Determination of amino acids by capillary electrophoresis with differential resonant contactless conductivity detector.
The impedance of a capacitively coupled contactless conductivity detector (C(4)D) in capillary electrophoresis (CE) was measured by an impedance analysis method. The influence of solution conductivity and capillary dimension on impedance parameters was investigated. Under the experimental conditions used, 86-99.9% of the total impedance of a C(4)D is composed by its imaginary part from the capillary wall capacitor. With increasing inner diameter of capillary and solution conductivity in detection zone, the wall capacitance increases, which results in the increase in the response signal of C(4)D. But the wall capacitance is only 0.5-12% of the predicted value according to a cylinder capacitor model. As the change in solution resistance is detected in a resonant C(4)D (RC(4)D), the sensitivity of contactless conductivity detection in CE is improved. The application of an end-to-end differential RC(4)D (DRC(4)D) system in CE was demonstrated in the determination of 10 amino acids. The running buffer consisted of 2M acetic acid and 0.1% hydroxyethylcellulose (pH 2.1). The limit of detection for amino acids is in the range of 0.1-0.4 μM. Under our experimental conditions, the sensitivity of DRC(4)D enhances by a factor of 15-29 as compared with C(4)D.


The effect of relaxation on the epitope mapping by saturation transfer difference NMR.
The effect of longitudinal relaxation of ligand protons on saturation transfer difference (STD) was investigated by using a known binding system, dihydrofolate reductase and trimethoprim. The results indicate that T1 relaxation of ligand protons has a severe interference on the epitope map derived from a STD measurement. When the T1s of individual ligand protons are distinctly different, STD experiments may not give an accurate epitope map for the ligand-target interactions. Measuring the relaxation times prior to mapping is strongly advised. A saturation time shorter than T1s is suggested for improving the potential epitope map. Reduction in temperature was seen to enhance the saturation efficiency in small to medium size targets.


Magnetic resonance imaging evaluation of articular disk position after orthognathic surgery with or without concomitant disk repositioning: a retrospective study.
The aim of this study was to compare the outcomes of 2 surgical treatment options: one for correction of class II malocclusion skeletal deformity and one for pre-existing temporomandibular joint (TMJ) disorders requiring orthognathic surgery (OS) for correction of dentofacial deformity. This retrospective study evaluated patients who underwent OS with maxillomandibular advancement (MMA) with or without concomitant TMJ surgery for articular disk repositioning (ADR). Patients were divided into 2 groups: group I (MMA) was treated with OS only (18 patients); and group II (MMA-ADR) was treated with OS and concomitant ADR (19 patients). The sample consisted of 74 TMJs (mean patient age 29.86 years). In group I, 38.5% of the disks that were originally in normal position became displaced after OS, and 33.3% of displaced disks with reduction became nonreducing after OS. In group II, 78.9% of disks exhibited normal position in the final evaluation, and 97.3% of patients showed improved disk position after surgery. There was significant symptom improvement in all patients in group II, but no significant improvement in group I. OS with ADR appears to produce stable and beneficial results in improving symptoms in patients with displaced disk and TMJ pain.


Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by a cerebral non-atherosclerotic, nonamyloid angiopathy mainly affecting the small arteries penetrating the white matter. In the brain vessels of two patients with CADASIL, abnormal patches of granular osmiophilic material have recently been described. Here we report the observation of similar granular osmiophilic material within the vessel walls of muscle and skin biopsies from a 54-year-old woman belonging to a CADASIL family, who suffered from subcortical dementia with leukoencephalopathy demonstrated on neuroimaging. Postmortem examination disclosed changes of the vessel walls in all the organs chiefly leading to cerebral lesions. Ultrastructural study showed destruction of the vascular smooth muscle cells (VSMC) and the granular osmiophilic material already found in muscle and skin biopsies in this patient. Both changes were found all along the arterial tree. The findings of this study indicate that CADASIL is a systemic vascular disease involving arterial VSMC and that the lesions are different in each organ and vessel wall, depending on their fine structure. Moreover, it emphasizes that skin and muscle biopsies might be useful for diagnosis of and research into CADASIL.


Beyond physiotherapy and pharmacological treatment for fibromyalgia syndrome: tailored tACS as a new therapeutic tool.
Fibromyalgia syndrome (FMS) is a complex pain disorder, characterized by diffuse pain and cognitive disturbances. Abnormal cortical oscillatory activity may be a promising biomarker, encouraging non-invasive neurostimulation techniques as a treatment. We aimed to modulate abnormal slow cortical oscillations by delivering transcranial alternating current stimulation (tACS) and physiotherapy to reduce pain and cognitive symptoms. This was a double-blinded, randomized, crossover trial conducted between February and September 2018 at the Rehabilitation Unit of a teaching Hospital (NCT03221413). Participants were randomly assigned to tACS or random noise stimulation (RNS), 5 days/week for 2 weeks followed by ad hoc physiotherapy. Clinical and cognitive assessments were performed at T0 (baseline), T1 (after stimulation), T2 (1 month after stimulation). Electroencephalogram (EEG) spectral topographies recorded from 15 participants confirmed slow-rhythm prevalence and provided tACS tailored stimulation parameters and electrode sites. Following tACS, EEG alpha1 ([8-10] Hz) activity increased at T1 (p = 0.024) compared to RNS, pain symptoms assessed by Visual Analog Scale decreased at T1 (T1 vs T0 p = 0.010), self-reported cognitive skills and neuropsychological scores improved both at T1 and T2 (Patient-Reported Outcomes in Cognitive Impairment, T0-T2, p = 0.024; Everyday memory questionnaire, T1 compared to RNS, p = 0.012; Montréal Cognitive Assessment, T0 vs T1, p = 0.048 and T0 vs T2, p = 0.009; Trail Making Test B T0-T2, p = 0.034). Psychopathological scales and other neuropsychological scores (Trail Making Test-A; Total Phonemic Fluency; Hopkins Verbal Learning Test-Revised; Rey-Osterrieth Complex Figure) improved both after tACS and RNS but earlier improvements (T1) were registered only after tACS. These results support tACS coupled with physiotherapy in treating FMS cognitive symptoms, pain and subclinical psychopathology.


Reduction of cephalic arteriovenous shunting by ergotamine is not mediated by 5-HT1-like or 5-HT2 receptors.
1. The potent, antimigraine drug ergotamine has affinity for both 5-HT1 and 5-HT2 binding sites and constricts arteriovenous anastomoses. Since 5-HT also constricts arteriovenous anastomoses (mainly via 5-HT1-like receptors), this study investigates the involvement of 5-HT receptors in the ergotamine-induced reduction of arteriovenous shunting in the carotid circulation of the cat and pig. 2. In the cat, ergotamine (3, 10 and 30 micrograms kg-1, i.v.) reduced carotid blood flow, predominantly by a reduction in arteriovenous anastomotic blood flow. Pretreatment with ketanserin (0.5 mg kg-1, i.v.) or methiothepin (1 mg kg-1, i.v.) did not antagonize the effects of ergotamine. 3. In the pig, ergotamine (2.5, 5, 10 and 20 micrograms kg-1, i.v.) also reduced carotid blood flow and arteriovenous shunting, which was not affected by pretreatment with methiothepin (1 mg kg-1, i.v.). 4. These results suggest that the reduction by ergotamine in the shunting of carotid arterial blood via cephalic arteriovenous anastomoses is not mediated by 5-HT1-like or 5-HT2 receptors.


Causality in complex interventions.
In this paper I look at causality in the context of intervention research, and discuss some problems faced in the evaluation of causal hypotheses via interventions. I draw attention to a simple problem for evaluations that employ randomized controlled trials. The common alternative to randomized trials, the observational study, is shown to face problems of a similar nature. I then argue that these problems become especially acute in cases where the intervention is complex (i.e. that involves intervening in a complex system). Finally, I consider and reject a possible resolution of the problem involving the simulation of complex interventions. The conclusion I draw from this is that we need to radically reframe the way we think about causal inference in complex intervention research.


Implementation of change: a wound assessment chart.
The implementation of change involves careful planning, particularly if it depends on the participation of others, such as the introduction of a new nursing tool. Those involved must be educated about the change so they can influence developments.


Frequency of infectious diseases in immigrants in a Western European country: a population-based study.
The aim of this population-based study was to assess the incidence rates of infectious diseases in native- (Italian) and foreign-born (immigrants) populations in a North Italy area, in 2006-2010. Crude, age-specific incidence rates (IRs) and age-standardised rate ratios (SRRs) between foreign- and native-born subjects and their 95% confidence intervals (95% CI) were estimated. A total of 32,554 cases of infectious diseases were found (9.9% in foreign-born subjects). The highest SRRs between foreign- and nativeborn subjects were found for tuberculosis (SRR = 27.1; 95% CI 21.3-34.3), malaria (SRR = 21.1; 14.6-30.4), scabies (SRR = 8.5; 7.6-9.4), AIDS (SRR = 2.5; 1.8-3.4) and viral hepatitis B (SRR = 3.3; 2.1-5.2). The highest IR was found for AIDS in people from the Americas (IR = 4.57; 95% CI 2.2-8.4), for malaria and tuberculosis in people from Africa (IR = 13.89; 11.6-16.5 and IR = 11.87; 9.8-14.3 respectively). Therefore immigrants are at a higher risk of acquiring some common infectious diseases compared to the native population in Western European countries.


