Asbestos-induced disruption of calcium homeostasis induces endoplasmic reticulum stress in macrophages.
Although the mechanisms for fibrosis development remain largely unknown, recent evidence indicates that endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) may act as an important fibrotic stimulus in diseased lungs. ER stress is observed in lungs of patients with idiopathic pulmonary fibrosis. In this study we evaluated if ER stress and the UPR was present in macrophages exposed to chrysotile asbestos and if ER stress in macrophages was associated with asbestos-induced pulmonary fibrosis. Macrophages exposed to chrysotile had elevated transcript levels of several ER stress genes. Macrophages loaded with the Ca(2+)-sensitive dye Fura2-AM showed that cytosolic Ca(2+) increased significantly within minutes after chrysotile exposure and remained elevated for a prolonged time. Chrysotile-induced increases in cytosolic Ca(2+) were partially inhibited by either anisomycin, an inhibitor of passive Ca(2+) leak from the ER, or 1,2-bis(2-aminophenoxyl)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular Ca(2+) chelator known to deplete ER Ca(2+) stores. Anisomycin inhibited X-box-binding protein 1 (XBP1) mRNA splicing and reduced immunoglobulin-binding protein (BiP) levels, whereas BAPTA-AM increased XBP1 splicing and BiP expression, suggesting that ER calcium depletion may be one factor contributing to ER stress in cells exposed to chrysotile. To evaluate ER stress in vivo, asbestos-exposed mice showed fibrosis development, and alveolar macrophages from fibrotic mice showed increased expression of BiP. Bronchoalveolar macrophages from asbestosis patients showed increased expression of several ER stress genes compared with normal subjects. These findings suggest that alveolar macrophages undergo ER stress, which is associated with fibrosis development.


Recent Developments in Upscalable Printing Techniques for Perovskite Solar Cells.
Just over a decade, perovskite solar cells (PSCs) have been emerged as a next-generation photovoltaic technology due to their skyrocketing power conversion efficiency (PCE), low cost, and easy manufacturing techniques compared to Si solar cells. Several methods and procedures have been developed to fabricate high-quality perovskite films to improve the scalability and commercialize PSCs. Recently, several printing technologies such as blade-coating, slot-die coating, spray coating, flexographic printing, gravure printing, screen printing, and inkjet printing have been found to be very effective in controlling film formation and improving the PCE of over 21%. This review summarizes the intensive research efforts given for these printing techniques to scale up the perovskite films as well as the hole transport layer (HTL), the electron transport layer (ETL), and electrodes for PSCs. In the end, this review presents a description of the future research scope to overcome the challenges being faced in the printing techniques for the commercialization of PSCs.


Decerebrate rigidity in animals.
Decerebrate rigidity (DR) in animals is caused by a release of spinal neurons from supraspinal inhibition, which results in a caricature of reflex standing and includes tonic neck and labyrinthine reflexes. The reticular formation, cerebellum, vestibular complex, spinal cord, and muscle spindle system and their neurophysiological interaction are critical to DR. Its discovery and investigation were essential to Sherrington's concept of the integrative action of the nervous system. There are two types of DR with different anatomical and physiological bases. Intercollicular decerebration yields rigidity in extensor muscles that results from bilateral destruction of the central tegmental tracts, is abolished by posterior root section, and is due to a facilitation of gamma motoneuron discharge (gamma animal). Anemic decerebration is characterized by excessive extensor rigidity, depends upon the release of tonic labryinthine reflexes from cerebellar inhibition, is independent of posterior root section, and is caused by excessive alpha motoneuron discharge (alpha animal). DR has provided an insight into the mechanisms of posture and standing, but the correlation of laboratory observations and results from animals to humans must be made with caution.


A computational system for Bayesian benchmark dose estimation of genomic data in BBMD.
Existing studies have revealed that the benchmark dose (BMD) estimates from short-term in vivo transcriptomics studies can approximate those from long-term guideline toxicity assessments. Existing software applications follow this trend by analyzing omics data through the maximum likelihood estimation and choosing the "best" model for BMD estimates. However, this practice ignores the model uncertainty and may result in over-confident inferences and predictions, leading to an inadequate decision. By generally following the National Toxicology Program Approach to Genomic Dose-Response Modeling, we developed a web-based dose-response modeling and BMD estimation system, Bayesian BMD (BBMD), for genomic data to quantitatively address uncertainty from various sources. The performances of BBMD are compared with BMDExpress. The system is primarily based on the previously developed BBMD system and further developed in a genomic perspective. Bayesian model averaging method is applied to BMD estimation and pathways analyses. Generally, the system is unique regarding the flexibility in preparing/storing data and in characterizing uncertainties. This system was tested and validated versus 24 previously published in-vivo microarray dose-response datasets (GSE45892) and 64 molecules data from the Open TG-Gates database. Short term transcriptional BMD values for the median pathway in BBMD are highly correlated with the long-term apical BMD values (R = 0.78-0.91). The BMD estimates obtained by BBMD were compared to those by BMDExpress. The results indicate that BBMD provides more adequate results in terms of less extreme values and no failure in BMD and BMDL calculations. Also, the pathway analysis in BBMD provides a conservative estimate because a broader confidence interval is established. Overall, this study demonstrates that dose-response modeling using genomic data can play a substantial role in support of chemical risk assessment. BBMD represents a robust and user-friendly alternative for genomic dose-response data analysis with outstanding functionalities to quantify uncertainty from various sources.


A Sensitive Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Direct Visual Detection of SARS-CoV-2.
A simple and rapid reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of SARS-CoV-2. The RT-LAMP assay was highly specific for SARS-CoV-2 and was able to detect one copy of transcribed SARS-CoV-2 RNA within 24 minutes. Assay validation performed using 50 positive and 32 negative clinical samples showed 100% sensitivity and specificity. The RT-LAMP would be valuable for clinical diagnosis and epidemiological surveillance of SARS-CoV-2 infection in resource-limited areas as it does not require the use of sophisticated and costly equipment.


Cell proliferation and drug resistance in hepatocellular carcinoma are modulated by Rho GTPase signals.
Hepatocellular carcinoma is highly resistant to chemotherapeutic agents, thus the need to discover effective therapeutic molecules to suppress cancer cell growth and to overcome drug resistance is urgent. The Rho GTPase is implicated in cancer and metastasis and is directly activated by the Lymphoid blast crisis (Lbc) protooncogene, a Rho guanine-nucleotide exchange factor. The aim of the study was to analyze the expression of Lbc in hepatocarcinoma and to determine the effect of Lbc-induced Rho signaling on expression, growth rate and resistance to genotoxic stress. We found, by immunohistochemical analysis of biopsy samples and Northern and Western blot analyses of cell lines, that Lbc is absent in normal adult liver but is abundantly expressed in hepatocarcinoma, implying an increased Rho pathway signaling. Lbc stably transfected hepatocarcinoma cells exhibit increased proliferation and levels of ERK and cyclin D1 activation, which are blocked by a Rho inhibitor. In contrast, AKT activation was not altered. Moreover, Lbc expression confers increased resistance to genotoxic stress induced by doxorubicin, which is associated with upregulation of Bcl-2 and BAD phosphorylation, and this is reversed by a Rho inhibitor. In conclusion, these data support a role for Rho in liver cancer progression and resistance to therapy and may provide a basis for developing effective treatment for hepatocarcinoma.


Options for primary femoral fixation in total hip arthroplasty. Cemented stems for all.
In considering the subject of choices for the planning of femoral fixation in total hip arthroplasty, the strength behind the argument that cementing should be preferred in all ages and all conditions comes from three major positions, all supported by excellent data. First, the long term data (15-20 years) for well performed cemented stems are excellent and unmatched. Second, with good cementing techniques, the long term results in patients younger than 50 years of age are equal to the results in patients older than 50 years of age. No longer is there validity to the prior arguments that cementing does not work well in younger patients or that younger patients should have cementless femoral stems. Third, improvements in cementing technique have been shown in nationwide studies to produce statistically significantly better results than the original techniques.


A dynamic model of HIV integrase inhibition and drug resistance.
Human immunodeficiency virus type 1 (HIV-1) integrase is one of three virally encoded enzymes essential for replication and, therefore, a rational choice as a drug target for the treatment of HIV-1-infected individuals. In 2007, raltegravir became the first integrase inhibitor approved for use in the treatment of HIV-infected patients, more than a decade since the approval of the first protease inhibitor (saquinavir, Hoffman La-Roche, 1995) and two decades since the approval of the first reverse transcriptase inhibitor (retrovir, GlaxoSmithKline, 1987). The slow progress toward a clinically effective HIV-1 integrase inhibitor can at least in part be attributed to a poor structural understanding of this key viral protein. Here we describe the development of a restrained molecular dynamics protocol that produces a more accurate model of the active site of this drug target. This model provides an advance on previously described models as it ensures that the catalytic DDE motif makes correct, monodentate interactions with the two active-site magnesium ions. Dynamic restraints applied to this coordination state create models with the correct solvation sphere for the metal ion complex and highlight the coordination sites available for metal-binding ligands. Application of appropriate dynamic flexibility to the core domain allowed the inclusion of multiple conformational states in subsequent docking studies. These models have allowed us to (1) explore the effects of key drug resistance mutations on the dynamic flexibility and conformational preferences of HIV integrase and to (2) study raltegravir binding in the context of these dynamic models of both wild type and the G140S/Q148H drug-resistant enzyme.


