Stimulating effect of pentagastrin on cancer cell proliferation kinetics in chemically induced colon cancer in rats.
Pharmacological doses of pentagastrin or gastrin are known to stimulate cell proliferation in normal colonic epithelium but the growth-promoting effect of gastrin on colon carcinoma is still controversial. In this study morphological parameters were measured to study the effect of pentagastrin (240 micrograms/kg) on the cell proliferation kinetics in experimental tumours. Colon cancer was produced in rats by weekly injections (20 mg/kg b.wt.) of 1.2-dimethylhydrazine for 24 weeks. Tritiated thymidine was given after administration of pentagastrin or the control solution to the animals. 75% of the animals from the pentagastrin group and 66% of the controls had at least one colon cancer. Autoradiographs of the colonic tumors were performed and the percentage of labeled cells in the cancer cell population was determined after counting 4000 to 16,000 cancer cells per tumor. The labeling index for cancer cells in the pentagastrin-treated group (21.49 +/- 1.76%) was higher (P less than 0.01) than in the control group (14.76 +/- 0.66%). In a second study vincristine sulphate (1 mg/kg) was given to the animals 20 h after administering pentagastrin or the control solution. The percentage of arrested metaphases in the tumours was determined after counting 10,000 to 24,000 cancer cells per histological section. Pentagastrin increased (P less than 0.01) the mean metaphase index by 108% (4.9 +/- 0.44% vs 2.35 +/- 0.32%). These data indicate that cell cycle manipulation of colon cancer is possible with hormonal peptides.


Two-dimensional J-resolved LASER and semi-LASER spectroscopy of human brain.
Two-dimensional J-resolved localized and semi-localized by adiabatic selective refocusing (LASER and semi-LASER) spectroscopy, named "J-resolved LASER" and "J-resolved semi-LASER", were introduced to suppress chemical shift artifacts, additional J-refocused artifactual peaks from spatially dependent J-coupling evolution, and sensitivity to radiofrequency (RF) field inhomogeneity. Three pairs of adiabatic pulses were employed for voxel localization in J-resolved LASER and two pairs in J-resolved semi-LASER. The first half of t1 period was inserted between the last pair of adiabatic pulses, which was proposed in this work to obtain two-dimensional adiabatic J-resolved spectra of human brain for the first time. Phantom and human experiments were performed to demonstrate their feasibility and advantages over conventional J-resolved spectroscopy (JPRESS). Compared to JPRESS, J-resolved LASER or J-resolved semi-LASER exhibited significant suppression of chemical shift artifacts and additional J-refocused peaks from spatially dependent J-coupling evolution, and demonstrated insensitivity to the change of RF frequency offset over large bandwidth. Experiments on phantoms and human brains verified the feasibility and strengths of two-dimensional adiabatic J-resolved spectroscopy at 3T. This technique is expected to advance the application of in vivo two-dimensional MR spectroscopy at 3T and higher field strengths for more reliable and accurate quantification of metabolites.


Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1.
Rac1 is a major regulator of actin dynamics, with GTP-bound Rac1 promoting actin assembly via the Scar/WAVE complex. CYRI competes with Scar/WAVE for interaction with Rac1 in a feedback loop regulating actin dynamics. Here, we reveal the nature of the CYRI-Rac1 interaction, through crystal structures of CYRI-B lacking the N-terminal helix (CYRI-BΔN) and the CYRI-BΔN:Rac1Q61L complex, providing the molecular basis for CYRI-B regulation of the Scar/WAVE complex. We reveal CYRI-B as having two subdomains - an N-terminal Rac1 binding subdomain with a unique Rac1-effector interface and a C-terminal Ratchet subdomain that undergoes conformational changes induced by Rac1 binding. Finally, we show that the CYRI protein family, CYRI-A and CYRI-B can produce an autoinhibited hetero- or homodimers, adding an additional layer of regulation to Rac1 signaling.


Population-based affective-disorder-related biomedical/biophysical multi-hyper-morbidity across the lifespan: A 16-year population study.
There are few if any life-span population-based studies of psychiatric disorder-associated biomedical and biophysical disorders and diseases (morbidity). To scope the present state of research regarding the biomedical and biophysical morbidity associated with affective and mental disorder in epidemiological samples, and to examine the life-span relationship between affective disorders and biomedical/biophysical disorders to illustrate a novel approach employing the odds ratio to represent the intensity of biomedical and biophysical morbidity associated in time in a population. A repeatable systematic literature search of PubMed was represented in summary. Additionally, a regional population-based dataset was constructed and analyzed to represent the age- and sex-specific diagnoses (International Classification of Diseases Version 9, ICD-9) for those with and without affective disorder. The analysis presents a novel index of the relative age-specific frequency of life-span biomedical and biophysical diagnoses associated with affective disorder. The volume of biomedical and biophysical morbidity associated with mental disorder literature has increased, yet few studies measure comprehensive temporal hyper-morbidity (over-representation of diseases over time, either before or after the index diagnostic event) in populations. Further, there have been only a few population-based studies examining the morbidity associated with affective disorder and only one that examines the full diagnostic range of lifespan morbidity. Substantial differences arose between males and females with more females than males having greater frequencies of diagnoses. The age-specific distributions of the maximum proportional diagnosis frequency ratios for each sex illustrate the greatest diagnosis-specific differences when comparing the biomedical and biophysical diagnoses of those with and without affective disorder when the same diagnosis was represented in each grouping at the same age. Clinical research needs to focus on more than one or two comorbid biomedical or biophysical disorders at a time. Comprehensive population-based examination of the lifespan biomedical and biophysical multi-morbidity associated with affective disorder has the potential to directly inform clinical practice. Representing the proportional ratios of age-specific frequency of diagnoses for the full range of ICD-9 diagnoses is a novel analytical model. Diagnostic frequency appears a viable representation of a given disease state, such as affective disorder. Fortunately, the WPA has developed a global education section to better understand the biomedical and biophysical morbidity associated with all psychiatric disorders. This has been identified by the WPA as the psychiatric practice challenge of the 21st century.


A randomised phase II trial of S-1 plus cisplatin versus vinorelbine plus cisplatin with concurrent thoracic radiotherapy for unresectable, locally advanced non-small cell lung cancer: WJOG5008L.
Cisplatin-based chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy. Eligible patients with unresectable stage III NSCLC were randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival rate at 2 years (2-year overall survival (OS)) (Study ID: UMIN000002420). From September 2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients, the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and 68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58-1.44). There were four treatment-related deaths in the SP arm and five in the VP arm. The null hypotheses for 2-year OS were rejected in both arms. The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study.


Epigenetic regulation of germ cells-remember or forget?
Unlike somatic cells, germ cells retain the potential to reproduce an entire new organism upon fertilization. In order to accomplish the process of fertilization, germ cells undergo an extreme cellular differentiation process known as gametogenesis in order to produce morphologically and functionally distinct oocyte and sperm. In addition to changes in genetic content changes from diploid to haploid, epigenetic mechanisms that modify chromatin state without altering primary DNA sequences have profound influence on germ cell differentiation and moreover, the transgenerational effect. In this review, we will go over the most recent discoveries on epigenetic regulations in germline differentiation and transgenerational inheritance across different metazoan species.


Visualization of preretinal membranes using trypan blue in patients with traction retinal detachments.
Surgical repair of complex tractional retinal detachments (TRDs) can be challenging due to the difficulty in delineating the fibroglial membranes from the underlying retinal surface. We describe the visual and retinal reattachment rate with the intraoperative use of trypan blue (TB) to visualize proliferative fibrous membranes in patients with TRDs. Retrospective study. Seventeen patients who underwent a pars plana vitrectomy for surgical TRD repair with TB use between January 1, 2005, and December 31, 2020. Patient charts were retrospectively evaluated for surgical details, preoperative and postoperative logMAR best-corrected visual acuity (BCVA) and status of retinal attachment om days 30 and 90 and at the most recent follow-up visit. In the cohort of 17 patients, TRDs were found to be secondary to proliferative diabetic retinopathy, complications from endophthalmitis, open globe injury, and neovascularization secondary to a retinal vein occlusion. Mean ± SD preoperative BCVA was 1.7 ± 1.7 logMAR (Snellen, 20/1000), whereas postoperative BCVA at the most recent follow-up visit was 1.4 ± 1.2 logMAR (Snellen, 20/500). The use of TB was successful in delineating the proliferative preretinal membranes in 100% of patients, with no residual staining of posterior segment tissues or adverse reactions related to the dye noted at postoperative visits. Eighty-eight percent (15 of 17) and 76% of retinas (13 of 17) were attached at postoperative month 3 and 6 visits, respectively. TB can be a useful adjunct tool to visualize and allow for a thorough removal of tractional fibrous proliferative epiretinal membranes in patients with complex TRDs, possibly yielding better surgical and long-term reattachment outcomes.


Multiscale relationships between fibronectin structure and functional properties.
Cell behavior is tightly coupled to the properties of the extracellular matrix (ECM) to which they attach. Fibronectin (Fn) forms a supermolecular, fibrillar component of the ECM that is prominent during development, wound healing and the progression of numerous diseases. This indicates that Fn has an important function in controlling cell behavior during dynamic events in vivo. The multiscale architecture of Fn molecules assembled into these fibers determines the ligand density of cell adhesion sites on the surface of the Fn fiber, Fn fiber porosity for cell signaling molecules such as growth factors, the mechanical stiffness of the Fn matrix and the adhesivity of Fn for its numerous soluble ligands. These parameters are altered by mechanical strain applied to the ECM. Recent efforts have attempted to link the molecular properties of Fn with bulk properties of Fn matrix fibers. Studies of isolated Fn fibers have helped to characterize the fiber's material properties and, in combination with models of Fn molecular behavior in the fibers, have begun to provide insights into the Fn molecular arrangement and intermolecular adhesions within the fibers. A review of these studies allows the development of an understanding of the mechanobiological functions of Fn.


