In situ localization and quantification of seventy-two-kilodalton type IV collagenase in aneurysmal, occlusive, and normal aorta.
Seventy-two-kilodalton type IV collagenase (MMP-2), a potent collagenase and elastase, is present in inflammatory disease states and may be important in the pathogenesis of aortic aneurysms. Alteration in expression of MMP-2 or its inhibitor, the tissue inhibitor of metalloproteinases type two (TIMP-2), could increase extracellular matrix degradation and lead to aneurysm formation. The purpose of this study is (1) to measure relative tissue levels of MMP-2 and TIMP-2 mRNA in aneurysmal, occlusive, and normal human infrarenal aorta; (2) to test for expression by cultured aneurysmal and normal vascular smooth muscle cells (VSMCs); and (3) to identify, in situ, the cells responsible for mRNA production within aneurysmal, occlusive, and normal aortic wall. Total RNA extracted from aneurysmal (n = 8), occlusive (n = 9), and normal (n = 7) tissue was subjected to Northern analysis. Signals for MMP-2 and TIMP-2 were normalized to alpha-tubulin. Mean values +/- SE were compared by use of analysis of variance. Aneurysmal and normal VSMCs were cultured, passaged, and grown to confluence before RNA extraction and Northern analysis. In situ hybridization with digoxigenin RNA probes localized cells responsible for MMP-2 and TIMP-2 mRNA production in histologic sections of aneurysmal (n = 7), occlusive (n = 4), and normal (n = 3) aorta. Tissue MMP-2 mRNA levels were significantly greater in aneurysmal aorta (1.032 +/- 0.164, n = 5) than in either occlusive (0.553 +/- 0.027, n = 4, p < 0.02) or normal aorta (0.230 +/- 0.038, n = 3, p < 0.002). Differences in TIMP-2 mRNA levels were not significant (aneurysmal aorta 0.207 +/- 0.042, n = 3; occlusive aorta 0.413 +/- 0.164, n = 3; normal aorta 0.260 +/- 0.079, n = 4; p = 0.34), although numbers were small. Cultured aneurysmal and normal VSMCs constitutively expressed both MMP-2 and TIMP-2. In situ studies colocalized tissue MMP-2 and TIMP-2 expression to VSMCs and macrophages surrounding inflammation in aneurysmal adventita, but to atherosclerotic plaque in occlusive aorta. MMP-2 and TIMP-2 are expressed in aneurysmal, occlusive, and normal aorta. MMP-2 expression is significantly greater in aneurysmal than in either occlusive or normal aorta. Cultured aneurysmal VSMCs constitutively express both MMP-2 and TIMP-2. Differential patterns of expression seen in situ and elevated tissue MMP-2 mRNA levels in aneurysmal versus occlusive aorta suggest that MMP-2 may be responsible for localized plaque remodeling in occlusive disease and for diffuse adventitial collagen and elastin destruction in aneurysms.


Ultrastructure of the ultimobranchial follicles of the laying chicken.
The ultimobranchial gland of the laying chicken consists of groups of C cells interspersed among a collection of intercommunicating follicles and ducts of variable size and shape. The epithelium lining this system ranges from squamous to columnar and includes stratified squamous and pseudostratified columnar elements. Four cell types are distinguished in this epithelium: F, mucous, C, and basal cells. F cells show microvilli and microfilaments. Pinocytotic activity and images of fusion of coated vesicles with the plasma membrane are evident. The rough-surfaced endoplasmic reticulum (RER) and the Golgi complex are moderately developed. Dense bodies are encountered apically in some cells. Mucous cells possess microvilli and secretory material in the typical form of partially fused droplets. C cells contain secretory granules and are invariably separated from the follicular lumen by other cell types. The smaller, pyramidal basal cells contain filaments, RER, small Golgi complexes, free ribosomes and hemidesmosomes. The lumina contain flocculent or granular material, cellular debris and desquamated cells. Morphological evidence demonstrates that features of the pharyngeal epithelium are retained and that the majority of the cell types, with the exception of C cells, are presumably nonendocrine.


Acquired colour deficiency in patients with Parkinson's disease.
The blue cone pathway is reported to be affected early in Parkinson's disease (PD) and acquired type three (tritan) defects may occur. Sixty-one patients attending a treatment and rehabilitation centre for PD were examined with clinical colour vision tests. Seven of 13 patients, for whom the diagnosis of PD was equivocal or who had other medical conditions, were identified as having tritan colour deficiency. Results for the remaining 44 PD patients were compared with 40 age matched controls. Ten PD patients (22.7%) had tritan defects. Tritan defects were not found in the control group but performance on some tests was age related. We conclude that clinical tests for tritan colour deficiency are unlikely to be helpful in identifying PD.


Cloning of the O-acetylserine lyase gene from the ruminal bacterium Selenomonas ruminantium HD4.
The gene coding for O-acetylserine lyase (OASL) was cloned from a Selenomonas ruminantium HD4 Lambda ZAP II genomic library by degenerative probe hybridization and complementation. Sequence analysis revealed a 933 bp ORF with a G + C content of 53%. The ORF had significant homology with enzymes involved in cysteine biosynthesis. A CuraBLASTN homology search showed that the ORF shared 59% nucleotide identity with the cysK of Bacillus subtilis. The deduced amino acid sequence exhibited high (>70%) similarity with the CysK of B. subtilis and other cysteine synthesis proteins from Mycobacterium tuberculosis, Mycobacterium leprae, and Spinacia oleracea. Further analysis predicted that the gene product was a member of the pyridoxal phosphate enzyme family and of cytoplasmic origin. Phylogenetic analysis clustered the S. ruminantium gene product with the OASLa isoform of B. subtilis and the OASLb isoforms of Streptococcus suis, Escherichia coli, and Campylobacter jejuni. The OASL of S. ruminantium HD4 was also able to complement the cysM cysK double mutations in Escherichia coli NK3 and allow for growth on minimal media that contained either sulfate or thiosulfate as the sole source of sulfur. These results suggest that the gene functions as a cysM in S. ruminantium HD4. In conclusion, this research describes the cloning and expression of an O-acetylserine lyase gene from the predominant ruminal anaerobe S. ruminantium HD4. To our knowledge, this is the first report characterizing genes involved in sulfur metabolism from the genus Selenomonas.


Coprophilous fungi: antibiotic discovery and functions in an underexplored arena of microbial defensive mutualism.
Microbial antibiotics can mediate mutualisms and interorganism communications. Herbivorous animal dung offers opportunities for discovery of new antibiotics from microbial communities that compete for a nutrient-rich, ephemeral resource. Distinct lineages form a specialized community of coprophilous (dung-colonizing) fungi. Bacteria, protists, invertebrates, the mammalian digestive system, and other fungi can pose challenges to their fitness in the dung environment. The well-characterized diversity of dung fungi offers accessible systems for dissecting the function of antibiotics and for exploring fungal genomes for new antibiotics. Their potential for antibiotic discovery is evidenced by a high frequency of antifungal antibiotics and bioactive secondary metabolites from limited prior efforts and from mapping biosynthetic pathways in the genomes of the coprophilous fungi Podospora anserina and Sordaria macrospora.


Misdiagnosed neurosyphilis associated with prolonged psychosis.
After the prevalence of syphilis had reached historic lows, the Center for Disease Control devised a plan to eradicate syphilis in the United States. Since that decree there has been a dramatic rise in new cases. Psychosis is an ominous symptom of neurosyphilis. We report a case of neurosyphilis that was misdiagnosed and staged incorrectly. Failure to diagnose neurosyphilis was associated with prolonged psychosis that has been refractory to antipsychotic treatment. Psychiatrists should renew their vigilance for neurosyphilis in the setting of a positive screening test and psychosis.


Factors involved in the formation of attitudes towards those who are mentally ill.
This research was conducted to examine the prediction that accuracy of particular kinds of knowledge of mental illness would be related to particular attitudes towards people with mental illness. An exploratory study examining attitudes to people suffering from mental illness is presented. A total of 169 participants, with a range of attitudes and knowledge, completed two questionnaires: attitudes were assessed using the Community Attitudes towards the Mentally Ill scale (Taylor and Dear 1981) which yields four attitude factors; knowledge was assessed using a questionnaire devised by Nunnally (1961), which yields ten knowledge factors. Multiple regression analyses provided some support for the hypothesis that some areas of knowledge (particularly knowledge concerning guidance and support, and knowledge concerning the role of avoidance of morbid thoughts in mental health) are predictive of specific attitudes, but much of the variance remained unexplained by the predictive knowledge variables. Post hoc analyses revealed that those people who had had personal experience of people with mental illness were generally more positive in their attitudes towards them. Selected knowledge factors only accounted for a modest amount of the variance in attitude factor scores. Affective (e. g. fear, revulsion, anxiety) information may explain a greater percentage of variance in attitude factor score. It is suggested that this should be considered in future research and the limitations of the present study are discussed.


Genome-wide analysis, transcription factor network approach and gene expression profile of GH3 genes over early somatic embryogenesis in Coffea spp.
Coffee production relies on plantations with varieties from Coffea arabica and Coffea canephora species. The first, the most representative in terms of coffee consumption, is mostly propagated by seeds, which leads to management problems regarding the plantations maintenance, harvest and processing of grains. Therefore, an efficient clonal propagation process is required for this species cultivation, which is possible by reaching a scalable and cost-effective somatic embryogenesis protocol. A key process on somatic embryogenesis induction is the auxin homeostasis performed by Gretchen Hagen 3 (GH3) proteins through amino acid conjugation. In this study, the GH3 family members were identified on C. canephora genome, and by performing analysis related to gene and protein structure and transcriptomic profile on embryogenic tissues, we point a GH3 gene as a potential regulator of auxin homeostasis during early somatic embryogenesis in C. arabica plants. We have searched within the published C. canephora genome and found 17 GH3 family members. We checked the conserved domains for GH3 proteins and clustered the members in three main groups according to phylogenetic relationships. We identified amino acids sets in four GH3 proteins that are related to acidic amino acid conjugation to auxin, and using a transcription factor (TF) network approach followed by RT-qPCR we analyzed their possible transcriptional regulators and expression profiles in cells with contrasting embryogenic potential in C. arabica. The CaGH3.15 expression pattern is the most correlated with embryogenic potential and with CaBBM, a C. arabica ortholog of a major somatic embryogenesis regulator. Therefore, one out of the GH3 members may be influencing on coffee somatic embryogenesis by auxin conjugation with acidic amino acids, which leads to the phytohormone degradation. It is an indicative that this gene can serve as a molecular marker for coffee cells with embryogenic potential and needs to be further studied on how much determinant it is for this process. This work, together with future studies, can support the improvement of coffee clonal propagation through in vitro derived somatic embryos.


