Association between electronic cigarette use and metabolic syndrome in the Korean general population: A nationwide population-based study.
Although smoking is known to have a negative impact in patients with metabolic syndrome (MetS), only a few studies have examined the association between electronic cigarette (e-cig) use and MetS. Among 22,948 participants in the 6th Korea National Health and Nutrition Examination Survey, 14,738 (13,459 [91.3%] never, 954 [6.5%] ever, and 325 [2.2%] current e-cig users) were selected. The relationship between e-cig exposure and MetS (based on the National Cholesterol Education Program Adult Treatment Panel [NCEP-ATP] III criteria) was evaluated using a multivariable logistic regression analysis. An unweighted analysis was performed to evaluate this association without a sampling weight. A subgroup analysis was performed among active smokers to compare dual users with never e-cig users. Among current e-cig users, 85.0% were dual users, 12.7% were former cigarette users, and 2.2% were only e-cig users. After adjustment for covariates, abdominal obesity and hypertriglyceridemia were significantly associated with current e-cig exposure (odds ratio [OR]: 1.88, 95% confidence interval [CI]: 1.41-2.50 and OR: 1.32, 95% CI: 1.00-1.74 respectively [compared with the never e-cig users group]). Compared with never e-cig users, current e-cig users showed an OR of 1.27 (95% CI: 0.96-1.70, Ptrend = 0.01) for MetS. In the unweighted analysis, the OR for MetS in current e-cig users was 1.40 (95% CI: 1.08-1.81, Ptrend <0.01). Compared with never e-cig users, dual users showed a higher OR for abdominal obesity (OR: 1.71, 95% CI: 1.25-2.34, Ptrend <0.001). Current e-cig exposure was associated with an increased risk of MetS. Dual use of e-cigs and cigarettes was associated with abdominal obesity. Further longitudinal studies and better assessment of e-cig use and type are needed to clarify this relationship.


Metabonomic analysis of rats with acute heart rejection.
Organs transplantation is an effective treatment for end-stage organ failure. Despite the use of modern immunosuppressants to decrease its incidence, acute rejection episodes (ARE), still present a problem for diagnosis, resolution, and prediction of long-term outcomes due to the absence of sufficiently robust biomarkers. Using an heterotopic heart transplantation model using Dark Agouti to Lewis rats, and sirolimus (rapamycin, Rapa) treatment by gavage, we divided recipients into four groups: controls, ARE, Rapa-14, and Rapa-7. We evaluated recipients by hematoxylin and eosin staining of grafts and reverse transcription polymerase chain reactions. Levels of plasma metabolites were quantified using gas chromatography/time-of-flight mass spectrometry. Data were evaluated employing partial least-squares discriminant analysis (PLS-DA), the area under the receiver operating characteristic curves with negative predictive values (NPV) and positive predictive values (PPV). The graft survival was prolonged by Rapa. Plasma levels of 10 metabolites differed significantly between the ARE and the Rapa-14 groups as illustrated by the total ion current. According to PLS-DA, proline, glycine, serine, phenylalanine, and isocitrate showed the greatest effects with areas under the curve of 0.944, 0.917, 1.0, 0.861, and 0.944 respectively. The NPV values were 85.7%, 85.7%, 100%, 83.3%, and 85.7% and PPV values, 100%, 100%, 100%, 83.3%, and 100% respectively. Therefore, these metabolites may be used to predict the occurrence and progression of ARE. The trend of changes suggested that plasma metabolites correlated with the immune state of recipients. Therefore, metabonomics may provide new biomarkers for graft injury in the early phases of ARE.


Diurnal variations of lipogenic enzyme mRNA quantities in rat liver.
The diurnal variations in mRNA quantities of lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase, malic enzyme and glucose-6-phosphate dehydrogenase) in rat livers were detected. When the rats began feeding actively after lights out at 1900 h, the mRNA quantities were high from 0500 h to 0900 h in the morning. The variation in fatty acid synthase mRNA quantities was the most dramatic. However, no measurable variation in any enzyme levels including fatty acid synthase was detected. It may be because the half-lives of the enzymes are too long to be effected by the mRNAs which were high for several hours.


Glial response to neuronal activity: GFAP-mRNA and protein levels are transiently increased in the hippocampus after seizures.
We have recently demonstrated that electrically induced seizures lead to dramatic increases in mRNA for GFAP in areas in which seizures occur. The present study evaluates the time course of the changes in the GFAP-mRNA levels after seizures and the relationship between these changes and GFAP protein levels to understand the role of neuronal activity in regulating glial gene expression. GFA protein and mRNA levels were measured in hippocampi from rats in which seizures were induced by: (1) 50-Hz stimulus trains delivered 12 times over the course of 1 day via indwelling electrodes implanted chronically in the CA3 region of the hippocampus; and (2) intraperitoneal injections of pentylenetetrazol. In the case of the electrically induced seizures, we also compared the glial response in animals that had never experienced a seizure with the response in animals that previously had been kindled but had not experienced a seizure for 30 days. Electrically induced seizures led to rapid transient increases in GFAP-mRNA levels in the hippocampus ipsi- and contralateral to the stimulation. GFAP-mRNA increased about five-fold 1 day after the end of seizure activity and returned to near-control levels by 4 days. There were no detectable increases in GFA protein at 1 day but by 2 days GFA protein levels had increased about two-fold. GFA protein levels remained elevated until 4 days poststimulation and then began to decrease. The responses were similar when seizures were induced in kindled animals, except that the GFAP protein levels remained elevated for somewhat longer.(ABSTRACT TRUNCATED AT 250 WORDS)


Stimuli-responsive hydrogel-silver nanoparticles composite for development of localized surface plasmon resonance-based optical biosensor.
In this paper, the development of a localized surface plasmon resonance (LSPR)-based optical enzyme biosensor using stimuli-responsive hydrogel-silver nanoparticles composite is described. This optical enzyme biosensor was constructed by immobilizing glucose oxidase (GOx) into the stimuli-responsive hydrogel. When a sample solution such as glucose was applied to the surface of this optical enzyme biosensor, the interparticle distances of the silver nanoparticles present in the stimuli-responsive hydrogel were increased, and thus the absorbance strength of the LSPR was decreased. Furthermore, hydrogen peroxide, which was produced by the enzymatic reaction, induced the degradation of highly clustered silver nanoparticles by the decomposition of hydrogen peroxide. Hence, a drastic LSPR absorbance change, which depends on the glucose concentrations, could be observed. On the basis of the abovementioned mechanism, the characterization of the LSPR-based optical enzyme biosensor was carried out. It was found that the LSPR-based optical enzyme biosensor could be used to specifically determine glucose concentrations. Furthermore, the detection limit of this biosensor was 10 pM. Therefore, this LSPR-based optical enzyme biosensor has the potential to be applied in cost-effective, highly simplified, and highly sensitive test kits for medical applications.


Inheritance and molecular characterization of broad range tolerance to herbicides targeting acetohydroxyacid synthase in sunflower.
Ahasl1 is a multilallelic locus where all the induced and natural mutations for herbicide tolerance were described thus far in sunflower (Helianthus annuus L.). The allele Ahasl1-1 confers moderate tolerance to imidazolinone (IMI), Ahasl1-2, and Ahasl1-3 provides high levels of tolerance solely to sulfonylurea (SU) and IMI, respectively. An Argentinean wild sunflower population showing plants with high level of tolerance to either an IMI and a SU herbicide was discovered and used to develop an inbred line designated RW-B. The objectives of this work were to determine the relative level and pattern of cross-tolerance to different AHAS-inhibiting herbicides, the mode of inheritance, and the molecular basis of herbicide tolerance in this line. Slight or no symptoms observed after application of different herbicides indicated that RW-B possesses a completely new pattern of tolerance to AHAS-inhibiting herbicides in sunflower. Biomass response to increasing doses of metsulfuron or imazapyr demonstrated a higher level of tolerance in RW-B with respect to Ahasl1-1/Ahasl1-1 and Ahasl1-2/Ahasl1-2 lines. On the basis of genetic analyses and cosegregation test, it was concluded that tolerance to imazapyr in the original population is inherited as a single, partially dominant nuclear gene and that this gene is controlling the tolerance to four different AHAS-inhibiting herbicides. Pseudo-allelism test permitted us to conclude that the tolerant allele present in RW-B is an allelic variant of Ahasl1-1 and was designated as Ahasl1-4. Nucleotide and deduced amino acid sequence indicated that the Ahasl1-4 allele sequence of RW-B has a leucine codon (TTG) at position 574 (relative to the Arabidopsis thaliana AHAS sequence), whereas the enzyme from susceptible lines has a tryptophan residue (TGG) at this position. The utilization of this new allele in the framework of weed control and crop rotation is discussed.


The effects of levobupivacaine versus levobupivacaine plus magnesium infiltration on postoperative analgesia and laryngospasm in pediatric tonsillectomy patients.
The aim of this study was to evaluate whether the addition of magnesium to levobupivacaine will decrease the postoperative analgesic requirement or not, and to investigate the possible preventive effects on laryngospasm. Seventy-five children undergoing elective tonsillectomy and/or adenoidectomy surgery. The drug was prepared as only NaCl 0.9% for the first group (Group S, n=25), levobupivacaine 0.25% for the second group (Group L, n=25), and levobupivacaine 0.25% plus magnesium sulphate 2mg/kg for the third group (Group M, n=25). Pain was recorded at 15th minute, 1st, 4th, 8th, 16th, and 24th hour postoperatively. Pain was evaluated using a modified Children's Hospital of Eastern Ontario pain scale (mCHEOPS). Incidence of postoperative nausea and vomiting (PONV) was assessed at various time intervals (0-2, 2-6, 6-24h) by numeric rank score. Patients were followed for laryngospasm for 1h in recovery room after extubation. Other complications appeared within 24h postoperatively were recorded. All postoperative CHEOPS values were lower than control in both groups. Analgesic requirement was decreased significantly in both groups in comparison with control patients, but this requirement was significantly lower in Group M (p<0.05). Although laryngospasm was not observed in Group M, the difference between groups was not statistically significant. PONV was similar in both groups. Levobupivacaine and Levobupivacaine plus magnesium infiltration decrease the post-tonsillectomy analgesic requirement. Insignificant preventive effect of low doses of magnesium infiltration on laryngospasm observed in this study needs to be clarified by larger series.


Whistleblower finds possible misconduct in his own papers.
Matthew Schrag confronts a mentor after their joint work is flagged on the PubPeer website.


