Total neoadjuvant treatment to increase the clinical complete response rate for distal locally advanced rectal cancer (TESS): A study protocol of a prospective, open-label, multicenter, single-arm, phase 2 trial.
Standard treatment of locally advanced rectal cancer (LARC) was neoadjuvant chemoradiotherapy (CRT), followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, attempts to deliver both systemic chemotherapy and neoadjuvant CRT prior to surgery. Patients treated with neoadjuvant chemotherapy were more likely to show higher tumor regression. The objective of this trial was to increase complete clinical rate (cCR) for LARC patients by optimizing tumor response, using TNT regimen as compared to conventional chemoradiotherapy. TESS, a prospective, open-label, multicenter, single-arm, phase 2 study, is underway. Main inclusion criteria include cT3-4aNany or cT1-4aN+ rectal adenocarcinoma aged 18-70y; Eastern Cooperative Oncology Group (ECOG) performance 0-1; location ≤5 cm from anal verge. Ninety-eight patients will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplatin) before, during, and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as Watch and Wait strategy) and adjuvant chemotherapy capecitabine 2 cycles. Primary endpoint is the cCR rate. Secondary endpoints include ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; local recurrence or metastasis; disease-free survival; locoregional recurrence-free survival; acute toxicity; surgical complications; long-term anal function; late toxicity; adverse effect, ECOG standard score, and quality of life. Adverse events are graded per Common Terminology Criteria for Adverse Events V5.0. Acute toxicity will be monitored during antitumor treatment, and late toxicity will be monitored for 3 years from the end of the first course of antitumor treatment. The TESS trial aims to explore a new TNT strategy, which is expected to increase the rate of cCR and sphincter preservation rate. This study will provide new options and evidence for a new sandwich TNT strategy in patients with distal LARC.


Potential anti-acanthamoebic effects through inhibition of CYP51 by novel quinazolinones.
Acanthamoeba spp. are free living amoebae which can give rise to Acanthamoeba keratitis and granulomatous amoebic encephalitis. The surface of Acanthamoeba contains ergosterol which is an important target for drug development against eukaryotic microorganisms. A library of ten functionally diverse quinazolinone derivatives (Q1-Q10) were synthesised to assess their activity against Acanthamoeba castellanii T4. The in-vitro effectiveness of these quinazolinones were investigated against Acanthamoeba castellanii by amoebicidal, excystation, host cell cytopathogenicity, and NADPH-cytochrome c reductase assays. Furthermore, wound healing capability was assessed at different time durations. Maximum inhibition at 50 μg/mL was recorded for compounds Q5, Q6 and Q8, while the compound Q3 did not exhibit amoebicidal effects at tested concentrations. Moreover, LDH assay was conducted to assess the cytotoxicity of quinazolinones against HaCaT cell line. The results of wound healing assay revealed that all compounds are not cytotoxic and are likely to promote wound healing at 10 μg/mL. The excystation assays revealed that these compounds significantly inhibit the morphological transformation of A. castellanii. Compound Q3, Q7 and Q8 elevated the level of NADPH-cytochrome c reductase up to five folds. Sterol 14alpha-demethylase (CYP51) a reference enzyme in ergosterol pathway was used as a potential target for anti-amoebic drugs. In this study using i-Tasser, the protein structure of Acanthamoeba castellanii (AcCYP51) was developed in comparison with Naegleria fowleri protein (NfCYP51) structure. The sequence alignment of both proteins has shown 42.72% identity. Compounds Q1-Q10 were then molecularly docked with the predicted AcCYP51. Out of ten quinazolinones, three compounds (Q3, Q7 and Q8) showed good binding activity within 3 Å of TYR 114. The in-silico study confirmed that these compounds are the inhibitor of CYP51 target site. This report presents several potential lead compounds belonging to quinazolinone derivatives for drug discovery against Acanthamoeba infections.


Alveolar echinococcosis as a cause of vertebral osteomyelitis and soft tissue infection with recurrent cutaneous fistula formation.
Echinococcus multilocularis is endemic in Germany. However, alveolar echinococcosis is a rare disease. Most commonly the parasite affects the liver, behaving like a malignant tumour. Bones are affected in less than 2% of cases. We report a case of vertebral osteomyelitis accompanied by recurrent cutaneous fistula formation.


First report of blaOXA-24 carbapenemase gene, armA methyltransferase and aac(6')-Ib-cr among multidrug-resistant clinical isolates of Proteus mirabilis in Algeria.
Carbapenemase-producing, or carbapenem-resistant, Enterobacteriaceae are an emerging threat to human and animal health because they are resistant to many of the last-line antimicrobials available for treatment of infection. The aim of this study was to analyse the antimicrobial resistance patterns and their encoding genes of Proteus mirabilis isolated in Constantine, Algeria. A total of 108 Proteus, Morganella and Providencia (PMP) strains were isolated from a large variety of clinical specimens at University Hospital of Constantine in Algeria. Isolates were identified using the API 20E system and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Diagnostic accuracy was determined by independent comparison of each method to phylogenetic analysis based on 16S rRNA gene sequencing. Antimicrobial susceptibility was determined by the standard disk diffusion and Etest methods. The presence of antimicrobial resistance genes was screened for by PCR amplification and sequencing. A total of 72 PMP strains were multidrug-resistant (MDR). Among them, one P. mirabilis isolate was resistant to imipenem with a minimum inhibitory concentration (MIC) of ≥12μg/mL. PCR and sequencing showed the presence of various antimicrobial resistance genes, including blaCTX-M-15, blaTEM-1, blaTEM-2, blaPER-1, blaSHV-11, aadA1, aadA2, armA, aac(6')-Ib, aac(6')-Ib-cr, aac(3)-Ia and ant(2″)-I, forming different resistance profiles. Moreover, the blaOXA-24 gene was detected in the imipenem-resistant P. mirabilis strain. In this study, a MDR P. mirabilis isolate harbouring the blaOXA-24, armA 16S rRNA methylase and aac(6)-Ib-cr genes was found for the first time in Algeria.


Liver transplantation in patients with atrial fibrillation.
In this study we described survival and incidence of perioperative and postoperative complications in liver transplant recipients with known atrial fibrillation. A total number of 717 patients underwent liver transplantation between January 2005 and December 2008 at our institution. In this population, preoperative paroxysmal or chronic-persistent atrial fibrillation was diagnosed in 32 patients (4.5%). Of these, 12 patients died during follow-up and 4 patients required liver retransplantation. Perioperative cardiac complications occurred in 10 patients (31%) resulting in 3 cardiac-related deaths. Median patient survival was 1613 days (range, 22-2492) and median graft survival was 1524 days (range, 10-2492). Twenty patients are still alive with a median survival of 1861 days (range, 1189-2492) after liver transplantation.


Meticillin-resistant Staphylococcus aureus (MRSA): global epidemiology and harmonisation of typing methods.
This article reviews recent findings on the global epidemiology of healthcare-acquired/associated (HA), community-acquired/associated (CA) and livestock-associated (LA) meticillin-resistant Staphylococcus aureus (MRSA) and aims to reach a consensus regarding the harmonisation of typing methods for MRSA. MRSA rates continue to increase rapidly in many regions and there is a dynamic spread of strains across the globe. HA-MRSA is currently endemic in hospitals in most regions. CA-MRSA clones have been spreading rapidly in the community and also infiltrating healthcare in many regions worldwide. To date, LA-MRSA is only prevalent in certain high-risk groups of workers in direct contact with live animals. CA-MRSA and LA-MRSA have become a challenge for countries that have so far maintained low rates of MRSA. These evolutionary changes have resulted in MRSA continuing to be a major threat to public health. Continuous efforts to understand the changing epidemiology of S. aureus infection in humans and animals are therefore necessary, not only for appropriate antimicrobial treatment and effective infection control but also to monitor the evolution of the species. The group made several consensus decisions with regard to harmonisation of typing methods. A stratified, three-level organisation of testing laboratories was proposed: local; regional; and national. The functions of, and testing methodology used by, each laboratory were defined. The group consensus was to recommend spa and staphylococcal cassette chromosome mec (SCCmec) typing as the preferred methods. Both are informative in defining particular strain characteristics and utilise standardised nomenclatures, making them applicable globally. Effective communication between each of the different levels and between national centres was viewed as being crucial to inform and monitor the molecular epidemiology of MRSA at national and international levels.


The Empusa code generator and its application to GBOL, an extendable ontology for genome annotation.
The RDF data model facilitates integration of diverse data available in structured and semi-structured formats. To obtain a coherent RDF graph the chosen ontology must be consistently applied. However, addition of new diverse data causes the ontology to evolve, which could lead to accumulation of unintended erroneous composites. Thus, there is a need for a gate keeping system that compares the intended content described in the ontology with the actual content of the resource. The Empusa code generator facilitates creation of composite RDF resources from disparate sources. Empusa can convert a schema into an associated application programming interface (API), that can be used to perform data consistency checks and generates Markdown documentation to make persistent URLs resolvable. Using Empusa consistency is ensured within and between the ontology and the content of the resource. As an illustration of the potential of Empusa, we present the Genome Biology Ontology Language (GBOL). GBOL uses and extends current ontologies to provide a formal representation of genomic entities, along with their properties, relations and provenance.


Release of chlorpheniramine maleate from fatty acid ester matrix disks prepared by melt-extrusion.
Chlorpheniramine maleate was incorporated into disks consisting of glyceryl fatty acid esters, polyethylene glycol fatty acid esters or a combination of the two. A melt-extrusion process was used to prepare the matrix disks containing the drug. The release of the drug into distilled water, pH 1.2 buffer, and pH 7.5 buffer showed the expected square root of time dependence. An increase in the fatty acid ester hydrophilic-lipophilic balance (HLB) from 1 to 14 resulted in a 10-fold increase in the drug release rate from 0.25 +/- 0.01 to 25.84 +/- 1.29 mg cm-2 h-1/2. The maximum release rate was seen from the fatty acid ester with a melting point of 44 degrees C. The pH of the dissolution medium had a small impact on the rate of drug release, but the rate of agitation had no significant influence on the rate of drug release. By blending a fatty acid ester of a high melting point (64 degrees C) and a low HLB value of 2 with esters of lower melting points (33 to 50 degrees C) or higher HLB values (10 to 14), it was possible to modify the release from 10.0 +/- 0.70 to 21.5 +/- 0.57 mg cm-2 h-1/2.