Impact of preoperative risk and perioperative morbidity on ICU stay following coronary bypass surgery.
Prolonged intensive care unit treatment (> 3 days) contributes to increased health costs and resource utilization. In order to devise strategies to limit intensive care unit stay, and provide cost-effective medical care, it is necessary to identify the pre- and perioperative risk factors of prolonged treatment. Over 100 potential risk variables were collected prospectively in 889 consecutive patients undergoing isolated coronary bypass surgery between 1990 and 1992. The incidence of intensive care unit therapy lasting > 3 days was 6.8%. Univariate statistics identified 23 pre- and perioperative variables that were potential contributors to prolonged intensive care unit therapy. However, multivariate analysis of preoperative risk variables identified only recent myocardial infarction (within 30 days of surgery) and continued preoperative smoking (within 30 days of surgery) to be independent risk factors. Only 6.3% of patients without preoperative myocardial infarction and 6.1% of non-smokers required prolonged intensive care unit treatment, compared with 14.8% of patients with preoperative myocardial infarction (P = 0.01) and 10.1% of smokers (P = 0.07). When multivariate analysis was repeated with both pre- and perioperative variables, only ischemic morbidity (inotropes, myocardial infarction and low-output syndrome; 138 patients) and non-ischemic morbidity (infection, stroke or bleeding; 37 patients) predicted prolonged intensive care unit treatment. Intensive care unit treatment for > 3 days occurred in 26.8% of patients with ischemic morbidity compared with 3.2% of patients without ischemic morbidity (P = 0.001). Prolonged intensive care stay occurred in 32.4% of patients who suffered non-ischemic complications compared with 5.7% of patients who did not suffer these complications. The multiple logistic regression analysis odds ratio for ischemic morbidity was 7.4 (95% c.i. 4.0-13.4) compared with 4.8 (95% c.i. 1.9-10.1) for non-ischemic morbidity. Strategies designed to reduce the incidence of prolonged intensive care unit treatment should include prevention of stroke, infection and bleeding. However, the greatest reduction of intensive care unit utilization would be mediated by prevention of ventricular dysfunction secondary to myocardial ischemia or inadequate myocardial preservation.


Brucella spp. are facultative anaerobic bacteria under denitrifying conditions.
Respiration is a fundamental and complex process that bacteria use to produce energy. Despite aerobic respiration being the most common, some bacteria make use of a mode of respiration in the absence of oxygen, called anaerobic respiration, which can yield advantages in adaptation to various environmental conditions. Denitrification is part of this respiratory process ensuring higher respiratory flexibility under oxygen depletion. Here, we report for the first time the evidence of anaerobic growth of Brucella spp. under denitrifying conditions, which implies that this genus should be reconsidered as facultative anaerobic. Our study further describes that efficient denitrification is not equally found within the Brucella genus, with atypical species showing a greater ability to denitrify, correlated with higher expression of the genes involved, as compared to classical species.


Furfuryl methacrylate plasma polymers for biomedical applications.
Furfuryl methacrylate (FMA) is a promising precursor for producing polymers for biomedical and cell therapy applications. Herein, FMA plasma polymer coatings were prepared with different powers, deposition times, and flow rates. The plasma polymer coatings were characterized using atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The results from AFM and SEM show the early growth of the coatings and the existence of particle aggregates on the surfaces. XPS results indicated no measureable chemical differences between the deposited films produced under different power and flow rate conditions. ToF-SIMS analysis demonstrated differing amounts of C5H5O (81 m/z) and C10H9O2 (161 m/z) species in the coatings which are related to the furan ring structure. Through judicious choice of plasma polymerization parameters, the quantity of the particle aggregates was reduced, and the fabricated plasma polymer coatings were chemically uniform and smooth. Primary human fibroblasts were cultured on FMA plasma polymer surfaces to determine the effect of surface chemical composition and the presence of particle aggregates on cell culture. Particle aggregates were shown to inhibit fibroblast attachment and proliferation.


Prostate specific antigen. A review.
Despite its identification in the 1970s, prostate specific antigen (PSA) has only recently gained widespread utility. In this review, we will describe significant aspects of the biochemistry of PSA, immunohistochemical applications, the effect of prostatic manipulation on the serum level of this analyte, and other considerations in the determination of the level of PSA. In addition, the effect of benign prostatic hyperplasia (BPH) on serum PSA will be described. Finally, the application of PSA in the detection, staging and monitoring of patients with prostatic carcinoma will be discussed.


Outcomes of Percutaneous Coronary Intervention in Cardiac Transplant Patients: A Binational Analysis Derived From the United Kingdom and United States.
To compare and contrast the indications, clinical and procedural characteristics, and periprocedural outcomes of patients with cardiac transplant undergoing percutaneous coronary intervention (PCI) in the United States and United Kingdom. The British Cardiovascular Intervention Society Registry (BCIS) (2007-2014) and the United States National Inpatient Sample (NIS) (2004-2014) data were utilized for this analysis. There were 466 PCIs (0.09%) and 1122 PCIs (0.02%) performed in cardiac transplant patients in the BCIS and NIS registries, respectively. The cardiac transplant PCI cohort was younger and mostly men, with an increased prevalence of chronic kidney disease, left main PCI, and multivessel disease, and with lower use of newer antiplatelets agents, antithrombotics, and radial artery access vs the non-cardiac transplant PCI cohort. In the BCIS registry, the cardiac transplant PCI cohort had similar in-hospital mortality (odds ratio [OR], 1.05; P=.91), 30-day mortality (OR, 1.38; P=.31), vascular complications (OR, 0.69; P=.46), and major adverse cardiovascular event (OR, 1.41; P=.26) vs the non-cardiac transplant PCI cohort. However, the cardiac transplant group had higher 1-year mortality (OR, 2.30; P<.001). The NIS data analysis revealed similar rates of in-hospital mortality (OR, 2.40; P=.14), cardiac complications (OR, 0.26; P=.17), major bleeding (OR, 0.36; P=.16), vascular complications (OR, 0.46; P=.45), and stroke (OR, 0.50; P=.40) in the cardiac transplant PCI cohort vs the non-cardiac transplant PCI cohort. PCI in cardiac transplant recipients was associated with similar short-term mortality and vascular complications compared with PCI in the general populace. However, a higher 1-year morality was observed in the BCIS cohort.


Visceral adiposity and renal function: an observational study from SPECT-China.
Lipid accumulation product (LAP) is a novel and effective index of visceral adiposity distribution based on waist circumference and triglycerides concentration. Few studies investigated the relationship between LAP and eGFR. We aimed to explore whether LAP was associated with declined renal function (eGFR < 60 mL/min/1.73m2), and also whether it exhibited obvious superiority in predicting kidney impairment compared with other obesity indices. In this cross-sectional study, 10,012 subjects were recruited from 22 sites in East China. LAP was calculated with the following formula: (WC-65) x TG for males, (WC-58) x TG for females. 4.7% participants with declined renal function had a higher LAP quartile. LAP was strongly associated with eGFR level (Beta: -0.073, P < 0.001) and declined renal function (P < 0.001) even after adjustment for age, sex, smoking, drinking, diabetes and hypertension. The risk of renal dysfunction increased 2.32-fold for the highest quartile LAP relative to the lowest quartile (OR: 2.32, 95%CI:1.52-3.53, P < 0.001). LAP exerted the largest area under the curve among different obesity indices (AUC ROC:0.644, 95%CI: 0.618-0.670, P < 0.001). Our findings showed that LAP strongly associated with declined renal function and could be one of markers for predicting the risk of renal dysfunction in the general Chinese population. ChiCTR-ECS-14005052 (WHO international clinical trials register platform in China). Registered 20 July 2014.


Intussusception in adults.
Intussusception in adults is a rare entity that it is generally caused by definable intraluminal pathology. We report four cases of adult intussusception caused by lymphoma of the terminal ileum (2), an inflamed appendix (1) and a mucosal polyp (1). All presented with a variety of nonspecific and chronic symptoms, including abdominal pain, nausea and vomiting, consistent with partial small bowel obstruction. Only one patient had palpable masses in the abdomen. The most useful diagnostic radiological method was computed tomography (CT), which showed "target" lesions. The presence of the characteristic "target" lesion may obviate the need for further studies, including a barium enema. As in the cases reported here, treatment involves more than simple reduction; surgical resection is usually indicated.


Therapeutic Potential of Metabolites from Lactobacillus rhamnosus and Mare's Milk in the Treatment of Dysbiosis.
Ulcerative colitis is an inflammatory bowel disease that forms ulcerations in the mucous membrane of the colon and rectum, in which gut microbiota plays a pivotal role in its pathogenesis. Agents modulating microbial dysbiosis caused by colitis can help in the remission of this disease. The current study describes the potential therapeutic effects of active metabolites from Lactobacillus rhamnosus and mare's milk which have potential therapeutic values on the intestinal microbiota and proinflammatory cytokines. The analysis of the V1-V3 16S rDNA site revealed significant changes in the intestinal microbiome composition before and after treatment in the treated group compared to the positive control group that was treated with 5-aminosalicylic acid (5-ASA). So the effect of the study product on dextran sulfate sodium-induced dysbiosis was shown to be more potent than the positive control, 5-ASA. The level of proinflammatory cytokines also decreased under the influence of a biological product.


Solvent Induced Transformations of n-π* Absorption in Formaldehyde, Acetaldehyde, and Acetone.
Absorption spectra of formaldehyde (FA), acetaldehyde (AA), and acetone are compared in the vapor phase, nonpolar, and polar solutions at 295 K. The vibronic n-π* transition of carbonyl chromophore is mainly composed of the overtones of >C═O stretching vibration. A new phenomenon is observed in liquid solutions, consisting of a relative increase of Franck-Condon factors for the second and third harmonics in FA, and the second to fourth replica in AA, with respect to the gas phase. In AA and acetone with poorly resolved vibronic structure, the redistribution of intensities produces a false "solvent shift" of the band maximum between the vapor and nonpolar liquid phase by -250 ± 50 cm(-1). Modification in vibronic coupling can also explain unusual narrowing of the band contour in the solution, reported earlier for acetone (Renge , I. J. Phys. Chem. A 2009, 113, 10678). No detectable shift occurs as a function of solvent polarizability (refractive index function (n(2) - 1)/(n(2) + 2)) in n-alkanes for FA, AA, and acetone, as well as for cyclopentanone and camphor. Incidentally, the bathochromic dispersive shift is almost exactly compensated by a hypsochromic induction shift. The latter is due to the diminishing dipole moment in the excited state of the carbonyl chromophore. Differences in polarizability α and dipole moments μ were estimated for FA (Δα = 0.33 ± 0.1 Å(3)), AA (Δμ = -1.05 ± 0.2 D, Δα = 0.5 ± 0.2 Å(3)), and acetone (Δμ = -1.3 ± 0.2 D, Δα = 0.65 ± 0.2 Å(3)). The increase of α by ∼10% upon excitation is plausible for a weak n-π* transition. By contrast, near doubling of α in the upper state has been reported recently for several ketones, with Δα reaching 10 Å(3) (Catalán, J.; Catalán, J. P. Phys. Chem. Chem. Phys. 2011, 13, 4072). Empirical partitioning of solvent shifts into repulsive-dispersive, induction, dipole-dipole, and hydrogen bonding contributions was proposed to serve as a benchmark in computer chemical calculations.


