Synthesis of 1alpha,25-dihydroxyvitamin D analogues featuring a S(2)-symmetric CD-ring core.
Three analogues of 1a,25-dihydroxyvitamin D(3) (calcitriol), featuring a trans-fused decalin C,D-core with local S(2)-symmetry, and possessing identical side-chain and seco-B,A-ring structures, have been synthesized starting from readily available (4aR,8aS)-octahydronaphthalene-1,5-dione (7). The very short sequences involve the simultaneous introduction of the side-chain and seco-B,A-ring fragments via Suzuki and Sonogashira coupling reactions. The analogues are devoid of relevant biological activity.


Engineering the van der Waals interaction in cross-linking-free hydroxide exchange membranes for low swelling and high conductivity.
What a swell for hydroxides: The typical trade-off between swelling control and ion conductivity in ion-conducting polymer membranes is overcome by enhancement of van der Waals interactions among polymer chains. Using a quaternary phosphonium-functionalized polymer, the simple combination of high electron density of the polymer and large dipole moment of the functional group leads to low membrane swelling, high hydroxide conductivity, and excellent hydroxide exchange membrane fuel cell performance.


A self-determination theory based investigation of life skills development in youth sport.
This study investigated if basic need satisfaction and frustration mediated the associations between autonomy-supportive and controlling coaching behaviours and participants' development of eight different life skills in youth sport. British sports participants (N = 309, Mage = 14.71) completed measures assessing the study variables. Correlational analyses showed that autonomy-supportive coaching behaviours were positively associated with the satisfaction of participants' three basic needs (autonomy, competence, and relatedness) and their development of all eight life skills, whereas controlling coaching behaviours were only positively related to the frustration of participants' three basic needs. Mediational analyses revealed that satisfaction of all three basic needs combined (total need satisfaction) mediated the associations between autonomy-supportive coaching behaviours and participants' development of the eight life skills. Relatedness satisfaction mediated the associations between autonomy-supportive coaching behaviours and participants' development of all eight life skills except for goal setting; autonomy satisfaction mediated the associations between autonomy-supportive coaching behaviours and participants' time management skills; and competence satisfaction mediated the associations between autonomy-supportive coaching behaviours and participants' goal setting and emotional skills. Based on such findings, coaches should look to display autonomy-supportive behaviours that help to satisfy participants' three basic psychological needs and promote their life skills development in sport.


miR-191 suppresses angiogenesis by activation of NF-κB signaling.
MicroRNAs (miRNAs) are powerful regulators of diverse biologic processes. However, the function of most miRNAs in angiogenesis remains elusive. In this study, we identified miR-191-5p (miR-191) as a potent inhibitor of blood vessel development. Transfection of human dermal microvascular endothelial cells with miR-191 mimic (miR-191m) inhibited their proliferation, migration, and tube formation. Moreover, vascular sprouting of miR-191m-transfected mouse aortic rings was significantly reduced when compared with controls. Transfection with miR-191 inhibitor (miR-191i) induced proangiogenic effects. The anti- and proangiogenic activities of miR-191m and -191i were further demonstrated in vivo Additional molecular biologic analyses revealed that miR-191m activates NF-κB signaling by up-regulating the mRNA expression of p65. miR-191 also increased the mRNA levels of the antiangiogenic factors p21 and tissue inhibitor of metalloproteinase-1 and reduced the expression of the proangiogenic factors eNOS and matrix metalloproteinase-1 and -9. Blockade of NF-κB activation with Bay 11-7082 reversed the antiangiogenic effects of miR-191m. These findings indicate that miR-191 effectively suppresses angiogenesis by activation of the NF-κB signaling pathway.-Gu, Y., Ampofo, E., Menger, M. D., Laschke, M. W. miR-191 suppresses angiogenesis by activation of NF-κB signaling.


Photo-gated and self-powered three-dimensional DNA motors with boosted biostability for exceptionally precise and efficient tracing of intracellular survivin mRNA.
Benefiting from the outstanding signal amplification effect and the admirable construction flexibility, the currently proposed DNA motors (particularly DNA walkers) based biosensing concepts have provided a forceful fluorescence imaging tool for intracellular detection. Even so, this promising sensing means is not only subject to poor controllability and prone to produce false signals but also requires exogenous powering forces owing to the common employment of DNAzyme. In response to these challenges, we are herein motivated to present some meaningful solving strategies. For one thing, the surfaces of gold nanoparticles are conducted with a photo-gated walking behavior by introducing a photocleave mode, under which the light-switchable DNA walkers are capable of being selectively activated via an external ultraviolet source to faultlessly prevent the sensing frame from being pre-initiated during cellular uptake and intracellular delivery. For another, the intracellular biothiols are consumed by MnO2 nanosheets to effectively avoid the competitions to Au-S bonds to eliminate potential false outputs and also self-supply sufficient cofactors (Mn2+) to actualize a self-powered operation pattern as well as facilitate the endocytosis process. Following these breakthroughs, a favorable analysis performance towards a model tumor biomarker (survivin mRNA) is endowed with the newly raised biosensor, whose sensitivity is low to pM level with a sound specificity for identifying single base mismatching. Moreover, the significantly improved autonomous three-dimensional DNA walkers can be used to determine and dynamically trace the targets in live cancer cells with an exceptional precise and efficient manner, commendably impelling the sensing ability of DNA motors in biological specimens.


Role of the clinical pharmacologist in meeting the educational needs of the primary care physician.
Delivery of education in better therapeutics to physicians is more difficult because many physicians develop a false sense of confidence in their prescribing expertise. It is difficult for physicians to realize that remedies relied on for years may be inferior to the best that can now be offered. Epidemiological studies of drug usage provide information that the medical profession follows an irrational path in certain therapies. Correction of faulty prescribing habits can best be achieved by laws mandating specific corrective courses with proper evaluation of effectiveness.


Gene expression changes during the development of acute lung injury: role of transforming growth factor beta.
Acute lung injury can occur from multiple causes, resulting in high mortality. The pathophysiology of nickel-induced acute lung injury in mice is remarkably complex, and the molecular mechanisms are uncertain. To integrate molecular pathways and investigate the role of transforming growth factor beta (TGF-beta) in acute lung injury in mice. cDNA microarray analyses were used to identify lung gene expression changes after nickel exposure. MAPPFinder analysis of the microarray data was used to determine significantly altered molecular pathways. TGF-beta1 protein in bronchoalveolar lavage fluid, as well as the effect of inhibition of TGF-beta, was assessed in nickel-exposed mice. The effect of TGF-beta on surfactant-associated protein B (Sftpb) promoter activity was measured in mouse lung epithelial cells. Genes that decreased the most after nickel exposure play important roles in lung fluid absorption or surfactant and phospholipid synthesis, and genes that increased the most were involved in TGF-beta signaling. MAPPFinder analysis further established TGF-beta signaling to be significantly altered. TGF-beta-inducible genes involved in the regulation of extracellular matrix function and fibrinolysis were significantly increased after nickel exposure, and TGF-beta1 protein was also increased in the lavage fluid. Pharmacologic inhibition of TGF-beta attenuated nickel-induced protein in bronchoalveolar lavage. In addition, treatment with TGF-beta1 dose-dependently repressed Sftpb promoter activity in vitro, and a novel TGF-beta-responsive region in the Sftpb promoter was identified. These data suggest that TGF-beta acts as a central mediator of acute lung injury through the alteration of several different molecular pathways.


Different types of dizziness in patients with peripheral vestibular diseases--their prevalence and relation to migraine.
Besides spontaneous attacks of vertigo or unsteadiness, other symptoms, i.e. drop attacks, lateropulsion, illusions that the room or body is tilted, 'walking on pillows' or 'stepping into a hole', occur without precipitating head movement in almost 50% of patients with peripheral vestibular dysfunctions. The sensation of static tilt was closely connected to migraine and Meniere's disease (MD). To record the prevalence of the different symptoms with respect to vestibular diagnosis and its relation to migraine. Data from 100 patients with MD, benign paroxysmal positional vertigo (BPPV), or unilateral peripheral vestibular impairment (UPVI) were analyzed with respect to vestibular diagnosis and migraine as a secondary diagnosis. Spontaneous attacks of vertigo or unsteadiness occurred in 74% and 48% of patients, respectively. Vertigo was significantly more often reported in patients with MD and BPPV. In patients with BPPV, the duration of spontaneous vertigo was shorter than in patients with MD. The relative incidence of other symptoms were: unsteadiness, 48%; 'stepping into a hole', 46%; lateropulsion, 35%; 'walking on pillows', 21%; and drop attacks, 19%. Only the sensation of static tilt, which occurred in 8% of patients, was significantly correlated to MD or to migraine.


[Initial clinical results of the prevention of intraoperative adhesions in children].
Postoperatively in 2 to 6% of all cases the result was an intestinal obstruction caused by adhesion. The usual measures were without permanent success. Intraoperatively we applied in 20 children streptokinase-streptodornase in the abdomen. During relaparotomy we saw no adhesions in 40% of these cases, whereas in a control group in all cases adhesions were found.


SILO: A Computational Method for Detecting Copy Number Gain in Clinical Specimens Analyzed on a Next-Generation Sequencing Platform.
Next-generation sequencing (NGS) has proved to be a beneficial approach for genotyping solid tumor specimens and for identifying clinically actionable mutations. However, copy number variations (CNVs), which can be equally important, are often challenging to detect from NGS data. Current bioinformatics methods for CNV detection from NGS often require comparison of tumor/normal pairs and/or the sequencing of whole genome or whole exome. These approaches are currently impractical for routine clinical practice. However, clinical practice does involve repeated use of the same gene panel on a large number of specimens over a long period of time. We take advantage of this repetitiveness and present SILO: a procedure for CNV detection based on NGS on a gene panel. The SILO algorithm analyzes coverage depth of the aligned reads from a sample and predicts CNV by comparing this depth to the average depth seen in a large training set of other samples. Such comparison is robust and can reliably detect copy number gain, although it is found to be unreliable in detecting copy number losses. Successful validation of SILO on NGS data from the Ion Torrent platform with two panels is presented: a small hotspot panel and a larger cancer gene panel.