New species and records of Sericini of India (Coleoptera: Scarabaeidae: Melolonthinae) II.
Here we present a new record of Microserica nicobarensis (Redtenbacher, 1868) and describe further two new species from India: Nepaloserica cheemaensis Bhunia, Gupta, Chandra Ahrens new species, and Maladera reyaensis Bhunia, Gupta, Chandra Ahrens, new species. Species morphology is described and illustrated, and their distribution is shown on a map.


RTS,S/AS01E malaria vaccine induces IgA responses against CSP and vaccine-unrelated antigens in African children in the phase 3 trial.
The evaluation of immune responses to RTS,S/AS01 has traditionally focused on immunoglobulin (Ig) G antibodies that are only moderately associated with protection. The role of other antibody isotypes that could also contribute to vaccine efficacy remains unclear. Here we investigated whether RTS,S/AS01E elicits antigen-specific serum IgA antibodies to the vaccine and other malaria antigens, and we explored their association with protection. Ninety-five children (age 5-17 months old at first vaccination) from the RTS,S/AS01E phase 3 clinical trial who received 3 doses of RTS,S/AS01E or a comparator vaccine were selected for IgA quantification 1 month post primary immunization. Two sites with different malaria transmission intensities (MTI) and clinical malaria cases and controls, were included. Measurements of IgA against different constructs of the circumsporozoite protein (CSP) vaccine antigen and 16 vaccine-unrelated Plasmodium falciparum antigens were performed using a quantitative suspension array assay. RTS,S vaccination induced a 1.2 to 2-fold increase in levels of serum/plasma IgA antibodies to all CSP constructs, which was not observed upon immunization with a comparator vaccine. The IgA response against 13 out of 16 vaccine-unrelated P. falciparum antigens also increased after vaccination, and levels were higher in recipients of RTS,S than in comparators. IgA levels to malaria antigens before vaccination were more elevated in the high MTI than the low MTI site. No statistically significant association of IgA with protection was found in exploratory analyses. RTS,S/AS01E induces IgA responses in peripheral blood against CSP vaccine antigens and other P. falciparum vaccine-unrelated antigens, similar to what we previously showed for IgG responses. Collectively, data warrant further investigation of the potential contribution of vaccine-induced IgA responses to efficacy and any possible interplay, either synergistic or antagonistic, with protective IgG, as identifying mediators of protection by RTS,S/AS01E immunization is necessary for the design of improved second-generation vaccines. ClinicalTrials.gov: NCT008666191.


Generalization of Respiratory Symptom Triggers.
Behavioral management of asthma and other chronic conditions depends upon the accurate identification of environmental factors that trigger symptom onset. In this study, we developed a lab-based conditioning method to study category-based acquisition and generalization of respiratory symptom triggers. During trigger acquisition, unique exemplars of two different categories were shown to a sample of healthy participants (n=48). CS+ exemplars were paired with CO2 inhalation on 50% of trials, while CS- exemplars were always paired with room air. Trigger categories differed in their conceptual similarity. In a generalization task, participants rated symptom expectancy for a set of triggers that included previously seen exemplars, novel exemplars, and exemplars from novel categories. Results show that participants acquired differential symptom expectancies based on category information, which generalized to novel CS+ exemplars and novel categories that shared similarity with the CS+ category. Greater similarity between CS+ and CS- categories increased differential effects for both old and novel exemplars of CS+ and CS- categories, and increased the proportion of novel CS+ exemplars that were remembered as being seen during acquisition. These findings suggest that a more narrowly defined contrast between triggers and nontriggers promotes category-based inference and could help to reduce uncertainty about potential triggers.


Cocaine inhibits extraneuronal O-methylation of exogenous norepinephrine in nasal and oral tissues of the rabbit.
Nasal mucosa (respiratory and olfactory) and lingual gingiva of the rabbit were depleted of their sympathetic nerves by superior cervical ganglionectomy. In the innervated nasal mucosa, exogenous tritiated norepinephrine (3H-NE) was metabolised mainly to tritiated 3,4-dihydroxyphenylethylene glycol (3HDOPEG) and 3,4-dihydroxy mandelic acid (3HDOMA), whereas after denervation it was metabolised mainly to tritiated normetanephrine (3HNMN). In the denervated mucosa, cocaine (30 umol/1) inhibited 3HNMN formation by 50-60%. Cocaine also inhibited 3HNMN formation by 60% in the denervated lingual gingiva. It is concluded that the tissues metabolise 3H-NE via a cocaine-sensitive extraneuronal uptake and O-methylating system similar to that which has been shown to be present in dental pulp.


Clinically important change on the Unified Dyskinesia Rating Scale among patients with Parkinson's disease experiencing dyskinesia.
The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)-the smallest change in a treatment outcome that a patient considers important-remains undefined for the UDysRS. To utilize pivotal amantadine delayed-release/extended-release (DR/ER) trial data to derive MCICs for the UDysRS total score in patients with PD experiencing dyskinesia. Pivotal trials included PD patients with ≥1 h daily ON time with troublesome dyskinesia and baseline scores ≥2 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, item 4.2. Patients randomized to amantadine DR/ER or placebo completed two consecutive 24-h diaries before each clinic visit and were evaluated during ON time with dyskinesia using the UDysRS, MDS-UPDRS, and Clinician Global Impression of Change (CGI-C). The UDysRS changes from baseline to week 12 were anchored to corresponding changes in MDS-UPDRS item 4.2 scores. A minimal clinically important improvement in the CGI-C and diary-reported ON time with troublesome dyskinesia (≥0.5 h) were supportive anchors. Receiver operating characteristic curves determined the UDysRS change values optimizing sensitivity and specificity to at least minimal improvement on each anchor. The analyses included 196 patients. Week 12 UDysRS total score reduction of ≥8 points corresponded to at least minimal MDS-UPDRS item 4.2 improvement. UDysRS reduction of ≥9 points corresponded to decreased ON time with troublesome dyskinesia of ≥0.5 h per patient diaries, and UDysRS reduction of ≥10 points corresponded to at least minimal improvement on the CGI-C. Anchored to the MDS-UPDRS Part IV, item 4.2, an 8-point reduction in the UDysRS total score can be considered an MCIC for PD patients with dyskinesia.


Seeds and the city: a review of municipal home food gardening programs in Canada in response to the COVID-19 pandemic.
In the wake of the COVID-19 pandemic in Canada, home food gardening articles have saturated popular media outlets. Home food gardening is more popular than ever, and community gardens and community greenhouses are at capacity with long waiting lists for plots. Several local governments across the country are also participating in the food gardening craze. This study compares 19 municipal urban home food gardening programs that ran in 2020. These municipalities provided program participants with free gardening supplies and instructions on how to grow food at home. This study reveals a complicated relationship among municipalities, food gardening programs and household and community food security. The study also determines that the social and emotional challenges brought about by the COVID-19 pandemic are somewhat alleviated through gardening. Ultimately, municipalities are limited in their policy capacities to adequately move the needle on food insecurity in Canada.


Successful pregnancy after pharmacologic suppression of a circulating anticoagulant in a woman with previous pregnancy losses and pulmonary emboli. A case report.
A woman had two second-trimester fetal deaths two weeks after genetic amniocenteses, and her puerperal courses were also complicated by pulmonary emboli. During her next pregnancy a circulating anticoagulant was demonstrated that had been absent between her pregnancies. It was suppressed with aspirin and prednisone. Amniocentesis was uneventful. Despite the development of steroid-induced diabetes, the pregnancy outcome was successful, with no postpartum complications.


Nutrient loads in the river mouth of the Río Verde basin in Jalisco, Mexico: how to prevent eutrophication in the future reservoir?
Since nutrients are emitted and mobilized in river basins, causing eutrophication of water bodies, it is important to reduce such emissions and subsequent nutrient loads. Due to processes of attenuation, nutrient loads are reduced during their mobilization in river basins. At the mouth of the Río Verde basin in western Mexico, the El Purgatorio dam is being constructed to supply water to the metropolitan area of the second most populated city in the country, Guadalajara. To analyze situations that allow protecting this future dam from eutrophication, nutrient loads in the mouth of the river basin were determined and their reduction scenarios evaluated by using the NEWS2 (Nutrient Export from Watersheds) model. For this, a nutrient emissions inventory was established and used to model nutrient loads, and modeling results were compared to an analysis of water quality data from two different monitoring sites located on the river. The results suggest that 96% of nitrogen and 99% of phosphorus emissions are attenuated in the watershed. Nutrient loads reaching the mouth of the river basin come mainly from wastewater discharges, followed by livestock activities and different land uses, and loads are higher as emissions are located closer to the mouth of the river basin. To achieve and maintain mesotrophic state of water in the future dam, different nutrient emission reduction scenarios were evaluated. According to these results, the reduction of 90% of the phosphorus loads in wastewater emissions or 75% of the phosphorus loads in wastewater emissions and at least 50% in emissions from livestock activities in the river basin are required.


High-performance nontarget analysis of halogenated organic compounds in tap water, fly ash, soil and sediment using ultrahigh resolution mass spectrometry and scripting approaches based on Cl/Br-specific search algorithms.
Halogenated organic compounds (HOCs) are a huge group of pollutants, which have caused severe environmental pollution worldwide. This study developed a nontarget analysis method for characterization of known and unknown HOCs in tap water, fly ash, soil and sediment using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) with aid of scripting data-processing approaches. The FT-ICR-MS was equipped with an electrospray ionization source operated in negative ion mode, and full scan at a mass resolution around 200,000 was applied. Data screening scripts were developed based on exact mass differences and abundance ratios between neighboring chlorine/bromine isotopologues. Cosine similarity analysis was applied to evaluating similarity between measured and simulated isotopologue distributions which were constituted by abundance ratios between neighboring isotopologues for identification of polychlorinated and polybrominated compounds. From huge amount of peaks in raw mass spectra, thousands of MS features of HOCs were screened out. In total 824 HOC formulae were finally identified, including 702 organochlorines, 108 organobromines, and 14 mix-chlorine/bromine-containing organic compounds (OClBrs), mainly being monochlorinated/monobrominated compounds (∼90%) whose abundances were also the most prominent. Dozens of HOCs were tentatively structurally elucidated, including halogenated phenols, carboxylic acids, benzenesulfonic acids, etc. Three novel OClBrs were structurally identified, i.e., bromochlorobenzoic acid, bromodichlorophenol and bromotrichlorophenol. The data-processing scripts and strategies can facilitate accurate and high-throughput nontarget analysis of both common and novel/emerging halogenated organic pollutants in complex matrices. The research results provide informative insights into pollution profiles of HOCs in the environment, suggesting that halogenated organic pollutants remain to be seriously concerned.


