JPN clinical practice guidelines 2021 with easy-to-understand explanations for the management of acute pancreatitis.
In preparing the Japanese (JPN) guidelines for the management of acute pancreatitis 2021, the committee focused the issues raised by the results of nationwide epidemiological survey in 2016 in Japan. In addition to a systematic search using the previous JPN guidelines, papers published from January 2014 to September 2019 were searched for the contents to be covered by the guidelines based on the concept of GRADE system. Thirty-six clinical questions (CQ) were prepared in 15 subject areas. Based on the facts that patients diagnosed with severe disease by both Japanese prognostic factor score and contrast-enhanced computed tomography (CT) grade had a high fatality rate and that little prognosis improvement after 2 weeks of disease onset was not obtained, we emphasized the importance of Pancreatitis Bundles, which were shown to be effective in improving prognosis, and the CQ sections for local pancreatic complications had been expanded to ensure adoption of a step-up approach. Furthermore, on the facts that enteral nutrition for severe acute pancreatitis was not started early within 48 h of admission and that unnecessary prophylactic antibiotics was used in almost all cases, we emphasized early enteral nutrition in small amounts even if gastric feeding is used and no prophylactic antibiotics are administered in mild pancreatitis. All the members of the committee have put a lot of effort into preparing the extensively revised guidelines in the hope that more people will have a common understanding and that better medical care will be spread.


Serotonin receptors: subtypes, functional responses and therapeutic relevance.
Recent, rapid progress in the molecular biology of serotonin (5-HT) receptors requires conceptual re-thinking with respect to receptor classification. Thus, based on operational criteria (agonist and antagonist rank order), as well as transduction mechanisms involved and the structure of the receptor protein, the Nomenclature Committee of the Serotonin Club has proposed the following classification and nomenclature: the main receptor types 5-HT1 to 5-HT4, recombinant receptors (e.g. 5-ht5 to 5-ht7) and 'orphan' receptors. The aim of the present review is to discuss the events leading to this classification, the criteria for and functional responses mediated by various 5-HT receptors, as well as the therapeutic possibilities with 5-HT ligands.


Triple oral antidiabetic therapy.
Our objective was to determine the efficacy of adding acarbose to the combination of metformin and a sulfonylurea in the treatment of type II diabetes mellitus. Acarbose was added to the treatment regimen of 11 type II diabetic patients who were not adequately controlled on the combination of a sulfonylurea and metformin. Glycosylated hemoglobin before and after the addition of acarbose was compared to assess the efficacy of this additional therapy. One patient did not tolerate acarbose therapy. Of the remaining ten patients, the mean improvement in glycosylated hemoglobin with the addition of acarbose was 1.4 percentage points, p = 0.01. Eight patients had improvements in glycosylated hemoglobin; mean improvement, 2.0 percentage points. Two patients' glycohemoglobin values worsened. Thus, the addition of acarbose to the treatment regimen of type II diabetic patients presently on a combination of a sulfonylurea and metformin improves glycemic control.


Predicted versus observed maximum oxygen consumption early after lung resection.
The objective of this study was to identify the predictors of underestimation and overestimation of postoperative maximum oxygen consumption (VO(2)max). A prospective analysis was performed on 229 patients who had 38 pneumonectomies, 171 lobectomies, and 20 segmentectomies. All patients performed a preoperative and postoperative (on average 9.2 days after surgery) maximal stair-climbing test. Predicted postoperative VO(2)max (ppoVO(2)max) was calculated on the basis of the number of functioning segments removed during operation. The patients were divided into three groups: group A (158 cases), patients with a ppoVO(2)max within 1 standard deviation of the observed postoperative VO(2)max; group B (56 cases), patients with a difference between the observed postoperative VO(2)max and ppoVO(2)max greater than 1 standard deviation (underestimation); and group C (15 cases), patients with a difference between ppoVO(2)max and the observed postoperative VO(2)max greater than 1 standard deviation (overestimation). Univariate and multivariate analyses were performed. The only significant predictor of underestimation was a high percentage of functional parenchyma removed during operation (p < 0.0001). The significant predictors of overestimation were a low percentage of functional parenchyma removed during operation (p = 0.01) and a high preoperative VO(2)max (p = 0.002). The prediction of postoperative VO(2)max was not accurate in all patients. Those with a large amount of functional lung tissue removed during operation tended to have a postoperative VO(2)max greater than expected. Conversely, those patients with a small amount of functional lung tissue resected tended to have a postoperative VO(2)max lower than predicted.


Generation of Human iPSCs by Episomal Reprogramming of Skin Fibroblasts and Peripheral Blood Mononuclear Cells.
Human-induced pluripotent stem cells (iPSCs) can be generated from patient-specific somatic cells by forced expression of the transcription factors OCT4, SOX2, KLF4, and c-MYC. Sustained expression of the transgenes during reprogramming is crucial for the successful derivation of iPSCs. Integrating retroviruses have been used to achieve the required prolonged expression; however, issues of undesirable transgene expression in the iPSC-derived cell types post reprogramming can occur. Alternative non-integrating approaches to reprogram somatic cells into pluripotency have been established. Here, we describe a detailed method for generating human iPSCs from fibroblasts and peripheral blood mononuclear cells (PBMCs) using the non-integrating episomal plasmids. The delivery of the episomal plasmids into the somatic cells is achieved using a nucleofection technique, and reprogramming is performed in chemically defined media. This process takes approximately 30 days to establish the iPSC colonies. We also describe a method for growing iPSCs on vitronectin as well as procedures for the long-term expansion of iPSCs on human fibroblast feeder cells.


Measurement of small time differences between EEG channels: method and application to epileptic seizure propagation.
Small time differences between the EEG activities of two channels were measured by a method based on the use of coherence and phase spectra over a certain frequency range. In many cases this method allowed to establish that time differences of the order of 5-50 msec were actually present between two channels which appeared synchronous on visual inspection. The method was applied to seizure activity from the penicillin and kindling models in the cat and to seizures recorded from scalp and intracerebral electrodes in epileptic patients. When the seizure activity was widespread but was known to be related to an epileptic focus, it was found that the area of the focus had a consistent time lead over the other recording sites. It was concluded that the method could frequently allow to: (1) assess the presence of an epileptic focus even when only widespread seizure activity could be recorded; (2) make inferences about the possible routes of propagation of seizure activity.


Hypertrophic subaortic stenosis. Operative methods utilized to relieve left ventricular outflow obstruction.
The methods currently used at the National Heart Institute in the operative treatment of patients with hypertrophic subaortic stenosis (IHSS) are described. Features of the operation that facilitate exposure of the septum and the criteria of an adequate myotomy are emphasized.


[Post-traumatic chronic instability of the shoulder joint. Therapy and results].
If posttraumatic chronic instability of the AC-joint causes subjective complaints, this is an indication for operative therapy. In our unit 38 patients were treated at all. In most cases previous treatment had been conservative. Syndesmoplasty was done with local tissue. 33 patients were examined radiological and clinical after a minimum time of twelve months after operative treatment. The AC-joints of 25 patients were stable, in five cases there was a slight instability, in three cases there was a severe instability. Only with four patients the diminuation of mobility was of consequence.


[Surgery of metastases of differentiated thyroid cancers].
84 (19.5%) of 431 patients with differentiated thyroid cancer developed distant metastases in bone and parenchymal organs. 78% of primary bone metastases and only 21% of primary lung metastases were treated operatively. High survival rates of 33-60% at 5 years supported the necessity of surgical interventions primarily in bone metastases to prevent early morbidity due to pathological fractures. Even in case of questionable increase in survival rate surgery of metastases from differentiated thyroid carcinomas doubtlessly improves the quality of life in these patients.


Wagner proposition in Nigeria: An econometric analysis.
Succinct exploration of Adolph Wagner's Proposition [WP] 1883 - Peacock and Wiseman 1961version was put to the validation test in the study. At least, this time, for a quinaquina octo annis period, representing the life span of Nigeria. Specific suspicion of shocks from data from the world indicator and monetary authority necessitated the adoption of the ADF test with structural breaks, which came out positive at alternating integrating order. This propelled the Autoregressive Distributed Lag ARDL model path having specified the lag selection automatically. Even though the series showed significant association in the short run, and bi-directional causality, the result of the Bound test - F-statistics (calculated) = 3.42 falls below upper Bound I(0) = 4.68 and lower bound I(1) = 5.15 hence, invalidates the WP position in the long - run in Nigeria. This is an indication that a reduction in non-economically viable and overlapping, funds-straining ministries/departments/agencies (MDA) is indispensable.


Advantages and robustness of partial VMAT with prone position for neoadjuvant rectal cancer evaluated by CBCT-based offline adaptive radiotherapy.
This study aims to explore the advantages and robustness of the partial arc combined with prone position planning technique for radiotherapy in rectal cancer patients. Adaptive radiotherapy is recalculated and accumulated on the synthesis CT (sCT) obtained by deformable image registration between planning CT and cone beam CT (CBCT). Full and partial volume modulation arc therapy (VMAT) with the prone position on gastrointestinal and urogenital toxicity, based on the probability of normal tissue complications (NTCP) model in rectal cancer patients were evaluated. Thirty-one patients were studied retrospectively. The contours of different structures were outlined in 155 CBCT images. First, full VMAT (F-VMAT) and partial VMAT (P-VMAT) planning techniques were designed and calculated using the same optimization constraints for each individual patient. The Acuros XB (AXB) algorithm was used in order to generate more realistic dose distributions and DVH, considering the air cavities. Second, the Velocity 4.0 software was used to fuse the planning CT and CBCT to obtain the sCT. Then, the AXB algorithm was used in the Eclipse 15.6 software to conduct re-calculation based on the sCT to obtain the corresponding dose. Furthermore, the NTCP model was used to analyze its radiobiological side effects on the bladder and the bowel bag. With a CTV coverage of 98%, when compared with F-VMAT, P-VMAT with the prone position technique can effectively reduce the mean dose of the bladder and the bowel bag. The NTCP model showed that the P-VMAT combined with the prone planning technique resulted in a significantly lower complication probability of the bladder (1.88 ± 2.08 vs 1.62 ± 1.41, P = 0.041) and the bowel bag (1.28 ± 1.70 vs 0.95 ± 1.52, P < 0.001) than the F-VMAT. In terms of robustness, P-VMAT was more robust than F-VMAT, considering that less dose and NTCP variation was observed in the CTV, bladder and bowel bag. This study analyzed the advantages and robustness of the P-VMAT in the prone position from three aspects, based on the sCT fused by CBCT. Whether it is in regards to dosimetry, radiobiological effects or robustness, P-VMAT in the prone position has shown comparative advantages.


