Rapid sample preparation procedure for As speciation in food samples by LC-ICP-MS.
This paper describes a rapid method for arsenic (As) speciation by LC-ICP-MS in several types of food samples. Prior to analysis, samples were milled and the As species extracted from biological tissues by sonication in only 2 min with a solution containing MeOH (10%, v/v) plus HNO₃ (2%, v/v). As species were separated by LC using an anion exchange column. Method detection limits for AsB, As³⁺, DMA, MMA and As⁵⁺ were 1.3, 0.9, 0.6, 0.7 and 0.8 ng g⁻¹, respectively. Method accuracy and precision were traceable to Certified Reference Materials SRM1577 bovine liver from the National Institute of Standards and Technology, CE278 mussel tissue from the Institute of Reference Materials and Measurements and DOLT-3 dogfish liver tissue and DORM-3 fish protein from the National Research Council of Canada. Finally, the method was applied to speciate As in food samples (egg, fish muscle, beef and chicken) purchased in Brazilian markets.


The Dysarthric Expressed Emotional Database (DEED): An audio-visual database in British English.
The Dysarthric Expressed Emotional Database (DEED) is a novel, parallel multimodal (audio-visual) database of dysarthric and typical emotional speech in British English which is a first of its kind. It is an induced (elicited) emotional database that includes speech recorded in the six basic emotions: "happiness", "sadness", "anger", "surprise", "fear", and "disgust". A "neutral" state has also been recorded as a baseline condition. The dysarthric speech part includes recordings from 4 speakers: one female speaker with dysarthria due to cerebral palsy and 3 speakers with dysarthria due to Parkinson's disease (2 female and 1 male). The typical speech part includes recordings from 21 typical speakers (9 female and 12 male). This paper describes the collection of the database, covering its design, development, technical information related to the data capture, and description of the data files and presents the validation methodology. The database was validated subjectively (human performance) and objectively (automatic recognition). The achieved results demonstrated that this database will be a valuable resource for understanding emotion communication by people with dysarthria and useful in the research field of dysarthric emotion classification. The database is freely available for research purposes under a Creative Commons licence at: https://sites.google.com/sheffield.ac.uk/deed.


The need for safeguards in advance care planning.
The recent uproar about Medicare "death panels" draws attention to public and professional concerns that advance care planning might restrict access to desired life-sustaining care. The primary goal of advance care planning is to promote the autonomy of a decisionally incapacitated patient when choices about life-sustaining treatments are encountered, but the safety of this procedure has not received deserved scrutiny. Patients often do not understand their decisions or they may change their mind without changing their advance care directives. Likewise, concordance between patients' wishes and the understanding of the physicians and surrogate decision makers who need to represent these wishes is disappointingly poor. A few recent reports show encouraging outcomes from advance care planning, but most studies indicate that the procedure is ineffective in protecting patients from unwanted treatments and may even undermine autonomy by leading to choices that do not reflect patient values, goals, and preferences. Safeguards for advance care planning should be put in place, such as encouraging physicians to err on the side of preserving life when advance care directives are unclear, requiring a trained advisor to review non-emergent patient choices to limit life-sustaining treatment, training of clinicians in conducting such conversations, and structured discussion formats that first address values and goals rather than particular life-sustaining procedures. Key targets for research include: how to improve completion rates for person wanting advance care directives, especially among minorities; more effective and standardized approaches to advance care planning discussions, including how best to present prognostic information to patients; methods for training clinicians and others to assist patients in this process; and systems for assuring that directives are available and up-to-date.


Hepatic gene expression profiling in zebrafish (Danio rerio) exposed to the fungicide chlorothalonil.
Chlorothalonil (tetrachloroisophtalonitrile) is a fungicide that is widely used on agricultural crops around the world and as such, it is a ubiquitous aquatic contaminant. Despite high usage, the effects of this fungicide on non-target aquatic organisms have not been fully investigated. The aim of the present study was to (1) determine the effects of chlorothalonil toxicity on adult male zebrafish (Danio rerio) and (2) characterize the effects of chlorothalonil on gene expression patterns in the liver using two different concentrations of the fungicide, 0.007mg/L (environmentally-relevant) and 0.035mg/L (sublethal). These concentrations were selected from range-finding experiments that showed that zebrafish survival was significantly different from control animals at concentrations higher than 0.035mg/L but not below. Male zebrafish in both treatments of chlorothalonil showed a decrease in liversomatic index. A commercial D. rerio microarray (4×44K) was used to determine gene expression profiles in male zebrafish liver following a 96h toxicological assay. Microarray analysis revealed that males exposed to both 0.007mg/L or 0.035mg/L of chlorothalonil showed increased transcriptional sub-networks related to cell division and DNA damage and decreased expression of gene networks associated with reproduction, immunity, and xenobiotic clearance. This study improves knowledge regarding whole animal exposures to chlorothalonil and identifies molecular signaling cascades that are sensitive to this fungicide in the fish liver.


Implantation and capsular bag stability of single-piece, foldable EasAcryl 1 intraocular lenses.
To assess the folding and implantation of the single-piece EasAcryl 1 intraocular lens (IOL) and the maintenance of the tunnel structure and capsular bag stability after implantation. S. Orsola Hospital Department of Pathophysiologic Optics, University of Bologna, Bologna, Italy. This study comprised 300 cases of EasAcryl 1 IOL implantation. First, a 3.2 mm corneal incision was made according to preoperative astigmatism followed by a 5.5 mm +/- 0.3 (SD) capsulorhexis. After sutureless phacoemulsification using a venturi pump, the 6.0 mm optic, 11.0 mm diameter IOL was implanted using a hexagonal cartridge. The IOLs were implanted using a 2-step maneuver when the superior haptic was grasped with the forceps (first case) or a 1-step maneuver when only the Microsert injector was used. The cartridge was never pushed beyond the tunnel. The preoperative and postoperative incision size and the corneal surgically induced astigmatism were recorded. The IOL rotation was measured 30 +/- 5 days and 8 +/- 1 months postoperatively. No intraoperative complications occurred after the learning curve. No alteration in astigmatism was observed. The mean IOL rotation was 1.04 +/- 0.5 degrees at 30 +/- 5 days and 1.02 +/- 0.2 degrees at 8 +/- 1 months. The EasAcryl 1 was easily implantation through a 3.2 mm tunnel without altering the natural architecture. The unfolding of the IOL was well controlled, and the IOL remained well centered. A short learning curve is required.


Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue. Study in 16,369 women.
We report the results of a large-scale trial with mifepristone (RU 486) followed by the administration of a prostaglandin (PG) analogue for the medical termination of early pregnancy. Altogether, 16,173 patients from 300 centers were evaluated. 48 women (0.3%) were lost to follow-up prior to, and 416 (2.6%) after the PG administration, and therefore the efficacy was evaluated in 15,709 women. Overall, the success rate was 95.3%, with no statistical difference regarding the nature and dose of PG used. The median duration of bleeding was 8 days, being 12 days or less in 89.7% of the women. Bleeding was significant enough to necessitate a vacuum aspiration or a dilatation and curettage in 0.8% of the cases. A blood transfusion was necessary in 0.1% of the women (11 patients). Serious cardio-vascular side-effects were reported in 4 cases after the PG (sulprostone) injection: they consisted of one acute myocardial infarction attributed to a coronary spasm, and in marked hypotension in the other 3 women. All patients recovered uneventfully. In conclusion, RU 486 followed by a PG analogue provides an efficient and safe medical alternative to surgery for early pregnancy termination, provided that the recommended protocol is adequately followed and the contraindications to prostaglandins are respected.


Extracellular self-photosensitizer combined with metal oxide-based nano bio-hybrid system encapsulated by alginate improves hydrogen production in the presence of oxygen.
The photocatalytic nano-biohybrid systems have great potential for the conversion of solar energy to fermentative hydrogen production. Herein, a whole-cell nano-biohybrid system consisting of biosynthesized cadmium sulfide, Enterobacter aerogenes cells, and metal oxide nanoparticles was constructed. The system was encapsulated with sodium alginate and used for light-driven biohydrogen production under anaerobic and in the presence of oxygen conditions. After 48 h incubation in the presence of oxygen, the E. aerogenes cells with the encapsulated hybrid system yielded 2.7 mmol H2/mmol glucose, a 13.5-fold higher than that of the E. aerogenes cells without encapsulation. The encapsulated hybrid system could produce hydrogen for up to 96 h and could produce hydrogen even under natural sunlight conditions. These results revealed that efficient hydrogen production is possible in the presence of oxygen. Overall, the present study demonstrated the potential of using proper nano-biohybrid system with encapsulation for the production of hydrogen under ambient air condition.


Exogenous expression of Msx1 renders myoblasts refractory to differentiation into myotubes and elicits enhanced biosynthesis of four unique mRNAs.
Murine myoblast cell lines stably transfected with expression vectors containing homeobox Msx1 cDNA in sense (F31-c) or antisense (F3R1) orientation have contrasting phenotypes. F3R1 cells readily differentiate in medium containing low serum whereas F31-c cells fail to differentiate under these conditions. The mechanism by which exogenous overexpression of Msx1 leads to the altered phenotype of F31-c cells and the downstream targets of Msx1 are unknown. Using the method of differential display, we have identified four cDNAs that represent transcripts up-regulated in F31-c. Two of these cDNAs are homologous to ribosomal proteins S23 and S24 while the third has homology to sequences in the murine Tcp-1 gene. A fourth cDNA does not have appreciable homology to cDNA sequences deposited in the NIH GenBank. Since withdrawal from the cell cycle and enhanced expression of MyoD commonly precede differentiation of myoblasts into myotubes, we also examined regulation of the major cell cycle proteins as well as MyoD by Western blot analysis. We show that the levels of Cdks 2, 4 and 6, cyclins A and D, and the Cdk inhibitor p27 in both proliferating and serum-starved F31-c cells were similar to those in F3R1. Finally, although MyoD protein levels increased in both cell types after 72 h incubation in serum depleted medium, the levels of MyoD in serum-starved F31-c cells were 2-4 fold lower. We postulate that the reduced amount of MyoD is sufficient to permit reversible withdrawal of F31-c cells from the cell cycle, but is inadequate to permit myogenesis.