The role of chromatin proteins in DNA damage recognition and repair.
The structure of chromatin is the major factor determining the rate and efficiency of DNA repair. Chromatin remodeling events such as rearrangement of nucleosomes and higher order chromatin structures are indispensable features of repair processes. During the last decade numerous chromatin proteins have been identified that preferentially bind to different types of DNA damage. The HMGB proteins, which preferentially interact with DNA intrastrand crosslinks induced by cisplatin, are the archetypal example of such proteins. Several hypothetical models have been proposed describing the role of such damage-binding chromatin proteins. The damage shielding model postulates that binding of chromatin proteins to damaged DNA might disturb damage recognition by repair factors and impair its removal. Alternatively, the damage-recognition/signaling model proposes that the binding of specific chromatin proteins to damaged DNA could serve as a hallmark to be recognized by repair proteins. Additionally, the binding of specific chromatin proteins to damaged DNA could induce chromatin remodeling at the damage site and indirectly affect its repair. This paper aims to critically review current experimental data in relation to such possible roles of chromatin proteins.


Transferrin as a muscle trophic factor.
Muscle cells grow by proliferation and protein accumulation. During the initial stages of development the participation of nerves is not always required. Myoblasts and satellite cells proliferate, fusing to form myotubes which further differentiate to muscle fibers. Myotubes and muscle fibers grow by protein accumulation and fusion with other myogenic cells. Muscle fibers finally reach a quasi-steady state which is then maintained for a long period. The mechanism of maintenance is not well understood. However, it is clear that protein metabolism plays a paramount role. The role played by satellite cells in the maintenance of muscle fibers is not known. Growth and maintenance of muscle cells are under the influence of various tissues and substances. Among them are Tf and the motor nerve, the former being the main object of this review and essential for both DNA and protein synthesis. Two sources of Tf have been proposed, i.e., the motor nerve and the tissue fluid. The first proposal is that the nervous trophic influence on muscle cells is mediated by Tf which is released from the nerve terminals. In this model, the sole source of Tf which is donated to muscle cells should be the nerve, and Tf should not be provided for muscle fiber at sites other than the synaptic region; otherwise, denervation atrophy would not occur, since Tf provided from TfR located at another site would cancel the effect of denervation. The second proposal is that Tf is provided from tissue fluid. This implies that an adequate amount of Tf is transferred from serum to tissue fluid; in this case TfR may be distributed over the entire surface of the cells. The trophic effects of the motor neuron have been studied in vivo, but its effects of myoblast proliferation have not been determined. There are few experiments on its effects on myotubes. Most work has been made on muscle fibers, where innervation is absolutely required for their maintenance. Without it, muscle fibers atrophy, although they do not degenerate. In contrast, almost all the work on Tf has been performed in vitro. Its effects on myoblast proliferation and myotube growth and maintenance have been established; myotubes degenerate following Tf removal. But its effects on mature muscle fibers in vivo are not well understood. Muscle fibers possess TfR all over on their cell surface and contain a variety of Fe-binding proteins, such as myoglobin. It is entirely plausible that muscle fibers require an amount of Tf, and that this is provided by TfR scattered on the cell surface.(ABSTRACT TRUNCATED AT 400 WORDS)


A Novel Method of Segmentation and Classification for Meditation in Health Care Systems.
Meditation improves positivity in behavioral as well as psychological changes, which are brought elucidated by knowing neuro-physiological consequences of meditation. In the field of cognitive science, neuroscience and physiological research, Electroencephalogram (EEG) is extensively utilized. The primary tasks of EEG signal analysis is to identify the noisy signal as well as enormous data that create signal processing and subsequent analysis. Beforehand any analysis of the EEG signal, the obtained raw signal must be preprocessed for eliminating undesirable artifacts as well as horrible noise. With the aim of resolving this issue, in this research, raw signals are preprocessed with the help of Band-Pass Filter (BPF) for noise removal method. Instead, in adaptive Sliding Window with Fuzzy C Means Clustering (SW-FCM) segmentation is presented, which precisely as well as automatically segments the signals. So as to analyze the accuracy, five features such as electroencephalography alpha spectrum, frequency of the main peak, Amplitude of the main peak, Higher Order Crossing (HOC), and wavelet features are used as the evaluating variables. Lastly to assess the meditation experience with Fuzzy Kernel least square Support Vector Machine (FKLSSVM) classifier, the presented method with a cross-sectional analysis is utilized. These two classifiers are utilized for meditation experience classification by utilizing an individual feature vector values from equivalent EEG signals. The dataset samples are gathered from Open source Brain-Computer Interface (Open BCI) platform. Outcomes attained are matched up for diverse techniques for identifying as well as for classifying signal segments features using MATLAB. Presented classifiers of the meditation process validate quick interpretation methods that differentiate meditation experience and valuable performance related to artificial approaches for the big-data analysis.


Quasi-quantum model of potentization.
Analytical time-dependent functions describing the change of the concentration of the solvent S(t) and the homeopathic active substance A(t) during decimal and centesimal dilution are derived. The function S(t) is a special case of the West-Brown-Enquist curve describing ontogenic growth, the increase in concentration of the solvent during potentization resembles the growth of biological systems. It is demonstrated that the macroscopic S(t) function is the ground state solution of the microscopic non-local Horodecki-Feinberg equation for the time-dependent Hulthèn potential at the critical screening. In consequence potentization belongs to the class of quasi-quantum phenomena playing an important role both in biological systems and homeopathy. A comparison of the results predicted by the model proposed with the results of experiments on delayed luminescence of a homeopathic medicine is made.


Group a streptococcus in the gynecologic patient.
Over the past few decades, physicians have been reminded of the potential for serious complications arising from group A streptococcal (GAS) infections. These infections continue to pose a serious threat, primarily because the pathophysiology of these infections is complex. This article reviews some of the features of GAS infections and presents two case reports of GAS pelvic infections in women. The two patients discussed both had unusual presentations for pelvic inflammatory disease. In both cases, there was strong concern that a serious gastrointestinal process was occurring. Both improved dramatically after aggressive irrigation of their abdominal cavities and administration of antibiotics. Appropriate and aggressive use of antibiotics and reduction of bacterial load through debridement and irrigation are crucial in treating serious GAS infections.


Reverse remodeling with resynchronization in an asymptomatic patient with dilated hypokinetic cardiomyopathy.
Cardiac resynchronization therapy (CRT) is a validated treatment for selected heart failure patients who remain highly symptomatic despite optimal drug treatment. Yet there is currently no indication for CRT in patients with few or no symptoms. We report a spectacular "reverse remodeling" effect after CRT in an asymptomatic patient with hypokinetic dilated myocardiopathy who needed pacing for atrio-ventricular conduction disorder. CRT was chosen to prevent deterioration of left ventricular function by conventional right apical pacing. Thus, CRT could be indicated in patients with hypokinetic dilated myocardiopathy before the appearance of symptoms.


Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials.
We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs). PubMed and EMBASE databases were searched to identify randomised trials studying HCQ. Ten RCTs were identified (n=5079 participants). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written. The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection. Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73). Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events. CRD42021285093.


Assessment of Purity, Functionality, Stability, and Lipid Composition of Cyclofos-nAChR-Detergent Complexes from Torpedo californica Using Lipid Matrix and Macroscopic Electrophysiology.
The main objective of the present study was to find detergents that can maintain the functionality and stability of the Torpedo californica nicotinic acetylcholine receptor (Tc-nAChR). We examined the functionality, stability, and purity analysis of affinity-purified Tc-nAChR solubilized in detergents from the Cyclofos (CF) family [cyclofoscholine 4 (CF-4), cyclofoscholine 6 (CF-6), and cyclofloscholine 7 (CF-7)]. The functionality of the CF-Tc-nAChR-detergent complex (DC) was evaluated using the Two Electrode Voltage Clamp (TEVC) method. To assess stability, we used the florescence recovery after photobleaching (FRAP) in Lipidic Cubic Phase (LCP) methodology. We also performed a lipidomic analysis using Ultra-Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS/MS) to evaluate the lipid composition of the CF-Tc-nAChR-DCs. The CF-4-Tc-nAChR-DC displayed a robust macroscopic current (- 200 ± 60 nA); however, the CF-6-Tc-nAChR-DC and CF-7-Tc-nAChR-DC displayed significant reductions in the macroscopic currents. The CF-6-Tc-nAChR and CF-4-Tc-nAChR displayed higher fractional florescence recovery. Addition of cholesterol produced a mild enhancement of the mobile fraction on the CF-6-Tc-nAChR. The lipidomic analysis revealed that the CF-7-Tc-nAChR-DC displayed substantial delipidation, consistent with the lack of stability and functional response of this complex. Although the CF-6-nAChR-DC complex retained the largest amount of lipids, it showed a loss of six lipid species [SM(d16:1/18:0); PC(18:2/14:1); PC(14:0/18:1); PC(16:0/18:1); PC(20:5/20:4), and PC(20:4/20:5)] that are present in the CF-4-nAChR-DC. Overall, the CF-4-nAChR displayed robust functionality, significant stability, and the best purity among the three CF detergents; therefore, CF-4 is a suitable candidate to prepare Tc-nAChR crystals for structural studies.


