Intermittent use of topical dimethyl sulfoxide in macular and papular amyloidosis.
Severe and therapy-resistant pruritus is the most prominent feature of macular (MA) and lichen (LA) amyloidosis that leads to further amyloid deposition by recurrent frictional trauma to the epidermis. Of the various therapeutic modalities with variable success, the most encouraging and beneficial effect has been observed with topical dimethyl sulfoxide (DMSO) therapy. In a previous study, we achieved marked clinical improvement in nine of 10 patients in a daily treatment regimen over 6-20 weeks, but relapses occurred in the post-treatment follow-up period. The aims of this study are to investigate whether the patients would benefit from intermittent therapy and to determine the optimal application interval of DMSO to maintain the relief of symptoms. Thirteen patients with histopathologically verified cutaneous amyloidosis (five MA, two LA and six biphasic) were enrolled in the study. They were treated once daily with a 50 or 100% DMSO solution until pruritus disappeared. Then, DMSO was applied at increasing intervals until the widest effective application interval for maintenance of relief was reached. Patients were regularly followed-up by a scoring system for pruritus, papules, and pigmentation, control biopsies, photographs, blood biochemistry, and side-effects. The mean time required for the disappearance of pruritus was 4.1 weeks. Remarkable flattening of the papules was achieved after an average therapy period of 9 weeks. After a total therapy period of 6.5 months, a nearly 50% remission in pigmentation and >70% flattening of papules were achieved. The widest effective DMSO application interval was 8.6 days. The side-effects of therapy were contact urticaria, desquamation, burning sensation, and garlic-like breath odor, which were more prominent with the higher concentration of DMSO. In interval therapy, side-effects were tolerated more easily than in daily therapy. No reduction of amyloid deposits was revealed in control biopsies. Locally applied DMSO can break the vicious "pruritus-amyloid deposition-pruritus" cycle in patients with MA and LA. In addition to its daily use, interval therapy seems to maintain this effect and enables patients to tolerate side-effects more easily.


Alterations to the signal peptide of an outer membrane protein (OmpA) of Escherichia coli K-12 can promote either the cotranslational or the posttranslational mode of processing.
The signal sequence of the precursor of the Escherichia coli outer membrane protein OmpA was altered by oligonucleotide insertions into the corresponding gene. In one case, OmpA-S1, the hydrophobic core of the signal peptide, is reduced from 12 to 10 residues, and one positive charge is added near the NH2-terminus. In another case, OmpA-P1, the hydrophobic core is extended from 12 to 16 residues. The pro-OmpA protein is normally processed partially co- and partially posttranslationally. Processing of the pro-OmpA-S1 protein was entirely posttranslational and that of the pro-OmpA-P1 protein strictly cotranslational. Evidence is presented which strongly suggests that posttranslational processing reflects posttranslational translocation across the plasma membrane. The generation times of cells expressing pro-OmpA-P1 or pro-OmpA-S1 were identical and the pro-OmpA-S1 polypeptide could be chased into the mature protein in the absence of protein synthesis. Hence, it does not matter which mode of processing, or rather translocation, is used. The same oligonucleotides were inserted into the ompA gene of plasmid pRD87; a plasmid which leads to overproduction of the protein and to massive accumulation of both the mature protein and the precursor. In the OmpA signal sequence encoded by pRD87-P2 the hydrophobic core is extended from 12 to 20 residues. This peptide was also rapidly removed. Therefore, regardless of whether the hydrophobic core contains 12, 16, or 20 lipophilic residues, not only does the signal sequence always function correctly to mediate export, but in each case, the cleavage site is always accessible to the signal peptidase.


Risk factors of tooth wear in permanent dentition: A scoping review.
Tooth wear (TW) prevalence is high and increasing and has important consequences on the patient's quality of life. Knowledge of risk factors is crucial to promote diagnosis, prevention strategies and timely interceptive treatment. Many studies have identified TW risk factors. This scoping review aims to map and describe suspected available factors associated with TW in permanent dentition based on quantitative measurement. The scoping review was conducted using the PRISMA extension of the Scoping Reviews checklist. The search was conducted in October 2022 from the Medline® (PubMed® interface) and Scopus® databases. Two independent reviewers selected and characterised the studies. 2702 articles were identified for assessment of titles and abstracts, and 273 articles were included in the review. The results show a need to standardise TW measurement indices and the study design. The included studies highlighted various factors, classified into nine domains: sociodemographic factors, medical history, drinking habits, eating habits, oral hygiene habits, dental factors, bruxism and temporomandibular disorders, behavioural factors, and stress. Results related to chemical TW (erosion) risk factors underline the importance of eating disorders, gastroesophageal reflux and lifestyle, particularly drinking and eating behaviours, which supports developing public health information campaigns and interventions. Besides chemical, this review identifies evidence of several mechanical TW risk factors, such as toothbrushing and bruxism; the influence of this last factor needs to be further explored. TW management and prevention require a multidisciplinary approach. Dentists are in the first line to detect associated diseases such as reflux or eating disorders. Consequently, practitioners' information and guideline diffusion should be promoted, and a TW risk factors checklist (the ToWeR checklist) is proposed to help diagnostic approaches.


Dose dependence specific and non-specific immune responses of Indian major carp (L. rohita Ham) to intraperitoneal injection of formalin killed Aeromonas hydrophila whole cell vaccine.
Specific and non-specific immune response to different doses of formalin killed whole cell vaccine of Aeromonas hydrophila to Indian major carp (Labeo rohita) was evaluated in laboratory condition. Three different doses (10(5) CFU/ml, 10(7) CFU/ml, 10(10) CFU/ml) were administered (0.2 ml/fish) intraperitoneally for 1 month. Among the three doses, 10(10) CFU/ml elicited the highest antibody and protective response followed by the doses 10(7) CFU/ml and 10(5) CFU/ml. Upon challenge with the virulent strain of A. hydrophila, the relative percentage of survival was recorded up to 80% at highest dose of 10(10) CFU/ml. The non-specific responses, similar to the specific immune responses were also maximum at highest dose of 10(10) CFU/ml. Similar to the specific immune responses, the non-specific responses were maximum at highest dose of 10(10) CFU/ml. Therefore, dose containing 10(10) CFU/ml of formalin killed cells was found to be the most effective dose for vaccination which increased the immunity in Indian major carp (Labeo rohita) to a larger extent.


Stromal cell-derived factor-1 promotes bone marrow-derived cells differentiation to cardiomyocyte phenotypes in vitro.
Recent studies have demonstrated the potential of bone marrow-derived cells (BMDC) to differentiate into cardiomyocytes. Up-regulation of stromal cell-derived factor-1 (SDF-1), a member of the chemokine CXC subfamily, mediating recruitment of BMDC has been documented in infarcted myocardium; however, it remains unknown whether SDF-1 plays a role in cardiomyogenesis of BMDC. Adherent BMDCs were cultured with SDF-1, or specific inhibitor for PI3K, CXCR4 or Akt with SDF-1, respectively. After 2 weeks, mRNAs and proteins from BMDCs were examined. Two weeks after supplementation with SDF-1, either murine or human adherent BMDC cultured in vitro expressed cardiac specific mRNAs (NKX2.5, atrial natriuretic factor and heavy chain beta-myosin) and proteins (troponin I and heavy chain cardiac myosin), and expression levels were partly decreased by combined treatment of CXCR4, PI3K or Akt inhibitor, with SDF-1. The novel findings suggest that beyond its role in mobilization and homing of BMDC, SDF-1 can promote BMDC to give rise to cardiomyocyte phenotypes in vitro, and the SDF-1/CXCR4/PI3K/Akt pathway may be one of the molecular mechanisms regulating cardiomyogenesis.


The changes in antibiotic resistance genes during 86 years of the soil ripening process without anthropogenic activities.
This study aimed to reveal the baseline of natural variations in antibiotic resistance genes (ARGs) in soil without anthropogenic activities over the decades. Nine soil samples with different time of soil formation were taken from the Yancheng Wetland National Nature Reserve, China. ARGs and mobile genetic elements (MGEs) were characterized using metagenomic analysis. A total of 196 and 192 subtypes of ARGs were detected in bulk soil and rhizosphere, respectively. The diversity and abundance of ARGs were stable during 69 years probably due to the alkaline pH soil environment but not due to antibiotics. Increases in ARGs after 86 years were probably attributed to more migrant birds inhabited compared with other sampling sites. Multidrug was the most abundant type, and largely shared by soil samples. It was further shown that soil samples could not be clearly distinguished, suggesting a slow process of succession of ARGs in the mudflat. The variation partitioning analysis revealed that the ARG profile was driven by the comprehensive effects exhibited by the bacterial community, MGEs, and environmental factors. Besides, pathogenic bacteria containing ARGs mediated by migrant birds in the area with 86 years of soil formation history nearing human settlements needed special attention. This study revealed the slow variations in ARGs in the soil ripening process without anthropogenic activities over decades, and it provided information for assessing the effect of human activities on the occurrence and dissemination of ARGs.


10-year survivorship of metal-backed, unicompartmental arthroplasty.
Between January 1985 and December 1987, 100 consecutive metal-backed, unicompartmental arthroplasties (MBUKAs) were performed and retrospectively reviewed; 5 patients died, and the surviving 95 patients were reviewed. Of these arthroplasties, 10 were uncemented and 85 were cemented. There were 2 failures in the uncemented arthroplasties and 10 failures in those that were cemented, resulting in an 87.4% survivorship at a mean follow-up of 10 years. After 5 years, 10 of these cases were revised because of progressive lateral compartment disease and lateral compartment pain. Despite improved function compared with tricompartmental arthroplasty, MBUKA is beneficial only in highly selective cases. In this series, after 5 years, survivorship declined because of progression of arthrosis in the nonreplaced compartment.


To Make and Keep Friends: The Role of Health Status in Adolescent Network Tie Formation and Persistence.
Health status may shape network structure through network dynamics (tie formation and persistence) and direction (sent and received ties), net of typical network processes. We apply Separable Temporal Exponential Random Graph Models (STERGMs) to National Longitudinal Study of Adolescent to Adult Health survey data (n = 1,779) to differentiate how health status shapes network sent and received tie formation and persistence. Results indicate that networks are shaped by withdrawal of adolescents experiencing poor health, highlighting the importance of separating distinct and directed processes of friendship formation and persistence when considering how health relates to adolescent social life.


