming units in human macrophages similar to that achieved by the anti-TB drug capreomycin. These results suggest that inhibition of TG2 activity is a potential novel approach for the treatment of TB.


Reliability of pre-operative biopsies in the histological grading of colorectal adenocarcinomas.
Management of colorectal cancer depends on many patient and tumour variables. Decisions are sometimes based on the histological grade of tumour as assessed by initial biopsy. This retrospective study looked at the reliability of grading colorectal cancer from pre-operative biopsies. 118 patients with a diagnosis of colorectal cancer, who had adequate pre-operative biopsies, were included in the study. A single consultant histopathologist re-examined all the preoperative biopsy slides, but was blinded to the final grading of the resection specimen. Of the 118 resection specimens, 41 were graded well-differentiated, 52 moderately differentiated and 25 poorly differentiated. When compared with postoperative grading, 37 (31%) initial biopsies were undergraded, 49 (43%) were correctly graded and 32 (26%) were overgraded. These results suggest that the histological grading of pre-operative specimens is inaccurate and should be used with caution to determine treatment. The difficulty with grading pre-operative biopsies in colorectal cancer may be owing to a lack of specific criteria such as is used in, for example, breast cancer.


The k-ZIG: flexible modeling for zero-inflated counts.
Many applications involve count data from a process that yields an excess number of zeros. Zero-inflated count models, in particular, zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models, along with Poisson hurdle models, are commonly used to address this problem. However, these models struggle to explain extreme incidence of zeros (say more than 80%), especially to find important covariates. In fact, the ZIP may struggle even when the proportion is not extreme. To redress this problem we propose the class of k-ZIG models. These models allow more flexible modeling of both the zero-inflation and the nonzero counts, allowing interplay between these two components. We develop the properties of this new class of models, including reparameterization to a natural link function. The models are straightforwardly fitted within a Bayesian framework. The methodology is illustrated with simulated data examples as well as a forest seedling dataset obtained from the USDA Forest Service's Forest Inventory and Analysis program.


A nude mouse xenograft model of fetal intestine development and differentiation.
This report describes a novel in vivo model of intestinal differentiation. Fourteen day, undifferentiated fetal rat small intestine, stripped of the major part of its mesenchyme, suspended in a type I collagen gel and then xenografted into a nude mouse, undergoes small intestinal morphogenesis and cytodifferentiation. All four major epithelial lineages, namely Paneth, goblet, columnar and endocrine are present. Double-label nonisotopic in situ hybridization, employing biotinylated and digoxigenin-labelled whole rat DNA and whole mouse DNA probes, was performed to distinguish donor cells from host cell types. The outer longitudinal smooth muscle layer, and the major part of the lamina propria, including pericryptal fibroblasts, are of host mouse origin; the inner circular smooth muscle layer is of donor rat origin. Cells of the muscularis propria and lamina propria acquired smooth muscle alpha-actin, presumably under the influence of the donor endoderm. Furthermore, this xenograft develops a host vascular network, and cells with the morphological appearance of lymphocytes are present within the intestinal epithelium. The production of chemotactic factors by the endoderm is postulated because grafting of collagen gel alone results in a minimal invasion by stromal cells which do not express smooth muscle alpha-actin.


[Differential atticoanthrotomy with type 1 tympanoplasty as the method of choice for the treatment of chronic perforating otitis media with expressed mucositis].
The authors report the results of surgical treatment of 37 patients (42 ears) presenting with chronic perforating otitis media and grade I-III mucositis. All the patients were treated by differential atticoanthrotomy with type 1 tympanoplasty. Most of them suffered seriously disturbed ventilation and drainage functions of the Eustachian tube. Mean bone conduction and air conduction audibility thresholds for the voice frequency (0.5-2 kHz) prior to surgery were 12.5 +/- 6.7 and 12.0 +/- 4.2, 14.2 +/- 4.6 and 45.1 +/- 11.7 dB, 46.2 +/- 8.4 and 58.4 +/- 8.6 dB, respectively. Large defects of the tympanic membrane necessitated the use of a composite flap (autofascia and autocartilage) as the tympanic membrane autograft. Excellent survival of the tympanic autograft was documented in 33 (78.6%) patients. The remaining 9 patients had perforations in the neotympanic membrane of different size. Mean bone conduction and air conduction audibility thresholds for the voice frequency upon discharge from the clinic were 14.3 +/- 4.2, 14.0 +/- 4.4, 16.2 +/- 4.2 and 35.9 +/- 12.4 dB, 36.2 +/- 10.4, 46.6 +/- 8.2 dB, respectively. The functional outcome of the surgical treatment further improved in half a year due to the fact that the sound-conducting system acquired a higher rigidity (mean audibility thresholds for air conduction became 32.6 +/- 8.4, 34.0 +/- 6.8, and 42.2 +/- 8.4 dB. Audibility thresholds for bone conduction remained practically unaltered compared with their vales upon discharge from the clinic.


Weight change and risk of colorectal cancer: a systematic review and meta-analysis.
Results from cohort studies of adult weight gain and risk of colorectal cancer are inconsistent. We conducted a systematic review and meta-analysis of prospective studies assessing the association of change in weight/body mass index with colorectal cancer risk. We searched Scopus and Web of Science up to June 2014 and supplemented the search with manual searches of the reference lists of the identified articles. Thirteen studies published between 1997 and 2014 were pooled by using a random-effects model, and potential heterogeneity was explored by fitting meta-regression models. The highest weight gain category, measured by weight/body mass index, compared with a reference category, was associated with increased risk of colorectal cancer (hazard ratio (HR) = 1.16, 95% confidence interval (CI): 1.08, 1.24), whereas no association was found for weight loss (HR = 0.96, 95% CI: 0.89, 1.05). There was no suggestion of heterogeneity across studies. For dose response, a 5-kg weight gain was associated with a slightly increased risk of colorectal cancer (HR = 1.03, 95% CI: 1.02, 1.05), with some heterogeneity observed (I(2) = 42%; P = 0.02), which was partially explained by sex (ratio of HRs = 1.03, 95% CI: 1.00, 1.07). In this meta-analysis, gain in weight/body mass index was positively associated with colorectal cancer risk.