Effect of rosiglitazone, an insulin sensitizer, on myelotoxicity caused by repeated doses of 5-fluorouracil.
Haematopoietic colony-stimulating factors are used frequently to moderate myelotoxicity, but administration of granulocyte-colony-stimulating factor (G-CSF) prior to chemotherapy actually may worsen the toxic effects on bone marrow. This is important in the design of clinical cancer treatment protocols. Previously, we found that rosiglitazone may protect granulocyte-macrophage progenitor cells (CFU-GM) against damage caused by a single dose of 5-fluorouracil (5-FU). Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects on bone marrow preservation when administered concurrently with repeated, daily doses of 5-FU while restricting regeneration time. Myelotoxicity characterized by the decrease in cellularity, frequency of granulocyte-macrophage progenitor cells and CFU-GM content of femoral bone marrow in mice. Five-day oral rosiglitazone pre-treatment decreased the susceptibility of granulocyte-macrophage progenitors to 5-FU damage. Significantly, more CFU-GM cells survived after the single intraperitoneal dose of 5-FU (100 mg kg(-1)). The increased frequency of CFU-GM cells with their intensive proliferation allowed faster restoration of the damaged CFU-GM compartment than was seen in the case of repeated daily administration of the cytostatic drug (25 or 50 mg kg(-1)) together with rosiglitazone for 7 consecutive days. The expansion of the CFU-GM compartment was 3 times and 50 times greater in the combined-treated mice than in their counterparts treated with repeated doses of 5-FU alone, although differences in absolute neutrophil counts were not significant. In conclusion, our results indicated that rosiglitazone has protective effects on bone marrow progenitor cells even after daily 5-FU treatment but further studies are warranted to evaluate the optimal treatment schedules.


Nutritional programming affects hypothalamic organization and early response to leptin.
Nutritional programming, taking place in utero or early after birth, is closely linked with metabolic and appetite disorders in adulthood. Following the hypothesis that nutritional programming impacts hypothalamic neuronal organization, we report on discrepancies of multiple molecular and cellular early events that take place in the hypothalamus of rats submitted to intrauterine growth restriction (IUGR). Expression screening performed on hypothalami from IUGR rats at birth and at postnatal d 12 identified changes in gene expression of neurodevelopmental process (cell differentiation and cytoskeleton organization). Additionally, a slight reduction of agouti-related protein and a strong reduction of alpha-MSH-immunoreactive efferent fibers were demonstrated in the paraventricular nucleus of IUGR rats. Rapid catch-up growth of IUGR rats, 5 d after birth, had a positive effect on neurodevelopmental factors and on neuronal projections emanating from the arcuate nucleus. The molecular and cellular anomalies detected in IUGR rats can be related to the reduced and delayed plasma leptin surge from d 0-16 when compared with control and IUGR rats with catch-up growth. However, the ability of leptin to activate intracellular signaling in arcuate nucleus neurons was not reduced in IUGR rats. Other mechanism such as epigenetic regulation of the major appetite-regulating neuropeptides genes was analyzed in parallel with their mRNA expression during postnatal development. This study reveals the importance of an early catch-up growth that reduces abnormal organization of hypothalamic pathways involved in energy homeostasis, whereas protein restriction, maintained during postnatal development leads to an important immaturity of the hypothalamus.


A quantitative analysis of the impact of cryopreservation on the implantation potential of human early cleavage stage embryos.
The impact of cryopreservation on the implantation potential of early cleavage stage (day 2) embryos was assessed by analysing the outcome from > 5000 thawed embryos in relation to the outcome from a similar number of fresh embryos. Analysis of procedures in which all transferred embryos fulfilled equivalent defined criteria revealed no significant difference in the implantation rates (fetal hearts/100 embryos transferred) of fresh 4-cell embryos (16.6%) and fully intact thawed 4-cell embryos (16.9%). Although 2-cell embryos implanted at significantly lower rates, there was again no significant difference between fresh (6.5%) and fully intact thawed (7.2%) embryos. Similar analysis of all embryos (irrespective of cell number on day 2) demonstrated that the implantation potential of partially intact thawed embryos was related to the extent of blastomere loss with the implantation rate of embryos with 50% cell survival (5.4%) being approximately half the rate of fully intact embryos (11.3%). Combining the values obtained from 'pure' data for the implantation rates of embryos with defined levels of survival with their relative prevalence in the total population of thawed embryos gave a predicted number of implantations (441) which was similar to the observed outcome (463). This number was approximately 30% less than the number expected had the same embryos been transferred fresh (635). The results suggest that intact thawed embryos have the same implantation potential as equivalent fresh embryos and that the impact of cryopreservation is limited to blastomere loss which is directly related to loss of implantation potential. The observed frequency of blastomere loss results in a reduction of approximately 30% in the implantation potential of a population of embryos following cryopreservation.


[Effect of Acupuncture at "Taichong"(LR 3) and "Neiguan"(PC 6) on Blood Pressure and Contents of Aspartic Acid and Glutamic Acid in the Rostral Ventrolateral Medulla in Spontaneous Hypertension Rats].
To explore the potential mechanism of acupuncture stimulation of "Taichong" (LR 3) and "Neiguan" (PC 6) in spontaneous hypertension rats (SHR) by investigating its effects on blood pressure and contents of aspartic acid(Asp) and glutamic acid (Glu) in the rostral ventrolateral medulla (RVLM) region. A total of 75 SHR were randomized into model group, Taichong (LR 3) group, Neiguan (PC 6) group, LR 3+non-acupoint group and LR 3 + PC 6 group (n=15 rats in each group), and 15 Wistar rats of the same age were used as the normal control group. The filiform needles were inserted into the abovementioned acupoints and non-acupoint, twirled for a while and then retained for 30 min. The treatment was conducted once per day, 15 times in total. The rats' tail blood pressure was examined on day 1, 3, 7 and 15 after acupuncture treatment by using a non-invasive blood pressure monitor. At the end of experiment, the contents of Asp and Glu in the RVLM were detected by high-performance liquid chromatography with UV technique. On day 1, 3, 7 and 15 after the acupuncture treatment, the raised systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) of PC 6, LR 3, LR 3 + non-acupoint and LR 3 + PC 6 groups were all decreased significantly compared with the model group (P<0.05). On day 15, the effect of the LR 3 + PC 6 group was significantly superior to that of the LR 3, PC 6, and LR 3 + non-acupoint groups in reducing the levels of SBP, DBP, and MBP (P<0.05).Compared with the normal control group, the contents of Asp and Glu in RVLM were significantly higher in the model group (P<0.05). After acupuncture intervention, both Asp and Glu levels in the PC 6, LR 3, LR 3 + non-acupoint, and LR 3 + PC 6 groups were markedly lower in comparison with the model group (P<0.05), and those of the LR 3 + PC 6 group were notably lower than those in the LR 3 and PC 6 groups (P<0.05). Acupuncture stimulation of PC 6, LR 3, LR 3 + non-acupoint and LR 3 + PC 6 (in particular) is effective in lowering blood pressure in spontaneous hypertension rats, which may be associated with its effects in lowering Asp and Glu contents in RVLM.


Characterization of circulating molecules and activities in plasma of patients after allogeneic and autologous intraoral bone grafting procedures: a prospective randomized controlled clinical trial in humans.
The objective was to assess whether intraoral bone augmentation procedures have an impact on the patient's plasma levels of circulating nucleic acids, exosomes, miRNA levels and caspase activities. The null hypothesis was tested, that no significant differences between the two groups will be found. In this prospective randomized controlled clinical trial 35 systemically healthy non-smoking participants were randomly allocated using sealed envelopes by a blinded clinician not involved in the clinical setting. Plasma samples were collected preoperatively and 3 times postoperatively (immediately, 5 weeks and 4 months postoperatively). The test group consisted of twenty-five patients who received allogeneic bone grafting material and the control group of ten patients who received autologous bone grafts. Levels of cell-free DNA (cfDNA) and microRNAs (miR-21, miR-27a, miR-218) were quantified by real-time PCR, caspase activities and exosome concentrations were determined by ELISA. Statistical evaluation reveled a significantly higher exosome level before surgery (p = 0.013) and the first postsurgical sample (p = 0.017) in the control group compared to the test group. The levels of miR-27a and miR-218 significantly differed between the plasma samples before surgery and after surgery in both groups. The levels of miR-21 only significantly differed between the pre- and postsurgical plasma samples in the test group, but not in the control group. All patients completed the study, no adverse events were recorded. Our data show the diagnostic potential of the plasma levels of miR-27a, miR-218 and miR-21 in detecting changes in bone metabolism after alveolar bone augmentation. Our very promising results indicate that there might be a high diagnostic potential in evaluating the plasma levels of the before mentioned miRNAs in order to detect bone resorption activities before they become clinically relevant. Trial registration Ethical commission of the Ärztekammer Hamburg, Germany (PV5211) on 11/03/2016 as well as by the German Registry of Clinical Studies (DRKS 00,013,010) on 30/07/2018 ( http://apps.who.int/trialsearch/ ).


[The role of ductal galactography in the differential diagnosis of breast carcinoma].
The authors report on a series of 1009 consecutive patients submitted to clinical examination, mammography, cytology and galactography for the presence of nipple discharge. Galactography was performed mainly in the presence of hematic nipple discharge. Surgical biopsy was performed in 392 cases, and 52 cancers (31 invasive and 21 intraductal lesions) were diagnosed, which were suspected at palpation, mammography, cytology and galactography in 17, 17, 18 and 31 cases, respectively. Forty of 52 cancers were suspected on the basis of combined exam findings, while 8 cancers (7 intraductal and 1 invasive lesions) were submitted to biopsy on the basis of a galactographic diagnosis of multiple benign papilloma, an (invasive) lesion with a diagnosis of single papilloma, and 3 (invasive) lesions because of persistent hematic discharge. Cancer was suspected with only one exam in 14 cases: 3 at cytology, 2 at mammography, 1 at clinical examination and 8 at galactography. Hematic discharge alone is not a sufficient reason to indicate surgery, because its positive predictive value for cancer is low (< or = 10%), while cytology is of limited help because of its poor sensitivity (34.6%). In contrast, galactography (59.6% sensitivity) gives a greater contribution to differential diagnosis and is always indicated in the presence of hematic discharge. Galactographic evidence suspicious for cancer (67.3% positive predictive value) or for multiple papilloma (9.7% positive predictive value) is sufficient to advise open biopsy. The surgical removal of single papillomas is of questionable benefit, since single papillomas are benign lesions, with no clear evidence of progression to cancer. In our series, only one cancer was misdiagnosed as a single papilloma at galactography (0.5% positive predictive value).