New hammock hypothesis-based method for the treatment of stress urinary incontinence: the first 29 urethral supports with a small fascial patch.
We have developed a new method requiring no manipulations of the retropubic passages, and carried out a retrospective study to assess the effectiveness, safety and early results of this new procedure in the treatment of female stress urinary incontinence. From January 2001 to September 2003, 29 patients underwent our new surgery for the treatment of SUI. A 3 x 2 cm vertical rectangle was harvested from the rectus fascia. A convex horizontal incision was made over the mid urethra and bladder neck. The retropubic space was entered to the urethropelvic ligament spreading toward the junctions between urethropelvic ligament and tendinous arc. One suture was made at the point lateral to the bladder neck. Another suture was made behind the pubic bone. These two sutures were sutured again and tied with the short side end of the harvested fascia. The same procedure was performed on the other side. Of 29 patients, 26 (89.7%) were cured of stress urinary incontinence and 3 were improved. None of the patients had difficulty in voiding after the operation. Maximum flow rates were almost the same before and after surgery. None of the patients had any adverse events. This procedure, which requires no manipulations of the retropubic passages, is safe and effective for the treatment of stress urinary incontinence.


The effects of electrogalvanic stimulation therapy on masticatory muscle dysfunction as determined by the pantronic reproducibility index.
Patients with temporomandibular joint dysfunctional activity (TM dysfunction) present with a diverse spectrum of clinical signs and symptoms. The multifactorial aetiology of such disorders has been noted. Diagnostic and therapeutic problems arise due to the inadequacy of quantifying the dysfunction. TM dysfunction can affect the muscles of mastication which are responsible for mandibular movement. A pantographic reproducibility index (PRI) is available to quantitatively and qualitatively measure a subjects ability to reproduce mandibular border movements. Physical therapy modalities are used in the management of TM dysfunction. Electrogalvanic stimulation (EGS) is such an example. The effect of electrogalvanic stimulation on subjects with and without TM dysfunction was assessed by Pantronic PRI appraisal in 20 subjects. No statistically significant differences were noted. At the individual level, some changes were observed in susceptible subjects.


Comparison of the amount of pectin in the human terminal ileum with the amount of orally administered pectin.
Dietary fiber by definition is resistant to digestion and absorption in the human small intestine, and it should naturally reach the large intestine. To date, there have been several reports that have examined in vivo how much dietary fiber actually reaches the terminal ileum in human subjects using glucose, with large differences in results. We compared the amount of pectin in the human terminal ileum with that of orally administered pectin. Seven healthy male volunteers ages 20 to 27 y were given a test meal containing 4.05 g of pectin. A double-lumen tube was placed in the terminal ileum by using the endoscopic retrograde bowel insertion method, and the ileal contents were aspirated through the tube. Amounts of pectin orally administered and collected from the terminal ileum were estimated as galacturonic acid concentrations (Englyst's method) and were compared with each other. The mean +/- standard deviation amount of pectin collected in the terminal ileum was 3.58 +/- 0.43 g, or 88.4 +/- 10.5% of pectin administered. Further, there were large individual differences in recovery, ranging from 76.8% to 105.1%. Approximately 90% of ingested pectin was recovered in the terminal ileum in this study. Ten percent may have been degraded by bacteria within the digestive tract, especially the terminal ileum.


[Comparative analysis of tests on in vitro and in vivo quantitative assessment of the immunogenicity of tick-borne encephalitis vaccine].
Many-year routine use of EIA as an in vitro test demonstrated it as a highly reproducible and technological test for assessing the efficacy of vaccine against tick-borne encephalitis and its semiproducts at the intermediate stages of vaccine production. The reproducibility of mouse protection test is notably inferior to that of EIA.


ROS-activatable biomimetic interface mediates in-situ bioenergetic remodeling of osteogenic cells for osteoporotic bone repair.
Bioenergy (ATP) is essentially required for supporting the osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs). However, factors such as high ROS levels and decreased glucose metabolism severely limit the bioenergy production in osteoporotic MSCs. We have prepared CaCO3-Quercetin- chromium (CaCO3-Qu-Cr) nanoparticles via ion coordination and packaged them into ROS-responsive gelatin/chitosan coating on titanium surface (Ti/Gel/CaCO3-Qu-Cr), aiming to improve the ATP production and cell mineralization by ameliorating ROS levels via Qu-mediated antioxidative effect and the promotional effect of Qu-Cr combination on glucose metabolism. Characterization results confirmed that Ti/Gel/CaCO3-Qu-Cr could be degraded in an ROS-responsive manner to release CaCO3-Qu-Cr nanoparticles continuously and eliminate excessive ROS in both the MSCs and microenvironment. Meanwhile, Ti/Gel/CaCO3-Qu-Cr significantly increased the glucose uptake and metabolism in osteoporotic MSCs and boosted their ATP and citrate production. This study laid the foundation for the development of functional titanium-based implants for the improvement of osteoporotic osseointegration.


A modified technique for the double-contrast small bowel enema.
A small bowel enema technique is described which makes it possible to achieve double-contrast images comparable to those routinely obtained in the stomach or colon. It is a biphasic procedure, requiring the transtubal injection of barium sulfate, followed by 0.5% methylcellulose. Adjustment of relative injection quantities and injection speeds can adapt each examination to a patient's individual diagnostic problem. Indications for the examination are discussed.


Pyrrolovesamicols--synthesis, structure and VAChT binding of two 4-fluorobenzoyl regioisomers.
This Letter describes the synthesis of two regioisomers of a new class of vesamicol analogs as possible ligands for imaging the vesicular acetylcholine transporter in future PET studies. The two pyrrolovesamicols (±)-6a and (±)-6b were synthesized by nucleophilic ring opening reaction of a tetrahydroindole epoxide precursor with 4-phenylpiperidine. The reaction mechanism of the synthesis was studied by HPLC and the molecular structures were determined by X-ray structure analysis. Unexpected low binding affinities to VAChT (K(i)=312±73 nM for (±)-6a and K(i)=7320±1840 nM for (±)-6b) were determined by competitive binding analysis using a cell line stably transfected with ratVAChT and (-)-[(3)H]vesamicol.


Determination of nursing diagnoses used by students in the first clinical practice.
This study was carried out descriptively with the purpose of determining nursing diagnoses that nursing freshmen students used in their first clinical practice. The sample of the study consisted of 61 nursing students. Data of the study were collected with the examination of 208 care plans that the students had prepared. Nursing diagnoses in the examined care plans were classified according to nursing diagnoses grouped under the domains of Taxonomy II NANDA-I. Students determined 31 different diagnoses in nine domains of NANDA-I. Total nursing diagnoses used in care plans were 635. It was determined that the nursing diagnoses that the students mostly used, according to classification of NANDA-I, were in the domains of safety/protection, activity/rest, comfort, elimination and exchange, and nutrition.


Structure and transcriptional regulation of BKJ, a novel AP-1 target gene activated during jun- or fos-induced fibroblast transformation.
The BKJ gene was originally identified based on its specific transcriptional activation in jun-transformed avian fibroblasts. We now show that BKJ is a direct transcriptional target of the AP-1 transcription factor components Jun and Fos. The complete structural organization of the quail BKJ gene was determined by nucleotide sequence analysis and transcriptional mapping. The gene contains three exons with the coding region confined to the third exon. A major mRNA species of 0.8 kb and a minor one of 1.3 kb are produced by variable usage of two transcriptional initiation sites. The BKJ promoter region contains two authentic AP-1 binding sites. By transactivation of reporter gene constructs and direct binding of Jun recombinant protein, the proximal AP-1 element was shown to be essential for BKJ promoter activation. Using polyclonal antiserum directed against recombinant BKJ protein, the activation of BKJ in jun-transformed avian fibroblasts was also demonstrated at the protein level. BKJ is a novel gene related to the avian beta-keratin gene family whose members display highly specific expression patterns during embryogenesis and epidermal development. Activation of BKJ in fibroblasts by retroviral or deregulated cellular jun or fos alleles may contribute to cell transformation.


Circadian variation in myocardial ischemia: the possible mechanisms involving in this phenomenon.
Circadian rhythms have long been recognized to occur in many biologic phenomena, including secretion of hormones as well as autonomic nervous system. There is increasing evidence that circadian rhythms have been also found in cardiovascular events, for example, myocardial infarction, sudden cardiac death as well as stroke have shown a circadian pattern of the distribution. Transient myocardial ischemia, detected by ambulatory ST segment monitoring, is also unevenly distributed during the day. The pathophysiology and the mechanism underlying these variations are the focus of much investigation, while it is not full understood up to date. Heart rate, blood pressure, neural and humoral vasoactive factors such as plasma norepinephrine levels and renin activity, and probably also contractility are increased in the morning hours, indicating that increase in myocardial oxygen demand contribute importantly to the increased prevalence of ischemia in the morning. Our recent study found that circadian rhythm of ischemic threshold detected by repetitive exercise treadmill tests in patients with chronic coronary artery disease is also apparently associated with levels of plasma ET-1. This information should enable better understanding as well as treatment on patients on circadian variation of cardiovascular events.


ZrO2 nanoparticles confined in metal organic frameworks for highly effective adsorption of phosphate.
Highly dispersed ZrO2 particles confined in the MIL-101 (denoted as MIL-101@Zr(DS)) with varied ZrO2 loading amounts were prepared by the double solvents method. For comparison, ZrO2 loaded MIL-101 samples were synthesized by the conventional impregnation method (denoted as MIL-101@Zr(I)) and the deposition method (denoted as MIL-101@Zr(D)). The characterization results indicated that for MIL-101@Zr(DS), ZrO2 particles were dominantly confined in MIL-101 with a much higher dispersion as compared with MIL-101@Zr(I) and MIL-101@Zr(D). The maximum phosphate adsorption capacity and ZrO2 content normalized phosphate adsorption capacity of the MIL-101@Zr(DS) were 21.28 mg P·g-1 and 1120.0 mg P·g-1, respectively. Additionally, the ZrO2 content normalized phosphate adsorption capacity was significantly larger than that for MIL-101@Zr(I) and MIL-101@Zr(D) as well as the reported values for other Zr-based adsorbents. The effects of solution chemistry on phosphate adsorption to MIL-101@Zr(DS), MIL-101@Zr(I) and MIL-101@Zr(D) were also examined. Compared with MIL-101@Zr(I) and MIL-101@Zr(D), the adsorption of phosphate on MIL-101@Zr(DS) was less affected by the coexistence of anions and dissolved humic acid. Increasing pH from 3 to 12 led to decreased phosphate adsorption capacity of MIL-101@Zr(DS) from 10.38 mg P·g-1 to 2.03 mg P·g-1. Accordingly, used MIL-101@Zr(DS) could be effectively regenerated under alkaline conditions and exhibited stable adsorption-desorption performance.