A strategy towards disentangling treatment refractory from misdiagnosed axial Spondyloarthritis.
Axial spondyloarthritis (axSpA) encompasses radiographic axial SpA (r-axSpA), formally designated as ankylosing spondylitis (AS) and non-radiographic axial SpA (nr-axSpA). The advent of MRI permitted the description of the "pre-radiographic" (nr-AxSpA) stage characterized by bone marrow oedema lesions, histologically an osteitis, not yet visible on X-rays. Most subjects with a diagnosis of nr-axSpA do not progress to r-axSpA and the risk of misdiagnosis of nr-axSpA is considerable because back pain related to malalignment, degenerative conditions or biomechanical stress including intense exercise may lead to positive MRI scans. Even when nr-axSpA or r-axSpA are accurately diagnosed only about 40-50% achieve the ASAS40 responses with licensed therapies. It is likely that spinal enthesitis/osteitis leading to structural damage and associated damage contributes to post inflammatory disc territory secondary pain responses. Things are complicated as the concept of refractory axSpA itself is not well defined since there is no gold standard test to capture the full burden of inflammatory disease and, in any event, MRI has not been systematically applied. Nevertheless, there is sufficient evidence to borrow from the refractory rheumatoid arthritis field to propose two types of refractory axial SpA- a persistent inflammatory refractory ax-SpA (PIRaxSpA) and non-inflammatory refractory ax-SpA (NIRaxSpA). Both axSpA refractoriness and misdiagnosis need careful considerations when evaluating treatment failure. The immunological basis for axSpA immunotherapeutics non-responses is still rudimentary beyond the knowledge of HLA-B27 positivity status, CRP elevation, and MRI bone oedema that represents osteitis being equated with responder status.


Developing in vivo EPR oximetry for clinical use.
This paper describes the rationale for carrying out electron paramagnetic resonance (EPR) oximetry studies in human subjects in the clinical setting and the potential approaches and specific steps needed to make such studies feasible and useful. While the approach is described specifically for EPR oximetry, many of the principles may apply to the initial clinical uses of other techniques. The suggested operational approach is to have the initial applications occur in as clinically useful and simple a manner as possible, with the expectation that once the technique is introduced and accepted in the clinical setting, that more complex and/or more technically difficult applications will be able to be developed. The initial approach will be based on EPR spectroscopy at 1.2 GHz focusing on applications for which in vivo EPR provides a clearly useful approach to important clinical problems for which currently there is no good alternative method. The EPR measurements can be carried out non-invasively by measurements within 10 mm of the surface after the placement of the paramagnetic material at the site of interest, or by the placement of a needle/catheter in the site of interest for the required time period. The suggested initial clinical applications are guiding therapy for individual patients with tumors or vascular disease, by direct measurements of tissue pO2.


Detection of asymptomatic bacteriuria in obstetric patients with a semiautomated urine screen.
Urine specimens (1215) from obstetric patients were evaluated for the presence of significant bacteriuria by the Bac-T-Screen (Marion Scientific Division, Marion Laboratories, Inc., Kansas City, Missouri) and a conventional semiquantitative culture method. Seventy (5.8%) specimens were not processed successfully by the Bac-T-Screen because pigments interfered with interpretation or the test filters clogged. The remaining 1145 specimens screened by the Bac-T-Screen were compared with a conventional culture method. The sensitivity, specificity, positive predictive value, and negative predictive value for specimens containing greater than or equal to 10(5) colony-forming units per milliliter were 97.4%, 70.4%, 19.0%, and 99.7%, respectively. These values for specimens containing greater than or equal to 10(4) colony-forming units per milliliter were 92.2%, 71.6%, 24.1%, and 98.9%, respectively.


Upper extremity ischemia from developmental failure of brachial artery-a case report.
Advances in medicine and technology have increased brachial artery utilization for diagnostic and interventional radiology. Hence, detection and assessment of variations in upper extremity vasculature are important regardless of the low surgical intervention rate in the upper extremity. Anomalies of the upper extremity artery are infrequently reported, and anomalies of the brachial artery are even less common. Presented here is a case of developmental failure of the brachial artery. A segment about 2.1 cm from its origin was treated with bypass surgery. This is presented as an uncommon variation of the brachial artery.


An Anthracene-Based Metal-Organic Framework for Selective Photo-Reduction of Carbon Dioxide to Formic Acid Coupled with Water Oxidation.
A Zr-based metal-organic framework has been synthesized and employed as a catalyst for photochemical carbon dioxide reduction coupled with water oxidation. The catalyst shows significant carbon dioxide reduction property with concomitant water oxidation. The catalyst has broad visible light as well as UV light absorption property, which is further confirmed from electronic absorption spectroscopy. Formic acid was the only reduced product from carbon dioxide with a turn-over frequency (TOF) of 0.69 h-1 in addition to oxygen, which was produced with a TOF of 0.54 h-1 . No external photosensitizer is used and the ligand itself acts as the light harvester. The efficient and selective photochemical carbon dioxide reduction to formic acid with concomitant water oxidation using Zr-based MOF as catalyst is thus demonstrated here.


[New prospects in physician-patient communication: role of the animated model].
Today information technology and multimediality play a key role in the field of medicine and only recently have been used to improve the doctor-patient relationship. The authors propose the use of induction movies also in this field improving communication between doctor and patient especially when handling surgical operations and complex procedures. These movies give detailed information to patients showing images and explaining in a simple way surgery, therapy and innovative procedures helping the patients to cope with surgery and therapy reducing anxiety and worry. This innovative method was also used successfully for the training of students helping them to understand important issues. An induction movie on CD regarding two different surgical techniques was shown to 20 patients (7 females and 13 males, average age 50.8), 20 doctors and 20 students. Doctors and patients appreciated this new communication method enabling doctors to better communicate with patients and patients to better understand operation procedures. Worry for operation was reduced and compliance before and after surgery was increased. As to the notion point of view students understood quicker and easier. This method is innovative and enables technical information to reach patients, doctors and students faster. Images are kept in mind easier and help patients to evaluate the pros and cons of surgery reducing worry. There was more communication between doctors and patients improving therefore their relationship and at the same time reducing communication barriers.


Analytical and preparative high-performance liquid chromatographic separation of the enantiomers of ifosfamide, cyclophosphamide and trofosfamide and their determination in plasma.
A high-performance liquid chromatography chiral stationary phase (HPLC-CSP) based upon cellulose-tris(3,5-dimethylphenylcarbamate), the OD-CSP, was used to stereochemically resolve three racemic anticancer drugs: ifosfamide (IFF), cyclophosphamide (CTX) and trofosfamide (TFF). The observed enantioselectivities (alpha) were 1.45 (IFF), 1.21 (CTX) and 1.10 (TFF). The OD-CSP was also used on a preparative scale to isolate the enantiomers of IFF with an optical purity greater than 97%. In addition, an analytical assay was developed for the determination of the enantiomeric composition of IFF and CTX in plasma using achiral-chiral coupled column chromatography. A racemic form of another CSP, the D,L-naphthylalanine-CSP, was used as the achiral pre-column. The sample clean-up prior to HPLC analysis was realized by liquid-liquid extraction with chloroform. The correlation coefficient was 0.987 for both standard curves (20-130 micrograms/ml) and the controls were within 10% of the real value. The analysis time for each serum sample was less than 30 min.


Cationic peptides containing tyrosine protect against radiation-induced oxidative DNA damage.
To examine the effect of the amino acid tyrosine on oxidatively or direct-type damaged DNA damage when it is present in a DNA binding ligand. We made use of tetralysine ligands to ensure binding to DNA and to condense the DNA, and simulated direct-type damage by using gamma irradiation in the presence of thiocyanate ions. These ligands contained an additional C terminal amino acid. Phenylalanine was used as a control for tyrosine. These ligands were used in conjuction with a plasmid substrate to quantify strand break yields. Base damage yields were estimated by measuring the strand break yield after incubation of the plasmid with the bacterial base excision repair enzyme formamidopyrimidine-DNA N-glycosylase (FPG). When the condensing ligand contains an additional tyrosine or tryptophan residue, the plasmid is protected against the effects of a single electron oxidation, as assayed by sensitivity to a base excision repair enzyme. This protection is significantly greater in condensed plasmid where the amino acid residues are in close proximity to the DNA, and can be observed even when only a small fraction of the ligand contains tyrosine. Bound tyrosine residues located in close proximity to DNA are capable of reversing oxidative DNA damage far more efficiently than when present unbound in the bulk solution. This suggests that tyrosine residues in DNA binding proteins may participate in the repair of DNA that has been oxidatively damaged by ionizing radiation.


Effect of using cinnamon oil encapsulated in maltodextrin as exogenous flavouring on flavour quality and stability of biscuits.
The flavour quality of biscuits could be lost during baking and storage. Therefor, the impact of using cinnamon essential oil (EO) encapsulated in maltodextrin (CO-MD), as exogenous flavour, on the flavour quality and stability of biscuits was evaluated. The results were compared with those of using cinnamon oil dissolved in propylene glycol (CO-PG), as a delivery solvent. The main volatile compounds in cinnamon oil were used as markers to monitor its stability in biscuits flavoured with CO-MD and CO-PG during baking and storage. The volatile components generated in flavoured biscuits and nonflavoured biscuits (control) were analyzed by headspace solid phase microextraction and gas chromatography-mass spectrometry. The retention of cinnamaldehyde, eugenol and β-caryophyllene in biscuits flavoured with CO-MD was significantly (P < 0.05) higher, over the shelf life test, than in biscuits flavoured with CO-PG. The Maillard reaction products showed the highest retention in biscuits flavoured with CO-MD compared with those flavoured with CO-PG and control sample. However, all of them showed a gradual decrease during storage. The lipid degradation products showed an opposite trend. Storage for 90 days revealed a gradual decrease in the overall acceptability for both samples. The results of aroma sensory analysis confirmed those of instrumental analysis. This study demonstrated that microencapsulated cinnamon EO affects positively the overall qualities of biscuits.