Deceleration, Acceleration, and Impacts Are Strong Contributors to Muscle Damage in Professional Australian Football.
Gastin, PB, Hunkin, SL, Fahrner, B, and Robertson, S. Deceleration, acceleration, and impacts are strong contributors to muscle damage in professional Australian football. J Strength Cond Res 33(12): 3374-3383, 2019-The purpose of this study was to investigate the relationships between serum creatine kinase [CK], an indirect marker of muscle damage, and specific indices of match load in elite Australian football. Twenty-six professional players were assessed during a competitive Australian Football League (AFL) season. [CK] was collected 24-36 hours before match and 34-40 hours after match during 8 in-season rounds. An athlete-tracking technology was used to quantify match load. Generalized estimating equations and random forest models were constructed to determine the extent to which match-load indices and pre-match [CK] explained post-match [CK]. There was a 129 ± 152% increase in [CK] in response to AFL competition. Generalized estimating equations found that number of impacts >3g (p = 0.004) and game time (p = 0.016) were most strongly associated with post-match [CK]. Random forest, with considerably lower errors (130 vs. 316 U·L), found deceleration, acceleration, impacts >3g, and sprint distance to be the strongest predictors. Pre-match [CK] accounted for 11% of post-match [CK], and considerable interindividual and intraindividual variability existed in the data. Creatine kinase, an indicator of muscle damage, was considerably elevated as a result of AFL competition. Parametric and machine-learning analysis techniques found several indices of physical load associated with muscle damage during competition, with impacts >3g and high-intensity running variables as the strongest predictors. [CK] may be used as a global measure of muscle damage in field team sports such as AF, yet with some caution given cost, invasiveness, and inherent variability. Quantifying physical load and the responses to that load can guide athlete management decision-making and is best undertaken within a suite of practical, sport-specific measures, where data are interpreted individually and with an understanding of the limitations.


Ganoderma lucidum Induces Myogenesis Markers to Avert Damage to Skeletal Muscles in Rats Exposed to Hypobaric Hypoxia.
Jatwani, Arti, and Rajkumar Tulsawani. Ganoderma lucidum induces myogenesis markers to avert damage to skeletal muscles in rats exposed to hypobaric hypoxia. High Alt Med Biol. 16:000-000, 2021. Background: Hypobaric hypoxia (HH) has been reported to induce skeletal muscle loss and impair myogenesis. Aqueous extract of G. lucidum (AqGL) contains bioactive metabolites attributed to various pharmacological effects. In this study, protective effect of AqGL in ameliorating muscle mass loss following acute HH has been reported. Materials and Methods: Male Sprague-Dawley rats were divided into following five groups of six rats in each group: unexposed control (Group 1), 6 hours of HH exposure (Group 2), 6 hours of HH exposure+AqGL extract 50 mg/kg body weight (BW) (Group 3), 6 hours of HH exposure+AqGL extract 100 mg/kg BW (Group 4), and 6 hours of HH exposure+AqGL extract 200 mg/kg BW (Group 5). Experimental animals from all groups, except Group, 1 were exposed to HH, simulated altitude of 25,000 ft for 6 hours. After exposure period, gastrocnemius muscle was collected, weighed, and morphological, biochemical, and molecular markers were analyzed. Results: HH-exposed rat muscle showed significant (p < 0.05) increase in oxidative stress markers (reactive oxygen species & malondialdehyde), which was concomitant with decrease in its mass compared to controls. AqGL treatment significantly (p < 0.05) prevented muscle oxidative stress, restored reduced glutathione content, reduced protein carbonyl content and advanced oxidation protein product, and restored muscle mass loss at effective dose of 100 mg/kg BW. Furthermore, AqGL supplementation enhanced Myf5 (p < 0.01), MyoD (p < 0.01), MyoG (p < 0.05), and Mrf4 (nonsignificantly), brain-derived neurotrophic factor (p < 0.01), and interleukin 6 (p < 0.01) expression along with restoration of tumor necrosis factor alpha (p < 0.001) and myostatin (p < 0.05) in hypoxia-exposed muscle, evidencing induction of myogenesis markers. Moreover, histological analysis showed increased myocyte number; nuclei shifted toward the periphery in the treatment group supporting muscle regeneration. Conclusion: AqGL supplementation attenuates muscle mass loss by preventing oxidative stress and inducing modulation in myogenesis markers under HH environment.


Swiss Stained-Glass Panels: An Analytical Study.
The history and iconography of Swiss stained glass dating between the 16th and 18th centuries are well studied. However, the chemical and morphological characteristics of the glass and glass paints, particularly the nature of the raw materials, the provenance of the glass, and the technology used to produce it are less well understood. In this paper, we studied two sets of samples from stained-glass panels attributed to Switzerland, which date from the 16th to 17th centuries: the first set comes from Pena National Palace collection, the second from Vitrocentre Romont. The aims were to identify the materials used in the production of the glass, to find out more about their production origin and to characterize the glass paints. Both glass and the glass paints were analysed by particle-induced X-ray emission; the paints were additionally analysed by scanning electron microscopy-electron-dispersive X-ray spectroscopy (SEM-EDS). The results show that the glass from both sets was probably produced in the same region and that wood ash was used as a fluxing agent. Different recipes have been used to make the blue enamels. However, the cobalt ore used as a coloring agent in all of the blue enamels came from the mining district in Schneeberg, Germany.


Diagnosis of infective and inflammatory disorders by flow cytometric analysis of blood neutrophils.
The utility of neutrophil parameters provided by two flow cytometric hematologic analyzers (the H-1 and H6000, Technicon Instruments Corporation, Tarrytown, NY) was investigated for the diagnosis of infective and/or inflammatory disorders. The test population of 156 hospital patients was selected on the basis of a blood culture request. Positivity or negativity for infective and/or inflammatory disease was inferred from chart review. The parameters evaluated included the absolute neutrophil count, the lobularity index, and the left shift flag from the H-1, the percentage of high peroxidase cells from the H6000, the routine laboratory band count, and a reference band count. Significant intercorrelations were observed between these parameters. The diagnostic performance of the routine laboratory band count was significantly inferior to that of all other parameters. At equivalent points on their receiver operating characteristic curves, the diagnostic efficiencies of the remaining tests ranged from 61.5% for the lobularity index to 67% for the left shift flag and the percentage of high peroxidase cells. These differences were not significant statistically.


Ozone as Modulator of Resorption and Inflammatory Response in Extruded Nucleus Pulposus Herniation. Revising Concepts.
Ozone therapy has been used to treat disc herniation for more than four decades. There are several papers describing results and mechanism of action. However, it is very important to define the characteristics of extruded disc herniation. Although ozone therapy showed excellent results in the majority of spinal diseases, it is not yet fully accepted within the medical community. Perhaps it is partly due to the fact that, sometimes, indications are not appropriately made. The objective of our work is to explain the mechanisms of action of ozone therapy on the extruded disc herniation. Indeed, these mechanisms are quite different from those exerted by ozone on the protruded disc herniation and on the degenerative disc disease because the inflammatory response is very different between the various cases. Extruded disc herniation occurs when the nucleus squeezes through a weakness or tear in the annulus. Host immune system considers the nucleus material to be a foreign invader, which triggers an immune response and inflammation. We think ozone therapy modulates this immune response, activating macrophages, which produce phagocytosis of extruded nucleus pulposus. Ozone would also facilitate the passage from the M1 to M2 phase of macrophages, going from an inflammatory phase to a reparative phase. Further studies are needed to verify the switch of macrophages.


