Integrated cognitive behavioral treatment for substance use and depressive symptoms: a homeless case series and feasibility study.
Homelessness is associated with high prevalence of psychiatric disorders such as substance use disorders, including alcohol use disorder, and depression. This case series and feasibility trial evaluated a novel integrated cognitive behavioral treatment (ICBT), which was adapted specifically for homeless individuals and developed to treat substance use and depressive symptoms simultaneously. The ICBT was delivered among four homeless individuals enrolled in the Treatment First program (a social services program where treatment is offered in conjunction with temporary transitional housing), who had access to stable and sober housing milieus. The ICBT was rated high in expectancy of improvement, credibility, and satisfaction, with few treatment-related adverse events, and fairly high treatment retention. At 12 months follow-up, three of four participants were not homeless anymore. Some participants experienced short-term reductions in substance use and/or depressive symptoms. The study provided preliminary support that the ICBT can be a feasible and potentially effective treatment for homeless individuals with substance use and/or depressive symptoms. However, the delivery format within the Treatment First program was not feasible. The ICBT could be offered within the social services Housing First program instead (where permanent housing is offered before treatment), or to non-homeless individuals. The study was registered retrospectively at ClinicalTrials.gov (NCT05329181).


Estradiol and leptin: no engagement without CITED1.
Ovarian estradiol and leptin are important modulators of whole-body energy homeostasis that act in the hypothalamus. In a recent paper in Cell Metabolism, González-García et al. demonstrate that CITED1 acts as a key hypothalamic cofactor that mediates the antiobesity effects of estradiol through potentiation of the anorectic actions of leptin.


Sexual orientation, gender: Where is the problem? Nowhere! Correct self-identification and minority stigma.
Self-concept, at the core of minority stress, is associated with negative mental health outcomes. We aimed to assess the effectiveness of a one-shot third-wave CBT intervention targeting correct self-identification to address suffering related to minority stress. The study population included 172 participants (n = 98 heterosexuals, n=13 transgenders). The intervention consisted of a 90 minutes conference including overview of LGBT's suffering related to distal and proximal factors, a wisdom understanding of the root of suffering (mistaken self-identification) followed by a Questions & Answers session. Participants completed online self-questionnaires assessing sociodemographic data, acceptance by others (external) and oneself (internal) for sexual orientation and gender variables before the conference, immediately after the conference, and three months later. The conference helped to improve external acceptance of transgender for the whole sample, especially among the majority group. Those belonging to the minority (LGBT) had a positive benefit from the conference by reducing their fear of judgment. Adding a Q&A session to the conference failed to show any additional benefits. A specific wisdom-based self-identification conference appears to be an effective and low-cost intervention to target minority stigma, and therefore mental health and social integration of LGBT people.


A strategy for promoting lipid production in green microalgae Monoraphidium sp. QLY-1 by combined melatonin and photoinduction.
Microalgae lipids are potential candidates for the production of renewable biodiesel. The combination of plant hormones and two-step cultivation regulates lipid production in microalgae. A strategy for promoting lipid accumulation in Monoraphidium sp. QLY-1 by combining exogenous melatonin (MT) and photoinduction was developed. The effects of melatonin on the lipid content, reactive oxygen species (ROS), and activities of three key fatty acid biosynthetic enzyme in Monoraphidium sp. QLY-1 were investigated. The lipid content increased by 1.32-fold under 1μM melatonin treatment. The maximum lipid content achieved was 49.6%. However, the protein and carbohydrate contents decreased rapidly from 57.21% to 47.96% and from 53.4% to 37.71%, respectively. Biochemical and physiological analyses suggested that the ROS and lipid biosynthesis-related enzyme activities correlated with increased lipid accumulation under photo-melatonin induction conditions.


Topography of the human factor VIII-von Willebrand factor complex.
Factor VIII circulates in noncovalent complex with von Willebrand factor (vWf). The topography of this complex was evaluated by fluorescence energy transfer using factor VIII subunits modified with N-(1-pyrenyl)maleimide (NPM; fluorescence donor) and vWf-derived fragments modified with 7-diethylamino-3-[4'-maleimidylphenyl]-4-methyl coumarin (CPM; fluorescence acceptor). Results from a previous study indicated an interfactor VIII subunit distance of 20 A separating Cys528 and Cys1858 in the factor VIII heavy and light chains, respectively (Fay, P.J., and Smudzin, T. M. (1989) J. Biol. Chem. 264, 14005-14010). Fluorophore modification of the vWf SPIII homodimer (residues 1-1365) indicated multiple attachment sites at Cys126/135/1360 as determined from sequence analysis of fluorescent tryptic peptides derived from the modified protein. Based upon donor quenching data, an interfluorophore distance of approximately 28 A was calculated separating NPM-factor VIII light chain or factor VIII reconstituted from NPM-light chain plus unmodified heavy chain, from CPM-SPIII. A similar value (29 A) was obtained for NPM-light chain paired with CPM-SPIII-T4 (vWf residues 1-272), suggesting that donor quenching resulted primarily from modified residue(s) Cys126/135 in the acceptor. No energy transfer was observed for the NPM-heavy chain/CPM-SPIII pairing. However, when NPM-heavy chain was reassociated with unmodified light chain prior to reaction with CPM-SPIII or CPM-SPIII-T4, energy transfer was observed with calculated interfluorophore distances of approximately 31 and 34 A, respectively. Levels of acceptor resulting in maximal donor quenching suggested an equimolar stoichiometry of factor VIII (light chain)/vWf fragment in the reconstituted complexes. These results indicate a close spatial arrangement among the A3 domain of factor VIII light chain, the A2 domain of factor VIII heavy chain, and the NH2 terminus region of vWf in the factor VIII-vWf complex.


Evaluation of the Temple Touch Pro™ noninvasive core-temperature monitoring system in 100 adults under general anesthesia: a prospective comparison with esophageal temperature.
Perioperative hypothermia is still common and has relevant complication for the patient. An effective perioperative thermal management requires essentially an accurate method to measure core temperature. So far, only one study has investigated the new Temple Touch Pro™ (Medisim Ltd., Beit-Shemesh, Israel). during anesthesia Therefore, we assessed the agreement between the Temple Touch Pro™ thermometer (TTP) and distal esophageal temperature (TEso) in a second study. After approval by the local ethics committee we studied 100 adult patients undergoing surgery with general anesthesia. Before induction of anesthesia the TTP sensor unit was attached to the skin above the temporal artery. After induction of anesthesia an esophageal temperature probe was placed in the distal esophagus. Recordings started 10 min after placement of the esophageal temperature probe to allow adequate warming of the probes. Pairs of temperature values were documented in five-minute intervals until emergence of anesthesia. Accuracy of the two methods was assessed by Bland-Altman comparisons of differences with multiple measurements. Core temperatures obtained with the TTP in adults showed a mean bias of -0.04 °C with 95% limits of agreement within - 0.99 °C to + 0.91 °C compared to an esophageal temperature probe. We consider the TTP as a reasonable tool for perioperative temperature monitoring. It is not accurate enough to be used as a reference method in scientific studies, but may be a useful tool especially for conscious patients undergoing neuraxial anesthesia or regional anesthesia with sedation. Trial registration This study was registered in the German Clinical Trials Register (DRKS-ID: 00024050), day of registration 12/01/2021.


Hyperbaric Oxygen Therapy Following Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.
Hyperbaric oxygen therapy (HBOT) is a promising treatment modality for ischemic heart disease including myocardial infarction where outcomes are frequently poor despite early revascularization. To compare single-photon emission computed tomography (SPECT) findings in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) treated with HBOT vs. control at 6 weeks. In this pilot study, 24 patients were randomly allocated to HBOT (n = 13) and control groups (n = 11). Both groups underwent PPCI and were treated following the guidelines for STEMI management. The HBOT group received additional 15 and 90-minute HBOT sessions. All participants underwent SPECT at initial presentation (within 48 h of PPCI) and at follow up. Baseline characteristics were similar in both groups. The number of affected SPECT segments in the HBOT group at baseline and 6 weeks were 47.1 ± 14.6% vs. 33.7 ± 16.2%, respectively, with p = 0.039, and in the control group, the number of affected segment at these times were 55.5 ± 19.5% vs. 45.9 ± 17.9%, respectively, with p = 0.090. At follow-up, a decrease in the summed rest score was noted in both groups (HBOT: 20 ± 6.0 vs. 12.7 ± 8.1; p = 0.0017; control: 23 ± 8.2 vs. 16.7 ± 6.6; p = 0.031). The left ventricular ejection fraction in the HBOT group improved from 44 ± 22.1% to 57.2 ± 15.4% (p = 0.011) and in the control group from 45.9 ± 18.2% to 55 ± 12.1% (p = 0.044). HBOT use in STEMI patients was associated with an improvement in perfusion and an increase in ejection fraction following PPCI. These observations warrant a larger randomized clinical trial.


Tipranavir (Aptivus): approval cautiously recommended.
A new protease inhibitor active against most HIV that is resistant to other protease inhibitors is likely to be approved in the U.S. soon, after an 11-3 vote of an advisory committee.


Expression and complex assembly of calcium-binding proteins MRP8 and MRP14 during differentiation of murine myelomonocytic cells.
In the present study we analyzed expression and biochemical properties of the two recently cloned calcium-binding proteins MRP8 and MRP14, both members of the S-100 family, in murine myelomonocytic cells. Expression of MRPs was found to be restricted to granulocytes and distinct stages of macrophage differentiation when compared to the expression of other markers (Mac-1, F4/80) in transformed macrophage cell lines (M1, RMB.TG, WEHI.TG, J774A, P388D) and resident and exudate peritoneal and tissue macrophages. Similarly, mRNA and protein levels of MRP8/MRP14 in murine bone marrow cells decreased during culture in L cell-conditioned medium. Applying a cross-linking technique, the formation of noncovalently associated heteromeric MRP8/MRP14 complexes of 25, 35, and 48 kd was demonstrated. Our data suggest that MRP8/MRP14 expression and complexation are characteristic for granulocytes and distinct stages of macrophage differentiation in mice. Analysis of the MRP8/MRP14+ phenotype of macrophages may provide further insights into the mechanisms underlying macrophage differentiation.


