Dietary supplementation with selenomethylselenocysteine produces a differential proteomic response.
Organic forms of selenium offer important health benefits including cancer prevention. Selenium intake has been traditionally quantified as glutathioneperoxidase activity or selenium concentration in blood or tissues. However, these indexes do not reflect organic selenium intake. Effect of dietary supplementation of rats with selenomethylselenocysteine on the blood plasma proteome was investigated in order to detect protein abundance differences between experimental (supranutritional selenium supplementation) and control [minimum selenium dose and sodium selenate instead of selenomethylselenocysteine (SeMSeCys)] groups. Four experimental groups and six control groups consisting of six rats each were fed with base diet supplemented with SeMSeCys or sodium selenate in different concentrations for different periods of time. A proteomic approach, comprising two-dimensional gel electrophoresis and mass spectrometry, was used to assess protein abundance in blood plasma. Statistically significant differences in the abundance of some proteins were detected in all the experimental groups. Four proteins were found to increase their abundance in response to the experimental conditions: apolipoprotein E, haptoglobin and alpha-1-antitrypsin abundance was related to the extent of supplementation period and transthyretin in response to SeMSeCys dose. Apolipoprotein E and transthyretin were not differentially expressed when diets were supplemented with sodium selenate instead of SeMSeCys. We postulate that these proteins are potential biomarkers of chemoprotective selenium intake.


Crossbreeding of exotic and indigenous cattle in Nigeria--haematological correlates.
The blood values of the German Brown, N'Dama and their three-quarter, half and quarter hybrids were studied to ascertain if and how some haematological parameters changed with crossbreeding. It was found that the red blood cell (RBC) and white blood cell (WBC) count and packed cell volume percentage (PCV) were significantly higher (P less than 0.01) in the N'Dama than in the German Brown; the crosses had values which were intermediate as compared to the two parent breeds. Generally, the changes in the mean blood values paralleled changes in the expected genotypes resulting from crossbreeding of the two parent breeds. The tendency of the blood values to change in direct proportion to the degree of N'Dama contribution was strongest for the WBC, followed by the PCV and RBC, respectively. A small random sample for leucocyte differential count did not reveal any differences amongst the genotypic groups.


Good clinical results with autologous matrix-induced chondrogenesis (Amic) technique in large knee chondral defects.
Autologous matrix-induced chondrogenesis (AMIC) is a treatment for focal full-thickness cartilage defects combining microfracturing with an exogenous I/III collagen matrix (Chondro-Gide). The aim of the present study was to determine the 7 years outcomes of patients treated with the AMIC technique for knee chondral defects larger than 2 cm2. The hypothesis was that the positive short-term outcomes achieved in the previous series would not deteriorate at a 7-year follow-up. Twenty-one patients treated with the AMIC technique were retrospectively analysed. Patients were assessed through the IKDC subjective knee evaluation questionnaire and the Lysholm scoring system. All patients underwent a complete imaging study including radiographs and magnetic resonance. The median defect size was found to be 4.3 (range 2.9-8) cm2. At a median follow-up of 7 (±1.4) years, the mean IKDC score improved from 31.7 (±8.9) points preoperatively, to 80.6 (±5.3) at the latest follow-up (p < 0.05). The mean Lysholm score improved from 38.8 (±12.4) points preoperatively to 72.6 (±19.5) points at the last follow-up (p < 0.05). At the last follow-up, 76.2% of patients were satisfied or extremely satisfied with their outcomes, while 66.6% of patients showed good quality repair tissue on magnetic resonance imaging. AMIC was found to be an effective method to treat full-thickness knee chondral defects larger than 2 cm2, with significant clinical and functional improvement maintained over a 7-year follow-up. IV.


Successful embryo transfer in the silver fox (Vulpes vulpes).
Surgical embryo transfer in the silver fox was investigated as part of a larger project concerning the conservation of endangered canine species using modern artificial reproduction techniques with the farmed fox as a model. The animals were chosen on the basis of synchrony in natural oestrus. The timing of ovulation and artificial insemination was determined by measuring electrical resistance in the vagina. Twenty-nine embryos were flushed from eight humanely killed donor females and transferred surgically into the uteri of eight recipients. One recipient female gave birth to two male pups 47 days after the transfer of four expanded blastocysts and one embryo at the 16-cell stage derived from a donor female flushed 10 days after artificial insemination.


Corticolimbic Circuitry in Chronic Pain Tracks Pain Intensity Relief Following Exposure In Vivo.
A subset of patients with chronic pain who receive exposure in vivo (EXP) treatment experience clinically relevant relief of pain intensity. Although pain relief is not an explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some patients but not others. This longitudinal study therefore aimed to characterize brain plasticity as well as to explore pretreatment factors related to pain relief. Resting-state functional magnetic resonance imaging data were acquired in 30 patients with chronic pain. Twenty-three patients completed EXP, and 6-month follow-up data were available in 20 patients (magnetic resonance imaging data in 17 patients). Pain-free control data were acquired at two time points (n = 29, n = 21). Seed-based resting-state functional connectivity (rsFC) analyses were performed, with seeds in the amygdala, hippocampus, and nucleus accumbens. Pain relief after EXP was highly variable, with 60% of patients reporting a clinically relevant improvement. Amygdala rsFC with the middle frontal gyrus decreased significantly over time in patients but was not associated with pain relief. In contrast, greater pain relief was associated with greater decreases over time in hippocampus rsFC with the precuneus, which was related to reductions in catastrophizing (EXP therapeutic target) as well. Greater pain relief was also associated with lower pretreatment rsFC between nucleus accumbens and postcentral gyrus. While changes in hippocampus rsFC were associated with pain relief after EXP, pretreatment nucleus accumbens rsFC showed potential prognostic value. Our findings further support the importance of corticolimbic circuitry in chronic pain, emphasizing its relation to pain relief and identifying potential underlying mechanisms and prognostic factors, warranting further testing in independent samples.


Modulating Nrf-2/HO-1, apoptosis and oxidative stress signaling pathways by gabapentin ameliorates sepsis-induced acute kidney injury.
Globally, sepsis, which is a major health issue resulting from severe infection-induced inflammation, is the fifth biggest cause of death. This research aimed to evaluate, for the first time, the molecular effects of gabapentin's possible nephroprotective potential on septic rats by cecal ligation and puncture (CLP). Sepsis was produced by CLP in male Wistar rats. Evaluations of histopathology and renal function were conducted. MDA, SOD, GSH, TNF-α, IL-1β, and IL-6 levels were measured. qRT-PCR was utilized to determine the expression of Bax, Bcl-2, and NF-kB genes. The expression of Nrf-2 and HO-1 proteins was examined by western blotting. CLP caused acute renal damage, elevated the blood levels of creatinine, BUN, TNF-α, IL-1β, and IL-6, reduced the expression of Nrf-2 and HO-1 proteins and the Bcl-2 gene expression, and upregulated NF-kB and Bax genes. Nevertheless, gabapentin dramatically diminished the degree of the biochemical, molecular, and histopathological alterations generated by CLP. Gabapentin reduced the levels of proinflammatory mediators and MDA, improved renal content of GSH and SOD, raised the expression of Nrf-2 and HO-1 proteins and Bcl-2 gene, and reduced the renal expression of NF-kB and Bax genes. Gabapentin mitigated the CLP-induced sepsis-related acute kidney injury through up-regulating Nrf-2/HO-1 pathway, repressing apoptosis, and attenuating the oxidative stress status by reducing the levels of the proinflammatory mediators and enhancing the antioxidant status.


The local microbiome after pediatric bladder augmentation: intestinal segments and the native urinary bladder host similar mucosal microbiota.
Next-generation sequencing (NGS) techniques have provided novel insights into the microbiome of the urinary bladder (UB). In children after bladder augmentation using either ileum (ileocystoplasty, ICP) or colon (colocystoplasty, CCP), the fate of the mucosal microbiome introduced into the urinary tract remains unknown. The aim was to compare the mucosal microbiome of the native UB vs the augmented intestinal segment (IS) using NGS. Twelve children after bladder augmentation (ICP n = 6, CCP n = 6) were included. Biopsies were taken during routine postoperative cystoscopy from the native UB and the IS. Specimens underwent whole-genome DNA extraction, 16S rRNA gene amplification, NGS, and Quantitative Insights Into Microbial Ecology (QIIME) data analysis. Downstream statistical data analyses were performed in Calypso. Patients' median age at the time of surgery was 11 years (6-17 years), and the median interval between augmentation and sampling was 7 years (4-13 years). α-Diversity (Shannon diversity index) was not significantly different between IS vs UB, ICP vs CCP, and male vs female. No general differences in the overall bacterial pattern (β-diversity) were found between IS, UB, ICP, and CCP groups. The groups overlapped in principal coordinate analysis (PCoA) and non-metric multidimensional scaling (NMDS) analysis (Figure). Age at sampling had a statistically significant influence on β-diversity at the genus level. Corynebacterium, Pseudoxanthomonas, Lactobacillus, Flavobacterium, and Micrococcus were the most dominating taxa detected over all samples. There was an obvious dominance of the genus Corynebacterium in the samples taken from the UB and IS in both ICP and CCP patients. Limitations of this study include the relatively small number of patients. After bladder augmentation, the native UB and augmented ISs (ICP and CCP) host similar microbiota despite their distinct differences of originating mucosal anatomy.


Ambulatory electronic medical records for large practices.
In summary, providers and vendors alike have made great strides in EMR adoption among physicians in large-scale ambulatory practices. However, there is still work to be done in the areas of physician use, adoption obstacles, workflow and physician satisfaction. As vendors continue to enhance EMR technology, advance workflow and solve challenges with integration and physician acceptance, adoption will grow and providers will be even closer to their specific efficiency, safety and effectiveness goals.


SCFFBXO28-mediated self-ubiquitination of FBXO28 promotes its degradation.
The F-box protein is the substrate recognition subunit of SCF (SKP1/CUL1/F-box) E3 ubiquitin ligase complex, a multicomponent RING-type E3 ligase involved in the regulation of numerous cellular processes by targeting critical regulatory proteins for ubiquitination. However, whether and how F-box proteins are regulated is largely unknown. Here we report that FBXO28, a poorly characterized F-box protein, is a novel substrate of SCF E3 ligase. Pharmaceutical or genetic inhibition of neddylation pathway that is required for the activation of SCF stabilizes FBXO28 and prolongs its half-life. Meanwhile, FBXO28 is subjected to ubiquitination and cullin1-based SCF complex promotes FBXO28 degradation. Moreover, deletion of F-box domain stabilizes FBXO28 and knockdown of endogenous FBXO28 strongly upregulates exogenous FBXO28 expression. Taken together, these data reveal that SCFFBXO28 is the E3 ligase responsible for the self-ubiquitination and proteasomal degradation of FBXO28, providing a new clue for the upstream signaling regulation for F-box proteins.


