Incorporating LC-MS/MS Analysis and the Dereplication of Natural Product Samples into an Upper-Division Undergraduate Laboratory Course.
Growth in the biomedical and biotechnology sectors requires a highly trained and highly skilled workforce to answer the next great scientific questions. Undergraduate laboratory courses incorporating hands-on training based in authentic research position soon-to-be graduates to learn in environments that mirror that of academic, industrial, and government laboratories. Mass spectrometry is one of the most broadly applied analyses carried out in the biomedical and pharmaceutical sciences and thus it is essential that upper-division students gain hands-on experience in techniques and analytical workflows in mass spectrometry. Our pre-course assessments identified weaknesses in student experience and knowledge in the fundamentals of mass spectrometry, supporting that it was a necessary area for improvement. We incorporated a laboratory experiment focused on tandem mass spectrometry and database searching into a preexisting mini-semester project devoted to identifying metabolites from medicinal plants. Implementation of the experiment allowed students to make more confident metabolite identifications, introduced them to a cutting-edge database analysis platform (GNPS: Global Natural Products Social Molecular Networking), and increased student experience and knowledge of mass spectrometry in addition to the principle of dereplication of samples derived from nature.


Attenuation of leptin and insulin signaling by SOCS proteins.
Leptin and insulin are key hormones involved in the regulation of energy balance and glucose homeostasis. Development of resistance to the action of these hormones, which can occur with age, obesity and inflammation, appears to have a prime role in the pathogenesis of obesity and type 2 diabetes. Specific members of the suppressor of cytokine signaling (SOCS) family of proteins are now thought to have a role in the development of leptin and insulin resistance owing to their ability to inhibit leptin and insulin signaling pathways. In the case of leptin, current evidence suggests that SOCS3 appears to be of particular importance in the development of leptin resistance, whereas the ability to diminish insulin action has been described for several SOCS proteins (SOCS1, SOCS3, SOCS6 and SOCS7).


Electronic speckle pattern interferometric measurements of the basilar membrane in the inner ear.
A setup incorporating electronic speckle pattern interferometry, reference beam phase modulation, chopped laser light, and a simple microscope has been used to observe vibrations of the basilar membrane in human temporal bones. A postmortem effect ensures that no special treatment of the semitransparent membrane is required. Amplitudes (down to 20 A) and phases of the membrane motion are analyzed both in real time and video recordings. Observations include phase variations across the membrane and motions of Mossbauer sources (pieces of cobalt) on the membranes.


Recent research into Behçet's disease in Japan.
Recent studies on Behçet's disease supervised by a national research committee are reported under the headings of epidemiology, the role of streptococcus infection, PMN activity, immunological changes and treatment, concluded with a revised set of diagnostic criteria.


After p Values: The New Statistics for Undergraduate Neuroscience Education.
Statistical inference is a methodological cornerstone for neuroscience education. For many years this has meant inculcating neuroscience majors into null hypothesis significance testing with p values. There is increasing concern, however, about the pervasive misuse of p values. It is time to start planning statistics curricula for neuroscience majors that replaces or de-emphasizes p values. One promising alternative approach is what Cumming has dubbed the "New Statistics", an approach that emphasizes effect sizes, confidence intervals, meta-analysis, and open science. I give an example of the New Statistics in action and describe some of the key benefits of adopting this approach in neuroscience education.


Lowering of the tumoricide activity of human serum with Varidase. II. Antibodies against Varidase in human serum measured by complement binding.
Active human serum manifests a tumoricide effect against cells of the Ehrlich ascites tumor. Sera of patients with Ca ventriculi show a higher effect than those of patients with a chronic streptococcal disorder, in comparison with intact subjects. This tumorcide effect is depressed by Varidase, the degree of depression being greatest in the group of patients with streptococcal infection, smaller in healthy subjects and least in carcinoma patients. The investigated sera contained antibodies against Varidase, but not against streptokinase. The anti-Varidase antibodies are found also in sera of the new-born children. The decline of the tumoricide activity of Varidase-treated sera is related to the quantity of anti-Varidase antibodies determined by complement fixing reaction in non-treated sera.


Prolonging life or hindering death? An Orthodox perspective on death, dying and euthanasia.
This article addresses death as a biological event and attempts to approach it as a mystery within the light of the Orthodox Christian theology and tradition. First, the value of the last moments of the life of a human being is analyzed; then the state of living is differentiated from the state of surviving that results, in some extreme cases, from the intrusion of technology in medicine. The article elaborates on the sacred and spiritual character of death which, when viewed within the light of the Christ's resurrection, is transformed into a great blessing. The last part of the article focuses on the newly emerged issue of euthanasia and the reasons behind it. It poses certain vital questions that ought to be answered before legalization gets on its way. Finally, the conclusion summarizes the position of the Orthodox Church of Greece on death, dying and euthanasia.


Changes in the hydrogen-bonding strength of internal water molecules and cysteine residues in the conductive state of channelrhodopsin-1.
Water plays an essential role in the structure and function of proteins, particularly in the less understood class of membrane proteins. As the first of its kind, channelrhodopsin is a light-gated cation channel and paved the way for the new and vibrant field of optogenetics, where nerve cells are activated by light. Still, the molecular mechanism of channelrhodopsin is not understood. Here, we applied time-resolved FT-IR difference spectroscopy to channelrhodopsin-1 from Chlamydomonas augustae. It is shown that the (conductive) P2(380) intermediate decays with τ ≈ 40 ms and 200 ms after pulsed excitation. The vibrational changes between the closed and the conductive states were analyzed in the X-H stretching region (X = O, S, N), comprising vibrational changes of water molecules, sulfhydryl groups of cysteine side chains and changes of the amide A of the protein backbone. The O-H stretching vibrations of "dangling" water molecules were detected in two different states of the protein using H2 (18)O exchange. Uncoupling experiments with a 1:1 mixture of H2O:D2O provided the natural uncoupled frequencies of the four O-H (and O-D) stretches of these water molecules, each with a very weakly hydrogen-bonded O-H group (3639 and 3628 cm(-1)) and with the other O-H group medium (3440 cm(-1)) to moderately strongly (3300 cm(-1)) hydrogen-bonded. Changes in amide A and thiol vibrations report on global and local changes, respectively, associated with the formation of the conductive state. Future studies will aim at assigning the respective cysteine group(s) and at localizing the "dangling" water molecules within the protein, providing a better understanding of their functional relevance in CaChR1.


The use of entertainment and communication technologies before sleep could affect sleep and weight status: a population-based study among children.
Short sleep duration and poor sleep quality have been demonstrated to be associated with childhood obesity. It has been suggested that electronic entertainment and communication devices (EECDs) including TVs, computers, tablets, video games and cell phones interfere with sleep in children and youth. The aim of this study was to assess the impact that the use of EECDs in the hour before bedtime has on sleep and weight status to inform sleep promotion interventions and programs to prevent childhood obesity. A provincially representative sample of 2334 grade 5 children and their parents in Alberta, Canada was surveyed. Parents reported their child's bedtime and wake-up time along with how often their child snored, felt sleepy during the day, woke-up at night and woke-up in the morning feeling unrefreshed. Sleep duration, sleep quality and sleep efficiency were derived from these indicators. Parents also reported on the presence of EECDs in their child's bedroom, while children reported use of EECDs during the day and frequency of using each of these devices during the hour before sleep. The height and weight of children were measured. Multivariable mixed effect linear and logistic regression models were used to determine how sleep duration, sleep quality, sleep efficiency and weight status are influenced by (i) access to EECDs in children's bedrooms, (ii) use of EECDs during the hour before sleep, and (iii) calming activities specifically reading during the hour before sleep. Sleep duration was shorter by -10.8 min (cell phone), -10.2 min (computer) and -7.8 min (TV) for those with bedroom access to and used these EECDs during the hour before sleep compared to no access and no use. Good sleep quality was hindered by bedroom access to and use of all EECDs investigated during the hour before sleep, particularly among users of cell phones (OR = 0.64, 95% CI: 0.58-0.71) and computers (OR = 0.72, 95% CI: 0.65-0.80). Very good sleep efficiency was decreased by access to and frequent use of a TV (54%), cell phone (52%), tablet (51%) and video games (51%). Odds of obesity were doubled by bedroom access to and use of a TV and computer during the hour before sleep. Children who rarely read a printed book in the bedroom during the hour before sleep had a shorter sleep duration and poorer sleep quality and sleep efficiency compared to their peers. Having access to an EECD in the bedroom was associated with increased obesity despite frequently reading during the hour before sleep. Our findings suggest that sleep duration, sleep quality, sleep efficiency and weight status are better among children who do not have EECDs in the bedroom and frequently read a book during the hour before sleep as opposed to those who use EECDs during this hour. Education of limits against EECD use by parents may improve sleep outcomes. These findings will inform health promotion messages and may give rise to national recommendations regarding EECD use. ClinicalTrials.gov NCT01914185 . Registered 31 July 2013 Retrospectively registered.


Cancer awareness among community pharmacist: a systematic review.
The WHO recognises that community pharmacists are the most accessible healthcare professionals to the general public. Most patients regularly visit community pharmacies for health information and also seek advice from pharmacists with respect to signs and symptoms of cancer. As readily accessible health care professionals, community pharmacists are also in the best position to include cancer-screening initiatives into their practice. Pharmacists are therefore in a good position to raise awareness when they counsel people who buy over-the-counter medication for the control of possible cancer-related symptoms. The aim of this review was to critically appraise evidence gathered from studies that; (1) explore or assess knowledge of community pharmacist on signs and symptoms of cancer, (2) explore or assess knowledge of community pharmacist on cancer screening. EMBASE (ovid), CINAHL (EBSCOhost) and MEDLINE (EBSCOhost) were systematically searched for studies conducted between 2005 to July 2017. Studies that focused on knowledge of community pharmacist in cancer screening, signs and symptoms were included. A total of 1538 articles were identified from the search, of which 4 out of the 28 potentially relevant abstracts were included in the review. Findings of the selected studies revealed lack of sufficient knowledge on breast cancer screening, signs and symptoms. Both studies attributed knowledge limitation as the cause of reason for the key findings of their studies. The selected studies focused largely on breast cancer, which hinder the generalizability and transferability of the findings. Hence there is a need for more studies to be conducted in this area to draw a better conclusion.