Utilization of acetate in Escherichia coli: structural organization and differential expression of the ace operon.
Growth of Escherichia coli on acetate as the sole source of carbon and energy requires operation of the glyoxylate bypass in connection with the expression of the polycistronic ace operon. The structural organization of this operon is presented, including the 3 structural genes coding respectively for malate synthase (aceB), isocitrate lyase (aceA) and isocitrate dehydrogenase kinase/phosphatase (aceK), and the surrounding genes iclR and metA. In addition, the differential expression of genes aceB, aceA, and aceK has been tested both in vivo in a minicell system and in vitro in a plasmid-directed transcription-translation coupled system. Moreover, the codon usage and adaptation to transfer RNA frequencies during translation of the corresponding messenger RNAs have been measured.


Evaluation of quality of life in patients with axial spondyloarthritis and its association with disease activity, functionality, mobility, and structural damage.
To evaluate quality of life (QoL) in patients with axial spondyloarthritis (axSpA) and its association with disease activity, functionality, structural damage, and spinal mobility, using patient-reported outcomes. This was an observational, cross-sectional, and single-center study in which 100 consecutive patients with axSpA were included. We obtained from all patients' sociodemographic data and values related to disease activity, functionality, structural damage, mobility, and quality of life. The Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) was considered as the primary outcome. Pearson r statistic, Student's T test, and univariate and multivariate linear regressions were performed to relate ASQoL with the studied covariates. Mean ASQoL score in all patients was 4.02 ± 2.81, with statistically significant differences between male and female (3.61 ± 2.80 vs. 4.83 ± 2.70). Patients with high disease activity (measured by the ASAS-endorsed Disease Activity Score, ASDAS > 2.1) showed higher mean score in ASQoL than those with low disease activity (ASDAS ≤ 2.1) (3.21 ± 0.74 vs. 1.43 ± 0.43, p < 0.001). ASQoL presented a significant linear correlation with BASDAI, BASFI, and ASDAS (r > 0.60). However, disease duration was not significantly correlated with ASQoL. Finally, the 68.9% of the ASQoL variability (R2 = 0.689) was determined by BASDAI, BASFI, and mSASSS, presenting mSASSS a negative regression coefficient (- 0.035). In our study, the impairment of QoL was mainly associated with disease activity (BASDAI) and worsening of functionality (BASFI). However, there is an inverse relationship between the worsening of QoL and structural damage. In addition, disease duration does not seem to influence the patient's welfare.


Migraine: a question and answer review.
Internists commonly treat migraine, which affects more than 29 million Americans yearly. This article reviews epidemiology, pathophysiology, comorbidity, clinical features, diagnostic testing, acute and preventive treatment, and women's issues. Physicians and migraineurs would like to see more effective and more tolerable medications.


Tetracycline-sensitive mutants of the F-like R factors R100 and R100-1.
The majority of tetracycline-sensitive (Tets) mutants of R100 and R100-1 are multisite (deletion) mutants. About 50% of these are also transfer-deficient, indicating that the Tetr locus is closely linked to the transfer genes. Tet(s) mutants with single-site lesions are also described.


A comparison of observed and self-reported helmet use and associated factors among motorcyclists in Hyderabad city, India.
India has a high burden of fatal road traffic injuries (RTIs). A large proportion of fatal RTIs in India are among motorcyclists. The overall goal of this study is to assess and compare observed and self-reported prevalence of helmet use; and to identify factors associated with helmet use and over-reporting in Hyderabad city, India. Roadside knowledge, attitude and practice interviews. Six rounds of roadside interviews were conducted with motorcyclists (drivers and pillion riders) between July 2011 and August 2013 using a structured tool developed for this study. Observations on helmet use were recorded and respondents were also asked if they 'always wear a helmet'. Prevalence of helmet use was calculated and a paired t-test was used to compare observed and self-reported helmet use proportions. Unadjusted and adjusted odds ratios were calculated to identify factors associated with helmet use and over-reporting. A total of 4872 respondents participated in the roadside interview. The response rate was 94.4%. The overall observed helmet use was 34.5% and 44.5% of respondents reported that they 'always wear a helmet'. As the observed helmet use increased, the over-reporting of helmet use was found to decrease. However, factors associated with observed and self-reported helmet use are similar. Male gender, youth (≤24 years), a lower level of education and non-ownership of helmet were associated with a higher risk of not wearing helmets. Male gender, youth (≤24 years), no schooling, riding a lower engine capacity motorcycle and using a motorcycle for purposes other than travelling to school/work were associated with over-reporting of helmet use. Self-reports provide an overestimate of helmet use that lessens as actual helmet use increases. Interviews also allow identification of factors associated with helmet use. Increasing helmet ownership and enhanced enforcement may help increase helmet use.


Chloride Channels and Transporters: Roles beyond Classical Cellular Homeostatic pH or Ion Balance in Cancers.
The canonical roles of chloride channels and chloride-associated transporters have been physiologically determined; these roles include the maintenance of membrane potential, pH balance, and volume regulation and subsequent cellular functions such as autophagy and cellular proliferative processes. However, chloride channels/transporters also play other roles, beyond these classical function, in cancerous tissues and under specific conditions. Here, we focused on the chloride channel-associated cancers and present recent advances in understanding the environments of various types of cancer caused by the participation of many chloride channel or transporters families and discuss the challenges and potential targets for cancer treatment. The modulation of chloride channels/transporters might promote new aspect of cancer treatment strategies.


Unimanual motor learning impaired by frontomedial and insular lesions in man.
We correlated impaired unimanual motor learning with the lesion site in 53 patients with chronic lesions predominantly of the frontal lobe. The lesions were assessed using computed tomography (CT), then transferred to standard templates of nine slices parallel to the canthomeatal plane and digitized with a raster matrix of 3 mm by 3 mm width. The learning task was to track a moving target on a computer screen with a dot guided by the preferred hand, while the horizontal coupling between hand movement and screen was inverted. The mean tracking error was recorded over eight successive trials of 80s duration. If the mean error of the last three trials was not lower than that of the first three trials, impaired motor learning was assumed. We correlated performance and lesion with a contingency table analysis for each raster element. Impaired motor learning was associated with a lesion within the supplementary motor area and adjacent anterior cingulate, and within the anterior insular region. Our results indicate that these regions are critical for motor learning and functional plasticity in man. Our data support activation patterns obtained with positron emission tomography.


Effect of hypoxia on erythroblasts from avian fetal liver: adenosine triphosphate levels and hemoglobin synthesis.
A system for the isolation and functional evaluation of fetal liver erythroblasts is described. Isolated erythroblasts were prepared from 14-day embryonic avian livers and incubated at various oxygen tension (0, 5, 12, and 95%). The concentration of ATP in erythroblasts remained constant for at least 4 hr at 37degree, but was rapidly reduced by incubation in nitrogen. Protein synthesis as measured by L-[14C]leucine incorporation into cell protein occurred at a linear rate in 5%, 12%, and 95% oxygen, whereas little protein synthesis occurred at 0% oxygen. The effect of hypoxia on the type of hemoglobin synthesized was studied in this system by isolating the hemoglobin A, hemoglobin D, and hemoglobin H fractions and determining the incorporation of L-[14C]leucine. The major fraction, hemoglobin A, contained most of the radioactivity; smaller amounts were present in hemoglobin D and hemoglobin H, respectively. The relative proportion of each hemoglobin synthesized was not altered by oxygen from 5% to 95%. These results argue against a direct effect of oxygen on the type of hemoglobin synthesized at this stage of development.


A simple operative procedure for the treatment of Stahl's ear.
Stahl's ear is a rather rare congenital deformity and operative procedures for its correction have seldom been reported. We recently devised a simple method of surgical treatment, which is briefly described as follows: incisions are made into the third crus cartilage to facilitate the formation of a helical fold, and the cartilage is sutured by means of a mattress suture. This method makes it possible to produce a natural helix, though it fails to eliminate the third crus.


Early onset of inflammation and later involvement of TGFbeta in Duchenne muscular dystrophy.
To identify stage-specific induction of molecular pathology pathways in Duchenne muscular dystrophy (DMD). We performed mRNA profiling using muscles from fetopsies, infants (aged 8 to 10 months), and symptomatic patients (aged 5 to 12 years) with DMD, and age- and sex-matched controls. We performed immunohistochemistry to determine changes at the protein level and protein localization. Activated tissue dendritic cells, expression of toll-like receptor 7, and strong induction of nuclear factor-kappaB pathways occurred soon after birth in DMD muscle. Two muscle wasting pathways, atrogin-1 and myostatin, were not induced at any stage of the disease. Normal muscle showed accumulation of glycolytic and oxidative metabolism capacity with increased age, but this accumulation failed in DMD. The transforming growth factor (TGF)-beta pathway was strongly induced in symptomatic patients, with expression of TGFbeta type II receptor and apoptosis signal-regulating kinase 1 proteins on subsets of mature DMD myofibers. Our data show stage-specific remodeling of human dystrophin-deficient muscle, with inflammatory pathways predominating in the presymptomatic stages and acute activation of TGFbeta and failure of metabolic pathways later in the disease.


Cholesterolosis in routine histopathological examination after cholecystectomy: what should a surgeon behold in the reports?
Cholecystectomy is one of the most common surgical procedures. Postoperative investigation of cholecystectomy specimen has a great value since histopathological reports may document some entities with significant clinical consequences. The aim of this study was to evaluate the association between cholesterolosis and the reports indicating some histopathological alterations in symptomatic cholecystitis. This paper is based on a retrospective study. Histopathological reports of 432 cholecystectomy specimens between January 2011 and June 2013 were reviewed. Three reports were excluded due to perioperative diagnosis of cancer. Reports of 429 cholecystectomy specimens of the acute and symptomatic chronic cholecystitis patients were analyzed. Standardization of the reporting was questioned. Age, gender, histopathological wall thickness of gallbladder, reporting rates of acute inflammation, cholesterolosis, polypoid lesions, epithelial hyperplasia, gastric or intestinal metaplasia, dysplasia and incidental cancer were investigated and compared between patients with and without cholesterolosis. Reported rates of histopathological findings were comparable between patients under and over 60 years old and patients with and without reported cholesterolosis. Reported histopathological findings were presented as acute inflammation in 46 (10.7%), cholesterolosis in 79 (18.4%), gallbladder polypoid lesions in 7 (1.6%), epithelial hyperplasia in 16 (3.7%), metaplasia of any type in 34 (7.9%) of 429 patients. Dysplasia was excluded whereas one incidental gallbladder carcinoma was reported. Epithelial hyperplasia and metaplasia were found to be related to age. Gallbladder wall thickness was decreased with cholesterolosis. However, only a correlation between cholesterolosis and gender or metaplasia was noted. Recent study suggests that cholesterolosis is somehow associated with metaplasia. Thus, surgeons should carefully interpret the histopathology reports based on unusual or exceptional findings corresponding to the cholecystectomy specimens. Any abnormal finding in the reports should be investigated in terms of the progress of the pathology and also its clinical consequences.


