Exploring the boundaries between borderline personality disorder and suicidal behavior disorder.
To compare clinical traits of suicidal vulnerability among in-patients with suicidal behavior disorder (SBD) with and without borderline personality disorder (BPD). we recruited adult patients with SBD, consecutively and voluntarily hospitalized in a specialized unit for affective disorders and suicidal behavior between July and October 2016. Ninety-two inpatients having attempted suicide within the past 2 years were divided into two subgroups according to the presence or absence of BPD. Clinical vulnerability traits for suicidal behavior were assessed. Half of the patients with SBD also had BPD. Patients with BPD were nine times more likely to be major suicide repeaters compared to those without. They were also more likely to display clinical and psychological vulnerability traits for suicidal behavior, even after considering potential confounders. Emotional dysregulation, shame-proneness, impulsiveness, preoccupied attachment pattern, and childhood trauma were high in both groups, but significantly increased in those with (vs. without) BPD status. Psychological traits remained stable in SBD-BPD patients, regardless of the time since the last suicide attempt (i.e. SBD in recent vs. early remission). Clinical and psychological traits associated with suicidal vulnerability are present in all SBD patients compared to non-suicidal populations, but comorbidity with BPD is associated with particularly high scores. BPD could be considered as a specifier for SBD diagnoses.


Explosive growth of facet joint interventions in the Medicare population in the United States: a comparative evaluation of 1997, 2002, and 2006 data.
The Office of Inspector General of the Department of Health and Human Services (OIG-DHHS) issued a report which showed explosive growth and also raised questions of lack of medical necessity and/or indications for facet joint injection services in 2006.The purpose of the study was to determine trends of frequency and cost of facet joint interventions in managing spinal pain. This analysis was performed to determine trends of frequency and cost of facet jointInterventions in managing spinal pain, utilizing the annual 5% national sample of the Centers forMedicare and Medicaid Services (CMS) for 1997, 2002, and 2006.Outcome measures included overall characteristics of Medicare beneficiaries receiving facet joint interventions, utilization of facet joint interventions by place of service, by specialty, reimbursement characteristics, and other variables. From 1997 to 2006, the number of patients receiving facet joint interventions per 100,000Medicare population increased 386%, facet joint visits increased 446%, and facet joint interventions increased 543%. The increases were higher in patients aged less than 65 years compared to those 65 or older with patients increasing 504% vs. 355%, visits increasing 587% vs. 404%, and services increasing 683% vs. 498%.Total expenditures for facet joint interventions in the Medicare population increased from over $229 million in 2002 to over $511 million in 2006, with an overall increase of 123%. In 2006, there was a 26.8-fold difference in utilization of facet joint intervention services in Florida compared to the state with the lowest utilization - Hawaii.There was an annual increase of 277.3% in the utilization of facet joint interventions by general physicians, whereas a 99.5% annual increase was seen for nurse practitioners (NPs) and certified registered nurse anesthetists (CRNAs) from 2002 to 2006. Further, in Florida, 47% of facet joint interventions were performed by general physicians. The reported explosive growth of facet joint interventions in managing spinal pain in certain regions and by certain specialties may result in increased regulations and scrutiny with reduced access.


A Multifunctional Platform for the Capture, Release, And Enumeration of Circulating Tumor Cells Based on Aptamer Binding, Nicking Endonuclease-Assisted Amplification, And Inductively Coupled Plasma Mass Spectrometry Detection.
Inductively coupled plasma mass spectrometry (ICP-MS) combined with element tags has been well designed and extensively applied in cell enumeration. It possesses superior quantitative capability, strong resistance to matrix interference, multiplex detection capability but destructive characteristic. Herein, we constructed an ICP-MS based multifunctional platform for capture, nondestructive enumeration, and release of circulating tumor cells (CTCs). Aptamer on capture probe recognized Mucin 1 (MUC1) on membrane of MCF-7 cells specifically, thus the cells were captured by probe and the Initiator originally hybridized with Aptamer was substituted by MUC1 and released into solution. Then the released Initiator was separated from the captured cells and hybridized with Tb labeled Substrate on detection probe to release a large amount of nicked Tb fragments through the nicking endonuclease assisted amplification for subsequent ICP-MS detection. Meanwhile, cells captured by probe were released by nuclease digestion for further reculture. Such a strategy effectively avoids CTCs destruction resulted from ICP-MS enumeration, increases the detection sensitivity of ICP-MS by involving nicking endonuclease assisted amplification, and realizes cell recovery for further analysis. A limit of detection of 87 MCF-7 cells and a linear range of 250-10 000 MCF-7 cells were realized for ICP-MS enumeration. A cell recovery of 52.7% (with capture and release efficiency of 63.9 and 82.5%, respectively) and a viability of 74.3% were obtained, meanwhile the released cells exhibited strong proliferation ability. This multifunctional platform for CTCs capture, enumeration, and release has great applicable potential in early diagnosis and individual treatment for cancer.


A single amino acid substitution in the antimicrobial defense protein cecropin B is associated with diminished degradation by leaf intercellular fluid.
Degradation is one of several factors that may affect the level of accumulation of transgene products in plants. In plants engineered to secrete antimicrobial proteins to the intercellular compartment of leaves, the degenerative activity of proteases residing in leaf intercellular fluid (IF) could be critical to achieving the expected transgene function. We synthesized a structural analogue (MB39) of the antibacterial protein cecropin B and compared the susceptibility of both proteins to degradation in vitro by IF extracted from leaves of various crops. The half-life of the two proteins in the various IF extracts ranged from 3 min to 25.5 h, with the analogue MB39 displaying the longer half-life in IF from nine of 10 species. Overall, the half-life of MB39 averaged 2.9 times greater than that of cecropin B. Analysis of the peptides produced by endopeptidase activity in potato iF indicated that the 5.7-fold lower degradation rate of MB39 was associated with the substitution of valine for methionine at residue 11 of cecropin B. These findings point to the possibility of tailoring antimicrobial protein genes to reduce the rate of protein degradation in a particular target crop.


Variations in drought tolerance components and their association with yield components in finger millet (Eleusine coracana).
Finger millet has gained considerable attention worldwide due to its nutritional and health benefits. Being a rainfed crop of semiarid and arid regions, drought is one of the major constraints to its yield stabilisation. To address this, a set of 38 accessions of finger millet were evaluated in both field and mini-lysimeters under both well-watered (WW) and water-stressed (WS) conditions. The objectives of the study were to identify the range of variations for yield components, water-use (WU) and transpiration efficiency (TE) and to examine the potential of the mini-lysimeter system in assessing the genotypic performance in the field conditions. Approximately 2-fold variations in shoot biomass and ~9-fold variations in grain yield under WS conditions were observed. Reproductive growth was more sensitive to WS than the vegetative growth. Our results indicate that in addition to yield potential under WW conditions, WU followed by TE were the other two major contributors toward shoot biomass, whereas, HI followed by TE were the major contributors toward grain yield under WS. The close association between the yield components recorded in the field and in mini-lysimeters suggests that the lysimetric system has the great potential to reflect the genotypic performance under field conditions. Regression analyses suggest that HI explained almost all the variations in grain yield under WW conditions, whereas under WS treatment, next to HI, both TE and WU had also contributed significantly to grain yield. The absence of interrelationship between WU and TE suggests that both these components contribute independently toward the yield components under WW or WS conditions. The accessions with higher shoot biomass and grain yield extract much more water during the post-anthesis stages than the poor performers under WS. Results also suggests that higher WU contributed more towards shoot biomass and higher TE contributed more towards grain yield by improving the harvest index.


Mortality and production characteristics of laying chickens fed high- and low-erucic acid rapeseed oils.
Laying pullets were fed a diet supplemented with three percent of either high-erucic acid rapeseed (HEAR) oil or low-erucic acid rapeseed (LEAR) oil for 39 weeks. Egg production for the period was 78.8 and 80.1% by the birds fed the respective oils. Average egg weights were 56.8 and 58.7 g. respectively. Gains in body weight, liver weight and adrenal gland weight were similar with the two types of oil fed. Feed consumption was similar for the two groups of birds. The efficiency of utilization of the diet containing HEAR oil was accordingly lower than that of the diet containing LEAR oil. In the birds fed HEAR and LEAR oil respectively mortality attributed to metabolic disorders of the reproductive system, liver, and kidney was 3.3% and 1.2%. Mortality from other causes in the birds fed the two oils was 3.2 and 3.8% of the original populations.


Prolonged endoplasmic reticulum stress promotes mislocalization of immunoglobulins to the cytoplasm.
Signal peptide-dependent insertion of newly synthesized proteins into the endoplasmic reticulum (ER) is a multi-step process, whose fidelity varies with the identity of the protein and the cell type. ER translocation of prions is sensitive to conditions of acute ER stress in a manner that pre-emptively prevents their aggregation and proteo-toxicity. While this has been documented for extreme ER stress conditions and for a special type of proteins, the impact of chronic ER stress on protein translocation in general has not been well characterized. The unfolded protein response (UPR) is a cytoprotective signaling pathway activated by ER stress. The transcription factor X-box-binding protein 1 (XBP-1) is a key element of the mammalian UPR, which is activated in response to ER stress. Deletion of XBP-1 generates constitutive chronic ER stress conditions. Chronic ER stress can also be produced pharmacologically, for example by prolonged treatment with proteasome inhibitors, which abrogates XBP-1 activation. We tested the impact of chronic ER stress on protein insertion into the ER with special emphasis on antibody secreting cells (ASCs), as these cells cope physiologically with prolonged stress conditions. We show that XBP-1 in plasmablasts and fibroblasts controls the ER translocation of US2, a viral-encoded protein with a priori poor insertion efficiency. Using monoclonal antibodies that preferentially recognize ER-mis-inserted micro Ig chains we demonstrate that prolonged treatment of plasmablasts with proteasome inhibitors, as well as deletion of XBP-1, impaired the translocation of mu chains to the ER. Our data suggest that ASCs under prolonged ER stress conditions endure cytoplasmic mislocalization of Ig proteins. This mislocalization may further explain the exquisite sensitivity of multiple myeloma to proteasome inhibitors.