Does the gender of nurses matter to patients? A qualitative analysis of gender preferences of patients.
This study argues that the gender of a nurse could give patients the emotional and psychological support they need in their healing process. Nonetheless, in many developing countries, these intricate preferences of patients are usually ignored due to poor staffing and logistical capacities of health facilities. As a contribution to this professional and operation gap, this paper explores patients' preference for nurses' gender in health care at the Komfo Anokye Teaching Hospital in Ghana. The paper further explores the importance of these preferences to the delivery of patient-centred care in Ghana and across Africa. The paper has two specific objectives: (a) to explore patients' preferences for the gender of nurses who attend to them while on admission; and (b) to find out the range of factors that inform these preferences. Qualitative exploratory descriptive design was used to select adult patients who were not seriously ill and nursed by male and female nurses at the medical and surgical wards of the Komfo Anokye Teaching Hospital in Ghana for at least 5 days from January to March 2017 and before their discharge. Participants were recruited using purposive sampling technique. A semi-structured interview guide was used to elicit information from 14 participants after seeking their written informed consent. The data were analysed using content analysis. Two major themes emerged. These were: the Preferred Gender of a Nurse in Nursing Care and the Reasons for the Preference or no Preference for Nurses' Gender in Nursing Care. Under each of these themes, the associated aspects were also discussed. Patients had varying preference for a particular nurse during care but gender was not particularly significant in patients' preference for nurses. Majority of the participants emphasized their preference for nurses with professional expertise and good virtues to determine a preferred nurse and both genders of nurses can possess these qualities. However, nurses of the same gender as the patient were preferred for intimate procedures to ensure privacy and satisfaction. The gender of a nurse is not on top of the preferences list of patients in the study context. This may be attributed to the long-term practice that the participants have not had the chance to be choosing a preferred nurse's gender, so most patients are tolerant and familiar with both male and female nurses. Instead, patients' preferences are determined by the performance and quality of service provided by nurses. Age, maturity and social connections were also found to influence patients' preferences.


Surveillance of suspect animal toxicoses with potential food safety implications in England and Wales between 1990 and 2002.
The potential chemical contamination incidents investigated by the Veterinary Laboratories Agency (VLA) between 1990 and 2002 are reviewed. Incidents were identified in the course of the VLA's surveillance of food animal disease and further investigations were carried out on behalf of the Food Standards Agency in order to identify and control the contamination of food animals and animal products with chemical hazards. In total 876 incidents were investigated, of which 588 involved the poisoning of cattle with heavy metals. There were 63 incidents involving the exposure of cattle, sheep, pigs and poultry to the accidental misuse of veterinary medicines, pesticides or rodenticides, and 50 incidents involving their exposure to microbiological toxins, particularly botulism.


[Effect of gamma-radiation on ultraviolet fluorescence of rat lymphocytes].
Changes in the level of the proper UV-fluorescence ( UVF ) of rat blood lymphocytes are considered as a function of radiation dose and time after gamma-irradiation of animals. 24 h following irradiation with a dose of 0.5 Gy the UVF intensity decreased; with doses of 1-8 Gy, the level of cytofluorescence exceeded the control values. The effect of fluorescence at this time was not related to changes in a cell diameter whereas at later times following irradiation part of the effect was related to the growth of cell dimensions.


Liquiritin (LT) exhibits suppressive effects against the growth of human cervical cancer cells through activating Caspase-3 in vitro and xenograft mice in vivo.
Cervical cancer is one of the most common female malignancies worldwide. Liquiritin (LT), a major constituent of Glycyrrhiza Radix, possesses a variety of pharmacological activities, including anti-cancer, anti-oxidative, anti-inflammatory and neuro-protective effects. However, its role in human cervical cancer remains to be elusive. In our study, we found that LT suppressed cervical cancer cell migration, invasion and cloning ability with little cytotoxicity to human normal cells. In addition, apoptosis was induced by LT in cervical cancer cells through activation of Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage. LT-triggered apoptosis was dependent on extrinsic and intrinsic pathways, which were relied on Fas-associated protein with death domain (FADD)- and Bcl-2/Bax-regulated pathways, leading to Caspase-8 and Caspase-9 cleavage, respectively. LT was found to increase FADD expression, while reduce Bcl-2 expression, contributing to Caspase-3 cleavage. And tumor suppressors, p21 and p53, were enhanced after LT treatment, inhibiting the growth of cervical cancer cells in vitro. Significantly, in vivo study suggested that tumor growth was impeded by LT in a dose-dependent manner through enhancing apoptosis. Together, the data here revealed that LT was an effective and promising candidate for preventing human cervical cancer progression via apoptosis enhancement.


Granular cell tumor of the neurohypophysis: a single-institution experience.
Granular cell tumor (GCT) is a rare neoplasm occurring in the sellar and suprasellar spaces. It is a primary tumor of the neurohypophysis, presumably arising from the pituicytes, a distinctive glial cell of the neurohypophysis. GCTs in most reported cases show biologically benign behavior with slow growth. Only 70 cases of hypophyseal GCTs have been reported in the literature. We report a case of GCT in the neurohypophysis of a 46-year-old woman and discuss the histological and clinical features of this neoplasm together with the treatment modalities, reviewing the pertinent literature.


The Fluorescence Enhancement of Mercury Detected in Food Based on Rhodamine Derivatives.
Recently, the problem of food security is more and more serious, and people pay attention to mercury because of the toxic of it. A new approach for the determination of mercury content in foodstuff is devised. In this paper, first, we design and synthesis a new kind of fluorescent probe whose matrix based on rhodamine B, hydrazine hydrate and hydroxy benzaldehyde. Through the analysis of H-NMR spectra of the synthesized product L1, we confirm that the synthetic substance is the adjacent carboxyl benzaldehyde hydrazone structure generation of rhodamine B. Then, we measure the fluorescence signal intensity of the probe with different concentrations of mercury ions fully upon complexation by fluorescence spectrometer and we can study the relationship between the mercury ion concentration and the fluorescence intensity and draw the standard working curve. Following, It's time to discuss the microwave digestion processing of tea, after digestion we use the synthetic probe Li for determination of mercury content in tea. The experimental results show that the maximum excitation wavelength of the probe and coordination compound are 568. 05 and 560. 00 nm, the maximum emission wavelength are 587. 94 and 580. 00 nm. Then we can find the best testing conditions to improve the degree of accuracy, that is: room temperature, 50% the methanol solution, 3. 0 mL pH 4. 0 buffer solution, in the extent of 30 min. The experimental results show that Na+, K+, Ca2+, Cu2+, Zn2+, Al3+ have little impact on the fluorescence intensity of the:probe. Fe3+, Mg2+, Ba2+ has a weak enhancement to the fluorescence intensity of the probe. While a low concentrations of Hg2+ have an obviously enhanced effect on the fluorescence intensity of the probe. In contrast to other metal ions, the probe for Hg2+ has a good selectivity. Linear relationship between the magnitude of increase in fluorescence intensity and concentration of mercury ion was in the range of 5~20 ng . L-1 with detection limit (3S/N) of 1. 9 ng . L-1. The proposed method was applied to determination of mercury ion in samples of tea and sausage and the obtained result and sample recovery were all satisfactory. The methods of analysis instrument has the advantages of simple structure, sensitivity, high accuracy, good selectivity and less volume of simple, without the need for enrichment, being very practical.


Red-light-mediated Barton decarboxylation reaction and one-pot wavelength-selective transformations.
In organic chemistry, selecting mild conditions for transformations and saving energy are increasingly important for achieving sustainable development goals. Herein, we describe a red-light-mediated Barton decarboxylation using readily available red-light-emitting diodes as the energy source and zinc tetraphenylporphyrin as the catalyst, avoiding explosive or hazardous reagents or external heating. Mechanistic studies suggest that the reaction probably proceeds via Dexter energy transfer between the activated catalyst and the Barton ester. Furthermore, a one-pot wavelength-selective reaction within the visible light range is developed in combination with a blue-light-mediated photoredox reaction, demonstrating the compatibility of two photochemical transformations based on mechanistic differences. This one-pot process expands the limits of the decarboxylative Giese reaction beyond polarity matching.


Effects of modafinil and sleep loss on physiological parameters.
The purpose of this study was to determine the effects of modafinil administration on physical performance, thermoregulation, and total energy expenditure (TEE) during continued wakefulness in Air Force operators. Participants (N = 12) were randomly assigned to the modafinil or placebo group. Participants performed physical performance and testing during 72 hours of wakefulness. There were no differences between groups for physical performance. Oral temperature was higher for modafinil compared to placebo (36.5 +/- 0.2 degrees C versus 36.3 +/- 0.2 degrees C for modafinil and placebo, respectively, p < 0.05). Daily water turnover (8.8 +/- 1.0 L x day(-1) and 9.0 +/- 1.5 L x day(-1)) and total energy expenditure (19.4 +/- 3.7 and 19.9 +/- 2.1 MJ) were similar between the modafinil and placebo groups, respectively. modafinil did not improve physical performance. Despite elevating oral temperature, water turnover and TEE were similar between treatments. These findings suggest it is unnecessary for operators taking modafinil to carry additional fluids and/or food.


