Imagined and extended contact experiences and adolescent bystanders' behavioral intentions in homophobic bullying episodes.
Bystanders' helping interventions in bias-based bullying are rare, although they have the potential to intervene on behalf of the victim and quickly stop the aggression. Two studies tested, experimentally, the impact of adolescents' imagined (Study 1, N = 113, Mage = 16.17) and extended contact experiences (Study 2, N = 174, Mage = 15.79) on assertive bystanders' behavioral intentions in the context of homophobic bullying, an under-researched but highly detrimental behavior that emerges mainly during early adolescence. Potential mediators (empathic concern, social contagion concerns, and masculinity/femininity threat) were also examined. Results showed that female younger participants revealed more behavioral intentions to help victims of homophobic bullying when asked to imagine an interaction with an outgroup member (Study 1). Younger participants revealed less masculinity/femininity threat in the positive extended contact condition, and female participants revealed less empathic concern in the negative extended contact condition (Study 2). Overall, these findings identify specific conditions (e.g., younger females) where indirect contact interventions (i.e., extended and imagined) are likely to have a stronger impact. Age and sex differences were found to illustrate how adolescents vary in their behavioral intentions, empathic concern, and threat; and also highlight the need to further examine age and sex differences regarding responses to homophobic bullying episodes.


LC-MS/MS method development and validation for the determination of polymyxins and vancomycin in rat plasma.
Simple, sensitive and robust liquid chromatography-tandem mass spectrometer (LC-MS/MS) methods were developed and validated for the determination of lipopeptide polymyxins and glycopeptide vancomycin in rat plasma. The effect of trichloroacetic acid (TCA) concentration on sample recoveries (peak area of sample recovered from plasma/peak area of sample from neat solvent solutions) was studied and an optimized concentration of 30% TCA were determined that gives the best sample recovery for the peptides from rat plasma. The effect of the TCA concentration on the chromatographic behavior of peptides was studied on a Phenomenex Jupiter C18 5μ 300Å 50mm×2mm column using a mobile phase with a pH of 2.8. Other than protein precipitation, TCA also acted as ion pairing reagent and was only present in the samples but not in the mobile phases. The data demonstrated that by increasing the TCA concentration, the analyte retention and sensitivity were improved. The absence of TCA in mobile phase helped to reduce the ion source contamination and to achieve good reproducibility. The plasma method was linearly calibrated from 5 to 5000ng/mL for polymyxins with precisions to be of 2.3-10.8%, and accuracies to be 91.7-107.4% for polymyxin B1, B2, E1, E2, respectively. For vancomycin the calibration is from 1 to 5000ng/mL with precisions to be of 7.8-10.3 and accuracies to be 96.2-102.0%. The LLOQs corresponding with a coefficient of variation less than 20% were 7.5, 18.1, 7.3, 5.0 and 1.0ng/mL for polymyxin B1, B2, E1, E2 and vancomycin, respectively.


Analytical and semipreparative enantiomeric separation of azole antifungal agents by high-performance liquid chromatography on polysaccharide-based chiral stationary phases. Application to in vitro biological studies.
High-performance liquid chromatography (HPLC) was used for the enantiomeric separation of chiral imidazole derivatives endowed with antimycotic activity. Enantioselective columns, containing carbamates of cellulose and amylose, were used. The influence of the nature and content of an alcoholic modifier in the mobile phase was studied. The isolated enantiomers, separated on semipreparative columns, were submitted to in vitro biological investigations.


Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes.
Screening for pulmonary hypertension (pHTN) has not yet become routine in sickle cell disease (SCD), despite clinical evidence of its high prevalence and associated mortality. Our objectives are to identify clinical conditions and laboratory findings predictive of/or associated with pHTN. One hundred twenty-five adult outpatients with Hb SS, SC, SOArab, Sbeta(0), or Sbeta(+) thalassemia, who underwent echocardiography and/or right heart catheterization due to cardiorespiratory symptoms, were studied. pHTN was identified in 36% (28/77) of SS/Sbeta(0) and in 25% (12/48) of SC/SOArab/Sbeta(+) patients studied. In SS/Sbeta(0) patients, pHTN was associated with low hemoglobin, low GFR, increasing age, no history of treatment with hydroxyurea and a history of leg ulcers, with trends for associations with higher total bilirubin, LDH levels, systolic systemic blood pressure, history of avascular necrosis, seizures, and cerebrovascular events. Twelve (40%) of the SS/Sbeta(0) patients with pHTN had >or= 1+ proteinuria. (P<0.039). The presence of proteinuria correlated with lower GFR and had a high positive predictive value (0.60) for pHTN in subjects with SS/Sbeta(0). The data also provided evidence that pHTN in this population is associated with right heart failure, with echocardiographic evidence of right ventricle enlargement and pericardial effusion. This study confirmed that even relatively mild elevations in pulmonary pressure are associated with high prospective mortality (hazard ratio: 15.9). We concluded that pHTN has a high prevalence in all Hb S related syndromes and is associated with increased mortality in SS/Sbeta(0). Kidney dysfunction, as indicated by proteinuria or decreased GFR, also represents sufficient reason to screen for pHTN.


Documented clinical experiences of primary care RN students: a preliminary report.
A student-patient encounter form was developed for documenting patients' visits in the practicums of three primary care courses--obstetric-gynecology, pediatrics, and general adult patients--and from January 1973 to June 1974, 22 registered nurse students completed 1,027 student-patient encounter forms. Health problems were identified, using the Weed system and classified by the International Classification of Disease adapted for use in the United States. The study demonstrated that the encounter form facilitated the documentation of base-line data for student practicums. Preliminary analysis of the data revealed that: 1) health problems of patients classified as "without sickness" were important in the case loads of registered nurse students in obstetric-gynecologic and pediatric practicums; 2) health problems of patients classified as "symptoms of ill-defined conditions" were also important in all three student practicums, particularly with general adult patients: and 3) students encountered a cluster of health problems in dealing with patients in the three practicums. The study suggested a need to develop a classification scheme for health problems encountered in primary care nursing services.


Measurement of long range H,C couplings in natural products in orienting media: a tool for structure elucidation of natural products.
In this paper we show that water insoluble compounds dissolved in poly-gamma-benzyl-glutamate are amenable to the measurement of a number of homo- and heteronuclear dipolar couplings. The sensitivity and experimental precision of dipolar couplings are sufficient to obtain a good match with the structure. In order to achieve the necessary precision for H,C dipolar couplings between protons and carbons that are not directly bound a new method for the measurement of heteronuclear long range couplings is introduced that allows a one-parameter fit to a HSQC-based experiment as reference experiment. The methodology is applied to menthol (1R, 3S, 4R).


Phase-assisted synthesis and DNA unpacking evaluation of biologically inspired metallo nanocomplexes using peptide as unique building block.
The goal of nanomaterials' surface modification using a biomaterial is to preserve the materials' bulk properties while modifying only their surface to possess desired recognition and specificity. Here, we have developed a phase-assisted, modified Brust-Schiffrin methodological synthesis of metallo nanocomplexes anchored by a peptide, N,N'-(1,3-propylene)-bis-hippuricamide. The spectral, thermal and morphological characterizations assure the formation of nanocomplexes. Therapeutic behavior of all the nanocomplexes has been well sighted by evaluating their DNA unpacking skills. In addition, we demonstrate their biological inspiration by targeting few bacterial and fungal strains. The in vitro antimicrobial investigation reports that all the nanocomplexes disrupt microbial cell walls/membranes efficiently and inhibit the growth of microbes. These sorts of nanocomplexes synthesized in large quantities and at low cost, deliver versatile biomedical applications, and can be used to treat various diseases which may often cause high mortality.


Correlation Analysis of Breast Cancer DWI Combined with DCE-MRI Imaging Features with Molecular Subtypes and Prognostic Factors.
This study aimed to deeply analyze the application of DWI and DCE-MRI imaging in breast cancer, the correlation between the imaging characteristics of DWI and DCE-MRI and the molecular subtypes and prognostic factors of breast cancer was studied. Firstly, DWI and DCE-MRI scans of all patients before interventional therapy were performed, and relevant information of the subjects was introduced in turn. Secondly, molecular subtypes were determined according to immunohistochemical results and gene amplification. Siemens 3.0 T post-processing workstation was used for image post-processing. The time signal curve (TIC), early enhancement rate (EER) and ADC values were measured, morphological characteristics were recorded, and the correlation between each image feature and molecular subtypes, prognostic factors (tumor size, pathological grade, lymph node metastasis, ER, PR, HER2, Ki67) was analyzed. The results showed that parameters such as ADC value, EER, lobulation sign, burr sign, enhancement way and TIC type were correlated with prognostic factors and molecular subtypes. And Bayesian model discriminant analysis showed that the above imaging parameters couldn't well predict the expression of immunohistochemical factors and molecular subtypes. However, the above characteristics had a good effect on the prediction of pathological grade, with a false diagnosis rate of 9.69%.


Removal of antimony (III) and cadmium (II) from aqueous solution using animal manure-derived hydrochars and pyrochars.
In this study, hydrochars and pyrochars prepared from animal manures were characterized and were used to remove Sb (III) and Cd (II) from aqueous solution. Fourier transform infrared spectroscopy (FTIR) analysis revealed the interaction between Cd (II) and CO and CO groups within biochars and between Sb (III) and CO, CO and OH groups, respectively. Additionally, the lower absolute value of zeta potential of biochar after loading Sb (III) and Cd (II) suggested the occurrence of surface complexation. Existing primarily in the form of Sb (OH)3, the maximum adsorption capacities (Qmax) for Sb (III) were lower than those for Cd (II). Due to the lower contents of surface polar functional groups and less negative surface charge, hydrochars exhibited lower Qmax for Sb (III) and Cd (II) than pyrochars. However, hydrochars in this study had higher sorption capacities for Cd (II) than most of plant-based pyrochars reported by other literature.


