Amelioration of hexavalent chromium-induced bioaccumulation, oxidative stress, tight junction proteins and immune-related signaling factors by Allium mongolicum Regel flavonoids in Ctenopharyngodon idella.
Chromium (Cr) is the most common heavy metal and that becomes toxic when present at higher concentrations in aquatic environments. Allium mongolicum Regel flavonoids (AMRF) has been documented to possess detoxification, antioxidant and anti-inflammatory properties. The aim of this study was to explore the potential of dietary AMRF and Cr exposure on bioaccumulation, oxidative stress, and immune response in Ctenopharyngodon idella. After acclimation, 360 fish were randomly distributed into six groups. The fish were fed with diets supplemented with Cr and/or AMRF for 4 weeks (28 days), the Cr concentrations were 0, 120, and 240 mg/kg and the concentrations of AMRF were 0 or 40 mg/kg, respectively. The results shown that Cr accumulation in the kidney, liver, spleen, intestine and gill were significantly increased following Cr exposure, dietary AMRF supplementation attenuated the increased in Cr accumulation. Dietary AMRF supplementation significantly reduced the levels of malondialdehyde (MDA) and protein carbonyl (PC) in liver, spleen and gill compared with the same Cr dose groups. When fish were supplemented with AMRF significantly increased lysozyme activity (LZM), complement 3 (C3) in kidney and intestine compared with the same Cr dose groups. Serum glutamic oxalate transaminase (GOT) and glutamic pyruvate transaminase (GPT) were significantly increased following exposure to Cr. Dietary AMRF supplementation significantly decreased GOT and GPT activity in the serum. In addition, AMRF supplementation can decrease the expression of inflammatory (NF-κB p65, TNF-α and IL-1β) and increased the expression of tight junction proteins (occludin and ZO-1) following Cr exposure in C. idella. These results indicate that AMRF has the potential to alleviate the effects of Cr toxicity in C. idella.


A method to quantify spontaneous and in vivo induced thioguanine-resistant mouse lymphocytes.
A clonogenic assay to quantify thioguanine (TG)-resistant (TGr) spleen lymphocytes in the mouse has been developed to support studies of in vivo mutation affecting the hypoxanthine phosphoribosyltransferase (hprt) locus. Lymphocytes are cultured in 96-well microtiter plates for 9 days with proliferation initiated by the mitogen concanavalin A and supported thereafter by conditioned medium containing interleukin-2. Lymphocytes are plated at high densities (4-8 X 10(5)/well) with TG and irradiated L5178Y lymphoma cells (10(4)/well) to detect the presence of TGr cells. To determine the cloning efficiency without TG lymphocytes are plated at a low density (10/well) with irradiated L5178Y cells and irradiated lymphocytes (4-8 X 10(5)/well). Proliferation of cells is detected by [3H]thymidine incorporation and scintillation spectrometry. Spontaneous frequencies of TGr clones are independent of TG dose from 0.2 to 10 micrograms/ml and independent of cell density over the range cited. The TGr clones tested have less than 10% hypoxanthine incorporation in vivo relative to unselected clones and have stable phenotypes in the absence of selection. The spontaneous frequency of TGr cells ranged from 1 to 3 X 10(-6). In vivo treatment of mice intraperitoneally with ethylnitrosourea 15 days prior to in vitro culture resulted in a linear dose-related increase of TGr cells, with 70.2 mg/kg inducing a frequency of TGr cells of 2 X 10(-5).


Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression.
In the present study, we investigated the inducibility of the drug conjugate transporter genes MRP1 and MRP2 by redox-active compounds such as tertiary butylated hydroquinone (tBHQ) and quercetin and by chemicals known to activate the pregnane X receptor (PXR) such as rifampicin and clotrimazol and by the metalloid compound arsenite. The human MRP2 gene was found to be inducible in HepG2 cells by rifampicin, clotrimazol, arsenite and tBHQ. As MRP1 expression is extremely low in HepG2 cells, its inducibility was studied in MCF-7 cells. However, only tBHQ and quercetin acted as inducers, but not the other compounds investigated. Reporter gene assays demonstrated that proximal promoter regions of the genes contribute to the induction by tBHQ, quercetin (MRP1) and clotrimazol (MRP2). However, the deletion of binding sites supposed to mediate the induction process (a PXR-binding element-like sequence for the clotrimazol effect and an ARE (antioxidative response element) for the tBHQ/quercetin effect) did not result in a significant decrease in the induction factor indicating that other parts of the promoter are probably involved in the induction process. In summary, expression of both genes can be up-regulated by redox-active compounds, while the other compounds tested induced only MRP2 but not MRP1 expression.


The Path to Better Cardiovascular Health in North Carolina: An Interview with a Family Physician and Lipidologist.
Cardiovascular disease remains a major health issue in North Carolina, significantly affecting longevity and health care costs. NCMJ Managing Editor Kaitlin Ugolik Phillips sat down with family physician Dr. Thomas White to discuss his experiences and perspectives on this disease process.


Informed consent in primary dental care: patients' understanding and satisfaction with the consent process.
The purpose of the consent process is to give patients enough information to allow them to make an informed decision and preserve their autonomy. The patient's satisfaction and also their understanding of the consent process are audited only rarely and reports of such audits in dental practice are sparse. Reports from other specialties indicate that patients' understanding of the process is incomplete and often incorrect. We set about to perform such an audit to assess both our patients' satisfaction and their understanding of the consent process itself. A prospective questionnaire study of adults with capacity. Primary care dental practice. A two-part questionnaire was designed, based on a questionnaire used for a similar purpose in paediatric surgery; the first part assessed the patient's opinion and satisfaction with the consent obtained by their dental professional and the second part assessed their understanding of the consent process in general and the legal issues around it. Part 1 - satisfaction with the consent process. Patients reported high level of satisfaction with the consent process at the practice (near 100% in major factors analysed). Part 2 - Understanding of the consent process. Significant misconceptions were identified: 60% thought that the form was for the protection of the dentist/hospital and 10-16% thought that by signing a consent form they relinquish their rights. A high level of patients' uncertainty (19-27%) was also evident for several of the questions. Although this study shows a very high level of patient satisfaction with the consent process at our dental practice, it also demonstrates very significant deficiencies in the patients' understanding of the consent process itself. This study corroborates the findings of other investigators in different medical disciplines and calls into question the adequacy of the current consent procedures as many patients are still unaware of the legal implications of consent; the majority of patients still do not recognise that the consent process should primarily be serving their interests by allowing them to express their autonomous choice pertaining to their treatment. Education will help reduce this discrepancy and promote a change from the past 'paternalistic' to the current 'informative, patient-centred' model of care.


Towards a molecular diagnosis of invasive aspergillosis and disseminated candidosis.
A lot of in-house polymerase chain reaction assays have been reported for diagnosis of invasive aspergillosis and disseminated candidosis. Encouraging results have been published to anticipate the diagnosis over the conventional microbiological methods. However, the absence of standardized methods has led to diverging results. As a consequence, these tests are not recognized as consensual diagnostic criteria, in contrast with some antigenemia detection kits. The major breakthrough for improving the results of these methods is the emergence of real-time technologies. This markedly improves the reliability of the PCR results by dramatically decreasing the risk of false positive results due to PCR products carryover. Moreover, using the quantitative results provided by this technique, this allows to rapidly compare the efficiency of primers, probes, and DNA extraction methods. Therefore, the hope is to identify the more specific and sensitive parameters to implement comparative studies. Automated DNA extraction should also be useful to achieve this goal. Whatever sophisticated technology is used, we still have to define the meaning of detecting nucleic acids in a given clinical sample. This seems simple in normally sterile anatomical sites but less obvious for example in respiratory specimens for invasive aspergillosis or in blood for candidosis in heavily colonized patients. Additional studies of the kinetics of fungal DNA are needed. The development of real-time technology should improve our knowledge in order to give the clinicians informative clues for making a decision.


Primary tumors of the renal pelvis: evaluation of clinical and pathological features in a consecutive series of 10 years.
We operated on 36 patients for primary carcinoma of the renal pelvis between 1975 and 1984. The patients were evaluated for etiological factors, symptoms, diagnostic modalities, treatment, histological type and grade of dedifferentiation, presence of invasion, abnormalities in the urothelium adjacent to the tumor, abnormalities in the epithelium of the collecting tubules and patient survival. No etiological factors were found. The main symptom was hematuria. Diagnosis was made by excretory urography with tomography. Urine cytology examination was of no help in the diagnosis. The survival was high in patients with low grade tumors, tumors without invasion and tumors without coexisting atypia in the adjacent urothelium but it was poor in those with high grade tumors, tumors with invasion and tumors with atypia of the adjacent urothelium.


Improving galegine production in transformed hairy roots of Galega officinalis L. via elicitation.
Galega officinalis L. is an herbaceous legume used to treat symptoms associated with hyperglycemia or diabetes mellitus because of its dominant alkaloid, galegine. In this study, we induced hairy roots in this plant using Rhizobium rhizogenes strain A4, and investigated the effect of type, concentration, and duration of elicitor application on galegine content and some phytochemical characteristics in the hairy roots. Hence, the best growing hairy root line in terms of growth rate was selected and subcultured for treatment with elicitors. Then, at the end of the log phase of growth, chitosan (100, 200, and 400 mg/L), salicylic acid (100, 200, and 300 mM), and ultrasound (1, 2, and 4 min) were applied to hairy roots culture medium. High-performance liquid chromatography (HPLC) showed that the content of galegine was significantly increased after elicitation compared with the control. Thus, the highest content of galegine (14.55 mg/g FW) was obtained 2 days after elicitation when ultrasonic waves were applied to the hairy root culture medium for 4 min. Also, elicitation resulted in a significant increase in the content of total phenol, flavonoid, H2O2 and MDA compared with the control. So that the highest total flavonoid content was obtained in hairy roots that were treated with ultrasonic waves for 4 min and harvested 2 days after elicitation; while, application of 400 mg/L chitosan for 4 days resulted in the highest total phenol (16.84 mg/g FW).


