A bio-defensive function induced by low-dose lipopolysaccharide pre-treatment against CCl4-induced fulminant hepatic failure in rats.
We have investigated the bio-defensive function of low-dose LPS pretreatment on CCl4-induced fulminant hepatic failure (FHF) in rats. In male Donryu rats treated with CCl4 at 1.0 ml/kg i.p., the serum alanine aminotransferase (ALT) increased up to a peak at 24 h. The increase in intracellular Ca2+ concentration was biphasic, i.e., a first peak at 1 h and a second at 3 days. However, when rats were treated daily with CCl4 at 1.0 ml/kg, serum ALT successively increased over several h after the second administration, but the rats died of FHF. The first Ca2+ peak occurred 1 h after CCl4 administration, but the concentration did not increase continually, until it reached the second peak. However, rats did not die when they were treated with lipopolysaccharide at 0.5 mg/kg 24 h prior to the initial dose of CCl4 at 1.0 ml/kg. The serum ALT value did not increase after administration of CCl4 at 1.0 ml/kg, but the second Ca2+ peak was sustained at > 1, 000 nM. We concluded that the second Ca2+ peak acts to protect the liver from injury.


Effect of parathyroidectomy on anemia and erythropoietin dosing in end-stage renal disease patients with hyperparathyroidism.
It has been suggested that parathyroidectomy for hyperparathyroidism (HPT) in end-stage renal disease (ESRD) may result in improvement in anemia and the response to erythropoiesis-stimulating drugs. This study examines the effect parathyroidectomy had on erythropoietin (EPO) dosing requirements and anemia in ESRD. A retrospective review was conducted. Patients were included if pre-operative and 12 month postoperative hemoglobin (Hg) and hematocrit (Hct) levels were available and they did not receive a kidney transplant or have failure of parathyroidectomy during the follow-up. Erythropoietin (EPO) dose and serum levels of calcium, phosphorus, alkaline phosphatase, albumin, and parathyroid hormone (PTH) were also obtained. Other data collections were at 1 and 2 mos. postoperatively. Thirty-seven patients met inclusion criteria. Parathyroidectomy resulted in decreased PTH from 1,871 +/- 236 (mean +/- SEM) to 172 +/- 29 pg/mL (P < .001) at 1 year. EPO dosing requirement showed a profound decrease from 10,086 +/- 1,721 to 3,514 +/- 620 units/week (P < .05). Hb and Hct levels followed an upward trend at 12 mos (11.4 +/- 0.3 to 12.1 +/- 0.2 g/dL and 35.7 +/- 1.0 to 37.1 +/- 0.6%, respectively). In ESRD, parathyroidectomy for HPT improves anemia and decreases requirements for exogenous erythropoietin suggesting either increased endogenous EPO production or improved response. As a result, we propose refractory ESRD-associated anemia as a secondary indication for parathyroidectomy resection in this population.


Haemodynamic changes induced by short- and long-term sodium chloride or sodium bicarbonate intake in deoxycorticosterone-treated rats.
The contribution of chloride to the haemodynamic changes of salt-dependent deoxycorticosterone (DOC) hypertension was studied in young Wistar rats subjected to dietary loading with sodium chloride (NaCl) or sodium bicarbonate (NaHCO3). Mean arterial pressure (MAP), cardiac output, systemic resistance (TPR) and arterial rigidity (estimated from pulse pressure/stroke volume ratio, PP/SV) were determined in conscious chronically cannulated rats. DOC-induced increase of MAP and TPR appeared earlier in NaCl-loaded than in NaHCO3-loaded rats. After 4-6 weeks of hypertensive treatment MAP, TPR and PP/SV ratio were higher in DOC-treated rats fed NaCl diet than in those fed NaHCO3 diet. In contrast, after a long-term hypertensive regimen (lasting for 7-9 weeks) there was no significant difference in either MAP or TPR between rats loaded with NaCl or NaHCO3. On the other hand, DOC hypertension induced by a long-term feeding of NaHCO3 diet was not associated with an increase of arterial rigidity which was characteristic for DOC-NaCl hypertensive rats. Thus, a sufficiently long selective dietary sodium loading is capable to increase the systemic resistance but not to alter the arterial rigidity. This was also confirmed by a comparison of blood pressure-matched DOC hypertensive rats fed NaCl or NaHCO3 diets. These animals did not differ in the degree of systemic resistance elevation but the arterial rigidity was increased only in NaCl-loaded rats.


Two-Dimensional Electrically Conductive Metal-Organic Frameworks as Chemiresistive Sensors.
Metal-organic frameworks (MOFs) have emerged as attractive chemical sensing materials due to their exceptionally high porosity and chemical diversity. Nevertheless, the utilization of MOFs in chemiresistive type sensors has been hindered by their inherent limitation in electrical conductivity. The recent emergence of two-dimensional conductive MOFs (2D c-MOFs) has addressed this limitation by offering enhanced electrical conductivity, while still retaining the advantageous properties of MOFs. In particular, c-MOFs have shown promising advantages for the fabrication of sensors capable of operating at room temperature. Thus, active research on gas sensors utilizing c-MOFs is currently underway, focusing on enhancing sensitivity and selectivity. To comprehend the potential of MOFs as chemiresistive sensors for future applications, it is crucial to understand not only the fundamental properties of conductive MOFs but also the state-of-the-art works that contribute to improving their performance. This comprehensive review delves into the distinctive characteristics of 2D c-MOFs as a new class of chemiresistors, providing in-depth insights into their unique sensing properties. Furthermore, we discuss the proposed sensing mechanisms associated with 2D c-MOFs and provide a concise summary of the strategies employed to enhance the sensing performance of 2D c-MOFs. These strategies encompass a range of approaches, including the design of metal nodes and linkers, morphology control, and the synergistic use of composite materials. In addition, the review thoroughly explores the prospects of 2D c-MOFs as chemiresistors and elucidates their remarkable potential for further advancements. The insights presented in this review shed light on future directions and offer valuable opportunities in the chemical sensing research field.


Lymphatic Invasion Might Be Considered as an Upstaging Factor in N0 and N1 Gastric Cancer.
(Background) The aim of this study was to investigate the prognostic impact of lymphatic invasion in gastric cancer, focusing on survival differences between N stage groups. (Methods) A total of 398 consecutive patients who underwent curative gastrectomy for primary gastric adenocarcinoma from January 2006 to December 2015 were analyzed retrospectively using data from a prospectively collected registry database. We compared various clinicopathological features and survival differences between lymphatic invasion-positive and -negative groups. (Results) Of the 398 patients, 141 (35.4%) showed lymphatic invasion. The lymphatic invasion-positive subgroup had poorer prognosis than the lymphatic invasion-negative subgroup in N0 (five-year survival rate: 87.8% vs. 73.6%, p = 0.048) and N1 (87.2% vs. 50%, p = 0.007) stage patients. The odds ratio (OR) of lymphatic invasion to five-year survival rate was 2.078 (95% confidence interval (CI), 1.103-3.916; p = 0.024). The presence of lymphatic invasion had worse effect on survival than age (OR, 1.807; 95% CI, 1.024-2.242; p = 0.029) or tumor depth (OR, 1.286; 95% CI, 1.078-1.897; p = 0.013) in N0 and N1 stage patients. The overall survival of patients with lymphatic invasion was not different from that of patients at a one-higher N stage without lymphatic invasion at any N stage. (Conclusions) The presence of lymphatic invasion may be the most important independent prognostic factor in N0 and N1 gastric cancer and might be an upstaging factor of N stage at any N stage. Therefore, in addition to the number of metastasized lymph nodes, the presence of lymphatic invasion should be included in N stage determination.


Considerations for Culturally Sensitive Research With Transgender Adults: A Qualitative Analysis.
Transgender (trans) individuals have historically been left out of research, and previous work has often conflated gender identity with sexual orientation. Furthermore, language used in psychology measures is often heteronormative and uses binary gendered language (e.g., "him"/"her"). The aim of the current study was to provide empirically derived guidance on conducting culturally sensitive research with transgender participants using qualitative data. We recruited trans individuals, ages 18 to 44, to participate in an anonymous, qualitative, national online survey as part of a quantitative study on the relationships among minority stress, sexual behavior, and mental health. The qualitative portion included four open-ended feedback questions. We identified four overarching themes regarding experiences with our survey: (a) emotional reaction; (b) insight gained; (c) being outside the box; and (d) value of the work. Research with trans adults should be more inclusive of diverse gender identities, sexual identities, and sexual behaviors. Steps in this direction may include soliciting feedback from community members regarding survey language and response options, allowing participants to contextualize their responses using open-ended questions, and clarifying language to distinguish between sexual behavior and sexual identity. A list of seven preliminary guidelines was proposed to aid scientists in conducting culturally sensitive research with trans individuals.


General practitioners' (GPs) understanding and views on breast density in Australia: a qualitative interview study.
To understand general practitioners' (GPs') awareness and knowledge of mammographic breast density (BD) and their perspectives around information and potential notification of BD for women. Qualitative study using semistructured telephone interviews. Interviews were audiorecorded, transcribed and analysed using framework analysis. Australia. Australian GPs (n=30). GPs had limited knowledge of BD and little experience discussing BD with women. There were mixed views on notification of BD with some GPs believing this information would help informed decision making about breast health and that women have the right to know any information about their bodies. While others were concerned about causing unnecessary anxiety and were worried about the uncertainty about what to advise women to do with this information, particularly in relation to supplemental breast screening. The need for an equitable system where all women are either notified or not, and also provided with publicly funded supplemental screening was raised by GPs. Overall, there was high interest in education, training and support around the topic of BD. Australian GPs require education, support and evidence-based guidelines to have discussions with women with dense breasts and help manage their risk, especially if widespread notification is to be introduced in population-based screening programmes.