Real life evaluation of the multi-organ effects of Lumacaftor/Ivacaftor on F508del homozygous cystic fibrosis patients.
Lumacaftor/Ivacaftor (LUM-IVA), a cystic fibrosis transmembrane conductance regulator (CFTR) protein corrector-potentiator combination, improves lung function and reduces pulmonary exacerbations (PEx) in F508del homozygous CF patients. However, the systemic effects of LUM-IVA outside the respiratory system have not yet been thoroughly investigated. A prospective, real-world, yearlong study was performed on F508del homozygous adult CF patients who commenced treatment with LUM-IVA. Pancreatic function, bone metabolism, fertility status, nutritional and pulmonary factors were evaluated. Twelve patients, mean age 28.3 years (18.6-43.9) were recruited. Following 12 months of treatment, no changes were detected in glucose, insulin, c-peptide or BMI values. A significant relative decrease in mean alkaline-phosphatase levels (122.8 U/L vs 89.4, p = 0.002) and a trend toward an increase in calcium levels (9.5 vs 9.9 mg/dL, p = 0.074) were observed. A non-significant improvement in mean DEXA spine t-score after a year of treatment (-2.1 vs -1.6, n = 4, p = 0.11) was detected. Sweat chloride concentrations decreased significantly (-21.4 mEq/L; p = 0.003). Pulmonary outcome revealed improvement in spirometry values during the first three months (FEV1 by 5.7% p = 0.009, FEF25-75 by 4.3% p = 0.001) with no change in chest CT Bhalla score and CFQR after one year. There was also a significant decrease in parenteral antibiotic events (17 vs 8, p = 0.039) with shift from IV to oral antibiotics for PEx treatment. After one year of treatment, stabilization was observed in the pancreatic indices, nutritional status, structure and function of the lungs, with a beneficial effect on bone mineral metabolism and CFTR function. Additional studies should investigate the effect of CFTR modulators on extra-pulmonary manifestations.


Total Synthesis and Stereochemical Assignment of Nostosin B.
Nostosins A and B were isolated from a hydrophilic extract of Nostoc sp. strain from Iran, which exhibits excellent tryps inhibitory activity. Nostosin A was the most potent natural tripeptide aldehyde as trypsin inhibitor up to now. Both R- and S-2-hydroxy-4-(4-hydroxy-phenyl) butanoic acid (Hhpba) were prepared and incorporated into the total synthesis of nostosin B, respectively. Careful comparison of the NMR spectra and optical rotation data of synthetic nostosin B (1a and 1b) with the natural product led to the unambiguous identification of the R-configuration of the Hhpba fragment, which was further confirmed by co-injection with the authentic sample on HPLC using both reversed phase column and the chiral AD-RH column.


Utility of neoadjuvant therapy in rectal GIST.
Neoadjuvant therapy with Imatinib is the preferred treatment for rectal GISTs in order to reduce the aggressiveness of a surgical resection. At present, surgical resection does not require wide surgical margins. There is also a lot of controversy with regard to the need for a broad anatomical resection or if a local resection is sufficient and maintains maximum oncological safety and minimum morbidity and mortality. We present a case report of a rectal GIST with a good response to neoadjuvant treatment which allowed a transanal resection.


Characteristics of Mycobacterium avium complex (MAC) pulmonary disease in previously treated lung cancer patients.
Mycobacterium avium complex (MAC) is responsible for a large portion of non-tuberculous mycobacterial (NTM) infections worldwide. Host factors such as active malignancy, immunosuppression, chronic obstructive pulmonary disease (COPD) and bronchiectasis increase the risk of MAC infection. However, the relationship between previously treated lung cancer with subsequent development of MAC pulmonary disease and treatment outcomes have not been previously studied. We retrospectively identified all patients with lung cancer and MAC pulmonary disease documented in medical records at Mayo Clinic between January 2005 and October 2016. Patients who were diagnosed with MAC pulmonary disease before or at the time of lung cancer diagnosis were excluded. Patients meeting all inclusion criteria underwent chart review for prior oncologic treatments, clinical characteristics, and MAC treatment response. We identified 13 patients with MAC pulmonary disease and prior lung cancer, including 4 men and 9 women. Eight patients had structural lung disease that can predispose to MAC pulmonary disease, including bronchiectasis (23.0%) and COPD (46.2%). Four (30.8%) had no apparent immunosuppression or other risk factor(s) for MAC pulmonary disease. Primary pulmonary malignancies included pulmonary carcinoid, adenocarcinoma, and squamous cell carcinoma. Ten (76.9%) patients were started on antimicrobial treatment for MAC, and 8 (61.5%) patients completed MAC treatment with 6 (46.1%) patients achieving symptomatic improvement. MAC pulmonary disease in previously treated lung cancer can occur without apparent risk factors for this NTM infection. Symptomatic improvement with MAC antimicrobial therapy appears to be lower than expected but comorbidities might influence outcomes in this patient population.


Tachyarrhythmia therapy utilizing electrical stimulation: a review.
The review is structured in such a way as to fall naturally into four main sections. These are as follows: clinical overview of the common mechanisms leading to the generation of tachyarrhythmias; commonly used sensing techniques and algorithms for the detection of tachyarrhythmias; electrical stimulation algorithms used to terminate many of the rhythms; existing implantable devices and a brief look at the future. The clinical overview introduces the reader unfamiliar with tachyarrhythmias to such mechanisms as sinus tachycardia, supraventricular tachycardias (SVTs), ventricular tachycardia, 'torsade de pointes', and ventricular fibrillation. SVT includes paroxysmal SVT, atrial flutter, atrial tachycardia and junctional tachycardia (enhanced automaticity). Also there is a brief introduction to alternative therapies (drugs, surgery etc.) The sensing techniques section covers input signal processing to enable the R wave to be adequately detected; while the tachycardia detection algorithms section discusses such areas as simple rate detect, rate of change of rate detect, stability of rate, the so-called probability density function technique and some other more complex detection algorithms. The section on electrical stimulation algorithms used for tachycardia therapy discusses burst pacing techniques, special cases such as automatically decrementing bursts and automatically incrementing bursts, defibrillation shock therapy (since fibrillation is a form of tachyarrhythmia) and several other more complex algorithms. The review finishes up with a discussion of current implantable antitachy pacemakers and defibrillators. There is also a speculative look at the future to enable the reader to obtain a full picture.


Factors driving the global decline of cycad diversity.
Mounting evidence indicates that we are witnessing the sixth mass extinction period. Given the important goods and services biodiversity delivers to humans, there is a need for a continued commitment to investigate what pre-disposes some taxa to greater risk of extinction. Here, we investigate this question using a phylogenetic comparative method and fitting a cumulative link mixed effect model on biological, ecological and evolutionary data of cycads, the most threatened lineage in the plant kingdom. We identified nine groups of threats to cycads, with habitat loss, over-collection, fire and reproduction failure being the most prominent, but only four of these threats (habitat loss, over-collection, medicinal uses and reproduction failure) clustered on the cycad tree of life. This clustering suggests that closely related species may be exposed to similar threats, perhaps because of geographic regionalization of cycad genera. Nonetheless, the diversity of threats and several variables linked to the biology and ecology of cycads correlate with extinction risk (e.g. altitude, height, diameter, geographic range), and different variables seem to be linked to different IUCN status of cycads. Although their predictive power is generally < 50 %, geographic range and maximum diameter stood out as the best predictors particularly for the Vulnerable (VU) category, with a predictive power of 87 % and 69 %, respectively. Using our best model for VU, we predicted all five Data Deficient (DD) species of cycads to be in the VU category. Collectively, our results elucidate the pattern of extinction risk in cycads and, since most threats that we identified as drivers of extinction risk of cycads are anthropogenically mediated, we recommend stronger legislation to regulate human-cycad interactions and the commitment of all governments globally to implement this regulation.


Tremor Detection Using Parametric and Non-Parametric Spectral Estimation Methods: A Comparison with Clinical Assessment.
In the clinic, tremor is diagnosed during a time-limited process in which patients are observed and the characteristics of tremor are visually assessed. For some tremor disorders, a more detailed analysis of these characteristics is needed. Accelerometry and electromyography can be used to obtain a better insight into tremor. Typically, routine clinical assessment of accelerometry and electromyography data involves visual inspection by clinicians and occasionally computational analysis to obtain objective characteristics of tremor. However, for some tremor disorders these characteristics may be different during daily activity. This variability in presentation between the clinic and daily life makes a differential diagnosis more difficult. A long-term recording of tremor by accelerometry and/or electromyography in the home environment could help to give a better insight into the tremor disorder. However, an evaluation of such recordings using routine clinical standards would take too much time. We evaluated a range of techniques that automatically detect tremor segments in accelerometer data, as accelerometer data is more easily obtained in the home environment than electromyography data. Time can be saved if clinicians only have to evaluate the tremor characteristics of segments that have been automatically detected in longer daily activity recordings. We tested four non-parametric methods and five parametric methods on clinical accelerometer data from 14 patients with different tremor disorders. The consensus between two clinicians regarding the presence or absence of tremor on 3943 segments of accelerometer data was employed as reference. The nine methods were tested against this reference to identify their optimal parameters. Non-parametric methods generally performed better than parametric methods on our dataset when optimal parameters were used. However, one parametric method, employing the high frequency content of the tremor bandwidth under consideration (High Freq) performed similarly to non-parametric methods, but had the highest recall values, suggesting that this method could be employed for automatic tremor detection.