Does the number of tissue fragments removed from the cervix with excisional treatment for CIN pathology affect the completeness of excision and cytology recurrence at follow-up? An observational cohort study.
The objective of our study was to determine whether removing multiple pieces of cervical tissue during large loop excision of the transformation zone (LLETZ) reduced the margin positivity of excision and cytology recurrence rates at follow-up. We conducted an observational cohort study and identified 462 women having had a single LLETZ treatment for cervical intraepithelial neoplasia (CIN) over a two-year period. Women with previous cervical treatment, cervical cancer on the excised tissue or missing follow-up data were excluded. Multiple regression analysis showed that removal of cervical tissue in multiple pieces did not offer any benefit in removing more disease and less recurrence rates. When multiple pieces were taken there was a four-fold increased risk for inconclusive excision margins as reported by the histopathologist. Removal of multiple pieces led to significantly more tissue being removed which may expose the patient to an increased risk of preterm delivery in a future pregnancy.


RNAi-mediated gene silencing to assess the role of synaptobrevin and cystatin in tick blood feeding.
In addition to being the conduit for pathogens into hosts, tick saliva contains a broad array of secretory products that facilitate prolonged tick attachment and blood feeding. Proteins found in tick saliva modulate host hemostasis and immune responses. However, it is not clear whether ticks manipulate the immune responses of their hosts by disrupting the antigen-processing pathways of the hosts. Protein secretion into tick saliva from the salivary glands is due to exocytosis of vesicular membrane-bound granular material regulated by SNARE complex proteins. Proteins associated with vesicles (v-SNAREs) are essential components of the exocytotic process. In this study, we assessed the functional significance of synaptobrevin, a SNARE protein, and cystatin, a cysteine protease inhibitor to blood feeding success, in the lone star tick, Amblyomma americanum, using in vivo RNA interference. In separate experiments, tick salivary cystatin and synpatobrevin genes were silenced by injecting adult ticks with 500 ng of dsRNA complementing each gene sequence. Silencing was demonstrated by reduced transcript in midguts and salivary glands. Additionally, disrupting expression of cystatin and synaptobrevin by RNAi reduced the ability of ticks to feed successfully, as demonstrated by feeding inhibition and reduced engorgement weights. Moreover, normal ticks exposed to a rabbit previously exposed to cystatin-silenced ticks exhibited significant resistance to tick feeding. Based on these findings, ticks appear to skillfully evade the host immune system by secreting cystatin, which disrupts normal antigen processing in antigen-presenting cells of hosts.


Effect of dietary fiber addition on the content and in vitro bioaccessibility of antioxidants in red raspberry puree.
The aim of the present study was to understand how the addition of pectin (2.5% and 5%) affected the content and bioaccessibility of phenolics in red raspberry puree. The results showed that the concentration of antioxidants in red raspberry puree was reduced with the addition of pectin. Similarly, addition of pectin to red raspberry puree significantly reduced the total phenolic content (15-20%), total antioxidant capacity (18-70%), and total monomeric anthocyanin (25-30%) after in vitro digestion. On the other hand, significant decreases in the bioaccessible amount of cyanidin (41%), cyanidin-3-glucoside (14%), cyanidin-3-rutinoside (17%), pelargonidin 3-glucoside (16%), and peonidin (28%) were observed after the addition of pectin (5% (w/w)) compared to the control (p < 0.05) as analyzed with the HPLC method. According to the LC-MS/MS analysis of red raspberry samples, five flavonoids (rutin, quercetin, kaempferol, myricetin, and phlorizin) and six phenolic acids (gallic acid, caffeic acid, chlorogenic acid, sinapic acid, p-coumaric acid, and ferulic acid) were detected. The effect of in vitro gastrointestinal digestion varied depending on the type of the phenolic compounds. Sinapic acid and phlorizin were not detected at all in the intestinal phase, indicating that they were completely degraded during digestion. The percentage bioaccessibility of gallic acid (49-88%), rutin (6-16%), and quercetin (23-33%) was decreased proportionally with the increase in the pectin content in red raspberry purees (p < 0.05). On the other hand, only 5% pectin addition to red raspberry puree resulted with a significant decrease in the amount of bioaccessible caffeic acid (8% to 5%), kaempferol (24% to 13%), ferulic acid (26% to 10%), and myricetin (91% to 57%) (p < 0.05). Overall, the present study highlighted that incorporation of pectin to red raspberry puree reduced the amount of bioaccessible polyphenols.


Design of a Brønsted acid with two different acidic sites: synthesis and application of aryl phosphinic acid-phosphoric acid as a Brønsted acid catalyst.
A Brønsted acid with two different acidic sites, aryl phosphinic acid-phosphoric acid, has been synthesized. Its catalytic performance was assessed in the hetero-Diels-Alder reaction of aldehyde hydrates with Danishefsky's diene, achieving high reaction efficiency.


Gap-scan deletion analysis of Bacillus subtilis RNase P RNA.
We carried out an exhaustive deletion analysis of Bacillus subtilis ribonuclease P (RNase P) RNA, seeking sequences that are essential for its catalytic activity. A collection of partially deleted RNase P RNA genes was used to construct templates for synthesis, by in vitro transcription, of circularly permuted RNA molecules that lack various wild-type sequences. The mutant RNAs were assayed for catalytic activity in vitro, using a precursor of B. subtilis tRNAAsp as a substrate. Gap-scan deletion analysis revealed that most of the RNase P RNA sequence is important for activity; only two substantive deletions did not dramatically inhibit pre-tRNA processing in vitro. One part of the molecule (nucleotides 225-270) seemed particularly sensitive to deletion, but considering a collection of mutants with overlapping deletion gaps, it was possible to remove every residue in the RNase P RNA without completely abolishing its catalytic activity. Thus, the catalytic mechanism of RNase P does not depend absolutely on a single, particular nucleotide or local sequence for activity.


Antispasmodic effects and composition of the essential oils from two South American chemotypes of Lippia alba.
Lippia alba (Mill.) N. E. Brown (Verbenaceae) is an aromatic species used in Central and South America as eupeptic for indigestion. In Argentina, it is used by the "criollos" from the Chaco province. There are several chemotypes which differ in the chemical composition of the essential oils. Nowadays, it is experimentally cultivated in some countries of the region, including Argentina. To compare the chemical composition and pharmacology of the essential oils from two chemotypes: "citral" (CEO) and "linalool" (LEO), in isolated rat duodenum and ileum. Contractile concentration-response curves (CRC) of acetylcholine (ACh) and calcium in 40mM K(+)-medium (Ca(2+)-CRC) were done in isolated intestine portions, in the absence and presence of CEO or LEO at different concentrations. Likewise verapamil, CEO and LEO induced a non-competitive inhibition of the ACh-CRC, with IC50 of 7.0±0.3mg CEO/mL and 37.2±4.2mg LEO/mL. l-NAME, a NO-synthase blocker, increased the IC50 of CEO to 26.1±8.7mg CEO/mL. Likewise verapamil, CEO and LEO non-competitively inhibited the Ca(2+)-CRC, with IC50 of 6.3±1.7mg CEO/mL, 7.0±2.5mg LEO/mL and 0.24±0.04mg verapamil/mL (pIC50: 6.28). CEO was proved to possess limonene, neral, geranial and (-)-carvone as the major components, while LEO was rich in linalool. Results suggest that CEO has five times more potency than LEO to inhibit muscarinic contractions. The essential oils of both chemotypes interfered with the Ca(2+)-influx, but with an IC50 about 28 times higher than that of verapamil. Moreover, CEO partially stimulated the NO production. These results show the medicinal usefulness of both Lippia alba chemotypes, thus validating its traditional use, potency and mechanism of action.


A Hybrid Teaching Method for Undergraduate Biomechanics Lab.
The main goal for this work was to provide information as to the possibilities of creating an online or hybrid option for an upper-level biomechanics laboratory that is in keeping with course goals. Conversion of the laboratory modules for online use was described with detailed setup and learning goals. The lecture portions and most labs could be easily converted to online-only options. Some of the other labs could be offered as part of a hybrid delivery method with reasons for what these labs could provide in-person students. Options are also given so that the course can be made completely online if needed. Troubleshooting of mechanical experiments is lost with a completely online presentation; however, experimental design and many other biomechanical techniques are maintained with the online environment.


Eight weeks of a lower limb resistance training protocol and gait performance in patients with symptomatic mild to moderate knee osteoarthritis.
The role of strengthening the lower limbs to optimize the biomechanics of the hip, knee and ankle during walking in patients with knee osteoarthritis, is still unclear. This study aimed to analyse the walking biomechanics of individuals with symptomatic mild to moderate knee osteoarthritis before and after a simplified lower limb resistance training protocol, focused on knee joint exercises with individualized load. Forty-one patients with symptomatic and radiographic mild to moderate knee osteoarthritis underwent 3D gait analysis pre-post 8 weeks lower limb resistance training protocol performed 3 times a week. Parameters investigated were spatiotemporal, sagittal range of motion, flexion and extension minimum and maximum values, power and moment of hip, knee and ankle, as well as self-reported pain and physical function by the Western Ontario MacMaster University Osteoarthritis Index. Paired t test, Wilcoxon, Spearman's correlation and a logistic model were used for statistical analysis, with p < 0.05. Pain improvement more than 2 points was considered clinically relevant. The effect size (ES) was calculated using Cohen's d. Post protocol walking speed increased 6.7% (ES: 0.711), cadence 3.7% (ES: 0.655), stride length 2.6% (ES: 0.542), and double support time reduced 6.9% (ES:0.459). It was also observed a significant increase in one maximum repetition test for legpress 46%, knee extension 23% and knee flexion chair 27% (p < 0.001). Patients reported a 62.5% reduction in pain (ES:1.518) and 64.9% improvement in physical function (ES:1.376). 82% of the patients presented more than 2 points improvement in pain. No evidence of strong correlations between pain, strength gains and gait parameters were found. There was a significant and clinical improvement of spatiotemporal gait parameters, pain, physical function, and strength after 8-week lower limb resistance training protocol. Patients who had a clinically relevant pain improvement presented better gait performance.


[Emergency response management near the tracks of the public railway network: special aspects of missions connected with the German national railway system].
Emergency response management and rescue operations concerning the railway network in Germany need special attention and implementation in several ways. The emergency response concerning the German national railway network managed by Deutsche Bahn AG is subject to various rules and regulations which have to be followed precisely. Only by following these rules and procedures is the safety of all emergency staff at the scene ensured. The German national railway network (Deutsche Bahn AG) provides its own emergency response control center, which specializes in managing its response to emergencies and dispatches an emergency response manager to the scene. This person serves as the primary Deutsche Bahn AG representative at the scene and is the only person who is allowed to earth the railway electrical power lines. This article will discuss different emergency situations concerning railway accidents and the emergency medical response to them based on a near collision with a high speed train during a rescue mission close to the railway track. Injury to personnel could only be avoided by chance and luck. The dangers and risks for rescue staff are specified. Furthermore, the article details practical guidelines for rescue operations around the German national railway track system.