Effects of propylthiouracil and methimazole on splanchnic hemodynamics in awake and unrestrained rats.
The treatment of alcoholic liver disease with propylthiouracil is based on its effect of suppressing the ethanol-induced increase in hepatic oxygen consumption. It has been postulated that liver necrosis ensues when the increase in oxygen demand by the liver exceeds oxygen delivery to this organ. Data are now presented which show that propylthiouracil also increases portal blood flow in awake, unrestrained rats. Liver blood flow was determined using the labeled microsphere technique in rats at various intervals (0.25, 0.5, 1.0, 3.0, 6.0 and 24 hr) after oral propylthiouracil (50 mg per kg). Administration of propylthiouracil (dose range: 6.25 to 100.0 mg per kg) produced a dose-dependent increase in portal blood flow when given either orally or intraarterially. Maximal flows were obtained with 50 mg per kg (controls = 37.8 +/- 1.5, oral propylthiouracil = 50.7 +/- 2.2 ml.kg-1.min-1). This increase in portal blood flow was accompanied by a decrease in preportal vascular resistance (controls = 2.61 +/- 0.16; propylthiouracil, 50 mg per kg = 1.79 +/- 0.09 mmHg per ml.kg-1.min-1). These effects were correlated with the plasma concentrations of propylthiouracil (r = 0.67, n = 68, p less than or equal to 0.001). The effect of oral propylthiouracil (50 mg per kg) on portal blood flow started at 0.5 hr and lasted for 6 hr after administration, whereas total liver blood flow was increased for 3 hr. Oral propylthiouracil (50 mg per kg) for 5 days resulted in a 53% increase in thyroid weight, an 85% reduction in 125I thyroid uptake and a 74% decrease in serum thyroxine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)


Biotechnology of natural and winery-associated strains of Saccharomyces cerevisiae.
A new body of evidence challenges the original consolidated theory of Pasteur on the natural (vineyard) origin of wine strains of Saccharomyces cerevisiae and instead indicates a local, winery-restricted life cycle. The findings open novel biotechnological perspectives for obtaining autochthonous selected starters for the wine industry. A local, individual, and specific fermenting yeast flora, mass selected year after year through many generations of S. cerevisiae in grape must, is present on the surfaces of every winery. These yeast strains are endowed with exceptional enological properties and capable of producing an assortment of volatile compounds apparently contributing to the specific bouquet of locally produced wines.


Long-term inducible resistance in birch foliage: triggering cues and efficacy on a defoliator.
Heavy damage of the mountain birch foliage, as well as application of small amounts of insect frass to the soil beneath the trees, reduced growth of Epirrita autumnata larvae reared in these trees in the following year. Foliage damage in the previous year decreased larval survival, too. Both foliage damage and insect frass in the soil decreased a fecundity index which combined the effects of size and survival. Because application of small amounts of fertilizers had an effect indistinguishable from that of insect frass, the effect of the frass may base on responses of trees to an increase in soil nutrient concentration in mid-summer. In previously untreated control trees, all performance indices (growth, survival, and egg production) of Epirrita correlated positively with the distance of the birch from the closest birch defoliated in the previous year, indicating "communication" between adjacent trees. Epirrita egg production in trees that had been both defoliated and treated with frass in the previous summer was at least 70% lower than in previously unmanipulated control trees.


Axonal expression of sodium channels in rat spinal neurones during postnatal development.
1. Postnatal expression of Na+ channels and development of somatic excitability were studied in dorsal horn neurones of rat using patch-clamp recordings from spinal cord slices in combination with the 'entire soma isolation' method. 2. The amplitude of Na+ current in the intact neurone in the slice increased with postnatal development (days 0-39) with a mean rate of 83 pA day-1. 3. The Na+ current in the neuronal soma did not increase with age and the soma, separated from the axon, was not able to fire spikes at any stage of development studied. 4. It is concluded that the postnatal development of the spinal dorsal horn neurone is accompanied by intensive expression of Na+ channels in the axonal but not somatic membrane. The estimated minimum density of Na+ channels in the axon initial segment is approximately 160 channels microm-2.


A case of metastatic lung cancer healed clinically with an extract from human tubercle bacilli (Maruyama vaccine--SSM).
1) A case of metastatic lung cancer derived from testicle is described which, in spite of continuing growth after the removal of the primary lesion, responded to the sole treatment of Maruyama vaccine (SSM) with completely satisfactory results and showed no recurrence over a period of 4 years. 2) The therapeutic course of the metastatic lung tumors in the present case showed a close correlation with the changes in the peripheral blood lymphocytes count and the alpha-2 globulin level. 3) The course of the response of the metastatic lung foci to the SSM therapy could be summarized as continued increase of tumors in size and number for the first 3 months, followed by shrinking, disappearance, and finally healing.


Harnessing immunoinformatics for developing a multiple-epitope peptide-based vaccination approach against SARS-CoV-2 spike protein.
COVID-19 has spread to over 200 countries with variable severity and mortality rates. Computational analysis is a valuable tool for developing B-cell and T-cell epitope-based vaccines. In this study, by harnessing immunoinformatics tools, we designed a multiple-epitope vaccine to protect against COVID-19. The candidate epitopes were designed from highly conserved regions of the SARS-CoV-2 spike (S) glycoprotein. The consensus amino acids sequence of ten SARS-CoV-2 variants including Gamma, Beta, Epsilon, Delta, Alpha, Kappa, Iota, Lambda, Mu, and Omicron was involved. Applying the multiple sequence alignment plugin and the antigenic prediction tools of Geneious prime 2021, ten predicted variants were identified and consensus S-protein sequences were used to predict the antigenic part. According to ElliPro analysis of S-protein B-cell prediction, we explored 22 continuous linear epitopes with high scores ranging from 0.879 to 0.522. First, we reported five promising epitopes: BE1 1115-1192, BE2 481-563, BE3 287-313, BE4 62-75, and BE5 112-131 with antigenicity scores of 0.879, 0.86, 0.813, 0.779, and 0.765, respectively, while only nine discontinuous epitopes scored between 0.971 and 0.511. Next, we identified 194 Major Histocompatibility Complex (MHC) - I and 156 MHC - II epitopes with antigenic characteristics. These spike-specific peptide-epitopes with characteristically high immunogenic and antigenic scores have the potential as a SARS-CoV-2 multiple-epitope peptide-based vaccination strategy. Nevertheless, further experimental investigations are needed to test for the vaccine efficacy and efficiency.


Catecholaminergic effects on inhibitory control depend on the interplay of prior task experience and working memory demands.
Catecholamines affect response inhibition, but the effects of methylphenidate on inhibitory control in healthy subjects are heterogenous. Theoretical considerations suggest that working memory demands and learning/familiarization processes are important factors to consider regarding catecholaminergic effects on response inhibition. The purpose of this study was to examine the role of working memory demands and familiarization for methylphenidate effects on response inhibition. Twenty-eight healthy adults received a single dose of methylphenidate (0.5 mg/kg) or placebo in a randomised, double-blind, crossover study design. The subjects were tested using a working memory-modulated response inhibition paradigm that combined a Go/Nogo task with a mental rotation task. Methylphenidate effects were largest in the most challenging mental rotation condition. The direction of effects depended on the extent of the participants' task experience. When performing the task for the first time, methylphenidate impaired response inhibition performance in the most challenging mental rotation condition, as reflected by an increased false alarm rate. In sharp contrast to this, methylphenidate seemed to improve response execution performance in the most challenging condition when performing the task for the second time as reflected by reaction times on Go trials. Effects of catecholamines on inhibitory control processes depend on the interplay of two factors: (a) working memory demands, and (b) learning or familiarization with a task. It seems that the net effect of increases in gain control and decreases in working memory processes determines the methylphenidate effect on response inhibition. Hence, crossover study designs likely underestimate methylphenidate effects on cognitive functions.


Investigation of asbestos concentration in ambient and lavage fluids of patients referred for bronchoscopy, Ahvaz.
The amount of fibers in the lungs is considered to reflect the cumulative intensity of past asbestos exposure, and bronchoalveolar lavage (BAL) has been proposed to be a good indicator of the presence and quantity of asbestos particles in the lungs. This study evaluated the asbestos concentration in BAL fluids of asbestos-exposed and unexposed pulmonary patients and the environment of Ahvaz city. This prospective study was conducted on 80 patients underwent diagnostic fiberoptic bronchoscopy referred to Imam Khomeini Hospital in Ahvaz, Iran, in 2019. Patients with Lung diseases were divided into three groups based on CT scan results: normal (n = 32), lung cancer (n = 40) and Interstitial lung disease (n = 8). The analysis of asbestos fiber concentration in BAL fluid was carried out by Scanning Electron Microscope (SEM). The positive asbestos test was detected in 69% of all subjects, including 64% of whom had asbestos-related jobs and 74.5% of those with non-related jobs (p = 0.240). The concentrations of asbestos fiber in the BAL in normal patients, lung cancer and interstitial fibrosis (ILD) were 8.13 ± 5.38, 9.66 ± 7.30 and 6.31 ± 1.98 f/ml, respectively (P = 0.492). There was no significant difference between the asbestos levels and exposure history (P = 0.877). The mean concentration of asbestos in the ambient air during the current year was 2.69 ± 0.57 f/ml (2.26-3.70), and the correlation between asbestos levels in BAL and the air was not significant (r = 0.147; P = 0.243). The exposure of different occupational and non-occupational groups to this carcinogenic substance indicates the need for environmental and individual control measures to reduce and prevent asbestos exposure.


Molecular characterization of an 18 kb segment of DNA puff C4 of Bradysia hygida (Diptera, sciaridae).
The data presented here are an extension of the molecular characterization of DNA puff C4 of Bradysia hygida. A cDNA related to a gene amplified in this puff and expressed when puff C4 expands was cloned and sequenced. Analysis of the amino acid sequence deduced from the open reading frame present in the cDNA indicate that the encoded protein is secreted and comprises mostly alpha-helical coiled-coil. An 18 kb genomic segment containing the transcription unit of this gene was also cloned and the structure and expression of the 1.4 kb mRNA was determined. Quantitative slot blot hybridization of DNA complementary to the transcription unit shows that this gene is amplified about 21 times in the salivary gland, confirming data previously obtained. Fragments upstream of the 5' end, and beyond the 3' end, of the gene transcription unit were also analysed and shown to be amplified at least eight and five times, respectively. Based on these data we discuss how amplification could occur at DNA puffs.