Integrated femtosecond pulse generator on thin-film lithium niobate.
Integrated femtosecond pulse and frequency comb sources are critical components for a wide range of applications, including optical atomic clocks1, microwave photonics2, spectroscopy3, optical wave synthesis4, frequency conversion5, communications6, lidar7, optical computing8 and astronomy9. The leading approaches for on-chip pulse generation rely on mode-locking inside microresonators with either third-order nonlinearity10 or with semiconductor gain11,12. These approaches, however, are limited in noise performance, wavelength and repetition rate tunability 10,13. Alternatively, subpicosecond pulses can be synthesized without mode-locking, by modulating a continuous-wave single-frequency laser using electro-optic modulators1,14-17. Here we demonstrate a chip-scale femtosecond pulse source implemented on an integrated lithium niobate photonic platform18, using cascaded low-loss electro-optic amplitude and phase modulators and chirped Bragg grating, forming a time-lens system19. The device is driven by a continuous-wave distributed feedback laser chip and controlled by a single continuous-wave microwave source without the need for any stabilization or locking. We measure femtosecond pulse trains (520-femtosecond duration) with a 30-gigahertz repetition rate, flat-top optical spectra with a 10-decibel optical bandwidth of 12.6 nanometres, individual comb-line powers above 0.1 milliwatts, and pulse energies of 0.54 picojoules. Our results represent a tunable, robust and low-cost integrated pulsed light source with continuous-wave-to-pulse conversion efficiencies an order of magnitude higher than those achieved with previous integrated sources. Our pulse generator may find applications in fields such as ultrafast optical measurement19,20 or networks of distributed quantum computers21,22.


COVID-19, Health, Conservation, and Shared Wellbeing: Details Matter.
Many have stridently recommended banning markets like the one where coronavirus disease 2019 (COVID-19) originally spread. We highlight that millions of people around the world depend on markets for subsistence and the diverse use of animals globally defies uniform bans. We argue that the immediate and fair priority is critical scrutiny of wildlife trade.


From East to West: Effects of the globalization of cultural practices.
Throughout the world, the marks and assimilation of traditional sociocultural values into popular, mainstream culture have become the new norm: from wedding ceremonial tradition, such as mehndi and bindi, to cosmetic hair removal, such as threading, have gained popularity among Western countries. The boundaries of dermatology practice also extend beyond the countries' borders. The knowledge regarding common cultural practices from East to West may help clinicians in the increasing globalized practice of dermatology.


Studies on the protective effect of prostacyclin in acute myocardial ischemia.
The ability of prostacyclin (PGI2) to alter responses to acute myocardial ischemia was studied in open-chest, anesthetized cats. PGI2 was infused intravenously at 0.5 nmoles kg-1 min-1 in cats subjected to 5 h of myocardial ischemia by occlusion of the LAD coronary artery, and in sham-operated controls. GI2 infusion resulted in significantly decreased arterial blood pressure and inhibition of platelet aggregation. Coronary ligation resulted in significant S-T segment elevations lasting 5 h in vehicle-treated animals but only 1 h in cats with myocardial ischemia and receiving PGI2. At 5 h, cats with ischemia and given the vehicle showed S-T segment elevations significantly greater than the other two groups. Ischemic myocardium from vehicle-treated animals exhibited significantly less creatine phosphokinase (CPK) specific activity than normal tissue from the same hearts or myocardial tissue from the other two groups. This loss of CPK from ischemic myocardium of the cats given vehicle was reflected in plasma CPK specific activities which were significantly greater than those of sham-operated cats. The cats with ischemia and treated with PGI2 exhibited lower plasma CPK activities. These changes were moderated by PGI2 infusion during myocardial ischemia. PGI2 infusion may protect the ischemic myocardium by reducing oxygen demand, primarily through reductions in cardiac work, and by perhaps inhibiting platelet aggregation and preserving myocardial cell integrity.


The pathway of isolated seminal vesicle invasion has a different impact on biochemical recurrence after radical prostatectomy and pelvic lymphadenectomy.
Prostate cancer with seminal vesicle invasion (SVI) has been considered an aggressive cancer. To evaluate the prognostic significance of different patterns of isolated SVI in patients undergoing radical prostatectomy (RP) and pelvic lymphadenectomy. We retrospectively analyzed all patients who underwent RP between 2007 and 2019. Inclusion criteria were localized prostate adenocarcinoma, SVI at RP, at least 24-months follow-up, and no adjuvant treatment. Patterns of SVI were following Ohori's classification: type 1: direct spread along the ejaculatory duct from inside; type 2: seminal vesicle invasion outside the prostate, through the capsule; type 3: the presence of cancer island(s) in the seminal vesicle with no continuity from the primary tumor (discontinuous metastases). Patients with type 3 SVI (isolated or in association) were included in the same group. Biochemical recurrence (BCR) was defined as any postoperative PSA ≥0.2 ng/ml. A logistic regression analysis was performed to assess predictors of BCR. Time to BCR was investigated using the Kaplan-Meier analysis with the log-rank test. Sixty-one out of 1,356 patients were included. Median age was 67(7.2) years. Median PSA was 9.4(8.92) ng/ml. Mean follow-up was 85.28 ± 45.27 months. BCR occurred in 28(45.9%) patients. Logistic regression showed that a positive surgical margin (OR 19.964, 95%CI:1.172-29.322, P = 0.038) was predictor of BCR. Kaplan-Meier analysis demonstrated that patients with pattern 3 had a significantly shorter time to BCR compared to other groups (log-rank, P = 0.016). The estimated time to BCR was 48.7 months in type 3, 60.9 months in pattern 1 + 2, 74.8, and 100.8 months in isolated patterns 1 and 2, respectively. In patients with negative surgical margins, pattern 3 confirmed a shorter time to BCR compared to other types of invasions, with an estimated time to BCR of 30.8 months. Patients with type 3 SVI demonstrated a shorter time to BCR compared to other patterns.


Co-existent cutaneous cryptococcosis of the forearm and cutaneous alternariosis of the leg in patient with metastatic thymoma.
Cryptococcosis and alternariosis are rare opportunistic infections often observed in immunocompromised patients. Because Cryptococcus and Alternaria are ubiquitous fungi found in soil, the presence of fungi in the dermis has to be observed on histological examination to confirm a real cutaneous, invasive, infection. We report the first case of concomitant cutaneous cryptococcosis and cutaneous alternariosis, in an immunocompromised patient treated for a metastatic thymoma. This observation underlines the fact that the possible co-existence of several rare infections in immunocompromised patients should take into consideration pathogen identification in order to adapt the therapy to individual patient requirements.


Adjustment of the surgical plan in repair of congenital heart disease: the power of cross-sectional imaging and three-dimensional visualization.
The purpose of this article is to study the importance of cross-sectional imaging in preoperative evaluation and surgical planning. Echocardiography is the modality of choice to diagnose cardiac diseases. However, in some cases, the data obtained from echocardiogram are insufficient or the image quality is poor. In these cases, additional modalities are being used to provide further information that can aid in guiding medical management of or surgical planning for the patient. Cross-sectional imaging has become widely available in many institutions. These imaging techniques, especially with three-dimensional reconstructions, provide realistic images that have imperative diagnostic values. Moreover, the possibility of sophisticated image-processing techniques provides important hemodynamic characteristics via less invasive methods. In this article, we present three cases in which additional cross-sectional imaging seemed to be a crucial step prior to surgical planning.


Ecchordosis physaliphora: Case report and brief review of the literature.
Ecchordosis physaliphora is a rare congenital benign hamartomatous lesion originating from nodal cord remnants. This is histopathologically indistinguishable from chordoma, and hence imaging plays a key role in diagnosis. These lesions are hypointense on T1-weighted and hyperintense on T2-weighted images, and follow CSF signal. In contrast to chordoma, Ecchordosis Physaliphora does not demonstrate contrast enhancement. Here, we present a case of 32-year-old male with no prior medical history, who presented to an outside facility for chronic headache workup and incidentally detected indeterminate lytic defect in the bony clivus with a well demarcated smoothly corticated margin. Further assessment with MRI brain showed findings characteristic of Ecchordosis physaliphora, a benign congenital hamartomatous lesion originating from nodal cord remnants requiring no additional follow-up imaging or intervention.


Sexual behavior and self-declaration of sexual orientation among people 18-64 years in Brazil: results from the Knowledge, Attitudes, and Practices survey, 2013 and the National Health Survey, 2019.
Population surveys involving the monitoring of high-risk sexual behavior have been recognized as important public health tools to control the HIV epidemic and other sexually transmitted infections (STIs). Using data from the Knowledge, Attitudes, and Practices survey (PCAP-2013) and from the National Health Survey (PNS-2019), indicators of sexual behavior were compared according to sociodemographic characteristics among individuals aged 18-64 years, including size (%) estimates of men who have sex with men (MSM) and women who have sex with women (WSW). Specifically, the PNS-2019 prevalence estimates of homosexual, bisexual, heterosexual males and females were compared with those from the PCAP-2013. To compare PCAP and PNS proportional distributions, the Pearson's chi-square test, adjusted by the Rao-Scott's correction, was applied. Size (%) estimates of MSM and WSW obtained by direct questions from the PCAP-2013, showed higher homosexuality prevalence estimates than those resulting from the PNS-2019 self-declared sexual orientation. Significant differences were found between the MSM proportions according to the PCAP-2013 (3.7%; 95% CI 3.1-4.4%) and to the PNS-2019 (2.2%; 95% CI 1.9-2.5), and between the WSW proportions (4.6%; 95% CI 4.0-5.4%) and (2.1%; 95% CI 1.8-2.4), respectively. Results from both surveys showed MSM and WSW prevalence estimates increase with educational level, decrease with age, and is larger among people who do not live with partner, live in urban areas and in state capitals. Regarding condom use at last sexual intercourse, no differences between the PCAP-2013 and the PNS-2019 estimates were found at the national level, but significant improvements were found for MSM, people aged 18-24 and 25-34 years, and individuals not living with a partner. The underestimation of MSM and WSW prevalence by self-declared sexual orientation suggests that sexual minorities face many difficulties related to disclosing their sexuality and reinforces the importance of developing public health interventions for changing population attitudes and promoting sexual orientation disclosure. Moreover, the low use of condoms in both surveys (PCAP-2013 and PNS-2019) carried out 6 years apart highlights the need of public policies to expand prevention strategies for HIV infection and other STIs.


Quantitative determination of styrene in biological samples and expired air by gas chromatography-mass spectrometry (selected ion monitoring).
Styrene, phenylethylene, is an oily liquid of commercial importance in the manufacture of various plastics, rubbers, resins, and insulating materials. A gas chromatographic-mass spectrometric method is described for the determination of low levels of styrene in biological samples. The procedure utilizes an internal standard and specificity is gained by monitoring selected ions.


[Hospitalisation at home of children seen in a pediatric outpatients (author's transl)].
The authors relate their experience of hospitalisation at home of 74 children selected in a pediatric outpatients over a period of 5 years. They show the advantages of this method of care which are much greater than the few disadvantages and regret that it is not used more often.