Resolution of the fluorescence equilibrium unfolding profile of trp aporepressor using single tryptophan mutants.
Single tryptophan mutants of the trp aporepressor, tryptophan 19-->phenylalanine (W19F) and tryptophan 99-->phenylalanine (W99F), were used in this study to resolve the individual steady-state and time-resolved fluorescence urea unfolding profiles of the two tryptophan residues in this highly intertwined, dimeric protein. The wild-type protein exhibits a large increase in fluorescence intensity and lifetime, as well as a large red shift in the steady-state fluorescence emission spectrum, upon unfolding by urea (Lane, A.N. & Jardetsky, O., 1987, Eur. J. Biochem. 164, 389-396; Gittelman, M.S. & Matthews, C.R., 1990, Biochemistry 29, 7011-7020; Fernando, T. & Royer, C.A., 1992, Biochemistry 31, 6683-6691). Unfolding of the W19F mutant demonstrated that Trp 99 undergoes a large increase in intensity and a red shift upon exposure to solvent. Lifetime studies revealed that the contribution of the dominant 0.5-ns component of this tryptophan tends toward zero with increasing urea, whereas the longer lifetime components increase in importance. This lifting of the quenching of Trp 99 may be due to disruption of the interaction between the two subunits upon denaturation, which abolishes the interaction of Trp 99 on one subunit with the amide quenching group of Asn 32 on the other subunit (Royer, C.A., 1992, Biophys. J. 63, 741-750). On the other hand, Trp 19 is quenched in response to unfolding in the W99F mutant. Exposure to solvent of Trp 19, which is buried at the hydrophobic dimer interface in the native protein, results in a large red shift of the average steady-state emission.(ABSTRACT TRUNCATED AT 250 WORDS)


Genomic organization and comparative chromosome mapping of the U1 snRNA gene in cichlid fish, with an emphasis in Oreochromis niloticus.
To better understand genomic and chromosomal organization and evolutionary patterns of the U1 snRNA gene in cichlid fish, the gene was cytogenetically mapped and comparatively analyzed in 19 species belonging to several clades of the group. Moreover, the distribution and organization of U1 snRNA gene was analyzed in the Oreochromis niloticus genome. The results indicated high conservation of one chromosomal cluster of U1 snRNA in the African, Asian, and South American species, with few variations in the chromosomal position of the clusters in the South American species. The genomic analysis of U1 revealed a distinct scenario from that observed under the cytogenetic mapping. An enrichment of the U1 gene on linkage group (LG) 14 was observed that did not correspond to the same chromosome that harbors the U1 cluster identified by cytogenetic mapping. Moreover, it was revealed that the presence of several distinct transposable elements in the U1 gene flanking regions could be involved in the spreading of this sequence, but the generation of new, large snRNA clusters (detectable by fluorescent in situ hybridization, FISH) is apparently hampered. These results contribute to the understanding of multigene families' evolution and reinforce the utility of integrative analysis and the use of cytogenetic and bioinformatic methods to address the genomic and chromosomal evolutionary patterns of repeated DNAs among vertebrates. Moreover, the U1 gene represents a useful new chromosomal marker for cytogenetic studies.


Variability and awareness of obstetric fistula among women of reproductive age in sub-Saharan African countries: A systematic review and meta-analysis.
Obstetric fistula among women of reproductive age is a significant public health issue in developing countries, including Sub-Saharan Africa. However, the pooled awareness of obstetric fistula among women of reproductive age in Sub-Saharan Africa and its variation between countries have not yet been studied. Hence, the review aims to assess variability and awareness of obstetric fistula among women of reproductive age in Sub-Saharan African Countries. Articles were searched using different electronic databases, such as PubMed, Web of science, science direct (Scopus), Google scholar, and HINARI and manual search without regard to publication date. A random-effects model was used to ascertain the pooled prevalence of obstetric fistula awareness among women of reproductive age in Sub-Saharan Africa. Publication bias was checked by using funnel plot and Egger's test at a 5% level of significance. I2 test statistics was performed to evaluate heterogeneity among included studies. In addition, to identify the possible reason for the potential heterogeneity between the studies, sub-group and meta-regression analyses were conducted. A sensitivity analysis was performed to determine the impact of individual research on the overall results. The data were extracted by using Microsoft excel and analyzed using statistical software STATA/SE version 17. A total of 22 studies with 79,693 women of reproductive age were included in this systematic review and meta-analyses. In Sub-Saharan Africa, the pooled prevalence of awareness towards obstetric fistula among women of reproductive age was 40.85% (95% CI: 33.48, 48.22%). Analysis of the subgroups by specific countries revealed significant variation. The highest awareness of obstetric fistula was found among Tanzanian women of reproductive age (61.10%, 95% CI: 55.87-66.33%), whereas the lowest awareness was found in research from the Gambia (12.80%, 95% CI: 12.20-13.40%).The likelihood of obstetric fistula awareness were lower by a factor of 0.424 among studies with sample sizes greater than 3542 (β = -0.424 (95% CI: -0.767 to 0.081), p -value <0.05). According to the current review, there is a low level of awareness about obstetric fistula among women of reproductive age in sub-Saharan Africa, and the results of the sub-group analysis by country showed wide variations. Therefore, we emphasize the need for country-specific public health initiatives to raise awareness about obstetric fistula among women of reproductive age, which could reduce the risk of delayed treatment.


Rhamnolipids and surfactin inhibit the growth or formation of oral bacterial biofilm.
Bacteria survive in various environments by forming biofilms. Bacterial biofilms often cause significant problems to medical instruments and industrial processes. Techniques to inhibit biofilm formation are essential and have wide applications. In this study, we evaluated the ability of two types of biosurfactants (rhamnolipids and surfactin) to inhibit growth and biofilm formation ability of oral pathogenic bacteria such as Aggregatibacter actinomycetemcomitans, Streptococcus mutans, and Streptococcus sanguinis. Rhamnolipids inhibited the growth and biofilm formation ability of all examined oral bacteria. Surfactin showed effective inhibition against S. sanguinis ATCC10556, but lower effects toward A. actinomycetemcomitans Y4 and S. mutans UA159. To corroborate these results, biofilms were observed by scanning electron microscopy (SEM) and confocal microscopy. The observations were largely in concordance with the biofilm assay results. We also attempted to determine the step in the biofilm formation process that was inhibited by biosurfactants. The results clearly demonstrated that rhamnolipids inhibit biofilm formation after the initiation process, however, they do not affect attachment or maturation. Rhamnolipids inhibit oral bacterial growth and biofilm formation by A. actinomycetemcomitans Y4, and may serve as novel oral drug against localized invasive periodontitis.


Clinical decision making and operative approaches to thoracic aortic aneurysms.
The care of the patient with thoracic aneurysms is quite complicated. The decision to treat an aneurysm must be based on the risk of rupture and the patient's life expectancy. The preoperative evaluation must include detailed imaging to allow proper preoperative planning. This is especially important to determine the need for hypothermic circulatory arrest or the potential to treat a descending aneurysm with an endovascular approach. Thorough preoperative preparation and intraoperative care are as important as surgical decision making and meticulous technique. Although significant advances have been made in operative approaches, cerebral and myocardial preservation, and postoperative care, the management of complicated aneurysms of the thoracic aorta is frequently a humbling experience.


Patterns of Occurrence and Marine Mammal Acoustic Behavior in Relation to Navy Sonar Activity Off Jacksonville, Florida.
Passive acoustic data collected from marine autonomous recording units deployed off Jacksonville, FL (from 13 September to 8 October 2009 and 3 December 2009 to 8 January 2010), were analyzed for detection of cetaceans and Navy sonar. Cetaceans detected included Balaenoptera acutorostrata, Eubalaena glacialis, B. borealis, Physeter macrocephalus, blackfish, and delphinids. E. glacialis were detected at shallow and, somewhat unexpectedly, deep sites. P. macrocephalus were characterized by a strong diel pattern. B. acutorostrata showed the strongest relationship between sonar activity and vocal behavior. These results provide a preliminary assessment of cetacean occurrence off Jacksonville and new insights on vocal responses to sonar.


System-size resonance for intracellular and intercellular calcium signaling.
Dynamical behaviors of unidirectionally, linearly coupled as well as isolated calcium subsystems are investigated by taking into account the internal noise resulting from finite system size and thus small numbers of interacting molecules. For an isolated calcium system, the internal noise can induce stochastic oscillations for a steady state close to the Hopf-bifurcation point, and the regularity of those stochastic oscillations depends resonantly on the system size, exhibiting system-size resonance. For the coupled system consisting of two subsystems, the system-size resonance effect observed in the subsystem subject to coupling is significantly amplified due to the nontrivial effects of coupling.


Solenoidal array coils.
New concepts are presented for inherent decoupling of multi-element solenoidal arrays. First, an uneven counter-rotational (UCR) coil is reported in which two counter-rotational sections are wound unevenly, resulting in a quasi-one-peak sensitivity profile with a null-B1 point. Adding a second solenoid element near the null-B1 point forms an inherently-decoupled solenoidal array. Unlike a sandwiched solenoidal array, an UCR solenoidal array allows for signal contribution at the center from both solenoid elements. Second, a double counter-rotational (DCR) coil is presented in which two null-B1 points are formed by having one counter-rotational winding on each side of the coil. Two solenoidal elements can be added to form a solenoidal array. Finally, more solenoid elements can be added to the array provided that the added coil elements are DCR elements. These DCR coil elements can be used as building blocks for more complex solenoidal arrays. These concepts are illustrated using numerical simulations and tested using prototype coils.


Direct linking of metabolism and gene expression in the proline utilization A protein from Escherichia coli.
The control of gene expression by enzymes provides a direct pathway for cells to respond to fluctuations in metabolites and nutrients. One example is the proline utilization A (PutA) protein from Escherichia coli. PutA is a membrane-associated enzyme that catalyzes the oxidation of L: -proline to glutamate using a flavin containing proline dehydrogenase domain and a NAD(+) dependent Delta(1)-pyrroline-5-carboxylate dehydrogenase domain. In some Gram-negative bacteria such as E. coli, PutA is also endowed with a ribbon-helix-helix DNA-binding domain and acts as a transcriptional repressor of the proline utilization genes. PutA switches between transcriptional repressor and enzymatic functions in response to proline availability. Molecular insights into the redox-based mechanism of PutA functional switching from recent studies are reviewed. In addition, new results from cell-based transcription assays are presented which correlate PutA membrane localization with put gene expression levels. General membrane localization of PutA, however, is not sufficient to activate the put genes.