Methanethiosulfonate derivatives of rhodamine and verapamil activate human P-glycoprotein at different sites.
The human multidrug resistance P-glycoprotein (P-gp, ABCB1) actively extrudes a broad range of potentially cytotoxic compounds out of the cell. Key steps in understanding the transport process are binding of drug substrates in the transmembrane domains, initiation of ATPase activity, and subsequent drug efflux. We used cysteine-scanning mutagenesis of the transmembrane segment residues and reaction with the thiol-reactive drug substrate analog of rhodamine, methane-thiosulfonate-rhodamine (MTS-rhodamine), to test whether P-gp could be trapped in an activated state with high levels of ATPase activity. The presence of such an activated P-gp could be used to further investigate P-gp-drug substrate interactions. Single cysteine mutants (149) were treated with MTS-rhodamine, and ATPase activities were determined after removal of unreacted MTS-rhodamine. One mutant, F343C(TM6), showed a 5.8-fold increase in activity after reaction with MTS-rhodamine. Pre-treatment of mutant F343C with rhodamine B protected it from activation by MTS-rhodamine, indicating that residue Cys-343 contributes to the rhodamine-binding site. The ATPase activity of MTS-rhodamine-treated mutant F343C, however, was not stimulated further by colchicine or calcein-AM. By contrast, verapamil and Hoechst 33342 stimulated and inhibited, respectively, the ATPase activity of the MTS-rhodamine-treated mutant F343C. These results indicate that the MTS-rhodamine binding site overlaps that of colchicine and calcein-AM but not that of verapamil and Hoechst 33342 within the common drug-binding pocket.


The Duration of Impella 2.5 Circulatory Support and Length of Hospital Stay of Patients Undergoing High-risk Percutaneous Coronary Interventions.
To evaluate the impact of duration of Impella 2.5 support (Abiomed, Danvers, MA) on hospitalization of patients after high-risk percutaneous coronary intervention (PCI). There has been a continuous increase in prevalence of coronary artery disease with more patients needing PCI during acute myocardial infarction. Some of these patients have to undergo high-risk revascularization with circulatory support like the Impella 2.5 device. This study was a single center retrospective study of patients admitted to our hospital who required Impella circulatory support during percutaneous coronary intervention. Patients' medical records, cardiac catheterization laboratory and 2-D echocardiography reports were reviewed to ascertain left ventricular ejection fraction, duration of Impella support, Coronary Care Unit (CCU) days and the length of stay in the hospital. A P-value of ≤ 0.05 was considered statistically significant. Over a 15-month period, we had 25 patients with 19 males and 6 females. Mean age of the patient cohort was 68 ± 10 years. Mean LVEF of the group was 32 ± 16%. Mean length of hospital stay was 8 ± 8 days and mean CCU stay was 4 ± 4 days. The Impella was successfully inserted in all cases with a median duration of support of 70 minutes (range, 4 - 5760 minutes). Bleeding complication occurred in 8%. Spearman's rank correlation coefficient between the duration of Impella support and hospital stay was 0.49 (P = 0.023) while it was 0.71 (P = 0.001) between Impella support duration and CCU days. Our study suggests that there is a positive correlation between the duration of Impella 2.5 circulatory support and hospital stay and/or CCU days. The correlation seems to be stronger with CCU days.


Towards environmental systems biology of Shewanella.
Bacteria of the genus Shewanella are known for their versatile electron-accepting capacities, which allow them to couple the decomposition of organic matter to the reduction of the various terminal electron acceptors that they encounter in their stratified environments. Owing to their diverse metabolic capabilities, shewanellae are important for carbon cycling and have considerable potential for the remediation of contaminated environments and use in microbial fuel cells. Systems-level analysis of the model species Shewanella oneidensis MR-1 and other members of this genus has provided new insights into the signal-transduction proteins, regulators, and metabolic and respiratory subsystems that govern the remarkable versatility of the shewanellae.


When Family Matters Most: A Test of the Association Between Sexual Minority Identity Disclosure Context and Diurnal Cortisol in Sexual Minority Young Adults.
Revealing one's sexual identity to others is a complex process marked by a shift in the types of stressors faced by sexual minority young adults. Such stressors influence the secretion of health-relevant hormones, including cortisol, yet how dimensions of disclosure (i.e., the degree and context) influence neuroendocrine functioning remains poorly understood. The current study examined the association between disclosure context (disclosure to family members, friends/co-workers/acquaintances, and members of religious groups) and diurnal cortisol while allowing disclosure to vary in degree (i.e., how much is disclosed). One hundred twenty-one sexual minority young adults (aged 18-35 years, 54.5% female, free of major psychiatric/endocrine disorders) completed an initial survey that assessed the degree and context of sexual minority identity disclosure. A randomly selected subset (n = 58) also provided salivary cortisol samples at wake, 45 minutes after wake, 12 hours after wake, and at bedtime for 1 week. Greater total disclosure and greater disclosure to family members were associated with reduced cortisol output, defined as Area Under the Curve relative to ground (AUCg; F(1,230) = 5.95, p = .015, and F(1,231) = 10.90, p = .001, respectively). Disclosure to co-workers, friends, acquaintances, or religious groups was unrelated to cortisol AUCg. All disclosure contexts tested were unrelated to the shape of diurnal cortisol slopes (including the cortisol awakening response). Disclosure to family members uniquely predicted cortisol AUCg. Therefore, these results suggest that effects of disclosure on diurnal cortisol and its associated health outcomes may occur in the context of familial relationships.


TMAO as a Novel Predictor of Major Adverse Vascular Events and Recurrence in Patients with Large Artery Atherosclerotic Ischemic Stroke.
To explore the association of plasma trimethylamine N-oxide (TMAO) concentration with large artery atherosclerotic (LAA) ischemic stroke and its role in predicting neurological outcome and major vascular event recurrence. We performed a case-control study that included patients with first-ever LAA stroke as cases (n = 291) and asymptomatic patients as controls (n = 235). Clinical data and venous blood samples were collected within 72 hours after stroke. All subjects were followed for 3 months. TMAO level was detected by liquid chromatography mass spectrometry (LC-MS). Logistic and Cox proportional hazard regression were performed to evaluate plasma TMAO concentration as a predictor of LAA stroke and major vascular event recurrence, respectively. Kaplan-Meier survival analysis was performed to compare major vascular event recurrence between patients with high and low TMAO concentration. After adjusting for traditional stroke risk factors, the plasma TMAO level was significantly higher in the LAA stroke group than the control group (OR = 1.031, 95% CI 1.024-1.037, P < .001). At a cutoff level of 106.9 pg/ml, TMAO had a sensitivity of 63.23% and specificity of 80.00% in discriminating the LAA stroke subjects from the controls in Receiver operator characteristic (ROC) analysis. Kaplan-Meier survival analysis demonstrated TMAO plasma concentration was significantly relevant with recurrent vascular events (Log Rank, P = .006). Moreover, this association was still existed after adjusting for traditional risks (adjusted HR, 3.128; 95% CI, 1.018-9.610) in Cox regression model. But TMAO plasma levels were not relevant with functional disability after 3 months of the LAA stroke. Elevated plasma TMAO concentration was independently associated with LAA ischemic stroke. The risk of major vascular event recurrence increased by 2.128 times in the LAA stroke subjects with plasma TMAO level higher than 126.83 pg/mL. Plasma TMAO concentration might be a potential biomarker of major vascular event recurrence.


Management of Hypothyroidism in Patients with Acute Myocardial Infarction.
Background and Objectives: Thyroid hormones (TH) affect cardiac function through effects on cardiac contractility and systemic vascular resistance. While TH replacement for patients with hypothyroidism might be necessary for restoration of cardiac output after an acute myocardial infarction (AMI), it could theoretically lead to excessively rapid restoration of the metabolic rate. The appropriate management of hypothyroidism in patients with AMI is unknown. We describe the practice patterns in the management of hypothyroidism in the setting of AMI as well as patients' clinical outcomes. Material and Methods: Retrospective study of patients that were admitted to a tertiary care hospital with AMI and newly diagnosed or uncontrolled hypothyroidism (TSH ≥ 10 mIU/L) between 2011-2018. Eligible patients were identified using diagnosis codes for AMI and laboratory values, followed by medical record review. We categorized patients according to treatment status with TH and by degree of hypothyroidism. Clinical outcomes included: 30-day mortality/readmission, bleeding, stroke, arrhythmia, sudden cardiac death, and new or worsening heart failure. Summary statistics and group comparisons are presented. Results: Sixty-four patients were included, their median age was 64 years and 61% (n = 39) were women. Most of the patients (59%) had a documented history of hypothyroidism. Of these, all were restarted on levothyroxine (LT4) during the index admission when compared to patients without a history of hypothyroidism, of which 54% received LT4 treatment (p = 0.001). The median TSH in those treated with LT4 was higher (25 mIU/L) when compared to those who were not (12 mIU/L), (p = 0.007). Patients who received intravenous LT4 had higher TSH levels and other variables suggesting worse clinical presentation, but these differences were not statistically significant. No statistically significant differences were noted on clinical outcomes according to LT4 treatment status. Conclusion: A history of hypothyroidism and the degree of TSH elevation seem to guide the management of hypothyroidism in patients with AMI. The clinical effect of correcting hypothyroidism in this setting requires further evaluation.


Synthesis and in vitro antibacterial activities of 3-thiazol-4-yl-1-carba-1-dethiacephalosporins.
The synthesis and microbiological evaluation of a new series of 3-thiazol-4-yl-carba-1-dethiacephalosporins is described. Structure activity relationship was achieved by changing substitution at the 2-position of the thiazole moiety. The result was a marked variance of microbiological activity in the C7 side-chain derivatives. ATMO derivatives possess potent activity against both Gram-positive and Gram-negative bacteria. For example, MICs (microgram/ml) of LY215226 against representative organisms are as follows: S. aureus 0.25, S. pneumoniae 0.008, H. influenzae 0.008, E. coli 0.25, K. pneumoniae 0.008, E. cloacae 0.5, S. typhi 0.25, and M. morganii 0.25.