Poly (l-lactic acid) bioresorbable scaffolds versus metallic drug-eluting stents for the treatment of coronary artery disease: A meta-analysis of 11 randomized trials.
Bioresorbable vascular scaffolds (BVS) have been proposed for overcoming the long-term limitations of permanent metallic stents, while theoretically warranting similar advantages in plaque stabilization and anti-restenotic drug delivery in the early postrevascularization phase. However, increased rates of malapposition, restenosis, or thrombosis have emerged from initial trials with BVS, that were nevertheless underpowered for the evaluation of the real outcome benefits of these coronary devices. The recent completion of newer randomized clinical trials paves the way to the present meta-analysis, aiming at the comparison of Poly (l-Lactic acid) BVS (PLLA-BVS) versus metallic drug-eluting stents (DES) in the treatment of coronary stenoses. Literature and main scientific session abstracts were searched for randomized clinical trials (RCTs) comparing drug-eluting BVS versus metallic DES for the treatment of coronary artery disease (CAD). The primary efficacy endpoint was mortality, secondary endpoints were cardiovascular death, myocardial infarction, target lesion revascularization (TLR), stent thrombosis and the composite of device-oriented target lesion failure (TLF). We included 11 randomized trials, for a total population of 10,707 patients, 54.5% treated with BVS. The major indication for PCI was stable CAD, whereas acute coronary syndrome represented 30% of the patients. At a mean follow-up of 2.64 years (1-5 years), mortality occurred in 2.71% of the patients, with no difference according to the type of implanted stent (OR[95%CI] = 0.94 [0.74, 1.20], p = .62). No interaction was observed according to patients' risk profile or the rate of diabetes and ACS. However, a significant increase in myocardial infarction, stent thrombosis, TLR and TLF was observed with BVS as compared to DES. The present meta-analysis provides the most updated data on the use of PLLA-BVS for the treatment of CAD. We documented a poorer performance of these new coronary devices, as compared to new generation metallic DES, being associated with an increased rate of recurrent cardiovascular events. However, such ischemic complications did not impact on mortality, with a comparable survival independently from the type of stent.


Review of the status of radioactivity profile in the oil and gas producing areas of the Niger delta region of Nigeria.
There is widespread degradation of the environment of the Niger Delta region of Nigeria such that the United Nations Environment Program described it as an ecological wasteland. The contamination is due mainly to unregulated oil and gas production activities leading to oil spills and illegal disposal of contaminated materials, indiscriminate industrial and domestic discharges into water bodies. This widespread contamination includes naturally occurring radioactive materials (NORM) and technologically enhanced radioactive materials (TENORM). NORMs are naturally associated with every mineral in the earth crust, thus the exploitation of such minerals may transport NORM to the surface as TENORM. If uncontrolled by operators and unregulated by government agencies, NORM can find its way into surface and ground water, seafood and even crops consumed by humans. The Niger Delta region is the hub of oil and gas activities providing huge employment and socioeconomic benefits to its indigenes and accounting for more than 90% of foreign exchange earnings for the country. However, uncontrolled spills and discharges from these activities have left the land desolate, degrading most of its aquifers and surface waters, leaving the indigenes with a Hobson choice, eating and drinking contaminated substances everyday of their lives. It is expedient that attention be drawn to this area as radionuclides such as Po-210, Pb-210 and Ra-226 have been confirmed as radiotoxic and may be responsible for several new cases of health challenges reported in the study area over the years.


Innovations in diagnostic and treatment options for pediatric epilepsy and their anesthetic implications.
To provide an overview of anesthetic techniques for innovative diagnostic and therapeutic epilepsy procedures performed on pediatric patients. Recent studies have been published on the anesthetic consideration for functional MRI, robotic-assisted stereoelectroencephalography, high-intensity focused ultrasound, and magnetoencephalography. These articles describe the anesthesia management, risks, and outcome for these procedures. The number of diagnostic and treatment options being used for the management of pediatric epilepsy has increased significantly. In the past few years, a handful of articles have been published, which describe the anesthetic considerations for these procedures. These studies are helpful to anesthesiologists who are planning an upcoming anesthetic or who are developing a 'best practice' model for their institution. Because unlike other diagnostic studies, failure to understand what effects anesthetics have on the brain, may negate the utility of the study. Although these new findings can be used to provide some anesthesia practice recommendations for epilepsy procedures in which the best management is still unclear, additional high-quality studies are needed.


Enhanced erythroid cell differentiation in hypoxic condition is in part contributed by miR-210.
Erythropoiesis, a process of erythroid production, is controlled by several factors including oxygen level. In this study, the effect of oxygen tension on erythropoiesis was investigated in K562 erythroleukemic cell line and erythroid progenitor cells derived from normal and β-thalassemia/hemoglobin (Hb) E individuals. The enhanced erythroid differentiation specific markers including increased levels of α-, β- and γ-globin gene expressions, numbers of HbF positive cells and the presence of glycophorin A surface marker were observed during cell culture under hypoxic atmosphere. The result also showed that miR-210, one of the hypoxia-induced miRNAs, was up-regulated in K562 and β-thalassemia/HbE progenitor cells cultured under hypoxic condition. Inhibition of miR-210 expression leads to reduction of the globin gene expression and delayed maturation in K562 and erythroid progenitor cells. This indicated that miR-210 contributes to hypoxia-induced erythroid differentiation in both K562 cells and β-thalassemia/HbE erythroid progenitor cells.


Cardiovascular responses to epinephrine-containing local anesthetics for dental use: a comparison of hemodynamic responses to infiltration anesthesia and ergometer-stress testing.
Cardiovascular effects of infiltration anesthesia have been documented in numerous studies. However, few studies have been carried out to compare the effects of infiltration anesthesia with the effects of exercise-stress testing. The purpose of this study was to examine this issue. Eight young and 13 older subjects were given infusions of epinephrine to produce cardiovascular responses comparable with those found in subjects undergoing infiltration anesthesia with 3.6 mL of lidocaine with 1:80,000 epinephrine (L-E). Cardiovascular responses to this drug treatment were evaluated with echocardiography and compared with those produced by ergometer exercise. The hemodynamic effects of L-E infiltration anesthesia were less than those produced by ergometer-stress testing at 25 watts (W) in young subjects and at 15 W in the older subjects. The workload of this ergometer-stress testing was about 4 metabolic equivalents (METS), which is approximately equivalent to the workload of walking 4.8 km/hr, doing light yard work (ie, raking leaves, weeding, or pushing a power mower), painting, or doing light carpentry. With the exception of some specific pathologic conditions, such as serious arrhythmia, infiltration anesthesia with 3.6 mL of L-E can be carried out safely on the patients who have exercise capacity of more than 4 METS.


Cell Attachment and Viability Study of PCL Nano-fiber Modified by Cold Atmospheric Plasma.
The field of tissue engineering is an emerging discipline which applies the basic principles of life sciences and engineering to repair and restore living tissues and organs. The purpose of this study was to investigate the effect of cold and non-thermal plasma surface modification of poly (ϵ-caprolactone) (PCL) scaffolds on fibroblast cell behavior. Nano-fiber PCL was fabricated through electrospinning technique, and some fibers were then treated by cold and non-thermal plasma. The cell-biomaterial interactions were studied by culturing the fibroblast cells on nano-fiber PCL. Scaffold biocompatibility test was assessed using an inverted microscope. The growth and proliferation of fibroblast cells on nano-fiber PCL were analyzed by MTT viability assay. Cellular attachment on the nano-fiber and their morphology were evaluated using scanning electron microscope. The result of cell culture showed that nano-fiber could support the cellular growth and proliferation by developing three-dimensional topography. The present study demonstrated that the nano-fiber surface modification with cold plasma sharply enhanced the fibroblast cell attachment. Thus, cold plasma surface modification greatly raised the bioactivity of scaffolds.


Evidence-based nutrition guidelines for cancer survivors in Europe: a call for action.
The aims of this study were to (1) document currently available guidelines aimed at healthcare professionals and including some information on the nutritional management of cancer survivors in Europe; (2) assess the quality of these guidelines and (3) document the nutrition recommendations promoted. Four search strategies were implemented in 2018 and updated in 2021 to locate guidelines. Papers were included if they described a European guideline or recommendation for cancer survivors that contained nutrition guidance and there were no language restrictions. Two reviewers independently assessed guideline quality using the AGREE II instrument and nutrition content was extracted and summarised. Five guidelines (of 593 documents located through the searches) met the inclusion criteria. The ESPEN guidelines were deemed to have the highest methodological quality. Limited information on nutrition was available in these guidelines with the majority of focus being on the promotion of fruit, vegetables and wholegrains and reducing fat, red meat and alcohol. Weight management was mentioned by all five guidelines. There was no detailed information available for cancer survivors or their healthcare team and no practical strategies for the implementation of recommendations. There is a need for nutrition guidelines specific for cancer survivors in a European setting. Current guidelines are limited and focus on broad recommendations, while lacking in practical strategies for implementation. There is also a tendency to recommend cancer prevention guidelines be used for cancer survivors rather than developing specific guidance for this group.


The effects of chronic hepatitis C and B virus infections on liver reduced and oxidized glutathione concentrations.
The aim of this study was to evaluate the effects of hepatitis B and C virus infections on liver glutathione status. Reduced and oxidized glutathione levels were determined in liver biopsy specimens obtained from patients with chronic liver disease including chronic active hepatitis and cirrhosis. In patients with hepatitis B virus infections, GSH and GSH/GSSG levels were significantly low compared with those in controls (P<0.01). There was a significant negative correlation between histological activity indices (HAI) and hepatic GSSG levels only in patients with chronic HCV infection (P<0.01; r=-0.895). In addition to this, we also found a positive correlation between indices (HAI) and GSH/GSSG of the same group (r=0.915; P<0.05). These observations suggest that HBV and HCV infections have different effects on liver glutathione status based on diverse mechanisms.


Fibrous dysplasia of bone and McCune-Albright syndrome.
Fibrous dysplasia of bone is a genetic, non-inheritable disease, characterized by bone pain, bone deformities and fracture, involving one or several bones. It is caused by mis-sense mutations occurring post-zygotically in the gene coding for the alpha-subunit of the stimulatory G-protein, Gs, in the guanine nucleotide binding, alpha stimulating (GNAS) complex locus in chromosome 20q13. This mutation results in osteoblastic differentiation defects, and bone resorption is often increased. The bone lesions may be associated with endocrine dysfunctions and café-au-lait spots; this is known as McCune-Albright syndrome. Patients with polyostotic fibrous dysplasia often have renal phosphate wasting. The disease, however, has a wide clinical spectrum, so many patients are asymptomatic. Diagnosis relies on radiographs and pathology. Bisphosphonates have been used in the treatment of fibrous dysplasia to relieve bone pain and improve lytic lesions, but they are still under clinical evaluation. Calcium, vitamin D and phosphorus supplements may be useful in some patients. Surgery is also helpful to prevent and treat fracture and deformities.