A three-dimensional comparison of intramedullary nail constructs for osteopenic supracondylar femur fractures.
This study developed a new 6 degree-of-freedom, unconstrained biomechanical model that replicated the in vivo loading environment of femoral fractures. The objective of this study was to determine whether various distal fixation strategies alter failure mechanisms and/or offer mechanical advantages when performing retrograde intramedullary nail (IMN) stabilization of supracondylar femur fractures in osteoporotic bone. Forty fresh-frozen human femora were allocated into 2 groups of matched pairs: "locked" (fixed angle locking construct with both distal locking screws rigidly attached to the IMN) versus "unlocked" (conventional locking technique with 2 distal locking screws targeted through the distal locking screw holes of the IMN) and "locked" versus "washer" (fixed angle locking with the most distal screw exchanged for a bolt with condyle washers) distal fixation of a retrograde IM nails. A comminuted fracture (OTA 33-A3) was simulated with a wedge osteotomy. Bone density measurements were completed on all specimens before instrumentation. Instrumented femurs were loaded axially to failure, whereas 6 degree-of-freedom translations and angulations were measured using Roentgen stereophotogrammetric analysis. Mean (± SD) load born by "locked" specimens (1609 ± 667 N) at clinical failure was 38.1% greater (P = 0.09) than the corresponding mean load born by "unlocked" specimens (1165 ± 772 N). Clinical failure for the "washer" group (1738 ± 772 N) was 29.9% greater (P = 0.07) than the corresponding mean of the "locked" counterparts (1338 ± 822 N). Failure load was most clearly related to bone density in the "unlocked" fixation group. Predicting failure load based on bone density using a least squares estimate suggests that the washer construct provides superior fixation to other treatment techniques. The failure mechanism for a comminuted, supracondylar fracture cannot be analyzed accurately with a 1-dimensional measurement. The most common failure mechanism in this model was medial translation and varus angulation.


Increased expression of insulin-like growth factor I augments the progressive phase of synaptogenesis without preventing synapse elimination in the hypoglossal nucleus.
The in vivo actions of insulin-like growth factor I (IGF-I) on synaptogenesis in the hypoglossal nucleus were investigated in transgenic mice that overexpress IGF-I in the brain postnatally and in normal nontransgenic littermate controls. In a previous study using these mice, we found that IGF-I increases the total volume of the hypoglossal nucleus by increasing the volume of neuropil rather than by increasing total neuron number; therefore, the progressive and regressive phases of synaptogenesis could be evaluated without the confounding effects of altered neuron number. The volume of the hypoglossal nucleus was significantly increased by 28% to 59% in transgenic mice after postnatal day (P) 7, whereas the total number of hypoglossal neurons did not differ significantly from controls. The numerical density of neurons was significantly decreased by 21% to 38% after P7, and the density of myelinated axons was significantly increased by 19%. Although the numerical density of synapses did not differ between groups at any age, the total number of synapses in transgenic mice was increased by 42% to 52% after P14. Total synapse number in controls increased from P7 (7.9 million) to peak values at P21 (36.0 million), followed by a significant decrease (33%) at P130 (24.2 million). In transgenic mice, total synapses increased from 8.2 million on P7 to 51.1 million on P21, followed by a significant decrease (28%) to 36.7 million at P130. Our results demonstrated that IGF-I can stimulate a persistent increase in the number of hypoglossal synapses, thereby augmenting the progressive phase of synaptogenesis without preventing synapse elimination during the regressive phase.


Fluorescence polarization studies on the conformational transition of bovine plasma albumin in acidic solutions.
The acid-induced isomerization (the N-F transition) and expansion of bovine plasma albumin were studied by measuring fluorescence polarization and lifetime of the excited state of tryptophyl fluorophors. Most of the changes (decreases) in the reciprocal of fluorescence polarization and lifetime of the excited state correlated exactly with the N-F1 transition and/or the initial part of the N-F transition. These findings suggest that though the N-F transition is the cooperative pH-dependent conformational transition, the N-F transition clearly involves an intermediate step, such as the N-F1 and F1-F2 transitions. Rotational relaxation times for the N- and F-forms obtained by Perrin plot of tryptophyl fluorescence polarization were approximately 75 and 120-180 ns, respectively. The unexpected short rotational relaxation time of 75 ns of the N-form might be due to the rotational freedom of the tryptophyl side chain itself and/or of small flexible loci where tryptophyl fluorophors attach.


Effects of the beta-lactam antibiotic ceftriaxone on nicotine withdrawal and nicotine-induced reinstatement of preference in mice.
Several studies suggest that repeated nicotine administration causes alterations in glutaminergic transmission that may play an important role in developing and maintaining nicotine addiction. Chronic nicotine administration in rats decreases the expression of the glutamate transporter-1 (GLT-1) and cysteine-glutamate exchanger (system xC-) in the nucleus accumbens. We hypothesized that ceftriaxone, a GLT-1 and system xC- activator, would decrease murine behavioral aspects of nicotine dependence. This study aimed to investigate the effect of repeated ceftriaxone administration on the behavioral effects of nicotine using mouse models of conditioned reward and withdrawal. Using male ICR mice, the ability of repeated ceftriaxone injections to modulate the development and reinstatement of a nicotine-conditioned place preference (CPP) was evaluated. Additionally, nicotine withdrawal-associated signs were assessed. These included both physical (somatic signs and hyperalgesia) and affective (anxiety-related behaviors) withdrawal signs in mice. Finally, the effects of ceftriaxone on nicotine-induced antinociception and hypothermia after acute nicotine injection were measured. Ceftriaxone had no effect on the development of nicotine preference but significantly attenuated nicotine-induced reinstatement of CPP. Furthermore, ceftriaxone reversed all nicotine withdrawal signs measured in mice. Altogether, these findings show that a β-lactam antibiotic reduces nicotine withdrawal and nicotine-seeking behavior. Our results suggest that the documented efficacy of ceftriaxone against cocaine and morphine dependence-related behaviors effects extends to nicotine.


von Willebrand factor contained in factor VIII concentrates of different purities supports platelet adhesion in blood samples from a heterogeneous group of patients with von Willebrand disease.
Plasma derived FVIII-VWF concentrates in which the VWF structure is reasonably maintained are recommended as substitutive therapy in VWD. Our aim was to assess platelet deposition and binding to subendothelial structures of VWF present in FVIII concentrates. Cryoprecipitate (CRY), intermediate-purity (IPC), or high-purity (HPC) FVIII concentrates were added in vitro to citrated blood samples from 11 patients affected by different subtypes of VWD, with the aim of normalizing VWF levels. Measurements of VWF:Ag, ristocetin cofactor (RiCof) activities, FVIII coagulant activity (FVIII:C), and platelet interaction with subendothelium under flow conditions (Baumgartner's perfusion method, computer-assisted morphometry, shear rate 1000 s-1, 10 min, 37 degrees C) were determined. Binding of VWF to the luminal surface of the perfused vessels was assessed by immunofluorescence microscopy. Paired t-test statistics were performed. Addition of FVIII-VWF preparations raised VWF:Ag from baseline (BSL) values of 0.3 (SD 0.2) to averages of 1.4 (SD 0.5, p < 0.001), 1.2 (SD 0.6, p < 0.001), and 0.4 (SD 0.3) IU mL-1 after CRY, IPC, and HPC, respectively. A positive labeling for VWF was observed by immunofluorescence in vessels perfused with blood containing any of the concentrates. Platelet adhesion of 13.2 (SD 7.6), 22.4 (SD 10.8), 24.8 (SD 7.8, p < 0.03), or 22.5 (SD 4.8)% was measured in BSL, CRY, IPC, or HPC tests, respectively. Our observations support the hypothesis above the mechanisms involved in the beneficial effects of commercial concentrates in von Willebrand disease: the VWF in these concentrates has functional capacity to bind to subendothelium and to support platelet adhesion.


Spike shape analysis of electromyography for parkinsonian tremor evaluation.
Standard electromyography (EMG) parameters have limited utility for evaluation of Parkinson disease (PD) tremor. Spike shape analysis (SSA) EMG parameters are more sensitive than standard EMG parameters for studying motor control mechanisms in healthy subjects. SSA of EMG has not been used to assess parkinsonian tremor. This study assessed the utility of SSA and standard time and frequency analysis for electromyographic evaluation of PD-related resting tremor. We analyzed 1-s periods of EMG recordings to detect nontremor and tremor signals in relaxed biceps brachii muscle of seven mild to moderate PD patients. SSA revealed higher mean spike amplitude, duration, and slope and lower mean spike frequency in tremor signals than in nontremor signals. Standard EMG parameters (root mean square, median, and mean frequency) did not show differences between the tremor and nontremor signals. SSA of EMG data is a sensitive method for parkinsonian tremor evaluation.


Adult T-cell leukemia with generalized cytomegalic inclusion disease and pneumocystis carinii pneumonia.
An autopsy case of adult T-cell leukemia with generalized cytomegalic inclusion disease and pneumocystis carinii pneumonia is reported. Tumor cells had T-cell characteristics (E-rosette) and cerebriform nucleus similar to Sèzary cells. Generalized lymphadenopathy, hepatosplenomegaly and an ectopic pancreas in the ileum were found at the time of autopsy. Histologically, leukemic infiltration was observed in almost every organ, and perivascular infiltration, vascular invasion were conspicuous findings. Cytomegalic inclusion bodies were observed in most organs (lungs, salivary glands, pancreas, liver, ectopic pancreas, sweat gland, stomach, thyroid gland, pituitary body, etc.). An acute hepatitis, probably caused by cytomegalovirus, was also noted. Presumed correlation of adult T-cell leukemia, cutaneous T-cell lymphoma and T-cell lymphoma was discussed.


Do we have a robust method for preoperative tumour depth assessment for oral cavity tumours with clinically negative necks?
Tumour depth is an important prognostic factor in head and neck cancer and has recently been included in the eighth edition of the Union for International Cancer Control TNM classification of malignant tumours for oral squamous cell carcinoma (OSCC). It is important to appraise the accuracy of depth assessments; however, there is little current evidence in the literature. Accurate depth assessment is particularly pertinent in cT1-T2N0 OSCC where it may influence neck management. A retrospective study was performed at two tertiary referral centres, in which surgically treated patients with cT1-T4N0 OSCC were audited. Preoperative tumour depth assessments from multimodality radiological staging scans were compared with the final histopathological depth. The predictive accuracy of intraoral ultrasound (IOUS), computed tomography (CT), and magnetic resonance imaging (MRI) for tumour depth was evaluated. Accuracy to within 3mm of the histopathological depth was seen in 56.7% of MRI scans and 57.1% of CT scans. IOUS appeared to have superior prediction, with 78.2% of measurements within 3mm. Over one third of CT and MRI imaging failed to detect a lesion; IOUS scans detected the lesions in all of these case. In conclusion, the reliability of preoperative imaging assessment of tumour depth should be considered when recommending treatment.