Kinetic rates of antibody binding correlate with neutralization sensitivity of variant simian immunodeficiency virus strains.
Increasing evidence suggests that an effective AIDS vaccine will need to elicit both broadly reactive humoral and cellular immune responses. Potent and cross-reactive neutralization of simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) by polyclonal and monoclonal antibodies is well documented. However, the mechanisms of antibody-mediated neutralization have not been defined. The current study was designed to determine whether the specificity and quantitative properties of antibody binding to SIV envelope proteins correlate with neutralization. Using a panel of rhesus monoclonal antibodies previously characterized for their ability to bind and neutralize variant SIVs, we compared the kinetic rates and affinity of antibody binding to soluble envelope trimers by using surface plasmon resonance. We identified significant differences in the kinetic rates but not the affinity of monoclonal antibody binding to the neutralization-sensitive SIV/17E-CL and neutralization-resistant SIVmac239 envelope proteins that correlated with the neutralization sensitivities of the corresponding virus strains. These results suggest for the first time that neutralization resistance may be related to quantitative differences in the rates but not the affinity of the antibody-envelope interaction and may provide one mechanism for the inherent resistance of SIVmac239 to neutralization in vitro. Further, we provide evidence that factors in addition to antibody binding, such as epitope specificity, contribute to the mechanisms of neutralization of SIV/17E-CL in vitro. This study will impact the method by which HIV/SIV vaccines are evaluated and will influence the design of candidate AIDS vaccines capable of eliciting effective neutralizing antibody responses.


Inbred mice as model hosts for cutaneous leishmaniasis. I. Resistance and susceptibility to infection with Leishmania braziliensis, L. mexicana, and L. aethiopica.
The susceptibility of 12 strains of inbred mice representing a broad genetic spectrum to infection of Leishmania braziliensis, L. mexicana and L. aethiopica was determined. Levels of susceptibility were evaluated by gross morphology of lesions, evidence of resolution, persistence of parasites at the site of inoculation, and visceralization to the spleen or liver following inoculation in noses. Very different patterns of responses were noted among the infections with the three species of Leishmania. Among the strains of inbred mice infected with L. braziliensis, patterns of cutaneous lesion development indicated a broad range of susceptibilities and responses. Two strains of inbred mice (AKR/J and CBA/J) showed only a slight and transient swelling of the nose. The SWR/J, C57L/J, A/J, A/HeJ and DBA/1J showed initial swellings or nodules which eventually resolved. In contrast, the BALB/cJ mice were ranked as most susceptible, based on progressive dermal lesions and visceralization. Four strains of inbred mice (C3H/HeJ, C57BL/6J, CBA/J and CBA/CaJ) showed no evidence of infection. Lesion development in most strains of inbred mice infected with L. mexicana occurred later than with L. braziliensis but was then more rapidly progressive with no indication of resolution. Two strains (C3H/HeJ and C57BL/6J) showed no evidence of infection. Only slight swellings of the nose were seen in the 12 strains of inbred mice infected with L. aethiopica; however, parasites were isolated by culture from apparently normal noses in five groups (A/HeJ, AKR/J, BALB/cJ, DBA/2J and SWR/J).


The gap-prepulse inhibition deficit of the cortical N1-P2 complex in patients with tinnitus: The effect of gap duration.
The present study aimed to investigate whether gap-prepulse inhibition (GPI) deficit in patients with tinnitus occurred in the N1-P2 complex of the cortical auditory evoked potential. Auditory late responses to the intense sound of the GPI paradigm were obtained from 16 patients with tinnitus and 18 age- and hearing loss-matched controls without tinnitus. The inhibition degrees of the N1-P2 complex were assessed at 100-, 50-, and 20-ms gap durations with tinnitus-pitch-matched and non-matched frequency background noises. At the 20-ms gap condition with the tinnitus-pitch-matched frequency background noise, only the tinnitus group showed an inhibition deficit of the N1-P2 complex. The inhibition deficits were absent in both groups with longer gap durations. These findings suggested that the effect of tinnitus emerged depending on the cue onset timing and duration of the gap-prepulse. Since inhibition deficits were observed in both groups at the same 20-ms gap condition, but with the tinnitus-pitch-non-matched frequency background noise, the present study did not offer proof of concept for tinnitus filling in the gap. Additional studies on the intrinsic effects of different background frequencies on the gap processing are required in the future.


Enhancing acetone biosynthesis and acetone-butanol-ethanol fermentation performance by co-culturing Clostridium acetobutylicum/Saccharomyces cerevisiae integrated with exogenous acetate addition.
Acetone is the major by-product in ABE fermentations, most researches focused on increasing butanol/acetone ratio by decreasing acetone biosynthesis. However, economics of ABE fermentation industry strongly relies on evaluating acetone as a valuable platform chemical. Therefore, a novel ABE fermentation strategy focusing on bio-acetone production by co-culturing Clostridium acetobutylicum/Saccharomyces cerevisiae with exogenous acetate addition was proposed. Experimental and theoretical analysis revealed the strategy could, enhance C. acetobutylicum survival oriented amino acids assimilation in the cells; control NADH regeneration rate at moderately lower level to enhance acetone synthesis but without sacrificing butanol production; enhance the utilization ability of C. acetobutylicum on glucose and direct most of extra consumed glucose into acetone/butanol synthesis routes. By implementing the strategy using synthetic or acetate fermentative supernatant, acetone concentrations increased to 8.27-8.55g/L from 5.86g/L of the control, while butanol concentrations also elevated to the higher levels of 13.91-14.23g/L from 11.63g/L simultaneously.


Estimating a brain network predictive of stress and genotype with supervised autoencoders.
Targeted brain stimulation has the potential to treat mental illnesses. We develop an approach to help design protocols by identifying relevant multi-region electrical dynamics. Our approach models these dynamics as a superposition of latent networks, where the latent variables predict a relevant outcome. We use supervised autoencoders (SAEs) to improve predictive performance in this context, describe the conditions where SAEs improve predictions, and provide modelling constraints to ensure biological relevance. We experimentally validate our approach by finding a network associated with stress that aligns with a previous stimulation protocol and characterizing a genotype associated with bipolar disorder.


Energy transfer mechanism in luminescence Eu(III) and Tb(III) complexes of coumarin-3-carboxylic acid: A theoretical study.
Excited state energy level diagrams of coumarin-3-carboxylic acid (HCCA) chromophore, Eu(CCA)Cl2(H2O)2 (1), Eu(CCA)2Cl(H2O)2 (2), Eu(CCA)3(H2O)3 (3), Tb(CCA)2Cl(H2O) (4) and Tb(CCA)2(NO3)(H2O) (5) in gas phase and polar solution have been calculated by means of DFT/TDDFT/ωB97XD methods. Based on these results, the ability of CCA to sensitize Eu(III) and Tb(III) luminescence has been examined. The competitive excited state processes in the complexes - fluorescence, intersystem crossing (ISC) and phosphorescence, were analyzed depending on the environment, number of the ligands, Ln(III) ion type (Eu and Tb) and counteranion (Cl- and NO3-). It has been found that the environment altered the S1 state energy, oscillator strength, fluorescence lifetime as well as the S1 character - polar solution stabilized the S1(ππ*) state, whereas non-polar solution (gas phase, solid state) stabilized the S1(nπ*) state. The S1(nπ*) state was decisive for the efficient energy transfer as it suppressed the S1 emission of CCA and favored ISC or direct transfer to the emitting levels of Eu(III). The HCCA triplet (T1) state minimum energy (~2.7, ~2.6ZPE eV) and (ππ*) character were retained in Eu/Tb-CCA complexes regardless of the environment. The energy gap between the higher energy T1 donor state and the acceptor levels 5D1 of Eu(III) (~0.5 eV) and 5D4 of Tb(III) (~0.1 eV) provided optimal resonance conditions for effective energy transfer for Eu(III), but less probability for Tb(III). The nonradiative energy (CCA → Eu(III)) transfer rates and quantum luminescence yield for 2 and 3 were calculated by a strategy combining DFT geometries, INDO/S excitation energies and calculated Judd-Ofelt parameters. The excitation channel T1 → 5D0 through an exchange mechanism was predicted as the most probable one to populate the main emissive Eu-centered state in complexes 2 and 3. The more efficient luminescence of 3 than that of 2 was discussed and explained.


Communication in cancer care: discussing complementary and alternative medicine.
In recent years, there has been an increased interest in complementary and alternative medicine (CAM) use among people with cancer. Many are looking for informed advice and desire communication with their physicians about CAM use. Communication is crucial in establishing trust with patients, gathering information, addressing patient emotions, and assisting patients in decisions about care. The quality of communication in cancer care has been shown to affect patient satisfaction, decision making, patient distress and well-being, compliance, and even malpractice litigation. Communication is now recognized as a core clinical skill in medicine, including cancer care, and is important to the delivery of high-quality care. A communication approach that fosters a collaborative relationship that includes adequate information exchange, responds to emotional needs, and manages uncertainty can lead to informed decisions about CAM use. This type of communication can help facilitate an open discussion with cancer patients and their families about integrating CAM use into their care and help physicians fulfill their roles in caring, comforting, and healing, even when cure is not possible. In this article, the authors discuss a possible model of effective patient-physician communication about CAM use in cancer care based on a comprehensive overview of the literature.


Long-term remission in three patients with childhood-onset systemic lupus erythematosus.
Abstract Three cases of childhood-onset systemic lupus erythematosus (childhood SLE) with long-term remission are reported. These cases were not complicated with collagen diseases and had no SLE disease activity index scores either 3 or 5 years after onset. We suggest that some patients with childhood SLE may be able to abandon the maintenance therapy, and that careful observation is needed for each individual case. Uniform remission criteria based on clinical trials are needed.


Life table (survival) analysis to generate cumulative pregnancy rates in assisted reproduction: an alternative method of calculating the cumulative pregnancy rate in assisted reproduction technology.
The current method of calculating cumulative pregnancy rate can lead to an overestimation of treatment efficacy, especially over many cycles of assisted reproduction treatment. The choice of scale of passage of time should be dependent upon the types of treatment to be evaluated. The number of treatment cycles to which patients' effort and commitment is directly related may be appropriate where the chance of pregnancy is expected to be significantly higher than non-treatment for them. Limiting the calculation of cumulative pregnancy rate only to the second or third cycle within 1 or 2 years will ensure that most patients are included in the calculation. More research is needed to assess different methods and develop better variables for assessing the efficacy of infertility treatment that can be informative for patients over the course of their treatment.


