Selective modulation of the prostaglandin F2α pathway markedly impacts on endometriosis progression in a xenograft mouse model.
Selective activation or blockade of the prostaglandin (PG) F2α receptor (FP receptor) affects ectopic endometrial tissue growth and endometriosis development. FP receptor antagonists might represent a promising approach for the treatment of peritoneal endometriosis. Eutopic and ectopic endometrium from women with endometriosis exhibit higher expression of key enzymes involved in the PGF2α biosynthetic pathway. It has also been shown that the PGF2α-FP receptor interaction induces angiogenesis in human endometrial adenocarcinoma. For this study, a mouse model of endometriosis was developed by inoculating human endometrial biopsies into the peritoneal cavity of nude mouse (n = 15). Mice were treated with AL8810 (FP receptor antagonist), Fluprostenol (FP receptor agonist) or PBS. Endometriosis-like lesions were collected and analysed for set of markers for angiogenesis, tissue remodelling, apoptosis, cell proliferation and capillary formation using qPCR and immunohistochemistry. We found that selective inhibition of the FP receptor with a specific antagonist, AL8810, led to a significant decline in the number (P < 0.01) and size of endometriosis-like lesions (P < 0.001), down-regulated the expression of key mediators of tissue remodelling (MMP9, P < 0.05) and angiogenesis (VEGF, P < 0.01) and up-regulated the pro-apoptotic factor (Bax, P < 0.01) as compared with controls. Immunohistochemical analyses further showed a marked decrease in cell proliferation and capillary formation in endometrial implants from AL8810-treated mice, as determined by proliferating cell nuclear antigen (PCNA) and von Willebrand factor (vWF) immunostaining, respectively. Moreover, Fluprostenol, a selective FP receptor agonist, showed the opposite effects. We carried out this study in nude mice, which have low levels of endogenous estrogens which may affect the lesion growth. Caution is required when interpreting these results to women. This study extends the role of PG signalling in endometriosis pathogenesis and points towards the possible relevance of selective FP receptor antagonism as a targeted treatment for endometriosis. Not Applicable. This work was supported by grant MOP-123259 to the late Dr Ali Akoum from the Canadian Institutes for Health Research. The authors have no conflict of interest.


Newton's constant and the twenty-first century laboratory.
The main aim of this paper is to describe the problems that confront experimentalists who attempt to determine Newton's constant of gravitation, G. I will motivate this work by discussing the role of Newton's constant of gravitation in classical physics and recent ideas as to its role in quantum physics. I will then discuss some key aspects of a precision determination of G. This will include criteria for the selection of the detector of the gravitational torque from the point of view of random uncertainties due to read-out noise, thermal and vibrational noise. Another important factor in precise determinations of G is the control of systematic effects (type B uncertainties) such as those due to uncertainties in absolute calibration of the gravitational torque, density homogeneity of source masses and length metrology. I will illustrate the discussion using the determination of G currently underway at the International Bureau of Weights and Measures in France, and describe other experimental configurations that have been used in the past or are being currently developed.


Knee extensor fatigue developed during high-intensity exercise limits lower-limb power production.
We investigated the association between changes in vastii electromyography (EMG) and knee extensor fatigue during high-intensity cycling, and the subsequent effect on lower-limb power and intermuscular coordination during all-out cycling. On two separate days, participants completed 30-s all-out cycling or 10-min of high-intensity cycling followed by 30-s all-out cycling. EMG for gluteus maximus (GMAX), rectus femoris (RF), vastii (VAS), hamstrings (HAM) and gastrocnemius (GAS); co-activation for GMAX/RF, VAS/HAM and VAS/GAS; isometric maximal voluntary force (IMVF) and resting twitch (RT) of the knee extensors were measured. VAS EMG increases during high-intensity cycling (6% to 14%, P < 0.05) were negatively correlated (r = -0.791, P < 0.05) with knee extensor IMVF decreases (-2% to-36%, P < 0.05) following the exercise. Knee extensor IMVF decreases were positively correlated (r = 0.757, P < 0.05) with all-out cycling power reductions (0% to -27%, P < 0.05). VAS/GAS co-activation did not change (P > 0.05) during all-out cycling while VAS and GAS EMG decreased. Larger increase in VAS EMG during high-intensity cycling was associated with greater knee extensor fatigue and larger power reduction during all-out cycling. High VAS/GAS co-activation potentially limited power reduction induced by knee extensor fatigue during all-out cycling.


Anthropometric, metabolic and molecular determinants of human epidermal growth factor receptor 2 expression in luminal B breast cancer.
Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors, and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (<25 vs ≥25), pre-treatment fasting glucose (<median value of 94 mg/dl vs. ≥94) and percentage of hormone receptors were tested for association with HER2 expression in regression models. In univariate models, BMI, fasting glucose and, at a lesser extent, percentage of estrogen receptors (ER) were significantly and inversely associated with HER2 expression (OR: 0.32, 95% CI: 0.16-0.66; 0.43, 0.23-0.82; 0.96, 0.94-0.97, respectively). The multivariate models confirmed the protective role of BMI and ER on HER2 expression, with luminal B HER2 positive patients being significantly less frequent among women within the highest category of BMI and percentage expression of ER compared with their counterparts (OR: 0.22, 95% CI: 0.09-0.53; 0.95, 0.93-0.97). In conclusions, BMI and percentage of ER representation are inversely associated with HER2 expression in luminal B breast cancers. Upon confirmatory findings, this might help identify patient subgroups who may best benefit from the use of interventions targeting insulin resistance in well depicted breast cancer scenarios.


[Role of musculocutaneous nerve in the relationship between "chutse" acupoint and heart].
Ligating fourty eight rabbits left ventricular branch of coronary artery made model of acute myocardial infarction (AMI) with indices of ECG and size of AMI. They were divided at random into four groups: "Chutse" acupoint group, cutting musculocutaneous nerve of "Chutse" acupoint group, cutting musculoutaneous nerve group, control group. Results showed that there is no role in laser acupuncture at "Chutse" acupoint for reducing myocardial injury and size of AMI after cutting musculocutaneous nerve of "Chutse" acupoint. It is illustrated that the musculocutaneous nerve might play an important role in the relationship between "Chutse" acupoint and heart.


[Facial erysipelas].
Facial erysipelas is quite uncommon today in Denmark. However, as the disease may be fatal without the proper treatment, the necessity for definite diagnosis is stressed on the basis of a case.


Real-time signal processing system based on FPGA for motional Stark effect diagnostic on EAST.
The plasma current density profile plays a key role in the development of a high poloidal beta scenario, which is essential for long-pulse and high-performance plasma operation on a tokamak. Based on the polarimetry technique, a Motional Stark Effect (MSE) diagnostic has been built on the Experimental Advanced Superconducting Tokamak. To be prepared for real-time (RT) feedback control of the plasma current density profile in the future, a RT signal processing system has been developed. The RT signal processing system is composed of three functional modules: analog-to-digital conversion (ADC) module, polarization information extraction module, and digital-to-analog conversion (DAC) module. The final objective of this system is to acquire the polarization information of the MSE. Based on the field-programmable gate array unit, fast Fourier transformation is adopted to process the Photoelastic Modulator (PEM) digital signal, which was converted from a PEM signal via the ADC module. By means of frequency spectrum separation, the components around double modulating frequencies are restored through inverse fast Fourier transformation. Furthermore, the two amplitudes of their corresponding components can be obtained through a digital harmonic analyzer technique. Afterward, the ratio of the two amplitudes is calculated by arc tangent so that the polarization angle is obtained. Finally, the information of this polarization angle is converted into a voltage signal by the DAC module and then output in RT. The test results based on the RT signal processing system are in good agreement with those based on the phase lock-in amplifiers. The working cycle of this system is shorter than 10 ms, which meets the requirements of the MSE diagnostic as a RT controller. The algorithm of RT signal processing and the relevant technology applied for building this system are presented in the main body of this paper in detail.


Associations of adiposity with prevalent coronary heart disease among elderly men: the Honolulu Heart Program.
To assess associations of adiposity with prevalent coronary heart disease (CHD) among elderly men. A cross-sectional epidemiologic study conducted between 1991 and 1993. 3741 Japanese-American men from the Honolulu Heart Program who were 71-93 y of age. CHD included documented myocardial infarction (electrocardiographic and enzyme criteria), acute coronary insufficiency, angina pectoris leading to surgical treatment identified through hospital surveillance, and reported history of heart attach or angina pectoris requiring hospitalization or surgical treatment. BMI was calculated as weight in kg divided by height in square meters. Waist circumference was measured at the horizontal level of the umbilicus and WHR was a ratio of waist circumference to hip circumference measured at the horizontal level of the maximal protrusion of the gluteal muscles. An elevated prevalence of CHD was observed in the elderly men with high BMI, WHR and waist circumference. The significant associations of BMI and waist circumference with CHD persisted after adjustment for fasting glucose, physical activity and pack-years of cigarette smoking but were no longer significant (odds ration (OR) = 1.03, 95% confidence level (CI) 0.94-1.12 and OR = 1.09, CI = 0.99-1.20, respectively) after adjustment for high density lipoprotein cholesterol (HDL-C). Also, the association of BMI with CHD was not found to be independent of abdominal adiposity. However, the associations of WHR and waist circumference remained significant (OR = 1.20, CI = 1.08-1.33 and OR = 1.17, CI = 1.01-1.37, respectively) after additional adjustment for BMI. In addition, the association of WHR with CHD was consistently significant and independent of fasting glucose, physical activity, smoking and HDL-C (OR = 1.11, CI = 1.00-1.23). WHR is associated with CHD independent of HDL-C and BMI, whereas the relation of BMI and waist circumference with CHD may be mediated through a relation of BMI and waist circumference with HDL-C level.