Evaluation of the balance function before and after total knee arthroplasty using Berg balance scale.
The purpose of this study was to evaluate balance function before and after total knee arthroplasty (TKA) using Berg balance scale (BBS). The study also aimed to identify factors associated with balance impairment. Ninety-three knees in 90 patients were prospectively evaluated using their BBS scores, passive knee extension/flexion angles, Visual analogue scale for pain scores, hip-knee-ankle angles, and knee extensor/flexor muscle strengths before and after TKA. A total BBS score of less than 45 indicates an enhanced risk of multiple falls. Multivariate logistic regression models were performed to elucidate factors associated with post-operative BBS score. A significant difference in mean pre- and post-operative BBS scores were noted (49.3 ± 6.4 vs. 52.2 ± 4.7) (p < 0.05). The percentage of pre- and post-operative BBS scores less than 45 were 20% and 10% (p < 0.05). Rheumatoid Arthritis (RA), lower pre-operative BBS score, and larger post-operative knee flexion contracture were significantly associated with lower post-operative BBS score (p < 0.01). The post-operative knee flexion contracture greater than 10° was significantly associated with substantially high odds of post-operative BBS scores less than 45 (Odds ratio 7.6; 95% confidential interval 1.69-34.17). While TKA significantly improved BBS scores, 10% of the patients remained at a risk for multiple falls. RA, lower pre-operative BBS score, and post-operative knee flexion contracture greater than 10° retained balance impairment even after TKA.


Integracides H-J: New tetracyclic triterpenoids from the endophytic fungus Fusarium sp.
Three new tetracyclic triterpenoids namely, integracides H (1), I (4), and J (5), along with integracides B (3) and F (2) have been isolated from the endophytic fungus Fusarium sp. isolated from the roots of Mentha longifolia L. (Labiatae) growing in Saudi Arabia. The structure elucidation of the isolated compounds was achieved by spectroscopic analysis including UV, IR, 1D ((1)H and (13)C) and 2D ((1)H(1)H COSY, TOCSY, HSQC, HMBC, and NOESY) NMR as well as HRESIMS and comparison with literature data. Integracides H (1) and J (5) showed significant anti-leishmanial activity towards Leishmania donovani with IC50 values of 4.75 and 3.29μM, respectively compared to pentamidine (IC50 6.35μM). Moreover, they displayed potent cytotoxic activity towards BT-549, SKOV-3, and KB cell lines with IC50 values of 1.82, 1.32, and 0.18μM and 2.46, 3.01, and 2.54μM, respectively.


Brain opioid-receptors are involved in mediating peripheral electric stimulation-induced inhibition of morphine conditioned place preference in rats.
Conditioned place preference (CPP) paradigm has been suggested as one of the animal models for drug craving. The present study was performed to examine the effect of 100 Hz peripheral electric stimulation (PES) on the expression of morphine-induced CPP. Rats were trained with morphine for 4 days to establish the CPP paradigm in a three-chamber "unbiased" apparatus. Morphine-induced CPP was maintained up to 4 weeks when tests were given once a week. PES of 100 Hz administered 30 min a day for 3 days significantly attenuated morphine-induced CPP (P<0.01). I.c.v. injection of the delta-opioid receptor antagonist naltrindole (NTI) or the kappa-antagonist norbinaltorphimine (nor-BNI) but not the mu-antagonist cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), completely blocked the inhibitory effect of 100 Hz PES on the expression of morphine-induced CPP (P<0.05-0.01). These results indicate that the anti-craving effects induced by repeated PES of 100 Hz is mediated by the activation of supra-segmental delta- and kappa-opioid receptors in the central nervous system.


The gelatin-based liquid marbles for cell cryopreservation.
As an alternative and a straightforward cryopreservation biotechnological tool, liquid marble provides a promising cryopreservation approach. Currently, effective cell preservation mainly based on the addition of dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS). As state-of-the-art cryoprotectant (CPA), DMSO, has intrinsic toxicity, which is the bottleneck of its widespread application. The complex compositions of FBS have the potential risks of pathogenic microorganism contamination. However, efficient cell cryopreservation using liquid marbles, a platform independent of DMSO and FBS, has not been well investigated yet. Herein, we explore the cryoprotection role of liquid marbles based on gelatin solution. Gelatin has a superior biocompatibility, which DMSO is incomparable. During a freeze-thaw cycle, gelatin produces negligible osmotic pressure, and has high ice recrystallization inhibition (IRI) activity to induce the formation of smaller and smooth ice crystals. Moreover, the specific structure of liquid marble also provides favorable supports for cell survival. The cryopreservation efficiency of mouse fibroblasts cells L929 via the gelatin-based liquid marble was as high as 90%, and the recovered cells could maintain their normal functionalities. This work opens a new window of opportunity for non-toxic and efficient cryopreservation of liquid marbles without the need of DMSO and FBS addition.


Development and environmental implication of pedotransfer functions of Cd desorption rate coefficients in historically polluted soils.
The desorption rate is an important factor determining cadmium (Cd) ecotoxicity and pollution remediation in soils. The pedotransfer functions (PTFs) of desorption rate coefficients of fresh Cd in soils have been developed in literature. We hypothesized that the aging of Cd pollution would alter Cd desorption process. Taking historically polluted soils as the object, this study aimed at testing the hypothesis and developing new PTFs of desorption rate coefficients for historical Cd. 15 d batch extraction experiments and 13 kinetic models were employed to define Cd desorption rate coefficients in 27 historically polluted soil samples. Compared with fresh Cd, the desorption rate coefficients of historical Cd were lower, and the break time of biphasic desorption processes was retarded to 3 d (4320 min). Different with the usual models for fresh Cd desorption (e.g. parabolic diffusion and two constant rate models), the best models to mimic the historical Cd desorption processes were the pseudo first order, logarithmic, Elovich, and simple Elovich models. The rate-limiting step controlling Cd desorption was changed from the intraparticle diffusion to the interface reaction with aging of pollution. New PTFs of desorption rate coefficients of historical Cd were established (R2 ≥ 0.71). Cd desorption rate coefficients increased with organic matter and clay contents, but decreased with oxalate extractable Fe content, solution pH, cation exchange capacity, and silt content. The key soil properties influencing desorption rate coefficients were not altered by the aging of pollution. The developed PTFs could guide us to adjusting the ecotoxicity and pollution remediation of Cd in historically polluted field soils.


Intramuscular aripiprazole in the acute management of psychomotor agitation.
To assess acute efficacy and safety of 9.75 mg of intramuscular (IM) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation. Open-label trial of IM injections of aripiprazole and 24-hour monitoring of clinical response in patients with major psychoses and acute agitation. Partial analysis of blood levels of the administered drug to correlate with clinical response. Acute psychiatric care wards in a single university hospital. A total of 201 acutely agitated patients (79 with schizophrenia and 122 with bipolar disorder I). Aripiprazole 9.75 mg IM injection. We evaluated clinical response using the Excitatory Component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation/Calmness Evaluation Scale (ACES), and the Clinical Global Impressions scale (CGI). Assessments were conducted 30, 60, 90, and 120 minutes and 24 hours after the first injection for PANSS-EC and ACES, and 2, 4, 6, and 24 hours for CGI. Response was at least a 40% decrease in PANSS-EC scores. We measured serum aripiprazole and dehydroaripiprazole levels in a subsample. IM aripiprazole significantly improved clinical measures. PANSS-EC improved progressively, starting after 30 minutes. ACES improved after 90 minutes and continued thereafter. Effects were sustained, with steadily decreasing CGI scores, until the 24th hour. Response rate was 83.6% after 2 hours, but with repeat injections, it rose to over 90% with no differences among diagnostic groups. Although there were gender differences in the response to individual PANSS-EC items, the responses were similar overall. Neither clinical monitoring nor patient reporting revealed any side effects. No therapeutic window was identified, and levels did not correlate with any clinical measure. Aripiprazole was effective and safe in reducing acute agitation in patients with bipolar disorder or schizophrenia. Our results compare favorably to double-blind trials, probably due to higher expectations in trials involving no placebo arm. Absence of side effects could be related to the short observation time.


Electrolyte gating in graphene-based supercapacitors and its use for probing nanoconfined charging dynamics.
Graphene-based nanoporous materials have been extensively explored as high-capacity ion electrosorption electrodes for supercapacitors. However, little attention has been paid to exploiting the interactions between electrons that reside in the graphene lattice and the ions adsorbed between the individual graphene sheets. Here we report that the electronic conductance of a multilayered reduced graphene oxide membrane, when used as a supercapacitor electrode, can be modulated by the ionic charging state of the membrane, which gives rise to a collective electrolyte gating effect. This gating effect provides an in-operando approach for probing the charging dynamics of supercapacitors electrically. Using this approach, we observed a pore-size-dependent ionic hysteresis or memory effect in reduced graphene oxide membranes when the interlayer distance is comparable to the ion diameter. Our results may stimulate the design of novel devices based on the ion-electron interactions under nanoconfinement.


Characterization of the G protein coupling of a somatostatin receptor to the K+ATP channel in insulin-secreting mammalian HIT and RIN cell lines.
1. The G protein-mediated coupling of a somatostatin (somatotropin-releasing inhibitory factor; SRIF) receptor to the ATP-dependent K+ channel (K+ATP channel) has been studied in insulin-secreting cells using the patch clamp technique. 2. In excised outside-out patches, the concentration-dependent stimulation of the K+ATP channel by SRIF was biphasic. Stimulation reached a maximum at 15 nM (EC50 = 5.5 nM), then decayed to a minimum at 50 nM and returned to maximum stimulation at 500 nM. 3. In cell-attached patches, bath-applied SRIF caused K+ATP channel stimulation in most experiments. In a few cases, however, SRIF suppressed channel activity, a response that was reversed by addition of dibutyryl cyclic AMP (DBcAMP). Channel stimulation by SRIF or by DBcAMP did not occur in the presence of glucose. 4. In excised inside-out patches, the alpha-subunits of Gi or G(o)-type G proteins stimulated the K+ATP channel (EC50 = 29 and 42 pM, respectively). The K+ATP channel stimulation by alpha i- or alpha o-subunits had no effect on the concentration-dependent inhibition by ATP. 5. In excised inside-out patches, K+ATP channel activity was reduced by inhibitors of protein kinase C (PKC) and stimulated by a PKC activator. The stimulatory effect of PKC was unaffected by the presence of pertussis toxin, but stimulation by exogenous alpha-subunits of the G protein Gi or G(o) was prevented by PKC inhibitors. 6. From these data we deduce that SRIF can affect K+ATP channel activity directly via a membrane-delimited pathway or indirectly via a pathway requiring diffusible messengers. In the former case, alpha i/alpha o may either enhance PLC activity, stimulating PKC and thus inducing K+ATP channel phosphorylation with consequent increase of activity, or channel phosphorylation by PKC may facilitate a direct stimulation of the channel by alpha i/alpha o. In the latter case, an alpha i/alpha o-induced fall in cAMP contributes to reduced PKA-mediated phosphorylation and suppression of channel activity.