Tumors and amyloidosis in mice painted with crude oil found on bathing beaches.
Oil lumps collected on the beaches of Israel in 1970, 1971 and 1973 were extracted with pure acetone and the extracts were used to paint the skin of mice twice weekly for 12 months. The oil lumps originated from crude oil spilled from tankers. The less recently collected oils induced papillomata and lymphomata in some animals. They were also more active than the recent oil in the induction of generalized amyloidosis. Mice painted for 12 months with acetone alone developed amyloidosis to a similar extent as those painted with the oldest oil. In previously reported experiments, however, acetone was much less active than the oil in producing amyloidosis after 5 months of painting. The possibility that acetone and oil might act both synergistically or to be antagonistic at different phases of amyloidogenesis is discussed.


Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of pyrrolopiperidinone acetic acids as CRTh2 antagonists.
Pyrrolopiperidinone acetic acids (PPAs) were identified as highly potent CRTh2 receptor antagonists. In addition, many of these compounds displayed slow-dissociation kinetics from the receptor. Structure-kinetic relationship (SKR) studies allowed optimisation of the kinetics to give potent analogues with long receptor residence half-lives of up to 23 h. Low permeability was a general feature of this series, however oral bioavailability could be achieved through the use of ester prodrugs.


The multiple linkages of personality and disease.
Associations between personality and health and longevity are increasingly well documented, but the causal inter-connections are often much more complex than originally anticipated. Multiple causal pathways may operate simultaneously as the individual travels an idiosyncratic route across the life-span. Therefore, a straightforward model of personality, immunity, and disease may never be established and validated, because it overlooks other key elements of the causal processes. Psychoneuroimmunology research may profit from closer integration into the broader conceptual understandings of personality and health, using a new life-span epidemiological personality approach.


Effects of irradiation on the ciliary activity of the eustachian tube and the middle ear mucosa.
Radiation-induced changes in the ciliary activity of the eustachian tube and middle ear mucosa were investigated in a laboratory model. Twenty-four guinea pigs were sacrificed, and a mucosa at the bony portion of each eustachian tube and from the middle ear proximal and distal to the tube were sampled. The mucosal samples were irradiated with 200 kV hard X-rays discretely at a dosage level of 0.5-30.0 Gy, and the induced changes in ciliary activity were expressed as a percent deviation from baseline levels before irradiation. The present study demonstrates that the cilia of the eustachian tube and middle ear mucosa show different reactions to irradiation according to their tympanic locations.


Detection and distribution of torque teno sus virus 1 in porcine reproductive and respiratory syndrome virus positive/negative pigs.
To investigate the detection rate and distribution of torque teno sus virus 1 (TTSuV1) in porcine reproductive and respiratory syndrome virus (PRRSV) positive/negative pigs, 2384 pathological tissues samples collected from 6 provinces of Eastern China from 2010 to 2013 were amplified using previously published PRRSV and TTSuV1 primers. The presence and viral load of TTSuV1 were investigated in a wide range of samples from 5 PRRSV positive/negative 4-week-old pigs by real-time TaqMan PCR. TTSuV1 was detected in 65.3% of 1115 PRRSV-positive samples, and 47.2% of 1269 negative samples. Viral DNA was most commonly detected in the immune organs, including spleen, lung, pancreas, and mesenteric and inguinal lymph nodes, followed by serum, liver, kidney, trachea, anal swabs, nasal swabs and sex glands of PRRSV-positive or negative pigs. TTSuV1 DNA loads in PRRSV-positive pigs increased from 2 to 5 times in almost all the corresponding parts compared with PRRSV-negative pigs. Statistical analysis showed that PRRSV may have a synergistic effect with TTSuV1, and promote the replication and proliferation of TTSuV1.


Optimized multi-axis spiral projection MR fingerprinting with subspace reconstruction for rapid whole-brain high-isotropic-resolution quantitative imaging.
To improve image quality and accelerate the acquisition of 3D MR fingerprinting (MRF). Building on the multi-axis spiral-projection MRF technique, a subspace reconstruction with locally low-rank constraint and a modified spiral-projection spatiotemporal encoding scheme called tiny golden-angle shuffling were implemented for rapid whole-brain high-resolution quantitative mapping. Reconstruction parameters such as the locally low-rank regularization parameter and the subspace rank were tuned using retrospective in vivo data and simulated examinations. B0 inhomogeneity correction using multifrequency interpolation was incorporated into the subspace reconstruction to further improve the image quality by mitigating blurring caused by off-resonance effect. The proposed MRF acquisition and reconstruction framework yields high-quality 1-mm isotropic whole-brain quantitative maps in 2 min at better quality compared with 6-min acquisitions of prior approaches. The proposed method was validated to not induce bias in T1 and T2 mapping. High-quality whole-brain MRF data were also obtained at 0.66-mm isotropic resolution in 4 min using the proposed technique, where the increased resolution was shown to improve visualization of subtle brain structures. The proposed tiny golden-angle shuffling, MRF with optimized spiral-projection trajectory and subspace reconstruction enables high-resolution quantitative mapping in ultrafast acquisition time.


The behavioral ecology of sympatric African apes: implications for understanding fossil hominoid ecology.
The behavioral ecology of the great apes is key evidence used in the reconstruction of the behavior of extinct ape and hominid taxa. Chimpanzees and gorillas have been studied in detail in the wild, and some studies of their behavioral ecology in sympatry have also been been carried out. Although the two ape species have divergent behavior and ecology in important respects, recent studies have shown that the interspecific differences are not as stark as previously thought and subsequently urge new consideration of how they share forest resources when sympatric. These new data require re-examination of assumptions about key aspects of chimpanzee-gorilla ecological divergence, such as diet, ranging and nesting patterns, and the mating system. Diet is a key component of the species' adaptive complexes that facilitates avoidance of direct competition from the other. While the nutritional basis for chimpanzee food choice remains unclear and no doubt varies from site to site, this species is a ripe fruit specialist and ranges farther during periods of ripe fruit scarcity. Gorillas in the same habitat also feed on ripe fruit when widely available, but fall back onto fibrous plant foods during lean periods. The inclusion of animal protein in the diet of the chimpanzees and its absence in that of the gorillas also distinguish the species ecologically. It may also offer clues to aspects of ecological divergence among early members of the hominid phylogeny. The paper concludes by suggesting likely characteristics of sympatric associations of Pliocene hominids, based on field data from extant sympatric apes.


The Jacki Jacket after mastectomy with reconstruction: a randomized pilot study.
Breast cancer patients undergoing mastectomy with reconstruction (TM + R) often experience post-operative discomfort from surgical drains. Despite a variety of garment options for use in the post-operative period, high-quality data assessing the impact of specific garments on post-operative pain are lacking. We report the results of a prospective randomized trial assessing the impact of the Jacki Jacket (JJ), a long-sleeve jacket with inner drain receptacle pockets, on post-discharge pain and quality of life (QOL) after TM + R. Breast cancer patients undergoing TM + R at a single institution were randomized post-operatively to receive a JJ or usual care (UC). Participant-reported demographics, pain intensity, and QOL were collected on post-operative day 1 (T1). Following discharge, participants completed a daily pain and medication dairy (T2); on day of drain(s) removal (T3), participants again completed pain and QOL questionnaires. Linear models were used to evaluate associations between JJ use, post-operative pain, and QOL. From 3/8/17 to 12/20/17, 139 women were randomized. All participants completed T1 measures, 102 returned the T2 diary, and 118 (84.9%) completed T3 questionnaires. There was no significant difference in pain scores between JJ and UC arms at any timepoint. Adjusting for surgery type, age, marital status, depression, and obesity, participants randomized to JJ reported significantly better body image scores (estimate = 12.94, p = 0.009). There were no adverse events. Although JJ garment use did not impact post-operative pain intensity scores, the significant impact of JJ use on body image supports consideration for inclusion of such garments in post-operative care for patients undergoing TM + R. Registered with ClinicalTrials.gov, NCT number NCT02976103, November 18, 2016.


Smart capsule for targeted proximal colon microbiome sampling.
The gastrointestinal (GI) tract, particularly the colon region, holds a highly diverse microbial community that plays an important role in the metabolism, physiology, nutrition, and immune function of the host body. Accumulating evidence has revealed that alteration in these microbial communities is the pivotal step in developing various metabolic diseases, including obesity, inflammatory bowel disease (IBD), and colorectal cancer. However, there is still a lack of clear understanding of the interrelationship between microbiota and diet as well as the effectiveness of chemoprevention strategies, including pre and probiotic agents in modifying the colonic microbiota and preventing digestive diseases. Existing methods for assessing these microbiota-diet interactions are often based on samples collected from the feces or endoscopy techniques which are incapable of providing information on spatial variations of the gut microbiota or are considered invasive procedures. To address this need, here we have developed an electronic-free smart capsule that enables site-specific sampling of the gut microbiome within the proximal colon region of the GI tract. The 3D printed device houses a superabsorbent hydrogel bonded onto a flexible polydimethylsiloxane (PDMS) disk that serves as a milieu to collect the fluid in the gut lumen and its microbiome by rapid swelling and providing the necessary mechanical actuation to close the capsule after the sampling is completed. The targeted colonic sampling is achieved by coating the sampling aperture on the capsule with a double-layer pH-sensitive enteric coating, which delays fluid in the lumen from entering the capsule until it reaches the proximal colon of the GI tract. To identify the appropriate pH-responsive double-layer coating and processing condition, a series of systematic dissolution characterizations in different pH conditions that mimicked the GI tract was conducted. The effective targeted microbial sampling performance and preservation of the smart capsule with the optimized design were validated using both realistic in vitro GI tract models with mixed bacteria cultures and in vivo with pigs as an animal model. The results from 16s rRNA and WideSeq analysis in both in vitro and in vivo studies showed that the bacterial population sampled within the retrieved capsule closely matched the bacterial population within the targeted sampling region (proximal colon). Herein, it is envisioned that such smart sampling capsule technology will provide new avenues for gastroenterological research and clinical applications, including diet-host-microbiome relationships, focused on human GI function and health. STATEMENT OF SIGNIFICANCE: The colonic microbiota plays a major role in the etiology of numerous diseases. Extensive efforts have been conducted to monitor the gut microbiome using sequencing technologies based on samples collected from feces or mucosal biopsies that are typically obtained by colonoscopy. Despite the simplicity of fecal sampling procedures, they are incapable of preserving spatial and temporal information about the bacteria through the gastrointestinal (GI) tract. In contrast, colonoscopy is an invasive and impractical approach to frequently assess the effect of dietary and therapeutic intake on the microbiome and their impact on the health of the patient. Here, we developed a non-invasive capsule that enables targeted sampling from the ascending colon, thereby providing crucial information for disease prediction and monitoring.