Structural and biochemical studies of a recombinant 25.5 kDa glutathione transferase of Taenia solium metacestode (rTs25GST1-1).
In this work, we studied a recombinant mu-class glutathione transferase of 25.5 kDa from Taenia solium metacestode (rTs25GST1-1) that follows Michaelis–Menten kinetics with 1-chloro-2,4-dinitrobenzene (CDNB). The kinetic parameters obtained for rTs25GST1-1 with CDNB and GSH were V(max) =12.04 μmol/min/mg and K(m)=1.38 mM, and V(max) =10.20 μmol/min/mg and K(m)=0.90, respectively. The optimal activity was found at pH 8 in the 37-40 °C temperature range. Circular dichroism studies for rTs25GST1-1 at different pH showed that it maintains a typical α-helix structure between pH 6.5-7.5, but loses it between pH 8 and 8.5. Thermal CD assays showed rTs25GST1-1 barely changed its secondary structure. Unfolding/refolding assays showed that rTs25GST1-1 retained its structure up to 40 °C without loss of its activity. Additionally, exposure of rTs25GST1-1 to cumene hydroperoxide did not produce significant changes in its structure and only affected 50% of its activity.


Sequential modeling of fecal coliform removals in a full-scale activated-sludge wastewater treatment plant using an evolutionary process model induction system.
We propose an evolutionary process model induction system that is based on the grammar-based genetic programming to automatically discover multivariate dynamic inference models that are able to predict fecal coliform bacteria removals using common process variables instead of directly measuring fecal coliform bacteria concentration in a full-scale municipal activated-sludge wastewater treatment plant. A sequential modeling paradigm is also proposed to derive multivariate dynamic models of fecal coliform removals in the evolutionary process model induction system. It is composed of two parts, the process estimator and the process predictor. The process estimator acts as an intelligent software sensor to achieve a good estimation of fecal coliform bacteria concentration in the influent. Then the process predictor yields sequential prediction of the effluent fecal coliform bacteria concentration based on the estimated fecal coliform bacteria concentration in the influent from the process estimator with other process variables. The results show that the evolutionary process model induction system with a sequential modeling paradigm has successfully evolved multivariate dynamic models of fecal coliform removals in the form of explicit mathematical formulas with high levels of accuracy and good generalization. The evolutionary process model induction system with sequential modeling paradigm proposed here provides a good alternative to develop cost-effective dynamic process models for a full-scale wastewater treatment plant and is readily applicable to a variety of other complex treatment processes.


Human serum metabolomic analysis reveals progression for high blood pressure in type 2 diabetes mellitus.
Type 2 diabetes mellitus (T2DM) is one of the most ordinary metabolic disorders and manifests as a high blood sugar level; 80%-90% of patients with T2DM will develop high blood pressure (HBP), which exacerbates irreversible organ damage. Understanding the metabolic basis of HBP is essential to facilitating early diagnosis and prompt treatments of diabetic complications. 34 patients who originally had T2DM and then developed HBP within 1 year were selected from physical examination participants. Using ultrahigh-performance liquid chromatography quadrupole time-of-flight metabolomic analysis, we compared the metabolomic profile of patients with 30 healthy controls. The results showed a clear discrimination in metabolomic profiles between T2DM and T2DM+HBP when employing orthogonal projection to latent structure with discriminant analysis with electrospray ionization modes. Eight differential metabolites changed significantly during disease progression, among which L-isoleucine, L-glutamic acid, pyroglutamic acid and linoleic acid decreased, while sphinganine, Cer(d18:0/16:0), Cer(d18:0/18:0), and citric acid increased. These metabolites are associated with the γ-glutamyl cycle, tricarboxylic acid cycle, and ceramide metabolism. These novel serum biomarkers may improve the management of T2DM and HBP complications, thus reducing the use of incorrect medical care.


Assessment of the novel estrogen receptor PET tracer 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES) by PET imaging in a breast cancer murine model.
The aim of this study was to compare the in vivo stability, uptake, and positron emission tomography (PET) imaging performance of a novel estrogen receptor PET tracer, 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES), with 16α-[(18)F]fluoroestradiol (FES). MC7-L1 and MC4-L2 (ER+) cell lines and their ERα-knockdown variants (ERαKD) were implanted subcutaneously in Balb/c mice. After 21 days, mice were imaged using either FES or 4FMFES. One hour post-injection, static images were acquired for 30 min and the tumor %ID/g uptake values were derived. Biodistribution data were also obtained 1 h following the injection of either FES or 4FMFES. Blood samples were taken at different times and analyzed on thin-layer chromatography to quantify the presence of radiometabolites for each radiotracer. To assess specific targeting to the estrogen receptors, mice bearing only ER+ tumors were treated with the competitive ER inhibitor fulvestrant 48 h prior to imaging with 4FMFES. Metabolic stability was found to be similar for both tracers in mice. Both FES and 4FMFES differentiated ER+ tumors from ERαKD tumors in biodistribution and PET imaging studies. 4FMFES achieved a significantly higher %ID/g uptake in ER+ tumors and MC4-L2 ERαKD tumors than FES in the PET imaging studies. Also, tumor-to-background ratio was higher in ER+ tumors using 4FMFES compared to FES. Dissection data showed a significantly higher %ID/g in all tested cell lines and ER-rich tissues using 4FMFES versus FES. Fulvestrant-treated mice had either low or undetectable tumor uptake. In a tumor-bearing mouse model, 4FMFES achieves better specific tumor uptake and better contrast than FES, making it a promising candidate for ER imaging.


Gas-phase reactivity and molecular modeling studies on triply protonated dodecapeptides that contain four basic residues.
Gas-phase deprotonation and hydrogen/deuterium (H/D) exchange reactions for ions from three model dodecapeptides were studied by Fourier transform ion cyclotron resonance mass spectrometry. Molecular dynamics calculations were employed to provide information on conformations and Coulomb energies. The peptides, (KGG)4, (K2G4)2, and K4G8, each contain four high basicity lysine residues and eight low basicity glycine residues; however, in the present work only three lysine residues were protonated. Proton transfer reactions with a series of reference amines revealed apparent gas-phase acidities in a narrow range of 207.3-209.6 kcal/mol, with deprotonation efficiencies following the order [K4G8 + 3H]3+ > [(KGG)4 + 3H]3+ > [(K2G4)2 + 3H]3+. The three ions also react similarly with d4-methanol: each exchanged a maximum of 23-25 of their 25 labile hydrogens, with the first 15-17 exchanges occurring at rate constants of (1.6-2.6) x 10(-11) cm3 molecule-1 s-1. The experimental results agree with molecular modeling findings of similar conformations and Coulomb energies for the three peptide ions. The [M + 3H]3+ data are compared to data obtained previously in our laboratory for the "fully" protonated [M + 4H]4+ (Zhang, X.; Ewing, N. P.; Cassady, C. J. Int. J. Mass Spectrom. Ion Phys., in press). For (KGG)4 and (K2G4)2, there is a marked difference in H/D exchange reactivity between 3+ ions and 4+ ions. The 4+ ions, which have diffuse conformations, slowly exchange only 14 hydrogens, whereas their more compact 3+ counterparts exchange 23-25 hydrogens at a 5-times greater rate. In contrast, the 3+ and 4+ ions of K4G8 have similar compact conformations and exchange reactivity. The results indicate that a multiply hydrogen-bonded intermediate between the deuterating reagent and the peptide ion is necessary for facile H/D exchange. The slower, incomplete H/D exchange of [(KGG)4 + 4H]4+ and [(K2G4)2 + 4H]4+ is attributed to the inability of their protonated lysine n-butylamino groups (which extend away from the peptide backbone) to form this intermediate.


EQ-5D-5L Value Set for Slovenia.
The aim of this valuation study was to produce a value set to support the use of EQ-5D-5L data in decision making in Slovenia. The study design followed the published EuroQol research protocol, and a quota sample was defined according to age, sex, and region. Overall, 1012 adult respondents completed 10 time trade-off and seven discrete choice experiment tasks in face-to-face interviews. The Tobit model was used to analyse the composite time trade-off (cTTO) data in order to generate values for the 3125 EQ-5D-5L health states. The data showed logical consistency, with more severe states being given lower values. The greatest disutility was shown in the pain/discomfort and anxiety/depression dimensions. In the EQ-5D-5L value set, the values range from -1.09 to 1. With the exception of UA5 (unable to perform usual activities), all other levels on all health dimensions were statistically different from 0 and from each other. Compared with the existing EQ-5D-3L value set, there is a slightly lower share of 'worse than dead' states (32.1% compared with 33.7%) and the minimum value is lower. Results have important implications for users of the EQ-5D-5L in Slovenia and regions. It is a robust and up-to-date value set and should be the preferred value set used in adults in Slovenia and in neighbouring countries without their own value set.


Classification of childhood arthritis: a work in progress.
The classification of chronic childhood arthritis has challenged physicians for a century. Currently used classifications are all based on clinical characteristics and because they are frequently used imprecisely, communication of scientific data has been difficult. The new classification of the International League of Associations of Rheumatologists (ILAR) represents the results of an international effort to clarify the classification of this group of diseases based on identification of clinically homogeneous groups. This classification process is ongoing, and will reflect the results of scientifically based studies as they become available.


Chitosan as a starting material for wound healing applications.
Chitosan and its derivatives have attracted great attention due to their properties beneficial for application to wound healing. The main focus of the present review is to summarize studies involving chitosan and its derivatives, especially N,N,N-trimethyl-chitosan (TMC), N,O-carboxymethyl-chitosan (CMC) and O-carboxymethyl-N,N,N-trimethyl-chitosan (CMTMC), used to accelerate wound healing. Moreover, formulation strategies for chitosan and its derivatives, as well as their in vitro, in vivo and clinical applications in wound healing are described.