Applicability of the Existing CVD Risk Assessment Tools to Type II Diabetics in Oman: A Review.
Patients with type II diabetes (T2DM) have an elevated risk for cardiovascular disease (CVD), and it is considered to be a leading cause of morbidity and premature mortality in these patients. Many traditional risk factors such as age, male sex, hypertension, dyslipidemia, glycemic control, diabetes duration, renal dysfunction, obesity, and smoking have been studied and identified as independent factors for CVD. Quantifying the risk of CVD among diabetics using the common risk factors in order to plan the treatment and preventive measures is important in the management of these patients as recommended by many clinical guidelines. Therefore, several risk assessment tools have been developed in different parts of the world for this purpose. These include the tools that have been developed for general populations and considered T2DM as a risk factor, and the tools that have been developed for T2DM populations specifically. However, due to the differences in sociodemographic factors and lifestyle patterns, as well as the differences in the distribution of various CVD risk factors in different diabetic populations, the external applicability of these tools on different populations is questionable. This review aims to address the applicability of the existing CVD risk models to the Omani diabetic population.


CLINICAL EVIDENCE OF THE MULTIFACTORIAL NATURE OF DIABETIC MACULAR EDEMA.
To report functional and morphologic outcomes, based on diabetic macular edema (DME) chronicity and baseline best-corrected visual acuity (BCVA), from a subanalysis of the fluocinolone acetonide for macular edema (FAME) trials. Patients were categorized by DME duration (nonchronic [ncDME] or chronic [cDME] DME) and three nonexclusive baseline vision strata. Anatomic and visual acuity VA outcomes of these cohorts were compared with treatment assignment. For all patients with ncDME and cDME who received sham control, 27.8% and 13.4%, respectively, gained ≥15 BCVA letters, whereas 22.3% and 34.0% of 0.2 μg/day fluocinolone acetonide (FAc)-treated patients, respectively, gained ≥15 BCVA letters. Among patients with ncDME who received sham control, as baseline vision decreased, the percentage gaining ≥15 BCVA letters increased; however, among those with cDME, the percentage gaining ≥15 BCVA letters did not change as baseline vision decreased. Conversely, among 0.2 μg/day FAc-treated patients, the percentage gaining ≥15 BCVA letters increased with decreasing baseline vision, regardless of DME chronicity. Anatomical outcomes were similar within treatment arms, regardless of the DME duration. Patients with cDME and poor baseline vision who were exposed to low-dose FAc experienced BCVA improvements that were not observed in a similar group from the sham-control arm. These data support the multifactorial pathogenesis of cDME.


Specialist nectar-yeasts decline with urbanization in Berlin.
Nectar yeasts are common inhabitants of insect-pollinated flowers but factors determining their distribution are not well understood. We studied the influence of host identity, environmental factors related to pollution/urbanization, and the distance to a target beehive on local distribution of nectar yeasts within Robinia pseudoacacia L. and Tilia tomentosa Moench in Berlin, Germany. Nectar samples of six individuals per species were collected at seven sites in a 2 km radius from each target beehive and plated on YM-Agar to visualise the different morphotypes, which were then identified by sequencing a section of the 26S rDNA gene. Multivariate linear models were used to analyze the effects of all investigated factors on yeast occurrence per tree. Yeast distribution was mainly driven by host identity. The influence of the environmental factors (NO2, height of construction, soil sealing) strongly depended on the radius around the tree, similar to the distance of the sampled beehive. Incidence of specialist nectar-borne yeast species decreased with increasing pollution/urbanization index. Given that specialist yeast species gave way to generalist yeasts that have a reduced dependency on pollinators for between-flower dispersal, our results indicate that increased urbanization may restrict the movement of nectar-specialized yeasts, via limitations of pollinator foraging behavior.


Features of YouTube™ videos produced by individuals who self-identify with borderline personality disorder.
Many individuals use YouTube™ to seek out information and share first-hand experiences about mental illnesses, as well as to gain a sense of community. YouTube™ use may be especially appealing when offline supports are lacking or difficult to access, and when there is a fear of stigmatisation. Borderline personality disorder (BPD), also referred to as emotionally unstable personality disorder (EUPD), is a complex and often stigmatised mental-health disorder. The primary objective of this study was to describe the dominant messages that individuals who self-identify with the diagnosis of BPD present through YouTube™ videos. The content analysis method was used to review 349 first-person YouTube™ uploads. Videos were coded for information regarding video and vlogger characteristics, video type, vlogger motivation and video content. Associations between video features including upload date and style and vlogger experience and motivation were examined. Findings indicate that more people who self-identify as being diagnosed with BPD are creating YouTube™ videos about their experiences, and these videos have shifted over time from being mostly anonymous multimedia productions to being monologues where the vlogger speaks directly to their audience. Discussions related to DSM-5 symptoms, treatment, effective coping and hope for the future are elements found in the uploads. The nature and content of BPD first-person YouTube™ uploads has increased and changed over time. Increased awareness of these changes may assist mental-health practitioners to support clients and direct them to explore uploads that offer hope and promote engagement in help-seeking and effective coping behaviours.


Total Structure Determination of Au16(S-Adm)12 and Cd1Au14(S tBu)12 and Implications for the Structure of Au15(SR)13.
Ultrasmall nanoclusters (e.g., Au15(SR)13) are crucial in not only real applications such as bioapplication but also in understanding the structure transition from gold complexes to gold nanoclusters. However, the determination of these transition-sized gold nanoclusters has long been a major challenge. In this work, two new nanoclusters in the transition regime, including the thus far smallest thiolated alloy nanocluster Cd1Au14(S tBu)12 and the homogold nanocluster Au16(S-Adm)12, are obtained and their atomic structures are fully determined by single crystal X-ray diffraction. Moreover, based on the structures of Cd1Au14(SR)12 and Au16(SR)12, we perform DFT calculations to predict the structure of the "transformation" nanocluster, Au15 (Au15(SR)12- and Au15(SR)13). Overall, this work bridges the gaps between gold complexes and nanoclusters.


Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: Case report of a rare lesion with novel genetic mutation.
Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare primary cancer of the thyroid. This tumor is analogous to other primary tumors of the salivary glands, breast, pancreas, and esophagus. We present a case of this rare tumor with characteristic clinical features, ultrasound images, cytopathology, histopathology, and a heretofore undocumented somatic gene mutation. Additionally, we provide a succinct review of the controversial literature for this uncommon lesion.


Metabolic syndrome in childhood obesity.
We determined the frequency of metabolic risk factors and the prevalence of Metabolic Syndrome in childhood obesity. 186 obese children (97 females and 89 males), aged 11.2 +/- 2.8 (6-16) years and 98 healthy children (46 females and 52 males), aged 10.9 +/- 3.2 (6-16) years were recruited for the study, as study and control groups, respectively. Subjects were evaluated for anthropometry, blood pressure (BP) and biochemical cardiovascular risk factors. Metabolic syndrome was defined in presence of > or = 3 of the following: (i) fasting triglyceride > or = 100 mg/dL; (ii) high density lipoprotein-cholesterol < 50 mg/dL, except in boys aged 15 to 19 years, in whom the cut-off point was 45 mg/dL; (iii) fasting glucose > or = 110 mg/dL; (iv) waist circumference > 75th percentile for age and gender and (v) systolic BP > 90th percentile. We found that 144 (77.4%) children in the obese group had one, two or more cardiovascular risk factors. Using a pediatric definition, the prevalence of metabolic syndrome was 2.1%. In the control group, the clustering of one, two and three risk factors was very rare. Childhood obesity is associated with increased frequency of cardiovascular risk factors and metabolic syndrome.


Near-resonant vibration-to-vibration energy transfer in the NO+-N2 collisions.
First principles model calculations of the vibration-to-vibration (VV) energy transfer (ET) processes NO(+)(nu=1)+N(2)(nu=n-1)-->NO(+)(nu=0)+N(2)(nu=n)+(28.64n-14.67) cm(-1) and NO(+)(nu=n)+N(2)(nu=0)-->NO(+)(nu=n-1)+N(2)(nu=1)+(32.52(n-1)+13.97) cm(-1) for n=1-3 in the 300-1000 K temperature range are performed. The VV ET probability is computed for three mechanisms: (1) The charge on NO(+) acting on the average polarizability of N(2) induces a dipole moment in N(2) which then interacts with the permanent dipole moment of NO(+) to mediate the energy transfer. (2) The charge on NO(+) acting on the anisotropic polarizability of N(2) induces a dipole moment in N(2) which then interacts with the permanent dipole moment of NO(+) to mediate the energy transfer. (3) The dipole moment of NO(+) interacts with the quadrupole moment of N(2) to mediate the energy transfer. Because the probability amplitudes of the second and third mechanisms add coherently the ET probability for these two mechanisms is given as a single number. The probability of energy transfer per collision is in the 5 x 10(-3) range. The results of this calculation are compared with the available experimental data. This calculation should help quantify the role of NO(+) in the energy budget of the upper atmosphere.


Identification of Nipaecoccus (Hemiptera: Coccomorpha: Pseudococcidae) species in the United States, with descriptions of Nipaecoccus bromelicola sp. n. and the male of N. floridensis Beardsley.
The adult female and male of Nipaecoccus bromelicola sp. n. are described, based on specimens on bromeliads in Californian nurseries and intercepted from Mexico and Guatemala, countries believed to be within the native range of this species. The male of N. floridensis Beardsley is also described, illustrated, and diagnosed from known congeners. An identification key to adult females of Nipaecoccus species recorded from the United States (including its overseas territories) is presented. Molecular characterizations based on COI are provided for N. bromelicola, N. floridensis, N. nipae and N. viridis.