Infiltration patterns in monoclonal plasma cell disorders: correlation of magnetic resonance imaging with matched bone marrow histology.
To investigate how plasma cell infiltration patterns detected by MRI match the plasma cell distribution in bone marrow biopsy. We assessed 50 patients with monoclonal plasma cell disorders of all clinical stages. MRI infiltration pattern was compared with matched BM histology from the same anatomic region. MRI revealed a minimal (n=11, 22%), focal (n=5, 10%), diffuse (n=14, 28%) and mixed (n=20, 40%) infiltration pattern. Diffuse MRI pattern was predominant in smoldering myeloma patients whereas the MRI patterns with "focal component" (i.e. focal and mixed) were most common in symptomatic myeloma (p<0.01). In histology an interstitial (n=13, 26%), nodular (n=23, 46%) and packed marrow (n=14, 28%) was found respectively. All three histological types of infiltration were observed in patients with diffuse and mixed MRI patterns. Minimal MRI pattern was found in all MGUS patients and was associated with an interstitial BM infiltration. In two patients with minimal MRI pattern an extensive micro-nodular BM infiltration was found in histology. Infiltration patterns in MRI represent different histological growth patterns of plasma cells, but the MRI resolution is not sufficient to visualize micro-nodular aggregates of plasma cells.


Recovery from acidification in the Tillingbourne catchment, southern England: catchment description and preliminary results.
Measurements of acid deposition and streamwater chemistry made in 1979-1982 and 1999-2000 are compared for a small, acid-sensitive catchment in Southeast England. The location, geology, soils, vegetation and hydrology of the catchment are described. The catchment is located on an acidic cretaceous sandstone with a low permeability clay sub-stratum. Soils are predominantly podzol and gley, with some mesotrophic peat. The catchment is forested. Mean volume-weighted concentrations in precipitation have changed approximately in proportion to emission changes. SO4(2-) has declined by 61%, H+ by 75%, both NO- and NH4+ by 37% and Cl- by 26%. Changes in wet deposition are greater, sulfate deposition declined by 69%, non-marine SO4(2-) by 73%, H+ deposition by 75%, NO3- and NH4+ by 50% and Cl- by 41%. Sulfate deposition in throughfall, a surrogate for total deposition measurement, has declined by 82% and non-marine SO4(2-) by 86%. Some of these changes are due to alterations in the tree cover and location of the collectors. In 1979-1982, the flux of NO3- and NH4+ in throughfall was less than in rainfall, 7.5 compared with 11.3 kg N ha(-1) year(-1), showing that N uptake by the canopy was greater than dry deposition of these species. However, in 1999-2000, the throughfall flux of N was greater than rainfall, 19.6 compared to 5.7 kg N ha year(-1), indicating that canopy uptake is not occurring to the same extent. Surface water was sampled at the same locations in the catchment during the two periods. At the catchment exit, mean pH increased, from 3.93 to 4.21 mg l(-1), and SO4(2-) declined from 20.2 to 16.7 mg l(-1) (18%). The decrease in SO4(2-) is much less than the reduction in deposition, suggesting that the predicted recovery is being delayed by release of sulfur from the soil. In contrast, NO3- concentrations in the catchment waters increased from 0.22 to 0.52 mg N l(-1) (133%) despite the reduction in N deposition. NH4+ concentrations were low during both study periods. It is concluded that recovery from acidification is probably occurring, but is possibly being delayed by desorption of soil S. The catchment is also showing signs of increasing N saturation, despite a reduction in N inputs.


Adult testicular torsion.
Testicular torsion in adulthood is thought to be relatively unusual. We compared a series of men 21 years old or older with testicular torsion with a concurrent series of younger patients with torsion. We reviewed the medical records of patients admitted with testicular torsion in a 9-year period to hospitals affiliated with our institution. Data included patient demographics, history, physical findings, radiographic results if any, operative findings and outcome (testicular salvage versus loss). The charts of 48 patients were evaluated. Excluded from study was a neonate with torsion and 3 males who underwent delayed surgery for presumed missed torsion. Of the remaining 44 patients we compared 17 who were 21 years old or older (range 21 to 34) with 27 younger than 21 (range 8 to 20). The salvage rate differed in the 2 age groups with 70.3% of testes salvaged in the younger group versus only 41% in the older group. A factor affecting salvage in each group was time to presentation. In the older age group patients in whom the testis was lost had a significantly higher mean delay in presentation than those in whom it was salvaged (102 versus 11 hours). A similar pattern was noted in the younger group with a mean time to presentation of 108 and 6.5 hours in those with testicular loss and salvage, respectively. Mean time between presentation and operation was 7.1 hours in the older and 4.8 in the younger group, which was not statistically different. A significant difference was noted in the degree of spermatic cord twisting. The cord was twisted a mean of 585 degrees in the adults versus 431 in the younger group. Testicular torsion in adults was more common in our series than expected. Salvage of the affected testis was better in younger patients, presumably due to less twisting of the cord.


Correlation of macroscopic aggregation behavior and microscopic adhesion properties of bacteria strains using a dimensionless Tabor's parameter.
Macroscopic adhesion-aggregation, floc formation, and subsequent transportation of microorganisms in porous media are closely related to the microscopic behavior and properties of individual cells. The classical Tabor's parameter in colloidal science is modified to correlate the macroscopic aggregation and microscopic adhesion properties of microorganisms. Seven bacterial strains relevant to wastewater treatment and bioremediation were characterized in terms of their macroscopic aggregation index (AI) using an optical method, and their microscopic coupled adhesion and deformation properties using atomic force microscopy (AFM). Single cells were indented to measure the range and magnitude of the repulsive-attractive intersurface forces, elastic modulus, thickness and density of the cellular surface substances (CSS). The strong correlation suggests that cost and time effective microscopic AFM characterization is capable of making reliable prediction of macroscopic behavior.


Silicone cap osteoarthroplasty for temporomandibular joint ankylosis, with a kinesiologic study.
In spite of the small experiences, silicone capping with gap osteoarthroplasty in high level is thought to be one of the valuable procedures for TMJ ankylosis. In the view of kinesiology, a normal joint cannot be reconstructed, because the mandibular movement in ankylosis is far from the normals.


Clinical complications in children with false-negative results in cystic fibrosis newborn screening.
To present signs and symptoms and clinical course in cystic fibrosis patients with false-negative newborn screening (CF NBS). All children presented in this paper were covered by CF NBS. The group of 1.869.246 newborns was screened in the Institute of Mother and Child in Warsaw within a period of 01.01.1999 - 31.05.2019. Screening protocols evolved over time from IRT/IRT to IRT/DNA/EGA. The authors identified 11 patients with false-negative NBS, in whom CF was diagnosed based on clinical symptoms or the examination of siblings with positive CF NBS. In the study group, the diagnosis was made significantly later in comparison to positive CF NBS patients ranging from 2 months to 15 years of age. CF NBS strategy does not significantly affect the sensitivity of the screening. In the presence of clinical symptoms, additional diagnostics must be implemented, in spite of the negative screening results. At first, the sweat test should be conducted, followed by a DNA analysis of the most common mutations in the given population. The diagnostic process requires searching for CFTR mutations not typically associated with a high chloride concentration in sweat. Repetition of sweat chloride concentration enables the diagnosis in children whose initial chloride values in sweat are borderline, and no CF-causing mutations are detected. In strong clinical indications, the extension of DNA analysis (EGA) is recommended in order to identify rare CF variants. In children with meconium ileus, genetic analysis is mandatory.


The use of an eccentric chainring during an outdoor 1 km all-out cycling test.
This study assessed whether an eccentric chainring that increases crank arm length at the downstroke and decreases it during the upstroke improves performance in a track cycling event: the 1000m time trial. It also determined whether selected physical and physiological variables and the velocity profile are associated with eccentric chainring performance. Twelve cyclists performed an outdoor 1000m time trial on a 333m banked, cement-surfaced track using two different chainrings, round and eccentric, in randomised order. The important findings of this study were that (1) performance did not significantly differ between chainrings; (2) neither the physiological variables (lactate and heart rate) nor the velocity profile (lap times) were affected by use of the eccentric design; (3) when time was saved with the eccentric chainring, it was significantly correlated with estimated lower limb muscle volume (r=-0.605), circumference (r=-0.739), estimated calf muscle volume (r=-0.772) and cross-sectional area (r=-0.745). Moreover, estimated lower limb muscle volume (r=-0.703), estimated calf muscle volume (r=-0.772) and cross-sectional area (r=-0.871) significantly predicted performance with the eccentric chainring. The physical variables associated with eccentric chainring performance were muscle anthropometric parameters. We have interpreted our results cautiously and suggest that the subjects who had greater lower limb muscle volume and greater calf muscle volume, seem to have had a significant advantage in performing with the eccentric chainring. Further testing with track specialists performing at national or international level would be helpful to define the maximal possibilities of this chainring.


Insulin-like growth factor-1 increases activity and surface levels of the GLAST subtype of glutamate transporter.
Glutamate uptake systems are the primary mechanisms involved in excitatory amino acids clearance, their regulation is extremely important for proper neuronal function. Using cultured chick cerebellar Bergmann glia cells, the involvement of receptor tyrosine kinases in glutamate uptake was studied. Treatment of the cells with insulin-like growth factor-1 but not epidermal growth factor or neuronal growth factor, induces a dose and time dependent increase in [(3)H]-D-aspartate uptake that is sensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase. Saturation experiments show a significant increase in V(max), suggesting that the amount of transporter molecules at the cell membrane under insulin-like growth factor-1 treatment is augmented. This interpretation was strengthen by equilibrium-binding experiments and by the fact that the increase in [(3)H]-D-aspartate uptake was not dependent on protein synthesis. The present studies suggest that insulin-like growth factor-1 signaling is involved in modulation of glutamate transporter cell surface expression.