Hallucinations as a trauma-based memory: implications for psychological interventions.
The relationship between hallucinations and life events is a topic of significant clinical importance. This review discusses the extent to which auditory and visual hallucinations may be directly related to traumatic events. Evidence suggests that intrusive images occur frequently within individuals who also report hallucinatory experiences. However, there has been limited research specifically investigating the extent to which hallucinations are the re-experiencing of a traumatic event. Our current theoretical understanding of these relationships, along with methodological difficulties associated with research in this area, are considered. Recent clinical studies, which adopt interventions aimed at the symptoms of posttraumatic stress disorder in people diagnosed with a psychotic disorder, are reviewed. There is a need for the development of evidence-based interventions in this area.


Betreuung durch ein Advanced Nursing Practice-Team - Erfahrungen Lymphombetroffener und ihrer Angehörigen.
Support by an advanced nursing practice team - Experiences of patients with lymphoma and their family members. A qualitative study Abstract. Background: Patients with lymphomas who are treated with high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are confronted with a life-threatening disease and a stressful therapeutic procedure. An advanced nursing practice (ANP) team was established at the Inselspital, Bern University Hospital to provide continuous, need-based care to these patients and their family members throughout the entire course of therapy. Little is known about experiences of concerned persons. Objective: With this study, patients' with lymphomas treated with HDC and ASCT and their family members' experiences of the care provided by the ANP team were explored. Methods: The qualitative research approach "interpretive description" provided orientation. Eight couple interviews with patients and their family members were conducted and evaluated by means of reflexive thematic analysis. Results: The participants experienced continuous caring by the nurse consultants throughout the entire course of therapy and received professional, administrative, and emotional support. They felt competently informed as well as advised, and had an easily accessible contact person for questions to whom they had built up an emotional relationship. This not only encouraged and strengthened them, but also provided security and the feeling of being in good hands. Conclusion: It is recommended to offer an ANP service to those affected, as for them the continuous support of a proficient, compassionate, familiar and committed contact person was essential.


Phosphorylation of D-glucosamine by rat liver glucokinase.
D-Glucosamine was found to be phosphorylated by a rat liver extract in the presence of a high concentration of glucose, which was formerly believed to be a strong competitive inhibitor of this reaction. Results suggested that glucosamine may be phosphorylated by high Km hexokinase, i.e. glucokinase [EC 220.127.116.11]. The enzyme involved was separated from specific N-acetyl-D-glucosamine kinase [EC 184.108.40.206]. The phosphorylation was not inhibited by a physiological level of glucose or glucose 6-phosphate, which strongly inhibited low Km hexokinase. The apparent Km of glucokinase for glucosamine was estimated as 8 mM, which is ten times that of low Km hexokinase.


Higher Diet Quality is Associated with Lower Odds of Low Hand Grip Strength in the Korean Elderly Population.
Single nutrients or food groups have been associated with physical performance. However, little is known about the association of overall diet quality with hand grip strength (HGS), a predictive parameter in the prognosis of chronic disease morbidity and mortality, or quality of life. This study examined the association between HGS and three indices-the Korean Healthy Eating Index (KHEI), the Alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)-using data obtained on Korean elderly persons aged ≥65 years (n = 3675) from a nationally representative database. The cross-sectional data was collected as part of the Korea National Health and Nutrition Examination Survey (KNHANES, 2014-2016). Dietary intake data from the 24-h recall method were used to calculate diet quality scores. The cutoff value for low HGS was defined as the value corresponding to the lowest 20th percentile of HGS of the study population (men, 28.6 kg; women, 16.5 kg). Higher index scores for diet quality were associated with 32%-53% lower odds of low HGS. Better overall diet quality may be associated with higher HGS in the elderly Korean population.


Phxnlme: An R package that facilitates pharmacometric workflow of Phoenix NLME analyses.
Pharmacometric analyses are integral components of the drug development process, and Phoenix NLME is one of the popular software used to conduct such analyses. To address current limitations with model diagnostic graphics and efficiency of the workflow for this software, we developed an R package, Phxnlme, to facilitate its workflow and provide improved graphical diagnostics. Phxnlme was designed to provide functionality for the major tasks that are usually performed in pharmacometric analyses (i.e. nonlinear mixed effects modeling, basic model diagnostics, visual predictive checks and bootstrap). Various estimation methods for modeling using the R package are made available through the Phoenix NLME engine. The Phxnlme R package utilizes other packages such as ggplot2 and lattice to produce the graphical output, and various features were included to allow customizability of the output. Interactive features for some plots were also added using the manipulate R package. Phxnlme provides enhanced capabilities for nonlinear mixed effects modeling that can be accessed using the phxnlme() command. Output from the model can be graphed to assess the adequacy of model fits and further explore relationships in the data using various functions included in this R package, such as phxplot() and phxvpc.plot(). Bootstraps, stratified up to three variables, can also be performed to obtain confidence intervals around the model estimates. With the use of an R interface, different R projects can be created to allow multi-tasking, which addresses the current limitation of the Phoenix NLME desktop software. In addition, there is a wide selection of diagnostic and exploratory plots in the Phxnlme package, with improvements in the customizability of plots, compared to Phoenix NLME. The Phxnlme package is a flexible tool that allows implementation of the analytical workflow of Phoenix NLME with R, with features for greater overall efficiency and improved customizable graphics. Phxnlme is freely available for download on the CRAN repository (https://cran.r-project.org/web/packages/Phxnlme/).


Diagnostics for fast ignition science (invited).
The ignition concept for electron fast ignition inertial confinement fusion requires sufficient energy be transferred from an approximately 20 ps laser pulse to the compressed fuel via approximately MeV electrons. We have assembled a suite of diagnostics to characterize such transfer, simultaneously fielding absolutely calibrated extreme ultraviolet multilayer imagers at 68 and 256 eV; spherically bent crystal imagers at 4.5 and 8 keV; multi-keV crystal spectrometers; MeV x-ray bremmstrahlung, electron and proton spectrometers (along the same line of sight), and a picosecond optical probe interferometer. These diagnostics allow careful measurement of energy transport and deposition during and following the laser-plasma interactions at extremely high intensities in both planar and conical targets. Together with accurate on-shot laser focal spot and prepulse characterization, these measurements are yielding new insights into energy coupling and are providing critical data for validating numerical particle-in-cell (PIC) and hybrid PIC simulation codes in an area crucial for fast ignition and other applications. Novel aspects of these diagnostics and how they are combined to extract quantitative data on ultrahigh intensity laser-plasma interactions are discussed.


Pharmacogenetics of disease-modifying antirheumatic drugs in rheumatoid arthritis: towards personalized medicine.
Rheumatoid arthritis is a disease showing considerable heterogeneity in all its aspects, including response to therapy. The efficacy of disease-modifying antirheumatic drugs (DMARDs), with or without biological activity, has been unambiguously established. DMARDs improve the symptoms associated with the disease, and, even more importantly, are capable of stagnating the joint damage associated with the disease. Nonetheless, a considerable proportion of patients fail to achieve an adequate response and/or experience toxicity. This variability in treatment response between individuals has given rise to an extensive search for prognostic markers in order to personalize and optimize therapy in rheumatoid arthritis patients. Pharmacogenetics, the study of genetic variation underlying differential responses to drugs, is a rapidly progressing field in rheumatology that might enable personalized therapy in rheumatic diseases. This review will summarize the pharmacogenetics of commonly used synthetic and biological DMARDs.


Skin prick test reactivity to lupin in comparison to peanut, pea, and soybean in atopic and non-atopic German subjects: A preliminary cross-sectional study.
The increasing use of lupin in food processing poses a problem of potential (cross-)allergic reactions. To evaluate the prevalence of sensitization to lupin in comparison to that of other legumes skin prick tests were performed with lupin, pea, peanut, and soybean in atopic (n = 81) and non-atopic (n = 102) German adults. Of these 183 subjects, 20 subjects had to be excluded due to invalid skin prick tests (reaction to histamine <3 mm or to sodium chloride >2 mm). Thus, skin prick tests of 163 subjects were included in final analyses. Of 163 subjects, 18 had a positive reaction to at least one legume tested. Overall skin prick test reactivity was different among non-atopic and atopic subjects (P = 0.005). Altogether, six subjects (4%) were sensitized to lupin, 12 (7%) to pea, 5 (3%) to peanut, and 8 (5%) to soybean. Two (2%) of the 92 non-atopic subjects and 4 (6%) of the 71 atopic subjects had a positive skin prick test to lupin. Of the 6 subjects sensitized to lupin, 3 (50%) were also sensitized to pea, 3 (50%) to peanut, and 5 (83%) to soybean. In conclusion, the prevalence rates of lupin sensitization were comparable to or even lower than those of pea, peanut, and soybean. To date, lupin allergy is suspected to be relatively uncommon in the overall German population since lupin sensitization occurred in only 2% of non-atopic subjects. However, there is a clear risk of a lupin allergy in predisposed subjects, since the frequency of lupin sensitization was 6% in atopic subjects. In particular, subjects with existing sensitization or allergy to other legumes are at higher risk for a sensitization or allergy to lupin due to cross-reactivity.


Gut and urinary microbiota: the causes and potential treatment measures of renal cell carcinoma.
Mounting evidence suggests that the gut microbiota plays a crucial role in the development and treatment of various cancers. Recent research on the urinary microbiota challenges the long-standing belief that urine is sterile, as urinary microbiota has been implicated in the development of bladder and prostate cancers, similar to the role of gut microbiota in cancer development. Although the precise involvement of microbiota in the proliferation and differentiation of renal cell carcinoma (RCC) remains unclear, dysbiosis is considered one possible mechanism by which microbiota may contribute to RCC development and treatment. This review summarizes potential mechanisms by which gut microbiota may contribute to the development of RCC, and provides evidence for the involvement of urinary microbiota in RCC. We also explore the role of gut microbiota in RCC treatment and propose that the composition of gut microbiota could serve as a predictive marker for the potential efficacy of immune checkpoint inhibitors (ICIs) in RCC patients. Additionally, evidence suggests that modulating the abundance and distribution of microbiota can enhance the therapeutic effects of drugs, suggesting that microbiota may serve as a promising adjuvant therapy for RCC. Overall, we believe that further investigation into the gut and urinary microbiome of RCC patients could yield valuable insights and strategies for the prevention and personalized treatment of RCC.