Purification and partial characterization of a 'short' insectotoxin-like peptide from the venom of the scorpion Parabuthus schlechteri.
A disulfide-rich, low-molecular-mass toxin-like peptide has been isolated from Parabuthus schlechteri venom using gel filtration, ion exchange, and reversed phase chromatography. Partial characterization of this peptide reveals a relationship with four-disulfide bridge proteins belonging to the family of 'short' insectotoxins (44% residue identity). In recognition hereof, the peptide was named PBITx1 (sITx10). Our work also reports on the deduced sequences of two other 'short' insectotoxins from Buthus eupeus, I3 and I4, and it provides a consensus sequence and nomenclature for all known 'short' insectotoxins. Finally, sequence similarities with K+ channel blockers (charybdotoxin, kappa-conotoxin), and a Cl- channel blocker (chlorotoxin) are highlighted.


Locally evoked potentials in slices of rat neostriatum: a tool for the investigation of intrinsic excitatory processes.
Field potentials, extracellular unitary discharges and intracellular potentials evoked by intrastriatal stimulation were recorded from slices (thickness 200-400 micron) of rat neostriatum maintained in an artificial medium. The field potentials consisted of two negative waves appearing at latencies of 0.5-1.5 ms (N-1) and 2-4 ms (N-2). Extracellular unitary records showed two typed of discharges, one with short but constant latencies at threshold level stimulation and the other with longer and variable latencies. In intracellular recordings the late discharge was seen to arise from EPSPs. Based on the intra- and extracellular unitary records, N-1 was identified as the population spike of antidromically or directly activated unitary discharges and N-2 as that of orthodromically activated discharges. This interpretation was substantiated by the fact that the N-2 potential was blocked in a perfusion medium containing a lower Ca++ or a higher Mg++ concentration than the standard solution. Neither interruption of ascending neostriatal inputs nor decortication 14 days prior to recording altered the configuration of the locally evoked potentials or the probability of synaptically driven discharge occurrence. Thus by intrastriatal stimulation, neostriatal neurons are activated antidromically or directly and/or orthodromically through intrinsic excitatroy synapses. Since the intracellular recordings showed that neostriatal neurons can be well preserved, this preparation can be regarded as a useful tool for electrophysiological and neuropharmacological investigations on intrinsic excitatory processes in the neostriatum.


Multiresolution wavelet analysis for efficient analysis, compression and remote display of long-term physiological signals.
Increased inter-equipment connectivity coupled with advances in Web technology allows ever escalating amounts of physiological data to be produced, far too much to be displayed adequately on a single computer screen. The consequence is that large quantities of insignificant data will be transmitted and reviewed. This carries an increased risk of overlooking vitally important transients. This paper describes a technique to provide an integrated solution based on a single algorithm for the efficient analysis, compression and remote display of long-term physiological signals with infrequent short duration, yet vital events, to effect a reduction in data transmission and display cluttering and to facilitate reliable data interpretation. The algorithm analyses data at the server end and flags significant events. It produces a compressed version of the signal at a lower resolution that can be satisfactorily viewed in a single screen width. This reduced set of data is initially transmitted together with a set of 'flags' indicating where significant events occur. Subsequent transmissions need only involve transmission of flagged data segments of interest at the required resolution. Efficient processing and code protection with decomposition alone is novel. The fixed transmission length method ensures clutter-less display, irrespective of the data length. The flagging of annotated events in arterial oxygen saturation, electroencephalogram and electrocardiogram illustrates the generic property of the algorithm. Data reduction of 87% to 99% and improved displays are demonstrated.


Performance of Hybrid Imaging in the Diagnosis of Coronary Artery Disease.
Single-photon emission computed tomography (SPECT) and computed tomography coronary angiography (CTCA) are usually performed independently in patients with suspected coronary artery disease. We assessed the hypothesis that hybrid SPECT/CTCA imaging results in higher diagnostic accuracy than either method alone, particularly in cases presenting with high levels of coronary calcification. A total of 243 major coronary vessels in 81 patients with known or suspected coronary artery disease were screened using SPECT with semiconductor detectors and CTCA with 256-detector row computed tomography. Patients who were diagnosed with myocardial ischemia underwent coronary angiography. Coronary angiography results were defined as positive for stenosis when the stenosis diameter was >70% or fractional flow reserve was <0.8. These data were then compared with a fused image of the SPECT and CTCA datasets generated using a dedicated workstation. To detect significant coronary artery stenosis, the respective sensitivity, specificity, and accuracy were 73%, 61%, and 67% with SPECT alone, 96%, 44%, and 67% with CTCA alone, and 95%, 75%, and 84% with hybrid imaging. Moreover, hybrid imaging allowed the accurate diagnosis of 47 vessels with severe calcification that CTCA alone could not evaluate correctly. Hybrid imaging shows greater diagnostic accuracy than single-modality evaluation through more comprehensive information on potential coronary stenosis and its hemodynamic significance.


Maternal near miss at Kathmandu Medical College: An analysis of severe maternal morbidity at a Nepalese tertiary care facility.
The World Health Organization (WHO) 'near miss' tool has been extensively used to audit maternal morbidity in low- and middle-income countries. Analysis of the cases of 'near miss' enables a better understanding of the associated factors, identifies deficiencies in the provision of maternity services and lays a foundation for better preventive measures in the future. To understand the epidemiology, aetiology and determine the aspects of preventability of maternal 'near miss' (MNM) at Kathmandu Medical College. A prospective audit of MNM and maternal deaths (MD) was undertaken at Kathmandu Medical College over a period of 12 months. The cases were identified using WHO 'near miss' criteria and areas of preventability in the provision of care determined using the modified Geller's criteria. The total number of deliveries and live births in the study period were 2747 and 2698 respectively. A total of 34 'near misses' and two MDs were identified. The common direct aetiologies of MNM and MDs identified were obstetric haemorrhage followed by hypertensive disorders with one-third of cases being of indirect aetiology. Fifty-five percent of cases had some aspects of provider- or system-related preventability with the leading delays being lack of diagnosis and recognition of high-risk status among patients and lack of interdepartmental communication. The WHO near miss rate at Kathmandu Medical College was 12.5/100 live births. Significant aspects of preventability, especially at the level of the provider, were noted among cases of MNM and MDs.


5-HT1A and 5-HT1C/1D receptor agonists produce reciprocal effects on male sexual behavior of rhesus monkeys.
Research has indicated that serotonin (5-HT) is involved in regulating male sexual behavior in rodent, as well as primate species. The present study was designed to further characterize 5-HT influences on male sexual behavior of rhesus monkeys. Experiment 1 examined the effects of 5-HT1A and 5-HT1C/1D receptor stimulation on penile erections and yawning behavior. Administration of the 5-HT1C/1D receptor agonist, m-chlorophenylpiperazine (m-CPP, 0.8 and 3.0 mg/kg), facilitated the occurrence of penile erection, and at doses greater than 0.2 mg/kg stimulated yawning. By contrast, the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-0.2 mg/kg) did not significantly influence penile erections or yawning behavior. Experiment 2 evaluated the effects of m-CPP and 8-OH-DPAT on the behavior of male monkeys in the presence of a sexually receptive female monkey which the males could see, hear and smell, but not physically contact. Administration of m-CPP along with presentation of a receptive female stimulated penile erections to a greater extent than they were stimulated by either one of these manipulations alone. Administration of 8-OH-DPAT (0.1 and 0.2 mg/kg) produced a decrease in the percent of monkeys exhibiting penile erections in the presence of the female. In this experiment, yawning was affected in opposite directions, with m-CPP stimulating and 8-OH-DPAT decreasing the frequency of yawning. Experiment 3 assessed the effects of m-CPP on male copulatory behavior of rhesus monkeys. Administration of m-CPP (0.8-3.0 mg/kg) produced a dose-dependent decline in the percent of males initiating copulation and achieving ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS)


Disrupted-in-Schizophrenia-1.
Chromosomal abnormalities can be powerful tools to identify genes that influence disease risk. The study of a chromosome translocation that segregated with severe psychiatric illness in a large family led directly to the discovery of a gene disrupted by a chromosomal breakpoint. Disrupted-in-Schizophrenia-1 (DISC1) is now an important candidate risk gene for schizophrenia and affective disorders. We review the work that led up to this discovery and the evidence that it is important in the wider population with schizophrenia and affective disorders. We also discuss the latest findings on the neuronal functions of the protein DISC1 encoded by the gene.


Cloning and expression of phosphoenolpyruvate carboxykinase from a cestode parasite and its solubilization from inclusion bodies using l-arginine.
Phosphoenolpyruvate carboxykinase is an essential regulatory enzyme of glycolysis in the cestode parasite, Raillietina echinobothrida, and is considered a potential target for anthelmintic action because of its differential activity from that of its avian host. However, due to the unavailability of its structure, the mechanism of regulation of PEPCK from R. echinobothrida (rePEPCK) and its interaction with possible modulators remain unclear. Hence, in this study, the rePEPCK gene was cloned into pGEX-4T-3 and overexpressed for its characterization. On being induced by IPTG, the recombinant rePEPCK was expressed as inclusion bodies (IBs); hence, various agents, like different inducer concentrations, temperature, time, host cell types, culture media, pH, and additives, were used to bring the protein to soluble form. Finally, a significant amount (∼46%) of rePEPCK was solubilized from IBs by adding 2M l-arginine. Near-UV circular dichroism spectra analysis indicated that l-arginine (2M) had no effect on the conformation of the protein. In this study, we have reported a yield of ∼73mg of purified rePEPCK per 1L of culture. The purified rePEPCK retained its biological activity, and Km of the enzyme for its substrate was determined and discussed. The availability of recombinant rePEPCK may help in biochemical- and biophysical-studies to explore its molecular mechanisms and regulations.


Treatment of ammonia by catalytic wet oxidation process over platinum-rhodium bimetallic catalyst in a trickle-bed reactor: effect of pH.
This work adopted aqueous solutions of ammonia for use in catalytic liquid-phase reduction in a trickle-bed reactor with a platinum-rhodium bimetallic catalyst, prepared by the co-precipitation of chloroplatinic acid (H2PtCl6) and rhodium nitrate [Rh(NO3)3]. The experimental results demonstrated that a minimal amount of ammonia was removed from the solution by wet oxidation in the absence of any catalyst, while approximately 97.0% of the ammonia was removed by wet oxidation over the platinum-rhodium bimetallic catalyst at 230 degrees C with an oxygen partial pressure of 2.0 MPa. The oxidation of ammonia has been studied as a function of pH, and the main reaction products were determined. A synergistic effect is manifest in the platinum-rhodium bimetallic structure, in which the material has the greatest capacity to reduce ammonia. The reaction pathway linked the oxidizing ammonia to nitric oxide, nitrogen, and water.