Allergenicity of peanut and soybean extracts altered by chemical or thermal denaturation in patients with atopic dermatitis and positive food challenges.
Peanuts and soybeans are two of the six most common foods to cause food hypersensitivity reactions in children. We used the serum of 10 patients with atopic dermatitis and positive double-blind, placebo-controlled, food challenges to peanut and two patients with atopic dermatitis and positive double-blind, placebo-controlled, food challenges to soybean to investigate the change in IgE-specific and IgG-specific binding to these proteins altered by either chemical or thermal denaturation. We used IgE- and IgG-specific ELISA-inhibition analyses to compare these effects on the crude peanut and crude soy extracts, as well as on the major allergenic fractions of both proteins. Heating the soy proteins at various temperatures and time intervals did not significantly change the IgE- or IgG-specific binding of the soy positive pooled serum. When the peanut proteins were subjected to similar heating experiments, the IgE- and IgG-specific binding did not change. When these same proteins were treated with enzymes in the immobilized digestive enzyme assay system used to mimic human digestion, the binding of IgE to the crude peanut and crude soy extracts was reduced; 100-fold for peanut and 10-fold for soybean. Therefore it appears that thermal denaturation of peanut and soybean protein extracts does not enhance or reduce IgE- and IgG-specific binding activity. Chemical denaturation appears to minimally reduce the binding of these proteins.


Artificial Intelligence in PET: An Industry Perspective.
Artificial intelligence (AI) has significant potential to positively impact and advance medical imaging, including positron emission tomography (PET) imaging applications. AI has the ability to enhance and optimize all aspects of the PET imaging chain from patient scheduling, patient setup, protocoling, data acquisition, detector signal processing, reconstruction, image processing, and interpretation. AI poses industry-specific challenges which will need to be addressed and overcome to maximize the future potentials of AI in PET. This article provides an overview of these industry-specific challenges for the development, standardization, commercialization, and clinical adoption of AI and explores the potential enhancements to PET imaging brought on by AI in the near future. In particular, the combination of on-demand image reconstruction, AI, and custom-designed data-processing workflows may open new possibilities for innovation which would positively impact the industry and ultimately patients.


Photoaffinity labelling of isopenicillin N synthetase by laser-flash photolysis.
Isopenicillin N synthetase (IPNS) from Acremonium chrysogenum was photolabelled by laser-flash photolysis in the presence of a diazirinyl-containing substrate, 2-[3-(3-trifluoromethyl-3H-diazirin-3-yl)-phenoxy]acetyl-S- methyloxycarbonylsulphenyl-L-cysteinyl-D-valine (DCV). Labelling of IPNS by DCV is partially inhibited in the presence of an excess of L-alpha-aminoadipoyl-L-cysteinyl-D-valine (ACV), the natural substrate. In the absence of light, DCV is converted into the corresponding penicillin with comparable Km but significantly depressed Vmax relative to ACV. Selective incorporation of [14C]DCV into IPNS has been demonstrated by fluorography of IPNS analysed by SDS/polyacrylamide-gel electrophoresis. Scintillation counting of labelled IPNS purified on an ion-exchange f.p.l.c. column confirms this result. This methodology may be applicable for studies aimed at investigating the binding of substrates to IPNS.


Recent advances in pyroptosis, liver disease, and traditional Chinese medicine: A review.
In recent years, the incidence of liver disease has increased, becoming a major cause of death. Various liver diseases are intricately linked to pyroptosis, which is one of the most common forms of programmed cell death. As a powerful weapon in the fight against liver diseases, traditional Chinese medicine (TCM) can affect pyroptosis via a number of routes, including the classical, nucleotide oligomerization domain-like receptors protein 3/caspase-1/gasdermin D (GSDMD) pathway, the nonclassical lipopolysaccharide/caspase-11/GSDMD pathway, the ROS/caspase-3/gasdermin E pathway, the caspase-9/caspase-3/GSDMD pathway, and the Apaf-1/caspase-11/caspase-3 pathway. In this review, we provide an overview of pyroptosis, the interplay between pyroptosis and liver diseases, and the mechanisms through which TCM regulates pyroptosis in liver diseases. The information used in the text was collected and compiled from the databases of PubMed, Web of Science, Scopus, CNKI, and Wanfang Data up to June 2023. The search was not limited with regard to the language and country of the articles. Research and review articles were included, and papers with duplicate results or unrelated content were excluded. We examined the current understanding of the relationship between pyroptosis and liver diseases as well as the advances in TCM interventions to provide a resource for the identification of potential targets for TCM in the treatment of liver diseases.


STUDIES ON PERMEABILITY OF MEMBRANES : V. THE DIFFUSION OF NON-ELECTROLYTES THROUGH THE DRIED COLLODION MEMBRANE.
A study has been made of the relative rates at which various organic non-electrolytes diffuse through the dried collodion membrane. It was found that acetone and urea pass through the membrane many times more rapidly than glycerine and that glycerine in its turn diffuses much faster than glucose. It was also demonstrated that the rate of diffusion varies directly with the difference in concentration between the solutions on the two sides of the membrane. It was shown that the presence of glycerine on the two sides of the membrane did not appreciably affect the rate of diffusion of acetone. In a study of the changes going on during the establishment of the stationary diffusion gradient with glucose experiments were described which strongly suggested that many of the membrane channels may gradually become clogged up with glucose molecules so that the diffusion rate decreases from day to day until the stationary gradient is finally reached. In explaining the various experimental data the conception of the collodion membrane as a sieve with pores approximating in smallness the size of individual molecules was utilized. The large differences in the diffusion rates between different substances were then referred to differences in molecular size, the relatively large molecules of glycerine and glucose being unable to pass through many of the smaller pores available for urea and acetone. From the data available it was possible to estimate that 98 per cent of the pore area distributed among holes large enough for the diffusion of acetone was unavailable for the passage of glycerine and that only 0.3 per cent of the pore area available for acetone could be utilized by glucose. In trying to correlate the ratio between the diffusion rates of two different substances with the characteristic concentration potential (Co P) given by the same membrane it was found (1) that with the acetone-glycerine ratio there is no correspondence (2) that with the acetone-glucose ratio a suggestive relation exists and (3) that with the glycerine-glucose ratio a definite correspondence can be shown, the higher ratios being obtained only with membranes giving high CO P values. A rational explanation for these facts was proposed.


MERCI 1: a phase 1 study of Mechanical Embolus Removal in Cerebral Ischemia.
To report the result of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) 1 study, a phase 1 trial to evaluate the safety and efficacy of mechanical embolectomy in the cerebral vasculature. MERCI 1 enrolled 30 patients in 7 US centers. Main inclusion criteria were: National Institutes of Health Stroke Scale score (NIHSS) > or =10; treatment performed within 8 hours from symptoms onset and contra-indication to intravenous thrombolysis; no large hypodensity on computed tomography; and occlusion of a major cerebral artery on the angiogram. Safety was defined by the absence of vascular injury or symptomatic intracranial hemorrhage. Efficacy was assessed by recanalization rate and clinical outcome at 1 month. Significant recovery was defined as 30-day modified Rankin of 0 to 2 in patients with baseline NIHSS 10 to 20 and 30-day modified Rankin of 0 to 3 in patients with baseline NIHSS >20. The procedures were performed with the Merci Retrieval System, a system specially designed for intracranial embolectomy. Twenty-eight patients were treated. Median NIHSS was 22. Median time from onset to completion of treatment was 6 hours and 15 minutes. Successful recanalization with mechanical embolectomy only was achieved in 12 (43%) patients, and with additional intra-arterial tissue plasminogen activator in 18 (64%) patients. There was one procedure related technical complication, with no clinical consequence. Twelve asymptomatic and no symptomatic intracranial hemorrhages occurred. At 1 month, 9 of 8 revascularized patients and 0 of 10 nonrevascularized patients had achieved significant recovery. This phase 1 study shows that cerebral embolectomy with the Merci Retriever was safe and that successful recanalization could benefit a significant number of patients, even when performed in an extended 8-hour time window.