Pediatricians' awareness of and attitudes about four clinical practice guidelines.
The increasing complexity of medical care and a desire to increase quality and control costs have led to growing use of clinical practice guidelines (CPGs). It is unclear how helpful these guidelines are to the practitioners expected to use them. We surveyed pediatricians about their knowledge and impressions of four well-publicized CPGs: the American Academy of Pediatrics' "Practice Parameter for Hyperbilirubinemia in Newborns" (hyperbilirubinemia), "A Guideline for the Management of Febrile Infants" (fever), the Agency for Health Care Policy and Research's "Guideline for Otitis Media With Effusion" (otitis), and the US Preventive Services Task Force Guide to Clinical Preventive Services (preventive care). 1) What percentage of practicing pediatricians are aware of these guidelines? 2) How helpful do they find them? 3) What are practitioners' perceived limitations of these guidelines? 4) Have these guidelines affected provider behavior? 5) Are there features of a provider's training or practice that are associated with changing practice as a result of guidelines? A national survey of 600 pediatricians selected at random from the American Medical Association master file. A total of 300 of 555 eligible participants (54%) returned surveys. Of the respondents, 66% were aware of the hyperbilirubinemia guideline, 64% of the fever guideline, 50% of the otitis guideline, but only 16% knew of the preventive care guidelines. Mean helpfulness scores (1 to 10 scale, where 1 = "not at all helpful" and 10 = "extremely helpful") ranged from 3.67 to 6.67 for the different guidelines. In terms of limitations, 15% to 33% of respondents reported that CPGs were "too cookbook," 6% to 19% reported that they were "too time-consuming," and 4% to 16% reported that they were "too cumbersome." Additional reported limitations were believing that a guideline left no room for personal experience and judgment, concern of increased liability risk, and poor parental acceptance of CPG recommendations. The proportions reporting change in management as a result of a CPG were 28% for the hyperbilirubinemia guideline, 36% for the fever guideline, 19% for the preventive care guidelines, and 28% for the otitis guideline. Mean helpfulness scores reported by nonuniversity-affiliated physicians were significantly higher than those reported by university-affiliated physicians. In a regression model of respondents aware of a particular guideline, more recent graduation from medical school and increased helpfulness scores were associated with guideline-related behavior change. In their present form, CPGs are not perceived as very helpful by most practitioners. More recent medical school graduates and nonuniversity-affiliated physicians are more likely to find them helpful and more likely to change their behavior because of them.


Cost implications of introducing a telecardiology service to support fetal ultrasound screening.
A district hospital in south-east England used a telecardiology service for fetal cardiac diagnosis alongside an existing arrangement for referring pregnant women directly to perinatal cardiologists in London for detailed fetal echocardiography. Women were identified for referral according to local protocols when having a second trimester anomaly scan. For the telemedicine referrals, the sonographers video-recorded images from the anomaly scans for transmission during monthly videoconferences. The cost of the women's antenatal care was calculated from the specialist assessment until delivery, while family costs were collected in a postal survey. Over 15 months, telemedicine was used in 52 cases, while 24 women were seen in London. The London women were more likely to have had an ultrasound abnormality (29% v 10%, P = 0.047). A telemedicine assessment of 5 min duration was more costly than an examination in London (mean cost per referral of pound206 v pound74, P < 0.001). However, the telecardiology service was cost neutral after 14 days and for the extended period until delivery. Travel costs for London women averaged pound37 compared with pound5.50 for the telemedicine referrals. Telemedicine may be useful to support perinatal cardiologists in the UK whose workloads are expanding in response to improved standards in antenatal ultrasound screening.


Human plasma glutathione oxidation in normal and pathological conditions.
Reduced glutathione added to human plasma disappears rapidly, and it is concomitantly recovered in its oxidized form. This oxidation is not due to the plasma metal content since it is not inhibited by EDTA or by passage of plasma through Chelex columns. Furthermore, this oxidation is not due to the peroxidase activity of glutathione S-transferases, which are usually undetectable in normal human serum, and it does not correlate with the amount of plasma glutathione peroxidase. A significant increase in the rate of glutathione oxidation was observed in plasma of patients with increased gamma-glutamyltranspeptidase activity. It is concluded that the side-oxidase activity of gamma-glutamyltransferase is responsible for the oxidation of glutathione in human plasma.


Accelerated orthodontic treatment - what's the evidence?
The demand and accessibility of orthodontic care has increased but has also been accompanied by patient requests for shorter treatment times. Longer orthodontic treatment increases the risk of decalcification, gingival recession, and root resorption and so shorter treatment times have multiple advantages as well as appealing to patient's desires. Numerous techniques and materials have been suggested to reduce treatment times but, in most cases, are based upon selected case reports with no prospective clinical trials to validate claims. The present review examines many of the current options purported to accelerate orthodontic tooth movement and the level of evidence presently available. There is some evidence to suggest that low-level laser therapy and a corticotomy involving the raising of a muco-periosteal flap are associated with accelerated orthodontic tooth movement; however, the current level of evidence is low to moderate in quality. For this reason, further research is required before routine application could be recommended.


Immune response and immunotherapy in intraepithelial and invasive lesions of the uterine cervix.
Infection with the human papillomavirus virus (HPV) induces innate and acquired immune responses in the cervical stroma, which are a delicate, balanced and generally unpredictable immunological defense. Because of the immunological breaks that the HPV virus causes, eradication of infected cells does not occur, potentially leading to development of intraepithelial and invasive lesions. Advances in our understanding of the immune system and in the definition of antigens in tumor cells has led to many new treatment strategies. As a result, immunotherapy has the potential to be the most specific treatment for tumors, and one that requires elaboration. Recently, immunotherapy with interferon and dendritc cells has been used on intrapepithelial and invasive cervical lesions with promising results.


James Ewing (1866-1943): "the chief".
"It is a growing conviction that to know cancer in man, one must study the disease most carefully in the human subject. Personally, I do not look for any startling advances or sensational discoveries, since it is much more likely that a steady reduction in the mortality from cancer will come chiefly from a large number of separate factors, of which the most significant appear to be increased control of the conditions leading to cancer, more general recognition of the preliminary stages of the disease, early diagnosis, and treatment of the established disease. From the consideration of these various functions of the modern cancer research hospital, I think that it must be evident that such an institution not only can justify its existence, but fills a very urgent need without which, progress of cancer research would be handicapped, and much relief that might early be extended to cancer victims would be unavailable. Nor is there any doubt that the function of supporting such an institution is properly exercised by the State, which support should be continuous and liberal"--James Ewing [2].


Physiologically significant inhibitory hypothalamic action of substance P on prolactin release in the male rat.
To evaluate a possible physiological role of endogenous substance P (SP) in the control of prolactin (PRL) release, conscious adult male rats were given injections of a specific antiserum against SP (anti-SP) into the third ventricle (3 microliters) or intravenously (0.5 ml). Third-ventricular injection of anti-SP induced a significant increase in plasma PRL levels when compared to values in control animals injected with normal rabbit serum (p less than 0.02). Plasma PRL concentrations were significantly elevated within 2 h after injection of antiserum and remained elevated for the 4-hour duration of the experiment. In contrast, injections of large doses of anti-SP intravenously had no effect on plasma PRL levels. In order to confirm the effect of SP itself, synthetic SP was injected intravenously and intraventricularly. Opposite effects of SP on PRL release were observed after intravenous and intraventricular injections of low or high doses of the peptide. A lower dose of SP (10 ng, 7.42 pmol) injected into the third ventricle suppressed the release of PRL (p less than 0.01), whereas higher doses (1 microgram, 0.74 nmol, or 5 micrograms, 3.71 nmol) had a stimulatory effect on PRL release (p less than 0.01). Similarly, a low dose of SP (0.1 microgram, 0.07 nmol) injected intravenously lowered plasma PRL (p less than 0.05). Large doses of intravenous SP (50 micrograms, 37.1 nmol) dramatically stimulated PRL release (p less than 0.001). To evaluate a possible direct action of SP on PRL release from the anterior pituitary, the peptide was incubated with dispersed anterior pituitary cells for 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)


[Obstructive hydrocephalus in cerebellar infarcts].
Large cerebellar ischaemic infarction may act as a space-occupying lesion and cause acute ventricular dilatation secondary to brain stem compression. 8 cases are regarded and the clinical course and therapy are discussed. After acute onset with vestibular and cerebellar symptoms, signs of progressive clouding of consciousness, accompanied often by signs of brain stem compression develop leading finally to decerebration syndrome. CT reveals an extensive hypodense area, usually in the lower part of the cerebellar hemisphere, compression and shift of the IVth ventricle and dilatation of 3rd and lateral ventricles. Drainage of ventricular fluid alone is not sufficient and the therapy of choice is the resection of infarcted tissue. Even in patients, who were operated in the early phase of decerebration excellent recovery was noted.


Clinical factors associated with trabecular bone score.
Dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) is the reference standard for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel grey-level texture measurement that can be extracted from DXA images, predicts osteoporotic fractures independent of BMD. Our aim was to identify clinical factors that are associated with baseline lumbar spine TBS. In total, 29,407 women ≥50 yr at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Multiple linear regression and logistic regression (lowest vs highest tertile) was used to define the sensitivity of TBS to other risk factors associated with osteoporosis. Only a small component of the TBS measurement (7-11%) could be explained from BMD measurements. In multiple linear regression and logistic regression models, reduced lumbar spine TBS was associated with recent glucocorticoid use, prior major fracture, rheumatoid arthritis, chronic obstructive pulmonary disease, high alcohol intake, and higher body mass index. In contrast, recent osteoporosis therapy was associated with a significantly lower likelihood for reduced TBS. Similar findings were seen after adjustment for lumbar spine or femoral neck BMD. In conclusion, lumbar spine TBS is strongly associated with many of the risk factors that are predictive of osteoporotic fractures. Further work is needed to determine whether lumbar spine TBS can replace some of the clinical risk factors currently used in fracture risk assessment.