Renin-angiotensin system modulation through enalapril and/or exercise training improves visceral adiposity in obese mice.
Obesity-related metabolic diseases occur as a result of disruptions in white adipose tissue (WAT) plasticity, especially through visceral fat accumulation and adipocyte hypertrophy. This study aimed to evaluate the impact of renin-angiotensin system (RAS) and bradykinin receptors modulation by enalapril treatment and/or exercise training on WAT morphology and related deleterious outcomes. Male C57BL/6 mice were fed either a standard chow or a high-fat (HF) diet for 16 weeks. At the 8th week, HF-fed animals were divided into sedentary (HF), enalapril treatment (HF-E), exercise training (HF-T), and enalapril treatment plus exercise training (HF-ET) groups. Following the experimental protocol, body mass gain, adiposity index, insulin resistance, visceral WAT morphometry, renin-angiotensin system, and bradykinin receptors were evaluated. The HF group displayed increased adiposity, larger visceral fat mass, and adipocyte hypertrophy, which was accompanied by insulin resistance, overactivation of Ang II/AT1R arm, and favoring of B1R in bradykinin receptors profile. All interventions ameliorated visceral adiposity and related outcomes by favoring the Ang 1-7/MasR arm and the B2R expression in B1R/B2R ratio. However, combined therapy additively reduced Ang II/Ang 1-7 ratio. Our results suggest that Ang 1-7/MasR arm and B2R activation might be relevant targets in the treatment of visceral obesity.


Maternal alcohol ingestion inhibits fetal glucose uptake and growth.
The distribution of maternally-derived glucose was determined in selected tissues of fetuses from ethanol-fed (EF) rats and from pair-fed (PF) and ad lib-fed (AF) controls. Maternal ethanol ingestion resulted in reduced fetal brain and liver weights and lower liver and lung glycogen levels compared to those of the PF or AF control groups. In addition, experimental fetuses exhibited reduced uptake of maternally-derived [3H] 2-deoxy-D-glucose (2-DG) by placenta and fetal brain. Fetal body, liver, lung, and brain weights correlated with fetal plasma 3H activity and with the fetal:maternal plasma 3H ratio, an indicator of the rate of placental glucose transfer. Brain weight correlated with 2-DG content per gram tissue weight. These observations suggest that reduced nutrient availability due to impaired placental transfer plays a role in the intrauterine growth retardation associated with maternal ethanol ingestion.


c-FLIP-L recombinant adeno-associated virus vector infection prevents Fas-mediated but not nerve growth factor withdrawal-mediated cell death in PC12 cells.
Fas is a cell surface death receptor that may play an important role in regulating cell death in neuronal cell types by activation of caspase 8. Cellular FLICE inhibitory protein-long (c-FLIP-L) is an endogenous inhibitor of the activation of caspase 8 by Fas. The current study addresses the role of c-FLIP-L in regulation of cell death in PC12 cells induced by nerve growth factor (NGF) withdrawal and Fas antibody, which acts as a Fas ligand and activates the Fas receptor. A recombinant adeno-associated virus (rAAV) vector that expresses c-FLIP-L was constructed. PC12 cells infected with the c-FLIP-L rAAV were resistant to apoptosis induced by treatment with Fas antibody compared to cells infected with enhanced green fluorescent protein (EGFP) expressing rAAV. Overexpression of c-FLIP-L rAAV inhibited cleavage of caspase 8 induced by Fas antibody treatment. In contrast, treatment with the c-FLIP-L rAAV did not protect PC12 cells from cell death induced by NGF withdrawal. In conclusion, overexpression of c-FLIP-L rAAV inhibits Fas antibody-mediated cell death, but not NGF withdrawal-mediated cell death in PC12 cells.


Plasmid R1--replication and its control.
Plasmid R1 is a low-copy-number plasmid belonging to the IncFII group. The genetics, biochemistry, molecular biology, and physiology of R1 replication and its control are summarised and discussed in the present communication. Replication of R1 starts at a unique origin, oriR1, and proceeds unidirectionally according to the Theta mode. Plasmid R1 replicates during the entire cell cycle and the R1 copies in the cell are members of a pool from which a plasmid copy at random is selected for replication. However, there is an eclipse period during which a newly replicated copy does not belong to this pool. Replication of R1 is controlled by an antisense RNA, CopA, that is unstable and formed constitutively; hence, its concentration is a measure of the concentration of the plasmid. CopA-RNA interacts with its complementary target, CopT-RNA, that is located upstream of the RepA message on the repA-mRNA. CopA-RNA post-transcriptionally inhibits translation of the repA-mRNA. CopA- and CopT-RNA interact in a bimolecular reaction which results in an inverse proportionality between the relative rate of replication (replications per plasmid copy and cell cycle) and the copy number; the number of replications per cell and cell cycle, n, is independent of the actual copy number in the individual cells, the so-called +n mode of control. Single base-pair substitutions in the copA/copT region of the plasmid genome may result in mutants that are compatible with the wild type. Loss of CopA activity results in (uncontrolled) so-called runaway replication, which is lethal to the host but useful for the production of proteins from cloned genes. Plasmid R1 also has an ancillary control system, CopB, that derepresses the synthesis of repA-mRNA in cells that happen to contain lower than normal number of copies. Plasmid R1, as other plasmids, form clusters in the cell and plasmid replication is assumed to take place in the centre of the cells; this requires traffic from the cluster to the replication factories and back to the clusters. The clusters are plasmid-specific and presumably based on sequence homology.


Structural dynamics of an isolated voltage-sensor domain in a lipid bilayer.
A strong interplay between the voltage-sensor domain (VSD) and the pore domain (PD) underlies voltage-gated channel functions. In a few voltage-sensitive proteins, the VSD has been shown to function without a canonical PD, although its structure and oligomeric state remain unknown. Here, using EPR spectroscopy, we show that the isolated VSD of KvAP can remain monomeric in a reconstituted bilayer and retain a transmembrane conformation. We find that water-filled crevices extending deep into the membrane around S3, a scaffold conducive to transport of protons/cations, are intrinsic to the VSD. Differences in solvent accessibility in comparison to the full-length KvAP allowed us to define an interacting footprint of the PD on the VSD. This interaction is centered around S1 and S2 and suggests a rotation of 70 degrees -100 degrees relative to Kv1.2-Kv2.1 chimera. Sequence-conservation patterns in Kv channels, Hv channels, and voltage-sensitive phosphatases reveal several near-universal features suggesting a common molecular architecture for all VSDs.


The effect of an empowerment program on the moral sensitivity and caring behaviors of emergency nurses in Iran.
The present study aimed to evaluate the effect of an empowerment program on the moral sensitivity and caring behaviors of nurses in emergency departments in Iran. Emergency department is often a high stress environment. Nurses who worked in the emergency departments are expected to work under pressure to many standards, guidelines and protocols related to patient care. It will expose emergency department nurses to psychological pressures and moral conflicts. A nurse's sensitivity to ethical issues is necessary to provide humane care; it is considered to be a professional competence for nurses. This study had a controlled quasi-experimental design. Data were collected before, immediately after, and 1 month after the intervention using a moral sensitivity questionnaire and a caring behavior questionnaire. A total of 131 emergency department nurses from 4 teaching hospitals were divided into an intervention group and a control group. The intervention group received six 60-minute training sessions; the control group did not receive the training. The mean moral sensitivity and caring behavior scores for both groups increased significantly immediately and 1 month after the intervention. However, the significance was higher in the intervention group than in the control group. A comparison of the mean moral sensitivity and caring behavior scores between the groups immediately and 1 month after the intervention did not show a statistically significant difference. Implementing a training program on ethical issues could thus have a significant impact on the clinical performance of nurses, which could be maintained through follow-up.


The effect of carbachol and pentagastrin on the gastric secretion of acid pepsin, and intrinsic factor (IF) in man.
Intravenous infusions of carbachol and pentagastrin were given separately or simultaneously in 6 healthy students. The volume of gastric secretion and the concentration and output of acid, pepsin, and IF increased significantly during infusion of carbachol alone, whereas the plasma gastrin concentration remained unchanged. Carbachol had no effect on the acid, pepsin, and IF secretion by pentagastrin. The results indicate an effect of carbachol on acid, pepsin, and IF secretion, independent of changes in plasma gastrin concentration. No synergistic or potentiating effect was demonstrated between carbachol and pentagastrin.


Impact of perceived inappropiate cardiopulmonary resuscitation on emergency clinicians' intention to leave the job: Results from a cross-sectional survey in 288 centres across 24 countries.
Cardiopulmonary resuscitation (CPR) in patients with a poor prognosis increases the risk of perception of inappropriate care leading to moral distress in clinicians. We evaluated whether perception of inappropriate CPR is associated with intention to leave the job among emergency clinicians. A cross-sectional multi-centre survey was conducted in 24 countries. Factors associated with intention to leave the job were analysed by conditional logistic regression models. Results are expressed as odds ratios with 95% confidence intervals. Of 5099 surveyed emergency clinicians, 1836 (36.0%) were physicians, 1313 (25.7%) nurses, 1950 (38.2%) emergency medical technicians. Intention to leave the job was expressed by 1721 (33.8%) clinicians, 3403 (66.7%) often wondered about the appropriateness of a resuscitation attempt, 2955 (58.0%) reported moral distress caused by inappropriate CPR. After adjustment for other covariates, the risk of intention to leave the job was higher in clinicians often wondering about the appropriateness of a resuscitation attempt (1.43 [1.23-1.67]), experiencing associated moral distress (1.44 [1.24-1.66]) and who were between 30-44 years old (1.53 [1.21-1.92] compared to <30 years). The risk was lower when the clinician felt valued by the team (0.53 [0.42-0.66]), when the team leader acknowledged the efforts delivered by the team (0.61 [0.49-0.75]) and in teams that took time for debriefing (0.70 [0.60-0.80]). Resuscitation attempts perceived as inappropriate by clinicians, and the accompanying moral distress, were associated with an increased likelihood of intention to leave the job. Interprofessional collaboration, teamwork, and regular interdisciplinary debriefing were associated with a lower risk of intention to leave the job. ClinicalTrials.gov; No.: NCT02356029.