A study of alkaline phosphatase isoenzyme electrophoresis on cellulose acetate compared with agar, agarose and acrylamide in the presence or absence of triton X-100.
The application of Triton X-100 in cellulose acetate electrophoresis and its effects on the separation of serum alkaline phosphatases is described. The cellulose acetate electrophoretic patterns of serum alkaline phosphatase found in liver and bone disease have been compared with the patterns found in agar, agarose, and polyacrylamide gel in the presence and absence of Triton X-100 and the differences described and discussed. Changes in the alkaline phosphatase electrophoretic pattern and the effects on certain electrophoretic variants have been noted following addition of Triton X-100 to all parts of the system.


Serum alpha fetoprotein heterogeneity as a means of differentiating between primary hepatocellular carcinoma and hepatic secondaries.
The concanavalin A binding characteristics of serum alpha-fetoprotein (AFP) were investigated in patients with primary hepatocellular carcinoma and hepatic secondaries using affinity column chromatography and radioimmunoassay. The primary hepatocellular carcinoma (n = 21) was associated with a median concanavalin A non-reactive AFP fraction of 7.4% (range 1.6 - 18.8) while the hepatic secondaries (n = 8) had a median concanavalin A non-reactive AFP fraction of 50.7% (range 26.6 - 91.7). A simple diagnostic test for differentiating between the two groups of patients is proposed.


What's new in in vitro studies of exocrine pancreatic cell injury?
Exocrine pancreas in vitro models are useful for the study of pancreatic differentiation, secretion mechanisms, cell injury, and lysosomal processing of secretory product. Syrian hamster pancreas in explant organ culture undergoes a series of morphologic changes which parallel in vitro acinar cell injury, differentiation, and phenotypic alteration. Within 48 hours, the cultured acinar cells show morphologic evidence of sublethal cell injury. Autophagy and crinophagy are particularly striking. The autophagic processes can be inhibited by the addition of the protein synthesis inhibitor cycloheximide or by culture at lowered temperatures (20 degrees C). Acinar cells lethally damaged show pyknotic nuclei, high amplitude swelling, and necrosis. Approximately 25% of each explant is viable after 72 hr in culture and the viability remains constant at 25-35% for up to 60 days of culture. The morphological changes of the explants are consistent with many of the features of pancreatitis and carcinoma of the exocrine pancreas. There is an increase in the ductal elements and a decrease in acini over time in culture. This may be due to: (a) an increased replication of ductal epithelial cells concomitant with necrosis of acinar epithelial cells and/or (b) phenotypic alteration of acinar cells to ductal cells. Acinar cell necrosis and phenotypic alterations may in part be due to the activation of lysosomal degradation pathways. Processes which inhibit lysosomal activation proved protective against these alterations, while processes which promote zymogen activation were deleterious.


Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis.
Both alarmins S100A8/A9 and canonical Wnt signaling have been found to play active roles in the development of experimental osteoarthritis (OA). However, what activates canonical Wnt signaling remains unknown. This study was undertaken to investigate whether S100A8 induces canonical Wnt signaling and whether S100 proteins exert their effects via activation of Wnt signaling. Expression of the genes for S100A8/A9 and Wnt signaling pathway members was measured in an experimental OA model. Selected Wnt signaling pathway members were overexpressed, and levels of S100A8/A9 were measured. Activation of canonical Wnt signaling was determined after injection of S100A8 into naive joints and induction of collagenase-induced OA in S100A9-deficient mice. Expression of Wnt signaling pathway members was tested in macrophages and fibroblasts after S100A8 stimulation. Canonical Wnt signaling was inhibited in vivo to determine if the effects of S100A8 injections were dependent on Wnt signaling. The alarmins S100A8/A9 and members of the Wnt signaling pathway showed coinciding expression in synovial tissue in an experimental OA model. Synovial overexpression of selected Wnt signaling pathway members did not result in increased expression of S100 proteins. In contrast, intraarticular injection of S100A8 increased canonical Wnt signaling, whereas canonical Wnt signaling was decreased after induction of experimental OA in S100A9-deficient mice. S100A8 stimulation of macrophages, but not fibroblasts, resulted in increased expression of canonical Wnt signaling members. Overexpression of Dkk-1 to inhibit canonical Wnt signaling decreased the induction of matrix metalloproteinase 3, interleukin-6, and macrophage inflammatory protein 1α after injection of S100A8. Our findings indicate that the alarmin S100A8 induces canonical Wnt signaling in macrophages and murine knee joints. The effects of S100A8 are partially dependent on activation of canonical Wnt signaling.


Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.
The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions.


Regulation of ANP-stimulated guanylate cyclase in the presence of Mn2+ in rat lung membranes.
The catalytic activity of guanylate cyclase (GCase) coupled to atrial natriuretic peptide (ANP) receptor depends on the metal co-factor, Mn2+ or Mg2+. ATP synergistically stimulates the ANP-stimulated GCase in the presence of Mg2+. We have now shown the ATP regulation of the ANP-stimulated GCase in the presence of Mn2+ in rat lung membranes. ANP stimulated the GCase 2.1-fold compared to the control. ATP enhanced both the basal (basal-GCase) and the ANP-stimulated GCase maximally 1.7- and 2.3- fold compared to the control, respectively, at a concentration of 0.1 mM. The stimulation by ATP was smaller in the presence of Mn2+ than in the presence of Mg2+. The addition of inorganic phosphate to the reaction mixture altered the GCase activities in the presence of Mn2+ with or without ANP and/or ATP. In the presence of 10 mM phosphate, ATP dose-dependently stimulated the basal GCase 5-fold compared to the control at a concentration of 1 mM and augmented the ANP-stimulated GCase, which was 4.2-fold compared to the basal-GCase, 5.5-fold compared to the control at a concentration of 0.5 mM. Protein phosphatase inhibitors, okadaic acid (100 nM), H8 (1 microM) and staurosporin (1 microM), did not alter the activity. Orthovanadate (1 mM), an inorganic phosphate analogue, significantly stimulated both the basal-GCase and the ANP-stimulated GCase, which were inhibited by ATP. It was assumed that phosphate and orthovanadate might interact with the GCase to regulate the activity in the opposite manner. This was the first report that inorganic phosphate and orthovanadate affected the ATP-regulation of the ANP-stimulated GCase in the presence of Mn2+.


Effect of light intensity of vesicle formation in chlorobium.
1. Chlorobium limicola forma sp. thiosulfatophilum was cultivated at 22 and 22000 lux. 2. The content of bchl d on a protein basis in the low light intensity cultures was about twice that of the high light intensity cultures; 3. After growth at 22 lux the red bchl d peak was at c. 743 nm, while at the higher intensity this peak was at c. 732 nm; 4. Electron microscopy of thin sections of Chlorobium revealed that vesicle size was greater at the low light intensity than at the high. 5. This was confirmed by sucrose density gradient centrifugation of differentially 14C-labelled vesicles from cultures grown at the two intensities. 6. The optimum temperature for growth was about 35 degrees C. Incubation at the optimum temperature was particularly beneficial at high light intensity.


Self-reported alcohol consumption among high school students in France. Epidemiological approach of the alcoholisation process and its evolution.
Very few data are available concerning alcohol consumption among adolescents in France. Three epidemiological surveys carried out by INSERM (Unit 185), focused on the evolution of drinking behaviour patterns among high school students. Consumption trends from 1971 to 1984 were studied: daily wine consumption fell by one-third between these periods; daily beer consumption remained steady; regular hard liquor use fell by about 50% between 1971 and 1978 but showed a marked increase thereafter. The experience of drunkeness increased very significantly among young people, especially among girls. It seems that alcohol consumption became of a more addictive type recently.


Health and economic impact of delaying large-scale HPV vaccination and screening implementation on cervical cancer in China: a modelling study.
Current uptake of HPV vaccination and screening in China is far below World Health Organization 2030 targets for cervical cancer elimination. We quantified health and economic losses of delaying large-scale HPV vaccination and screening implementation in China. We used a previously validated transmission model to project lifetime health benefits, costs, effectiveness, and timeline for cervical cancer elimination of alternative scenarios, including combining HPV vaccination initiated from 2022 to 2030 with screening in different modalities and coverage increase rates, as well as screening alone. All women living or projected to be born in China during 2022-2100 were considered. We employed a societal perspective. Regardless of vaccine type, immediate large-scale vaccination initiated in 2022 and achieving 70% coverage of HPV-based screening in 2030 (no-delay scenario) would be the least costly and most effective. Compared with the no-delay scenario, delaying vaccination by eight years would result in 434,000-543,000 additional cervical cancer cases, 138,000-178,000 deaths, and $2863-4437 million costs, and delay elimination by 9-10 years. Even with immediate vaccination, the gradual scale-up of LBC-based screening to 70% coverage in 2070 would result in 2,530,000-3,060,000 additional cases, 909,000-1,040,000 deaths, and $5098-5714 million costs compared with no-delay scenario, and could not achieve elimination if domestic 2vHPV or 4vHPV vaccines are used (4.09-4.21 cases per 100,000 woman in 2100). Delaying large-scale HPV vaccination and/or high-performance screening implementation has detrimental consequences for cervical cancer morbidity, mortality, and expenditure. These findings should spur health authorities to expedite large-scale vaccine rollout and improve screening. Bill & Melinda Gates Foundation (INV-031449 and INV-003174) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-004).


Structural basis for autoactivation of human Mst2 kinase and its regulation by RASSF5.
The tumor-suppressive Hippo pathway controls tissue homeostasis through balancing cell proliferation and apoptosis. Activation of the kinases Mst1 and Mst2 (Mst1/2) is a key upstream event in this pathway and remains poorly understood. Mst1/2 and their critical regulators RASSFs contain Salvador/RASSF1A/Hippo (SARAH) domains that can homo- and heterodimerize. Here, we report the crystal structures of human Mst2 alone and bound to RASSF5. Mst2 undergoes activation through transautophosphorylation at its activation loop, which requires SARAH-mediated homodimerization. RASSF5 disrupts Mst2 homodimer and blocks Mst2 autoactivation. Binding of RASSF5 to already activated Mst2, however, does not inhibit its kinase activity. Thus, RASSF5 can act as an inhibitor or a potential positive regulator of Mst2, depending on whether it binds to Mst2 before or after activation-loop phosphorylation. We propose that these temporally sensitive functions of RASSFs enable the Hippo pathway to respond to and integrate diverse cellular signals.