Gut microbiota influences feeding behavior via changes in olfactory receptor gene expression in Colorado potato beetles.
The Colorado potato beetle (CPB) is an internationally recognized plant quarantine pest that causes serious losses to potato agricultural production. The gut microbiota plays an important role in its growth and development, and the olfactory system plays an important role in insect feeding behavior. The gut microbiota is known to be capable of inducing changes in the olfactory systems of insects. However, the way these associated gut microbes influence the feeding-related behaviors of CPBs remains unclear. To explore the relationship between them, fresh potato leaves immersed in a mixture of five antibiotics (tetracycline, penicillin, ofloxacin, ciprofloxacin, and ampicillin) at specific concentrations for 1 h were fed to adult CPBs to reduce the abundance of gut microbes. We found that the feeding behavior of CPBs was significantly affected by the gut microbiota and that Pseudomonas was significantly higher in abundance in the control group than in the antibiotic group. We then used transcriptome sequencing to explore the differences in olfactory receptor genes in the heads of non-treatment and antibiotic-fed CPBs. Through Illumina Hiseq™ sequencing and screening of differential genes, we found that the olfactory receptor gene LdecOR9 was significantly upregulated and LdecOR17 was significantly downregulated after antibiotic feeding. A real-time polymerase chain reaction was used to verify the changes in olfactory receptor gene expression in the non-treatment groups and antibiotic-treated groups. The feeding behavior was partially rescued after CPBs were re-fed with intestinal bacteria. These results indicate that a certain amount of gut microbiota can result in the loss of the olfactory discrimination ability of CPBs to host plants. In summary, this study investigated the relationship between gut microbiota and olfactory genes, providing a reference for research on microbial control.


The individual's right to informed consent.
Every individual has the right to informed consent before becoming a human subject in research ( 1 ). As is the case with all other rights that individuals have, one would find it very difficult to justify any denial of the right to informed consent. Behi and Nolan ( 2 ) have stated that problems and uncertainties arise, however, because of the difficulty 'in defining what is informed consent and in knowing when one can claim it has genuinely been given and achieved.' Nurse researchers should understand and be aware of the issues that face them when seeking informed consent so that they are in a position to achieve genuine consent. This article will consider these issues in detail, but not the legal aspects of informed consent which is a major topic in its own right.


Understanding Charge-Transfer Characteristics in Crystalline Nanosheets of Fullerene/(Metallo)porphyrin Cocrystals.
Cocrystals in the form of crystalline nanosheets comprised of C70 and (metallo)porphyrins were prepared by using the liquid-liquid interfacial precipitation (LLIP) method where full control over the morphologies in the C70/(metallo)porphyrins nanosheets has been accomplished by changing the solvent and the relative molar ratio of fullerene to (metallo)porphyrin. Importantly, the synergy of integrating C70 and (metallo)porphyrins as electron acceptors and donors, respectively, into nanosheets is substantiated in the form of a near-infrared charge-transfer absorption. The presence of the latter, as reflection of ground-state electron donor-acceptor interactions in the nanosheets, in which a sizable redistribution of charge density from the electron-donating (metallo)porphyrins to the electron-accepting C70 occurs, leads to a quantitative quenching of the localized (metallo)porphyrin fluorescence. Going beyond the ground-state characterization, excited-state electron donor-acceptor interactions are the preclusion to a full charge transfer featuring formation of a radical ion pair state, that is, the one-electron reduced fullerene and the one-electron oxidized (metallo)porphyrin.


Three new cytotoxic annonaceous acetogenins from the seeds of Annona squamosa.
Three new annonaceous acetogenins, annotemoyin L (1), annotemoyin Y (2) and annotemoyin X, (3) were isolated from the seeds of Annona squamosa Linn. Their structures were ascertained by chemical methods and spectral data. The cytotoxic activities of compounds against three multidrug-resistant cancer cell lines were evaluated, and compound 3 exerted strong cytotoxicity against SMMC 7721/ADR (IC50 0.163 μM), A549/T (IC50 0.064 μM) and MCF-7/ADR (IC50 0.057 μM).


The CXCL13 Index as a Predictive Biomarker for Activity in Clinically Isolated Syndrome.
Multiple sclerosis (MS) is a clinically heterogenous disease. Currently, we cannot identify patients with more active disease who may potentially benefit from earlier interventions. Previous data from our lab identified the CXCL13 index (ICXCL13), a measure of intrathecal production of CXCL13, as a potential biomarker to predict future disease activity in MS patients two years after diagnosis. Patients with clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS) underwent a lumbar puncture and blood draw, and the ICXCL13 was determined. They were then followed for at least 5 years for MS activity. Patients with high ICXCL13 were more likely to convert to clinically definite MS (82.4%) compared to those with low ICXCL13 (10.0%). The data presented below demonstrate that this predictive ability holds true in CIS and RIS patients, and for at least five years compared to our initial two-year follow-up study. These data support the concept that ICXCL13 has the potential to be used to guide immunomodulatory therapy in MS.


Morpholino and phosphorothioate antisense oligomers compared in cell-free and in-cell systems.
Morpholino and phosphorothioate (S-DNA) antisense oligos were compared in both cell-free and in-cell translation systems. In the most stringent test of specificity in the cell-free system, a globin-targeted S-DNA oligo was found to inhibit its target sequence at concentrations of 10 nM and above, but the sequence-specific component of this inhibition dropped below 50% at concentrations of 100 nM and above. A corresponding Morpholino oligo achieved even higher inhibition at 10 nM, but in contrast to the S-DNA, with the Morpholino, the sequence-specific component of this inhibition remained above 93% at a concentration of 3000 nM. In this same cell-free test system, several S-DNA oligos exhibited substantial undesired nonantisense effects at concentrations of 300 nM and above, whereas corresponding Morpholino oligos exhibited little or no nonantisense activity through a concentration of 3000 nM. In scrape-loaded HeLa cells, both globin-targeted and HBV-targeted S-DNAs (both antisense and control oligos) generally failed to achieve significant translational inhibition at extracellular concentrations up to 3000 nM. In contrast, the Morpholino oligos achieved effective and specific translational inhibition at extracellular concentrations ranging from 30 nM to 3000 nM.


Membrane conductance and potassium permeability of the rat lens.
The membrane potential, electrical impedance and 86Rb+ efflux rate constants were measured in the rat lens perifused at 35 degrees C. The membrane conductance was obtained from the difference between the magnitude of the impedance at low (less than 0.1 Hz) and high (greater than 100 Hz) frequencies. Values of the rubidium permeability coefficients (PRb) were obtained from the rate constant and potential data. The values for the membrane potential and conductance in control solution (5 mM potassium) were -69.6 mV and 5.5 X 10(-4) S respectively, while the computed permeability was 2.9 X 10(-8) m.s-1. On perifusing with 35 mM potassium, the membrane depolarized by 25 mV and the conductance and rubidium permeability increased considerably. These increases could be blocked by quinine (0.3 mM), tetraethylammonium (30 mM) and 4-aminopyridine (10 mM). The latter agent was more effective at alkaline pH (8.3). It is suggested that there are voltage-gated potassium channels that are inhibited by these three agents. After the initial depolarization in high potassium, there was little further change in membrane potential with any of the inhibitors. All three agents, however, produced a marked depolarization when applied in control solution. This was accompanied by a decrease in conductance and rubidium permeability, suggesting that, in the rat lens, some voltage-gated potassium channels are activated at the resting potential.


Acute effects of gamma-vinyl GABA (vigabatrin) on hippocampal GABAergic inhibition in vitro.
The acute effects of gamma-vinyl-GABA (GVG) on GABAergic inhibition were investigated in the hippocampal slice preparation using the paired-pulse test of inhibition during extracellular recordings. Superfusion of GVG (100-500 microM) for 60 min resulted in a concentration-dependent decrease in GABAergic inhibition. Slices superfused with higher concentrations of GVG (0.5-1 mM) were hyperexcitable as demonstrated by the appearance of multiple spikes. Binding studies showed that GVG (1 mM) had no effect on the binding of [3H]flunitrazepam or [3H]TBOB and displaced no more than 15% of specific [3H]GABA binding, which indicates that GVG-induced disinhibition is not mediated through an action at the GABAA receptor complex. Consistent with this suggestion is the finding that GVG (500 microM) had little effect on the inhibition of the orthodromically evoked CA1 population spike produced by the GABAA receptor agonist muscimol (10 microM), whereas this inhibition was considerably attenuated by the GABAA receptor antagonist, bicuculline methiodide (5 microM). The results of this study suggest that the acute actions of GVG on the GABAergic neurotransmitter system are not involved in its anticonvulsant effect.


Enantiomeric separation of mirtazapine and its metabolites by nano-liquid chromatography with UV-absorption and mass spectrometric detection.
Mirtazapine (MIR) and two of its main metabolites, namely, 8-hydroxymirtazapine and N-desmethylmirtazapine, were separated in totheir enantiomers by nanoLC in a laboratory-made fused-silica capillary column (75 microm ID) packed with a vancomycin-modified silica stationary phase. The simultaneous separation of the three couples of the studied enantiomers was achieved in less than 33 min, using an experimentally optimized mobile phase delivered in the isocratic mode. Optimization of the mobile-phase composition was achieved by testing the influence of the buffer pH and concentration, the water concentration, the organic modifier type and concentration, and on the retention and resolution of the analytes. The optimum mobile-phase composition contained 500 mM ammonium acetate pH 4.5/water/MeOH/MeCN, 1:14:40:45 v/v/v/v. Using a UV detector at 205 nm, the method was validated studying several experimental parameters such as LOD and LOQ, intraday and interday repeatability, and linearity. Good results were achieved: LOD and LOQ were in the range 5-15 and 10-40 microg/mL, respectively (the highest value was obtained for the DEMIR enantiomers); correlation coefficients, 0.9993-0.9999; the intraday and interday precision was acceptable (RSD < 2%) using an internal standard. The method was tested for the separation of the studied enantiomers in an extracted (solid-phase) serum sample spiked with standard racemic mixture of MIR and its two metabolites. Finally, the nanoLC system was connected to a mass spectrometer through a nanoelectrospray interface and the MS, MS2, and MS3 spectra were acquired showing the potential of the system used for characterization and identification of the separated analytes.


Mobile health solutions for the aging population: A systematic narrative analysis.
Introduction The ubiquitous nature of mobile technology coupled with the acceptance of mobile health (mHealth) among the elderly offers an opportunity to augment the existing medical workforce in long-term care. The objective of this review and narrative analysis is to identify and analyse facilitators and barriers to adoption of mHealth for the elderly. Methods Studies over the last year were identified in multiple database indices, and three reviewers examined abstracts ( k = 0.82) and analysed articles for themes which were tallied in affinity diagrams to identify frequency of occurrence in the literature (n = 36). Results The three facilitators mentioned most often were independence (18%), understanding (13%), and visibility (13%). The three barriers mentioned most often were complexity (21%), limited by users (12%) and ineffective (12%). Discussion and conclusions The reviewers concluded that the work done so far illustrates that mHealth enables a perception of independence. Future research should focus on the barriers of complexity of technology and improving existing medical literacy in order to facilitate further adoption.