Sensitivity enhanced NIR photoacoustic CO detection with SF6 promoting vibrational to translational relaxation process.
A challenge for slowly relaxing carbon monoxide (CO) molecules detection using photoacoustic spectroscopy (PAS) is to promote the vibration-translation (V-T) relaxation process. Addressing this challenge, a sensitivity enhanced photoacoustic CO sensor with sulfur hexafluoride (SF6) as the promotor is investigated and demonstrated. A 1568 nm near-infrared (NIR) laser diode and a customized optical amplifier are used as the excitation source to generate the photoacoustic signal. A differential photoacoustic cell is simulated and designed to obtain identical laminar flow distribution in the resonant cell to suppress the flow noise. The modulation frequency and added SF6 volume ratio are optimized experimentally to achieve optimal sensitivity. Feasibility and performance of the CO sensor with a small amount of SF6 as promotor is discussed and evaluated, obtaining a ~ 2 times improvement of signal value compared to the one with pure N2 background and resulting in a minimum detection limit of 467.5 ppb for CO detection.


Sexual dimorphism in the three-dimensional detailed crown structure of maxillary first premolars.
Maxillary first premolars have a unique shape because of their curvature features, positional relationship of the cusps, and most prominent points, making them different from other teeth. This study aimed to quantitatively analyze the detailed three-dimensional morphometric structure of maxillary first premolars and sexual dimorphism. The study participants were 60 elementary and junior high school students (30 boys and 30 girls) in Japan. The distance between landmarks was measured using the three-dimensional coordinates of plaster casts, and the data collected was statistically analyzed. Sexual dimorphism was greater in the lingual cusp, showing greater variation in size than the buccal cusp. Boys exhibited significantly larger relative distances in the mesiodistal and buccolingual directions than girls; particularly, regarding mesiodistal diameter of the central groove, mesial slope of the buccal cusp, and distal slope of the lingual cusp. These results may be due to a slight difference in the timing of secondary enamel knots between boys and girls during the developmental stage, which was reflected in the sexual dimorphism of the completed teeth. Curvature features, cusp positions, and most prominent points were considered individual traits because they were not interrelated. Subtle differences during the developmental stage may lead to sexual dimorphism of the completed crown. Furthermore, the morphological characteristics of the maxillary first premolars may be related to their location in the dental arch.


SELDI-TOF-MS: the proteomics and bioinformatics approaches in the diagnosis of breast cancer.
Breast cancer has never had any good serum tumor markers. Therefore, we developed and evaluated a proteomics approach to searching for new biomarkers and building diagnostic models. SELDI-TOF-MS ProteinChip was used to detect the serum protein patterns of 49 breast cancer patients, 51 patients with benign breast diseases, and 33 healthy women. The diagnostic models were developed and validated using bioinformatics tools such as artificial neural networks and discriminant analysis. In total, four models were built and their sensitivities and specificities were satisfactory. The abilities of these models to diagnose stage I breast cancer were not worse than for stages II-IV (P>0.05). Four candidate biomarkers of breast cancer were found. The high sensitivity and specificity achieved by this method show great potential for the early detection of breast cancer and facilitation of discovering new and improved biomarkers.


Characterisation of the arabinose-rich carbohydrate composition of immature and mature marama beans (Tylosema esculentum).
Marama bean (Tylosema esculentum) is an important component of the diet around the Kalahari Desert in Southern Africa where this drought resistant plant can grow. The marama bean contains roughly 1/3 proteins, 1/3 lipids and 1/3 carbohydrates, but despite its potential as dietary supplement little is known about the carbohydrate fraction. In this study the carbohydrate fraction of "immature" and "mature" marama seeds are characterised. The study shows that the marama bean contains negligible amounts of starch and soluble sugars, both far less than 1%. The cell wall is characterised by a high arabinose content and a high resistance to extraction as even a 6M NaOH extraction was insufficient to extract considerable amounts of the arabinose. The arabinose fraction was characterised by arabinan-like linkages and recognised by the arabinan antibody LM6 and LM13 indicating that it is pectic arabinan. Two pools of pectin could be detected; a regular CDTA (1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid) or enzymatically extractable pectin fraction and a recalcitrant pectin fraction containing the majority of the arabinans, of which about 40% was unextractable using 6M NaOH. Additionally, a high content of mannose was observed, possibly from mannosylated storage proteins.


LRRC8A influences the growth of gastric cancer cells via the p53 signaling pathway.
Leucin-rich repeat containing protein A (LRRC8A), a component of the volume-regulated anion channel (VRAC), is activated by cell swelling and mediates regulatory volume decrease. We previously reported the expression of and important roles for several ion transporters in various gastrointestinal cancers, which have potential as novel targets for cancer treatment; however, the significance of LRRC8A in gastric cancer (GC) remains unclear. Knockdown experiments were performed by transfecting human GC cell lines with LRRC8A siRNA. Gene expression was then assessed using microarray analysis. Samples from 132 patients with GC were subjected to immunohistochemistry (IHC) for LRRC8A, and its relationships with clinicopathological factors and prognosis were examined. The knockdown of LRRC8A suppressed the proliferation and movement of cells and enhanced apoptosis. The results of the microarray analysis showed the up- or down-regulated expression of genes related to the p53 signaling pathway (JNK, p53, p21, Bcl-2, and FAS) in LRRC8A-knockdown cells. IHC revealed a correlation between the expression of LRRC8A and the pT status (p = 0.015), and multivariate analysis identified the strong expression of LRRC8A as an independent prognostic factor for 5-year survival in GC patients (p = 0.0231). The present results indicate that LRRC8A functions as a mediator of and/or biomarker for GC.


Rice husks and their hydrochars cause unexpected stress response in the nematode Caenorhabditis elegans: reduced transcription of stress-related genes.
Currently, char substrates gain a lot of interest since soils amended with such substrates are being discussed to increase in fertility and productivity, water retention, and mitigation of greenhouse gases. Char substrates can be produced by carbonization of organic matter. Among different process conditions, temperature is the main factor controlling the occurrence of organic and inorganic contaminants such as phenols and furfurals, which may affect target and non-target organisms. The hydrochar produced at 200 °C contained both furfural and phenol with concentrations of 282 and 324 mg kg(-1) in contrast to the 300 °C hydrochar, which contained only phenol with a concentration of 666 mg kg(-1). By washing with acetone and water, these concentrations were significantly reduced. In this study, the potential toxic effects of hydrochars on the free-living nematode Caenorhabditis elegans were investigated via gene transcription studies using the following four matrices: (i) raw rice husk, (ii) unwashed rice char, (iii) acetone/water washed rice char, and (iv) the wash water of the two rice chars produced at 200 and 300 °C via hydrothermal carbonization (HTC). Furthermore, genetically modified strains, where the green fluorescent protein (GFP) gene sequence is linked to a reporter gene central in specific anti-stress regulations, were also exposed to these matrices. Transgenic worms exposed to hydrochars showed very weak, if any, fluorescence, and expression of the associated RNAs related to stress response and biotransformation genes was surprisingly downregulated. Similar patterns were also found for the raw rice husk. It is hypothesized that an unidentified chemical trigger exists in the rice husk, which is not destroyed during the HTC process. Therefore, the use of GFP transgenic nematode strains cannot be recommended as a general rapid monitoring tool for farmers treating their fields with artificial char. However, it is hypothesized that the observed reduced transcriptional response with the subsequent lack of energy-consuming stress response is an energy-saving mechanism in the exposed nematodes. If this holds true in future studies, this finding opens the window to an innovative new field of stress ecology.


Syndrome-related outcomes following posterior vault distraction osteogenesis.
The most commonly occurring syndromic craniosynostoses are Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, and Saethre-Chotzen syndrome. There is insufficient data regarding postoperative syndrome-related outcomes following the posterior vault distraction osteogenesis (PVDO) procedure, as well as data addressing whether or not additional procedures will be subsequently necessary to comprehensively treat children who undergo PVDO. Thus, the objective of this study is to describe and compare syndrome-related potential complications and outcomes associated with the PVDO procedure. An observational retrospective study was performed on consecutive patients (n=24) with Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, or Saethre-Chotzen syndrome, respectively, who underwent PVDO between 2012 and 2019. Demographic data (patient gender and age when the PVDO procedure was performed), diagnosis, surgery-related data, and outcome data (perioperative and midterm complications and need for additional surgery) were verified. Total relative blood transfusion volumes per kilogram for the patients were as follows: 22.75 ± 9.30 ml for Apert syndrome, 10.73 ± 2.28 ml for Crouzon syndrome (Apert versus Crouzon, p<0.05), 18.53 ± 8.08 ml for Pfeiffer syndrome, and 19.74 ± 9.12 ml for Saethre-Chotzen syndrome. None of the patients required a secondary procedure to alleviate intracranial pressure except for a Saethre-Chotzen patient. PVDO is an effective technique to address elevated intracranial pressure in SC patients that alleviates the need for secondary procedures at midterm follow-up. Apert syndrome patients presented relatively higher total blood transfusion rates than Crouzon syndrome patients who were operated on at a later age and weighed more.