Association of polypharmacy at hospital discharge with nutritional intake, muscle strength, and activities of daily living among older patients undergoing convalescent rehabilitation after stroke.
Matsumoto A, Yoshimura Y, Shimazu S, Nagano F, Bise T, Kido Y, Shiraishi A, Sunahara T. Association of polypharmacy at hospital discharge with nutritional intake, muscle strength, and activities of daily living among older patients undergoing convalescent rehabilitation after stroke. Jpn J Compr Rehabil Sci 2022; 13: 41-48. To investigate the association between polypharmacy at discharge and nutritional intake, muscle strength, and activities of daily living (ADL) among older patients undergoing convalescent rehabilitation after stroke. This cross-sectional study involved hospitalized patients aged 65 or older who underwent convalescent rehabilitation after stroke. Polypharmacy was defined as the use of six or more medications. Study outcomes included energy intake, protein intake, handgrip strength (HG), and motor subscore of Functional Independence Measure (FIM-motor) at hospital discharge. Multiple linear regression analysis was used to examine the association between polypharmacy at discharge and outcomes. Of 361 eligible patients (mean [±SD] age, 78.3 ± 7.7 years; 49.3% male), 62.9% had polypharmacy. Multiple regression analysis revealed that polypharmacy at discharge was negatively associated with energy intake (β = -0.122, p = 0.003), protein intake (β = -0.133, p = 0.013), HG (β = -0.070, p = 0.022), and FIM-motor score (β = -0.069, p = 0.031) at discharge. The impact of polypharmacy should be considered when designing nutritional management strategies for rehabilitation patients to maximize rehabilitation outcomes.


A mechanism-based pharmacokinetic model of fenofibrate for explaining increased drug absorption after food consumption.
Oral administration of drugs is convenient and shows good compliance but it can be affected by many factors in the gastrointestinal (GI) system. Consumption of food is one of the major factors affecting the GI system and consequently the absorption of drugs. The aim of this study was to develop a mechanistic GI absorption model for explaining the effect of food on fenofibrate pharmacokinetics (PK), focusing on the food type and calorie content. Clinical data from a fenofibrate PK study involving three different conditions (fasting, standard meals and high-fat meals) were used. The model was developed by nonlinear mixed effect modeling method. Both linear and nonlinear effects were evaluated to explain the impact of food intake on drug absorption. Similarly, to explain changes in gastric emptying time for the drug due to food effects was evaluated. The gastric emptying rate increased by 61.7% during the first 6.94 h after food consumption. Increased calories in the duodenum increased the absorption rate constant of the drug in fed conditions (standard meal = 16.5%, high-fat meal = 21.8%) compared with fasted condition. The final model displayed good prediction power and precision. A mechanistic GI absorption model for quantitatively evaluating the effects of food on fenofibrate absorption was successfully developed, and acceptable parameters were obtained. The mechanism-based PK model of fenofibrate can quantify the effects of food on drug absorption by food type and calorie content.


Cervical dystonia associated with tumors of the posterior fossa.
Cervical dystonia was associated with posterior fossa tumors in three patients. The onset of dystonia paralleled the appearance of other focal neurologic signs. All patients had extraaxial tumors located in the cerebellopontine angle that were removed via suboccipital approaches. The tumors were identified as schwannomas arising from the glossopharyngeal nerve and from the vagus/accessory nerves; and a meningioma. Postoperatively, the cervical dystonia improved markedly during a period of 8 years in one patient, and it remitted completely within 1 year in another patient. In the third patient, cervical dystonia persisted. The combination of the clinical findings and the temporal relationship of their appearance suggest a causal association between the posterior fossa tumors and cervical dystonia in three cases. Possible pathogenic mechanisms are reviewed.


Clinical approach to diagnosis of syncope. An Overview.
Effective management of the syncope patient is critically dependent on excluding conditions in which altered consciousness is not due to syncope (e.g., seizure and sleep disorders) then establishing the basis for syncopal symptoms. The initial diagnostic step in syncope patients is differentiation of those individuals with normal cardiovascular status from those with structural heart disease. In the former, tilt-table testing and related studies of autonomic nervous system function are usually the most productive direction in which to proceed. In patients with structural heart disease, a functional assessment of the suspected structural disturbance (i.e., hemodynamic, angiographic, imaging as appropriate) and evaluation for susceptibility to symptomatic arrhythmias by monitoring or conventional electrophysiologic testing is appropriate. Autonomic function testing should follow if the diagnosis remains unclear. In only a few instances should specialized neurologic studies be undertaken as an initial step. The ultimate objective is always to obtain a sufficiently strong correlation between syncopal symptoms and detected abnormalities to feel confident in the diagnosis, permit an accurate assessment of prognosis, and develop an appropriate treatment plan.


Learning temporal sequences from examples in a local feedback neural network.
Statistical-mechanical techniques are used to study temporal sequence association in a local feedback neural network consisting of an input layer of context units and a single output unit. Each context unit has a feedback connection onto itself such that it accumulates an exponentially decaying moving average or trace of previous inputs to that unit. The formation of these traces allows the network to extract temporal information over an interval delta, where delta = 1/magnitude of ln gamma and gamma is the decay-rate of the moving average. The particular problem of learning a rule from examples is considered where the rule is generated by a teacher local feedback network. The replica method and other mean-field theory techniques are used to determine how the resulting generalization error of the network varies as a function of sequence length M and decay-rate gamma.


u-PA expression in benign, borderline and malignant ovarian tumors.
The malignant potential of solid tumors is related to their ability to invade adjacent tissue and to metastasize. The plasminogen activation system is one of the critical factors in tumor progression since it is involved in tumor invasion and metastasis. This study was performed to examine the expression of u-PA in benign, borderline and malignant tumors of the ovary by immunohistochemical evaluation on formalin-fixed, paraffin-embedded specimens applying monoclonal antibody 3689 directed to the b-chain of u-PA. Normal epithelial cells of the ovary (n = 5) showed no staining of u-PA but some stromal cells were slightly stained. Invasive carcinomas (n = 16) and borderline tumors (n = 15) showed a moderate to strong diffuse cytoplasmic staining. Benign tumors (n = 20) showed a variety of staining. The observation of randomly positive u-PA stromal cells is noteworthy. The percentage of u-PA-positive tumors was higher in carcinomas than in other tumors. There was no correlation with other known risk factors of malignancy such as differentiation, stage or type of tumor. In conclusion there are noticeable differences in u-PA expression among ovarian tumors and u-PA increase in ovarian tumors can be attributed to an increased diffuse cytoplasmic content in the neoplastic epithelial cells.


HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells.
In this study we found that Tat protected vincristine-treated Kaposi's sarcoma cells from apoptosis and from down-regulation of several anti-apoptotic genes such as AKT-1, AKT-2, BCL2, BCL-XL, and insulin-like growth factor I and induced the de novo expression of the interleukin-3 gene. Moreover, we found that Tat enhanced phosphorylation of AKT and BAD proteins. The inhibition of phosphatidylinositol 3-kinase with two unrelated pharmacological inhibitors, wortmannin and LY294002, abrogated both the anti-apoptotic effect and the phosphorylation of AKT induced by Tat. After treatment with Tat, the AKT enzymatic activity showed a biphasic increase: an early activation (15 min), independent from protein synthesis; and a delayed activation (24 h), which was significantly decreased upon blockage of protein synthesis. Experiments with a function blocking anti-vascular endothelial cell growth factor receptor-2 antibody suggested that both the early and delayed AKT activation and the protection from apoptosis were triggered by the interaction of Tat with vascular endothelial cell growth factor receptor-2. Moreover, experiments with function-blocking antibodies directed against insulin-like growth factor I/insulin-like growth factor I receptor or interleukin-3 indicated their involvement in the delayed activation of AKT and their contribution to the anti-apoptotic effect of Tat on vincristine-treated Kaposi's sarcoma cells.


Integrin ανβ3 modulates lipopolysaccharide-induced hyperpermeability in cardiac microvascular endothelial cells.
Previous studies suggest an association of cardiac microvascular endothelial cells (CMECs) hyperpermeability with sepsis-related cardiac injury. Our results showed that CMECs permeability was dependent upon concentration and time of lipopolysaccharides (LPS) stimulation. Integrin ανβ3 expression decreased after LPS stimulation. Pretreatment with anti-integrin ανβ3 antibody enhanced LPS-induced hyperpermeability. Upregulation of integrin ανβ3 decreased LPS-induced hyperpermeability. F-actin remodeling was enhanced after LPS stimulation and was inhibited by up-regulation of integrin ανβ3. Inhibition of Src or Rac1 reduced CMECs permeability after LPS stimulation, but there were no differences in the phosphorylation of Src and Rac1 when over-expressing or blocking integrin β3. After pretreatment with Src or Rac1 inhibitor, no significant difference was found in the expression of integrin ανβ3 in LPS-induced CMECs. These finding suggested that integrin ανβ3 overexpression decreased LPS-stimulated CMECS permeability by inhibition of cytoskeletal remodeling, but the mechanism might not be mediated via Src/Rac1 signaling.


Electrochemical Strategy for Low-Cost Viral Detection.
Sexually transmitted infections, including the human immunodeficiency virus (HIV) and the human papillomavirus (HPV), disproportionally impact those in low-resource settings. Early diagnosis is essential for managing HIV. Similarly, HPV causes nearly all cases of cervical cancer, the majority (90%) of which occur in low-resource settings. Importantly, infection with HPV is six times more likely to progress to cervical cancer in women who are HIV-positive. An inexpensive, adaptable point-of-care test for viral infections would make screening for these viruses more accessible to a broader set of the population. Here, we report a novel, cost-effective electrochemical platform using gold leaf electrodes to detect clinically relevant viral loads. We have combined this platform with loop-mediated isothermal amplification and a CRISPR-based recognition assay to detect HPV. Lower limits of detection were demonstrated down to 104 total copies of input nucleic acids, which is a clinically relevant viral load for HPV DNA. Further, proof-of-concept experiments with cervical swab samples, extracted using standard extraction protocols, demonstrated that the strategy is extendable to complex human samples. This adaptable technology could be applied to detect any viral infection rapidly and cost-effectively.