The Hawthorne Effect: Quality and Outcomes in Neurosurgery.
Measure something, and it gets better-this is what is called as the Hawthorne effect (also known as the observer effect). The Hawthorne factory experiments in 1920s were remarkable industrial data collection and analysis exercises that lead to Edwards Deming's quality revolution. The Harvard Medical Practice Study (1991), Leape's "Error in Medicine" (1994), and the Bristol pediatric cardiac report (2001) are among many documents that have revealed the huge gap between best practices and actual medical practice. Alarmed by the poor standards of quality at the most respected institutions, the medical fraternity therefore began visiting facilities in different fields and observing their quality assessment processes. The next leap for neurosurgery is to realize that it is unacceptable to treat patients with no regard for the standard of clinical outcomes. The traditional neurosurgery residency training has long ignored the most important issues of self-assessment, reappraisal, relearning, and measurement of skill and surgical outcomes. However, the experience taken from disparate fields, especially cardiac surgery, may encourage research and progress in measurement and improvement of quality in neurosurgery. Like cardiac surgeons, neurosurgeons must examine and analyze the results of their interventions. The concept of quality measurement is the most important single advance we can make in neurosurgery practice. Meticulous and precise measurement of outcomes will allow future progress of our specialty.


Antithrombotic treatment in atrial fibrillation.
Atrial fibrillation (AF) is the most common sustained arrhythmia, that substantially increases morbidity and mortality. AF is gaining in clinical and economic importance, with stroke and thromboembolism being major complications. In this article, the evidence for AF treatment trial of antithrombotic therapy is reviewed. Stroke risk stratification of patients with AF is discussed, and practical recommendations for thromboprophylaxis are presented.


Spontaneous pneumothorax in the newborn: a report of two fatalities.
Spontaneous pneumothorax is present in 1 to 2% of healthy full-term newborn infants. Virtually all cases have resolution of the pneumothorax without sequelae and in fact without the condition being diagnosed. Two fatal cases are presented. Anyone doing medicolegal autopsies should be aware of this entity so that X-rays or other appropriate methods to demonstrate it can be used.


The GP--an instrument of change.
This commentary is not so much about Mr B's battle with alcohol dependency but the evolution of a doctor-patient relationship. It focuses more on some of the motivating forces involved in helping such patients improve their lifestyles.


MDMA administration attenuates hippocampal IL-β immunoreactivity and subsequent stress-enhanced fear learning: An animal model of PTSD.
Post-traumatic stress disorder (PTSD) is a devastating disorder that involves maladaptive changes in immune status. Using the stress-enhanced fear learning (SEFL) paradigm, an animal model of PTSD, our laboratory has demonstrated increased pro-inflammatory cytokine immunoreactivity in the hippocampus following severe stress. Recent clinical trials have demonstrated 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy as an effective novel treatment for PTSD. Interestingly, MDMA has been shown to have an immunosuppressive effect in both pre-clinical and clinical studies. Therefore, we predict MDMA administration may attenuate SEFL, in part, due to an immunosuppressive mechanism. The current studies test the hypothesis that MDMA is capable of attenuating SEFL and inducing alterations in expression of TNF-α, IL-1β, glial fibrillary acidic protein (GFAP), an astrocyte specific marker, and ionized calcium-binding adapter molecule -1 (IBA-1), a microglial specific marker, in the dorsal hippocampus (DH) following a severe stressor in male animals. To this end, experiment 1 determined the effect of MDMA administration 0, 24, and 48 h following a severe foot shock stressor on SEFL. We identified that MDMA administration significantly attenuated SEFL. Subsequently, experiment 2 determined the effect of MDMA administration following a severe stressor on the expression of TNF-α, IL-1β, GFAP, and IBA-1 in the DH. We found that MDMA administration significantly attenuated stress-induced IL-1β and stress-reduced IBA-1 but had no effect on TNF-α or GFAP. Overall, these results support the hypothesis that MDMA blocks SEFL through an immunosuppressive mechanism and supports the use of MDMA as a potential therapeutic agent for those experiencing this disorder. Together, these experiments are the first to examine the effect of MDMA in the SEFL model and these data contribute significantly towards the clinical PTSD findings.


IL-5 expression in the sputum of patients with bronchial asthma.
Expression of IL-5 mRNA and the content of IL-5 in the sputum of patients with asthma of different severity were studied before and after treatment. The expression of IL-5 mRNA in mild asthma differed from that in severe and moderate asthma before and after treatment. The level of IL-5 before therapy was different in patients with mild and severe disease. In patients with severe asthma the level of IL-5 differed before and after treatment.


Effects of fish feed addition scenarios with prometryn on Microcystis aeruginosa growth and water qualities.
The number of undesirable environmental impacts of fish feed has been reported widely. Although repeated fish feed exposures are more prospective to occur in water, previous studies were mostly conducted as a single exposure of fish feed. In order to fill these gaps, a 40 days incubator experiment was conducted to explore the effects of fish feed addition scenarios during the lag phase with prometryn on both Microcystis aeruginosa growth and concentrations of nutrients. The maximum algae densities in groups of single exposure were 6.0-26.2% and 8.8-74.4% higher than those in groups of double and triple exposures, respectively (P < 0.05). At the beginning of the experiment, concentrations of nutrients in groups with different feed exposure scenarios were significantly different. The pattern of nutrient limitation showed a transformation from phosphorus limitation to nitrogen limitation generally. Furthermore, the average inhibition rates of algae by prometryn in the case of a single fish feed exposure were 4.6-9.4% lower than those under double exposures, and 22.0-26.8% lower than those under triple exposures (P < 0.05). In addition, algae growth rates have been developed as a function of concentrations of consumed nutrients (R2 = 0.410-0.932). Based on the above results, we concluded that in terms of limiting algae growth multiple low-dosage additions of fish feed were considered as a better addition pattern. By optimizing feed addition scenarios, there is considerable potential to increase the environmental sustainability of aquaculture.


Current and emerging perspectives on pathophysiology, diagnosis, and management of hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is the most common genetically inherited cardiomyopathy with an autosomal dominant inheritance pattern. A disease-causing gene is found between 34% and >60% of the times and the two most frequently mutated genes, which encode sarcomeric proteins, are MYBPC3 and MYH7. HCM is a diagnosis of exclusion since secondary causes of left ventricular hypertrophy should first be ruled out. These include hypertension, aortic stenosis, infiltrative disease, metabolic and endocrine disorders, mitochondrial cardiomyopathies, neuromuscular disorders, malformation syndromes and some chronic drug use. The disease is characterized by great heterogeneity of its clinical manifestations, however diastolic dysfunction and increased ventricular arrhythmogenesis are commonly seen. Current HCM therapies focus on symptom management and prevention of sudden cardiac death. Symptom management includes the use of pharmacological agents, elimination of medication promoting outflow track obstruction, control of comorbid conditions and invasive procedures, whereas in the prevention of sudden cardiac death, implantable cardiac defibrillators and antiarrhythmic drugs are used. A targeted therapy for LVOTO represented by allosteric cardiac myosin inhibitors has been developed. In terms of sport participation, a more liberal approach is recently recommended, after careful evaluation and common-shared decision. The application of the current therapies has lowered HCM mortality rates to <1.0%/year, however it appears to have shifted focus to heart failure and atrial fibrillation, as the predominant causes of disease-related morbidity and mortality and, therefore, unmet treatment need. With improved understanding of the genetic and molecular basis of HCM, the present decade will witness novel treatments for disease prevention and modification.


Effects of LED Light Illumination on the Growth, Digestive Enzymes, and Photoacclimation of Goniopora columna in Captivity.
Goniopora columna is a stony coral valued for its reef-building potential and its unique appearance. Thus, identifying the optimal culture conditions for G. columna would enable efficient cultivation and prevent the illegal exploitation of marine resources. Light sources are crucial for the growth of corals because zooxanthellae provide them with basic nutrients through photosynthesis. Different corals and zooxanthellae have different photoacclimation characteristics; therefore, selecting a suitable light wavelength remains the key inhibitor of coral maintenance in marine aquariums. Accordingly, this study investigated the effects of different light wavelengths on G. columna. It was illuminated for 6 or 12 h a day under white light, yellow light, red light (LR), green light (LG), blue light (LB), or purple light (LP) for 8 weeks. During the experiment, R(R; i.e., a formula feed that combines sodium alginate, protein and probiotics) of 5% (w/v) of G. columna tissue and skeletal dry weight was fed every day. Coral polyps were counted, zooxanthellae density, chlorophyll a concentration, specific growth rates, and survival rates were calculated; polyp stretching and contractile behaviors were observed; and body composition and digestive enzyme activity were analyzed. LB or LP (but not LG or LR) illumination for at least 6 h per day significantly promoted the growth, survival, protein content, and protease activity of the G. columna specimens. Furthermore, coral polyp extension reached 100% after 30 min of LP and LB light irradiation. Although no significant differences in the zooxanthellae density or chlorophyll a concentration were noted under various light wavelengths, significant reductions were detected in the absence of light. To achieve energy-efficient coral aquaculture with regard to G. columna cultivation, 6 h of LB or LP illumination per day can improve the growth.


Long-term organ culture of adult rat colon.
Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants that remained viable, there was an initial phase of degeneration of the surface and crypt cells, later these areas were repopulated in one week, showing well-formed crypts, goblet cells, and ultrastructural features such as extensive lateral interdigitations, microvilli and glycocalyx--typical of colon. The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial differentiation with well-formed crypts up to 13 weeks.