High-efficiency solar thermoelectric conversion enabled by movable charging of molten salts.
Solar energy as an abundant renewable resource has been investigated for many years. Solar thermoelectric conversion technology, which converts solar energy into thermal energy and then into electricity, has been developed and implemented in many important fields. The operation of solar-thermal-electric conversion systems, however, is strongly affected by the intermittency of solar radiation, which requires installation of thermal storage subsystems. In this work, we demonstrated a new solar-thermal-electric conversion system that consists of a thermoelectric converter and a rapidly charging thermal storage subsystem. A magnetic-responsive solar-thermal mesh was used as the movable charging source to convert incident concentrated sunlight into high-temperature heat, which can induce solid-to-liquid phase transition of molten salts. Driven by the external magnetic field, the solar-thermal mesh can move together with the receding solid-liquid interface thus rapidly storing the harvested solar-thermal energy within the molten salts. By connecting with a thermoelectric generator, the harvested solar-thermal energy can be further converted into electricity with a solar-thermal-electric energy conversion efficiency up to 2.56%, and the converted electrical energy can simultaneously light up more than 40 orange-colored LEDs. In addition to stable operation under sunlight, the charged thermal storage subsystem can release the stored heat and thus enables the solar-thermal-electric system to continuously generate electricity after removal of solar illumination.


The diversity and abundance of gut microbiota are associated with the pain sensation threshold in the Japanese population.
Small fibre neuropathy (SFN) is an initial pathology of diabetic polyneuropathy (DPN). Serum lipopolysaccharide binding protein levels are positively correlated with the pain threshold in the foot, suggesting that the abundance of gut Gram-negative bacilli, which are a source of lipopolysaccharides, may be involved in the development of DPN. Furthermore, the abundance of the gut and oral microbiota is assumed to be involved in the pathogenesis of diabetes. Nevertheless, the association between SFN and the microbiota has not been clarified. A total of 1056 individuals were recruited in the 2018 Iwaki Health Promotion Project. Pain sensation was evaluated based on the pain threshold from intraepidermal electrical stimulation (PINT). Patients with PINT scores <0.15 mA were categorized into the low-PINT group (n = 718); otherwise, they were categorized into the high-PINT group (n = 283). Furthermore, each group was divided into the subjects with or without glucose tolerance based on HbA1c levels, fasting blood glucose levels and diabetic history. Principal coordinate analysis and α- and β-diversity of the microbiota were evaluated. The correlation between clinical and microbiota data was examined. Oral microbiota diversity showed no structural differences according to PINT scores, whereas principal coordinate analysis and α- and β-diversity revealed significant structural differences in gut microbiota (p < 0.01, p < 0.05 and p < 0.05, respectively), even after the participants with glucose intolerance were excluded (p < 0.01, p < 0.05 and p < 0.05, respectively). The relative abundance of the genus Bacteroides was significantly lower in high-PINT participants compared with low-PINT participants (10 ± 6.7% vs. 11.3 ± 7.0%, p < 0.01), even after the exclusion of subjects with diabetes and impaired fasting glucose (10.0 ± 6.5% vs. 11.2 ± 6.9%, p < 0.05). In univariate linear regression analyses, PINT was significantly correlated with metabolic syndrome parameters, eGFR, uric acid level and the abundance of Bacteroides. The correlation between Bacteroides and PINT scores remained significant after adjustment for multiple factors (β = -0.07181, p < 0.05). Changes of bacterial diversity and a low abundance of gut Bacteroides were correlated with elevated PINT scores in the Japanese population. This correlation may represent a new therapeutic option for SFN.


Human neutrophil plasma membrane. Specific labelling, topological distribution of proteins and surface antigen detection.
We describe here the major protein components of a highly purified human neutrophil plasma membrane fraction analyzed by uni- and two-dimensional gel electrophoresis, as well as their glycoprotein nature as determined by PAS staining, [125I]-Con A binding and [3H]-sodium borohydride labelling. A polypeptide of about 150 kDa appeared as the main Con A binding protein. The topology of the polypeptides has also been determined by protein labelling from the outside of the cell surface by lactoperoxidase catalyzed iodination and from within the bilayer by using the hydrophobic reagent [125I]-iodonaphtylazide. The antigenic features of some cell surface polypeptides have also been determined by the use of monoclonal antibodies. In this context we have detected by immunoprecipitation in human neutrophils the antigen MAC 120, previously found in monocytes and putatively associated with antigen presenting function.


Effects of systemic morphine and epidural bupivacaine on postoperative oxygen consumption during rewarming.
The alterations in hemodynamics and oxygen consumption as a consequence of continuous epidural infusions of bupivacaine at room temperature and conventionally administered morphine were studied during recovery from general anesthesia for total hip replacement. Twenty-four patients were randomized to receive either bupivacaine or morphine in the recovery room. The bupivacaine group received from 6 to 12 ml per hour of 0.25% bupivacaine epidurally. Patients in the morphine group received 0.1 mg/kg of morphine intramuscularly no more frequently than every 4 hours. A pulmonary artery flotation catheter was inserted into each patient to determine hemodynamics and oxygen consumption at three instances: before analgesia, when pulmonary artery blood temperature reached 36 degrees C, and when it reached 37 degrees C. During the rewarming there was a decrease in mean arterial blood pressure and the systemic vascular resistance index and an increase in heart rate. The whole body oxygen consumption index increased in the bupivacaine group at the last measuring point but was stable in the morphine group. There was no effect on the arterial-venous oxygen content difference in either group. At 37 degrees C, the cardiac index and oxygen consumption index were significantly higher in the bupivacaine group than in the morphine group. In contrast to regional analgesia, systemic morphine administration can partially antagonize cardiovascular response to postoperative rewarming because it induces a stable oxygen demand.


A randomized controlled trial to explore the efficacy and safety of transcranial direct current stimulation on patients with post-stroke fatigue.
Post-stroke fatigue seriously affects the quality of life for stroke patients. There is no effective treatment at present. transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation which may have therapeutic effect on post-stroke fatigue. This study will explore about this. A total of 60 patients with post-stroke fatigue were randomly divided into the control group and the treatment group with 30 patients each by minimization randomization. Both groups received basic treatment and conventional rehabilitation. In the treatment group, patients were treated with active tDCS, while in the control group, sham tDCS. Both active and sham tDCS were administered 6 times a week for 4 weeks. Before and after the trial, the Fatigue Severity Scale (FSS), Fugl-Meyer Assessment (FMA) and Modified Barthel Index (MBI) were evaluated and analyzed. And comparisons were made among groups. And there were an 8-week follow-up after the intervention. Before the intervention, there were no significant differences in baseline data and assessment scores between the groups (P > 0.05). After 4 weeks of intervention, FSS scores in the treatment group were significantly lower than those in the control group (P = 0.012), and FMA and BMI scores were significantly higher than those in the control group (P < 0.05). There was no significant change in FSS scores after 8 months of follow-up (P > 0.05). TDCS is a safe treatment that can effectively reduce the degree of fatigue after stroke, improve the motor function and daily activity ability of patients after stroke, and the efficacy is better than only routine rehabilitation training. Chinese Clinical Trial Registry, ChiCTR2000031120. Registered on March 22, 2020.


Investigating the effect of electrosprayed alginate/PVA beads size on the microbial growth kinetics: Phenol biodegradation through immobilized activated sludge.
The presence of cyclic organic compounds, including phenol, in the wastewater of many industries has made phenol removal an important issue. Meanwhile, the biological methods of removing phenol have attracted the attention of researchers in recent years. Recently, the use of immobilized microbial cells is proposed as a new approach in industrial wastewater treatment. In this research, the aim is to study the effect of immobilized beads size on the phenol biodegradation efficiency and specific microbial growth rate. For this purpose, electrospray technique was used to immobilize activated sludge in hybrid matrix of alginate and polyvinyl alcohol (PVA). The fabricated alginate/PVA beads were characterized using Fourier transform infrared spectroscopy (FTIR). Evaluation of the results related to the free and immobilized cell systems in the shake flask experiments showed that at low phenol concentrations the immobilized cell system had the same performance as the free cell system, while the immobilized cell system at higher concentrations had a better performance in removing phenol so that at a concentration of 2000 mg/L, removal percentage has increased from 15% to 25-34%. On the other hand, in this survey, the kinetic behavior of activated sludge was in good agreement with Haldane's equation. Moreover, the maximum specific growth rate was measured 0.033 and 0.041 (h-1) beside 544 and 636 mg/L substrate inhibition constant, for free and immobilized cell systems, respectively. This result shows that the phenol biodegradation has been improved by using the cell immobilization technique especially with applying the smaller beads, which is due to improved mass transfer and microbial cell protection from harsh environments.