Elevation of urinary liver-type fatty acid-binding protein as predicting factor for occurrence of contrast-induced acute kidney injury and its reduction by hemodiafiltration with blood suction from right atrium.
Although contrast-induced acute kidney injury (CI-AKI) has a great impact on patients' prognosis, few data exist regarding predictors of CI-AKI in patients with severe renal dysfunction who have undergone contrast angiography. Therefore, we prospectively studied 25 patients with renal dysfunction, which was defined as the estimated glomerular filtration rate (eGFR) level <45 ml/min/1.73 m(2), undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). We performed hemodiafiltration with blood suction from the right atrium (RA-HDF). The mean level of urinary liver-type fatty acid-binding protein (L-FABP) at baseline was significantly higher in the CI-AKI group than in the non-CI-AKI group (59.8 ± 45.6 vs 13.4 ± 11.9 μg/gCr, P = 0.0003). Multivariate regression analysis demonstrated that baseline urinary L-FABP was an independent significant predictor of CI-AKI (β = 0.741, P = 0.013). Receiver-operating characteristic analysis showed that baseline urinary L-FABP exhibited 100 % sensitivity and 81.8 % specificity for predicting CI-AKI when the cutoff value was defined as 19.0 μg/gCr. Interestingly, the incidence of CI-AKI after CAG or PCI was reduced in the RA-HDF group in a comparison with 41 control patients (12 % vs 27 %) with eGFR level <45 ml/min/1.73 m(2) who underwent PCI before the introduction of RA-HDF. In conclusion, baseline L-FABP levels can be a predictor for occurrence of CI-AKI. We suggest that RA-HDF may prevent the development of CI-AKI in patients with severe renal dysfunction undergoing coronary procedures, although further large-scale prospective study is necessary to confirm our conclusions.


Non-mosaic trisomy 20 in amniotic fluid cultures with minor anomalies in the fetus.
A non-mosaic trisomy 20 was discovered in all cells in two separate cultures from an age-related genetic amniocentesis. Karyotypes of cells obtained via amniocentesis at the time of termination and of cells cultured from the placenta gave the same unambiguous results. However, the fetus, under macro- and microscopic analysis, showed only two minor anomalies: left simian crease and low-set ears. These findings are more suggestive of a normal or at most mosaic trisomy 20 state. The significance of this finding for prenatal diagnosis is discussed.


Effects of public-health measures for zeroing out different SARS-CoV-2 variants.
Targeted public health interventions for an emerging epidemic are essential for preventing pandemics. During 2020-2022, China invested significant efforts in strict zero-COVID measures to contain outbreaks of varying scales caused by different SARS-CoV-2 variants. Based on a multi-year empirical dataset containing 131 outbreaks observed in China from April 2020 to May 2022 and simulated scenarios, we ranked the relative intervention effectiveness by their reduction in instantaneous reproduction number. We found that, overall, social distancing measures (38% reduction, 95% prediction interval 31-45%), face masks (30%, 17-42%) and close contact tracing (28%, 24-31%) were most effective. Contact tracing was crucial in containing outbreaks during the initial phases, while social distancing measures became increasingly prominent as the spread persisted. In addition, infections with higher transmissibility and a shorter latent period posed more challenges for these measures. Our findings provide quantitative evidence on the effects of public-health measures for zeroing out emerging contagions in different contexts.


Early behavior characteristics and sleep disturbance in Rett syndrome.
This paper reviews the early features of Rett syndrome (RTT). The behavioral characteristics of RTT were analyzed retrospectively by taking history and asking about early infancy behaviors. The earliest behavioral characteristics are thought to be autistic features and hypotonia of trunkal muscles. Analysis of sleep-wake rhythm and all-night polysomnography suggested that the initial lesion is serotonergic and noradrenargic hypofunction at brainstem level. Dopaminergic (DA) hypofunction associated with DA receptor supersensitivity follows as the brain matures. Characteristic symptoms developing at specific age ranges are based on the neuronal connections of the brainstem aminergic neurons and DA neurons with the pedunculo-pontine nuclei, projecting to specific cortical areas.


Structural reliability of road accidents reconstruction.
Reconstruction of road accidents combines objective and subjective action. The former concerns science, the latter assessment of human behavior in the context of objective findings. It is not uncommon for experts equipped with an arsenal of tools to obtain similar results of calculations, but to present radically different conclusions about the cause of the accident. The use of sophisticated methods of uncertainty analysis does not guarantee improvement in quality of reconstruction, because, increasingly, the most serious source of reduced reliability of reconstruction is problems in logical inference. In the article the structure of uncertainty and reliability of accident reconstruction was described. A definition of reliability of road accident reconstruction based on the theory of conditional probability and Bayesian network, as a function of modeling, data and expert reliability (defined in the text) was proposed. The uncertainty of reconstruction was made dependent only on the uncertainty of the data. This separation makes it possible to conduct a qualitative and quantitative analysis of reconstruction reliability and to analyze its sensitivity to component parameters, independently of the uncertainty analysis. An example of calculation was presented. The proposed formalism constitutes a tool helpful to explain, among other things, the paradox of reliable reconstruction despite its uncertain results or unreliable reconstruction despite high precision of results. This approach is of great importance in the reconstruction of road accidents, which goes far beyond the analysis of a single, homogeneous subsystem.


Development of the perceptual span in reading: A longitudinal study.
The perceptual span is a standard measure of parafoveal processing, which is considered highly important for efficient reading. Is the perceptual span a stable indicator of reading performance? What drives its development? Do initially slower and faster readers converge or diverge over development? Here we present the first longitudinal data on the development of the perceptual span in elementary school children. Using the moving window technique, eye movements of 127 German children in three age groups (Grades 1, 2, and 3 in Year 1) were recorded at two time points (T1 and T2) 1 year apart. Introducing a new measure of the perceptual span, nonlinear mixed-effects modeling was used to separate window size effects from asymptotic reading performance. Cross-sectional differences were well replicated longitudinally. Asymptotic reading rate increased monotonously with grade, but in a decelerating fashion. A significant change in the perceptual span was observed only between Grades 2 and 3. Together with results from a cross-lagged panel model, this suggests that the perceptual span increases as a consequence of relatively well-established word reading. Stabilities of observed and predicted reading rates were high after Grade 1, whereas the perceptual span was only moderately stable for all grades. Comparing faster and slower readers as assessed at T1, in general, a pattern of stable between-group differences emerged rather than a compensatory pattern; second and third graders even showed a Matthew effect in reading rate and the perceptual span, respectively.


6-Methyluracil derivatives as peripheral site ligand-hydroxamic acid conjugates: Reactivation for paraoxon-inhibited acetylcholinesterase.
New uncharged conjugates of 6-methyluracil derivatives with imidazole-2-aldoxime and 1,2,4-triazole-3-hydroxamic acid units were synthesized and studied as reactivators of organophosphate-inhibited cholinesterase. Using paraoxon (POX) as a model organophosphate, it was shown that 6-methyluracil derivatives linked with hydroxamic acid are able to reactivate POX-inhibited human acetylcholinesterase (AChE) in vitro. The reactivating efficacy of one compound (5b) is lower than that of pyridinium-2-aldoxime (2-PAM). Meanwhile, unlike 2-PAM, in vivo study showed that the lead compound 5b is able: (1) to reactivate POX-inhibited AChE in the brain; (2) to decrease death of neurons and, (3) to prevent memory impairment in rat model of POX-induced neurodegeneration.


Defective HIV-1 quasispecies in the form of multiply drug-resistant proviral DNA within cells can be rescued by superinfection with different subtype variants of HIV-1 and by HIV-2 and SIV.
HIV-1 generates swarms of similar, but genetically distinct, variants termed quasispecies and many of these variants can be defective. A relevant question is whether such defective species can contribute to viral pathogenesis. Indeed, we previously reported that a presumed recombination of defective proviral DNA with other complementary defective proviral DNA or with wild-type viral DNA in the aftermath of superinfection could lead to the rescue of defective provirus and the production of replication-competent virus. We then wished to determine whether such rescue could be affected by viruses of different subtypes or even by other members of the retrovirus family. Here, we have used drug resistance mutations within the HIV genome as markers of potential recombination. We show that a defective proviral DNA within cells can be rescued by the superinfection of MT2 cells by various subtypes of HIV-1, and by HIV-2 and simian immunodeficiency virus, but not by human T cell leukaemia virus type 1 or by human herpes virus-6. The drug-resistance phenotype of the rescued HIV was confirmed in a second round of infection. Defective proviral HIV-1 can be rescued by the infection by different variants of HIV-1 and by several other retroviruses as well.


Characterization of the stimulus-induced release of immunoreactive substance P from the myenteric plexus of the guinea-pig small intestine.
The release of immunoreactive substance P (I-SP) from the myenteric plexus of the isolated guinea-pig small intestine and some of its characteristics have been investigated. Depolarizing stimuli, i.e. elevation of the extracellular K+ concentration or electrical field stimulation, increased the release of I-SP, the extent of the increase being dependent on the strength of the stimulus. Omission of Ca2+ from the bath medium prevented the stimulus-induced release of I-SP. Tetrodotoxin inhibited only the increase in I-SP release brought about by electrical stimulation but not that caused by elevated K+ concentrations. Gel exclusion chromatography on Sephadex G-25 showed that all the I-SP released by depolarization was co-eluted with authentic substance P. The methionine enkephalin analogue FK 33-824 significantly reduced the stimulus-induced release of I-SP, an effect that was prevented by the opiate antagonist naloxone. Naloxone alone significantly enhanced the stimulus-induced release of I-SP, which suggests that endogenously released opioid peptides also exert an inhibitory action on myenteric substance P-containing neurons. Putative excitatory neurotransmitters of the myenteric plexus, such as acetylcholine, bombesin, cholecystokinin octapeptide, and neurotensin, stimulated the release of I-SP in a tetrodotoxin-sensitive manner, whereas 5-hydroxytryptamine seemed ineffective. Capsaicin, known to release substance P from sensory neurons, also failed to alter the release of I-SP. The finding of a Ca2+-dependent release of I-SP caused by depolarizing stimuli further supports the concept that substance P is a neurotransmitter within the myenteric plexus. The activity of myenteric substance P-containing neurons appears to be controlled by a number of other putative enteric neurotransmitters.