Monotheism versus an innate bias towards mentalizing.
Norenzayan et al.'s account for the spread of monotheistic "Big God" religions sees these religions originating as by-products of innate cognitive biases. These biases produce polytheistic rather than monotheistic systems, however, and so do not explain the origin of monotheism. Accounts where monotheism arises from polytheism (for political reasons, for example) appear better able to explain the spread of monotheism.


Decreased myo-inositol uptake is associated with reduced bradykinin-stimulated phosphatidylinositol synthesis and diacylglycerol content in cultured neuroblastoma cells exposed to L-fucose.
L-Fucose is a potent, competitive inhibitor of myo-inositol transport by cultured mammalian cells. Chronic exposure of neuroblastoma cells to L-fucose causes a concentration-dependent decrease in myo-inositol content, accumulation, and incorporation into phosphoinositides. In these studies, L-fucose supplementation of culture medium was used to assess the effect of decreased myo-inositol metabolism and content on bradykinin-stimulated phosphatidylinositol synthesis and diacylglycerol production. Chronic exposure of cells to 30 mM L-fucose caused a sustained decrease in bradykinin-stimulated, but not basal, 3H-inositol phosphate release and 32P incorporation into phosphatidylinositol in cells incubated in serum-free, unsupplemented medium. In addition, 32P incorporation into phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate was not altered in L-fucose-conditioned cells. Acute exposure of cells to serum-free medium containing 30 mM L-fucose did not affect either basal or bradykinin-stimulated 32P incorporation into phosphatidylinositol. Basal diacylglycerol content was decreased by 20% in cells chronically exposed to 30 mM L-fucose, although analysis of the molecular species profile revealed no compositional change. Bradykinin stimulated diacylglycerol production in neuroblastoma cells by increasing the hydrolysis of both phosphoinositides and phosphatidylcholine. Bradykinin-stimulated production of total diacylglycerol was similar for control and L-fucose-conditioned cells. However, there was a decrease in the bradykinin-induced generation of the 1-stearoyl-2-arachidonoyl diacylglycerol molecular species in the cells chronically exposed to 30 mM L-fucose. This molecular species accounts for about 70% of the composition of phosphoinositides, but only 10% of phosphatidylcholine. The results suggest that a decrease in myo-inositol uptake results in diminished agonist-induced phosphatidylinositol synthesis and phosphoinositide hydrolysis in cultured neuroblastoma cells grown in L-fucose-containing medium.


Synthesis of bimetallic silver-gold nanoparticle composites using a cellulose dope: Tunable nanostructure and its biological activity.
Introducing functional metal nanoparticles (NPs) into flexible substrate is being increasingly attempted to expand their application. Here, we extend the synthesis of cellulose to its unmodified dope achieving freestanding nanocomposite decorated with bimetallic Ag-Au NPs through the one pot reaction. In the procedure, cellulose chain not only acts as a reducing agent but also a biocompatible support for NPs with a mean size of 7.9-9.7 nm. Meanwhile, changing the addition order of Ag+ and AuCl4- generated different atom arrangement in the bimetallic NPs. Moreover, the correlation of bioactivity to NP atom arrangement was studied. The result revealed that the nanocomposite containing NPs with an ultrathin Ag-rich outermost shell around an Au-rich core showed better bactericidal ability while lower cytotoxicity. In addition, the nanocomposite exhibited a sensitive SERS property for determination of R6G with a high enhancement factor of 108.


Long head of the biceps brachii tendon: unenhanced MRI versus direct MR arthrography.
We sought to determine the diagnostic accuracy of unenhanced MRI and direct MR arthrography (MRA) for evaluation of the intra-articular long head of the biceps brachii tendon (LHBT) using arthroscopy as the gold standard. A retrospective review of patients who underwent shoulder MRI (n = 132) and MRA (n = 67) within 12 months prior to arthroscopy was performed. MR images were independently reviewed by two blinded musculoskeletal radiologists. Routinely recorded arthroscopic photos/videos were reviewed by an orthopedic surgeon. The LHBT was graded as normal, tendinosis, partial thickness tear less or greater than 50%, and complete tear. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for tendinosis and tear detection were calculated. MRI correctly diagnosed fewer normal LHBTs compared to MRA (39-54% versus 74-84%, respectively; p < 0.005). MRI and MRA did not differ significantly in the diagnosis of tendinosis (18-36% and 15-38%, respectively; p > 0.05) and tears (75-83% and 64-73%, respectively; p > 0.05). For tendinosis, MRI versus MRA showed 18-36% and 15-38% sensitivity, 69-79% and 83-91% specificity, 22-28% and 18-50% PPV, 74-76% and 80-86% NPV, and 61-64% and 70-81% accuracy; respectively. For tears, MRI versus MRA showed 75-83% and 64-73% sensitivity, 73-75% and 82-91% specificity, 66-69% and 41-62% PPV, 82-87% and 92-94% NPV, and 74-78% and 79-88% accuracy; respectively. No significant difference was found between unenhanced MRI and direct MRA for the detection of tendinosis and tears of LHBTs.


Reduced arterial compliance in patients with psychiatric diagnoses.
Peripheral arterial compliance is a measure of elasticity of the arteries that has been found to be a robust predictor of prevalent arteriosclerosis as well as incident stroke and myocardial infarction. Psychiatric diagnoses and second generation antipsychotics may contribute to cardiovascular risk and stroke, but effects on peripheral arterial compliance are unknown. This study compared peripheral arterial compliance in healthy male controls to male patients with psychiatric diagnoses who were treated with quetiapine or risperidone or off antipsychotics at time of testing. The groups consisted of 63 patients with mental illness taking quetiapine, risperidone, or no antipsychotics. There were 111 males in the control group. Mean thigh and calf arterial compliance among four groups were compared by ANCOVA, adjusting for body mass index and Framingham Risk Score. All patients were also compared to the control group. Compliance was measured with a computerized plethysmography device. Patients (n=63) had significantly lower arterial compliance in both thigh and calf than the controls. Arterial compliance in the calf was significantly lower in the subgroups of quetiapine (n=16) and risperidone (n=19) treated, and in unmedicated (n=28) patients than in controls. In the thigh, patients taking either quetiapine or risperidone had significantly lower arterial compliance than controls. These subgroups did not differ from each other in arterial compliance. The presence of psychiatric diagnoses is associated with reduced arterial compliance. A large study may be required to measure any specific affects of antipsychotics such as quetiapine and risperidone on compliance compared to controls.


From Passos the Indian to Doctor Chernoviz: experiments to cure leprosy in nineteenth-century Pará.
This article analyzes an experiment to cure leprosy using the assacu plant (Hura crepitans L.) conducted in Santarém, Pará, in 1847, by an Indigenous man named Antonio Vieira dos Passos. The experiment was later repeated in other Brazilian provinces and abroad. This article establishes relationships between medical practices in other parts of the country while focusing on the dialog between official and Indigenous medicine. Newspaper articles and official documents of the time show that Indigenous knowledge of medicinal plants was widely recognized and utilized by physicians wishing to incorporate it into the official therapeutic repertoire.


miR-758-5p regulates cholesterol uptake via targeting the CD36 3'UTR.
miR-758-3p plays an important role via regulting ABCA1-mediated cholesterol efflux in atherosclerosis. However, the mechanism of miR-758-5p in cholesterol metabolism is still unclear. Here, we revealed that miR-758-5p decreased total cholesterol accumulation in THP-1 macrophage derived foam cells through markedly reducing cholesterol uptake, and no effect on the cholesterol efflux. Interestingly, computational analysis suggests that CD36 may be a target gene of miR-758-5p. Our study further demonstrated that miR-758-5p decreased CD36 expression at both protein and mRNA levels via targeting the CD36 3'UTR in THP-1 macrophage derived foam cells. The present present study concluded that miR-758-5p decreases lipid accumulation of foam cell via regulating CD36-mediated the cholesterol uptake. Therefore, targeting miR-758-5p may offer a promising strategy to treat atherosclerotic vascular disease.


Comparison of the Effects of Bathing and the Dry Technique on the Skin Condition of Early Neonates: A Prospective Observational Study.
In Japan, neonates have typically been bathed in a bathtub immediately after birth because bathing is a custom for cleansing impurities. However, dry technique has been introduced into many institutions since 2000. There is little scientific evidence on the benefit or harmfulness of either method to neonatal skin, and consequently, opinion remains split on which method is superior. The purpose of the present study was to determine whether bathing or the dry technique of cleaning is better in maintaining skin health in the early neonatal period. Transepidermal water loss (TEWL) and skin pH, considered an index of skin barrier function, were measured in each group. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, which are inflammatory cytokines released by keratinocytes, were measured by skin blotting. TEWL and skin pH of neonates were lower with the dry technique than with bathing. The expression level of IL-6 and TNF-α in chest skin of neonates was higher with bathing than with the dry technique. These results suggest that the dry technique may maintain skin health better than bathing in the early neonatal period.


Combined rotational atherectomy and aortic balloon valvuloplasty as a bridge to transcatheter aortic valve replacement.
Patients with obstructive coronary artery disease and severe aortic stenosis have traditionally been managed with open heart surgery. In the era of transcatheter aortic valve replacement (TAVR) and high-risk coronary interventions many of those patients who were previously considered "terminal" can now be successfully managed with percutaneous coronary intervention (PCI) and TAVR. Although simple PCI can be safely combined with TAVR in the same procedure, high-risk coronary interventions often need to be performed separately. We report the first case of combined rotational atherectomy with balloon aortic valvuloplasty as a bridge to TAVR in a frail patient with complex coronary artery disease and critical aortic stenosis.


Mutagen-induced changes in cellular deoxycytidine triphosphate and thymidine triphosphate in Chinese hamster ovary cells.
Deoxynucleoside triphosphate concentrations in Chinese hamster ovary cell lines, CHO-K1 and Mut 8-16, were examined following exposure of cells to UV or dimethylsulfate. Marked decreases in dCTP were observed 2 hr after exposure to both mutagens. In contrast, dTTP concentrations increased with increased cell killing after exposure to UV but not after exposure to dimethylsulfate. Examination of DNA synthesis in permeabilized cells in the presence of excess concentrations of dNTP substrates suggests that excess dCTP enhances replication while excess of dTTP inhibits replication. We therefore ask whether the increase in the dTTP/dCTP ration in mutagenized whole cells either contributes to or prolongs induced inhibition of replication. In addition we proposed that such an induced dNTP imbalance may also contribute to an increase in mutations by enhancing the probability for base-misincorporation.