Antagonistic activity of the food-related filamentous fungus Penicillium nalgiovense by the production of penicillin.
Defined strains of the genus Penicillium used as starter cultures for food and strains isolated from mold-fermented foods were analyzed for their ability to inhibit the growth of Micrococcus luteus DSM 348 used as an indicator organism. Most of the strains belonging to the species Penicillium nalgiovense showed antagonistic activity in agar diffusion assays. Penicillium camemberti and Penicillium roqueforti strains proved to be inactive in these tests. The inhibitory substance excreted by P. nalgiovense strains was totally inactivated when treated with beta-lactamase (penicillinase), indicating that a beta-lactam antibiotic is produced by these strains. This observation was verified by PCRs with primer sets specific to the [delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine] synthetase gene (pcbAB), the isopenicillin-N-synthase gene (pcbC), and the acyl coenzyme A:6-aminopenicillanic acid acyltransferase gene (penDE) from Penicillium chrysogenum using chromosomal DNA of the fungal strains as a template. These results indicate that penicillin biosynthesis is a characteristic often found in strains of P. nalgiovense. No specific PCR signal could be identified with DNA from P. camemberti and P. roqueforti.


Systemic lentivirus-mediated delivery of short hairpin RNA targeting calcium release-activated calcium channel 3 as gene therapy for collagen-induced arthritis.
Immune cells, including T cells, B cells, and osteoclasts, in conjunction with their associated cytokines, have been studied as primary molecular therapeutic targets for the management of rheumatoid arthritis (RA) patients. The increase in cytosolic Ca(2+) levels through the activation of store-operated Ca(2+) release-activated channels (CRACs) is involved in mediating a disparate array of cellular responses by these immune cells. This study was undertaken to investigate the feasibility and efficiency of the regulation of Ca(2+) entry in the treatment of RA. To moderately suppress Ca(2+) entry via CRACs, we gene silenced CRACM3, which was induced by systemic application of specific short hairpin RNAs (shRNAs) using a lentiviral-delivery system, in a murine model of collagen-induced arthritis (CIA). The inflammatory responses were determined by measuring the levels of a panel of cytokines and chemokines in the joints and serum. Ag-specific responses were evaluated by determining the cytokine profile of T cells stimulated with autoantigen. We also analyzed the ability of specific CRACM3-shRNA to regulate mature osteoclast function in CIA mice. The therapeutic effect of lentiviral-delivered CRACM3-shRNA was associated with gene silencing of CRACM3, along with the successful biodistribution of the virus. Extracellular Ca(2+) influx in the splenocytes, thymocytes, and knee joint synovial cells was moderately suppressed. Inflammatory responses and autoimmune responses were reduced by CRACM3 gene silencing. A decrease in mature osteoclast activity also was observed in CRACM3-shRNA-treated CIA mice. These results indicate that regulation of Ca(2+) entry through lentivirus-mediated CRACM3 gene silencing is beneficial in the treatment of RA.


Cost-Effectiveness of Hydroxyurea for Sickle Cell Anemia in a Low-Income African Setting: A Model-Based Evaluation of Two Dosing Regimens.
The disease burden of sickle cell anemia (SCA) in sub-Saharan African (SSA) countries is substantial, with many children dying without an established diagnosis or proper treatment. The global burden of SCA is increasing each year, making therapeutic intervention a high priority. Hydroxyurea is the only disease-modifying therapy with proven feasibility and efficacy suitable for SSA; however, no one has quantified the health economic implications of its use. Therefore, from the perspective of the health care provider, we estimated the incremental cost-effectiveness of hydroxyurea as a fixed-dose regimen or maximum tolerated dose (MTD) regimen, versus SCA care without hydroxyurea. We estimated the cost of providing outpatient treatment at a pediatric sickle cell clinic in Kampala, Uganda. These estimates were used in a discrete-event simulation model to project mean costs (2021 US$), disability-adjusted life years (DALYs), and consumption of blood products per patient (450 mL units), for patients between 9 months and 18 years of age. We calculated cost-effectiveness as the ratio of incremental costs over incremental DALYs averted, discounted at 3% annually. To test the robustness of our findings, and the impact of uncertainty, we conducted probabilistic and one-way sensitivity analyses, scenario analysis, and price threshold analyses. Hydroxyurea treatment averted an expected 1.37 DALYs and saved US$ 191 per patient if administered at the MTD, compared with SCA care without hydroxyurea. In comparison, hydroxyurea at a fixed dose averted 0.80 DALYs per patient at an incremental cost of US$ 2. The MTD strategy saved 11.2 (95% CI 11.1-11.4) units of blood per patient, compared with 9.1 (95% CI 9.0-9.2) units of blood per patient at the fixed-dose alternative. Hydroxyurea at MTD is likely to improve quality of life and reduce the consumption of blood products for children with SCA living in Uganda. Compared with a fixed dose regimen, treatment dosing at MTD is likely to be a cost-effective treatment for SCA, using realistic ranges of hydroxyurea costs that are relevant across SSA. Compared with no use of the drug, hydroxyurea could lead to substantial net savings per patient, while reducing the disease morbidity and mortality and increasing quality of life.


Durvalumab as Consolidation Therapy in Post-Multimodal Interventional Treatment for Patients with Advanced Solid Tumors: A Preliminary Study.
With 2.1 million unique cases of lung tumors and 1.8 million mortalities in China, advanced solid tumors continue to be the primary source of cancer mortality rates. Nearly two-thirds of lung cancer individuals display advanced-stage tumors at the time of testing, with a 5-year survival ratio of 7%. People with advanced solid tumors have an appalling outcome, with a 5-year total survival ratio of roughly 15%. Immunotherapy inhibitors, like those for programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), have ushered in a novel period in cancer diagnosis and therapy. Three resistant medications were authorized for advanced solid tumors: nivolumab, pembrolizumab, and atezolizumab. Durvalumab, an anti-PD-L1 antigen, is currently being researched. Durvalumab's pharmacologic characteristics, clinical efficacy, and security as consolidation therapy in post-multimodal interventional therapies for people with advanced solid tumors are discussed in this paper. We have also shared details of two patients who were identified with advanced solid tumors and were provided with durvalumab medication. The performance measures like Progression-Free Survival (PFS), Overall Survival (OS), and Overall Response Rate (ORR) are also contrasted for different antibodies. The research findings imply that durvalumab consolidation therapy is a cost-efficient therapy, while health policymakers should address the financial consequences.


[Efficacy of acupuncture combined with hydro-acupuncture for transverse processes syndrome of the third lumbar vertebra].
To observe the clinical efficacy differences between acupuncture combined with hydro-acupuncture and acupuncture alone for transverse processes syndrome of the third lumbar vertebra. One hundred patients were randomly divided into an observation group and a control group, 50 cases in each one. The patients in the control group were treated with regular acupuncture at Weizhong (BL 40), ashi points, Jiaji (L2~L4) and Shenshu (BL 23); the acupuncture was given once a day, six treatments per week for consecutive 2 weeks. Based on the acupuncture treatment in the control group, in the observation group the No.5 injection needle was applied to relieve the tenderness points on the transverse process and articular process of the third lumbar vertebra, followed by hydro-acupuncture with Danshen injection (1 mL per point, 7 days per injection for 2 weeks). The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) scale and Oswestry disability index (ODI) were observed before treatment, after treatment and during six-month follow-up visit in the two groups. In addition, the clinical efficacy was compared between the two groups. Forty-eight patients completed treatment and 2 patients dropped off in the observation group, while 47 patients completed treatment and 3 patients dropped off in the control group. The total effective rate was 91.7% (44/48) in the observation group, which was significantly superior to 76.6% (36/47) in the control group (P<0.05). Compared before treatment, the VAS and ODI in the two groups were reduced after treatment and during six-month follow-up visit, while the JOA was increased (all P<0.05); the VAS and ODI in the observation group was lower than that in the control group, while JOA in the observation group was higher than that in the control group (all P<0.05). Acupuncture combined with hydro-acupuncture are effective for transverse processes syndrome of the third lumbar vertebra, and could significantly improve lumbar function and relieve the pain symptoms, which is superior to regular acupuncture.


Low-level environmental arsenic exposure correlates with unexplained male infertility risk.
Humans are exposed to arsenic via drinking water, dietary intake and inhaled particulates. Endemic chronic arsenic exposure related reproductive toxicity is well documented, but the effect of low-level general environmental arsenic exposure on unexplained male infertility (UMI) remains unclear. In this case-control study, we aimed to investigate the relationship between non-geogenic environmental arsenic exposure and UMI risk. One hundred and one infertile men with normal semen as cases and sixty one fertile men as controls were recruited. Five urinary arsenic species: pentavalent arsenate (Asi(V)), trivalent arsenite (Asi(III)), methylated to monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), arsenobetaine (AsB) were quantitatively measured by liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS). To assess the semen quality, semen volume, sperm concentration, total motility, and progressive motility were measured. The nonparametric Mann-Whitney U test was used to compare the differences of arsenic species and index between the case and the control group; we observed that concentrations of Asi(V), AsB, MMA(V), DMA(V), total inorganic As and total As were significantly higher in the cases than the controls. The urine Asi(V) level increased more than twenty folds in case group. Moreover, higher redox index (Asi(V)/Asi(III)) and lower primary arsenic methylation index (PMI=MMA(V)/Asi) were observed for case group. Furthermore, through the logistic regression analysis, we observed that the urine Asi(V) level and PMI were most significantly associated with UMI risk among the observations. Specifically, in comparison to the first quartile, the subjects with higher Asi(V) levels were more likely to exhibit UMI with increasing adjusted odds ratios (AORs) (adjusted by age, body mass index, drinking status and smoking status) of 8.39 [95% confidence interval (CI), 2.59-27.17], 13.12 (95% CI, 3.44-50.12) and 36.51 (95% CI, 8.25-161.66) at the second, third and fourth quartiles, respectively. Also a concentration-dependent decrease of AOR was also observed for PMI in comparison to the fourth quartile: 15.43 [95% CI, 4.28-55.69], 9.69 (95% CI, 2.78-33.78) and 6.93 (95% CI, 2.21-21.76) at the first, second and third quartiles, respectively. These findings provide evidences that low-level environmental arsenic exposure was positively associated with UMI risk.