Response of Phragmites australis to increasing As(V) concentrations: Accumulation and speciation of As, and plant oxidative stress.
The use of macrophytes has been proposed recently as a suitable option for the phytostabilization or rhizofiltration of soils or waters contaminated by trace elements. As one of the most representative species of this type of plant, common reed (Phragmites australis (Cav.) Trin. ex Steud.) has shown tolerance to high concentrations of potentially hazardous elements, as is the case of arsenic. However, a deeper knowledge of how these plants deal with this toxicity, including their oxidative response, is needed for the optimum utilization of this species in phytoremediation procedures. In fact, little is known about how common reed plants react to As toxicity or the tolerance limits and accumulation potential of this species. In this work, common reed plants were exposed to a range of As(V) mass concentrations (0.5-10 mg L-1) in a hydroponic experiment, and the performance of the plants (growth, photosynthetic pigments, and oxidative stress related parameters) was evaluated and related to the major As species present in the different parts of the plants. The plants did not show any apparent symptom of toxicity and no significant effects were found for any of the different plant parameters analyzed. Arsenic was mostly accumulated as As(III) in the roots of the plants, and almost no translocation to the aerial part of the plants was observed for any of the As species analyzed. Common reed has shown a high capacity for As accumulation in its roots with no signs of toxicity, despite small nutrient imbalances. Thus, it can be considered to be a good candidate for use in the rhizofiltration and phytostabilization of As contaminated waters and soils, respectively.


Ultra-long Pt nanolawns supported on TiO2-coated carbon fibers as 3D hybrid catalyst for methanol oxidation.
In this study, TiO2 thin film photocatalyst on carbon fibers was used to synthesize ultra-long single crystalline Pt nanowires via a simple photoreduction route (thermally activated photoreduction). It also acted as a co-catalytic material with Pt. Taking advantage of the high-aspect ratio of the Pt nanostructure as well as the excellent catalytic activity of TiO2, this hybrid structure has the great potential as the active anode in direct methanol fuel cells. The electrochemical results indicate that TiO2 is capable of transforming CO-like poisoning species on the Pt surface during methanol oxidation and contributes to a high CO tolerance of this Pt nanowire/TiO2 hybrid structure.


Factors influencing Ghanaian midwifery students' willingness to work in rural areas: a computerized survey.
Lack of midwives in rural and remote areas of Ghana is a national concern as the country attempts to reach targets set by Millennium Development Goals to reduce maternal and child mortality by 2015. To understand factors influencing third-year Ghanaian midwifery students' willingness to work in rural areas. Two of the largest midwifery schools in Ghana. Third-year midwifery students (n=238) about to graduate and enter the workforce. Based on focus group discussions with midwifery students, we refined a computerized survey to assess students' preferences for rural posting after graduation. We then administered this survey to midwifery students in Ghana. We used Pearson's chi-squared to compare the top reasons for choosing job location between those students likely and not likely to work in a rural area. Logistic regression models were used to calculate the odds ratios. An opportunity to gain additional education was the most important factor for the midwifery students in deciding where they would eventually work (72%). Poor quality of clinical facilities (26%), poor quality of education for children (19%), and lack of social amenities (17%) were major deterrents to working in rural communities. For student midwives willing to work in rural areas the top reasons cited included to serve humanity (74%), and increased opportunities to gain clinical experience (62%). More experiences overall with rural communities resulted in greater odds of being willing to work in a rural area. Being born in a rural area (OR: 1.95, 95% CI: 0.736, 5.16) and living in a rural area after age 5 for one-year or more (OR: 1.52, CI: 0.857, 2.70). An exception to this was midwifery students who performed health work for six weeks or more in a rural area during training. These students were found to have 0.83 lower odds of willingness to work in a rural area (95% CI: 0.449, 1.55). By better understanding the motivating factors for rural healthcare workers, specific policy interventions can be established to improve the distribution of midwives thereby decreasing the burden of maternal and infant mortality.


Measurement of serotonin turnover rate in rat dorsal raphe nucleus by in vivo electrochemistry.
5-Hydroxytryptamine (5-HT; serotonin) turnover rate in dorsal raphe nucleus of the urethane-anesthetized rat was estimated by using the in vivo electrochemical detector to measure the decay of extraneuronal 5-hydroxyindole acetic acid (5-HIAA) after monoamine oxidase inhibition. Carbon paste electrodes were scanned by semiderivative voltammetry and revealed two peaks: one at +0.15 V and the other at +0.25 V. The higher potential peak is composed primarily of the 5-HT metabolite 5-HIAA. After administration of pargyline, 75 mg/kg i.p., this peak declined exponentially. Regression analysis of these data by an exponential decay model yielded the fractional rate constant 0.82 +/- 0.06 h-1 (mean +/- SEM). This rate constant of 5-HIAA disappearance measured by in vivo electrochemistry is identical to the rate constant found by others measuring 5-HIAA disappearance by direct tissue assay methods. In animals not treated with pargyline, tissue 5-HIAA concentrations in the dorsal raphe nucleus were measured by HPLC with electrochemical detection. The average 5-HT turnover rate calculated as the product of the fractional rate constant and steady-state tissue 5-HIAA concentration was 12.6 nmol/g/h. These results demonstrate that electrochemical detection of extraneuronal 5-HIAA combined with monoamine oxidase inhibition can be used to measure neurotransmitter turnover in vivo in a discrete brain region.


NAFL screening score: A basic score identifying ultrasound-diagnosed non-alcoholic fatty liver.
Several non-invasive diagnostic scores for non-alcoholic fatty liver (NAFL) have been developed, but the clinical application is limited because of their complexity. To develop and validate an easy-to-calculate scoring system to identify ultrasound-diagnosed NAFL. 48,489 patients from 2 centers were included in this study. Multivariable logistic regression models were employed for model development. Ultrasonography was applied to diagnose NAFL. The selected variables were assigned an integer score proportional to the estimated coefficient from the logistic regression analysis, namely NAFL Screening Score (NSS). The ability of the NSS to identify NAFL was assessed by analyzing the area under the receiver operating characteristic curve (AUROC) and was tested in an independent validation cohort. Additionally, the performance of NSS was compared with existing models. NSS was developed as a basic score comprising of age, body mass index (BMI), triglyceride (TG), ALT/AST, fasting plasma glucose (FPG) and uric acid (UA) in both sexes. NSS showed a relatively good discriminative power (AUROC=0.825 for males, 0.861 for females in the validation cohort) in comparison with other models. The optimal cut-off point was 32 for males and 29 for females. We developed and validated NSS, an easy-to-use score sheet identify ultrasound-diagnosed NAFL. NSS may be clinically useful for initial diagnosing NAFL.


Relaxin augments the inflammatory IL6 response in the choriodecidua.
Intrauterine infection frequently leads to preterm birth (PTB), with the pathophysiology involving activation of the innate immune system and its associated inflammatory response. The choriodecidua produces relaxin (RLN) and elevated levels are associated with preterm premature rupture of the fetal membranes. However, it is not increased in bacterially-mediated PTB, but may act as an endogenous sterile inflammatory mediator. Elevated systemic RLN levels from the corpus luteum are also associated with PTB, but the mechanism is unknown. In clinical obstetrics, intrauterine inflammation or infection can coexist with elevated RLN. Therefore, in this study, we further characterized the effects of RLN alone or together with an inflammatory mediator on the production of IL1B, CSF2 (GM-CSF), IL6, IL8 and TNF, from chorionic cytotrophoblasts (CyT), decidual fibroblasts (DF) and stromal cells (DSC), using interleukin-1 beta (IL1B) to mimic sterile inflammation or lipopolysaccharide (LPS) for bacterial infection. Endogenous differences between the cells showed that the CyT expressed more RLN, its receptor RXFP1 and the RXFP1 splice variant D. CyT also showed the most robust cAMP response to RLN with increased IL6 secreted after 4 h, preceded by increased transcription at 1 h, likely due to activation of RXFP1 and cAMP. When all cell types were treated with IL1B and RLN, RLN augmented secretion of IL6 and IL8 from CyT and DF, but not DSC. Similarly, RLN augmented LPS-induced IL6 secretion from CyT and DF. Despite the structural similarity between TLR4 and RXFP1, blocking TLR4 in CyT had no effect on RLN-induced IL6 secretion, suggesting specific activation of RXFP1. Thus, we have shown that in the presence of a low level of intrauterine inflammation/infection, elevated RLN could act on the CyT and DF to augment the inflammatory response, contributing to the pathophysiology of PTB. RLN augments the inflammatory responses induced by IL1B or LPS in chorionic cytotrophoblasts and decidual fibroblasts.


Coping with menopausal symptoms: An internet survey of Belgian postmenopausal women.
An internet survey was performed to obtain data on the current use in Belgium of hormone replacement therapy and alternative treatments for the alleviation of menopausal symptoms. A supplementary aim was to assess the use of opt-in internet opinion panels (TalkToChange, http://www.talktochange.com, and GMI, http://www.gmi-mr.com/global-panel) as a potential new way to obtain data on menopausal issues. Data were collected via an internet platform from 696 postmenopausal women aged 45-60 years. Respondents were asked questions about their socio-demographic profile, their experience of the menopause, the burden of the menopause, its impact on their quality of life and the treatment of menopausal symptoms (if any). The opt-in internet opinion panels proved a quick way (19days) to obtain reliable information with a low error margin (3.7%). The online survey collected detailed socio-demographic data. Almost all of the women (98%) had heard about the menopause before. Sixty-one percent perceived the menopause as a temporary phase (17% thought it lasted for one or two years and 44% thought it lasted for three to five years) and only 39% realized the menopause would last for the rest of their life. Twenty-three percent of the women reported any kind of impact of the menopause on their quality of life. However, for the other 77% the menopause had resulted in complaints. No differences according to the women's age, level of education or professional status were found in this respect. Sixty-nine percent of the women had 'ever' used some type of treatment for menopausal symptoms and 53% were currently using a treatment. Forty percent of those with more than three symptoms were currently untreated. Of those who were not on hormone replacement therapy (HRT), 61% would not consider taking it (54% were 'strongly opposed' and 7% simply 'opposed'), while 8% would consider asking their doctor for HRT. Among those women who were opposed to HRT, 25% indicated that they were afraid of the increased risk of breast cancer, 34% cited cardiovascular risks and 26% were worried about weight gain. In this Belgian sample, HRT was used significantly more often by French-speaking women (32%) than by Dutch-speaking women (9%) (OR 4.4, p<0.0001). The alternatives to HRT had a high satisfaction rate among users. Relaxation techniques, regular physical activity, acupuncture and avoiding stress had satisfaction rates similar to that with HRT. It was not possible to compare the alternatives in the same women. Nor was it possible to assess whether more pronounced symptoms required a specific treatment. Opt-in internet opinion panels proved a quick and efficient way to gather data on menopausal issues in Belgium. Despite the high levels of awareness and knowledge, there is some confusion concerning the duration of the menopause, and its common perception as a temporary condition is likely to mean that the menopausal burden is substantially underestimated. Many symptomatic women are untreated.