Spray with Nitric Oxide Donor Accelerates Wound Healing: Potential Off-the-Shelf Solution for Therapy?
Ditrosyl iron complexes (DNIC) are endogenous donors of nitric oxide. The possibility of their application to stimulate regeneration has been studied for more than 15 years. However, the most effective dose and form of delivery have not yet been determined. The aim of this research was to develop a spray form of DNIC that accelerates wound healing. We prepared a series of DNIC sprays with spray dosages of 10, 50 and 100 μg. We modelled full-thickness skin wounds in 24 Wistar rats and treated them with distilled water (n = 6), 10 (n = 6), 50 (n = 6) and 100 μg (n = 6) for three post-operative days. On the fourth day, the excised wound tissues were studied by morphological, immunohistochemical and morphometric methods. We demonstrated that 50 μg of DNIC spray had the most beneficial effect on wound healing: the thickness of the granulation tissue layer was 140% higher, vimentin positive fibroblasts predominated and the intensity of inflammation was significantly lower than in the control. There was a dose-dependent decrease in the functional activity of mast cells in the experimental groups compared to the control. DNIC spray is a potential effective dosage form for the treatment of large-area skin lesions.


Spin-trappers and vitamin E prolong endurance to muscle fatigue in mice.
The involvement of free radicals in endurance to muscle effort is suggested by experimental and clinical data. Therefore, experiments have been performed to observe the effect of trapping free radicals on endurance to swimming in mice. Animals were injected intraperitoneally with each of three spin-trappers [N-tert-Butyl-alpha-Phenyl-Nitrone (PBN),alpha-4-Pyridyil-1-Oxide-N-tert-Butyl-Nitrone (POBN) and 5,5-Dimethyl-1-Pirrolyn-N-Oxide (DMPO): 0.2 ml of 10(-1) molar solution]. Each mouse was submitted to a swimming test to control resistance to exhaustion a) without any treatment, b) after administration of each spin-trapper in a random order c) after saline. Control experiments were performed with saline and with vitamin E. Endurance to swimming was greatly prolonged by pretreatment with all the spin-trappers (DMPO less than 0.0001; POBN less than 0.0001; PBN less than 0.001) and with Vitamin E. Experiments state that compared to treatment with spin-trappers or Vitamin E, administration of saline alone did not enhance time to exhaustion so that the increase in time to exhaustion with the various free radical scavengers was not the effect of training. Therefore, free radicals could be considered as one of the factors terminating muscle effort in mice.


Eph/Ephrin signaling in injury and inflammation.
The Eph/ephrin receptor-ligand system plays an important role in embryogenesis and adult life, principally by influencing cell behavior through signaling pathways, resulting in modification of the cell cytoskeleton and cell adhesion. There are 10 EphA receptors, and six EphB receptors, distinguished on sequence difference and binding preferences, that interact with the six glycosylphosphatidylinositol-linked ephrin-A ligands and the three transmembrane ephrin-B ligands, respectively. The Eph/ephrin proteins, originally described as developmental regulators that are expressed at low levels postembryonically, are re-expressed after injury to the optic nerve, spinal cord, and brain in fish, amphibians, rodents, and humans. In rodent spinal cord injury, the up-regulation of EphA4 prevents recovery by inhibiting axons from crossing the injury site. Eph/ephrin proteins may be partly responsible for the phenotypic changes to the vascular endothelium in inflammation, which allows fluid and inflammatory cells to pass from the vascular space into the interstitial tissues. Specifically, EphA2/ephrin-A1 signaling in the lung may be responsible for pulmonary inflammation in acute lung injury. A role in T-cell maturation and chronic inflammation (heart failure, inflammatory bowel disease, and rheumatoid arthritis) is also reported. Although there remains much to learn about Eph/ephrin signaling in human disease, and specifically in injury and inflammation, this area of research raises the exciting prospect that novel therapies will be developed that precisely target these pathways.


Adverse technical events in home hemodialysis.
There is a growing interest in home hemodialysis because of its clinical benefits. However, given that patients are responsible for performing a complex medical procedure at home, adverse-event reporting is important to ensure patient safety. The purpose of this study was to describe adverse technical events in a large cohort of home hemodialysis patients. Retrospective cohort study. All consecutive patients undergoing home hemodialysis at a large tertiary-care center from 1999 through 2011 (last follow-up, July 2012). Overall rate of adverse technical events and number/rate of severe adverse events (defined as those requiring intervention). The cohort consisted of 202 patients with total follow-up of 757 patient-years. The cohort underwent a median of 5 dialysis treatments per week and 8 hours per session. 22 first adverse events and 7 recurrent events were identified. Adverse event rates were 0.049 per arteriovenous fistula access-year, 0.015 per arteriovenous graft access-year, and 0.022 per dialysis catheter access-year. Event rates per 1,000 dialysis treatments were 0.208, 0.068, and 0.087 for arteriovenous fistula, arteriovenous graft, and dialysis catheter access, respectively. Most adverse events were related to needle dislodgement (n=18) or air embolism (n=6). 8 adverse events resulted in emergency department visits and 5 required hospital admission. The rate of severe adverse events was 0.009 per patient-year of home hemodialysis and 0.038 per 1,000 dialysis treatments. Interventions included 3 blood transfusions, 2 catheter changes, 1 use of intravenous fluids, and 1 need for urgent dialysis. Attempts were made to retrain or review the technique in all patients with a first adverse event. Events that were not severe may have been under-reported by patients. Serious adverse technical events in home hemodialysis are relatively rare. Strategies to further prevent these events may include patient retraining and periodic vascular access technique audit.


Female teachers' child abuse reporting role in Oman: Results from focus groups.
Schoolteachers are in a good position to identify and report suspected child abuse and neglect cases; however, they still fail to report all the cases. Recently, the Sultanate of Oman, which is a collectivistic culture, mandated schoolteachers to report any suspected case. However, there is a lack of evidence known to us about the factors associated with Omani teachers' reporting behavior. Such evidence is needed to inform the interventions that are designed to enhance teachers' reporting behavior. The current study was designed to address this gap by exploring the factors that affect Omani schoolteachers reporting behavior of suspected child abuse and neglect cases. A total of 26 participants were recruited from five basic education schools in the Muscat governorate in Oman. This is a descriptive qualitative study. Five focus group discussions were conducted. Thematic coding was used for data analysis. Three themes were discerned from the data analysis. The factors that affect Omani schoolteachers as described by the participants were: 1) reporting within an environment of educational resource scarcity; 2) reporting within an environment of competing female social roles and their professional reporting role; and 3) reporting within an environment of complex and diverse abuse and neglect cases. Our findings highlight the role of culture in reporting behavior. Implications for research and practice are discussed.


Bupivacaine anesthesia--a clinical trial for endodontic therapy.
In this double-blind clinical trial, thirty-two patients were randomly assigned to two groups of sixteen and administered 0.5 percent bupivacaine 1/200,000 epinephrine or 2 percent lidocaine 1/100,000 epinephrine for endodontic therapy. The onset and profundity of anesthesia were similar for the two groups. However, the bupivacaine group had prolonged anesthesia following treatment and a significant decrease in postoperative pain.


Heterologous Overexpression of Human FAD Synthase Isoforms 1 and 2.
The study of human FAD synthase enzymes requires a recombinant strategy to produce large amount of purified proteins in a soluble form. E. coli was exploited to this aim. To achieve the production of FAD synthase in a large scale, E. coli strains, plasmids (promoter, tags), growth temperature, inducer concentration, medium composition, and osmotic pressure were optimized. To date there is no universal protocol for protein expression, but for each protein a specific combination of "expression parameters" can be selected in order to maximize the results. An experimental protocol for the expression of two isoforms of the human FAD synthase was set up. The final procedures are based on the use of E. coli Rosetta(DE3) strain. Two different plasmids were used to obtain optimal amount of the two protein isoforms. In both cases, following the addition of the IPTG inducer, the growth temperature was lowered to increase the solubility of the recombinant protein. The detailed procedures for FAD synthase isoform 1 and isoform 2 overproduction are described in this protocol.


Optically-controlled extinction ratio and Q-factor tunable silicon microring resonators based on optical forces.
Tunability is a desirable property of microring resonators to facilitate superior performance. Using light to control light, we present an alternative simple approach to tuning the extinction ratio (ER) and Q-factor of silicon microring resonators based on optical forces. We design an opto-mechanical tunable silicon microring resonator consisting of an add-drop microring resonator and a control-light-carrying waveguide ("controlling" waveguide). One of the two bus waveguides of the microring resonator is a deformable nanostring put in parallel with the "controlling" waveguide. The tuning mechanism relies on the optical force induced deflection of suspended nanostring, leading to the change of coupling coefficient of microring and resultant tuning of ER and Q-factor. Two possible geometries, i.e. double-clamped nanostring and cantilever nanostring, are studied in detail for comparison. The obtained results imply a favorable structure with the microring positioned at the end of the cantilever nanostring. It features a wide tuning range of ER from 5.6 to 39.9 dB and Q-factor from 309 to 639 as changing the control power from 0 to 1.4 mW.


Traumatic chemical oral ulceration: a case report and review of the literature.
A 34-year-old man experienced extensive oral ulceration as a consequence of attempted ingestion of sulphuric acid as part of an act of deliberate self harm. All oral lesions healed within 28 days after local and systemic therapy. Oral ulceration has many potential causes ranging from physical trauma to malignancy. Chemicals are a less common cause of traumatic ulceration. Most chemical burns are characterised by mild to moderate tissue damage that heals spontaneously within seven to 15 days without scarring.


Urinary 6-sulphatoxymelatonin excretory rhythms in laboratory rats: effects of photoperiod and light.
The excretion rhythm of the melatonin metabolite, 6-sulphatoxymelatonin, was determined in rats maintained on contrasting 14 h L:10 h D and 10 h L:14 h D photoperiods. The novel use of a high protein liquid diet together with an automatic urine collection system facilitated the monitoring of the onset, offset and total production of metabolite before, during and after a 57.5% reduction in the dark period (5.75 h and 8 h delay in lights off). In 14 L:10 D, melatonin metabolite excretion increased 2.7 +/- 0.2 h after lights off, whereas in 10 L:14 D, the onset occurred 5.1 +/- 0.2 h after lights off. Duration of melatonin metabolite excretion was not different between the two photoperiods. Reduction of the dark period by 57.5% delayed the appearance of melatonin metabolite excretion until 2.15 +/- 0.4h and 2.9 +/- 0.4h after darkness in both long and short photoperiods. Upon restoration of the original photoperiod on the third day, the onset of metabolite excretion was significantly delayed by 1.4 +/- 0.4 h (P < 0.05) in long day animals and 2.2 +/- 0.2 h (P < 0.05) in short day-length compared to the first day. This study highlights the utility of urinary 6-sulphatoxymelatonin determinations in rats and provides new information on the acute effects of extended evening light on pineal melatonin secretion.