A haplotype-based analysis of the PTPN22 locus in type 1 diabetes.
A recent addition to the list of widely confirmed type 1 diabetes risk loci is the PTPN22 gene encoding a lymphoid-specific phosphatase (Lyp). However, evidence supporting a role for PTPN22 in type 1 diabetes derives entirely from the study of just one coding single nucleotide polymorphism, 1858C/T. In the current study, the haplotype structure of the PTPN22 region was determined, and individual haplotypes were tested for association with type 1 diabetes in family-based tests. The 1858T risk allele occurred on only a single haplotype that was strongly associated with type 1 diabetes (P = 7.9 x 10(-5)). After controlling for the effects of this allele, two other haplotypes were observed to be weakly associated with type 1 diabetes (P < 0.05). Sequencing of the coding region of PTPN22 on these haplotypes revealed a novel variant (2250G/C) predicted to result in a nonsynonymous amino acid substitution. Analysis of PTPN22 transcripts from a subject heterozygous for this variant indicated that it interfered with normal mRNA splicing, resulting in a premature termination codon after exon 17. These results support the conclusion that the 1858C/T allele is the major risk variant for type 1 diabetes in the PTPN22 locus, but they suggest that additional infrequent coding variants at PTPN22 may also contribute to type 1 diabetes risk.


Crystal-Templated Colloidal Clusters Exhibit Directional DNA Interactions.
Spherical colloids covered with grafted DNA have been used in the directed self-assembly of a number of distinct crystal and gel structures. Simulation suggests that the use of anisotropic building blocks greatly augments the variety of potential colloidal assemblies that can be formed. Here, we form five distinct symmetries of colloidal clusters from DNA-functionalized spheres using a single type of colloidal crystal as a template. The crystals are formed by simple sedimentation of a binary mixture containing a majority "host" species that forms close-packed crystals with the minority "impurity" species occupying substitutional or interstitial defect sites. After the DNA strands between the two species are hybridized and enzymatically ligated, the results are colloidal clusters, one for each impurity particle, with a symmetry determined by the nearest neighbors in the original crystal template. By adjusting the size ratio of the two spheres and the timing of the ligation, we are able to generate clusters having the symmetry of tetrahedra, octahedra, cuboctahedra, triangular orthobicupola, and icosahedra, which can be readily separated from defective clusters and leftover spheres by centrifugation. We further demonstrate that these clusters, which are uniformly covered in DNA strands, display directional binding with spheres bearing complementary DNA strands, acting in a manner similar to patchy particles or proteins having multiple binding sites. The scalable nature of the fabrication process, along with the reprogrammability and directional nature of their resulting DNA interactions, makes these clusters suitable building blocks for use in further rounds of directed self-assembly.


Genetic stability of the D1Z2 region: implications for DNA genotyping and paternity testing.
The aim of the present study was to examine a single locus variable number tandem repeat for the purpose of DNA genotyping ("fingerprinting"). DNAs of 175 individuals from five ethnic groups (Black, Chinese, Japanese, Caucasian, and Melanesian) were analyzed. Restriction fragment length polymorphic analysis of random individuals revealed individual specific DNA patterns in all but one group. Among 20 Melanesian inhabitants of the Vanuatu islands in the southwest Pacific, three individuals were found to share a common pattern. This island population represents a "genetic isolate" and illustrates the importance of carrying out population studies on individual ethnic groups of interest. The complexity and the genetic stability of the D1Z2 region as revealed by the probe hMF1 make it an excellent candidate for DNA genotyping in paternity testing as 101 Caucasian individuals each had unique patterns for PstI and SinI digests.


Transscleral sustained ranibizumab delivery using an episcleral implantable device: Suppression of laser-induced choroidal neovascularization in rats.
Successful treatment of age-related macular diseases requires an effective controlled drug release system with less invasive route of administration in the eye to reduce the burden of frequent intravitreal injections for patients. In this study, we developed an episcleral implantable device for sustained release of ranibizumab, and evaluated its efficacy on suppression of laser-induced choroidal neovascularization (CNV) in rats. We tested both biodegradable and non-biodegradable sheet-type devices consisting of crosslinked gelatin/chitosan (Gel/CS) and photopolymerized poly(ethyleneglycol) dimethacrylate that incorporated collagen microparticles (PEGDM/COL). In vitro release studies of FITC-labeled albumin showed a constant release from PEGDM/COL sheets compared to Gel/CS sheets. The Gel/CS sheets gradually biodegraded in the sclera during the 24-week implantation; however, the PEGDM/COL sheets did not degrade. FITC-albumin was detected in the retina during 18 weeks implantation in the PEGDM/COL sheet-treated group, and was detected in the Gel/CS sheet-treated group during 6 weeks implantation. CNV was suppressed 18 weeks after application of ranibizumab-loaded PEGDM/COL sheets compared to a placebo PEGDM/COL sheet-treated group, and to the intravitreal ranibizumab-injected group. In conclusion, the PEGDM/COL sheet device suppressed CNV via a transscleral administration route for 18 weeks, indicating that prolonged sustained ranibizumab release could reduce the burden of repeated intravitreal injections.


Flight loss linked to faster molecular evolution in insects.
The loss of flight ability has occurred thousands of times independently during insect evolution. Flight loss may be linked to higher molecular evolutionary rates because of reductions in effective population sizes (Ne) and relaxed selective constraints. Reduced dispersal ability increases population subdivision, may decrease geographical range size and increases (sub)population extinction risk, thus leading to an expected reduction in Ne. Additionally, flight loss in birds has been linked to higher molecular rates of energy-related genes, probably owing to relaxed selective constraints on energy metabolism. We tested for an association between insect flight loss and molecular rates through comparative analysis in 49 phylogenetically independent transitions spanning multiple taxa, including moths, flies, beetles, mayflies, stick insects, stoneflies, scorpionflies and caddisflies, using available nuclear and mitochondrial protein-coding DNA sequences. We estimated the rate of molecular evolution of flightless (FL) and related flight-capable lineages by ratios of non-synonymous-to-synonymous substitutions (dN/dS) and overall substitution rates (OSRs). Across multiple instances of flight loss, we show a significant pattern of higher dN/dS ratios and OSRs in FL lineages in mitochondrial but not nuclear genes. These patterns may be explained by relaxed selective constraints in FL ectotherms relating to energy metabolism, possibly in combination with reduced Ne.


Zoster vaccine to prevent postherpetic neuralgia.
In 2006, the U.S. Food and Drug Administration approved the first vaccine for the prevention of acute herpes zoster neuralgia (shingles). This vaccine has important implications in reducing the incidence and severity of the common neuropathic pain condition postherpetic neuralgia. The new vaccine is described.


Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings.
The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg(-1), 50 Bq kg(-1) and 500 Bq kg(-1), respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg(-1), with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h(-1), and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y(-1). For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y(-1) but complies with the upper dose principle of 1 mSv y(-1).


Visual and automatic grading of coronary artery stenoses with 64-slice CT angiography in reference to invasive angiography.
The aim of this study was to assess the performance of a software tool for quantitative coronary artery analysis of computed tomography coronary angiography (CT-QCA) in comparison with invasive coronary angiography with quantitative analysis (CAG-QCA) as standard of reference. Two radiologists reviewed the CT angiography data sets (Siemens Sensation 64) of 25 patients, grading coronary artery stenoses visually and with a software tool (Circulation, Siemens). Twenty-three data sets with sufficient image quality were included in the final analysis. CAG revealed a total of 30 wall irregularities and 28 stenoses, of which 17 were graded as moderate and nine as hemodynamically significant. CT-QCA showed a better agreement to CAG-QCA, with a systematic overestimation of the degree of stenosis of 6.1% and limits of agreement of +36.1% and -23.9; the correlation coefficient was 0.82 (p < 0.0001). Using CT-QCA, sensitivity, specificity, and positive and negative predictive value were 89%, 100%, 89%, and 100%, respectively, for significant area stenoses greater than 75%. The positive predictive value for the visual assessment amounted to 53%. Interobserver variability between CT-QCA and visual assessment showed a kappa value of 0.72. In conclusion, software-supported CT-QCA makes it possible to quantify significant coronary artery stenoses automatically, with good agreement to CAG-QCA.


Brain amyloid and cognition in Lewy body diseases.
Many patients with PD develop PD with dementia (PDD), a syndrome that overlaps clinically and pathologically with dementia with Lewy bodies (DLB); PDD and DLB differ chiefly in the relative timing of dementia and parkinsonism. Brain amyloid deposition is an early feature of DLB and may account, in part, for its early dementia. We sought to confirm this hypothesis and also to determine whether amyloid accumulation contributes to cognitive impairment and dementia in the broad range of parkinsonian diseases. Twenty-nine cognitively healthy PD, 14 PD subjects with mild cognitive impairment (PD-MCI), 18 with DLB, 12 with PDD, and 85 healthy control subjects (HCS) underwent standardized neurologic and neuropsychological examinations and Pittsburgh compound B (PiB) imaging with PET. Apolipoprotein E (ApoE) genotypes were obtained in many patients. PiB retention was expressed as the distribution volume ratio using a cerebellar tissue reference. PiB retention was significantly higher in DLB than in any of the other diagnostic groups. PiB retention did not differ across PDD, PD-MCI, PD, and HCS. Amyloid burden increased with age and with the presence of the ApoE ε4 allele in all patient groups. Only in the DLB group was amyloid deposition associated with impaired cognition. DLB subjects have higher amyloid burden than subjects with PDD, PD-MCI, PD, or HCS; amyloid deposits are linked to cognitive impairment only in DLB. Early amyloid deposits in DLB relative to PDD may account for their difference in the timing of dementia and parkinsonism.


[A de novo partial 5p deletion and cryptic 18p duplication detected by SNP-Array in a boy featuring Cri du Chat syndrome].
To determine the karyotype of a boy suspected to have Cri du Chat syndrome with severe clinical manifestations, and to assess the recurrence risk for his family. High-resolution GTG banding was performed to analyze the patient and his parents. Fluorescence in situ hybridization (FISH) with Cri du Chat syndrome region probe as well as subregional probes mapped to 5pter, 5qter, 18pter, 18qter, and whole chromosome painting probe 18 was performed to analyze the patient and his parents. In addition, single nucleotide polymorphism-based arrays (SNP-Array) analysis with Affymetrix GeneChip Genome-wide Human SNP Nsp/Sty 6.0 were also performed to analyze the patient. Karyotype analysis indicated that the patient has carried a terminal deletion in 5p. FISH with Cri du Chat syndrome region probe confirmed that D5S23 and D5S721 loci are deleted. SNP-Array has detected a 15 Mb deletion at 5p and a 2 Mb duplication at 18p. FISH with 5p subtelomeric probes and 18p subtelomeric probe further confirmed that the derivative chromosome 5 has derived from a translocation between 5p and 18p, which has given rise to a 46,XY,der(5)t(5;18)(p15.1;p11.31)dn karyotype. A de novo 5p partial deletion in conjunction with a cryptic 18p duplication has been detected in a boy featuring Cri-du-Chat syndrome. His parents, both with negative findings, have a low recurrence risk. For its ability to detect chromosomal imbalance, SNP-Array has a great value for counseling of similar patients and assessment of recurrence risks.