Oxime-metabolizing activity of liver aldehyde oxidase.
Liver aldehyde oxidase in the presence of its electron donor exhibited a significant oxime-metabolizing activity toward some different types of oximes under anaerobic conditions. Acetophenone oxime and salicylaldoxime were exclusively converted to the corresponding oxo compounds, whereas benzamidoxime was converted to the corresponding ketimine. With d-camphor oxime, the formation of both the corresponding oxo compound and ketimine was observed. Stoichiometric studies showed that the formation of oxo compounds is accompanied by nearly equimolar ammonia. We propose a mechanism of oxime biotransformation that liver aldehyde oxidase catalyzes the reduction of oximes to the corresponding ketimines which in turn undergo, depending on their chemical stability, nonenzymatic hydrolysis to the corresponding oxo compounds and ammonia.


How the central domain of dystrophin acts to bridge F-actin to sarcolemmal lipids.
Dystrophin is a large intracellular protein that prevents sarcolemmal ruptures by providing a mechanical link between the intracellular actin cytoskeleton and the transmembrane dystroglycan complex. Dystrophin deficiency leads to the severe muscle wasting disease Duchenne Muscular Dystrophy and the milder allelic variant, Becker Muscular Dystrophy (DMD and BMD). Previous work has shown that concomitant interaction of the actin binding domain 2 (ABD2) comprising spectrin like repeats 11 to 15 (R11-15) of the central domain of dystrophin, with both actin and membrane lipids, can greatly increase membrane stiffness. Based on a combination of SAXS and SANS measurements, mass spectrometry analysis of cross-linked complexes and interactive low-resolution simulations, we explored in vitro the molecular properties of dystrophin that allow the formation of ABD2-F-actin and ABD2-membrane model complexes. In dystrophin we identified two subdomains interacting with F-actin, one located in R11 and a neighbouring region in R12 and another one in R15, while a single lipid binding domain was identified at the C-terminal end of R12. Relative orientations of the dystrophin central domain with F-actin and a membrane model were obtained from docking simulation under experimental constraints. SAXS-based models were then built for an extended central subdomain from R4 to R19, including ABD2. Overall results are compatible with a potential F-actin/dystrophin/membrane lipids ternary complex. Our description of this selected part of the dystrophin associated complex bridging muscle cell membrane and cytoskeleton opens the way to a better understanding of how cell muscle scaffolding is maintained through this essential protein.


The effect of pH on the conformation and stability of the structure of plant toxin-ricin.
The effect of pH on the conformation of ricin and its A- and B-chains has been studied by measuring their intrinsic fluorescence. At pH 5.0 and 7.5, the structural stability of toxin and subunits was estimated according to the denaturing action of guanidine hydrochloride. It was demonstrated that the fluorescence of native toxin and catalytic A-subunit does not depend significantly on pH in the range pH 3-8, whereas ricin B-chain undergoes a structural transition at pH less than 5.0. The structural stability of ricin and isolated chains differs significantly at pH 7.5 and 5.0; the structural stability of ricin and the A-chain increases, whereas that of the B-chain decreases.


An 11-year retrospective study of totally implanted central venous access ports: complications and patient satisfaction.
We wanted to assess the factors that predict complications and patient satisfaction of totally implanted central venous access ports (TIAP). We reviewed 550 patients with breast or gynaecological malignancies who had initial port placement for chemotherapy between 1995 and 2006. We retrospectively assessed all TIAP complications, port duration and follow-up care until the TIAPs were removed (or the last known recorded documentation) or until the death of the patient. TIAP-related patient satisfaction was also assessed via a questionnaire-based survey of 356 patients. 561 TIAPs were placed in 550 cancer patients (11 patients received 2 TIAPs during the study period); the median time of port duration was 22.5 months. There were 104 complications in this group. Of these, 81 occurred during chemotherapy treatment that lasted a median time of 182 days. Removal secondary to complication was observed in 48 cases. TIAPs placed on the left chest side, through the subclavian vein or with the catheter tip localized in the peripheral part of superior vena cava demonstrated the highest incidence of complications. Patients with a BMI >28.75 had an increased risk for developing complications. Our follow-up questionnaire revealed a 93% patient satisfaction rate with the TIAP. Patients with left-sided ports, catheter tips lying in the upper part of the superior vena cava and implantation via the subclavian vein are at a higher risk for TIAP-associated complications. Being excessively overweight was assessed as another risk factor for developing complications. TIAPs are highly accepted and further recommended by patients.


Sensing approaches on paper-based devices: a review.
Paper has been present in the world of analytical chemistry for centuries, but it seems that just a few years back it was rediscovered as a valuable substrate for sensors. We can easily list some of the countless advantages of this simple cellulosic substrate, including mechanical properties, three-dimensional fibrous structure, biocompatibility and biodegradability, easiness of production and modification, reasonable price, and availability all over the world. Those characteristics make paper a first-choice substrate for disposable sensors and integrated sensing platforms. Nowadays, numerous examples of paper-based sensors are being presented in the literature. This review describes some of the most prominent examples classifying them by type of detection: optical (colorimetric, fluorescence, surface-enhanced Raman spectroscopy, and transmittance methods) and electrochemical (voltammetric, potentiometric, and conductivity-based methods). We take a closer look at recent advances in immunoassays fabricated on paper, excluding simple lateral flow tests assembled on nitrocellulose. This review also summarizes the main advantages and disadvantages of the use of paper as a substrate for sensors, as well as its impact on their performance and application, presents a short history of paper in analytical chemistry, and discusses fabrication methods and available sources of paper.


Interaction of gut microflora with tannins in feeds.
Tannins (hydrolyzable and condensed) are water-soluble polyphenolic compounds that exert antinutritional effects on ruminants by forming complexes with dietary proteins. They limit nitrogen supply to animals, besides inhibiting the growth and activity of ruminal microflora. However, some gastrointestinal microbes are able to break tannin-protein complexes while preferentially degrading hydrolyzable tannins (HTs). Streptococcus gallolyticus, Lonepinella koalarum and Selenomonas ruminantium are the dominant bacterial species that have the ability to degrade HTs. These tanninolytic microorganisms possess tannin-degrading ability and have developed certain mechanisms to tolerate tannins in feeds. Hence, selection of efficient tanninolytic microbes and transinoculation among animals for long-term benefits become areas of intensive interest. Here, we review the effects of tannins on ruminants, the existence and significance of tannin-degrading microorganisms in diverse groups of animals and the mechanisms that tannin-degrading microorganisms have developed to counter the toxic effects of tannin.


Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis: a prospective, comparative study.
To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis (PMNE), a new modified 3-day weekend frequency-volume chart (FVC) was designed, and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society (ICCS) recommended voiding diary. A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary. The primary outcome measure was the compliance, assessed by comparing the completing index and the quality score of diaries between two groups. The secondary outcome measure was the validity, evaluated by comparing the constituent of subtypes, micturition parameters and response rate to desmopressin. Among the 1200 participants enrolled in the study, 447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary. The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group. In addition, there was no significant difference between these two groups in the subtype classification, or in the response rate to desmopressin. The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.


MET immunolabelling is a useful predictive tool for MET gene amplification in glioblastoma.
MET gene amplification is rare in glioblastoma (GBM) and represents a potential target for MET inhibitors. An immunohistochemical screening may be useful to identify MET amplification. The aim of our study was to establish how MET immunolabelling correlates with MET amplification. Three cohorts including 108 GBM (cohort 1, prospective), 104 GBM (cohort 2, retrospective) and 52 GBM (cohort 3, prospective) were investigated for MET expression by immunohistochemistry. MET amplification was assessed by comparative genomic hybridization on microarray (CGH-array) in all cohorts and by fluorescent in situ hybridization (FISH) in cohorts 2 and 3. Active form of MET was assessed using p-MET (Y1349) immunohistochemistry. Diffuse MET amplification detectable by CGH-array was associated with diffuse, strong MET immunolabelling (four cases in cohort 1 and one case in cohort 2). Focal MET amplification detectable only by FISH was observed in small foci of strongly immunopositive cells in two GBM (cohort 2). In both cohorts, MET amplification was never detected in GBM devoid of strongly immunopositive cells. MET overexpression, observed in 23% of unamplified GBM, was associated with a predominant weak-to-moderate staining intensity and with necrosis (P < 0.005). p-MET was detected in all MET-amplified GBM and in perinecrotic areas of nonamplified GBM. A strong MET immunostaining intensity, at least focal and distant from necrosis, showed 100% sensitivity and 84% specificity for predicting MET amplification in cohort 3. MET amplification is characterized by strongly immunopositive cells. Only GBM showing strong MET immunostaining is appropriate for the assessment of MET amplification.


Rapidly progressive interstitial pneumonia associated with anti-NXP2 antibody secondary to malignancy.
The diagnosis of a diffuse lung disease is challenging for physicians and it requires a multidisciplinary team approach to solve this problem. Herein, we present a case of common bile duct obstruction from pancreatic ductal adenocarcinoma after biliary stent placement, which developed a rapidly progressive bilateral lung infiltration after oesophagogastroduodenoscopy. After a diagnostic evaluation based on clinical, radiographic, and pathological findings, a diagnosis of rapidly progressive interstitial pneumonia associated with anti-nuclear matrix protein (NXP) 2 antibody secondary to malignancy was made. In patients with interstitial lung disease with unclear aetiologies, autoantibodies, including antinuclear antibody and myositis-specific antibodies should be evaluated, even if there are no clinical signs of autoimmune disease. Although this is the first case report of an acute interstitial pneumonitis-associated anti-NXP2 antibody, physicians should recognise this condition as it can rapidly cause acute fulminant respiratory failure.


Micro-arterial anastomosis using only two sutures and an autogenous cuff.
Microvascular anastomosis using only two sutures and an autogenous cuff was carried out in an experimental model of Wistar albino rats. 40 femoral and 40 epigastric arteries were used for this cuff technique and compared with conventional technique in the same number of vessels. The cuff technique is simple, quick, causes less trauma to the vessel wall and gives a good patency rate. Anastomosis of an artery 0.5mm in diameter is very easy with the cuff technique (98% patency) which remains difficult using conventional technique (0% patency). The disadvantage of this technique may be leakage of blood just after releasing the clamps due to restoration of blood flow, but this is easily controlled within few minutes by mild compression.