Distribution of phenotypic and genotypic antimicrobial resistance and virulence genes in Vibrio parahaemolyticus isolated from cultivated oysters and estuarine water.
A total of 594 Vibrio parahaemolyticus isolates from cultivated oysters (n = 361) and estuarine water (n = 233) were examined for antimicrobial resistance (AMR) phenotype and genotype and virulence genes. Four hundred forty isolates (74.1%) exhibited resistance to at least one antimicrobial agent and 13.5% of the isolates were multidrug-resistant strains. Most of the V. parahaemolyticus isolates were resistant to erythromycin (54.2%), followed by sulfamethoxazole (34.7%) and trimethoprim (27.9%). The most common resistance genes were qnr (77.8%), strB (27.4%) and tet(A) (22.1%), whereas blaTEM (0.8%) was rarely found. Four isolates (0.7%) from oysters (n = 2) and estuarine water (n = 2) were positive to tdh, whereas no trh-positive isolates were observed. Significantly positive associations among AMR genes were observed. The SXT elements and class 1, 2 and 3 integrons were absent in all isolates. The results indicated that V. parahaemolyticus isolates from oysters and estuarine water were potential reservoirs of resistance determinants in the environment. This increasing threat of resistant bacteria in the environment potentially affects human health. A 'One Health' approach involved in multidisciplinary collaborations must be implemented to effectively manage antimicrobial resistance.


Use of anti-osteoporosis medication dispensing by patients with hip fracture: could we do better?
Although Scandinavian countries have the highest incidence of hip fracture in the world, trends in anti-osteoporosis medication use have not been studied. We found less than one-third of Danish hip fracture patients had dispensing of anti-osteoporosis medication over a 10-year period using routinely collected data from population-based registries. To examine trend in dispensing of anti-osteoporosis medication before and after hip fracture surgery in Denmark over a 10-year period using routinely collected data from population-based registries. From the Danish Multidisciplinary Hip Fracture Registry, we included 65,011 patients aged 65 years or older with an incident hip fracture in 2005-2015. We calculated, for each calendar year of hip fracture diagnosis, the prevalence of use of anti-osteoporosis medication (at least one dispensing of bisphosphonates, strontium ranelate, denosumab, selective estrogen receptor modulators, or teriparatide) in the year before and in the year following hip fracture diagnosis. Among those without a dispensing in the year before hip fracture, we computed 1-year cumulative incidence of use following hip fracture. We treated death as a competing risk and stratified the analysis on sex, age, and comorbidity. The prevalence of use before hip fracture varied between 7 and 12%, increasing slightly from 2005 to 2015. The cumulative incidence of use following hip fracture decreased from 16% in 2005 to 13% in 2010, whereupon it increased to 20%. A similar pattern was seen with each stratum of sex, age groups, and comorbidity. The overall prevalence of use after hip fracture was below 22% in all calendar years. Less than one-third of hip fracture patients had dispensing of anti-osteoporosis medication up to 1 year after hip fracture. We observed only a slight increase in dispensing after hip fracture over the study period, irrespective of patient sex, age, and comorbidity at the time of hip fracture.


Domain organization and quaternary structure of the Saccharomyces cerevisiae silent information regulator 3 protein, Sir3p.
The silent information regulator protein 3 (Sir3p) functions in the initiation, propagation, and maintenance of transcriptionally silenced chromatin in Saccharomyces cerevisiae. To better understand the physicochemical basis for its effects on chromatin architecture, recombinant full-length S. cerevisiae Sir3p has been purified to near homogeneity on the large-scale and characterized by circular dichroism, limited protease digestion, and analytical ultracentrifugation. Results indicate that the Sir3p monomer has a unique tripartite domain organization, including a nearly 300-amino-acid residue stretch of intrinsically disordered residues that lies internal to its structured N- and C-terminal regions. Sir3p self-associates extensively in moderate salt and at micromolar protein concentrations producing a broad range of oligomers that sediment from 8 to in excess of 85 S. These results provide new insight into Sir3p domain organization and quaternary structure and support a nucleosome bridging model for Sir3p-dependent regulation of chromatin architecture.


Branched poly(ethyleneimine): a versatile scaffold for patterning polymer brushes by means of remote photocatalytic lithography.
Patterning of functional surfaces is one of the cornerstones of nanotechnology as it allows the fabrication of sensors and lab-on-a-chip devices. Here, the patterning of self-assembled monolayers of branched poly(ethyleneimine) (bPEI) on silica was achieved by means of remote photocatalytic lithography. Moreover, when 2-bromoisobutyryl-modified bPEI was used, the resulting pattern could be amplified by grafting polymer brushes by means of surface-initiated atom transfer radical polymerization. In contrast to previous reports for the patterning of bPEI, the present approach can be conducted in minutes instead of hours, reducing the exposure time to UV radiation and enhancing the overall efficiency. Furthermore, our approach is much more user-friendly, allowing a facile fabrication of patterned initiator-modified surfaces and the use of inexpensive instrumentation such as a low-power UV source and a simple photomask. Considering the versatility of bPEI as a scaffold for the development of biosensors, patterning by means of remote photocatalytic lithography will open new opportunities in a broad field of applications.


CFTR dysfunction predisposes to fibrotic liver disease in a murine model.
Cystic fibrosis liver disease (CFLD) is a rapidly progressive biliary fibrosis, resembling primary sclerosing cholangitis that develops in 5-10% of patients with cystic fibrosis. Further research and evaluation of therapies are hampered by the lack of a mouse model for CFLD. Although primary sclerosing cholangitis is linked to both ulcerative colitis and loss of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function, induction of colitis with dextran sodium sulfate (DSS) in cftr(-/-) mice causes bile duct injury but no fibrosis. Since profibrogenic modifier genes are linked to CFLD, we examined whether subthreshhold doses of the profibrogenic xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), along with DSS-induced colitis, lead to bile duct injury and liver fibrosis in mice that harbor loss of CFTR function. Exon 10 heterozygous (cftr(+/-)) and homozygous (cftr(-/-)) mice treated with DDC demonstrated extensive mononuclear cell inflammation, bile duct proliferation, and periductular fibrosis. In contrast, wild-type (cftr(+/+)) littermates did not develop bile duct injury or fibrosis. Histological changes corresponded to increased levels of alkaline phosphatase, hydroxyproline, and expression of profibrogenic transcripts for transforming growth factor-β(1), transforming growth factor-β(2), procollagen α(1)(I), and tissue inhibitor of matrix metaloproteinase-1. Immunohistochemistry demonstrated fibrosis and activation of periductal fibrogenic cells based on positive staining for lysyl oxidase-like-2, α-smooth muscle actin, and collagen I. These data demonstrate that subthreshold doses of DDC, in conjunction with DSS-induced colitis, results in bile duct injury and periductal fibrosis in mice with partial or complete loss of CFTR function and may represent a useful model to study the pathogenic mechanisms by which CFTR dysfunction predisposes to fibrotic liver disease and potential therapies.


The antiphospholipid antibodies.
Antiphospholipid antibodies (APLAs) are a group of autoantibodies directed against certain phospholipids, or their protein cofactors. Assay of APLAs is important because their interaction with anionic phospholipid-protein cofactors can generate a syndrome of hypercoagulability associated with a wide variety of thromboembolic events. This article presents the characteristics of some APLAs [anticardiolipin antibodies (aCLAs), lupus anticoagulant (LA) and anti-beta2-glycoprotein I antibodies (anti-beta2-GPIAs)], their action, and their interaction with blood and endothelial cells. The presence of APLAs has been reported in many diseases (autoimmune diseases, atherosclerosis, infections, malignancies), being related to pathogenic mechanisms and/or to a more severe evolution of the disease.


[Long-acting injectable microspheres of glucagon-like peptide-1].
To prepare glucagon-like peptide-1 (GLP-1) loaded long-acting injectable microspheres and to evaluate their in vitro release behavior as well as its pharmacodynamics. GLP-1 loaded microspheres were prepared with poly (lactic-co-glycolic acid) (PLGA) as carrier materials by dowble emulsion (W/O/W) method. Physical and chemical characteristics of microspheres, such as mean diameter, morphology and drug loading were evaluated. The in vitro release behavior and its influencing factors were determined by HPLC, also the bioactivity of GLP-1 in the course of encapsulation process and in vitro release were evaluated by in vivo animal experiments. The effect of reducing plasma glucose about GLP-1 microspheres were evaluated on the diabetes mice. Microspheres with good shape and dispersive quality were prepared. The drug entrapment efficiency was more than 80%. The accumulated release in one month is up to 85% and the release equation is in accord with zero-class release model. The bioactivity of GLP-1 was conserved with glutin as inner water phase, but in the course of in vitro release, the specific activity of CLP-1 in the microspheres decreased a little. GLP-1 microspheres can decrease the plasma glucose significantly and the effect can go on for one month. GLP-1 can be encapsulated in injectable microspheres to yield one-month continuous release when using biodegradable polymers PLGA as carrier material, and this technique will have a favorable perspective in the near future.


The N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP.
GTP cyclohydrolase I (GTPCH) is the rate-limiting enzyme for biosynthesis of tetrahydrobiopterin (BH4), an obligate cofactor for NO synthases and aromatic amino acid hydroxylases. BH4 can limit its own synthesis by triggering decameric GTPCH to assemble in an inhibitory complex with two GTPCH feedback regulatory protein (GFRP) pentamers. Subsequent phenylalanine binding to the GTPCH·GFRP inhibitory complex converts it to a stimulatory complex. An N-terminal inhibitory peptide in GTPCH may also contribute to autoregulation of GTPCH activity, but mechanisms are undefined. To characterize potential regulatory actions of the N-terminal peptide in rat GTPCH, we expressed, purified, and characterized a truncation mutant, devoid of 45 N-terminal amino acids (Δ45-GTPCH) and contrasted its catalytic and GFRP binding properties to wild type GTPCH (wt-GTPCH). Contrary to prior reports, we show that GFRP binds wt-GTPCH in the absence of any small molecule effector, resulting in allosteric stimulation of GTPCH activity: a 20% increase in Vmax, 50% decrease in KmGTP, and increase in Hill coefficient to 1.6, from 1.0. These features of GFRP-stimulated wt-GTPCH activity were phenocopied by Δ45-GTPCH in the absence of bound GFRP. Addition of GFRP to Δ45-GTPCH failed to elicit complex formation or a substantial further increase in GTPCH catalytic activity. Expression of Δ45-GTPCH in HEK-293 cells elicited 3-fold greater BH4 accumulation than an equivalent of wt-GTPCH. Together, results indicate that the N-terminal peptide exerts autoinhibitory control over rat GTPCH and is required for GFRP binding on its own. Displacement of the autoinhibitory peptide provides a molecular mechanism for physiological up-regulation of GTPCH activity.


[Antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism and its common pharmacodynamic substances].
This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.


Knowledge, Concerns, and Psychological Distress Among Caregivers of Patients Seeking Emergency Medical Care for Non-COVID-19-Related Illness During the COVID-19 Pandemic: A Cross-Sectional Study.
Introduction During the active phase of the COVID-19 pandemic, the global healthcare system failed to meet the increased demand for healthcare resources, infrastructures, and facilities. The brunt of the healthcare crisis was faced not only by COVID-19 victims; a large majority of non-COVID patients were deprived of routine and emergency care. Factors that possibly affected resource utilization, healthcare-seeking behavior, service delivery patterns, and national health systems' priority during the pandemic were the knowledge and attitudinal concerns related to the COVID-19 disease and its control measures. Here, we evaluated the knowledge, concern, and psychological distress among the caregivers of the patients attending the emergency department at a tertiary healthcare center in India. Methodology We conducted a survey-based study using a pre-validated questionnaire on the caregivers of the patients visiting the emergency department (ED) from June to September 2020 (during the first wave of the COVID-19 pandemic). The demographic details and responses of the participants were documented in the semi-structured proforma. A pre-validated COVID-19 Peritraumatic Distress Index (CPDI) questionnaire was used to assess psychological stress. Results Out of 1014 participants interviewed, the majority were male attendants (72%), aged 18-45 (82%), and seeking medical attention for patients with chronic illnesses (76%). Acute onset emergencies like stroke, myocardial infarction, trauma, etc. were the ED presentation in only one-fifth of patients. COVID-19-related knowledge was adequate for questions related to age groups at risk for the viral infection (97% agreed that all age groups were at risk), mode of transmission (75-90% were aware of the common modes of transmission), and >65% knew the common symptoms of COVID-19 infection. However, only 38.5% knew about frequent handwashing as a protective measure. More than half of the participants considered the COVID-19 vaccine as the sole ray of hope and disregarded the effectiveness of alternative medicines such as Ayurvedic/homeopathic/allopathic medicines as preventive options. One-third were first-time visitors to the hospital, while two-thirds of all participants were afraid to visit any hospital during the COVID-19 pandemic. The majority (84%) faced difficulty in accessing the index tertiary care center due to transport, socioeconomic support, or lockdown-related restrictions. In comparison, 60% reported some form of discrimination at almost all levels of healthcare settings due to COVID-19-related priority changes. Nearly half (48%) of all enrolled caregivers reported experiencing mild-to-moderate distress (CPDI score=28-51), and 15.7% felt severe distress (CPDI score >51) while seeking treatment for the non-COVID-19 illness of their patient. Age and socioeconomic status were significantly associated with COVID-19-related psychological distress levels (p<0.001 in logistic regression), while gender, education, and residence showed no significant associations. Conclusion Most of the patient caregivers visiting the emergency department during the COVID-19 pandemic had an adequate understanding of risk factors and preventive measures. The major barriers to accessing healthcare facilities were transport, financial issues, and lockdown-related restrictions. Almost two-thirds of the caregivers revealed mild-to-moderate to severe psychological distress due to the pandemic and lockdown-related concerns.


Mortality and associated factors in a thoracic surgery ICU.
To assess mortality and identify mortality risk factors in patients admitted to a thoracic surgery ICU. We retrospectively evaluated 141 patients admitted to the thoracic surgery ICU of the Denizli State Hospital, located in the city of Denizli, Turkey, between January of 2006 and August of 2008. We collected data regarding gender, age, reason for admission, invasive interventions and operations, invasive mechanical ventilation, infections, and length of ICU stay. Of the 141 patients, 103 (73.0%) were male, and 38 (23.0%) were female. The mean age was 52.1 years (range, 12-92 years), and the mortality rate was 16.3%. The most common reason for admission was trauma. Mortality was found to correlate with advanced age (p < 0.05), requiring invasive mechanical ventilation (OR = 42.375; p < 0.05), prolonged ICU stay (p < 0.05), and specific reasons for admission-trauma, gunshot wound, stab wound, and malignancy (p < 0.05 for all). Among patients in a thoracic surgery ICU, the rates of morbidity and mortality are high. Increased awareness of mortality risk factors can improve the effectiveness of treatment, which should reduce the rates of morbidity and mortality, thereby providing time savings and minimizing costs.


Prevention of accidental intraocular injection following inadvertent needle perforation of the eyeball.
To prevent accidental intraocular injection after inadvertent single needle perforation of the eyeball, the authors recommend moving the needle and watching for corresponding movement of the globe following peribulbar or retrobulbar placement of the needle and prior to injecting. The authors have found this technique to be safe and reliable, with negligible morbidity.


Effect of frying instructions for food handlers on acrylamide concentration in French fries: an explorative study.
The objective of this study was to obtain insight into the effect of frying instructions on food handlers' control decisions in restaurants and to investigate the impact of control decisions on the variation and concentration of acrylamide in French fries. The concentrations of acrylamide and reducing sugars were analyzed, the frying temperature and time were measured, and thawing practices were observed. The results obtained before and after instructions were provided to the food handlers were compared for restaurants as a group and for each restaurant. Frying instructions supported food handlers' decisions to start frying when the oil temperature reached 175°C; all handlers started frying at the correct temperature. However, the effect of the instructions on the food handlers' decisions for frying time differed; most handlers increased the frying time beyond 240 s to achieve crispier French fries with a final color dictated by their preference. Providing instructions did not result in a significant difference in the mean concentration of acrylamide in French fries for the restaurants as a group. However, data analyzed for each restaurant revealed that when food handlers properly followed the instructions, the mean concentration of acrylamide was significantly lower (169 μg/kg) than that before instructions were provided (1,517 μg/kg). When food handlers did not complying with the frying instructions, mean acrylamide concentrations were even higher than those before instructions were provided. Two different strategies were developed to overcome the noncompliant behavior of food handlers: establishing requirements for the features of commercial fryers and strict monitoring of compliance with instructions.


Grand canonical Monte Carlo using solvent repacking: Application to phase behavior of hard disk mixtures.
A new "solvent repacking Monte Carlo" strategy for performing grand canonical ensemble simulations in condensed phases is introduced and applied to the study of hard-disk systems. The strategy is based on the configuration-bias approach, but uses an auxiliary biasing potential to improve the efficiency of packing multiple solvent particles in the cavity formed by removing one large solute. The method has been applied to study the coexistence of ordered and isotropic phases in three binary mixtures of hard disks with a small mole fraction (xL < 0.02) of the larger "solute" component. A chemical potential of 12.81 ± 0.01 kBT was found to correspond to the freezing transition of the pure hard disk "solvent." Simulations permitted the study of partitioning of large disks between ordered and isotropic phases, which showed a distinct non-monotonic dependence on size; the isotropic phase was enriched approximately 10-fold, 20-fold, and 5-fold over the coexisting ordered phases at diameter ratios d = 1.4, 2.5, and 3, respectively. Mixing of large and small disks within both phases near coexistence was strongly non-ideal in spite of the dilution. Structures of systems near coexistence were analyzed to determine correlations between large disks' positions within each phase, the orientational correlation length of small disks within the fluid phases, and the nature of translational order in the ordered phase. The analyses indicate that the ordered phase coexists with an isotropic phase resembling a nanoemulsion of ordered domains of small disks, with large disks enriched at the disordered domain interfaces.


WF-10129, a novel angiotensin converting enzyme inhibitor produced by a fungus, Doratomyces putredinis.
WF-10129 is an angiotensin converting enzyme (ACE) inhibitor produced by Doratomyces putredinis. IC50 of the compound is 1.4 X 10(-8) M for the ACE activity. WF-10129 was purified from cultured filtrate by successive ion exchange chromatography and HPLC. The chemical structure 1 was elucidated on the basis of spectroscopic and chemical evidence. The compound is a dipeptide composed of L-tyrosine and a novel amino acid. WF-10129 inhibits the pressor response of angiotensin I when administered intravenously at 0.3 mg/kg in rats.


Neurotropic enteroviruses co-opt "fair-weather-friend" commensal gut microbiota to drive host infection and central nervous system disturbances.
Some neurotropic enteroviruses hijack Trojan horse/raft commensal gut bacteria to render devastating biomimicking cryptic attacks on human/animal hosts. Such virus-microbe interactions manipulate hosts' gut-brain axes with accompanying infection-cycle-optimizing central nervous system (CNS) disturbances, including severe neurodevelopmental, neuromotor, and neuropsychiatric conditions. Co-opted bacteria thus indirectly influence host health, development, behavior, and mind as possible "fair-weather-friend" symbionts, switching from commensal to context-dependent pathogen-like strategies benefiting gut-bacteria fitness.


Physicians' use of the personal digital assistant (PDA) in clinical decision making.
This study examined how frequently attending physicians and physicians in training used personal digital assistants (PDAs) for patient care and explored physicians' perceptions of the impact of PDA use on several areas of clinical decision making. The 108 participants included 59 attending physicians and 49 physicians in training from teaching hospitals in Tennessee, Florida, Alabama, Kentucky, and Pennsylvania. Respondents completed a questionnaire designed to explore PDA use in a clinical setting. Eighty-seven percent of the respondents reported PDA use for patient encounters. Fifty-five percent of respondents reported frequent use, and 32% reported occasional use of a PDA for patient care. Of the frequent PDA users, 85% said PDA use had influenced their overall clinical decision making and 73% mentioned treatment alterations specifically. Approximately 60% of the participants reporting occasional PDA use indicated that the PDA had influenced their overall clinical decision making, while 54% specifically mentioned a change to their patient's treatment plan. Attending physicians and physicians in training who used a PDA during patient encounters perceived that even occasional PDA use had an impact on their clinical decision making and treatment choices. Health sciences librarians are perfectly positioned to provide PDA training and assistance not only to physicians who are frequent PDA users, but also to those who are occasional users.