Peptide hormones and neuropeptides. Proteolytic processing of the precursor regulatory peptides.
Regulatory peptides are initially synthesized as large protein precursors which must undergo proteolytic processing to yield the biologically active peptide. The proteolytic enzymes involved in this post-translational processing remove the signal peptide, a hydrophobic peptide located at the amino-terminus of the precursor. Further processing steps are the cleavage at single or two adjacent basic residues by endoproteases, followed by a removal of basic residues located at the C-terminus of the peptides by a carboxypeptidase-like enzyme. The selective processing may play an important role in determining which peptides are finally released by the cell. This article reviews the selectivities of various enzymes known to play a role in the proteolytic processing of various regulatory peptides.


Management of spinal cord injury-related scoliosis using pedicle screw-only constructs.
Almost all pediatric patients who incur a spinal cord injury (SCI) will develop scoliosis, and younger patients are at highest risk for curve progression requiring surgical intervention. Although the use of pedicle screws is increasing in popularity, their impact on SCI-related scoliosis has not been described. The authors retrospectively reviewed the radiographic outcomes of pedicle screw-only constructs in all patients who had undergone SCI-related scoliosis correction at a single institution. Medical records and radiographs from Shriner's Hospital for Children-Philadelphia for the period between November 2004 and February 2011 were retrospectively reviewed. Thirty-seven patients, whose mean age at the index surgery was 14.91±3.29 years, were identified. The cohort had a mean follow-up of 33.2±22.8 months. The mean preoperative coronal Cobb angle was 65.5°±25.7°, which corrected to 20.3°±14.4°, translating into a 69% correction (p<0.05). The preoperative coronal balance was 24.4±22.6 mm, with a postoperative measurement of 21.6±20.7 mm (p=1.00). Preoperative pelvic obliquity was 12.7°±8.7°, which corrected to 4.1°±3.8°, translating into a 68% correction (p<0.05). Preoperative shoulder balance, as measured by the clavicle angle, was 8.2°±8.4°, which corrected to 2.7°±3.1° (67% correction, p<0.05). Preoperatively, thoracic kyphosis measured 44.2°±23.7° and was 33.8°±11.5° postoperatively. Thoracolumbar kyphosis was 18.7°±12.1° preoperatively, reduced to 8.1°±7.7° postoperatively, and measured 26.8°±20.2° at the last follow-up (p<0.05). Preoperatively, lumbar lordosis was 35.3°±22.0°, which remained stable at 35.6°±15.0° postoperatively. Pedicle screw constructs appear to provide better correction of coronal parameters than historically reported and provide significant improvement of sagittal kyphosis as well. Although pedicle screws appear to provide good radiographic results, correlation with clinical outcomes is necessary to determine the true impact of pedicle screw constructs on SCI-related scoliosis correction.


Does input influence uptake? Links between maternal talk, processing speed and vocabulary size in Spanish-learning children.
It is well established that variation in caregivers' speech is associated with language outcomes, yet little is known about the learning principles that mediate these effects. This longitudinal study (n = 27) explores whether Spanish-learning children's early experiences with language predict efficiency in real-time comprehension and vocabulary learning. Measures of mothers' speech at 18 months were examined in relation to children's speech processing efficiency and reported vocabulary at 18 and 24 months. Children of mothers who provided more input at 18 months knew more words and were faster in word recognition at 24 months. Moreover, multiple regression analyses indicated that the influences of caregiver speech on speed of word recognition and vocabulary were largely overlapping. This study provides the first evidence that input shapes children's lexical processing efficiency and that vocabulary growth and increasing facility in spoken word comprehension work together to support the uptake of the information that rich input affords the young language learner.


[The first Danish experiences with neonatal extracorporeal membrane oxygenation].
In 1995, neonatal extra-corporeal membrane oxygenation (ECMO) was established at the Department of Neonatology, Rigshospitalet, Copenhagen. The indication for ECMO is circulatory or respiratory failure with arterial oxygen tension below 8 kPa despite maximal conventional treatment. During the first two and a half years 17 newborn infants and one child of 21 months have been treated with ECMO at the Rigshospital. Fifteen survived, of 12 followed at least nine months, 11 have normal development and one has cerebral palsy. There were problems including surgical placement of the cannula, technical difficulties or bleeding in 12 patients. During the same two years at least eight newborns in Denmark fulfilled the ECMO indication, but were not treated, half were not transferred to the Rigshospital. Seven of these eight infants died. The need for ECMO treatment in newborn infants is documented but small. We have succeeded in establishing this complicated treatment due to teamwork between different specialities with a good result.


Comparison of drying methods in the fabrication of collagen scaffold via indirect rapid prototyping.
Porous collagen scaffolds with predefined 3-dimesional (3-D) networks of internal channels are fabricated via an indirect rapid prototyping technique. To obtain the scaffolds, two drying methods, namely critical point drying and freeze-drying were investigated. The latter was found to be a more suitable process as it induced less shrinkage and reproduced the design morphology accurately. The resulting scaffold contained internal hollow channels with porous foam-like structure occupying the surrounding volume. The mean diameter of the pores was 180 +/- 60 microm and the channels diameter obtained was measured as 437 +/- 100 microm. The channels were defined and strengthened by a layer of skin due to the process of freeze-drying. These networks of internal channels serve to enhance the mass transport rate through the scaffold and help to increase the depth of cells penetration in the scaffold.


Asynchrony Injures Lung and Diaphragm in Acute Respiratory Distress Syndrome.
Patient-ventilator asynchrony is often observed during mechanical ventilation and is associated with higher mortality. We hypothesized that patient-ventilator asynchrony causes lung and diaphragm injury and dysfunction. Prospective randomized animal study. University research laboratory. Eighteen New Zealand White rabbits. Acute respiratory distress syndrome (ARDS) model was established by depleting surfactants. Each group (assist control, breath stacking, and reverse triggering) was simulated by phrenic nerve stimulation. The effects of each group on lung function, lung injury (wet-to-dry lung weight ratio, total protein, and interleukin-6 in bronchoalveolar lavage), diaphragm function (diaphragm force generation curve), and diaphragm injury (cross-sectional area of diaphragm muscle fibers, histology) were measured. Diaphragm RNA sequencing was performed using breath stacking and assist control ( n = 2 each). Inspiratory effort generated by phrenic nerve stimulation was small and similar among groups (esophageal pressure swing ≈ -2.5 cm H 2 O). Breath stacking resulted in the largest tidal volume (>10 mL/kg) and highest inspiratory transpulmonary pressure, leading to worse oxygenation, worse lung compliance, and lung injury. Reverse triggering did not cause lung injury. No asynchrony events were observed in assist control, whereas eccentric contractions occurred in breath stacking and reverse triggering, but more frequently in breath stacking. Breath stacking and reverse triggering significantly reduced diaphragm force generation. Diaphragmatic histology revealed that the area fraction of abnormal muscle was ×2.5 higher in breath stacking (vs assist control) and ×2.1 higher in reverse triggering (vs assist control). Diaphragm RNA sequencing analysis revealed that genes associated with muscle differentiation and contraction were suppressed, whereas cytokine- and chemokine-mediated proinflammatory responses were activated in breath stacking versus assist control. Breath stacking caused lung and diaphragm injury, whereas reverse triggering caused diaphragm injury. Thus, careful monitoring and management of patient-ventilator asynchrony may be important to minimize lung and diaphragm injury from spontaneous breathing in ARDS.


Multicentric leiomyosarcoma in a young male horse.
A 2-year-old male Thoroughbred was evaluated for multiple firm, raised nodules of the maxilla and mandible that had been present since 6 months of age. The horse was evaluated as a yearling with a final histologic diagnosis of fibrosarcoma. As a 2-year-old, the colt made a loud upper airway sound and was agitated after strenuous exercise. Results of upper airway endoscopy indicated severe narrowing of the nasal passages and pharynx with normal resting function. Radiography revealed multiple circular bony lesions in the mandible, maxilla, multiple long bones, and cervical vertebrae. Biopsy specimens of the left mandible and right facial bone were obtained. A diagnosis of leiomyosarcoma with extensive metastatic bone formation was made on the basis of histologic features and the immunohistochemical staining properties of the biopsy specimens. Because of the diffuse distribution of the lesions, prognosis was guarded; 4 years after diagnosis, the horse had not pursued an athletic career.


Ultrasonic assessment of the peri- and postmenopausal ovary.
To analyze the role of B-mode ultrasound, color and power Doppler examination and three-dimensional ultrasound with and without power Doppler facilities in evaluation of the peri- and postmenopausal ovaries. Review of the literature on ultrasonic assessment of the ovaries in postmenopausal patients. Ultrasound has assumed an increasing role in the evaluation of the peri- and postmenopausal ovaries. Ovarian lesions are a cause of great concern because of their malignant potential and the limited ability to distinguish accurately between benign and malignant lesions using morphological sonographic criteria alone. Superimposed color Doppler imaging enables the visualization of vascularization and blood flow characteristics of the ovaries and/or ovarian lesions. It becomes possible to detect normal, suspicious and pathologic blood flow characteristics even in small blood vessels. Owing to superb quality of the images, three-dimensional sonography enables precise assessment of the ovarian lesions. Three-dimensional power Doppler ultrasound permits effective targeting and rendering of ovarian tumor vasculature, thus providing new diagnostic possibilities for early detection of ovarian malignancy and differentiation of benign from malignant ovarian pathology. Further technological development will contribute to more objective evaluation of ovarian tumor morphology and vasculature which will give us tremendous support in clinical decision making and planning the management.