Life-threatening metabolic coma caused by levofloxacin.
Patients with diabetes mellitus are often susceptible to hypoglycemic episodes while on therapy. Most of these are attributed to inappropriate dosing of hypoglycemic agents, dietary indiscretion, or acute illness. Medications being used concomitantly should be reviewed closely when the etiology of hypoglycemia is unclear. A fifty-six-year-old woman with a history of diabetes mellitus (on metformin monotherapy) was found unresponsive at home. Her fingerstick glucose was 15 mg/dL for which she received 50% dextrose intravenously. The patient never had any previous documented hypoglycemic episodes. She had recently been diagnosed with pneumonia and was prescribed oral levofloxacin therapy. The patient had taken 4 doses of levofloxacin before the onset of hypoglycemia. These episodes recurred over the next 2 days needing close intensive care unit monitoring, dextrose infusion, and glucagon administration. Basic blood/urine investigations, cortisol and thyroid profile were normal except for low blood glucose and renal insufficiency (serum creatinine 1.4 mg/dL and creatinine clearance 42 mL/min). HbA1c was 6.8% (4.4%-6.4%), insulin 51.3 μU/mL (2.6-24.9 μU/mL), IGF-1 301 ng/mL (27-223 ng/mL), and C peptide 9.3 ng/mL (0.8-3.5 ng/mL). These levels were elevated but were deemed nondiagnostic because of fluctuating glucose values after glucagon administration. A blood screen for sulfonylureas and metaglinides was negative. A seventy-two-hour fast was performed to rule out hyperinsulinemic hypoglycemic syndromes; however, blood glucose values remained consistently above 120 mg/dL during this period. Thus, after exclusion of other causes, we utilized the adverse drug reaction probability scale and concluded that hypoglycemia was probably related to recent use of levofloxacin.


Papules and pustules of the elbows and knees: an uncommon clinical sign of dermatomyositis in oriental children.
We report two children with dermatomyositis in whom the initial manifestation was a papular eruption on the extensor surfaces of the elbows and knees. In each there was a follicular component to the eruption and one child had pustular lesions. The extensor eruption predated the onset of muscle weakness by 1 year in the first child and by 2 years in the second. Both children had Vietnamese parents. There is some evidence in the literature that Oriental patients may be predisposed to this type of eruption.


Ontogeny of benzo(a)pyrene hydroxylase, epoxide hydrolase and glutathione-S transferase in the brain, lung and liver of C57Bl/6 mice.
Typical developmental patterns of three drug-metabolizing enzymes in C57Bl/6 mouse brain, lung and liver could be divided into three stages: stage I, at the end of intrauterine life, where an increase in enzymatic activity was observed; stage II, during the first days after birth, where a decrease was seen; and stage III from the 6th day until weaning, where there was a gradual increase, reaching the same values as in the adult animal. However, pulmonary benzo(a)pyrene hydroxylase activity showed an abrupt burst starting on day 6 of postnatal life, then decreased slowly to become steady, and finally increased again. Our data show that the major metabolic pathways catalyzed by glutathione-S transferase and epoxide hydrolase are operative in mouse fetal brain and lung, just as in liver. In addition, we show that enzymatic systems are inducible during fetal life by exogenous compounds such as 5,6-benzoflavone. The early developmental evolution of the drug-metabolizing enzymes should help understand feto-toxicological and teratological phenomena.


Economic analyses of rapid population growth.
"Discussion of the macroeconomic consequences of rapid population growth is organized into three schools: pessimists, optimists, and the recent revisionists. For the revisionists, differing views are presented about the pervasiveness and relevance of market failures, such as the negative externalities of childbearing, and about the ability of families and institutions to adjust rapidly to changes brought on by rapid population growth. A welfare economics approach is used to review the merits of various public policies to reduce fertility, including public financing of family planning services and taxes and incentives associated with childbearing." The focus is on developing countries.


Impact of acne vulgaris on quality of life and self-esteem.
The psychological impact of acne is determined by various factors including age, sex, personality, grade of disease, scarring, and environmental and ethnic background. Apart from managing the clinical manifestations of acne, clinicians also have to deal with the psychological aspects of the disease by assessing patients' quality of life (QOL) and self-esteem. These measures will aid in better management of acne patients. This study examined the relationship between acne and QOL and self-esteem. The results showed that acne severity may have a considerable adverse impact on QOL and self-esteem. Dermatologists need to emphasize the psychosocial sequelae of acne through awareness programs and encourage medical treatment along with basic psychosomatic remedies in the management of acne.


Intrinsic Adaptation of SHR Right Atrium Reduces Heart Rate.
Hypertension represents an autonomic dysfunction, characterized by increased sympathetic and decreased parasympathetic cardiovascular tone leading to resting tachycardia. Therefore, studies assessing hypertension-associated changes in isolated cardiac tissues were conducted under electric field stimulation to stimulate the neurons. Herein, we characterize the influence of the autonomic neurotransmitter on the baseline atrial chronotropism of unpaced isolated right atria of normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). Our results revealed a resting bradycardia in tissues from SHR in comparison to NWR. The release of autonomic neurotransmitters, acetylcholine or norepinephrine, still occurs in the electrically unstimulated right atrium, after excision of the sympathetic nerve, which could explain differences in basal heart rate between NWR and SHR. Nicotine and the acetylcholinesterase inhibitor physostigmine reduced the chronotropism of right atria from either NWR or SHR. Conversely, the muscarinic receptor antagonist atropine did not affect the basal chronotropism of tissues from both strains. Furthermore, tyramine increased the chronotropism of NWR and SHR atria indicating availability of the neuronal stocks of noradrenaline. Although the monoamine uptake inhibitor cocaine increased right atrium chronotropism in both strains, the basal heart rate was not affected by the β-adrenoceptor antagonist propranolol. In summary, after acute section of the sympathetic nerve, autonomic neurotransmitters are still released either in resting conditions or upon pharmacological stimulation of right atria from both strains. Nevertheless, autonomic neurotransmission does not affect resting chronotropism, nor is the responsible for reduced basal heart rate of the isolated right atrium of hypertensive rats.


Certifying examination performance and patient outcomes following acute myocardial infarction.
To establish whether successful certifying examination performances of doctors are associated with their patients' mortality and length of stay following acute myocardial infarction. Risk adjusted mortality and survivors' length of stay were compared for doctors who had satisfactorily completed training in internal medicine or cardiology and attempted the relevant examination. Specifically, the study investigated the joint effects of hospital location, availability of advanced cardiac care, doctors' specializations, certifying examination performances, year certification was first attempted and patient volume. Data on all acute myocardial infarctions in Pennsylvania for the calendar year 1993 were collected by the Pennsylvania Health Care Cost Containment Council. These data were combined with physician information from the database of the American Board of Internal Medicine. Holding all variables constant, successful examination performance (i.e. certification in internal medicine or cardiology) was associated with a 19% reduction in mortality. Decreased mortality was also correlated with treatment in hospitals located outwith either rural or urban settings and with management by a cardiologist. Shorter stays were not related to examination performance but were associated with treatment by high volume cardiologists who had recently finished training and who cared for their patients in hospitals located outwith rural or urban settings. The results of the study add to the evidence supporting the validity of the certifying examination and lend support to the concept that fund of knowledge is related to quality of practice.


Development and evaluation of a prediction model for underestimated invasive breast cancer in women with ductal carcinoma in situ at stereotactic large core needle biopsy.
We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery. From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic large core needle biopsy, drawn from the prospective COBRA (Core Biopsy after RAdiological localization) and COBRA2000 cohort studies, were used to fit the multivariable model and assess its overall performance, discrimination, and calibration. 348 women with large core needle biopsy-proven ductal carcinoma in situ were available for analysis. In 100 (28.7%) patients invasive carcinoma was found at subsequent surgery. Nine predictors were included in the model. In the multivariable analysis, the predictors with the strongest association were lesion size (OR 1.12 per cm, 95% CI 0.98-1.28), number of cores retrieved at biopsy (OR per core 0.87, 95% CI 0.75-1.01), presence of lobular cancerization (OR 5.29, 95% CI 1.25-26.77), and microinvasion (OR 3.75, 95% CI 1.42-9.87). The overall performance of the multivariable model was poor with an explained variation of 9% (Nagelkerke's R(2)), mediocre discrimination with area under the receiver operating characteristic curve of 0.66 (95% confidence interval 0.58-0.73), and fairly good calibration. The evaluation of our multivariable prediction model in a large, clinically representative study population proves that routine clinical and pathological variables are not suitable to select patients with large core needle biopsy-proven ductal carcinoma in situ for sentinel node biopsy during primary surgery.


A psychometric evaluation of the Chinese version of the Cardiovascular Limitations and Symptoms Profile in patients with coronary heart disease.
The aim of this study was to translate from English and evaluate the validity, reliability and cultural relevance of the Cardiovascular Limitations and Symptoms Profile (CLASP) as a health-related quality-of-life (HRQL) measure in Chinese patients with coronary heart disease. Improvement in HRQL is increasingly used as a primary outcome in determining the treatment benefit using a generic instrument. However, disease-specific instruments are being cited as more responsive and sensitive in detecting even the smallest changes in health status. Therefore, valid and reliable disease-specific measures for patients with coronary heart disease are now being developed and evaluated. Questionnaire design. The translation equivalence and content validity of the Chinese version of CLASP were evaluated by an expert panel. Measurement performance was tested on a convenience sample of 369 Chinese coronary heart disease patients. The instrument demonstrated good content validity (content validity index 0.94), acceptable internal consistency (>0.70), except for two subscales of angina and tiredness and significant positive correlations among the subscales of CLASP, Hospital Anxiety Depression Scale and the Short Form 36 Health Survey. Principal components analysis revealed nine factors that together explained 69% of the variance. The results of this study support that CLASP is a valid and reliable disease-specific health status measure for Chinese patients with coronary heart disease. However, further item modifications and testings are needed when considering the cross-cultural context. The use of disease-specific HRQL measures could effectively evaluate nursing interventions in clinical practice. Further validations of CLASP among different diagnostic groups, such as patients with heart failure and those who have survived an acute myocardial infarction, would provide further empirical support for its use with all patients with heart disorders.


Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice.
Aging is one of the risk factors of non-alcoholic fatty liver disease (NAFLD). Yet, the mechanism underlying the aging-associated NAFLD-like syndrome is not fully understood. Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, has protective effects against aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of aging-induced NAFLD. NR supplemented food (2.5 g/kg food) was applied to aged mice for three months while normal chow to the other groups. Body weight, food intake, liver weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammatory infiltration. NR repletion significantly reduced fat pat mass in aged mice, while not altered the body weight, food intake, and liver weight. NR repletion significantly rescued the NAD reduction in aged mice. The total cholesterol and triglyceride levels could be lowered by NR repletion in aged mice. The AST level was also significantly reduced by NR repletion in aged group, while the ALT level lowered but without significance. Notably, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis could be markedly corrected by NR repletion. In addition, Kupffer cells accumulated and inflammatory infiltration could also be remarkably reversed by NR repletion in aged mice. Aging was associated with NAFLD-like phenotypes in mice, which could be reversed by oral NR repletion. Therefore, oral NR uptake might be a promising strategy to halt the progression of NAFLD.


A Novel Inflammatory-Nutritional Prognostic Scoring System for Patients with Early-Stage Breast Cancer.
We attempted to explore the prognostic value of baseline inflammatory and nutritional biomarkers at diagnosis in patients with early-stage breast cancer and develop a novel scoring system, the inflammatory-nutritional prognostic score (INPS). We collected clinicopathological and baseline laboratory data of 1259 patients with early-stage breast cancer between December 2010 and November 2012 from Sun Yat-sen University Cancer Center. Eligible patients were randomly divided into training and validation cohorts (n = 883 and 376, respectively) in a 7:3 ratio. We selected the most valuable biomarkers to develop INPS by the least absolute shrinkage and selection operator (LASSO) Cox regression model. A prognostic nomogram incorporating INPS and other independent clinicopathological factors was developed based on the stepwise multivariate Cox regression method. Then, we used the concordance index (C-index), calibration plot, and time-dependent receiver operating characteristic (ROC) analysis to evaluate the prognostic performance and predictive accuracy of the predictive nomogram. Four inflammatory-nutritional biomarkers, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), prognostic nutritional index (PNI), and albumin-alkaline phosphatase ratio (AAPR), were selected using the LASSO Cox analysis to construct INPS, which remained an independent prognostic indicator per the multivariate Cox regression analysis. Patients were stratified into low- and high-INPS groups based on the cutoff INPS determined by the maximally selected rank statistics. The prognostic model for overall survival consisting of INPS and other independent clinicopathological indicators showed excellent discrimination with C-indexes of 0.825 (95% confidence interval [CI]: 0.786-0.864) and 0.740 (95% CI: 0.657-0.822) in the training and validation cohorts, respectively. The time-dependent ROC curves showed a higher predictive accuracy of our prognostic nomogram than that of traditional tumor-node-metastasis staging. Baseline INPS is an independent indicator of OS in patients with early-stage breast cancer. The INPS-based prognostic nomogram could be used as a practical tool for individualized prognostic predictions.


Daptomycin.
Daptomycin is a cyclic lipopeptide antibiotic used for the treatment of Gram-positive infections including complicated skin and skin structure infections, right-sided infective endocarditis, bacteraemia, meningitis, sepsis and urinary tract infections. Daptomycin has distinct mechanisms of action, disrupting multiple aspects of cell membrane function and inhibiting protein, DNA and RNA synthesis. Although daptomycin resistance in Gram-positive bacteria is uncommon, there are increasing reports of daptomycin resistance in Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis. Such resistance is seen largely in the context of prolonged treatment courses and infections with high bacterial burdens, but may occur in the absence of prior daptomycin exposure. Furthermore, use of inadequate treatment regimens, irregular drug supply and poor drug quality have also been recognized as other important risk factors for emergence of daptomycin-resistant strains. Antimicrobial susceptibility testing of Gram-positive bacteria, communication between clinicians and laboratories, establishment of internet-based reporting systems, development of better and more rapid diagnostic methods and continuous monitoring of drug resistance are urgent priorities.


Formaldehyde-induced DNA cross-link of indolizino[1,2-b]quinolines derived from the A-D rings of camptothecin.
Camptothecin consists of a lactone E ring adjacent to tetracyclic A-D rings of a planar chromophore, which are essential for topoisomerase I inhibition and DNA interaction. The A-D rings can be exploited to develop DNA-sequence-reading molecules. Indolizino[1,2-b]quinoline derivatives substituted with a piperidinoethyloxy side chain and an aminomethyl function on rings A and D, respectively, were synthesized, and their DNA binding and formaldehyde-mediated bonding properties were investigated.


Cubital tunnel syndrome. Treatment by decompression without transposition of ulnar nerve.
Cubital tunnel syndrome is the second most common entrapment neuropathy in the upper limb; however, surgical treatment of the ulnar nerve entrapment at the elbow remains controversial. None of the presently advocated procedures (simple decompression of the ulnar nerve, medial epicondylectomy, subcutaneous, submuscular or intramuscular anterior transposition of the ulnar nerve) has proven optimal regarding long-term results. This paper presents the experience of treating cubital tunnel syndrome with simple decompression in 40 patients. Three months after surgery 23/36 patients did not feel any pain in their operated hands. In 11/36 cases we observed an improvement of preoperative pain. Sensory disturbances disappeared completely in 24/40 cases. 11/40 patients reported an improvement of preoperative dysesthesia or hypesthesia. In 12/22 patients we observed complete recovery of preoperative pareses of adductor muscle of thumb or hypothenar muscles weakness. 7/22 cases demonstrated an improvement of these pareses. In total 28 patients (70 %) had an excellent outcome without residual symptoms. For 5 patients treatment results were classified as good with slight residual pain and sensory disturbance (12.5 %). In 4 cases (10 %) we only observed a fair outcome with persistent severe sensory and motor deficits but slow improvement over the last three months. Three patients did not demonstrate any improvement (7.5 %). The mean duration of postoperative disablement in our working patients (18/40) was 28 days. In summary, simple decompression of the ulnar nerve seems to be an adequate and successful minimally invasive technique for the treatment of cubital tunnel syndrome.


Role of miRNAs in Epicardial Adipose Tissue in CAD Patients with T2DM.
Background. Epicardial adipose tissue (EAT) is identified as an atypical fat depot surrounding the heart with a putative role in the involvement of metabolic disorders, including obesity, type-2 diabetes mellitus, and atherosclerosis. We profiled miRNAs in EAT of metabolic patients with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) versus metabolically healthy patients by microarray. Compared to metabolically healthy patients, we identified forty-two miRNAs that are differentially expressed in patients with CAD and T2DM from Xinjiang, China. Eleven miRNAs were selected as potential novel miRNAs according to P value and fold change. Then the potential novel miRNAs targeted genes were predicted via TargetScan, PicTar, and miRTarbase, and the function of the target genes was predicted via Gene Ontology (GO) analysis while the enriched KEGG pathway analyses of the miRNAs targeted genes were performed by bioinformatics software DAVID. Then protein-protein interaction networks of the targeted gene were conducted by online software STRING. Finally, using microarray, bioinformatics approaches revealed the possible molecular mechanisms pathogenesis of CAD and T2DM. A total of 11 differentially expressed miRNAs were identified and among them, hsa-miR-4687-3p drew specific attention. Bioinformatics analysis revealed that insulin signaling pathway is the central way involved in the progression of metabolic disorders. Conclusions. The current findings support the fact that miRNAs are involved in the pathogenesis of metabolic disorders in EAT of CAD patients with T2DM, and validation of the results of these miRNAs by independent and prospective study is certainly warranted.


[Modulation of renin-angiotensin system for vascular protection in hypertensive patients and in patients with diabetic nephropathy].
Angiotensin II intervenes in the genesis of arterial hypertension and in the organic damage associated to arterial hypertension and to diabetes mellitus. Because of its proinflammatory effects, angiotensin II participates in the process of atherogenesis. Hemodynamic mechanisms and several citokines whose production is promoted by angiotensin II participate in left ventricular hypertrophy associated to arterial hypertension. Angiotensin II also contributes to renal damage secondary to diabetes mellitus by its actions in the intraglomerular hemodynamics and by its glomerular and interstitial fibrogenic effects. The intervention on the renin-angiotensin system should be part of therapy of patients with high cardiovascular risk with hypertensive disease and/or diabetes mellitus.


Transient expression of serotonin 5-HT4 receptors in the mouse developing thalamocortical projections.
The serotonin 5-HT(4) receptor (5-HT(4)-R) is an unusually complex G-protein coupled receptor that is likely to play important roles in brain development and that may underlie the comorbidity of central and peripheral abnormalities in some developmental disorders. We studied the expression of 5-HT(4)-Rs in the developing mouse forebrain at embryonic days 13, 15, 17, and at postnatal days 3 and 14 by using immunohistochemistry, tract tracing, and quantitative RT-PCR. The developing thalamocortical projections transiently expressed 5-HT(4)-Rs in the embryonic brain and the 5-HT(4)-R expression in the forebrain changed from axonal to somatic around birth. From embryonic days 13-17, the forebrain mRNA levels of the 5-HT(4(a))-R and 5-HT(4(b))-R splice variants increased nine- and fivefold, respectively, whereas the levels of the 5-HT(4(e))-R and 5-HT(4(f))-R variants remained relatively low throughout the studied period of embryonic development. These results suggest that during development 5-HT(4)-R expression undergoes a dynamic regulation and that this regulation may be important for the normal development of sensory and limbic processing.