Lung environment determines unique phenotype of alveolar macrophages.
Alveolar macrophages (AM) are the most abundant antigen-presenting cells in the lungs, and they play a critical role in regulating pulmonary immune responses to inhaled pathogens and to allergens. However, compared with macrophages in other body sites, AM have an unusual phenotype that, in many respects, resembles the phenotype of dendritic cells (DC). Therefore, to more fully define the unique nature of AM, we compared the phenotype and function of AM with the phenotype and function of resident peritoneal lavage-derived macrophages (PLM). We found striking phenotypic differences between AM and PLM, particularly with regard to CD11c expression, and we also observed that AM had a significantly better antigen-presenting capability than PLM. Therefore, we investigated the role of the local airway environment in generation of the unusual phenotype of AM. We carried out cell transfer experiments to compare macrophage differentiation in the airways with that in the peritoneal cavity. We observed significant upregulation of CD11c expression on bone marrow macrophages and peritoneal macrophages when they were adoptively transferred into the airways. In contrast, CD11c expression was not upregulated after cell transfer into the peritoneal cavity, whereas CD11b expression was significantly increased. In vitro, culture of bone marrow-adherent cells with surfactant protein D (SP-D) or granulocyte/macrophage colony-stimulating factor (GM-CSF) induced significant upregulation of CD11c expression, and in vivo GM-CSF concentrations were significantly higher in bronchoalveolar than in peritoneal lavage fluid. Finally, GM-CSF(-/-) mice failed to develop CD11c(+) AM, but CD11c(+) AM were present in SP-D(-/-) mice. However, macrophages from GM-CSF(-/-) bone marrow could upregulate CD11c expression when transferred to the airways of wild-type mice. These results suggest that the airway environment promotes development of macrophages with unique DC-like characteristics and that this unusual phenotype is determined, to a large degree, by locally high concentrations of GM-CSF and, possibly, SP-D.


β-Cyclocitral is a conserved root growth regulator.
Natural compounds capable of increasing root depth and branching are desirable tools for enhancing stress tolerance in crops. We devised a sensitized screen to identify natural metabolites capable of regulating root traits in Arabidopsis β-Cyclocitral, an endogenous root compound, was found to promote cell divisions in root meristems and stimulate lateral root branching. β-Cyclocitral rescued meristematic cell divisions in ccd1ccd4 biosynthesis mutants, and β-cyclocitral-driven root growth was found to be independent of auxin, brassinosteroid, and reactive oxygen species signaling pathways. β-Cyclocitral had a conserved effect on root growth in tomato and rice and generated significantly more compact crown root systems in rice. Moreover, β-cyclocitral treatment enhanced plant vigor in rice plants exposed to salt-contaminated soil. These results indicate that β-cyclocitral is a broadly effective root growth promoter in both monocots and eudicots and could be a valuable tool to enhance crop vigor under environmental stress.


Protein-tyrosine phosphatase expression in pre-B cell NALM-6.
Protein-tyrosine phosphatase (PTP)-related complementary DNAs from NALM-6 (pre-B cell line) were amplified by reverse transcriptase polymerase chain reaction using primers corresponding to the conserved catalytic domains of PTPs. Thirty-three polymerase chain reaction products, identified as PTP related complementary DNAs, were classified to RPTP-alpha, PTP1B, and 4 novel PTPs, which were designated as BPTP-1-4. Their expressions in NALM-6 and other cell lines were confirmed by Northern blot analysis. BPTP-1 and -2 exhibited extensive homology with the first and the second catalytic domains, respectively, of leukocyte common antigen related molecule (LAR) and human PTP delta. The transcriptional sizes of BPTP-1 and BPTP-2 are the same (7.2 kilobases) as that of LAR. The expression of BPTP-1 was abundant in lymphoid cell lines TALL-1 and NALM-6 but small in colon cell line BM314, which is in sharp contrast to the expression of LAR. These data suggest that the expression levels of BPTP-1 and LAR are altered in a cell specific manner, probably making them cell type associated PTPs.


Dominant negative suppression of Rad leads to QT prolongation and causes ventricular arrhythmias via modulation of L-type Ca2+ channels in the heart.
Disorders of L-type Ca2+ channels can cause severe cardiac arrhythmias. A subclass of small GTP-binding proteins, the RGK family, regulates L-type Ca2+ current (I(Ca,L)) in heterologous expression systems. Among these proteins, Rad (Ras associated with diabetes) is highly expressed in the heart, although its role in the heart remains unknown. Here we show that overexpression of dominant negative mutant Rad (S105N) led to an increase in I(Ca,L) and action potential prolongation via upregulation of L-type Ca2+ channel expression in the plasma membrane of guinea pig ventricular cardiomyocytes. To verify the in vivo physiological role of Rad in the heart, a mouse model of cardiac-specific Rad suppression was created by overexpressing S105N Rad, using the alpha-myosin heavy chain promoter. Microelectrode studies revealed that action potential duration was significantly prolonged with visible identification of a small plateau phase in S105N Rad transgenic mice, when compared with wild-type littermate mice. Telemetric electrocardiograms on unrestrained mice revealed that S105N Rad transgenic mice had significant QT prolongation and diverse arrhythmias such as sinus node dysfunction, atrioventricular block, and ventricular extrasystoles, whereas no arrhythmias were observed in wild-type mice. Furthermore, administration of epinephrine induced frequent ventricular extrasystoles and ventricular tachycardia in S105N Rad transgenic mice. This study provides novel evidence that the suppression of Rad activity in the heart can induce ventricular tachycardia, suggesting that the Rad-associated signaling pathway may play a role in arrhythmogenesis in diverse cardiac diseases.


Association between catheter ablation of atrial fibrillation and mortality or stroke.
Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. Patients who underwent catheter ablation were healthier (mean CHA2DS2-VASc score 1.4±1.4 vs 1.6±1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5±2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.