Culture-independent analysis of the microbial composition of the African traditional fermented foods poto poto and dégué by using three different DNA extraction methods.
The microbial composition of the traditional fermented foods poto poto (a maize dough from the Rep. of Congo) and dégué (a millet dough from Burkina Faso) was studied by a culture-independent approach using TTGE to separate the amplified target V3 region of the 16S rRNA gene from total microbial community, followed by DNA sequencing and homology search. Three different extraction methods were used. Guanidium thiocyanate-based DNA extraction provided better performance regarding purity and DNA yield, allowing the detection of a higher number of DNA bands by TTGE in poto poto. By contrast, all three methods yielded similar results for dégué samples, indicating that the performance of the DNA extraction method largely depends on the food composition. Sequencing of DNA bands from TTGE gels corresponding to poto poto samples revealed the presence of Lactobacillus gasseri, Enterococcus sp., Escherichia coli, Lactobacillus plantarum/paraplantarum, Lactobacillus acidophilus, Lactobacillus delbrueckii, Bacillus sp., Lactobacillus reuteri and Lactobacillus casei. The following bacteria were identified in dégué: L. gasseri, Enterococcus sp., E. coli, Lactobacillus fermentum, Lactobacillus brevis, and L. casei.


Ultra-low-crosstalk multicore fiber-integrated pump-signal combiner for a core-pumped EDFA.
Fiber-integrated, submersible-qualified, core-pumped, multicore EDFAs are indispensable for space-division-multiplexing envisioned for the next generation of submarine communication lines. Here we demonstrate a fully packaged, 63-dB counter-propagating crosstalk, and 70-dB-return-loss four-core pump-signal-combiner. This enables core-pumping of a four-core EDFA.


Hydrogel-derived non-precious electrocatalysts for efficient oxygen reduction.
The development of highly active, cheap and robust oxygen reduction reaction (ORR) electrocatalysts to replace precious metal platinum is extremely urgent and challenging for renewable energy devices. Herein we report a novel, green and especially facile hydrogel strategy to construct N and B co-doped nanocarbon embedded with Co-based nanoparticles as an efficient non-precious ORR catalyst. The agarose hydrogel provides a general host matrix to achieve a homogeneous distribution of key precursory components including cobalt (II) acetate and buffer salts, which, upon freeze-drying and carbonization, produces the highly active ORR catalyst. The gel buffer containing Tris base, boric acid and ethylenediaminetetraacetic acid, commonly adopted for pH and ionic strength control, plays distinctively different roles here. These include a green precursor for N- and B-doping, a salt porogen and a Co(2+) chelating agent, all contributing to the excellent ORR activity. This hydrogel-based process is potentially generalizable for many other catalytic materials.


Maslinic acid, a triterpenic anti-tumoural agent, interferes with cytoskeleton protein expression in HT29 human colon-cancer cells.
Maslinic acid (MA) is an anti-tumoural agent which shows potent anti-proliferative properties against the HT29 colon-cancer cells. To shed light upon the active mechanism of MA we have investigated its effects upon the cytoskeleton. We used a proteomics procedure based on two-dimensional gel electrophoresis, mass analysis and peptide mass fingerprinting. The incubation of HT29 cells with MA led to G1 cell-cycle arrest. After 24hours' exposure to 3.7μM (IC50/8) and 30μM (IC50) MA fourteen differentially expressed cytoskeletal proteins could be discerned. One group of these proteins, made up of keratin 2, keratin 8, keratin type II cytoskeletal 8, keratin type I cytoskeletal 9, keratin type I cytoskeletal 18, cytokeratins 18 and 19, and β-actin, exert a structural function, whilst another group, made up of lamin B1, gelsolin 1, septin 2, villin 1, actin-related protein 2 and moesin, is related to the nucleation of actin and cytoskeleton formation. Changes in the expression of moesin, villin 1 and β-actin identified by the proteomics techniques were corroborated by Western blotting. This is the first evidence obtained of the regulatory effects of MA on the cytoskeleton, which may prove to be one of the bases of its anti-proliferative effect against colon-cancer cells. In this paper we describe the changes in the expression of different cytoskeleton proteins identified by the proteomics techniques and corroborated by Western blotting. This is the first evidence obtained of the regulatory effects of MA on the cytoskeleton, which may prove to be one of the bases of its anti-proliferative effect against colon-cancer cells.


Association between genetic predisposition and disease burden of stroke in China: a genetic epidemiological study.
Stroke ranks second worldwide and first in China as a leading cause of death and disability. It has a polygenic architecture and is influenced by environmental and lifestyle factors. However, it remains unknown as to whether and how much the genetic predisposition of stroke is associated with disease burden. Allele frequency from the whole genome sequencing data in the Chinese Millionome Database of 141,418 individuals and trait-specific polygenic risk score models were applied to estimate the provincial genetic predisposition to stroke, stroke-related risk factors and stroke-related drug response. Disease burden including mortality, disability-adjusted life years (DALYs), years of life lost(YLLs), years lived with disability (YLDs) and prevalence in China was collected from the Global Burden Disease study. The association between stroke genetic predisposition and the epidemiological burden was assessed and then quantified in both regression-based models and machine learning-based models at a provincial resolution. Among the 30 administrative divisions in China, the genetic predisposition of stroke was characterized by a north-higher-than-south gradient (p < 0.0001). Genetic predisposition to stroke, blood pressure, body mass index, and alcohol use were strongly intercorrelated (rho >0.6; p < 0.05 after Bonferroni correction for each comparison). Genetic risk imposed an independent effect of approximately 1-6% on mortality, DALYs and YLLs. The distribution pattern of stroke genetic predisposition is different at a macroscopic level, and it subtly but significantly impacts the epidemiological burden. Further research is warranted to identify the detailed aetiology and potential translation into public health measures. Beijing Municipal Science and Technology Commission (Z191100006619106), CAMS Innovation Fund for Medical Sciences (CAMS-I2M, 2023-I2M-1-001), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17), National Natural Science Foundation of China (32000398, 32171441 to X.J.), Natural Science Foundation of Guangdong Province, China (2017A030306026 to X.J.), and National Key R&D Program of China (2022YFC2502402).


Findings on Repeat Posttraumatic Brain Computed Tomography Scans in Older Patients With Minimal Head Trauma and the Impact of Existing Antithrombotic Use.
Evaluate the utility of routine rescanning of older, mild head trauma patients with an initial negative brain computed tomography (CT), who is on a preinjury antithrombotic (AT) agent by assessing the rate of delayed intracranial hemorrhage (dICH), need for surgery, and attributable mortality. Participating centers were trained and provided data collection instruments per institutional review board-approved protocols. Data were obtained from manual chart review and electronic medical record download. Adults ≥55 years seen at Level I/II Trauma Centers, between 2017 and 2019 with suspected head trauma, Glasgow Coma Scale 14 to 15, negative initial brain CT, and no other Abbreviated Injury Scale injuries >2 were identified, grouped by preinjury AT therapy (AT- or AT+) and compared on dICH rate, need for operative neurosurgical intervention, and attributable mortality using univariate analysis (α=.05). A total of 2,950 patients from 24 centers were enrolled; 280 (9.5%) had a repeat brain CT. In those rescanned, the dICH rate was 15/126 (11.9%) for AT- and 6/154 (3.9%) in AT+. Assuming nonrescanned patients did not suffer clinically meaningful dICH, the dICH rate would be 15/2001 (0.7%) for AT- and 6/949 (0.6%) for AT+. No surgical operations were done for dICH. All-cause mortality was 9/2950 (0.3%) and attributable mortality was 1/2950 (0.03%). The attributable death was an AT+, dICH patient whose family declined intervention. In older patients with an initial Glasgow Coma Scale of 14 to 15 and a negative initial brain CT scan, the dICH rate is low (<1%) and of minimal clinical consequence, regardless of AT use. In addition, no patient had operative neurosurgical intervention. Therefore, routine rescanning is not supported based on the results of this study.


Four incision radial keratotomy.
Radial keratotomy is a constantly evolving procedure. This paper investigates the value of four incision radial keratotomy. The possible advantages of fewer incisions include increased corneal stability, lower risk of perforation, less potential of endothelial cell loss, decreased chance of overcorrection, and simplification of the procedure. We evaluated the results of four incision radial keratotomy in 55 eyes of 31 patients. Follow-up ranged from one to 18 months. Results in low myopia (-2.00 to -3.12 diopters) show 93% of the patients were 20/40 or better, 90% were within +/- 1 diopter of emmetropia, and no patients were overcorrected greater than 1 diopter. In moderate myopia (-3.25 to -4.37 diopters), 84% of the patients were 20/40 or better, 92% were within +/- 1 diopter of emmetropia, and no patients were overcorrected greater than 1 diopter. Regression analysis was performed and it was determined that the postoperative result was equal to .262 + [1.293 x preop spherical equivalent] - [1.166 x optical zone] + [0.56 x depth] + [.038 x age], R = .87.


Spitz Nevus and Other Spitzoid Tumors in Children. Part 2: Cytogenetic and Molecular Features. Prognosis and Treatment.
Melanocytic neoplasms with spitzoid morphology (Spitz nevi, atypical Spitz tumors, and spitzoid melanomas) may be benign or malignant. Because the malignant potential of atypical Spitz tumors is uncertain, the proper therapeutic approach has been much debated over the years. Promising new techniques for molecular analysis have enabled better predictions of the biological behavior of these tumors. We review their cytogenetic features and prognosis and also provide an update of the most recent recommendations for management.


Cost Effectiveness of Sequencing 34 Cancer-Associated Genes as an Aid for Treatment Selection in Patients with Metastatic Melanoma.
To determine whether a next-generation sequencing (NGS) panel of 34 cancer-associated genes would cost-effectively aid in the treatment selection for patients with metastatic melanoma, compared with a single-site BRAF V600 mutation test. A decision model was developed to estimate the costs and health outcomes of the two test strategies. The cost effectiveness of these two strategies was analyzed from a payer perspective over a 2-year time horizon with model parameters taken from the literature. In the base case, the gene sequencing panel strategy resulted in a cost of US$120,022 and 0.721 quality-adjusted life years (QALYs) per patient, whereas the single-site mutation test strategy resulted in a cost of US$128,965 and 0.704 QALYs. Thus, the gene sequencing panel strategy cost US$8943 less per patient and increased QALYs by 0.0174 per patient. Sensitivity analyses showed that, compared with the single-site mutation test strategy, the gene sequencing panel strategy had a 90.9% chance of having reduced costs and increased QALYs, with the cost of the gene sequencing panel test having minimal effect on the incremental cost. Compared with the single-site mutation test, the use of an NGS panel of 34 cancer-associated genes as an aid in selecting therapy for patients with metastatic melanoma reduced costs and increased QALYs. If the base-case results were applied to the 8900 patients diagnosed with metastatic melanoma in the USA each year, the gene sequencing panel strategy could result in an annual savings of US$79.6 million and a gain of 155 QALYs.