Characteristic Comparison Between 131I-Interferon-α and 131I-Interferon-α-Immunoglobulin-Fc Hybrid Protein in Rats Using Molecular Imaging.
Interferon-α (IFN-α) is produced to act locally and transiently with a relatively short circulation half-life in vivo. Hybridization of IFN-α with human immunoglobulin Fc, renamed as IFN-α-Fc, may overcome this limitation. In the present study, (131)I-IFN-α-Fc and (131)I-IFN-α were compared in the aspects of stability, pharmacokinetics, tissue distribution and molecular imaging quality in an animal model. Both IFN-α-Fc and IFN-α were labelled with (131)I. Biodistributions and pharmacokinetics of both labelled proteins in Sprague-Dawley rats were assayed. Micro-single-photon emission computed tomography/computed tomography was used to non-invasively monitor the longitudinal distribution of both proteins. (131)I-IFN-α-Fc was shown to have higher stability than (131)I-IFN-α in whole blood, plasma, kidney, liver and stomach from the biodistribution study. The area under curve analyzed from plasma in the phomacokinetics study was 10-fold higher for (131)I-IFN-α-Fc than for (131)I-IFN-α. At 0-1 h post tail-vein injection, both labelled proteins are mainly accumulated in the kidneys and liver. Notably, (131)I-IFN-α-Fc is degraded more slowly than (131)I-IFN-α. We demonstrated that (131)I-IFN-α-Fc has longer blood circulation time and better biostability than (131)I-IFN-α, suggesting the potential application of the immunoglobulin Fc-conjugated cytokine for long-term treatment of diseases.


Nicotine-induced conditioned place preference and conditioned place aversion in mice.
The motivational effects of nicotine were examined in mice using an unbiased place conditioning design. Swiss-Webster mice received four 15-min parings of a tactile stimulus with different doses of nicotine (0.25-2.0 mg/kg, IP). A different tactile stimulus was paired with saline injections. During conditioning, nicotine produced locomotor depression at the 2.0-mg/kg dose, with the greatest reduction in activity occurring during the latter part of each nicotine conditioning session. After four trials, nicotine produced increases in locomotor activity during the initial part of the nicotine sessions at doses 0.5 mg/kg or above. Upon testing, nicotine-induced conditioned place preference was noted in mice receiving 0.5 mg/kg nicotine. Conditioned place aversion was noted in mice receiving 2.0 mg/kg nicotine whereas doses of 0.25 and 1.0 mg/kg produced no conditioning. These results indicate that nicotine has dose-dependent rewarding and aversive effects measured in an unbiased place conditioning paradigm using mice.


Identification of tumor epithelium and stroma in tissue microarrays using texture analysis.
The aim of the study was to assess whether texture analysis is feasible for automated identification of epithelium and stroma in digitized tumor tissue microarrays (TMAs). Texture analysis based on local binary patterns (LBP) has previously been used successfully in applications such as face recognition and industrial machine vision. TMAs with tissue samples from 643 patients with colorectal cancer were digitized using a whole slide scanner and areas representing epithelium and stroma were annotated in the images. Well-defined images of epithelium (n = 41) and stroma (n = 39) were used for training a support vector machine (SVM) classifier with LBP texture features and a contrast measure C (LBP/C) as input. We optimized the classifier on a validation set (n = 576) and then assessed its performance on an independent test set of images (n = 720). Finally, the performance of the LBP/C classifier was evaluated against classifiers based on Haralick texture features and Gabor filtered images. The proposed approach using LPB/C texture features was able to correctly differentiate epithelium from stroma according to texture: the agreement between the classifier and the human observer was 97 per cent (kappa value = 0.934, P < 0.0001) and the accuracy (area under the ROC curve) of the LBP/C classifier was 0.995 (CI95% 0.991-0.998). The accuracy of the corresponding classifiers based on Haralick features and Gabor-filter images were 0.976 and 0.981 respectively. The method illustrates the capability of automated segmentation of epithelial and stromal tissue in TMAs based on texture features and an SVM classifier. Applications include tissue specific assessment of gene and protein expression, as well as computerized analysis of the tumor microenvironment. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4123422336534537.


Multistakeholder Collaborative Effort to Enhance Long-Term Follow-Up in the Abdominal Core Health Quality Collaborative.
To determine the effectiveness of a clinical call center in performing focused long-term patient reported outcome (PRO)-based follow-up for ventral hernia patients in routine practice. Long-term follow-up remains the mainstay of assessing quality of care in hernia management. Achieving acceptable rates of long-term follow-up outside of clinical trials in the routine care of patients has been very difficult to achieve. A prospective quality improvement intervention using a clinical call center in 1000 random patients eligible for long-term (1 year or greater) follow-up after ventral hernia repair in the Abdominal Core Health Quality Collaborative was performed. The primary outcome measure was the proportion of patients with successfully completed PRO-based long-term follow-up. Between 2013 and 2017, the baseline long-term follow-up PRO completion rate was 2167/13,950 (15.5%). For the Focus on Follow-Up initiative, 890 patients were eligible for contact; a completion rate of 450/890 (50.6%, P < 0.001) was achieved. Clinical call center-based patient contact can greatly facilitate the completion of PROs utilized for long-term follow-up in ventral hernia repair. This has important implications for quality improvement programs and postmarket device surveillance.


Effects of exercise intervention in breast cancer patients: is mobile health (mHealth) with pedometer more effective than conventional program using brochure?
To investigate and compare the effects of mobile health (mHealth) and pedometer with conventional exercise program using a brochure on physical function and quality of life (QOL). The study was a prospective, quasi-randomized multicenter trial where 356 patients whose cancer treatment had been terminated were enrolled. All patients were instructed to perform a 12-week regimen of aerobic and resistance exercise. The mHealth group received a pedometer and a newly developed smartphone application to provide information and monitor the prescribed exercises. Those in the conventional group received an exercise brochure. Physical measurements were conducted at baseline, 6 weeks, and 12 weeks. Self-reported physical activity (international physical activity questionnaire-short form), general QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30), and breast cancer-specific QOL (Quality of Life Questionnaire Breast Cancer Module 23) were assessed at baseline and 12 weeks. A user satisfaction survey was assessed in the mHealth group. Basic characteristics were not different between the two groups except for age and previous radiotherapy. Physical function, physical activity, and QOL scores were significantly improved regardless of the intervention method, and changes were not significantly different between the two groups. Additionally, the mean Likert scale response for overall satisfaction with the service was 4.27/5 in the mHealth group. Overall, both the mHealth coupled with pedometer and conventional exercise education using a brochure were effective in improving physical function, physical activity, and QOL. This study provides a basis of mHealth research in breast cancer patients for progressing further developing field, although superiority of the mHealth over the conventional program was not definitely evident.


Molecular pathogenesis of subretinal fibrosis in neovascular AMD focusing on epithelial-mesenchymal transformation of retinal pigment epithelium.
Age-related macular degeneration (AMD) is a leading cause of vision loss among elderly people in developed countries. Neovascular AMD (nAMD) accounts for more than 90% of AMD-related vision loss. At present, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is widely used as the first-line therapy to decrease the choroidal and retinal neovascularizations, and thus to improve or maintain the visual acuity of the patients with nAMD. However, about 1/3 patients still progress to irreversible visual impairment due to subretinal fibrosis even with adequate anti-VEGF treatment. Extensive literatures support the critical role of epithelial-mesenchymal transformation (EMT) of retinal pigment epithelium (RPE) in the pathogenesis of subretinal fibrosis in nAMD, but the underlying mechanisms still remain largely unknown. This review summarized the molecular pathogenesis of subretinal fibrosis in nAMD, especially focusing on the transforming growth factor-β (TGF-β)-induced EMT pathways. It was also discussed how these pathways crosstalk and respond to signals from the microenvironment to mediate EMT and contribute to the progression of nAMD-related subretinal fibrosis. Targeting EMT signaling pathways might provide a promising and effective therapeutic strategy to treat subretinal fibrosis secondary to nAMD.


Sleep deprivation-induced hyperthermia following antigen challenge due to opioid but not interleukin-1 involvement.
Eight hours total sleep deprivation does not affect colonic temperature. The combination of a subpyrogenic challenge of sheep red blood cells with sleep loss however, can produce a significant rise in colonic temperature that peaks during the third hour of the sleep deprivation vigil. The regulation of this increase in colonic temperature appears to be opioid in nature and not because of the release of the cytokine interleukin-1. It would appear that the combination of sleep loss and low dose antigen challenge, both manipulations of themselves nonpyrogenic, produces a synergistic rise in colonic temperature. The implication of a psychologically-derived stress response via the opioid system may explain this finding.


Irregular fog as a water source for desert dune beetles.
Three methods of fog-water uptake have been observed in three tribes of Namib desert dune tenebrionid beetles, Adesmiini, Eurychorini and Zophosini. The methods used correlate with distribution and gross morphology of each species but cut across phylogenetic affinities. Of the three methods described, none involve obvious fine anatomical or physical adaptations of the beetles for fog-water uptake. Rather, the beetles have evolved specific behavioural patterns for drinking water condensed on vegetation, their own dorsum or sand.Use of fog-water necessitates surface activity at times when surface temperatures and wind velocities are not optimal for these diurnal or crepuscular species. Behavioural adaptation has enabled these beetles to use irregular and unpredictable fogs as a moisture source.