Multiple Rapid Swallows (MRS) Complements Single-Swallow (SS) Analysis for High-Resolution Esophageal Manometry (HREM).
Multiple rapid swallows (MRS) during HREM assess post-deglutitive inhibition, LES relaxation, and subsequent esophageal contraction. (1) To determine the relationship between MRS and single-swallow (SS) responses and (2) to determine if MRS provides information for symptomatic patients. Healthy volunteers (HVs) and patients underwent HREM [30-s landmark, ten 5-mL SS, MRS (5 consecutive 2-mL swallows every 2-3 s)] and were analyzed with ManoView software version 3 with CC version 3.0. In 20 HVs, MRS response consisted of: (1) reduction in GEJ pressure; (2) absence of esophageal contractile activity during MRS; and (3) post-MRS peristaltic contraction greater than SS contractions. In 20 HVs and 403 patients, MRS IRP correlated with SS IRP (r = 0.65; p < 0.0001) and post-MRS contraction DCI correlated with SS DCI (r = 0.76; p < 0.0001). Abnormally elevated MRS IRP was seen in 68% type 2 achalasia, 50% type 3 achalasia, 47% EGJOO, and 9% jackhammer. Increased MRS DCI was seen in 53% type 2 achalasia, 92% type 3 achalasia, 10% EGJOO, 22% jackhammer, and 18% DES. Increased DCI post-MRS was seen in 38% patients with jackhammer, 8% type 3 achalasia, 12% EGJOO, and 9% DES. 14 out of 143 (10%) patients with normal or indeterminate results on SS analysis had at least one abnormality on MRS. MRS IRP correlated with SS IRP, and post-MRS DCI correlated with SS DCI. Patients with defined CC disorders have abnormalities on MRS. There were MRS abnormalities in some patients with normal SS studies, most notably suggesting impaired LES relaxation and/or spastic esophageal motility. MRS may complement the baseline SS study analysis.


Rapid fluorescent staining of histones in sodium dodecyl sulfate-polyacrylamide gels.
The increase in the fluorescence intensity of 1-anilinonaphthalene-8-sulfonate (ANS) produced by core histones is higher than that produced by very lysine-rich histones (H1 and H5). In the presence of the anionic detergent sodium dodecyl sulfate (SDS) the enhancement of ANS fluorescence caused by these two groups of histones is roughly the same, but much lower than that observed for core histones in the absence of this detergent. However, the increase of ANS fluorescence produced by histone-SDS complexes is high enough to use it for the staining of these proteins separated in SDS-polyacrylamide gels. Histone bands are stained with ANS after electrophoresis and visualized by transillumination of the gel with a uv light source. The method described in this work allows the rapid detection of less than 0.5 microgram of histone per band.


Thermodynamic profiling of conformationally constrained cyclic ligands for the PDZ domain.
Inspired by structure-based design and tailored for combinatorial preparation, a series of novel cyclic peptides has been developed to yield binding ligands for the third PDZ domain (PDZ3) of PSD-95. These side chain-side chain bridged peptides permit the systematic expansion or contraction of ring size, which is intended to maximize the conformational diversity of the ensemble. Isothermal titration calorimetry (ITC) was used to measure the dissociation constants (K(d)) and associated thermodynamic binding parameters.


A pilot study of EVAP/ABV chemotherapy in 25 newly diagnosed children with Hodgkin's disease.
Twenty five children with newly diagnosed Hodgkin's disease were clinically staged and treated with a chemotherapy protocol designed to reduce delayed toxicity. Four patients without macroscopic residual disease after biopsy received three cycles of hybrid EVAP/ABV. All remain in CR 31-46 months from diagnosis. One other developed fever and rash considered to be due to Ara-C and was treated with MOPP. Twenty patients had macroscopic residual disease after biopsy and were treated with two cycles of EVAP alone and reassessed with imaging and gallium scans. Twelve achieved CR, seven PR and one was not evaluable. Patients in CR were subsequently treated with 2-4 cycles of hybrid EVAP/ABV, while those in PR received 3-4 cycles. At a median follow up of 37 months the overall survival was 100%, relapse free 79% and treatment failure free 60%. Eight patients had mediastinal widening > 1/3 thoracic width. At the completion of the protocol five achieved CR, two PR and one was withdrawn from study at investigator preference. One patient has subsequently relapsed. Of the evaluable ten patients without a mediastinal presentation all achieved CR but three relapsed at 10, 13 and 18 months from diagnosis. Patients who achieved a PR only, relapsed or were withdrawn from study have been salvaged with MOPP or Ch1VPP chemotherapy.


Cytomegalovirus prostatitis.
Tissue demonstration of cytomegalovirus (CMV) within the male genital tract has rarely been reported. We present a case of extensive CMV prostatitis in a homosexual patient with acquired immune deficiency syndrome (AIDS) dying of disseminated CMV infection.


Visualizing Dynamic Performance of Lipid Droplets in a Parkinson's Disease Model via a Smart Photostable Aggregation-Induced Emission Probe.
Parkinson's disease (PD) is a complex neurodegenerative disease affected by diverse factors, and lipid droplets (LDs) are increasingly recognized as major players in PD because of their relevance to neuron activity. However, long-term dynamic changes of LDs and their relative activity remain unclear. Here, an aggregation-induced emission (AIE) probe named 2-DPAN was prepared and employed to visualize dynamic processes of LDs in a 6-hydroxydopamine model of PD for the first time, and LDs' accumulation-peak/plateau-decrease were confirmed. We further found a close relationship between LDs and variation in mitochondrial activity. Strikingly, the progression of cell death was accelerated by lipase, whereas pre-stimulation of LDs by unsaturated fatty acid-oleic acid decreased the death process by inhibiting excessive reactive oxygen species (ROS) and fatty acid production, thereby protecting mitochondria. The utilization of 2-DPAN demonstrates the importance of LDs in neuronal homeostasis, and effective tuning of LDs may prevent or inhibit PD progression.


The localization of [3H]-desipramine in central nerve terminals studied with electron microscope autoradiography and subcellular fractionation.
The cellular and subcellular distribution of [3H]-desipramine (DMI) in rat brain was studied by electron microscope (EM) autoradiography and by subcellular fractionation. A considerable proportion of label was found to be bound to the membranes of presynaptic nerve terminals, as well as to sites inside those terminals.


Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.
Previous studies have shown that AMPK plays an important role in cerebral ischemia-reperfusion injury by participating in apoptosis, but the exact mechanism and target of action remains unclear. This study aimed to investigate the protective mechanism of AMPK activation on brain injury secondary to cardiac arrest. HE, Nills and TUNEL assays were used to evaluate neuronal damage and apoptosis. The relationships between AMPK, HNF4α and apoptotic genes were verified by ChIP-seq, dual-luciferase and WB assays. The results showed that AMPK improved the 7-day memory function of rats, and reduced neuronal cell injury and apoptosis in the hippocampal CA1 region after ROSC, while the use of HNF4α inhibitor weakened the protective effect of AMPK. Further research found that AMPK positively regulated the expression of HNF4α, and AMPK could promote the expression of Bcl-2 and inhibit the expression of Bax and Cleaved-Caspase 3. In vitro experiments showed that AMPK ameliorated neuronal injury by inhibiting apoptosis through the activation of HNF4α. Combined with ChIP-seq, JASPAR analysis and Dual-luciferase assay, the binding site of HNF4α to the upstream promoter of Bcl-2 was found. Taken together, AMPK attenuates brain injury after CA by activating HNF4α to target Bcl-2 to inhibit apoptosis.


Sperm antibodies and human in vitro fertilization.
In order to directly evaluate the effects of sperm antibodies in human in vitro fertilization (IVF), the authors preincubated donor sperm in female sera containing sperm antibodies and then inseminated supernumerary human oocytes from a gamete intrafallopian transfer (GIFT) program. The sperm were incubated for 30 minutes in medium containing 20% serum with antisperm activity (Test); or no antisperm activity (Control) as assessed by the immunobead test (IBT). Each oocyte was inseminated with 1 to 2 X 10(5)/ml of the preincubated motile sperm with Control or Test treatments allocated on a random basis. Six positive sera were tested in 17 experiments, resulting in a fertilization rate of 41% (25/61) versus 84% (36/43) for controls (P less than 0.001). When considered individually, three of six positive sera caused significant inhibition. The only serum that gave complete inhibition had the highest titer for IgG (10,000) and lower IgA (100). Absorption with protein A reduced the IgG titer to less than 10 and removed the fertilization inhibitory activity. These results confirm that sperm antibodies from female sera can inhibit human IVF.


The effect of glutamine supplementation on serum levels of some inflammatory factors, oxidative stress, and appetite in COVID-19 patients: a case-control study.
Malnutrition is seen in COVID-19 patients, and reducing malnutrition with appropriate therapies may improve these patients' health. This case-control study aimed to assess and compare serum levels of some inflammatory factors, oxidative stress, and appetite in COVID-19 patients with respiratory infections that receive glutamine treatment with a control group. In this study, patients who consented to use glutamine were considered as the case group and other patients who did not use glutamine were considered as a control group. Two hundred twenty-two COVID-19 patients (51.2 ± 6.7) using L-Glutamine and 230 COVID-19 patients (51.3 ± 8.2) with similar age, gender, and clinical status, as the control group, were included in the study. For 5 days, the case group consumed 10 g of glutamine supplement three times per day. At the end of the 5 days, blood samples were taken again to test for serum levels of IL1β, tumor necrosis factor-α, malondialdehyde, and total antioxidant capacity, then all data were analyzed. Serum levels of β-1 interleukin, tumor necrosis factor-α and hs-CRP were significantly reduced with five days of glutamine supplementation (p < 0.05), and patients' appetite during 5 days of glutamine supplementation compared with the control group had a significant increase (p < 0.05). Glutamine supplementation in COVID-19 patients with respiratory infection significantly reduces serum levels of interleukin-1 β, hs-CRP, and tumor necrosis factor-α and significantly increases appetite, so glutamine supplementation may be useful for COVID-19 patients in the hospital.