Development, pilot testing and psychometric validation of a short version of the coronary artery disease education questionnaire: The CADE-Q SV.
To develop, pilot test and psychometrically validate a shorter version of the coronary artery disease education questionnaire (CADE-Q), called CADE-Q SV. Based on previous versions of the CADE-Q, cardiac rehabilitation (CR) experts developed 20 items divided into 5 knowledge domains to comprise the first version of the CADE-Q SV. To establish content validity, they were reviewed by an expert panel (N=12). Refined items were pilot-tested in 20 patients, in which clarity was provided. A final version was generated and psychometrically-tested in 132CR patients. Test-retest reliability was assessed via the intraclass correlation coefficient (ICC), the internal consistency using Cronbach's alpha, and criterion validity with regard to patients' education and duration in CR. All ICC coefficients meet the minimum recommended standard. All domains were considered internally consistent (α>0.7). Criterion validity was supported by significant differences in mean scores by educational level (p<0.01) and duration in CR (p<0.05). Knowledge about exercise and nutrition was higher than knowledge about medical condition. The CADE-Q SV was demonstrated to have good reliability and validity. This is a short, quick and appropriate tool for application in clinical and research settings, assessing patients' knowledge during CR and as part of education programming.


Regulation of brain polyunsaturated fatty acid uptake and turnover.
The brain is particularly enriched in glycerophospholipids with either arachidonic or docosahexaenoic acid esterified in the stereospecifically numbered-2 position. In this paper, we review how combining a kinetic approach to study the uptake and turnover of arachidonic and docosahexaenoic acids within brain phospholipids of unanesthetized rats, along with chronic administration of antimanic drugs (lithium, valproate and carbamazepine), have advanced our understanding of how polyunsaturated fatty acids (PUFA) enter the brain, and the mechanisms that regulate their turnover within brain phospholipids. The incorporation rates of arachidonic and docosahexaenoic acid from the plasma unesterified pool into brain phospholipids closely approximate independent measures of their consumption rates by the brain, suggesting this is quantitatively the major pool for uptake of these PUFA. Antimanic drugs (lithium and carbamazepine) that downregulate the activity of the calcium-dependent cytosolic phospholipase A(2) (cPLA(2)) transcription factor AP-2, and in turn the expression and activity of cPLA(2,) lead to a selective downregulation in brain arachidonic acid turnover. Furthermore, targeting arachidonoyl-CoA formation via ordered, non-competitive inhibition of an acyl-CoA synthetase with valproate also selectively decreases brain arachidonic acid turnover. Drugs that increase brain cPLA(2) activity (N-methyl-d-aspartic acid and fluoxetine) are correlated with increased turnover of arachidonic acid in brain phospholipids. Altered PUFA metabolism has been implicated in several neurological disorders, including bipolar disorder and Alzheimer's disease. Identifying the enzymes that regulated brain PUFA metabolism could lead to new therapeutic approaches for these disorders.


Analysis of cell variants showing differential susceptibilities to radiation- or chemical-induced neoplastic transformation: differences in their responses to growth factors.
The induction of DNA synthesis in quiescent, density-arrested Balb/c 3T3 cells is known to be controlled by the sequential action of at least two functionally distinct sets of growth factors, so-called "competence factors" and "progression factors." Here we examined this induction pathway in Balb/c 3T3 A31-I variants, which showed differential susceptibilities to radiation- and chemical-induced neoplastic transformation despite their similar susceptibilities to radiation- or chemical-induced cell killing and mutagenesis. DNA synthesis was acquired only with the exposure to progression factors in a highly susceptible cell variant (A31-1-13) whereas both competence factors and progression factors were required for a less susceptible cell variant (A31-I-1). The competent state constitutively produced by an autologous mechanism in the highly transformation-susceptible A31-I-13 cells suggests the existence of an endogenous promoter that acts for the expression of the transformed phenotype in an autocrine fashion when the cells have been initiated by radiation or chemical carcinogens. The growth factor requirements acting as a determining factor for susceptibilities to transformation are discussed.


Highly oriented photosynthetic reaction centers generate a proton gradient in synthetic protocells.
Photosynthesis is responsible for the photochemical conversion of light into the chemical energy that fuels the planet Earth. The photochemical core of this process in all photosynthetic organisms is a transmembrane protein called the reaction center. In purple photosynthetic bacteria a simple version of this photoenzyme catalyzes the reduction of a quinone molecule, accompanied by the uptake of two protons from the cytoplasm. This results in the establishment of a proton concentration gradient across the lipid membrane, which can be ultimately harnessed to synthesize ATP. Herein we show that synthetic protocells, based on giant lipid vesicles embedding an oriented population of reaction centers, are capable of generating a photoinduced proton gradient across the membrane. Under continuous illumination, the protocells generate a gradient of 0.061 pH units per min, equivalent to a proton motive force of 3.6 mV⋅min-1 Remarkably, the facile reconstitution of the photosynthetic reaction center in the artificial lipid membrane, obtained by the droplet transfer method, paves the way for the construction of novel and more functional protocells for synthetic biology.


Pupation and fecundity of Molophilus ater Meigen (Diptera: Tipulidae) in relation to larval weight.
The life cycle of the cranefly Molophilus ater Meigen on an area of Pennine moorland in Britain is described. The later recruitment of females into the adult population is referable to a slightly longer period of larval development for females than for males, and not to any difference in the duration of the pupal stage. Significant relationships exist between larval weight and sex of pupae, and pupal weight and adult fecundity. Implications of these findings to the preparation of population budgets for the species are discussed.


Comparing Risk Factors for Adverse Outcomes in Virgin Inflatable Penile Prosthesis Implantations and Revisions: A Retrospective Cohort Study.
Recent studies place the risk of infection following inflatable penile prosthesis (IPP) implantation at 1-2%. This risk may be underestimated due to the exclusion of high-risk patients, such as patients undergoing multiple revisions or revision following IPP infection, from data. To calculate the rate of postoperative complications for all patients undergoing IPP implantation and revision, and to determine the risk factors predictive of complications following virgin implantation and revision independently. The charts of 280 patients undergoing 331 IPP implantations performed over the last 20 years at a large academic medical center were reviewed for postoperative complications and suspected preoperative and operative risk factors. This included the prevalence of adverse operative outcomes including postoperative infection and device malfunction. 63 (20.7%) surgeries resulted in postoperative complications: 38 (12.5%) resulting in device malfunction and 25 (8.20%) resulting in infection. Smoking (odds ratio [OR] = 4.14, P = .00) was associated with overall postoperative complications. Within subgroups, concomitant procedures (OR = 4.77, P = .03) were associated with infection for those undergoing virgin implantation, but not those undergoing revision procedures. Alternatively, diabetes mellitus (DM) (OR = 28.3, P = .02) was associated with postoperative infection for those undergoing revision procedures, but not those undergoing virgin implantation. The rate of postoperative infection for all patients undergoing IPP was found to be 8.20%, a higher estimate than historically recorded. To varying degrees, smoking, concomitant procedures, and DM were associated with adverse operative outcomes. Subset analyses revealed significant associations between postoperative infections and either concomitant procedures or DM in those undergoing virgin implantations or revision surgeries, respectively. Miller JA, Bennett NE. Comparing Risk Factors for Adverse Outcomes in Virgin Inflatable Penile Prosthesis Implantations and Revisions: A Retrospective Cohort Study. J Sex Med 2020;8:388-395.


Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group.
Influenza affects many people worldwide each year and has many troublesome symptoms. We investigated the efficacy and safety of the inhaled antiviral agent zanamivir as a treatment for influenza A and B infection. In a randomised, double-blind, placebo-controlled trial, we recruited 455 patients aged 12 years and older with influenza-like symptoms of 36 h duration or less who lived in Australia, New Zealand, and South Africa. Eligible patients were randomly assigned 10 mg inhaled zanamivir (n=227) or placebo (n=228) twice daily for 5 days. All patients recorded symptoms on diary cards four times daily during treatment and twice daily for 9 days after treatment. We analysed all patients by intention to treat, influenza-positivity, and high risk of developing complications. Compared with placebo, zanamavir relieved influenza symptoms a median of 1.5 days earlier in the intention-to-treat (p=0.011) and influenza-positive (p=0.004) populations, and 2 days earlier in patients who were febrile at entry [corrected]. In high-risk patients treated with zanamivir, symptoms were alleviated a median of 2.5 days earlier (p=0.048), fewer had complications (p=0.004), and fewer used complication-associated antibiotics (p=0.025) compared with placebo. The adverse event profiles were similar for zanamivir and placebo. Zanamivir was well-tolerated and effective in decreasing the duration and severity of symptoms. Complications were also decreased in high-risk patients but these findings need to be confirmed in future studies due to the limited number of patients [corrected].


Reproduction and the energy cost of defense in a Batesian mimicry complex.
The amount of energy invested in reproduction and in defense was examined in a Batesian mimicry complex consisting of the modelEleodes obscura and the mimicStenomorpha marginata (both Coleoptera: Tenebrionidae). Models live up to 4 y as adults while mimic adults live only 3 mo. The energy content of the eggs of the model and mimic was determined by microbomb calorimetry. The energy content of the defensive secretions produced by the model was determined by computational chemistry and MNDO computer programming. Contrary to the predictions of some life-history theory, the long-lived model annually produces many small eggs each of low energetic content, while the short-lived mimic annually produces fewer, larger eggs each of high energetic content. However, in terms of total energy, the long-lived model has an annual investment in reproduction equal to that of the short-lived mimic. During the 3 mo of co-ocurrence of models and mimics within a year, an average individual model's cost in using defensive secretions against potential predators is 12% of the amount of energy tied up in the eggs that it produces within the year. The annual cost of defense for the model is 18% of the energy contained in the mean number of eggs produced. When the energy allocated to eggs is added to that allocated to defense, the model has an annual investiment that is greater than the annual investment in reproduction by the mimic. Although the energy invested in defense by the model is small relative to the energy invested in egg production, it buys the model considerable protection from predation. Nevertheless, the cost of defense does not explain the deviations from the predictions of life-history theory.