Differences in the fiber composition of the pyramidal tract in two- and 14-month-old rats.
The present study is aimed at an electron-microscopic morphometrical analysis of the pyramidal tract of 14-month-old rats at the level of the pyramis medullae and the second cervical segment, and a comparison with data obtained for rats of two months of age. Between 2 and 14 months of age there is, at the level of the pyramis medullae of the left pyramidal tract, a statistically significant increase of the number of myelinated fibers, from 91,000 to 118,000, whereas the total number of unmyelinated fibers decreases from 133,000 to 101,000. On the right side at the same level there is no statistically significant change in the number of myelinated fibers, whereas there is a significant decrease of unmyelinated fibers at this side, from 148,000 to 89,000. At the second cervical level, a statistically significant increase in the number of myelinated fibers has been noted at both sides (from 43,000 to 60,000) between 2 and 14 months, whereas the mean total number of unmyelinated fibers at this level decreases somewhat (from 35,000 to 28,000), but is not statistically significant. Several processes which might be involved in the age-related changes observed are discussed, including the possibility of a shift from unmyelinated fibers to myelinated ones, withdrawal of corticobulbar fibers and ongoing outgrowth of myelinated corticofugal fibers after two months of age, and a summarizing scheme is presented. We conclude that the pyramidal tract of the rat changes in composition after the age of two months and that continuing outgrowth of myelinated corticospinal fibers is an important aspect of this continuing development.


Left ventricular apical and atrial appendage thrombus with hypertrophic cardiomyopathy in sinus rhythm: a case report.
A 47-year-old female with a history of untreated hypertension and diabetes mellitus was referred because of a left ventricular echocardiographic mass with congestive heart failure. At the time of admission, she had already had a cardio-embolic stroke with loss of recent memory and slight paralysis of the right upper arm. It was difficult to distinguish between thrombus and tumor. However, her clinical condition required surgical resection as soon as possible. We performed cardiac CT to evaluate the coronary arteries and to scan the mass at the left ventricular apex. This CT evaluation revealed another mass at the left atrial appendage. Thus, these two masses were highly suggestive of thrombi. Subemergency surgical resection of the two masses and a part of the myocardium at the left ventricular apex was successfully performed. The pathological results showed that both the mass in the left ventricular apex and the mass in the left atrial appendage were thrombi, and the myocardial disarray confirmed the echocardiographic diagnosis as hypertrophic cardiomyopathy.


Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.
A 57-year-old woman, receiving TNF-alpha inhibitor adalimumab for psoriasis, presented with early Lyme neuroborreliosis (Bannwarth's syndrome). Discontinuation of adalimumab and 14-day therapy with ceftriaxone resulted in a smooth course and favorable outcome of Lyme borreliosis. This is the first report on Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.


Undergraduate physical activity and depressive symptoms: a national study.
To study the effects of college students' physical activity and gender on depressive and suicidal symptoms. The National College Health Assessment survey was administered to college students nationwide. Data were analyzed with 4x2 ANOVAs and Games-Howell post hoc tests when appropriate. More frequent physical activity related to less frequent depressive symptoms and consideration of suicide, but not with attempted suicide. Males reported depressive symptoms less frequently than did females. Depression research has implications for an increasingly sedentary college population. Institutions should provide increased access and knowledge pertaining to emotional health and psychological benefits through physical activity.


Disaster Relief Nurses: Exploring the Impetus to Respond to Multiple Efforts.
Little is known about the impact that disaster volunteerism has on nurses. It is important to hear the experiences of those who return again to better understand the reasons that call them back. Using grounded theory methodology, 20 nurses who responded to more than one disaster event participated in semistructured interviews. Capacity for the art of nursing, confidence in performing the role, fostering the team among the chaos, and humanistic symbiosis emerged, leading to a core category, facilitating self-transcendence, guided by Reed's middle-range theory. With repeat deployments come enhanced personal rewards that provide meaningful opportunities for self-transcendence.


Dataset for the performance of 15 lumbar movement control tests in nonspecific chronic low back pain.
The ability to actively control movements of the lumbar spine (LMC) is believed to play an important role in non-specific chronic low back pain (NSCLBP). However, because NSCLBP is a multifactorial problem and LMC a complex ability, different aspects of LMC are still debated including the influence of pain, the question whether LMC is a cause or consequence of NSCLBP or whether differences in LMC are due to population variance. The complexity of LMC is reflected in the large number of described tests, hence it is not possible to evaluate LMC by a single test. LMC ability should be understood as a latent construct. The structure of LMC and how to summarize results of different single LMC tests is unknown. The dataset provided in this article was used to analyse the structural validity of LMC in NSCLBP. 277 participants (age 42.4 years (± 15.8), 61% female) performed 15 different test movements. 21 experienced physiotherapists rated the performance of each test movement on a nominal scale (correct/incorrect including the direction of test movement). A test was rated as "incorrect" if movement in the lumbar spine occurred prematurely and/or excessively based on the visual observation of a trained physiotherapist. In addition to the judgement whether the test performance was correct/incorrect the direction of test movement and the presence of pain was noted. For statistical analysis, raw data was converted to a binary scale (correct/incorrect). Item response theory (IRT) is recommended to analyse the data because the underlying statistical model is reflective, the single LMC tests are binary scaled (correct/incorrect) and the underlying ability (LMC) measured on a continuous scale. First dimensionality and local independence were analysed, followed by selection of the best fitting IRT model. Finally, IRT modelling was used to describe the psychometric properties of each item and each battery of tests. The datasets provided in this article are useful for calibration and for group comparisons. Besides they support a better understanding of LMC. ***Link to publication of original article in "musculoskeletal science and practice"**.


Population and structure of nerve cells in mouse submandibular ganglion.
The anatomy of the mouse submandibular ganglion, and population and fine structure of nerve cells were studied by light and electron microscopy. The submandibular ganglion is a plexus containing up to forty ganglia along the main and the smaller excretory ducts of the submandibular gland. Measurements of the volume of nerve cell bodies display a pattern of distribution with two main peaks, suggesting the presence of large and small types of the intraganglionic neuron. The large neurons mainly have axo-dendritic synapses in which the postsynaptic element is a small spine-like process, while axo-somatic synapses are more common in the small neurons. In some small neurons nuclear chromatin is unusually conspicuous, and accumulations of vesicles of fairly uniform size occur within the cell body. Decentralized ganglia contain almost no synapses showing the absence of definite interneurons.


Recent developments of novel matrices and on-tissue chemical derivatization reagents for MALDI-MSI.
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a fast-growing technique for visualization of the spatial distribution of the small molecular and macromolecular biomolecules in tissue sections. Challenges in MALDI-MSI, such as poor sensitivity for some classes of molecules or limited specificity, for instance resulting from the presence of isobaric molecules or limited resolving power of the instrument, have encouraged the MSI scientific community to improve MALDI-MSI sample preparation workflows with innovations in chemistry. Recent developments of novel small organic MALDI matrices play a part in the improvement of image quality and the expansion of the application areas of MALDI-MSI. This includes rationally designed/synthesized as well as commercially available small organic molecules whose superior matrix properties in comparison with common matrices have only recently been discovered. Furthermore, on-tissue chemical derivatization (OTCD) processes get more focused attention, because of their advantages for localization of poorly ionizable metabolites and their' in several cases' more specific imaging of metabolites in tissue sections. This review will provide an overview about the latest developments of novel small organic matrices and on-tissue chemical derivatization reagents for MALDI-MSI. Graphical abstract.


A chemometric study of phosphodiesterase 5 inhibitors.
This work presents a chemometric classification for a set of phosphodiesterase 5 inhibitors, based on a pattern recognition method widely used in quantitative structure-activity (QSAR) studies, hierarchical cluster analysis (HCA) and principal component analysis (PCA), aiming to access the most relevant structural and physicochemical variables related to phosphodiesterase 5 inhibition and to quantify the similarity of the structures within the set of inhibitors. Our model is capable of classifying a test set of 26 known phosphodiesterase 5 inhibitors in terms of similarity, the results being consistent with published experimental data.


Nanoscale temperature measurement during temperature controlled in situ TEM using Al plasmon nanothermometry.
Over recent years, the advent of microelectromechanical system (MEMS)-type microheaters has pushed the limits of temperature controlled in situ transmission electron microscopy (TEM). In particular, by enabling the observation of the structure of materials in their application environments, temperature controlled TEM provides unprecedented insights into the link between the properties of materials and their structure in real-world problems, a clear knowledge of which is necessary for rational development of functional materials with new or improved properties. While temperature is the key parameter in such experiments, accessing the precise temperature of the sample at the nanoscale during observations still remains challenging. In the present work, we have applied aluminium plasmon nanothermometry technique that monitors the temperature dependence of the volume plasmon of Al nanospheres using electron energy loss spectroscopy for in situ local temperature determination over MEMS-type microheaters. With access to local temperatures between room temperature to 550 ∘C, we have assessed the spatial and temporal stabilities of these microheaters when they operate at different setpoint temperatures both under vacuum and in the presence of a static H2 gas environment. Temperature comparisons performed under the two environments show discrepancies between local and setpoint temperatures.


A policy case study of blood in Australia.
In 2008 the Australian government decided to remove white blood cells from all blood products. This policy of universal leucodepletion was a change to the existing policy of supplying leucodepleted products to high risk patients only. The decision was made without strong information about the cost-effectiveness of universal leucodepletion. The aims for this policy analysis are to generate cost-effectiveness data about universal leucodepletion, and to add to our understanding of the role of evidence and the political reality of healthcare decision-making in Australia. The cost-effectiveness analysis revealed universal leucodepletion costs $398,943 to save one year of life. This exceeds the normal maximum threshold for Australia. We discuss this result within the context of how policy decisions are made about blood, and how it relates to the theory and process of policy making. We conclude that the absence of a strong voice for cost-effectiveness was an important omission in this decision.