The covalent structure of calf skin type III collagen. III. The amino acid sequence of the cyanogen bromide peptide alpha 1(III)CB4 (positions 403--551).
The cyanogen bromide peptide alpha 1(III)CB4 comprises the sequence region from position 403 to 551 of the alpha 1(III) chain. Almost the entire sequence of this region was elucidated using two hydroxylamine- and one chymotrypsin-derived fragments for automated Edman degradation. The sequence analysis of alpha 1(III)CB4 was completed with the help of trypsin and one protease V8-derived peptide. Comparison with the corresponding region of the alpha 1(I) chain revealed a striking homology between the two chains in this region which is higher than for the entire alpha chains.


Sensitization to the major allergen of Brazil nut is correlated with the clinical expression of allergy.
Only a few studies have investigated the clinical role of food allergens, especially the relationship between sensitization to a given allergen and occurrence of adverse reactions when eating the relevant food item. This study evaluated the clinical role of the allergens of Brazil nut by comparing the patterns of IgE binding in sera from 11 patients with anaphylaxis after eating Brazil nuts with those from 10 subjects with no symptoms to this food item. Both groups had specific IgE to Brazil nut. Allergens in the in-house extract of Brazil nut were identified by SDS-PAGE/immunoblotting, the major allergen was purified by HPLC, and its N-terminal sequence was determined by a protein sequencer. SDS-PAGE/immunoblotting detected a number of allergenic components with molecular weights ranging from 4 to 58 kd. All sera from symptomatic patients recognized a 9-kd allergen corresponding (as established by amino acid sequencing) to a 2S albumin already described as a major allergen of Brazil nut, whereas the other allergens each bound IgE from less than 50% of sera. No sera from asymptomatic subjects showed IgE binding to the 9-kd allergen, but they did recognize components from 25 to 58 kd, which are minor allergens. These findings indicate that the allergen underlying clinical reactions to Brazil nut is a 2S albumin of 9 kd and that in vitro reactivity to this allergen identifies subjects who react in vivo to ingestion of this food.


Single agent therapy of interferon for brain tumours: correlation between natural killer activity and clinical course.
The anti-tumour effect of mouse interferon (IFN) on an intracranially transplanted 203-glioma in C 57BL mice and the natural killer (NK) activity of spleen cells were studied. As a clinical trial, five patients with glioblastomas were treated with human fibroblast IFN and the anti-tumour effect of IFN and the NK activity of peripheral blood lymphocytes were also studied. The NK activity increased after the beginning of IFN therapy but there was no remarkable anti-tumour effect of IFN in both mouse and human studies. There was no marked correlation between the increased NK activity and the anti-tumour effect of IFN in this study.


Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment.
Hippocampal volume decrease associated with illness burden is among the most replicated findings in unipolar depression. The absence of hippocampal volume changes in most studies of individuals with bipolar disorder (BD) may reflect neuroprotective effects of lithium (Li). We recruited 17 BD patients from specialized Li clinics, with at least two years of regularly monitored Li treatment (Li group), and compared them to 12 BD participants with < 3 months of lifetime Li exposure and no Li treatment within two years prior to the scanning (non-Li group) and 11 healthy controls. All BD patients had at least 10 years of illness and five episodes. We also recruited 13 Li-naïve, young BD participants (15-30 years of age) and 18 sex- and age-matched healthy controls. We compared hippocampal volumes obtained from 1.5-T magnetic resonance imaging (MRI) scans using optimized voxel-based morphometry with small volume correction. The non-Li group had smaller left hippocampal volumes than controls (corrected p < 0.05), with a trend for lower volumes than the Li group (corrected p < 0.1), which did not differ from controls. Young, Li-naïve BD patients close to the typical age of onset had comparable hippocampal volumes to controls. Whereas patients with limited lifetime Li exposure had significantly lower hippocampal volumes than controls, patients with comparable illness burden, but with over two years of Li treatment, or young Li-naïve BD patients, showed hippocampal volumes comparable to controls. These results provide indirect support for neuroprotective effects of Li and negative effects of illness burden on hippocampal volumes in bipolar disorders.


Timing in the visual cortex and its investigation.
While many high-level cortical areas have been implicated in timing, timing activity has also been observed even in the earliest cortical stages of the visual system over the past decade. This activity has been formally modeled as one arising from a reinforcement signal, leading to testable hypotheses with recent experimental support, demonstrating the necessity and sufficiency of that reinforcement signal. As observed in other cortical areas implicated in timing, interval timing activity within the visual cortex abides by the temporal scalar property. Finally, perturbations of the visual cortex during interval timing results in lawful shifts in timing. These and related observations advance the notion that visual cortex is a substrate for learning and expressing visually-associated temporal expectations governing behaviorally-relevant actions.


One calcitriol dose transiently increases Helios+ FoxP3+ T cells and ameliorates autoimmune demyelinating disease.
Multiple sclerosis (MS) is an incurable inflammatory demyelinating disease. We investigated one calcitriol dose plus vitamin D3 (calcitriol/+D) as a demyelinating disease treatment in experimental autoimmune encephalomyelitis (EAE). Evidence that calcitriol-vitamin D receptor pathway deficits may promote MS, and data showing calcitriol enhancement of autoimmune T cell apoptosis provided the rationale. Whereas vitamin D3 alone was ineffective, calcitriol/+D transiently increased central nervous system (CNS) Helios(+)FoxP3(+) T cells and sustainably decreased CNS T cells, pathology, and neurological deficits in mice with EAE. Calcitriol/+D, which was more effective than methylprednisolone, has potential for reversing inflammatory demyelinating disease safely and cost-effectively.


Benefits of statins in chronic obstructive pulmonary disease patients with pulmonary hypertension: A meta-analysis.
This meta-analysis was performed to evaluate the efficacy of statins in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH). A systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases. Randomized clinical trials on treatment of COPD-PH with the statins, compared with placebo, were reviewed. Studies were pooled to weighted mean differences (WMD), with 95% confidence interval (CI). Five trials (enrolling 270 participants) met the inclusion criteria. Compared with placebo, the statins presented significant effects on systolic pulmonary artery pressure (WMD -4.52 mmHg; 95% CI -6.32 to -2.72 mmHg) and 6-min walk distance (6MWD) (WMD 32.46 m; 95% CI 13.63-51.29 m). Statins therapy significantly improves PH and 6MWD in COPD patients with PH.


[Study on chemical constituents from the root of Hemerocallis citrina].
To study the chemical constituents root of Hemerocallis citrina. The chemical constituents were extracted by microwave method and purified by silica gel column. Their structures were elucidated by their physical and chemical properties and spectral methods. 7 compounds were isolated and identified as: chrysophanol(I), 2-methoxy-obtusifolin(II), obtusifolin (III), rhein (IV), aloe-emodin (V), hemerocallone ( VI) and hemerocallin (VII). Compounds IV and VI are isolated from this plant for the first time.


Lactose Stabilization Prolongs In Vivo Retention of Cross-linked Fish Collagen Subcutaneous Grafts in Nude Mice.
Bovine-derived collagen gel has been used in the medical field as an injection formulation, but there are concerns about cross-infection such as bovine spongiform encephalopathy. In this study, we attempted to use fish as a safe alternative to bovine collagen. Fish collagen has not been used in clinical settings, so we examined its potential by comparing its properties with those of bovine-derived collagen. Collagen was extracted from the ventral skin of flatfish. It was cross-linked with 1%, 3%, or 5% of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and treated with 1%, 5%, or 10% of lactose. Hydroxyproline contents and Young's modulus (elasticity) were measured. In addition, these were injected under the back of BALB/c nude mice and the amount of hydroxyproline was observed. Histological examination of the samples was also conducted. The amount of hydroxyproline in fish collagen was 3.3 ± 0.3 μg/mg. The 3% collagen gel treated with 5% EDC and 5% lactose had the highest Young's modulus and was closest to the bovine-derived collagen injection formulation. When injected into mice, it was retained in vivo for about 90 days. Fish collagen has a low denaturation temperature and is unstable and easily biodegrades in mammalian organisms. However, it is possible to approach the properties of conventional mammalian collagen by cross-linking and lactose treatment, suggesting that fish collagen can be used as a scaffold for cells in regenerative medicine.


Bacterial extracellular polymeric substances: Biosynthesis and interaction with environmental pollutants.
Extracellular polymeric substances (EPS) are highly hydrated matrices produced by bacteria, containing various polymers such as polysaccharides, proteins, lipids, and DNA. Extracellular polymer concentrations, ions, and functional groups provide physical stability to the EPS. Constituents of EPS form the three-dimensional architecture and help acquire nutrition for the bacteria. Structural and functional diversity of the extracellular polymer depends on the specific glycosyltransferases, polymerase and transporter proteins. These enzymes are encoded by specific genes present in operons such as crd, alg, wca, and gum reported in Agrobacterium, Pseudomonas, Enterobacteriaceae, and Xanthomonas. The operons regulate the biosynthesis of extracellular polymers such as curdlan, alginate, colonic acid, and xanthan, respectively. Various functional groups in the EPS, such as carbonyl, hydroxyl, phosphoryl, and amide, provide the sorption site for interaction with environmental pollutants. Hydrophobic interactions and coordinate bonds mainly dominate the binding of EPS with environmental pollutants. EPS binds, emulsifies, and solubilizes the organic compounds, enhancing the degradation process. EPS binds with heavy metals through complexation, surface adsorption, precipitation, and ion exchange mechanisms. The biodegradability efficiency and nontoxicity properties of EPS make it an excellent biopolymer for decontaminating environmental pollutants. This review summarizes an overview of the biosynthetic mechanisms and interaction of the bacterial extracellular polymer with environmental pollutants. Interaction mechanisms of pollutants with EPS and EPS-mediated bioremediation will help develop removal applications. Moreover, understanding the genes responsible for EPS production, and implementation of new genetic methodology can be helpful for the enhanced biosynthesis of EPS to control pollution by sequestrating more environmental pollutants.