Current status of HIV therapy: I. Antiretroviral agents.
Zidovudine has proved to be an important palliative agent in all stages of HIV infection. It delays progression of disease in patients with asymptomatic or mildly symptomatic infection and decreases the frequency and severity of opportunistic disease in those with AIDS. The search for other, more effective antiretroviral agents goes on, with some promising possibilities.


Acute and sub-chronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents.
The present investigation was carried out to evaluate the safety of an aqueous extract of Herniaria glabra (caryophyllaceae) (HG) plant by determining its potential toxicity after acute and sub-chronic administration in rodents. For the acute study, a lyophilized aqueous extract of HG plant was administered to adult IOPS OFA mice in single doses of 5-14.5 g/kg given by gavage. General behavior adverse effects and mortality were determined for up to 14 days. In the sub-chronic dose study, the HG-extract was administered orally at doses of 1, 2 and 4 g/kg daily for 90 days to Wistar rats. Selected biochemical and hematological parameters were determined after 30 and 60 days, and then at the end of 90 days of daily administration. In the acute study in mice, the crude aqueous extract of HG plant caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the HG extract was 5 g/kg and the lowest-observed adverse effect levels (LOAEL) was 5.5 g/kg. Mortality increased with increasing doses: the calculated LD50 was 8.50 +/- 0.42 g/kg in mice. In the sub-chronic study in rats, daily oral administration of the crude HG extract for up to 90 days resulted in a significant attenuation of the normal increase in the body weight. At the highest dose, the HG-extract caused a significant increase in erythrocytes, leukocytes (WBC), platelets, and eosinophils, but it had no effect on the differential WBC counts (lymphocytes, monocytes, neutrophils and basophils). Only at the highest dose, the HG-extract caused a significant increase in serum levels of the liver enzymes, alanine aminotransferase and aspartate aminotransferase, as well as serum creatinine, indicating toxic effect of the high dose of the extract on the liver and kidney. The organ toxicity was confirmed by histopathological examination, which showed centrolobular sinusoidal congestion, disruption of the central vein and hepatocellular necrosis in the liver, and interstitial and intraglomerular congestion, tubular atrophy, and inflammation in the kidney. This study also revealed the hypoglycemic activity of the HG-extract in normoglycemic rats. The suppression of the normal weight gain and the hypoglycemic action of HG-extract should be investigated further for possible therapeutic implications. Because of the relatively high NOAEL values in the acute study in mice, and lack of mortality or clinically significant changes in the biological (except for hypoglycemia) and hematological parameters in rats after 90 days of daily dosing, it may be concluded that the HG extract does not appear to have significant toxicity (except at high doses). In view of the doses consumed empirically in traditional medicine in Morocco, there is a wide margin of safety for the therapeutic use of Herniaria glabra.


Fluoride distribution and biological availability in the fallout from mount st. Helens, 18 to 21 may 1980.
Concentrations of fluoride in the ash fallout in central Washington from the 18 May 1980 eruption of Mount St. Helens varied severalfold, but none are high enough to constitute any immediate hazard to animal life. The heaviest fallout (Moses Lake) contained 113 parts per million (ppm) of acid-labile fluoride, but of this only 11 ppm was water-soluble and 20 ppm was available to rats. The fluoride concentrations in the urine of cattle feeding for 4 days on hay contaminated with this ash were essentially normal. Samples of ash from other areas generally had higher concentrations of acid-labile fluoride but lower concentrations of water-soluble fluoride. The concentration of water-soluble fluoride was inversely correlated with the coarseness of the fallout.


Influence of an interdisciplinary diabetes specialist team on short-term outcomes of diabetes at a community health center.
To assess the effect on short-term diabetes outcomes of intervention with an interdisciplinary diabetes specialist team at a primary-care community health center in East Harlem, New York City. An interdisciplinary diabetes specialist team, consisting of a diabetologist, a bicultural certified diabetes nurse-educator, and a nutritionist, attended weekly clinics at a primary-care community health center in East Harlem. Emphasis was placed on communicating in the patient's primary language and providing nutritional counseling, diabetes education, and diabetes management. After 1 year, a retrospective review of medical records for patients seen by the diabetes team was performed to assess the influence of this intervention on performance of home glucose monitoring (HGM), frequency of hypoglycemia, and changes in diabetes treatment regimens. Of 70 patients referred to the diabetes team by their primary-care providers, 50 underwent follow-up for at least 6 months and were included in the statistical analysis. Of the 50 study patients, 94% had type 2 diabetes, with a mean duration of 11.2 years. Eighty-two percent were Hispanic, and 18% were Afro-American. The mean age was 54.6 years. Microvascular complications were present in 44%, and macrovascular complications were present in 22%. HGM was done by 13 patients (26%) before and 33 patients (66%) after diabetes team intervention (P<0.001). Before intervention by the diabetes team, 14 patients (28%) were having episodes of unrecognized hypoglycemia. Unrecognized hypoglycemia resolved after intervention in all but two patients with type 1 diabetes (P<0.001). Before intervention, diabetes treatment was dietary in 6 patients, a sulfonylurea in 19, and insulin in 25; after intervention, 5 patients had dietary management of their diabetes, 14 were taking a sulfonylurea, and 31 were receiving insulin (P<0.05). Providing access to an interdisciplinary diabetes specialist team at the site of primary care had a beneficial effect on short-term diabetes outcomes in inner-city Hispanic and Afro-American patients with diabetes. Providing specialty care in the primary-care setting may be one model for improving the quality and long-term outcomes of diabetes care, particularly in high-risk populations.


Oxygen binding and activation by the complexes of PY2- and TPA-appended diphenylglycoluril receptors with copper and other metals.
The copper(I) complexes of diphenylglycoluril basket receptors and , appended with bis(2-ethylpyridine)amine (PY2) and tris(2-methylpyridine)amine (TPA), respectively, and their dioxygen adducts were studied with low-temperature UV-vis and X-ray absorption spectroscopy (XAS). The copper(I) complex of, [.Cu(I)2] or, forms a micro-eta2:eta2 dioxygen complex, whereas the copper(I) complex of, [.Cu(I)2] or, does not form a well defined dioxygen complex, but is oxidized to Cu(II). Dioxygen is bound irreversibly to and the formed complex is stable over time. The coordination geometries of the above complexes were determined by XAS, which revealed that pyridyl groups and amine N-donors participate in the coordination to Cu(I) ions in the complexes of both receptors. The catalytic activities of various metal complexes of and , that were designed as mimics of dinuclear copper enzymes that can activate dioxygen, were investigated. Phenolic substrates that were expected to undergo aromatic hydroxylation, showed oxidative polymerization without insertion of oxygen. The mechanism of this polymerization turns out to be a radical coupling reaction as was established by experiments with the model substrate 2,4-di-tert-butylphenol. In addition to Cu(II), the Mn(III) complex of and the Fe(II) complex of were tested as oxidation catalysts. Oxidation of catechol was observed for the Cu(II) complex of receptor but the other metal complexes did not lead to oxidation.


In vitro evaluation of granules obtained from 3D sphene scaffolds and bovine bone grafts: chemical and biological assays.
Sphene is an innovative bone graft material. The aim of this study was to investigate and compare the physicochemical and biological properties of Bio-Oss® (BO) and in-lab synthesized and processed sphene granules. BO granules of 1000-2000 μm (BO-L), 250-1000 μm (BO-S) and 100-200 μm (BO-p) for derived granules, and corresponding groups of sphene granules obtained from 3D printed blocks (SB-L, SB-S, SB-p) and foams (SF-L, SF-S and SF-p) were investigated. The following analyses were conducted: morphological analysis, specific surface area and porosity, inductively coupled plasma mass spectrometry (ICP-MS), cytotoxicity assay, Alizarin staining, bone-related gene expression, osteoblast migration and proliferation assays. All pulverized granules exhibited a similar morphology and SF-S resembled natural bone. Sphene-derived granules showed absence of micro- and mesopores and a low specific surface area. ICP-MS revealed a tendency for absorption of Ca and P for all BO samples, while sphene granules demonstrated a release of Ca. No cellular cytotoxicity was detected and osteoblastic phenotype in primary cells was observed, with significantly increased values for SF-L, SF-S, BO-L and BO-p. Further investigations are needed before clinical use can be considered.


MRI Correlation of Radial Head Fractures and Forearm Injuries.
Background: Radial head fractures can be associated with soft tissue injuries of the forearm and wrist. The Essex-Lopresti injury can lead to significant morbidity, especially if the diagnosis is not made acutely. Better identification of such injuries is needed to allow optimal surgical treatment and prevent long-term sequelae. We used magnetic resonance imaging (MRI) to correlate the degree of soft tissue injuries with radial head fractures. Methods: Sixteen pairs of forearms with an associated radial head fracture in 15 patients prospectively underwent an MRI within 2 weeks of their injury. MRI findings were correlated with fracture type, associated soft tissue injury, and presence of symptomatic wrist pain. Results: According to the modified Mason classification, there were 8 type I, 5 type II, and 3 type III radial head fractures. Wrist pain was reported in 8 of 16 extremities, and 2 had associated wrist pathology, including an acute scaphoid fracture in 1 patient and a preexisting stage II scapholunate advanced collapse (SLAC) wrist in another patient. The MRI findings included an elbow effusion in all 16 patients, edema in the proximal third of the radius in 15 extremities, which extended to the middle third in 3 extremities, edema of the interosseous membrane (IOM) in 5 extremities, and edema of the soft tissues including the supinator and/or pronator quadratus in 13 extremities. Conclusions: Eighty percent of patients with edema of the IOM had associated wrist pain. Soft tissue injuries of the forearm did not correlate with the severity of the radial head fracture.