Effects of caffeine on pyrimidine biosynthesis and 5-phosphoribosyl 1-pyrophosphate metabolism in Chinese hamster cells.
Caffeine, at doses which enhance killing by UV light, inhibits the biosynthesis of pyrimidines in Chinese hamster ovary cells (K1) in culture. This inhibition was measured as a decrease in [14C]UTP and [14C]CTP accumulation after a 3-h incubation with [14C]aspartate or [14C]orotate and a similar decrease in Urd-A cells (which lack the first three enzymes of the pathway) using [14C]orotate as substrate. There was no such inhibition in Urd-C cells (which lack the last two enzymes) using [14C]aspartate as substrate and measuring accumulation of orotate. There is some inhibition of the fifth enzyme of the pathway, orotate phosphoribosyltransferase by caffeine in vitro and this is most striking at low 5-phosphoribosyl 1-pyrophosphate concentrations. The level of 5-phosphoribosyl 1-pyrophosphate is decreased in Chinese hamster ovary K1 cells by about 20% after 3 h and by about 70% after 16 h in the presence of caffeine. It is suggested that inhibition of pyrimidine biosynthesis by caffeine over a 16-h period may be due mainly to decreased intracellular 5-phosphoribosyl 1-pyrophosphate levels but that in the decrease in pyrimidine accumulation over 3 h, direct inhibition of orotate phosphoribosyltransferase by caffeine may also play a role.


Ectopic activation of the canonical wnt signaling pathway affects ectodermal patterning along the primary axis during larval development in the anthozoan Nematostella vectensis.
The primary axis of cnidarians runs from the oral pole to the apical tuft and defines the major body axis of both the planula larva and adult polyp. In the anthozoan cnidarian Nematostella vectensis, the primary oral-aboral (O-Ab) axis first develops during the early embryonic stage. Here, we present evidence that pharmaceutical activators of canonical wnt signaling affect molecular patterning along the primary axis of Nematostella. Although not overtly morphologically complex, molecular investigations in Nematostella reveal that the O-Ab axis is demarcated by the expression of differentially localized signaling molecules and transcription factors that may serve roles in establishing distinct ectodermal domains. We have further characterized the larval epithelium by determining the position of a nested set of molecular boundaries, utilizing several newly characterized as well as previously reported epithelial markers along the primary axis. We have assayed shifts in their position in control embryos and in embryos treated with the pharmacological agents alsterpaullone and azakenpaullone, Gsk3β inhibitors that act as canonical wnt agonists, and the Wnt antagonist iCRT14, following gastrulation. Agonist drug treatments result in an absence of aboral markers, a shift in the expression boundaries of oral markers toward the aboral pole, and changes in the position of differentially localized populations of neurons in a dose-dependent manner, while antagonist treatment had the opposite effect. These experiments are consistent with canonical wnt signaling playing a role in an orally localized wnt signaling center. These findings suggest that in Nematostella, wnt signaling mediates O-Ab ectodermal patterning across a surprisingly complex epithelium in planula stages following gastrulation in addition to previously described roles for the wnt signaling pathway in endomesoderm specification during gastrulation and overall animal-vegetal patterning at earlier stages of anthozoan development.


Survival Risk Analysis of Small Cell Lung Cancer Patients with Pre-Existing Type 2 Diabetes Mellitus: A Single-Center Retrospective Cohort Study.
We aimed to investigate the clinicopathological characteristics and survival risk factors in small cell lung cancer (SCLC) patients with preexisting type 2 diabetes mellitus (preDM). All patients with SCLC admitted to our hospital between January 2013 and August 2018 were followed up until August 2020 and retrospectively analyzed. Clinical characteristics of SCLC patients with and without preDM were extracted. Cox proportional hazards models were conducted to identify potential independent prognostic factors. Of 628 eligible individuals, 88 individuals had preDM. preDM was independently significantly associated with distant metastasis in all SCLC patients (p =0.016, OR=1.80, 95% CI 1.11-2.91), while preDM did not affect the outcome of SCLC patients (p=0.803, HR=1.04, 95% CI 0.79-1.36) by multivariate analysis. In the preDM group, the median overall survival (OS) was shorter in the insulin group than in the non insulin group (13.93 months versus 21.77 months, p=0.024). Multivariate analysis identified that insulin treatment was an independent unfavorable factor associated with OS (p =0.009, HR=2.10, 95% CI 1.19-3.64). In addition, poorer performance status (PS) and liver metastasis were also independent unfavorable prognostic factors (all p<0.01), while thoracic therapy significantly improved OS and decreased mortality risk in diabetic patients with SCLC (p<0.05). preDM may promote distant metastasis of SCLC while it is insulin therapy and not preDM which adversely affects the prognosis of SCLC patients. These findings indicate that enhancing blood glucose control and reducing insulin analog use may be essential to the improvement of the long-term survival of the diabetic population with SCLC.


Multiple keratin granulomata: A potential histologic clue to cutaneous squamous cell carcinoma responding to programmed cell death protein 1 inhibitor therapy.
We present histologic features of a locally advanced cutaneous squamous cell carcinoma (cSCC) treated with the programmed cell death protein-1 (PD-1) antagonist, pembrolizumab, with a partial response. This contributes to a growing body of literature supporting the efficacy of pembrolizumab in treatment of surgically unresectable cSCC. We also provide a detailed description of the histologic features, particularly keratin granulomata with adjacent lymphocytic aggregates and fibrosis, observed in cSCC under treatment with a PD-1 antagonist.


Impact of stimulus frequency and recording electrode on electrocochleography in Hybrid cochlear implant users.
This report explores the impact of recording electrode position and stimulus frequency on intracochlear electrocochleography (ECoG) responses recorded from six Nucleus L24 Hybrid CI users. Acoustic tone bursts (250 Hz, 500 Hz, 750 Hz, and 1000 Hz) were presented to the implanted ear via an insert earphone. Recordings were obtained from intracochlear electrodes 6 (most basal), 8, 10, 12, 14, 16, 18, 20, and 22 (most apical). Responses to condensation and rarefaction stimuli were subtracted from one another to emphasize hair cell responses (CM/DIF) and added to one another to emphasize neural responses (ANN/SUM). For a fixed stimulus frequency, the CM/DIF and ANN/SUM magnitudes increased as the recording electrode moved apically. For a fixed recording electrode, as the stimulus frequency was lowered, response magnitudes increased. The CM/DIF and ANN/SUM response phase were generally stable across recording electrodes, although substantial phase shifts were noted for a few conditions. Given the recent interest in ECoG for assessing peripheral auditory function in CI users, the impact of stimulus frequency and recording electrode position on response magnitude should be considered. Results suggest optimal ECoG responses are obtained using the most apical recording electrode and a low frequency acoustic stimulus (250 Hz or 500 Hz).


Population-Based Opioid Prescribing and Overdose Deaths in the USA: an Observational Study.
Rising opioid-related death rates have prompted reductions of opioid prescribing, yet limited data exist on population-level associations between opioid prescribing and opioid-related deaths. To evaluate population-level associations between five opioid prescribing measures and opioid-related deaths. An ecological panel analysis was performed using linear regression models with year and commuting zone fixed effects. People ≥10 years aggregated into 886 commuting zones, which are geographic regions collectively comprising the entire USA. Annual opioid prescriptions were measured with IQVIA Real World Longitudinal Prescription Data including 76.5% (2009) to 90.0% (2017) of US prescriptions. Prescription measures included opioid prescriptions per capita, percent of population with ≥1 opioid prescription, percent with high-dose prescription, percent with long-term prescription, and percent with opioid prescriptions from ≥3 prescribers. Outcomes were age- and sex-standardized associations of change in opioid prescriptions with change in deaths involving any opioids, synthetics other than methadone, heroin but not synthetics or methadone, and prescription opioids, but not other opioids. Change in total regional opioid-related deaths was positively correlated with change in regional opioid prescriptions per capita (β=.110, p<.001), percent with ≥1 opioid prescription (β=.100, p=.001), and percent with high-dose prescription (β=.081, p<.001). Change in total regional deaths involving prescription opioids was positively correlated with change in all five opioid prescribing measures. Conversely, change in total regional deaths involving synthetic opioids was negatively correlated with change in percent with long-term opioid prescriptions and percent with ≥3 prescribers, but not for persons ≥45 years. Change in total regional deaths in heroin was not associated with change in any prescription measure. Regional decreases in opioid prescriptions were associated with declines in overdose deaths involving prescription opioids, but were also associated with increases in deaths involving synthetic opioids (primarily fentanyl). Individual-level inferences are limited by the ecological nature of the analysis.


Gender factor in longer P100 latency of elderly persons.
Monocular pattern-shift visual evoked potentials (PSVEPs) were obtained in 26 neurologically and ophthalmologically normal elderly community volunteers (mean age 59.4, males 15, females 11), and compared with similarly obtained data in 26 sex-matched young subjects (mean age 28.1). Elderly males were age-matched with elderly females, and young males were age-matched with young females. Data analyses at both the midoccipital-linked ears and midoccipital-midcentral derivations revealed that the combined-eye mean P100 latency in the elderly as a whole was significantly longer than the young sex-matched controls (P less than 0.02). However, the latency in the elderly males was not significantly different from that of sex-matched young males, or age-matched elderly females. The latency in young female subjects, on the other hand, was significantly shorter both when compared to that of age-matched young males (P less than 0.01) and sex-matched elderly females (P less than 0.01). The differences in other PSVEP variables, namely, interocular P100 latency differences, P100 amplitudes and interocular P100 amplitude ratios were not significant between the groups and subgroups studied. It is concluded that females account for the major contribution towards the longer P100 latency in the elderly.


Comparison of the intracuff pressures of three different tracheostomy tubes.
The purpose of this study was to compare the cuff pressures of three tracheostomy tubes, MERA sofit CLEAR, Blue Line Tracheostomy Tube, and Tracheosoft. Each tracheostomy tube with an internal diameter of 7.0 mm was put into a plastic column. The cuff was then inflated with air to seal the column, and the column was filled with water. The air in the cuff was withdrawn gradually and the cuff pressure at the point of water leakage was measured. Six columns of different size were used. In columns with an internal diameter of 18-21 mm, the water leakage pressure was lower in the following order: MERA sofit CLEAR < Tracheosoft < or = Blue Line Tracheostomy Tube. A mongrel dog was tracheotomized, and each tracheostomy tube with an internal diameter of 7.5 mm was intubated. The cuff air was increased by 1 ml from 4 ml to 10 ml, and the intracuff pressure was then measured. The intracaff pressure of the Blue Line Tracheostomy Tube was the highest at the same cuff volume, and that of the Tracheosoft was next. Based on these results, the MERA sofit CLEAR was found to maintain most safely the lowest intracuff pressure to seal the trachea among the three tracheostomy tubes tested.