Reaction profile in patch testing with allergens formed during vulcanization of rubber.
Vulcanization of rubber changes its allergen pattern. To estimate the contact allergic reactivity profile of users of finished rubber products. Twenty-four patients with known contact allergy to rubber accelerators were patch tested with 21 compounds found in chemical analyses of vulcanized rubber products. No diphenylguanidine, p-phenylenediamine antioxidants or thioureas were included in the study. Thiuram monosulfides formed during vulcanization showed generally stronger test reactions than the corresponding thiuram disulfides. We also obtained more positive thiuram reactions to the monosulfides than to the disulfides. A positive reaction to a dithiocarbamate was accompanied by a positive reaction to the corresponding thiuram, except for 1 patient. The nitrogen substituents showed only minor differences between the methyl, ethyl and pentamethylene groups, but the butyl derivatives gave, in most cases, a negative response. Dialkylthiocarbamyl benzothiazole sulfides, formed between thiurams and mercaptobenzothiazoles during vulcanization, showed strong test reactions in almost all patients who were sensitive to dithiocarbamates, thiurams, or mercaptobenzothiazoles. We found thiuram monosulfides to be better markers of thiuram sensitivity than the corresponding disulfides or dithiocarbamates. Surprisingly, the dialkylthiocarbamyl benzothiazole sulfides were good markers of both thiuram and mercaptobenzothiazole sensitivity. This is an unexpected finding that needs to be confirmed in a larger study.


Sustained azoospermia in squirrel monkey, Saimiri sciureus, resulting from a single intratesticular glycerol injection.
Previous studies in rats had shown that a single intratesticular injection of glycerol resulted in long-term suppression of spermatogenesis without marked alterations in hormone levels. Studies were undertaken to determine the effect of similar treatment in squirrel monkeys (Saimiri sciureus). Ten monkeys received an intratesticular injection of saline (controls) and ten of glycerol solution (treated). Semen and blood samples were obtained on a weekly or bi-weekly basis one month prior to, during the 8 months following and at 22 months after the injection. Sperm numbers in the semen samples of controls remained at 160-435 x 10(6) per ml throughout the experiment. Sperm numbers in treated animals declined to near zero within two months and remained at zero. Serum testosterone and progesterone levels were not significantly different between control and treated animals. Serum LH and FSH levels were not significantly different between control and treated animals except during months 6-8 after the injection, when levels in the treated were higher. At termination (22 months), the weights and sperm contents of epididymides of the glycerol-treated animals were highly significantly reduced. Steroidogenesis (based on amounts and kinds of steroids formed from 14C-progesterone) by testicular tissue was not altered by the glycerol treatment when measured on a per testis basis. This is the first evidence that a single intratesticular injection of glycerol results in long-term suppression of spermatogenesis in primates, without altering testicular steroidogenesis and serum hormone levels.


Risk of serotonin syndrome in acutely ill patients receiving linezolid and opioids concomitantly: a retrospective cohort study.
Linezolid is an oxazolidinone antibiotic with a reversible, non-selective, monoamine oxidase inhibitory effect. Combining linezolid with serotonergic agents may increase serotonin syndrome (SS) risk.Linezolid is recommended in patients with suspected or confirmed resistant Gram-positive bacterial infections, especially if vancomycin cannot be used. However, it is unclear whether co-administration of linezolid with opioids increases the risk of serotonin syndrome. To establish whether combining linezolid with opioids will increase the incidence of SS in acutely ill patients. This was a retrospective observational study. All adult patients who were admitted and received linezolid between March and September 2020 were included in the study. The primary outcome was the prevalence of SS, as defined by Hunter's criteria. The study included 106 patients, most whom were males (91.5%). More than half of the cohort (56.6%) received a concomitant opioid agent. Morphine and fentanyl were the most prescribed opioids (37.7% and 34%, respectively). Among patients who received opioids, only one patient (1.6%) had spontaneous clonus. However, this patient developed spontaneous clonus post cardiac arrest, which made an association with the linezolid-opioids combination less likely. In this study, the incidence of SS was low in acutely ill patients who received concomitant linezolid and opioids. However, larger prospective studies are required to confirm this finding.


Improving the impact of non-pharmaceutical interventions during COVID-19: examining the factors that influence engagement and the impact on individuals.
During an evolving outbreak or pandemic, non-pharmaceutical interventions (NPIs) including physical distancing, isolation, and mask use may flatten the peak in communities. However, these strategies rely on community understanding and motivation to engage to ensure appropriate compliance and impact. To support current activities for COVID-19, the objectives of this narrative review was to identify the key determinants impacting on engagement. An integrative narrative literature review focused on NPIs. We aimed to identify published peer-reviewed articles that focused on the general community (excluding healthcare workers), NPIs (including school closure, quarantine, isolation, physical distancing and hygiene behaviours), and factors/characteristics (including social, physical, psychological, capacity, motivation, economic and demographic) that impact on engagement. The results revealed that there are a range of demographic, social and psychological factors underpinning engagement with quarantine, school closures, and personal protective behaviours. Aside from the factors impacting on acceptance and compliance, there are several key community concerns about their use that need to be addressed including the potential for economic consequences. It is important that we acknowledge that these strategies will have an impact on an individual and the community. By understanding the barriers, we can identify what strategies need to be adopted to motivate individuals and improve community compliance. Using a behavioural framework to plan interventions based on these key barriers, will also ensure countries implement appropriate and targeted responses.


Can electroencephalographic analysis be used to determine sedation levels in critically ill patients?
Prolonged use of sedative drugs frequently leads to oversedation of intensive care patients. Clinical assessment scales are not reliable in deeply sedated patients. Parameters obtained from spectral and bispectral analysis of electroencephalogram (EEG) records have been combined to create an index (BIS) to monitor anesthesia depth. The role of such parameters in monitoring the depth of the sedation in intensive care unit (ICU) patients has yet to be determined. We designed the present prospective study to redefine and calculate available spectral and bispectral parameters from raw EEG records and estimate their clinical relevance for the diagnosis of under- or oversedation levels in ICU patients. Forty adult patients receiving continuous midazolam and morphine sedation were included. We obtained 167 clinical evaluations of sedation level using Ramsay and COMFORT scales along with an EEG record of 300 s. Six spectral parameters-relative power of 4 frequency bands (beta, alpha, Theta, and delta), 95th percentile of the power spectrum (SEF95), and 50th percentile of the power spectrum (SEF50) and four bispectral parameters, real triple product, bispectrum (Bispectrum), bicoherence, and ratio 10-were calculated. The relevance of each of these parameters and combinations in predicting too light (Ramsay 1 and 2) or deep (Ramsay 5 and 6) sedation levels was assessed. These calculations were performed before and after exclusion of the agitated patients, whose COMFORT 4 score was above 2. The most relevant parameters for predicting levels of deep sedation (Ramsay 5 and 6) were ratio 10 (area under the curve = 0.763; 95% confidence interval, 0.679-0.833) and SEF95 (area under the curve = 0.687; 95% confidence interval, 0.597-0.767). The most relevant parameters for predicting light levels of sedation (Ramsay 1 and 2) were also ratio 10 (area under the curve = 0.829; 95% confidence interval, 0.695-0.917) and SEF95 (area under the curve = 0.798; 95% confidence interval, 0.650-0.898). There is a modest improvement in relevance of their linear combination in predicting sedation level. Results were similar after exclusion of agitated patients. We conclude that various calculated EEG descriptive parameters exhibited large interindividual variability. There was a strong correlation between EEG spectral and bispectral parameters. Bispectral analysis slightly improves the predictive power of simple spectral analysis in distinguishing too light or deep sedation levels in ICU patients. Spectral edge frequency 95 and Ratio 10 are the most relevant electroencephalogram (EEG) indexes for monitoring the level of sedation in intensive care unit patients but calculated EEG values exhibited large interindividual variability. Bispectral analysis of EEG provides a slight improvement over simple spectral analysis.


An investigation of the sleep macrostructure of girls with Rett syndrome.
Methyl-CpG-binding protein 2 (MeCP2) is of utmost importance in neuronal function. We aim to characterize phenotypic traits in the sleep of individuals with Rett Syndrome (RTT, OMIM # 312750), a rare disorder predominantly caused by mutations of the MECP2 gene. An overnight polysomnographic recording was performed. Outcomes investigated were parameters of nocturnal sleep macrostructure, and sample stratification per genetic and clinical characteristics, and six key features of clinical severity was applied. The sleep of our 21 RTT female subjects with a mutant MECP2 gene, aged 8.8 ± 5.4 years, showed no significant differences within strata. However, compared to a normative dataset, we found longer duration of wake time after sleep onset and total sleep time (TST) but shorter sleep onset latency, in RTT. Regarding the proportion of sleep stages per TST, higher stage N3 (%) with lower stage N2 (%) and REM (%) were generally seen. Such abnormalities became more uniformly expressed at the severe level of clinical features, particularly for hand functioning and walking. RTT girls with MECP2 mutations in our study demonstrated an increased deep sleep and reduced rapid eye movement sleep proportion, which is mostly allied with their hand dysfunction severity. Poor sleep-on/off switching in RTT since embryogenesis is possibly linked to (psycho)motor impairment in the cases with MECP2 mutations.


Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers.
Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously shown to control timing of events in mitotic stem cell lineages, is reutilized in postmitotic neurons to control postdifferentiation events.


Heroin overdose masquerades as methomyl poisoning: a case report.
Methomyl is the most common cause of suicidal death but heroin is the most common cause of accidental death. The problem is to determine the exact cause and manner of death between methomyl or heroin toxicity. The evidence from autopsy includes crime scene investigation, toxicological analysis by liquid chromatography with mass spectrometry, and knowledge of methomyl and heroin intoxication. A 35-year-old Thai man and a 30-year-old Thai woman were found showing evidence of cyanosis, with a fine froth around the nose and mouth. Postmortem interval time was 24 hours. According to the police's and hotel owner's records, the couple stayed together for 1 day before being found dead in bed, naked, with a foul and a fine froth around the nose and mouth. A methomyl insecticide sachet and a plastic box containing white powder form of heroin were found at the scene. Laboratory tests of the male corpse identified the presence of methomyl in the blood of the stomach and morphine, codeine, methadone, and tramadol in the systemic blood. Blood cholinesterase enzyme activity and morphine concentration was 3416 U/L or 53% (normal 6400 U/L) and 0.058 μg/ml respectively. Laboratory test of the female corpse identified the presence of methomyl in the stomach and blood, and cholinesterase enzyme activity was 1965 U/L or 30.7%. Cause of death of the male corpse was deemed to be due to heroin intoxication as the blood concentration of morphine was more than the lethal concentration with a morphine/codeine ratio of more than 1:1. Methomyl intoxication of the male corpse was unlikely to be the cause of death because methomyl systemic blood concentration was found to be very low, < 2.5 μg/ml, and cholinesterase enzyme levels did not indicate lethal activity (< 10-15% of normal). The main problem regarding an insurance claim is that the policy will not pay out in the case of heroin-associated deaths, as it is an addictive drug. The policy would pay out on death by suicide with methomyl insecticide, which was not prohibited by the insurance company after 1 year of insurance. So, it is not clear whether or not the family will receive money from the insurance company.