Stimulation of adenosine 3',5'-monophosphate formation in mononuclear leukocytes by toad venoms.
The content of adenosine 3',5'-monophosphate in human mononuclear leukocytes was enhanced 3-5-times by venoms obtained from African toad (Bufo africanus), American toad (Bufo americanus), Colorado river toad (Bufo arenarum) and Marine toad (Bufo marinus) at 25 micrograms/ml for 5 min of incubation at 37 degrees C. The maximum stimulation was observed after 1-5 min of incubation. The half-maximal stimulation was observed at 0.1 micrograms/ml venom obtained from Colorado river toad (Bufo arenarum). The increased content of adenosine 3',5'-monophosphate in the mononuclear leukocytes persisted without significant change for at least 30 min of incubation at 37 degrees C.


Targeting abnormal lipid metabolism of T cells for systemic lupus erythematosus treatment.
Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system attacks its own tissues and organs. However, the causes of SLE remain unknown. Dyslipidemia is a common symptom observed in SLE patients and animal models and is closely correlated to disease activity. Lipid metabolic reprogramming has been considered as a hallmark of the dysfunction of T cells in patients with SLE, therefore, manipulating lipid metabolism provides a potential therapeutic target for treating SLE. A better understanding of the underlying mechanisms for the metabolic events of immune cells under pathological conditions is crucial for tuning immunometabolism to manage autoimmune diseases such as SLE. In this review, we aim to summarize the cross-link between lipid metabolism and the function of T cells as well as the underlying mechanisms, and provide light on the novel therapeutic strategies of active compounds from herbals for the treatment of SLE by targeting lipid metabolism in immune cells.


Topical cyclodextrin reduces amyloid beta and inflammation improving retinal function in ageing mice.
Retinal ageing results in chronic inflammation, extracellular deposition, including that of amyloid beta (Aβ) and declining visual function. In humans this can progress into age-related macular degeneration (AMD), which is without cure. Therapeutic approaches have focused on systemic immunotherapies without clinical resolution. Here, we show using aged mice that 2-Hydroxypropyl-β-cyclodextrin, a sugar molecule given as eye drops over 3 months results in significant reductions in Aβ by 65% and inflammation by 75% in the aged mouse retina. It also elevates retinal pigment epithelium specific protein 65 (RPE65), a key molecule in the visual cycle, in aged retina. These changes are accompanied by a significant improvement in retinal function measured physiologically. 2-Hydroxypropyl-β-cyclodextrin is as effective in reducing Aβ and inflammation in the complement factor H knockout (Cfh(-/-)) mouse that shows advanced ageing and has been proposed as an AMD model. β-cyclodextrin is economic, safe and may provide an efficient route to reducing the impact of retinal ageing.


3D chitinous scaffolds derived from cultivated marine demosponge Aplysina aerophoba for tissue engineering approaches based on human mesenchymal stromal cells.
The recently discovered chitin-based scaffolds derived from poriferans have the necessary prosperities for potential use in tissue engineering. Among the various demosponges of the Verongida order, Aplysina aerophoba is an attractive target for more in-depth investigations, as it is a renewable source of unique 3D microporous chitinous scaffolds. We found these chitinous scaffolds were cytocompatible and supported attachment, growth and proliferation of human mesenchymal stromal cells (hMSCs) in vitro. Cultivation of hMSCs on the scaffolds for 7days resulted in a two-fold increase in their metabolic activity, indicating increased cell numbers. Cells cultured onto chitin scaffolds in differentiation media were able to differentiate into the chondrogenic, adipogenic and osteogenic lineages, respectively. These results indicate A. aerophoba is a novel source of chitin scaffolds to futher hMSCs-based tissue engineering strategies.


Role of miRNA dysregulation in sepsis.
Sepsis is defined as a state of multisystem organ dysfunction secondary to a dysregulated host response to infection and causes millions of deaths worldwide annually. Novel ways to counteract this disease are needed and such tools may be heralded by a detailed understanding of its molecular pathogenesis. MiRNAs are small RNA molecules that target mRNAs to inhibit or degrade their translation and have important roles in several disease processes including sepsis. The current review adopted a strategic approach to analyzing the widespread literature on the topic of miRNAs and sepsis. A pubmed search of "miRNA or microRNA or small RNA and sepsis not review" up to and including January 2021 led to 1140 manuscripts which were reviewed. Two hundred and thirty-three relevant papers were scrutinized for their content and important themes on the topic were identified and subsequently discussed, including an in-depth look at deregulated miRNAs in sepsis in peripheral blood, myeloid derived suppressor cells and extracellular vesicles. Our analysis yielded important observations. Certain miRNAs, namely miR-150 and miR-146a, have consistent directional changes in peripheral blood of septic patients across numerous studies with strong data supporting a role in sepsis pathogenesis. Furthermore, a large body of literature show miRNA signatures of clinical relevance, and lastly, many miRNAs deregulated in sepsis are associated with the process of endothelial dysfunction. This review offers a widespread, up-to-date and detailed discussion of the role of miRNAs in sepsis and is meant to stimulate further work in the field due to the potential of these small miRNAs in prompt diagnostics, prognostication and therapeutic agency.


Factors influencing the surgery intentions and choices of women with early breast cancer: the predictive utility of an extended theory of planned behaviour.
Women diagnosed with early breast cancer (stage I or II) can be offered the choice between mastectomy or breast conservation surgery with radiotherapy due to equivalence in survival rates. A wide variation in the surgical management of breast cancer and a lack of theoretically guided research on this issue highlight the need for further research into the factors influencing women's choices. An extended Theory of Planned Behaviour (TPB) could provide a basis to understand and predict women's surgery choices. The aims of this study were to understand and predict the surgery intentions and choices of women newly diagnosed with early breast cancer, examining the predictive utility of an extended TPB. Sixty-two women recruited from three UK breast clinics participated in the study; 48 women, newly diagnosed with early breast cancer, completed online questionnaires both before their surgery and after accessing an online decision support intervention (BresDex). Questionnaires assessed views about breast cancer and the available treatment options using items designed to measure constructs of an extended TPB (i.e., attitudes, subjective norms, perceived behavioural control, and anticipated regret), and women's intentions to choose mastectomy or BCS. Objective data were collected on women's choice of surgery via the clinical breast teams. Multiple and logistic regression analyses examined predictors of surgery intentions and subsequent choice of surgery. The extended TPB accounted for 69.9% of the variance in intentions (p <.001); attitudes and subjective norms were significant predictors. Including additional variables revealed anticipated regret to be a more important predictor than subjective norms. Surgery intentions significantly predicted surgery choices (p <.01). These findings demonstrate the utility of an extended TPB in predicting and understanding women's surgery intentions and choices for early breast cancer. Understanding these factors should help to identify key components of interventions to support women while considering their surgery options.


The impact of having foreign domestic workers on informal caregivers of persons with dementia - findings from a multi-method research in Singapore.
Informal caregivers of persons with dementia (PWDs) sometimes engage foreign domestic workers (FDWs) to support their caregiving journey. However, there has not been much research to establish if this is really beneficial. The current study aims to investigate whether engaging FDWs specifically for caregiving of PWDs truly moderates caregiver stress and to explore caregivers' experiences of engaging FDWs. A multi-method study design with a quantitative and qualitative sub-study was adopted. For the quantitative sub-study, 282 informal caregivers of PWDs were recruited. Propensity score matching analysis was used. For the qualitative sub-study, 15 informal caregivers with FDWs were interviewed. Inductive thematic analysis was conducted. The quantitative sub-study confirmed that engaging FDWs did moderate the depressive symptoms of informal dementia caregivers (marginal effect = -3.35, p = 0.0497). However, such support did not affect their caregiving burden, self-efficacy, and perceived positive aspects of caregiving. The qualitative sub-study suggested that engaging FDWs is an ambivalent experience, which entails both support and challenges. The current study confirmed previous research findings, that engaging FDWs moderated depressive symptoms among caregivers of PWDs, and it could be through their physical support such as in daily caregiving activities. Policy-makers may consider providing more subsidies to caregivers caring for PWDs with mobility issues to hire FDWs. They may also consider providing training to FDWs on dementia caregiving skills and improving the intake of such training as this might be helpful for both FDWs and caregivers during this journey.


Down-regulated expression of miR-134 contributes to paclitaxel resistance in human ovarian cancer cells.
MiR-134 has been reported to have a role in the development and progression of various cancers. In this study, we found that miR-134 expression was significantly decreased in chemo-resistant serous epithelial ovarian cancer (EOC) patients. Over-expression of miR-134 enhanced the sensitivity of SKOV3-TR30 cells to paclitaxel, and increased paclitaxel-induced apoptosis. Further, Pak2 was identified as a direct target of miR-134, and Pak2-specific siRNA increased cell inhibition rate and promoted paclitaxal-induced apoptosis. By regulating Pak2 expression, miR-134 could mediate Bad phosphorylation at Ser112 and Ser136, which affected cell survival and apoptosis. In conclusion, our findings indicate that repression of miR-134 and consequent up-regulation of Pak2 might contribute to paclitaxel resistance.


Occult melanoma in lymph nodes detected by antiserum to S-100 protein.
Sections of 1,273 nodes from 58 patients with melanoma were stained in an immunoperoxidase assay using an antiserum to S-100 protein and aminoethyl carbazole as indicator. By the hematoxylin and eosin (H. and E.) technique, 128 nodes were seen to contain melanoma (10%); by the anti-S-100 protein technique, 363 (29%) were found to be tumor-positive. The additional tumor-positive nodes contained single tumor cells or small groups of tumor cells and were adjacent to nodes that were partly or wholly replaced by melanoma. Penetration of nodes by single tumor cells was seldom seen in node groups containing no tumor that was visible on H. and E. staining. The anti-S-100 protein approach more accurately identified those patients who would die of their recurrent disease less than 5 years after lymphadectomy.


Development of inositol 1,4,5-trisphosphate 3-kinase immunoreactivity in cerebellar Purkinje cells in vivo and in vitro.
Development profiles in vivo and in vitro of inositol 1,4,5-trisphosphate 3-kinase (IP3K) were investigated immunohistochemically in the cerebellar Purkinje cells. In in vivo preparations of rat cerebellum, IP3K immunoreactivity appeared in Purkinje cell bodies and dendrites shortly after birth, increased rapidly by postnatal day 5, and was subsequently confined to their dendritic processes by day 20. The appearance and shift of IP3K immunoreactivity in Purkinje cells showed an identical time course even when Purkinje cells were placed under culture conditions commencing on day 0, suggesting that Purkinje cells have their own biological clock on the expression of IP3K in the absence of external influences.