Glutathione and cysteine enhance and diethylmaleate reduces thiabendazole teratogenicity in mice.
The effects of cysteine (CYS), glutathione (GSH) and diethylmaleate (DM) on the teratogenicity of thiabendazole (TBZ) were investigated. On day 9 of gestation mice were given ip a dose of 0, 50 or 100 mg CYS/kg body weight, or 0, 400 or 800 mg GSH/kg, or 0, 0.05, 0.10, 0.15 or 0.60 DM/kg. One hr later they were dosed orally with 0, 250, 500 or 1000 mg TBZ/kg. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. The number of malformed foetuses was increased in mice pretreated with CYS or GSH and was decreased in those pretreated with DM, in comparison with numbers in the corresponding group treated with TBZ alone GSH pretreatment enlarged the area under the curve (AUC) of TBZ and 5-hydroxyTBZ, a representative metabolite, in foetal tissue. DM pretreatment reduced the AUC of TBZ and 5-hydroxyTBZ.


Protecting innovation in bioinformatics and in-silico biology.
Commercial success or failure of innovation in bioinformatics and in-silico biology requires the appropriate use of legal tools for protecting and exploiting intellectual property. These tools include patents, copyrights, trademarks, design rights, and limiting information in the form of 'trade secrets'. Potentially patentable components of bioinformatics programmes include lines of code, algorithms, data content, data structure and user interfaces. In both the US and the European Union, copyright protection is granted for software as a literary work, and most other major industrial countries have adopted similar rules. Nonetheless, the grant of software patents remains controversial and is being challenged in some countries. Current debate extends to aspects such as whether patents can claim not only the apparatus and methods but also the data signals and/or products, such as a CD-ROM, on which the programme is stored. The patentability of substances discovered using in-silico methods is a separate debate that is unlikely to be resolved in the near future.


Rhythmicity of torpor in a marsupial hibernator, the mountain pygmy-possum (Burramys parvus), under natural and laboratory conditions.
Circadian rhythms have been observed in most mammals, but their importance and function remain controversial with respect to daily cycles during hibernation. We investigated the timing of arousals from and entries into hibernation for both free-living and captive mountain pygmy-possums (Burramys parvus). Under both natural and laboratory conditions most arousals and entries were entrained with the light-dark cycle. Entries occurred mainly during the night and arousals preferably around dusk, which coincides with the onset of the normal activity phase for the nocturnal pygmy-possums. This entrainment prevailed throughout the hibernation season although only the laboratory animals were constantly subjected to photoperiodic stimuli, whereas under natural conditions hibernacula are shielded from photic cues and diurnal temperature fluctuations. Nevertheless, possums left their hibernacula frequently throughout winter and were occasionally trapped close to the snow surface suggesting that during the periods of post-arousal normothermia they can be exposed to environmental stimuli. It thus appears that the synchronisation with the photocycle was governed by a temperature-compensated circadian clock which was reset periodically during short activity periods. For the mountain pygmy-possum, entrainment with the photocycle probably has two functions: 1. Entrainment ensures that foraging bouts during the hibernation season remain synchronised with the dark phase. 2. Information about the prevailing climatic conditions sampled during short activity periods enables them to time final spring emergence from hibernation when snow melt begins and ensures that the breeding season can commence as early as possible.


Contemporary transatlantic developments concerning compelled medical treatment of pregnant women.
This paper had identified a contemporary ethicolegal dilemma concerning the circumstances, if any, in which a pregnant woman's refusal of medical treatment may be judicially overridden either in her interests or those of the unborn child. On the one hand, the obstetrician will be concerned about the interests of both his patients in potentially life-threatening situations when they can be protected by what might be regarded as relatively straightforward procedures and where to fail to take those steps might expose the practitioner (at least outside New Zealand where its accident compensation legislation has impact in this regard) to allegations of negligence. On the other hand, the imposition of treatment in these circumstances will necessarily interfere with the woman's rights of autonomy and self-determination. In such cases also, the conduct of medical procedures in the face of an express prohibition by the woman may give rise to liability for battery. (In New Zealand, such a potential liability would not, in the writer's view, be affected by the prohibition on proceedings for damages for medical misadventure as contained in the Accident Rehabilitation and Compensation Insurance Act 1992.) At the heart of an analysis of this issue is the status of the fetus as it is the fact of the woman patient's pregnancy which distinguishes the cases discussed in this paper from others in which the Courts have had to deal with refusals of treatment by those competent to do so. In regard to this aspect, the approach of the Courts in various jurisdictions has arguably been confused and contradictory.(ABSTRACT TRUNCATED AT 250 WORDS)


Excellent rates of recanalization and good functional outcome after stent-based thrombectomy for acute middle cerebral artery occlusion. Is it time for a paradigm shift?
The natural history of untreated acute middle cerebral artery (MCA) occlusion is poor, with high rates of mortality (5-33%) and severe long-term disability (40-80% of survivors), despite therapy with intravenous tissue plasminogen activator. We analyzed outcomes in 31 consecutive patients with major ischemic stroke due to acute proximal MCA occlusion who were treated at the Hadassah-Hebrew University Medical Center from February 2010 to October 2012 by endovascular means, using the Solitaire stent (Covidien, Irvine, CA, USA) as a thrombectomy device. Patients had a mean age of 63.3±16.2 years (range, 26-92). The admission National Institutes of Health Stroke Scale score was 19.5±4.3 (median 20). Mean time from symptom onset to femoral artery puncture was 3.8±1.1 hours (median 4 hours). Mean time to recanalization was 46.9±11.1 minutes. Successful recanalization by means of stent-based thrombectomy alone was achieved in 90% of cases and reached 100% after combining definitive stent implantation in three patients. There was no arterial rupture or subarachnoid hemorrhage. Hemorrhagic transformation developed in seven patients (23%), but was symptomatic in only one. Post-procedure CT scan or MRI demonstrated >90% sparing of cortex at risk in all patients. Functional outcome at 90 day follow-up was modified Rankin Score 0-2 in 77% of all patients and 88% of patients younger than 80 years. Three patients (10%) died during hospitalization due to mesenteric event, sepsis, or pulmonary embolism. Our experience suggests that stent-based thrombectomy in selected patients for acute MCA occlusions is safe, very effective in terms of arterial recanalization, and associated with improved neurological outcome. If validated by other groups, endovascular treatment may be proposed as the therapy of choice for MCA occlusion.


Situational factors that influence overreaching on a ladder during a gutter clearing task among older adults.
Ladder falls from overreaching are a problem in older adults. Evidence suggests ladder use behavior to be dependent on interfacing user and environmental circumstances (i.e. situational factors). This study investigates the effects of situational factors (remaining debris, ladder position, time into task, hand dominant reach, reaching disposition) on reaching during a gutter clearing task on a ladder in 104 older adults. Reaching was quantified as the maximum lateral center of pressure (COP) displacement from the ladder's center. A reach was classified as an overreach when the COP displaced outside the ladder width, indicative of a ladder tip. Reaching disposition, remaining debris, ladder position, and the interaction of reaching disposition and remaining debris predicted 20% of the reaching variability during the ladder task. Overreaching was observed in 40% of participants accounting for 13% of all extended reaches (beyond ladder). This work can guide interventions on mitigating overreaching and improving ladder safety.


Provision of domiciliary dental service to residential aged care facilities: A 3-year descriptive summary.
This cross-sectional descriptive study described the oral health status and types of domiciliary dental treatment received by residents living in residential care after an oral health assessment (OHAT). Twenty-one facilities were recruited where consenting participants received OHAT followed by a referral for further domiciliary dental treatments. Data were captured and stored as Reach-OHT database where 2017-2019 data were analyzed. Overall, 88% of residents consented. 69.1% were referred for treatment after completion of OHAT. More than half had one or more caries; 40% showed sign of periodontal disease; a higher proportion of dentate participants had an unsatisfactory level of oral cleanliness. Of those received domiciliary dental treatment, diagnostic and preventive service was the combination most frequently provided. These comprised an average of 71.9% of total treatment provided across the 3-year period. This study contributes to the understanding and knowledge around the provision of domiciliary dental services in residential care. A large number of older people in residential care can be assessed and treated through a domiciliary service pathway. As the vast majority of services provided were diagnostic, preventive, and restorative care, the feasibility of utilizing the skillset of the entire dental team should be explored.


Foliar zinc reduced Cd accumulation in grains by inhibiting Cd mobility in the xylem and increasing Cd retention ability in roots1.
Cadmium (Cd) pollution endangers the safe utilization of paddy soils, and foliar zinc (Zn) can reduce the toxic effects of Cd. However, little is known about the effects of foliar Zn application on the transport and immobilization of Cd in key rice tissues and the physiological state of rice plants. A pot experiment was conducted to explore the effects of spraying 0.2% and 0.4% Zn (ZnSO4) during the early grain-filling stage on Cd transport in rice, photosynthesis, glutathione (GSH) levels, Cd concentrations in xylem sap, and the expression of Zn transporter genes. The results showed that grain Cd concentrations in the 0.2% Zn and 0.4% Zn treatments were 24% and 31% lower, respectively, than those of the control treatments at maturity. Compared with the control treatments, the 0.4% Zn treatment increased Cd by 60%, 69%, 23%, and 22% in husks, rachises, first internodes, and roots, respectively. Application of Zn reduced xylem Cd content by up to 26% and downregulated transporter genes (OSZIP12, OSZIP4, and OSZIP7a) in flag leaves. Foliar Zn increased Cd bioaccumulation in roots while decreasing Cd bioaccumulation in grains. Zn reduced GSH concentration in flag leaves and stems, inhibiting photosynthesis (intercellular CO2 concentration, transpiration rate). Taken together, foliar Zn can reduce the expression of Zn transporter genes and the mobility of Cd in the xylem, promoting the fixation of Cd in husks, rachises, first internodes, and roots, ultimately reducing Cd concentration in rice grains.