Selective adsorption of antibiotics on manganese oxide-loaded biochar and mechanism based on quantitative structure-property relationship model.
In this study, MnCl2-impregnated biomass was oxygen-limited pyrolyzed to produce manganese oxide-loaded biochar (MBC), its adsorption behaviors and influencing factors on tetracycline (TTC), norfloxacin (NOR), and sulfamethoxazole (SMX) were systematically investigated. Three antibiotics exhibited enhanced adsorption behavior on MBC, with maximum adsorption capacity as accurately described by Sips isotherm: TTC (534 mg/g) > NOR (67 mg/g) > SMX (28 mg/g). Hydrogen bonding, n/π-π interactions, electrostatic interaction, surface coordination, and hydrophobic interaction are the major mechanisms for the improved adsorption. Manganese oxide particles on MBC promoted surface coordination and hydrogen bonding. Antibiotic molecules with more hydroxyl oxygen-containing functional groups are more susceptible to migrate to biochar surfaces and to be adhered. Moreover, the quantitative structure-property relationship (QSPR) model was constructed and revealed that hydrogen bonding and π-π interactions were crucial for tetracycline antibiotics selective adsorption. Hence, MBC was a prospective adsorbent with promising applications for antibiotic removal in sewage processing.


Prognostic Effect of Low Subcutaneous Adipose Tissue on Survival Outcome in Patients With Multiple Myeloma.
Increasing evidence suggests that decreased skeletal muscle mass (sarcopenia) or adipose tissue assessed using computed tomography (CT) predicts negative outcomes in patients with solid tumors. However, the prognostic value of such an assessment in multiple myeloma (MM) remains unknown. Consecutive patients with newly diagnosed symptomatic MM were retrospectively analyzed. The cross-sectional area of skeletal muscles and subcutaneous or visceral adipose tissue was measured using CT. Body composition indexes (skeletal muscle index, subcutaneous adipose tissue index [SAI], and visceral adipose tissue index) were calculated. The association between these indexes and overall survival (OS) was examined. Of 56 evaluable patients, 37 (66%) had sarcopenia. The 2-year OS in patients with SAI < median was 58% compared with 91% in those with SAI ≥ median (P = .006). In multivariate analyses, SAI < median was significantly associated with poor OS (hazard ratio, 4.05; P = .02). Sarcopenia was not associated with OS. The maximum value of the standardized uptake value was significantly higher in patients with SAI < median (P = .02). The findings of this study suggest that low subcutaneous adipose tissue at baseline predicts poor survival outcome in patients with MM.


A chromatographic method to analyze products from photo-oxidation of anthropogenic and biogenic mixtures of volatile organic compounds in smog chambers.
A method for quantifying secondary organic aerosol compounds (SOA) and water soluble secondary organic aerosol compounds (WSOA) produced from photo-oxidation of complex mixtures of volatile organic compounds (VOCs) in smog chambers by gas chromatography/mass spectrometry (GC/MS) has been developed. This method employs a double extraction with water and methanol jointly to a double derivatization with N,O-bis (trimethylsilil) trifluoroacetamide (BSTFA) and O-(2,3,4,5,6)-pentafluorobenzyl-hydroxylamine hydrochloride (PFBHA) followed by an analysis performed by GC/MS. The analytical procedure complements other methodologies because it can analyze SOA and WSOA compounds simultaneously at trace levels. As application, the methodology was employed to quantify the organic composition of aerosols formed in a smog chamber as a result of photo-oxidation of two different mixtures of volatile organic compounds: an anthropogenic mixture and a biogenic mixture. The analytical method allowed us to quantify up to 17 SOA compounds at levels higher than 20 ng m(-3) with reasonable recovery and a precision below 11%. Values found for applicability, selectivity, linearity, precision, recovery, detection limit, quantification limit and sensitivity demonstrated that the methodology can be satisfactorily applied to quantify SOA and WSOA.


Comparison of steroid receptor expression in normal, dysplastic, and neoplastic canine and feline mammary tissues.
Steroid receptor expression was assessed by immunohistochemistry in neoplastic, hyperplastic/dysplastic, and normal mammary tissue samples removed from 68 queens and 47 bitches, using monoclonal antibodies against human oestrogen-alpha (ER) and progesterone receptors (PR). Mammary lesions were classified according to World Health Organization (WHO) criteria, and all animals with invasive carcinomas were clinically followed for 2 years. Stromal and/or lymphatic invasion and histological grading were also recorded. In both species, ER expression was significantly higher in healthy tissues, hyperplastic/dysplastic lesions, and benign tumours than in carcinomas. The loss of ER expression was more marked in feline than in canine carcinomas. In queens, PR expression increased in dysplastic lesions and "in situ" carcinomas and decreased in invasive carcinomas, even if parts of these tumours were still PR-positive. In bitches no significant variation in PR expression was observed between normal tissue, dysplasias, and benign neoplasms, but was significantly lower in carcinomas. In both species ER and PR expression in invasive carcinomas did not correlate either with histological parameters or overall survival time. This study demonstrates several differences in steroid hormone dependency between the two species. The percentage of PR-positive feline carcinomas suggests a possible role of progesterone in promoting early tumour cell growth in queens. The low percentage of ER-positive invasive carcinomas further demonstrated the aggressive phenotype and behaviour of feline mammary tumours.


Kainic acid seizures cause enhanced expression of cholecystokinin-octapeptide in the cortex and hippocampus of the rat.
Immunocytochemistry and in situ hybridization techniques were used for investigating changes in cholecystokinin immunoreactivity and mRNA in the cerebral cortex and hippocampus after kainic acid-induced limbic seizures in the rat. Marked increases in cholecystokinin mRNA concentrations were observed in layers II/III and V/VI of the cerebral cortex, in CA1 pyramidal neurons of the hippocampus, and in presumptive basket cells of the dentate gyrus 1 and 2 days after the acute seizures. Whereas cholecystokinin mRNA contents returned to normal in the cerebral cortex and the CA1 sector at later intervals, high concentrations were observed in basket cells even 2 months after the initial seizures. Accordingly, cholecystokinin-like immunoreactivity was intensified in the cerebral cortex, CA1 sector and in presumed basket cells of the hippocampus 30 days after kainic acid. Besides its high content in basket cells, cholecystokinin-like immunoreactivity was primarily present in neuronal fibers or diffusely distributed in the respective brain area. In the hippocampus, strongly enhanced staining for cholecystokinin was also observed in the alveus, the stratum lacunosum moleculare, and in the inner molecular layer, suggesting increased concentrations of the peptide in afferent and efferent fibers of the hippocampus. The present experiments suggest a strong activation of cholecystokinin systems in the brain after kainic acid-induced limbic seizures in the rat. This is indicated by pronounced increases in cholecystokinin mRNA in the cortex and individual cell types of the hippocampus (basket cells, granule cells, and CA1 pyramidal neurons). The subsequent increases in cholecystokin immunoreactivity even surpass those in mRNA. The observed changes may be part of the self-defense mechanisms that protect the animals during subsequent epileptic episodes.


Diethyl ether fraction of Labrasol having a stronger absorption enhancing effect on gentamicin than Labrasol itself.
In our previous study, we had reported that Labrasol has a good gastrointestinal (GI) absorption enhancing effect on poorly absorbable drugs. In order to improve further absorption enhancing effect of Labrasol on gentamicin (GM), which is a representative water-soluble, poorly absorbable drug, Labrasol was fractionated with hexane, diethyl ether, ethyl acetate and water. The absorption enhancing effect of each fraction of Labrasol and Labrasol alone were evaluated in vivo using rats. Each test formulation of GM was administered into the rat colon at a dose of 5.0 mg/kg and plasma GM concentrations were measured by a HPLC method. Among the four fractions of Labrasol and Labrasol, diethyl ether fraction showed the strongest absorption enhancing effect on GM. When the doses of diethyl ether fraction were 1.0, 0.5 and 0.1 ml/kg, the Cmax values were 8.95 +/- 1.46, 8.02 +/- 2.14 and 7.41 +/- 1.25 microg/ml, respectively. Moreover, AUC(0-6) values were also maintained at high level, i.e. 27.28 +/- 5.90, 20.32 +/- 3.79 and 19.61 +/- 2.09 microg h/ml. Based on the AUC(0-6) values obtained with each fraction, the rank order of absorption enhancing effect on GM was diethyl ether > ethyl acetate=hexane > aqueous fraction.


Life histories of desert geophytes -the demographic consequences of reproductive biomass partitioning patterns.
During five consecutive growing seasons (winters) ca. 110 plants of the desert geophyte Bellevalia desertorum were marked individually in a 25 m2 plot on a south-facing slope in the central Negev Desert of Israel. The number of rosette leaves of each plant was recorded, as well as whether it flowered and produced seeds. Multiple regression analysis of the data on the B. desertorum individuals showed that the reproductive state of a plant was determined by 1) its previous size and 2) the current conditions (rainfall), but not by previous conditions, nor by previous reproductive activity. Plant surveys supported these findings. These demographic results were consistent with the current understanding of the reproductive resource allocation pattern of B. desertorum. Flowering was most affected by rainfall until January of the same season, the number of leaves by rainfall until March and seed set was by the total annual amount. Surveys in populations ofB. eigii, a species of more mesic habitats in the Negev Desert suggested that in this species there is a negative effect of previous reproduction in combination with the previous and current conditions, which is also expected from its biomass partitioning pattern.The significance of demographic studies of individual plants in natural populations for the interpretation of experimentally determined resource partitioning patterns was discussed.