Development and Validation of the Orthostatic Tremor Severity and Disability Scale (OT-10).
Limited tools are available for the assessment of orthostatic tremor severity and disability. To develop and validate a self-administered orthostatic tremor scale. After expert consensus and literature review generating a list of 42 items, the scale was developed and modified for validation after a patient focus group, multiple rounds of Delphi panels, and cognitive interviews. Clinimetric evaluations included assessing content validity, internal consistency, measurement error and reliability, construct validity, and concurrent validity anchored on the examiner's Clinical Global Impression score. Eleven items ranked on a Likert scale from 0 (no disability/severity) to 5 (maximal disability/severity) were evaluated in 54 orthostatic tremor patients (16 men and 38 women; mean age: 69.17 ± 9.64 years; disease duration: 13.83 ± 11.24 years) to probe severity and disability over the preceding 1-week period. The 11-item scale showed good internal consistency (Cronbach's alpha = 0.863) and acceptable (>0.40) item-to-total correlation. However, one item was removed at the final Delphi panel because of significant floor effect, poor item-to-total correlation, and poor factor-loading, leaving the scale with 10 items (10-item Orthostatic Tremor Severity and Disability Scale). Test-retest reliability at 2 weeks was excellent (two-way random intraclass correlation coefficient > 0.90), and the individual item test-retest reliability showed good agreement, with a threshold weighted kappa >0.60 for all items. Exploratory factor analyses revealed a parsimonious two-factor construct accounting for 57.7% of the scale's variance. The 10-item Orthostatic Tremor Severity and Disability Scale scores correlated with the CGI. The self-administered 10-item Orthostatic Tremor Severity and Disability Scale scale is valid and reliable for capturing orthostatic tremor-related severity and disability. © 2020 International Parkinson and Movement Disorder Society.


Nurses' willingness and the predictors of willingness to provide palliative care in rural communities of taiwan.
The aims of this study are to identify the willingness of district nurses to provide palliative care in the rural communities in Taiwan and determine the predictors of this willingness. A questionnaire was sent to all 1,121 community nurses of the 174 government health stations assigned to all the rural areas of Taiwan. The overall response rate was 86.4%, with 940 valid questionnaires retrieved. The majority of respondents (93.0%) expressed a willingness to provide palliative care if they encountered a terminal cancer patient. However, they would limit their services to consultation and referral (91.6% and 87.3%), and were less likely to provide home visiting (51.0%) or bereavement support of family (38.4%). With regard to knowledge, the accurate answers to the philosophy/principles and clinical practice of palliative care were 88.5% and 43%, respectively. The results of stepwise logistic regression analysis showed that "palliative care knowledge," "the belief in external control by authority," and "the belief in external control by chance" were the most significant variables related to the willingness of district nurses to provide palliative care (OR=12.83, 95% CI=2.46-66.76, P<0.01; OR=2.11, 95% CI=1.32-3.35, P<0.01; OR=0.54, 95% CI=0.31-0.95, P<0.05, respectively). However, regarding the content of services, the willingness to provide home visiting was affected positively by the level of information resources, subjective norms, and the belief in external control by authority. This willingness was negatively affected by age of the patient. These data suggest that effective training courses focused on practical knowledge of palliative care for these district nurses, the incorporation of the palliative care into nursing education, and active health policy administration are critical for the community palliative care movement in Taiwan.


Fura-2 calcium transients in frog skeletal muscle fibres.
1. Intact single twitch fibres from frog muscle were mounted at long sarcomere spacing (3.5-4.2 microns) on an optical bench apparatus for the measurement of absorbance and fluorescence signals following the myoplasmic injection of either or both of the Ca2+ indicator dyes Fura-2 and Antipyrylazo III. Dye-related signals were measured at 16-17 degrees C in fibres at rest and stimulated electrically to give a single action potential or brief train of action potentials. 2. The apparent diffusion constant of Fura-2 in myoplasm, Dapp, was estimated from Fura-2 fluorescence measured as a function of time and distance from the site of dye injection. On average (N = 7), Dapp was 0.36 x 10(-6) cm2 s-1, a value nearly 3-fold smaller than expected if all the Fura-2 was freely dissolved in the myoplasmic solution. The small value of Dapp is explained if approximately 60-65% of the Fura-2 molecules were bound to relatively immobile sites in myoplasm. 3. In resting fibres the fraction of Fura-2 in the Ca2+-bound form was estimated to be small, on average (N = 11) 0.06 of total dye. However, because of the large fraction of Fura-2 not freely dissolved in myoplasm, and the indirect method employed for estimating Ca2+-bound dye, calibration of the resting level of myoplasmic free Ca2+ ([Ca2+]) from the fraction of Ca2+-bound dye was not considered reliable. 4. In response to a single action potential, large changes in Fura-2 fluorescence (delta F) and absorbance (delta A) were detected, which had identical time courses. As expected, the directions of these transients corresponded to an increase in Ca2+-dye complex. For wavelengths, lambda, between 380 and 460 nm, peak delta A(lambda) was closely similar to the Ca2+-dye difference spectrum for Fura-2 determined in in vitro calibrations. Beer's law was used to calibrate the concentration of Ca2+-dye complex formed during activity (delta[CaFura-2]) from the delta A(lambda) signal. Peak delta[CaFura-2] was found to vary between 0.01 and 0.4 mM, depending on the total concentration of injected Fura-2 ([Fura-2T]), which ranged as high as 0.9 mM. 5. In fibres in which peak delta[CaFura-2] was less than 0.06 mM, delta[CaFura-2] had a limiting minimal half-width of 50-60 ms. However, as peak delta[CaFura-2] increased (up to 0.3-0.4 mM), delta[CaFura-2] half-width became markedly prolonged (up to 150-200 ms), indicative of a strong buffering action of large concentrations of Fura-2 on the underlying [Ca2+] transient (delta[Ca2+]).(ABSTRACT TRUNCATED AT 400 WORDS)


Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women.
Type 2 diabetes mellitus (T2DM) is associated with high levels of disability and mortality. Regular exercise prevents premature disability and mortality, but people with T2DM are generally sedentary for reasons that are not fully established. We previously observed that premenopausal women with T2DM report greater effort during exercise than their counterparts without diabetes, as measured by the Rating of Perceived Exertion (RPE) scale. We hypothesized that RPE is greater in older women with T2DM versus no T2DM. We enrolled overweight, sedentary women aged 50-75 years with (n=26) or without T2DM (n=28). Participants performed submaximal cycle ergometer exercise at 30 W and 35% of individually-measured peak oxygen consumption (35% VO2peak). We assessed exercise effort by RPE (self-report) and plasma lactate concentration. VO2peak was lower in T2DM versus controls (p=0.003). RPE was not significantly greater in T2DM versus controls (30 W: Control, 10.4±3.2, T2DM, 11.7±2.3, p=0.08; 35% VO2peak: Control, 11.1±0.5, T2DM, 12.1±0.5, p=0.21). However, lactate was greater in T2DM versus controls (p=0.004 at 30 W; p<0.05 at 35% VO2peak). Greater RPE was associated with higher lactate, higher heart rate, and a hypertension diagnosis (p<0.05 at 30 W and 35% VO2peak). Taken together, physiological measures of exercise effort were greater in older women with T2DM than controls. Exercise effort is a modifiable and thereby targetable end point. In order to facilitate regular exercise, methods to reduce exercise effort in T2DM should be sought. NCT00785005.


Prevention of Alcohol-Related Crime and Trauma (PACT): brief interventions in routine care pathway - a study protocol.
Globally, alcohol-related injuries cause millions of deaths and huge economic loss each year . The incidence of facial (jawbone) fractures in the Northern Territory of Australia is second only to Greenland, due to a strong involvement of alcohol in its aetiology, and high levels of alcohol consumption. The highest incidences of alcohol-related trauma in the Territory are observed amongst patients in the Maxillofacial Surgery Unit of the Royal Darwin Hospital. Accordingly, this project aims to introduce screening and brief interventions into this unit, with the aims of changing health service provider practice, improving access to care, and improving patient outcomes. Establishment of Project Governance: The project governance team includes a project manager, project leader, an Indigenous Reference Group (IRG) and an Expert Reference Group (ERG).Development of a best practice pathway: PACT project researchers collaborate with clinical staff to develop a best practice pathway suited to the setting of the surgical unit. The pathway provides clear guidelines for screening, assessment, intervention and referral. The developed pathway is introduced to the unit through staff training workshops and associate resources and adapted in response to staff feedback. File audits, post workshop questionnaires and semi-structured interviews are administered. This project allows direct transfer of research findings into clinical practice and can inform future hospital-based injury prevention strategies.


Effect of estradiol-17 beta on the cytology of the liver, gonads and pituitary, and on plasma electrolytes in the female freshwater eel.
Female freshwater eels injected with estradiol-17 beta (E2) for 15--78 days appear paler and secrete more mucus than controls. The resulting strongly opalescent blood plasma indicates that vitellogenin synthesis occurs in the liver, which shows a significant hypertrophy, an increased vacuolization (lipid material) and glycogen depletion. Plasma sodium is lowered, but calcium levels are considerably increased. The gonosomatic index increases (0.92 +/- 0.1 to a maximum of 2.21). Oocytes are enlarged, but the incorporation of vitellogenin remains discrete. Gonadotrophs (GTH cells), small and scarcely visible in the pituitary of control eels, are hypertrophied and contain numerous glycoprotein granules after E2-administration. E2 may act on the pituitary and/or hypothalamus via a positive feedback to induce gonadotrophin (GTH) synthesis; GTH release seems to be very limited as indicated by the ovarian response. The differentiation of GTH cells in eels treated with fish pituitary extracts is most probably due to secretion of E2 by the ovary, which reacts on the pituitary. Various hypotheses are considered to explain the low GTH release. Thyrotrophs, somatotrophs and prolactin cells of the pituitary are stimulated. In the pars intermedia, MSH and PAS-positive cells appear less active. A possible antidopaminergic effect of E2 is discussed. E2 administration constitutes a simple and economic technique to induce the synthesis of GTH and will facilitate the biochemical and biological study of the latter hormone in eels.


Rapid cycling depression in adolescence. A case treated with family therapy and carbamazepine.
This report aims at alerting the clinician to the existence of rapid cycling depression in adolescence. The importance of integrating psychodynamic, social and pharmacological modalities in evaluation and treatment is emphasized.