Anti-tetanus toxin titers in sera of the women who gave births in 1985 and 1989 in Gipuzkoa (Basque Country, Spain).
14.9% (208/1400) of the women who gave births in 1985 and 1989 in Gipuzkoa (Basque Country, Spain), was considered to have 'protective' levels (> or = 0.01 IU/ml) of tetanus antitoxin as measured by the passive haemagglutination test. Prevalence of protective antibodies was correlated to the years when women were born: 54.7% (64/117) of those born after 1965 were considered to have 'protective' levels (> or = 0.01 IU/ml) of tetanus antitoxin in contrast to those born before 1956 [only 6.2% (21/338)]. This is considered to be due to the infant immunization campaign introduced in 1965 in the Basque Country. Thus, we conclude that the tetanus immunization campaigns in the Basque Country adult population is urgent.


Regioselective modification of a xyloglucan hemicellulose for high-performance biopolymer barrier films.
Biobased polymers such as starch and hemicelluloses from wood are of interest for packaging applications, but suffer from limitations in performance under moist conditions. Xyloglucan from industrial tamarind seed waste offers potential, but its Tg is too high for thermal processing applications. Regioselective modification is therefore performed using an approach involving periodate oxidation followed by reduction. The resulting polymer structures are characterized using MALDI-TOF-MS, size-exclusion chromatography, FTIR and carbohydrate analysis. Films are cast from water and characterized by thermogravimetry, dynamic mechanical thermal analysis, dynamic water vapor sorption, oxygen transmission and tensile tests. Property changes are interpreted from structural changes. These new polymers show much superior performance to current petroleum-based polymers in industrial use. Furthermore, this regioselective modification can be carefully controlled, and results in a new type of cellulose derivatives with preserved cellulose backbone without the need for harmful solvents.


Insertion of circularly permuted cyan fluorescent protein into the ligand-binding domain of inositol 1,4,5-trisphosphate receptor for enhanced FRET upon binding of fluorescent ligand.
Binding of fluorescent ligand (FL) to the cyan fluorescent protein (CFP)-coupled ligand-binding domain of the inositol 1,4,5-trisphosphate (IP3) receptor (CFP-LBP) produces fluorescence (Förster) resonance energy transfer (FRET). A competitive fluorescent ligand assay (CFLA), using the FRET signal from competition between FLs and IP3, can measure IP3 concentration. The FRET signal should be enhanced by attaching a FRET donor to an appropriate position. Herein, we inserted five different circularly permuted CFPs in the loop between the second and third α-helices to generate membrane-targeted fluorescent ligand-binding proteins (LBPs). Two such proteins, LBP-cpC157 and LBP-cpC173, localized at the plasma membrane, displayed FRET upon binding the high-affinity ligand fluorescent adenophostin A (F-ADA), and exhibited a decreased fluorescence emission ratio (480 nm / 535 nm) by 1.6- to 1.8-fold that of CFP-LBP. In addition, binding of a fluorescent low-affinity ligand (F-LL) also reduced the fluorescence ratio in a concentration-dependent manner, with EC50 values for LBP-cpC157 and LBP-cpC173 of 34.7 nM and 27.6 nM, respectively. These values are comparable to that with CFP-LBP (29.2 nM), indicating that insertion of cpC157 and cpC173 did not disrupt LBP structure and function. The effect of 100 nM F-LL on the decrease in fluorescence ratio was reversed upon addition of IP3, indicating binding competition between F-LL and IP3. We also constructed cytoplasmic fluorescent proteins cyLBP-cpC157 and cyLBP-cpC173, and bound them to DYK beads for imaging analyses. Application of F-ADA decreased the fluorescence ratio of the beads from the periphery to the center over 3 - 5 min. Application of F-LL also decreased the fluorescence ratio of cyLBP-cpC157 and cyLBP-cpC173 by 20-25%, and subsequent addition of IP3 recovered the fluorescence ratio in a concentration-dependent manner. The EC50 value and Hill coefficient obtained by curve fitting against the IP3-dependent recovery of fluorescence ratio can be used to estimate the IP3 concentration.


Nasal tip bossae in rhinoplasty. Etiology, predisposing factors, and management techniques.
To identify preoperative risk factors and surgical techniques that influence the risk of developing postoperative nasal tip bossae in rhinoplasty. A secondary objective was to review the characteristics, management techniques, and outcomes of those study patients with postoperative bossae. Univariate and multivariate analysis carried out in a case series. Private facial plastic surgery practice. All patients who underwent aesthetic nasal surgery that included surgical modification of the nasal tip, and in whom documentation was complete and photographic follow-up was available, were considered eligible. The study group consisted of 875 patients of whom 37 (4.2%) developed bossae postoperatively. Potential risk factors for postoperative bossae included age, sex, previous nasal surgery, preoperative tip asymmetry, preoperative lobular bifidity, preoperative bossae, skin thickness, surgical tip technique, use of columellar struts, columellar battens, lobular crushed cartilage grafts, and tip shield grafts. In the univariate analysis, females, patients undergoing primary rhinoplasty, younger age groups (12- to 22-year-olds), thin skin, and widened interdomal distance (bifidity) were all noted to have moderate or strong associations with nasal tip bossae. In the multivariate analysis, the younger age group, thin skin, and bifidity were statistically significant and independently associated with nasal tip bossae, independent of the type of tip surgery. In addition, clinically relevant associations were noted in females and patients undergoing primary rhinoplasty. Recognition of risk factors, preventive measures, and treatment methods is recommended.


Ontogenetic development of the G protein-mediated adenylyl cyclase signalling in rat brain.
Maturation of the brain adenylyl cyclase (AC) signalling system was investigated in the developing rat cortex, thalamus and hippocampus. Expression of AC type II, IV and VI measured by Western blot dramatically increased in all tested brain regions during the first 3 weeks after birth and these levels were maintained in adulthood. AC type I did not change during ontogenesis. In parallel, AC enzyme activities were determined in order to obtain the functional correlates to the preceding structural (immunoblot) analyses of trimeric G proteins [Ihnatovych et al., Dev. Brain Res. (2002) in press]. Surprisingly, basal, manganese-, fluoride-, forskolin- and GTP-stimulated adenylyl cyclase developed similarly. The relatively low enzyme activities, which were determined at birth, progressively increased (about four times) to a clear maximum around postnatal day PD 12. This was followed by a progressive regression to adulthood so that activity of AC at PD 90 was comparable with the low neonatal level. The peak of AC activities at PD 12 was detected in all tested brain regions. Stimulatory (isoproterenol) effect on basal AC activity as well as inhibitory (baclofen) effect on forskolin-stimulated AC activity were unchanged between PD 12 and PD 90. Thus, comparison of results of the structural and functional analyses of adenylyl cyclase signalling system revealed a clear dissociation between the increase in the amount protein of various AC isoforms and the decrease of total G-protein mediated enzyme activities between PD 12 and adulthood. As none of the complex changes in trimeric G protein levels can explain this difference, the future research has to be oriented to identification of potential negative regulators of AC in the course of brain development. Among these, the newly discovered group of GTPase activating proteins, RGS, appears to be of primary importance because these proteins represent potent negative regulators of any G protein-mediated signalling in brain.


Membranoproliferative glomerulonephritis and circulating cryoglobulins.
Previous studies on membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemic glomerulopathy (CG) were based upon case series that were performed before hepatitis C virus (HCV) infection was routinely investigated. Therefore, it remains unknown how far HCV contributes to MPGN or CG, and there have only been a few reports about HCV-negative idiopathic MPGN. Thirty-five patients with MPGN diagnosed by renal biopsy who underwent examination for HCV infection at our institute between 1990 and 2008 were recruited for this study. Patients with HCV infection at presentation were included, but patients with complications such as underlying lymphoproliferative disorders, autoimmune diseases like lupus nephritis, infection, and liver disease due to hepatitis B virus or alcohol abuse were excluded. A total of 35 patients were enrolled and they were divided into two groups according to the presence/absence of circulating cryoglobulins (cryo). The 23 patients who had cryo-negative and HCV-negative idiopathic MPGN were divided into subgroups with type 1 and type 3 disease. In the cryo-positive group (n = 9), 7 patients were positive for HCV infection, while 2 patients were negative. In the cryo-negative group (n = 26), 3 patients were positive for HCV infection, while 23 patients were negative (idiopathic MPGN). Compared with the cryo-negative group, the cryo-positive group had several characteristics such as more severe thrombocytopenia, higher serum immunoglobulin (Ig)G and IgM levels, lower levels of hemolytic complement (CH50) and complement component (C)4, predominant IgM staining, and type 1 histology. Patients with cryo-negative and HCV-negative 'idiopathic' MPGN showed predominant staining for IgG in both type 1 and type 3 cases, unlike the predominant staining for IgM in the cryo-positive group. Compared with type 3 cases, type 1 cases had a younger age, lower levels of CH50, C3 and C4, and less proteinuria. In the cryo-positive group, 4 patients (44.4 %) died, with death from B cell lymphoma and liver failure in 2 patients each, while 1 patient (8 %) developed end-stage renal failure requiring dialysis. In contrast, all patients in the cryo-negative group remained alive during follow-up, although 4 patients (2 type 1 cases and 2 type 3 cases) required dialysis. Cryo-positive MPGN shows a close relationship with HCV infection and IgM, resulting in a poor prognosis. Cryo-negative and HCV-negative idiopathic MPGN has a close relationship with IgG staining, and type 1 cases feature characteristics such as a younger age, more severe hypocomplementemia, and less proteinuria than in type 3 cases.


The relationship between insulin resistance and CpG island methylation of LMNA gene in polycystic ovary syndrome.
We sought to investigate the relationship between the changes of CpG island methylation status of LMNA gene and insulin resistance in polycystic ovary syndrome (PCOS) patients. The genome-wide methylation microarray screening was done in three PCOS cases of insulin resistance and one case of a normal woman. The PCOS insulin resistance-related genes were identified as indicated by the results of gene chip screening. Then, 24 cases of insulin-resistant PCOS patients and 24 cases of normal individuals were studied to identify the effects of the candidate genes using genome-wide study of DNA from the peripheral blood analyzed by MassARRAY(®)EpiTYPER™ DNA methylation analysis technique. We found that the methylation status of CpG island in the promoter area of LMNA gene was changed. The 20 CG sites in CpG island of LMNA gene were examined using case control experiment among which 12 CpG sites differed significantly (P < 0.05) between two groups while the remaining eight CpG sites differed non-significantly. We, therefore, concluded that the changes in the hypermethylation status of CpG island of LMNA gene were related to the insulin resistance in PCOS patients, indicating that this gene may be involved in the regulation of PCOS-associated insulin resistance.