Mastomys natalensis as an experimental host for Leishmania mexicana mexicana.
Young multimammate rats (Mastomys natalensis) can be readily infected when inoculated intradermally with the amastigotes of Leishmania mexicana mexicana. Lesions appear at the site of inoculation in the second week of infection and continue to increase in size for the first month; amastigotes can be detected during this period. In the second month, lesions begin to decrease in size and it is more difficult to detect amastigotes. Three months after inoculation, the rats show no sign of infection. The results suggest that M. natalensis could be a useful laboratory host for immunological studies on dermatotropic Leishmania and for chemotherapeutic assays.


Acute and chronic ketanserin in essential hypertension: antihypertensive mechanisms and pharmacokinetics.
1. In nine patients with essential hypertension, following single and multiple doses of ketanserin, assessments were made of blood pressure and heart rate, QT interval, and pressor responses to phenylephrine and angiotensin II. 2. Significant reductions in blood pressure occurred for 6 h after the first dose, on average 23/14 mm Hg supine, and there was a comparable antihypertensive effect after 1 month's treatment. 3. There were small but significant rightward shifts (1.5 to 2-fold) in the phenylephrine pressor-response curves but no changes in the responsiveness to angiotensin II. 4. The QT interval (QTc) was significantly increased after 1 month's treatment: at 1 h after dosing 334 +/- 32 ms after 1 month of ketanserin compared with 302 +/- 31 ms after placebo. 5. The elimination half-life and AUC for ketanserin were both significantly increased at steady state compared with the first dose: respectively 13.4 vs 4.3 h for half-life and 830 vs 437 ng ml-1 h for AUC. 6. Ketanserin had no significant effects on baroreflex function, plasma renin activity, aldosterone, catecholamines and 24 h urinary excretion.


Androgen resistance in female mice increases susceptibility to DMBA-induced mammary tumors.
Hormones, notably estrogens, are pivotal in the origins of breast cancer but androgenic effects, while supported by persistence of AR expression in breast cancers, remain controversial. This study determined the role of the androgen actions via androgen receptor (AR) in experimental mammary cancer. Androgen-resistant female and male mice (ARKO) were generated using Cre/loxP technique and featured a global AR inactivation. The effect of AR inactivation and influence of genetic background on 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis was confirmed using two separate ARKO models with different genetic backgrounds. The onset of palpable mammary tumors was significantly faster in ARKO females (median time 22 vs 34 weeks, respectively; (p = 0.0024; multivariate Cox regression) compared to WT and independent of the mouse genetic background. The cumulative incidence at 9 months was 81 ± 10% [mean ± SE] for ARKO compared to 50 ± 13% in WT females. The increased DMBA susceptibility of ARKO females was associated with a higher epithelial proliferation index but not with major structural or receptor (estrogen or progesterone) expression differences between the virgin WT or ARKO female mammary glands. AR inactivation allowed substantial ductal extension in ARKO males while WT males displayed only rudimentary epithelial branches or complete regression of epithelial structures. Yet, DMBA did not induce epithelial mammary tumors in WT or ARKO males, demonstrating that AR inactivation alone is insufficient to promote mammary tumors. These results demonstrate that AR inactivation accelerates mammary carcinogenesis in female mice exposed to the chemical carcinogen DMBA regardless of mouse genetic background but require prior exposure to endogenous ovarian hormones.


Association of the haptoglobin phenotype (1-1) with falciparum malaria in Sudan.
The haptoglobin phenotypes of Sudanese patients with complicated and uncomplicated falciparum malaria, and those of uninfected randomly selected individuals, were determined by electrophoresis of sera on polyacrylamide gels followed by benzidine staining of the gels. Among 273 malaria patients, the proportions with haptoglobin phenotypes (1-1), (2-1) and (2-2) were 60.8%, 29.7% and 9.5%, respectively, and in 72 cerebral malaria patients the proportions were 63.9%, 29.2%, and 6.9%. The distribution among 208 control individuals was 26.0%, 55.8% and 18.3%, respectively. The difference between patients and controls was highly significant (P < 0.001). The distribution of the different haptoglobin phenotypes among the randomly selected group of 208 Sudanese individuals was comparable to that in many other populations. The results suggests that the haptoglobin phenotype (1-1) is associated with susceptibility to falciparum malaria and the development of severe complications; alternatively, the other phenotypes may confer resistance.


The senior obstetrician requesting obstetric privileges.
As the American physician workforce matures in age, senior physicians on the active clinical staff may become vulnerable to diminished professional performance. Many physicians compensate by using experiential rather than analytic methods to effectively solve clinical problems. Surgical expertise also may be at risk in these circumstances. Organized medical staffs must confront these realities before adverse events are reported as patient safety is their primary responsibility. The appropriate credentialing process will enable talented and experienced senior clinicians to continue to provide high quality medical care.


Molecular phylogeny and systematics of Polyblastia (Verrucariaceae, Eurotiomycetes) and allied genera.
Phylogenetic relationships of the lichen genus Polyblastia and closely related taxa in the family Verrucariaceae (Verrucariales, Chaetothyriomycetidae) were studied. A total of 130 sets of sequences (nuLSU rDNA, nuITS rDNA and RPB1 region A-D), including 129 newly generated sequences, were analysed. Phylogenetic relationships were inferred using a Bayesian approach based on two datasets. A first analysis of a larger, two-locus dataset (nuLSU and RPB1) for 128 members of the Verrucariaceae, confirmed the polyphyly of Polyblastia, Thelidium, Staurothele, and Verrucaria, as currently construed. The second analysis focused on 56 Polyblastia and allied taxa, but using an additional locus (nuITS rDNA) and two closely related outgroup taxa. The latter analysis revealed strongly supported groups, such as Polyblastia s. str., the Thelidium group (a mixture of Polyblastia, Thelidium, Staurothele and Verrucaria species). The genus Sporodictyon, which is here accepted, also accommodates Sporodictyon terrestre comb. nov. Morphological features traditionally used for characterizing Polyblastia, Thelidium, Staurothele and Verrucaria, such as spore septation and colour, occurrence of hymenial photobiont, involucrellum structure, and substrate preference, were found to be only partially consistent within the strongly supported clades, and thus are not always reliable features for characterizing natural groups.


Endoscopic ultrasound-guided versus percutaneous drainage for the management of post-operative fluid collections after distal pancreatectomy.
Post-operative pancreatic fluid collections (POPFCs) can be drained using percutaneous or endoscopic approaches. The primary aim of this study was to compare rates of clinical success between endoscopic ultrasound-guided drainage (EUSD) with percutaneous drainage (PTD) in the management of symptomatic POPFCs after distal pancreatectomy. Secondary outcomes included technical success, total number of interventions, time to resolution, rates of adverse events (AEs), and POPFC recurrence. Adults who underwent distal pancreatectomy from January 2012 to August 2021 and developed symptomatic POPFC in the resection bed were retrospectively identified from a single academic center database. Demographic data, procedural data, and clinical outcomes were abstracted. Clinical success was defined as symptomatic improvement and radiographic resolution without requiring an alternate drainage modality. Quantitative variables were compared using a two-tailed t-test and categorical data were compared using Chi-squared or Fisher's exact tests. Of 1046 patients that underwent distal pancreatectomy, 217 met study inclusion criteria (median age 60 years, 51.2% female), of whom 106 underwent EUSD and 111 PTD. There were no significant differences in baseline pathology and POPFC size. PTD was generally performed earlier after surgery (10 vs. 27 days; p < 0.001) and more commonly in the inpatient setting (82.9% vs. 49.1%; p < 0.001). EUSD was associated with a significantly higher rate of clinical success (92.5% vs. 76.6%; p = 0.001), fewer median number of interventions (2 vs. 4; p < 0.001), and lower rate of POPFC recurrence (7.6% vs. 20.7%; p = 0.007). AEs were similar between EUSD (10.4%) and PTD (6.3%, p = 0.28), with approximately one-third of EUSD AEs due to stent migration. In patients with POPFCs after distal pancreatectomy, delayed drainage with EUSD was associated with higher rates of clinical success, fewer interventions, and lower rates of recurrence than earlier drainage with PTD.


Polyoncogenicity and insulinoma-inducing ability of BK Virus, a human Papovavirus, in Syrian golden hamsters.
Newborn hamsters were inoculated intracerebrally with a series of purified and concentrated BK virus samples originating from a single stock of Gardner's original strain. Most (60-100%) of the hamsters developed various tumors 3-9 months later. The frequent types of tumors were ventricular tumors (choroid plexus papillomas and ependymomas: 7-53%), malignant insulinomas (0-92%), and osteosarcomas (0-50%). The T-antigen was positive in 59 of 60 tumors tested, but the virus was rescued by the cell fusion method from only 1 of 11 cell lines derived from these tumors. The incidence of insulinomas varied greatly with the virus sample; the two samples that showed the highest incidence (47 and 92%) originated from one parental virus stock, and all the other samples with the lower incidences (0-9%) originated from another ancestral stock. These results suggest the presence of a BK virus mutant(s) differing in capacity to induce insulinoma. A functional insulinoma cell line was thus established.


The extreme energy events project: Bring science inside schools.
The Extreme Energy Events Project is an experiment devoted to the study of cosmic ray physics. It consists in a network of about 60 detectors based on the Multigap-Resistive Plate Chamber technology, distributed in the Italian territory and at CERN. In particular, the detectors are installed in high-school buildings, and the scientific activity is carried on in strong cooperation with students and professors. In this perspective, the project relies on citizen science, since non-professional people are fully involved in the constant monitoring of the operations. Furthermore, students participate in many stages of the scientific process, from the building of the detectors at CERN to the installation and commissioning of the telescopes inside their schools, to data collection and analysis, and to publication and dissemination of results.