[Mechanism and experimental verification of "Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus" combination in treatment of acute gouty arthritis based on network pharmacology].
Based on network pharmacology, the mechanism of Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus(PL) combination against acute gouty arthritis(AGA) was explored and preliminarily verified by animal experiment. The chemical components and corresponding targets of PL were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The active components with oral bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were screened based on literature, and the related protein targets were collected. Then the protein targets were standardized with the help of UniProt database. The AGA-related targets were searched from GeneCards, NCBI, and DrugBank. The common targets of the disease and the medicinals were yielded by FunRich V3, and the protein-protein interaction(PPI) network was constructed to screen the key targets, followed by Gene Ontology(GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the key targets. Afterwards, some of the key targets were verified by sodium urate crystal-induced AGA mouse model. A total of 25 active components and 287 targets of PL, 811 targets of AGA, and 88 common targets were screened out. PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), and interleukin-1β(IL-1β) may be the core targets of PL in the treatment of AGA. The key targets were mainly involved in 566 GO terms(P<0.05), including multiple biological processes such as inflammatory response and immune response. Moreover, they were related to 116 KEGG pathways and these pathways were involved in inflammation and immunity, mainly including NOD-like receptor signaling pathway and TNF signaling pathway. Animal experiment confirmed that PL can alleviate ankle swelling, improve abnormal gait, and down-regulate the protein expression of TNF-α, IL-6, and IL-1β in AGA mice, indicating that PL can treat AGA through TNF-α, IL-6, and IL-1β and the feasibility of network pharmacology to predict drug targets. This study preliminarily discussed the key targets and biological signaling pathways involved in the treatment of AGA with PL combination, which reflected the multi-pathway and multi-target action characteristics of Chinese medicine. Moreover, this study laid a scientific basis for research on the treatment of AGA with PL combination, as well as the mechanism of action.


Sexual activity, sexual and partnership satisfaction in ageing men--results from a German representative community study.
Age-related changes in men have only recently received widespread scientific attention. Although a reduction in sexual interest and satisfaction are common in the 'ageing male', little is known about sexual activity and satisfaction in the general population. We therefore investigated age-related changes in men's sexual activity, and their sexual and partnership satisfaction. We also tried to identify psychosocial determinants of sexual and partnership satisfaction. A representative community-based sample of 1299 men between 18 and 92 years was interviewed, based on a set of standardised questionnaires, on life satisfaction, physical complaints, personality and interpersonal problems. Comparing the 3 age groups (18-40, 41-60, 61-92 years), we found the proportion of sexually active men to be fairly constant up to the age of 60 (84-85%); while above the age of 60, the proportion declined to 51%. The proportion of men without a partner (32% of the total sample) who were sexually active was lower; in this group sexual activity started to decline between 41 and 60 years (from 74% to 56%), and comparably fewer older men without a partner were sexually active (17%). We also found an age-related decline in sexual satisfaction, and a slight increase in partnership satisfaction. Sexual activity was a major determinant of sexual satisfaction; sexual and partnership satisfaction were compromised in men who were dissatisfied with their health, and reported somatoform complaints and interpersonal problems. Our results emphasise the contribution of psychosocial factors to declining sexual activity and satisfaction. Future studies in the ageing male should take account of existence and quality of a partnership, and recent sexual activity.


[The effectiveness of eradication therapy of the 1st line of Helicobacter pylori infection in patients with type 2 diabetes mellitus].
Evaluation of the efficacy and safety of eradication therapy of infection Helicobacter pylori in patients with H. pylori- associated pathology of the upper gastrointestinal tract and concomitant type 2 diabetes mellitus (DM). The prospective randomized study involving 180 patients (87 men and 93 women) with H. pylori- associated pathology of the upper gastrointestinal tract was carried out. The patients were divided into four groups of 45 people: 1 patients without diabetes who received the classic triple eradication therapy; 2 patients with type 2 DM who received the classic triple eradication therapy; 3 patients without DM who underwent quadrotherapy with bismuth preparations; 4 patients with type 2 DM who underwent quadrotherapy with bismuth preparations. Eradication therapy was carried out for 14 days. Evaluation of the effectiveness of eradication using a breath test was carried out 4 weeks after completion of the course of treatment. Eradication success was assessed separately for ITT and PP analyzes. The effectiveness of classical triple eradication therapy in patients with concomitant type 2 DM is 64.4% in the ITT group and 69.05% in the PP: quadrotherapy 73.34 and 80.49%, respectively. The effectiveness of first line eradication therapy is higher in patients without DM compared with groups of patients with concomitant type 2 DM: ITT 83.33%, PP 88.23% and ITT 68.89%, PP 74.70%, respectively. The incidence of side effects in patients with type 2 DM: with the use of classical triple therapy 22.23%, quadrotherapy 31.12%. The data of the study of the efficacy and safety of line I eradication therapy make it possible to recommend the four-component therapy based on bismuth for use in clinical practice, especially in patients with DM.


Long-term outcome in children with chronic hepatitis B: a 24-year observation period.
Chronic hepatitis B seems to manifest as mild disease in children and young adults. However, data regarding the long-term course of hepatitis B in untreated and interferon-treated children are still scarce. This study investigates the long-term outcome of disease in a large series of untreated and treated children with hepatitis B virus (HBV) infection. Clinical, biochemical, virological, and histological features were evaluated in children (age range, 2-18 years) with chronic HBV infection who did not have concomitant chronic systemic diseases other than HBV infection and who were admitted to the liver unit in the Department of Pediatrics at University "Frederico II" (Naples, Italy) during the period 1981-2005. One hundred eight consecutive patients observed for up to 24 years were studied. During the observation period, 67 children remained untreated, and 41 were treated with interferon-alpha. After a median period of observation of 12.1 years (range, 5-23 years), hepatitis B early antigen loss and serum HBV DNA clearance occurred in 43 untreated patients (69.3%) who were hepatitis B early antigen positive at study entry and in 33 treated children (80%; the P value is not statistically significant). In addition, 6 untreated patients (9.7%) and 4 treated patients (9.7%) became anti-HBs [corrected] positive at the end of the follow-up period. Histological assessment, evaluated for 57 children, showed mild-to-moderate disease in 91.2% of cases of HBV infection. No patient developed end-stage liver disease or hepatocellular carcinoma. Children with chronic HBV infection are symptom free, with morphologically mild liver disease. Considering that the overall long-term outcomes did not differ between treated and untreated patients, the real impact of therapy on the long-term course of HBV infection remains to be established. Additional studies are needed to confirm our conclusions.


Comparison of Tono-Pen AVIA intraocular pressure measurements performed at limbus with central corneal Tono-Pen AVIA intraocular pressure.
To compare Tono-Pen AVIA (TPA) intraocular pressure (IOP) measurements performed at the limbus with central corneal Tono-Pen AVIA (TPA) intraocular pressure. Fifty-one patients attending our outpatient department with a best corrected visual acuity of ≥ 20/40, no corneal disease, and no astigmatism greater than 1.5 diopters underwent routine ophthalmological examination. Patients with ametropia greater than or equal to ± 5 diopters, a history of recent contact lens wear, and central corneal thickness of <480 µm or >550 µm were excluded from the study. IOP was recorded first in the corneal center, followed by tonometry measurements obtained from the temporal, nasal, superior, and inferior limbus using TPA. IOP measurements were compared using the paired t test. Correlation was derived by Pearson correlation coefficient, and regression equations were derived. The mean age of patients in our study was 43.86 ± 15.39 years. The mean TPA IOP from the central cornea was 16.59 ± 3.75 mm Hg. There was a statistically significant difference between Tono-Pen IOP from the central cornea and that recorded from all 4 limbal positions (P < 0.001). There was a positive correlation between the central and the limbal IOP obtained with Tono-Pen. Correlation was maximum for the temporal limbus. Limbal TPA IOP is significantly higher than central TPA IOP. There remains a good correlation between central and limbal IOP. This was found to be greatest for the temporal limbus.


Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice.
Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant.


Species richness and endemism in the native flora of California.
California's vascular flora is the most diverse and threatened in temperate North America. Previous studies of spatial patterns of Californian plant diversity have been limited by traditional metrics, non-uniform geographic units, and distributional data derived from floristic descriptions for only a subset of species. We revisited patterns of sampling intensity, species richness, and relative endemism in California based on equal-area spatial units, the full vascular flora, and specimen-based distributional data. We estimated richness, weighted endemism (inverse range-weighting of species), and corrected weighted endemism (weighted endemism corrected for richness), and performed a randomization test for significantly high endemism. Possible biases in herbarium data do not obscure patterns of high richness and endemism at the spatial resolution studied. High species richness was sometimes associated with significantly high endemism (e.g., Klamath Ranges) but often not. In Stebbins and Major's (1965) main endemism hotspot, Southwestern California, species richness is high across much of the Peninsular and Transverse ranges but significantly high endemism is mostly localized to the Santa Rosa and San Bernardino mountains. In contrast, species richness is low in the Channel Islands, where endemism is significantly high, as also found for much of the Death Valley region. Measures of taxonomic richness, even with greater weighting of range-restricted taxa, are insufficient for identifying areas of significantly high endemism that warrant conservation attention. Differences between our findings and those in previous studies appear to mostly reflect the source and scale of distributional data, and recent analytical refinements.


A unilateral teratoid Wilms' tumor with raised serum alpha-fetoprotein level.
Teratoid Wilms' tumor with raised serum alpha-fetoprotein level is an unusual type of tumor. We, here, describe a twelve month old boy presenting with lumbar mass. Clinical features, radiological findings, gross examination, and histomorphological features are studied, and various differential diagnoses like Wilms' tumor with heterologous elements, intrarenal teratoma and metastatic germ cell tumor are taken into consideration.