Characterization and source identification of nitrogen in a riverine system of monsoon-climate region, China.
There are increasing concerns in nitrogen (N) pollution worldwide, especially in aquatic ecosystems, and thus quantifying its sources in waterways is critical for pollution prevention and control. In this study, we investigated the spatio-temporal variabilities of inorganic N concentration (i.e., NO3-, NH4+) and total dissolved N (TDN) and identified their sources in waters and suspended matters using an isotopical approach in the Jinshui River, a river with a length of 87km in the monsoon-climate region of China. The spatio-temporal inorganic N concentrations differed significantly along the longitudinal gradient in the river network. The NO3-, NH4+ and TDN concentrations ranged from 0.02 to 1.12mgl-1, 0.03 to 4.28mgl-1, and 0.33 to 2.78mgl-1, respectively. The 15N tracing studies demonstrated that N in suspended organic matter was in the form of suspended particulate nitrogen (SPN) and was primarily from atmospheric deposition and agricultural fertilizer. In contrast, N in stream waters was mainly in the form of nitrate and was from atmospheric deposition, fertilizers, soil, and sewage. Meanwhile, both δ15N-SPN and δ15N-NO3- peaked in the rainy season (i.e., July) because of higher terrigenous sources via rain runoff, demonstrating the dominant diffusive N sources in the catchment. Thus, our results could provide critical information on N pollution control and sustainable watershed management of the riverine ecosystem in monsoon-climate region.


Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: Phase 1b study.
This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.


Discrimination, Self-Esteem, and Mental Health Across Ethnic Groups of Second-Generation Immigrant Adolescents.
The relation between discrimination and higher depression by way of reductions in self-esteem has been documented among some racial and ethnic minority populations. Yet, the extent to which the results extend to general forms of discrimination as well as multiple second-generation immigrant ethnic groups remains underexamined. This article assessed the mediating role of self-esteem in the relation between general forms of perceived discrimination and depression symptoms among second-generation immigrant adolescents and assessed the extent to which the relations were invariant across ethnic sub-groups. Analyses were based on data from the Children of Immigrants Longitudinal Study over two periods spanning adolescence (N = 4288; Mage = 14 and 17). The mediating role of self-esteem was tested via path analysis for the full sample, and multiple-group path analyses compared these results across White, Black, Asian, Hispanic, and other (multiracial) immigrants. Indirect effects were obtained via 5000 bootstrapped replications. In the full sample, the relation between discrimination and depression was mediated by self-esteem with approximately 30% of the total effect mediated. Said mediated relation was only confirmed among White and Asian sub-groups, with 27% and 49% of the total effects mediated, respectively. The results suggest that the process by which discrimination relates to mental health may vary between immigrant racial/ethnic sub-groups. In addition, the results highlight the value of considering broader categorizations of perceived discrimination beyond race or ethnicity to understand complexities associated with intersecting marginalized identities among this population.


Stiffness-responsive feedback autoregulation of DDR1 expression is mediated by a DDR1-YAP/TAZ axis.
Increased matrix stiffness is sensed by the collagen-binding receptor tyrosine kinase discoidin domain receptor 1 (DDR1). We have previously shown that DDR1 stimulates a positive feedback loop to increase its own expression in vascular smooth muscle cells (VSMCs). The transcriptional co-factors YAP/TAZ are stiffness sensing molecules that have not previously been investigated in DDR1 signaling. Here, we test the hypothesis that DDR1 signals through YAP/TAZ to auto-regulate its own expression. We used vascular smooth muscle cells (VSMCs) from wild-type and DDR1 knockout mice stimulated with collagen and/or substrates of different stiffness. We show that DDR1 controls YAP/TAZ nuclear localization and activity, whereas knockdown of YAP/TAZ attenuates DDR1 expression. In response to increased substrate stiffness, collagen stimulation, or RhoA activation, YAP/TAZ translocate to the nucleus and bind to chromatin. Finally, collagen stimulation promotes increased YAP/TAZ association with the Ddr1 promoter. These findings reveal the mechanism by which DDR1 regulates YAP/TAZ activity which can then mediate positive feedback regulation of DDR1 expression by promoting transcription of the DDR1 gene.


Cross-bridge dynamics in the contracting heart.
The mechanical characteristics of the myosin motor is one of the key determinants of ventricular function. In small mammals there are two myosin isoforms, V1 and V3, with profoundly different performance characteristics. We used myothermal and mechanical analysis of intact papillary muscles from thryoxine (V1) and popylthiouracil (V3) treated rabbit hearts to assess the mechanical attributes of the myosin cross-bridge cycle. The average cross-bridge force time integral for V1 papillary muscles is 0.15 +/- 0.02 pNs for the entire isometric twitch and 0.19 +/- 0.03 pNs for the portion of the isometric twitch between 0.9 peak isometric force for the rising and declining portions of the twitch. The ratio of V1/V3 for the cross-bridge force time integral for the entire twitch and at the peak of the twitch is 0.5 (p < 0.05) and 0.4 (p < 0.05), respectively. Since the peak of the twitch measurements minimize internal shortening only these will be presented below. The average unitary force and attachment time during the peak of the twitch for V1 hearts was 1.55 +/- 0.37 pN and 140 +/- 20 msec, respectively. The ratios of V1/V3 for these parameters were 0.6 (p < 0.05) and 0.8 (ns). The cycling rate and duty cycle for V1 were 4.37 +/- 0.81 cycles per head-second and 0.66 +/- 0.22. The ratios of V1/V3 for cycling rate and duty cycle were 2.8 (p < 0.05) and 2.7 (ns). These measurements are consistent with and help explain the energetic and mechanical function of the intact heart.


Clinical arthritis associated with positive radiological and serological findings in Finnish adults.
The Mini-Finland Health Survey was designed to analyse the epidemiology of major public health problems. The study covered a representative sample of the Finnish population aged 30 years or over, and initially comprised 8,000 people. Serum rheumatoid factor was determined in 7,124 cases (89%). There were 138 cases of clinical arthritis in the series, corresponding to a prevalence of 1.9% (1.0% in males and 2.7% in females). Fifty-nine of the cases (0.8% of the population) were seropositive, and 50 cases (0.7%) had in their hand radiographs changes characteristic of rheumatoid arthritis. Twelve of the X-ray positive cases were seronegative. One-half of these proved to be seroconversion cases or rheumatoid variants typically seronegative, such as early-onset juvenile rheumatoid arthritis.


A picture with a caption: Using photovoice as cultural self-reflection in communication sciences and disorders.
Self-reflection is an essential component of developing cultural competence. However, there is a paucity of research on how to best accomplish cultural self-reflection in CSD courses. Therefore, the purpose of this research study is to examine the teaching and learning practice of using Photovoice as a means of cultural self-reflection in a foundational, multicultural course in CSD. This qualitative investigation employed a phenomenological approach with emphasis on the scholarship of teaching and learning. Data gathering involved completion of a Photovoice assignment and a prompted reflection of the assignment. The Photovoice assignment entailed the students reflecting and examining their culture. Then, the students submitted two photographs, one that represents a strength of a culture they identify with and one that represents a challenge of a culture they identify with. The students presented their cultural strength and challenges in small and large group discussions. The prompted reflection required the students to address questions in a written or video-recorded response. When the course was completed, the researcher commenced line-by-line focused coding to cluster frequently used terms and common experiences into specific themes. The student participants shared photos of cultural strengths and challenges, discussed these photos in small and large groups, and completed a prompted reflection of the Photovoice assignment. While each student's project and reflection were unique, common themes prevailed. The themes of safety, privilege, and mental health emerged from the Photovoice projects and the themes of learning and formating arose from the reflections on use of the project toward cultural competence. The results of this study suggests that Photovoice is a valuable tool for cultural self-reflection and learning in all courses in CSD programs. In this way cultural self-reflection and the progression toward cultural competence is an on-going process where students are better prepared to provide client-centered, culturally competent care for all people.


Selection and lineage specification in the thymus: commitment 4-stalled.
How CD4(+)CD8(+) thymocytes commit to CD4 helper versus CD8 cytotoxic lineages is a central unresolved question in developmental immunology. In this issue, show that engineering CD4 for shutoff immediately after positive selection misdirects cells to the cytotoxic lineage. The result highlights the distinction between positive selection and lineage commitment and provides new impetus for reexamining lineage models.


Psychological treatments for negative symptoms.
Psychological training programmes for patients presenting with negative symptoms have developed from an environmentally based approach (the token economy) through interactive programmes (social and life skills training) to programmes which focus directly on facilitating and enhancing the cognitive skills of the individual patient (self-instructional training and problem-solving). It is clear that this sequence of research has generated a range of approaches which are probably undervalued in the management of patients suffering from negative symptoms. Problems remain with respect to the generalisation of some procedures but it seems likely that these problems may be overcome by tailoring treatments to the particular cognitive deficits of different groups of patients. This will obviously require a detailed analysis of the structure of negative symptoms and the deficits associated with them. The distinction between difficulties in initiating behavior and difficulties in organising behaviour may prove to be particularly important in this respect.


Acute renal effects of sulindac and indomethacin in chronic renal failure.
The effects of 2 days of oral dosing with sulindac (200 mg twice a day) or indomethacin (75 mg twice a day) on glomerular filtration rate, urinary excretion of prostaglandin E2, sodium homeostasis, and other renal function parameters were investigated in eight patients with chronic stable impaired renal function. Indomethacin reduced creatinine clearance (from 41.0 +/- 7.9 to 30.3 +/- 6.3 ml/min) and increased serum levels of creatinine and beta 2-microglobulin. Sulindac had no effect on any of these parameters. Both drugs induced depression of urinary prostaglandin E2 excretion; this depression was greater after indomethacin. Urinary sodium excretion fell from 144.4 +/- 18.7 to 85.5 +/- 9.7 mmol/24 hr after indomethacin and from 131.7 +/- 11.6 to 103.4 +/- 13.3 mmol/24 hr after sulindac. Body weight increased 1.2 kg after indomethacin but was not changed by sulindac. Plasma renin activity was reduced from 2.3 +/- 0.8 to 1.7 +/- 0.6 nmol/L/hr by sulindac and from 2.8 +/- 0.8 to 1.5 +/- 0.5 nmol/L/hr by indomethacin. Urinary N-acetyl-beta-glucosaminidase and kallikrein excretion was not changed by either drug. Our data suggest that sulindac affects renal prostaglandin E2 synthesis and sodium excretion in patients with severe renal failure to a lesser extent than does indomethacin. Sulindac still seems to be the drug of choice in this group of patients, but glomerular filtration rate, body weight, and electrolyte balance should be carefully monitored.


Influence of the Brownian step size in off-lattice Monte Carlo simulations of irreversible particle aggregation.
The influence of the Brownian step size in off-lattice Monte Carlo simulations of the aggregation and gelation of spheres is studied. It is found that the kinetics are strongly influenced if the step size is larger than the mean smallest distance between the sphere surfaces. The structure of the clusters and the gels is influenced, but only over length scales smaller than the step size. Using large step sizes leads to a narrower size distribution of the clusters. Implications of the present results are discussed for simulations reported in the literature in which the Brownian step size was chosen equal to the sphere diameter.