The Antidiabetic and Antihypercholesterolemic Effects of an Aqueous Extract from Pecan Shells in Wistar Rats.
Pecan shell decoction has been used to treat diabetes and obesity-related diseases. In this study, the effects of a pecan shell aqueous extract (PSAE) were evaluated in diabetic and hypercholesterolemic Wistar rats, analyzing clinical signs and biochemical as well as genotoxic and mutagenic parameters, to assess its safe use and efficacy. Diabetes mellitus and hypercholesterolemia were induced with streptozotocin (STZ) and tyloxapol, respectively. Animals were orally administered PSAE (100 mg/kg body weight, b.w.) for 28 days. Biochemical analyses and genotoxicity were evaluated in blood samples and mutagenicity was evaluated in bone marrow. PSAE treatment decreased the blood glucose level and stabilized clinical signs of diabetes in diabetic rats. PSAE diminished the increase in total cholesterol and triglyceride levels in hypercholesterolemic rats. The urea levels were higher in diabetic rats than in treated ones; however, creatinine values were the same in all groups. Elevated transaminase levels were suggestive of liver injuries in diabetic rats, and were not altered by PSAE treatment. PSAE did not show genotoxic or mutagenic activities in diabetic and hypercholesterolemic rats, indicating its safe use at 100 mg/kg b.w. not only in healthy rats but also in rats with induced metabolic alterations. The findings on PSAE's efficacy may indicate that its successful and popular use is in accordance with our results. Thus, PSAE might be a potential candidate for medical purposes as a complementary treatment of diabetes and hypercholesterolemia.


Optimization of a serum-free culture medium for mouse embryonic stem cells using design of experiments (DoE) methodology.
The in vitro culture behaviour of embryonic stem cells (ESC) is strongly influenced by the culture conditions. Current culture media for expansion of ESC contain some undefined substances. Considering potential clinical translation work with such cells, the use of defined media is desirable. We have used Design of Experiments (DoE) methods to investigate the composition of a serum-free chemically defined culture medium for expansion of mouse embryonic stem cells (mESC). Factor screening analysis according to Plackett-Burman revealed that insulin and leukaemia inhibitory factor (LIF) had a significant positive influence on the proliferation activity of the cells, while zinc and L: -cysteine reduced the cell growth. Further analysis using minimum run resolution IV (MinRes IV) design indicates that following factor adjustment LIF becomes the main factor for the survival and proliferation of mESC. In conclusion, DoE screening assays are applicable to develop and to refine culture media for stem cells and could also be employed to optimize culture media for human embryonic stem cells (hESC).


A Crosslinked Ionic Organic Framework for Efficient Iodine and Iodide Remediation in Water.
Iodine is widely used as an antimicrobial reagent for water disinfection in the wilderness and outer space, but residual iodine and iodide need to be removed for health reasons. Currently, it is challenging to remove low concentrations of iodine and iodide in water (≈5 ppm). Furthermore, the remediation of iodine and iodide across a broad temperature range (up to 90 °C) has not previously been investigated. In this work, we report a nitrate dimer-directed synthesis of a single-crystalline ionic hydrogen-bonded crosslinked organic framework (HC OF-7). HC OF-7 removes iodine and iodide species in water efficiently through halogen bonding and anion exchange, reducing the total iodine concentration to 0.22 ppm at room temperature. Packed HC OF-7 columns were employed for iodine/iodide breakthrough experiments between 23 and 90 °C, and large breakthrough volumes were recorded (≥18.3 L g-1 ). The high iodine/iodide removal benchmarks recorded under practical conditions make HC OF-7 a promising adsorbent for water treatment.


Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy.
The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan-Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0-10, 17.8%; RS 11-25, 62.5%; RS 26-100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0-10, 11-25, and 26-100: 2.6% (95% confidence interval [CI], 1.1-6.2%), 6.1% (95% CI, 4.4-8.6%), and 13.1% (95% CI, 9.4-18.3%), respectively (P < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1-5.1%), 2.2% (95% CI, 1.3-3.7%), and 9.5% (95% CI, 6.0-14.9%) (P < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0-10/11-25), 10-year distant recurrence and BCSM rates for RS 0-10 patients were 2.7% (95% CI, 1.1-6.5%) and 0.8% (95% CI, 0.1-5.3%), respectively, and for RS 11-25 patients, 5.7% (95% CI, 3.9-8.3%) and 2.0% (95% CI, 1.1-3.7%), respectively. For RS 11-25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0-25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26-100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.


[Correlation between beta-thromboglobulin and metabolic compensation in diabetes type I].
In 37 type I diabetic out-patients without any apparent vascular complication and in 9 diabetics with ketoacidosis we have studied the behavior of beta-TG and of glycemia, GSP and HbA1 which are indexes of the short, medium and long-term glycemic control, respectively. In the out-patients beta-TG was found to be correlated only with the GSP. During the recovery of glycemic control, a progressive decrease in the level of beta-TG was found. Therefore, we conclude that also the metabolic derangement of diabetes takes part in the platelet activation.


Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder.
Human genes MAGE-1 and MAGE-3 code for distinct antigens, which are recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). These antigens may constitute useful targets for anti-cancer immunotherapy, since no expression of MAGE genes has been observed in normal tissues other than testis. Out of 57 samples of primary transitional-cell carcinomas of the bladder, 12 (21%) expressed MAGE-1 and 20 (35%) expressed MAGE-3. All but one of the tumors expressing MAGE-1 also expressed MAGE-3. Genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3, were expressed by 30% and 33% of the tumors respectively. MAGE expression was more frequent in advanced tumor stages: 61% of the invasive tumors (stage > or = T2) were positive for expression of at least one of the four genes, whereas only 28% of the superficial tumors (stages Ta and T1) expressed these genes.


Self-rated health and social role as predictors for 6-year total mortality among a non-disabled older Japanese population.
We examined whether social role and self-rated health in an older population were predictors for 6-year total mortality among a non-disabled community-dwelling older population in Saku City, Nagano Prefecture, Japan, surveyed in 1992 and 1998. A total of 8090 men and women aged 65-99 years who reported no disability in performing activities of daily living (ADL) at the time of the survey in 1992 and provided information on their survival status at follow-up 6 years later were analyzed in this study. One dependent variable was survival status in 1998 and independent variables were various factors potentially associated with total mortality, which were obtained from a questionnaire survey at the baseline. During the 6-year interval, having poor self-rated health and poor social roles were identified as significant predictors for total mortality among both men and women. This study revealed that social role and self-rated health are independent predictors for 6-year total mortality for non-disabled Japanese aged 65 years or older.


Dual Cross-Linked Starch-Borax Double Network Hydrogels with Tough and Self-Healing Properties.
Herein, we have fabricated starch-borax double cross-linked network (DC) hydrogels with tough and self-healing properties using a one-pot method. The addition of borax significantly increased the storage modulus and loss modulus of these starch-borax DC hydrogels. The maximum compression stress (~288 kPa) of starch-borax DC hydrogels containing 5% borax was about ten times greater than that of a pure-starch hydrogel. The texture profile analysis values of the DC hydrogels-including hardness, springiness, cohesiveness, and adhesiveness-increased compared to pure-starch hydrogels. In addition, starch-borax DC hydrogels exhibited excellent self-healing and shape-recovery properties. These DC hydrogels, with a variety of excellent properties, have potential applications in agricultural, biomedical, and industrial fields.


Science and society: children and incompetent adults in genetic research: consent and safeguards.
Recent changes to the legal and ethical criteria that govern the inclusion of children and incompetent adults in genetic research are likely to lead to advances in research, but might leave the rights of the participants in this research in need of additional safeguards. Here, we discuss why this might be and propose policy considerations that could help to protect the rights of these particularly vulnerable groups of research participants.


The interplay between psychological well-being, stress, and burnout: Implications for translators and interpreters.
As far as translation is concerned, translators and interpreters are required to cope with multiple challenges during their careers such as managing time constraints related to performing their job. Indeed, a translation job is a challenging task that is very demanding cognitively as it entails deep concentration that also involves the different psychological aspects of humans. Such complicated operations including linguistic, and cognitive ones can induce overwhelming stress and anxiety. Similarly, burnout has been the main issue in this context, and it needs to be investigated in this domain. In recent years, an increasing attention has been drawn to translators' health and well-being as it is a key sustainable development goal and an essential prerequisite to coping with stress. Correspondingly, studies have shown that people's well-being has a constructive impact on their performance and success. It is worth noting that the present literature can bring about useful benefits to educational institutes, and other stakeholders and authorities working in the educational arena as the research findings help them to reflect on the contributions of positive emotions to learning, which results in a reduction in the level of stress and burnout and hence educational flourishing. This review makes an effort to arrange for some implications for translators and interpreters.


In situ hybridization of myoglobin mRNA: results on the skeletal muscles of normal subjects and patients with neuromuscular diseases.
The intracellular localization of myoglobin(Mb) mRNA in the skeletal muscles of normal subjects and patients with Duchenne muscular dystrophy(DMD) or amyotrophic lateral sclerosis(ALS) was examined by in situ hybridization using a biotin-labeled cDNA probe. In cross sections of normal muscles, Mb mRNA signals were demonstrated to be diffusely distributed as granular reaction products throughout the sarcoplasm, and in longitudinal sections the products were observed preferentially on the A-band. In DMD or ALS muscles, the distribution of granular mRNA signals showed some similarities with that in normal muscles, although degenerated fibers revealed a heterogenous distribution of the signals. In DMD muscles, the optical density(OD) of stained signal was higher in non-atrophic fibers and lower in atrophic fibers than in normal muscles. In ALS muscles, the OD was lower than in normal muscles. These results suggest that Mb mRNA is distributed preferentially on the A-band of the muscle fibers, and that in diseased muscle fibers Mb synthesis is affected by pathological changes.


Functionalization of GlucoPyranosides at position 5 by 1,5 C-H insertion of Rh(II)-Carbenes: Dramatic influence of the anomeric configuration.
Herein, a C-H bond functionalization approach is reported as a new route towards non-natural glycosides having a quaternary position 5. The development of this transformation furthermore reveals that insertion of Rh(II)-carbenes into the C5-H bond is controlled by remote stereoelectronic effects induced by the axial or equatorial orientation of the aglycone.


[Use of stoma for decompression of the paralytic ileus (author's transl)].
Indications for the construction of a stoma in the handling of paralytic ileus caused by peritonitis should be ascertained early and completely, since this method is probably the safest and fastest way to relieve advanced intestinal paralysis. There is no need for a secondary laparotomy in order to close the stoma when a catheter-entero- or colostomy is performed. Replacement of lost fluid and electrolytes through the stoma should no longer present serious problems because of the possibilities offered by modern intensive care treatment.


Correction to: Cost-Utility and Budget Impact Analysis for Stopping the Inappropriate Use of Proton Pump Inhibitors After Cessation of NSAID or Low‑Dose Acetylsalicylic Acid Treatment.
Errors were subsequently identified in the article, and the following corrections should be noted.