Randomized, controlled phase II study of post-surgery radiotherapy combined with recombinant adenoviral human p53 gene therapy in treatment of oral cancer.
The aim of this study is to evaluate clinical benefits of recombinant adenoviral human p53 (rAd-p53) gene therapy combined with radiotherapy in prevention of oral cancer recurrence after a radical resection. A total of 51 patients with tongue cancer (TCa) and 56 patients with gingival carcinoma (GCa) satisfying the inclusion criteria were randomly assigned to two groups: the experiment group (EG) and the control group (CG). The EG group received multipoint injections of rAd-p53 into the surgical wound surface at a dose of 1 × 10¹² viral particles after a radical resection. Patients in both EG and CG were given radiotherapy at a total dose of 60 Gy at 3 weeks after surgery. All these patients were followed up for at least 3 years. Two cases (2/27) of TCa and 2 (2/30) in GCa patients had a local recurrence in EG, but 8 (8/24) TCa and 8 (8/26) GCa patients in CG had a local recurrence. Both recurrent rates of TCa (33.3%) and GCa (30.8%) in CG are statistically significantly higher than those of TCa (7.4%) and GCa (6.7%) in EG, respectively. The overall recurrent rate in EG is 7%, which is also statistically significantly lower than that (32%) in CG. The 3-year overall survival (OS) rate and 3-year disease-free survival (DFS) rate of EG is 100% and 93%, respectively. The 3-year OS and DFS rates of CG are 94 and 68%, respectively. Mild or medium fever and flu-like symptoms were more frequently observed in EG and were considered to be associated with application of rAd-p53. Post-tumorectomy wound surface injection of rAd-p53 combining with radiotherapy is a safe and effective regimen for the patients with TGa or GCa.


A rapid calcium influx during exocytosis in Paramecium cells is followed by a rise in cyclic GMP within 1 s.
The synchrony of trichocyst exocytosis in Paramecium allows temporal correlation of associated events. Using quenched flow we observed a Ca2+ influx concurrent with exocytosis within 80 ms after stimulation with the secretagogue aminoethyldextran. Cyclic AMP did not change in depency of stimulation. Cyclic GMP transiently increased after 500 ms, culminating at 2 s, and thus considerably lags behind exocytosis induction and influx of Ca2+. Both Ca2+ influx and rise in cGMP are known to be induceable also by Ba2+ or veratridine, allegedly via the opening of ciliary Ca2+ channels. However, only veratridine stimulated exocytosis. We conclude that both aminoethyldextran and veratridine induce an exocytosis-associated Ca2+ influx, which is responsible for the rise in cGMP, through an as yet unknown pathway.


Quantifying the heritability of glioma using genome-wide complex trait analysis.
Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) influencing glioma risk. While these SNPs only explain a small proportion of the genetic risk it is unclear how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to three GWAS datasets totalling 3,373 cases and 4,571 controls and performed a meta-analysis to estimate the heritability of glioma. Our results identify heritability estimates of 25% (95% CI: 20-31%, P = 1.15 × 10(-17)) for all forms of glioma - 26% (95% CI: 17-35%, P = 1.05 × 10(-8)) for glioblastoma multiforme (GBM) and 25% (95% CI: 17-32%, P = 1.26 × 10(-10)) for non-GBM tumors. This is a substantial increase from the genetic variance identified by the currently identified GWAS risk loci (~6% of common heritability), indicating that most of the heritable risk attributable to common genetic variants remains to be identified.


Combining the analyses of introgressive hybridisation and linkage mapping to investigate the genetic architecture of population divergence in the lake whitefish (Coregonus clupeaformis, Mitchill).
Adaptation and reproductive isolation, the engines of biological diversity, are still elusive when discussing the genetic bases of speciation. Namely, the number of genes and magnitude of selection acting positively or negatively on genomic traits implicated in speciation is contentious. Here, we describe the first steps of an ongoing research program aimed at understanding the genetic bases of population divergence and reproductive isolation in the lake whitefish (Coregonus clupeaformis). A preliminary linkage map originating from a hybrid cross between dwarf and normal ecotypes is presented, whereby some of the segregating AFLP markers were found to be conserved among natural populations. Maximum-likelihood was used to estimate hybrid indices from non-diagnostic markers at 998 AFLP loci. This allowed identification of the most likely candidate loci that have been under the influence of selection during the natural hybridisation of whitefish originating from different glacial races. As some of these loci could be identified on the linkage map, the possibility that selection of traits in natural populations may eventually be correlated to specific chromosomal regions was demonstrated. The future prospects and potential of these approaches to elucidate the genetic bases of adaptation and reproductive isolation among sympatric ecotypes of lake whitefish is discussed.


Experimental study of forearm compartmental pressures.
Chronic compartment syndrome is well recognized, although it is rare in the forearm. Diagnosis is based on history, clinical examination, and compartment pressure readings. Existing normal pressure ranges for the forearm are based on lower limb measurements. This study aimed to establish normal pre- and post-exercise forearm compartment pressures. Using a Stryker intracompartmental pressure monitor (Stryker, Kalamazoo, MI), 41 volunteers had pressure measurements of the extensor and flexor forearm compartments before and after exercise. Normal ranges were established for pre-exercise extensor compartment (2-27 mm Hg; upper confidence interval [CI] 18.8-25.2 mm Hg), post-exercise extensor compartment (2-24 mm Hg; upper CI 16.8-22.8 mm Hg), pre-exercise flexor compartment (1-19 mm Hg; upper CI 13.3-17.4 mm Hg), and post-exercise flexor compartment (0-19 mm Hg; upper CI 16-21.4 mm Hg) pressures. No significant difference was found between pressures before and after exercise. There was no correlation between whether pressures increased or decreased following exercise. There was a significant gender difference. Normal ranges were 0 to 25.2 mm Hg for the extensor compartment and 0 to 21.4 mm Hg for the flexor compartment. This study has shown a significant difference in normal forearm compartment pressures between genders. A normal reference range of flexor and extensor forearm compartment pressures to aid diagnosis of chronic compartment syndrome has been determined. This might also prove useful in aiding the diagnosis of acute forearm compartment syndrome.


An optimized design of in-shoe heel lifts reduces plantar pressure of healthy males.
Conventional heel lift with a flat surface increases the risk of foot problems related to higher plantar pressure and decreased stability. In this study, an optimized design of in-shoe heel lifts developed to maintain the midfoot function was tested to investigate if the plantar pressure distribution was improved. The design was based on three dimensional foot plantar contour which was captured by an Infoot 3D scanning system while the heel was elevated by a heel wedge. To facilitate midfoot function, an arch support was designed to support the lateral longitudinal arch, while allowing functional movement of the medial longitudinal arch. Twenty healthy male subjects were asked to walk along an 8m walkway while wearing high-cut footwear with and without the optimized heel lift. Peak pressure, contact area and force-time integral were measured using the Pedar insole system. Range and velocity of medial-lateral center of pressure during forefoot contact phase and foot flat phase were collected using a Footscan pressure plate. Compared to the shoe only condition, peak pressure under the rearfoot decreased with the optimized heel lift, while no increase of peak pressure was observed under the forefoot and midfoot regions, indicating improved plantar pressure distribution. The findings of this study suggest that this optimized heel lift has better biomechanical performance than a conventional flat heel lift. Results from this study may have implications for insole and shoe last design, especially for people who need additional heel height without sacrificing midfoot function.


Structural Evolution of Nanoscale Zero-Valent Iron (nZVI) in Anoxic Co(2+) Solution: Interactional Performance and Mechanism.
The structures of nanoscale zero-valent iron (nZVI) particles evolving during reactions, and the reactions are influenced by the evolved structures. To understand the removal process in detail, it is important to investigate the relationships between the reactions and structural evolution. Using high resolution-transmission electron microscopy (HR-TEM), typical evolved structures (sheet coprecipitation and cavity corrosion) of nZVI in anoxic Co(2+) solutions were revealed. The system pH (pH measured in mixture), which controls the stability of coprecipitation and the nZVI corrosion rate, were found to be the determining factors of structural evolutions. X-ray photoelectron spectroscopy (XPS) results indicated that the formation and dissolution of sheet structure impacts on the ratio of Fe(0) on the nZVI surface and the surface Co(2+) reduction. The cavity structure provides the possibility of Co migration from the surface to the bulk of nZVI, leading to continuous removal. Subacidity conditions could accelerate the evolution and improve the removal; the results of structurally controlled reactions further indicated that the removal was suspended by the sheet structure and enhanced by cavity structure. The results and discussion in this paper revealed the "structural influence" crucial for the full and dynamical understanding of nZVI reactions.


Addressing the severity and intensity of poverty in Sub-Saharan Africa: how relevant is the ICT and financial development pathway?
The study examines the effectiveness of ICT diffusion and financial development in reducing the severity and intensity of poverty in Sub-Saharan Africa (SSA). Using data from the World Development Indicators and the Global Consumption and Income Project (1980-2019), we provide evidence, robust to several specifications from the dynamic system GMM and the panel corrected standard errors estimation techniques, to show that, compared to financial access, ICT usage, and ICT access, ICT skills is remarkable in reducing both the severity and intensity of poverty. The results further revealed that, though ICT skills reduce poverty, the effect is more pronounced in the presence of enhanced financial development. Policy recommendations are provided in line with the region's green growth agenda and technological progress.


Effects of monovalent cations on AMP nucleosidase from Azotobacter vinelandii.
The effect of monovalent cations on the purified AMP nucleosidase (AMP phosphoribohydrolase, EC 184.108.40.206) from Azotobacter vinelandii was investigated. All the monovalent cations were activators of the enzyme: Rb+ and Cs+ were the most effective, followed by K+, Na+, NH4+ and Li+ in that order. The apparent Ka for MgATP and nH values (Hill's interaction coefficient) decreased from 0.9 to 0.1 mM, and from 4 to 1, respectively, with the increase in K+ concentration, suggesting that the cation effects are on MgATP binding rather than catalysis. Gel filtration studies have revealed that the enzyme forms a non-dissociable enzyme species with a Stokes radius of 6.0--6.2 nm in the presence of saturating concentrations of monovalent cations, which can be distinguished from the 5.5-nm enzyme species showing temperature-dependent dissociation of the molecule in sulfate or phosphate. These results suggest that these ligands affect the association of the subunits through changes in the environment of the hydrophobic side chains of the enzyme molecules.