Effects of the bHLH domain on axial coordination of heme in the PAS-A domain of neuronal PAS domain protein 2 (NPAS2): conversion from His119/Cys170 coordination to His119/His171 coordination.
Neuronal PAS domain protein 2 (NPAS2), which is a CO-dependent transcription factor, consists of a basic helix-loop-helix domain (bHLH), and two heme-containing PAS domains (PAS-A and PAS-B). In our previous study on the isolated PAS-A domain, we concluded that His119 and Cys170 are the axial ligands of the ferric heme, while Cys170 is replaced by His171 upon reduction of heme (Uchida et al., J. Biol. Chem. 270, (2005) 21358-21368.). Recently, we characterized the PAS-A domain combined with the N-terminal bHLH domain, and found that some spectroscopic features were different from those of the isolated PAS-A domain (Mukaiyama et al., FEBS J. 273, (2006) 2528-2539.). Therefore, we reinvestigated the coordination structure of heme in the bHLH-PAS-A domain and prepared four histidine and one cysteine mutants. Resonance Raman spectrum of the Cys170Ala mutant is the same as that of wild type with a dominant 6-coordinate heme in the ferric form. In contrast, His119Ala and His171Ala mutants significantly increase amounts of the 5-coordinate species, indicating that His119 and His171, not Cys170, are axial ligands of the ferric heme in the bHLH-PAS-A domain. We had confirmed that the coordination structure of the isolated PAS-A domain is in equilibrium between Cys-Fe-His and His-Fe-His coordinated species but newly found that interaction of the PAS-A domain with the bHLH domain shifts the equilibrium toward the latter structure. Such flexibility in the heme coordination structure seems to be in favor of signal transduction in NPAS2.


Metformin ameliorates 5-fluorouracil-induced intestinalinjury by inhibiting cellular senescence, inflammation, and oxidative stress.
5-Fluorouracil (5-Fu), which inhibits metabolism, isanessentialpartof the first-line treatment of colorectal cancer but causes severe side effects, including nausea, vomiting, anorexia, and gastrointestinal injury with severe diarrhea, and requires dose reduction or treatment deferral, resulting in a poor prognosis. Metformin has anti-inflammatory effects, but its role in the mechanism of treatment in intestinal injury caused by 5-Fu remains unclear. In our present research, we assessed the impact of metformin on damagetotheintestinefrom5-Fuby inhibiting cellular senescence, intestinalcanal inflammation, and oxidative stress by using HUVECs, HIECs, and male BALB/c mice. It has been found that intestinal damage caused by 5-Fu is associated with the accumulation of senescent cells. Metformin relieved intestinaldamage by suppressing the activity of senescence-β-galactosidase (SA-β-gal) and the development of the senescence-associated secretory phenotype (SASP). Furthermore, we observed that the anti-aging effect was closely correlated with mTOR suppression in cell and mouse models. In conclusion, this is the first time that metformin has been able to reduce intestinaldamage related to chemotherapy by inhibiting cellular senescence and oxidative stress.


Extensive synthesis of poly[r(G-C)] using Escherichia coli RNA polymerase.
Conditions have been found that allow for extensive synthesis of poly[r(G-C)] using Escherichia coli RNA polymerase with a poly[d(I-C) X poly[d(I-C)] template. The extensive synthesis, in which many copies of the template were produced by the enzyme, continued for 24 h. Repeated addition of the template was necessary for synthesis to continue, as the poly[r(G-C)] appeared to be binding to the template, inhibiting transcription by the polymerase. Four hundred ODU, or 20 mg of the poly[r(G-C)] has been prepared using 0.3 mg of protein.


Interaction between cigarette smoke condensate and radiation for the induction of genotoxic effects in yeast.
Induction of gene conversion in diploid yeast strains BZ34 and D7 was investigated following exposure to cigarette smoke condensate (CSC) and gamma radiation. Cells treated with CSC for 1 h showed 5-10-fold increase in gene conversion over the background frequency. Log-phase cells were 2-3 times more sensitive compared to stationary-phase cells. Cells exposed to a combination of CSC and radiation suggested an additive response of the 2 agents, irrespective of the order of the 2 treatments.


Transmastoid Labyrinthectomy for Menière's Disease: Experience and Outcomes.
To characterize presurgical symptoms and treatment history and postoperative course in patients with medically recalcitrant Menière's disease undergoing transmastoid labyrinthectomy in the post-intratympanic gentamicin era. Retrospective case series. Tertiary academic medical center. All patients who underwent transmastoid labyrinthectomy for medically recalcitrant Menière's disease in 2003 to 2019 by the senior author. Review of patients' medical records for: preoperative history of drop attacks, gentamicin injections, endolymphatic sac decompression or vestibular neurectomy, preoperative audiograms, length of hospital stay, postoperative complications, and persistent symptoms or challenging recovery. Presurgical clinical history and proximal postoperative outcomes. Seventy-two patients with a mean age of 56.7 (standard deviation [SD] 10.7) were included. All cases were unilateral. Forty-three patients (59.7%) suffered from drop attacks. Sixty-two (86.1%) had failed sufficient symptom control with gentamicin injections. The mean preoperative word recognition score was 36.4% (SD 23.7) versus 95.1% (SD 8.5) in the contralateral ear. The mean pure-tone average (PTA) of the ipsilateral ear before surgery was 65.5 dB (SD 18.0) versus 16.2 (SD 13.5) for the contralateral ear. Mean hospital stay was 2.0 days (SD 0.87 days, range of 1-5 d). Three patients (4.2%) had prolonged postoperative vertigo. Transmastoid labyrinthectomy at our center is performed for unilateral Menière's disease, generally when intratympanic gentamicin has failed. A majority of surgical patients suffer from drop attacks preoperatively. Hospital stay is typically brief.


Aluminum recovery as a product with high added value using aluminum hazardous waste.
The samples of hazardous aluminum solid waste such as dross were physically and chemically characterized. A relationship between density, porosity and metal content of dross was established. The paper also examines the chemical reactions involving aluminum dross in landfill and the negative consequences. To avoid environmental problems and to recovery the aluminum, a processing method was developed and aluminum was recovered as an added value product such as alumina. This method refers to a process at low temperature, in more stages: acid leaching, purification, precipitation and calcination. At the end of this process aluminum was extracted, first as Al(3+) soluble ions and final as alumina product. The composition of the aluminum dross and alumina powder obtained were measured by applying the leaching tests, using atomic absorption spectrometry (AAS) and chemical analysis. The mineralogical composition of aluminum dross samples and alumina product were determined by X-ray diffraction (XRD) and the morphological characterization was performed by scanning electron microscopy (SEM). The method presented in this work allows the use of hazardous aluminum solid waste as raw material to recover an important fraction from soluble aluminum content as an added value product, alumina, with high grade purity (99.28%).


A randomized clinical trial of smartphone self-managed recovery support services.
This study examines the effectiveness of smartphone-based ecological momentary interventions (EMI) and assessments (EMA), delivered separately and combined, to provide recovery support following substance use disorder (SUD) treatment engagement. We recruited adults (N = 401) from SUD treatment programs in Chicago and, after engagement for at least two sessions, nights, or medication dosages, we randomly assigned them to one of four conditions that lasted 6 months: (1) EMI only, (2) EMA only, (3) both EMI and EMA, and (4) control condition of neither EMI nor EMA. EMIs provided support for recovery through applications on the phone or links to other resources; EMAs were delivered randomly 5 times per day asking participants to indicate recent substance use and situational risk and protective factors. The primary dependent variable was days of abstinence in the 6 months following study intake. Rates of EMI and EMA utilization indicated high compliance, although EMI use decreased over time. There was a small direct effect of time across conditions (F(2,734) = 4.33, p = .014, Cohen's f = 0.11) and a small direct effect of time-by-EMI use (F(2,734) = 4.85, p = .009, f = 0.11) on days of abstinence. There was no significant direct effect of time-by-EMAs nor interaction effect of time-by-EMI-by-EMA. However, secondary path model analyses showed a small but significant indirect effect of EMA on abstinence via EMI use. Stepwise modeling identified a simplified model based on the proportion of weeks using ≥1 EMI and the EMI to listen to music, which predicted 7.2% of the variance in days of abstinence (F(2,195,) = 7.56, p < .001). Combined delivery of EMI and EMA shows potential for increasing abstinence above and beyond the effect of SUD treatment engagement and for addressing the limited national capacity for recovery support.


[Analysis of zinc- and copper-containing tablets in multicomponent mineral nutritional preparations].
The aim of this study was to elaborate and optimize the working conditions for the identification and determination of zinc and copper present in the multicomponent mineral preparations Zinok Walmark and TrikrátSedem FeCuZn by a modern electrochemical analytical method--galvanostatic stripping chronopotentiometry, and a nuclear analytical method--X-ray fluorescence analysis. The proposed analytical methods were compared with each other and the obtained results concerning the quantity of determined elements were in good agreement.


Recovery of hematopoiesis after blood-group-incompatible bone marrow transplantation with red-blood-cell-depleted grafts.
Severe hemolytic transfusion reactions may complicate major blood-group-incompatible bone marrow transplantations (BMT). Probably the most appropriate way to avoid this complication is removal of the incompatible red blood cells (RBC) from the bone marrow graft. In this report we describe a method to eliminate incompatible RBCs that is based on repeated dilution of the graft with donor-and-recipient--compatible third-party erythrocytes. Four patients with ABO incompatibility and one patient with Rh-C incompatibility were transplanted using this technique. After the procedure 86 +/- 8% (mean +/- SD) of the nucleated cells, 95 +/- 14% of CFU-GM, 88 +/- 14% of BFU-e, and 103 +/- 30% of CFU-e were recovered, but only +/- 1% of the incompatible RBCs was left in the transfusate (1-3 ml). No signs of hemolysis were observed. All patients engrafted promptly. The patients with low titers of antibody had normal reticulocyte recoveries. Maturation of erythropoiesis was suppressed only when high titers of antibody were present. However, despite high antibody titers, erythroid progenitor cells (CFU-GEMM, BFU-e, and CFU-e) could be cultured from the bone marrow of the recipient after BMT. Thus, anti-A and anti-Rh-C antibodies give little, if any, inhibition of stem-cell proliferation. The method described to remove incompatible RBCs appears to be simple, safe, and--in most cases--sufficient.