Antigenic diversity found in isolates of Plasmodium falciparum from Papua New Guinea by using monoclonal antibodies.
Monoclonal antibodies were used to demonstrate antigenic diversity in over 100 primary isolates of Plasmodium falciparum collected from one area of Papua New Guinea. The frequencies of several parasite antigens in our sample is calculated. One particular antigen which had previously been shown to be absent in one-third of established isolates collected from several countries appeared ubiquitous in our sample from Papua New Guinea. A method is presented that can be used to test for associations between antigens; the analysis also reveals whether other variables affect these associations. Several associations between antigens were revealed. In one instance, the association between two particular parasite antigens was affected by the donor's age. The importance of characterizing the antigenic structure of P. falciparum populations, and its relevance to the introduction of an antimalarial vaccine are discussed.


Expanding the Potential of the Solvent-Assisted Method to Create Bio-Interfaces from Amphiphilic Block Copolymers.
Artificial membranes, as materials with biomimetic properties, can be applied in various fields, such as drug screening or bio-sensing. The solvent-assisted method (SA) represents a straightforward method to prepare lipid solid-supported membranes. It overcomes the main limitations of established membrane preparation methods, such as Langmuir-Blodgett (LB) or vesicle fusion. However, it has not yet been applied to create artificial membranes based on amphiphilic block copolymers, despite their enhanced mechanical stability compared to lipid-based membranes and bio-compatible properties. Here, we applied the SA method on different amphiphilic di- and triblock poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PDMS-b-PMOXA) copolymers and optimized the conditions to prepare artificial membranes on a solid support. The real-time membrane formation, the morphology, and the mechanical properties have been evaluated by a combination of atomic force microscopy and quartz crystal microbalance. Then, selected biomolecules including complementary DNA strands and an artificial deallylase metalloenzyme (ADAse) were incorporated into these membranes relying on the biotin-streptavidin technology. DNA strands served to establish the capability of these synthetic membranes to interact with biomolecules by preserving their correct conformation. The catalytic activity of the ADAse following its membrane anchoring induced the functionality of the biomimetic platform. Polymer membranes on solid support as prepared by the SA method open new opportunities for the creation of artificial membranes with tailored biomimetic properties and functionality.


Volatile Organic Compound Profiles of Cystoseira corniculata (Turner) Zanardini 1841 and Ericaria amentacea (C.Agardh) Molinari and Guiry 2020 (ex. Cystoseira amentacea (C.Agardh) Bory de Saint-Vincent, 1832).
The volatile organic compounds (VOCs) of fresh (FrCC) and air-dried (DrCC) Cystoseria corniculata and fresh (FrEA) and air-dried (DrEA) Ericaria amentacea from the Adriatic Sea were investigated by headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD) and analysed by gas chromatography and mass spectrometry (GC-MS). In HS-FrCC and HS-DrCC, aliphatic compounds were dominant, with decan-5-ol as the most abundant in HS-FrCC, but in HS-DrCC pentadecane dominated. Monoterpenes (β-cyclocitral, β-citral, and β-cyclohomocitral) and sesquiterpenes (cubenol) were abundant in HS-FrCC. Notable differences between fresh and air-dried samples were found for benzene derivatives. Fatty acids and their derivatives were the most abundant in HD-FrCC and HD-DrCC. In HS-FrEA and HS-DrEA, saturated aliphatic compounds as well as unsaturated aliphatic compounds (particularly hexan-1-ol and (Z)-hex-3-en-1-ol) predominantly showed decrements after drying. Pentadecane, heptadecane, pentadecanal, and hexan-1-ol were predominant in HD-FrEA, and their percentage decreased in HD-DrEA. The percentage of monoterpenes decreased after drying, but the percentages of diterpenes and especially sesquiterpenes increased. δ-Selinene was the major terpene and the most abundant in HD-DrEA. A significant increment after drying could be noticed for fatty acids and their derivatives. The great diversity of identified VOCs among these two macroalgae supports their different botanical classifications.


A modification of the Hammett equation for predicting ionisation constants of p-vinyl phenols.
Currently there are several compounds used as drugs or studied as new chemical entities, which have an electron withdrawing group connected to a vinylic double bond in a phenolic or catecholic core structure. These compounds share a common feature--current computational methods utilizing the Hammett type equation for the prediction of ionisation constants fail to give accurate prediction of pK(a)'s for compounds containing the vinylic moiety. The hypothesis was that the effect of electron-withdrawing substituents on the pK(a) of p-vinyl phenols is due to the delocalized electronic structure of these compounds. Thus, this effect should be additive for multiple substituents attached to the vinylic double bond and quantifiable by LFER-based methods. The aim of this study was to produce an improved equation with a reduced tendency to underestimate the effect of the double bond on the ionisation of the phenolic hydroxyl. To this end a set of 19 para-substituted vinyl phenols was used. The ionisation constants were measured potentiometrically, and a training set of 10 compounds was selected to build a regression model (r2 = 0.987 and S.E. = 0.09). The average error with an external test set of six compounds was 0.19 for our model and 1.27 for the ACD-labs 7.0. Thus, we have been able to significantly improve the existing model for prediction of the ionisation constants of substituted p-vinyl phenols.


[The surgical treatment of intracranial aneurysms from the pterion approach using small trephining openings].
In the past decade, there has been a clear trend for the use of low-invasive surgical interventions in many divisions of neurosurgery. Since each operation is bound to be followed by tissue traumatization, a decrease in the sizes of skull trepanation should be regarded as a way of reducing the incidence of intra- and extracranial complications. The proposed variant of a pterion access to intracranial aneurysms by using small trepanation holes may substantially decrease the duration of surgical interventions and to avoid postoperative epidural and subdural hematomas without preventing the visualization of arteries in both anterior and posterior Willis' circle and at the same time the variant exerts no negative effect on the possibilities of hemostasis in intraoperative aneurysm rupture. The operation yields a good cosmetic effect.


New plant growth-modifying properties of the Agrobacterium T-6b oncogene revealed by the use of a dexamethasone-inducible promoter.
Agrobacterium 6b oncogenes induce tumours on Nicotiana glauca and enations and associated modifications in transgenic N. tabacum plants. 2x35S-AB-6b tobacco rootstocks produced a graft-transmissible factor that induced enations in wild-type scions; the nature of this enation factor remains to be identified. Here, we report on the properties of tobacco plants carrying a dexamethasone-inducible T-6b gene (dex-T-6b). Induction with dex led to complex growth modifications, many of which have not been reported previously. Modifications were only found in growing tissues; mature tissues remained unaffected. Growth could be either stimulated or inhibited. Dex induction of young plants led to morphogenetic gradients that included enations, tubular leaves and fragmented leaf primordia. Root elongation was increased or slowed down, while radial root growth was strongly enhanced. Additional cell divisions were found in the root pericycle and vasculature. Enation factor import from mature tissues did not have the same effects on growing tissues as local T-6b synthesis: normal scions grafted on induced dex-T-6b rootstocks formed enations, whereas local dex-T-6b induction at the shoot apex led to numerous dark-green spots on the abaxial side of the leaves. In leaf patch assays, the 23-kDa T-6b protein was found to move through leaves and to enter the vascular system. This and the fact that rootstocks of spontaneous tobacco enation mutants did not modify wild-type scions contrary to 6b plants indicate that the 6b protein might be the enation factor.