Emboli capture using the Embol-X intraaortic filter in cardiac surgery: a multicentered randomized trial of 1,289 patients.
Particulate emboli are thought to play a significant role in the development of cardiac surgical complications. Intraaortic filtration of particulate emboli may reduce the burden of this morbidity in cardiac patients. A multiinstitutional randomized trial was designed and enrolled 1,289 patients at 22 centers. Six hundred forty-five patients were assigned to the treatment arm and received the Embol-X intraaortic filter, whereas 644 patients were assigned to the control arm. The endpoints examined were mortality, stroke, transient ischemic attack, renal insufficiency/failure, myocardial infarction, gastrointestinal complications, and limb-threatening ischemia. All filters were examined for histologic evidence of particulate emboli. Particulate emboli were identified in 598 (96.8%) of 618 filters successfully deployed. Composite event rates for the clinical endpoints were similar in both the filtered and nonfiltered arm (110/645 = 17% vs 122/644 = 19%, respectively). Individual event rates were also similar in both arms. A post hoc comparison of patients with moderate or greater preoperative risk scores demonstrated event reduction favoring the filtered group for renal complications (17/124 = 14% vs 28/117 = 24%, p = 0.04) and for the composite endpoint (30/124 = 24% vs 42/117 = 36%, p = 0.047). No clinically evident complications attributed to the use of the filter were identified. The use of the Embol-X intraaortic filter is both safe and effective, as demonstrated by the emboli capture rate of 97%. In addition, post hoc analysis indicates a reduction in postoperative renal complications for patients with moderate or greater preoperative risk. Further study of high-risk patients is warranted.


The evaluation of the use of 2D shear-wave ultrasound elastography in differentiation of clinically insignificant and significant liver fibrosis in pediatric age group.
To determine the accuracy of 2D shear-wave elastography (2D-SWE) in pediatric age group patients in differentiating clinically insignificant and significant liver fibrosis using METAVIR fibrosis scoring system as the gold standard. Liver biopsy has long been the gold standard in liver fibrosis diagnosis. However, due to probable complications and sampling variabilities, the need for more accurate and non-invasive techniques has increased. 2D-SWE is a non-invasive technique used in the evaluation of liver stiffness and utilized more and more in routine clinical practice with recent advances and researches. In this retrospective single-center study, we included 46 pediatric age group patients who had a liver parenchymal biopsy and 2D-SWE evaluation regardless of etiology. For 2D-SWE, the LOGIQ E9 system (GE Medical Systems, Wisconsin, USA) and, for histopathological evaluation, METAVIR fibrosis scoring system were utilized. Patients were further subgrouped as clinically insignificant (METAVIR Score F0-1) and significant (METAVIR Score F2-4). The Kolmogorov-Smirnov and Mann-Whitney U tests were employed for statistical analysis. The diagnostic accuracy of 2D-SWE was assessed, and cutoff values were set by ROC curve analysis. kPa values were statistically different between clinically significant and insignificant fibrosis patient groups (p < 0.001). kPa value of 8.92 was designated as the best cutoff value according to the Youden Index. 2D-SWE is one of the non-invasive techniques in the evaluation of liver fibrosis. Our findings suggest that 2D-SWE accurately differentiate clinically insignificant and significant liver fibrosis.


Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells.
Tail-anchored (TA) proteins contain a single transmembrane domain (TMD) at the C-terminus that anchors them to the membranes of organelles where they mediate critical cellular processes. Accordingly, mutations in genes encoding TA proteins have been identified in a number of severe inherited disorders. Despite the importance of correctly targeting a TA protein to its appropriate membrane, the mechanisms and signals involved are not fully understood. In this study, we identify additional peroxisomal TA proteins, discover more proteins that are present on multiple organelles, and reveal that a combination of TMD hydrophobicity and tail charge determines targeting to distinct organelle locations in mammals. Specifically, an increase in tail charge can override a hydrophobic TMD signal and re-direct a protein from the ER to peroxisomes or mitochondria and vice versa. We show that subtle changes in those parameters can shift TA proteins between organelles, explaining why peroxisomes and mitochondria have many of the same TA proteins. This enabled us to associate characteristic physicochemical parameters in TA proteins with particular organelle groups. Using this classification allowed successful prediction of the location of uncharacterized TA proteins for the first time.


LPS expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let-7e axis.
Myeloid-derived suppressor cells (MDSCs) represent a group of immature myeloid cells composed of myeloid progenitor cells and immature myeloid cells that can negatively regulate immune responses by inhibiting T-cell function. In mice, MDSCs are broadly defined by the expression of CD11b and Gr1. We and others have shown that injection of a lethal or sublethal dose of lipopolysaccharide (LPS) into mice could result in the expansion of MDSCs in the bone marrow (BM), spleen and blood. Until now, the molecular mechanisms responsible for this expansion are poorly studied; specifically, the roles of the individual microRNAs (miRNAs) which may be involved remain largely unknown. We performed microarray analysis to compare the miRNA expression profiles of CD11b+ Gr1+ cells sorted from the BM of LPS-injected and phosphate-buffered saline-injected mice. We identified let-7e, which was highly upregulated in the LPS-treated group, as a potent regulator of LPS-induced MDSC expansion. Furthermore, let-7e overexpression in BM chimeric mice led to a noticeable increase in the population of CD11b+ Gr1+ cells, which resulted from reduced cellular apoptosis. Further studies showed that let-7e could directly target caspase-3 to inhibit cell apoptosis, and upregulation of let-7e in LPS-stimulated MDSCs could be due to the relieved repression of let-7e transcription exerted by downregulated GATA2. Our findings suggest that LPS expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let-7e axis.


Efficacy of ezetimibe for reducing serum low-density lipoprotein cholesterol levels resistant to lifestyle intervention in patients with non-alcoholic fatty liver disease.
To investigate the efficacy of ezetimibe and lifestyle intervention for treating patients with non-alcoholic fatty liver disease (NAFLD) and residual dyslipidemia via a combination of ezetimibe and lifestyle intervention. Patients with NAFLD with residual dyslipidemia after a 6-month lifestyle intervention program were included. After completion of the 6-month program, the patients received p.o. administration of ezetimibe at 10 mg/day, in addition to lifestyle intervention, for 6 months. Of the 59 patients with NAFLD who had participated in the 6-month lifestyle intervention program between 2007 and 2012, 21 with residual dyslipidemia (10 males and 11 females) were enrolled. Median age was 58 years (range, 27-75), median bodyweight was 63.0 kg (range, 39.4-109.0), median body mass index was 25.4 kg/m2 (range, 18.2-37.1), median alanine aminotransferase was 23 IU/L (14-73), median high-density lipoprotein (HDL) was 58 mg/dL (range, 37-93), median triglycerides (TG) was 105 mg/dL (range, 42-216) and median low-density lipoprotein (LDL) was 153 (66-209) mg/dL. After 6 months of treatment with ezetimibe, serum LDL levels were improved in 15 of 20 (75%) patients (P = 0.0015), while no improvements were observed in the remaining five patient (25%). Ezetimibe was discontinued in one patient who developed skin rash. Ezetimibe is effective for treating residual dyslipidemia after lifestyle intervention in patients with NAFLD.


Rapid determination of caffeine in tea leaves.
For the purpose of efficient screening of low-caffeine tea shoots, a method for the rapid determination of caffeine was developed using high-performance liquid chromatography. Polyvinylpolypyrrolidone was packed in a pre-column and used to remove polyphenols from tea extracts on-line. The concentrations of caffeine extracted from powdered tea leaves at 50 degrees C during 1 day could be analyzed in 2-5 min intervals. The pre-column and the analytical column could be used for the analysis of more than 2000 samples.


Evaluating the Effect of a Home-Delivered Meals Service on the Physical and Psychological Wellbeing of a UK Population of Older Adults - A Pilot and Feasibility Study.
We evaluated the effectiveness of a 3-week, daily meal provision service by a non-profit provider on the physical and psychological wellbeing of an older adult population. We further examined the feasibility of carrying out such measures in participant's homes. 19 older adult participants (8M, 11F; 78.3 ± 8.7 years) received 3 meals per day for 21 days and supplemented these meals ad libitum. Risk of malnutrition (Mini Nutritional Assessment; MNA) body composition, blood pressure, handgrip strength, balance, mobility, loneliness, social capital, satisfaction with life and mood were evaluated in participant's homes before and after the intervention. Following the intervention, MNA score increased significantly and participants rated themselves as significantly less depressed. We describe a methodology that was largely feasible and outline ways in which it could be improved. We have demonstrated that even short-term, home meal deliveries improve MNA scores and can positively alter some measures of mood.


Fumonisin B1 - Isolation and analytical characterisation for the application as reference material.
A procedure for the production of Fumonsin B1 with a purity of more than 97% has been worked out. The isolated material was characterised by NMR and GC-MS and showed good agreement to literature data, thus proving the identity of the analysed FB1. For the purity assessment with LC-FLD and LC-MS a commercially available standard and the isolated FB1 sample were analysed under the same conditions. The overall purity of the FB1 samples was estimated as 91.9±8.1% (reference) and 97.6±2.4% (biopure), respectively.


Mechanism of drug interaction between a Kampo medicine, byakkokaninjinto, and tetracycline in rats.
We have previously reported that concomitant oral administration of the Kampo medicine, byakkokaninjinto (TJ-34), in extract granules, reduced the plasma concentrations of tetracycline (TC) and ciprofloxacin in humans, which might be the result of forming a chelate with Ca(2+). In the present study, we investigated the effect of a chelating agent, ethylenediaminetetraacetic acid (EDTA), on the plasma concentration-time profiles of TC after coadministration of TJ-34 dried extract and TC in rats to clarify whether metal ions contained in the TJ-34 dried extract contribute to this interaction. TJ-34 dried extract significantly reduced the plasma concentration of TC. The values of maximum concentration (C (max)), area under the plasma concentration-time curve and percentage of urinary recovery (f (e)) of TC were reduced to 42%, 40%, and 45%, respectively. On the other hand, treatment with EDTA significantly counteracted the effect of TJ-34 dried extract to reduce absorption of TC, indicating that metal ions mainly account for the interaction. Next, we investigated the effect of staggered administration of TJ-34 dried extract and TC to avoid the drug interaction between them. Administration of TJ-34 dried extract 2 h before TC had no effect on plasma concentrations and pharmacokinetic parameters of TC. These results provide a precise mechanism of the interaction TJ-34 and TC, suggesting a safe and effective dosage regimen to coadminister TJ-34 and TC in clinical use.


6-(Levulinyloxymethyl)-3-methoxy-2-nitrobenzoyl and 2-(levulinyloxymethyl)-5-methoxy-4-nitrobenzoyl groups as novel base-labile groups for 5'-hydroxy protection in solid-phase oligonucleotide synthesis.
The 6-(levulinyloxymethyl)-3-methoxy-2-nitrobenzoyl (LMMoNBz) and 2-(levulinyloxymethyl)-5-methoxy-4-nitrobenzoyl (LMMpNBz) groups were developed as novel base-labile groups for 5'-hydroxy protection in solid-phase oligonucleotide synthesis. A comparative study of the utility of LMMoNBz, LMMpNBz, and 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) groups is described.