Validation of PET/MRI attenuation correction methodology in the study of brain tumours.
This study aims to compare proton density weighted magnetic resonance imaging (MRI) zero echo time (ZTE) and head atlas attenuation correction (AC) to the reference standard computed tomography (CT) based AC for 11C-methionine positron emission tomography (PET)/MRI. A retrospective cohort of 14 patients with suspected or confirmed brain tumour and 11C-Methionine PET/MRI was included in the study. For each scan, three AC maps were generated: ZTE-AC, atlas-AC and reference standard CT-AC. Maximum and mean standardised uptake values (SUV) were measured in the hotspot, mirror region and frontal cortex. In postoperative patients (n = 8), SUV values were additionally obtained adjacent to the metal implant and mirror region. Standardised uptake ratios (SUR) hotspot/mirror, hotspot/cortex and metal/mirror were then calculated and analysed with Bland-Altman, Pearson correlation and intraclass correlation reliability in the overall group and subgroups. ZTE-AC demonstrated narrower SD and 95% CI (Bland-Altman) than atlas-AC in the hotspot analysis for all groups (ZTE overall ≤ 2.84, - 1.41 to 1.70; metal ≤ 1.67, - 3.00 to 2.20; non-metal ≤ 3.04, - 0.96 to 3.38; Atlas overall ≤ 4.56, - 1.05 to 3.83; metal ≤ 3.87, - 3.81 to 4.64; non-metal ≤ 4.90, - 1.68 to 5.86). The mean bias for both ZTE-AC and atlas-AC was ≤ 2.4% compared to CT-AC. In the metal region analysis, ZTE-AC demonstrated a narrower mean bias range-closer to zero-and narrower SD and 95% CI (ZTE 0.21-0.48, ≤ 2.50, - 1.70 to 2.57; Atlas 0.56-1.54, ≤ 4.01, - 1.81 to 4.89). The mean bias for both ZTE-AC and atlas-AC was within 1.6%. A perfect correlation (Pearson correlation) was found for both ZTE-AC and atlas-AC compared to CT-AC in the hotspot and metal analysis (ZTE ρ 1.00, p < 0.0001; atlas ρ 1.00, p < 0.0001). An almost perfect intraclass correlation coefficient for absolute agreement was found between Atlas-, ZTE and CT maps for maxSUR and meanSUR values in all the analyses (ICC > 0.99). Both ZTE and atlas-AC showed a good performance against CT-AC in patients with brain tumour.


Measurement of craniocaudal catheter displacement between fractions in computed tomography-based high dose rate brachytherapy of prostate cancer.
The objective of this work is to measure the cranio-caudal displacement of catheters occurring between consecutive fractions of transrectal ultrasound (TRUS) guided high dose rate (HDR) prostate brachytherapy. Ten consecutive patients were treated with 2 fractions of 9.5 Gy TRUS guided HDR brachytherapy using dental putty for the fixation of catheters. For each patient, a CT scan with 3 mm slice thickness was acquired before each of the two fractions. Two different references were employed to measure the catheter displacement between fractions: the ischial bone as a bony marker (BM) and the center of two gold markers (COGM) implanted in the prostate. The catheter displacement was calculated by multiplying the thickness of CT slice with the difference in number of CT slices between the reference slice and the slice containing the tip of a catheter. The average (range) magnitude of caudal catheter displacement was 2.7 mm (-6.0 to 13.5 mm) for BM method and 5.4 mm (-3.75 to 18.0 mm) for COGM method, respectively. The measurement data obtained from BM and COGM methods verified that both prostate movement and catheter displacement occurred independently between fractions. The most anterior and medial two catheters (catheter position 8 and 12) had the greatest tendency to be displaced in the caudal direction because they were located at the most distant position from the fulcrum, susceptible to the rotation of the dental putty in lateral plane due to the movement of patient legs between fractions. In conclusion, the use of both BM and COGM methods can demonstrate the prostate and catheter movement relative to the BM between fractions. We found a pattern of catheter displacement using our technique. Based on our finding further improvement of our results may be possible by modification of our current technique.


Minimally Invasive Valve Replacement for Late Tricuspid Regurgitation After Left-Sided Valve Surgery.
Late severe tricuspid regurgitation after left-sided valve surgery can negatively affect long-term prognosis and quality of life. Because of extensive surgical trauma and poor right heart function, perioperative mortality after reoperation for tricuspid regurgitation historically remained high. A number of minimally invasive techniques were adopted at our center recently, including endoscopy-assisted right minithoracotomy, vacuum-assisted single femoral venous drainage without dissecting or snaring vena cava, direct right atriotomy through pericardium, and the beating-heart technique. Moreover, the tricuspid valves were replaced with bioprostheses in the majority of those patients at our center. The midterm outcomes of minimally invasive bioprosthetic tricuspid valve replacement were favorable.


Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 2. Design, synthesis, and evaluation of a novel series of phenyl oxazole derivatives.
Synthesis and initial in vitro evaluation of a novel series of phenyl oxazole derivatives are described. An SAR study of the novel dual-acting TRA/TSI agent has revealed that the lipophilicity of the oxazole amide substituents greatly influences the TRA activity but not the TSI. The chain length of the alkenoic acid side chain affects both TRA and TSI. The optimal chain length for the combined activities was found to be n = 4 (heptenoic acid).


Divergent Synthesis of Cyclopropane-Containing Lead-Like Compounds, Fragments and Building Blocks through a Cobalt Catalyzed Cyclopropanation of Phenyl Vinyl Sulfide.
Cyclopropanes provide important design elements in medicinal chemistry and are widely present in drug compounds. Here we describe a strategy and extensive synthetic studies for the preparation of a diverse collection of cyclopropane-containing lead-like compounds, fragments and building blocks exploiting a single precursor. The bifunctional cyclopropane (E/Z)-ethyl 2-(phenylsulfanyl)-cyclopropane-1-carboxylate was designed to allow derivatization through the ester and sulfide functionalities to topologically varied compounds designed to fit in desirable chemical space for drug discovery. A cobalt-catalyzed cyclopropanation of phenyl vinyl sulfide affords these scaffolds on multigram scale. Divergent, orthogonal derivatization is achieved through hydrolysis, reduction, amidation and oxidation reactions as well as sulfoxide-magnesium exchange/functionalization. The cyclopropyl Grignard reagent formed from sulfoxide exchange is stable at 0 °C for > 2 h, which enables trapping with various electrophiles and Pd-catalyzed Negishi cross-coupling reactions. The library prepared, as well as a further virtual elaboration, is analyzed against parameters of lipophilicity (ALog P), MW and molecular shape by using the LLAMA (Lead-Likeness and Molecular Analysis) software, to illustrate the success in generating lead-like compounds and fragments.


Peak and fixed-time high-sensitive troponin for prediction of infarct size, impaired left ventricular function, and adverse outcomes in patients with first ST-segment elevation myocardial infarction receiving percutaneous coronary intervention.
The clinical use of advanced imaging modalities for early determination of infarct size and prognosis is limited. As a specific indicator of myocardial necrosis, cardiac troponin T (cTnT) can be used as a surrogate measure for this purpose. The present study sought to investigate the use of peak and serial 6-hour fixed-time high-sensitive (hs) cTnT for estimation of infarct size, left ventricular (LV) function, and prognosis in consecutive patients with ST-segment elevation myocardial infarction. The infarct size was expressed as the 48-hour cumulative creatine kinase release. LV function at 3 months was assessed using the echocardiographic wall motion score index and LV ejection fraction using radionuclide ventriculography. Adverse outcomes, comprising all-cause death, implantable cardioverter-defibrillator implantation, or hospitalization for heart failure, were recorded at 1 year of follow-up. In 188 patients, the peak and all fixed-time values correlated significantly with the 48-hour cumulative creatine kinase release, wall motion score index, and LV ejection fraction. The hs-cTnT value at 24 hours demonstrated the greatest correlation (r = 0.86, r = 0.47, and r = -0.59, respectively; p <0.001 for all). In the multivariate regression models adjusted for the clinical parameters, almost all were independently associated with the 48-hour cumulative creatine kinase release, wall motion score index, and LV ejection fraction, with the hs-cTnT value at 24 hours having the largest effect. Moreover, all cTnT values independently predicted adverse outcomes, again, with the hs-cTnT value at 24 hours showing the largest influence (hazard ratio 3.77, 95% confidence interval 2.12 to 6.73, p <0.001). In conclusion, not only peak, but all fixed-time hs-cTnT values were associated with infarct size, LV function at 3 months, and adverse outcomes 1 year after ST-segment elevation myocardial infarction. The value 24 hours after the onset of symptoms had the closest associations with all outcomes. Therefore, serial sampling for a peak value might be redundant.


Inviting family to be present during cardiopulmonary resuscitation: Impact of education.
Encouraging and permitting family members to stay together during cardiopulmonary resuscitation benefits the patient, family and staff. Health care professionals (HCP) attitudes and experiences are documented as barriers to initiating family presence during cardiopulmonary resuscitation (FPDR). The aim of this pilot study was to explore the influence of education on changing HCPs attitudes and intent to provide families with the option to be present at the next cardiac arrest. A purposive sample of 29 HCP from an acute care hospital participated in this quasi-experimental study. 18 of the original 29 HCP completed both the education package and the post-test questionnaire. The majority of participants in this study had previous experience with FPDR (62%) and supported FPDR (69%). While participants had slightly more positive attitudes towards FPDR post education, this change was not significant (p = 0.79). Similarly, participation in education did not change participants concerns about safety issues or increase participant's intention to invite a family member to be present at the next cardiac arrest. The majority of participants strongly supported the development of a dedicated family support person. Education has limited impact on change participant's attitudes or intentions to invite family to be present at the next cardiac arrest.


[Thyroid gland carcinomas. Statistical study of 79 cases (author's transl)].
Experience with 79 adult patients treated for thyroid cancer. The authors study different parameters of these cancers, particularly sex and age, circumstances of discovery and histological distribution. The state precisely their operative procedure and arguments on account of total thyroidectomy.


Lunate loads following different osteotomies used to treat Kienböck's disease: A 3D finite element analysis.
One of most accepted principles for treating Kienböck's disease before wrist degeneration settles in is to decompress the lunate by an osteotomy. Several osteotomies have been proposed since 1935. However, they are based on biomechanical hypotheses that are sometimes conflicting: This study compares the decompression effect of radius transverse shortening, radius lateral closing and medial closing wedge osteotomies, capitate shortening - with and without hamate shortening - and a Camembert-type radius wedge osteotomy with and without ulnar head shortening according to Sennwald. We built a 3D wrist model using finite elements that included the metacarpal, carpal and forearm bones. All wrist ligaments and Triangular Fibrocartilage Complex were incorporated in the simulation. Load was applied on the metacarpals with the forearm bones fixed. We then applied the different osteotomies to the model. When load was applied to the wrist, the osteotomies that best unloaded the lunate were the capitate shortening osteotomy combined with hamate shortening and the Camembert osteotomy combined with ulna shortening; the latter was the only osteotomy that completely unloaded the lunate. We think the association of the radius Camembert osteotomy and ulna Sennwald's shortening osteotomy is the most effective procedure to propose in Kienböck's disease.