Analysis of factors influencing skin reactions to sunscreens, skin whitening products, and deodorants: Results from a large-scale patch test dataset in China.
Cosmetic products are widely used in daily life and can cause skin reactions. However, to date, few studies have investigated the prevalence and associated factors of skin reactions to different types of cosmetic products using patch test results. To investigate the frequency and associated factors of skin reactions to sunscreens, skin whitening products, and deodorants using patch test results in China. This cross-sectional analysis used data collected during 2004-2017 at the Shanghai Skin Disease Hospital, China. Skin reactions were measured using patch tests following internationally standardized protocols. In total, 151 280 patch tests comprising 16 477 cosmetic products conducted in 4029 healthy volunteers were analyzed. The frequencies of skin reactions to different cosmetic products were 1.07%, 1.28%, and 4.41% for sunscreens, skin whitening products, and deodorants, respectively. With increasing age, a higher frequency of reactions to sunscreens in women (p < 0.001) and a lower frequency of reactions to skin whitening products in men (p < 0.05) were observed. In addition, men were more likely to develop skin reactions to deodorants compared to women (p < 0.05). Skin reactions were more frequent in winter (p < 0.05), which was true for different types of cosmetic products. The frequency of patch testing for different cosmetic products was 1.07-4.41%. The effects of age, sex, and season vary among the different types of cosmetic products. We hope that these findings can offer guidance for a healthy skincare concept.


Orofacial manifestations in HIV positive children attending Mildmay Clinic in Uganda.
The aim of this study was to assess the orofacial manifestations and their influence on oral function in human immunodeficiency virus (HIV) positive children attending Mildmay Clinic in Uganda. This was a cross-sectional study based on clinical examination, medical records and a structured questionnaire of 368 children aged between 1.5 and 17 years. The clinical examination for dental caries was based on decayed, extracted and filled teeth (deft) and decayed, missing and filled teeth (DMFT) indices as defined by World Health Organisation. The soft tissue orofacial lesions were assessed using the classification and diagnostic criteria as described by the Collaborative Workgroup on the Oral Manifestations of Pediatric HIV Infections. Approximately 67.4% of the children were on highly active antiretroviral therapy (HAART). The majority (77.4%) of the children had at least one orofacial lesion associated with HIV, pseudomembranous candidiasis being the most prevalent. Overall, 61.7% of the children with orofacial lesions reported at least one form of discomfort in the mouth. Discomfort was particularly associated with swallowing. The prevalence of orofacial lesions was significantly higher in children with poor oral hygiene and lower in those on HAART than in their respective counterparts. The CD4+ cell count, age and gender of the children did not significantly influence the distribution of orofacial lesions. The mean deft and DMFT scores were 11.8 and 2.7, respectively. The d- and D-components contributed 54.7 and 42.1%, respectively. Consumption of sugary snacks was directly associated with dental caries. Despite these children attending an HIV care centre of excellence, they have a high prevalence of orofacial manifestations associated with HIV. The majority of the children experienced discomfort in the oral cavity, particularly during swallowing.


The regulation of the complement system: insights from genetically-engineered mice.
The complement system is very tightly regulated by fluid-phase and membrane-bound factors that prevent injury to self-tissues. The study of genetically engineered animals with targeted deletion or gain of function mutations has highlighted the important role that many of the complement inhibitors play in vivo. The advantages and disadvantages of this type of approach are discussed and the insights gained from the investigation of these animals are reviewed.


Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials.
Young age has been shown to be an independent predictor of poor outcome in breast cancer. In HER2-positive breast cancer, the effects of aging remain largely unknown. A total of 4,547 patients were included [3,132 from North Central Cancer Treatment Group (NCCTG) N9831 and 1,415 from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31]. Pathologic stromal tumor-infiltrating lymphocyte (sTIL) and molecular tumor infiltrating lymphocyte (mTIL) signatures were evaluated. In NCCTG N9831, comparable benefit of trastuzumab was observed in all patients [age ≤ 40; HR, 0.43; 95% confidence interval (CI), 0.28-0.66; P < 0.001; and age > 40; HR, 0.56; 95% CI, 0.45-0.69; P < 0.001]. Similar results were observed in NSABP B-31 (age ≤ 40; HR, 0.45; 95% CI, 0.29-0.68; P < 0.001; and age > 40; HR, 0.42; 95% CI, 0.33-0.54; P < 0.001). Among patients who received chemotherapy alone, younger age was associated with poor outcome in the hormone receptor-positive subset, but not the hormone receptor-negative subset, in both trials. Although there was no association between sTILs and age, a small, but significant increase in mTIL CD45 and some immune subset signatures were observed. Among patients who received chemotherapy alone, patients over 40 years of age with lymphocyte-predominant breast cancer had excellent outcome, with 95% remaining recurrence free at 15 years. Among patients treated with trastuzumab, there was no significant difference in outcome related to age. Our study suggests that trastuzumab can negate the poor prognosis associated with young age.


Comparison of the ability of eosinophils and neutrophils, and of eosinophils from patients with S. mansoni infection and normal individuals, to mediate in vitro damage to schistosomula of S. mansoni.
A reliable and reproducible method that produces separate fractions of pure eosinophils and neutrophils from normal peripheral blood was described. The interaction of eosinophils and neutrophils with antibody coated schistosomula was examined in vitro. Neutrophils were highly active in the 51Cr release assay and most formed rosettes with antibody coated red cells, but they adhered poorly to schistosomula and did not kill the organisms. Eosinophils, although they were less active in the 51Cr release assay than neutrophils and few formed rosettes, adhered strongly to schistosomula and, in the presence of antibody, were able to kill organisms. Organisms from patients with S. mansoni infection and eosinophilia were more effecient than eosinophils from normal individuals in their capacity to release 51Cr from labelled somula in the presence of antibody.


Impact of chronic and acute high-fat feeding on acute experimental pancreatitis complicated by endotoxinaemia.
Obesity is associated with increased severity in patients with acute pancreatitis (AP). The underlying mechanisms are unknown. Genetically obese rats exhibit decreased survival rate in experimental AP, but the clinical relevance of this model of obesity may be questioned. It is proposed that development of organ failure in AP occurs in two stages: initial priming of leucocytes followed by a second inflammatory attack. The aim was to evaluate the impact of diet-induced obesity on outcome in a 'two-hit' model of AP. Lipopolysaccharide (LPS) was injected i.p. 3 h after retrograde bile duct infusion of sodium taurocholate in rats. Three experiments were done: 1) an LPS dose-response experiment, 2) chronic high-fat feeding (HF) for 16 weeks, and 3) acute HF for 10 days. Control rats received normal chow. Obesity, morphology and survival rate were assessed. LPS dose-dependently decreased survival rate and increased morphological severity. HF increased weight, intra-abdominal and liver fat. Only acute HF induced hyperlipidaemia. In AP, acute obese rats exhibited less pancreatic inflammation, but total histological severity between groups was not different. In the chronic experiment only obese animals succumbed before 24 h of pancreatitis, but 72-h survival rate was not statistically different in either high-fat experiment. An addition of LPS to AP decreases survival rate and intensifies the peri-pancreatic processes. Despite significant obesity, neither hyperlipidaemia nor increased intra-abdominal or hepatic fat influenced local pancreatic injury or survival negatively. The amount of fat per se seems not to be responsible for the deleterious influence of obesity on acute pancreatitis.


Solanoflavone, a new biflavonol glycoside from Solanum melongena: seeking for anti-inflammatory components.
A new biflavonol glycoside named as solanoflavone (1) was isolated from aerial part of Solanum melongena. The chemical structure was elucidated as isorhamnetin-3-O-beta-D-glucopyranoside-(4'-->O-->4''')-galangin-3''-O-beta-D-glucopyranoside on the basis of physicochemical and spectroscopic methods, including 2D NMR spectral techniques.


Structural and biochemical studies elucidate the mechanism of rhamnogalacturonan lyase from Aspergillus aculeatus.
We present here the first experimental evidence for bound substrate in the active site of a rhamnogalacturonan lyase belonging to family 4 of polysaccharide lyases, Aspergillus aculeatus rhamnogalacturonan lyase (RGL4). RGL4 is involved in the degradation of rhamnogalacturonan-I, an important pectic plant cell wall polysaccharide. Based on the previously determined wild-type structure, enzyme variants RGL4_H210A and RGL4_K150A have been produced and characterized both kinetically and structurally, showing that His210 and Lys150 are key active-site residues. Crystals of the RGL4_K150A variant soaked with a rhamnogalacturonan digest gave a clear picture of substrate bound in the -3/+3 subsites. The crystallographic and kinetic studies on RGL4, and structural and sequence comparison to other enzymes in the same and other PL families, enable us to propose a detailed reaction mechanism for the β-elimination on [-,2)-α-l-rhamno-(1,4)-α-d-galacturonic acid-(1,-]. The mechanism differs significantly from the one established for pectate lyases, in which most often calcium ions are engaged in catalysis.


Separation of a group of N-phenylpyrazole derivatives by micellar electrokinetic chromatography: application to the determination of solute-micelle association constants and estimation of the hydrophobicity.
Micellar electrokinetic chromatography (MEKC) was applied to the separation of a group of N-phenylpyrazole derivatives. Sodium dodecyl sulfate (SDS) as micellar system and 2-(N-cyclohexylamino)ethanesulfonic acid (CHES) as separation buffer (pH 10) were employed in the absence and presence of different percentages of medium chain alcohols (n-propanol or n-butanol). The separation of multicomponent mixtures of the solutes studied enabled the rapid determination of their retention factors which, in turn, allowed the study of the separation selectivity of compounds and the determination of their solute-micelle association constants (from the linear variation of the retention factors as a function of the total surfactant concentration in the separation buffer). Separation selectivity was studied according to the elution range and number of solutes separated in all the electrolyte solutions employed (45 micellar phases). The effect of the buffer concentration (0.05, 0.08 and 0.10 M), the alcohol nature (n-propanol or n-butanol) and the alcohol percentage (1, 3 or 5%) of the values obtained for the solute-micelle association constants was also studied. The best separation (12 solutes) was performed when a 0.08 M CHES buffer, pH 10, 0.02 M SDS modified by 5% n-butanol was used. The possibilities of using MEKC for evaluating the hydrophobicity of compounds was investigated through the study of the correlation between the logarithm of the retention factors of N-phenylpyrazole derivatives and their logarithm of the octanol-water distribution coefficients estimated by high performance liquid chromatography (HPLC).