The role of cardiac pericytes in health and disease: therapeutic targets for myocardial infarction.
Millions of cardiomyocytes die immediately after myocardial infarction, regardless of whether the culprit coronary artery undergoes prompt revascularization. Residual ischaemia in the peri-infarct border zone causes further cardiomyocyte damage, resulting in a progressive decline in contractile function. To date, no treatment has succeeded in increasing the vascularization of the infarcted heart. In the past decade, new approaches that can target the heart's highly plastic perivascular niche have been proposed. The perivascular environment is populated by mesenchymal progenitor cells, fibroblasts, myofibroblasts and pericytes, which can together mount a healing response to the ischaemic damage. In the infarcted heart, pericytes have crucial roles in angiogenesis, scar formation and stabilization, and control of the inflammatory response. Persistent ischaemia and accrual of age-related risk factors can lead to pericyte depletion and dysfunction. In this Review, we describe the phenotypic changes that characterize the response of cardiac pericytes to ischaemia and the potential of pericyte-based therapy for restoring the perivascular niche after myocardial infarction. Pericyte-related therapies that can salvage the area at risk of an ischaemic injury include exogenously administered pericytes, pericyte-derived exosomes, pericyte-engineered biomaterials, and pharmacological approaches that can stimulate the differentiation of constitutively resident pericytes towards an arteriogenic phenotype. Promising preclinical results from in vitro and in vivo studies indicate that pericytes have crucial roles in the treatment of coronary artery disease and the prevention of post-ischaemic heart failure.


Synaptic modulation by astrocytes via Ca2+-dependent glutamate release.
In the past 15 years the classical view that astrocytes play a relatively passive role in brain function has been overturned and it has become increasingly clear that signaling between neurons and astrocytes may play a crucial role in the information processing that the brain carries out. This new view stems from two seminal observations made in the early 1990s: 1. astrocytes respond to neurotransmitters released during synaptic activity with elevation of their intracellular Ca2+ concentration ([Ca2+]i); 2. astrocytes release chemical transmitters, including glutamate, in response to [Ca2+]i elevations. The simultaneous recognition that astrocytes sense neuronal activity and release neuroactive agents has been instrumental for understanding previously unknown roles of these cells in the control of synapse formation, function and plasticity. These findings open a conceptual revolution, leading to rethink how brain communication works, as they imply that information travels (and is processed) not just in the neuronal circuitry but in an expanded neuron-glia network. In this review we critically discuss the available information concerning: 1. the characteristics of the astrocytic Ca2+ responses to synaptic activity; 2. the basis of Ca2+-dependent glutamate exocytosis from astrocytes; 3. the modes of action of astrocytic glutamate on synaptic function.


Single molecule PCR in mtDNA mutational analysis: Genuine mutations vs. damage bypass-derived artifacts.
The area of somatic mtDNA mutation measurement is in a crisis because the methods used to quantify mtDNA mutations produce results varying by multiple orders of magnitude. The reason for these discrepancies is not clear, but given that most methods involve PCR, the prime suspect is PCR artifacts (e.g. spontaneous errors by the DNA polymerases used). In addition to simple misincorporation, another important source of artificial mutations is the conversion of chemically modified (e.g. damaged) nucleotides into mutations when bypassed by a thermostable DNA polymerase. These latter mutations are particularly difficult to account for because appropriate controls are not available. Here, we argue that single molecule PCR (smPCR) is uniquely positioned to account for these bypass-related artificial mutations and discuss the methodology involved in employing this technique.


A pathway analysis of the impact of childhood domestic violence on depression in middle-aged and elderly people from the perspective of life course.
Negative life events in early life have a cumulative effect on health trajectory changes in middle and old age, and some scholars have used life course theory as a guide to empirically explore the effect of childhood adversity or adverse experiences on depression in the elderly, but few study focuses on violence within the family. To explore the influence mechanism of domestic violence experience on depression in later life in middle-aged and elderly people, and to provide academic support for the whole society to pay attention to good family function and intergenerational interaction, and to propose whole-life health promotion strategies. This paper selects the 2014 life course survey data and 2018 cross-sectional data of the China Health and Elderly Care Longitudinal Survey for analysis, and the research objects are middle-aged and elderly people aged 45 and above. Based on a retrospective survey of 3008 middle-aged and elderly people, this study analyzed the influence path of domestic violence on depression level in childhood by using multiple mediation models, and used the Bootstrap method to test the significance of indirect effects. Based on controlling for gender, age, age square, household registration, marital status, community environment and education level, childhood domestic violence had a direct positive effect on depression level in the elderly (P < 0.001), and childhood domestic violence also had an indirect effect on the depression level of the elderly through childhood health status, income logarithm and IADL (P < 0.05). As a life experience in early life, childhood domestic violence has a cumulative effect on depression in middle-aged and elderly people, is an important risk factor for depression, and has an important impact on mental health in later life.


Parkinson's disease and anxiety: comorbidity with depression.
Parkinson's disease (PD) is frequently accompanied by symptoms of depression and anxiety. However, the relationship between anxiety and depression has not been rigorously defined in these patients. In this study, 42 patients with PD and 21 matched medical controls were evaluated using DSM-III-R criteria and a variety of psychiatric rating scales. Twelve (29%) PD patients but only one medical control had a formal anxiety disorder diagnosis. Of the 12 patients with PD who had an anxiety disorder diagnosis, 11 (92%) had a comorbid depressive disorder diagnosis. Of the 18 patients with a depressive disorder, 12 (67%) also had an anxiety disorder diagnosis. Furthermore, a stepwise regression analysis found that the depression measure explained 44% of the variance in anxiety measures whereas neither the severity of illness variables nor the levodopa dose contributed significantly to the variance. This study suggests that the excess anxiety found in PD patients is unlikely to be primarily a psychologic reaction to the illness or a side effect of levodopa treatment. Rather, we suggest that anxiety and depression are related manifestations of the underlying neurochemical changes of PD itself.


Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools.
Pyruvate carboxylase is the predominant anaplerotic enzyme in CNS tissues, and thus provides for net utilization of glucose to generate citric acid cycle intermediates such as alpha-ketoglutarate and malate for replenishment of the neurotransmitter pools of glutamate, GABA and aspartate. Studies reported in this paper involving immunocytochemical and biochemical techniques demonstrate: (1) the enzyme is localized in astrocytes as visualized by immunofluorescence in sections of cerebellum and (2) the enzyme activity in astrocyte-enriched populations is 3 X higher than in granule cell-enriched populations isolated from the cerebellum; similarly activity in different synaptosomal preparations parallels that for glutamine synthetase. We conclude from these results that the enzyme pyruvate carboxylase is an astrocyte-specific marker. This localization substantiates some recent hypotheses for astrocyte functions, including CO2 fixation in the CNS and the replenishment of citric acid cycle intermediates by astrocytes as precursors for amino acid neurotransmitter pools.


Quantification, characterization and fatty acid composition of lysophosphatidic acid in different rat tissues.
The amount and composition of lysophosphatidate present in different rat tissues have been estimated by an internal standard method in which a synthetic unnatural isomer (1-heptadecanoyl-rac-glycerol-3-phosphate) was added to the total lipid extracts, and the fatty acid composition of purified lysophosphatidate was determined. Lipids from tissues were extracted under acidic conditions, and the lysophosphatidate was purified by solvent partitions followed by thin-layer chromatography in multiple solvent systems. The purified lipid was shown to be 1-acyl-sn-glycerol-3-phosphate by chromatographic and chemical analysis, by its resistance to hydrolysis when treated with phospholipase A2 and also by its complete conversion to 1-acyl-sn-glycerol when treated with alkaline phosphatase. The fatty acid constituents of this lipid were determined by gas-liquid chromatography of the derived methyl esters. The concentrations (nmol/g of tissue) of lysophosphatidate in various tissues were: 86.2 +/- 4.2 in brain, 60.3 +/- 6.3 in liver, 46.4 +/- 6.5 in kidney, 30.6 +/- 5.0 in testis, 22.3 in heart and 19.3 in lung. Mostly (80%) saturated fatty acids were found to be present in this lyso lipid. A significantly high level of stearic acid was present in this lipid from all the tissues (50-60% in liver, kidney, brain and testis, and about 40% in heart and lung) compared to palmitic acid (10-15% in liver, kidney and brain and 25-30% in testis, heart and lung). The fatty acid compositions of phosphatidic acid, the putative product of lysophosphatidate acylation, from different tissues were also determined and palmitate was found to be the major saturated fatty acid.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimization of Extraction and Quality Evaluation of Abri Herba by Response Surface Methodology Combined with Quantitative Analysis of Multi-Components by a Single Marker.
Abri Herba (AH) is a famous medicinal and edible traditional Chinese medicine, which is usually used for liver disease. To date, few studies have been conducted on the ultrasonic extraction (UAE) process for AH and the application of quality analysis of multi-components by the single-marker (QAMS) method to evaluate the quality. To optimize the UAE process for AH, and develop and validate the quality evaluation of AH by the QAMS method. The UAE conditions of AH were optimized by response surface methodology with the total contents of protocatechuic acid, hydantoin, gardeniaine, vicenin-2, salvoside and isosalvoside as indicators, the ultrasonic time, methanol concentration and liquid to material ratio as parameters. The content of protocatechuic acid, hypaphorine, abrine, vicenin-2, schaftoside, and isoschaftoside in 12 batches of AH was first determined by the external standard method (ESM) using HPLC. After that, based on abrine as the internal standard, the relative correction factors (RCF) for protocatechuic acid, hypaphorine, vicenin-2, schaftoside and isoschaftoside were established, and the ESM method was used to verify the QAMS method. The results show that the optimal extraction process parameters for AH are an ultrasonic time of 22 min, a methanol concentration of 45%, and liquid to material ratio of 26 (mL/g). The QAMS results show that the relative correction factor has good reproducibility, and there is no significant difference between the results of the ESM method and the QAMS method for each chemical constituent, indicating that the research is feasible. The optimized extraction process of AH and the established QAMS-based quality control method are stable and can be used for the quality control of AH. A response surface methodology was used to optimize the ultrasonic extraction process for AH, and a QAMS method was established for evaluating the quality of AH.