Cognitive map formation in the blind is enhanced by three-dimensional tactile information.
For blind individuals, tactile maps are useful tools to form cognitive maps through touch. However, they still experience challenges in cognitive map formation and independent navigation. Three-dimensional (3D) tactile information is thus increasingly being considered to convey enriched spatial information, but it remains unclear if it can facilitate cognitive map formation compared to traditional two-dimensional (2D) tactile information. Consequently, the present study investigated the impact of the type of sensory input (tactile 2D vs. tactile 3D vs. a visual control condition) on cognitive map formation. To do so, early blind (EB, n = 13), late blind (LB, n = 12), and sighted control (SC, n = 14) participants were tasked to learn the layouts of mazes produced with different sensory information (tactile 2D vs. tactile 3D vs. visual control) and to infer routes from memory. Results show that EB manifested stronger cognitive map formation with 3D mazes, LB performed equally well with 2D and 3D tactile mazes, and SC manifested equivalent cognitive map formation with visual and 3D tactile mazes but were negatively impacted by 2D tactile mazes. 3D tactile maps therefore have the potential to improve spatial learning for EB and newly blind individuals through a reduction of cognitive overload. Installation of 3D tactile maps in public spaces should be considered to promote universal accessibility and reduce blind individuals' wayfinding deficits related to the inaccessibility of spatial information through non-visual means.


The glycine transporter GLYT1 interacts with Sec3, a component of the exocyst complex.
Evidence is accumulating that the glycine transporter GLYT1 regulates NMDA receptor function by modulating the glycine concentration in glutamatergic synapses. In this article, we describe a physical and functional interaction between GLYT1 and the exocyst complex. Through a yeast two-hybrid screen to search for proteins capable of interacting with the intracellular C-terminal tail of GLYT1, we identified a protein that is highly homologous to the human and mouse Sec3 protein, a component of the exocyst complex. Pull-down and immunoprecipitation assays confirmed the physical interaction between the C-terminus of GLYT1 and Sec3. Subsequently, immunofluorescence experiments indicated that Sec3-GFP was partially recruited to the plasma membrane upon coexpression with GLYT1. The interaction of GLYT1 with exocyst components was also observed in the native rat brain since complexes immunoprecipitated from brain extracts with anti-GLYT1 antibodies contained both Sec6 and Sec8. Functional assays revealed that Sec3 increased the transporter capacity of GLYT1, suggesting that the exocyst favors insertion of GLYT1 into the plasma membrane.


Authorship Policies at U.S. Doctoral Universities: A Review and Recommendations for Future Policies.
Intellectual contribution in the form of authorship is a fundamental component of the academic career. While research has addressed questionable and harmful authorship practices, there has largely been no discussion of how U.S. academic institutions interpret and potentially mitigate such practices through the use of institution-level authorship policies. To gain a better understanding of the role of U.S. academic institutions in authorship practices, we conducted a systematic review of publicly available authorship policies for U.S. doctoral institutions (using the 266 2018 Carnegie-classified R1 and R2 Universities), focusing on components such as specification of authorship criteria, recommendations for discussing authorship, dispute resolution processes, and guidance for faculty-student collaborations. We found that only 24% of the 266 Carnegie R1 and R2 Universities had publicly available authorship policies. Within these policies, the majority (93%) specified criteria for authorship, but provided less guidance about actual processes for applying such criteria (62%), handling authorship disputes (62%), and managing faculty-student author teams (49%). Further, we found that any discussion of dispute resolution practices typically lacked specificity. Recommendations grounded in these findings are offered for institutions to leverage their ability to guide the authorship process by adopting an authorship policy that acknowledges disciplinary diversity while still offering substantive guidance.


Frequent Offenders and Patterns of Injury.
Given the liver's role in drug metabolism, it is uniquely sensitive to potential drug-induced liver injury (DILI) despite inherent protective mechanisms. In this article, we focus on the most common causes of DILI and their patterns of injury. Although not comprehensive, we attempt to cover several classes of commonly used drugs, and their associated patterns of injury and management.


Extending photoinduced charge separation lifetimes by using supramolecular design: guanine-perylenediimide G-quadruplex.
We report here a potassium-induced guanine quadruplex as a supramolecular platform for controlled assembly of electron donor-acceptor systems. A monodisperse, C4-symmetric octamer of a guanine-perylene-3,4,9,10-bis(dicarboximide) conjugate (GPDI) was prepared in tetrahydrofuran. The two layers of cyclic guanine tetramers have the same direction of rotation, and the PDI moiety between the layers adopts a nearly eclipsed relationship (H-aggregation), as revealed by small- and wide-angle X-ray scattering, NMR spectroscopy, and steady-state UV/vis absorption. Following photoexcitation of the PDI moiety in the quadruplex, charge separation occurs in τCS = 98 ± 12 ps to give G(+•)-PDI(-•) that recombines in τCR = 1.2 ± 0.2 ns, which is >100 times longer than that in the monomeric GPDI dyad. The transient absorption spectrum of G(+•)-PDI(-•) within the GPDI quadruplex suggests the formation of a radical anion delocalized over the neighboring PDI units, and this result is consistent with the more favorable electrochemical reduction potential for PDIs in the quadruplex relative to the monomer.


Enhancing the solubility of natural compound xanthotoxin by modulating stability via cocrystallization engineering.
A comprehensive cocrystal study for the insoluble natural pharmaceutical compound xanthotoxin (XT) was conducted, in which xanthotoxin-para aminobenzoic acid (XT-PABA) and xanthotoxin-oxalic acid (XT-OA) cocrystals were obtained. The xanthotoxin cocrystals were characterized by powder X-ray diffraction, thermal analysis, and FT-IR spectra, and the crystal structures were determined by single-crystal X-ray diffraction. Crystal structures and thermal analysis showed that XT-OA was more stable than XT-PABA. Energy framework calculation indicated that H-bond and π···π interactions generated in XT-OA were stronger than that in XT-PABA and xanthotoxin. The powder dissolution experiments of xanthotoxin and its cocrystals suggested the XT-OA cocrystal might be applied as an alternative formulation of API, on account of its enhanced solubility and stability in the hydrochloric acid buffer solution (pH 1.2). The cocrystallization engineering can prolong the enhanced apparent solubility via modulating the stability.


Plasma and platelet skimming at T-junctions.
Separation of plasma, erythrocytes, and platelets was studied in T-shaped bifurcations prepared by a casting technique. The diameters of the side and main channel were 100 microns and 200 microns, respectively. Small blood samples (about 20 microliters) were collected from the side channel for determination of erythrocyte and platelet concentrations which were compared to the corresponding values in the reservoir. Conversely to the well-known erythrocyte reduction due to plasma skimming a relative enrichment of platelets in the side branch was observed. The thickness of the plasma layer in the main channel was found to depend on the aggregation tendency of the erythrocytes for Reynolds numbers around 0.3.


Readmission for Acute Exacerbation within 30 Days of Discharge Is Associated with a Subsequent Progressive Increase in Mortality Risk in COPD Patients: A Long-Term Observational Study.
Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge. The prognostic significance of early readmission is not fully understood. The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients. The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge. Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years. Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity. Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51-4.05) was the only variable independently associated with 30-day readmission. The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10-5.59). In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5). In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death.


Evaluation of nanoparticles as oral vehicles for immunotherapy against experimental peanut allergy.
The aim of this work was to evaluate the potential application of an original oral immunotherapy, based on the use of nanoparticles, against an experimentally induced peanut allergy. In this context, a roasted peanut extract, containing the main allergenic proteins, were encapsulated into poly(anhydride) nanoparticles. The resulting peanut-loaded nanoparticles (PE-NP) displayed a mean size of about 150nm and a significantly lower surface hydrophobicity than empty nanoparticles (NP). This low hydrophobicity correlated well with a higher in vitro diffusion in pig intestinal mucus than NP and an important in vivo capability to reach the intestinal epithelium and Peyer's patches. The immunotherapeutic capability of PE-NP was evaluated in a model of pre-sensitized CDI mice to peanut. After completing therapy of three doses of peanut extract, either free or encapsulated into nanoparticles, mice underwent an intraperitoneal challenge. Anaphylaxis was evaluated by means of assessment of symptom scores and mouse mast cell protease-1 levels (mMCPT-1). PE-NP treatment was associated with significant lower levels of mMCPT-1, and a significant survival rate after challenge, confirming the protective effect of this formulation against the challenge. In summary, this nanoparticle-based formulation might be a valuable strategy for peanut-specific immunotherapy.


The assessment of personality disorder: methodological, developmental, and contextual considerations.
The reliable and valid assessment of personality disorders (PDs) faces several challenges in different domains. In particular, the variety of methods, settings, and informants relevant for PD assessment raises questions about best practices. Additionally, issues surrounding assessment across the lifespan, including youth and the elderly, further complicate PD assessment. We review these issues here and point toward future directions in PD assessment, with an emphasis on the utility of dimensional PD assessment.


Biochemical characterization of different molecular forms of the neural cell adhesion molecule L1.
The neural cell adhesion molecule L1 is a phosphorylated, integral membrane glycoprotein that is recovered from adult mouse brain tissue by immunoaffinity chromatography as a set of polypeptides with apparent molecular masses of 200, 180, 140, and 80 kilodaltons (L1-200, L1-180, L1-140, and L1-80, respectively). It has been shown that L1-140 and the phosphorylated L1-80 is generated from L1-200 by mild proteolytic treatment of intact cells. In the present study we have investigated the structural relationships between the different molecular forms of L1 and their location with regard to the surface membrane. We could show that L1-200 has two preferred cleavage sites, one that generates the amino terminal, extracellularly exposed L1-140 and the carboxy terminal L1-80 that spans the membrane. Cleavage at the other site leads to the generation of the amino terminally located L1-180 and the membrane-attached, phosphorylated carboxy terminal L1-30. This site is cleaved during treatment of live cultured cells with broad-spectrum, protease-free phospholipase C (but not phosphatidylinositol-specific phospholipase C) or exposure to sodium azide or cyanogen bromide. Other conditions that cause damage to cells do not lead to the generation of L1-180 and L1-30, suggesting a particular cell-intrinsic cleavage mechanism. L1-180 is truly soluble in aqueous solutions, since it can be recovered from culture supernatants and in the supernatant of a crude membrane fraction after incubation for 2 h at 37 degrees C. Although trypsin treatment alone does not release L1-140 into the supernatant, combination of phospholipase C and mild tryptic treatment leads to the release of L1-140 and L1-50, the latter being most likely the extracellularly exposed domain of L1-80 that is complementary to the membrane-integrated phosphorylated L1-30. Phase separation experiments with Triton X-114 show that the released forms of L1-180 and L1-140 distribute into the aqueous phase, whereas they distribute into the detergent phase when in association with L1-200 or L1-80. However, when L1-80 is cleaved to yield the soluble L1-50 and membrane-anchored L1-30, L1-140 is released into the supernatant together with L1-50. A strong affinity of L1-200, L1-140, and L1-80 to each other is also indicated by the fact that they incorporate together into liposomes and separate only under strong detergent conditions.(ABSTRACT TRUNCATED AT 400 WORDS)


Living and working with latex allergies: personal perspectives from a nurse.
Living with the limitations of latex sensitivity can be devastating. Even more devastating is when the diagnosis can end a career. For a registered nurse, latex allergy can be a career ender, or it can spur the individual to become increasingly clever in coping with the allergy while maintaining a productive personal and professional life. This article describes the personal struggle an individual registered nurse has overcome to maintain her position in nursing.