Bonding of cartilage matrices with cultured chondrocytes: an experimental model.
The capacity of isolated chondrocytes to join separate masses of cartilage matrix was investigated with composites implanted in subcutaneous pouches in nude mice. Slices of articular cartilage were harvested from lambs and were devitalized by cyclic freezing and thawing. The slices were then either co-cultured with viable allogeneic lamb chondrocytes (experimental) or cultured without such chondrocytes (control). Composites of three slices were constructed with use of fibrin glue and were implanted in nude mice for periods ranging from 7 to 42 days. Bonding of the experimental matrices with viable chondrocytes was achieved at 28 and 42 days, as assessed by direct examination, histology, thymidine uptake, and fluorescence. No bonding occurred in the control composites without viable chondrocytes. We conclude that devitalized cartilage matrix is a scaffold to which isolated chondrocytes can attach and begin to repopulate.


Chordae tendineae rupture resulting in pulmonary edema in a patient with discrete subvalvular aortic stenosis--a case report and literature review.
This report concerns an apparently healthy elderly woman who presented with gradually worsening mitral regurgitation secondary to chordae tendineae rupture leading to pulmonary edema in the presence of discrete subvalvular aortic stenosis with a severe gradient reflecting the left ventricular outflow tract obstruction. The gradual worsening of heart failure took place parallel to the increase in severity of mitral regurgitation in a short period. The patient underwent successful mitral valve replacement with myectomy. Surgical inspection revealed rupture of the chordae tendineae to the posterior leaflets without any significant primary intrinsic disease of the mitral valve. The predominant mechanism of chordae tendineae rupture in this patient with discrete subvalvular aortic stenosis is a severe pressure gradient. It is suggested that increased awareness of chordae tendineae rupture as a cause of mitral regurgitation and the prompt use of appropriate diagnostic tools may facilitate the timely recognition of this potentially fatal, but treatable, cause of mitral regurgitation in patients with left ventricular outflow tract obstruction.


Post-traumatic growth in advanced cancer patients receiving palliative care.
To develop the Greek version of the Post-traumatic Growth Inventory (PTGI-Gr), and assess its psychometric properties in a palliative care patient sample. The scale was translated with the forward-backward procedure to Greek. It was administered twice, with a 3-day interval, to 131 eligible patients with advanced cancer. Together with the PTGI, the patients also completed the Greek version of the Impact of Events Scale-Revised scale (IES-R-Gr). The reliability was assessed by the internal consistency (Cronbach's alpha coefficients), test/retest (Spearman's r value), and inter-item correlations. Validity was demonstrated by factor analysis, inter-scale correlations, construct validity with the IES-R-Gr, and combined with the Eastern Cooperative Oncology Group (ECOG) performance status. The PTGI-Gr yielded a five-factor structure, explaining 73.5% of the variance. Cronbach's alphas for the five factors ranged from .66 to .87, respectively. Overall test-retest reliability was satisfactory with a range between .85 and .92 (p<.0005), and inter-item correlations ranged between .47 and .63. Inter-scale correlations were found satisfactory (p<.0005, p<.005, and p<.05). Validity as performed using combined validity analysis showed good results. Satisfactory construct validity was supported by the correlation analysis between the PTGI-Gr and the IES-R-Gr scales. PTGI-Gr is an instrument with satisfactory psychometric properties, and is a valid research tool for the post-traumatic growth of advanced cancer patients.


Gambling Risk Groups are Not All the Same: Risk Factors Amongst Sports Bettors.
Sports betting is increasing worldwide, with an associated increase in sports betting-related problems. Previous studies have examined risk factors for problem gambling amongst sports bettors and have identified demographic, behavioural, marketing, normative and impulsiveness factors. These studies have generally compared those in problem gambling, or a combination of moderate risk and problem gambling, groups to non-problem gamblers, often due to statistical power issues. However, recent evidence suggests that, at a population level, the bulk of gambling-related harm stems from low risk and moderate risk gamblers, rather than problem gamblers. Thus it is essential to understand the risk factors for each level of gambling-related problems (low risk, moderate risk, problem) separately. The present study used a large sample (N = 1813) to compare each gambling risk group to non-problem gamblers, first using bivariate and then multivariate statistical techniques. A range of demographic, behavioural, marketing, normative and impulsiveness variables were included as possible risk factors. The results indicated that some variables, such as gambling expenditure, number of accounts with different operators, number of different types of promotions used and impulsiveness were significantly higher for all risk groups, while others such as some normative factors, age, gender and particular sports betting variables only applied to those with the highest level of gambling-related problems. The results generally supported findings from previous literature for problem gamblers, and extended these findings to low risk and moderate risk groups. In the future, where statistical power allows, risk factors should be assessed separately for all levels of gambling problems.


Pathogenesis of thoracic and abdominal aortic aneurysms.
The major disease processes affecting the aorta are aortic aneurysms and dissections. Aneurysms are usually described in terms of their anatomic location, with thoracic aortic aneurysms (TAAs) involving the ascending and descending aorta in the thoracic cavity and abdominal aortic aneurysms (AAAs) involving the infrarenal abdominal aorta. Both thoracic and abdominal aortas are elastic arteries, and share similarities in their physical structures and cellular components. However, thoracic and abdominal aortas differ in their biochemical properties and the origin of their vascular smooth muscle cells (VSMCs). These similarities and differences between thoracic and abdominal aortas provide the basis for the various pathologic mechanisms observed in this disease. This review focuses on the comparison of the pathologic mechanisms involved in TAA and AAA.


Change in angiogram-derived management strategy of patients with chest pain when some FFR data are available: How consistent is the effect?
The assessment of patients presenting with angina using invasive angiography alone is imperfect. By contrast, fractional flow reserve (FFR) allows for assessment of lesion-specific ischemia, which is predictive of clinical outcome. A series of studies has demonstrated that the availability of FFR data at the time of diagnostic angiography leads to significant differences in the management of those patients. The objective of this paper is to assess the consistency in the difference in management resulting from an FFR-directed versus and angiogram-directed strategy in appropriate observational and randomized trials. A methodical search was made using MEDLINE, Current Contents Connect, Google Scholar, EMBASE, Cochrane library, PubMed, Science Direct, and Web of Science. Eight studies were identified using the eligibility criteria. A total of 2468 patients were recommended to have optimal medical therapy (OMT) alone after initial angiographic assessment but, after FFR results were available, a total of 716 (29.0%) were referred for revascularization (PCI 626 patients [25.36%]; CABG 90 patients [3.64%]). Similarly, 3766 patients were originally committed to PCI after initial angiography: of these 1454 patients (38.61%) were reconsidered to be suitable for OMT alone and 71 individuals (1.8%) were deemed suitable for CABG after FFR data were available. Further, of 366 patients referred for CABG based on angiographic data, the availability of FFR data changed the final decision to OMT alone in 65 patients (17.76%) and PCI in 51 patients (13.9%). Overall, the angiogram-derived management was changed in 22%-48% of these study populations when FFR data were available. Some use of FFR during coronary angiography alters the angiogram-directed management in a remarkably consistent manner. These data suggest that routine use of FFR at the diagnostic angiogram would improve patient care.


Slow pathway elimination using antegrade conduction improvement with fast atrial pacing during AVNRT radiofrequency ablation: a proof-of-concept study.
Radiofrequency (RF) ablation of slow pathway (SP) is usually performed in sinus rhythm while monitoring the occurrence of a slow junctional rhythm (JR). JR although sensitive, is not specific for elimination of SP conduction. Our objective was to prospectively evaluate feasibility and safety of SP elimination using fast atrial rate pacing (FAP) during RF delivery. Consecutive patients admitted for atrioventricular nodal re-rentrant tachycardia (AVNRT) ablation were included. The rate of proximal coronary sinus (CS) pacing was set to a value constantly yielding antegrade SP conduction, while carefully monitoring the AH interval. RF delivery (at the lower part of Koch's triangle) was considered successful if the AH shortened ≥ 14 ms or if transition from Wenckebach (WK) periods to a 1:1 conduction occurred. 24 patients were included (54 ± 20 y). Typical AVNRT was induced in all (cycle length 349 ± 83 ms). RF delivery during CS pacing (335 ± 73 ms) led to AH shortening by 51 ± 25 ms in 13 patients. In 10 patients, a transition from 3:2 or 4:3 WK periods to 1:1 conduction occurred during the successful pulse. In one patient, atrial fibrillation was systematically induced during FAP, requiring conventional ablation. Non-inducibility, and SP conduction disappearance was obtained in all patients. No patient developed AV block. After a follow-up of 12 ± 3 months, no recurrences were observed. SP ablation using FAP during RF delivery allows direct visualisation of its disappearance. In our cohort of patients, this technique was feasible without safety compromise.


Targeting Pathological Tau by Small Molecule Inhibition of the Poly(A):MSUT2 RNA-Protein Interaction.
Neurofibrillary tangles composed of aberrantly aggregating tau protein are a hallmark of Alzheimer's disease and related dementia disorders. Recent work has shown that mammalian suppressor of tauopathy 2 (MSUT2), also named ZC3H14 (Zinc Finger CCCH-Type Containing 14), controls accumulation of pathological tau in cultured human cells and mice. Knocking out MSUT2 protects neurons from neurodegenerative tauopathy and preserves learning and memory. MSUT2 protein functions to bind polyadenosine [poly(A)] tails of mRNA through its C-terminal CCCH type zinc finger domains, and loss of CCCH domain function suppresses tauopathy in Caenorhabditis elegans and mice. Thus, we hypothesized that inhibiting the poly(A):MSUT2 RNA-protein interaction would ameliorate pathological tau accumulation. Here we present a high-throughput screening method for the identification of small molecules inhibiting the poly(A):MSUT2 RNA-protein interaction. We employed a fluorescent polarization assay for initial small molecule discovery with the intention to repurpose hits identified from the NIH Clinical Collection (NIHCC). Our drug repurposing development workflow included validation of hits by dose-response analysis, specificity testing, orthogonal assays of activity, and cytotoxicity. Validated compounds passing through this screening funnel will be evaluated for translational effectiveness in future studies. This preclinical drug development pipeline identified diverse FDA approved drugs duloxetine, saquinavir, and clofazimine as potential repurposing candidates for reducing pathological tau accumulation.