Long noncoding RNA LeXis promotes osteosarcoma growth through upregulation of CTNNB1 expression.
Osteosarcoma (OS) is the most common primary bone cancer in adolescents and children. Long noncoding RNAs (lncRNAs) contain > 200 nucleotides and do not have protein-coding ability. Liver-expressed LXR-induced sequence (LeXis) is a newly identified functional lncRNA. However, its expression pattern, biological function, and molecular mechanism in OS progression are unclear. The present study is the first to show that LeXis expression was upregulated in OS tissues. Increased LeXis expression was significantly correlated with high tumor stage, large tumor size, and poor prognosis. Our findings highlight the oncogenic activity of lncRNA LeXis in OS growth. Results of functional assays showed that LeXis promoted OS growth both in vitro and in vivo. Mechanistic investigation showed that LeXis directly interacted with miR-199a and suppressed its expression. Moreover, LeXis increased CTNNB1 expression by functioning as a ceRNA of CTNNB1 against miR-199a. These findings may have important implications for developing novel therapeutic strategies for OS.


Combined therapy with external beam irradiation and hepatic arterial epirubicin infusion through an implanted port for advanced hepatocellular carcinoma.
Nineteen patients with advanced stage IV hepatocellular carcinoma for which transcatheter arterial embolization and percutaneous ethanol injection were not indicated have been treated by combined therapy with external beam irradiation and repeated hepatic arterial epirubicin infusion through an implanted port. The response rate was 47%, and the median survival was 11.6 months (range, 4.0 to 27.1 months). Eighteen of the 19 patients were able to undergo the infusion therapy on an outpatient basis 3 to 7 weeks after initiation of therapy. This combined therapy was effective in improving tumor-bearing survival and less stressful for the patients because of the minimal therapy-related toxicity and brief hospitalization.


Rotational relaxation of HF by collision with ortho- and para-H2 molecules.
The first quantum mechanical investigation of the rotational deactivation of HF induced by collisions with ortho- and para-H(2) molecules is reported. Ab initio potential energy calculations are carried out at the coupled cluster level with single and double excitations, using a quadruple-zeta basis set. The global rigid rotor four-dimensional potential energy surface is obtained by fitting ab initio points with a least squares procedure for the angular terms and interpolating the radial coefficients with cubic splines. It is shown that the equilibrium structure of the H(2)-HF complex is T-shaped and the well depth is found to be 359 cm(-1). Close coupling scattering calculations are performed at collision energy ranging from 10(-2) to 1600 cm(-1). A comparison of the rotational quenching of HF with para-H(2) and (4)He is used to validate our potential energy surface. The rotational quenching cross sections of HF by ortho- and para-H(2) are also compared and found to be very different. An explanation of these differences based on a resonance mechanism is proposed.


Photocatalytic Hydrogenation of Graphene Using Pd Nanocones.
Plasmonic photocatalytic processes typically use the interaction of light with metallic nanoparticles to drive chemical reactions on their surfaces. Here we show that a plasmonic photocatalyst can also induce a reaction on an adjacent material. A combination of spontaneous H2 dissociation and plasmon-induced H desorption from tilted palladium (Pd) nanocones yields reactive H atoms which, in the direct vicinity of a graphene monolayer, results in its local hydrogenation. The conversion of pristine to hydrogenated graphene, a semiconductor, is detectable by visible local fluorescence of the hydrogenated regions of the graphene sheet, as well as by Raman spectroscopic analysis. These results may lead to new approaches for local, light-driven functionalization of graphene and other 2D materials and for precision patterning of functional devices.


Quantitative changes in the protein and miRNA cargo of plasma exosome-like vesicles after exposure to ionizing radiation.
Multiple cell types secrete exosome-like extracellular vesicles (ELVs) to the extracellular environment. Pathological conditions can produce characteristic changes to the vesicle cargo. We investigated if ionizing radiation is capable of inducing changes in the protein and microRNA (miRNA) cargo of ELVs. Whole blood samples from healthy donors were irradiated with 2 Gy gamma rays and then peripheral blood mononuclear cells and plasma were separated from residual blood and co-cultivated for 24 h. The released ELVs were collected by differential ultracentrifugation from irradiated and non-irradiated samples. microRNAs and proteins were quantified by qPCR and label-free proteomics. Here we report a first characterization of radiation-induced changes in the protein and miRNA cargo of ELVs isolated from plasma. Proteome analysis of ELVs identified 214 proteins, of which nine significantly changed their abundance after irradiation. The radiation-induced down-regulation of afamin and serpine peptidase F1 was confirmed by immunoblotting. miRNA expression profiling identified 58 different exosomal miRNAs, the expression of miR-204-5p, miR-92a-3p and miR-31-5p was significantly increased in ELVs from irradiated samples. This study provides evidence that radiation-induced changes occur in the protein and miRNA cargo of plasma ELVs. These data imply a novel systemic communication pathway between irradiated and non-irradiated cells and tissues.


Veteran-Centered Exemplars in a Prelicensure Nursing Program Curriculum.
Veterans have unique health care needs that must be addressed. Seventy-five percent of veterans are treated outside Veteran Health Administration facilities, so all health care providers should be educated on how to better serve veterans and their families. Nurses are in a prime position to lead the way in these efforts, beginning in prelicensure nursing education. In this article, the authors describe a model and exemplars for integrating veteran-centered care into an existing curriculum, from beginning through advanced levels.


Needs assessment to strengthen capacity in water and sanitation research in Africa: experiences of the African SNOWS consortium.
Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project. We reviewed the reports of two needs assessments. The first was a detailed needs assessment led by one northern partner, with follow-up visits which included reciprocal representation from the African universities. The second assessment, led by another northern partner, focused primarily on training needs. The reports from both needs assessments were read and stated needs were extracted and summarised. Key common issues identified in both assessments were supervisory skills, applications for external research funding, research management, and writing for publication in the peer-reviewed scientific literature. The bureaucratisation of university processes and inconsistencies through administration processes also caused problems. The lack of specialist laboratory equipment presented difficulties, particularly of inaccessibility through a lack of skilled staff for operation and maintenance, and of a budget provision for repairs and running costs. The lack of taught PhD modules and of research training methods also caused problems. Institutionally, there were often no mechanisms for identifying funding opportunities. On the other hand, grantees were often unable to understand or comply with the funders' financial and reporting requirements and were not supported by their institution. Skills in staff recruitment, retention, and performance were poor, as were performance in proposal and paper writing. The requirements for ethical clearance were often not known and governance issues not understood, particularly those required by funders. SNOWS believes that working with African universities to develop networks that support African-led research driven by the local context is an effective approach to develop and retain research skills needed to change policy and practice in water, sanitation, and hygiene in Africa.


Changing incidence of trachoma in the West Midlands.
An increasing incidence of trachoma in an urban Midland population has been shown to be mainly due to immigration of infected carriers from the Punjab. In areas where trachoma is common special clinics should be established for the treatment and follow-up of patients and contacts. Public health measures should be introduced to prevent the spread of the infection. Laboratory methods should be more widely used in the diagnosis and control of trachoma.


Requirements for adherens junction components in the interaction between epithelial tissues during dorsal closure in Drosophila.
Dynamic interactions between epithelial sheets are a regular feature of morphogenetic processes. Dorsal closure in Drosophila relies on the coordinated movements of two epithelia, the epidermis and the amnioserosa, and provides an excellent model system for a genetic and cell biological approach. Here, we have analyzed the contribution of junctional organization of these epithelia to dorsal closure. We observe a stringent requirement for adherens junctions at the leading edge, the interface between the amnioserosa and the epidermis, for the transmission of the forces generated during the process. We also find that interactions between Armadillo and E-cadherin play an important role in maintaining the adhesion at the leading edge, revealing the particular dynamics of this interface. Our results show that regulated cell adhesion is a crucial element of the interactions that shape epithelial sheets in morphogenetic processes.


Concurrent initiation of intra-aortic balloon pumping with extracorporeal membrane oxygenation reduced in-hospital mortality in postcardiotomy cardiogenic shock.
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in postcardiotomy cardiac shock (PCS). The factors that affect mortality in patients who receive ECMO for PCS remain unclear. In this study, we analyzed the outcomes, predictive factors and complications of ECMO use for PCS. A total of 152 adult subjects who received VA-ECMO for PCS in Fuwai Hospital were consecutively included. We retrospectively collected the baseline characteristics, outcomes and complications. Baseline characteristics were compared between survivors with non-survivors, and logistic regression was performed to identify predictive factors for in-hospital mortality. The mean age of the subjects was 49.5 ± 14.1 years, with a male dominancy of 73.7%. The main surgical procedures were heart transplantation (32.2%), coronary artery bypass graft (17%) and valvular surgery (11.8%). Intra-aortic balloon pumping (IABP) was initiated concurrently with ECMO in 32.2% subjects and sequentially in 18.4% subjects. The ECMO weaning rate was 56.6%, and the in-hospital mortality was 52.0%. When compared with non-survivors, survivors had less hypertension (15.1% vs. 35.4%, p = 0.004), secondary thoracotomy before ECMO initiation (19.2% vs. 39.2%, p = 0.007), pre-ECMO cardiac arrest/ventricular fibrillation (11.0% vs. 34.2%, p = 0.001), bedside implantation of ECMO (11.0% vs. 41.8%, p < 0.001), and more transplant procedure (45.2% vs. 20.3%, p = 0.001), concurrent IABP initiation with ECMO (41.1% vs. 24.1%, p = 0.025). Multivariate logistic regression indicated concurrent IABP initiation with ECMO was the only independent protective factor for in-hospital mortality (OR = 0.375, p = 0.041, 95% CI 0.146-0.963). Concurrent IABP initiation with ECMO had less need for continuous renal replacement therapy (30.6% vs. 49.3%, p = 0.039) and less neurological complications (8.2% vs. 22.7%, p = 0.035), but more thrombosis complications (18.4% vs. 2.7%, p = 0.007). Concurrent initiation of IABP with ECMO provides better short-term survival for PCS, with reduced peripheral perfusion complications.


Investigating the implementation of telehealth and digital technologies during public health crisis: A qualitative review.
Public health crises such as the Coronavirus disease 2019 (COVID-19) pandemic across the world overstrained the health care system. Accordingly, telehealth and digital technologies were implemented. Telehealth and digital technologies refer to the provision of health care at a distance using electronic means for diagnosis, evaluation, treatment, monitoring, and education of patients. This approach, while extremely useful, can be challenging for both patients and physicians, mainly as this is a new mode of health care to health practitioners and patients. Intrinsically, when managing the massive disruption to the routine of patient health care workflow, it is important to understand the important factors associated with an accelerated introduction of telehealth and digital technologies for the effective and safe continuation of healthcare during a public health crisis. Accordingly, this current study performed a qualitative review analysis of 40 scientific sources from 2019 to 2022. Findings present health practitioners that implemented telehealth and digital technologies during the public health emergency. Additionally, findings from this study presents a workflow approach for telehealth visit cycle and also discusses the current telehealth and virtual applications being implemented during public health crisis. This study provides implications to support health care managers and policymakers of health centres to be virtually informed regarding digital applications being implemented by patients and health practitioners on how to implement an effective telehealth system during public health crises.