Polarization diversity of human CD4+ stem cell memory T cells.
T cells are considered to develop through three stages, from naïve T (Tn) into central memory T (Tcm) and finally into effector memory T (Tem). Among the subsets of Tn, stem cell memory T (Tscm) were recently found to be the least developed memory subset. While this subset was revealed to possess self-reproducibility and multipotentiality, little is known about the relationship between development and polarity. We conducted transcriptome analysis of human CD4(+) T subsets and found that Tscm was a clearly distinct subset, located between Tn and Tcm. Surface antigen analysis and differentiation assay showed that the flexibility of polarity and the cytokine production progressively changed as the differentiation of CD4(+) T cells advanced. Interestingly, we found that most cells of the CD45RO(-)CCR7(+)CCR6(+) subset, hitherto considered the naïve precursor of Th17, were in fact Tscm. These findings may advance our understanding of the highly heterogeneous human helper T cells.


Systematic versus Endoscopy-driven Treatment with Azathioprine to Prevent Postoperative Ileal Crohn's Disease Recurrence.
Prophylactic azathioprine (AZA) is efficacious in preventing postoperative Crohn's disease (CD) recurrence. However, it is unknown whether AZA should be started immediately after surgery. We compared the efficacy of systematic vs endoscopy-driven AZA in preventing CD recurrence at week 102. This prospective, multicentre trial included CD patients undergoing curative resection with ileocolonic anastomosis and at higher risk of recurrence. Patients were randomized to systematic AZA initiated ≤2 weeks from surgery, or endoscopy-driven AZA in which therapy was only initiated in case of endoscopic recurrence (Rutgeerts' score ≥i2) at weeks 26 or 52 following surgery. The primary endpoint was endoscopic remission (i0-i1) at week 102. Secondary endpoints included complete endoscopic remission (i0) and clinical remission. The study was prematurely stopped due to slow recruitment. Between 2005 and 2011, 63 patients (28 male, median age 36 years) were randomized to systematic (n = 32) or endoscopy-driven AZA (n = 31). Twenty-one patients withdrew prematurely (8 clinical recurrence, 6 adverse reactions to AZA, 7 patient's preference). In the endoscopy-driven AZA group, 14 patients had to initiate AZA (11 at week 26, 3 at week 52). Endoscopic remission was achieved by 50% in the systematic and 42% in the endoscopy-driven AZA group (p = 0.521). No difference in secondary endpoints was found. Systematic AZA therapy in patients at higher risk of postoperative CD recurrence is not superior to endoscopy-driven treatment. Early postoperative endoscopic evaluation between weeks 26 and 52 seems most appropriate to guide further therapy, but larger studies are warranted. (ClinicalTrials.gov NCT02247258.).


The effects of the components of the renin-angiotensin system on the isolated perfused human placental cotyledon.
Angiotensins I, II, and III, renin substrate, and des-Asp1-angiotensin I were injected as a bolus into either the maternal or fetal circulation of human placental cotyledons perfused in vitro. All drugs tested produced dose-related increments in fetal perfusion pressure when injected into the fetal circulation, with the order of potency being angiotensin I approximately equal to angiotensin II approximately equal to angiotensin III greater than or equal to des-Asp1-angiotensin I greater than or equal to renin substrate. The responses to all the drugs could be blocked by the competitive inhibitor of angiotensin II, (Sar1, Ala8)-angiotensin II, but only the actions of angiotensin I, renin substrate, and des-Asp1-angiotensin I could be blocked by angiotensin converting enzyme inhibitor. When the agents were injected into the maternal circulation, only angiotensins II and III caused dose-related increments in fetal perfusion pressure. Possibly, the placenta may be the main site of conversion of angiotensin I to angiotensin II in the fetoplacental unit, and angiotensin II produced by the placenta could act locally to control fetoplacental blood flow.


An alternative solution for computer controlled tuning and matching of existing NMR probes.
Tuning and matching of NMR probes is necessary for many fields of NMR application including temperature dependent NMR, thermoporometry and cryoporometry, or when significantly different types of samples are measured in automation using sample changers. Mismatch of the probe is an especially critical issue in the case of high magnetic fields, polar or ionic solvents, or extreme thermal conditions. Careful tuning is particularly important for quantitative NMR measurements. Manual tuning and matching of the NMR probe is not possible in the case of automated or remotely controlled measurements. Spectrometer manufacturers offer modern probes equipped with automatic tuning/matching mechanics, like Bruker ATM™, suitable for these experiments. The disadvantages of probes with built-in ATM™ are the significantly higher price, and the non-detachable and non-portable construction. Computer controlled tuning and matching is highly desirrable in solid state NMR since no industrial solution has been developed yet for MAS NMR probes. We present an alternative solution for computer controlled tuning and matching of existing Bruker probes. Building costs are significantly lower, since only commercially available components and ICs are used.


Sub-lethal plasma ammonia accumulation and the exercise performance of salmonids.
The proposal that plasma ammonia accumulation might impair the swimming performance of fish was first made over a decade ago, and has now proven to be the case for a number of salmonid species. The first experimental evidence was indirect, when a negative linear relationship between plasma ammonia concentrations and maximum sustainable swimming speed (U(crit)) was found following the exposure of brown trout (Salmo trutta) to sub-lethal concentrations of copper in soft acidic water. Since then, negative linear relationships between plasma ammonia concentration and U(crit) have been demonstrated following exposure of brown trout, rainbow trout (Oncorhynchus mykiss) and coho salmon (Oncorhynchus kisutch) to elevated water ammonia. For brown trout, the relationships between plasma ammonia and U(crit) were remarkably similar following either exposure to elevated water ammonia or to sub-lethal copper. This indicates that the impairment of swimming performance resulting from exposure to sub-lethal concentrations of heavy metals may be attributable in large part to an accumulation of endogenous ammonia. The negative relationship between plasma ammonia concentration and U(crit) was similar in size-matched rainbow and brown trout but, under similar regimes of ammonia exposure, rainbow trout were able to maintain a significantly lower plasma ammonia concentration, revealing inter-specific differences in ammonia permeability and/or transport. One primary mechanism by which ammonia accumulation may impair exercise performance is a partial depolarisation of membrane potential in tissues such as the brain and white muscle. This may prejudice the co-ordination of swimming movements and reduce or abolish the development of muscle tension, thus, compromising swimming efficiency and performance at the top end of the range.


Radiation dermatitis caused by a bolus effect from an abdominal compression device.
American Association of Physicists in Medicine (AAPM) Task Group 176 evaluated the dosimetric effects caused by couch tops and immobilization devices. The report analyzed the extensive physics-based literature on couch tops, stereotactic body radiation therapy (SBRT) frames, and body immobilization bags, while noting the scarcity of clinical reports of skin toxicity because of external devices. Here, we present a clinical case report of grade 1 abdominal skin toxicity owing to an abdominal compression device. We discuss the dosimetric implications of the utilized treatment plan as well as post hoc alternative plans and quantify differences in attenuation and skin dose/build-up between the device, a lower-density alternative device, and an open field. The description of the case includes a 66-year-old male with HER2 amplified poorly differentiated distal esophageal adenocarcinoma treated with neoadjuvant chemo-radiation and the use of an abdominal compression device. Radiation was delivered using volumetric modulated arc therapy (VMAT) with 2 arcs using abdominal compression and image guidance. The total dose was 50.4Gy delivered over 40 elapsed days. With 2 fractions remaining, the patient developed dermatitis in the area of the compression device. The original treatment plan did not include a contour of the device. Alternative post hoc treatment plans were generated, one to contour the device and a second with anterior avoidance. In conclusion, replanning with the device contoured revealed the bolus effect. The skin dose increased from 27 to 36Gy. planned target volume (PTV) coverage at 45Gy was reduced to 76.5% from 95.8%. The second VMAT treatment plan with an anterior avoidance sector and more oblique beam angles maintained PTV coverage and spared the anterior wall, however at the expense of substantially increased dose to lung. This case report provides an important reminder of the bolus effect from external devices such as abdominal compression. Special consideration must be given to contour and/or avoiding beam entrance to the device, and to the use of such devices in patients who may have heightened radiosensitivity, such as those who are human immunodeficiency virus (HIV)-positive.


Detecting early changes in Alzheimer's disease with graph theory.
This scientific commentary refers to 'Single-subject grey matter network trajectories over the disease course of autosomal dominant Alzheimer disease', by Vermunt et al. (https://doi.org/10.1093/braincomms/fcaa102).