Pharmacogenetic-based strategy using de novo tacrolimus once daily after kidney transplantation: prospective pilot study.
The once daily tacrolimus formulation (Tac-OD) has been associated with better patient adherence and low variability in exposure. Patients carrying the CYP3A5*1 allele show accelerated clearance of Tac. Authors prospectively evaluate a simplified strategy for Tac-OD administration. After grafting, 151 patients were divided into four groups and received a daily dose calculated according to CYP3A5 genotypes and unchanged for the first 3 days: CYP3A5*3/*3: 0.20 mg/kg/day, CYP3A5*3/*3: 0.25 mg/kg/day, CYP3A5*1/*3: 0.30 mg/kg/day and CYP3A5*1/*1: 0.35 mg/kg/day. The dose was adaptated on day 4 and remained unchanged a further three days and so on. On day 3, median Cmin fell within the therapeutic range in all study groups. CYP3A5 expressors require significantly higher Tac-OD throughout the follow-up period to achieve a comparable Cmin. This simplified strategy does not hamper treatment efficacy.


GGDMLE: a computer program which finds maximum likelihood estimates for the generalized log gamma distribution.
A FORTRAN program is described which finds maximum likelihood estimates for the generalized log gamma model for survival time data. The model includes regression variables which are assumed to be linearly related to log survival time and handles censored data. The shape parameter is treated as fixed in the optimization procedure (a modification of Powell's hybrid method), but the program can find maximum likelihood estimates (MLE) for several different values of the shape parameter in one run. The other parameters can be optionally fixed so special cases of the generalized log gamma (GLG) model, such as the log exponential, extreme value and normal models, can be studied. A subroutine is included which calculates initial parameter estimates for a given shape parameter value which can be used to start the optimization procedure. After some background mathematics, a description of how to use the program is given, including input/output features, a description of the subroutines and an explanation of the flow of control. An application, using data from Princess Margaret Hospital, Toronto, is presented to illustrate the program's use.


Importance of microscopic residual disease at the bronchial margin after resection for non-small-cell carcinoma of the lung.
A total of 805 patients underwent lung resection for non-small-cell lung carcinoma at the University of Munich Medical Center, Klinikum Grosshadern, from 1978 through 1988. Microscopic residual disease at the bronchial margin was found in 21 patients (2.6%). The tumor residues showed either a mucosal (1%) or a extramucosal (1.6%) spreading pattern. Patients with extramucosal microscopic residual disease had a poorer prognosis (median survival 10.3 months) than patients with mucosal microscopic residual disease (median survival 25 months). The prognosis was better if the tumor was squamous cell as opposed to adenocarcinoma or large-cell carcinoma. The most important prognostic factor was tumor stage. Patients with microscopic tumor infiltration and stage I or II disease survived longer than the comparable stage III group. We suggest that these patients should undergo reoperation, if possible. Patients with stage III disease, mediastinal lymph node involvement, and microscopic residual disease have the same marked reduction in survival as patients with stage III disease but without microscopic tumor infiltration. We do not recommend a follow-up operation in these patients. Complete histologic examination of mucosal and extramucosal peribronchial tissues at the resection line by frozen section is mandatory to avoid leaving microscopic tumor behind, which may adversely affect patient survival.


Vestiges of underplating and assembly in the central North China Craton based on S-wave velocities.
The destruction of the North China Craton (NCC) is a controversial topic among researchers. In particular, the crustal structure associated with the craton's destruction remains unclear, even though a large number of seismic studies have been carried out in this area. To investigate the crustal structure and its dynamic implications, we perform noise tomography in the central part of the NCC. In this study, continuous vertical-component waveforms spanning one year from 112 broadband seismic stations are used to obtain the group velocity dispersion curves of Rayleigh waves at different periods, and surface wave tomography is employed to extract the Rayleigh wave group velocity distributions at 9-40 s. Finally, the S-wave velocity structure at depths of 0-60 km is determined by the inversion of pure-path dispersion data. The results show obvious differences in the crustal structure among the Western Block (WB), the Trans-North China Orogen (TNCO) and the Eastern Block (EB). The lower crust of the northern part of the EB exhibits a high-velocity S-wave anomaly, which may be related to magmatic underplating in the lower crust induced by an upwelling mantle plume. The S-wave velocity of the WB is lower than that of the TNCO in the upper and middle crust and is lower than that of both the TNCO and the EB in the lower crust. The crust of the TNCO shows higher S-wave velocities than the WB and EB in the upper and middle crust, and its overall S-wave velocity structure is clearly different from those of the WB and EB, implying that the crustal structure of the TNCO may contain vestiges of the Paleoproterozoic collision between the WB and EB and their subsequent assembly. This study marks the first time these findings are identified for the NCC.


Initial histological evaluation of anti-washout type fast-setting calcium phosphate cement following subcutaneous implantation.
Anti-washout-type fast-setting calcium phosphate cement using chitosan (aw-FSCPC(chi)), conventional CPC (c-CPC), CPC mixed with citric acid (CPC(citric)) and CPC mixed with polyacrylic acid (CPC(acrylic)) were implanted subcutaneously in rats immediately after mixing to shed some light on the understanding of the appearance of excellent tissue response to CPC. CPC(citric) and CPC(acrylic) set quickly, similar to aw-FSCPC(chi), but the former two stopped their transformation to apatitic minerals. The c-CPC, which required a long setting time, was found to be crumbled, but the other CPCs maintained the shape at implantation. The aw-FSCPC(chi) and CPC(citric) showed no inflammatory response whereas c-CPC and CPC(acrylic) showed an inflammatory response one week after implantation. A component of the aw-FSCPC(chi) and c-CPC was an apatitic mineral whereas CPC(citric) and CPC(acrylic) showed no transformation to apatite. We concluded that the non-crumbling property plays a more dominant role in the appearance of excellent tissue response to CPC than the transformation to apatite. Also, a non-crumbling property is not a sufficient condition, but a necessary condition for the appearance of the excellent tissue response to CPC.


"One-off" complete radiofrequency ablation of hepatocellular carcinoma adjacent to the gallbladder by a novel laparoscopic technique without gallbladder isolation.
The main objective of this study is to assess the feasibility and safety of treating hepatocellular carcinoma (HCC) proximal to the gallbladder using laparoscopic radiofrequency ablation (RFA). Surgical ablation of tumor located adjacent to the gallbladder may damage the gallbladder wall, even with a laparoscope and this ablation method is not precise and incomplete and is frequently combined with alcohol injections with need for further RFA treatment. Four patients were included in this study, with typical HCC where the tumor was present on the left, right, or bed side surrounding the gallbladder. The gallbladder was not separated or removed during larascopic inspection. In the RFA treatment procedure, the tumor lesion was pre-heated for 10 min, and heating was continued for 20 min. The integrity of the gallbladder wall was properly maintained. A follow-up to check for possible local recurrence was carried out 1 year after the RFA. The goal of "one-off" tumor complete RFA is to achieve thorough ablation of the tumor in a single treatment and limiting the possibility of recurrence within 6 months. Seven days after RFA, liver functions of all the patients returned to near-preoperative levels. The patients experienced slight pain in the upper right abdomen, which disappeared in 2-3 days. Results of B ultrasound on days 3-5 showed thickening of the periphery of the ablation area, without significant effusion. Enhanced CT on day 3 showed that RFA low-density area completely covered the lesions. No significant abnormality was observed in the gallbladder and its vicinity. One month after the surgery, B ultrasound and CT examination revealed no significant abnormalities. All patients had an intact gallbladder, and no extrahepatic or intrahepatic bile duct dilatation occurred. There was no evidence of damage to the bile duct or the vessels. Follow-up for 18-32 months found that all patients were in good condition. "One-off" complete RFA can be safely implemented to ablate HCC close to the gallbladder with the assistance of a laparoscope while maintaining integrity and continuity of the gallbladder, and without the need for secondary treatments.


Xenogeneic cytotoxic T-cell clones recognize alloantigenic determinants on HLA-A2.
Long-term murine cytotoxic T-cell clones arising in response to stimulation with human lymphoblastoid cells and reactive with the HLA-A2 antigen are characterized. These clones distinguish between HLA-A2 and 21 other serologically defined HLA-A and -B antigens. In addition, most clones discriminate between prototypical HLA-A2 antigens, expressed by the majority of HLA-A2-positive individuals, and variant HLA-A2 antigens, which are serologically identical with the prototype, but distinguishable by human cytotoxic T cells and by biochemical analysis. This discrimination is reflected as an inability to cause any significant lysis of variant HLA-A2-expressing target cells at effector-to-target ratios 10- to 100-fold greater than those giving 50% lysis of prototype HLA-A2-expressing cells. By screening a panel of serologically HLA-A2-positive cells, a new variant HLA-A2-expressing cell line has been defined. The recognition patterns of these xenogeneic clones are suggested to reflect recognition of alloantigenic polymorphic determinants. Based on the strong bias in the xenogeneic T-cell repertoire for such determinants, we propose a model for T-cell recognition of class I products of the major histocompatibility complex.


A note on the transneuronal transport of wheat germ agglutinin-conjugated horseradish peroxidase in the avian and rodent visual systems.
While using horseradish peroxidase conjugated to the plant lectin wheat germ agglutinin (WGA-HRP) as an anterograde marker to label the developing retinofugal projection in the chick, we have found that a significant amount of the tracer can escape from the axons and axon terminals of retinal ganglion cells and be subsequently taken up and transported both anterogradely and retrogradely by neighboring neurons and/or axon terminals. The release and uptake of the tracer appears to be nonspecific, and is particularly striking at embryonic stages; at these stages there is also appreciable uptake of the WGA-HRP by ependymal cells and by radial glial processes. Subsequent experiments in rats have shown that as early as 2 days after an injection of WGA-HRP into an eye there is clear labeling of geniculo-cortical axons in the striate cortex. Since WGA-HRP is being used increasingly in neuroanatomical studies, it is now clear that when interpreting the results of experiments with this marker the possibility of transneuronal labeling must be borne in mind, and especially after relatively long post-labeling survival periods. At the same time the secondary transport of WGA-HRP may, in certain neural systems, provide a useful tool for analyzing second-order connections.


Disparities in Mental Health and Well-Being Among Black and Latinx Patients With Kidney Disease.
Black and Latinx individuals in the United States are afflicted disproportionately with kidney disease. Because of structural racism, social risk factors drive disparities in disease prevalence and result in worse outcomes among these patient groups. The impact of social and economic oppression is pervasive in physical and emotional aspects of health. In this review, we describe the history of race and ethnicity among black and Latinx individuals in the United States and discuss how these politicosocial constructs impact disparities in well-being and mental health. Lastly, we outline future research, clinical considerations, and policy considerations to eliminate racial and ethnic disparities in well-being among black and Latinx individuals with kidney disease.