Can patient-reported outcome measures be used to predict consultation needs in patients with psoriasis?: A survey study.
Patient-reported outcome measures (PROMs) are emerging tools used to capture a patient's daily health status and enhance communication between patients and healthcare professionals. This study examined whether PROMs can be used to predict consultation needs in an outpatient clinic setting including patients diagnosed with psoriasis. We evaluated a nationally developed set of PROMs for psoriasis patients, which included a standard set of questionnaires that capture patients' perceptions of their experience and quality of life. Patients (n = 187) answered the psoriasis PROMs prior to an in-person consultation. Their responses were evaluated alongside patient, doctor, and nurse opinions on whether the subsequent consultation was necessary. Additionally, comments about the consultations from the patient, doctor, and nurse were collected and provided insights as to why certain consultations were deemed necessary. Comparing the patient, doctor, and nurse responses addressing a need for consultation compared to the coded psoriasis PROMs results (red or green/yellow outcome), 23% of the patients with a green/yellow outcome were in need of a doctor's consultation. Upon considering a subset of psoriasis PROMs questionnaires that reflect subjective responses (e.g., DLQI, PEST, MDI-2, and side effects), the proportion of patients that yielded a green/yellow outcome and were identified to require a doctor consultation increased to approximately 45%. The preliminary results show that the psoriasis PROMs were supportive in the consultation but alone cannot sufficiently guide healthcare professionals to determine whether in-person consultations are required.


A Predictive Model for Severe COVID-19 in the Medicare Population: A Tool for Prioritizing Primary and Booster COVID-19 Vaccination.
Recommendations for prioritizing COVID-19 vaccination have focused on the elderly at higher risk for severe disease. Existing models for identifying higher-risk individuals lack the needed integration of socio-demographic and clinical risk factors. Using multivariate logistic regression and random forest modeling, we developed a predictive model of severe COVID-19 using clinical data from Medicare claims for 16 million Medicare beneficiaries and socio-economic data from the CDC Social Vulnerability Index. Predicted individual probabilities of COVID-19 hospitalization were then calculated for population risk stratification and vaccine prioritization and mapping. The leading COVID-19 hospitalization risk factors were non-white ethnicity, end-stage renal disease, advanced age, prior hospitalization, leukemia, morbid obesity, chronic kidney disease, lung cancer, chronic liver disease, pulmonary fibrosis or pulmonary hypertension, and chemotherapy. However, previously reported risk factors such as chronic obstructive pulmonary disease and diabetes conferred modest hospitalization risk. Among all social vulnerability factors, residence in a low-income zip code was the only risk factor independently predicting hospitalization. This multifactor risk model and its population risk dashboard can be used to optimize COVID-19 vaccine allocation in the higher-risk Medicare population.


Factors associated with presenteeism among employed Australian adults reporting lifetime major depression with 12-month symptoms.
Employees experiencing depression can take a sickness absence or continue working ('presenteeism'). However, little is known about the factors associated with these behaviors within this population. This study aimed to determine the relative importance of socio-demographic, financial, work and health-related factors associated with presenteeism. The 2007 Australian National Survey of Mental Health and Wellbeing provided data from employed individuals reporting lifetime major depression with 12-month symptoms (N=320). Survey adjusted multivariable logistic regression assessed classification of 12-month, depression-related presenteeism on the basis of socio-demographic, financial, work and health factors. Acceptable classification of cases was 70% or greater. Classification of cases based on socio-demographic factors, age, sex and marital status, was reasonable (62%). Adding work factors (work hours and occupation type) produced a 1% increase in successfully classified cases (63%). Health factors further increased correctly classified cases (67%). Marital status, housing tenure and co-morbid mental disorders were important indicators of presenteeism behavior. Work-related variables were restricted to available measures. Potentially important psychosocial work environment factors were unavailable. Cross-sectional data precluded causal inference. Using available factors, model discrimination did not reach an acceptable level i.e. 70% of presenteeism cases successfully classified. This highlighted the contribution of unmeasured factors to presenteeism behavior. Future research should explore the relative importance of psychosocial work environment and personality factors such as work demands, effort/reward imbalance and conscientiousness. The identified associations between socio-demographic, financial and health factors on work attendance behaviors could inform disease management guidelines for employers via recognition of employees at risk of presenteeism.


Game format alters the physiological and activity demands encountered during small-sided football games in recreational players.
Conditioning in the form of football small-sided games (SSG) is being increasingly utilized as a health-promoting and performance-enhancing activity. The aim of this study was to quantify and compare the physiological responses and activity demands encountered during 3-a-side, 4-a-side, and 5-a-side football SSG in recreational players. Heart rate, blood lactate (BLa), rating of perceived exertion (RPE) and activity demands were measured across 2 × 20-min football sessions played on a 40 × 20-m pitch in 12 recreationally active college students. Data were collected over a period of two weeks using a repeated-measures crossover design. Mean heart rate was higher (moderate) during 5-a-side than 4-a-side (p = 0.02) and 3-a-side SSG (p < 0.001). BLa tended to be higher (small) in 3-a-side compared to 4-a-side (p = 0.12) and 5-a-side SSG (p = 0.46). The total distance covered was lower (large) during 5-a-side than 4-a-side SSG (p = 0.02), while the total number of accelerations (p = 0.01) and decelerations (p = 0.02) were higher (large) during 5-a-side than 4-a-side SSG. These data suggest: 1) 5-a-side SSG require a greater intermittent workload and exacerbated HR responses; 2) 4-a-side SSG require more sustained activity (distance); and 3) 3-a-side SSG result in higher BLa compared to other SSG formats. The observed intermittent workload and exacerbated HR response in 5-a-side SSG were likely due to greater turnover rates with more frequent interceptions. Sustained activity in 4-a-side SSG might be underpinned by format-specific structures permitting optimal team work, while isolated guarding of players in 3-a-side SSG may have exacerbated BLa responses.


Applied optics at corning glass works.
Corning Glass Works was established at Corning, New York, 100 years ago, and a research laboratory was formally established sixty years ago. For more than the 100 years, however, the company has applied scientific methods in its operations. A historical review is made of the research and development work at Corning that has led to new materials and new uses for materials used in a wide variety of applications of optical sciences.The author is with the Research and Development Laboratories, Corning Glass Works, Corning, New York 14830.


Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors.
We have previously reported that genetically increased angiotensin-converting enzyme levels, or absence of the bradykinin B2 receptor, increase kidney damage in diabetic mice. We demonstrate here that this is part of a more general phenomenon - diabetes and, to a lesser degree, absence of the B2 receptor, independently but also largely additively when combined, enhance senescence-associated phenotypes in multiple tissues. Thus, at 12 months of age, indicators of senescence (alopecia, skin atrophy, kyphosis, osteoporosis, testicular atrophy, lipofuscin accumulation in renal proximal tubule and testicular Leydig cells, and apoptosis in the testis and intestine) are virtually absent in WT mice, detectable in B2 receptor-null mice, clearly apparent in mice diabetic because of a dominant mutation (Akita) in the Ins2 gene, and most obvious in Akita diabetic plus B2 receptor-null mice. Renal expression of several genes that encode proteins associated with senescence and/or apoptosis (TGF-beta1, connective tissue growth factor, p53, alpha-synuclein, and forkhead box O1) increases in the same progression. Concomitant increases occur in 8-hydroxy-2'-deoxyguanosine, point mutations and deletions in kidney mitochondrial DNA, and thiobarbituric acid-reactive substances in plasma, together with decreases in the reduced form of glutathione in erythrocytes. Thus, absence of the bradykinin B2 receptor increases the oxidative stress, mitochondrial DNA damage, and many senescence-associated phenotypes already present in untreated Akita diabetic mice.


Approaches to community-based palliative care provision by children's hospices in the UK.
The number of children in the UK with life-limiting conditions and the demand for home-based palliative care is increasing. Children's hospices remain a dominant provider of palliative care. This study aimed to determine the approaches taken by children's hospices across the UK in meeting the planned and unplanned health needs of children and their families who receive palliative care at home. In addition, the survey aimed to identify the professional composition of community teams and the number of children and families supported by each service. An internet-based questionnaire survey was sent to all children's hospices in the UK, comprising ten questions exploring the size of the team, geographical areas covered, workforce composition, services offered and approaches to managing unplanned, out of hours care. Responses were received from 14 (26%) of the hospices. A total of 1,618 children and their families were being cared for by these hospices, of whom 825 received care at home. Registered nurses constituted the greatest proportion of staff and were employed by all teams. Care provided at home was broadly split into two categories: planned short breaks and responsive palliative nursing. The latter comprised advance care planning, anticipatory prescribing and active symptom control. Out of hours care was usually offered in the form of telephone support. Models of community-based care are evolving to include nurses practising at specialist and advanced levels, allowing more children with increasingly complex conditions to be cared for at home.


Genomic epidemiology and characterization of Staphylococcus aureus isolates from raw milk in Jiangsu, China: emerging broader host tropism strain clones ST59 and ST398.
Staphylococcus aureus is highly pathogenic and can cause disease in both humans and domestic animals. The aim of this study was to investigate the genomic epidemiology of S. aureus isolates from raw milk in Jiangsu Province, China, to identify predominant lineages and their associated genomic and phenotypic characteristics. In this study, we identified 117 S. aureus isolates collected from 1,062 samples in Jiangsu Province between 2021 and 2022. Based on whole-genome sequencing (WGS) data from 117 S. aureus isolates, molecular analyses indicated CC1-ST1 (26.50%, 31/117), CC97-ST97 (18.80%, 22/117), CC398-ST398 (10.26%, 12/117), CC8-ST630 (7.69%, 9/117) and CC59-ST59 (2.56%, 3/117) were the major lineages. The prevalence of mecA-positive strains was 11.11%. Four methicillin-resistant S. aureus (MRSA) lineages were found, including MRSA-ST59-t172 (n = 3), OS-MRSA-ST398-t011 (n = 1), MRSA-ST630-t2196 (n = 2) and OS-MRSA-ST630-t2196 (n = 7). Phenotypic resistance to penicillin (30.77%, 36/117), ciprofloxacin (17.09%, 20/117) and erythromycin (15.38%, 18/117) was observed which corresponded with resistance genotypes. All of the isolates could produce biofilms, and 38.46% (45/117) of isolates had invasion rates in mammary epithelial cells (MAC-T) of greater than 1%. Interestingly, most biofilm-producing and invading isolates harbored ebp-icaA-icaB-icaC-icaR-clfA-clfB-fnbA-fnbB-sdrC-sdrD-sdrE-map-can (27.35%, 32/117) and ebp-icaA-icaB-icaC-icaD-icaR-clfA-clfB-fnbA-fnbB-sdrC-sdrD-sdrE-map (33.33%, 39/117) adherence-associated gene patterns and belonged to lineages CC1 and CC97, respectively. Virulence factor assays showed that 47.01% of the isolates contained at least enterotoxin genes. Isolates harboring the immune evasion cluster (IEC) genes (sea, sak, chp, and scn) were predominantly categorized as STs 464, 398, and 59. IEC-positive ST398 and ST59 isolates contained a very high proportion of virulence genes located on prophages, whereas most IEC-negative ST398 clade isolates carried broad-spectrum drug resistance genes. Meanwhile, the IEC-positive ST398 clade showed a close genetic relationship with isolates from the pork supply chain and hospital surgical site infections. MRSA-ST59 strains showed the closest genetic relationship with an isolate from quick-frozen products. High-risk livestock-associated strains ST398 and MRSA-ST59 were detected in raw milk, indicating a potential public health risk of S. aureus transmission between livestock and humans. Our study highlights the necessity for S. aureus surveillance in the dairy industry.


Functional reconstitution of a voltage-gated potassium channel in giant unilamellar vesicles.
Voltage-gated ion channels are key players in cellular excitability. Recent studies suggest that their behavior can depend strongly on the membrane lipid composition and physical state. In vivo studies of membrane/channel and channel/channel interactions are challenging as membrane properties are actively regulated in living cells, and are difficult to control in experimental settings. We developed a method to reconstitute functional voltage-gated ion channels into cell-sized Giant Unilamellar Vesicles (GUVs) in which membrane composition, tension and geometry can be controlled. First, a voltage-gated potassium channel, KvAP, was purified, fluorescently labeled and reconstituted into small proteoliposomes. Small proteoliposomes were then converted into GUVs via electroformation. GUVs could be formed using different lipid compositions and buffers containing low (5 mM) or near-physiological (100 mM) salt concentrations. Protein incorporation into GUVs was characterized with quantitative confocal microscopy, and the protein density of GUVs was comparable to the small proteoliposomes from which they were formed. Furthermore, patch-clamp measurements confirmed that the reconstituted channels retained potassium selectivity and voltage-gated activation. GUVs containing functional voltage-gated ion channels will allow the study of channel activity, distribution and diffusion while controlling membrane state, and should prove a powerful tool for understanding how the membrane modulates cellular excitability.


Sex differences in perceived weight-based stigmatization among African Americans.
This study examined sex differences in calculated and perceived weights and weight-based stigmatization. 371 African Americans (females=258) responded to a health and wellness survey. Body mass index (BMI) was calculated from self-reported height and weight and categorized as underweight (7.0%), normal (48.2%), overweight (29.9%), and obese (14.8%). Perceived weight was measured by asking participants, "Do you consider yourself to be overweight?" Responses were then dichotomized as accurate or inaccurate. Stigmatization was constructed from 16 statements regarding perceived treatment due to weight status. Males and females differed in their perceptions of their weights. More than 20% of the participants had inaccurate perceptions of their weights, with the majority of the inaccurate participants (82.5%) perceiving their weight status lower than their actual weight status. More overweight or obese males than overweight or obese females did not perceive themselves as overweight (60.3% vs. 28.3%, respectively, P <.001). While male and female perceptions of weight-based stigmatization were not statistically different (P = .071), participants who accurately perceived themselves to be overweight had higher perceived weight-based stigma scores than inaccurate participants who were overweight (P =.001). Males and females who were inaccurate were less likely to perceive weight-based stigmatization.