Oesophago-pericardial fistula and cardiac tamponade after oesophagoscopy.
A case of oesophago-pericardial fistula following oesophagoscopy and dilatation is reported. This is a rare and usually fatal complication of oesophageal instrumentation. This case is of further interest as cardiac tamponade following a Niopam swallow subsequently occurred, and the patient survived emergency surgery.


Design and synthesis of KNT-127, a δ-opioid receptor agonist effective by systemic administration.
We have reported previously the novel δ-opioid agonist, SN-28, which was more potent in in vitro assays than the prototype δ-agonists, TAN-67 and SNC-80. However, when administered by subcutaneous injection, this compound showed no analgesic effect at dosages greater than 30mg/kg in the acetic acid writhing test. We speculated that SN-28 was not effective in the test because the presence of the charged ammonium groups prevented its penetration through the blood-brain barrier. On the basis of our proposal, we designed the novel δ-agonist, KNT-127, which was effective with systemic administration.


Phylogeny and ecophysiology of opportunistic "snow molds" from a subalpine forest ecosystem.
Mats of coenocytic "snow molds" are commonly observed covering the soil and litter of alpine and subalpine areas immediately following snow melt. Here, we describe the phylogenetic placement, growth rates, and metabolic potential of cold-adapted fungi from under-snow mats in the subalpine forests of Colorado. SSU rDNA sequencing revealed that these fungi belong to the zygomycete orders Mucorales and Mortierellales. All of the isolates could grow at temperatures observed under the snow at our sites (0 degrees C and -2 degrees C) but were unable to grow at temperatures above 25 degrees C and were unable to grow anaerobically. Growth rates for these fungi were very high at -2 degrees C, approximately an order of magnitude faster than previously studied cold-tolerant fungi from Antarctic soils. Given the rapid aerobic growth of these fungi at low temperatures, we propose that they are uniquely adapted to take advantage of the flush of nutrient that occurs at the soil-snow interface beneath late winter snow packs. In addition, extracellular enzyme production was relatively high for the Mucorales, but quite low for the Mortierellales, perhaps indicating some niche separation between these fungi beneath the late winter snow pack.


Gender and baboon aortic steroid hormone receptors.
To examine the potential of steroid hormones to serve as putative regulators of aortic cell function, we defined hormone receptor content and distribution in intact baboons. Total androgen receptor content in baboon aortic arch, thoracic arch, and abdominal aorta of young mature males was indistinguishable from that of proestrus females. However, 30% to 40% of male aortic androgen receptors were in the nuclear fraction, whereas all aortic androgen receptors of proestrus females were in the cytoplasmic fraction. Cytoplasmic fraction estrogen receptor content of aortic arch and thoracic aorta of intact males was indistinguishable from that of proestrus females. However, cytoplasmic fraction estrogen receptor content of abdominal aorta of proestrus females was significantly greater than that of males. Nuclear fraction estrogen receptors were not detectable in either male or proestrus female baboon aortas. To assess effects of endogenous estrogen on aortic progesterone receptor content, we quantified cytoplasmic fraction progesterone receptors and found that content of proestrus female aortic arch was not significantly different from that of males. However, cytoplasmic fraction progesterone receptor content of thoracic and abdominal aorta of proestrus females was significantly higher than that of males. To determine whether differences in aortic receptor content or distribution were associated with changes in aortic cell function, we quantified the activity of two enzymes of glycosaminoglycan metabolism. Aortic beta-glucuronidase activity was not different in male or proestrus female baboons.(ABSTRACT TRUNCATED AT 250 WORDS)


Acute exacerbations in patients with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial lung disease that primarily affects older adults. Median survival after diagnosis is 2-3 years. The clinical course of IPF may include periods of acute deterioration in respiratory function, which are termed acute exacerbations of IPF (AEx-IPF) when a cause cannot be identified. AEx-IPF may represent a sudden acceleration of the underlying disease process of IPF, or a biologically distinct pathological process that is clinically undiagnosed. An AEx-IPF can occur at any time during the course of IPF and may be the presenting manifestation. The incidence of AEx-IPF is hard to establish due to variation in the methodology used to assess AEx-IPF in different studies, but AEx-IPF are believed to occur in between 5 and 10% of patients with IPF every year. Risk factors for AEx-IPF are unclear, but there is evidence that poorer lung function increases the risk of an AEx-IPF and reduces the chances of a patient surviving an AEx-IPF. The presence of comorbidities such as gastroesophageal reflux disease (GERD) and pulmonary hypertension may also increase the risk of an AEx-IPF. AEx-IPF are associated with high morbidity and mortality. Patients who experience an AEx-IPF show a worsened prognosis and AEx-IPF are believed to reflect disease progression in IPF. Current treatments for AEx-IPF have only limited data to support their effectiveness. The latest international treatment guidelines state that supportive care remains the mainstay of treatment for AEx-IPF, but also give a weak recommendation for the treatment of the majority of patients with AEx-IPF with corticosteroids. There is emerging evidence from clinical trials of investigational therapies that chronic treatment of IPF may reduce the incidence of AEx-IPF. Additional clinical trials investigating this are underway.


Acetaminophen hepatotoxicity.
Acetaminophen is a commonly used antipyretic and analgesic agent. It is safe when taken at therapeutic doses; however, overdose can lead to serious and even fatal hepatotoxicity. The initial metabolic and biochemical events leading to toxicity have been well described, but the precise mechanism of cell injury and death is unknown. Prompt recognition of overdose, aggressive management, and administration of N-acetylcysteine can minimize hepatotoxicity and prevent liver failure and death. Liver transplantation can be lifesaving for those who develop acute liver failure.


The implication of microRNAs and endo-siRNAs in animal germline and early development.
Germ cells provide maternal mRNAs that are stored in the oocyte, and later translated at a specific time of development. In this context, gene regulation depends mainly on post-transcriptional mechanisms that contribute to keep maternal transcripts in a stable and translationally silent state. In recent years, small non-coding RNAs, such as microRNAs have emerged as key post-transcriptional regulators of gene expression. microRNAs control the translation efficiency and/or stability of targeted mRNAs. microRNAs are present in animal germ cells and maternally inherited microRNAs are abundant in early embryos. However, it is not known how microRNAs control the stability and translation of maternal transcripts. In this review, we will discuss the implication of germline microRNAs in regulating animal oogenesis and early embryogenesis as well as compare their roles with endo-siRNAs, small RNA species that share key molecular components with the microRNA pathway.


An uncommon coronary artery fistula causing survived sudden cardiac death in a young woman.
Although most patients suffering from a coronary artery fistula remain asymptomatic during childhood and adolescence, many of them develop complications in adulthood due to volume overload, endocarditis or ischemia. Here we present a young woman surviving a sudden cardiac death due to myocardial ischemia with subsequent ventricular fibrillation caused by thrombosis of a coronary artery fistula deriving from the left main coronary artery. Parts of the thrombus had been embolized into the circumflex artery causing posterior myocardial infarction. The thrombosis might have been initiated by local compression from a round extracardiac mass of 3 cm with liquid and solid content located between the vena cava superior and the ascending aorta. This structure was suspected to be a hematoma which had been caused by a blunt thoracic trauma while playing soccer 2 weeks before.


A mathematical model for the absorption and metabolism of formaldehyde vapour by humans.
Epidemiological studies of occupational exposure to formaldehyde gas (HCHO) have suggested possible links between concentration and duration of exposure, and elevated risks of leukaemia and other cancers at sites distant from the site of contact. Formaldehyde is a highly water soluble gas which, when inhaled, reacts rapidly at the site of contact and is quickly metabolised by enzymes in the respiratory tissue. Inhaled formaldehyde is almost entirely absorbed in the respiratory tract and, for formaldehyde induced toxicity to occur at distant sites, HCHO must enter the blood and be transported to systemic tissues via the circulatory system. A mathematical model describing the absorption and removal of inhaled formaldehyde in the nasal tissue is therefore formulated to predict the proportion of formaldehyde entering into the blood. Accounting for the spatial distribution of the formaldehyde concentration and the metabolic activity within the mucosa, the concentration of formaldehyde in the mucus, the epithelium and the blood has been determined and was found to attain a steady-state profile within a few seconds of exposure. The increase of the formaldehyde concentration in the blood was predicted to be insignificant compared with the existing pre-exposure levels in the body, indicating that formaldehyde is rapidly removed in the nasal tissue. The results of the model thus suggest that it is highly unlikely that following inhalation by the nose, formaldehyde itself will cause toxicity at sites other than the initial site of contact in the respiratory tract.


NMR and mutagenesis of human copper transporter 1 (hCtr1) show that Cys-189 is required for correct folding and dimerization.
The human high-affinity copper transporter (hCtr1) is a membrane protein that is predicted to have three transmembrane helices and two methionine-rich metal binding motifs. As an oligomeric polytopic membrane protein, hCtr1 is a challenging system for experimental structure determination. The results of an initial application of solution-state NMR methods to a truncated construct containing residues 45-190 in micelles and site-directed mutagenesis of the two cysteine residues demonstrate that Cys-189 but not Cys-161 is essential for both dimer formation and proper folding of the protein.


Mouse models for the study of HCV infection and virus-host interactions.
Hepatitis C virus (HCV) is a major cause of chronic liver disease including steatosis, cirrhosis and hepatocellular carcinoma. The development of transgenic mice expressing HCV proteins and the successful repopulation of SCID/Alb-uPA mice with human hepatocytes provides an important tool for unraveling virus-host interactions in vivo. Several of these mouse models exhibit aspects of HCV-related liver disease. Thus, these in vivo models play an important role to further understand the pathogenesis of HCV infection and to evaluate the pre-clinical safety and efficacy of new antiviral compounds against HCV. This review summarizes the most important mouse models currently used to study HCV pathogenesis and infection. Finally, the perspective of these models for future HCV research as well as the design of novel small animal models is discussed.