[Conflict play and its modification in the course of treating children].
The authors report their experience with a special form of psychodrama for the treatment in small groups of neurotic children aged five to fifteen. The acting out of ambivalent, partly unconscious and restrained tendencies and inclinations by playing, i.e., by taking roles in spontaneous performances, is followed by alternation of identification in the group and, possibly, careful indirect verbalization by the therapeutist and/or group, of which the purpose is to arrive at a reorientation of the attitudes of patients and a consolidation of the newly won attitude.


Iodomethylated fatty acid metabolism in mice and dogs.
The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono beta) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono beta into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.


A specific role for tocopherol and of chemical singlet oxygen quenchers in the maintenance of photosystem II structure and function in Chlamydomonas reinhardtii.
alpha-Tocopherol concentrations were determined at low and high light intensities and compared with the rate of photosynthesis, photosystem II (PS II) and its reaction center D1 protein. Blocking of tocopherol biosynthesis at the 4-hydroxyphenylpyruvate dioxygenase by the herbicide pyrazolynate led to a quick disappearance of alpha-tocopherol in high light, as well as of PS II activity and the D1 protein. Homogentisic acid rescued all activities. It is concluded that alpha-tocopherol has a continuous turnover as a scavenger of the singlet oxygen that arises from the quenching by oxygen of the triplet of the PS II reaction center and triggers the degradation of the D1 protein. Thus tocopherols are essential to keep photosynthesis active. We suggest that this is why plants make and need tocopherols. Chemical quenchers of singlet oxygen, notably diphenylamines, completely protect PS II, prevent D1 protein degradation and keep tocopherol levels even at very high light intensities. This supports the notion that 1O2 is the intermediate in light triggered D1 protein turnover.


Synthesis and crystal structure of poly[[di-μ3-tetra-thio-anti-monato-tris-[(cyclam)cobalt(II)]] aceto-nitrile disolvate dihydrate] (cyclam = 1,4,8,11-tetra-aza-cyclo-tetra-deca-ne).
Reaction of Co(ClO4)2·6H2O with cyclam (cyclam = 1,4,8,11-tetra-aza-cyclo-tetra-deca-ne) and Na3SbS4·9H2O (Schlippesches salt) in a mixture of aceto-nitrile and water leads to the formation of crystals of the title compound with the composition {[Co3(SbS4)2(C10H24N4)3]·2CH3CN·2H2O} n or {[(Co-cyclam)3(SbS4)2]·2(aceto-nitrile)·2H2O} n . The crystal structure of the title compound consists of three crystallographically independent [Co-cyclam]2+ cations, which are located on centers of inversion, one [SbS4]3- anion, one water and one aceto-nitrile mol-ecule that occupy general positions. The aceto-nitrile mol-ecule is disordered over two orientations and was refined using a split model. The CoII cations are coordinated by four N atoms of the cyclam ligand and two trans-S atoms of the tetra-thio-anti-monate anion within slightly distorted octa-hedra. The unique [SbS4]3- anion is coordinated to all three crystallographically independent CoII cations and this unit, with its symmetry-related counterparts, forms rings composed of six Co-cyclam cations and six tetra-thio-anti-monate anions that are further condensed into layers. These layers are perfectly stacked onto each other so that channels are formed in which acetontrile solvate mol-ecules that are hydrogen bonded to the anions are embedded. The water solvate mol-ecules are located between the layers and are connected to the cyclam ligands and the [SbS4]3- anions via inter-molecular N-H⋯O and O-H⋯S hydrogen bonding.


Rise of the RNA machines - self-amplification in mRNA vaccine design.
mRNA vaccines have won the race for early COVID-19 vaccine approval, yet improvements are necessary to retain this leading role in combating infectious diseases. A next generation of self-amplifying mRNAs, also known as replicons, form an ideal vaccine platform. Replicons induce potent humoral and cellular responses with few adverse effects upon a minimal, single-dose immunization. Delivery of replicons is achieved with virus-like replicon particles (VRPs), or in nonviral vehicles such as liposomes or lipid nanoparticles. Here, we discuss innovative advances, including multivalent, mucosal, and therapeutic replicon vaccines, and highlight novelties in replicon design. As soon as essential safety evaluations have been resolved, this promising vaccine concept can transform into a widely applied clinical platform technology taking center stage in pandemic preparedness.


A therapeutic concept to resolve a possible coronary desaturation under Ecpella support and maximize the potential for myocardial recovery: combination of veno-arteriovenous extracorporeal membrane oxygenation and Impella (VAVEcpella).
Ecpella, a combination of veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) and Impella, may result in the differential hypoxia in patients with cardiogenic shock and severe lung dysfunction. Here, we report a solution of this Ecpella-induced unfavorable phenomenon. A 70-year-old man developed cardiogenic shock from fulminant myocarditis. As we established Ecpella but immediately significant differential hypoxia became apparent, the ECMO configuration was switched from V-A to veno-arteriovenous (V-AV): a combination of V-AV ECMO and Impella, newly termed VAVEcpella, was instituted. The differential hypoxia resolved, and he was successfully weaned from mechanical circulatory support. VAVEcpella is an effective configuration to resolve Ecpella-induced differential hypoxia and may contribute to restoration of normal cardiac function.


Tangential excision of scalp burns: experience from the Bradford fire disaster.
Tangential excision of deep dermal scalp burns does not appear to be widely practised. During the Bradford Football fire victims sustained mixed depth scalp burns. These were mainly as a result of radiant heat, although falling molten bitumen was the cause of injury in a few patients. Deep dermal or full thickness burns of the scalp were tangentially excised and skin grafted. One patient did not have a graft applied after tangential excision. The early results of graft take were satisfactory. Subsequently, however, 56 per cent required further grafting; the reasons for this are discussed. Ten months after the incident there is no difference in appearance between areas of primary grafting and areas of secondary healing.


Bone density in myasthenia gravis patients receiving long-term prednisolone therapy.
Osteoporosis is an adverse effect of prednisolone therapy, although no study has been conducted on myasthenia gravis patients receiving high-dose prednisolone. We measured bone density in 36 patients (26 females and 10 males) who had undergone long-term prednisolone administration, and found a decrease in bone density in 31% of female patients and osteoporosis in only 11.5% (three cases). This frequency is lower than the presumptive rate of the general population in Japan (22.6%). No osteoporosis was detected in male patients. In conclusion, prednisolone-treated patients with myasthenia gravis have an acceptable risk of bone loss if prophylactic medication is administered.


A new ciprofloxacin stepdown program in the treatment of high-risk febrile neutropenia: a clinical and economic analysis.
To determine treatment outcomes and economic impact of a ciprofloxacin stepdown program for high-risk febrile neutropenic adults from the hospital's perspective. Unblinded, two-phase, single-center study. Adult leukemia and stem cell transplant unit. High-risk adults with febrile neutropenia. Two conditions were analyzed: a multidisciplinary ciprofloxacin stepdown program involving a reduction in parenteral ciprofloxacin dose from 400 to 200 mg (i.v.-i.v.) and conversion to oral ciprofloxacin (i.v.-p.o.) when criteria were met; and no i.v.-i.v. stepdown program. Forty-six sequential treatment courses were compared with 42 treatment course from 6-month periods in preintervention (P1) and postintervention (P2) phases. Assessed parameters were clinical and microbiologic outcomes, adverse drug reactions (ADRs), and direct medical resource use and costs (1998 $Canadian) for the episode of febrile neutropenia. A decision analytic model was used to map probabilities and costs and to conduct sensitivity analyses. To supplement standard statistical testing, 1,000 bootstrap samples were created, and the mean cost difference was calculated between phases for each sample. Patient demographics, percentage i.v.-p.o. stepdown, and duration of therapy were similar between phases. Clinical success (83% P1, 81% P2), microbiologic eradication (15% P1, 24% P2), and possible ADRs (6% P1, 9% P2) did not differ. Intravenous-to-intravenous dose stepdown occurred in 33% of P2 and no P1 treatment courses (p<0.001). Resource use and costs were similar between phases, although a reduction was seen in the drug's mean total cost/day ($58 P1, $52 P2, p=0.04). There was also a trend toward a decrease in mean total treatment costs ($4,843 P1, $3,493 P2, p=0.08). In 1,000 bootstrap samples, 99.8% showed a cost advantage for P2. The model was robust to sensitivity analyses. This intervention influenced administration of ciprofloxacin without apparent compromise of patient outcomes and resulted in a reduction in total costs of treating febrile neutropenia.


Reduction of prolonged bilateral temporomandibular joint dislocation by midline mandibulotomy.
Various surgical procedures have been used to reduce prolonged bilateral dislocation of the temporomandibular joint, but with some complications. A prolonged bilateral dislocation of the mandibular condyle was simply reduced by a midline mandibulotomy without any complications. One year postoperatively, joint function was unimpeded and there was no recurrence of condylar dislocation.


Assessment of 0.5 T static field exposure effect on yeast and HEK cells using electrorotation.
This study aims to examine the influence of a 0.5 T static magnetic field (SMF) on yeast and human embryonic kidney (HEK) 293 cell using electrorotation (ROT). Following 48 h exposition to the SMF, no difference was noted between ROT spectra of unexposed and exposed yeast cells, which extend previous reports on the absence of SMF effects on yeast. We also compared the ROT spectrum and the extracted electrical characteristics of HEK cells exposed during 72 h to a 0.5 T uniform static magnetic field with those of unexposed cells. SMF potential effects on HEK proliferation kinetics and cell morphology were also assessed by using the trypan blue exclusion method and scanning electron microscopy, respectively. At last, no significant differences were observed between control and exposed HEK cells concerning electrical properties, growth, and morphology.


Squamous cell carcinoma in a young circumcised man.
A 34-year-old white man is described with multifocal invasive squamous cell carcinoma of the penis. Adequate circumcision had been performed at birth.