Status of percutaneous catheter drainage of abscesses.
The definitive role of catheter drainage in the therapy of abscesses has not yet been totally elucidated. The resolution rate of intra-abdominal infection with catheter drainage is highly variable, depending on the inclusion criteria employed. Certain infections are very effectively treated (i.e., abscesses that are single, not communicating with abdominal viscera, noncancerous, and bacterial) with simple catheter drainage, whereas others (i.e., infected pancreatic tumor phlegmon) prove to be much more resistant to simple catheter drainage. When all intra-abdominal "abscesses" are collected, the success of catheter drainage ranges from 47 per cent to 73 per cent. The wide variation should be seen not so much as a reflection of differences in technical ability of the radiologist to introduce a catheter, but rather as emblematic of the highly variable nature of the cause of intra-abdominal infection and the definition of an abscess. Hospitals with a large number of complex problems such as malignancy, transplant and other immunosuppressed patients, and referrals of patients with complex long-standing intra-abdominal infections are likely to have a much lower rate of success with percutaneously placed catheters than are those institutions that derive their series from post-traumatic or primary diseases such as appendiceal or diverticular disease. In the former series, a higher morbidity and mortality rate would be expected from any form of treatment when compared to a series from a practice based on more primary care problems. Intra-abdominal infections are a heterogeneous set of processes, and the role of interventional radiology in the diagnostic and therapeutic approach cannot be underestimated. In planning for the care of a patient with a presumed intra-abdominal infectious process, percutaneous aspiration of a fluid mass is an effective tool for establishing the diagnosis of an abscess. The brief introduction of a catheter has rarely led to contamination of an otherwise sterile collection. However, it often effects dramatic symptomatic relief if the fluid collection is infected. It has therefore been an evolving recommendation to employ the techniques of interventional radiology aggressively in a diagnostic capacity. Subsequently, therapeutic interventions can be undertaken in joint agreement among the physician, surgeon, and radiologist. The diagnosis and treatment of intra-abdominal infections can often times be carried out in a relatively easy and non-morbid manner that effects cure in a significant percentage of patients.(ABSTRACT TRUNCATED AT 400 WORDS)


Renoprotective mechanisms of sodium-glucose co-transporter 2 (SGLT2) inhibitors against the progression of diabetic kidney disease.
Sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) have emerged as a promising class of antidiabetic drugs with cardioprotective and renoprotective effects in patients with type 2 diabetes (T2D). The sodium-glucose co-transporters 1 and 2 (SGLT 1 and SGLT2) located in the renal proximal tubules are responsible for glucose reabsorption from the glomerular filtrate back into the systemic circulation. Inhibition of SGLT2, which accounts for about 90% of the glucose reabsorption, leads to a significant reduction in blood glucose levels and a concomitant increase in the urinary excretion of glucose (glycosuria). Multiple mechanisms contribute to the nephroprotective effects of SGLT2-Is in T2D patients. These include: (1) Restoration of the tubuloglomerular feedback by increasing sodium delivery at macula densa, leading to afferent arteriolar constriction and reduced glomerular hyperfiltration, (2) Decreased activation of the intra-renal renin-angiotensin-aldosterone system, which also contributes to reducing glomerular hyperfiltration, (3) Increased production of ketone bodies, which serves as an alternate fuel for adenosine triphosphate production in mitochondria, which helps in attenuating inflammation, and (4) Protection against hypoxia, oxidative stress, and fibrosis. This review elaborates on the key mechanisms that underlie the nephroprotective effects and the adverse effects of SGLT2-Is in T2D patients with progressive diabetic kidney disease.


Bladder cancer-associated transcript 1 promotes melanoma cell proliferation and invasion via the miR-374b-5p/U2-associated factor homology motif kinase 1 axis.
Melanoma is a malignancy derived from melanocytes and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been confirmed to be pivotal regulators in multiple types of cancer. Many lncRNAs are aberrantly expressed in tumors and perform vital functions in cancer progression. Nevertheless, the biological role of lncRNA bladder cancer-associated transcript 1 (BLACAT1) in melanoma progression remains unexplored. In this study, the collected data showed that BLACAT1 was highly expressed in melanoma. Mechanistically, miR-374b-5p bound to BLACAT1, and U2-associated factor homology motif kinase 1 (UHMK1) was a downstream target of miR-374b-5p. BLACAT1 upregulated UHMK1 expression by acting as a competing endogenous RNA for miR-374-5b. BLACAT1 deficiency resulted in the upregulation of miR-374b-5p expression and the downregulation of UHMK1 expression in melanoma cells. Moreover, BLACAT1 activated PI3K and AKT signaling by upregulating UHMK1 expression, as shown by western blotting analyses. Functionally, UHMK1 overexpression or miR-374b-5p knockdown reversed the suppressive effect of BLACAT1 depletion on melanoma cell proliferation and invasion. In conclusion, BLACAT1 promotes melanoma cell proliferation and invasion by upregulating UHMK1 expression via miR-374b-5p to activate the PI3K/AKT pathway. These results might provide promising insight into the investigation of prognostic biomarkers of melanoma.


Urinary androgen metabolites and recurrence rates in early breast cancer.
Androsterone and aetiocholanolone were measured in urine specimens obtained from 218 women with early breast cancer. Patients who excreted less than the median amount of these steroids had a significantly higher recurrence rate (P less than 0.005) than patients excreting more than the median value. The relationship between androgen excretion and recurrence is stronger in pre-menopausal women that in the post-menopausal group. The androgen assays are still associated with recurrence rates when patients are stratified by pathological stage, but no clear relationship was found with histological grade.


De-Implementation of Low-Value Care for Women 70 Years of Age or Older with Low-Risk Breast Cancer During the COVID-19 Pandemic.
Older women with early-stage estrogen receptor-positive (ER+) invasive breast cancer (IBC) are at risk for overtreatment. Guidelines allow for sentinel lymph node biopsy (SLNB) and radiotherapy omission after breast-conserving surgery (BCS) for women 70 years of age or older with T1, clinical node negativity (cN0), and ER+ IBC. The study objective was to evaluate radiotherapy and SLNB de-implementation in older women with low-risk IBC after the resource limitations of the COVID-19 pandemic. An institutional database was analyzed to identify women 70 years of age or older who received BCS for IBC from 2012 to 2022. The patients were divided into two cohorts: (1) patients with low-risk IBC (pT1, cN0, and ER+/HER2-) who were eligible for radiotherapy and SLNB omission and (2) patients with high-risk IBC (pT2-T4, cN+, ER-, or HER2+) who were ineligible for therapy omission. Clinicopathologic variables in both cohorts were analyzed. The study enrolled 881 patients. For the patients with low-risk IBC, the annual rates of radiotherapy were stable from 2012 to 2019. However, radiotherapy utilization decreased significantly from 2020 to 2022 (58% in 2012 vs 36% in 2022; p = 0.04). In contrast, radiotherapy usage among the patients with high-risk IBC was stable from 2012 to 2022 (79% in 2012 vs 79% in 2022; p = 0.95). Among the patients with low-risk IBC, SLNB rates decreased from 86% in 2012 to 56% in 2022, but this trend predated those in 2020. The factors significantly associated with SLNB and receipt of radiotherapy among the patients with low-risk IBC were younger age, larger tumors, grade 3 disease, and involved nodal status (p < 0.01). This study demonstrated appropriate and sustained de-escalation of radiotherapy in older women with low-risk IBC after the COVID-19 pandemic.


Gender-specific expression of liver organic anion transporters in rat.
Sex differences in drug pharmacokinetics have been well recognized and gender has been considered a risk factor for adverse events to medications. The aim of this study was to investigate the effect of gender on the expression of hepatocellular transport proteins involved in uptake and secretion of organic anions in rat. Expression of the rat liver organic anion transporting polypeptides (Oatps) and multidrug resistance proteins (Mrps) was analysed by reverse transcription polymerase chain reaction (RT-PCR), immunoblot analysis and immunofluorescence microscopy in male and female rats. Regulation of these transport proteins in response to the steroid dehydroepiandrosterone (DHEA) was investigated. In untreated rats, protein expression significantly differed between genders being higher (Mrp2, Mrp3), comparable [Oatp1a1 (Oatp1); Oatp1b2 (Oatp4)] or lower [Oatp1a4 (Oatp2)] in female than in male rat. DHEA treatment over 3 days (100 mg d(-1)) led to a further increase in Mrp3 expression only in female rats. Mrp2 expression was not influenced by DHEA treatment. Oatp1a1 and Oatp1b2 were significantly down-regulated after DHEA treatment in both male and female rats. In contrast, Oatp1a4 was down-regulated in male rats only. In rat, liver transport proteins of the Oatp and Mrp family are expressed and regulated in a gender-specific manner according to sexual differences in the hepatic metabolism of steroids and drugs. These findings may partly explain the well-known sex differences in hepatic handling of organic anions.


Scorpion venom exhibits adjuvant effect by eliciting HBsAg-specific Th1 immunity through neuro-endocrine interactions.
The Hottentotta rugiscutis scorpion venom (Hrv) contains neurotoxins, which elicit a strong innate immune response through the activation of the Hypothalamus-pituitary-adrenal axis, which could improve the quality of adaptive immunity. Hence, the Hrv was used as an adjuvant for the Hepatitis-B virus surface antigen (HBsAg) and assessed its ability in the activation of innate (NGF, CORT, cellularity, NO) and adaptive (IgM, IgG, IgG1/IgG2a/IgG2b/IgG3, Th1/Th2 cytokines, avidity) immunity. Here, the Hrv and HBsAg were given in the mixed form (HBsAg-Hrv) as well as in a separate form (HBsAg+Hrv). The NGF levels in plasma/spleen and CORT in plasma were found to be elevated optimally at 5 h and 6 h post-Hrv injection, respectively. Further studies showed that CORT and NGF levels were also highly upregulated in the HBsAg-Hrv group. The HBsAg-specific IgM titer was found to be increased in the HBsAg+Hrv group and total IgG was relatively similar among alum and Hrv-test groups, but IgG2a/IgG2b/IgG3 levels were higher along with IL-1β in HBsAg-Hrv groups. The study showed that the venom from H. rugiscutis acts as a vaccine adjuvant for HBsAg to develop strong antigen-specific Th1 immunity. The Hrv also enhances the antibody-avidity which may improve the neutralizing ability of antibodies with systemic infectious agents. The study also elucidated that the venom acts by neuroendocrine-immune mechanism and majorly impacts splenocytes through NGF and corticosterone.