Peritoneal mesothelioma presenting as an acute surgical abdomen due to jejunal perforation.
Peritoneal mesothelioma is a rare disease associated with poor prognosis. Acute abdomen as the first presentation is an extremely rare occurrence. We report an exceptional case of a patient who was found to have a jejunal perforation due to infiltration of peritoneal mesothelioma. A 62-year-old man was admitted with clinical signs of peritonitis. Computerized tomographic scans showed a mass distal to the ligament of Treitz, thickening of the mesentery and a small amount of ascites. Emergency laparotomy revealed a perforated tumor 15 cm distal to the ligament of Treitz and diffuse peritoneal disease. Segmental small bowel resection and suboptimal cytoreduction were performed. Histopathology and immunohistochemistry showed infiltration of malignant mesothelioma. During the postoperative period pleural mesothelioma was also diagnosed. Despite adjuvant chemotherapy, the patient died of disseminated progressive disease 7 months after surgery. Peritoneal mesothelioma is a rare malignancy with grim prognosis. Small bowel involvement is a poor prognostic indicator. Our case of a small bowel perforation due to direct infiltration by peritoneal mesothelioma appears to be the first reported in the English literature.


Diagnosis of Epstein-Barr and cytomegalovirus infections using decision trees: an effective way to avoid antibiotic overuse in paediatric tonsillopharyngitis.
The incidence of tonsillopharyngitis is especially prevalent in children. Despite the fact that viruses cause the majority of infections, antibiotics are frequently used as a treatment, contrary to international guidelines. This is not only an inappropriate method of treatment for viral infections, but it also significantly contributes to the emergence of antibiotic-resistant strains. In this study, EBV and CMV-related tonsillopharyngitis were distinguished from other pathogens by using machine learning techniques to construct a classification tree based on clinical characteristics. In 2016 and 2017, we assessed information regarding 242 children with tonsillopharyngitis. Patients were categorized according to whether acute cytomegalovirus or Epstein-Barr virus infections were confirmed (n = 91) or not (n = 151). Based on symptoms and blood test parameters, we constructed decision trees to discriminate the two groups. The classification efficiency of the model was characterized by its sensitivity, specificity, positive predictive value, and negative predictive value. Fisher's exact and Welch's tests were used to perform univariable statistical analyses. The best decision tree distinguished EBV/CMV infection from non-EBV/CMV group with 83.33% positive predictive value, 88.90% sensitivity and 90.30% specificity. GPT (U/l) was found to be the most discriminatory variable (p < 0.0001). Using the model, unnecessary antibiotic treatment could be reduced by 66.66% (p = 0.0002). Our classification model can be used as a diagnostic decision support tool to distinguish EBC/CMV infection from non EBV/CMV tonsillopharyngitis, thereby significantly reducing the overuse of antibiotics. It is hoped that the model may become a tool worth considering in routine clinical practice and may be developed to differentiate between viral and bacterial infections.


Fluid flow influences ultrasound-assisted endothelial membrane permeabilization and calcium flux.
The local fluid dynamics experienced by circulating microbubbles vary across different anatomical sites, which can influence ultrasound-mediated therapeutic delivery efficacy. This study aimed to elucidate the effect of fluid flow rate in combination with repeated short-pulse ultrasound on microbubble-mediated endothelial cell permeabilization. Here, a seeded monolayer of human umbilical (HUVEC) or brain endothelial cells (HBEC-5i) was co-perfused with a solution of microbubbles and propidium iodide (PI) at either a flow rate of 5 or 30 ml/min. Using an acoustically coupled inverted microscope, cells were exposed to 1 MHz ultrasound with 20-cycle bursts, 1 ms PRI, and 2 s duration at a peak negative pressure of 305 kPa to assess the role of flow rate on ultrasound-stimulated endothelial cell permeability, as well as Ca2+ modulation. In addition, the effect of inter-pulse delays (∆t = 1s) on the resulting endothelial permeability was investigated. Our results demonstrate that under an identical acoustic stimulus, fast-flowing microbubbles resulted in a statistically significant increase in cell membrane permeability, at least by 2.3-fold, for both endothelial cells. Likewise, there was a substantial difference in intracellular Ca2+ levels between the two examined flow rates. In addition, multiple short pulses rather than a single pulse ultrasound, with an equal number of bursts, significantly elevated endothelial cell permeabilization, at least by 1.4-fold, in response to ultrasound-stimulated microbubbles. This study provides insights into the design of optimal, application-dependent pulsing schemes to improve the effectiveness of ultrasound-mediated local therapeutic delivery.


Evaluation of two anti-hepatitis E virus IgM kits.
To evaluate two commercial anti-hepatitis E virus (HEV) IgM kits used for differential diagnosis of acute enteric viral hepatitis. The kit for IgM capture assay, was produced with a recombinant HEV structural protein protecting primates against experimental infection by different HEV genotypes, while the other kit for indirect ELISA was produced with recombinant structural proteins from different HEV genotypes. The serum specimens were taken from 241 cases with a confirmed or presumptive diagnosis of hepatitis A and 74 cases with a confirmed or presumptive diagnosis of hepatitis E. The sensitivity and specificity of the IgM capture assay kit were 97% and 100%, respectively, and the corresponding values for the other kit were 70% and 78%, respectively. The IgM capture assay kit has higher sensitivity and specificity in diagnosing acute enteric viral hepatitis E.


Dental visits among smoking and nonsmoking US adults in 2000.
To examine dental visits among smoking and nonsmoking adults in a nationally representative sample. Logistic regression analysis was performed, using a sample of 15,250 US adults from the Medical Expenditure Panel Survey Household Component 2000. Current smokers were less likely to report dental visits (32.9%) than were nonsmokers (45.0%) during 2000. Differences were statistically significant even after accounting for other predictors of dental care use. Efforts to optimize the oral health of smokers and reduce serious oral diseases may benefit from addressing this lower use of dental services among smokers.


The association between fetal head station at the first diagnosis of the second stage of labor and delivery outcomes.
Controversy surrounds the impact of the fetal head station on labor duration and mode of delivery. Although an extensive body of evidence has been published evaluating fetal head station in early labor, there is a paucity of data on the impact of fetal head descent during the second stage. This study aimed to explore the association between fetal head station at the diagnosis of the second stage of labor and the second stage duration and the risk of operative delivery. This is a retrospective cohort study of all singleton vertex deliveries in a single tertiary center (2011-2016). Women were grouped according to fetal head station upon the diagnosis of the second stage of labor as follows: above (S<0), at the level (S=0), and below (S>0) the level of the ischial spine. The duration of the second stage and the risk of operative delivery were compared between the groups and stratified by parity. Overall, 34,334 women met the inclusion criteria. Of these, 18,743 (54.6%) were nulliparous and 15,591 (45.4%) were multiparous. Of the nulliparous women, 8.1%, 35.8%, and 56.1% were diagnosed as having fetal head above, at the level, and below the ischial spine upon second stage diagnosis. Of the multiparous women, 19.7%, 35.6%, and 44.7% were diagnosed as having fetal head above, at the level, and below the ischial spine. Fetal head station upon second stage diagnosis was independently and significantly associated with second stage duration (P<.001); however, its contribution was 4.5-fold among nulliparous women compared with multiparous women. In multivariable analysis, after controlling for maternal age, gestational age at delivery, prepregnancy body mass index, epidural anesthesia, and birthweight, the risk of operative delivery was substantially increased in a dose-dependent pattern for both nulliparous and multiparous women. The fetal head station at the first diagnosis of the second stage is significantly and independently associated with the duration of the second stage and correlated with the risk of operative delivery in both nulliparous and multiparous women (P<.001).


Interpretation of electron micrographs of adenovirus hexon arrays using a crystallographic molecular model.
Two types of two-dimensional arrays of purified adenovirus type 2 hexon have been obtained and analyzed by Fourier filtration of their electron micrographs. One array contained continuously close-packed hexons, distributed on a hexagonal p3 lattice, with a unit cell dimension of 94 +/- 2 A. The other array contained close-packed hexons with a regular absence, so that rings of six hexons related by sixfold symmetry formed a p6 unit cell. The cell dimension of the hexagonal array was 153 +/- 3 A, with neighboring hexons separated by 88 +/- 2 A. Smaller p6 arrays were also formed by hexons freed from complete virions on the microscope grid by treatment with distilled water. A molecular model of hexon, known from the X-ray crystallographic structure, was used to interpret Fourier-filtered images of the arrays, and to determine the relative orientations of the hexon molecules. The hexon-hexon interaction in the p3 array is that found in the virion facet, whereas that in the p6 array is a planar form of the interaction between peripentonal hexons around the vertex.


Association between n-3 polyunsaturated fatty acids in erythrocytes and metabolic syndrome in Chinese men and women.
Evidence of an association between n-3 polyunsaturated fatty acids (PUFAs) and metabolic syndrome (MS) is limited and inconsistent. We investigated the association between n-3 PUFAs in erythrocytes and the presence of MS in Chinese adults. The levels of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in erythrocytes were measured using gas chromatography in 3072 participants (900 men and 2172 women) aged 30-75 years from Guangzhou, China. Cardiometabolic factors were determined, and MS was defined using the updated Adult Treatment Panel III criteria. Other covariates were collected via interviewer-administered questionnaires. After adjusting for age and other confounders, higher levels of marine-derived n-3 PUFAs, including EPA, DPA, and DHA, were associated with a lower presence of metabolic syndrome in both men and women. The odds ratios (95 % confidence interval) for MS obtained by comparing extreme quartiles were 0.55 (0.35-0.88) (EPA), 0.54 (0.34-0.87) (DPA), 0.45 (0.27-0.73) (DHA), and 0.52 (0.32-0.84) (total n-3 PUFAs) in men (p trend <0.05 for all results); and 0.74 (0.56-0.99) (EPA), 0.73 (0.55-0.98) (DPA), 0.75 (0.56-1.02) (DHA), and 0.71 (0.53-0.96) (total n-3 PUFAs) in women, respectively. No significant association of ALA with MS was observed (p trend > 0.05). Higher levels of total n-3 PUFAs, EPA, DPA, and DHA, but not of ALA, in erythrocyte membranes are associated with a lower presence of metabolic syndrome in Chinese adults.