Molecular and fluorescence in situ hybridization characterization of the breakpoints in 46 large supernumerary marker 15 chromosomes reveals an unexpected level of complexity.
Supernumerary marker chromosomes (SMCs) of chromosome 15, designated "SMC(15)s," are the most common SMC in humans, accounting for as much as 60% of all those observed. We report the characterization of 46 large SMC(15)s, using both fluorescence in situ hybridization and polymerase chain reaction analysis within and distal to the Prader-Willi/Angelman syndrome critical region (PWACR). Our aim was to establish detailed information on origin, content, and breakpoints, to address the formation of SMC(15)s, and to facilitate genotype-phenotype correlations. For all patients in whom we were able to establish the parental origin, the SMC(15)s were maternally derived. Two patients were observed who had familial SMC(15)s, both inherited from the mother; however, in all remaining patients for whom parental samples were available, the SMC(15)s were shown to have arisen de novo. With one exception, all the SMC(15)s were shown to include the entire PWACR. Detailed investigations of the distal breakpoints categorized the SMC(15)s into two groups. Group A, representing approximately two-thirds of the SMC(15)s, had a breakpoint beyond the standard distal PWS/AS deletion breakpoint BP3, at a position close to the microsatellite marker D15S1010 and the bacterial artificial chromosome 10I10. The group B SMC(15)s were shorter, with more variable breakpoints located around BP3. The majority of the SMC(15)s were shown to have asymmetrical breakpoints, with the two inverted arms of the SMC being unequal in length. Our study revealed an unexpected level of complexity and heterogeneity among SMC(15)s that is not seen in other chromosome 15 rearrangements, such as deletions and duplications. This suggests that multiple mechanisms are involved in the formation of large SMC(15)s.


Design and synthesis of a novel class of constrained tricyclic pyrrolizidinone carboxylic acids as carbapenem mimics.
A series of tricyclic pyrrolizidinone carboxylic acids harboring an angular methano group were synthesized as mimics of carbapenems and carbapenams. A key reaction involved a novel intramolecular cyclopropanation mediated by a trimethylstannylmethyl group and an adjacent iminium ion. Enolate chemistry on a tricyclic lactam ring unit allowed the introduction of various substituents. Further elaboration afforded tricyclic pyrrolidinone carboxylic acids, which were found to be inactive as inhibitors against a panel of bacterial strains. However, the antibacterial activity of ceftazidine was enhanced in the presence of the tricyclic analogues.


Development of robust finite element models of porcine tibiofemoral joints loaded under varied flexion angles and tibial freedoms.
The successful development of cartilage repair treatments for the knee requires understanding of the biomechanical environment within the joint. Computational finite element models play an important role in non-invasively understanding knee mechanics, but it is important to compare model findings to experimental data. The purpose of this study was to develop a methodology for generating subject-specific finite element models of porcine tibiofemoral joints that was robust and valid over multiple different constraint scenarios. Computational model predictions of two knees were compared to experimental studies on corresponding specimens loaded under several different constraint scenarios using a custom designed experimental rig, with variations made to the femoral flexion angle and level of tibial freedom. For both in vitro specimens, changing the femoral flexion angle had a marked effect on the contact distribution observed experimentally. With the tibia fixed, the majority of the contact region shifted to the medial plateau as flexion was increased. This did not occur when the tibia was free to displace and rotate in response to applied load. These trends in contact distribution across the medial and lateral plateaus were replicated in the computational models. In an additional model with the meniscus removed, contact pressures were elevated by a similar magnitude to the increase seen when the meniscus was removed experimentally. Overall, the models were able to capture specimen-specific trends in contact distribution under a variety of different loads, providing the potential to investigate subject-specific outcomes for knee interventions.


Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer-Predisposing Mutations in Pheochromocytomas and Paragangliomas.
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes.Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes. Methylation profiling, metabolite assessment and additional analyses were also performed in selected cases.Results: One of the 11 tumors was found to carry a known cancer-predisposing somatic mutation in IDH1 A variant in GOT2, c.357A>T, found in a patient with multiple tumors, was associated with higher tumor mRNA and protein expression levels, increased GOT2 enzymatic activity in lymphoblastic cells, and altered metabolite ratios both in tumors and in GOT2 knockdown HeLa cells transfected with the variant. Array methylation-based analysis uncovered a somatic epigenetic mutation in SDHC in a patient with multiple pheochromocytomas and a gastrointestinal stromal tumor. Finally, a truncating germline IDH3B mutation was found in a patient with a single paraganglioma showing an altered α-ketoglutarate/isocitrate ratio.Conclusions: This study further attests to the relevance of the Krebs cycle in the development of PCC and PGL, and points to a potential role of other metabolic enzymes involved in metabolite exchange between mitochondria and cytosol. Clin Cancer Res; 23(20); 6315-24. ©2017 AACR.


Pulmonary hypertension: role of combination therapy.
Over the past decade different effective treatment options for use in pulmonary arterial hypertension (PAH) have been developed. Due to multiple pathophysiological pathways in PAH and unsatisfactory overall results with the use of monotherapy in a substantial number of PAH patients, there is a pharmacological rationale for combination therapy. The currently approved substances target the prostacyclin, the endothelin and the NO (nitric oxide) -pathways. Those agents have shown a varying degree of improvement in different categories of PAH associated limitations like hemodynamics, exercise capacity, functional class, and quality of life. However, clinical worsening over time is still significant in most patients irrespective of the treatment utilized. The recently published ESC-ERS (European Society of Cardiology and European Respiratory Society) guidelines on pulmonary hypertension suggest the use of combination therapy in patients who do not respond adequately to monotherapy.This article reviews and critically discusses the available data on combination therapy in PAH.


The Interactions of Aquaporins and Mineral Nutrients in Higher Plants.
Aquaporins, major intrinsic proteins (MIPs) present in the plasma and intracellular membranes, facilitate the transport of small neutral molecules across cell membranes in higher plants. Recently, progress has been made in understanding the mechanisms of aquaporin subcellular localization, transport selectivity, and gating properties. Although the role of aquaporins in maintaining the plant water status has been addressed, the interactions between plant aquaporins and mineral nutrients remain largely unknown. This review highlights the roles of various aquaporin orthologues in mineral nutrient uptake and transport, as well as the regulatory effects of mineral nutrients on aquaporin expression and activity, and an integrated link between aquaporins and mineral nutrient metabolism was identified.


Advanced Electrocardiography Identifies Left Ventricular Systolic Dysfunction in Non-Ischemic Cardiomyopathy and Tracks Serial Change over Time.
Electrocardiogram (ECG)-based detection of left ventricular systolic dysfunction (LVSD) has poor specificity and positive predictive value, even when including major ECG abnormalities, such as left bundle branch block (LBBB) within the criteria for diagnosis. Although machine-read ECG algorithms do not provide information on LVSD, advanced ECG (A-ECG), using multiparameter scores, has superior diagnostic utility to strictly conventional ECG for identifying various cardiac pathologies, including LVSD. We evaluated the diagnostic utility of A-ECG in a case-control study of 40 patients with LVSD (LV ejection fraction < 50% by echocardiography), due to non-ischemic cardiomyopathy (NICM), and 39 other patients without LVSD. Diagnostic sensitivity and specificity for LVSD were determined after applying a previously validated probabilistic A-ECG score for LVSD to stored standard (10 s) clinical 12L ECGs. In 25 of the NICM patients who had serial ECGs and echocardiograms, changes in the A-ECG score versus in echocardiographic LV ejection fraction were also studied to determine the level of agreement between the two tests. Analyses by A-ECG had a sensitivity of 95% for LVSD (93% if excluding N = 11 patients with LBBB) and specificity of 95%. In the 29 NICM patients without LBBB who had serial ECGs, sensitivity improved to 97% when all ECGs were considered. By comparison, human readers in a busy clinical environment had a sensitivity of 90% and specificity of 63%. A-ECG score trajectories demonstrated improvement, deterioration or no change in LVSD, which agreed with echocardiography, in 76% of cases (n = 25). A-ECG scoring detects LVSD due to NICM with high sensitivity and specificity. Serial A-ECG score trajectories also represent a method for inexpensively demonstrating changes in LVSD. A-ECG scoring may be of particular value in areas where echocardiography is unavailable, or as a gatekeeper for echocardiography.


Risk Factors for Postoperative Infections Following Appendectomy of Complicated Appendicitis: A Meta-analysis and Retrospective Single-institutional Study.
Patients with complicated appendicitis have an increased risk for postoperative infections. Potential risk factors for postoperative infections through a meta-analysis and retrospective chart review are discussed. A meta-analysis consisting of 35 studies analyzing complicated appendicitis treated with an appendectomy noting at least 1 postoperative infection was performed. A retrospective review was then conducted in patients diagnosed with complicated appendicitis after appendectomy. Of 5326 patients in total, 15.4% developed postoperative infections. Laparoscopic surgery and perioperative hyperoxygenation were found to be protective factors for the development of infection. Retrospectively, 53.2% of patients presented with complicated appendicitis. Patients with complicated appendicitis were more likely to be older in age and have an increased length of stay. Patient demographics, operative time, and comorbid status had no effect on postoperative infection or readmission rate. Physicians should strongly consider minimally invasive techniques to treat all cases of complicated appendicitis irrespective of comorbidities, age, sex, or body mass index.


TIGIT-Fc Promotes Antitumor Immunity.
T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is a checkpoint receptor that mediates both T-cell and natural killer (NK)-cell exhaustion in tumors. An Fc-TIGIT fusion protein was shown to induce an immune-tolerance effect in a previous report, but the relevance of the TIGIT-Fc protein to tumor immunity is unknown. Here, we found that TIGIT-Fc promotes, rather than suppresses, tumor immunity. TIGIT-Fc treatment promoted the effector function of CD8+ T and NK cells in several tumor-bearing mouse models. TIGIT-Fc treatment resulted in potent T cell- and NK cell-mediated tumor reactivity, sustained memory-induced immunity in tumor rechallenge models, enhanced therapeutic effects via an antibody against PD-L1, and induction of Th1 development in CD4+ T cells. TIGIT-Fc showed a potent antibody-dependent cell-mediated cytotoxicity effect but had no intrinsic effect on tumor cell development. Our findings elucidate the role of TIGIT-Fc in tumor immune reprogramming, suggesting that TIGIT-Fc treatment alone or in combination with other checkpoint receptor blockers is a promising anticancer therapeutic strategy.