Author Correction: Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


A Case of Epididymo-orchitis after intravesical bacille Calmette-Guérin therapy for superficial bladder carcinoma in a patient with latent tuberculosis infection.
Intravesical instillation of bacille Calmette-Guérin (BCG) has been established as efficient therapy for superficial bladder carcinoma. Overall, intravesical BCG is well tolerated and results in complications of less than 5 %. However, adverse effects such as granulomatous prostatitis, pneumonitis, hepatitis, sepsis, and hypersensitivity reactions may occur. The reported rate for tuberculous orchitis after BCG intravesical therapy is 0.4 %. We report a case of monolateral tuberculous orchitis occurring one month after the second course of intravescical instillation of bacille Calmette-Guérin in a patient with proven superficial bladder carcinoma and latent tuberculosis infection. In our opinion intravesical instillation of BCG should be considered on an individual patient basis, with full patient disclosure of the potentially significant risks. A screening with an intradermal Mantoux before starting the first cycle of BCG instillation should be recommended and isoniazid would be indicated as the treatment for latent tuberculosis infection.


bin3C: exploiting Hi-C sequencing data to accurately resolve metagenome-assembled genomes.
Most microbes cannot be easily cultured, and metagenomics provides a means to study them. Current techniques aim to resolve individual genomes from metagenomes, so-called metagenome-assembled genomes (MAGs). Leading approaches depend upon time series or transect studies, the efficacy of which is a function of community complexity, target abundance, and sequencing depth. We describe an unsupervised method that exploits the hierarchical nature of Hi-C interaction rates to resolve MAGs using a single time point. We validate the method and directly compare against a recently announced proprietary service, ProxiMeta. bin3C is an open-source pipeline and makes use of the Infomap clustering algorithm ( https://github.com/cerebis/bin3C ).


Systematic review finds risk of bias and applicability concerns for models predicting central line-associated bloodstream infection.
To systematically review the risk of bias and applicability of published prediction models for risk of central line-associated bloodstream infection (CLA-BSI) in hospitalized patients. Systematic review of literature in PubMed, Embase, Web of Science Core Collection, and Scopus up to July 10, 2023. Two authors independently appraised risk models using CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) and assessed their risk of bias and applicability using Prediction model Risk Of Bias ASsessment Tool (PROBAST). Sixteen studies were included, describing 37 models. When studies presented multiple algorithms, we focused on the model that was selected as the best by the study authors. Eventually we appraised 19 models, among which 15 were regression models and four machine learning models. All models were at a high risk of bias, primarily due to inappropriate proxy outcomes, predictors that are unavailable at prediction time in clinical practice, inadequate sample size, negligence of missing data, lack of model validation, and absence of calibration assessment. 18 out of 19 models had a high concern for applicability, one model had unclear concern for applicability due to incomplete reporting. We did not identify a prediction model of potential clinical use. There is a pressing need to develop an applicable model for CLA-BSI.


Medicinal plants enter the single-cell multi-omics era.
Elucidating biosynthetic pathways of plant specialized metabolites is a tricky but essential task for the biotechnological production of plant drugs. In a new report, Li et al. used a single-cell multi-omics approach to provide an integrative view of the architecture and regulation of anticancer alkaloid routes in Madagascar periwinkle.


Cross-cultural validation of the St. Louis Inventory of Community Living Skills for Chinese patients with schizophrenia in Hong Kong.
The study validated a culturally sensitive community living skills rating scale for Chinese patients by adapting the St. Louis Inventory of Community Living Skills (SLICLS). The Chinese version (SLICLS-C) was produced by forward and backward translation. An expert panel evaluated its content validity. Its internal consistency, inter-rater reliability, construct and concurrent validity were tested on 80 DSM-IV schizophrenia inpatients in a long-term facility. For predictive validity, the above sample was extended to ensure at least 20 subjects discharged to each of three levels of community care were included in the study sample. The SLICLS-C was psychometrically sound and could be used for predicting level of community care, program evaluation and measuring outcome.


Prevention of stress ulcer bleeding with cimetidine in severe burns.
This paper presents clinical observations on the preventive effect of cimetidine for stress ulcer bleeding in severe burns. It shows that gastrointestinal bleeding after severe burn is significantly reduced, and the incidence of acute gastro-duodenal ulcer lowered by administration of cimetidine.


Prediction and analysis of COVID-19 positive cases using deep learning models: A descriptive case study of India.
In this paper, Deep Learning-based models are used for predicting the number of novel coronavirus (COVID-19) positive reported cases for 32 states and union territories of India. Recurrent neural network (RNN) based long-short term memory (LSTM) variants such as Deep LSTM, Convolutional LSTM and Bi-directional LSTM are applied on Indian dataset to predict the number of positive cases. LSTM model with minimum error is chosen for predicting daily and weekly cases. It is observed that the proposed method yields high accuracy for short term prediction with error less than 3% for daily predictions and less than 8% for weekly predictions. Indian states are categorised into different zones based on the spread of positive cases and daily growth rate for easy identification of novel coronavirus hot-spots. Preventive measures to reduce the spread in respective zones are also suggested. A website is created where the state-wise predictions are updated using the proposed model for authorities,researchers and planners. This study can be applied by other countries for predicting COVID-19 cases at the state or national level.


Oxidation of 3'-methoxyflavone, 4'-methoxyflavone, and 3',4'-dimethoxyflavone and their derivatives having 5,7-dihydroxyl moieties by human cytochromes P450 1B1 and 2A13.
Oxidation of 3'-methoxyflavone, 4'-methoxyflavone, and 3',4'-dimethoxyflavone and their derivatives containing 5,7-dihydroxyl groups by human cytochrome P450 (P450 or CYP) 1B1 and 2A13 was determined using LC-MS/MS systems.3'-Methoxyflavone and 4'-methoxyflavone were mainly O-demethylated to form 3'-hydroxyflavone and 4'-hydroxyflavone, respectively, and then 3',4'-dihydroxyflavone at higher rates with CYP1B1 than with CYP2A13. 4'-Methoxy-5,7-dihydroxyflavone (acacetin) was found to be demethylated by CYP1B1 and 2A13 to form 4',5,7-trihydroxyflavone (apigenin) at rates of 0.098-1 and 0.42 min-1, respectively. 3'-Methoxy-5,7-dihydroxyflavone was also demethylated by both P450s, with CYP2A13 being more active.3',4'-Dimethoxyflavone was a good substrate for CYP1B1 but not for CYP2A13 and was found to be mainly O-demethylated to form 3',4'-dihydroxyflavone (at a rate of 4.2 min-1) and also several ring-oxygenated products having m/z 299 fragments. Molecular docking analysis supported the proper orientation for formation of these products by CYP1B1.Our present results showed that 3'- and 4'-methoxyflavone can be oxidised to their O-demethylated products and, to a lesser extent, to ring oxidation products by both P450s 1B1 and 2A13 and that 3',4'-dimethoxyflavone is a good substrate for CYP1B1 in forming both O-demethylated and ring-oxidation products. Introduction of a 57diOHF moiety into these methoxylated flavonoids caused decreased in oxidation by CYP1B1 and 2A13.


Intra-hippocampal injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) inhibits partial and generalized seizures induced by kindling stimulation in cats.
This study assessed the effects of microinjections of a serotonin (5-HT) 1A agonist, 8-OH-DPAT, into the feline hippocampus (HIP) on seizure response induced by electrical stimulation of this region. Intra-HIP injection of 8-OH-DPAT (10 nmol) produced a significant elevation in the afterdischarge threshold of partial HIP seizures, with a significant reduction in the duration of focal afterdischarge. Similarly, microinjection of 8-OH-DPAT at the same dose significantly raised the seizure threshold for eliciting generalized seizures in HIP-kindled cats. The present results demonstrate that focally applied 8-OH-DPAT possesses a potent anticonvulsant action, and provide further evidence for the inhibitory role of 5-HT1A receptors in the generation of HIP seizures.


Oxidative stress responses in zebrafish Danio rerio after subchronic exposure to atrazine.
Atrazine is one of the most used pesticides all over the world and it is frequently detected in surface water. The aim of this study was to investigate if zebrafish exposure to atrazine could induce oxidative stress and changes in detoxifying system. Juvenile fish were exposed to sublethal concentrations of 0.3, 3, 30, or 90 μg L(-1) for 28 days. The level of oxidized lipids increased in experimental groups exposed to atrazine at 30 and 90 μg L(-1) compared to control. Activity of glutathione S-transferase decreased in group with the highest concentration compared to control. A significant decline was observed in catalase activity in all experimental groups compared to control. Activity of superoxide dismutase increased only in experimental group exposed to atrazine at 30 μg L(-1) compared to control. Activity of glutathione peroxidase and reductase (GR) increased in experimental groups exposed to atrazine at 0.3 (only for GR activity) and 90 μg L(-1) compared to control. Our results showed that atrazine exposure had profound influence on the oxidative stress markers and detoxifying enzyme of the exposed zebrafish. The changes in antioxidant enzyme activities could be an adaptive response to protect the fish from the atrazine-induced toxicity.


A possible role of ectopic action potentials in the in vitro hippocampal sharp wave-ripple complexes.
Sharp wave-ripple (SPW-R) complexes are physiological pattern of network activity in the hippocampus thought to play important role in memory consolidation. During SPW-R activity the excitability of both pyramidal cells and certain types of interneurons in the CA1 region is transiently increased. As a result pyramidal cells receive inhibitory input during network oscillation, yet a relatively small group of pyramidal cells transmit their output to CA1 targets. However, the exact nature of CA1 output during SPW-R activity is not clear. In this study, using simultaneous intracellular and field recordings from rat ventral hippocampal slices maintained at 32 degrees C and spontaneously generating SPW-R complexes we show that 20% of CA1 pyramidal cells fired putative ectopic action potentials (e-APs) phase-related to SPW-Rs. The highest probability of ectopic discharge occurred at the maximal amplitude of the ripple oscillation and always during the period of SPW-R-associated inhibitory postsynaptic potentials (IPSPs) in pyramidal cells. Both e-APs and IPSPs were abolished under blockade of GABA(A) receptor-mediated synaptic transmission by bicuculline. Ectopic APs phase-locked to SPW-R events were also evoked by Schaffer collateral stimulation subthreshold for and with longer latency than monosynaptic orthodromic APs. A fraction of CA1 pyramidal cells (25.7%), most of them distinct from the cells firing e-APs, fired orthodromic APs with highest probability before the onset of SPW-Rs. We hypothesize that putative ectopic spikes in pyramidal cells, presumably triggered by GABAergic synaptic mechanisms, by serving as output of the CA1 region might provide a reliable mechanism for optimized information transfer between hippocampus and its cortical targets during SPW-R activity. On the other hand, orthodromic APs might contribute to the initiation and synchronization of the population activity.