Divergent Soybean Calmodulins Respond Similarly to Calcium Transients: Insight into Differential Target Regulation.
Plants commonly respond to stressors by modulating the expression of a large family of calcium binding proteins including isoforms of the ubiquitous signaling protein calmodulin (CaM). The various plant CaM isoforms are thought to differentially regulate the activity of specific target proteins to modulate cellular stress responses. The mechanism(s) behind differential target activation by the plant CaMs is unknown. In this study, we used steady-state and stopped-flow fluorescence spectroscopy to investigate the strategy by which two soybean CaMs (sCaM1 and sCaM4) have evolved to differentially regulate NAD kinase (NADK), which is activated by sCaM1 but inhibited by sCaM4. Although the isolated proteins have different cation binding properties, in the presence of Mg2+ and the CaM binding domains from proteins that are differentially regulated, the two plant CaMs respond nearly identically to rapid and slow Ca2+ transients. Our data suggest that the plant CaMs have evolved to bind certain targets with comparable affinities, respond similarly to a particular Ca2+ signature, but achieve different structural states, only one of which can activate the enzyme. Understanding the basis for differential enzyme regulation by the plant CaMs is the first step to engineering a vertebrate CaM that will selectively alter the CaM signaling network.


YVO4 cascaded Raman laser for five-visible-wavelength switchable emission.
We report switchable emission of visible light at five wavelengths generated in a $\text{YVO}_4$YVO4 cascaded Raman cavity driven by an acousto-optic ${Q}$Q-switched Nd:YAP laser at 1080 nm. The second-harmonic generation and sum-frequency generation of the fundamental, first-Stokes, and second-Stokes waves were realized based on the angle-tuned BBO crystal. The phase-match angle tuning span of a BBO crystal is only approximately 2.3° to allow the frequency mixing to produce five visible wavelengths on demand. At an absorbed pump power of 5.96 W and a pulse repetition frequency of 10 kHz, average output powers of 800, 340, 460, 190, and 326 mW were obtained for 539.9, 567.2, 597.4, 631.0, and 668.5 nm lasers, respectively. The results show that the cascaded Raman laser system with an angle-tuned BBO crystal can provide a convenient and efficient method to achieve wavelength-switchable visible emission for multi-wavelength laser applications.


Some protease inhibitors are also inhibitors of poly(ADP-ribose) polymerase.
The low-molecular-weight peptide protease inhibitors, tosyl-lysine-chloromethyl ketone, antipain and leupeptin, inhibited poly(ADP-ribose) [poly(ADP-Rib)] polymerase in permeable cells. The concentrations required for 50% inhibition were 3.6, 5 and 29 mM, respectively. Two peptides without protease inhibitor activity, fibrinopeptide A and phenylalanine-leucine-(glutamine)2-leucine, also inhibited poly (ADP-Rib) synthesis; doses required for 50% inhibition were 0.37 and 11.2 mM, respectively. These concentrations lie within a range bracketed by the 50% inhibition concentrations of the strong and weak poly(ADP-Rib) synthesis inhibitors, 3-amino-benzamide (0.15 mM) and caffeine (greater than 100 mM), respectively. N-Ethylmaleimide also inhibited poly(ADP-Rib) synthesis, at a 50% inhibitory dose of 0.3 mM, in the absence of exogenous thiol reagents. High-molecular-weight protease inhibitors, such as soybean (including Bowman-Birk reagent) and lima bean trypsin inhibitors and human alpha 1-protease inhibitor, had no effect on poly(ADP-Rib) synthesis up to 2 mg/ml. Interference with transformation and other cellular effects that have been reported in carcinogen-damaged cells treated with low-molecular-weight peptide protease inhibitors may therefore involve common mechanisms with poly(ADP-Rib) inhibitors. Similar effects of high-molecular-weight protease inhibitors presumably involve different mechanisms.


Airway dendritic cell maturation in children exposed to air pollution.
Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ≤ 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 μg/m3, n = 138), middle (25.6 to 26.8 μg/m3, n = 126), and upper (26.8 to 31.0 μg/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p<0.05). There was a higher percentage of cDC1 cells in the lower tertile of exposure (6.63% (2.48 to 11.64) vs. 2.63% (0.72 to 7.18), p<0.05). Additionally; children in the lower exposure tertile had increased FEV1 compared with children in the upper tertile; (median z-score 0.15 (-0.59 to 0.75) vs. -0.21 (-0.86 to 0.48), p<0.05. Our data reveal that children attending schools in the highest areas of PM exposure in London exhibit increased numbers of "mature" airway cDCs, as evidenced by their expression of the surface marker CD86. This data is supportive of previous in vitro data demonstrating an alteration in the maturation of airway cDCs in response to exposure to pollutants.


Annual biomass spatial data for southern California (2001-2021): Above- and belowground, standing dead, and litter.
Biomass estimates for shrub-dominated ecosystems in southern California have been generated at national and statewide extents. However, existing data tend to underestimate biomass in shrub vegetation types are limited to one point in time, or estimate aboveground live biomass only. In this study, we extended our previously developed estimates of aboveground live biomass (AGLBM) based on the empirical relationship of plot-based field biomass measurements to Landsat normalized difference vegetation index (NDVI) and multiple environmental factors to include other vegetative pools of biomass. AGLBM estimates were made by extracting plot values from elevation, solar radiation, aspect, slope, soil type, landform, climatic water deficit, evapotranspiration, and precipitation rasters and then using a random forest model to estimate per-pixel AGLBM across our southern California study area. By substituting year-specific Landsat NDVI and precipitation data, we created a stack of annual AGLBM raster layers for each year from 2001 to 2021. Using these AGLBM data as a foundation, we developed decision rules to estimate belowground, standing dead, and litter biomass pools. These rules were based on relationships between AGLBM and the biomass of the other vegetative pools derived primarily from peer-reviewed literature and an existing spatial data set. For shrub vegetation types (our primary focus), rules were based on literature estimates by the postfire regeneration strategy of each species (obligate seeder, facultative seeder, obligate resprouter). Similarly, for nonshrub vegetation types (grasslands, woodlands) we used literature and existing spatial data sets specific to each vegetation type to define rules to estimate the other pools from AGLBM. Using a Python language script that accessed Environmental Systems Research Institute raster geographic information system utilities, we applied decision rules to create raster layers for each of the non-AGLBM pools for the years 2001-2021. The resulting spatial data archive contains a zipped file for each year; each of these files contains four 32-bit tiff files for each of the four biomass pools (AGLBM, standing dead, litter, and belowground). The biomass units are grams per square meter (g/m2 ). We estimated the uncertainty of our biomass data by conducting a Monte Carlo analysis of the inputs used to generate the data. Our Monte Carlo technique used randomly generated values for each of the literature-based and spatial inputs based on their expected distribution. We conducted 200 Monte Carlo iterations, which produced percentage uncertainty values for each of the biomass pools. Results showed, using 2010 as an example, mean biomass for the study area and percentage uncertainty for each of the pools as follows: AGLBM (905.4 g/m2 , 14.4%); standing dead (644.9 g/m2 , 1.3%); litter (731.2 g/m2 , 1.2%); and belowground (776.2 g/m2 , 17.2%). Because our methods are consistently applied across each year, the data produced can be used to inform changes in biomass pools due to disturbance and subsequent recovery. As such, these data provide an important contribution to supporting the management of shrub-dominated ecosystems for monitoring trends in carbon storage and assessing the impacts of wildfire and management activities, such as fuel management and restoration. There are no copyright restrictions on the data set; please cite this paper and the data package when using these data.


Statistical analysis on morphology development of some semialicyclic polyimides using atomic force microscopy.
The morphological features and surface texture parameters of some polyimide films prepared from a flexible and alicyclic dianhydride, in combination with five aromatic diamines, were evaluated by atomic force microscopy (AFM) in order to determine their applicability in electronics. By means of the surface roughness, shape of the surface height distribution, and angular and radial texture, a precise description of the actual surface topographies at the interface with other materials was made. The polyimide structures led to the development of different surface morphologies (from granular to porous and from bumpy to spiky). The relief diversity was described by the entropy of morphology, which had a similar trend with the root mean square roughness, which presents low values, i.e. 0.5-1.8 nm. Three-dimensional AFM images and the corresponding angular spectra, together with texture aspect ratio and texture direction index (close to 1), indicate that no predominant orientation exists on the investigated surfaces. The redundancy in the morphology was associated with the concept of fractals, the maximum redundancy being achieved for the polyimide with the most complex polymer chain conformation. These results provide useful insights in selecting the polyimide structure, which has the optimal morphology, roughness, orientation, bearing properties, or self-similarity for microelectronic applications such as: substrate for display backplanes, planar technology, microelectronic packaging, etc.