Isoform B of myosin II heavy chain mediates actomyosin contractility during TNFalpha-induced apoptosis.
Cells that are treated long-term with TNFalpha or short-term with TGFalpha together with cycloheximide (CHX) undergo apoptosis. Cell shrinkage and detachment during apoptosis is dependent on actomyosin contractility. Myosin II heavy chain (MHCII) isoforms have shared and distinct functions. Here, we investigated whether the involvement of MHCII isoforms A and B (MHCIIA and MHCIIB, respectively) in cell shrinkage and detachment differs during apoptosis. We show that TNFalpha induces caspase-dependent MHCIIA degradation, whereas MHCIIB levels and association with the cytoskeleton remained virtually unchanged in TtT/GF cells and NIH 3T3 fibroblasts. MHCIIA proteolysis also occurred in fibroblasts that lack MHCIIB when treated with TNFalpha and CHX together. The absence of MHCIIB did not affect cell death rate. However, MHCIIB-/- cells showed more resistance to TNFalpha-induced actin disassembly, cell shrinkage and detachment than wild-type fibroblasts, indicating the participation of MHCIIB in these events. Moreover, inhibition of atypical PKCzeta, which targets MHCIIB but not MHCIIA, blocked TNFalpha-induced shrinkage and detachment in TtT/GF cells and wild-type fibroblasts, but the inhibitory effect was significantly reduced in MHCIIB-/- fibroblasts. TNFalpha treatment increased cytoskeleton-associated myosin light chain (MLC) phosphorylation but did not induce actin cleavage. In conclusion, our results demonstrate that MHCIIB, together with MLC phosphorylation and actin, constitute the actomyosin cytoskeleton that mediates contractility during apoptosis.


[Sarcoid febrile hepatic granulomatosis. Description of a case associated with initial liver cirrhosis].
A case of febrile hepatic granulomatosis was examined and the many aetiologies to be considered in the differential diagnosis of the condition evaluated. This is not a separate disease but a specific histological peculiarity of the liver. The case in question was diagnosed as hepatic granulomatosis originating in sarcoidosis. This diagnosis requires, it is though, the presence of characteristic granulomas in the liver biopsy sample but more important in the Kweim reaction or preferably in more specific tissue biopsies (spleen, lymph nodes, mesentery). In the present case the histologically revealed initial cirrhosis may be purely concomitant though certain authorities believe that sarcoidotic hepatic granulomas may develop into cirrhosis.


Association of dynamic change of triglyceride-glucose index during hospital stay with all-cause mortality in critically ill patients: a retrospective cohort study from MIMIC IV2.0.
Biomarker of insulin resistance, namely triglyceride-glucose index, is potentially useful in identifying critically ill patients at high risk of hospital death. However, the TyG index might have variations over time during ICU stay. Hence, the purpose of the current research was to verify the associations between the dynamic change of the TyG index during the hospital stay and all-cause mortality. The present retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV) critical care dataset, which included data from 8835 patients with 13,674 TyG measurements. The primary endpoint was 1-year all-cause mortality. Secondary outcomes included in-hospital all-cause mortality, the need for mechanical ventilation during hospitalization, length of stay in the hospital. Cumulative curves were calculated using the Kaplan-Meier method. Propensity score matching was performed to reduce any potential baseline bias. Restricted cubic spline analysis was also employed to assess any potential non-linear associations. Cox proportional hazards analyses were performed to examine the association between the dynamic change of TyG index and mortality. The follow-up period identified a total of 3010 all-cause deaths (35.87%), of which 2477 (29.52%) occurred within the first year. The cumulative incidence of all-cause death increased with a higher quartile of the TyGVR, while there were no differences in the TyG index. Restricted cubic spline analysis revealed a nearly linear association between TyGVR and the risk of in-hospital all-cause mortality (P for non-linear = 0.449, P for overall = 0.004) as well as 1-year all-cause mortality (P for non-linear = 0.909, P for overall = 0.019). The area under the curve of all-cause mortality by various conventional severity of illness scores significantly improved with the addition of the TyG index and TyGVR. The results were basically consistent in subgroup analysis. Dynamic change of TyG during hospital stay is associated with in-hospital and 1-year all-cause mortality, and may be superior to the effect of baseline TyG index.


Pilomatricoma in childhood: a retrospective study from three European paediatric centres.
Pilomatricoma is characterised as a common, slowly growing benign cutaneous tumour that appears generally within the first decades of life. The clinical diagnosis is frequently missed, especially by the paediatrician unfamiliar with these tumours. We present the experience gained in three European tertiary care paediatric centres with the treatment of pilomatricoma and also current data on the aetiology, clinical presentation and management. A retrospective study was carried out in 83 patients suspected for pilomatricoma during a 7-year period (1996-2002) at the departments of Paediatric Surgery of the Children's University Hospital "Federico II", Naples, Hospital "San Bortolo", Vicenza and "Aghia Sophia" Children's Hospital, Athens. The age range was from 10 months to 17 years, median age 8 years. All patients were treated by surgical excision and all specimens were examined by histopathological assessment. The follow-up varied from 5 months to 6 years. The correct diagnosis was made preoperatively in 68 patients (82%). The female/male ratio was 2:1. The sites of occurrence were the head (47.5%), especially in the periorbital region, the neck (9%), the upper limbs (35.5%), the inferior limbs (4%) and the thorax (4%). Each patient exhibited a single pilomatricoma except for two patients who had multiple lesions (2.4%). One of them had Steinert disease (myotonic dystrophy). No recurrences were observed during the follow-up period. Pilomatricoma is one of the most common cutaneous adnexal neoplasms in children. Surgical excision including clear margins and its overlying skin in most cases is the treatment of choice. The recurrence as well as malignant evolution is rare.


Association of FokI polymorphism of vitamin D receptor with urothelial bladder cancer in Tunisians: role of tobacco smoking and plasma vitamin D concentration.
The aim of the study was to test whether the VDR FokI polymorphism is associated with the risk of urothelial bladder cancer (UBC) in Tunisians. The study included 200 unrelated patients with UBC and 200 healthy controls. Genotyping of the VDR FokI polymorphism was determined by PCR-RFLP method. Plasma 25-hydroxyvitamin D concentrations were measured by immunoassay. Binary logistic regression model was applied to test how the association of VDR FokI polymorphism is independent of potential confounding factors. Genotype distribution (FF, 45 vs. 55 %; Ff, 52.1 vs. 47.9 %, and ff, 12 vs. 5.5 %, respectively) and allele frequencies (F, 66.5 vs. 74.8 % and f, 33.5 vs. 25.2 %, respectively) were significantly different between UBC patients and controls. The "ff" genotype [OR (95 % CI), 2.66 (1.24-5.73); p = 0.012] and "f" allele [1.49 (1.09-2.02); p = 0.010] were associated with increased risk of UBC. The association remained significant in multivariate analysis. Stratified analyses showed that VDR FokI polymorphism is only associated with UBC risk in ever-smokers, subjects exposed to chemical carcinogens and those with plasma 25-hydroxyvitamin D over 12 μg/L. The "f" allele of VDR FokI polymorphism is associated with a higher risk of UBC in Tunisians, especially in smokers as well as subjects with occupational exposition and subjects without vitamin D deficiency. These results should be replicated in other ethnic groups and the influence of other genetic factors and environments on this association should be investigated.


The impact of violence reduction initiatives on emergency department attendance.
Recent violence reduction initiatives in Glasgow have led to a reduction in recorded levels of violent crime.(1) This study evaluates the impact of these initiatives on assault-related emergency department attendances and admissions. A retrospective observational study conducted in Glasgow Royal Infirmary's emergency department comparing assault-related emergency department attendances and hospital admissions over two 30-day study periods (April 2010 and April 2012). The primary outcome measure was the change in assault-related emergency department attendances. The secondary outcome measure was the impact on assault-related hospital and critical care admissions. In April 2010, there were 6098 emergency department attendances, 301 (4.9%) were due to assault. In April 2012, there were 7236 emergency department attendances, 263 (3.6%) were due to assault, representing a significant reduction in assault-related attendances (p < 0.01). There were significant reductions in level 1 admissions 2010 n = 56 (19.2%), 2012 n = 36 (14.0%) p = 0.04 and critical care admissions, 2010 n = 5 (1.7%), 2012 n = 1 (0.4%) p = 0.04. Violence reduction initiatives in Glasgow have contributed to a reduction in assault-related emergency department attendance at Glasgow Royal Infirmary. The reduction in hospital admissions, in particular critical care admissions, suggests a reduction in morbidity and cost to the National Health Service.