Human immunoglobulin G stimulates human adipocyte lipogenesis.
The effect of human IgG on human adipocytes has been investigated. Polyclonal IgG prepared from sera of normal subjects, monoclonal IgG from sera of patients with myeloma and IgG harvested from lymphocytes cultures were equally potent in stimulating lipogenesis in human adipocytes. Fc fragments prepared from IgG fractions also stimulated lipogenesis, whereas Fab fractions were inactive. Pre-incubation of IgG and Fc fragments with gamma-chain specific anti-IgG and anti-Fc antisera neutralised the stimulatory activity of both IgG and Fc fractions. The stimulatory effect of IgG on lipogenesis was demonstrated both on adipocyte suspensions and on adipose tissue. These data demonstrate that human IgG has a specific stimulatory effect on lipogenesis by human adipocytes and that this effect is mediated through the Fc moiety.


Coordinate regulation of Gram-positive cell surface components.
The cell surface of Gram-positive pathogens represents a complex association of glycopolymers that control cell division, homeostasis, immune evasion, tissue invasion, and resistance to antimicrobials. These glycopolymers include the peptidoglycan cell wall, wall-teichoic acids, lipoteichoic acids, and capsular polysaccharide. Disruption of individual factors often results in pleiotropic effects, making it difficult to discern regulation and function. In this review we collate recent work describing these pleiotropic phenotypes, and propose that this is due to coordinated regulation of biosynthesis or modification of these cell surface components. A better understanding of the regulatory networks that control the relative prevalence of each factor on the cell surface or their modulated functions may help facilitate the identification of new targets for antimicrobial therapy.


Determination of ciprofloxacin with functionalized cadmium sulfide nanoparticles as a fluorescence probe.
A novel assay of ciprofloxacin with a sensitivity at the microgram level is proposed based on the measurement of enhanced fluorescence intensity signals resulting from the interaction of functionalized nano-CdS with ciprofloxacin. The CdS nanoparticles was synthesized by thioacetamide (TAA) and cadmium nitrate (Cd(NO(3))(2)) in the alkaline solution. At pH 7.4, the fluorescence signals of functionalized nano-CdS were greatly enhanced by ciprofloxacin with the increase concentration of ciprofloxacin. Linear relationship can be established between the enhanced fluorescence intensity and ciprofloxacin concentration in the range of (1.25-8.75)x10(-4) mg mL(-1) ((3.77-26.4) x 10(-4)mmol L(-1)) or (8.75-1200) x 10(-4)mg mL(-1) ((26.4-3625) x 10(-4) mmol L(-1)). The limit of detection is 7.64 x 10(-6) mg mL(-1) (2.31 x 10(-5)mmol L(-1)). Based on this, a new direct quantitative determination method for ciprofloxacin in human serum samples without separation of foreign substances was established. The contents of ciprofloxacin in human serum samples were determined with recovery of 95-105% and relative standard deviation (R.S.D.) of 1.5-2.5%. This method was proved to be very sensitive, rapid, simple and tolerance of most interfering substances.


Ancient events and climate adaptive capacity shaped distinct chloroplast genetic structure in the oak lineages.
Understanding the origin of genetic variation is the key to predict how species will respond to future climate change. The genus Quercus is a species-rich and ecologically diverse woody genus that dominates a wide range of forests and woodland communities of the Northern Hemisphere. Quercus thus offers a unique opportunity to investigate how adaptation to environmental changes has shaped the spatial genetic structure of closely related lineages. Furthermore, Quercus provides a deep insight into how tree species will respond to future climate change. This study investigated whether closely related Quercus lineages have similar spatial genetic structures and moreover, what roles have their geographic distribution, ecological tolerance, and historical environmental changes played in the similar or distinct genetic structures. Despite their close relationships, the three main oak lineages (Quercus sections Cyclobalanopsis, Ilex, and Quercus) have different spatial genetic patterns and occupy different climatic niches. The lowest level and most homogeneous pattern of genetic diversity was found in section Cyclobalanopsis, which is restricted to warm and humid climates. The highest genetic diversity and strongest geographic genetic structure were found in section Ilex, which is due to their long-term isolation and strong local adaptation. The widespread section Quercus is distributed across the most heterogeneous range of environments; however, it exhibited moderate haplotype diversity. This is likely due to regional extinction during Quaternary climatic fluctuation in Europe and North America. Genetic variations of sections Ilex and Quercus were significantly predicted by geographic and climate variations, while those of section Cyclobalanopsis were poorly predictable by geographic or climatic diversity. Apart from the different historical environmental changes experienced by different sections, variation of their ecological or climatic tolerances and physiological traits induced varying responses to similar environment changes, resulting in distinct spatial genetic patterns.


Medical students taking the role of the mother in paediatric interview evaluation.
Medical students develop the skills required to interview parents and children through practice and by receiving feedback. Parental perceptions of medical student skills in child health interviews can be used to enhance student learning. To integrate maternal perspectives of medical student interviews into student learning, and to compare student and maternal evaluations of simulated medical student interviews. A sample of 45 medical students viewed 2 standardised videotapes in which a 'medical student' interviewed the mother of a sick child. The videotapes demonstrated contrasting levels of 'student' clinical competence and patient-centeredness. After each interview students were asked to rate their satisfaction and recall of information as if they were the mother in the interview. Student satisfaction was measured using the Interpersonal Skills Rating Scale (IPS). Recall of interview information was assessed by questionnaire, with student answers coded independently before analysis. Following both videotapes, students reviewed transcripts of the interviews and discussed their evaluations. Student responses were compared with maternal satisfaction and recall responses after viewing of the same videotapes. Student IPS ratings were higher following the high clinical competence, high patient-centred interview (P < 0.0001). Student recall of specific information was greater for some items following the high clinical competence, high patient-centred interview, but was lower for others. Maternal and student satisfaction and recall were similar following the 2 interviews. Students and mothers agreed on the qualities of a successful interview. Experiencing an interview through the 'eyes' of a mother provided students with valuable insights regarding interview skills.


Stigma Predicts Treatment Preferences and Care Engagement Among Veterans Affairs Primary Care Patients with Depression.
Whereas stigma regarding mental health concerns exists, the evidence for stigma as a depression treatment barrier among patients in Veterans Affairs (VA) primary care (PC) is mixed. This study tests whether stigma, defined as depression label avoidance, predicted patients' preferences for depression treatment providers, patients' prospective engagement in depression care, and care quality. We conducted cross-sectional and prospective analyses of existing data from 761 VA PC patients with probable major depression. Relative to low-stigma patients, those with high stigma were less likely to prefer treatment from mental health specialists. In prospective controlled analyses, high stigma predicted lower likelihood of the following: taking medications for mood, treatment by mental health specialists, treatment for emotional concerns in PC, and appropriate depression care. High stigma is associated with lower preferences for care from mental health specialists and confers risk for minimal depression treatment engagement.


Kinetics of plasma and erythrocyte metformin after acute administration in healthy subjects.
Although the existence of a deep compartment for metformin has long been hypothesized, there is still little direct information concerning metformin distribution in individual tissues in man. The only available study involves chronic metformin therapy. In that study, the measurement of metformin in erythrocytes provided a reliable indicator of metformin distribution and of potential accumulation. To determine the kinetics of metformin in plasma and in erythrocytes after acute oral administration, we performed the present study in healthy subjects after a single oral dose of metformin and compared the pharmacokinetics parameters in erythrocytes to those in plasma. Six nondiabetic participants took the study dose of 850 mg metformin at 8: 00 AM after a non-standardized breakfast (i.e., as recommended in clinical practice). Blood samples were collected for metformin measurement in plasma and in erythrocytes at 0, 1, 2, 3, 4, 6, 9, 24, 33, 48, 57, and 72 h. Maximum metformin concentration was attained at 3.0 +/- 0.3 h in plasma and 4.7 +/- 0.5 h in erythrocytes. This difference was not significant. Metformin concentrations peaked at a maximum almost 6 times higher in plasma than in erythrocytes (1.7 +/- 0.1 and 0.3 +/- 0.0 mg/l, respectively). However, because the elimination half-life of metformin was much longer in erythrocytes (23.4 +/- 1.9 h vs. 2.7 +/- 1.2 h), there was no difference in area under the curve between plasma and erythrocytes. The distribution volume (plasma) was calculated to be 146 +/- 11 l. Plasma and erythrocytes concentration-time curves showed that metformin was not detectable in plasma 24 hours after the oral administration, while it remained detectable in erythrocytes up to 48 hours. Metformin concentrations crossed approximately 13 hours after having reached their maximum values in plasma, approximately 16 h after metformin intake. Having demonstrated the rapid elimination of metformin from plasma and its slow disappearance from erythrocytes, the presents results should contribute to adjustment of metformin dosage to renal function, assessment of drug compliance, and retrospective analysis (when blood samples are drawn with delay) of the link between metformin and development of lactic acidosis. Most importantly, the present findings should help to ascertain the optimal dosage of metformin, particularly in elderly patients.