Pancreatic alpha cell glucagon-liver FGF21 axis regulates beta cell regeneration in a mouse model of type 2 diabetes.
Glucagon receptor (GCGR) antagonism ameliorates hyperglycaemia and promotes beta cell regeneration in mouse models of type 2 diabetes. However, the underlying mechanisms remain unclear. The present study aimed to investigate the mechanism of beta cell regeneration induced by GCGR antagonism in mice. The db/db mice and high-fat diet (HFD)+streptozotocin (STZ)-induced mice with type 2 diabetes were treated with antagonistic GCGR monoclonal antibody (mAb), and the metabolic variables and islet cell quantification were evaluated. Plasma cytokine array and liver RNA sequencing data were used to screen possible mediators, including fibroblast growth factor 21 (FGF21). ELISA, quantitative RT-PCR and western blot were applied to verify FGF21 change. Blockage of FGF21 signalling by FGF21-neutralising antibody (nAb) was used to clarify whether FGF21 was involved in the effects of GCGR mAb on the expression of beta cell identity-related genes under plasma-conditional culture and hepatocyte co-culture conditions. FGF21 nAb-treated db/db mice, systemic Fgf21-knockout (Fgf21-/-) diabetic mice and hepatocyte-specific Fgf21-knockout (Fgf21Hep-/-) diabetic mice were used to reveal the involvement of FGF21 in beta cell regeneration. A BrdU tracing study was used to analyse beta cell proliferation in diabetic mice treated with GCGR mAb. GCGR mAb treatment improved blood glucose control, and increased islet number (db/db 1.6±0.1 vs 0.8±0.1 per mm2, p<0.001; HFD+STZ 1.2±0.1 vs 0.5±0.1 per mm2, p<0.01) and area (db/db 2.5±0.2 vs 1.2±0.2%, p<0.001; HFD+STZ 1.0±0.1 vs 0.3±0.1%, p<0.01) in diabetic mice. The plasma cytokine array and liver RNA sequencing data showed that FGF21 levels in plasma and liver were upregulated by GCGR antagonism. The GCGR mAb induced upregulation of plasma FGF21 levels (db/db 661.5±40.0 vs 466.2±55.7 pg/ml, p<0.05; HFD+STZ 877.0±106.8 vs 445.5±54.0 pg/ml, p<0.05) and the liver levels of Fgf21 mRNA (db/db 3.2±0.5 vs 1.8±0.1, p<0.05; HFD+STZ 2.0±0.3 vs 1.0±0.2, p<0.05) and protein (db/db 2.0±0.2 vs 1.4±0.1, p<0.05; HFD+STZ 1.6±0.1 vs 1.0±0.1, p<0.01). Exposure to plasma or hepatocytes from the GCGR mAb-treated mice upregulated the mRNA levels of characteristic genes associated with beta cell identity in cultured mouse islets and a beta cell line, and blockage of FGF21 activity by an FGF21 nAb diminished this upregulation. Notably, the effects of increased beta cell number induced by GCGR mAb were attenuated in FGF21 nAb-treated db/db mice, Fgf21-/- diabetic mice and Fgf21Hep-/- diabetic mice. Moreover, GCGR mAb treatment enhanced beta cell proliferation in the two groups of diabetic mice, and this effect was weakened in Fgf21-/- and Fgf21Hep-/- mice. Our findings demonstrate that liver-derived FGF21 is involved in the GCGR antagonism-induced beta cell regeneration in a mouse model of type 2 diabetes.


Genetic connection between cell-wall composition and grain yield via parallel QTL analysis in indica and japonica subspecies.
Grain yield is a complicated trait, which is highly associated with biomass productivity. The cell wall is a central element of biomass, and its biogenesis contributes to plant architecture and development. However, the genetic link between cell-wall property and grain yield is largely unclear. Here, we report on identification of quantitative trait loci (QTLs) for grain yield-related traits and cell-wall composition with a set of chromosomal segment substitution lines (CSSLs) that were generated by using 9311, an indica cultivar as donor, and Nipponbare, a japonica cultivar as recipient. Nipponbare and 9311 showed significant differences in grain yield-related traits and cell-wall composition. Genotyping with molecular markers, 125 lines covering 95.6% of the whole genome of 9311 were employed for phenotypic and chemical examinations. Thirty-seven QTLs for grain yield-related traits and nineteen QTLs for cell-wall composition have been identified. In addition to correlation analysis, we found overlapped and closely linked QTLs for two sets of traits. Fine-mapping further narrowed a QTL for cellulose content together with HD17, a known QTL for heading date and grain yield, suggesting that plants may regulate cell wall biogenesis and grain yield via related means. Our study provided genetic clues for cloning QTLs for both complicated traits.


The efficiency and reliability of the Dentometer for detecting root canal length.
The accuracies of an analog-indicating electronic device, the Dentometer, and of an audio-indicating device, the Sono-Explorer, were compared to each other and to the radiographic method of tooth length determination. Readings obtained by the Dentometer were shorter, an average of 0.28 +/- 0.64 mm than those obtained by the Sono-Explorer (p less than 0.001) and 0.32 +/- 0.63 mm shorter than the results obtained by the calculated working length (p less than 0.001). No statistically significant difference was found between the readings of the Sono-Explorer and the calculated radiographic working length. The results indicate that the measurements calculated by the radiographic method were longer than those obtained by the electronic method of tooth length determination. The statistically significant difference found between the two devices indicates that to determine the accuracy of electronic devices, they should be tested and compared to other methods or devices.


Desiccation tolerant 'resurrection' grasses from Kenya and West Africa.
Only a very small proportion of angiospermae have foliage which can recover (within 24 h) from full airdryness. The number of such plants was extended by five grass species, in the genera Eragrostis, Sporobolus and Tripagon, and by two sedges, Kyllinga spp. The basal leaf meristematic zones in most species survived equilibration to air of 0 to 5% RH, whereas mature leaf tissue in most survived 5 to 30% RH.


Cholera amid COVID-19: Call from three nations; India, Bangladesh, and Nepal.
Covid-19 was a major pandemic of the 21st century that flinched away every individual worldwide. The extensive impact of this rapidly spreading deadly virus doomed the health care systems with the unexpected wave wreaked havoc leading to a global health crisis. It has been a high burden on the functioning existing medical system, overloads health professionals, disruption of the medical supply chain. The economy of the nations has been at losses with a significant slowing down in revenue growth over the past 2 years. After taking its toll, drawing away other diseases including cholera. The three developing nations; India, Bangladesh and Nepal, are now at the verge of facing an outbreak of Cholera. It is not surprising to hear cholera in this nation but the fact that its negligence due to Covid-19 pandemic and monkeypox along with a crumbled health system due to the pandemic has made these nations vulnerable for health crisis. Along with this three nations, cholera has made its way to different parts of this globe and it is high time that attention must be drawn towards it as mismanagement could even cause life.


Search trends preceding increases in suicide: A cross-correlation study of monthly Google search volume and suicide rate using transfer function models.
Various associations between monthly Google search volumes (MGSVs) and monthly suicide rates (MSRs) have been reported. However, these studies often analyzed a limited number of search terms using suboptimal statistical methods. While controlling for spurious associations, this study examined a wide array of suicide-related search terms to elucidate if their MGSVs correlated with future MSRs. MGSVs of 111 candidate suicide-related terms were calculated by averaging 10 time-series data per term obtained from Google Trends. Box-Jenkins transfer function modeling was applied to time-series data of MGSV and MSR among the total, male, and female populations of the United States between 2004 and 2017. Cross-correlation coefficients between MGSVs and MSRs were calculated at lags -3, -2, and -1. Sensitivity analysis identified cross-correlations whose direction and significance (p<0.05) persisted in two other time spans: 126 and 84 months. Eighty-nine terms were analyzed. MGSVs of 31 terms significantly correlated with MSRs in the total, male, or female population. In the sensitivity analysis, three terms stably exhibited significant positive correlation: "generalized anxiety disorder" (total; lag -3), "anxiety disorder" (total and male; lag -3), and "laid off" (total, male, and female; lag -2). The term sleep problem (total and female; lag -1) consistently showed significant negative correlations. Sex- or age-specific search-volume data, lags of less than a month, and potential confounding factors of MGSV and MSR were not explored. trends in MGSV of four terms tend to precede changes in MSR. These terms may enable more accurate forecasting of future suicides.


A suppressor of transcriptional activity is present upstream from the rat c-Ha-ras promoter.
We report the presence of an element in the rat c-Ha-ras 5'-flanking region that has a suppressive effect on the promoter of this gene. Promoter activity was determined using constructs of different regions of the c-Ha-ras 5'-flanking region linked to the reporter gene chloramphenicol acetyl transferase (CAT) transfected into NIH-3T3 cells. The presence of the tract 400 base-pairs upstream from the promoter region reduced promoter activity tenfold. This suppressor element was effective in either orientation and was not produced by other DNA fragments of similar length. Transfection with different amounts of plasmid suggested that a trans-acting factor in limiting amounts was acting on the suppressor region. Gel-retardation assays demonstrated that a nuclear protein was present in 3T3 cells that specifically interacted with the 400-base fragment containing the suppressor element.


A review of spatial Markov models for predicting pre-asymptotic and anomalous transport in porous and fractured media.
Heterogeneity across a broad range of scales in geologic porous media often manifests in observations of non-Fickian or anomalous transport. While traditional anomalous transport models can successfully make predictions in certain geological systems, increasing evidence suggests that assumptions relating to independent and identically distributed increments constrain where and when they can be reliably applied. A relatively novel model, the Spatial Markov model (SMM), relaxes the assumption of independence. The SMM belongs to the family of correlated continuous time random walks and has shown promise across a wide range of transport problems relevant to natural porous media. It has been successfully used to model conservative as well as more recently reactive transport in highly complex flows ranging from pore scales to much larger scales of interest in geology and subsurface hydrology. In this review paper we summarize its original development and provide a comprehensive review of its advances and applications as well as lay out a vision for its future development.


[A case of severe intravascular hemolysis after double mechanical heart valve implantation].
A case report of a patient with a triple cardiac valve replacement complicated by severe postoperative intravascular hemolysis is presented. The patient had neither prosthetic valvular dysfunction nor paravalvular leak and had an excellent hemodynamic response to the operation. Replacement of the aortic and mitral prostheses with stented porcine prosthesis alleviated the problem.