Aerobic growth and survival of Campylobacter jejuni in food and stream water.
When 40 Campylobacter jejuni isolates from human clinical cases, raw chicken and water were tested, 29 (72.5%) could be adapted to grow on nutrient agar under aerobic conditions. Once adapted, these isolates could grow on repeated aerobic subculture. An aerobically-grown Camp. jejuni isolate survived almost as well as the same isolate grown microaerophilically in sterile chicken mince at 5 degrees C, and survival of a cocktail of Camp. jejuni isolates under both atmospheres was comparable at 25 degrees C. However, at 37 degrees C, the decline in numbers of the aerobically-grown cells was greater. Survival of cells on chicken nuggets was poorer than in chicken mince. In filter-sterilized stream water incubated aerobically at 5 degrees C, survival of inocula grown under different atmospheres was again similar, but slightly better with the microaerophically-grown cells. Adaptation to aerobic growth was not found to enhance survival under aerobic conditions.


Which Users Should Be the Focus of Mobile Personal Health Records? Analysis of User Characteristics Influencing Usage of a Tethered Mobile Personal Health Record.
This study was conducted to analyze the usage pattern of a hospital-tethered mobile personal health records (m-PHRs) application named My Chart in My Hand (MCMH) and to identify user characteristics that influence m-PHR usage. Access logs to MCMH and its menus were collected for a total of 18 months, from August 2011 to January 2013. Usage patterns between users without a patient identification number (ID) and users with a patient ID were compared. Users with a patient ID were divided into light and heavy user groups by the median number of monthly access. Multiple linear regression models were used to assess MCMH usage pattern by characteristics of MCMH user with a patient ID. The total number of MCMH logins was 105,603, and the median number of accesses was 15 times. Users (n = 7,096) mostly accessed the "My Chart" menu, but "OPD [outpatient department] Service Support" and "Health Management" menus were also frequently used. Patients with chronic diseases, experience of hospital visits including emergency room and OPD, and age group of 0-19 years were more frequently found among users with a patient ID (n = 2,186) (p < 0.001). A similar trend was found in the heavy user group (n = 1,123). Submenus of laboratory result, online appointment, and medication lists that were accessed mostly by users with a patient ID were associated with OPD visit and chronic diseases. This study showed that focuses on patients with chronic disease and more hospital visits and empowerment functions in a tethered m-PHR would be helpful to pursue the extensive use.


An Examination of Infection Incidence and Management in Systemic Lupus Erythematosus Patients: A Five-Year Review from a Saudi Arabian Center.
BACKGROUND Systemic lupus erythematosus (SLE) is a chronic autoimmune condition often associated with an increased susceptibility to infections. The infections in patients with SLE, primarily involving the skin, respiratory tract, and urinary tract, can significantly complicate disease management. This study aimed to evaluate the occurrence, management, and patient outcomes associated with infections in a group of 74 SLE patients at a single center in Saudi Arabia, spanning a 5-year period. MATERIAL AND METHODS An observational, retrospective study was conducted at the King Khalid University Hospital, Riyadh, Saudi Arabia. Patient medical records from January 2016 to December 2020 were examined. All adult SLE patients (age >14 years, as per hospital policy), confirmed by SLICC criteria, and admitted due to infections (determined by quick Sequential Organ Failure Assessment or qSOFA scores) were included in the study. RESULTS Of the 74 SLE patients studied, 79.7% were administered hydroxychloroquine. A majority (83.8%) were classified as low-risk for sepsis-associated mortality based on qSOFA scores (0-1), a fact noted by 41.9% of rheumatology fellows. The sputum cultures most frequently identified were Klebsiella pneumoniae, yeast, and Haemophilus influenzae (each accounting for 33.3% of cases). Furthermore, 4.1% of patients had extended-spectrum beta-lactamases infections, and 2.7% tested positive for COVID-19. A history of sepsis was more commonly observed among non-survivors (P=0.010). CONCLUSIONS The majority of patients were classified as low-risk for sepsis-associated mortality based on qSOFA scores, with two-thirds prescribed antibiotics within 1 h. The primary causes of death were multiorgan failure and cardiac arrest.


Prolonged use of aspirin alters human and rat intestinal cells and thereby limits the absorption of clopidogrel.
Clopidogrel therapy to prevent atherothrombosis faces the challenge of reduced responsiveness. The absorption of clopidogrel is regulated by multidrug-resistance protein 1 (MDR1) in the intestinal epithelium. Given that aspirin induces MDR1 in cancer cells and peripheral blood cells, it may induce MDR1 in intestinal epithelial cells as well, thereby affecting the absorption of clopidogrel. In this study, aspirin treatment induced the expression of MDR1 in human epithelial colorectal (Caco-2) cells in vitro and in rat intestine in vivo, as evidenced by dose-dependent increases in gene, protein, and efflux function. Along with the upregulation of MDR1 proteins by aspirin, clopidogrel absorption was significantly decreased in the aspirin-treated Caco-2 cells and in rat intestine. Our data provide evidence that prolonged use of aspirin may reduce the intestinal absorption of clopidogrel. Further human studies would be necessary to clarify whether these data have any relevance to prevention of stroke or myocardial infarction.


Calcium in the spine apparatus of dendritic spines in the dentate molecular layer.
With a pyroantimonate precipitation technique, we have demonstrated Ca2+ in the sacs of the dendritic spine apparatus in the SER of dendrites and axon terminals, in synaptic vesicles, multivesicular bodies, mitochondria, and glial processes of the dentate molecular layer. It is speculated that the spine apparatus may be a Ca2+ sequestering organelle which may regulate levels of intraspinal and intradendritic Ca2+ during synaptic activity.


Investigations on the antiproliferative effects of amino acid antagonists targeting for aminoacyl-tRNA synthetases. Part I--The antibacterial effect.
Amino acid antagonists with proven or potentially inhibitory activities on aminoacyl-tRNA synthetases were tested for their antiproliferative effect against E. coli B. The compounds 4- and 6-fluoro-tryptophan, 5-methyltryptophan, selenocystine and beta-(2-thienyl)alanine gave strong growth inhibition in minimal medium, which disappeared after addition of structurally related natural amino acids or in an enriched broth. The inhibitory effect on amino-acyl-tRNA synthetases and the minimal inhibitory concentration for growth inhibition in minimal medium could not be correlated.


Histamine release from rat mast cells induced by an extract from the sea urchin Toxopneustes pileolus.
The extract caused a dose-dependent release of histamine from rat peritoneal mast cells which was slower in onset than that of compound 48/80. It is also suggested that the extract-induced histamine release is dependent on aerobic glycolysis.


Acetylcholine receptors in spider peripheral mechanosensilla.
Peripherally located parts of spider mechanosensory neurons are modulated by several neurotransmitters released from apposed efferent fibers. Activities of acetylcholine (ACh) synthesizing enzyme choline acetyltransferase (ChAT) and ACh degrading enzyme acetylcholine esterase (AChE) were previously found in some efferent fibers. ChAT activity was also present in all the mechanosensory neurons, while AChE activity was only found in some. We show that spider mechanosensory neurons and probably some efferent neurons are immunoreactive to a monoclonal antibody against muscarinic ACh receptors (mAChRs). However, application of muscarinic agonists did not change the physiological responses or membrane potentials of neurons in the lyriform organ VS-3. Similarly, the sensitivities of the neurons of trichobothria (filiform hairs) remained unchanged after application of these agonists. Therefore, activation of mAChRs may only modulate the function of spider mechanosensory neurons indirectly, for example, by affecting the release of other transmitter(s). However, a subgroup of VS-3 neurons was inhibited by ACh, which also depolarized the membrane similar to these neurons' responses to GABA, suggesting that ACh activates anion channels in these neurons. Interestingly, all of the neurons responding to ACh were the rapidly adapting Type A neurons that were previously shown to express AChE activity.


Double-bundle anterior cruciate ligament reconstruction technique has advantages in chondroprotection and knee laxity control compared with single-bundle technique : A long-term follow-up with a minimum of 12 years.
To compare the long-term clinical outcomes of single-bundle anterior cruciate ligament reconstruction (SBR) and double-bundle anterior cruciate ligament reconstruction (DBR) in patients with isolated anterior cruciate ligament (ACL) rupture, presenting no meniscus injury and no obvious preoperative cartilage degeneration. One hundred and three patients (38.6 ± 9.5 years) with a median follow-up of 151.6 months (range, 144-189 months) completed the retrospective study (SBR group: n = 51; DBR group: n = 52). Clinical outcomes were evaluated with physical examinations, KT-2000 anterior and posterior stability measurement with the knee in 30º of flexion, International Knee Documentation Committee (IKDC) subjective score, Tegner score, Lysholm score; magnetic resonance imaging (MRI) (3.0 T) was performed, and International Cartilage Repair Society (ICRS) cartilage degeneration grades were determined. Multivariate analysis was performed to identify factors associated with cartilage degeneration. There were significant differences in the pre- and postoperative IKDC, Lysholm and Tegner scores between the SBR and DBR groups. The SBR group had over double the rate of positive pressure/rub patellar test results (SBR vs DBR, 43.1% vs. 19.2%, p < 0.011). The KT-2000, pivot-shift and Lachman test results were stratified and analyzed, and significant differences between the SBR and DBR groups were found (p < 0.05, respectively). The distribution of ICRS grades differed significantly between the groups at the last follow-up (p = 0.013). A multivariate analysis found that age and operation procedures were significant predictors of 0 and non-0 ICRS grades (odds ratio, 6.077 [95% CI 2.117-17.447] and 0.210 [95% CI 0.068-0.654], respectively) (p < 0.05). Both SBR and DBR achieved overall good long-term results. DBR had advantages in objective outcome measures and was superior in preventing the occurrence of cartilage degeneration. Age was identified as a preoperative risk factor for significant postoperative cartilage degeneration. III. ClinicalTrials.gov: NCT03984474.


Potential value of Plasmodium falciparum-associated antigen and antibody detection for screening of blood donors to prevent transfusion-transmitted malaria.
Malaria antibody detection is a valuable tool in the prevention of transfusion-transmitted malaria in countries with a high proportion of donors with travel exposure to malaria. The immunofluorescent antibody test (IFAT) is still the reference method, but it is not suitable for screening of blood donors. ELISA would be an interesting alternative to the IFAT, but it lacks sensitivity. To evaluate the potential value of a combined screening strategy based on malaria antigen and antibody detection, plasma samples from 203 patients infected with Plasmodium falciparum were tested with an ELISA for the detection of malaria antibodies (Malaria IgG CELISA, Cellabs) and a P. falciparum histidine-rich protein-2 kit (Malaria P.f., ICT Diagnostics) for the detection of malaria antigens. Among patients with positive IFAT results, CELISA had a sensitivity of 71 percent, whereas the combined screening tests (CELISA and Malaria P.f.) had a sensitivity of 88 percent (p < 0.001). Sequential samples from 50 patients were tested. The combined screening tests shortened the detection of seroconversion from 11.4 +/- 1.6 to 5.3 +/- 1.1 days (p < 0.001). Combined malaria antigen and antibody detection, with methods compatible with mass screening, may constitute an attractive alternative to the IFAT for blood donor screening.