Autocrine regulation of rheumatoid arthritis synovial cell growth in vitro.
Rheumatoid arthritis (RA), and not osteoarthritis (OA) synovial cells proliferate in serum-free medium, a finding that suggests that, in vitro, RA synovial cells may be stimulated to grow by the continuous autocrine production of at least one polypeptide growth factor. Adding monoclonal antibody 1D11.16, or rabbit polyclonal anti-tumor growth factor beta (anti-TGF-beta) antibodies (both neutralizing antibodies to TGF-beta 1 and TGF-beta 2) to RA synovial cells, in culture, caused a significant reduction in cell growth, an effect not seen when other growth factor antibodies (platelet-derived growth factor [PDGF], epidermal growth factor [EGF], or EGF receptor) were added to the culture medium. Taken together, these data are consistent with the concept that RA synovial cell growth in vitro is driven endogenous TGF-beta. Moreover, when EGF was added to the culture medium, this caused the numbers of RA, and not OA, synovial cells to increase significantly. This finding suggests that RA synovial cells are in G1 phase of the cell cycle; an effect that could be mediated by endogenous TGF-beta.


Identification of common antigens of three pathogenic Nocardia species and development of DNA vaccine against fish nocardiosis.
Fish nocardiosis is a chronic granulomatous bacterial disease and three pathogens have been reported so far, including Nocardia asteroids, N. seriolae and N. salmonicida. However, the absence of antigen markers is a bottleneck for developing effective vaccines against fish nocardiosis. In this study, the antigenicity of whole-cell protein of these three pathogenic Nocardia species were profiled by immunoproteomic analysis and 7 common immunogenic proteins were identified as follows: molecular chaperone DnaK (DnaK), molecular chaperone GroEL (GroEL), 30 S ribosomal protein S1 (RpsA), TerD family protein (TerD), FHA domain-containing protein (FHA), 50 S ribosomal protein L7/L12 (RplL) and PspA/IM30 family protein (PspA). Furthermore, the DNA vaccine encoding FHA gene against fish nocardiosis was developed and its efficacy was investigated in hybrid snakehead. The results suggested that it needed at least 7 d to transport pcDNA-FHA DNA vaccine from injected muscle to head kidney, spleen and liver and stimulate host's immune system for later protection. In addition, non-specific immunity paraments (serum lysozyme (LYZ), peroxidase (POD), acid phosphatase (ACP), alkaline phosphatase (AKP) and superoxide dismutase (SOD) activities), specific antibody (IgM) titers production and immune-related genes (MHCIα, MHCIIα, CD4, CD8α, IL-1β and TNFα) were used to evaluate the immune response induced in pcDNA-FHA vaccinated hybrid snakehead, it proved that all these mentioned immune activities were significantly enhanced after immunization. The results also showed hybrid snakehead vaccinated with pcDNA-FHA had higher survival rate (79.33%) compared with the controls after challenge with N. seriolae, indicating that the pcDNA-FHA DNA vaccine can supply immune protection against N. seriolae infection. Taken together, this study may warrant further development of these common immunogenic proteins as the antigens for vaccine or diagnosis and facilitate the prevention and treatment of fish nocardiosis.


Non-invasive cardiac output determination by two-dimensional independent Doppler during and after cardiac surgery.
This study was to compare noninvasive measurement of cardiac output (CO) using a novel Doppler technique with invasive CO measurements in the postcardiac surgical intensive care unit. Thirty-six patients (67.2 +/- 10 years, New York Heart Association functional class 3.1 +/- 0.3) undergoing coronary revascularization were prospectively examined postoperatively. One hundred eighty paired CO and stroke volume measurements were compared from the noninvasive USCOM device (Sydney, Australia) and the invasive Swan-Ganz catheter at varying COs. Eighteen measurements were performed intraoperatively by direct insonation of the right ventricular outflow tract. Mean noninvasive and invasive CO values were 5.15 +/- 1.98 L/min and 4.92 +/- 2.0 L/min, respectively (r = 0.870; p < 0.01). The mean difference between methods was -0.23 +/- 1.01 L/min greater than a range of CO values from 2.5 to 9.9 L/min. Mean central venous saturation percentage was 72 +/- 9%, correlating with both noninvasive and invasive CO (r = 0.474 and 0.606, respectively, p < 0.01). Intraoperatively, both direct and invasive CO were identical. Using the ultrasonic cardiac output monitoring (USCOM) device it is possible to determine noninvasive beat-to-beat CO in postcardiac surgery patients without the possible complications associated with invasive right heart catheterization. The USCOM CO and stroke volume showed a very good agreement with invasive Swan-Ganz measures and correlated with central venous saturation percentage.


In vitro assessment of CYP1A2 and 2C9 inhibition potential of Withania somnifera and Centella asiatica in human liver microsomes.
Several herbal drugs and allopathic medicines when co-administered can lead to severe herb-drug interactions. Hence, this study was undertaken in order to assess the in vitro inhibition potential of Withania somnifera and Centella asiatica with cytochrome P450 (CYP) 1A2 and 2C9 enzyme using human liver microsomes. Inhibitory potential of crude extracts of both the medicinal plants along with their principal phytoconstituents were investigated using selective probe substrate technique. IC50, Ki values and mode of inhibition were determined. The results of the study revealed that W. somnifera showed no significant interaction with both the isoforms of CYP. However, ethanolic extract of C. asiatica significantly inhibited both CYP1A2 (IC50 value - 42.23±3.65 μg/mL/Ki value - 14.93±4.59 μg/mL) and 2C9 enzyme (IC50 value - 48.41±4.64 μg/mL/Ki value - 23.89±3.14 μg/mL) in a competitive manner. The flavonoids, quercetin and kaempferol showed potent (IC50 values less than 10 μM) inhibition of CYP1A2 activity with no significant inhibition of CYP2C9 enzyme. Thus, these findings of the study might be helpful for safe and effective use of C. asiatica in clinical practice. However, its in vivo interaction study in humans is still warranted.


Role of oxidative stress in various stages of psoriasis.
Psoriasis is a chronic inflammatory, proliferative skin disease characterized by pathological skin lesions due to various exogenous and endogenous factors. It is associated with a number of biochemical and immunological disturbances. Recently, it has been suggested that increased reactive oxygen species (ROS) production and compromised function of antioxidant system may be involved in the pathogenesis of this disease. In the present study, 90 psoriasis patients were selected. Disease severity was assessed by psoriasis area severity index score and grouped as mild, moderate and severe (each group consists of 30 subjects) and compared with 30 healthy controls. Serum levels of malondialdehyde, nitric oxide end products and the activities of antioxidant enzymes such as erythrocyte-superoxide dismutase, catalase and total antioxidant status were investigated in these groups/subjects. As compared to controls, we found severitywise significantly increased serum malondialdehyde, nitric oxide end products with decrease in erythrocyte-superoxide dismutase activity, catalase activity and total antioxidant status in patients with psoriasis suggesting worsening of the disease. It seems to be linked with the enhancement of Reactive Oxygen Species production and decreased antioxidant potential in psoriasis.


Correction to: The association of urinary pentosidine levels with the prevalence of osteoporotic fractures in postmenopausal women.
In the original publication of the article, the following sentence under the abstract section was published incorrectly as "A multivariable logistic regression analysis revealed that urinary pentosidine was significantly associated with the prevalence of fracture after adjustment for known risk factors for fracture (odds ratio 1.92, 95% CI 1.09-3.37, P = 0.023)."


Dietary factors relate to cardiovascular risk factors in early life. Bogalusa Heart Study.
Relationships between diet and cardiovascular disease risk factors were studied in a cohort of infants in Bogalusa, Louisiana. The 24-hour dietary recalls and cardiovascular measurements were obtained on each child at age 6 months, yearly through age 4, and again at age 7 (cardiovascular measurements only). At ages 4 and 7, children with persistently high intakes of dietary cholesterol (three or more measurements in the upper tertile) had levels of serum total cholesterol approximately 14 mg/dl higher than children whose intakes of cholesterol were not persistently high. Children in the upper tertile for dietary cholesterol had levels of low density lipoprotein cholesterol (15 mg/dl at age 4 and 18 mg/dl at age 7) higher than children in the lower tertile for dietary cholesterol. Children with high intakes of animal fat were 2 to 6 kg heavier (p less than 0.05) than those with lower intakes. Changes in dietary cholesterol correlated significantly with changes in serum total cholesterol (r = 0.42) and low density lipoprotein cholesterol (r = 0.50) from 6 months to 4 years of age. Changes in subscapular skinfold measurements correlated significantly with changes in intake of total protein (r = 0.31), total fat (r = 0.25), starch (r = 0.31), and energy (r = 0.39) from ages 6 months to 4 years. Results indicate that tracking of dietary components and their relationships with cardiovascular disease risk factors can be detected at an early age. These findings may well be the groundwork for later studies of obesity and the early onset of hyperlipoproteinemia.


Evidence of latitudinal migration in tri-colored bats, Perimyotis subflavus.
Annual movements of tri-colored bats (Perimyotis subflavus) are poorly understood. While this species has been considered a regional migrant, some evidence suggests that it may undertake annual latitudinal migrations, similar to other long distance North American migratory bat species. We investigated migration in P. subflavus by conducting stable hydrogen isotope analyses of 184 museum specimen fur samples and comparing these results (δD(fur)) to published interpolated δD values of collection site growing season precipitation (δD(precip)). Results suggest that the male molt period occurred between June 23 and October 16 and 33% of males collected during the presumed non-molt period were south of their location of fur growth. For the same time period, 16% of females were south of their location of fur growth and in general, had not travelled as far as migratory males. There were strong correlations between δD(fur) from the presumed molt period and both growing season δD(precip) (males--r(2) = 0.86; p<0.01; females--r(2) = 0.75; p < 0.01), and latitude of collection (males--r(2) = 0.85; p<0.01; females--r(2) = 0.73; p<0.01). Most migrants were collected at the northern (>40 °N; males and females) and southern (<35 °N; males only) extents of the species' range. These results indicate a different pattern of migration for this species than previously documented, suggesting that some P. subflavus engage in annual latitudinal migrations and that migratory tendency varies with latitude and between sexes. We suggest that this species' hibernation ecology makes it particularly susceptible to long winters, making migration from the northern extent of the species' range to more southern hibernacula preferable for some individuals. Fur δD values for some of the northern individuals may indicate an increase in the currently accepted northern range of this species. Sex-biased differences in migration may be the result of differences in reproductive pressures.