One-year cost-effectiveness of tiotropium versus ipratropium to treat chronic obstructive pulmonary disease.
The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new, once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease (COPD). This prospective cost-effectiveness analysis was performed alongside two 1-yr randomised, double-blind clinical trials in the Netherlands and Belgium. Patients had a diagnosis of COPD and a forced expiratory volume in one second (FEV1) < or = 65% predicted normal. Patients were randomised to tiotropium (18 microg once daily) or ipratropium (2 puffs of 20 microg administered four times daily) in a ratio of 2:1. The mean number of exacerbations was reduced from 1.01 in the ipratropium group (n = 175) to 0.74 in the tiotropium group (n = 344). The percentages of patients with a relevant improvement on the St. George's Respiratory Questionnaire (SGRQ) were 34.6% and 51.2%, respectively. Compared to ipratropium, the number of hospital admissions, hospital days and unscheduled visits to healthcare providers was reduced by 46%, 42% and 36% respectively. Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 Euro (SEM 160) in the tiotropium group and 1,541 Euro (SEM 163) in the ipratropium group (difference 180 Euro). Incremental cost-effectiveness ratios were 667 Euro per exacerbation avoided and 1084 Euro per patient with a relevant improvement on the SGRQ. Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 Euro per patient per year.


Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice.
Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell-specific reduction of HMG-CoA reductase (Hmgcr m-/m- ), which is the rate-limiting enzyme in cholesterol biosynthesis, protects against atherosclerosis by inhibiting macrophage migration in mice. We hypothesized that ATMs are harder to accumulate in Hmgcr m-/m- mice than in control Hmgcr fl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcr m-/m- and Hmgcr fl/fl mice a high-fat diet (HFD) for 24 weeks and compared plasma glucose metabolism as well as insulin signaling and histology between the two groups. Myeloid cell-specific reduction of Hmgcr improved glucose tolerance and insulin sensitivity without altering body weight in the HFD-induced obese mice. The improvement was due to a decrease in the number of ATMs. The ATMs were reduced by decreased recruitment of macrophages as a result of their impaired chemotactic activity. These changes were associated with decreased expression of proinflammatory cytokines in adipose tissues. Myeloid cell-specific reduction of Hmgcr also attenuated hepatic steatosis. In conclusion, reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity.


Report to the 58th World Health Assembly: Health Action in Relation to Crises and Disasters.
This Summary Report was prepared for Agenda item 13.3 for the meeting of the World Health Assembly convened at the World Health Organization (WHO) Headquarters in Geneva, Switzerland on 20 May 2005. It was in part, prepared from the Reports generaged by the Conference, Health Actions in Relation to Crises and Disasters, convened by the WHO in Phuket, Thailand, 04-06 May 2005.


A propensity score matching study of totally robotic right hemicolectomy versus robot-assisted right hemicolectomy.
To compare and analyze the differences in safety, feasibility and short-term efficacy between robot-assisted right hemicolectomy (RARH) and totally robotic right hemicolectomy (TRRH). We collected the information of 184 patients who underwent right hemicolectomy in the Second Xiangya Hospital of Central South University from July 2016 to December 2021. We matched 148 patients (74 with robot-assisted right hemicolectomy and 74 with totally robotic right hemicolectomy) to conduct a retrospective analysis of their clinical outcomes. The incision lengths were 5.14 ± 0.60 cm in the RARH group and 4.74 ± 0.55 cm in the TRRH (p < 0.001). The blood losses were 86.28 ± 52.57 mL in the RARH group and 69.19 ± 44.78 mL in the TRRH (p = 0.035). The operative times were 197.50 min (171.25-242.25) in the RARH group and 160.00 min (145.00-188.75) in the TRRH (p < 0.001). The postoperative hospital stays were 11.18 ± 4.32 days in the RARH group and 9.53 ± 4.42 days in the TRRH (p = 0.023). The NRS pain scores were 3.05 ± 0.23 in the RARH group and 2.96 ± 0.26 in the TRRH (p = 0.019). The abdominal drainage extraction times were 7.54 ± 1.44 days in the RARH group and 7.00 ± 1.25 days in the TRRH (p = 0.016). Postoperative complications in the RARH group are fewer than TRRH (p = 0.033). TRRH is safe and feasible. Compared with RARHs, the TRRHs resulted in shorter incision lengths, operative times, intraoperative blood losses, postoperative hospital stays, first flatus times, first liquid diet times, and drainage tube removal times, and they improved NRS pain scores and postoperative complication frequencies.


Low-concentration uranium enters the HepG2 cell nucleus rapidly and induces cell stress response.
This study aimed to compare the cell stress effects of low and high uranium concentrations and relate them to its localization, precipitate formation, and exposure time. The time-course analysis shows that uranium appears in cell nuclei as a soluble form within 5 min of exposure, and quickly induces expression of antioxidant and DNA repair genes. On the other hand, precipitate formations began at the very beginning of exposure at the 300-μM concentration, but took longer to appear at lower concentrations. Adaptive response might occur at low concentrations but are overwhelmed at high concentrations, especially when uranium precipitates are abundant.


Intraaxonal uptake and transport of marker proteins: novel ways of tracing peripheral nerve regeneration.
Disruption of peripheral nerve continuity occurs after accidents or in obstetrics. Brachial plexus palsy is accompanied by loss of function of the upper extremity. For optimal regeneration, surgical reconstruction should be performed within 6 months after injury. Postoperative monitoring is difficult because reliable diagnostic tools are not available. Here we present a hypothesis how to monitor peripheral nerve regeneration taking into account two intriguing features of nerve repair. First, the nerve itself with its numerous axons has been neglected as transportation pathway hitherto. Second, growth associated proteins are exclusively upregulated during peripheral nerve repair and development providing excellent target molecules. Contrast media could be designed using truncated forms of these proteins. Previous studies showed that peripheral nerves have the ability to incorporate proteins with a size up to 240 kDa. After wounding, growth associated proteins are transported intraaxonally and incorporated into growth cone membranes. We hypothesize that injection of contrast media close to nerve cell bodies or into the end organ of the injured nerve would lead to protein uptake and transport to the injury site. Sprouting of peripheral nerves could be monitored by magnetic resonance imaging or single photon emission computer tomography using adequate tracer-coupled proteins. By this new method, nerve repair could be monitored non-invasively, selectively and repeatedly. Less contrast media at lower price would be needed and only the injured part of the body would be exposed to the diagnostic apparatus. Aberrant nerve repair could be detected easily followed by surgical therapy within the critical time frame of sustained nerve regeneration.


Discontinuities of pattern and rules for regeneration in limbs of crayfish.
The most caudal limb in crayfish, the uropod, has two rami, the exopodite and the endopodite. Results of earlier experiments (J.E. Mittenthal et al. (1985) W. Roux's Arch. Dev. Biol. 194, 121-130) indicated that ramus morphogenetic fields in the two rami are equivalent and tandem. Thus the proximal (inner) junction of the rami, where intersegmental membrane separates them from each other and from the coxa, is analogous to a boundary between segments of the body or of a leg. In this region a discontinuity in the positional information carried by the ramus fields might occur. To characterize the morphogenetic fields in the region near this junction we have exchanged the medial and lateral margins of the two rami, performing the four possible grafting operations of this kind. While an experimentally generated discontinuity between the lateral margin of the exopodite and the medial margin of the endopodite (outer-to-outer junction) triggers intercalation of supernumerary rami, a discontinuity of pattern between the medial margin of the exopodite and the lateral margin of the endopodite (inner-to-inner junction) is stable despite the absence of intervening intersegmental membrane. Where intercalation does occur, it can proceed in either direction along the margin of a supernumerary ramus. These results suggest that there is no discontinuity of positional value at the boundary between the rami. The results of all of our experiments on the uropod indicate that a conjunction of separate proximodistal, dorsoventral, and mediolateral component fields may give positional information for generating the uropod. Intercalation restores the continuity of pattern in the proximodistal field. In the mediolateral field a discontinuity of pattern may result from a preferred polarity of intercalation: Outer cells may be competent to generate inner cells, but not vice versa. According to this hypothesis the two rami have tandem ramus fields but mirror-symmetric polarity of competence. Alternatively, intercalation may eliminate a mediolateral discontinuity only if the mismatch of mediolateral positional values at the discontinuity exceeds a threshold. The threshold criterion may be a weighted sum of limb field and ramus field positional values.


TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization.
Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore, potentially an important target for therapeutics. It was found in this work that a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in cytosolic calcium concentration ([Ca(2+)](c)) and reactive oxygen species (ROS) production in synoviocytes isolated from a rat model of collagen-induced arthritis. The increases in both [Ca(2+)](c) and ROS production were completely abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial membrane depolarization and reduction in cell viability; such effects were inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium. Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA expression in the isolated synoviocytes. Taken together, these data indicated that TRPV1 activation triggered synoviocyte death by [Ca(2+)](c) elevation, ROS production, and mitochondrial membrane depolarization.


Influence of essential amino acids and keto acids on protein metabolism and the anaemia of patients on chronic intermittent haemodialysis.
Ten patients were treated with 10 g essential amino acids per day orally; 9 patients received 9.5 g of a mixture of essential amino acids (Lys, Thr, Try, His, Tyr) and ketoanalogues of Ile, Leu, Phe, Val, Met per day and a control group of 11 patients received no supplementation. All patients were on a liberal food intake amounting to 1g protein/kg body weight and 31 kcal/kg body weight daily. Before and three months after the beginning of supplementation the following parameters were measured: serum concentrations of albumin, transferrin, urea, creatinine, blood haemoglobin content and haematocrit, activities of the enzymes delta-aminolevulinic acid dehydrase and porpho-bilinogen desaminase, and globin synthesis in peripheral red blood cells. After treatment with either essential amino acids or keto acids a significant stimulation of globin synthesis occurred. None of the other parameters was altered. It is concluded that in well-nourished patients supplements of essential amino acids or keto acids are ineffective.