Stability comparison of anterior cruciate ligament between double- and single-bundle reconstructions.
The purpose of this study was to evaluate the intra-operative stability during double-bundle anterior cruciate ligament (ACL) reconstructions (20 knees) using a navigation system and compare the results with those obtained from single-bundle reconstructions (20 knees). After registering the reference points during ACL reconstruction, antero-posterior and rotational stability tests with 30 degrees knee flexion using a navigation system were measured before and after reconstructions on both groups. The change of antero-posterior translation after and before reconstruction was 12.5 mm in the double-bundle group and 10.5 mm in the single-bundle group, showing significant inter-group difference (p=0.014, from 17.5 mm to 5.1 mm in the double-bundle and from 16.6 mm to 6.1 mm in the single-bundle group). The mean rotational stability of the double-bundle group also showed more significant improvement after reconstruction compared to that of the single-bundle group (9.8 degrees in the double- and 5.6 degrees in the single-bundle groups, p<0.001). These findings suggest that a double-bundle ACL reconstruction restores greater knee stability with respect to the antero-posterior and rotational stability than a single-bundle reconstruction.


Comparing pathological complete response rate using oral capecitabine versus infusional 5-fluorouracil with preoperative radiotherapy in rectal cancer treatment.
Infusional 5-fluorouracil (5-FU) has been the standard radiation sensitizer in patients undergoing preoperative long-course chemoradiotherapy (CRT) for locally advanced rectal cancer in Australia. Capecitabine (Xeloda) is an oral 5-FU prodrug of comparable pharmacodynamic activity, currently preferred in place of 5-FU infusion, its established counterpart in neoadjuvant CRT for rectal cancer. The few studies quantifying pathological complete response (pCR) of Xeloda versus 5-FU have produced inconsistent results. We reviewed our own data to determine if the rates of pCR of oral capecitabine were non-inferior to intravenous 5-FU in patients undergoing neoadjuvant CRT for rectal cancer. A retrospective study was performed from a prospectively kept database. Four hundred and fifty-two patients received preoperative CRT from January 2006 to January 2016. Pelvic radiotherapy was delivered concurrently with capecitabine (n = 42) or infusional 5-FU (n = 341). The remaining received different chemotherapy regimens. Surgery was performed 6-12 weeks of CRT completion. Pathological responses were assessed using Dworak regression grading score (0-4). Clinical outcomes were evaluated in terms of local control and recurrence-free survival. The proportion of patients who had a tumour regression score of 4 (pCR) after CRT was 4/42 (9.5%) in the capecitabine group and 71/341 (20%) in the infusional 5-FU group (P = 0.082). pCR was an independent predictor for survival in this group of patients (hazard ratio: 0.002, P = 0.0001, 95% confidence interval: 0.0001-0.027). The use of capecitabine as neoadjuvant chemotherapy in patients with rectal cancer was associated with a reduced rate of pCR. However this difference did not achieve statistical significance.


Endoclip migration after laparoscopic splenectomy combined with pericardial devascularization: Case report and literature review.
Endoclip migration(ECM) after laparoscopic splenectomy combined with pericardial devascularization (LESD) is a rare and dangerous postoperative complication. The emergence of such cases led to our consideration of the timing of use of nonabsorbable endoclips. This case report describes a patient with cirrhosis and portal hypertension who underwent LESD. Two years after the operation, an endoclip was found in the fornix of the fundus of his stomach by gastroscopy. A 66-year-old male patient had a history of liver cirrhosis for 9 years. Two years prior, LESD was performed on this patient in our hospital. This time, due to 'repeated black stool for 1 month, and hematemesis 1 time', the patient was admitted to the hospital. A diagnosis of 'liver cirrhosis with esophageal and gastric variceal bleeding' was considered. Gastroscopy revealed a fundal foreign body, and upon review of the patient history, the foreign body was found to be a nonabsorbable endoclip. Foreign literature has reported cases of biliary endoclip migration after laparoscopic cholecystectomy, but no cases of ECM after LESD have been reported. For such cases, we should consider the timing of the application of nonabsorbable endoclips during vascular devascularization to avoid ECM after the operation. In addition, we should also comprehensively evaluate whether the ectopic endoclips should be removed.


Laparoscopic adrenalectomy for bilateral metachronous aldosteronomas.
Primary aldosteronism affects 5% to 13% of patients with hypertension. Idiopathic bilateral hyperplasia (IHA) and unilateral aldosterone-producing adenoma (APA) are the most common types of primary aldosteronism. Bilateral APA is a very rare entity with only a few reports in the literature. We present the case of a patient with metachronous bilateral APA treated with metachronous bilateral total and near total adrenalectomy. A 66-year-old female was evaluated for hypokalemia and hypertension refractory to medical therapy 2 years after laparoscopic adrenalectomy for right APA. Follow-up abdominal CT scan revealed a new 1.1-cm left adrenal mass. The patient underwent a laparoscopic near total adrenalectomy for her new left adrenal mass. Pathology examination revealed a new APA. The operation and the patient's postoperative course were uneventful. Potassium levels were normalized and her hypertension became well controlled. APA can present metachronously months to years after adrenalectomy for APA in the contralateral adrenal gland. Laparoscopic adrenalectomy remains the approach of choice for this pathology.


Chest radiograph screening for severe acute respiratory syndrome in the ED.
The purpose of the study was to evaluate the use of chest radiography for the screening of severe acute respiratory syndrome (SARS). We retrospectively analyzed all patients who attended an Emergency Department SARS screening clinic during the outbreak in Hong Kong, from March 10 to June 5, 2003. Patients with clinical and epidemiologic suspicion of SARS were evaluated by serial chest radiography. All radiographs were reported by consensus from 2 radiologists, blinded to the clinical records. The prevalence of SARS was 13.3% among 1328 patients included. The initial radiograph had sensitivity 50.3%, specificity 95.0%, positive likelihood ratio 10.06, negative likelihood ratio 0.52, positive predictive value 61.5%, and negative predictive value 92.3% for diagnosing SARS. Serial chest radiography had sensitivity 94.4%, specificity 93.9%, positive likelihood ratio 15.48, negative likelihood ratio 0.06, positive predictive value 71.4%, and negative predictive value 99.0%. The initial chest radiograph has poor sensitivity, and serial radiographs are required to rule out SARS.


Pharmacokinetics of levofloxacin during continuous venovenous hemodiafiltration and continuous venovenous hemofiltration in critically ill patients.
To assess the pharmacokinetics of levofloxacin during continuous venovenous hemodiafiltration (CVVHDF) and continuous venovenous hemofiltration (CVVH). Nonrandomized pharmacokinetic evaluation. University surgical intensive care unit. Six critically ill patients. Five patients received levofloxacin 500 mg/day and one patient received levofloxacin 125 mg/day All patients received continuous renal replacement therapy: CVVHDF on day 1 and CVVH on day 2, using an acrylonitrile hollow-fiber 0.9-m2 filter, constant blood flow rate of 90 ml/minute, substitution flow rate of 1 L/hour predilution, and dialysate flow rate of 1 L/hour (CVVHDF). Serum, ultrafiltrate, and dialysate concentrations of levofloxacin were determined by high-performance liquid chromatography. Extracorporeal clearance was 26.05 +/- 4.66 ml/hour during CVVHDF and 15.71 +/- 2.73 ml/hour during CVVH (p<0.05). Elimination half-life was 28.08 +/- 4.5 hours and 45.9 +/- 17.7 hours, and distribution volume was 1.51 +/- 0.52 L/kg and 1.42 +/- 0.42 L/kg for CVVHDF and CVVH, respectively. Saturation was 0.76 +/- 0.13 for CVVHDF versus a sieving coefficient of 0.77 +/- 0.16 for CVVH. Marked extracorporeal elimination of levofloxacin occurs, requiring a dosage adjustment that can be calculated from the characteristics of CVVH and CVVHDF.


Identification and characterization of cellouronate (β-1,4-linked polyglucuronic acid) lyase from the scallop Mizuhopecten yessoensis.
The semisynthetic polysaccharide cellouronate is a β-1,4-linked polyglucuronic acid prepared from regenerated cellulose by chemical oxidation. Here, we isolated a novel enzyme, MyAly, as a cellouronate lyase from a scallop Mizuhopecten yessoensis. Its optimum temperature, pH, and NaCl concentration for cellouronate degradation were determined to be 30 °C, 6.9, and 200-500 mM, respectively. MyAly endolytically degraded cellouronate into unsaturated di-, tri-, and tetrasaccharides with kcat of 31.1 s-1. MyAly also showed an alginate-degradation activity with a kcat value of 0.58 s-1. However, there was no significant difference in Km values between cellouronate and alginate. MyAly consisted of 280 amino acids and shared 36.5-44.1 % identity with known marine gastropod alginate lyases belonging to the polysaccharide lyase family 14. This is the first study to identify and characterize a cellouronate-degrading lyase from a marine organism, providing a better understanding of the biodegradability of the industrially important polysaccharide, cellouronate, in marine environments.


Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications.
In western countries, the Kirsten ras oncogene homolog gene (KRAS) mutation rate is high in patients with nonsmall cell lung cancer (NSCLC), especially in those with adenocarcinoma (30%-50%), but the epidermal growth factor receptor gene (EGFR) mutation rate is very low (3%-8%). In addition, KRAS mutations reportedly were associated with EGFR tyrosine kinase inhibitor (EGFR-TKI) resistance. In Taiwan, high EGFR mutation rates associated with high EGFR-TKI response rates in patients with NSCLC have been reported; however, KRAS mutation data are limited and have not been correlated with TKI response. KRAS mutation analysis was performed on 237 NSCLC specimens, and the results were correlated with clinicopathologic features. All but 2 tumors also underwent EGFR mutation analysis. KRAS mutations were identified in only 9 of 237 patients (3.80%). Five patients were women who were nonsmokers, and 4 patients were men who were ever-smokers. The mutation rate was 5.03% in patients with adenocarcinoma (8 of 159 patients) and 1.56% in patients with squamous cell carcinoma (1 of 64 patients). Four mutations were G12V, 3 mutations were G12D, 1 mutation was L19F, and 1 was the duplication insertion mutation dupT50_M72. In contrast, EGFR mutations were detected in 96 of 235 patients (40.8%) and in 90 of 157 adenocarcinomas (57.3%). None of the KRAS mutations coexisted with EGFR mutations. KRAS mutations were not associated significantly with any clinicopathologic characteristics, including smoking status. Among the 53 patients who had received TKI monotreatment, only 1 patient had a KRAS mutation and had progressive disease. The KRAS mutation rate was too low to play a significant role in TKI resistance or tumorigenesis among Taiwanese patients with NSCLC, which was the complete reverse of the results reported in western countries.