Loss of Ca(2+)-permeable AMPA receptors in synapses of tonic firing substantia gelatinosa neurons in the chronic constriction injury model of neuropathic pain.
Synapses transmitting nociceptive information in the spinal dorsal horn undergo enduring changes following peripheral nerve injury. Indeed, such injury alters the expression of the GluA2 subunit of glutamatergic AMPA receptors (AMPARs) in the substantia gelatinosa and this predicts altered channel conductance and calcium permeability, leading to an altered function of excitatory synapses. We therefore investigated the functional properties of synaptic AMPA receptors in rat substantia gelatinosa neurons following 10-20d chronic constriction injury (CCI) of the sciatic nerve; a model of neuropathic pain. We measured their single-channel conductance and sensitivity to a blocker of calcium permeable AMPA receptors (CP-AMPARs), IEM1460 (50μM). In putative inhibitory, tonic firing neurons, CCI reduced the average single-channel conductance of synaptic AMPAR from 14.4±3.5pS (n=12) to 9.2±1.0pS (n=10, p<0.05). IEM1460 also more effectively antagonized evoked, spontaneous and miniature EPSCs in tonic neurons from sham operated animals than in those from animals that had been subjected to CCI. By contrast, CCI did not change the effectiveness of IEM1460 in delay firing neurons although average single channel conductance was increased from 7.6±1.2pS (n=11) to 12.2±1.5pS (n=10, p<0.01). CCI thus elicits plastic changes in a specific set of glutamatergic synapses of substantia gelatinosa due to subunit recomposition and loss of GluA2-lacking CP-AMPAR. These insights reveal a molecular mechanism of nerve injury acting at synapses of inhibitory neurons to reduce their drive and therefore inhibitory tone in the spinal cord, therefore contributing to the central sensitization associated with neuropathic pain.


Effect of sodium hypochlorite decontamination on the DNA recovery from human teeth.
Genetic identification of skeletal human remains is often realized by short tandem repeat (STR) genotyping of nuclear DNA. Dental DNA is preferred to DNA from bone for the better protection of the endogenous DNA. Especially if whole tooth grinding is intended to access the DNA, contaminations with exogenous DNA have to be avoided. The immersion of the tooth in sodium hypochlorite (NaOCl, known as bleach) is one common procedure to clean the outer surface from extraneous DNA and PCR inhibitors. To investigate the impact of bleaching on endogenous DNA and the decontamination success, 71 recently extracted teeth were differently treated with sodium hypochlorite (2.5 or 5.0% NaOCl for 30 or 60 s, 5.0% NaOCl for 10 min, and control group) in the beginning of the extraction process, whereas equally handled afterwards. Quantitative and qualitative evaluation of the extracted DNA was performed. There was a great variation for the DNA concentration of the extracts even within a group of the same NaOCl treatment. Complete DNA profiles from single persons with alleles for the 16 ESS (European Standard Set) STR loci were obtained for all regarded teeth. A statistically significant difference between the DNA yields of the treatment groups was not determined. Moreover, a negative effect of NaOCl (2.5% and 5.0%) on the DNA recovery could not be observed. Significant larger amounts of DNA were extracted from anterior teeth in contrast to posterior teeth.


Respect and admiration differentially activate the anterior temporal lobe.
Admiration and respect are positive social emotions often experienced when recognizing excellent behavior in another person. Although both strongly rely on appraisal of behavior, admiration focuses on the admirable behavior of a person, while respect focuses on the person as a whole. The evaluation and interpretation of the social behavior of another person are dependent on semantic memory. Social semantic knowledge is represented in the anterior temporal lobe (ATL), and ATL activity is modulated by conceptual details of semantic knowledge. As respect requires evaluation of not only excellent behavior but also of the person as a whole, we hypothesized that the ATL is differentially activated by admiration and respect. To test our hypothesis, we conducted functional magnetic resonance imaging experiments. We presented participants with vignettes describing admirable behavior of fictitious characters and asked them to imagine and report how they would normally feel when encountering the situation described in the vignettes, i.e., admiration or respect and its intensity. A part of the left ATL was more strongly modulated by the intensity of respect than of admiration. Although admiration and respect are often considered to be closely related, our results indicate that the neural substrates underlying these emotions are different.


Survey on infectious disease telephone hotlines in primary care: General practitioners' satisfaction and compliance with advice.
Infectious disease (ID) advice is a major part of antimicrobial stewardship programs. The objective of this study was to assess general practitioners' (GPs)' opinions and compliance with advice given by ID hotlines. This multicenter survey was based on the 7-day assessment of initial advice requested by GPs to a hotline set up by volunteer hospital ID teams to record advice for 3 years. The primary endpoint was the GPs' satisfaction with the advice given by ID specialists. Ten ID teams participated in the study and recorded 4138 requests for advice, of which 1325 requests included a proposal for antibiotic therapy and justified a follow-up call at seven days. Only 398 follow-up calls (30%) were carried out because many GPs were not reachable. GPs were very satisfied with ID hotlines: 58% considered them indispensable and 38% very useful. The recommendations provided by ID specialists were followed by GPs in more than 80% of cases. The two main motivations for GPs to call the hotline were to get quick advice (86%) and to receive help in managing a patient (76%). The ID telephone consultations and advice systems for GPs are highly appreciated and are effective in terms of following the recommendations.


Sorption of four hydrophobic organic contaminants by biochars derived from maize straw, wood dust and swine manure at different pyrolytic temperatures.
Sorption behavior of acetochlor (ACE), dibutyl phthalate (DBP), 17α-Ethynyl estradiol (EE2) and phenanthrene (PHE) with biochars produced from three feedstocks (maize straw (MABs), pine wood dust (WDBs) and swine manure (SWBs)) at seven heat treatment temperatures (HTTs) was evaluated. The bulk polarity of these biochars declined with increasing HTT while the aromaticity and CO2-surface area (CO2-SA) rose. The surface OC contents of biochars were generally higher than bulk OC contents. The organic carbon (OC)-normalized CO2-SA (CO2-SA/OC) of biochars significantly correlated with the sorption coefficients (n and logK(oc)), suggesting that pore filling could dominate the sorption of tested sorbates. SWBs had higher logK(oc) values compared to MABs and WDBs, due to their higher ash contents. Additionally, the logK(oc) values for MABs was relatively greater than that for WDBs at low HTTs (≤400 °C), probably resulting from the higher CO2-SA/OC, ash contents and aromaticity of MABs. Surface polarity and the aliphatic C may dominate the sorption of WDBs obtained at relatively low HTTs (≤400 °C), while aromatic C affects the sorption of biochars at high HTTs. Results of this work aid to deepen our understanding of the sorption mechanisms, which is pivotal to wise utilization of biochars as sorbents for hazardous organic compounds.


A microcomputer-based prosthetic limb controller: design and implementation.
This paper describes the design and implementation of a microcomputer based myoelectric limb controller. This controller was constructed for use as a feasibility study of, and a development tool for, microcomputer-based myoelectric limb controller applications. Features of this approach include flexibility and computational power. The present design uses low-power CMOS technology to provide a system in which most of the new computationally and decision orientated myoelectric signal processing algorithms can be used. Two CMOS microprocessors, a CD80C86 and a MC146805E2, are used, but microcomputer power consumption is only 120 mA.


Modification of chemical and conformational properties of natural organic matter by click chemistry as revealed by ESI-Orbitrap mass spectrometry.
A click reaction is reported here for the first time as a useful technique to control the conformational stability of natural organic matter (NOM) suprastructures. Click conjugates were successfully formed between a previously butynylated NOM hydrophobic fraction and a hydrophilic polyethylene glycol (PEG)-amino chain. The click products were shown by size exclusion chromatography (HPSEC) hyphenated with Orbitrap mass spectrometry (MS) in electrospray ionization (ESI) (+), while precursors were visible in ESI (-). Despite their increase in molecular weight, HPSEC elution of click conjugates occurred after that of precursors, thus showing their departure from the NOM supramolecular association. This indicates that the click-conjugated NOM molecules were varied in their hydrophilic and cationic character and lost the capacity to accommodate in the original hydrophobic suprastructures. The most abundant product had the C16H30O5N4 formula, a click conjugate of butanoic acid, while other products were short-chained (C4-C8) linear unsaturated and hydroxylated carboxylic acids. Tandem MS revealed formation of triazole rings in clicked conjugates and their two fragmentations at the ester and the C-N alkyl-aryl bonds. The behavior of NOM molecules modified by click chemistry confirms that hydrophobicity and ionic charge of humic molecules play a pivotal role in stabilizing intermolecular forces in NOM. Moreover, the versatility of the click reaction may become useful to decorate NOM molecules with a variety of substrates, in order to alter NOM conformational and chemical properties and diversify its applications in the environment.


Pouch volume and pouch migration after Roux-en-Y gastric bypass: a comparison of gastroscopy and 3 D-CT volumetry: is there a "migration crisis"?
Roux-en-Y gastric bypass (RYGB) is the second most frequently performed bariatric procedure worldwide. While pouch migration is a common phenomenon after sleeve gastrectomy, it has hardly been documented after RYGB so far. The aim of this study was to correlate the diagnostic performance of gastroscopy of the gastroesophageal junction with 3-dimensional computed tomography (CT) during postoperative care of patients revised due to weight regain after RYGB, with particular attention to intrathoracic pouch migration (ITM) and pouch volume. University Hospital Setting, Austria. Thirty RYGB patients that were revised owing to weight regain (median age 37.5 yr) before December 2017 were included in this prospective study. CT findings were correlated with gastroscopy regarding pouch size and ITM. Pouch distention was achieved with both oral contrast and effervescent granules. All patients had CT and gastroscopy on the same day. In addition, patients were evaluated for reflux disease based on clinical history. ITM was found in 20 of 30 (66.7%) patients in CT, whereas gastroscopy did not correctly identify any herniation. In 16 of 28 (57.1%) patients pouch measurements at gastroscopy and CT showed a difference <40%. In 2 patients, pouch distention was not sufficient for CT volumetry. The intraclass correlation coefficient proved to be .594. Symptomatic reflux was present in 10 of 30 (33.3%) patients, 5 of whom had ITM. ITM is an underreported finding after revised RYGB and missed in gastroscopy. In terms of pouch volume, 3-dimensional-CT volumetry demonstrated only moderate agreement with gastroscopy.