Persistent painless ST-segment depression after exercise testing and the effect of age.
The relation between the duration of ischemic ST-segment depression (1 mm or more 60 ms after the J point) and the clinical awareness of chest pain was studied in 31 patients (aged 39-73 years) undergoing symptom-limited, graded treadmill exercise testing. The response of these patients to nitrate therapy (spray or sublingual tablet) given immediately on cessation of exercise was also studied. During exercise, angina pectoris appeared at an estimated workload of 4.6 +/- 2.2 metabolic equivalents (METS) (mean +/- SD), and pathological ST-segment depression at 4.9 +/- 1.9 METS (p = NS.) On cessation of exercise, angina disappeared after 3.0 +/- 1.9 min, but ST-segment depression persisted for more than twice as long (6.6 +/- 4.1 min) (p less than 0.0001). The ratio of time to ST-segment recovery/time to relief of pain (a quantitative measure of silent ischemia during recovery) increased with age (r = 0.49, p = 0.002), and in 16 patients over 60 years of age was higher than in 15 younger patients (3.6 +/- 2.5 vs. 2.1 +/- 1.4) (p less than 0.04). The silent ischemia ratio after exercise tended to decrease, although not significantly so (p = 0.2), in patients who received oral nitrates; there was no difference in the response to spray or tablet in this regard. We conclude that ST-segment depression frequently persists after relief of exercise-induced angina pectoris and more so in elderly patients.


Magnesium-Encapsulated Injectable Hydrogel and 3D-Engineered Polycaprolactone Conduit Facilitate Peripheral Nerve Regeneration.
Peripheral nerve injury is a challenging orthopedic condition that can be treated by autograft transplantation, a gold standard treatment in the current clinical setting. Nevertheless, limited availability of autografts and potential morbidities in donors hampers its widespread application. Bioactive scaffold-based tissue engineering is a promising strategy to promote nerve regeneration. Additionally, magnesium (Mg) ions enhance nerve regeneration; however, an effectively controlled delivery vehicle is necessary to optimize their in vivo therapeutic effects. Herein, a bisphosphonate-based injectable hydrogel exhibiting sustained Mg2+ delivery for peripheral nerve regeneration is developed. It is observed that Mg2+ promoted neurite outgrowth in a concentration-dependent manner by activating the PI3K/Akt signaling pathway and Sema5b. Moreover, implantation of polycaprolactone (PCL) conduits filled with Mg2+ -releasing hydrogel in 10 mm nerve defects in rats significantly enhanced axon regeneration and remyelination at 12 weeks post-operation compared to the controls (blank conduits or conduits filled with Mg2+ -absent hydrogel). Functional recovery analysis reveals enhanced reinnervation in the animals treated with the Mg2+ -releasing hydrogel compared to that in the control groups. In summary, the Mg2+ -releasing hydrogel combined with the 3D-engineered PCL conduit promotes peripheral nerve regeneration and functional recovery. Thus, a new strategy to facilitate the repair of challenging peripheral nerve injuries is proposed.


Effects of cardiac resynchronization therapy on ventricular remodeling.
Remodeling reflects the structural and functional deterioration that occurs in heart failure. Indices of remodeling constitute an important marker of the severity of heart failure, and reverse remodeling is an accepted goal in the treatment of heart failure. Cardiac resynchronization therapy (CRT) has been shown to reverse the remodeling process by improving ventricular size, shape, and mass and reducing mitral regurgitation in the short and long term. Diastolic function, right ventricular size, and atria exhibit reverse remodeling. Trials of medical therapy for heart failure strongly link remodeling indices with outcomes, and emerging data suggest that remodeling indices may be among the most accurate predictors of long-term morbidity and mortality in heart failure patients with CRT devices. This review discusses remodeling and focuses on the evidence for CRT-induced reverse remodeling.


Optimal techniques for the immunocytochemical demonstration of beta-thromboglobulin, platelet factor 4, and fibrinogen in the alpha granules of unstimulated platelets.
The distribution of beta-thromboglobulin, platelet factor 4, and fibrinogen in unstimulated platelets was investigated by several immunocytochemical techniques. All three substances were found to be localized in the majority of platelet alpha granules either by immunoperoxidase methods on saponin-treated platelets or by colloidal gold immunoconjugates on frozen thin sections. The optimal conditions for preparing and fixing platelets for immunocytochemistry were also determined. Platelets obtained from blood dripped directly into fixative or anticoagulated blood were compared systematically with respect to shape. Temperature was found to be the most important variable. Immediately fixed platelets were generally disc-shaped, regardless of the temperature of the fixative. Reducing the temperature of blood (stored with anticoagulant) before fixation resulted in more swollen and fewer disc-shaped platelets. However, if the blood was mixed with an anticoagulant and maintained at 37 degrees C for 1 h before fixation, the same number of disc-shaped platelets were present as in samples from blood fixed immediately. The intracellular localization of beta-thromboglobulin, platelet factor 4, and fibrinogen was consistent regardless of platelet preparatory procedure, but several technical problems were encountered with respect to plasma membrane labelling when control experiments were analysed. Immediately fixed, non-permeabilized platelet plasma membranes were always labelled, no matter which control substances or immunoperoxidase markers were used. However, when platelets were washed by centrifugation, the plasma membranes were negative. Exposure to saponin markedly diminished labelling of the plasma membranes. Optimal techniques for the immunocytochemical demonstration of these alpha granule proteins in platelets are presented in this report.


Effect of a single application of silver diamine fluoride on root caries after 12 months in institutionalised older adults-A randomised clinical trial.
Silver diamine fluoride (SDF) has been shown to be highly effective against caries, in particular for arresting root surface caries and for dentine caries in primary teeth. SDF may complement fluoride varnish routines for treatment of root caries in nursing home residents. The aim of this randomised, single-blinded, placebo-controlled trial was to evaluate the additive effect of a single annual application of SDF for prevention and treatment of incipient root caries in older adult nursing home residents. Four hundred older adult nursing home residents (≥70 years old) with at least one exposed root surface (on teeth 15, 14, 13, 23, 24, or 25) were identified during routine dental examination visits in the domiciliary dental care setting. Eligible patients, who were able to understand the implication of consenting to the study, were invited to participate. Their cleaned root surfaces were randomly allocated to treatment with SDF (Advantage Arrest Silver Diamine Fluoride 38%, Advantage Arrest, LLC, Redmond, OR 97756, USA, Lot 16 152) or with placebo (tap water), each for 1 minute. Of the 400 eligible individuals, 42 declined to participate and two forms were destroyed. The remaining 356 participants (89.0%; mean age 87.7 years) were randomly allocated, with 174 going to the SDF group and 182 to the placebo group. At 1 year, 273 participants (76.7%) were available for assessment: 135 in the SDF group and 138 in the placebo group. By that time, 109 individuals (39.9%) demonstrated root caries progression or regression. Among those 118 (16.7%) of the 708 included root surfaces had developed caries There were no statistically significant differences in the primary outcome related to treatment with SDF or placebo, at either patient or root surface level. Based on the finding of this clinical trial, it is concluded that a single SDF application to complement a risk-based preventive programme including fluoride varnish applications did not have a statistically significant additional preventive effect on root caries development in a group of older adult nursing home residents with limited caries activity and cognitive capacity to cooperate in oral care activities.


Mercury-binding capacity of organic and inorganic selenium in rat blood and liver.
The mercury-binding capacity of seleno-DL-methionine and selenium dioxide was assessed in male Wistar rats. Mercury was supplied as fish loaves made of northern pike or rainbow trout. We used a selenium concentration of 3.4 mg/kg fish, about sixfold compared to the equivalent quantity of mercury. Seleno-DL-methionine had a tendency to increase both methyl mercury and total mercury in blood, although it also seemed to reduce the proportion of methyl mercury of total mercury. Selenium dioxide lowered mercury levels by 24-29% both in the blood and in the liver of rats that were fed with northern pike.


Arabidopsis YAK1 regulates abscisic acid response and drought resistance.
Abscisic acid (ABA) is an important phytohormone that controls several plant processes such as seed germination, seedling growth, and abiotic stress response. Here, we report that AtYak1 plays an important role in ABA signaling and postgermination growth in Arabidopsis. AtYak1 knockout mutant plants were hyposensitive to ABA inhibition of seed germination, cotyledon greening, seedling growth, and stomatal movement. atyak1-1 mutant plants display reduced drought stress resistance, as evidenced by water loss rate and survival rate. Molecular genetic analysis revealed that AtYak1 deficiency led to elevated expression of stomatal-related gene, MYB60, and down-regulation of several stress-responsive genes. Altogether, these results indicate that AtYak1 plays a role as a positive regulator in ABA-mediated drought response in Arabidopsis.


Spatial patterns in pollution discharges from livestock and poultry farm and the linkage between manure nutrients load and the carrying capacity of croplands in China.
The rapid development of livestock and poultry farming in China has resulted in an increasing threat of water pollution. In particular, mitigating livestock-related pollutant discharges is a key issue for environmental sustainability, especially for inland surface water bodies. In order to ensure the effective control of pollution and the efficient utilization management of livestock manure, spatially explicit surveys of pollutant generation and discharge from the livestock sector must be performed. In the present study, we estimated the grid cell-level distributions in the generation and discharge of four typical pollutants (chemical oxygen demand, ammonium nitrogen, total nitrogen and total phosphorus) from the livestock sector across the country with a spatial resolution of 30 arc-seconds. The distributions were estimated using the most recent pollution source census data and multi-sourced ancillary materials by a dasymetric mapping approach. We further investigated the feasibility of the resource utilization of livestock manure by comparing manure-source nutrients with the carrying capacity of adjacent croplands. Our results show that low-intensive farming generated and discharged the majority of livestock farming pollution, with other cattle and pigs breeding identified as the two major sources of pollution from the livestock sector. Southwest, Central and East China suffered the highly densified pollutants generation and discharges. Furthermore, cropland exceeding its carrying capacity was concentrated in these regions. Our findings provide additional insights into livestock and poultry farming in the context of relocation, strengthening regulation, transforming breeding operations, and rationalizing the resource use of manure, all of which are important measures for the sustainable development of both agriculture and the environment.


A methodology for resource allocation in health care for South Africa. Part I. Rationale and prerequisites.
A strategy for the equitable allocation of health care resources is needed in South Africa. The existing health administrative structures are obstacles to achieving this goal. An attempt is made to describe a framework in which the prerequisites for the equitable allocation of resources are a major restructuring of health services into a number of regional health authorities in a unified health service, and to establish a formula which is adapted from the RAWP (Resource Allocation Working Party) model used in the UK.