The history of the Read Codes: the inaugural James Read Memorial Lecture 2011.
General practitioner (GP) computing has its origins in the 1970s when the benefits of clinical coding and prescribing were demonstrated. During the early 1980s Dr James Read, working with Abies Informatics Ltd, developed the eponymous Read Codes, which were broader and more comprehensive than other schemes, yet intuitive and easy to use. In 1988 a joint working party of the Royal College of General Practitioners (RCGP) and the British Medical Association (BMA) recommended that the Read Codes be adopted nationally. The Read Codes have been used by almost all GPs in the UK since the mid-1990s. Many developments in general practice, including GP fundholding (where GPs held the budgets to commission elective care for their patients), the Quality and Outcomes Framework (QOF - pay for performance for improving chronic disease management) and GP commissioning (the current NHS reform in which primary care leads commissioning of services for their patients) would have been impossible without all GPs using a common clinical coding scheme. Systematized Nomenclature For Medicine - Clinical Terms (SNOMED CT) is a merger of the Read Codes with SNOMED RT - the original SNOMED reference terminology developed by the American College of Pathologists.


Isolation of brevistin, a new peptide antibiotic. Studies on antibiotics from the genus Bacillus. IX.
A new peptide antibiotic, brevistin, was isolated from the culture broth of Bacillus brevis 342-14. Brevistin is an acylpeptide with an approximate empirical formula of C63H91N15O18 containing aspartic acid, threonine, glycine, valine, isoleucine, phenylalanine, tryptophan and 2,4-diaminobutyric acid. The antibiotic is soluble in acid and alkaline water. Its hydrochloride is soluble in methanol. Brevistin is active against Ggam-positive bacteria in vitro and in vivo, and is of low toxicity to mice.


Information systems tools available to the case manager.
Regardless of the setting, the role of the nurse as a manager of care continues to grow and develop. The nurse case manager needs to have vital information readily available to facilitate critical thinking, analysis, and decision-making on the appropriateness of care provided to patients and to ensure that optimal outcomes are achieved. While there are a variety of clinical information systems available, it is evident that the complexity of the case manager's information needs presents challenges for software developers. Accordingly, nurse case managers must take an active role in defining and communicating their needs. The purpose of this article (the first of two) is to present a general overview of the information needs of the nurse case manager and the computerized information system tools available (and emerging) to meet these needs. A follow-up article in the next issue of Nursing Case Management will focus on a typical clinical information system selection process; outline specific ways the nurse case manager can effectively influence that process; and provide a checklist that will enable the nurse case manager to assist the institution in selecting and implementing the most appropriate system.


SNPAAMapperT2K: A genome-wide SNP downstream analysis and annotation pipeline for species annotated with NCBI.tbl data files.
SNPAAMapper, a genome-wide SNP downstream analysis and annotation pipeline, was designed to classify detected variants according to genomic regions and report the mutation class by processing whole-genome and/or whole-exome sequencing data. A widely used sequence and data annotation table format "knownGene.txt" has not yet been created for many popular model organisms (e.g. Arabidopsis). Instead, NCBI .tbl annotation format files are provided for these species. Therefore, it is of interest to describe SNPAAMapperT2K, a genome-wide SNP downstream analysis and annotation pipeline for species annotated with NCBI .tbl data files (e.g. Arabidopsis). The pipeline is tested with a deeply sequenced Arabidopsis thaliana strain (Seattle-0). The SNPAAMapperT2K can also annotate and report SNP classes for other species, whose chromosome files are annotated as NCBI .tbl format, but do not have their annotated knownGene.txt files available. Perl scripts and required input files are available on the web at http://isu.indstate.edu/ybai2/SNPAAMapperT2K.


Suggestibility and signal detection performance in hallucination-prone students.
Auditory hallucinations are associated with signal detection biases. We examine the extent to which suggestions influence performance on a signal detection task (SDT) in highly hallucination-prone and low hallucination-prone students. We also explore the relationship between trait suggestibility, dissociation and hallucination proneness. In two experiments, students completed on-line measures of hallucination proneness (the revised Launay-Slade Hallucination Scale; LSHS-R), trait suggestibility (Inventory of Suggestibility) and dissociation (Dissociative Experiences Scale-II). Students in the upper and lower tertiles of the LSHS-R performed an auditory SDT. Prior to the task, suggestions were made pertaining to the number of expected targets (Experiment 1, N = 60: high vs. low suggestions; Experiment 2, N = 62, no suggestion vs. high suggestion vs. no voice suggestion). Correlational and regression analyses indicated that trait suggestibility and dissociation predicted hallucination proneness. Highly hallucination-prone students showed a higher SDT bias in both studies. In Experiment 1, both bias scores were significantly affected by suggestions to the same degree. In Experiment 2, highly hallucination-prone students were more reactive to the high suggestion condition than the controls. Suggestions may affect source-monitoring judgments, and this effect may be greater in those who have a predisposition towards hallucinatory experiences.


[Stoma procedures in the congenital digestive tract malformations].
The authors analyze options for intestinal stoma procedures for congenital digestive tract malformations. A primary anastomosis is considered the principal procedure, however, the authors advice against its risky performance. Although a stoma being the ultimate treatment option, indications for stoma procedures should be considered carefully and the procedure should be performed on time, to avoid any potential later pathology development in the anastomosis. The authors compare and critically assess the following principal three types of the stoma procedures: 1. The modified Gross procedure; 2. The Bishop-Koop Roux Y anastomosis; 3. The Santulli-Blanc Roux Y anastomosis. The authors do not favour any of the above and they stress out that for each individual malformation, its own optimal procedure should be selected and performed.


Case report: increased levothyroxine requirement in a patient with cryptic celiac-sprue disease.
An increased requirement for levothyroxine may be due to poor patient compliance, pregnancy, low potency levothyroxine preparations, interfering drugs and small intestinal disease. Data on thyroid hormone absorption in celiac sprue disease is limited to a single study involving four patients without thyroid disease, in which malabsorption of a single dose of radiolabeled levothyroxine was noted in three of the four subjects. Increased levothyroxine requirements have not been reported in hypothyroid patients with celiac sprue. Furthermore, cryptic celiac sprue has never been described to cause levothyroxine malabsorption. We report such a patient in whom cryptic celiac sprue was an important cause of levothyroxine malabsorption with increased thyroid hormone requirement.


Compensatory increase in choline acetyltransferase activity in salivary glands and diaphragm muscle of the rat.
When the function of salivary glands was abolished by applying ligatures to their ducts and the function of one half of the diaphragm muscle was abolished by sectioning of its phrenic nerve, the choline acetyltransferase activity was found to be increased in not duct-ligated glands and in the intact hemidiaphragm 4 weeks later. The increase was not seen within the first week. The increase in activity appears to be particularly manifested in the nerve endings, since it was seen in the hemidiaphragm but not in the phrenic nerve. Increased stream of impulses in the efferent nerves is thought to be the cause of this increase in choline acetyltransferase activity.


Anticancer drug-loaded quantum dots engineered polymeric nanoparticles: Diagnosis/therapy combined approach.
Primary Effusion Lymphoma (PEL) is an HHV-8-related non Hodgkin lymphoma localized in body cavities (as pleural, peritoneal and pericardial) presenting lymphomatous effusion that, until now, lack of an effective therapy. Curcumin was reported to display pro-apoptotic effect via the inhibition of the JAK/STAT pathway, that is overexpressed in PEL cells, as consequence of virus infection. The administration of curcumin is severely restricted by its physicochemical properties, mainly its low solubility in biological fluid and consequently low bioavailability. Encapsulation into biocompatible and biodegradable PLGA nanoparticles (NPs) could be a strategy to overcome biological limits of curcumin, offering a valuable step forward for its clinical application. In this study we described single-emulsion process for curcumin loading into NPs (encapsulation efficiency about 35%). We applied a post-formulation strategy (NHS/EDC reaction) to decorate the surface of the curcumin-loaded NPs with quantum dots (QDs) as imaging agents (QDs-NPs-Cur, 24pmol of QDs per 100mg of NPs) obtaining tools useful for possible application in theranostic approach. Bifunctionalized NPs were tested in vitro on two PEL's cell line (BCBL-1 and HBL-6). The efficacy of the treatment was evaluated by cytofluorimetric assay by measuring both cell viability and cell density. We found that the NPs significantly improve the cellular effect of curcumin (respect to free drug). Moreover, by means of confocal microscopy, both the localization of bifunctional NPs and of the released drug were easily detectable. Thus, we conclude that the delivery of curcumin using bifunctional traceable NPs is a promising future approach for the diagnosis and the treatment of PEL.


Removal of crude oil from highly contaminated natural surfaces with corexit dispersants.
Dispersants are used to reduce the impact of oil spills in marine environment. Experiments were conducted with natural materials which were contaminated by direct application of fresh Louisiana crude oil. The natural materials evaluated included sea sand (South Beach in Miami, Florida), red mangrove leaves (Rhizophora mangle), and sea shells (Donax variabili). Salt water at two different salinities (17 and 34 ppt) was used with two types of Corexit dispersant solutions (9500A and 9527A) in concentrations ranging from 100 to 3500 mg/L. Washing of the contaminated samples was conducted by a three-step mixing procedure (salt water only, then with the addition of the dispersant solution to the salt water, and salt water) to simulate oil-saltwater-dispersant interactions. In general, increasing dispersant concentration increased the percentage of oil dispersed into the aqueous phase up to dispersant solutions containing 400 mg/L for Corexit 9500A and 300 mg/L Corexit 9527A. Increasing the dispersant concentration above these levels also decreased the dispersion of oil from the surfaces. At very high concentrations of dispersant solutions (above 1500 mg/L), the percentage of oil dispersed into the solution from the contaminated surfaces was about one half what was observed at 400 mg/L with Corexit 9500A and 300 mg/L Corexit 9527A. Although dispersants were most effective for removing the fresh Louisiana crude oil from sand particles and dispersing into the solution due to large surface area of the particles per unit weight; the residual oil remaining on the sand particles was relatively high in comparison to mangrove leaves and sea shells due to clustering of sand particle with oil. There was some oil penetration into the porous structure of the sea shells (at the microscopic level) which could not be removed.