The nurse shortage problem in Japan.
This article discusses the serious problem of the shortage of about 50,000 nurses in Japan today. If efficient measures to solve it are not adopted by administrators, it is clear that the shortage will become still more alarming in the future, in a society with more people in advanced years and in which the numbers in the younger generation will decrease from now on. The main factors behind the Japanese nursing labour shortage are, among others: a rapid increase in the number of hospital beds between 1986 and 1989, poor working conditions; and nurses' low social position in their places of work. Behind these factors, there has always been a contempt for the art of nursing in our society. Why has Japanese society made light of nursing? Three points can be identified: traditional discrimination against women; our disregard for a religious mentality; and our short history of hospital nursing. To overcome these problems, we must first of all change fundamentally our sense of values, such as love for one another and compassion. We must now reconstruct a caring culture in our society.


Myocardial Infarction with Non-Obstructive Coronary Artery Disease: The Labyrinth of Investigations. Case Report and Review of the Literature.
Myocardial infarction with non-obstructive coronary artery disease (MINOCA) accounts for approximately 5-15% of acute myocardial infarctions (MI). This infarction type raises a series of questions about the underlying mechanism of myocardial damage, the diagnostic pathway, optimal therapy, and the outcomes of these patients when compared to MI associated with obstructive coronary artery disease. We present the case of a 60-year-old patient with multiple cardiovascular risk factors and comorbidities who is admitted in an emergency setting. The patient is known with a conservatively treated inferior myocardial infarction which occurred 3 months prior, with reduced left ventricular ejection fraction. Emergency coronary angiography revealed normal epicardial coronary arteries, which led to further investigations of the underlying cause. Considering the absence of epicardial and microvascular spasm, CMR (cardiac magnetic resonance) confirmation of two transmural myocardial infarctions in the territories tributary to coronary arteries, and a high index of myocardial resistance in culprit arteries, we concluded the diagnosis of MINOCA due to the microvascular endothelial dysfunction. Although the concept of MINOCA was devised almost a decade ago, and these patients are an important part of MI presentations, it still represents a diagnostic challenge with multiple explorations required to establish the precise etiology.


Research progress on detachable microneedles for advanced applications.
Microneedles (MNs) have undergone great advances in transdermal drug delivery, and commercialized MN applications are currently available in vaccination and cosmetic products. Despite the development of MN technologies, common limitations of MN products still exist. Typical MN patches are applied to target tissues, where the substrate of an MN patch must remain until the drug is delivered, which reduces patients' compliance and hinders the applicability of the MN technique to many diseases in various tissues. MN research is ongoing to solve this issue. Most recent MNs developed by combining various biomaterials with appropriate fabrication processes are detachable MNs (DeMNs). Because of advances in biomaterials and fabrication techniques, various DeMNs have been rapidly developed. In this review, we discuss four types of DeMN: substrate-separable, multi-layered, crack-inducing, and shell DeMN. These DeMNs deliver various therapeutic agents ranging from small- and large-molecular-weight drugs to proteins and even stem cells for regeneration therapy. Furthermore, DeMNs are applied to skin as well as non-transdermal tissues. It has become increasingly evident that novel MN technologies can be expected in terms of designs, fabrication methods, materials, and even possible application sites given the recent advances in DeMNs.


Protein loss from axonal transport occurs without diminution of vesicle traffic.
Protein loss from the rapid anterograde axonal transport system of amphibian sensory nerve fibers was compared with the numbers and sizes of anterogradely transported vesicles in the axons. Protein was found to be lost at a rate of approximately 2% per millimeter of nerve traversed. However, no changes were observed in either the numbers or sizes of vesicles in the nerve at two locations separated by 60-75 mm. The results show that protein loss is not explained as a loss of vesicles from the transport system nor by a reduction in vesicle size.


MDR1 haplotypes derived from exons 21 and 26 do not affect the steady-state pharmacokinetics of tacrolimus in renal transplant patients.
This retrospective study investigated the influence of MDR1 haplotypes derived from the polymorphisms 2677G > T (exon 21) and 3435C > T (exon 26) on the pharmacokinetics of the immunosuppressant drug tacrolimus in 73 renal transplant patients. Based on both variants of SNPs 2677 and 3435, four different haplotypes and eight different genotypes were identified in the study sample. Tacrolimus trough concentrations (C(0)) were compared between different SNP variants and genotypes, as well as between carriers and noncarriers of each haplotype. Additionally, CYP3A5 genotype (6956G > A) was determined. No significant differences were observed between groups. Differences in mean tacrolimus C(0) values between carriers and noncarriers of each haplotype ranged from -0.04 microg/litre (95% confidence interval: -0.53 to 0.60) to -23 microg/litre (-1.07 to 1.53). No association was found between CYP3A5*1/*3 genotype and tacrolimus Co concentractions. MDR1 haplotypes derived from the SNPs 2677G > T (exon 21) and 3435C > T (exon 26) do not influence the pharmacokinetics of tacrolimus in renal transplant patients.


In vitro biocompatibility evaluation of novel urethane-siloxane co-polymers based on poly(ϵ-caprolactone)-block-poly(dimethylsiloxane)-block-poly(ϵ-caprolactone).
Novel polyurethane co-polymers (TPUs), based on poly(ϵ-caprolactone)-block-poly(dimethylsiloxane)-block-poly(ϵ-caprolactone) (PCL-PDMS-PCL) as soft segment and 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD) as hard segment, were synthesized and evaluated for biomedical applications. The content of hard segments (HS) in the polymer chains was varied from 9 to 63 wt%. The influence of the content and length of the HS on the thermal, surface, mechanical properties and biocompatibility was investigated. The structure, composition and HS length were examined using (1)H- and quantitative (13)C-NMR spectroscopy. DSC results implied that the synthesized TPUs were semicrystalline polymers in which both the hard MDI/BD and soft PCL-PDMS-PCL segments participated. It was found that an increase in the average HS length (from 1.2 to 14.4 MDI/BD units) was accompanied by an increase in the crystallinity of the hard segments, storage moduli, hydrophilicity and degree of microphase separation of the co-polymers. Depending on the HS content, a gradual variation in surface properties of co-polymers was revealed by FT-IR, AFM and static water contact angle measurements. The in vitro biocompatibility of co-polymers was evaluated using the endothelial EA.hy926 cell line and protein adsorption on the polyurethane films. All synthesized TPUs adsorbed more albumin than fibrinogen from multicomponent protein mixture, which may indicate biocompatibility. The polyurethane films with high HS content and/or high roughness coefficient exhibit good surface properties and biocompatible behavior, which was confirmed by non-toxic effects to cells and good cell adhesion. Therefore, the non-cytotoxic chemistry of the co-polymers makes them good candidates for further development as biomedical implants.


Comparative lipidomic profiling of xylose-metabolizing S. cerevisiae and its parental strain in different media reveals correlations between membrane lipids and fermentation capacity.
Phospholipids (PLs) serve as the foundation for structure and function in most cell membranes. In order to reveal the correlations between PLs composition and fermentation performance of cells, a comparative lipidomics study was carried out using a recombinant xylose fermenting yeast strain Saccharomyces cerevisiae 424A(LNH-ST) and its parental strain 4124. Profiling of yeast lipids was performed using ultra performance liquid chromatography (UPLC)-MS/MS, leading to identification of 123 PL species. PL compositions were determined for both strains grown in rich medium (yeast extract peptone), limited medium (yeast nitrogen base), and ammonia fiber expansion pretreated corn stover hydrolysate. Principal component analysis of lipidomic data revealed that the PL profile for both strains varied significantly depending upon cultivating media composition. Further analysis of different classes of PLs revealed that the phosphatidylinositol/phosphatidylserine (PI/PS) ratio was closely related to cell growth rates. Both strains possessed higher phosphatidylcholine (PC) levels at an expense of phosphatidylethanolamine (PE) levels when entering stationary phase and the PC/PE ratios showed consistency with glucose utilization rates. Interestingly, PI synthesis lagged behind when available nutrients were limited, and PI levels were closely correlated with xylose metabolism.


Which Tools in Multimedia Are Best for Learning Outcomes? A Study Grounded in Cognitive Load Structures.
The main objective of this study is to investigate the importance of three compositions in multimedia for learning outcomes (LOs) in relation to individual differences in short-term memory (STM) capacity. The study is based on a survey of 378 individuals at the bachelor level (military officers, teachers, and psychology students). The LOs of three different multimedia compositions (means) were tested. This applied to individuals with low, medium, and high STM capacity. The results show that the successive presentation (Type II) of learning materials through multiple representation forms/channels (speech, pictures, and screen text/labels) provides a better LO than just speech (Type I) and simultaneous presentation (Type III). Overall, visual and verbal channel capacities did not contribute to the LO in any of the three tools tested, but some specific STM capacity types or substructures (visual and verbal progressive capacities) and non-verbal (RAPM) types have significance, particularly in exploiting successive presentation (Type II) for learning. Although the tools used in the multimedia educational material had a low cognitive load, the individuals with low capacity learned relatively less than the individuals with higher capacity. A symbolic form of expression was introduced concerning the relationship between cognitive load structure (CLS) and LOs through various tools in multimedia as an aid in the theoretical and empirical analyses. This is referred to as the CLS-LO formula. The main assumption of this study, based on previous empirical and theoretical ones, is that the relationship between CLS and LO is expressed with the following CLS-LO formula: CLS Type III > CLS Type II > CLS Type I → LO Type III > LO Type I > LO Type II . Based on this study, the relationship became: CLS Type III > CLS Type I > CLS Type II → LO Type II > LO Type I = LO Type III . This basic research study is primarily a contribution to understanding underlying cognitive processes in STM and their importance for learning in multimodal forms compared with analogue text. The findings will also be relevant as a basis for performance analysis and decision-making under high information pressure, risk, and unpredictable conditions.


Real time sonographic diagnosis of adrenal haemorrhage.
The diagnosis of adrenal haemorrhage in 4 infants using a linear real-time ultrasound scanner is described. The resolution of real-time equipment appears to be sufficient for such a diagnosis and its flexibility is well suited for small babies.