Spinal versus general anesthesia for elective cesarean delivery: a prospective comparative study.
To study the efficacy and safety of spinal anesthesia for elective cesarean section as compared with general anesthesia. 175 women undergoing elective cesarean section were studied prospectively. They were allocated into two groups; the first group (n=60) received spinal anesthesia, and the second one (n=115) received general anesthesia for elective cesarean section. Preoperative and intraoperative BP and IV fluids were recorded. Chi-Square and Fisher's exact tests were used to compare differences between the two groups; p < 0.05 was considered significant. There were no differences between the two groups in terms of demographics, indication for elective cesarean section, operative time, gestational age, 1 and 5-min Apgar scores, and the means of preoperative and postoperative systolic and diastolic BP. A statistically significant increase was observed in terms of hypotension, postoperative analgesia, pre-induction and intraoperative IV fluids in the spinal group as compared to the general anesthesia group (p < 0.001, p < 0.01, and p < 0.01, respectively). Spinal anesthesia is as effective as a general anesthesia. Maternal and fetal outcome are favorable. Maternal hypotension can be managed successfully with modest doses of ephedrine and IV fluid infusions. It provides sufficient postoperative analgesia allowing the mother to have more vitality and comfort than those who receive general anesthesia.


Fast, simple and cheap: method modified from conventional cultivation for tuberculosis diagnosis allows seeding on Löwenstein-Jensen of any swab-embedded pulmonary samples decontaminated with sodium hydroxide.
Few tuberculosis (TB) control programmes in low-income countries have access to culture facilities in their primary care diagnostic centres and this scenario may have worsened with the coronavirus disease 2019 pandemic. Thus the aim was to develop and evaluate a simpler TB test that allows seeding on Löwenstein-Jensen (LJ) medium of several swab-embedded samples decontaminated with sodium hydroxide (NaOH). A cotton swab containing each sample was decontaminated in NaOH before being dipped into a slightly acidic solution to neutralize the pH in order to allow the culture to develop on LJ medium. Samples (n=543) from suspected or confirmed pulmonary TB were analysed in two phases: standardization (n=167) and evaluation of the study method (n=376). The study method showed sensitivity >95% and specificity >93% using Ogawa-Kudoh (OK) and modified Petroff (MP) as standards and was comparable to MP-LJ (p>0.05) and slightly superior to OK (p=0.03) for sputum culture and more comprehensive than the latter for other pulmonary specimens. This article reports a more comprehensive, simpler and less costly method for diagnosing TB in the laboratory with fewer economic resources and biosafety equipment. Thus a patent application was filed (BR1020190103841).


Leaf water relations characteristics of Lupinus angustifolius and L. cosentinii.
Lupins (Lupinus angustifolius and L. cosentinii) growing in 321 containers in a glasshouse were exposed to drought by withholding water. Leaf water potential (Ψ1), and leaf osmotic potential (Ψs) were measured daily as soil water became depleted. Leaf water relations were further assessed by a pressure-volume technique and by measuring Ψs and relative water content of leaves after rehydration. Analysis by pressure-volume or cryoscopic techniques showed that leaf osmotic potential at saturation (Ψs100) decreased from -0.6 MPa in well watered to -0.9 MPa in severely droughted leaves, and leaf water potential at zero turgor (Ψzt) decreased from about -0.7 to -1.1 MPa in well watered and droughted plants, respectively. Relative water content at zero turgor (RWCzt) was high (88%) and tended to be decreased by drought. The ratio of turgid leaf weight to dry weight was not influenced by drought and was high at about 8.0. The bulk elastic modulus (ɛ) was approximately halved by drought when related to leaf turgor potential (Ψp) and probably mediated turgor maintenance during drought. The latter was found to be negatively influenced by rate of drought. Supplying the plants with high levels of K salts did not promote adjustment or turgor maintenance.


[Preparation conditions optimization of Epimedium polysaccharide liposome].
To optimize the preparation conditions of Epimedium polysaccharide liposome (EPSL). EPSL was prepared by membrane distribution-supersound method. In preparation of EPSL test, an orthogonal L9 (3(4)) test was used to optimize the preparation conditions, with four factors of ratio of drug to lipid, ratio of lecithin to cholesterol, ultrasonic time and water bath temperature and two indexes of encapsulation efficiency and drug-loading rate. The encapsulation efficiency of EPSL was determined by protamine method. Optimal preparation condition of EPSL was that ratio of drug to lipid, ratio of lecithin to cholesterol, ultrasonic time and water bath temperature were 1: 30, 4: 1,10 min and 40 degrees C respectively. EPSL prepared under Optimal conditions has the property of high encapsulation efficiency and drug-loading rate.


Reply to Jue, J.S.; Alameddine, M. Role of PSA Density and MRI in PSA Interpretation. Comment on "Lumbreras et al. Variables Associated with False-Positive PSA Results: A Cohort Study with Real-World Data. Cancers 2023, 15, 261".
We thank you and your co-authors for the comment [...].


Dead cells release a 'necrosignal' that activates antibiotic survival pathways in bacterial swarms.
Swarming is a form of collective bacterial motion enabled by flagella on the surface of semi-solid media. Swarming populations exhibit non-genetic or adaptive resistance to antibiotics, despite sustaining considerable cell death. Here, we show that antibiotic-induced death of a sub-population benefits the swarm by enhancing adaptive resistance in the surviving cells. Killed cells release a resistance-enhancing factor that we identify as AcrA, a periplasmic component of RND efflux pumps. The released AcrA interacts on the surface of live cells with an outer membrane component of the efflux pump, TolC, stimulating drug efflux and inducing expression of other efflux pumps. This phenomenon, which we call 'necrosignaling', exists in other Gram-negative and Gram-positive bacteria and displays species-specificity. Given that adaptive resistance is a known incubator for evolving genetic resistance, our findings might be clinically relevant to the rise of multidrug resistance.


Building trust and collaboration between physicians and administrators.
If you think someone else's behavior is blocking you from achieving a goal, think again. As a physician leader, there may be something you can do to take responsibility for a situation and make the necessary changes. Learn how you can help build the trust and cooperation needed to make change happen.


NMR as a Tool to Investigate the Processes of Mitochondrial and Cytosolic Iron-Sulfur Cluster Biosynthesis.
Iron-sulfur (Fe-S) clusters, the ubiquitous protein cofactors found in all kingdoms of life, perform a myriad of functions including nitrogen fixation, ribosome assembly, DNA repair, mitochondrial respiration, and metabolite catabolism. The biogenesis of Fe-S clusters is a multi-step process that involves the participation of many protein partners. Recent biophysical studies, involving X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and small angle X-ray scattering (SAXS), have greatly improved our understanding of these steps. In this review, after describing the biological importance of iron sulfur proteins, we focus on the contributions of NMR spectroscopy has made to our understanding of the structures, dynamics, and interactions of proteins involved in the biosynthesis of Fe-S cluster proteins.


Increasing the CD4+ T cell precursor frequency leads to competition for IFN-gamma thereby degrading memory cell quantity and quality.
The precursor frequency of naive CD4(+) T cells shows an inverse relationship with the number of memory cells generated after exposure to cognate Ag. Using the lymphocytic choriomeningitis virus (LCMV) model, we show here that only when the initial number of naive virus-specific CD4(+) T cell precursors is low (< or =10(4) per spleen) do they give rise to abundant and homogeneous memory cells that are CD62L(low), IL-7R(high), and imbued with an enhanced capacity to produce cytokine, proliferate, and survive over time. Furthermore, memory cells derived from a high naive precursor number show functional deficits upon secondary exposure to virus. The negative effect of higher naive precursor frequency was not attributable to competition for limiting amounts of Ag, because LCMV-naive CD4(+) TCR-transgenic CD4 T cells were recruited into the LCMV-induced response even when their initial number was high. Instead, the T cells appear to compete for direct IFN-gamma signals as they differentiate into memory cells. These results are consistent with a model of T cell development in which the most fit effector T cells that receive sufficient direct IFN-gamma signals are selected to differentiate further into memory cells.


How do Neoseiulus californicus (Acari: Phytoseiidae) females penetrate densely webbed spider mite nests?
The persea mite Oligonychus perseae is a pest of avocado trees that builds extremely dense webbed nests that protect them against natural enemies, including phytoseiid mites. Nests have one or two marginal entrances that are small and flattened. The predatory mite Neoseiulus californicus co-occurs with O. perseae in the avocado orchards of the south-east of Spain. Penetration inside nests through the entrances by this predator is thought to be hindered by its size and its globular-shaped body. However, in the field it has repeatedly been found inside nests that were clearly ripped. Perhaps penetration of the nests has been facilitated by nest wall ripping caused by some other species or by unfavourable abiotic factors. However, to assess whether N. californicus is also able to enter the nest of O. perseae by itself, we carried out laboratory experiments and made a short film. They show how this predator manages to overcome the webbed wall, and that it can penetrate and forage inside nests of O. perseae.


Iranian patients co-infected with COVID-19 and mucormycosis: the most common predisposing factor, clinical outcomes, laboratory markers and diagnosis, and drug therapies.
The newly emerged pandemic of coronavirus disease-2019 (COVID-19) is the world's main health challenge because infected patients become vulnerable to a variety of opportunistic diseases. This study aimed to assess clinical outcomes, diagnosis, utilized drug therapies, and ongoing COVID-19 practices in Iranian cases co-infected with COVID-19 and mucormycosis. A case-series analysis was conducted in the presence of 10 patients with COVID-19 and mucormycosis co-infection (two men and eight women; mean age of 48.8 years) from March to October 2020. Demographic variables, signs/symptoms, and comorbidities of all patients were recorded. COVID-19 was confirmed with reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab tests and high-resolution computed tomography (HR-CT)_ scans. All patients had a positive RT-PCR for SARS-CoV-2. Eight patients had a history of diabetes, while three of them exhibited a hypertension history. Remarkable laboratory findings were elevated fasting blood sugar in 6 cases and anaemia in four patients. A rhino-orbital-cerebral of mucormycosis in all patients was detected based on HR-CT scans and otorhinolaryngological or ophthalmological examinations. Neurological disorders including facial, trigeminal, optic, and oculomotor nerve involvement resulted in paraesthesia, pain, ptosis, no light perception, blurred vision, and papilledema in five cases. Maxillary and ethmoid sinuses were the most common sites of involvement. Vulnerable COVID-19 patients with comorbidities, any facial involvements, or treated by excessive doses of glucocorticoids and antibiotics should undergo precise examinations during the appearance of early signs and hospitalization to diagnose and treat mucormycosis using the standard care and antifungal treatments.