Cyber dating abuse among teens using school-based health centers.
To estimate the prevalence of cyber dating abuse among youth aged 14 to 19 years seeking care at school-based health centers and associations with other forms of adolescent relationship abuse (ARA), sexual violence, and reproductive and sexual health indicators. A cross-sectional survey was conducted during the 2012-2013 school year (participant n = 1008). Associations between cyber dating abuse and study outcomes were assessed via logistic regression models for clustered survey data. Past 3-month cyber dating abuse was reported by 41.4% of this clinic-based sample. More female than male participants reported cyber dating abuse victimization (44.6% vs 31.0%). Compared with no exposure, low- ("a few times") and high-frequency ("once or twice a month" or more) cyber dating abuse were significantly associated with physical or sexual ARA (low: adjusted odds ratio [aOR] 2.8, 95% confidence interval [CI] 1.8-4.4; high: aOR 5.4, 95% CI 4.0-7.5) and nonpartner sexual assault (low: aOR 2.7, 95% CI 1.3-5.5; high: aOR 4.1, 95% CI 2.8-5.9). Analysis with female participants found an association between cyber dating abuse exposure and contraceptive nonuse (low: aOR 1.8, 95% CI 1.2-2.7; high: aOR 4.1, 95% CI 2.0-8.4) and reproductive coercion (low: aOR 3.0, 95% CI 1.4-6.2; high: aOR 5.7, 95% CI 2.8-11.6). Cyber dating abuse is common and associated with ARA and sexual assault in an adolescent clinic-based sample. The associations of cyber dating abuse with sexual behavior and pregnancy risk behaviors suggest a need to integrate ARA education and harm reduction counseling into sexual health assessments in clinical settings.


DNA--a molecule in search of additional functions: recipient of pool wave emissions? A hypothesis.
Almost the entire nucleotide sequence of human DNA is functionally unaccounted for, although large parts of the human genome are transcribed. The genes, as defined by current molecular biology, comprise about 1.5-2% of the DNA molecule. It is proposed that DNA encodes additional, hitherto unrecognized functions. In this discussion, the total information inside and outside the universe we live in is termed the pool or the sum total, known or unknown, of all laws, matter, energy, concepts and events. In a hypothetical model, a Gedankenexperiment, it is suggested that the total of all information emits pool waves of an unknown physical nature. They could be related to black energy or have completely different qualities. The designation pool waves should not imply any similarity to electromagnetism. Further, DNA is suggested to have the capability of interacting with the pool waves and thus permit humans - to some partly genetically determined and yet very limited extent - to perceive information from the pool. Pool emissions might be one of the forces that have been instrumental in and are still driving evolution from simple oligonucleotides to DNA with ever more complex recipient capacities. It will be a major challenge for researchers in the field to unravel these and less hypothetical undetected coding principles in DNA. It is uncertain whether the current trend to search the available DNA sequences with ever more refined computer technology on the basis of our present understanding of biology will detect unknown coding systems. For molecular medicine, research into the genetics of the most common human diseases could profit from the elucidation of presently still ephemeral codes in human DNA. Young scientists with a proven record of original research deserve support for the pursuit of unconventional ideas. This concept of granting priorities will be of the utmost importance in advancing the field beyond current concepts in molecular biology.


Detecting stable individual differences in the functional organization of the human basal ganglia.
Moving from group level to individual level functional parcellation maps is a critical step for developing a rich understanding of the links between individual variation in functional network architecture and cognitive and clinical phenotypes. Still, the identification of functional units in the brain based on intrinsic functional connectivity and its dynamic variations between and within subjects remains challenging. Recently, the bootstrap analysis of stable clusters (BASC) framework was developed to quantify the stability of functional brain networks both across and within subjects. This multi-level approach utilizes bootstrap resampling for both individual and group-level clustering to delineate functional units based on their consistency across and within subjects, while providing a measure of their stability. Here, we optimized the BASC framework for functional parcellation of the basal ganglia by investigating a variety of clustering algorithms and similarity measures. Reproducibility and test-retest reliability were computed to validate this analytic framework as a tool to describe inter-individual differences in the stability of functional networks. The functional parcellation revealed by stable clusters replicated previous divisions found in the basal ganglia based on intrinsic functional connectivity. While we found moderate to high reproducibility, test-retest reliability was high at the boundaries of the functional units as well as within their cores. This is interesting because the boundaries between functional networks have been shown to explain most individual phenotypic variability. The current study provides evidence for the consistency of the parcellation of the basal ganglia, and provides the first group level parcellation built from individual-level cluster solutions. These novel results demonstrate the utility of BASC for quantifying inter-individual differences in the functional organization of brain regions, and encourage usage in future studies.


Topical heparin as an effective and safe treatment for patients with capecitabine-induced hand-foot syndrome: results of a phase IIA trial supported by proteomic profiling of skin biopsies.
Hand-foot syndrome (HFS) is a common adverse reaction associated with capecitabine chemotherapy that significantly affects the quality of life of patients. This study evaluates the safety and effectiveness of a topical heparin (TH) treatment on the clinical manifestations and anatomopathological alterations of capecitabine-induced HFS. In addition, we performed proteome profiling of skin biopsies obtained from patients with HFS at baseline and after heparin treatment. Patients with grade ⩽ 2 HFS associated with capecitabine were included in this study. The primary end point was the effectiveness of TH in reducing HFS of any grade. Clinical improvement was evaluated by clinicians, and an improvement was perceived by patients who performed a weekly visual analog scale questionnaire. Secondary end points included a comparative histological analysis and protein expression in skin biopsies at baseline and after 3 weeks of HT treatment. Proteomic profiling was carried out using quantitative isobaric labelling and subsequently validated by a T-array. Twenty-one patients were included in the study. The median TH treatment time was 7.6 weeks (range = 3.6-41.6 weeks), and the median response time was 3.01 weeks (95% CI = 2.15-3.97). At the end of treatment, 19 of 21 patients (90.48%) responded to treatment with a decrease in one or more grades of HFS. None of the patients experienced adverse effects related to TH usage, nor did they suspend chemotherapy treatment. The main findings observed in skin biopsies after treatment were a decrease in hyperkeratosis and lymphocytic infiltrates. The proteomic analysis showed altered expression of 34 proteins that were mainly related to wound healing, cell growth, and the immune response. Based on our results, topical heparin is an effective and safe treatment for clinical manifestations of HFS, probably due to the restauration of skin homeostasis after heparin treatment, as supported by our proteomics-derived data. EudraCT 2009-018171-13.


Evaluation of skeletal muscle mass as a predictor of prognosis in patients treated in hospital for COVID-19 infection.
Skeletal muscle indexes are known to be one of the important prognostic indicators in many clinical situations. This study aims to evaluate the effects of laboratory values and muscle mass measures such as skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle density (SMD) and skeletal muscle gauge (SMG) obtained from the 12th thoracic vertebra (T12) level of patients hospitalized for COVID-19 infection on prognosis. The patients' age, comorbidity index (CCI) scores, gender, anthropometric criteria such as height, weight, and BMI, laboratory values, development of NIMV and IC need during follow-up, length of hospital stay, and hospital mortality were retrospectively screened. The relationship between clinical and laboratory variables, SMA, SMI, SMD, and SMG values, and patient outcomes such as the need for non-invasive mechanical ventilation (NIMV), need for intensive care, and mortality was investigated using multivariate logistic regression analysis. It was shown in multilinear regression analysis that T12SMD (β=-0.254; p=0.036), albumin (β=-0.465; p=0.005), and procalcitonin values (β=-0.292; p=0.026) were independent risk factors on mortality for intensive care in patients hospitalized due to COVID-19 infection. T12SMD has been shown to be significantly associated with various negative outcomes such as mortality, need for NIMV, and need for intensive care independently of body mass index (BMI) in our study (Tab. 5, Fig. 2, Ref. 25).


"Low T3 syndrome" in cirrhosis: effect of beta-blockade.
The so-called "low T3 syndrome" has frequently been reported in patients with cirrhosis. In this study, we aimed to determine whether administration of propranolol to such patients leads to further changes in plasma thyroid hormones, since it can affect their peripheral metabolism. Twenty cirrhotics (11 with ascites) whom we investigated showed no clinical evidence of thyroid dysfunction. The free fractions of plasma T3 and T4 (FT3, FT4) were determined by radioimmunoassay before and after the achievement of an effective beta-blockade by propranolol. The activity of the sympathetic nervous system also was evaluated by measuring plasma norepinephrine concentration. Under basal conditions, cirrhotics showed a reduced FT3 (2.45 +/- 0.11 SEM vs 3.55 +/- 0.16 pg/ml; p less than 0.001) and comparable FT4 (7.62 +/- 0.79 vs 9.2 +/- 0.42 pg/ml) and FT3/FT4 ratio (0.38 +/- 0.04 vs 0.42 +/- 0.013) with respect to healthy controls. When patients with ascites were considered apart, a reduction of FT4 was also found (6.78 +/- 0.74 pg/ml; p less than 0.01). In these patients, many of whom showed an increased plasma norepinephrine concentration, an inverse correlation between log FT3/FT4 and log plasma norepinephrine concentration was found (r = -0.79; p less than 0.01). The effective beta-blockade did not lead to significant changes in either FT3 or FT4 or FT3/FT4, whether the patients were considered as a whole (2.52 +/- 0.19 pg/ml, 9.3 +/- 1.41 pg/ml, and 0.36 +/- 0.04, respectively), or were split into groups according to the presence of ascites. When administered to cirrhotics, propranolol did not worsen thyroid hormone abnormalities, thus appearing to be safe in this respect. This may result from an impaired influence of the sympathoadrenergic system on thyroid hormone metabolism.