Li-CO2 and Na-CO2 Batteries: Toward Greener and Sustainable Electrical Energy Storage.
Metal-CO2 batteries, especially Li-CO2 and Na-CO2 batteries, offer a novel and attractive strategy for CO2 capture as well as energy conversion and storage with high specific energy densities. However, some scientific issues and challenges existing restrict their practical applications. Here, recent progress of crucial reaction mechanisms on cathodes in Li-CO2 and Na-CO2 batteries are summarized. The detailed reaction pathways can be modified by operation conditions, electrolyte compositions, and catalysts. Besides, specific discussions from aspects of catalyst design, stability of electrolytes, and anode protection are presented. Perspectives of several innovative directions are also put forward. This review provides an intensive understanding of Li-CO2 and Na-CO2 batteries and gives a useful guideline for the practical development of metal-CO2 batteries and even metal-air batteries.


Portal venous collateral drainage in IVC obstruction.
Collateral venous drainage via the portal venous system has been demonstrated in three patients with testicular teratoma and IVC obstruction using contrast venography and enhanced computed tomography (CT). The use of CT in assessing the extent of the collateral circulation in IVC obstruction together with implications for surgical management are discussed.


Differential effects on sensory functions and measures of epidermal nerve fiber density after application of a lidocaine patch (5%) on healthy human skin.
Topical application of lidocaine is an effective approach for treatment of post-herpetic neuralgia and other painful neuropathies. Lidocaine inhibits voltage-gated Na(+) channels and it most likely reduces excitability of cutaneous sensory neurons which can be hyperexcitable or spontaneously active in states of neuropathic pain. However, lidocaine and other local anesthetics also exert a pronounced neurotoxicity and they activate the irritant receptors TRPV1 and TRPA1. In this randomized and double-blinded study, we explored the ability of lidocaine patches (5%) to alter sensory function and epidermal nerve fiber density in skin of healthy volunteers. As assessed by quantitative sensory testing, significantly elevated thresholds for touch, pin prick pain and mechanically induced wind-up were observed in skin treated with lidocaine patches. These effects reversed to baseline values within 2days after termination of the treatment. Pressure pain and thresholds for heat and cold-induced pain were not affected by the lidocaine patch. A moderate but significant decrease in epidermal nerve fiber density was observed in skin blister roofs obtained after 42days of treatment with lidocaine patches. The placebo patch did not induce any changes in sensory thresholds or nerve fiber density. In conclusion, lidocaine patches seem to have differential effects on sensory modalities in healthy skin. A degeneration of epidermal nerve fibers has previously been demonstrated for patches containing the TRPV1-agonist capsaicin and our findings suggest that this effect might also be relevant for lidocaine patches. These data warrant further studies on molecular mechanisms mediating a relief of neuropathic pain by topical lidocaine.


Herpes simplex meningitis presenting as headache in pregnancy: A case report.
There are few case reports of meningitis caused by herpes simplex virus (HSV) as the initial presentation in a pregnant patient, making pregnancy management and delivery planning challenging for obstetricians encountering this patient presentation. A 35-year-old parous woman at 35 weeks of gestation with prenatal care complicated by her history of pre-term delivery and systemic lupus erythematous (SLE) presented to the emergency department with worsening headache not responding to medication. Due to her history of SLE, rheumatology was consulted, although her flare symptoms were not consistent with her initial presentation. Neurology was consulted after she developed symptoms consistent with meningitis. She was started on broad-spectrum antibiotics while awaiting lumbar puncture results. The latter indicated the patient was positive for HSV-2 IgG, suggesting a recurrent process. She denied a personal history of HSV infection, although she had a positive unspecified HSV IgM titer upon chart review. The patient was transitioned to intravenous acyclovir and responded well. Upon clinical improvement, she was transitioned to oral antiviral therapy and subsequently discharged home. After consultation with the pediatrics and pediatric infectious disease departments, vaginal delivery was deemed to be safe. However, the patient elected for primary cesarean. Providers encountering a patient with an unrelenting headache in the absence of other causes should have a high suspicion for meningitis, regardless of clinical HSV history.


The pH-unrelated influence of salt, temperature and manganese on aroma formation by Staphylococcus xylosus and Staphylococcus carnosus in a fermented meat model system.
The influence of manganese (0.01-0.1-1.0 microg/g), temperature (15-24 degrees C) and salt (3-4% w/w) on volatile formation in model minces inoculated with Pediococcus pentosaceus and either Staphylococcus xylosus or Staphylococcus carnosus was studied in a full factorial experiment. In order to study the direct, pH-unrelated effect of the parameters, data were analysed by use of multiple linear regression and partial least-squares regression both before and after transformation of the volatile responses into pH-orthogonal (pH-unrelated) responses. By using the pH-orthogonalised data, the overall interpretability of the experiment was increased, and new cause-and-effect relations were suggested. Approximately 50% of the total variance in volatile levels was due to differences caused by S. xylosus and S. carnosus, and another 30% was related to differences in pH development. The remaining 20% covered pH-orthogonal effects of manganese, temperature and salt plus the experimental noise. From this, it was concluded that most of the variation in volatile profiles caused by manganese, temperature and salt was in fact directly or indirectly caused by changes in lactic acid bacterial activity and pH.


Effect of ozone on platelet activating factor metabolism in phorbol-differentiated HL60 cells.
The mechanisms of ozone (O3) toxicity in the lung may involve the formation of lipid inflammatory mediators. We have previously demonstrated that exposure to O3 in vitro results in increased accumulation and release of platelet activating factor (PAF) in the macrophage-like cell line HL60 differentiated with phorbol ester (dHL60). In the present study we have examined possible biochemical mechanisms responsible for the O3-induced increase in PAF levels in dHL60 cells. Specifically, we studied the effect of O3 on phospholipase A2 (PLA2), acetyltransferase, acetylhydrolase, and reacylation activities. dHL60 cells were exposed to 1.0 ppm O3 or air alone. O3 exposure was found to significantly decrease dHL60 cell acetylhydrolase activity by 36%. Additional experiments demonstrated that extracellular acetylhydrolase activity, but not intracellular acetylhydrolase activity, was inhibited by O3 exposure of dHL60 cells. O3 exposure resulted in a small (13%) but statistically significant reduction in reacylation activity in dHL60 cells. In addition, a significant (22%) contribution of PLA2 activation to the O3-induced increase in PAF levels was also found. Basal and calcium ionophore-induced acetyltransferase activity was found to be unaffected by exposure of dHL60 cells to O3. These data suggest that in vitro exposure to O3 affects both synthetic and degradative pathways of PAF metabolism in dHL60 cells.


Raman spectroscopy of the system iron(III)-sulfuric acid-water: an approach to Tinto River's (Spain) hydrogeochemistry.
Acid mine drainage is formed when pyrite (FeS(2)) is exposed and reacts with air and water to form sulfuric acid and dissolved iron. Tinto River (Huelva, Spain) is an example of this phenomenon. In this study, Raman spectroscopy has been used to investigate the speciation of the system iron(III)-sulfuric acid-water as an approach to Tinto River's aqueous solutions. The molalities of sulfuric acid (0.09 mol/kg) and iron(III) (0.01-1.5 mol/kg) were chosen to mimic the concentration of the species in Tinto River waters. Raman spectra of the solutions reveal a strong iron(III)-sulfate inner-sphere interaction through the nu(1) sulfate band at 981 cm(-1) and its shoulder at 1005 cm(-1). Iron(III)-sulfate interaction may also be facilitated by hydrogen bonds and monitored in the Raman spectra through the symmetric stretching band of bisulfate at 1052 cm(-1) and a shoulder at 1040 cm(-1). Other bands in the low-frequency region of the Raman spectra are attributed to the hydrogen-bonded complexes formation as well.


Assessing the economic effects of the covid-19 pandemic on Swedish shrimp fishers.
This paper explores the effect of the perceived risk of the Swedish people of Covid-19 on daily auctioned shrimp prices from the start of the pandemic to the end of the year 2021. This topic is of interest to see whether the government intervention in the shrimp market to aid fishers with possible losses was justified. The Swedish shrimp fishery was for a long time managed by Regulated Open Access, but in January 1, 2017, it was transformed to a Strong User Rights Fishery by the introduction of Individual Transferable Quotas (ITQs). We use empirical data from the period from 2018 to 2021. We find that auction prices were negatively affected by covid-19 cases by SEK 19.83/kg (-9.37%), and that fishers have suffered a loss of SEK 21.5 million.


The binding of monoclonal antibodies to cell surface molecules. Quantitative analysis of the reactions and cross-reactions of an antibody (MB40.3) with four HLA-B molecules.
The MB40.3 monoclonal antibody binds to four distinct HLA-B molecules; B7, B40, B40*, and B27. With Fab' fragments only the interaction with B7 and B40 was detected and the affinity for both was the same (1-2 X 10(8) M-1) suggesting the epitope is shared by the two molecules. Unlike many antibodies for which low affinity is due to a high-dissociation constant, that of MB40.3 results from a very low-association rate constant, coupled with a low-dissociation constant. In consequence, the affinity and avidity of Fab', F(ab')2, and IgG for B7 and B40 were found to be of a similar magnitude, soluble B7 was a more efficient competitor for antibody than cell surface B7 and in practice antibody bivalency was of little importance. The forward rate constant could be increased by removing Fc from the antibody or by removing sialic acid from the cells by treatment with neuraminidase. The neuraminidase treatment also produced an increase in the number of detectable cell surface HLA-A,B molecules. The affinity of MB40.3 for B40* and B27 was estimated to be less than 4 X 10(6) as no binding with Fab' was detected due to a high-dissociation rate. For these two HLA-B molecules bivalent attachment was critical, and it increased the strength of interaction with cell surface B40* and B27 to a point where the avidities were comparable to those obtained with B7 and B40, with B40* interacting more strongly than B27. The epitopes recognized by MB40.3 on B40* and B27 were thus shown to be structurally different from each other and from those on B7 and B40. The properties of this antibody contrast with those of other anti-HLA-A,B we have studied (Ways, J.P., and Parham, P. (1983) Biochem. J. 216, 423-432).