Photochemically assisted fast abiotic oxidation of manganese and formation of δ-MnO2 nanosheets in nitrate solution.
This study introduces a new and previously unconsidered fast abiotic formation of Mn(iv) oxides. We report photochemically assisted fast abiotic oxidation of Mn2+ (aq) to Mn(iv) (s) by superoxide radicals generated from nitrate photolysis. This photochemical pathway generates randomly stacked layered birnessite (δ-MnO2) nanosheets.


Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change.
Study protocols in endocrinological research and the neurosciences often employ repeated measurements over time to record changes in physiological or endocrinological variables. While it is desirable to acquire repeated measurements for finding individual and group differences with regard to response time and duration, the amount of data gathered often represents a problem for the statistical analysis. When trying to detect possible associations between repeated measures and other variables, the area under the curve (AUC) is routinely used to incorporate multiple time points. However, formulas for computation of the AUC are not standardized across laboratories, and existing differences are usually not presented when discussing results, thus causing possible variability, or incompatibility of findings between research groups. In this paper, two formulas for calculation of the area under the curve are presented, which are derived from the trapezoid formula. These formulas are termed 'Area under the curve with respect to increase' (AUCI) and 'Area under the curve with respect to ground' (AUCG). The different information that can be derived from repeated measurements with these two formulas is exemplified using artificial and real data from recent studies of the authors. It is shown that depending on which formula is used, different associations with other variables may emerge. Consequently, it is recommended to employ both formulas when analyzing data sets with repeated measures.


Emergence of 16S rRNA methylase-producing Acinetobacter baumannii and Pseudomonas aeruginosa isolates in hospitals in Vietnam.
16S rRNA methylase-producing Gram-negative bacteria are highly resistant to all clinically important aminoglycosides. We analyzed clinical strains of 16S rRNA methylase-producing Acinetobactor baumannii and Pseudomonas aeruginosa obtained from clinical isolates in medical settings in Vietnam. From 2008 to 2011, 101 clinical strains of A. baumannii and 15 of P. aeruginosa were isolated from patients in intensive care units (ICUs) in two medical settings in Vietnam. Antimicrobial susceptibilities were determined using the microdilution method and epidemiological analysis was performed by pulsed-field gel electrophoresis and MLST. Genes encoding the 16S rRNA methylases, OXAs and CTX-Ms were analyzed by PCR and sequence analysis. 16S rRNA methylase-producing Gram-negative pathogens were detected in two hospitals in Vietnam. Of the 101 clinical isolates of A. baumannii and the 15 of P. aeruginosa isolated from two ICUs in these hospitals, 72 (71.3%) were highly resistant to amikacin, arbekacin and gentamicin, with MICs greater than 1,024 mg/L. The 16S rRNA methylases ArmA and RmtB were produced by 61 and 9 isolates of A. baumannii, respectively, and RmtB was produced by 2 isolates of P. aeruginosa. Moreover, 52 of the A. baumannii isolates producing 16S rRNA methylases harbored both blaOXA-23-like and blaOXA-51-like genes. Most A. baumannii isolates producing 16S rRNA methylase obtained in hospital A in Hanoi were ST91 and ST231, whereas most from hospital B in Ho Chi Minh City were ST136, ST195, and ST254. Gram-negative bacteria producing the 16S rRNA methylases ArmA and RmtB are emerging in medical settings in Vietnam. A. baumannii isolates in northern and southern regions of Vietnam may be of different lineages.


Effect of repeated episodes of drug-induced ventricular dyskinesia on subsequent regional function in the dog: comparison with myocardial stunning produced by repeated coronary occlusions.
Stunned myocardium can be produced by repeated short episodes of ischemia. Histochemical and ultrastructural abnormalities such as sarcomere lengthening and myofiber thinning have been noted in myocardium soon after the onset of ischemia and have been attributed to the mechanical stretching that occurs during ventricular systole. To test whether mechanical forces alone could produce the residual dysfunction seen in stunned myocardium, regional dyskinesia was produced in open chest dogs by six repeated intracoronary infusions of either potassium chloride, 0.2 mEq/min for 2.5 minutes, or lidocaine, a 10 mg bolus followed by 1 to 3 mg/min for 5 minutes. These dogs were matched with dogs that had six repeated coronary occlusions of 2.5 and 5 minutes' duration, respectively. Regional function was analyzed using fractional systolic shortening and the load-independent end-systolic pressure-length relation. Both potassium chloride and lidocaine produced regional dyskinesia that was similar to the dyskinesia produced by coronary occlusion. Although regional ventricular function after repeated coronary occlusions remained significantly reduced, function returned completely to normal within 5 minutes after the last drug-induced dyskinesia. In conclusion, regional dysfunction produced by potassium chloride and lidocaine does not produce residual dysfunction despite mechanical forces during systole similar to those seen during coronary occlusion.


A higher radiotherapy dose is associated with more durable palliation and longer survival in patients with metastatic melanoma.
Oncologists are often reluctant to recommend radiotherapy (RT) to palliate metastatic melanoma due to a perception that this tumor is "radioresistant." The Mayo Clinic experience was analyzed to determine the efficacy of palliative RT. Eighty-four consecutive patients with 114 lesions that were not metastatic to the central nervous system (CNS) were evaluated for the response of the presenting symptom, the duration of response, and survival after RT. The median dose delivered was 30 grays (Gy) and the median biologic effective dose (BED) was 39.0 Gy(10). Performance status was not uniformly available for all patients. Complete resolution of the presenting symptom occurred in 10 lesions (9%). Of the lesions treated, there was partial improvement in 86 (75%), no change in 12 (11%), and worsening in 6 (5%) lesions. The median survival was 3.8 months and freedom from disease progression (FFP) for individual lesions was 6 months. Patients treated with >30 Gy had significantly longer FFP compared with patients given </=30 Gy (P = .01). In addition, patients treated with >30 Gy had a significantly longer survival than those given a lesser dose (median of 2 months vs 8 months; P < .0001). Similarly, patients receiving a BED >39.0 Gy(10) also were found to have longer FFP (P = .03) and survival (median of 2 months vs 8 months; P < .0001) compared with those receiving a BED </=39.0 Gy(10). The dose per fraction, number of previous therapies, and location of the lesions did not appear to impact the effectiveness of RT. RT was found to provide effective palliation of non-CNS metastasis from malignant melanoma and should be considered for symptomatic patients. RT doses >30 Gy and a BED >39.0 Gy(10) were found to be associated with longer palliation.


Relationship between piglets' survivability and farrowing kinetics in hyper-prolific sows.
Prolonged farrowing and more piglets born with low birth weight are undesirable consequences of genetic selection for increased litter size. The objective of the present observational study was to evaluate the relationship between piglets' survivability and farrowing kinetics in hyperprolific sows. A total of 58 sows of different parities and 1190 piglets were included. The entire farrowing process was monitored and the following parameters were recorded: inter-piglet birth interval, birth order, total born, live born, dead born, and mummified piglets, obstetric intervention, weight at birth and 24h, colostrum yield and intake. The sows included in this study had on average 20.6 ± 0.6 total piglets born, of which 16.4 ± 0.6 were live born, 3.3 ± 0.4 were stillborn and 0.9 ± 0.2 were mummified piglets. The average farrowing duration and average birth interval were 411.3 ± 31.6 and 20.6 ± 1.7 min, respectively. Farrowing duration was positively associated (p < 0.05) with parity, number of stillborn and mummified piglets. Piglet mortality 24h after birth was negatively affected (p < 0.01) by birth weight and positively affected (p < 0.01) by cumulative birth interval. The last tercile of piglets born (birth order ≥ 17) had the highest (p < 0.01) inter-piglet birth interval (IPBI) (43.4 ± 4.17 min) compared to piglets born in the first (birth order between 2 and 7) (26.5 ± 3.8 min) and second (birth order between 8 and 16) terciles (21.9 ± 3.8 min). Cumulative birth interval, birth weight, occurrence of stillborn piglets and manual intervention were positively associated (p < 0.05) with IPBI. Piglet birth weight was also positively associated (p < 0.01) to individual colostrum intake. Piglets ingesting more colostrum had lower (p < 0.01) mortality from 24h after birth until weaning. Sow's parity and cumulative birth interval were positively associated with the presence of stillborn piglets (p = 0.02 and p < 0.01, respectively). Reducing farrowing duration may be crucial to decrease stillbirth rate and neonatal mortality in hyperprolific sows. Moreover, special care must be provided to the lighter piglets within a litter to increase their colostrum intake and minimize piglet's mortality throughout lactation.


In silico analyses for molecular genetic mechanism and candidate genes in patients with Alzheimer's disease.
This study aimed to identify candidate genes and explore the molecular pathogenesis of Alzheimer's disease (AD). Exon microarray data composed by of three human entorhinal cortex samples of AD patients and three non-demented controls (NDC) were analyzed, then expression profile data were preprocessed with the Oligo package and differentially expressed genes (DEGs) were identified by limma package in R/Bioconductor. In addition, protein-protein interaction (PPI) network was predicted and constructed using the STRING database. Finally, gene ontology (GO)-biological processes (BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by DEGs were recognized. A total of 124 up-regulated and 218 down-regulated genes were identified. TGF-beta-activated kinase 1/MAP3K7 binding protein 2 (TAB 2) and chromogranin B (secretogranin 1) (CHGB) were the significantly up- and down-regulated genes, respectively. In addition, DEGs of DnaJ (Hsp40) homolog, subfamily B, member 1 (DNAJB1) and heat shock 70 kDa protein 1A (HSPA1A) were in the up-regulated network, while synaptophysin (SYP) and somatostatin (SST) were in the down-regulated network. Furthermore, the up-regulated genes were enriched in GO-BP terms of protein stimulus, unfolding and organic substance, etc., and pathways of ECM-receptor interaction, etc. The down-regulated genes were mainly associated with nerve-related transmission and neuroactive substances transportation. Protein folding abnormality and altered synaptic transmission could have a synergistic effect on the pathomechanism of AD. DEGs including DNAJB1 and HSPA1A may be involved in both the processes, while CHGB, SYP and SST may be important for the regulation of synaptic transmission to contribute to the progress and development of AD.