The transactional model of stress and coping as guidance for understanding adolescent patients' experience with thalassemia: Case report.
This case report investigated the transactional model of stress and coping as guidance for nursing care of an adolescent patient with thalassemia. A case study of a 15-year-old female patient with β-thalassemia major. Data were collected using patient medical records, an interview with the patient and physical examination. Four issues related to coping were isolated: Worsening physical symptoms; psychosocial consequences, coping process, and building supportive networks. These issues and the patient's adaption are explored via the transactional model. Having thalassemia was cognitively appraised by the patient as a stressful and taxing situation with detrimental consequences, such as changes in physical appearance, stigmatization, and depression. Nurses should evaluate each patient's physical and psychosocial needs, utilizing appropriate theoretical models for designing a suitable care plan. As the case study demonstrates, the transactional model was an effective guide for nurses in planning care of an adolescent patient with thalassemia.


Global cardiovascular health: urgent need for an intersectoral approach.
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with more than 80% of CVD deaths occurring in low- and middle-income countries (LMICs). There have been several calls for action to address the global burden of CVD, but there remains insufficient investment in and implementation of CVD prevention and disease management efforts in LMICs. To catalyze the action needed to control global CVD, the Institute of Medicine recently produced a report, Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. This paper presents a commentary of the Institute of Medicine's report, focusing specifically on the intersectoral nature of intervention approaches required to promote global cardiovascular health. We describe 3 primary domains of intervention to control global CVD: 1) policy approaches; 2) health communication programs; and 3) healthcare delivery interventions. We argue that the intersectoral nature of global CVD interventions should ideally occur at 2 levels: first, all 3 domains of intervention must be activated and engaged simultaneously, rather than only 1 domain at a time; and second, within each domain, a synergistic combination of interventions must be implemented. A diversity of public and private sector actors, representing multiple sectors such as health, agriculture, urban planning, transportation, finance, broadcasting, education, and the food and pharmaceutical industries, will be required to collaborate for policies, programs, and interventions to be optimally aligned. Improved control of global CVD is eminently possible but requires an intersectoral approach involving a diversity of actors and stakeholders.


Detection of high-risk papillomavirus DNA with commercial invader-technology-based analyte-specific reagents following automated extraction of DNA from cervical brushings in ThinPrep media.
We compared the performances of the Third Wave Technology Invader method and the Digene Hybrid Capture 2 assay to detect high-risk human papillomaviruses in 87 cervical brushing specimens submitted in Cytyc ThinPrep media. Two different methods for the extraction of DNA from squamous epithelial cells were also evaluated.


A randomised trial to assess the efficacy and safety of chlorproguanil/dapsone + artesunate for the treatment of uncomplicated Plasmodium falciparum malaria.
We tested the efficacy and safety of chlorproguanil/dapsone co-administered with artesunate (CD+A) for the treatment of uncomplicated Plasmodium falciparum malaria in children compared with amodiaquine+sulfadoxine/pyrimethamine (AQ+SP) at two different sites in Rwanda. The trial was open label and 800 patients were randomly assigned to AQ+SP (n=400) or CD+A (n=400). Patients were hospitalised for 3 days and then followed-up weekly until Day 28 after treatment. Clinical and parasitological outcomes were recorded. Results showed that neither treatment was adequately efficacious. At one site, the adequate clinical and parasitological response (ACPR), PCR-adjusted, was 73.3% in the CD+A arm and 87.8% in the AQ+SP arm (P<0.001), and at the second site the ACPR, PCR-adjusted, was 70.5% in the CD+A arm and 38.1% in the AQ+SP arm (P<0.001). The combination CD+A is considered an alternative to, or replacement for, SP in Africa because CD has been shown to be effective in patients for whom SP treatment has failed and, with its short half-life, it is expected to exert less selection pressure for resistant parasites than SP. However, the results of this trial indicate that in an area of high SP resistance, CD+A may not be the best choice.


The potential for enhancement of mouse melanoma metastasis by diagnostic and high-amplitude ultrasound.
The potential for enhancement of the metastatic spread of cells from mouse melanoma tumors was examined for exposure to diagnostic ultrasound (DUS) and high-amplitude ultrasound (HAUS) without and with ultrasound (US) contrast agent. The melanoma cell line B16-D5, which is metastatic specifically to lung, was cultured and implanted on a hind leg of female C57/bl6 mice. For DUS, tumors were scanned using 1.5-MHz harmonic B-mode imaging with 1-Hz intermittent frame triggering at 2.1 MPa (equivalent MI = 1.7) in a 37 degrees C water bath. For HAUS, a 1.35-MHz focused transducer directed 1-ms bursts at 5 MPa to the tumor at a 1-Hz rate. A total dose of 1 mL/kg Optison was injected during exposures. Exposure without contrast agent received the same exposure followed by the contrast agent with the US off. The primary tumor was removed surgically one day after US. Lungs were removed after four weeks for evaluation of metastases. Experiments involved exposure without and with contrast agent in groups of 20 mice. For DUS, mean counts of 0.8 +/- 0.3 (standard error) and 1.3 +/- 0.9 (P = 0.62) metastases were found for groups exposed without and with contrast, respectively. For HAUS, mean counts of 3.4 +/- 1.2 and 5.9 +/- 1.7 (P = 0.35) metastases were found for groups exposed without and with contrast, respectively. The lack of effect of DUS exposure with contrast confirms a previous finding. However, the HAUS counts and incidence were significantly larger than the DUS results (P < 0.05) in a two-way analysis of variance. This indicates a potential for HAUS to enhance metastasis.


Behavior of acyl carrier proteins on western blots.
Acyl carrier proteins (ACPs) from Escherichia coli and Euglena were analyzed on Western blots using rabbit antibodies raised against E. coli ACP. Euglena ACP, unlike that from E. coli, behaves upon electrophoresis under denaturing conditions as its size would predict. Oligomeric forms of both ACPs were evident on Western blots, but the bacterial ACP had more tendency to aggregate. That the oligomeric forms were not due to impurities was shown by their regeneration from low-Mr protein, reaction with antibodies isolated from low-Mr protein, and by molecular weight determination of the ACP by low-angle laser light scattering.


Inflammasome and toll-like receptor signaling in human monocytes after successful cardiopulmonary resuscitation.
Whole body ischemia-reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) induces a generalized inflammatory response which contributes to the development of post-cardiac arrest syndrome (PCAS). Recently, pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and inflammasomes, have been shown to mediate the inflammatory response in IRI. In this study we investigated monocyte PRR signaling and function in PCAS. Blood samples were drawn in the first 12 hours, and at 24 and 48 hours following return of spontaneous circulation in 51 survivors after cardiac arrest. Monocyte mRNA levels of TLR2, TLR4, interleukin-1 receptor-associated kinase (IRAK)3, IRAK4, NLR family pyrin domain containing (NLRP)1, NLRP3, AIM2, PYCARD, CASP1, and IL1B were determined by real-time quantitative PCR. Ex vivo cytokine production in response to stimulation with TLR ligands Pam3CSK4 and lipopolysaccharide (LPS) was assessed in both whole blood and monocyte culture assays. Ex vivo cytokine production of peripheral blood mononuclear cells (PBMCs) from a healthy volunteer in response to stimulation with patients' sera with or without LPS was assessed. The results were compared to 19 hemodynamically stable patients with coronary artery disease. Monocyte TLR2, TLR4, IRAK3, IRAK4, NLRP3, PYCARD and IL1B were initially upregulated in patients following cardiac arrest. The NLRP1 and AIM2 inflammasomes were downregulated in resuscitated patients. There was a significant positive correlation between TLR2, TLR4, IRAK3 and IRAK4 expression and the degree of ischemia as assessed by serum lactate levels and the time until return of spontaneous circulation. Nonsurvivors at 30 days had significantly lower mRNA levels of TLR2, IRAK3, IRAK4, NLRP3 and CASP1 in the late phase following cardiac arrest. We observed reduced proinflammatory cytokine release in response to both TLR2 and TLR4 activation in whole blood and monocyte culture assays in patients after CPR. Sera from resuscitated patients attenuated the inflammatory response in cultured PBMCs after co-stimulation with LPS. Successful resuscitation from cardiac arrest results in changes in monocyte pattern recognition receptor signaling pathways, which may contribute to the post-cardiac arrest syndrome. The trial was registered in the German Clinical Trials Register ( DRKS00009684 ) on 27/11/2015.


Photoreversible switching between assembly and disassembly of a supramolecular polymer involving an azobenzene-bridged pillar[5]arene dimer.
We report a photo-reversible switching system between assembly and disassembly of a supramolecular polymer consisting of an azobenzene-bridged pillar[5]arene dimer.


Recovery kinetics of creatine in mild plantar flexion exercise using 3D creatine CEST imaging at 7 Tesla.
Two-dimensional creatine CEST (2D-CrCEST), with a slice thickness of 10-20 mm and temporal resolution (τRes ) of about 30 seconds, has previously been shown to capture the creatine-recovery kinetics in healthy controls and in patients with abnormal creatine-kinase kinetics following the mild plantar flexion exercise. Since the distribution of disease burden may vary across the muscle length for many musculoskeletal disorders, there is a need to increase coverage in the slice-encoding direction. Here, we demonstrate the feasibility of 3D-CrCEST with τRes of about 30 seconds, and propose an improved voxel-wise B1+ -calibration approach for CrCEST. The current 7T study with enrollment of 5 volunteers involved collecting the baseline CrCEST imaging for the first 2 minutes, followed by 2 minutes of plantar flexion exercise and then 8 minutes of postexercise CrCEST imaging, to detect the temporal evolution of creatine concentration following exercise. Very good repeatability of 3D-CrCEST findings for activated muscle groups on an intraday and interday basis was established, with coefficient of variance of creatine recovery constants (τCr ) being 7%-15.7%, 7.5%, and 5.8% for lateral gastrocnemius, medial gastrocnemius, and peroneus longus, respectively. We also established a good intraday and interday scan repeatability for 3D-CrCEST and also showed good correspondence between τCr measurements using 2D-CrCEST and 3D-CrCEST acquisitions. In this study, we demonstrated for the first time the feasibility and the repeatability of the 3D-CrCEST method in calf muscle with improved B1+ correction to measure creatine-recovery kinetics within a large 3D volume of calf muscle.