Incompatibility between mitochondrial and nuclear genomes during oogenesis results in ovarian failure and embryonic lethality.
Mitochondrial dysfunction can cause female infertility. An important unresolved issue is the extent to which incompatibility between mitochondrial and nuclear genomes contributes to female infertility. It has previously been shown that a mitochondrial haplotype from D. simulans (simw501 ) is incompatible with a nuclear genome from the D. melanogaster strain Oregon-R (OreR), resulting in impaired development, which was enhanced at higher temperature. This mito-nuclear incompatibility is between alleles of the nuclear-encoded mitochondrial tyrosyl-tRNA synthetase (Aatm) and the mitochondrial-encoded tyrosyl-tRNA that it aminoacylates. Here, we show that this mito-nuclear incompatibility causes a severe temperature-sensitive female infertility. The OreR nuclear genome contributed to death of ovarian germline stem cells and reduced egg production, which was further enhanced by the incompatibility with simw501 mitochondria. Mito-nuclear incompatibility also resulted in aberrant egg morphology and a maternal-effect on embryonic chromosome segregation and survival, which was completely dependent on the temperature and mito-nuclear genotype of the mother. Our findings show that maternal mito-nuclear incompatibility during Drosophila oogenesis has severe consequences for egg production and embryonic survival, with important broader relevance to human female infertility and mitochondrial replacement therapy.


A successful treatment of life-threatening bleeding from polycystic kidneys with antifibrinolytic agent tranexamic acid.
We describe a successful treatment of a severe, persistent bleeding from both kidneys in a patient with autosomal dominant polycystic kidney disease (ADPKD) with tranexamic acid (TXA), a potent antifibrinolytic agent. The bleeding could not be controlled by intensive conservative treatment, it became life-threatening and urgent bilateral nephrectomy was intended. Since local and systemic hyperfibrinolysis play a role in bleeding in ADPKD patients, we tried TXA treatment. In fact, the massive bleeding promptly stopped, and haematuria gradually ceased. Removal of both kidneys was prevented. After 5 days both ureters became obstructed by blood clots, but placing J-catheters in each pyelon successfully solved this complication. Our case shows that it is reasonable to try antifibrinolytic treatment with TXA in such devastating uncontrolled bleeding.


The use of metformin, insulin, sulphonylureas, and thiazolidinediones and the risk of fracture: Systematic review and meta-analysis of observational studies.
Certain glucose-lowering medications have been implicated in the risk of fracture. While there is convincing evidence from randomized controlled trials (RCTs) that thiazolidinedione use is associated with a higher risk of fracture, the effects of metformin, insulin, and sulphonylureas on the risk of fracture remain equivocal because these medications are not generally investigated in RCTs. A meta-analysis of observational studies to provide further insights into the association between the use of metformin, insulin, sulphonylureas, or thiazolidinediones and the risk of fracture was performed. PubMed and Web of Science databases were searched to identify relevant observational studies. A random effects model was used to estimate the summary relative risks (RRs) with 95% confidence intervals (CIs). The use of insulin (RR 1.49, 95% CI 1.29, 1.73; n = 23 studies), sulphonylureas (RR 1.30, 95% CI 1.18, 1.43; n = 10), and thiazolidinediones (RR 1.24, 95% CI 1.13, 1.35; n = 14) was associated with an increased risk of fracture, whereas the use of metformin was associated with a reduced risk of fracture (RR 0.86, 95% CI 0.75, 0.99; n = 12). Regarding types of thiazolidinediones, both pioglitazone (RR 1.38, 95% CI 1.23, 1.54; n = 5) and rosiglitazone (RR 1.34, 95% CI 1.14, 1.58; n = 5) were positively associated with the risk of fracture. In summary, there is compelling evidence to discourage the use of thiazolidinediones in individuals with an increased risk of fracture, whereas metformin appears to have a good safety profile for the risk of fracture. The reduced risk of fracture with metformin could possibly be due to the reduced overall risk of fracture among metformin users, as this medication is typically prescribed in the early stages of type 2 diabetes mellitus. The use of insulin or sulphonylureas may increase fracture risk; this risk is most likely attributed to an increased risk of hypoglycaemia-induced falls. Further confirmation by additional RCTs is required to determine whether the observed association between the use of metformin, insulin, or sulphonylureas and the risk of fracture is due to treatment with these medications or confounding factors.


Loewald's "binocular vision" and the art of analysis.
In his 1988 monograph on sublimation, Hans Loewald describes the process as a transformation of the drives aimed at re-creating what he presumes to be the subjective experience of infantile attachment. To describe this experience, he invokes a state of mind that he calls "binocular vision." He maintains that this mental state may arise not only in activities usually associated with sublimation, such as the creation and enjoyment of art, but in all forms of sublimation, including effective psychoanalysis. Because Loewald's discussion is largely theoretical, it does not convey how the concept of binocular vision may inform clinical technique and interdisciplinary study. A comparative application of his theory to psychoanalytic process and to the viewer's response to art enables one to grasp binocular vision as a common aspect of both. It emerges as a useful model with which to conceptualize and integrate the ambiguous reality of analytic experience.


Morphological and phylogenetic identification of Botrytis sinoviticola, a novel cryptic species causing gray mold disease of table grapes (Vitis vinifera) in China.
Seventy-five isolates of Botrytis collected from table grapes (Vitis vinifera) with gray mold symptoms in China were identified based on morpho-cultural characteristics on potato dextrose agar (20 C) and/or phylogenetic analysis using the sequences of three nuclear genes (G3PDH, HSP60, RPB2). Isolates of different species of Botrytis were compared with fenhexamid sensitivity, Bc-hch gene-RFLP haplotyping and pathogenicity to V. vinifera. The 75 isolates comprise two species, B. cinerea (63 isolates) and an undescribed Botrytis sp. (12 isolates) described here as Botrytis sinoviticola Zhang et al. sp., nov. Both B. sinoviticola (Bs) and B. cinerea (Bc) were found to have 20 C optimum for mycelial growth and 25 C for conidial germination. Sensitivity to fenhexamid was significantly greater (P < 0.05) for Bc (EC50 = 0.04 ± 0.01 μg mL(-1)) than for Bs (EC50 = 0.08 ± 0.02 μg mL(-1)). Digestion of the PCR amplicons of the Bc-hch gene with Hha I generated two haplotypes, Group I haplotype for Bs and Group II haplotype for Bc. Bs infected table grapes (leaves, berries) only through wounds, whereas Bc infected both injured and non-injured tissues of table grapes. This study suggests that Bs is a cryptic species sympatric with Bc on table grapes in China.


Study on the application value of red blood cell distribution width and platelet distribution width in neonatal exchange transfusion with hyperbilirubinemia.
The study aimed to evaluate the application of Red Blood Cell Distribution Width (RDW) and Platelet Distribution Width (PDW) in the treatment of neonatal exchange transfusion (ET) with hyperbilirubinemia as well as to provide relevant reference materials for clinical diagnosis and treatment. This was a retrospective study in a single center. Between January 2011 and December 2020, a total of 198 neonates, who were admitted to Fujian Maternity and Child Health Hospital for hyperbilirubinemia and treated with ET therapy were selected. They were divided into blood group antibody negative (BGAbN) ET (n = 92) and blood group antibody positive (BGAbP) ET (n = 106) groups. We analyzed changes in serum total bilirubin (STB), serum indirect bilirubin (SIB), and platelet count(PLT) before and after ET; The clinical data of the neonates with hyperbilirubinemia were collected, and RDW and PDW were compared in the two groups before ET.. The concentrations of STB, SIB, and platelet count were much higher before ET and decreased significantly after ET; the difference was statistically significant (p<.001); There were significant differences between the two groups in RDW and PDW before ET. ET therapy is the most timely and effective treatment method for severe hyperbilirubinemia in neonates clinically; RDW and PDW can help determine neonatal hemolysis caused by blood group antibodies.


Recovery of memory after general anaesthesia: clinical findings and somatosensory evoked responses.
Mid-latency somatosensory evoked responses are used to monitor the integrity of the sensory pathways intra-operatively. They can quantify the effects of anaesthetics on the central nervous system. Mid-latency auditory evoked responses have been related to cognition during anaesthesia, but there are no detailed studies using median nerve somatosensory evoked responses (MnSSER). We studied 49 patients during recovery from general anaesthesia (isoflurane/nitrous oxide or propofol) to assess implicit and explicit memory function in relation to mid-latency MnSSER. The MnSSER recordings were made before anaesthesia, during steady-state anaesthesia, and at the end of the recovery period. The patients were interviewed 24 h later about their memory for the immediate wake up phase. Statistical analysis was by multivariate analysis of variance. Out of 49 patients, 23 recalled the recovery period, 11 had implicit memory for an object shown to them during the recovery period, and 15 did not have any memory for the recovery period. At RECOVERY the patients with recall had significantly shorter MnSSER latencies N45 and P50 and inter-wave conduction times LatN35-LatP45 than patients without memory (P<0.05). We conclude that MnSSER components warrant further investigation for studying the effects of anaesthetic drugs on cognitive function.


Impact of perioperative anticoagulation on artificial urinary sphincter device survival.
The aim of this study was to evaluate the impact of perioperative anticoagulation on artificial urinary sphincter (AUS) device outcomes. Following institutional review board approval, patients undergoing AUS surgery from 1983 to 2014 were evaluated to assess device survival in patients with warfarin use compared to individuals without warfarin use. Hazard regression analysis was used to determine the association between warfarin use and device outcomes. From 1983 to 2014, there were 2125 AUS procedures at Mayo Clinic. Of these, information regarding anticoagulation use was available in 651, including 43 patients who were on warfarin and 608 who were not. On univariate analysis, the use of warfarin was associated with an increased rate of infection/erosion [hazard ratio (HR) 2.58, p = 0.02]. However, there was no increased risk of overall AUS failure (HR 1.66, p = 0.06), malfunction of AUS (HR 1.19, p = 0.74) or urethral atrophy (HR 1.09, p = 0.88). Kaplan-Meier assessment of device survival for individuals not on warfarin versus individuals on warfarin at 1 and 5 years was 91% versus 83% and 72% versus 57%, respectively (p = 0.058). On multivariate analysis, warfarin was not associated with an increased risk of infection/erosion (HR 1.37, p = 0.51). Perioperative management of AUS patients on warfarin requires expert care; however, long-term AUS device survival is not significantly affected by warfarin use. Recognition of these outcomes is important for improving preoperative patient counseling and surgical patient selection.