How drought and salinity affect arbuscular mycorrhizal symbiosis and strigolactone biosynthesis?
This paper reviews the importance of AM symbiosis in alleviating plant stress under unfavourable environmental conditions, making emphasis on the role of strigolactones. A better understanding of the mechanisms that regulate this beneficial association will increase its potential use as an innovative and sustainable strategy in modern agriculture. Plants are very dynamic systems with a great capacity for adaptation to a constantly changing environment. This phenotypic plasticity is particularly advantageous in areas damaged or subjected to intensive agriculture. Nowadays, global crop production systems are intensifying the impact on natural resources, such as water availability. Therefore, there is an urgent need to find more sustainable alternatives. One of the plant strategies to improve phenotypic plasticity is to establish mutualistic beneficial associations with soil microorganisms, such as the arbuscular mycorrhizal (AM) fungi. The establishment of AM symbiosis requires a complex network of interconnected signalling pathways, in which phytohormones play a key role. Strigolactones (SLs) are plant hormones acting as modulators of the coordinated development under nutrient shortage. SLs also act as host detection signals for AM fungi, favouring symbiosis establishment. In this review, current knowledge on the effect of water-related stresses, such as drought and salinity, in AM symbiosis and in SL production is discussed. Likewise, how the symbiosis helps the host plant to alleviate stress symptoms is also reviewed. Finally, we highlight how interactions between hormonal signalling pathways modulate all these responses, especially in the cross-talk between SLs and abscisic acid (ABA). Understanding the intricate mechanisms that regulate the establishment of AM symbiosis and the plant responses under unfavourable conditions will contribute to implement the use of AM fungi as bioprotective agents against these stresses.


In vivo particle tracking and photothermal ablation using plasmon-resonant gold nanostars.
Gold nanostars offer unique plasmon properties that efficiently transduce photon energy into heat for photothermal therapy. Nanostars, with their small core size and multiple long thin branches, exhibit high absorption cross-sections that are tunable in the near-infrared region with relatively low scattering effect, making them efficient photothermal transducers. Here, we demonstrate particle tracking and photothermal ablation both in vitro and in vivo. Using SKBR3 breast cancer cells incubated with bare nanostars, we observed photothermal ablation within 5 minutes of irradiation (980-nm continuous-wave laser, 15 W/cm2). On a mouse injected systemically with PEGylated nanostars for 2 days, extravasation of nanostars was observed and localized photothermal ablation was demonstrated on a dorsal window chamber within 10 minutes of irradiation (785-nm continuous-wave laser, 1.1 W/cm2). These preliminary results of plasmon-enhanced localized hyperthermia are encouraging and have illustrated the potential of gold nanostars as efficient photothermal agents in cancer therapy. Gold nanostars are tunable in the near-infrared region with low scattering, thus enable photothermal therapy. Encouraging preliminary results of plasmon-enhanced localized hyperthermia both in vitro and in vivo demonstrate that Au nanostars may be efficient photothermal agents for cancer therapy.


Effect of lameness on breeding soundness examination results of beef bulls.
Studies suggest that high cortisol resulting from lameness-associated pain decreases testosterone and disrupts spermatogenesis leading to decreased fertility. The objective of this study was to investigate the effect of lameness on cortisol and testosterone concentrations and breeding soundness examination of beef bulls presented to a veterinary teaching hospital. Bulls, two-years of age or older, that presented for lameness, foot trim, and/or breeding soundness examination were enrolled. Blood samples were collected for cortisol and testosterone evaluation. A complete breeding soundness examination (BSE) was performed in all bulls. Subsequently, a complete lameness examination was performed, and limb/foot lesions recorded. A blinded evaluator used a lameness score of 1-5 to classify each bull as lame (>1) or not-lame (1). A total of 60 bulls were enrolled (34 with a satisfactory BSE and 26 with an unsatisfactory BSE result). Cortisol and testosterone were not different between the unsatisfactory and satisfactory groups (P = 0.26 and 0.32, respectively). The most common limb/foot lesions found in the unsatisfactory and satisfactory groups were laminitis-related (61.50% and 41.20%, respectively). There was no difference in the proportion of lame and not-lame bulls in the unsatisfactory and satisfactory groups (P = 0.17). The odds of a satisfactory BSE result were 4.40 times higher in not-lame bulls when compared with lame bulls. Therefore, lameness is associated with an unsatisfactory BSE result in beef breeding bulls.


Bombesin marine toxin conjugates inhibit the growth of lung cancer cells.
Hemiasterlin (Hem) and dolastatin (Dol) are marine natural products which are cytotoxic for cancer cells. Hem, a tripeptide, and Dol, a hexapeptide, were conjugated with linkers (L) to the universal BB agonist DPhe-Gln-Trp-Ala-Val-betaAla-His-Phe-Nle-NH2(BA1) and the effects of the Hem-BB and Dol-BB conjugates investigated on NCI-H1299 lung cancer cells. Hem-LA-BA1 and Hem-LB-BA1 inhibited specific (125I-Tyr4)BB binding to NCI-H1299 cells, which have BB2 receptors (R), with IC50 values of 15 and 25 nM, respectively. Addition of Hem-LA-BA1 and Hem-LB-BA1 to Fura-2 AM loaded cells containing BB2R, caused elevated cytosolic Ca2+. In a growth assay, Hem-LA-BA1 and Hem-LB-BA1 inhibited the proliferation of NCI-H1299 cells. Dol-succinamide (Dols)-LD-BA1 and Dols-LE-BA1 bound with high affinity to NCI-H1299 cells and elevated cytosolic Ca2+, but did not inhibit the proliferation of NCI-H1299 cells. Also, Hem-LA-BA1 inhibited 125I-DTyr-Gln-Trp-Ala-Val-betaAla-His-Phe-Nle-NH2 (BA2) binding to Balb/3T3 cells transfected with BB1R or BB2R as well as with BRS-3 with IC50 values of 130, 8, and 540 nM, respectively. These results show that Hem-BB conjugates are cytotoxic for cancer cells containing BB2R.


Effects of intravenous atropine on static P-V curves of the lung in normal man.
In eight normal subjects we studied the effects of intravenous (i.v.) injection of 2 mg atropine sulfate on the static lung recoil pressure-volume (PV) curves, plethysmographic airway resistance (Raw), and maximum expiratory flow rates (Vmax). In addition, we determined the influence of atropine injection in esophageal elastance (Ees) by measuring the esophageal pressure with an esophageal balloon containing five different volumes (0.5 to 4 ml) of air and by calculating the change in esophageal pressure per unit change in balloon volume (delta Pes/delta Vb). This procedure allowed us to obtain static lung recoil pressure (Pst(1] at a balloon volume extrapolated to zero, thus avoiding the interference of changes in esophageal tone following atropine administration with the measurement of Pst(1). After vagal blockade with atropine, Pst(1) significantly decreased with a shift to the left of PV curves, Raw decreased, and Vmax increased mainly at lower lung volumes. Ees also decreased with parasympathetic blockade. We interpret these findings to indicate that inhibition of vagal tone results in dilatation of large and small airways, and also in the relaxation of smooth muscle in terminal lung units.


Deprescribing Potentially Inappropriate Preventive Cardiovascular Medication: Barriers and Enablers for Patients and General Practitioners.
The use of preventive cardiovascular medication by patients with low cardiovascular disease (CVD) risk is potentially inappropriate. The aim of this study was to identify barriers to and enablers of deprescribing potentially inappropriate preventive cardiovascular medication experienced by patients and general practitioners (GPs). A total of 10 GPs participating in the ECSTATIC trial (Evaluating Cessation of STatins and Antihypertensive Treatment In primary Care) audiotaped deprescribing consultations with low-CVD-risk patients. After initial conventional content analysis, 2 researchers separately coded all barriers to and enablers of deprescribing medication using framework analysis. We performed a within-case and cross-case analysis to explore barriers and enablers among both patients and GPs. Patients (n = 49) and GPs (n = 10) expressed barriers and enablers with regard to the appropriateness of the medication and the deprescribing process. A family history for CVD was identified as a barrier to deprescribing medication for both patients and GPs. Patients feared possible consequences of deprescribing and were influenced by the opinion of their GP. Additionally, a presumed disapproving opinion from specialists influenced the GPs' willingness to deprescribe medication. Patients appreciated discussing their doubts regarding deprescribing potentially inappropriate preventive cardiovascular medication. Furthermore, they acknowledged their GP's expertise and took their opinion toward deprescribing into consideration. The GPs' decisions to deprescribe were influenced by the low CVD risk of the patients, additional risk factors, and the alleged specialist's opinion toward deprescribing. We recommend deprescribing consultations to be patient centered, with GPs addressing relevant themes and probable consequences of deprescribing preventive cardiovascular medication.


Disinfecting the acrylic resin plate using electrolyzed acid water and 2% glutaraldehyde: a comparative microbiological study.
Marked bactericidal activity of the electrolyzed acid water (EAW) and its less undesirable effects on biological tissues and the environment has been successfully utilized in dental practice. A review of literature reveals that not many studies have been performed to determine the disinfection effect of EAW on heat cured acrylic denture bases. The objective of the study is to determine the efficacy of EAW in disinfecting heat cured acrylic resin specimens as compared to the efficacy of disinfecting the specimens using 2% glutaraldehyde. Heat cured acrylic resin plates were immersed in Bacteria suspensions of Staphylococcus aureus and later disinfected using EAW which was produced using a custom made electrolyzing apparatus and 2% glutaraldehyde for different time intervals. The numbers of surviving bacteria were counted. As the control, the bacteria attached on the specimens were counted with out any disinfection treatment. The results obtained were statistically analyzed using ANOVA and post-hoc test. The disinfection potential of 2% glutaraldehyde was better than EAW when the specimens were disinfected for 1 and 3 min. Where as when the disinfection time was increased to 5 min there was no difference between EAW and 2% glutaraldehyde. However considering that the disinfecting time can be easily extended to 5 min, EAW can be effectively used for disinfecting the acrylic denture.


Complications of upper cervical spine trauma in elderly subjects. A systematic review of the literature.
The frequency of cervical spine trauma in elderly patients is increasing with most injuries occurring in the upper cervical spine. These fractures are associated with a risk of sometimes life-threatening complications, although very few studies have specifically analyzed this. The goal of this study was to identify the incidence of complications in the literature (mortality and morbidity) following upper cervical spine trauma in elderly patients. A systematic search was performed on the MEDLINE database without limiting the search by language or date to identify all studies reporting the rate of complications after upper cervical spine trauma in patients over the age of 60. Twenty-four observational studies were included, four were comparative. These studies included a total of 857 patients, mean age 76. Nearly all traumas were odontoid process fractures, and most were treated surgically (57%). The median mortality rate was 9.2% (Q1-Q3: 2.5-19.6) and the median rate of short-term complications was 15.4% (Q1-Q3: 5.8-26.9). The main late stage complication was nonunion, which developed in a mean 10 to 12% depending on the type of treatment. Complications following cervical spine trauma are frequent in elderly patients whatever the type of treatment. Knowledge of the rate of complications in the literature and the potential risk factors is essential for the clinician to improve the information provided to patients and to prevent complications. Systematic review of the literature. Level of evidence IV.