Audit of ultrasound usage in emergency departments in greater metropolitan Brisbane.
The Australasian College for Emergency Medicine identifies five ultrasound applications which the College deem core to the practice of emergency medicine but there is scant information as to the uptake of ultrasound or the qualification of users. This study aims to determine the percentage of ED physicians in one metropolitan area who utilise ultrasound for core diagnostic and procedural applications in participating hospitals and the percentage of users who have been formally assessed in any ultrasound application. The EDs of eight major public hospitals in greater metropolitan Brisbane area participated in this audit. Data-collectors at each participating ED approached every senior house officer, registrar and senior medical officer in the department and, after obtaining informed consent, asked the participant six questions pertaining to their use of ultrasound for five core applications and about ultrasound training and recorded the answers without information as to the identity of the participant. 94.4% of the physicians participated. Of those participating, 90% used ultrasound for venous access, with progressively fewer using E-FAST (69%), AAA (51%), Lung (40%) and BELS (29%) for diagnostic purposes. Ninety-eight percent of participants were in favour of enhanced departmental training. Only 33% of participants had their ultrasound skills assessed by a qualified person for even one application. While use of ultrasound in some applications is widespread, few users have had their skills assessed. Assessment being a routine part of structured training, it cannot be assumed that these users can competently use ultrasound for procedural or diagnostic applications.


Evaluation of the Effectiveness of Newer Helmet Designs with Emergent Shell and Padding Technologies Versus Older Helmet Models for Preserving White Matter Following a Season of High School Football.
We aimed to objectively compare the effects of wearing newer, higher-ranked football helmets (HRank) vs. wearing older, lower-ranked helmets (LRank) on pre- to post-season alterations to neuroimaging-derived metrics of athletes' white matter. Fifty-four high-school athletes wore an HRank helmet, and 62 athletes wore an LRank helmet during their competitive football season and completed pre- and post-season diffusion tensor imaging (DTI). Longitudinal within- and between-group DTI metrics [fractional anisotropy (FA) and mean/axial/radial diffusivity (MD, AD, RD)] were analyzed using tract-based spatial statistics. The LRank helmet group exhibited significant pre- to post-season reductions in MD, AD, and RD, the HRank helmet group displayed significant pre- to post-season increases in FA, and both groups showed significant pre- to post-season increases in AD (p's < .05 [corrected]). Between-group analyses revealed the pre- to post-season increase in AD was significantly less for athletes wearing HRank compared to LRank (p < .05 [corrected]). These data provide in vivo evidence that wearing an HRank helmet may be efficacious for preserving white matter from head impact exposure during high school football. Future prospective longitudinal investigations with complimentary imaging and behavioral outcomes are warranted to corroborate these initial in vivo findings.


Recent radiation in West African Taterillus (Rodentia, Gerbillinae): the concerted role of chromosome and climatic changes.
West African gerbils of the genus Taterillus constitute a complex of seven sibling species distributed from sudano-guinean to saharo-sahelian regions. They display radically rearranged karyotypes despite low genic divergence and a very recent differentiation, that is, within the last 0.4 Myr for the six most derived species. We here provide a comparison of the seven specific karyotypes and perform a cladistic analysis using chromosomal rearrangements character states. When a posteriori polarized mutations were mapped onto the phylogenetic tree, 38 rearrangements were identified as fixed during the evolution of these rodents. This makes Taterillus one of the most striking examples of accelerated chromosomal evolution within placental mammals. Taking into account the types of chromosomal changes involved, divergence times between lineages, genetic distances, as well as reassessed geographic distributions, we suggest that (1) speciation in West African Taterillus was driven by chromosomal changes, and (2) the paleoclimatic oscillations of the Sahara desert have played a major role in their evolution. In particular, elevated plasticity of the Taterillus genome, as suggested by the patterns observed for some repetitive elements, would have led to a higher probability of mutation. We hypothesize that the process underpinning cladogenesis most probably involved highly underdominant genomic rearrangements that were fixed following pronounced populational bottlenecks resulting from drastic climatic and subsequent environmental changes. Major African rivers formed significant barriers to dispersal, limiting expansion during the more moist and so favorable periods. This scenario would explain the current parapatric species distributions and their relationship to the West African hydrographic features.


Prognostic value of prealbumin, N-terminal pro-B-type natriuretic peptide, heart type fatty acid binding protein, and cardiac troponin I in elderly patients for heart failure and poor outcomes.
This study aimed to investigate the prognostic value of serum prealbumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), heart type fatty acid binding protein (hFABP), and cardiac troponin I (cTnI) for heart failure and cardiac death in elderly patients. We studied 426 consecutive patients with New York Heart Association classes I to IV who were recruited between February 2014 and 2018. Cardiac mortality was the primary end point. Receiver operator characteristic curves were created to analyze predictive values. When prealbumin, NT-proBNP, hFABP, and cTnI were combined, the areas under the receiver operator characteristic curve reached 0.930 and 0.903 for heart failure and cardiac death, respectively. Prealbumin, NT-proBNP, hFABP, and cTnI levels changed differently during therapy in patients in different prognosis groups. These parameters improved in patients who did not develop major adverse cardiovascular events (MACEs), but were unchanged or deteriorated in patients with MACEs. Multivariate Cox regression analysis showed that these parameters were significant independent risk factors for MACEs and cardiac death. Our study shows that serum prealbumin, NT-proBNP, hFABP, and cTnI levels are significant prognostic factors for elderly patients with poor cardiac function. These parameters are more accurate for prognosis when used together.


An Asymptomatic Case With MEN1 Slipping Through Genetic Screening by SNV-dependent Allelic Dropout.
Genetic testing is useful not only for the diagnosis of the MEN1 proband but also for determining the putative asymptomatic variant carriers to improve the prognosis or to avoid unnecessary medical intervention. However, we must be aware of the putative pitfalls of polymerase chain reaction (PCR)-based genetic testing in specific conditions that lead to medical mismanagement. To warn of the putative pitfalls of PCR-based genetic testing, we report an overlooked case of MEN1 due to PCR allelic dropout. A 69-year-old man was clinically diagnosed with MEN1, and genetic testing revealed that he had a pathogenic variant in the MEN1 gene. His 36-year-old son was completely asymptomatic. As the son was 50% at risk of MEN1, he was willing to undergo genetic testing himself after genetic counseling. Genetic testing was carried out in 2 independent laboratories. Although laboratory A showed that he carried a pathogenic variant, laboratory B showed that he had the wild-type genotype of MEN1. The discrepancy in these results was due to PCR allelic dropout by single-nucleotide variations of the MEN1 gene in the 5' region. The surveillance revealed that he had asymptomatic primary hyperparathyroidism and a neuroendocrine tumor of the pancreas. PCR-dependent genetic analysis may be susceptible to PCR allelic dropout in an SNV-specific manner. We must be careful when genetically testing individuals of relatives with clinical MEN1 disease.


Non-randomness in side-chain packing: the distribution of interplanar angles.
We analyze the distributions of interplanar angles between interacting side chains with well-defined planar regions, to see whether these distributions correspond to random packing or alternatively show orientational preferences. We use a non-homologous set of 79 high-resolution protein chain structures to show that the observed distributions are significantly different from the sinusoidal one expected for random packing. Overall, we see a relative excess of small angles and a paucity of large interplanar angles; the difference between the expected and observed distributions can be described as a shift of 5% of the interplanar angles from large (> or = 60 degrees) to small (< 30 degrees) values. By grouping the residue pairs into categories based on chemical similarity, we find that some categories have very non-sinusoidal interplanar angle distributions, whereas other categories have distributions that are close to sinusoidal. For a few categories, observed deviations from a sinusoidal distribution can be explained by the electrostatic anisotropy of the isolated pair potential energy. In other cases, the observed distributions reflect the longer range effects of different possible interaction geometries. In particular, geometries that disrupt external hydrogen bonding are disfavored.


First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B.
Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10-8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10-5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10-10; OR = 1.47; 95% CI, 1.38-1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10-16; OR = 1.75; 95% CI, 1.64-1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes.


In vivo ameliorative effect of cerium oxide nanoparticles in isoproterenol-induced cardiac toxicity.
Cerium oxide nanoparticles have gained much more attention especially in the field of nanomedicine. This work represents cerium oxide nanoparticles as a new prophylactic model for heart failure progression. To investigate the potential protective effect of cerium oxide nanoparticles on Isoproterenol (ISO)-induced cardiac toxicity in rats. Cerium oxide nanoparticles (5±1nm) were synthesized by reverse micelle method and characterized using High Resolution Transmission Electron Microscopy, X-Ray Diffraction and particle size analyzer. The experiments were performed on 96 male Wistar rats. The rats were randomly allocated into eight groups. Namely; two Negative and positive control groups, captopril administered group, Nano-ceria (low dose) group, Nano-ceria (high dose) group, Captopril- Isoproterenol group, Nano-ceria (low dose)-Isoproterenol group and Nano-ceria (high dose)-Isoproterenol group. Cardio toxic rat model was induced by subcutaneous administration of Isoproterenol (ISO) (30mg/kg) for two consecutive days in adult male rats. Two doses (0.5 and 5μg/kg/week) of cerium oxide nanoparticles were applied for five weeks and 50mg/kg/day of Captopril was used as a reference drug. Cardiac marker enzymes, Cortisol and Aldosterone hormones were assessed in serum. Oxidant-antioxidant parameters and histopathological examination in heart tissues were also determined. These dose of nano-ceria, showed a promising ameliorative and prophylactic effect against cardiac toxicity compared to Captopril reference drug. Serum cardiac markers were decreased by noticeable percentage, CK-MB (50% and 57%), LDH (47% and 57.7%), AST (38% and 36.5%) and ALT (33.5% and 30.6%) for both doses respectively, while increased tissues level of the antioxidant enzymes, catalase (48% - 26%) and superoxide dismutase (64%, 143%). These consistent biochemical and histopathological results suggest that, nano-ceria could be used as effective antioxidant in prophylactic protocols for management of cardiac disorders associated with oxidative stress.