Feasibility and acceptability of a culturally-adapted Women's Wellness After Cancer Programme for Chinese women treated for gynaecological cancer: A pilot randomised controlled trial.
To assess the feasibility and acceptability of a culturally-adapted Women's Wellness After Cancer Programme (WWACPHK) for improving health-related quality of life, anxiety and depressive symptoms and enhancing self-efficacy in engaging in healthy lifestyles among Chinese women treated for gynaecological cancer. This pilot randomised controlled trial was conducted from May to December 2018. Twenty-six women aged 18 or above who had completed treatment for gynaecological cancer were recruited from a gynaecology outpatient clinic of a public hospital in Hong Kong. They were randomised into intervention (n = 15) or control (n = 11) groups. All data collectors were blinded to the group allocation. Intervention participants were given access to the WWACPHK website and an online discussion forum facilitated by a trained research nurse for 12 weeks, while control participants received standard care. Trial feasibility was assessed by recruitment, consent, and retention rates and website use. Acceptability was explored through semi-structured interviews. Additionally, we trialed the data collection procedure and collected preliminary data on health-related quality of life, anxiety and depressive symptoms, dietary and exercise self-efficacy. Of the 26 participants (Median age = 53.5 years) randomised, three participants dropped out of the study. Recruitment, consent and retention of participants and website use were satisfactory. No posting was made on the discussion forum. The intervention participants (n = 13) exhibited significantly greater improvement than the controls (n = 10) in perceived self-efficacy in adhering to an exercise routine at post-intervention (Cohen's d effect size(d) = 1.06, 95% confidence interval (CI): 0.18, 1.92) and 12-weeks after completion (d = 1.24, 95% CI: 0.32, 2.13). All participants were satisfied with the intervention. The WWACPHK is feasible and acceptable to Chinese women treated for gynaecological cancer and may improve their exercise self-efficacy. A larger-scale study is required to confirm its effects. Trial registrationhttps://www.isrctn.com identifier: ISRCTN12149499.


Are the UK clinical guidelines for H1N1 influenza infection valid in the hospital setting?
The diagnosis of pandemic influenza is clinical. This prospective study questions the validity of the Department of Health guidelines in 77 children admitted to hospital. The positive predictive value for the guidelines was 0.39. Although H1N1 was identified in a sizeable minority of cases using the guidelines, virology testing is still required.


Spinal epidural abscess associated with infliximab treatment for psoriatic arthritis. Case report.
Tumor necrosis factor-alpha inhibitors are used to treat numerous chronic inflammatory and rheumatological diseases, such as Crohn disease, rheumatoid arthritis, and psoriatic arthritis. Because the mechanism of these inhibitors is to decrease the body's inflammatory response, the primary complication of treatment is infection. The authors present the first case of a spinal epidural abscess in a patient receiving long-term infliximab therapy for severe psoriatic arthritis. Infliximab and its side-effect profile are discussed, along with other associated complications.


Zein based oil-in-glycerol emulgels enriched with β-carotene as margarine alternatives.
Structuring edible oils into solid lipids without saturated and trans fats has attracted increasing interest due to the benefits for human health and promises potential as novel delivery systems for lipophilic bioactive ingredients. The study shows that a zein stabilized high (ϕ=0.6) oil-in-glycerol (O/G) emulgels enriched with β-carotene was performed, by a facile one-step homogenization. Rheological measurements and morphologies observations indicated that increasing β-carotene resulted in a progressive strengthening of gel-like network and improving their spreadability in the O/G emulgels stabilized by zein, which was closely related to the hydrophobic interaction of zein and β-carotene. The formation of emulgels significantly enhanced the UV photo-stability of β-carotene, and more than 88% of β-carotene was retained in 64h storage under UV exposure, and consequently retarded oil oxidation while storage. Further, cakes prepared using zein-based O/G emulgels as a margarine alternative showed comparable functionalities (texture and sensory attributes) to the standard cake.


Alveolar capillary dysplasia with misalignment of the pulmonary veins: a rare but fatal cause of neonatal respiratory failure.
Respiratory failure in the neonate that is refractory to maximal medical management is a frequent indication for extracorporeal life support (ECLS). Alveolar capillary dysplasia with misalignment of the pulmonary veins is an irreversible cause of respiratory failure that cannot be diagnosed on clinical grounds alone and would not be expected to respond to ECLS therapy. A recent experience with a patient prompted us to review the literature regarding this condition for the purpose of identifying factors suggestive of this diagnosis. This condition should be considered in neonates with presumed pulmonary hypertension who cannot be weaned from ECLS. If the diagnosis is made by antemortem open-lung biopsy, a costly, protracted, and unnecessary continued course of ECLS may be avoided.


CCK, PYY and PP: the control of energy balance.
The control of food intake consists of neural and hormonal signals between the gut and central nervous system (CNS). Gut hormones such as CCK, PYY and PP signal to important areas in the CNS involved in appetite regulation to terminate a meal. These hormones can act directly via the circulation and activate their respective receptors in the hypothalamus and brainstem. In addition, gut vagal afferents also exist, providing an alternative pathway through which gut hormones can communicate with higher centres through the brainstem. Animal and human studies have demonstrated that peripheral administration of certain gut hormones reduces food intake and leads to weight loss. Gut hormones are therefore potential targets in the development of novel treatments for obesity and analogue therapies are currently under investigation.


Advances in Design and Development of Lumi-Solve: A Novel Drug-Eluting Photo-Angioplasty Device.
The Lumi-Solve photo-angioplasty drug eluting balloon catheter (DEBc) may afford safety advantages over current DEBc. Lumi-Solve utilises the guidewire (GW) port and lumen to deliver fibre-optic UV365nm light to the angioplasty balloon which may be problematic. We explore and evaluate alternative Lumi-Solve design options to circumvent fibre-optic use of the GW port and lumen which may enhance efficacy and clinical utility. Effects of guidewire shadowing (GWS) on visible and UV365nm light transmission were evaluated and modelled in-silico. To evaluate the effect of a dedicated intra-balloon fibre-optic port, modified angioplasty balloons and sections of translucent polyethylene terephthalate (PET) GW port tubing were utilised. Investigation of the effect of GWS on chemical and biological photo-activation of balloon surface drug was performed utilising LCMS analysis and inhibition of histone deacetylase activity (HDACi) was measured in human umbilical vein endothelial cells (HUVEC). Parallel fibre-optic and GW port configurations generated a GWS of approximately 18.0% of the evaluable balloon surface area and attenuated both visible and UV light intensity by 20.0-25.0% and reduced chemical photo-activation of balloon surface drug and HDACi by at least 40-45%. Alternative fibre-optic port configurations including a spiral design significantly mitigated GWS effects on UV light transmission. To avoid use of the GW port and its associated complications a dedicated third port and lumen for the Lumi-Solve fibre-optic may be required. To maximize balloon surface chemical and biological photo-activation, non-parallel, intra-balloon, fibre-optic lumen trajectories, including a spiral design may be useful.


The role of a fadA ortholog in the growth and development of Colletotrichum graminicola in vitro and in planta.
A transposon-based split-marker protocol was used to produce insertional mutations in the fadA ortholog of the maize anthracnose pathogen Colletotrichum graminicola. The mutants grew more slowly in culture, produced fewer oval spores, produced fusiform rather than falcate phialospores, lost their normal clockwise spiral growth pattern in culture, and were significantly reduced in their pathogenicity to maize stalks and leaves. The differential effect of the fadA mutation on oval spore versus phialospore production suggests that there are differences in the signaling pathways that regulate these two types of sporulation. It has been suggested that oval spores function in anthracnose lesion extension. In maize stalks, production of oval spores appeared to be relatively unaffected in the mutant strains, but production of vegetative hyphae and elongation of primary lesions were both reduced. This suggests that vegetative hyphae play a more important role than oval spores in primary lesion development. However, production of discontinuous secondary lesions in maize stalks infected by mutant strains did not appear to be seriously affected, and thus oval spores may play a more important role in that process.


Role of potassium channels in cerebral blood vessels.
Hyperpolarization of vascular muscle in response to activation of potassium channels is a major mechanism of vasodilatation. In cerebral blood vessels, four different potassium channels have been described: ATP-sensitive potassium channels, calcium-activated potassium channels, delayed rectifier potassium channels, and inward rectifier potassium channels. Activation of ATP-sensitive and calcium activated potassium channels appears to play a major role in relaxation of cerebral arteries and arterioles in response to diverse stimuli, including receptor-mediated agonists, intracellular second messengers, and hypoxia. Both calcium-activated and delayed rectifier potassium channels may contribute to a negative feedback system that regulates tone in large cerebral arteries. The influence of ATP-sensitive and calcium-activated potassium channels is altered in disease states such as hypertension, diabetes, and atherosclerosis. Activation of potassium channels is a major mechanism of cerebral vasodilatation. Alteration of activity of potassium channels and impairment of vasodilatation may contribute to the development or maintenance of cerebral ischemia or vasospasm.


An integrative analysis of lncRNAs and mRNAs highlights the potential roles of lncRNAs in the process of follicle selection in Taihang chickens.
Taihang chickens are a domestic breed distributed throughout Hebei province in the Taihang Mountains of China and are characterized by their high meat and egg quality. However, the relatively limited egg production by this breed constrains their more widespread commercial utilization. The follicle selection process is closely linked to oocyte development and ovulation, making it a key determinant of laying performance and fecundity in hens. To understand the biological basis for such follicle selection and to identify the associated regulatory pathways, we conducted a genome-wide analysis of long noncoding RNAs (lncRNAs) and mRNAs from the pre-hierarchical follicles and hierarchical follicles of Taihang laying hens. We identified 81 lncRNAs and 528 mRNAs that were differentially expressed during follicle selection, and integrated network analyses suggested that these RNAs were associated with the cell cycle, focal adhesion, oocyte meiosis, peroxisome proliferator-activated receptor signaling, and steroid hormone biosynthesis pathways. The identified lncRNAs were also predicted to influence a series of target genes in cis and trans, suggesting that they may be important regulators of ovarian follicular development. Overall, the present analysis of lncRNA and mRNA expression patterns associated with ovarian follicle development offers a new foundation for future studies of reproductive physiology in Taihang chickens, highlighting new opportunities to improve the laying performance of this important domestic breed.


Designing transient binding drugs: a new concept for drug discovery.
A multitude of weak, or transient, biological interactions (dissociation constant: K(d)>microM), either working alone or in concert, occur frequently throughout biological systems. We are starting to appreciate their importance in complex biological networks. This realization has important implications to drug discovery as we can question the current paradigm of drug design to find the highest possible binders (drugs) to a given target (receptor). Development of transient drugs, defined by their binding to target, can be based on high-off-rates, multivalent approaches or multiple targets. Now, techniques are available to discover such drug candidates. The greatest problem yet to overcome is probably the mind-set of the individual researcher that weak binders are undesired and therefore of no benefit.