Description of a new species of Aleuroclava Singh, 1931 (Hemiptera, Aleyrodidae) infesting Schima superba from China.
A new whitefly species, Aleuroclava schimae Wang, sp. nov. infesting leaves of Schima superba (Parietales, Theaceae) is described and illustrated from Zhejiang, China. Puparia of the new species are elliptical, broad at the transverse molting suture region and broadly truncate posteriorly. Thoracic and caudal tracheal pores are discernible. In life, the puparia are covered by a thin layer of white wax.


[Regulation of spontaneous oscillations in the ureteral membrane potential by using physiologically active compounds].
I. a. perfusion of the Krebs solution of the cat ureter virtually altered characteristics of slow wave activity (SWA) observed with the blood circulation. Introduction of physiologically active substances into the solution restored some characteristics of the SWA. The SWA seems to depend not only on ionic exchange and properties of electrically controlled channels, but also on the set of native physiologically active substances.


[Phacoemulsification of intumescent cataract, IOL implantation and reconstruction of congenital iris coloboma through one anterior chamber superior opening. Case report].
To report a phacoemulsification of intumescens cataract and repair of congenital iris coloboma through one superior incision. Retrospective case report. Postoperative repair resulted in adequate pupil restoration, exact IOL position that allowed good visual rehabilitation. Cataract surgery in most cases is performed through superior incision. Congenital iris coloboma repair using the same incision is difficult but provides good cosmetic and functional results.


Direction of topological isomers of silver(I) coordination polymers induced by solvent, and selective anion-exchange of a class of PtS-type host frameworks.
The construction of two types of coordination polymers with closely related 4-connected topologies [PtS and lvt (4(2).8(4))] were achieved based on a well-designed bent dipyrazine linker, and the topological differences only result from the stereochemistry of silver(I) coordination sphere with the same coordination donors. Selective anion-exchange functions of the series of PtS-type coordination networks containing different counter anions (from small BF4- to very large SbF6-) were identified.


Ulcerative enteritis--atypical features.
A 40 year old man with two month history of vomiting and weight loss, was found to have multiple strictures in his small bowel. Investigations outruled known causes of small bowel ulceration, and the flat bowel mucosa did not respond to a gluten free diet. Treatment with steroids conferred a temporary benefit, however, small bowel ulceration persisted.


The kidneys play a central role in the clearance of rhGH in rats.
The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rhGH in non-anesthetized rats, anesthetized rats and in nephrectomized anesthetized rats. Clearance in non-anesthetized rats was 290 ml/h/kg. This was reduced to 185 ml/h/kg by anesthesia and further reduced to 18 ml/h/kg by nephrectomy. As nephrectomy was able to reduce clearance with 90%, we conclude that renal clearance plays a pivotal role in the elimination of rhGH in rats.


Drugs of abuse testing in a psychiatric outpatient service.
Drug testing of patients in a psychiatric outpatient service is an effective way to identify patients who relapse into renewed use of drugs of abuse and in monitoring the effectiveness of ongoing medical and psychological therapy. Most of this testing involves the analysis of urine specimens with immunoassays. Hair testing affords an alternative specimen matrix that is easy to obtain and not readily adulterated and offers the advantage of a wider surveillance window. Hair analysis is technically demanding, and the possibility of false-positives caused by environmental contamination renders it a controversial alternative. Sweat and saliva are potentially useful testing matrices, but their usefulness in clinical practice must await validation by additional clinical and laboratory experience. The correct interpretation of drug test results is predicated on knowing the performance characteristics of the analytical method, route of administration, and pharmacokinetics of the drug. All questionable positive results need confirmation testing to verify true positivity.


SCAP knockout in SM22α-Cre mice induces defective angiogenesis in the placental labyrinth.
The placental labyrinth is important for the exchange of nutrients and gases between the mother and the embryo in mice. This interface contains cells of both trophoblast and allantoic mesodermal origin that together produce maternal blood sinuses and placental blood vessels. However, the molecular mechanisms that take place during process of placental labyrinth development, especially concerning fetal capillaries, are not well understood. SREBP cleavage-activating protein (SCAP), a membrane protein, is required for the synthesis of fatty acids and cholesterol. Recently, when we crossed the offspring of the cross between smooth muscle 22 alpha (SM22α)- Cre recombinase (Cre) mice and SCAPloxp/loxp mice to research the function of SCAP in vascular smooth muscle cells (VSMCs) during certain pathological processes, we found that there were no resultant SM22α-Cre-specific SCAP knockout (KO) pups (SM22α-Cre+SCAPflox/flox; hereafter referred to as SCAP KO). Through anatomic studies of these embryos and placentas, we found that SCAP KO resulted in defective placental vessels and abnormal fetal morphology. Further immunohistochemical and immunocytochemical analyses suggested that SCAP is knocked out in the pericytes of the placental labyrinth. Compared to wildtype mice, SCAP KO placentas had abnormal vasculature in the labyrinth and lower levels of angiogenesis. By using RNA-seq and western blotting, we found that the expression of some genes and proteins in SCAP KO placentas was changed, including those related to pericyte/endothelial interactions genes and angiogenesis. Our results suggest that the proper organizational structure of the placental labyrinth depends on SCAP expression in pericytes.


Alpha2C-adrenoceptors play a prominent role in sympathetic constriction of porcine pulmonary arteries.
Enhanced pulmonary vasoconstriction in response to injuries of the central nervous system and hypoxia result in pulmonary edema due to increased sympathetic activation. This study aimed to characterize α(2)-adrenoceptor (AR)-mediated responses in porcine pulmonary arteries. α(2)-AR-mediated vasoconstriction was studied using a tissue bath protocol. α(2)-AR protein was determined by Western blotting. UK14304 (α(2)-AR agonist) elicited only a slight contraction in pulmonary arteries compared to veins. Verapamil (voltage-operated Ca(2+) channel blocker), 2-APB (store-operated Ca(2+) channel inhibitor), and P1075 (K(ATP) channel opener) induced a marked decrease of the basal tone in veins, but not in arteries. The UK14304-induced contraction in arteries was enhanced by (S)-(-)-Bay K 8644 (L-type Ca(2+) channel activator), N (ω)-nitro-L: -arginine methyl ester hydrochloride (L-NAME, eNOS inhibitor), and (S)-(-)-Bay K 8644 plus L-NAME to the same extent. Endothelium denudation failed to affect the UK14304 response. (S)-(-)-Bay K 8644 did not increase the maximal noradrenaline (non-selective α-AR agonist) or phenylephrine (α(1)-AR agonist) response. The rightward shift of the concentration-response curve to noradrenaline by prazosin (α(1)-AR antagonist) plus (S)-(-)-Bay K 8644 was smaller and non-parallel compared to that in the presence of prazosin alone. UK14304 responses were inhibited by MK912 (α(2C)-AR antagonist). Affinity of MK912 (pA(2) 9.76) and Western blotting analysis argue for an involvement of α(2C)-ARs in noradrenaline-induced contraction of pulmonary arteries. It is concluded that postjunctional α(2C)-ARs predominantly mediate contraction in porcine pulmonary arteries when the cytosolic Ca(2+) concentration is elevated. α(2C)-AR antagonists may be beneficial in the treatment of pulmonary edema.


α/Sulfono-γ-AA peptide hybrids agonist of GLP-1R with prolonged action both in vitro and in vivo.
Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t 1/2 > 14 days) compared to t 1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.


[Possible pathogenetic factors of gallstone formation in populations with a high standard of living (author's transl)].
The present work points out the variety of conditions favouring gallstone formation.--Recent research suggests that fibre-depleted, high-fat foods may lead to cholesterol gallstone formation in man. On the other side civilized diets contribute to the carcinogenesis of large bowel.--Experimental observations have indicated that hypovitaminosis C may favour pathogenesis of these diseases in a different way.


Two global haemostatic assays as additional tools to monitor treatment in cases of haemophilia A.
Haemophilia A patients with similar levels of factor VIII (FVIII) may have different bleeding phenotypes and responses to treatment with FVIII concentrate. Therefore, a test which determines overall haemostasis may be appropriate for treatment monitoring in some patients. We studied two global haemostatic methods:endogenous thrombin potential (ETP) and overall haemostatic potential(OHP) before and after injection of FVIII concentrate in patients with haemophilia A treated prophylactically and on-demand. A significant correlation between FVIII and both ETP and OHP was observed, while ETP and OHP differed between patients with severe and mild clinical phenotypes. Both ETP and OHP differed significantly between severe, moderate and mild haemophilia A and controls. ETP and OHP increased after intravenous injection of FVIII concentrate in both groups of patients, but in spite of higher pre-treatment values of both ETP and OHP in patients treated prophylactically, and much higher post-treatment FVIII levels in comparison with the values in patients treated on-demand, no difference after treatment was observed for either ETP or OHP. ETP and OHP may be additional alternatives for monitoring (and even for individual tailoring) treatment in patients with haemophilia A.


Arteriogenesis and Therapeutic Angiogenesis-An Update.
Vascular occlusive diseases such myocardial infarction, peripheral artery disease of the lower extremities, or stroke still represent a substantial health burden worldwide [...].


Polyethylene glycol plus ascorbic acid is as effective as sodium picosulfate with magnesium citrate for bowel preparation: A randomized trial.
This study was aimed to evaluate the efficacy and safety of two low-volume agents, polyethylene glycol (PEG)-3350 plus ascorbic acid (PEG + Asc) and sodium picosulfate with magnesium citrate (SPMC), for bowel preparation. We performed a prospective, endoscopist-blinded, single-center, randomized controlled trial comparing PEG + Asc with SPMC to evaluate the bowel cleansing efficacy of the two regimens using the modified Ottawa bowel preparation scale (OBPS) and the Aronchick scale. Patients' taste and overall tolerance were assessed with a questionnaire. In total, 200 patients were randomized to receive either PEG + Asc (n = 98) or SPMC (n = 102). Both treatments were similarly efficacious in bowel cleansing, based on the modified OBSP (PEG + Asc 4.01 ± 2.29 vs SPMC 3.86 ± 2.47, P = 0.62) and Aronchick scale (PEG + Asc 1.96 ± 0.70 vs SPMC 1.89 ± 0.70, P = 0.42). Patient-reported taste and tolerance of each regimen, as reported by the questionnaire, were significantly greater in the PEG + Asc group than in the SPMC group (P = 0.01). In terms of adverse events, dizziness was more frequently observed in the PEG + Asc group (P = 0.03), whereas nausea was more common in the SPMC group (P = 0.02). PEG + Asc and SPMC show similar efficacy for bowel preparation. However, patient's overall tolerance is higher in the PEG + Asc group.