Can We Predict the Outcome of Oral Dissolution Therapy for Radiolucent Renal Calculi? A Prospective Study.
We prospectively assessed the efficacy and the predictors of the success of oral dissolution therapy by alkalization for lucent renal calculi. Patients with radiolucent renal stones were counseled to undergo oral dissolution therapy, which entails oral potassium citrate 20 mEq 3 times daily, 3 L daily fluid intake and a dietary regimen. The study primary end point was the achievement of a 6-month stone-free rate with oral dissolution therapy. The other end point was a change in stone surface area as measured by noncontrast computerized tomography at 3 and 6 months. Between February 2015 and January 2016 only 182 of the 212 eligible patients who agreed to participate were compliant with oral dissolution therapy and included in the final analysis. Mean stone surface area at enrollment was 1.3 cm (range 0.16 to 11.84). At 3 months 97 (53.2%), 65 (35.7%) and 20 (11.1%) patients were oral dissolution therapy responders (stone-free), partial responders and nonresponders, respectively. Oral dissolution therapy achieved a 6-month stone-free rate of 83%, including 97 and 54 patients after 3 and 6 months of oral dissolution therapy, respectively. On regression analysis the initial 3-month response to oral dissolution therapy (p = 0.001), lower stone density (p = 0.03) and higher urine pH 12 weeks after treatment (p = 0.01) independently predicted the oral dissolution therapy response at 6 months. Regardless of stone size, oral dissolution therapy was an effective treatment approach for lucent renal stones. The initial response to oral dissolution therapy after 3 months was the key factor in determining the potential oral dissolution therapy response after 6 months. In addition, treatment compliance in achieving the targeted urine pH and low stone density has an independent role in the oral dissolution therapy response.


ATF4 Targets RET for Degradation and Is a Candidate Tumor Suppressor Gene in Medullary Thyroid Cancer.
Medullary thyroid cancer (MTC) is an aggressive tumor that harbors activating mutations of the RET proto-oncogene. We previously reported that RET inhibits transcriptional activity of ATF4, the master regulator of the stress response pathway, to prevent cell death. We hypothesized that loss of function of ATF4 plays a role in initiation of MTC. Targeted deletion of Atf4 in mice was used to assess ATF4 function in the thyroid gland. ATF4 overexpression was achieved by adenoviral and lentiviral vectors. We used immunohistochemical analysis and western blotting of MTC tumors to determine protein levels of RET and ATF4 and the Kaplan-Meier method to determine their association with clinical outcome. Targeted deletion of Atf4 in mice causes C-cell hyperplasia, a precancerous lesion for MTC. Forced ATF4 expression decreased survival of MTC cells and blocked the activation of RET downstream signaling pathways (phosphorylated ERK, phosphorylated AKT, and p70S6K). ATF4 knockdown decreased sensitivity to tyrosine kinase inhibitor-induced apoptosis. Moreover, ATF4 expression decreased RET protein levels by promoting RET ubiquitination. We found decreased or loss of ATF4 in 52% of MTC tumors (n = 39) compared with normal thyroid follicle cells. A negative correlation was observed between RET and ATF4 protein levels in MTC tumors, and low ATF4 expression was associated with poor overall survival in patients with MTC. ATF4 was identified as a negative regulator of RET, a candidate tumor suppressor gene, and may be a molecular marker that distinguishes patients at high risk of MTC from those with a longer survival prognosis.


Management of anxiety in dental practice in the UK.
A postal questionnaire was sent to a random sample of dentists in the United Kingdom. The response rate was 59.9%. Anxiety was reported as a significant problem by 66% of dentists and information was gained regarding the techniques used to manage this anxiety. 'Patient management' and general anaesthesia were the techniques most commonly employed. The frequency of usage of intravenous and inhalational sedation varied according to the age of the patient. Only 55.3% of dentists in general practice had any training in a sedative technique.


Client factors as predictors of restraint and seclusion in people with intellectual disability.
To gain more insight into the antecedent factors of restraint in institutionalised people with intellectual disability (ID), the role played by several demographic and psychological client variables was investigated. The data of 475 people (age range 12-95 years) who were residents in a Dutch institution for people with ID were collected. The severity of restraint was rated on an ordinal scale. None of the demographic variables height, weight, age, or length of stay were related to the application of restraint. Significant predictors were the psychological variables: low adaptive functioning, the presence of challenging behaviours, and a relatively high intellectual level. Of the challenging behaviours, specifically behaviours other than actual aggressiveness proved to be predictors of restraint. The fact that actual aggressiveness plays a minor role in predicting restraint is a new finding and should be further examined in future research.


Comparison of primary graft survival following penetrating keratoplasty and Descemet's stripping endothelial keratoplasty in eyes with prior trabeculectomy.
To compare corneal graft survival rate after primary Descemet's stripping endothelial keratoplasty (DSEK) and primary penetrating keratoplasty (PK) in patients with prior trabeculectomy or medically managed glaucoma. A retrospective chart review was conducted on consecutive patients who underwent DSEK or PK. Inclusion criteria consisted of eyes with a diagnosis of glaucoma prior to corneal transplantation and ≥ 6 months of follow-up. Graft failure was defined as an oedematous cornea with failure to maintain deturgescence lasting beyond a period of 1 month of intense steroid therapy or vascularisation and scarring resulting in irreversible loss of central graft clarity. Corneal graft survival was calculated using Kaplan-Meier survival analysis. Patients were divided into four groups: trabeculectomy-DSEK, trabeculectomy-PK, medical-DSEK or medical-PK. Fifty eyes (30 DSEK, 20 PK) of 50 patients (mean age 77 ± 10 years) met the enrollment criteria. Mean follow-up was 17.4 ± 14.2 months. A significantly higher proportion of the DSEK grafts (50%) compared with PK grafts (10%) failed at last follow-up (p = 0.005). Kaplan-Meier analysis identified a significant difference between the groups with respect to time to graft failure (p = 0.006). Patients with trabeculectomy who underwent DSEK had earlier graft failures than all other groups (p ≤ 0.035), but there were no differences between the medical-DSEK, medical-PK and trabeculectomy-PK groups (all p > 0.35). Eyes with prior glaucoma showed higher rates of DSEK graft failure compared with PK. Patients with prior trabeculectomy demonstrated higher and earlier corneal graft failure rates with DSEK than with PK.


What can ecological studies tell us about death?
Using an ecological study design, Gordon et al. (Isr J Health Policy Res 6:39, 2017) demonstrate variations in mortality patterns across districts and sub-districts of Israel during 2008-2013. Unlike other epidemiological study designs, the units of analysis in ecological studies are groups of people, often defined geographically, and the exposures and outcomes are aggregated, and often known only at the population-level. The ecologic study has several appealing characteristics (such as reliance on public-domain anonymous data) alongside a number of important potential limitations including the often mentioned 'ecological fallacy'. Advantages and disadvantages of the ecological design are described briefly below.


Do State Community Health Worker Laws Align with Best Available Evidence?
Community health workers (CHWs) are expected to improve patient care and population health while reducing health care costs. Law is a tool states are using to build a supportive infrastructure for the CHW workforce. This study assessed the extent existing state law pertaining to the CHW workforce aligned with best available evidence. We used the previously developed Quality and Impact of Component (QuIC) Evidence Assessment method to identify and prioritize those components that could comprise an evidence-informed CHW policy at the state level. We next assessed the extent codified statutes and regulations in effect as of December 31, 2014 for the 50 states and D.C. included the components identified in the evidence assessment. Fourteen components of an evidence-informed CHW policy were identified; eight had best, three had promising, and three had emerging evidence bases. Codified law in 18 states (35.3 % of 51) pertained to the CHW workforce. Fifteen of these 18 states authorized at least one of the 14 components from the evidence assessment (maximum: nine components, median: 2.5). The most frequently authorized component was a defined scope of practice for CHWs (authorized by eight states) followed by a standard core competency curriculum and inclusion of CHWs in multidisciplinary health care teams (each authorized by six states). States could consider the components presented in this article when developing new or strengthening existing law.


Phosphatidylserine binding is essential for plasma membrane recruitment and signaling function of 3-phosphoinositide-dependent kinase-1.
3-Phosphoinositide-dependent kinase-1 (PDK1) is a ubiquitously expressed serine/threonine kinase that functions downstream of phosphoinositide 3-kinase. Although binding of 3'-phosphoinositides, phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate, to the pleckstrin homology (PH) domain of PDK1 is known to be essential for its interaction with and activation of downstream kinases, the mechanism by which PDK1 is recruited to the plasma membrane remains controversial. Our surface plasmon resonance analysis of the PDK1 PH domain and selected mutants shows that the PH domain specifically binds phosphatidylserine using a site that is separate from the canonical phosphoinositide-binding site. Further cell studies show that this specific phosphatidylserine binding is important for the plasma membrane localization and signaling function of PDK1.


Analysis of volatile organic compounds in exhaled breath to diagnose ventilator-associated pneumonia.
Ventilator-associated pneumonia (VAP) is a nosocomial infection occurring in the intensive care unit (ICU). The diagnostic standard is based on clinical criteria and bronchoalveolar lavage (BAL). Exhaled breath analysis is a promising non-invasive method for rapid diagnosis of diseases and contains volatile organic compounds (VOCs) that can differentiate diseased from healthy individuals. The aim of this study was to determine whether analysis of VOCs in exhaled breath can be used as a non-invasive monitoring tool for VAP. One hundred critically ill patients with clinical suspicion of VAP underwent BAL. Before BAL, exhaled air samples were collected and analysed by gas chromatography time-of-flight mass spectrometry (GC-tof-MS). The clinical suspicion of VAP was confirmed by BAL diagnostic criteria in 32 patients [VAP(+)] and rejected in 68 patients [VAP(-)]. Multivariate statistical comparison of VOC profiles between VAP(+) and VAP(-) revealed a subset of 12 VOCs that correctly discriminated between those two patient groups with a sensitivity and specificity of 75.8% ± 13.5% and 73.0% ± 11.8%, respectively. These results suggest that detection of VAP in ICU patients is possible by examining exhaled breath, enabling a simple, safe and non-invasive approach that could diminish diagnostic burden of VAP.


Nosocomial infection of C. auris in COVID-19 Intensive Care Unit in Türkiye and Phylogenetic Analysis of Isolates.
The difficulties in the identification of C. auris and the delays in the implementation of infection control precautions contribute to outbreaks. This study analyzed 10 patients with COVID-19 and C. auris candidemia, their characteristic and clinical features and phylogenetic features, and the antifungal susceptibilities of the isolates. C. auris were detected in the COVID-19 ICU of a university hospital between January and August 2021. Identification to species level was performed using MALDI-TOF MS. Antifungal susceptibilities were determined by the Sensititre YeastOne YO10 panel. The isolates were whole genome sequenced to assess genetic relatedness and a phylogenetic tree was drawn including various C. auris clades. The mean growth time in blood cultures was 38.8 h. C. auris candidemia developed on the average 27th day of ICU admission. All were susceptible to anidulafungin and micafungin, while they were resistant to fluconazole and amphotericin B. Only three isolates were found to be resistant to caspofungin. All patients died. With the WGS method, all isolates were found in a close resemblance to each other in terms of total nucleotide similarity (with a minimum of 96% pairwise alignment). Our isolates showed the closest similarity to South Asian clade (Clade I). This study is the first to evaluate the phylogenetic characteristics of C. auris using WGS and to determine antifungal susceptibilities in Türkiye on COVID-19 patients. The mortality rate was very high in patients who have both COVID-19 and C. auris candidemia.