Sodium-glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.
To evaluate the efficacy and safety of combined therapy with sodium-glucose cotransporter 2 (SGLT-2) inhibitors plus pioglitazone versus pioglitazone alone in type 2 diabetic patients. Systematic literature searches were performed across PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from 1966 to September 2018 to identify randomized, controlled trials. Mean difference (MD) or odds ratio (OR) was used to evaluate efficacy and safety end-points (active group vs control group), wherever appropriate. Heterogeneity was assessed by P value of χ2 statistics and I 2. Four randomized controlled trials with 1411 diabetic patients were included. Pooling data from included trials showed that HbA1c change was significantly larger in both low-dose SGLT-2 inhibitors (MD: -0.59%, 95% CI: -0.77 to -0.41%) and high-dose SGLT-2 inhibitors (MD: -0.65%, 95% CI: -0.78 to -0.53%) plus pioglitazone than pioglitazone alone in 24-26 weeks. Favourable outcomes were also found in fasting blood glucose level reduction and more patients achieving HbA1c <7% in SGLT-2 inhibitor plus pioglitazone (OR: 3.21, 95% CI: 1.99 to 5.16). Also, SGLT-2 inhibitor plus pioglitazone vs pioglitazone, reduced weight and blood pressure. The risks of death, heart failure, hypoglycaemia and urinary tract infection were not different between active and control groups although genital tract infection was more frequently seen in SGLT-2 inhibitor group. Compared to pioglitazone alone, SGLT-2 inhibitor plus pioglitazone improved glycaemic control, reduced body weight and lowered blood pressure, but increased genital tract infection.


Antibacterial activity of Veronica montana L. extract and of protocatechuic acid incorporated in a food system.
This study was designed to evaluate the antibacterial activity of the Veronica montana L. water extract and its main phenolic compound, protocatechuic acid. The antibacterial activity was determined by microdilution assay against six strains of Gram-positive and Gram-negative bacteria. Listeria monocytogenes was the most sensitive of the tested bacterial species. Antibacterial preserving properties of protocatechuic acid were also evaluated after its incorporation in cream cheese, using L. monocytogenes as commonly cheese contaminant. The compound successfully inhibited L. monocytogenes development in cream cheese, at room temperature and in refrigerator (25°C and 4°C, respectively), after 3days of inoculation. Sensory evaluation was carried out in order to validate the mentioned food system. A possible mode of action of the tested compound towards bacterial cells was assessed and appears to be direct lysis of pathogenic cytoplasmic membrane. Prediction of pharmacokinetic properties was also performed using computational analyzes. The obtained results can serve as an important platform for the development of effective natural preservatives.


Microbial siderophores as molecular shuttles for metal cations: sources, sinks and application perspectives.
Iron is one of the highly abundant elements on the earth's crust, an essential micronutrient for a majority of life forms, and exists in two frequent oxidation states such as ferrous (Fe2+) and ferric (Fe3+). These two oxidation states are interconvertible by redox reactions and form complexes with a wide range of siderophores. At neutral pH in soil, Fe2+ is highly soluble upto 100 mM but have less biological value, whereas Fe3+ is less soluble upto 10-9 M. This reduced bioavailability of Fe3+ induces competition among microorganisms. As many microorganisms need at least 10-6 M of Fe3+ form of iron for their growth, siderophores from these microbes readily withdraw Fe3+ iron from a variety of habitats for their survival. In this review, we bring into light the several recent investigations related to diverse chemistry of microbial siderophores, mechanisms of siderophore uptake, biosynthetic gene clusters in microbial genomes, various sources of heavy metal cations in soil, siderophore-binding protein receptors and commercialisation perspectives of siderophores. Besides, this review unearths the recent advancements in the characterisation of novel siderophores and its heavy metal complexes alongside the interaction kinetics with receptors.


A Biomimetic Nanoplatform with Improved Inflammatory Targeting Behavior for ROS Scavenging-Based Treatment of Ulcerative Colitis.
Ulcerative colitis (UC), a refractory disease, has become a global problem. Herein, a biomimetic nanoplatform (AU-LIP-CM) comprising Au cluster enzymes (AU)-loaded liposomes (AU-LIP) camouflaged with the fusion membrane (CM) consisting of neutrophil (NC) and red blood cell (RBC) membrane is designed for the treatment of UC. Briefly, revealed by second near-infrared (NIR-II) imaging through collection of fluorescence emitting >1200 nm from AU, the improved inflammatory targeting behavior contributed by CM cloaking, which inherits abilities of inflammatory targeting and immune escape from NC and RBC, respectively, promotes specific accumulation of AU within inflammatory intestines with up to ≈11.5 times higher than that of bare AU. Afterward, AU possessing superoxide dismutase- and catalase-like activities realizes high-efficiency scavenging of reactive oxygen species (ROS), leading to repair of intestinal barriers, regulation of the immune system, and modulation of gut microbiota, which surpass first-line UC drug. In addition, study of underlying therapeutic mechanism demonstrated that the treatment with AU-LIP-CM can alter the gene signature associated with response to ROS for UC mice to a profile similar to that of healthy mice, deciphering related signal pathways. The strategy developed here provides insights of learning from properties of natural bio-substances to empower biomimetic nanoplatform to confront diseases.


Patient Satisfaction in Academic Pain Management Centers: How Do We Compare?
The aim of the study was to investigate patient satisfaction amongst academic pain management centers and associated factors. Approximately 25% of pain management centers perform better than other practices on Press Ganey surveys. The majority of respondents (96%) indicated that pain management practices were uniquely positioned to receive poorer scores on patient satisfaction surveys. The majority of respondents (20/26), who reported a reason, indicated that limiting opioid prescribing led to poor patient satisfaction scores. Eighty-three percent of respondents indicated that they received pressure from administrators to improve patient satisfaction scores. The opioid epidemic in the USA must be addressed in order to diminish the senseless loss of life that is occurring in staggering numbers. The quality of care physicians provide has increasingly been assessed via patient satisfaction surveys. The results of these surveys often are utilized to provide financial incentives to physicians to obtain higher satisfaction scores. In the field of pain management, physicians may experience pressure to prescribe opioids in order to obtain higher patient satisfaction scores.


Ventilatory functions of normal children and young adults--Mexican-American, white, and black. I. Spirometry.
This is a study of the ventilatory functions of 1,805 normal Mexican-American, white, and black students of six public schools in Houston, Texas, with ages ranging from 7 to 20. A roll-seal piston type spirometer was used. The best performed forced vital capacity curve of each student was selected by the computer program from which the following measurements were extracted: FVC, FEV1, FEV1/FVC ratio, PEFR, and MMEF. Each student also had the peak expiratory flow rate measured by the Wright peak flowmeter to establish normal values with this instrument. Significant differences of lung volume and flow rate exist among the three races, and between male and female subjects. Prediction equations and prediction curves for each race and sex are presented. The results of the present study are compared with those of previously published works.


Neurologic spectrum of chronic liver failure and basal ganglia T1 hyperintensity on magnetic resonance imaging: probable manganese neurotoxicity.
An atypical form of parkinsonism has been described in patients with chronic liver disease, associated with increased T1 signal in the basal ganglia on magnetic resonance imaging. The magnetic resonance imaging signal changes are characteristic of manganese accumulation, which has been neuropathologically confirmed. Manganese neurotoxicity may result in additional neurologic findings besides parkinsonism. To fully characterize patients with chronic central nervous system symptoms and chronic liver failure associated with basal ganglia T1 hyperintensity. Prospective and retrospective case study. Mayo Clinic, Rochester, Minn. Eight patients referred for neurologic evaluation and studied prospectively, and 7 additional retrospectively identified patients who had been examined by Mayo Clinic neurologists. Neurologic syndromes identified. Three syndromes were recognized in these 15 patients with liver failure and basal ganglia T1 hyperintensity on magnetic resonance imaging: (1) isolated parkinsonism, (2) gait ataxia plus other neurologic findings (ataxia-plus), and (3) cognitive impairment with psychiatric features. All but 1 patient had elevated blood manganese levels. Ammonia levels were normal in most, and the neurologic syndromes did not appear to reflect the well-known toxic-metabolic encephalopathy of liver disease. Chronic liver failure may result in heterogeneous neurologic syndromes that cut across a variety of liver diseases. We selected cases on the basis of evidence of brain manganese accumulation, and this may be a crucial component of these syndromes. Further studies are necessary to explore this issue.


Population niche structure : Differential response of Abutilon theophrasti progeny to resource gradients.
The response of twenty maternal families of the annual Abutilon theophrasti to two resource gradients, nutrient and light, was investigated. The structure of the population niche for both biomass and reproductive output was found to be quite different on the two gradients. On the light gradient there was a great diversity of responses among the families while on the nutrient gradient the families responded in a similar manner. On both gradients the plants showed a significant genotype/environment interaction. Three strategies for the production of seed variation have been proposed-all offspring are adapted to the same restricted environment, each offspring of an individual is adapted to a particular environment somewhat different thant that of its siblings, and all the offspring are able to grow in a wide range of environments. We found evidence for all three of these strategies amongst the families. The range of responses seen amongst families (of the same species) in this study was as broad as that found in previous studies among species of the old field annual community to which Abutilon theophrasti belongs. This has significant implications to the nature of competitive interactions and to the evolution of differential resource use in plant populations.