Improved analysis ZIC-HILIC-HCD-Orbitrap method for mapping the glycopeptide by mass spectrometry.
Glycosylation is one of the most common post-translational modifications (PTMs). Protein glycosylation analysis is the bottleneck to deeply understand their functions. At present, the LC-MS analysis of glycosylated post-translational modification is mainly focused on the analysis of glycopeptides. However, the factors affecting the identification of glycopeptides were not fully elucidated. In the paper, we have carefully studied the factors, e.g., HILIC materials, search engines, protein amount, gradient duration, extraction solution, etc. According to the results, HILIC materials were the most important factors affecting the glycopeptides identification, and the amphoteric sulfoalkyl betaine stationary phase enriched glycopeptides 6-fold more compared to the amphiphilic ion-bonded fully porous spherical silica stationary phase. We explored the influence of the extraction solutions on glycan identification. Comparing sodium dodecyl sulfate (SDS) and urea (UA), the results showed that N-glycolylneuraminic acid (NeuGc) type of glycan content was found to be increased 1.4-fold in the SDS compared to UA. Besides, we explored the influence of the search engine on glycopeptide identification. Comparing pGlyco3.0 and MSFragger-Glyco, it was observed that pGlyco3.0 outperformed MSFragger-Glyco in identifying glycopeptides. Then, using our optimized method we found that there was a significant difference in the distribution of monosaccharide types in plasma and brain tissue, e.g., the content of NeuAc in brain was 5-fold higher than that in plasma. To importantly, two glycoproteins (Neurexin-2 and SUN domain-containing protein 2) were also found for the first time by our method. In summary, we have comprehensively studied the factors influencing glycopeptide identification than any previous research, and the optimized method could be widely used for identifying the glycoproteins or glycolpeptides biomarkers for disease detection and therapeutic targets.


Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management.
Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.


The oncogenicity of avian adenoviruses. IV. Confirmatory evidence for recombination between viral and cellular DNA sequences and repetition of the recombinant in cells of a tumor line.
On the basis of hybridization analyses with viral DNA fragments as probes, we previously concluded that, in DNAs of many fowl adenovirus type 1-induced rodent tumors, units consisting of viral DNA segments flanked on both sides by cellular DNA segments are repeated more than 100 times per diploid genome of cell. Molecular cloning of virus-cellular junction fragments and analyses of their sequence arrangement in the present study confirmed that the previous conclusion was basically correct.


Intraobserver reliability of contact pachymetry in children.
Central corneal thickness (CCT) is an important measurement in the treatment and management of pediatric glaucoma and potentially of refractive error, but data regarding reliability of CCT measurement in children are limited. The purpose of this study was to evaluate the reliability of CCT measurement with the use of handheld contact pachymetry in children. We conducted a multicenter intraobserver test-retest reliability study of more than 3,400 healthy eyes in children aged from newborn to 17 years by using a handheld contact pachymeter (Pachmate DGH55; DGH Technology Inc, Exton, PA) in 2 clinical settings--with the use of topical anesthesia in the office and with the patient under general anesthesia in a surgical facility. The overall standard error of measurement, including only measurements with standard deviation ≤5 μm, was 8 μm; the corresponding coefficient of repeatability, or limits within which 95% of test-retest differences fell, was ±22.3 μm. However, standard error of measurement increased as CCT increased, from 6.8 μm for CCT less than 525 μm, to 12.9 μm for CCT 625 μm and greater. The standard error of measurement including measurements with standard deviation >5 μm was 10.5 μm. Age, sex, race/ethnicity group, and examination setting did not influence the magnitude of test-retest differences. CCT measurement reliability in children via the Pachmate DGH55 handheld contact pachymeter is similar to that reported for adults. Because thicker CCT measurements are less reliable than thinner measurements, a second measure may be helpful when the first exceeds 575 μm. Reliability is also improved by disregarding measurements with instrument-reported standard deviations >5 μm.


Isolation of a human seminal plasma peptide with bombesin-like activity.
Bombesin (BN) and BN-like peptides such as gastrin-releasing peptide (GRP) belong to the growing group of regulatory peptides. Bombesin and GRP share the same carboxyl-terminal heptapeptide sequence that is essential for receptor recognition and biologic activity. Immunohistochemical findings have indicated the presence of a BN-like peptide in the neuroendocrine cells of the human prostate. These findings, together with the high concentrations of different regulatory peptides recently found in seminal plasma, prompted us to characterize a BN-like peptide in human semen by gel-filtration chromatography, reverse-phase high-pressure liquid chromatography, and in vitro bioassay. Here we demonstrate that human semen contains high levels (mean +/- standard deviation, 288.9 +/- 114.39 pg/ml) of a substance that closely resembles the 14-27 carboxyl-terminal fragment of GRP (GRP 14-27). The partially purified peptide obtained from this source, examined on an in vitro bioassay that is especially useful for testing BN-like activities, elicits a contractile response of the rat uterus that is indistinguishable from that stimulated by standard BN and GRP 14-27. The GRP 14-27 present in human seminal plasma may be involved in some aspect of the process of fertilization.


Effects of reconstructed magnetic field from sparse noisy boundary measurements on localization of active neural source.
Localization of active neural source (ANS) from measurements on head surface is vital in magnetoencephalography. As neuron-generated magnetic fields are extremely weak, significant uncertainties caused by stochastic measurement interference complicate its localization. This paper presents a novel computational method based on reconstructed magnetic field from sparse noisy measurements for enhanced ANS localization by suppressing effects of unrelated noise. In this approach, the magnetic flux density (MFD) in the nearby current-free space outside the head is reconstructed from measurements through formulating the infinite series solution of the Laplace's equation, where boundary condition (BC) integrals over the entire measurements provide "smooth" reconstructed MFD with the decrease in unrelated noise. Using a gradient-based method, reconstructed MFDs with good fidelity are selected for enhanced ANS localization. The reconstruction model, spatial interpolation of BC, parametric equivalent current dipole-based inverse estimation algorithm using reconstruction, and gradient-based selection are detailed and validated. The influences of various source depths and measurement signal-to-noise ratio levels on the estimated ANS location are analyzed numerically and compared with a traditional method (where measurements are directly used), and it was demonstrated that gradient-selected high-fidelity reconstructed data can effectively improve the accuracy of ANS localization.


Biochemical characterization of lysosomes in unfertilized eggs of Xenopus laevis.
Relations between lysosomes and yolk platelets of amphibian eggs have been suggested. This work demonstrates the presence of acid hydrolases in oocytes induced to ovulate in vitro. About 40% of the acid hydrolases are found in a sedimentable fraction, and, in accordance with the lysosomal concept, they display structural latency. Biochemical data did not indicate any association between lysosomal enzymes and yolk platelets. The mechanism of yolk resorption is discussed and it is suggested that the fusion of lysosomes and yolk platelets might be one of the mechanisms involved in yolk digestion.


Amino acid metabolism in Ancylostoma ceylanicum and Nippostrongylus brasiliensis.
Ancylostoma ceylanicum and Nippostrongylus brasiliensis decarboxylated most of the amino acids examined, but only a few at significant rates. The former nematode in general possessed higher activities. Striking differences between the two parasites were, however, noticed regarding the metabolism of some of the amino acids. For instance, while alanine followed by aspartate produced highest amounts of 14CO2 in the presence of A. ceylanicum, proline exhibited maximum decarboxylation in case of N. brasiliensis. Tyrosine and lysine, on the other hand, did not liberate detectable CO2 with either parasite. Likewise, although large number of amino acids underwent transamination with 2-oxoglutarate, only some of them elicited appreciable activity for any of the two parasites.


Prophylactic effects of interleukin-2 receptor antagonists against graft-versus-host disease following unrelated donor peripheral blood stem cell transplantation.
Basiliximab and daclizumab, two interleukin-2 receptor antagonists (IL-2RAs), prevent graft failure in renal transplantation, which also effectively treat steroid-refractory graft-versus-host disease (GVHD). However, only a few studies report that IL-2RAs prevent GVHD. Here we first retrospectively explored the prophylactic effects of basiliximab or daclizumab against GVHD in 82 patients with hematologic malignancies following unrelated donor-peripheral blood stem cell transplantation (URD-PBSCT). All recipients achieved engraftment. The rates of grade II-IV and III-IV acute GVHD (aGVHD) were 35.4% and 15.9%, respectively. Chronic GVHD (cGVHD) developed in 38.7% of evaluable patients. The transplantation-related mortality was 13.4%, while relapse rate was 8.5%. The 2-year overall survival (OS) reached 77.1% and disease-free survival (DFS) accumulated to 72.2%. The side effects of basiliximab and daclizumab were moderate and tolerable. There were no significant differences in aGVHD onset and survival between the daclizumab and basiliximab groups. However, basiliximab presented superior prophylactic effects on cGVHD than daclizumab. In conclusion, basiliximab or daclizumab prevents GVHD efficiently and feasibly following URD-PBSCT, and contributes to favorable outcome. Basiliximab has a similar effect on aGVHD but superior activity against cGVHD. Further prospective and randomized control studies are needed.


Antibiotic resistance genes, class 1 integrons, and IncP-1/IncQ-1 plasmids in irrigation return flows.
Surface waters could be a dominant route by which antibiotic resistance genes (ARGs) are disseminated. In the present study we explored the prevalence and abundance of ARGs [blaCTX-M-1, erm(B), sul1, tet(B), tet(M), and tet(X)], class 1 integron-integrase gene (intI1), and IncP-1 and IncQ-1 plasmids in eight irrigation return flows (IRFs) and a background site (Main Line Canal, MLC) in the Upper Snake Rock watershed in southern Idaho. Grab samples were collected on a monthly basis for a calendar year, which were processed to extract microbial DNA, followed by droplet digital PCR to quantify the gene copies on an absolute (per 100 mL) and relative (per 16S rRNA gene copies) basis. The antibiotic resistance and intI1 genes and IncP-1/IncQ-1 plasmids were recovered at all IRF sampling sites with detections ranging from 55 to 81 out of 81 water sampling events. The blaCTX-M-1 gene was detected the least frequently (68%), while the other genes were detected more frequently (88-100%). All of the genes were also detected at MLC from April to Oct when water was present in the canal. The genes from lowest to greatest relative abundance in the IRFs were: blaCTX-M-1 < erm(B) < tet(B) < IncQ-1 < tet(M) < sul1 < intI1 = IncP-1 < tet(X). When compared to the average annual relative gene abundances in MLC water samples, they were found to be at statistically greater levels (P ≤ 0.008) except that of the IncP-1 and IncQ-1 plasmids (P = 0.8 and 0.08, respectively). The fact that most IRFs contained higher levels than found in the canal water, indicates that IRFs can be a point source of ARGs that ultimately discharge into surface waters.