Epidemiology of Streptococcus pneumoniae causing acute otitis media among children in Southern Catalonia throughout 2007-2013: Incidence, serotype distribution and vaccine's effectiveness.
This study investigated incidence and serotype distribution of Streptococcus pneumoniae causing acute otitis media (AOM) in Catalonian children, evaluating vaccination effectiveness in the current era of extended valency pneumococcal conjugate vaccines (PCVs). Population-based surveillance study that included all AOM cases with isolation of pneumococcus (from otic fluids/otorrea) identified among children ≤14 years in the region of Tarragona (Southern Catalonia, Spain) from 01/01/2007 to 31/12/2013. Prevalence of infections caused by serotypes covered by the different PCVs formulations were calculated for the periods before and after 30/06/2010 (date of PCV7/PCV13 replacement). The indirect cohort method was used to estimate PCV7/13 effectiveness against vaccine-type infections. A total of 78 children with a pneumococcal AOM were identified across study period, which meant an incidence rate of 23 cases per 100,000 population-year. Thirty-six cases (46.2%) occurred within the late PCV7 era and 42 cases (53.8%) during the early PCV13 era. Overall, the most common serotypes were type 19A (21.7%), type 3 (13.3%) and type 15B (6.7%). Prevalence of cases caused by serotypes included in PCV7 did not substantially change between the first and the second study period (from 10.3% to 12.9%), whereas prevalence of cases caused by PCV13 serotypes showed a decreasing trend between both periods (from 65.5% to 48.4%). The aggregate PCV7/13 effectiveness against vaccine-type infections was 72% (95% confidence interval: -26 to 94). Pneumococcal conjugate vaccination appears an acceptable preventive option to prevent pneumococcal AOM in infants. However, its serotype coverage and clinical effectiveness are not optimal.


Microbiological etiology in prosthetic valve endocarditis: A nationwide registry study.
Prosthetic valve endocarditis (PVE) is a feared complication after heart valve surgery. Studies on differences in bacteriology in various types of PVE are limited. This study aimed to investigate the microbiology of PVE depending on the type of prosthetic valve and timing of diagnosis. A retrospective study based on the Swedish Registry on Infective Endocarditis focusing on PVE was conducted. The cohort was divided into mechanical and bioprosthetic valves; into endocarditis localization in the aortic, mitral, or tricuspid valve; and into early and late PVE. The microbiology in these groups was compared. Predictors of Staphylococcus aureus as the cause of PVE were examined by multivariable logistic regression. A total of 780 episodes of PVE in 749 patients were compared regarding the distribution of causative microbiological agents. The most common agents included alpha-hemolytic streptococci (29%), S. aureus (22%), enterococci (14%), coagulase-negative staphylococci (CoNS) (12%), and Cutibacterium acnes (6%). S. aureus was more commonly found on mechanical valves compared to bioprosthetic ones (36% vs. 17%, p < 0.001) whereas alpha-hemolytic streptococci, enterococci, and CoNS were more common on bioprosthetic valves. There were no significant differences in the microbiology of PVE affecting mitral or aortic valves or in cases of early and late PVE. Predictors for S. aureus as the cause of PVE were end-stage renal disease, intravenous drug use, mechanical valve, and tricuspid localization of endocarditis. The type of prosthetic heart valve is associated with the causative pathogen. Patients with mechanical valves are more likely to have PVE caused by S. aureus.


Identification of product-substrate pattern for erythrocyte membranes self-digestion using the original two-dimensional electrophoretic technique.
Ghost proteins immobilized in polyacrylamide gel after SDS-PAGE (first dimension) were degraded by endogenous membrane proteases. Fragments of the gels were submitted to SDS-PAGE (second dimension). Undigested proteins appeared on a diagonal, whereas products of proteolysis were evident below the substrates on electropherograms. The typical product patterns for spectrin, band 3, 4.1 and 4.2 proteins for human and bovine ghosts, are described.


Complete Versus Culprit-Only Revascularization in Patients Presenting With ST-Segment Elevation Myocardial Infarction: A Meta-Analysis of Randomized Control Trials.
In patients with ST elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) of the culprit vessel is the preferred treatment option. For patients with multivessel disease, the benefit of revascularization of the non-culprit artery is not well known. This meta-analysis aims to assess the efficacy and safety of complete versus culprit vessel only revascularization. Randomized control trials (RCT) that compared head-to-head complete versus culprit-vessel only revascularization in STEMI patients and reported main outcomes of interest such as mortality, myocardial infarction, and revascularization, were included in this meta-analysis. We found ten RCTs satisfying our inclusion criteria. Data was extracted and used to estimate the risk ratio (RR) and 95% confidence interval (CI) for dichotomous variables. Our study included 7030 patients (3426 complete revascularization, and 3604 culprit-only revascularization). Complete revascularization (CR) (both immediate and staged) significantly reduced the risk of MACE compared with culprit only (CO) revascularization (10.7% vs 20.1%, RR 0.53; 95% CI 0.43 to 0.64; P < 0.0001), reinfarction (5.0% vs 6.9%, RR 0.69; 95 CI 0.51 to 0.93; P < 0.01), and revascularization (4.2% vs 12.7%, RR 0.37; 95 CI 0.26 to 0.54; P < 0.0001). Our analysis did not find any significant difference in all-cause mortality between CR and CO (4.6% vs 5.0%, RR 0.89; 95 CI 0.72 to 0.1.10; P = 0.27). In conclusion, complete revascularization was associated with a significant reduction in major adverse cardiovascular events, revascularization and reinfarction.


Histological types of laryngotracheal tumors induced in Syrian golden hamsters by nitrosomorpholine and nitrosopiperidine.
The chronic oral administration of nitrosomorpholine (NM) and nitrosopiperidine (NP) to 360 adult Syrian golden hamsters of both sexes resulted in the induction of a high incidence of laryngo-tracheal tumors, which in the group treated with 0.01% solution of NM affected up to 80% of the males. A total of 232 different laryngo-tracheal tumors were found. 36 of these were located within the supraglottic and glottic larynx, 62 were within the subglottic and glottic larynx, and 134 arose within the trachea. Among the laryngeal supraglottic and glottic tumors there were 18 squamous cell carcinomas, 16 squamous cell papillomas and only 2 mixed cell mucoepidermoid papillomas. All the subglottic laryngeal tumors and tracheal tumors were mixed cell mucoepidermoid papillomas. In this study, the squamous cell carcinomas observed within the larynx of hamsters bear morphological and biological similarities to their tumor counterpart found in the larynx of adult man. The laryngeal squamous papillomas observed in this experiment are not similar to the squamous papillomas occurring in man during infancy and childhood. The mixed cell mucoepidermoid papillomas of the hamster trachea and subglottis are a peculiar neoplasm of this species, which morphologically and biologically differs from the cases of tracheal papillomatosis described in man, as well as from the mucoepidermoid tumors of major and minor salivary gland origin also seen in this latter species.


Systems genetics of wood formation.
In woody plants, xylogenesis is an exceptionally strong carbon sink requiring robust transcriptional control and dynamic coordination of cellular and metabolic processes directing carbon allocation and partitioning into secondary cell wall biosynthesis. As a biological process, wood formation is an excellent candidate for systems modeling due to the strong correlation patterns and interconnectedness observed for transcriptional and metabolic component traits contributing to complex phenotypes such as cell wall chemistry and ultrastructure. Genetic variation in undomesticated tree populations provides abundant perturbation of systems components, adding another dimension to plant systems biology (besides spatial and temporal variation). High-throughput analysis of molecular component traits in adult trees has provided the first insights into the systems genetics of wood, an important renewable feedstock for biomaterials and bioenergy.


Suitable classification of mortars from ancient Roman and Renaissance frescoes using thermal analysis and chemometrics.
Literature on mortars has mainly focused on the identification and characterization of their components in order to assign them to a specific historical period, after accurate classification. For this purpose, different analytical techniques have been proposed. Aim of the present study was to verify whether the combination of thermal analysis and chemometric methods could be used to obtain a fast but correct classification of ancient mortar samples of different ages (Roman era and Renaissance). Ancient Roman frescoes from Museo Nazionale Romano (Terme di Diocleziano, Rome, Italy) and Renaissance frescoes from Sistine Chapel and Old Vatican Rooms (Vatican City) were analyzed by thermogravimetry (TG) and differential thermal analysis (DTA). Principal Component analysis (PCA) on the main thermal data evidenced the presence of two clusters, ascribable to the two different ages. Inspection of the loadings allowed to interpret the observed differences in terms of the experimental variables. PCA allowed differentiating the two kinds of mortars (Roman and Renaissance frescoes), and evidenced how the ancient Roman samples are richer in binder (calcium carbonate) and contain less filler (aggregate) than the Renaissance ones. It was also demonstrated how the coupling of thermoanalytical techniques and chemometric processing proves to be particularly advantageous when a rapid and correct differentiation and classification of cultural heritage samples of various kinds or ages has to be carried out. Graphical abstractPCA analysis of TG data allows differentiating mortar samples from different ages (Roman era and Renaissance).


Microbiome in Anxiety and Other Psychiatric Disorders.
Initial studies suggested that the fluctuations in the quantity, variety, and composition of the gut microbiota can significantly affect disease processes. This change in the gut microbiota causing negative health benefits was coined dysbiosis. Initial research focused on gastrointestinal illnesses. However, the gut microbiome was found to affect more than just gastrointestinal diseases. Numerous studies have proven that the gut microbiome can influence neuropsychiatric diseases such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis.


Synthetic cell biology.
Synthesis of data into formal models of cellular function is rapidly becoming a necessary industry. The complexity of the interactions among cellular constituents and the quantity of data about these interactions hinders the ability to predict how cells will respond to perturbation and how they can be engineered for industrial or medical purposes. Models provide a systematic framework to describe and analyze these complex systems. In the past few years, models have begun to have an impact on mainstream biology by creating deeper insight into the design rules of cellular signal processing, providing a basis for rational engineering of cells, and for resolving debates about the root causes of certain cellular behaviors. This review covers some of the recent work and challenges in developing these "synthetic cell" models and their growing practical applications.