Inhibition of UGT1A1 by natural and synthetic flavonoids.
Flavonoids are widely distributed phytochemicals in vegetables, fruits and medicinal plants. Recent studies demonstrate that some natural flavonoids are potent inhibitors of the human UDP-glucuronosyltransferase 1A1 (UGT1A1), a key enzyme in detoxification of endogenous harmful compounds such as bilirubin. In this study, the inhibitory effects of 56 natural and synthetic flavonoids on UGT1A1 were assayed, while the structure-inhibition relationships of flavonoids as UGT1A1 inhibitors were investigated. The results demonstrated that the C-3 and C-7 hydroxyl groups on the flavone skeleton would enhance UGT1A1 inhibition, while flavonoid glycosides displayed weaker inhibitory effects than their corresponding aglycones. Further investigation on inhibition kinetics of two strong flavonoid-type UGT1A1 inhibitors, acacetin and kaempferol, yielded interesting results. Both flavonoids were competitive inhibitors against UGT1A1-mediated NHPN-O-glucuronidation, but were mixed and competitive inhibitors toward UGT1A1-mediated NCHN-O-glucuronidation, respectively. Furthermore, docking simulations showed that the binding areas of NHPN, kaempferol and acacetin on UGT1A1 were highly overlapping, and convergence with the binding area of bilirubin within UGT1A1. In summary, detailed structure-inhibition relationships of flavonoids as UGT1A1 inhibitors were investigated carefully and the findings shed new light on the interactions between flavonoids and UGT1A1, and will contribute considerably to the development of flavonoid-type drugs without strong UGT1A1 inhibition.


Ammonia exposure affects the mRNA and protein expression levels of certain Rhesus glycoproteins in the gills of climbing perch.
The freshwater climbing perch, Anabas testudineus, is an obligate air-breathing and euryhaline teleost capable of active ammonia excretion and tolerant of high concentrations of environmental ammonia. As Rhesus glycoproteins (RhGP/Rhgp) are known to transport ammonia, this study aimed to obtain the complete cDNA coding sequences of various rhgp isoforms from the gills of A. testudineus, and to determine their mRNA and protein expression levels during 6 days of exposure to 100 mmol l-1 NH4Cl. The subcellular localization of Rhgp isoforms in the branchial epithelium was also examined in order to elucidate the type of ionocyte involved in active ammonia excretion. Four rhgp (rhag, rhbg, rhcg1 and rhcg2) had been identified from the gills of A. testudineus They had conserved amino acid residues for NH4+ binding, NH4+ deprotonation, channel gating and lining of the vestibules. Despite inwardly directed NH3 and NH4+ gradients, there were significant increases in the mRNA expression levels of the four branchial rhgp in A. testudineus at certain time points during 6 days of ammonia exposure, with significant increases in the protein abundances of Rhag and Rhcg2 on day 6. Immunofluorescence microscopy revealed a type of ammonia-inducible Na+/K+-ATPase α1c-immunoreactive ionocyte with apical Rhag and basolateral Rhcg2 in the gills of fish exposed to ammonia for 6 days. Hence, active ammonia excretion may involve NH4+ entering the ionocyte through the basolateral Rhcg2 and being excreted through the apical Rhag, driven by a transapical membrane electrical potential generated by the apical cystic fibrosis transmembrane conductance regulator Cl- channel, as suggested previously.


Vaccination and variants: Retrospective model for the evolution of Covid-19 in Italy.
The last year of Covid-19 pandemic has been characterized by the continuous chase between the vaccination campaign and the appearance of new variants that puts further obstacles to the possibility of eradicating the virus and returning to normality in a short period. In the present paper we develop a deterministic compartmental model to describe the evolution of the Covid-19 in Italy as a combined effect of vaccination campaign, new variant spreading and mobility restrictions. Particular attention is given to the mechanism of waning immunity, appropriately timed with respect to the effective progress of the vaccination campaign in Italy. We perform a retrospective analysis in order to explore the role that different mechanisms, such as behavioral changes, variation of the population mobility, seasonal variability of the virus infectivity, and spreading of new variants have had in shaping the epidemiological curve. We find that, in the large time window considered, the most relevant mechanism is the seasonal variation in the stability of the virus, followed by the awareness mechanism, that induces individuals to increase/relax self-protective measures when the number of active cases increases/decreases. The appearance of the Delta variant and the mobility variations have had instead only marginal effects. In absence of vaccines the emerging scenario would have been dramatic with a percentage difference in the number of total infections and total deaths, in both cases, larger than fifty per cent. The model also predicts the appearance of a more contagious variant (the Omicron variant) and its becoming dominant in January 2022.


Control of Ca2+ and metabolic homeostasis by the Na+/Ca2+ exchangers (NCXs) in health and disease.
Spatial and temporal control of calcium (Ca2+) levels is essential for the background rhythms and responses of living cells to environmental stimuli. Whatever other regulators a given cellular activity may have, localized and wider scale Ca2+ events (sparks, transients, and waves) are hierarchical determinants of fundamental processes such as cell contraction, excitability, growth, metabolism and survival. Different cell types express specific channels, pumps and exchangers to efficiently generate and adapt Ca2+ patterns to cell requirements. The Na+/Ca2+ exchangers (NCXs) in particular contribute to Ca2+ homeostasis by buffering intracellular Ca2+ loads according to the electrochemical gradients of substrate ions - i.e., Ca2+ and sodium (Na+) - and under a dynamic control of redundant regulatory processes. An interesting feature of NCX emerges from the strict relationship that connects transporter activity with cell metabolism: on the one hand NCX operates under constant control of ATP-dependent regulatory processes, on the other hand the ion fluxes generated through NCX provide mechanistic support for the Na+-driven uptake of glutamate and Ca2+ influx to fuel mitochondrial respiration. Proof of concept evidence highlights therapeutic potential of preserving a timed and balanced NCX activity in a growing rate of diseases (including excitability, neurodegenerative, and proliferative disorders) because of an improved ability of stressed cells to safely maintain ion gradients and mitochondrial bioenergetics. Here, we will summarize and review recent works that have focused on the pathophysiological roles of NCXs in balancing the two-way relationship between Ca2+ signals and metabolism.


High expression of the classical swine fever virus (CSFV) envelope protein E2 by a single amino acid mutation and its embedded in the pseudorabies virus (PRV) vector for immunization.
Pseudorabies (PR) and classical swine fever (CSF) are economically important infectious diseases in pigs. Most pig farms in China are vaccinated against these two diseases. Gene-deleted pseudorabies virus (PRV) can be used to develop promising and economical multivalent live attenuated viral vector vaccines. It has been reported that recombinant PRV can express a truncated E2 protein (1-338 aa), but it has not been reported that recombinant PRV can express a full-length E2 protein. We constructed nine groups of E2 proteins with different expression forms and found that the E2 protein could be expressed in vitro only when the transmembrane region of E2 was removed and the signal peptide was added. Analysis of the transmembrane region of E2 revealed that the high hydrophobicity of the E2 transmembrane region was the main reason for its inability to express. By mutating an amino acid to reduce the hydrophobicity of the transmembrane region, it was found that the full-length mutant of E2 (E2FL-muta3 or E2FL-muta4) could be expressed. The expressed full-length mutant E2 could also localize to the cell membrane. Mice immunized with a PRV vector vaccine expressing E2FL-muta3 or E2FL-muta4 developed specific cellular immunity to the E2 protein and stimulated higher levels of E2 antibody than mice immunized with a PRV vector expressing truncated E2. After immunizing the rabbits, the lethal challenge by PRV-ZJ2013 and the febrile response elicited by CSFV were simultaneously prevented. These results suggest that rPRV-dTK/gE-E2FL-muta4 is a promising bivalent vaccine against CSFV and PRV infections.


Different modes of action of inhibitors of bacterial D-amino acid transaminase. A target enzyme for the design of new antibacterial agents.
D-Amino acid transaminase from Bacillus sphaericus shows a deuterium kinetic isotope effect (VH/VD) between 2 and 3 in the transamination of alpha-protio- or alpha-deuterio-D-alanine and alpha-ketoglutarate, suggesting that alpha-proton abstraction is at least partially rate-limiting for this reaction. This transaminase also catalyzes a beta-elimination reaction with substrates such as beta-fluoroalanine with no detectable deuterium isotope effect (VH/BD = 1). These results, taken together with previous work (Soper, T. S., and Manning, J. M. (1978) Biochemistry 17, 3377-3384) suggest that the rate-limiting step in the beta-elimination reaction is solvolysis of an alpha-aminoacrylate-pyridoxal-P Schiff's base intermediate. D-Cycloserine is an active site titrant of D-amino acid transaminase. Inactivation by cycloserine can be completely reversed by dialysis against pyridoxal phosphate at neutral pH. Gabaculine is also an efficient inhibitor of this enzyme and possesses some antibacterial activity. The latter two inhibitors probably act by sequestration of the coenzyme rather than by alkylation of the protein as with the beta-halo derivatives of D-alanine.


Factors affecting the expression of acetylcholine receptors on rat sensory neurones in culture.
Sensory neurones from nodose ganglia of new-born rats were grown in dissociated tissue culture either with or without satellite cells. When cultured without satellite cells, most neurones developed sensitivity to acetylcholine (ACh); time-course experiments indicated that the neurones acquire their sensitivity during the second to third week in culture. Most neurones co-cultured with satellite cells did not develop ACh sensitivity. Delayed removal of satellite cells 8-12 days after plating resulted in few neurones acquiring ACh sensitivity. Delayed addition of satellite cells to neuronal cultures that were initially grown without satellite cells had no effect on the number of ACh-sensitive neurones. The potential to develop ACh sensitivity in culture without satellite cells decreases with the age of the neurones at the time of culturing; few neurones from 2-week-old animals developed sensitivity to ACh when cultured without satellite cells. These results indicate that there is some influence from satellite cells that prevents nodose neurones from developing ACh sensitivity in culture and suggests that this influence may also operate in vivo.