Differential roles of MMP-9 in early and late stages of dystrophic muscles in a mouse model of Duchenne muscular dystrophy.
Matrix metalloprotease (MMP)-9 is an endopeptidase associated with the pathogenesis of Duchenne muscular dystrophy (DMD). The precise function of MMP-9 in DMD has not been elucidated to date. We investigated the effect of genetic ablation of MMP-9 in the mdx mouse model (mdx/Mmp9(-/-)). At the early disease stage, the muscles of mdx/Mmp9(-/-) mice showed reduced necrosis and neutrophil invasion, accompanied by down-regulation of chemokine MIP-2. In addition, muscle regeneration was enhanced, which coincided with increased macrophage infiltration and upregulation of MCP-1, and resulted in increased muscle strength. The mdx/Mmp9(-/-) mice also displayed accelerated upregulation of osteopontin expression in skeletal muscle at the acute onset phase of dystrophy. However, at a later disease stage, the mice exhibited muscle growth impairment through altered expression of myogenic factors, and increased fibroadipose tissue. These results showed that MMP-9 might have multiple functions during disease progression. Therapy targeting MMP-9 may improve muscle pathology and function at the early disease stage, but continuous inhibition of this protein may result in the accumulation of fibroadipose tissues and reduced muscle strength at the late disease stage.


Characterization of alpha-1,6-mannosyltransferase responsible for the synthesis of branched side chains in Candida albicans mannan.
A particulate insoluble fraction from Candida albicans NIH B-792 (serotype B) strain cells was obtained as the residue after extracting a 105000 x g pellet of cell homogenate with 1% Triton X-100. Incubation of this fraction with a mannopentaose, Man alpha 1-->3Man alpha 1-->2Man alpha 1-->Man alpha 1-->2Man, in the presence of GDP-mannose and Mn2+ at pH 6.0 gave a branched mannohexaose, [sequence: see text] 6 the structure of which was identified by means of sequential off assignment. However, the enzyme fraction obtained from Candida parapsilosis gave Man alpha 1-->2Man alpha 1-->3Man alpha 1-->2Man alpha 1-->2 Man alpha 1-->2Man under the same conditions. These results demonstrate the finding that the structural difference in the mannans of these two species is due to the presence of alpha-1.6-linked branching mannose units in the C. albicans mannan [Shibata, N., Ikuta, K., Imai, T., Satoh, Y., Satoh, R., Suzuki, A., Kojima, C., Kobayashi, H., Hisamichi, K. & Suzuki, S. (1995) J. Biol. Chem. 270, 1113-1122]. The substrate-specificity study of the enzyme indicated that the structural requirement of the alpha-1,6-mannosyltransferase is Man alpha 1-->3Man alpha 1-->. The alpha-1,6-mannosyltransferase also transferred the alpha-1,6-linked branching mannose unit to the mannan of Saccharomyces cerevisiae. The transformation of the mannan was detected by the appearance of antigenic factor 4 using an enzyme-linked immunosorbent assay and two-dimensional homonuclear Hartmann-Hahn spectroscopy.


[Evaluation of Tl-20 lung uptake and impairment of pulmonary perfusion on scintigraphies in pulmonary tuberculosis].
Tl-201 lung uptake in 74 patients (85 lesions) and pulmonary perfusion in 105 patients were studied to evaluate clinical usefulness of Tl-201 lung uptake and perfusion lung scintigraphy in pulmonary tuberculosis, using a scintillation camera with a mini-computer system. As indices of Tl-201 lung uptake, lung (lesion) to upper mediastinum uptake ratio (L/M) and visual grading were used. L/M in pulmonary tuberculosis was 1.96 +/- 0.66, which was significantly larger than 1.04 +/- 0.24 in healthy controls and lower than that in heart diseases with left heart failure and idiopathic interstitial pneumonia, and showed no significant differences with that in acute pneumonia, pyothorax, primary lung cancer and malignant mediastinal tumor. L/M in pulmonary tuberculosis did not correlate with CRP, erythrocyte sedimentation rate, Gaffky number of sputum and body temperature. It correlated with the type of pulmonary tuberculosis according to the Gakken Classification reflecting the disease activity. It was larger in the exudative type, caseo-infiltrative one, disseminated one, one with cavity in infiltrative lesion than the fibro-caseous one. On perfusion lung scintigram, impairment of pulmonary perfusion larger than area of the entire unilateral lung was observed in 68 cases (64.8%). Area of hypoperfused lung field, which correlated with % vital capacity (r = 0.60, p = 0.0002) and PaO2 (r = 0.39, p = 0.0024), was significantly larger in patients with silicosis and those with bilateral pleural involvements such as pleural callosity than in those with type III according to the Gakkai Classification. Most of the patients showed decreased pulmonary perfusion and Tl-201 accumulation of which grade reflects the disease activity in active tuberculous lesion. Patients with miliary tuberculosis and those with silicotuberculosis showed diffuse Tl-201, accumulation in the both lungs. Tl-201 lung scintigraphy seems to be useful for visualizing active tuberculous lesions, particularly the ones that could not be detected by the chest radiograph in patients with destroyed lung and with pleural callosity. Joint use of Tl-201 and perfusion lung scintigraphies provides useful informations about the pathophysiology and disease process in pulmonary tuberculosis.


Lung deformation estimation and four-dimensional CT lung reconstruction.
Four-dimensional (4D) computed tomography (CT) image acquisition is a useful technique in radiation treatment planning and interventional radiology in that it can account for respiratory motion of lungs. Current 4D lung reconstruction techniques have limitations in either spatial or temporal resolution. In addition, most of these techniques rely on auxiliary surrogates to relate the time of CT scan to the patient's respiratory phase. In this paper, we propose a novel 4D CT lung reconstruction and deformation estimation algorithm. Our algorithm is purely image based. The algorithm can reconstruct high quality 4D images even if the original images are acquired under irregular respiratory motion. The algorithm is validated using synthetic 4D lung data. Experimental results from a swine study data are also presented.


Analysis of the serotype-specific epitopes of avian infectious bronchitis virus strains Ark99 and Mass41.
The Ark and Mass serotype-specific epitopes of infectious bronchitis virus were studied by immunofluorescence and immunoprecipitation of mutant and recombinant spike glycoproteins (S protein) expressed in mouse L cells. Serotype-specific monoclonal antibodies could bind to the recombinant proteins of Ark99 and Mass41 expressed from the chimeras in which the N-terminal thirds of the S1 sequences were reciprocally exchanged. Therefore, it appears that the respective serotype-specific epitopes of both strains were localized within the C-terminal two-thirds of the S1 proteins. Deletion and insertion of a five-amino-acid fragment on the S1 proteins of Ark99 and Mass41, altered the serotype-specific epitopes. This result implies that the five-amino-acid insertion on the S1 protein of the Ark serotype was involved in determining the conformation of the protein, probably acting as a spacer. In addition, it appears that an interaction between sequences of the N-terminal third and the remaining portion of the S1 protein determines the tertiary structure of the protein as well as the conformation of the serotype-specific epitope.


In-hospital case fatality ratio due to COVID-19 in four Brazilian state capitals and its possible temporal relationship with the Gamma variant, 2020-2021.
To describe in-hospital and intensive care unit (ICU) case fatality ratios due to COVID-19 in four Brazilian state capitals, during the months of epidemic peaks and previous months. This was an ecological study using monthly data from the Influenza Epidemiological Surveillance Information System, between 2020-2021, in individuals aged 20 years or older. Case fatality ratio and mortality rate were estimated with 95% confidence intervals (95%CI). In Manaus, the capital city of the state of Amazonas, ICU case fatality ratio among those >59 years old was lower in December/2020 (80.9%; 95%CI 78.4;83.3) and during the peak in January/2021 (79.9%; 95%CI 77.4;82.5), compared to the peak in April/2020 (88.2%; 95%CI 86.1;90.3). In São Paulo, the capital city of the state of São Paulo, Curitiba, the capital city of the state of Paraná, and Porto Alegre, the capital city of the state of Rio Grande do Sul, there was a decrease or stability in ICU and in-hospital case fatality ratio in January/2021, compared to the reference month in 2020. In January/2021, in-hospital and ICU case fatality ratios decreased or remained stable in the four state capitals, especially in Manaus, and during the epidemic peak with the prevalence of the Gamma variant.


Biological miracles and misadventures: identification of sensitization and asthma in enzyme detergent workers.
The discovery that the enzymes used in biological washing powders were asthma-causing sensitizers derived initially from the concern of an industrial physician as to the possibility of pulmonary damage due to the proteolytic nature of the material. This caused a search for possible cases of enzyme-related illness. Careful history-taking led to a hypothesis concerning sensitization and allergic illness which was supported experimentally by skin prick tests and inhalation challenge tests, and later by radioallergosorbent tests (RAST). It seems that the consequences of handling this potentially allergenic material as a fine powder had not been anticipated; and failure to analyze cases of sickness, to identify asthma, and to consider its workplace source had prevented its recognition elsewhere. Contributing to this failure was the pattern of development and manifestations of allergic illness, which seldom occurred in the workplace and was not confined to enzyme workers or atopics. In some cases the incidence of illness had been suppressed, or investigation prevented.


Notch2-induced COX-2 expression enhancing gastric cancer progression.
Gastric carcinoma is one of the most common and mortal types of malignancy worldwide. To date, the mechanisms controlling its aggressiveness are not yet fully understood. Notch signal pathway can function as either an oncogene or a tumor suppressor in tumorigenesis. Four members (Notch1-4) of Notch receptors were found in mammals and each exhibits distinct roles in tumor progression. Previous study showed that the activated Notch1 receptor promoted gastric cancer progression through cyclooxygenase-2 (COX-2). This study addressed whether Notch2 signal pathway is also involved in gastric cancer progression. Constitutive expression of Notch2 intracellular domain (N2IC), the activated form of Notch2 receptor, promoted both cell proliferation and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. The colony formation, migration, invasion, and wound-healing abilities of SC-M1 cells were enhanced by N2IC expression, whereas these abilities were suppressed by Notch2 knockdown. Similarly, Notch2 knockdown inhibited cancer progressions of AGS and AZ521 gastric cancer cells. Expression of N2IC also caused epithelial-mesenchymal transition in SC-M1 cells. Furthermore, N2IC bound to COX-2 promoter and induced COX-2 expression through a CBF1-dependent manner in SC-M1 cells. The ability of N2IC to enhance tumor progression in SC-M1 cells was suppressed by knockdown of COX-2 or treatment with NS-398, a COX-2 inhibitor. Moreover, the suppression of tumor progression by Notch2 knockdown in SC-M1 cells was reversed by exogenous COX-2 or its major enzymatic product PGE(2) . Taken together, this study is the first to demonstrate that the Notch2-COX-2 signaling axis plays an important role in controlling gastric cancer progression.