Lymphoscintigraphy findings in patients with chylothorax: influence of biochemical parameters.
Chylothorax is a condition that can be challenging to diagnose due to its nonspecific clinical presentation. Several biochemical parameters of chylous pleural effusion have been identified as important indicators for the diagnosis of chylothorax. Lymphoscintigraphy is utilized to assess chylothorax and determine the location of chyle leakage. The present study aimed to evaluate the correlation between the biochemical parameters of chylous pleural effusion and 99mTc-dextran (99mTc-DX) lymphoscintigraphy in diagnosing chylothorax. A total of 120 patients were enrolled in the study, 83 of the patients with unilateral chylothorax, and 37 with bilateral chylothorax. All patients underwent both 99mTc-DX lymphoscintigraphy and pleural effusion laboratory analysis. The 99mTc-DX lymphoscintigraphy images were categorized as positive or negative groups based on the presence or absence of abnormal radioactive tracer accumulation in the thorax, respectively. The biochemical parameters of the two groups were subsequently compared. Among these patients, 101 (84.17%) had exudative effusions, while 19 (15.83%) had transudative effusions, as determined by the levels of pleural effusion protein, lactate dehydrogenase and cholesterol. Abnormal tracer accumulation in thorax was observed in 82 patients (68.33%). Our findings indicated that lymphoscintigraphy results were not associated with exudative and transudative chylothorax (P = 0.597). The lymphoscintigraphy positive group displayed significantly higher levels of pleural effusion triglyceride and pleural effusion triglyceride/serum triglyceride ratio in all biochemical parameters, compared to the negative group (P = 0.000 and P = 0.005). We identified cutoff values of 2.870 mmol/L for pleural effusion triglycerides and 4.625 for pleural effusion triglyceride/serum triglyceride ratio, respectively, which can facilitate differentiating the positive and negative cases on lymphoscintigraphy. Lymphoscintigraphy technique is a dependable diagnostic tool for the qualitative assessment of chylous pleural effusion. Higher pleural effusion triglyceride level and pleural effusion triglyceride/serum triglyceride ratio indicate a positive result in patients with chylothorax on lymphoscintigraphy, with the cutoff values of 2.870 mmol/L and 4.625 aiding in the diagnosis.


Influence of crystalloid and colloid replacement solutions on hemodynamic variables during acute normovolemic hemodilution.
To determine whether, in maintaining normovolemia during acute normovolemic hemodilution, replacement fluid choice influences intraoperative hemodynamic variables. Prospective, randomized, single-blinded study. Operating room of a tertiary-care university hospital. 40 adult, ASA physical status I, II, and III patients scheduled for acute normovolemic hemodilution during radical prostatectomy. Patients were randomly assigned to four replacement fluid groups to receive 1) Ringer's lactate, 2) 5% albumin, 3) 6% dextran 70, or 4) 6% hetastarch. A standardized general anesthetic was used, and patients underwent moderate hemodilution to a target hemoglobin of 9 gm/dL. Hemodynamic variables were recorded using standard monitors, 5-lead electrocardiography, radial arterial catheter, and pulmonary artery catheter. Red blood cell loss for the entire hospitalization was calculated. Demographic and clinical outcome data were similar among the groups. During acute normovolemic hemodilution, heart rate and pulmonary capillary wedge pressure were unchanged from baseline in all groups, but patients receiving Ringer's lactate or albumin had greater declines in mean arterial pressure at the end of acute normovolemic hemodilution. Cardiac and oxygen consumption indexes were stable during acute normovolemic hemodilution, but oxygen extraction increased. During hemodilution, anesthetized patients maintain whole body oxygenation by increasing oxygen extraction. The administration of hetastarch or dextran as the replacement fluid during acute normovolemic hemodilution is associated with a more stable mean arterial pressure, but overall acute normovolemic hemodilution is well tolerated irrespective of the replacement fluid used.


The apple RING-H2 protein MdCIP8 regulates anthocyanin accumulation and hypocotyl elongation by interacting with MdCOP1.
COP1, an important RING ubiquitin ligase E3, is a molecular switch for light regulation in plant development. As an interacting protein of COP1, CIP8 contains a RING-H2 domain, but its biological function is unclear. Here, the apple MdCIP8 was identified based on its homology with AtCIP8 in Arabidopsis. MdCIP8 was constitutively expressed at different levels in various apple tissues, and the expression level of MdCIP8 was not affected by light and dark conditions. MdCIP8 reversed the short hypocotyl phenotype of the cip8 mutant under light conditions. Furthermore, the yeast two-hybrid experiment showed that MdCIP8 interacted with the RING domain of MdCOP1 through its RING-H2 domain. MdCIP8-OX/cop1-4 exhibited the phenotype of the cop1-4 mutant, indicating that CIP8 acts upstream of COP1. In addition, an apple transient injection experiment showed that MdCIP8 inhibited anthocyanin accumulation in an MdCOP1-dependent pathway. Overall, our findings reveal that CIP8 plays an inhibitory role in the light-regulation responses of plants.


Antiretroviral drug resistance among patients with human immunodeficiency virus who act as sources or potential sources in occupational accidents involving healthcare workers.
To determine human immunodeficiency virus (HIV) type 1 genotypic antiretroviral drug resistance profiles of patients presenting a risk or potential risk for occupational exposure of healthcare workers. Observational survey involving HIV-infected patients. Blood samples collected from source-patients and potential source-patients underwent HIV-1 genotypic antiretroviral resistance testing and determination of CD4 counts and viral load. Affected healthcare workers were monitored for 6 months after exposure. The survey was conducted in a tertiary-care hospital located in Sao Paulo, Brazil. Sao Paulo is considered the epicenter of the HIV-acquired immunodeficiency (AIDS) virus epidemic in Brazil. Source-patients, potential source-patients, and affected healthcare workers. A total of 371 occupational exposures to biological materials were reported, 46 (12.3%) of which were from HIV-seropositive source-patients. Samples from 18 source-patients and 26 patients considered "potential sources for accidents" were analyzed. Of these 44 samples, 18 (41%) presented resistance-related mutations in reverse transcriptase, protease, or both. Of these 18 samples, 16 (89%) had resistance to drugs included in the prophylactic schedule recommended by the Brazilian Ministry of Health. Use of the Centers for Disease Control and Prevention-Brazilian post-exposure prophylaxis regimen will result in the administration of antiretroviral agents to which the source HIV-1 isolate will often be resistant. Therefore, it would be advisable to carefully investigate the history of use of antiretroviral agents by source-patients and adjust the prophylactic therapy based on those data and, subsequently, the results of resistance testing.


Postperfusion coronary stenosis.
A patient is described who had left main coronary artery stenosis four months after aortic valve replacement. He was seen with unstable angina, and subsequent catheterization revealed stenosis of a previously normal left main coronary artery. The diagnosis, treatment, and means of prevention are discussed.


Improved evidence for direct CP violation in B0-->pi+pi- decays and model-independent constraints on phi2.
We present a new measurement of the time-dependent CP-violating parameters in B(0)--> pi(+)pi(-) decays with 275 x 10(6) BB pairs collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider operating at the Gamma(4S) resonance. We find 666 +/- 43 B(0) --> pi(+)pi(-) events and measure the CP-violating parameters: S(pipi) = -0.67 +/- 0.16(stat) +/- 0.06(syst) and A(pipi) = +0.56 +/- 0.12(stat) +/- 0.06(syst). We find evidence for large direct CP violation with a significance greater than 4 standard deviations for any S(pipi) value. Using isospin relations, we obtain 95.4% confidence intervals for the Cabibbo-Kobayashi-Maskawa quark-mixing matrix angle phi(2) of 0 degree < phiv(2) < 19 degrees and 71 degrees < phi(2) < 180 degrees.


[The role of hypertrophy and left ventricular function on the occurrence of ventricular arrhythmias in arterial hypertension].
To evaluate the role of left ventricular hypertrophy (LVH), left ventricular systolic function an other clinical parameters on prevalence and complexity of ventricular arrhythmias in hypertension. Ventricular arrhythmias were studied in 39 hypertensives by 24 hours ambulatory electrocardiographic monitoring. Frequency and complexity of ventricular arrhythmias were compared among 3 groups: A and B, respectively without and with LVH, both with normal left ventricular function; and C with LVH and systolic dysfunction. LVH and systolic dysfunction were established echocardiographically. Linear regression analysis was performed in order to identify an independent correlation between clinical parameters and presence of arrhythmias. Group C patients were older and had significantly higher systolic and diastolic blood pressures, greater mass index, diastolic posterior wall thickness and end-systolic stress and increased prevalence of electrocardiographic strain. Left ventricular diastolic diameter in C group patients was increased only when compared to A group. Frequencies of cases with more than 10 ectopic ventricular beats/hour, pairs and nonsustained ventricular tachycardia episodes were all significantly increased in C when compared to B and to A. However, only left ventricular mass index or diastolic posterior wall thickness identified independently patients with ventricular arrhythmias. Left ventricular hypertrophy is the main predictor of potential high risk rhythm disturbances in hypertension.