Juvenile river herring habitat use and marine emigration trends: comparing populations.
Juvenile habitat use and early life migratory behaviors of successfully recruited adult fish provide unique insight into critical habitats for a population, and this information allows restoration plans to be tailored to maximize benefits. Retrospective analysis of adult otolith chemistry combined with fish-otolith growth models were used to assess juvenile nursery habitat selection and size at egress to adult habitats (marine waters) for anadromous alewife and blueback herring from 20 rivers throughout the eastern US. Between-species differences in the size of emigrants were small, with blueback herring found in freshwater nurseries ~ 8% more frequently than alewives, and alewives using a combination of freshwater and estuarine nurseries ~ 9% more than bluebacks. Estuarine nursery use was more common in populations at lower latitudes. No clear trends in sizes of emigrants or habitat use were observed between the species in watersheds where both co-occur. Principal component analysis of latitude, watershed area, estuary area, accessible river kilometers, and percentage of the watershed in urban use indicated that the combined effects of these watershed characteristics were correlated with size at egress. These results highlight the considerable plasticity in early life habitat use among populations of anadromous fishes as well as the effect of watershed characteristics on early life migration timing and strategies.


Propitious role of bone marrow-derived mononuclear cells in an experimental bile duct ligation model: potential clinical implications in obstructive cholangiopathy.
To evaluate the role of bone marrow-derived mononuclear cells (BMC) in rat bile duct ligation (BDL) model. Wistar rats were categorized into four Groups A-D. Normal liver biopsy was taken from Group A. BDL model was created in Groups B and C (15 each). Normal saline and BMC were injected through portal vein (PV) in Groups B and C, respectively. In Group D (healthy rat), only BMC were infused through PV. Groups B and C were compared for body weight, liver functions, survival, and histopathological changes. Serum bilirubin was lower in Group C at day 6 (p = 0.0010). Median survival time was 5 (4, 6) and 13 (9, 17) days in Groups B and C (p = 0.0147), respectively. Portal edema (p = 0.013) and portal inflammation (p = 0.025) were less in Group C vs Group B. On post hoc subgroup analysis of rats surviving 8-26 days, portal inflammation (p = 0.004), bile duct proliferation (p = 0.016) and portal fibrosis (p = 0.038) were less in Group C vs Group B. Hepatocyte regeneration was found in four rats in Group C. CD34-positive cells were prominent in sinusoids and portal tracts in the BDL rat model. BMC have shown to delay fibrosis, facilitate hepatocyte regeneration and improve survival in an experimental BDL model, with potential clinical implication in obstructive cholangiopathy.


Whole genome sequencing and evolutionary analysis of G8P [8] rotaviruses emerging in Japan.
Unusual DS-1-like intergenogroup reassortant rotaviruses with a bovine-like G8 genotype (DS-1-like G8P [8] rotaviruses) have emerged and rapidly spread in several countries. In this study, the nucleotide sequences of seven human rotavirus G8P [8] strains in 2017 and 2019 in Japan were determined using viral metagenomics. Its genomic constellation (VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes) was defined as G8-P [8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Our genetic analysis revealed that the Japanese G8P [8] rotavirus strains in 2017 and 2019 were classified into the same lineages G8-5 and P [8]-3, but they were phylogenetically located on separate branches and belonged to distinct clusters. Our study is the first attempt to investigate the evolution of emerging rotavirus G8P [8] in Japan.


Prehospital qSOFA, mSOFA, and NEWS2 performance for sepsis prediction: A prospective, multi-center, cohort study.
Nowadays, there is no gold standard score for prehospital sepsis and sepsis-related mortality identification. The aim of the present study was to analyze the performance of qSOFA, NEWS2 and mSOFA as sepsis predictors in patients with infection-suspected in prehospital care. The second objective is to study the predictive ability of the aforementioned scores in septic-shock and in-hospital mortality. Prospective, ambulance-based, and multicenter cohort study, developed by the emergency medical services, among patients (n = 535) with suspected infection transferred by ambulance with high-priority to the emergency department (ED). The study enrolled 40 ambulances and 4 ED in Spain between 1 January 2020, and 30 September 2021. All the variables used in the scores, in addition to socio-demographic data, standard vital signs, prehospital analytical parameters (glucose, lactate, and creatinine) were collected. For the evaluation of the scores, the discriminative power, calibration curve and decision curve analysis (DCA) were used. The mSOFA outperformed the other two scores for mortality, presenting the following AUCs: 0.877 (95%CI 0.841-0.913), 0.761 (95%CI 0.706-0.816), 0.731 (95%CI 0.674-0.788), for mSOFA, NEWS, and qSOFA, respectively. No differences were found for sepsis nor septic shock, but mSOFA's AUCs was higher than the one of the other two scores. The calibration curve and DCA presented similar results. The use of mSOFA could provide and extra insight regarding the short-term mortality and sepsis diagnostic, backing its recommendation in the prehospital scenario.


Widespread distribution of substance P- and somatostatin-immunoreactive elements in the spinal cord of the neonatal rat.
The distribution of substance P (SP)- and somatostatin (SOM)-immunoreactive elements in the spinal cord of the neonatal rat was examined. With few exceptions, the distribution of SP-immunoreactive elements is similar to that described for the adult. A major difference is the obvious presence of SP-immunoreactive fibers in all funiculi of neonatal cords. In addition, an obvious small bundle of longitudinal SP immunoreactive fibers is seen in the base of the dorsal horn at rostral cervical levels. Unlike that of the adult, the neonatal spinal cord shows a widespread distribution of SOM-immunoreactivity. SOM-immunoreactive fibers are present in all funiculi. SOM-immunoreactive perikarya of various shapes and sizes are widely dispersed throughout the gray matter. The cell density is increased in the superficial laminae of the dorsal horn, in a region ventral-lateral to the central canal and in the ventral horn. SOM-immunoreactive varicosities are present in moderate amounts in the superficial laminae of the dorsal horn but are extremely sparse in other regions of the gray matter. A few SOM-immunoreactive fibers course longitudinally at the base of the dorsal horn at rostral levels of the cord. These fibers are found in the same region occupied by the longitudinal SP-immunoreactive fibers referred to above.


Influence of pretreatment ideal body weight percentile and albumin on prognosis of nasopharyngeal carcinoma: Long-term outcomes of 512 patients from a single institution.
The purpose of this study was to investigate the relationship between pretreatment nutritional status and prognosis of nasopharyngeal carcinoma (NPC). Pretreatment nutritional status was evaluated by ideal body weight percentile (IBW%) and serum albumin for 512 patients with NPC who underwent radical radiotherapy. Kaplan-Meier methods, log-rank test, and a Cox model were applied for survival analysis. Before radiotherapy, IBW% <90% was related to poorer overall survival (OS) and distant metastasis-free survival (DMFS; p = .031 and p = .012, respectively); albumin ≤43.0 g/L was related to poorer OS and DMFS (p < .001 and p = .042, respectively); both IBW% and albumin were independent prognostic factors for OS; those patients with IBW% <90% and albumin ≤43.0 g/L simultaneously had the worst OS and DMFS. Decrease of pretreatment IBW% and albumin was related to poorer survival of NPC.


One step electrodeposition of dendritic gold nanostructures on β-lactoglobulin-functionalized reduced graphene oxide for glucose sensing.
Dendritic gold nanostructures (AuNDs) were successfully synthesized by one step electrodeposition on reduced graphene oxide (rGO) functionalized by a globular protein, β-lactoglobulin (BLG), for the first time. Owing to its sulfhydryl groups, water-soluble BLG-rGO provided a superb platform for the growth of AuNDs. Scanning electron microscopy, Raman spectroscopy and X-ray spectroscopy analysis were used to investigate the as prepared BLG-rGO-AuNDs nanocomposite. Electrocatalytic ability of the nanocomposite was evaluated by cyclic voltammetry and chronoamperometric method. In order to prove the superiority of BLG-rGO-AuNDs, we developed a novel glucose biosensor on the nanocomposite modified glassy carbon electrode (GCE) through a cross-linking method. The biosensor exhibited a remarkable sensitivity of 46.2 μA mM(-1) cm(-2), a wide linear range of 0.05-6 mM glucose, a low detection limit of 22.9 µM (S/N=3), and a rapid response time (within 6 s). The prepared biosensor also used to detect glucose in human serum and statistical analysis in the respect of reproducibility was done.


Racial, Ethnic, and Rural/Urban Disparities in HIV and Sexually Transmitted Infections in South Carolina.
Examining the current incidence rates of HIV and STIs among racial and ethnic minority and rural residents is crucial to inform and expand initiatives and outreach efforts to address disparities and minimize the health impact of these diseases. A retrospective, cross-sectional study was conducted using Medicaid administrative claims data over a 2-year period (July 2019-June 2021) in South Carolina. Our main outcomes of interest were claims for chlamydia, gonorrhea, syphilis, and HIV. Any beneficiary with at least one claim for a relevant diagnosis throughout the study period was considered to have one of these diseases. Descriptive analyses and multivariable regression models were used to estimate the association between STIs, HIV, race and ethnicity, and rurality. Overall, 158,731 Medicaid beneficiaries had at least one medical claim during the study period. Most were female (86.6%), resided in urban areas (66.6%), and were of non-Hispanic Black race/ethnicity (42.6%). In total, 6.3% of beneficiaries had at least one encounter for chlamydia, 3.2% for gonorrhea, 0.5% for syphilis, and 0.8% for HIV. In multivariable models, chlamydia, gonorrhea, and HIV claims were significantly associated with non-Hispanic Black or other minority race/ethnicity compared to non-Hispanic white race/ethnicity. Rural residents were more likely to have a claim associated with chlamydia and gonorrhea compared to urban residents. The opposite was observed for syphilis and HIV. Providing updated evidence on disparities in STIs and HIV among racial/ethnic minority and rural populations in a southern state is essential for shaping state Medicaid policies to address health disparities.


Musical pitch perception with pulsatile stimulation of single electrodes in patients implanted with the Nucleus cochlear implant.
Subjects implanted with a Nucleus cochlear implant participated in closed-set melody recognition and musical pitch experiments in which pitch was mediated by systematic changes in pulse rate on single intracochlear electrodes. The results suggest that temporal information is sufficient for musical interval perception.