Beyond toxicity: a regulatory role for mitochondrial cyanide.
In non-cyanogenic plants, cyanide is a co-product of ethylene and camalexin biosynthesis. To maintain cyanide at non-toxic levels, Arabidopsis plants express the mitochondrial β-cyanoalanine synthase CYS-C1. CYS-C1 knockout leads to an increased level of cyanide in the roots and leaves and a severe defect in root hair morphogenesis, suggesting that cyanide acts as a signaling factor in root development. During compatible and incompatible plant-bacteria interactions, cyanide accumulation and CYS-C1 gene expression are negatively correlated. Moreover, CYS-C1 mutation increases both plant tolerance to biotrophic pathogens and their susceptibility to necrotrophic fungi, indicating that cyanide could stimulate the salicylic acid-dependent signaling pathway of the plant immune system. We hypothesize that CYS-C1 is essential for maintaining non-toxic concentrations of cyanide in the mitochondria to facilitate cyanide's role in signaling.


Effects of vanadate on heart and circulation.
In anesthetized cats vanadate (Na3VO4) up to 0.5 mg/kg increased blood pressure and left ventricular end-diastolic pressure (LVEDP) but decreased the force of contraction and heart rate. At 1 mg/kg, LVEDP increased markedly in parallel with an elevation of the ST segment of the electrocardiogram and a pronounced decrease in blood pressure; these effects were reversible within a few minutes. In isolated Langendorff heart preparations of guinea pigs perfused at constant pressure, vanadate decreased flow rate (EC50 = 5.3 mumoles/liter) and contractile force (EC50 = 6.9 mumoles/liter). Vanadate increased tension in isolated aortic strips of cats (EC50 = 115 mumoles/liter) and rabbits (EC50 = 435 mumoles/liter). Vanadate also increased the force of isometric contractions of papillary muscles of guinea pigs, cats, and rabbits, the EC50 values being 124, 110, or 66 mumoles/liter, respectively. We conclude that the negative ionotropic action of vanadate is brought about by marked coronary constriction occurring at concentrations which are too low to have a direct positive action on ventricular myocardium.


An update on the status of breast cancer screening in Brazil after the covid-19 pandemic.
We have previously reported the impact of covid-19 pandemic on breast cancer screening, in Brazil: among women aged 50-69 years, mammography attendance decreased by 42% in public healthcare (SUS), comparing 2019 and 2020. In this short communication, we wish to present: a) an update of the number of mammograms performed, in 2021; b) an exploratory analysis of the characteristics of the screened population between 2019 and 2021. A total of 1.675.307 mammograms were performed in 2021, nearly 15% lower than pre-pandemic levels. Almost a third, 29.5% of them, had intervals greater than three years. In accordance with our previous study, the number of patients with palpable lumps on physical exam increased. The consequences of postponing breast cancer screening during the pandemic are still uncertain. Unfortunately, as of December 2021, screening attendance has not resumed. On the contrary, our results show an increase in the fraction of women with mammography delayed beyond three years.


Epidemiology of COVID-19 in older persons, Wuhan, China.
the epidemiological characteristics of older patients with COVID-19 was far from clear. to explore the epidemiology of older patients with COVID-19 in Wuhan, China. a retrospective cross-sectional study. a population-based study. the resident older patients (>65 years) diagnosed with COVID-19. city-wide case series reported to Wuhan Center for Disease Control and Prevention from 12 December 2019 to 17 March 2020 were included. The epidemic curves were constructed by dates of disease onset. 14,238 confirmed COVID-19 cases were older persons. The number of male cases were slightly less than female cases (1:1.01). The attack rate of COVID-19 in the older persons was 11.49‰ in Wuhan. There was a rapid increase of disease at the early stage of the epidemic and then a gradual and steady decrease was performed. 3,723 (26.15%) and 734 (5.16%) patients were diagnosed as severe and critical cases, respectively. The attributable crude fatality ratio of COVID-19 in the older population was 222.57/100,000, and the crude fatality ratio of COVID was 19.37%. The proportion of severe and critical cases, and fatality ratio were both higher in downtown area and increased with age. the older persons are sensitive to COVID-19. The proportion of severe and critical cases and fatality ratio are higher than that in children and younger adults. Strengthen the protection and control strategies for the older adults are of priorities. More detailed epidemiological and clinical information should be measured in further studies.


Thermal dilution and ultrasound: alternative techniques for measuring cardiac output.
We evaluated 5 TD CO units, 4 modules and 1 stand-alone, from 5 manufacturers. All units are rated Acceptable. Most of the test results met our accuracy and precision criteria; other results that demonstrated a small margin of error were still clinically useful. The utility of the TD method depends largely on proper technique, as well as the volume and temperature of the injection, number of injections, and the type of probe used. Purchasing decisions should be based primarily on the compatibility of the proposed TD units with existing physiologic monitors and whether a module or a stand-alone unit is more appropriate.


Scaling up Xpert MTB/RIF technology: the costs of laboratory- vs. clinic-based roll-out in South Africa.
The World Health Organization recommends using Xpert MTB/RIF for diagnosis of pulmonary tuberculosis (PTB), but there is little evidence on the optimal placement of Xpert instruments in public health systems. We used recent South African data to compare the cost of placing Xpert at points of TB treatment (all primary clinics and hospitals) with the cost of placement at sub-district laboratories. We estimated Xpert's cost/test in a primary clinic pilot and in the pilot phase of the national Xpert roll-out to smear microscopy laboratories; the expected future volumes for each of 223 laboratories or 3799 points of treatment; the number and cost of Xpert instruments required and the national cost of using Xpert for PTB diagnosis for each placement scenario in 2014. In 2014, South Africa will test 2.6 million TB suspects. Laboratory placement requires 274 Xpert instruments, while point-of-treatment placement requires 4020 instruments. With an Xpert cartridge price of $14.00, the cost/test is $26.54 for laboratory placement and $38.91 for point-of-treatment placement. Low test volumes and a high number of sites are the major contributors to higher point-of-treatment costs. National placement of Xpert at laboratories would cost $71 million/year; point-of-treatment placement would cost $107 million/year, 51% more. Placing Xpert technology at points of treatment is substantially more expensive than placing the instruments in smear microscopy laboratories. The incremental benefits of point-of-treatment placement, in terms of better patient outcomes, will have to be equally substantial to justify the additional cost to the national health budget.


Impact of personality characteristics on patient satisfaction after multifocal intraocular lens implantation: results from the "happy patient study".
This prospective multicenter study assessed personality characteristics that may influence patient satisfaction after implantation of multifocal intraocular lenses (MIOLs). One hundred eighty-three patients who underwent bilateral implantation of different MIOLs were enrolled. Uncorrected and corrected distance visual acuity for distance and near (ie, UDVA, UNVA, CDVA, and CNVA) were assessed preoperatively and 3 and 6 months after implantation. Before surgery, personality characteristics were evaluated using a questionnaire based on the NEO Personality Inventory Test and the Compulsiveness Inventory Test. At the 3- and 6-month postoperative visits, patients answered a questionnaire concerning overall satisfaction, need for spectacles at different distances, visual function at different distances and lighting conditions, photic phenomena, and ease of performing daily activities. Three months after surgery (n = 163), mean CDVA was 0.03 ± 0.09 logMAR, UDVA was 0.05 ± 0.09 logMAR, and UNVA was 0.04 ± 0.11 logMAR. At the 6-month visit (n = 131), mean CDVA was 0.02 ± 0.07 logMAR, UDVA was 0.06 ± 0.09 logMAR, and UNVA was 0.05 ± 0.01 logMAR. Most patients (82.2%) would opt for an MIOL again, 3.7% would not, and 14.1% were uncertain. Overall satisfaction with the procedure was correlated to low astigmatism, good visual function, low spectacle dependence, and less halos or glare. The personality characteristics of compulsive checking, orderliness, competence, and dutifulness were statistically significantly correlated to subjective disturbance by glare and halos. Postoperative patient satisfaction after MIOL implantation is correlated to visual performance, spectacle independence, and less photic phenomena. Personality characteristics have an impact on subjective disturbance by photic phenomena and thus are important for patient satisfaction.


Joint effects of C-reactive protein and glycated hemoglobin in predicting future cardiovascular events of patients with advanced atherosclerosis.
C-reactive protein (CRP) and glycohemoglobin (HbA1c) are established risk factors for the development of cardiovascular disease. We investigated the joint effects of these parameters on cardiovascular outcome of patients with advanced atherosclerosis. We studied 454 patients with advanced atherosclerosis (median age, 69 years; 264 male). Cardiovascular risk profile, high-sensitivity CRP (hs-CRP), and HbA1c were obtained at baseline, and patients were followed for a median of 21 months (interquartile range, 13 to 26) for the occurrence of major adverse cardiovascular events (MACE) (myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death). We observed 166 MACE in 128 patients (28%). Cumulative event-free survival rates at 6, 12, and 24 months were 91%, 85%, and 73%, respectively. Adjusted hazard ratios for the occurrence of MACE according to increasing quartiles of hs-CRP and HbA1c were 1.35 (P=0.31), 1.90 (P=0.026) and 2.13 (P=0.007), and 1.40 (P=0.26), 1.81 (P=0.059), and 2.36 (P=0.023), respectively, compared with the lowest quartiles. Considering both parameters jointly, we found that patients with hs-CRP >0.44 mg/dL and HbA1c >6.2% (upper quartiles) were at highest risk for MACE, with each parameter adding to the prognostic information of the other. Inflammation, indicated by hs-CRP, and hyperglycemia, indicated by HbA1c, jointly contribute to the cardiovascular risk of patients with advanced atherosclerosis. Patients with both hs-CRP and HbA1c in the upper quartiles (>0.44 mg/dL and >6.2%, respectively) are at particularly high risk for poor cardiovascular outcome.