Leiperia cincinnalis Sambon, 1922 (Pentastomida) from Nile crocodiles Crocodylus niloticus in the Kruger National Park, South Africa, with a description of the male.
A single male and several adult females of the pentastomid Leiperia cincinnalis were recovered from the trachea of five of six Nile crocodiles examined in 1995 and 1998. Infective larvae, pre-adult males and females, as well as mature males, occurred in clusters in the pulmonary artery but infective larvae and pre-adult females were also occasionally taken from the lungs. Irrespective of the developmental stage, the intensity of infection was 3, 6, 48, 72 and 79. Sixty-four percent of eggs recovered from the posterior part of the uterus of a patent L. cincinnalis female contained fully-developed primary larvae and these were used to infect 24 Mozambique bream Oreochromis mossambicus. Within a week of infection all the fish died and hatched primary larvae were recovered from the stomach and anterior part of the intestine. Eggs that had not hatched were found to be unsegmented. The total primary larval count in seven fish was 18, 12, 1, 25, 16, >40 and >50. Descriptions with detailed measurements are given of the females, the males, the eggs, the primary larvae and the infective larvae of L. cincinnalis.


Evaluation of fine-needle aspiration cytology of breast masses in males.
The reliability of fine-needle aspiration cytology (FNAC) of breast masses in males could be compromised by lack of experience because breast carcinoma is rare in males and FNAC is not often used. In addition, FNAC of the more often encountered gynecomastia may lead to overdiagnosis. Therefore, in the current study the authors evaluated their experience with FNAC of breast masses occurring in males. A total of 153 FNACs of the male breast obtained between 1985 until the end of 2000 were retrieved from the electronic files of the study institution. A total of 141 FNACs were taken from unilateral lesions in men age > 24 years, the group of men believed to be most at risk for breast carcinoma. Histologic follow-up was retrieved from the same files and was available for 72 FNACs. For specimens without histologic follow-up the nationwide pathology database was consulted and no cases of breast carcinoma were found. The inadequate rate was 13%. When inadequate FNACs were included in the calculations, the sensitivity was found to be 87% and the specificity 78%. When the inadequate FNACs were excluded from the calculations the sensitivity was reported to be 100% and the specificity 89%. The positive predictive value of a diagnosis of malignancy was 100%. During the study period the authors' institution examined approximately 10,000 FNAC specimens from male and female breasts and 399 resection specimens from the breasts of men age > 24 years with unilateral lesions. In this last group, preoperative FNAC reduced the benign-to-malignant ratio from 19.8:1 to 3.5:1. FNAC of the male breast is a reliable procedure in a setting in which sufficient numbers of FNACs of the breast are examined. The authors believe FNAC should be used more often in the preoperative evaluation of breast lesions occurring in males.


Association Between Subclinical Thyroid Dysfunction and Fracture Risk.
Clinical hyperthyroidism accelerates bone resorption without compensatory bone formation, reducing bone density and increasing the risk of fracture. The association between subclinical hyperthyroidism and fracture risk is less clear. To investigate the association of endogenous subclinical thyroid dysfunction and fracture risk, independent of clinical confounders. This cohort study included 10 946 participants from the Atherosclerosis Risk in Communities Study, an ongoing prospective cohort study of community-dwelling individuals conducted from 1987-1989 through December 31, 2019, in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis, Minnesota. Participants were not taking thyroid medications and had no history of fractures. Thyrotropin and free thyroxine levels were measured at visit 2 (1990-1992). Subclinical hyperthyroidism was defined as a thyrotropin level lower than 0.56 mIU/L, subclinical hypothyroidism as a thyrotropin level higher than 5.1 mIU/L, and euthyroidism as a thyrotropin level of 0.56 to 5.1 mIU/L, with normal free thyroxine levels from 0.85 to 1.4 ng/dL. Incident fracture was ascertained using hospitalization discharge codes through 2019 and linkage to inpatient and outpatient Medicare claims through 2018. Of 10 946 participants (54.3% women; mean [SD] age, 57 [5.7] years), 93.0% had euthyroidism, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism. During a median follow-up of 21 years (IQR, 13.0-27.3 years), there were 3556 incident fractures (167.1 per 10 000 person-years). The adjusted hazard ratios of fracture were 1.34 (95% CI, 1.09-1.65) for those with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism compared with individuals with euthyroidism. Among those with normal free thyroxine levels, thyrotropin levels in the lower-than-normal range were significantly associated with higher fracture-related hospitalization risk; fracture risk was greater among individuals with thyrotropin concentrations below 0.56 mIU/L. This community-based cohort study suggests that subclinical hyperthyroidism was an independent risk factor associated with fracture. The increased risk for fracture among individuals with a thyrotropin level lower than 0.56 mIU/L highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease.


Dual-specificity protein phosphatase Msg5 controls cell wall integrity and virulence in Fusarium oxysporum.
Mitogen-activated protein kinase (MAPK) cascades are key signaling modules controlling development and virulence in fungal pathogens. Down-regulation of MAPK activity by protein phosphatases provides a critical layer of control during desensitization or adaptation to stimuli. In Saccharomyces cerevisiae, the dual-specificity phosphatase Msg5 dephosphorylates target threonine and tyrosine residues in the two MAPKs Mpk1 and Fus3, which regulate the cell wall integrity (CWI) and pheromone responses, respectively. Here we studied the role of the Msg5 ortholog in Fusarium oxysporum, a soilborne phytopathogen that infects host plants through the roots to cause vascular wilt and plant death. F. oxysporum mutants lacking Msg5 showed constitutively high levels of Mpk1 phosphorylation and increased sensitivity to the cell wall targeting compound Calcofluor White. Moreover, these mutants displayed reduced colony growth and conidiation. Importantly, msg5Δ mutants were impaired in hyphal chemotropism towards host plant roots and in virulence on tomato plants. These results reveal a key role of Msg5 in regulation of the CWI MAPK cascade of F. oxysporum as well as in infection-related signaling of this important fungal pathogen.


Type I and type II pyrethroids increase inhibition in the hippocampal dentate gyrus of the rat.
Urethane-anesthetized rats were prepared for stimulation of the perforant path and for recording from the granule cell region of the hippocampal dentate gyrus. Subjects were administered varying doses of allethrin (a prototype type I pyrethroid) or deltamethrin (a prototype type II pyrethroid), and the excitability of the perforant path and granule cells was tested. Both pyrethroids produced a dose-dependent decrease in the responsiveness of granule cells, following stimulation of the perforant path, that lasted up to 100 msec. Analysis suggested that the pyrethroid-induced effects were associated with an increase in interneuronally mediated inhibition. Neither the perforant path axon or terminal nor the granule cell was affected by doses which appeared to affect interneurons. Basal excitability of the granule cells was also decreased by deltamethrin. This effect may have been secondary to an increase in tonic inhibition evoked by the same mechanisms responsible for the increase in phasic inhibition.


Inhibition of ATP-sensitive K+ channels by substituted benzo[c]quinolizinium CFTR activators.
The substituted benzo[c]quinolizinium compounds MPB-07 and MPB-91 are novel activators of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. High homologies between CFTR and the sulfonylurea receptor (SUR), which associates with the potassium channel Kir6.2 to form the ATP-sensitive K(+) (K(ATP)) channel, prompted us to examine possible effects of these compounds on K(ATP) channels using electrophysiological recordings and binding assays. Activity of recombinant K(ATP) channels expressed in Xenopus oocytes was recorded in the inside-out configuration of the patch-clamp technique. Channels were practically unaffected by MPB-07 but were fully blocked by MPB-91 with half-inhibition achieved at approximately 20 microM MPB-91. These effects were similar on channels formed by Kir6.2, and either the SUR1 or SUR2A isoforms were independent of the presence of nucleotides. They were not influenced by SUR mutations known to interfere with its nucleotide-binding capacity. MPB-91, but not MPB-07, was able to displace binding of glibenclamide to HEK cells expressing recombinant SUR1/Kir6.2 channels. Glibenclamide binding to native channels from pancreatic MIN6 cells was also displaced by MPB-91. A Kir6.2 mutant able to form channels without SUR was also blocked by MPB-91, but not by MPB-07. These observations demonstrate that neither MPB-07 nor MPB-91 interact with SUR, in spite of its high homology with CFTR, and that MPB-91 blocks K(ATP) channels by binding to the Kir6.2 subunit. Thus, caution should be exercised when planning to use MPB compounds in cystic fibrosis therapy, specially MPB-91 which could nonetheless find interesting applications as the precursor of a new class of K channel blockers.


Upper gastrointestinal cancer in a population-based screening program with fecal occult blood test for colorectal cancer.
Screening with Hemoccult-II (H-II) followed by colonoscopy, when fecal occult blood is demonstrated, reduces mortality from colorectal cancer. Whether upper gastrointestinal investigation is necessary when colonoscopy does not reveal any significant colorectal lesion is doubtful, and is the subject of this study. In 1985, 30,967 persons from the general population register of Funen were randomized to biennial H-II screening. A positive test was followed by colonoscopy and no attempt was made to evaluate the upper gastrointestinal tract. Based on the information from the Funen Patient Database, the National Board of Health's Register of Death Causes, the Cancer Register and the National Register of Patients, all persons with malignancy of the gastrointestinal tract were identified. During 15 years and 8 screening rounds, 1,767 tests were positive; 1,536 complete colonic investigations detected colorectal cancer in 182 persons, adenoma > or = 10 mm in 440 persons, and in 879 investigations no colorectal lesion was found. Upper GI cancers were diagnosed in 209 persons within 2 years of the H-II test (199 after a negative H-II and no more than 10 persons within 2 years of a positive test). Among the 10, two were diagnosed as a consequence of symptoms at the time of screening. It is unjustified to perform upper gastrointestinal investigation in asymptomatic persons with a positive H-II in a Danish population screening for colorectal cancer.