A method for the comparison of performance of gamma-ray spectrometry calibration cocktails.
In order to make quantitative assessments about the usefulness of different gamma-ray emitting radionuclide cocktails to carry out efficiency calibrations of gamma-ray spectrometers, a method has been developed that allows the comparison of their different performances and to optimize the choice of gamma energy lines for the radionuclides within a specific cocktail. The method has been applied to compare different cocktail configurations obtained from measurements made in the laboratory with monoenergetic radionuclides, and their relative performances are presented and discussed.


The spectrum of retinal dystrophies caused by mutations in the peripherin/RDS gene.
Peripherin/rds is an integral membrane glycoprotein, mainly located in the rod and cone outer segments. The relevance of this protein to photoreceptor outer segment morphology was first demonstrated in retinal degeneration slow (rds) mice. Thus far, over 90 human peripherin/RDS gene mutations have been identified. These mutations have been associated with a variety of retinal dystrophies, in which there is a remarkable inter- and intrafamilial variation of the retinal phenotype. In this paper, we discuss the characteristics of the peripherin/RDS gene and its protein product. An overview is presented of the broad spectrum of clinical phenotypes caused by human peripherin/RDS gene mutations, ranging from various macular dystrophies to widespread forms of retinal dystrophy such as retinitis pigmentosa. Finally, we review the proposed genotype-phenotype correlation and the pathophysiologic mechanisms underlying this group of retinal dystrophies.


Age-related changes in mechanical properties of semitendinosus tendon used for anterior cruciate ligament reconstruction.
Hamstring tendons are a popular choice for autografts in anterior cruciate ligament (ACL) reconstruction. However, there is increasing evidence that hamstring tendon autografts carry a high risk of revision and residual instability in young patients. To elucidate the reasons for the inferior outcome of the reconstructed ACL with hamstring tendon autografts in young patients, we investigated the Young's modulus and the extent of cyclic loading-induced slackening of the semitendinosus tendon used for ACL reconstruction across a broad range of ages. Twenty-six male patients (aged 17-53 years), who were scheduled for ACL reconstruction surgery using the semitendinosus tendon autograft, participated in this study. The distal portion of the harvested semitendinosus tendon, which was not used to construct the autograft, was used for cyclic tensile testing to calculate the Young's modulus and the extent of slackening (i.e., increase in slack length). Spearman correlation analysis revealed that the Young's modulus of the semitendinosus tendon was positively correlated with the patient's age (ρ = 0.559, P = 0.003). In contrast, the extent of tendon slackening did not correlate with the patient's age. We demonstrated that the Young's modulus of the semitendinosus tendon increases with age, indicating that the semitendinosus tendon used for ACL reconstruction is compliant in young patients.


The effects of different inspiratory muscle training intensities on exercising heart rate and perceived exertion.
This study investigated the relationship between the intensity of an inspiratory muscle training programme and its effect on respiratory muscle strength, exercising heart rate, and ratings of perceived exertion. A total of 66 subjects were randomly assigned to one of three groups. One group trained at 100% of maximum inspiratory pressure (MIP) for 6 weeks (MAX, n=22). A second group performed 6 weeks of inspiratory muscle training at 80% of MIP (SUB, n=21) and a third control group received no inspiratory training (CON, n=23). Both the MAX and SUB training groups improved MIP relative to the control group [32 (19) cmH(2)O, P=0.01; 37 (25) cmH(2)O, P=0.001, respectively]. A significant decrease in heart rate [-6 (9) beats min(-1), P=0.02] and rating of perceived exertion [-0.5 (1.4), P=0.04] was observed for the MAX group only. It is concluded that 6 weeks of both MAX and SUB training were sufficient to improve inspiratory muscle strength. However, exercising heart rate and perceived exertion decreased with MAX training only.


Non-invasive in vivo mapping of tumour vascular and interstitial volume fractions.
Non-invasive measurement of haemodynamic parameters and imaging of neovasculature architecture is of importance in determining tumour prognosis, in directing tissue sampling and in assessing treatment efficacy. In the current research we investigated a dual tracer nuclear magnetic resonance (NMR) technique to map the tumour vascular (VVF) and interstitial volume fraction (IVF) non-invasively in vivo. We hypothesised that a NMR signal emanating after intravenous administrations of a vascular paramagnetic probe (MPEG-PL-GdDTPA) can be maximised so that additional signal after administration of a second interstitial probe (GdDTPA) would only reflect the IVF but not the VVF. The method and its assumptions were verified and experimental conditions optimised both in phantoms and in C6 glioma bearing rats. Data derived from in vivo studies show tumoral VVF and IVF values that are consistent with histology data and literature values; the relative ranking order of values was tumour > muscle > brain. Image maps showed intratumoral and intertumoral heterogeneity of both parameters at submillimetre pixel resolution. The method is applicable to a wide variety of tumour models and can theoretically be performed repeatedly to study tumour growth or involution during therapy.


Value of staging squamous cell carcinoma of the anal margin and canal using the sentinel lymph node procedure: an update of the series and a review of the literature.
Inguinal metastases in patients affected by anal cancer are an independent prognostic factor for local failure and overall mortality. Since 2001, sentinel lymph node biopsy was applied in these patients. This original study reports an update of personal and previous published series, which were compared with Literature to value the incidence of inguinal metastases T-stage related and the overall incidence of false negative inguinal metastases at sentinel node. In all, 63 patients diagnosed with anal cancer submitted to inguinal sentinel node. Furthermore a research in the Pub Med database was performed to find papers regarding this technique. In our series, detection rate was 98.4%. Inguinal metastases were evidentiated in 13 patients (20.6%). Our median follow-up was 35 months. In our series, no false negative nodes were observed. Sentinel node technique in the detection of inguinal metastases in patients affected by anal cancer should be considered as a standard of care. It is indicated for all T stages in order to select patients to be submitted to inguinal radiotherapy, avoiding related morbidity in negative ones. An overall 3.7% rate of false negative must be considered acceptable.


Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinase gamma.
Polarization of chemotaxing cells depends on positive feedback loops that amplify shallow gradients of chemoattractants into sharp intracellular responses. In particular, reciprocal activation of phosphatidylinositol 3-kinases (PI3Ks) and small GTPases like Rac leads to accumulation, at the leading edge, of the PI3K product phosphatidylinositol 3,4,5-trisphosphate (PIP3). Mice carrying a "knockin" allele of the G protein-coupled receptor (GPCR)-activated PI3Kgamma, encoding a plasma membrane-targeted protein appeared normal, but their leukocytes showed GPCR-uncoupled PIP3 accumulation. In vivo, the mutation increased proliferation and decreased apoptosis, leading to leukocytosis and delayed resolution of inflammation in wound healing. Mutant leukocytes showed significantly impaired directional cell migration in response to chemoattractants. Stimulated mutant macrophages did not polarize PIP3 and showed a shortened Rac activation because of enhanced PI3K-dependent activation of RacGAPs. Together with the finding that chemoattractants stimulate a PIP3-dependent GAP activation in wild-type macrophages, these results identify a molecular mechanism involving PI3K- and RacGAP-dependent negative control of Rac that limits and fine-tunes feedback loops promoting cell polarization and directional motility.


Auricularia auricula-judae (Bull.) polysaccharides improve obesity in mice by regulating gut microbiota and TLR4/JNK signaling pathway.
Obesity has emerged as a crucial factor impacting people's lives, and gut microbiota disorders contribute to its development and progression. Auricularia auricula-judae (Bull.) polysaccharides (AAPs), a traditional functional food in Asia, exhibit potential anti-obesity effects. However, the specific mechanism still needs to be further confirmed. This study investigated the beneficial effects and specific mechanisms of AAPs on obesity. Firstly, AAPs showed significant improvements in overweight, insulin resistance, glucose and lipid metabolism disorders, and liver damage in obese mice. Additionally, AAPs ameliorated gut microbiota disorders, promoting the proliferation of beneficial bacteria like Lactobacillus and Roseburia, resulting in increased levels of SCFAs, folate, and cobalamin. Simultaneously, AAPs inhibited the growth of harmful bacteria, thereby protecting intestinal barrier function, improving endotoxemia, and decreasing the levels of inflammatory factors such as TNF-α and IL-6. Furthermore, AAPs can inhibit the TLR4/JNK signaling pathway while promoting the activation of AKT and AMPK. Importantly, our study underscored the pivotal role of gut microbiota in the anti-obesity effects of AAPs, as evidenced by fecal microbiota transplantation experiments. In conclusion, our findings elucidated that AAPs improve obesity by regulating gut microbiota and TLR4/JNK signaling pathway, offering novel perspectives for further conclusion the anti-obesity potential of AAPs.


Wet bone-in ageing and effect on beef quality technological parameters.
This study aimed to evaluate the effect of wet ageing on chemical-physical characteristics of sirloin and bone-in rib eye steaks obtained from 18 months old young bulls and 27 months old heifers. A positive beef tenderization effect of wet ageing was observed with lower values constantly detected in the rib-eye samples and significantly lower shear force values showed in heifer steaks if compared to bulls. The pH values detected both in pre- and post-ageing samples fell in the normal range for meats. The water holding capacity of sirloin samples increased with ageing while in rib eye steaks, no significant differences were detected among samples taken before and after ageing. Meat ageing resulted in a decrease of cooking loss, while meat colour parameters were not influenced by ageing and fell within the normal range. An evident improvement of the sensorial quality of bone-in wet aged beef, especially in tenderness, was achieved.


Post-hemorrhagic hydrocephalus: Recent advances and new therapeutic insights.
Post-hemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation, is caused by disturbances in cerebrospinal fluid (CSF) flow or absorption following hemorrhage in the brain. As one of the most serious complications of neonatal/adult intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), PHH is associated with increased morbidity and disability of these events. Common sequelae of PHH include neurocognitive impairment, motor dysfunction, and growth impairment. Non-surgical measures to reduce increased intracranial pressure (ICP) in PHH have shown little success and most patients will ultimately require surgical management, such as external ventricular drainage and shunting which mostly by inserting a CSF drainage shunt. Unfortunately, shunt complications are common and the optimum time for intervention is unclear. To date, there remains no comprehensive strategy for PHH management and it becomes imperative that to explore new therapeutic targets and methods for PHH. Over past decades, increasing evidence have indicated that hemorrhage-derived blood and subsequent metabolic products may play a key role in the development of IVH-, SAH- and TBI-associated PHH. Several intervention strategies have recently been evaluated and cross-referenced. In this review, we summarized and discussed the common aspects of hydrocephalus following IVH, SAH and TBI, relevant experimental animal models, clinical translation of in vivo experiments, and potential preventive and therapeutic targets for PHH.