The origin of plasma proteins in human amniotic fluid: the significance of alpha 1-antichymotrypsin complexes.
12 proteins were studied in serum and amniotic fluid from 20 women in late pregnancy by two-dimensional immunoelectrophoresis. A close inverse relationship was observed between the amniotic fluid/serum concentration ratios of 11 proteins and their Stokes radii. These proteins enter the liquor from the maternal blood by molecular filtration. The concentration of alpha 1-antichymotrypsin in amniotic fluid was often higher than expected and the protein was often partially complexed. alpha 1-Antichymotrypsin is probably not actively secreted into amniotic fluid but may be selectively retained after complexing.


Apparent physical brightness of graphemes is altered by their synaesthetic colour in grapheme-colour synaesthetes.
Grapheme-colour synaesthesia is a condition in which the visual perception of letters or numbers induces a specific colour sensation. In this study, we demonstrated that the apparent physical brightness of graphemes is modulated by the synaesthetic colours elicited by them. Synaesthetes first selected a synaesthetic colour corresponding to each capital letter and digit. Then, we selected a grapheme stimulus with a bright synaesthetic colour and one with a dark colour for each synaesthete. Finally, synaesthetes and non-synaesthete controls participated in a brightness judgment task, in which each participant judged the real brightness of each of the two stimuli compared to a standard stimulus. Compared to non-synaesthetes, synaesthetes judged a grapheme with a bright synaesthetic colour to be brighter than one with a dark synaesthetic colour, suggesting that the synaesthetic colour experience of synaesthetes alters their brightness perception. Such alteration in real brightness perception was observed both in those who experienced synaesthetic colours in external space (projector-type synaesthetes) and in those who experienced such colours 'in the mind's eye' (associator-type synaesthetes). These results support the view that early visual processing is modulated by feedback transmitted from the V4 colour area, the neural activation of which accompanies synaesthetic colour experience.


The physical treatment of upper limb edema.
Edema of the upper limb, without any doubt, constitutes the most invalidating complication of breast carcinoma treatment. The swelling of the limb results from decreased liquid evacuation by surgical intervention at the axillary level and also by the eventual treatment by cobaltotherapy. The physical treatment for edema of the limb consists of a combination of therapies that were tested for their effectiveness in laboratories on healthy students and also on patients who underwent surgery for breast carcinoma. The treatment consists of the application of manual lymphatic drainage (type Leduc), the use of multilayered bandages, and the use of intermittent pneumatic compression. The population studied was represented by 220 patients who underwent breast surgery. The authors followed their evolution during the first 2 weeks of treatment. Patients were not hospitalized. The edema was measured by using marks tattooed on the skin. The limb that developed edema was compared with the healthy limb. The most important reduction was obtained in the first week. The decrease was equivalent to 50% of the average of the difference between both upper limbs. During the second week, the results obtained stabilized; however, there was a slight decrease at the end of the second week. The physical treatment of edema represents the preferred therapeutic approach. However, it must answer to well-defined criteria to be efficient and for long-lasting effects. The physical treatment is used to treat outpatients, allowing them to follow a normal lifestyle.


Automatic microscopic diagnosis of diseases using an improved UNet++ architecture.
Anthrax is a severe infectious disease caused by the Bacillus anthracis bacterium. This paper aims to design and implement a fast and reliable system based on microscopic image processing of patient tissue samples for the automatic diagnosis of anthrax and other tissues diseases, metastasis detection, patient prognosis, etc. An improved UNet++ architecture is proposed to segment microscopic images of patient tissue samples. The proposed model combines multi-scale features by adding skip connections in two paths; the forward path from the encoder to the decoder and the decoder path to the output. These new connections improve the performance of the UNet++. Integration of the squeeze and excitation-inception blocks in the new skip connections provides the network with features at different scales with different kernel sizes. Several convolutional networks are used as the backbone to extract powerful representations in the encoder section. The use of batch normalization, dropout technique, and LRelu activation function in this model accelerates convergence and increases the generalization power of the model. To overcome the problem of data imbalance of different classes, a weighted hybrid loss function is proposed, which further improved segmentation efficiency. The semantic segmentation results are converted to the instance segmentation using the marker-based watershed algorithm. Experimental results show that despite many challenges of microscopic image analysis, the proposed model is a reliable system for the automatic diagnosis of anthrax and other tissues diseases. It produces better results than state-of-the-art architectures.


Profiling of 2'-O-Me in human rRNA reveals a subset of fractionally modified positions and provides evidence for ribosome heterogeneity.
Ribose methylation is one of the two most abundant modifications in human ribosomal RNA and is believed to be important for ribosome biogenesis, mRNA selectivity and translational fidelity. We have applied RiboMeth-seq to rRNA from HeLa cells for ribosome-wide, quantitative mapping of 2'-O-Me sites and obtained a comprehensive set of 106 sites, including two novel sites, and with plausible box C/D guide RNAs assigned to all but three sites. We find approximately two-thirds of the sites to be fully methylated and the remainder to be fractionally modified in support of ribosome heterogeneity at the level of RNA modifications. A comparison to HCT116 cells reveals similar 2'-O-Me profiles with distinct differences at several sites. This study constitutes the first comprehensive mapping of 2'-O-Me sites in human rRNA using a high throughput sequencing approach. It establishes the existence of a core of constitutively methylated positions and a subset of variable, potentially regulatory positions, and paves the way for experimental analyses of the role of variations in rRNA methylation under different physiological or pathological settings.


[Flea detection (Siphonaptera) in dogs at the intake area of the Magdeburg polyclinic for small house and zoo animals].
Two random investigations carried out in 1981/1982 established 203 fleas of 5 species in a sex incidence of 1:2.4 (60 males/143 females) on 48 dogs: Ctenocephalides felis occurred most frequently in an extent of infestation of 13 (1981) and 9 (1982) in 24 dogs with a population density of 1.1 to 1.9 specimens/animals, followed by C. canis with 8 (1981) and 11 (1982) from 24 dogs in a greater density of 2.3 to 5 per host. In this C. felis occurs more frequently in "town dogs": 15 identifications from Magdeburg and 3 from the county towns of Quedlinburg, Schönebeck and Burg as opposed to only 2 from country communities. Pulex irritans in an extent of infestation of 5 out of 24 dogs in 1982 reached a density of 5 per animal. The results confirm the fact that the range of species of fleas on dogs depends or the keeping conditions and the specific breed activity of the hosts.


Protective effects of an herbal formulation of Radix Astragali, Radix Codonopsis and Cortex Lycii on streptozotocin-induced apoptosis in pancreatic beta-cells: an implication for its treatment of diabetes mellitus.
Hyperglycemia is one of the main causes of oxidative stress in type 2 diabetes mellitus. During hyperglycemia, the increased level of various reducing sugars in the blood enhances the production of reactive oxygen species (ROS) and triggers tissue damage, especially in pancreatic beta-cells. Streptozotocin (STZ) is a diabetogen that causes diabetes mellitus via ROS-induced apoptosis in beta-cells. In this study, SR10, an herbal formulation consisting of the aqueous extracts of Radix Astragali, Radix Codonopsis and Cortex Lycii was examined for its antidiabetic effects in vitro. SR10 treatment resulted in significant enhancement of survival rate of rat pancreatic beta-cells which were treated by streptozotocin. SR10 apparently reduced apoptosis of streptozotocin-treated beta-cells by decreasing DNA fragmentation, sub-G(1) peak area and percentage of apoptotic cells. Nitric oxide (NO) production in streptozotocin-treated cells was inhibited by SR10 via the suppression of the expression of inducible nitric oxide synthase (iNOS). The implication of SR10 in treating type 2 diabetes mellitus was discussed.


Apoptosis of vasopressinergic hypothalamic neurons in chronic diabetes mellitus.
The hyperosmolality associated with diabetes mellitus triggers an increase in neuronal activity and vasopressin production within magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus (SON). In this study, we examined the effect of chronic diabetes on the function and survival of these neurons. After 6 months, but not 6 weeks, of streptozotocin (STZ)-induced diabetes, we observed an increase in the appearance of small hyperchromatic neurons and a decrease in SON neuronal density. A subpopulation of neurons within the SON at this time point demonstrated positive staining for cleaved caspase-3 and TUNEL, two markers of apoptosis. In addition, the number of vasopressin-positive neurons was decreased. Markers for apoptosis did not colocalize with vasopressin immunopositivity; this was probably due to a diabetes-induced degenerative process causing downregulation of vasopressin expression or depletion of neuropeptide. Although the phenotypes of the apoptotic neurons were not identified, other SON neurons including oxytocin-producing neurons are unlikely to be affected by chronic hyperglycemia. Microglial hypertrophy and condensation were also observed in the 6-month diabetic SON. Although upregulation of vasopressin production in response to acute hyperosmolality is adaptive, prolonged overstimulation of vasopressin-producing neurons in chronic diabetes results in neurodegeneration and apoptosis.


Design of phenothiazine-based cationic amphiphilic derivatives incorporating arginine residues: Potential membrane-active broad-spectrum antimicrobials combating pathogenic bacteria in vitro and in vivo.
Multidrug-resistant bacteria infections pose an increasingly serious threat to human health, and the development of antimicrobials is far from meeting the clinical demand. It is urgent to discover and develop novel antibiotics to combat bacterial resistance. Currently, the development of membrane active antimicrobial agents is an attractive strategy to cope with antimicrobial resistance issues. In this study, the synthesis and biological evaluation of cationic amphiphilic phenothiazine-based derivatives were reported. Among them, the most promising compound 30 bearing a n-heptyl group and two arginine residues displayed potent bactericidal activity against both Gram-positive (MICs = 1.56 μg/mL) and Gram-negative bacteria (MICs = 3.125-6.25 μg/mL). Compound 30 showed low hemolysis activity (HC50 = 281.4 ± 1.6 μg/mL) and low cytotoxicity (CC50 > 50 μg/mL) toward mammalian cells, as well as excellent salt resistance. Compound 30 rapidly killed bacteria by acting on the bacterial cell membrane and appeared less prone to resistance. Importantly, compound 30 showed potent in vivo efficacy in a murine model of bacterial keratitis. Hence, the results suggested compound 30 has a promising prospect as a broad-spectrum antibacterial agent for the treatment of drug-resistant bacterial infections.