Ultrastructural observation of oocytes in six types of stony corals.
In this study, the ultrastructure of the oocytes of 6 types of scleractinian corals was observed by transmission electron microscopy (TEM). Moreover, histological and ultrastructural analyses were performed to improve our understanding of the organelles involved in coral oocyte formation. In all 6 stony coral species, the microvilli were tubular and directly grew from the surface of the oocyte membrane; yolk bodies, lipid granules, and cortical alveoli accounted for most of the volume inside the oocytes, suggesting that they are associated with energy storage and buoyancy. Clear differences were observed in the size of yolk bodies and lipid granules in the oocytes of the 6 stony coral species, which occupied approximately 55%-80% of the inner space of the oocytes. Galaxea fascicularis exhibited the largest lipid granule volume, but the oocytes contained only an average number of 12.45 lipid granules per unit area. Only Montipora incrassata oocytes contained symbiotic algae. The smallest size and proportion of lipid granules in M. incrassata oocytes may be attributed to the presence of symbiotic algae and large yolk bodies, which may help oocytes produce energy and function as a nutritional source. This study is crucial for improving the understanding of the basic biology of coral reproduction, and the ensuing datasets is critical for conservation-oriented studies seeking to cryopreserve corals during these times of dramatic global climate change.


Cortical nicotinic enhancement of tone-evoked heightened activities and subcortical nicotinic enlargement of activated areas in mouse auditory cortex.
Systemic nicotine administration regulates neuronal activities in mouse auditory cortex. How nicotine regulates the spread of the activities across auditory cortical areas is not well known. We investigate this using flavoprotein fluorescence imaging. 20 kHz amplitude-modulated (AM) tones increased the peak intensity of flavoprotein fluorescence in presumptive primary auditory cortex (A1). 5 kHz AM tones activated at least three cortical areas, which are presumably A1, anterior auditory field, and secondary auditory cortex. Nicotine enlarged tone-activated cortical areas and enhanced both 20 kHz and 5 kHz tone-evoked fluorescence intensities at their respective, optimal frequency peak sites and at non-optimal frequency peak sites in A1. The extent of this enhancement was greater at non-optimal frequency sites than at optimal frequency sites. A cortical injection of dihydro-β-erythroidine, an inhibitor of nicotinic acetylcholine receptors composed of α4 and β2-subunits (α4β2*-nAChRs), blocked the enhancement of fluorescence intensity at the peak sites but did not appear to block the enlargement of activated areas. These results suggest that nicotine exposure activates cortical α4β2*-nAChRs to enhance tone-evoked local neuronal activities at an optimal frequency site. The nicotine-induced enlargement of a tone-activated area may depend on the nicotinic enhancement of cortical inputs or other activities.


Role of LONP2 in head and neck squamous cell carcinoma.
Lon Peptidase 2, Peroxisomal (LONP2) is a peptidase in peroxisomes that selectively degrades oxidatively damaged proteins in cells and is upregulated in several cancers. In this study, we found both the mRNA and protein level of LONP2 was upregulated in head and neck squamous cell carcinoma (HNSCC) samples. Ectopic overexpressed LONP2 enhanced HNSCC cell growth and migration. Nevertheless, LONP2 silencing suppressed tumor growth in vitro and in vivo. It was also indicated that knockdown of LONP2 also impaired the cell cycle progression and improved apoptosis rate of HNSCC cells. The results of RNA sequencing showed that plastin 3 (PLS3) was heavily downregulated after LONP2 silencing. PLS3 is an actin-bundling protein that functions as an oncogene in several cancers. Furthermore, knockdown of PLS3 inhibited the cell proliferation induced by LONP2 overexpression. In conclusion, we identified an oncogenic effect of LONP2 on cell proliferation and migration in HNSCC via positively regulating the expression of PLS3.


Groundwater quality with special reference to fluoride concentration in the granitic and basaltic contact zone of southern India.
The main focus of this data article is to evaluate the groundwater and surface water quality from a granitic-basaltic watershed in a semi-arid region. The obtained values are evaluated concerning the drinking water quality standards proposed by WHO, specifically for the semi-arid regions. All the physio-chemical parameters (fourteen) required for the calculation of water-quality indices and source appreciation were derived. Person correlation analysis for the measured parameters is presented with high to poor correlation groups in the study region. A brief description of the methods and calculation of water quality indices is mentioned. The data can be re-used to calculate to evaluate the suitability for drinking and agriculture needs of the basin; besides, it can be helpful to the authorities to make policies to mitigate the water quality vulnerability.


Technical-economic and environmental protection performance evaluation of a novel hybrid solar-nuclear thermally coupled power and desalination plant.
Clean energy complementary system can reduce environmental pollution effectively and is considered as a future energy development direction. In this paper, an innovative solar-nuclear thermally coupled power and desalination plant for electricity and freshwater productions is proposed. As solar power and nuclear power are combined, this multi-energy system is a clean energy system and basically has no emissions of soot, sulfur oxides, carbon dioxide, and nitrogen oxides. The operating behavior assessment results of the multi-energy system show that the power generation and freshwater production systems can operate synergistically. The electric power and corresponding efficiency of the multi-energy system are 290.7 MW and 38.2%, in which the solar proportion is about 38.1%. The daily freshwater production of the multi-energy system is 3761.3 t. The economic assessment results reveal that the levelized costs of electricity and freshwater of the multi-energy system are 0.361 yuan/(kWh) and 1.645 yuan/t. The environmental protection analysis results show that in contrast with a coal-fired system, the annual emission reductions of soot, sulfur oxides, carbon dioxide, and nitrogen oxides of the multi-energy system are 7350.94 t, 12,634.42 t, 513,034.14 t, and 11,945.28 t, revealing a significant environmental protection performance.


Promoter analysis of the rice stemar-13-ene synthase gene OsDTC2, which is involved in the biosynthesis of the phytoalexin oryzalexin S.
A rice diterpene cyclase, OsDTC2, functions as a stemar-13-ene synthase that converts syn-copalyl diphosphate into stemar-13-ene, a putative diterpene hydrocarbon precursor of the phytoalexin oryzalexin S. The transcriptional expression of OsDTC2 is induced by treatment of suspension-cultured rice cells with a chitin oligosaccharide elicitor. To investigate the molecular mechanisms of the elicitor signaling pathway that leads to OsDTC2 expression, we carried out deletion and mutation analysis of the region -1939 bp upstream of the transcription start site of OsDTC2 in rice cells using dual luciferase assays. The region between -1709 and -1450 bp was found to contain six W-box motifs, which are putative recognition sites for WRKY transcription factors, as cis elements involved in elicitor-responsiveness and/or basic promoter activity of OsDTC2.


[Ewing's sarcoma of the ethmoid bone. Case report].
Ewing's sarcoma is rarely located at the base of the skull. We report a case of ethmoid Ewing's sarcoma. Diagnosis was established on microscopic examination. A complete surgical resection was performed, followed by cranial base reconstruction. During the postoperative period, a combined course of chemotherapy and radiotherapy was performed. We also present a review of the literature.


Molecular biology of flower development in Antirrhinum majus (snapdragon).
In recent years, isolation of several genes affecting flower development in Antirrhinum majus made this species a major model system to study this important developmental process. Genes like SQUAMOSA and FLORICAULA are involved in determination of the floral meristem. Their mutation results in the development of bract-forming shoots at positions where normally flowers would develop. The phenotypes obtained upon mutation of the genes found to affect floral organogenesis fall into three major categories. In each category, always the floral organs in two adjacent whorls become homeotically transformed. Based on this observation a simple genetic model has been proposed to explain the establishment of floral organ identity in the four concentric whorls of the flower. The model hypothesizes the independent induction of two developmental pathways specifying floral organ identity after the formation of sepals as the basic type of organ following induction of a floral meristem. One of these pathways is under the control of the PLENA gene, the other is controlled by the DEFICIENS and GLOBOSA genes. These genes, as well as SQUAMOSA, encode transcription factors sharing a conserved DNA binding domain: the MADS-box. In vitro DNA-binding studies complemented with molecular genetic analysis of the respective mutants show that the DEF and GLO proteins may act together in the form of a heterodimer in the regulation of their target genes as well as in autoregulation. The possible interactions between other MADS-box proteins and their role in flower development is under current investigation.


Enhancing the research and publication efforts of health sciences librarians via an academic writing retreat.
This case study describes the South Central Chapter of the Medical Library Association (SCC/MLA) initiative to develop an academic writing retreat for members who sought the necessary time and support to advance their research projects toward publication. SCC/MLA staged a dedicated writing retreat to coincide with the organization's 2012, 2013, and 2014 annual meetings. Each cohort met over two days to write and to workshop their peers' manuscripts. Organizers distributed an online survey one month after each retreat to evaluate attendees' perceptions. Three years' worth of writing retreats yielded fourteen peer-reviewed articles and one book chapter. Participants indicated that the retreat helped them meet or exceed their writing goals by offering protected time and a setting conducive to productivity. The format of the retreat is cost effective and easily adaptable for fellow professionals who wish to organize a formal event as a conference offering or simply support a writing group at their home institutions. In SCC/MLA, the retreat revitalized interest in writing and demystified the scholarly publication process.


Neuron derived fractalkine promotes microglia to absorb hematoma via CD163/HO-1 after intracerebral hemorrhage.
Hematoma leads to progressive neurological deficits and poor outcomes after intracerebral hemorrhage (ICH). Early clearance of hematoma is widely recognized as an essential treatment to limit the damage and improve the clinical prognosis. CD163, alias hemoglobin (Hb) scavenger receptor on microglia, plays a pivotal role in hematoma absorption, but CD163 on neurons permits Hb uptake and results in neurotoxicity. In this study, we focus on how to specially promote microglial but not neuronal CD163 mediated-Hb uptake and hematoma absorption. RNA sequencing was used to explore the potential molecules involved in ICH progression, and hematoma was detected by magnetic resonance imaging (MRI). Western blot and immunofluorescence were used to evaluate the expression and location of fractalkine (FKN) after ICH. Erythrophagocytosis assay was performed to study the specific mechanism of action of FKN in hematoma clearance. Small interfering RNA (siRNA) transfection was used to explore the effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) on hematoma absorption. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum FKN concentration in ICH patients. FKN was found to be significantly increased around the hematoma in a mouse model after ICH. With its unique receptor CX3CR1 in microglia, FKN significantly decreased the hematoma size and Hb content, and improved neurological deficits in vivo. Further, FKN could enhance erythrophagocytosis of microglia in vitro via the CD163/ hemeoxygenase-1 (HO-1) axis, while AZD8797 (a specific CX3CR1 inhibitor) reversed this effect. Moreover, PPAR-γ was found to mediate the increase in the CD163/HO-1 axis expression and erythrophagocytosis induced by FKN in microglia. Of note, a higher serum FKN level was found to be associated with better hematoma resolution in ICH patients. We systematically identified that FKN may be a potential therapeutic target to improve hematoma absorption and we shed light on ICH treatment.