A review of the pharmacotherapeutic considerations for managing epilepsy in people with autism.
Autism, like other neurodevelopmental disorders (NDDs), has a strong association with epilepsy. There are known common genetic pathways in both autism and epilepsy. There are also specific genetic syndromes associated with both complex epilepsy and the autism phenotype. This review explores the evidence for common genetic etiologies and pathophysiological pathways in relation to both epilepsy and autism. Autism with comorbid epilepsy are associated with a high prevalence of medical and psychiatric comorbidities. This paper discusses how this influences assessment, treatment, and outcomes. The evidence for the treatment of specific seizure types in the context of NDDs is also examined alongside clinical commentary. Despite the strong association, there is a limited evidence base to support the efficacy and tolerability of anti-seizure medications specifically in autism, with no Level 1 evidence or National Guidance available. Autism and epilepsy should be approached under a NDD model with cautious introduction and titration of anti-seizure medication. Alongside this, there is evidence to support a move toward precision medicine in specific genetic syndromes such as Tuberous Sclerosis Complex and other genetic seizure disorders. The first-line treatments that should be considered for focal seizures include carbamazepine, lamotrigine, and levetiracetam.


Active and dormant microorganisms on glacier surfaces.
Glacier and ice sheet surfaces host diverse communities of microorganisms whose activity (or inactivity) influences biogeochemical cycles and ice melting. Supraglacial microbes endure various environmental extremes including resource scarcity, frequent temperature fluctuations above and below the freezing point of water, and high UV irradiance during summer followed by months of total darkness during winter. One strategy that enables microbial life to persist through environmental extremes is dormancy, which despite being prevalent among microbial communities in natural settings, has not been directly measured and quantified in glacier surface ecosystems. Here, we use a combination of metabarcoding and metatranscriptomic analyses, as well as cell-specific activity (BONCAT) incubations to assess the diversity and activity of microbial communities from glacial surfaces in Iceland and Greenland. We also present a new ecological model for glacier microorganisms and simulate physiological state-changes in the glacial microbial community under idealized (i) freezing, (ii) thawing, and (iii) freeze-thaw conditions. We show that a high proportion (>50%) of bacterial cells are translationally active in-situ on snow and ice surfaces, with Actinomycetota, Pseudomonadota, and Planctomycetota dominating the total and active community compositions, and that glacier microorganisms, even when frozen, could resume translational activity within 24 h after thawing. Our data suggest that glacial microorganisms respond rapidly to dynamic and changing conditions typical of their natural environment. We deduce that the biology and biogeochemistry of glacier surfaces are shaped by processes occurring over short (i.e., daily) timescales, and thus are susceptible to change following the expected alterations to the melt-regime of glaciers driven by climate change. A better understanding of the activity of microorganisms on glacier surfaces is critical in addressing the growing concern of climate change in Polar regions, as well as for their use as analogues to life in potentially habitable icy worlds.


Graph rigidity reveals well-constrained regions of chromosome conformation embeddings.
Chromosome conformation capture experiments result in pairwise proximity measurements between chromosome locations in a genome, and they have been used to construct three-dimensional models of genomic regions, chromosomes, and entire genomes. These models can be used to understand long-range gene regulation, chromosome rearrangements, and the relationships between sequence and spatial location. However, it is unclear whether these pairwise distance constraints provide sufficient information to embed chromatin in three dimensions. A priori, it is possible that an infinite number of embeddings are consistent with the measurements due to a lack of constraints between some regions. It is therefore necessary to separate regions of the chromatin structure that are sufficiently constrained from regions with measurements that do not provide enough information to reconstruct the embedding. We present a new method based on graph rigidity to assess the suitability of experiments for constructing plausible three-dimensional models of chromatin structure. Underlying this analysis is a new, efficient, and accurate algorithm for finding sufficiently constrained (rigid) collections of constraints in three dimensions, a problem for which there is no known efficient algorithm. Applying the method to four recent chromosome conformation experiments, we find that, for even stringently filtered constraints, a large rigid component spans most of the measured region. Filtering highlights higher-confidence regions, and we find that the organization of these regions depends crucially on short-range interactions. Without performing an embedding or creating a frequency-to-distance mapping, our proposed approach establishes which substructures are supported by a sufficient framework of interactions. It also establishes that interactions from recent highly filtered genome-wide chromosome conformation experiments provide an adequate set of constraints for embedding. Pre-processing experimentally observed interactions with this method before relating chromatin structure to biological phenomena will ensure that hypothesized correlations are not driven by the arbitrary choice of a particular unconstrained embedding. The software for identifying rigid components is GPL-Licensed and available for download at http://cbcb.umd.edu/kingsford-group/starfish.


Increased carbon dioxide production in two patients with malignant hyperpyrexia and its control by dantolene.
Two patients with successfully treated malignant hyperpyrexia are reported. Carbon dioxide output, calculated from the respiratory minute volume and PaCO2, was found to be greatly increased in both patients. In the patient who received dantolene 7.5 mg kg-1 the carbon dioxide output decreased rapidly to normal values, whereas in the other patient carbon dioxide output remained increased for several hours.


Hemorrhagic cystitis after bone marrow transplantation. Risk factors and complications.
Hemorrhagic cystitis (HC) is a major cause of morbidity after BMT; we have analyzed its incidence, risk factors, and complications in 977 patients undergoing BMT between 1974 and 1988. Despite vigorous hydration and frequent voiding in all patients receiving cyclophosphamide, 135/977 (15% by Kaplan-Meier projection) developed HC (micro- or gross hematuria, dysuria, bladder pain) between -11 and +100 days (median +22) after BMT. Of these, 60 had severe HC, including major urinary obstruction (4/60), renal failure (13/60), or need for surgical or chemical bladder cauterization (16/60). By univariate analysis, allogeneic BMT recipients had more frequent HC than autologous patients (17% vs. 9%, P = 0.002). In addition, allogeneic patients with adenoviruria were at increased risk for the development of HC. Patients with aplastic anemia conditioned with high dose cyclophosphamide and total lymphoid irradiation had the highest rate of HC (22%) versus those with hematologic malignancies (15%, P = 0.03). A Cox proportional hazards regression model was used to further identify those factors independently associated with HC. In all regression models, the factor most highly associated with the development of HC was the finding of adenovirus in the urine preceding the onset of hematuria. HC-related morbidity, and its associated increased hospitalization costs, frequently complicates BMT. Improved prophylactic measures, perhaps including the use of 2-mercaptoethane sulfonate, are needed, at least for allogeneic BMT patients with their attendant risk of adenovirus infection.