Transcriptome analysis reveals key transcription factors and pathways of polian vesicle associated with cell proliferation in Vibrio splendidus-challenged Apostichopus japonicus.
Polian vesicle is thought to produce coelomocytes and contribute to the sea cucumber's immune system. Our previous work has indicated that polian vesicle was responsible for cell proliferation at 72 h post pathogenic challenge. However, the transcription factors related to the activation of effector factors and the molecular process behind this remained unknown. In this study, to reveal the early functions of polian vesicle in response to the microbe, a comparative transcriptome sequencing of polian vesicle in V. splendidus-challenged Apostichopus japonicus, including normal group (PV 0 h), pathogen challenging for 6 h (PV 6 h) and 12 h (PV 12 h) was performed. Compared PV 0 h to PV 6 h, PV 0 h to PV 12 h, and PV 6 h to PV 12 h, we found 69, 211, and 175 differentially expressed genes (DEGs), respectively. KEGG enrichment analysis revealed the DEGs, including several transcription factors such as fos, FOS-FOX, ATF2, egr1, KLF2, and Notch3 between PV 6 h and PV 12 h were consistently enriched in MAPK, Apelin and Notch3 signaling pathways related to cell proliferation compared with that in PV 0 h. Important DEGs involved in cell growth were chosen, and their expression patterns were almost the same as the transcriptome profile analysis by qPCR. Protein interaction network analysis indicated that two DEGs of fos and egr1 were probably significant as key candidate genes controlling cell proliferation and differentiation in polian vesicle after pathogenic infection in A. japonicus. Overall, our analysis demonstrates that polian vesicles may play an essential role in regulating proliferation via transcription factors-mediated signaling pathway in A. japonicus and provide new insights into hematopoietic modulation of polian vesicles in response to pathogen infection.


Posttraumatic delayed subdural tension pneumocephalus.
Pneumocephalus is a complication of head injury in 3.9-9.7% of the cases, it also appears after supratentorial craniotomy in 100% of cases. The accumulation of intracranial air can be acute (<72 hours) or delayed (≥72 hours). When intracranial air causes intracranial hypertension and has a mass-effect with neurological deterioration, it is called tension pneumocephalus. We represent a clinical case of a 75-year-old male patient with open penetrating head injury, complicated by tension pneumocephalus on the fifth day after trauma and underwent urgent surgical correction. Operation performed: Burr-hole placement in the right frontal region, evacuation of tension pneumocephalus. Tension pneumocephalus is a life-threatening neurosurgical emergency case, which needs to undergo immediate surgical or conservative treatment.


[Visual rehabilitation training for homonymous field defects].
Homonymous field defects cause reading and orientation disorders. The reading disorder depends on the size of the macular sparing, the side of the field defect (unfavorable in reading direction) and spontaneous adaptive mechanisms. Methods which support compensation strategies should be recommended as evidence-based training procedures: optokinetic training with scrolled text for reading disorders and saccade training for orientation disorders. By optimized utilization of the total field of gaze, general exploration of the environment, reaction times during search tasks and quality of life can be improved.


Selective aqueous oxidation of aromatic alcohols under solar light in the presence of TiO2 modified with different metal species.
A set of metals modified TiO2 photocatalysts were prepared starting from titanium tetraisopropoxyde and different metal precursors to study the influence of the addition of the various foreign agents on the physico-chemical and photocatalytic properties of the catalysts. The powders were characterized by X-ray diffraction, Raman spectroscopy, specific surface area measurements, scanning electron microscopy, energy dispersive X-ray spectroscopy, UV-Vis diffuse reflectance spectroscopy, photoluminescence, temperature programmed desorption after CO2 adsorption. The photocatalytic activity was evaluated using as probe reactions the partial oxidation of three aromatic alcohols: benzyl alcohol (BA), 4-methoxy benzyl alcohol (4-MBA), and 4-hydroxy benzyl alcohol (4-HBA) under simulated solar light irradiation. Different oxidation and selectivity values were obtained for the three substrates depending not only on the type of metals but also on the nature and position of the substituent in the phenyl ring of benzyl alcohol. As a general behaviour, the doped samples allowed the achievement of a greater selectivity especially for 4-MBA even if sometimes with minor conversions. The presence of W or Nb was beneficial for both conversion and selectivity for all the substrates with respect to bare TiO2.


Topical application of cream-emulsified CD86 siRNA ameliorates allergic skin disease by targeting cutaneous dendritic cells.
Induction of the co-stimulatory molecule CD86 on dendritic cells (DCs) in the peripheral tissues is a critical event in triggering antigen-specific immune responses. In this study, we propose a new small interfering RNA (siRNA)-based therapy using cream-emulsified CD86 siRNA, targeting DCs for murine contact hypersensitivity (CH) and atopic dermatitis (AD)-like disease. Topical application of CD86 siRNA efficiently inhibited CH and markedly decreased the numbers of infiltrating CD86(+) or major histocompatibility complex (MHC) class II(+) cells in murine ear skin. The total number of cells, the percentage of hapten-carrying DCs, and their CD86 expression in the regional lymph nodes (RLNs) also significantly decreased. These results suggest that the silencing of CD86 in local DCs inhibits the recruitment and migration of DCs into the skin and RLNs, respectively, resulting in reduced antigen-specific local inflammation. The therapeutic efficacy of the CD86 siRNA was confirmed in AD-prone NC/Nga mice. Treatment produced marked amelioration in the clinical manifestations of AD and reduced the antigen-specific production of interleukin-4 (IL-4) and serum immunoglobulin E (IgE) and IgG1. Our results suggest that the targeting of cutaneous DCs by CD86 siRNA may be a promising strategy in the treatment of allergic skin disease.


MR lymphangiography for the assessment of the lymphatic system in patients undergoing microsurgical reconstructions of lymphatic vessels.
To assess the morphology of the lymphatic system pre- and postoperatively in patients undergoing microsurgical reconstructions of the lymphatic vessels. 8 lower extremities in 4 consecutive patients with secondary unilateral lymphedema of the lower extremities were examined by MR lymphangiography. 18 mL of gadoteridol and 1 mL of mepivacainhydrochloride 1% were subdivided into 10 portions and injected intracutaneously into the dorsal aspect of each foot at the region of the four interdigital webs and medial to the first proximal phalanx. MR imaging was performed with a 1.5-T system equipped with high-performance gradients. For MR lymphangiography a 3D-spoiled gradient-echo sequence was used. For evaluation of the lymphedema a heavily T2-weighted 3D-TSE sequence was performed. In 2 patients the 3D-TSE sequence demonstrated a decrease of the epifascial lymphedema in the postoperative acquisitions, whereby MR lymphangiography displayed an improvement of dermal-back areas and collateral lymphatic vessels. In one patient the epifascial lymphedema of the lower extremity decreased, whereas the diameter of the lymphatic vessels showed a constant diameter of 2 mm. In one patient with a lymphocutaneous fistula at the level of the right groin, the feeding lymphatic vessels and contrast media extravasation could clearly be visualized. The 3D-TSE sequence demonstrated an epi- as well as subfascial lymphedema of the right leg. MR lymphangiography is a safe and accurate diagnostic imaging method for the pre- and postoperative evaluation of the lymphatic circulation in patients undergoing microlymphatic surgery. Due to the minimal-invasiveness and lack of radiation, diagnostic follow-up MR lymphangiography examinations can be performed routinely and with no risk for the patient.


Caffeine Exacerbates Postictal Hypoxia.
A stroke-like event follows seizures which may be responsible for the postictal state and a contributing factor to the development of seizure-induced brain abnormalities and behavioral dysfunction associated with epilepsy. Caffeine is the world's most popular drug with ∼85% of people in the USA consuming it daily. Thus, persons with epilepsy are likely to have caffeine in their body and brain during seizures. This preclinical study investigated the effects of acute caffeine on local hippocampal tissue oxygenation pre and post seizure. We continuously measured local oxygen levels in the CA1 region of the hippocampus and utilized the electrical kindling model in rats. Rats were acutely administered either caffeine, or one of its metabolites, or agonists and antagonists at adenosine sub-receptor types or ryanodine receptors prior to the elicitation of seizures. Acute caffeine administration caused a significant drop in pre-seizure hippocampal pO2. Following a seizure, caffeine, as well as two of its metabolites paraxanthine, and theophylline, increased the time below the severe hypoxic threshold (10 mmHg). Likewise, the specific A2A receptor antagonist, SCH-58261, mimicked caffeine by causing a significant drop in pre-seizure pO2 and the area and time below the severe hypoxic threshold. Moreover, the A2A receptor agonist, CGS-21680 was able to prevent the effect of both caffeine and SCH-58261 adding further evidence that caffeine is likely acting through the A2A receptor. Clinical tracking and investigations are needed to determine the effect of caffeine on postictal symptomology and blood flow in persons with epilepsy.


How's my dosing? A one-step, math-free guide for comparing your clinic's maintenance immunotherapy doses to current practice parameter recommendations.
Immunotherapy dose recommendations for allergens specified in practice parameter updates have varied from version to version, and no convenient methods are available to incorporate dose changes or targets into maintenance vial formulations for patients. To compare the allergen immunotherapy dose recommendations published between 2003-2011, and to provide math-free dosing tables that translate dose targets for single or multiple extracts into maintenance vial compositions. Dose recommendations obtained from immunotherapy practice parameters published in 2003, 2007 and 2011, plus a worksheet created in 2004, were tabulated and compared. Conversion tables were created based on the fixed mathematical relationships between extract concentrate strengths and maintenance immunotherapy dose targets. Considerations of stock mixes, glycerin levels, and allergen compatibilities were applied using two examples of common extract formulations. Changes to immunotherapy dose ranges for standardized extracts included adjustment of upper limits (short ragweed), lower limits (pasture grasses), or both (cat, dust mites, Bermuda grass). Dose ranges for non-standardized products have also been modified over time. Conversion tables specified the extract concentrate volumes or percentages required to deliver minimum, midrange and maximum recommended doses with 0.5 mL injection volumes. These dosing guides, used in conjunction with cross-reactivity, compatibility and glycerin tolerance information, provide clinicians with a convenient and systematic method for determining the numbers and strengths of extracts that can be combined into treatment vials at various dose levels, and can facilitate optimization of maintenance immunotherapy mixtures for patients exhibiting a wide range of allergen sensitivities and specificities.