Unilateral breast cancer: screening of contralateral breast by using preoperative MR imaging reduces incidence of metachronous cancer.
To investigate the clinical effect of a single magnetic resonance (MR) imaging screening examination of the contralateral breast at preoperative evaluation in women with unilateral breast cancer. The institutional review board approved this study and waived informed consent. Among women with unilateral breast cancer who underwent curative surgery from 2004 to 2008, 1323 women (mean age, 46.8 years; range, 18-81 years) underwent mammography and ultrasonography (US) alone (comparison group) between January 2004 and December 2006; 1771 consecutive women (mean age, 48.2 years; range, 22-85 years) underwent mammography, US, and MR imaging (contralateral MR imaging-screened group) between January 2007 and December 2008. The incidence of synchronous cancer and the incidence of metachronous cancer in the contralateral breast were compared between groups. Multivariate Cox analysis was performed. Median follow-up was 56 months (range, 13-94 months). Twenty-five synchronous contralateral cancers (13 invasive cancers, 12 ductal carcinomas in situ; mean invasive size, 14 mm [range, 1-35 mm]; 92% [12 of 13] of invasive tumors were node negative) were additionally detected with MR imaging in the MR imaging-screened group. The cumulative incidence of contralateral breast cancer at 45 months was 0.5% (nine of 1771) (95% confidence interval [CI]: 0.23%, 0.96%) for the MR imaging-screened group and 1.4% (18 of 1323) (95% CI: 0.81%, 2.14%) for the comparison group (P = .02). Contralateral MR imaging screening (hazard ratio, 0.37; 95% CI: 0.15, 0.92; P = .03) and estrogen receptor negativity (hazard ratio, 3.98; 95% CI: 1.60, 9.92; P = .003) were associated with risk of contralateral cancer diagnosis in multivariate analysis. A single MR imaging screening examination of the contralateral breast in women with unilateral breast cancer increased synchronous cancer detection and was associated with decreased diagnosis of metachronous contralateral cancer within 45 months.


Reproductive tract infections in a family planning population in rural Bangladesh.
In contrast to social, religious, and economic determinants of acceptance and sustained use of family planning in developing countries, perceived side effects resulting from reproductive tract infections can usually be ameliorated easily and expeditiously. This population-based study examines the magnitude and nature of morbidity due to reproductive tract infections among users of various contraceptive methods and among nonusers in a rural community in Bangladesh. Overall, 22 percent of the 2,929 women surveyed reported symptoms of reproductive tract infection. Of the 472 symptomatic women examined, 68 percent had clinical or laboratory evidence of infection. Users of intrauterine devices and tubectomy were each approximately four times as likely to report symptoms and seven times as likely to have examination-confirmed infection as nonusers. The epidemiology of reproductive tract infections in this population is addressed, and the findings are discussed in terms of their potential programmatic impact.


Expression Profiling of lncRNAs, miRNAs, and mRNAs and Their Differential Expression in Leiomyoma Using Next-Generation RNA Sequencing.
The objective of this study was to identify the expression profile of long noncoding RNAs (lncRNAs) with concurrent assessment of microRNA (miRNA) and messenger RNA (mRNA) profiles in leiomyomas and paired myometrium using next-generation RNA sequencing and assembly of RNA transcripts. Total RNA was isolated from leiomyoma and paired myometrium (N = 8) and samples from 3 pairs were subjected to RNA sequencing. Normalized assembly of over 48 000 lncRNAs resulted in identification of 45 936 lncRNAs. Of these lncRNAs, 22 148 representing overlapping, intergenic, intronic, and antisense subtypes were expressed in all paired tissues, with 5941 (2813 up- and 3128 downregulated at ≥1.5 fold) differentially expressed in leiomyomas. Concurrent RNA sequencing revealed the expression of 2588 miRNAs and 21 814 mRNAs, of which 392 miRNAs and 16 559 mRNAs were expressed in all paired tissues. Of these transcripts, 56 and 92 miRNAs and 2030 and 1825 mRNAs were up- or downregulated at ≥1.5 fold, respectively, in leiomyoma as compared to myometrium. Using quantitative reverse transcription-polymerase chain reaction (QRT-PCR), we confirmed the expression of hepatocellular carcinoma upregulated (HULC), lnc-maternally expressed 3 (MEG3), long intergenic ncRNA 890 (LINC00890), TSIX, long intergenic ncRNA 473 (LINC00473), lnc-KLF9-1, and lnc-POTEM-3 (lncRNA-ATB) in leiomyoma and matched myometrium (N = 8). Collectively, the results presented here provide a comprehensive expression profile of lncRNAs in leiomyomas with concurrent integrated expression of miRNAs and mRNAs and implicate potential regulatory functions of lncRNAs through interactions with specific miRNAs and mRNAs which are known to be critical in the pathogenesis of leiomyoma.


"Health inequalities in Armenia--analysis of survey results".
Prevailing sociopolitical and economic obstacles have been implicated in the inadequate utilization and delivery of the Armenian health care system. A random survey of 1,000 local residents, from all administrative regions of Armenia, concerned with health care services cost and satisfaction was conducted. Participation in the survey was voluntary and the information was collected using anonymous telephone interviews. The utilization of health care services was low, particularly in rural areas. This under-utilization of services correlated with low income of the population surveyed. The state funded health care services are inadequate to ensure availability of free-of-charge services even to economically disadvantaged groups. Continued reliance on direct out-of pocket and illicit payments, for medical services, are serious issues which plague healthcare, pharmaceutical and medical technology sectors of Armenia. Restructuring of the health care system to implement a cost-effective approach to the prevention and treatment of diseases, especially disproportionately affect the poor, should be undertaken. Public payments, increasing the amount of subsidies for poor and lower income groups through a compulsory health insurance system should be evaluated and included as appropriate in this health system redesign. Current medical services reimbursement practices undermine the principle of equity in financing and access. Measures designed to improve healthcare access and affordability for poor and disadvantaged households should be enacted.


Enhanced therapeutic effects of liposome-associated 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine.
The ether-lipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3) has anticancer activity, but systemic toxicity has restricted its therapeutic use. In this report "free" ET-18-OCH3 and a stable, well-characterized, liposome-based formulation of ET-18-OCH3 (ELL-12) were compared for in vivo toxicity in normal mice and for therapeutic efficacy in three mouse tumor model systems. The entrapment of ET-18-OCH3 in liposomes decreased the acute toxicity of ET-18-OCH3 after i.v. administration. The maximum tolerated dose for a single i.v. dose of free ET-18-OCH3 was found to be approximately 25 mg/kg, whereas the maximum tolerated dose for ELL-12 was approximately 200 mg/kg. ELL-12 was much less hemolytic in vivo than ET-18-OCH3. The therapeutic efficacy of free ET-18-OCH3 and ELL-12 was investigated against i.p. P388 leukemia, Lewis lung cancer lung metastases, and B16/F10 melanoma (lung tumor nodules) in mice. Although ET-18-OCH3 had some anticancer activity, it was found that ELL-12 was more effective than ET-18-OCH3 in all three tumor models at lower and nontoxic dose schedules. These results suggest that association of ET-18-OCH3 in stable, well-characterized liposomes transforms it into an effective antitumor agent.


Creation of the bone bank of the Rabat and Casablanca region in Morocco.
For a long time the use of bone grafting has demonstrated its interest in orthopedic surgery and traumatology. The autografts which are still very frequently used present various problems. On the one hand, it is necessary to find a correct mechanical quality and a sufficient quantity of bone. On the other hand, the graft removal lengthens the operative time and generally painful in postoperative. These disadvantages of autografts have led to the development of bone allografts. Indeed, the low immunogenic power of the bone, the good integration of the graft and the ease of bone preservation techniques make it possible to overcome the various problems posed by bone autografts. The increasing use of bone allografts has resulted in the need for a structure allowing the management of graft stocks. The purpose of this work is to demonstrate the mode of operation of a bone bank, whose conservation activity is limited to the femoral heads treated by cryopreservation and without secondary sterilization process. The bank collaborates with all orthopedic surgeons in the Rabat and Casablanca city at first and then with all orthopedic surgeons in Morocco. It provides allografts in quality and safety.


Wzy-dependent bacterial capsules as potential drug targets.
The bacterial capsule is a recognized virulence factor in pathogenic bacteria. It likely works as an antiphagocytic barrier by minimizing complement deposition on the bacterial surface. With the continual rise of bacterial pathogens resistant to multiple antibiotics, there is an increasing need for novel drugs. In the Wzy-dependent pathway, the biosynthesis of capsular polysaccharide (CPS) is regulated by a phosphoregulatory system, whose main components consist of bacterial-tyrosine kinases (BY-kinases) and their cognate phosphatases. The ability to regulate capsule biosynthesis has been shown to be vital for pathogenicity, because different stages of infection require a shift in capsule thickness, making the phosphoregulatory proteins suitable as drug targets. Here, we review the role of regulatory proteins focusing on Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli and discuss their suitability as targets in structure-based drug design.


A Novel Method for Electrophysiological Analysis of EMG Signals Using MesaClip.
In electrophysiology, many methods have been proposed for the analysis of action potential firing frequencies. The aim of this study was to present an algorithm developed for a continuous wavelet transform that enables the filtering out of frequencies contributing to the shapes of action potentials (spikes), whilst retaining the frequencies that encode the periodicity of spike trains. The continuous wavelet transform allows us to decompose a signal into its constituent frequencies. A signal with a single event, such as a spike, is composed of frequencies that characterize the shape of the spike. A signal with two spikes will also be composed of frequencies characterizing the shape of the action potential, but in addition will include a substantial portion of its power at the frequency corresponding to the time-difference between the two spikes. This is achieved by clipping peaks from the wavelet amplitudes that are narrower than a given minimum number of phase cycles. We present some application examples in both synthetic signals and electrophysiological recordings. This new approach can provide a major new analytical tool for analysis of electrophysiological signals.