Effects of deuterium substitution alpha and beta to the reaction centre, 18O substitution in the leaving group, and aglycone acidity on hydrolyses of aryl glucosides and glucosyl pyridinium ions by yeast alpha-glucosidase. A probable failure of the antiperiplanar-lone-pair hypothesis in glycosidase catalysis.
Neither kcat. nor kcat./Km for five aryl alpha-D-glucopyranosides correlates with aglycone pKa, and isotope effects, described according to the convention used by Cleland [(1982) CRC Crit. Rev. Biochem. 13, 385-428], of 18(V) = 1.002 +/- 0.008, alpha D(V) = 1.01 +/- 0.04 and alpha D(V/K) = 0.969 +/- 0.035 are observed for p-nitrophenyl, and one of beta D(V) = 1.02 +/- 0.04 for phenyl alpha-D-glucopyranoside; kcat. but not kcat./Km, correlates with aglycone pKa for five alpha-D-glucopyranosyl pyridinium ions with a Brønsted coefficient of -0.61 +/- 0.06, and isotope effects of alpha D(V) = 1.22 +/- 0.02, beta D(V) = 1.13 +/- 0.01 and alpha D(V/K) = 1.018 +/- 0.046 for the 4-bromoisoquinolinium, and alpha D(V) = 1.15 +/- 0.02 and beta D(V) = 1.085 +/- 0.011 for the pyridinium salts are observed. These data require that a non-covalent event, fast in the case of the N-glycosides but slow in the case of the O-glycosides, precedes bond-breaking, and that bond-breaking involves substantial charge development on the glycone and near-perpendicularity of the C2-H bond to the planar oxocarbonium ion system. A model meeting these requirements is that the non-covalent event is a conjoint change of protein and substrate conformation which puts the pyranose ring in the 2,5B conformation of the bond-breaking transition state. This model also explains the contrast between the powerful inhibition of the enzyme by deoxynojirimycin (Ki = 23 +/- 3 microM) and feeble inhibition by castanospermine [Saul, Chambers, Molyneux & Elbein (1983) Arch. Biochem. Biophys. 221, 593-597], but is directly contrary to the predictions of Deslongchamps' 'Theory of Stereoelectronic Control' [Deslongchamps (1975) Tetrahedron 31, 2463-2490; (1983) Stereoelectronic Effects in Organic Chemistry, p. 39, Pergamon Press, Oxford].


ASA grade and Charlson Comorbidity Index of spinal surgery patients: correlation with complications and societal costs.
The Charlson Comorbidity Index (CCI) and the American Society of Anesthesiologists (ASA) Physical Status Classification System (ASA grade) are useful for predicting morbidity and mortality for a variety of disease processes. To evaluate CCI and ASA grade as predictors of complications after spinal surgery and examine the correlation between these comorbidity indices and the cost of care. Prospective observational study. All patients undergoing any spine surgery at a single academic tertiary center over a 6-month period. Direct health-care costs estimated from diagnosis related group and Current Procedural Terminology (CPT) codes. Demographic data, including all patient comorbidities, procedural data, and all complications, occurring within 30 days of the index procedure were prospectively recorded. Charlson Comorbidity Index was calculated from International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and ASA grades determined from the operative record. Diagnosis related group and CPT codes were captured for each patient. Direct costs were estimated from a societal perspective using Medicare rates of reimbursement. A multivariable analysis was performed to assess the association of the CCI and ASA grade to the rate of complication and direct health-care costs. Two hundred twenty-six cases were analyzed. The average CCI score for the patient cohort was 0.92, and the average ASA grade was 2.65. The CCI and ASA grade were significantly correlated, with Spearman ρ of 0.458 (p<.001). Both CCI and ASA grade were associated with increasing body mass index (p<.01) and increasing patient age (p<.0001). Increasing CCI was associated with an increasing likelihood of occurrence of any complication (p=.0093) and of minor complications (p=.0032). Increasing ASA grade was significantly associated with an increasing likelihood of occurrence of a major complication (p=.0035). Increasing ASA grade showed a significant association with increasing direct costs (p=.0062). American Society of Anesthesiologists and CCI scores are useful comorbidity indices for the spine patient population, although neither was completely predictive of complication occurrence. A spine-specific comorbidity index, based on ICD-9-CM coding that could be easily captured from patient records, and which is predictive of patient likelihood of complications and mortality, would be beneficial in patient counseling and choice of operative intervention.


Pertussis toxin-sensitive G-proteins in the sino-atrial node and right atrium of bovine heart.
Three apparently distinct pertussis toxin (PTX)-sensitive substrates, with Mrs of 39, 40 and 41 kDa, were identified in membranes prepared from the sino-atrial (SA) node and right atrium of bovine heart. Based on their biochemical characterization, the effects of guanine nucleotides/MgCl2 on their PTX-catalyzed [32P]ADP ribosylation, and the PTX-induced decrease in radiolabelled agonist high-affinity binding to muscarinic acetylcholine receptors present in these membranes, we tentatively identify these proteins as the alpha-subunits of the G0 and Gi subtypes of G-proteins. These results indicate that PTX alters the G-protein modulation of SA nodal and atrial muscarinic acetylcholine receptors by disrupting at least one of a group of PTX-sensitive G-proteins present in these tissues.


Hybrid male sterility between Drosophila willistoni species is caused by male failure to transfer sperm during copulation.
The biological concept of species stresses the importance of understanding what mechanisms maintain species reproductively isolated from each other. Often such mechanisms are divided into premating and postmating, with the latest being the result of either prezygotic or postzygotic isolation barriers. Drosophila willistoni quechua and Drosophila willistoni willistoni are two subspecies that experience reproductive isolation. When a D. w. quechua female is crossed with a D. w. willistoni male, the hybrid males (F1QW) are unable to father progeny; however, the reciprocal cross produces fertile hybrids. Thus, the mechanism of isolation is unidirectional hybrid male sterility. However, the sterile F1QW males contain large amounts of motile sperm. Here we explore whether pre-copulatory or post-copulatory pre-zygotic mechanisms serve as major deterrents in the ability of F1QW males to father progeny. Comparisons of parental and hybrid males copulation durations showed no significant reduction in copulation duration of F1QW males. Interrupted copulations of the parental species confirmed that sperm transfer occurs before the minimum copulation duration registered for F1QW males. However, we found that when females mate with F1QW males, sperm is not present inside the female storage organs and that the lack of sperm in storage is due to failure to transfer sperm rather than spillage or active sperm dumping by females. Sterility of F1QW hybrid males is primarily driven by their inability to transfer sperm during copulation.


The role of 5-HT3 receptors in drug dependence.
Since the discovery of serotonin receptor subtypes in 1957, the classification of serotonin receptors now includes 5-HT1 through 5-HT7 receptors, with further subtypes of receptors in each family. Unique among this expanding group of 5-HT receptor subtypes is the 5-HT3 receptor, which is the only known 5-HT receptor that directly gates an ion channel. The channel conducts primarily Na+ and K+, resulting in rapid depolarization followed by a rapid desensitization. The immediate consequence of neuronal depolarization resulting from 5-HT3 receptor activation is the release of stored neurotransmitter. The subsequent release of stored neurotransmitter, particularly dopamine in the mesolimbic pathways, suggest a potentially important role for this receptor system in neuronal circuitry involved in drug abuse. The following review broadly covers the structure, function and distribution of the 5-HT3 receptor system in the CNS and data addressing the potential role of this receptor system in modulating the effects of a wide variety of abused drugs. Most of the evidence indicates an association between the ability of 5-HT3 antagonists to decrease mesolimbic dopamine levels and to attenuate the psychomotor stimulant effects of drugs. However 5-HT3 receptor antagonists are less robust at attenuating other drug effects that are believed to be related to their abuse liability, such as discriminative stimulus and reinforcing effects. The one exception may be ethanol, which directly potentiates the effects of 5-HT at the 5-HT3 receptor channel complex. In addition to the implications of an interaction with the mesolimbic dopaminergic system, the ability of 5-HT3 receptor antagonists to function as anxiolytics suggest they could be useful pharmacotherapies during drug withdrawal. However, further studies are needed since currently available 5-HT3 receptor antagonists do not have uniform behavioral effects, may interact with other receptor systems, and have atypical dose-response effects.


Attenuation of amphetamine-stereotypy by mesostriatal dopamine depletion enhances plasma corticosterone: implications for stereotypy as a coping response.
The relationship between amphetamine-induced stereotyped behavior and a neuroendocrine index of arousal, plasma corticosterone (CCS), was investigated. 6-Hydroxydopamine lesions of the caudate-putamen, which produced dopamine depletions of 60%, blocked stereotypy and prolonged the elevation in corticosterone associated with d-amphetamine treatment (5 mg/kg). Similar dopamine depleting lesions of the nucleus accumbens, which attenuated the locomotor, but not the stereotypic, response to AMPH did not have this effect on CCS. This pattern of results supports the hypothesis that stereotypy has a coping function which may serve to alter arousal and further suggests important differences between the nigrostriatal and mesolimbic dopamine projections in modulating the responsiveness of the neuroendocrine system. These results have implications for understanding the function of behavioral stereotypies common to a number of psychopathological conditions, including schizophrenia and childhood autism.


Acupuncture for the treatment of trigeminal neuralgia: A systematic review and meta-analysis.
Few systematic reviews have examined the effects of acupuncture on trigeminal neuralgia. This review aims to provide up-to-date evidence on the efficacy of acupuncture for managing pain in patients with trigeminal neuralgia. Eleven databases were searched from inception until November 2022 for relevant articles Two researchers independently conducted study selection, data extraction, and evaluation. The present review solely targeted randomized controlled trials (RCTs). The Cochrane risk of bias assessment tool 2.0 was employed to assess the risk of bias. Data were compiled using RevMan 5.4.1 software, and the quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Thirty studies involving 2295 patients were included in this review. Compared with carbamazepine, acupuncture led to improvements in pain scores (15 RCTs, mean difference (MD) - 1.40, 95% confidence interval (CI)-1.82 to -0.98 [95% prediction interval, -3.137,0.343], p < 0.00001, low certainty of evidence (CoE)), response rates (29 RCTs, risk ratio (RR) 1.20, 95% CI 1.15 to 1.25 [95% prediction interval, 1.067, 1.346], p < 0.00001, low CoE), frequency of pain attacks (2 RCTs, MD -2.53, 95% CI -4.11 to -0.96, P = 0.002, low CoE), and adverse effects (13 RCTs, risk difference (RD) -0.15, 95% CI -0.19 to -0.11 [95% prediction interval, -0.193, -0.108], P < 0.00001, very low CoE). Although the quality of evidence is low, compared with carbamazepine, acupuncture may improve trigeminal neuralgia-related pain. Further rigorously designed studies are warranted to confirm the effects of acupuncture on patients with trigeminal neuralgia.