Three-dimensional ultrasound improves the interobserver reliability of antral follicle counts and facilitates increased clinical work flow.
To compare the interobserver reliability of antral follicle counts made using real-time two-dimensional (2D) ultrasound with offline counts made from stored three-dimensional (3D) data and to assess the time required for such counts. Two observers conducted transvaginal ultrasound examinations in 45 subfertile women in the early follicular phase of the menstrual cycle. Antral follicles were counted using real-time 2D ultrasound and the time taken was recorded. A 3D volume was then acquired from each ovary and stored for subsequent offline analysis using the multiplanar view. The time taken for each step was recorded and the total time was calculated. Intraclass correlation coefficients (ICC) and limits of agreement were used to assess reliability. There was no difference in the mean antral follicle counts using real-time 2D (16.51 +/- 11.51) and 3D (16.33 +/- 12.13) ultrasound. According to ICCs, there was a significantly higher interobserver reliability for counts made using 3D (mean, 0.992; 95% CI, 0.986-0.996) compared with real-time 2D (mean, 0.961; 95% CI, 0.940-0.977) (P < 0.01) ultrasound. 3D ultrasound was also associated with narrower limits of agreement (-2.7 to + 3.1) than was 2D ultrasound (-6.9 to + 6.4). Whilst the total time taken was significantly longer for the 3D technique (239.3 +/- 71.4 s vs. 103.1 +/- 28.6 s, P < 0.001), the time required for the actual ultrasound examination was significantly less (46.4 +/- 7.4 s vs. 103.1 +/- 28.6 s, P < 0.001). 3D ultrasound significantly improves the interobserver reliability of antral follicle counts. While this is at the expense of time overall, the duration of the actual ultrasound examination and patient exposure is significantly reduced using 3D compared with real-time 2D ultrasound.


[Compliance of extramural hospital treatment and long-term survival status in patients with acute myocardial infarction].
To explore the compliance of extramural hospital treatment and the long-term survival status in patients with acute myocardial infarction (AMI) in Chongqing. A total of 636 patients with AMI, from grade 3 and first-class hospitals in Chongqing during Jan 2005 and Jan 2009, were enrolled for this study. The patients were followed-up for 5 years to investigate the extramural hospital treatment and influential factors. A total of 574 patients finished a five-year follow-up, and 180 cases died from cardiac death. The mortality was 31.4%. The poor compliance was a major feature in the pass away patients. The low treatment compliance is the independent risky factor for 5-year prognosis.


Remediation measures and displacement of pollutants in soils affected by the spill of a pyrite mine.
The soils affected by the spill of a pyrite mine were analysed in 100 sampling points at three depths (0-10, 10-30, and 30-50 cm) in 1998 (after the tailings were removed), 1999 (after the cleaning of the highly contaminated areas), and 2004 (after the tilling of the upper 20-25 cm). The comparative study reveals that the removal of the tailings left a heterogeneous distribution pattern of the contaminants, with highly polluted spots alternating with less contaminated areas. The cleanup did not substantially lower the concentration in the highly polluted soils, and the spread of the pollutants increased the concentration in As and Pb in the uppermost 10 cm of 60% of the soils, while the Zn and Cd concentrations increased in only 30% of the soils. Given the high concentration of pollutants in the topsoil (especially As), the tilling of the upper 20-25 cm, despite reducing the average concentration of pollutants in the uppermost 10 cm, did not substantially lower the percentage of soils that exceeded the concentration of 40 mg As kg(-1) dry soil and almost doubled the percentage of soils that surpassed this concentration between 10 and 30 cm. Meanwhile, the displacement of Zn and Cd within the soil supported the reduction in the percentage of soils that in the upper 10 cm exceeded the reference concentrations of these elements (900 mg Zn kg(-1) dry soil and 2 mg Cd kg(-1) dry soil), and the percentage of soils exceeding these concentrations between 10 and 50 cm in depth did not increase. Six years after the spill and at the end of all remediation measures, the intervention levels defined by the Environmental Agency of the Regional Government of Andalusia for natural parks were exceeded in the uppermost 10 cm in 35% of the soils.


Folic acid-mediated targeting of cowpea mosaic virus particles to tumor cells.
Cowpea mosaic virus (CPMV) is a well-characterized nanoparticle that has been used for a variety of nanobiotechnology applications. CPMV interacts with several mammalian cell lines and tissues in vivo. To overcome natural CPMV targeting and redirect CPMV particles to cells of interest, we attached a folic acid-PEG conjugate by using the copper-catalyzed azide-alkyne cycloaddition reaction. PEGylation of CPMV completely eliminated background binding of the virus to tumor cells. The PEG-folate moiety allowed CPMV-specific recognition of tumor cells bearing the folate receptor. In addition, by testing CPMV formulations with different amounts of the PEG-FA moiety displayed on the surface, we show that higher-density loading of targeting ligands on CPMV may not be necessary for efficient targeting to tumor cells. These studies help to define the requirements for efficiently targeting nanoparticles and protein cages to tumors.


Action potential refractory period in ureter smooth muscle is set by Ca sparks and BK channels.
In excitable tissues the refractory period is a critical control mechanism preventing hyperactivity and undesirable tetani, by preventing subsequent stimuli eliciting action potentials and Ca2+ entry. In ureteric smooth muscle, peristaltic waves that occur as invading pacemaker potentials produce long-lasting action potentials (300-800 ms) and extraordinarily long (more than 10 s) refractory periods, which prevent urine reflux and kidney damage. For smooth muscles neither the mechanisms underlying the refractory period nor the link between excitability and refractoriness are properly understood. Here we show that a negative feedback process, which depends on Ca2+ loading the sarcoplasmic reticulum (SR) during the action potential and on the subsequent activation of local releases of Ca2+ from the SR (sparks), stimulating plasmalemmal Ca2+-sensitive K+ (BK) channels, determines the refractory period of the action potential. As sparks gradually reduce the Ca2+ load in the SR, electrical inhibition is released, the refractory period is terminated and peristaltic contractions occur again. The refractory period can be manipulated, for example from 10 s to 100 s, by altering the Ca2+ content of the SR or release mechanism or by inhibiting BK channels. This insight into the control of excitability and hence function provides a focus for therapies directed at pathologies of smooth muscle.


MIS TLIF, EndoTLIF, and the Ability of Navigation/Robotics to Enable Spinal Surgery in an Ambulatory Care Setting.
Technical Report. Performing surgeries in the ambulatory surgery center affords improved efficiencies in terms of cost and speed. However, ambulatory surgery is only successful if complications, re-admissions, and re-operations are avoided. This report describes the San Diego Outpatient Lumbar Fusion Program, a culmination of cumulative incremental improvements in patient selection and patient education, meticulous peri-operative management, minimally invasive techniques together with navigation/robotics. Retrospective review of prospectively collected data on 1-2 level minimally invasive transforaminal lumbar interbody fusions (MIS TLIF). Healthy patients (age 72 years old or less, BMI less than 50, ASA 1 or 2) with good social support and reasonable pre-operative function (ODI 50 or less) treated with the MIS TLIF technique can be discharged home in less than 1 midnight with good clinical results. Relatively young, healthy patients can safely and effectively undergo 1-2 level lumbar fusion surgery in the ASC setting when using contemporary minimally invasive techniques and computer-assisted navigation/robotics.


Outflow reconstruction of tetralogy of Fallot using a Gore-Tex valve.
The right ventricular outflow tract was reconstructed in patients with tetralogy of Fallot using a wide transannular patch bearing a large unicuspid or bicuspid valve. The shape of the valve was designed to limit the degree of pulmonary regurgitation. The characteristics of the valve and the water-repellent nature of the polytetrafluoroethylene sheet make calcification and pseudointimal formation less common than with traditional bioprosthetic valves.


Impairment of soil health due to fly ash-fugitive dust deposition from coal-fired thermal power plants.
Thermal power stations apart from being source of energy supply are causing soil pollution leading to its degradation in fertility and contamination. Fine particle and trace element emissions from energy production in coal-fired thermal power plants are associated with significant adverse effects on human, animal, and soil health. Contamination of soil with cadmium, nickel, copper, lead, arsenic, chromium, and zinc can be a primary route of human exposure to these potentially toxic elements. The environmental evaluation of surrounding soil of thermal power plants in Odisha may serve a model study to get the insight into hazards they are causing. The study investigates the impact of fly ash-fugitive dust (FAFD) deposition from coal-fired thermal power plant emissions on soil properties including trace element concentration, pH, and soil enzymatic activities. Higher FAFD deposition was found in the close proximity of power plants, which led to high pH and greater accumulation of heavy metals. Among the three power plants, in the vicinity of NALCO, higher concentrations of soil organic carbon and nitrogen was observed whereas, higher phosphorus content was recorded in the proximity of NTPC. Multivariate statistical analysis of different variables and their association indicated that FAFD deposition and soil properties were influenced by the source of emissions and distance from source of emission. Pollution in soil profiles and high risk areas were detected and visualized using surface maps based on Kriging interpolation. The concentrations of chromium and arsenic were higher in the soil where FAFD deposition was more. Observance of relatively high concentration of heavy metals like cadmium, lead, nickel, and arsenic and a low concentration of enzymatic activity in proximity to the emission source indicated a possible link with anthropogenic emissions.


Echocardiographic techniques for assessing normal and abnormal fetal cardiac anatomy.
Diagnostic quality images of the fetal heart in utero can be obtained as early as 18 to 20 weeks of gestation. The cardiac structures can be imaged primarily by cross-sectional echocardiography and augmented by a combination of simultaneous M-mode echocardiography and range-gated pulsed Doppler ultrasonography. Cross-sectional images from planes through the fetal heart equivalent to planes that can be obtained after birth can be generated in utero. In a study of 168 pregnancies, 10 structural cardiac abnormalities have been defined. These abnormalities and others that have been reported indicate the potential for in utero cardiac diagnosis. The recognition of structural congenital heart disease in utero has been helpful in genetic counseling, planning the method of labor and delivery and making decisions regarding termination of pregnancy and planning postnatal care. Fetal echocardiography offers the potential to change the pattern of health care delivery to those with suspected congenital heart disease.


Limb articulation in caridoid crustaceans revisited - new evidence from Euphausiacea (Malacostraca).
The propodial articulation of thoracopods in Malacostraca is revisited. Two major joints at the base of the limb, a thorax-coxa joint and a coxa-basis joint permit promotion-remotion and abduction-adduction, respectively. In representatives of Decapoda, Anaspidacea and Euphausiacea, the coxa forms proximally a dicondylic articulation with the thorax, permitting promotion-remotion, and distally another dicondylic joint with the basis, permitting abduction-adduction. In Lophogastrida and Mysida, the thorax-coxa hinge line is antero-posteriorly oriented, as is the coxa-basis hinge line. Promotion-remotion in Mysida and Lophogastrida is possible because of the presence of an intrabasal joint which is also present in Euphausiacea and Anaspidacea. In Mysida, Lophogastrida and Euphausiacea, the intrabasal joint is only present anteriorly, just distally of the anterior coxa-basis joint between a small, triangular proximal part of the basis and a larger distal part. In Anaspidacea, the intrabasal joint is also present posteriorly and permits abduction-adduction. Homology with the intrabasal joint of the other taxa seems doubtful. Limb articulation in Anaspidacea shows, nevertheless, correspondences with that in Euphausiacea, Lophogastrida and Mysida: the coxa is posteriorly invaginated and has an open ring-like structure very different from the solid coxa in decapods. Despite the high level of structural correspondence between the intrabasal joint in Euphausiacea and that in Lophogastrida and Mysida, their different functional roles make homology implausible. In Lophogastrida and Mysida the intrabasal joint is thought to replace the promotion-remotion movement of the thorax-coxa articulation, which in these taxa permits abduction-adduction only, probably in connection with the evolution of the marsupium. In Euphausiacea, the intrabasal joint might play a role in feeding mechanisms. Neither the feeding basket nor a marsupium can reasonably be suggested for any common ancestor of Euphausiacea and Mysidacea (or Peracarida).