Transdiagnostic neural markers of emotion-cognition interaction in psychotic disorders.
Deficits in working memory (WM) and emotion processing are prominent impairments in psychotic disorders, and have been linked to reduced quality of life and real-world functioning. Translation of knowledge regarding the neural circuitry implementing these deficits into improved diagnosis and targeted treatments has been slow, possibly because of categorical definitions of disorders. Using the dimensional Research Domain Criteria (RDoC) framework, we investigated the clinical and practical utility of transdiagnostic behavioral and neural measures of emotion-related WM disruption across psychotic disorders. Behavioral and functional MRI data were recorded while 53 participants with psychotic disorders and 29 participants with no history of psychosis performed a modified n-back task with fear and neutral distractors. Hierarchical regression analyses showed that psychotic symptoms entered after diagnosis accounted for unique variance in fear versus neutral accuracy and activation in the ventrolateral, dorsolateral, and dorsomedial prefrontal cortex, but diagnostic group entered after psychotic symptoms did not. These results remained even after controlling for negative symptoms, disorganized symptoms, and dysphoria. Finally, worse accuracy and greater prefrontal activity were associated with poorer social functioning and unemployment across diagnostic groups. Present results support the transdiagnostic nature of behavioral and neuroimaging measures of emotion-related WM disruption as they relate to psychotic symptoms, irrespective of diagnosis. They also provide support for the practical utility of these markers in explaining real-world functioning. Overall, these results elucidate key aspects of the RDoC construct of WM maintenance by clarifying its transdiagnostic importance and clinical utility in psychotic disorders. (PsycINFO Database Record


A ZnCl2 water-in-salt electrolyte for a reversible Zn metal anode.
We report a low-cost water-in-salt electrolyte, of 30 m ZnCl2, which enables a dendrite-free Zn metal anode to possess a high coulombic efficiency (CE). In asymmetric Zn‖Zn cells with a limited mass of plated Zn as the working electrode, the ZnCl2 WiSE improves the average CE of the Zn anode to 95.4% from 73.2% in 5 m ZnCl2.


Cross-polarisation, making it practical.
The author investigated the use of cross-polarisation for day-to-day practice after a request from a clinician to remove specular highlights from intra-oral photographs. The paper evaluates camera and light source devices for image capture using cross-polarisation. Following this it defines ways to calibrate the camera to the correct white balance. It then develops by carrying out a series of tests to define the point of influence in regard to signal-to-noise ratio. These tests showed that the anti-aliasing filters of some cameras are more prominent than others and therefore can have a significant affect. In conclusion, when the appropriate equipment is employed, cross-polarisation is a viable and practical technique that has application within the medical, scientific, and forensic fields.


Physical Aspects of Fruit Growth: STRESS DISTRIBUTION AROUND LENTICELS.
The skin around a lenticel on a soft fruit has been modelled as a thin elastic plate with a rigid circular inclusion and applied tensile loads at the edges. A solution for the stress distribution in the skin has then been found using the linear theory of elasticity. From that solution the severity of the stress concentration and the location and form of initial cuticular failure have been deduced, the latter two being in broad agreement with observed crack initiation in the cuticle of grapes.


Osteopoikilosis: a case with osteopenia.
Osteopoikilosis is a benign osteosclerotic dysplasia of unknown origin, which is an inherited autosomal disorder. It is usually asymptomatic and may only be recognized on radiological examination. We report a 20-year-old man who suffers from back and shoulder pain during the routine physical examinations performed prior to the military recruitment. Numerous symmetric, small, ovoid and circular sclerotic bone lesions were found on the X-rays of the spine and shoulder. Dual energy X-ray absorptiometry (DXA) examination revealed osteopenia. In conclusion, typical radiographic examination of osteopoikilosis is usually diagnostic. However, it may sometimes be difficult to rule out the other diseases like osteoblastic metastatic lesions as it is an uncommon disease. Physicians should be aware of possible coexisiting osteopenia or osteoporosis as reported in our case.


Experimentally excellent beaming in a two-layer dielectric structure.
We demonstrate both experimentally and theoretically that a two-layer dielectric structure can provide collimation and enhanced transmission of a Gaussian beam passing through it. This is due to formation of surface localized states along the layered structure and the coupling of these states to outgoing propagating waves. A system of multiple cascading two-layers can sustain the beaming for large propagation distances.


Isolation and characterization of Pseudomonas aeruginosa exotoxin A binding glycoprotein from mouse LM cells.
A Pseudomonas aeruginosa exotoxin A (PE) binding glycoprotein was affinity purified from toxin sensitive mouse LM cells. The binding protein was solubilized with Triton X-100 or Nonidet P-40 and purified on a PE-Sepharose affinity column. Polyacrylamide gel electrophoresis yielded a single band with an estimated molecular mass of greater than 300,000 Da. N-Linked carbohydrate was present, accounting for approximately 10% of the total mass of the molecule. The purified protein specifically bound PE. Incubation of purified protein specifically bound PE. Incubation of purified PE binding protein with toxin reduced toxicity to LM cells. We speculate on the role of this toxin binding glycoprotein in the intoxication process.


Selective Deposition of Candle Soot on a Cellulose Membrane for Efficient Solar Evaporation.
Owing to their natural abundance, seawater together with sunlight has a potential to meet the global challenges in terms of water scarcity and energy crisis. Herein, we demonstrate a solar vapor generator composed of an inner flame candle soot (IFCS) deposited on a cellulose filter paper (FP) prepared by a simple two-step process. The resultant IFCS/FP device exhibits a high photothermal conversion ability owing to the broadband solar absorption of the IFCS layer along with the multiple scattering of the incoming sunlight in the porous microstructure of the cellulose FP. Additionally, the low thermal conductivity of the IFCS effectively localizes the photothermally generated heat at the IFCS/FP surface, thereby significantly suppressing the conduction heat losses to the underlying bulk water. Meanwhile, the capillary action of the FP supplies an adequate amount of water to the heated surface for accelerating the evaporation process. Benefitting from the synergistic effect of these characteristics, the IFCS/FP achieves high evaporation rates of ∼1.16 and ∼4.09 kg m-2 h-1 and their corresponding efficiencies of ∼75.1 and 90.9% under one and three sun illumination, respectively. Moreover, the IFCS/FP device presents an excellent longevity owing to the persistent performance over 15 repeated cycles under one and three sun illumination. Hence, the facile fabrication, fine mechanical strength, desalination, and the salt-resistance ability of our IFCS/FP make it a suitable candidate for practical applications.


The response to particulate debris.
The most common cause of failure of total hip and other arthroplasties is aseptic loosening of the prosthesis. Substantial evidence suggests that the adverse tissue response to prosthesis wear particles is an important contributor to bone loss around implants. The results may be an increased risk of loosening and severe bone loss, which makes revision surgery more difficult. Studies in humans have demonstrated that the appearances of the periprosthetic tissues are related to the type, number, and size of wear particles. The appearance and tissue response around any given prosthesis is related to the balance among the rate of production of wear particles, the ability of the tissues to deal with the particles, and the rate of clearance of the particles from the joint. Prosthesis wear particles may be produced by wear at the articulating surface, particularly if there is three-body wear, by abrasion due to movement at the prosthesis-bone interface of uncemented prostheses, by abrasion at the prosthesis-cement and cement-bone interfaces of cemented prostheses, or at any articulation of the components of modular prostheses. Future in vivo and in vitro studies of the effects of wear particles should focus on quantitative measurement of the effects of particles and on the use of particles of comparable size and in concentrations similar to those found in the tissues surrounding failed prostheses.


Two cases of multiple eccrine spiradenoma with linear or localized formation.
We report two rare cases of recurrent, multiple eccrine spiradenoma. Both cases presented with extensive lesions comprised of multiple red papules of various sizes and a soft blue-red nodule. The first case was a 30-year-old woman. Her lesions followed a linear arrangement on her chin, and extended down the right side of the neck with spontaneous pain. The second case was a 57-year-old woman with tumors in a localized group on the left occipital region without pain. A search of the literature revealed only 15 reported cases of linear/zosteriform/nevoid multiple eccrine spiradenoma. Both cases were treated by surgical excision. Most of the red papules displayed typical histological features including two cell types: large clear cells with low-density cytoplasm; and small dark cells with high-density cytoplasm. The large soft tumors exhibited a variable histological appearance. In the first case, the cystic tumors displayed an homogeneous structure comprised of eosinophilic material. In the second case, the cystic tumors included abundant interstitial tissue.


Remineralization of artificial carious lesions using a novel fluoride incorporated bioactive glass dentifrice.
Remineralization potential of dentifrices with novel compositions that can restore minerals back into incipient carious lesions has not been extensively studied so far. The aim of this study was to assess the efficacy of a dentifrice based on novel fluoride incorporated bioactive glass in remineralizing artificial carious lesions in human enamel, and compare it with a standard fluoride-containing dentifrice. Twenty-four human extracted teeth were sectioned at the cementoenamel junction to obtain enamel blocks. These blocks (n = 24) were randomly divided into 3 groups, with each group containing 8 specimens: group 1 (negative control group; distilled water), group 2 (positive control group; fluoride toothpaste) and group 3 (test group; BioMinTM F toothpaste). Artificial carious lesions were produced in the enamel surfaces by exposing them to a demineralization solution (6% citric acid, pH 2.2) for 96 h. After demineralization, the specimens were brushed with manual toothbrushes in a toothbrush simulation machine (each sample received 800 strokes). For brushing the specimens from group 1, 20 mL of distilled water was used, for group 2 - 20 mL of slurry of toothpaste mixed with artificial saliva, and for group 3 - 20 mL of slurry of toothpaste (BioMin F) mixed with artificial saliva. The micro-hardness data (VHN - Vickers hardness number) was collected at baseline (sound enamel), post-demineralization and post-remineralization. The biggest difference between the post-remineralization and post-demineralization values was observed in group 3 (mean VHN = 118.73), followed by group 2 (mean VHN = 60.54) and group 1 (mean VHN = 47.44). All the groups revealed significant differences (p < 0.05) when the post-demineralization and post-remineralization values were compared to baseline values within each group. The BioMin F group outperformed the other 2 groups in terms of remineralizing the demineralized enamel structure.