Correlation of some biochemical parameters with clinical features of protein energy malnutrition.
The authors report on a study correlating the laboratory findings of children with protein energy malnutrition (PEM) with their clinical presentations. Forty-nine cases of marasmus, 17 of kwashiorkor and 28 of marasmic-kwashiorkor, as well as 20 controls, were studied and monitored in hospital. Fasting plasma samples obtained on days 2, 14 and 21 were analyzed for total proteins, albumin, triglycerides and cholesterol. Blood glucose and haemoglobin were also determined. The total plasma proteins and albumin were significantly lower in all the malnourished cases compared to the controls, with marked hypoproteinaemia among those cases with kwashiorkor. Plasma triglycerides were significantly lower in the malnourished group, when compared to controls. With dietary treatment, plasma triglycerides rose significantly accompanied with regression in liver size. Four out of the 17 children with kwashiorkor, had died; they had the lowest serum albumin concentrations of all the cases studied. The mean haemoglobin concentration of those who died was also significantly lower than that of the survivors.


Preventive effect of zinc acexamate administration in streptozotocin-diabetic rats: Restoration of bone loss.
The preventive effect of zinc compounds on bone loss in streptozotocin (STZ)-diabetic rats was investigated. Rats received a single subcutaneous administration of STZ (6.0 mg/100 g body weight), and 7, 14 or 21 days later the animals were sacrificed by bleeding. STZ administration caused a significant decrease in body weight and a significant increase in serum glucose and triglyceride levels, indicating diabetic condition. Femoral-diaphyseal and -metaphyseal alkaline phosphatase activity, calcium and deoxyribonucleic acid (DNA) contents were significantly decreased by STZ administration, showing that diabetic condition causes bone loss. Zinc sulfate (2.5 mg Zn/100 g) or zinc acexamate (2.5 mg Zn/100 g) was orally administered once daily for 14 days to rats received a single subcutaneous administration of STZ (6.0 mg/100 g). STZ administration-induced increase in serum glucose and triglyceride levels and decrease in body weight, femoral-diaphyseal and -metaphyseal alkaline phosphatase activity, DNA and calcium contents were significantly prevented by the administration of zinc acexamate. The preventive effect of zinc sulfate on bone components was not seen. The present results demonstrate that the administration of zinc acexamate has a preventive effect on bone loss in STZ-diabetic rats in vivo.


Surgical Considerations and Challenges for Bilateral Continuous-Flow Durable Device Implantation.
The concept of biventricular support with durable centrifugal pumps is evolving, and the surgical strategy and best practice guidelines for implantation of right-sided devices are still unknown. We present optimal strategy for bilateral HeartWare continuous-flow ventricular assist device (HVAD) implantation in a series of four patients. Patients were implanted with the HVAD pumps simultaneously or sequentially. This report offers a perspective on surgical considerations such as right ventricular positioning, implications related to potential risks of obstruction from the tricuspid apparatus, the role if any of downsizing the outflow anastomosis, and considerations for speed adjustments. In this series, one patient died on support and three patients experienced pump thrombosis requiring device revision. All other patients survived until orthotopic heart transplantation, although one of these patients died from perioperative complications, 2 days posttransplantation. Surgical management of patients with medically refractory biventricular heart failure remains challenging and associated with a high incidence of pump thrombosis. Best practice guidelines from experts' consensus are still needed to address this challenging population.


Hematogenous vertebral osteomyelitis due to Staphylococcus aureus in the adult: clinical features and therapeutic outcomes.
Staphylococcus aureus is the most common cause of hematogenous vertebral osteomyelitis in adults. To better define clinical features and therapeutic outcomes, the charts of 40 adult patients with S aureus hematogenous vertebral osteomyelitis were retrospectively reviewed. Retrospective chart review using standardized data collection form. S aureus hematogenous vertebral osteomyelitis commonly occurred in the settings of recent invasive procedures (55% of patients), insulin use (28%), and hemodialysis (20%). Ten percent of patients had S aureus bacteremia or vascular catheter infection within the preceding 6 months. Median time from first symptom to diagnosis was 51.3 days. A portal of entry for S aureus was identified in 13 patients (32.5%); intravenous catheters were the likely origin in 9 of those 13 patients. Concurrent endocarditis was present in 4 patients. Forty-eight percent of patients had neurologic abnormalities and 60% of patients had an epidural, paraspinous, or psoas abscess demonstrated by neuroimaging. S aureus was isolated through fine-needle aspiration in 17 of 23 patients (74%) and from blood cultures in 23 of 34 patients (68%). Infection was due to methicillin-susceptible S aureus in 67.5% of patients. All patients received intravenous antibiotics for a mean duration of 58.6 days; 36 of 40 (90%) also received concomitant rifampin. Twenty-seven percent and 12.5% of patients underwent surgical debridement and CT-guided drainage of abscesses, respectively. After intravenous therapy, 19 of 30 eligible patients received oral continuation treatment. The mean duration of total antibiotic therapy was 142.2 days. Cure of infection was achieved in 83% (24/29) of evaluable patients, but 50% of those achieving cure still had infection-related sequelae. Intravenous antibiotic therapy for at least 8 weeks was the only clinical factor associated with cure (P = 0.05, two-tailed Fisher exact test).


Ensure nurse research is rigorous.
DR LESLIE Gelling is a Reader in Research Ethics and a nurse in the Faculty of Health, Social Care and Education at Anglia Ruskin University in Cambridge. Between 2008 and this edition, Leslie has been the editor of Nurse Researcher and he is now moving to the Journal of Clinical Nursing.


Effects of Interventions to Prevent Work-Related Asthma, Allergy, and Other Hypersensitivity Reactions in Norwegian Salmon Industry Workers (SHInE): Protocol for a Pragmatic Allocated Intervention Trial and Related Substudies.
Workers in the salmon processing industry have an increased risk of developing respiratory diseases and other hypersensitivity responses due to occupational exposure to bioaerosols containing fish proteins and microorganisms, and related allergens. Little is known about effective measures to reduce bioaerosol exposure and about the extent of skin complaints among workers. In addition, while identification of risk factors is a core activity in disease prevention strategies, there is increasing interest in health-promoting factors, which is an understudied area in the salmon processing industry. The overall aim of this ongoing study is to generate knowledge that can be used in tailored prevention of development or chronification of respiratory diseases, skin reactions, protein contact dermatitis, and allergy among salmon processing workers. The main objective is to identify effective methods to reduce bioaerosol exposure. Further objectives are to identify and characterize clinically relevant exposure agents, identify determinants of exposure, measure prevalence of work-related symptoms and disease, and identify health-promoting factors of the psychosocial work environment. Data are collected during field studies in 9 salmon processing plants along the Norwegian coastline. Data collection comprises exposure measurements, health examinations, and questionnaires. A wide range of laboratory analyses will be used for further analysis and characterization of exposure agents. Suitable statistical analysis will be applied to the various outcomes of this comprehensive study. Data collection started in September 2021 and was anticipated to be completed by March 2023, but was delayed due to the COVID-19 pandemic. Baseline data from all 9 plants included 673 participants for the health examinations and a total of 869 personal exposure measurements. A total of 740 workers answered the study's main questionnaire on demographics, job characteristics, lifestyle, health, and health-promoting factors. Follow-up data collection is not completed yet. This study will contribute to filling knowledge gaps concerning salmon workers' work environment. This includes effective workplace measures for bioaerosol exposure reduction, increased knowledge on hypersensitivity, allergy, respiratory and dermal health, as well as health-promoting workplace factors. Together this will give a basis for improving the work environment, preventing occupational health-related diseases, and developing occupational exposure limits, which in turn will benefit employees, employers, occupational health services, researchers, clinicians, decision makers, and other stakeholders. ClinicalTrials.gov NCT05039229; https://www.clinicaltrials.gov/study/NCT05039229. DERR1-10.2196/48790.


Combination of IL-34 and AFP improves the diagnostic value during the development of HBV related hepatocellular carcinoma.
IL-34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBV-HCC). Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV-HCC patients. Serum IL-34 and MCSF, or intrahepatic IL-34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined using ELISA or immunohistochemistry. Serum IL-34 was 1.7, 1.3 or 2.3-fold higher in HBV-HCC than that of CHB, HBV related cirrhosis or healthy control, which was inhibited following trans-hepatic arterial chemoembolization (TACE) in HBV-HCC patients. Intra-hepatic IL-34 was higher in HBV-HCC than that of the other three groups. Intra-hepatic IL-34 was associated with high HBV-DNA, HBeAg-, poor differentiation and small tumor size of HBV-HCC patients. Intra-hepatic TAMs in HBV-HCC were increased 1.7 or 1.3-fold, compared to that from CHB or HBV-cirrhosis patients. Intra-hepatic TAMs were associated with high HBV-DNA, high tumor differentiation, small tumor size, abnormal AFP and more tumor number. AFP plus serum IL-34, showed the highest AUC (0.837) with sensitivity (0.632) and highest specificity (0.931), suggesting that AFP plus IL-34 enhances the reliability for prediction of the development of HBV-HCC among CHB patients. Circulating and intra-hepatic IL-34 was upregulated gradually in HBV disease progression from CHB, cirrhosis and HCC. IL-34 may be used as a diagnostic biomarker and potential therapeutic target for the management of HBV-HCC.


Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding.
Assembly of functional neural circuits relies on the ability of axons to navigate a complex landscape of guidance cues in the extracellular environment. In this report, we investigate localized cell signaling in response to these cues by combining a microfabricated compartmentalization chamber with multicomponent, protein-micropatterned surfaces; this system offers improved spatial resolution and new capabilities for targeted manipulation of neuronal axons. We illustrate the potential of this system by addressing the role of fibroblast growth factor receptor (FGFR) signaling in modulating axon guidance by N-cadherin. Motor neurons that were derived from embryonic stem cells extend axons from one compartment through a microchannel barrier and into a second compartment containing patterns of N-cadherin, against a background of laminin. N-cadherin was effective in both guiding and accelerating motor axon outgrowth. Using the chamber system to target the application of pharmacological agents to specific parts of the neuron, we demonstrate that FGFR signaling in the axon but not the cell body increases the rate of axon outgrowth while not affecting guidance along N-cadherin. These results demonstrate that cell signaling must take into account the spatial layout of the cell. This new platform provides a powerful tool for understanding such effects over a wide range of signaling systems.