The role of AT1-receptor blockade on reactive oxygen species and cardiac autonomic drive in experimental hyperthyroidism.
The objective of this study was to explore the influence of the renin-angiotensin system on cardiac prooxidants and antioxidants levels and its association to autonomic imbalance induced by hyperthyroidism. Male Wistar rats were divided into four groups: control, losartan (10mg/kg/day by gavage, 28 day), thyroxine (T4) (12 mg/L in drinking water for 28 days), and T4+losartan. Spectral analysis (autonomic balance), angiotensin II receptor (AT1R), NADPH oxidase, Nrf2 and heme-oxygenase-1 (HO-1) myocardial protein expression, and hydrogen peroxide (H2O2) concentration were quantified. Autonomic imbalance induced by hyperthyroidism (~770%) was attenuated in the T4+losartan group (~32%) (P<0.05). AT1R, NADPH oxidase, H2O2, as well as concentration, Nrf2 and HO-1 protein expression were elevated (~172%, 43%, 40%, 133%, and 154%, respectively) in T4 group (P<0.05). H2O2 and HO-1 levels were returned to control values in the T4+losartan group (P<0.05). The overall results demonstrate a positive impact of RAS blockade in the autonomic control of heart rate, which was associated with an attenuation of H2O2 levels, as well as with a reduced counter-regulatory response of HO-1 in experimental hyperthyroidism.


Does Primary Productivity Turn Up the Volume? Exploring the Relationship Between Chlorophyll a and the Soundscape of Coral Reefs in the Pacific.
Chlorophyll is the basis for ecosystem productivity in most marine environments. We report on an ongoing effort to examine whether ambient sounds are tied to chlorophyll levels. We hypothesized that an increase in food-web available energy will be distributed across trophic levels, eventually reaching sound-producing animals and increasing acoustic levels. To test our hypothesis, we compared reef environments to explore links between soundscapes and chlorophyll a concentrations. The study sites resided in disparate oceanographic regimes that experienced substantially different oceanographic conditions. We anticipated that the results would show differing patterns of primary productivity between sites and therefore would be reflected in the soundscapes.


A study of patients not registered in the Swedish Cancer Register but reported to the Swedish Register of Palliative Care 2009 as deceased due to cancer.
The Swedish Cancer Register (SCR), an old and reputable health data register, contributes a large amount of data used in research. The quality of the research using SCR data depends on the completeness and validity of the register. In Sweden, every healthcare provider is obligated to report newly detected cases of cancer to the SCR regardless of the diagnostic basis. This study aimed to clarify whether there is an under-reporting of patients with cancer to the SCR or an over-reporting of cancer as cause of death to the SRPC as all patients do not appear in both registers. In addition, this study looked at the distribution of under-reporting or over-reporting related to age, sex, type of cancer, diagnostic basis, and department responsible for cancer diagnosis. Of the 10 559 patients whose cause of death was cancer as reported to the SRPC (2009), 1394 patients (13.2%) were not registered in the SCR (1958-2009). Medical records from a representative sample of 203 patients were collected and reviewed. The medical records for 193 patients were obtained; of those, 183 (95%) patients should have been reported to the SCR. Among these, radiologic investigation was the most common basis for diagnosis and there was a significant over-representation of cancer of the pancreas, lung, liver, and bile ducts. This study cannot quantify the completeness of the SCR. The findings indicate that 12.5% of patients dying of cancer in palliative care are not reported, that specialized hospital departments diagnose the vast majority of the unreported patients, and that routines for how to report patients to the SCR based on radiological findings should be revised.


The apparent plasticizing effect of polyethylene glycol (PEG) on the crystallinity of spray dried lactose/PEG composites.
Aqueous solutions of lactose and polyethylene glycol (PEG) were spray dried in a Büchi Model 191 spray dryer with the aim to investigate the effect of PEG on the crystallinity of the composite. A PEG concentration of 10.7% by weight of solids was studied for PEG 200, 600, 1500, 4000 and 8000. For PEG 200 and 4000 additional concentrations from 1.5-19.3% to 1.5-32.4%, respectively, were investigated. The spray dried composites were analysed with X-ray powder diffraction and modulating differential scanning calorimetry. The crystallinity of lactose in the composites varied from 0% to 60%, dependent on the molecular weight and concentration of PEG. Apparently, lactose crystallinity is promoted by low molecular weight and high concentration of the PEG. PEG did not affect the lactose glass transition temperature. It is suggested that lactose and PEG are solidified separately during spray drying and that partial crystallization of lactose is associated with effects of PEG on the rate of drying.


Lack of genotoxicity with beta-carotene.
A literature review was conducted on adverse effects of carotenoids on human and animal development. The data suggest that beta-carotene administration prevented genetic damage caused by mutagens both in bacterial and cell culture systems, and that large doses of pure beta-carotene do not cause embryotoxicity in rodents. In addition, studies of individuals with congenitally high levels of plasma carotenoids and babies born carotenemic because of their mothers' intake of large amounts of carotenoid-containing foods during pregnancy reveal no abnormalities attributable to the carotenoid molecule.


Promoting sensitive colorimetric detection of hydroquinone and Hg2+ via ZIF-8 dispersion enhanced oxidase-mimicking activity of MnO2 nanozyme.
Reducing the agglomeration and improving the dispersibility in water of two-dimensional (2D) nanozymes is one of the effective ways to improve their enzyme-like activity. In this work, we propose a method by constructing zeolitic imidazolate framework-8 (ZIF-8)-dispersed 2D manganese-based nanozymes to achieve the specific regulated improvement of oxidase-mimicking activity. By in-situ growth of manganese oxides nanosheets of MnO2(1), MnO2(2) and Mn3O4 on the surface of ZIF-8, the corresponding nanocomposites of ZIF-8 @MnO2(1), ZIF-8 @MnO2(2), and ZIF-8 @Mn3O4 were prepared at room temperature. The Michaelis-Menton constant measurements indicated that ZIF-8 @MnO2(1) exhibits best substrate affinity and fastest reaction rate for 3,3',5,5'-tetramethylbenzidine (TMB). The ZIF-8 @MnO2(1)-TMB system was exploited to detection of trace hydroquinone (HQ) based on the reducibility of phenolic hydroxyl groups. In addition, by employing the fact that the cysteine (Cys) with the excellent antioxidant capacity can bind the Hg2+ based on the formation of "S-Hg2+" bonds, the ZIF-8 @MnO2(1)-TMB-Cys system was applied to detection of Hg2+ with high sensitivity and selectivity. Our findings not only provide a better understanding of the relationship between dispersion of nanozyme and enzyme-like activity, but also provide a general method for the detection of environmental pollutants using nanozymes.


Pyogenic liver abscesses: a comparison of older and younger patients.
To evaluate whether older patients with pyogenic liver abscess have distinctive presenting features or if their management differs from that of younger patients. Retrospective chart review of all cases occurring from 1982 to 1992. A regional trauma centre and two large community hospitals. A total of 38 individuals with a final diagnosis of pyogenic liver abscess. Seventeen patients aged 70 or older comprised the study group and 21 patients under age 70 the comparison group. Clinical features, laboratory data, therapeutic interventions and outcomes were sought. The presumed aetiology of the abscess was determined. The study group had fewer men (47% vs 81%, P=0.028), less abdominal tenderness on physical examination (41% vs 76%, P=0.028) and fewer positive blood cultures in those sampled (31% vs 67%, P=0.04) than the comparison group. No study group patient had a history of trauma. Times to diagnosis were 3.2 and 5.9 days (P=0.14) and lengths of stay 21.6 and 29.3 days (P=0.08) for study and comparison groups, respectively. There were no differences in mortality or other demographic, clinical, laboratory or pathological variables. Elderly patients with pyogenic liver abscess have some subtle differences in clinical and laboratory presentation, but these do not appear to delay diagnosis. Active management is tolerated well, with no difference in mortality.


Controlled nonlinear magnetic damping in spin-Hall nano-devices.
Large-amplitude magnetization dynamics is substantially more complex compared to the low-amplitude linear regime, due to the inevitable emergence of nonlinearities. One of the fundamental nonlinear phenomena is the nonlinear damping enhancement, which imposes strict limitations on the operation and efficiency of magnetic nanodevices. In particular, nonlinear damping prevents excitation of coherent magnetization auto-oscillations driven by the injection of spin current into spatially extended magnetic regions. Here, we propose and experimentally demonstrate that nonlinear damping can be controlled by the ellipticity of magnetization precession. By balancing different contributions to anisotropy, we minimize the ellipticity and achieve coherent magnetization oscillations driven by spatially extended spin current injection into a microscopic magnetic disk. Our results provide a route for the implementation of efficient active spintronic and magnonic devices driven by spin current.


Using DVS-NIR to assess the water sorption behaviour and stability of a griseofulvin/PVP K30 solid dispersion.
The purpose of this work was to investigate the distribution of water in a physically unstable amorphous solid dispersion (polyvinylpyrrolidone (PVP) and griseofulvin (as a model hydrophobic drug)), both as the sample absorbs water and during prolonged exposure to elevated humidity by use of dynamic vapour sorption combined with near infrared (DVS-NIR). The solid dispersion absorbed much less water than the sum of the water sorption of the individual components. This suggests that griseofulvin hindered PVP from absorbing water through the formation of the solid dispersion. Prolonged storage of the solid dispersion at 75% RH resulted in no significant mass change. Whilst this would usually be interpreted as the absence of crystallization, the NIR spectra demonstrated that crystallization occurred. The reason for the lack of a weight loss was that the expelled water from amorphous griseofulvin was sorbed by PVP, meaning that as the dispersion was broken by the crystallisation of griseofulvin, the PVP was once again free to sorb water (in line with the higher water sorption shown by PVP alone, and in contrast with the lower sorption of water by the solid dispersion). As water is a key factor in the physical stability of amorphous systems, understanding how and where water is absorbed and how this is liable to change is an important advance and offers promise in understanding the mechanism of stabilisation of solid dispersions, and therefore may be useful to predict the stability of new API dispersions.