Effects of message-framed informational videos on diabetes management knowledge and self-efficacy.
Nurses play an essential role in improving health-related knowledge and self-efficacy of patients through health education. This study aimed to investigate the effects of message-framed informational videos on diabetes management knowledge and self-efficacy in patients with type 2 diabetes. A quasi-experimental pretest and posttest design with two experimental and one standard care comparison groups was carried out to examine the effects of the message-framed videos. The two message-framed informational videos were developed to provide health teachings about diabetes self-care. The knowledge and self-efficacy of the two video groups and lecture comparison group were measured before and after the intervention using valid and reliable instruments established by the authors. After the intervention, the knowledge and self-efficacy of the two experimental groups were significantly higher than the comparison group. No significant difference was found in the knowledge scores between the two experimental groups, but a significant difference was noted in the average increase in their self-efficacy. Message-framed informational videos can be effective in increasing the diabetes management knowledge and self-efficacy, and a gain-framed rather than loss-framed approach can be superior in increasing self-efficacy.


A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.
Although prostate cancer typically runs an indolent course, a subset of men develop aggressive, fatal forms of this disease. We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer. The goal of this work is to identify susceptibility genes using the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of neuroendocrine prostate cancer. Quantitative trait locus (QTL) mapping was performed in transgene-positive (TRAMPxNOD/ShiLtJ) F2 intercross males (n = 228), which facilitated identification of 11 loci associated with aggressive disease development. Microarray data derived from 126 (TRAMPxNOD/ShiLtJ) F2 primary tumors were used to prioritize candidate genes within QTLs, with candidate genes deemed as being high priority when possessing both high levels of expression-trait correlation and a proximal expression QTL. This process enabled the identification of 35 aggressive prostate tumorigenesis candidate genes. The role of these genes in aggressive forms of human prostate cancer was investigated using two concurrent approaches. First, logistic regression analysis in two human prostate gene expression datasets revealed that expression levels of five genes (CXCL14, ITGAX, LPCAT2, RNASEH2A, and ZNF322) were positively correlated with aggressive prostate cancer and two genes (CCL19 and HIST1H1A) were protective for aggressive prostate cancer. Higher than average levels of expression of the five genes that were positively correlated with aggressive disease were consistently associated with patient outcome in both human prostate cancer tumor gene expression datasets. Second, three of these five genes (CXCL14, ITGAX, and LPCAT2) harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. This study is the first example of using a systems genetics approach to successfully identify novel susceptibility genes for aggressive prostate cancer. Such approaches will facilitate the identification of novel germline factors driving aggressive disease susceptibility and allow for new insights into these deadly forms of prostate cancer.


Long-term (35 years) cryopreservation of Echinococcus multilocularis metacestodes.
The metacestode of Echinococcus multilocularis is the etiological agent of alveolar echinococcosis. The metacestode stage used for research is maintained in rodents by serial passages. In order to determine whether cryopreservation of E. multilocularis metacestodes would be suitable for long-term maintenance and replace serial passages, isolates of different geographic origin were cryopreserved in 1984-1986. The aim of the current study was to test the viability of cryopreserved isolates following long-term cryopreservation (up to 35 years) and to determine the phylogenetic clades these isolates belonged to. Cryopreserved isolates were tested for viability in vitro and in vivo in gerbils. In vitro results of 5 isolates indicated protoscolex survival in 13 of 17 experiments (76%) and metacestode survival in 5 of 12 (42%) in vivo experiments. In vivo results showed 'abortive lesions' in 13 of the 36 animals, 15 were negative and 8 harboured proliferating metacestode tissue containing protoscoleces. Genetic analysis confirmed the isolates belonged to European, Asian and North-American clades. In conclusion, the results of the current study indicate that metacestodes of E. multilocularis are able to survive long-term cryopreservation. Therefore, cryopreservation is a suitable method for long-term storage of E. multilocularis metacestode isolates and reduces the number of experimental animals.


Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia.
In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p=<0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.


Trace Element Uptake by Herbaceous Plants from the Soils at a Multiple Trace Element-Contaminated Site.
The uptake of trace elements by wild herbaceous plants in a multiple trace element-contaminated site was investigated. The bioaccumulation factor (BF) of trace elements was markedly variable among the different plant species. On average, the BF for various trace elements was in the following decreasing order: Zn > Cu > Mn > Ni > As > Pb > Cr. The translocation factor among the investigated plant species was also considerably variable and showed the following decreasing order: Mn > Zn > Ni > Cu > Cr > As > Pb. Several hyperaccumulating plants were identified: Artemisia vulgaris for As, Mn and Zn, Phalaris arundinacea for Mn and Ni, Heracleum sphondylium for Cr and Zn, and Bistorta officinalis for Mn and Zn. The marked accumulation of trace elements in the plant tissue suggests that the site may not be suitable for urban agricultural production. The plant tissue-borne trace elements could affect microbial activities and consequently interfere with the ecosystem functioning in the affected areas.


Gene-Environment Interactions-What Can These Tell Us about the Relationship between Asthma and Allergy?
Asthma is a common condition, which is associated with atopy and allergic conditions including hay fever, eczema, and food allergies. Asthma and atopy are both complex conditions where genetic and environmental factors are implicated in causation. Interactions between genetic and environmental factors, likely via epigenetic mechanisms, are widely thought to be important in determining the risk for developing asthma and atopy. The nature of the relationship between asthma and atopy is unclear and the answer to the question "does atopy cause asthma?" remains unknown. This review explores the relationship between asthma and atopy from a gene-environment interaction perspective and tackles the question "are similar gene-environment interactions present for asthma and atopy?" The main finding is that gene-environment interactions are described for asthma and atopy in children but these interactions are seldom sought for both asthma and atopy in the same population. In the few instances where a gene-environment interaction is related to both asthma and atopy, there is no consistent evidence that similar interactions are common to asthma and atopy. Many plausible gene-environment interactions for asthma and atopy are yet to be explored. Overall, from the gene-environment interaction perspective, there is absence of evidence to better understand the complex relationship between asthma and atopy.


Hypertension control and risk of colonic diverticulosis.
The prevalence of diverticulosis has increased in our aging population, but the risk factors for diverticulosis are not fully understood. The role of hypertension in the risk of diverticulosis remains uncertain. This study investigated whether hypertension is associated with asymptomatic colorectal diverticulosis. This study enrolled asymptomatic patients who received a colonoscopy as part of a health check. Hypertension was defined by actual measured blood pressure. Logistic regression models were used to examine the relationship between hypertension and diverticulosis. In addition, we established three logistic regression models for covariate adjustment, and further stratified patients with hypertension into three subgroups based on their type of hypertension. The study group consisted of 2748 participants, including 141 participants with diverticulosis and 2607 participants without diverticulosis. After adjustments for potential covariates, the odds ratio (OR) for having diverticulosis was 1.83 (95% confidence interval, 1.21-2.75, p = 0.004) in the hypertension group compared with the group without hypertension. In subgroup analyses, hypertension without antihypertensive medication use, and hypertension despite the use of antihypertensive medication were also significantly associated with the occurrence of asymptomatic diverticulosis (OR = 1.73, p = 0.028; OR = 2.07, p = 0.013, respectively). Current normal blood pressure under antihypertensive drug therapy was not associated with diverticulosis (OR = 1.74, p = 0.092). Our findings suggest a positive association between hypertension and diverticulosis. Participants with poorly controlled blood pressure were found to have a higher risk of asymptomatic diverticulosis. Our study presents epidemiologic evidence for future prevention strategies against diverticulosis.


Outcomes of Patients Undergoing PCI of Ostial Coronary Lesions: A Single-Center Study.
Ostial coronary lesions are a subset of proximal coronary lesions, which are relatively more difficult to treat and were associated with worse clinical outcomes in the early percutaneous coronary intervention (PCI) era. Data regarding the outcomes of ostial lesions' PCI in the contemporary era are lacking. We conducted a single-center, all-comer, prospective registry study, enrolling patients undergoing PCI with the use of contemporary drug-eluting stents (DES) between July 2016 and February 2018. Included in the present analysis were only patients treated for proximal lesions. Clinical outcomes were compared between patients undergoing PCI of ostial versus proximal nonostial lesions. The primary endpoint was target vessel revascularization (TVR). Secondary endpoints included target lesion revascularization (TLR) and major cardiovascular adverse events (MACE) at 12 months. A total of 334 (84.7% male, 67.3 ± 10.7 years) patients were included, of which 91 patients were treated for ostial lesions and 243 were treated for proximal nonostial lesions. Baseline and procedural characteristics were similar between the two groups. At 12 months, TVR and TLR were numerically higher among patients undergoing PCI of ostial versus nonostial lesions without reaching statistical significance (5.5% vs. 3.3%; p = 0.35 and 4.4% vs. 2.5%; p = 0.47, respectively). The rate of MACE was similar between the two groups. In patients undergoing PCI with the use of contemporary DES, clinical outcomes were similar among patients treated for ostial compared to proximal nonostial lesions. Larger studies are required to further evaluate the performance of contemporary DES in this subset of lesions.


Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy.
The M-type phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients. In retrospective studies, the PLA2R-autoantibody titer in the serum was sometimes negative indicating their measurement alone may be inconclusive. In order to better differentiate between primary and secondary membranous nephropathy, we conducted a prospective study that included 88 patients with a histologic diagnosis of membranous nephropathy. Immunohistochemical analysis for PLA2R was faintly positive in kidneys from normal individuals and patients with various other glomerular injuries. In 61 of the 88 patients, PLA2R expression was strongly positive in glomeruli, and in 60 of these patients PLA2R autoantibodies were also detected in the serum. The 27 patients negative for serum PLA2R autoantibodies were faintly positive for PLA2R staining in glomeruli and in 15 of these patients a secondary cause was found. The remaining 12 patients have a yet undetected secondary cause of membranous nephropathy or have different glomerular antigens other than PLA2R. Thus, increased staining for PLA2R in glomeruli of renal biopsies tightly correlates with the presence of PLA2R autoantibodies in the serum and this may help discriminate between primary and secondary membranous nephropathy.