Developing models for pediatric residency training in managed care settings.
The preparation of pediatric residents to function optimally in managed care environments challenges educators to create a new set of educational objectives and competencies and to incorporate these into curricula that are already full. Many of the skills needed to practice managed care are those that have been required for the practice of pediatrics in any setting. Nevertheless, the emergence of managed care requires the identification of new knowledge to be acquired and new skills and attitudes to be incorporated into daily practice. These competencies can be identified most thoroughly through collaboration among physicians, educators, and leaders of managed care organizations. This joint effort should also serve to establish a foundation on which collaborative, mutually beneficial learning environments can be created. The development of curricula that provide the opportunities needed to attain managed care proficiencies requires an individualized approach for each program that takes into account the degree of managed care penetration in each training environment. Programs in which a managed care approach to patient care predominates will be able to promote most easily their trainees' incorporation of these principles into routine practice. Those with less regular exposure will be forced either to promote managed care principles in an environment in which they may not be accepted or practiced, or to join in partnership with managed care organizations (MCOs) to train residents. Regardless of the setting, evaluation methodologies must be developed to ensure that each of the core competencies has been learned, can be applied to clinical situations, and is retained throughout the training period. These efforts require the development of faculty who understand and can model a managed care approach to patient management. The ongoing evolution of managed care systems encourages the development of new, creative strategies to train faculty, who may find themselves learning about this emerging environment at the same time as are their trainees.


Revisiting Centrioles in Nematodes-Historic Findings and Current Topics.
Theodor Boveri is considered as the "father" of centrosome biology. Boveri's fundamental findings have laid the groundwork for decades of research on centrosomes. Here, we briefly review his early work on centrosomes and his first description of the centriole. Mainly focusing on centriole structure, duplication, and centriole assembly factors in C. elegans, we will highlight the role of this model in studying germ line centrosomes in nematodes. Last but not least, we will point to future directions of the C. elegans centrosome field.


POEMS syndrome complicated with multiple ischemic vascular events: case report and review of literature.
POEMS syndrome (acronym consisting of: polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) is an uncommon disorder associated with an underlying plasma cell dyscrasia. There is no single specific test for POEMS, and due to its rarity and heterogeneity, patients are often mis- or underdiagnosed. Castleman disease (CD) is a rare lymphoproliferative disorder, closely related to POEMS syndrome; ~11%-30% of POEMS patients are associated with concomitant CD. In contrast to frequently published reports on vascular events in POEMS syndrome affecting coronary arteries or lower limbs, cases of cerebrovascular events are rarely mentioned in literature. We hereby report a patient with POEMS syndrome accompanied by CD who presented recurrent strokes and splenic infarction.


Comparison of growth kinetics for healthy and heat-injured Listeria monocytogenes in eight enrichment broths.
Detection of Listeria in food products is often limited by performance of enrichment media used to support growth of Listeria to detectable levels. In this study, growth curves were generated using healthy and heat-injured Listeria monocytogenes strain F5069 in three nonselective and five selective enrichment broths. Nonselective enrichment media included the current Food and Drug Administration Bacteriological Analytical Manual Listeria enrichment broth base (BAM), Listeria repair broth (LRB), and Trypticase soy broth. Selective enrichment media included BAM with selective agents and LRB with selective agents, BCM L. monocytogenes preenrichment broth, Fraser broth, and UVM-modified Listeria enrichment broth. The Gompertz equation was used to model the growth of L. monocytogenes. Gompertz parameters were used to calculate exponential growth rate, lag-phase duration (LPD), generation time, maximum population density (MPD), and time required for repair of injured cells. Statistical differences (P < 0.05) in broth performance were noted for LPD and MPD when healthy and injured cells were inoculated into the broths. With the exception of Fraser broth, there were no significant differences in the time required for the repair of injured cells. Results indicate that the distinction between selective and nonselective broths in their ability to grow healthy Listeria and to repair sublethally injured cells is not solely an elementary issue of presence or absence of selective agents.


[Patterns of neuronal activity in the basal ganglia nucleus in parkinsonian patients with levodopa-induced dyskinesia].
To explore the patterns of neuronal activity in the basal ganglia nucleus in parkinsonian patients with levodopa-induced dyskinesia (LID). Sixteen idiopathic parkinsonian patients, 11 males and 5 female: 5; aged 56.1 +/- 11.9, with the mean disease duration of (10.1 +/- 6.6). years and Hoehn & Yahr score ranging 2 -4, all with the symptoms of tremor, rigidity, and bradykinesia, 8 with severe LID [with the mean unified Parkinson's disease rating scale (UPDRS) IV score of 6.8 +/- 1.5] underwent pallidotomy (n = 8) or subthalamic nucleus (STN) deep brain stimulation (DBS) implantation (6 bilaterally and 2 unilaterally). Microrecording was performed in the globus pallidus internus (GPi) and STN. Electromyogram (EMG) on the contralateral limbs to surgery was simultaneously recorded. Single unit analysis was performed. The interspike interval (ISI) and coefficient of variation (CV) of ISI were calculated. One-way ANOVA and rank test were employed to compare the ISI and CV among the patients. Two hundred and thirty-eight neurons were identified from the GPi (n = 8) and STN (n = 14). 22.6% of them were tremor-related neurons, 33.8% were rapid tonic neuronal activity[ related, and 29.0% were irregular neuronal activity-related. It was discovered that 8. 0% of the neurons from GPi and STN were with grouped discharge following long period pause with the CV of 87 +/- 0.55, and 7.5% of the neurons were with low frequency firing with the mean frequency of (17.7 +/- 5.9) Hz. ANOVA revealed that in the STN the CV of the neurons with irregular with grouped discharge was significantly higher than those of the neurons with irregular neuronal activity and with low frequency firing (both P < 0.05), the ISI of the neurons with irregular grouped discharge was significantly higher than that of the neurons with low frequency firing and significantly higher than that of the neurons irregular neuronal activity (both P < 0.05); and in the GPi the CV of the neurons with irregular grouped discharge was significantly lower than those of the neurons with irregular neuronal activity and those with low frequency firing and the ISI of the neurons with irregular grouped discharge was significantly higher than those of the other groups (all P < 0.05). Chi square test showed that majority of the neurons with grouped discharge and neurons with low frequency firing mainly existed in the GPi and STN of the PD patients with LID (all P < 0.05). The altered neuronal activity in the basal ganglia nucleus of GPi and STN plays an important role in the pathophysiology of PD and LID.


Global Health - emergence, hegemonic trends and biomedical reductionism.
Global Health has increasingly gained international visibility and prominence. First and foremost, the spread of cross-border infectious disease arouses a great deal of media and public interest, just as it drives research priorities of faculty and academic programmes. At the same time, Global Health has become a major area of philanthropic action. Despite the importance it has acquired over the last two decades, the complex collective term "Global Health" still lacks a uniform use today. The objective of this paper is to present the existing definitions of Global Health, and analyse their meaning and implications. The paper emphasises that the term "Global Health" goes beyond the territorial meaning of "global", connects local and global, and refers to an explicitly political concept. Global Health regards health as a rights-based, universal good; it takes into account social inequalities, power asymmetries, the uneven distribution of resources and governance challenges. Thus, it represents the necessary continuance of Public Health in the face of diverse and ubiquitous global challenges. A growing number of international players, however, focus on public-private partnerships and privatisation and tend to promote biomedical reductionism through predominantly technological solutions. Moreover, the predominant Global Health concept reflects the inherited hegemony of the Global North. It takes insufficient account of the global burden of disease, which is mainly characterised by non-communicable conditions, and the underlying social determinants of health. Beyond resilience and epidemiological preparedness for preventing cross-border disease threats, Global Health must focus on the social, economic and political determinants of health. Biomedical and technocratic reductionism might be justified in times of acute health crises but entails the risk of selective access to health care. Consistent health-in-all policies are required for ensuring Health for All and sustainably reducing health inequalities within and among countries. Global Health must first and foremost pursue the enforcement of the universal right to health and contribute to overcoming global hegemony.


Meet the players: local translation at the synapse.
It is widely believed that activity-dependent synaptic plasticity is the basis for learning and memory. Both processes are dependent on new protein synthesis at the synapse. Here, we describe a mechanism how dendritic mRNAs are transported and subsequently translated at activated synapses. Furthermore, we present the players involved in the regulation of local dendritic translation upon neuronal stimulation and their molecular interplay that maintain local proteome homeostasis. Any dysregulation causes several types of neurological disorders including muscular atrophies, cancers, neuropathies, neurodegenerative, and cognitive disorders.


[Relationship between cognitive function and physical activities: a longitudinal study among community-dwelling elderly].
The purpose of this study was to evaluate whether physical activities reduce the risk of cognitive decline in community-dwelling elderly. We investigated correlations between cognitive functions at baseline and physical activities, correlations between cognitive functions at baseline and cognitive decline over 4 years, as well as correlations between physical activity at baseline and cognitive decline over 4 years. At baseline, 2,431 community-dwelling elderly completed the cognitive screening by telephone (TICS-J), and answered the questionnaires about physical activities. Of these, 1,040 subjects again completed the TICS-J over 4 years. Physical activities contained moving ability, walking frequency, walking speed, the exercise frequency. At baseline, 870 elderly (age 75.87±4.96 (mean±SD) years, duration of education 11.05±2.41) showed normal cognitive functions and 170 (79.19±6.22, 9.61±2.23) showed cognitive impairment. The total TICS-J score was significantly higher in cognitive normal subjects compared with that of cognitive impaired subjects (36.02±1.89, 30.19±2.25, respectively, p<0.001). Logistic regression analyses showed that moving ability significantly reduced the risk of cognitive impairment in an unadjusted model, and walking speed also reduced the risk of cognitive impairment at baseline even in an adjusted model. Cognitive function at baseline might be a predictor of cognitive function over 4 years. The longitudinal study revealed that walking speed and exercise frequency significantly correlate with maintenance of cognitive function over 4 years. This study provides that physical activities, especially walking speed have significant correlation with cognitive function.