Early experience of aspirative lipoplasty of the abdomen.
The author evaluates his early 2 1/2-year experience with closed aspirative lipoplasty, first introduced in the United States by Illouz. Although his experience with the technique during this period has resulted in good to excellent overall results, the abdomen, however, seems to have inherent problems unique to this area of the torso. He provides the reader with an understanding of these problems and methods to correct them.


Sodium-Taste Cells Require Skn-1a for Generation and Share Molecular Features with Sweet, Umami, and Bitter Taste Cells.
Taste buds are maintained via continuous turnover of taste bud cells derived from local epithelial stem cells. A transcription factor Skn-1a (also known as Pou2f3) is required for the generation of sweet, umami (savory), and bitter taste cells that commonly express TRPM5 and CALHM ion channels. Here, we demonstrate that sodium-taste cells distributed only in the anterior oral epithelia and involved in evoking salty taste also require Skn-1a for their generation. We discovered taste cells in fungiform papillae and soft palate that show similar but not identical molecular feature with sweet, umami, and bitter taste-mediated Type II cells. This novel cell population expresses Plcb2, Itpr3, Calhm3, Skn-1a, and ENaCα (also known as Scnn1a) encoding the putative amiloride-sensitive (AS) salty taste receptor but lacks Trpm5 and Gnat3Skn-1a-deficient taste buds are predominantly composed of putative non-sensory Type I cells and sour-sensing Type III cells, whereas wild-type taste buds include Type II (i.e., sweet, umami, and bitter taste) cells and sodium-taste cells. Both Skn-1a and Calhm3-deficient mice have markedly decreased chorda tympani nerve responses to sodium chloride, and those decreased responses are attributed to the loss of the AS salty taste response. Thus, AS salty taste is mediated by Skn-1a-dependent taste cells, whereas amiloride-insensitive salty taste is mediated largely by Type III sour taste cells and partly by bitter taste cells. Our results demonstrate that Skn-1a regulates differentiation toward all types of taste cells except sour taste cells.


Author Correction: Simultaneous Inhibition of Glycolysis and Oxidative Phosphorylation Triggers a Multi-Fold Increase in Secretion of Exosomes: Possible Role of 2',3'-cAMP.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Life threatening presentation of thoracic duct injury post thyroid surgery; a case report.
Injury to thoracic duct is a rare potential complication of time-honored conventional thyroidectomy. Nevertheless, it can be a cause of significant morbidity, and sometimes life-threatening. A 78-year-old female patient with a previous surgical history of thyroid lobectomy for nodular disease presented with primary hyperparathyroidism, and a nodule in the remaining thyroid lobe. The patient underwent completion thyroidectomy and parathyroidectomy. Less than 24h post operatively, the patient developed progressive shortness of breath and neck swelling requiring immediate intubation and re-exploration. A large amount of chyle was drained and an injured thoracic duct was identified and ligated. In experienced hands thyroid surgery is safe. Nevertheless, factors such as the type of pathology and its extent, the level of surgery, and re-operative surgery increase the risk of postoperative complications. Immediate surgical exploration is necessary when patients present with neck swelling and respiratory distress. In our case, a high output chyle leak in a confined space was life threatening. Timely re-exploration following thyroid surgery and thorough knowledge of the anatomy of neck structures is crucial in sparing patients potential morbidity and/or mortality.


NMR-based metabolomic studies on the toxicological effects of cadmium and copper on green mussels Perna viridis.
Traditional toxicology studies have focused on selected biomarkers to characterize the biological stress induced by metals in marine organisms. In this study, a system biology tool, metabolomics, was applied to the marine mussel Perna viridis to investigate changes in the metabolic profiles of soft tissue as a response to copper (Cu) and cadmium (Cd), both as single metal and as a mixture. The major metabolite changes corresponding to metal exposure are related to amino acids, osmolytes, and energy metabolites. Following metal exposure for 1 week, there was a significant increase in the levels of branched chain amino acids, histidine, glutamate, glutamine, hypotaurine, dimethylglycine, arginine and ATP/ADP. For the Cu+Cd co-exposed mussels, the levels of lactate, branched chain amino acid, succinate, and NAD increased, whereas the levels of glucose, glycogen, and ATP/ADP decreased, indicating a different metabolic profile for the single metal exposure groups. After 2 weeks of exposure, the mussels showed acclimatization to Cd exposure based on the recovery of some metabolites. However, the metabolic profile induced by the metal mixture was very similar to that from Cu exposure, suggesting that Cu dominantly induced the metabolic disturbances. Both Cu and Cd may lead to neurotoxicity, disturbances in energy metabolism, and osmoregulation changes. These results demonstrate the high applicability and reliability of NMR-based metabolomics in interpreting the toxicological mechanisms of metals using global metabolic biomarkers.


Urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine levels in patients with type 2 diabetes.
Obesity modifies the association between sodium and potassium intake and blood pressure. However, the impact of obesity on the relationship between the sodium-potassium balance and cardiovascular risk in type 2 diabetes (T2DM) patients remains unclear. We investigated the relationship between the 24-h urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine (ADMA) level, which is a cardiovascular risk factor, in Japanese T2D patients with or without obesity. This cross-sectional study included 243 patients with T2DM who were hospitalized for diabetes education. Urinary sodium-to-potassium ratios were calculated from 24-h urine collection. The subjects were divided into two groups according to their BMIs (<25 and ≥25). The serum ADMA levels positively correlated with the urinary sodium-to-potassium ratios in non-obese patients, but not in obese patients. Multivariate linear regression analyses showed that the serum ADMA levels positively correlated with the urinary sodium-to-potassium ratios after adjustment for other confounders in non-obese patients. This correlation was observed in non-obese patients with hypertension, but not in those without hypertension. Measurement of the pulse wave velocity and intima-media thickness revealed that elevation of the serum ADMA levels was significantly associated with an increase in the degree of atherosclerotic progression in subjects with T2DM. Additionally, an assessment of dietary intake showed that the consumption of dairy products as well as of green and yellow vegetables was negatively associated with urinary sodium-to-potassium ratios in patients with T2DM. In conclusion, elevation of serum ADMA may be positively associated with the urinary sodium-to-potassium ratio in Japanese non-obese patients with T2DM.


Randomized controlled trial investigating potential effects of relaxation on mitochondrial function in immune cells: A pilot experiment.
This study aimed to investigate the effect of a relaxation response induced by hypnosis on the mitochondrial energy production of immune cells compared to an everyday relaxing situation. Chronically stressed individuals (88% women) with at least moderate suggestibility were randomized to a hypnosis (20 min relaxation hypnosis; n = 20) or a control condition (20 min documentary; n = 22). Before and after intervention, peripheral blood was collected. The primary outcomes were mitochondrial respiration and density in immune cells measured by high-resolution respirometry and citrate synthase activity assays. As secondary outcome, perceived stress, anxiety, and depressive mood were assessed. The intervention led to no significant Group × Time effects on mitochondrial bioenergetic parameters but a significant Time effect (ηp2 = .09 -.10). Thus, there were no differences in the experimental conditions concerning the measured parameters of mitochondrial bioenergetics. Exploratory subanalyses indicated that stress, anxiety, and depressive mood were linked to lower mitochondrial respiration. Individuals with higher anxiety had less decrease in routine respiration over time than those with lower anxiety (ηp2 = .09). This study explores the effects of relaxation in the form of hypnosis compared to watching a video on the energy metabolism of immune cells. Relaxation, whether in targeted (hypnosis) or untargeted (documentary) form, affected mitochondrial respiration. Further research should focus on the long-term effects of relaxation on bioenergetics. The trial was retrospectively registered on 07/12/2021, DRKS00027356, https://drks.de/search/de/trial/DRKS00027356.


The immobilized leukoagglutinin from the seeds of Maackia amurensis binds with high affinity to complex-type Asn-linked oligosaccharides containing terminal sialic acid-linked alpha-2,3 to penultimate galactose residues.
We recently reported that the purified leukoagglutinin (designated MAL) from the seeds of the leguminous plant Maackia amurensis is a potent leukoagglutinin for the mouse lymphoma cell line BW5147 (Wang, W.-C., and Cummings, R. D. (1987) Anal. Biochem. 161,80). We and others have shown that this lectin is a weak hemagglutinin of human erythrocytes (Kawaguchi, T., Matsumoto, I., and Osawa, T. (1974) J. Biol. Chem. 249, 2786). We now report that leukoagglutination by MAL is inhibited by low concentrations of 2,3-sialyllactose (NeuAc alpha 2,3Gal beta 1,4Glc), but it is not inhibited by either 2,6-sialyllactose (NeuAc alpha 2,6Gal beta-1,4Glc), lactose, or free NeuAc. To further study the carbohydrate-binding specificity of this lectin, we investigated the interactions of immobilized MAL with glycopeptides prepared from the mouse lymphoma cell line BW5147 and from purified glycoproteins. We found that immobilized MAL interacts with high affinity with complex-type tri- and tetraantennary Asn-linked oligosaccharides containing outer sialic acid residues linked alpha 2,3 to penultimate galactose residues. Glycopeptides containing sialic acid linked only alpha 2,6 to penultimate galactose did not interact detectably with the immobilized lectin. Our analyses indicate that the interactions of complex-type Asn-linked chains with the lectin are dependent on sialic acid linkages and are not dependent on either the branching pattern of the mannose residues or the presence of poly-N-acetyllactosamine sequences.


Maximising the highs and minimising the lows: harm reduction guidance within ecstasy distribution networks.
Little is known about how users build and share knowledge concerning the highs and lows of Ecstasy and the role that Ecstasy sellers play in the exchange of this information. These findings are based on a National Institute on Drug Abuse-funded project, "An Exploratory Study of Ecstasy Distribution," conducted between 2003 and 2006. We completed in-depth interviews with 120 men and women in the San Francisco Bay Area who had sold 5 or more doses 5 or more times in the 6 months prior to the interview. The research focused on buyer-seller relationships and the influence of these relationships on users' health. Users constructed harm reduction strategies in attempts to maximise the Ecstasy high and minimise the risks. The social context of Ecstasy use allowed for the exchange of harm reduction information and advice on how to maximise the pleasurable aspects of Ecstasy. Some participants served as "guides" to ensure that their customers had safe and enjoyable experiences while using Ecstasy. These findings suggest that Ecstasy sellers are important points of intervention for the dissemination of harm reduction information as friendship networks were the primary link in creating awareness of safer Ecstasy use.