Reduced glutathione in amyotrophic lateral sclerosis: an open, crossover, randomized trial.
The present study set out to define the possible effect of reduced glutathione (GSH), the substrate of glutathione peroxidase (GSH-Px), a free radical inactivating enzyme, in amyotrophic lateral sclerosis (ALS). Thirty-two patients affected by definite ALS seen in our institution between August 1993 and July 1994 were admitted to the study. The effect of GSH was studied in an open, crossover, randomized study. GSH was given at the dose of 600 mg each day intramuscularly for 12 weeks. The patients, taken sequentially, were randomly assigned to two groups. The first group received the drug while the second received only symptomatic therapies for 12 weeks. After a week of washout, the second group received GSH and the first only symptomatic therapies for 12 weeks. The rate of progression of the diseases was compared in the two groups. Clinical evaluation included manual test for muscle strength, Norris scale, bulbar scale, and forced vital capacity (FVC) percent. No significant difference was found in the progression of ALS in the two periods, although a slight slowing of the disease progression rate was found during the period of treatment, probably related to the open design of the study. Our data do not show any significant effect of reduced glutathione in modifying the progression of ALS.


On protection of the maternal perineum during birth.
The author's experience and a review of the medical literature suggest that prophylactic episiotomy is not indicated.


Truncus arteriosus with interrupted aortic arch: successful correction using autologous flap.
A newborn baby with type II truncus arteriosus and type B interrupted aortic arch was successfully treated by creating a pulmonary tract using autologous flap made from truncal wall without excision of the pulmonary artery and by reconstructing the aortic arch with direct anastomosis. This method provided excellent hemodynamics with wide reconstruction of the pulmonary tract without conduit.


Evaluation of the antioxidative capability of commonly used antioxidants in dermocosmetics by in vivo detection of protein carbonylation in human stratum corneum.
We present an in vivo test platform to evaluate the antioxidative capability of seven frequently used dermocosmetic antioxidants on the human stratum corneum (SC). It has been reported that the protein carbonylation could be used as a biomarker for oxidative stress. The current study detects the change of the level of exposed protein carbonyl group in the most outer layer of human SC. The concentration of the antioxidant in each subject emulsion formulation was 0.5% (w/w). The data indicated that alpha-tocopherol (α-Vit E) and ascorbic acid (Vit C) have excellent antioxidative capability and α-Vit E-acetate possesses better than the average antioxidative capability. The bioconversion of α-Vit E-acetate to α-Vit E may occur in the human SC during a less than 2 weeks time course test. Lipoic acid possessed moderate antioxidative capability. Ascorbyl 6-palmitate had a low antioxidative capability. Ascorbic acid 2-glucoside represented an insignificant antioxidative capability. Glutathion (GSH) had no effect on reducing oxidative damage to human SC proteins, implying that the GSH recycling system could be absent in human SC. This test platform is an useful tool to evaluate the antioxidative efficiency of antioxidants on human SC proteins.


Rational Design of RN15m4 Cathelin Domain-Based Peptides from Siamese Crocodile Cathelicidin Improves Antimicrobial Activity.
Antimicrobial peptides are becoming a new generation of antibiotics due to their therapeutic potential and ability to decrease drug-resistant bacteria development. Cathelicidins are known as effective peptides of vertebrate immunity that play crucial roles in the defensive strategy against pathogens. To improve its potency, the RN15 antibacterial peptide derived from the cathelin domain of Crocodylus siamensis cathelicidin has been modified and its antimicrobial properties investigated. Peptides were derived by template-based and physicochemical designation. The RN15 derivative peptides were predicted through their structure modeling, antimicrobial potency, and peptide-membrane calculation. The antimicrobial and cytotoxic activities of candidate peptides were investigated. Simultaneous consideration of physicochemical characteristics, secondary structure modeling, and the result of antimicrobial peptide tools prediction indicated that RN15m4 peptide was a candidate derivative antimicrobial peptide. The RN15m4 peptide expresses antimicrobial activity against most Gram-positive and Gram-negative bacteria and fungi with a lower minimum inhibition concentration (MIC) than the parent peptide. Besides, the time-killing assay shows that the designed peptide performed its ability to quickly kill bacteria better than the original peptide. Scanning electron microscopy (SEM) displayed the destruction of the bacterial cell membrane caused by the RN15m4 peptide. In addition, the RN15m4 peptide exhibits low hemolytic activity and low cytotoxic activity as good as the template peptide. The RN15m4 peptide performs a range of antimicrobial activities with low cell toxicity. Our study has illustrated the combination approach to peptide design for potent antibiotic peptide discovery.


[Procedure in case of suspected mycobacterial infection of lymph nodes of the neck. 2. Therapy].
In the treatment of tuberculosis the patients normally receive a two month daily treatment with Isoniazid, Rifampicin, Pyrazinamid and Ethambutol, followed by a daily treatment with Isoniazid and Rifampicin for four month. The atypical mycobacterial infections can be addressed as a local infection and are amendable to surgical therapy, eventually followed by a daily treatment with antibiotics for four to twelve weeks. In Germany it is obligatory to inform the local public health department about typical mycobacterial infections. Hygiene procedures following German law are discussed in this review.


Cerebellar afferents from the lateral reticular nucleus in the rat.
The projection from the lateral reticular nucleus to the cerebellum was examined using the retrograde fluorescent double labelling method in the rat. A quantitative analysis of the extent of axonal branching and of nucleotopic (topographic) organization in this projection was carried out. It was shown that lateral reticular nucleus neurons show axonal branching both within and between parasagittal zones of the cerebellar cortex, but that branching within zones is more common. Neurons projecting to different zones were found to be significantly spatially separated, but those projecting to different sites within the same zone were intermingled. Thus a limited degree of nucleotopic organization was found. The results are discussed in relation to the parasagittal zonation in the olivocerebellar projection.


The protective effect of fenofibrate, triptorelin, and their combination against premature ovarian failure in rats.
Cyclophosphamide (CP) is a chemotherapy alkylating agent that causes a lot of side effects including premature ovarian failure (POF). This study aimed to evaluate the possible protective effect of fenofibrate (FEN) in CP-induced POF. Rats were randomly divided into five groups as follows: negative control, CP, triptorelin (TRI)-treated, FEN (FEN)-treated, and FEN + TRI-treated. Histological study, collagen area fraction, and immunoexpression of proliferating cell nuclear antigen (PCNA) were evaluated. Also, estrogen, anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and ovarian malondialdehyde (MDA), nitric oxide (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were measured. CP significantly reduced ovarian follicle count, as compared with the control group (1.00 ± 0.76 versus 7.75 ± 1.83, respectively). Meanwhile, FEN, either solely or in combination with TRI, significantly increased ovarian follicle count, as compared with the CP group (3.88 ± 0.83 and 5.75 ± 1.39, respectively). As compared with the control group, CP increased the levels of MDA, NOx, IL-10, TNF-α, FSH, LH, and collagen area fraction; however, levels of GSH, SOD, VEGF, AMH, estrogen, and PCNA immunoexpression were reduced with CP. Administration of FEN either solely or in combination with TRI showed significant improvement in all the parameters previously mentioned. FEN can protect the ovary from CP-induced side effects possibly through antioxidant and anti-inflammatory actions.


Prevalence and etiological classification of thrombocytopenia among a group of pregnant women in Erbil City, Iraq.
To determine prevalence and define causes of pregnancy associated thrombocytopenia A total of 850 pregnant women at different ages of gestation were screened for thrombocytopenia. A control group of 150 age-matched nonpregnant women were tested for platelet count. Neoborns of thrombocytopenic women were tested within 24 hours of delivery and reassessment of women's platelets was done within 7-10 days post delivery.  The mean platelet count in pregnant women was significantly lower than in nonpregnant women (221±59.9 vs. 273±66.9). Thrombocytopenia affected 8% of cases, with peak incidence during the third trimester. Gestational thrombocytopenia was found to be the principal cause (73.8%); hypertensive disorders caused thrombocytopenia in 23% of cases and two cases (4%) were due to immune thrombocytopenic purpura. No maternal or fetal complications were noted. The mean platelet count of 51 neoborns of thrombocytopenic women was (240 ± 7.1). Two neoborns (4%) had low platelet counts. Majority of thrombocytopenias were mild gestational and occurred in late in pregnancy. No maternal or neonatal bleeding complications were observed.


Heterologous overexpression of a monotopic glucosyltransferase (MGS) induces fatty acid remodeling in Escherichia coli membranes.
The membrane protein monoglucosyldiacylglycerol synthase (MGS) from Acholeplasma laidlawii is responsible for the creation of intracellular membranes when overexpressed in Escherichia coli (E. coli). The present study investigates time dependent changes in composition and properties of E. coli membranes during 22h of MGS induction. The lipid/protein ratio increased by 38% in MGS-expressing cells compared to control cells. Time-dependent screening of lipids during this period indicated differences in fatty acid modeling. (1) Unsaturation levels remained constant for MGS cells (~62%) but significantly decreased in control cells (from 61% to 36%). (2) Cyclopropanated fatty acid content was lower in MGS producing cells while control cells had an increased cyclopropanation activity. Among all lipids, phosphatidylethanolamine (PE) was detected to be the most affected species in terms of cyclopropanation. Higher levels of unsaturation, lowered cyclopropanation levels and decreased transcription of the gene for cyclopropane fatty acid synthase (CFA) all indicate the tendency of the MGS protein to force E. coli membranes to alter its usual fatty acid composition.


Race, religious involvement and depressive symptomatology in a southeastern U.S. community.
A growing literature suggests that aspects of religious involvement may hold beneficial implications for mental health, and some also suggest that religion is an especially valuable mental health resource for racial minorities in the United States. These issues are explored empirically using data from a large (N = 2956) community sample drawn in the southeastern U.S. Findings include the following: (1) frequency of church attendance is inversely associated with depressive symptoms among whites, but not among blacks. (2) Absence of denominational affiliation is positively associated with depressive symptoms among blacks, but not among whites. (3) Frequency of private devotional activities (e.g. prayer) is positively associated with depressive symptoms among both racial groups. These results are discussed in terms of the distinctive history of the Black Church in the southern U.S. Several promising directions for further inquiry are outlined.