Magnesium incorporation in fibrinogen scaffolds promotes macrophage polarization towards M2 phenotype.
The host inflammatory response to biomaterials conditions their capacity to promote tissue repair, and macrophage polarization shift from M1 to M2 is determinant in this process. Previous work showed that extracts of a combination between fibrinogen and metallic magnesium materials acted synergistically to reduce macrophage inflammatory phenotype. The hypothesis underlying the current work was that the ability of magnesium-modified fibrinogen scaffolds to modulate macrophage phenotype depends on the concentration of magnesium. Thus, Fibrinogen (Fg) scaffolds incorporating precise concentrations of magnesium sulfate (Mg: 0, 10, 25, 50 mM) were developed and characterized. Mg incorporation in Fg scaffolds increased surface charge, while porosity decreased with increasing Mg concentrations, but only Fg scaffolds with 10 mM of Mg (FgMg10) had significantly improved mechanical properties. Human macrophages cultured on FgMg10 scaffolds, showed increased M2 and decreased M1 polarization, when compared to those cultured on scaffolds with 0, 25 and 50 mM of Mg. Macrophage polarization results were independent of the anion used (chloride or sulfate). Macrophage modulation by FgMg10 scaffolds involved reduced NF-κB p65 nuclear translocation, and impacted production of pro-inflammatory mediators (e.g. IFNγ, IL-12, TNF-⍺, IP-10). Importantly, FgMg10 scaffolds implanted in vivo increased the expression of M2 marker CD163, in macrophages from inflammatory exudates, compared to Sham and Fg-implanted animals, increasing the M2:M1 ratio. A cytokine/chemokine array showed that, while both Fg and FgMg10 scaffolds decreased inflammatory mediators, only FgMg10 decreased IL-1β, IP-10, MIP-2, MDC and MIP-3⍺, compared to Sham-operated animals. This study demonstrated that incorporation of 10mM of Mg modulated inflammation, promoting M2 macrophage polarization in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Developing biomaterials that can modulate inflammation and promote macrophage phenotype switch from M1 to M2 is crucial to promote a regenerative microenvironment. Our previous work showed that extracts of a combination between fibrinogen (Fg) and metallic magnesium (Mg) materials synergistically reduced macrophage pro-inflammatory phenotype. Herein, we tested the hypothesis that macrophage modulation was dependent on Mg concentration. A new family of Fg porous scaffolds incorporating different amounts of Mg (0, 10, 25 and 50 mM) was produced and characterized. We observed that only the combination of Fg scaffolds with 10 mM of Mg (FgMg10) significantly changed the scaffolds mechanical properties and directed macrophages towards a M2 phenotype, reducing the production of inflammatory mediators, both in vitro and in vivo.


Glassy dynamics of polymers confined to nanoporous glasses revealed by relaxational and scattering experiments.
The glassy dynamics of poly(propylene glycol) (PPG) and poly(dimethyl siloxane) (PDMS) confined to a nanoporous host system revealed by dielectric spectroscopy, temperature-modulated DSC and neutron scattering is compared. For both systems the relaxation rates estimated from dielectric spectroscopy and temperature-modulated DSC agree quantitatively indicating that both experiments sense the glass transition. For PPG the segmental dynamics is determined by a counterbalance of adsorption and confinement effect. The former results form an interaction of the confined macromolecules with the internal surfaces. A confinement effect originates from an inherent length scale on which the underlying molecular motions take place. The increment of the specific-heat capacity [Formula: see text] at the glass transition vanishes at a finite length scale of 1.8 nm. Both results support the conception that a characteristic length scale is relevant for glassy dynamics. For PDMS only a confinement effect is observed which is much stronger than that for PPG. Down to a pore size of 7.5 nm, the temperature dependence of the relaxation times follows the Vogel-Fulcher-Tammann dependence. At a pore size of 5 nm this changes to an Arrhenius-like behaviour with a low activation energy. At the same pore size [Formula: see text] vanishes for PDMS. Quasielastic neutron scattering experiments reveal that also the diffusive character of the relevant molecular motions --found to be characteristic above the glass transition-- seems to disappear at this length scale. These results gives further strong support that the glass transition has to be characterised by an inherent length scale of the relevant molecular motions.


Clinical signs and symptoms are not enough for the correct diagnosis of allergic conjunctivitis.
Allergic Conjunctivitis (AC) has a high incidence in the general population and sometimes it is difficult to make a correct diagnosis, distinguish among the different subtypes of AC, and therefore, to indicate the suitable therapy. To determine the best way to carry out an appropriate diagnosis of AC. Thirty-one patients with clinical manifestations of AC and eleven controls were studied by measuring allergic and immunologic parameters. Only those patients confirmed as having AC were treated with ketotifen fumarate and further evaluated. According to allergic and immunological parameters, patients were divided into two groups. Group I patients had positive prick test toward at least one allergen, 60% exhibited high levels of tear-IgE, and only 36% conjunctival eosinophils. By contrast, patients from Group II had negative prick tests and laboratory findings similar to the control group. In group I there was a good correlation between levels of tear-IgE and eosinophils (r = 0.55; p = 0.009); key symptoms and signs and prick test (r = 0.52; p = 0.015), and prick test and eosinophils (r = 0.50 p = 0.022). The cardinal signs and symptoms scores dropped significantly in Group I as a consequence of the treatment (p < 0.0001). In order to have a reliable AC diagnosis, allergen-skin prick test, IgE in tears, and conjunctival eosinophils must be studied. Serum IgE is less important.


Effects of eccentric-emphasized leg curl intervention on muscle strength imbalance markers in professional soccer players during pre-season.
The effects of strength training on muscle strength imbalance are unclear in professional soccer players. As a result, this study examined the effects of an 8-week strength training program comprising eccentric-emphasized prone leg curl adjusted according to the individual strength imbalance status. Ten professional soccer players (26.0 ± 3.6 yrs) participated in the study. Players who had a ≥ 10% contralateral imbalance in knee flexors eccentric peak torque (n = 6) performed two additional repetitions per set in the low-strength limb (high-volume, HV) compared to the high-strength limb (low-volume, LV). Isokinetic concentric knee extension and concentric and eccentric knee flexion peak torque (PT) and derived contralateral imbalances and conventional and functional hamstring-to-quadriceps ratios (H:Q) were assessed at baseline and after 8 weeks. Differences at baseline were assessed using paired-sample T-tests, and a two-way (limb x time) repeated measures analysis of covariance (ANCOVA) for changes over time. A significant improvement in the eccentric knee flexion PT was observed in both limbs after 8 weeks (P < 0.05), with greater effects observed in the HV limb (25.0 N m, 95% CI: 15.1-34.9 N m). Significant decreases were also observed in the contralateral imbalances from concentric knee extension and flexion and eccentric knee flexion PT (P < 0.05). Differences were not observed in concentric knee extension and flexion PT (P > 0.05). A short-term eccentric-emphasized leg curl intervention adjusted by the initial knee flexors eccentric strength was an efficient method to improve knee flexors strength imbalance in professional soccer players.


Diketopyrrolopyrrole-based Conjugated Polymers Bearing Branched Oligo(Ethylene Glycol) Side Chains for Photovoltaic Devices.
Conjugated polymers are essential for solution-processable organic opto-electronic devices. In contrast to the great efforts on developing new conjugated polymer backbones, research on developing side chains is rare. Herein, we report branched oligo(ethylene glycol) (OEG) as side chains of conjugated polymers. Compared with typical alkyl side chains, branched OEG side chains endowed the resulting conjugated polymers with a smaller π-π stacking distance, higher hole mobility, smaller optical band gap, higher dielectric constant, and larger surface energy. Moreover, the conjugated polymers with branched OEG side chains exhibited outstanding photovoltaic performance in polymer solar cells. A power conversion efficiency of 5.37 % with near-infrared photoresponse was demonstrated and the device performance could be insensitive to the active layer thickness.


Research on the alternatives in a strategic environmental assessment based on the extension theory.
The main purpose of a strategic environmental assessment (SEA) is to facilitate the early consideration of potential environmental impacts in decision-making processes. SEA alternative identification is a core issue within the SEA framework. However, the current methods of SEA alternative formulation and selection are constrained by the limited setting range and lack of scientific evaluation. Thus, the current paper attempts to provide a new methodology based on the extension theory to identify a range of alternatives and screen the best one. Extension planning is applied to formulate a set of alternatives that satisfy the reasonable interests of the stakeholders. Extension priority evaluation is used to assess and optimize the alternatives and present a scientific methodology for the SEA alternative study. Thereafter, the urban traffic plan of Dalian City is used as an example to demonstrate the feasibility of the new method. The traffic planning scheme and the environmental protection scheme are organically combined based on the extension theory, and the reliability and practicality of this approach are examined.


Functional dissection of a Rice Dr1/DrAp1 transcriptional repression complex.
We characterized rice cDNA sequences for OsDr1 and OsDrAp1, which encode structural homologs of the eukaryotic general repressors Dr1 and DrAp1, respectively. OsDr1 and OsDrAp1 are nuclear proteins that interact with each other and with the TATA binding protein/DNA complex. In vitro and in vivo functional analyses showed that OsDrAp1 functions as a repressor, unlike its role in other eukaryotic systems, in which DrAp1 is a corepressor. OsDr1 and OsDrAp1 functioned together as a much stronger repressor than either one alone. Functional dissections revealed that the N-terminal histone-fold domains of OsDr1 and OsDrAp1 were necessary and sufficient for their repression and protein-protein interaction with each other. The unique glutamine- and proline-rich domain of OsDr1 had no repression activity. The basic amino acid-rich region and an arginine and glycine repeat domain of OsDrAp1 enhanced its repression activity. Thus, although OsDr1 and OsDrAp1 function as repressors, the functions of the two components are reversed compared with those of their nonplant counterparts.


PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer.
Prostate cancer has the second highest incidence among cancers in men worldwide and is the second leading cause of cancer deaths of men in the United States. Although androgen deprivation can initially lead to remission, the disease often progresses to castration-resistant prostate cancer (CRPC), which is still reliant on androgen receptor (AR) signaling and is associated with a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance invariably emerges, and new therapies are urgently needed. Recently, inhibitors of bromodomain and extra-terminal (BET) family proteins have shown growth-inhibitory activity in preclinical models of CRPC. Here, we demonstrate that ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. Unlike BET inhibitors, ARV-771 results in suppression of both AR signaling and AR levels and leads to tumor regression in a CRPC mouse xenograft model. This study is, to our knowledge, the first to demonstrate efficacy with a small-molecule BET degrader in a solid-tumor malignancy and potentially represents an important therapeutic advance in the treatment of CRPC.


Characterization and in vivo evaluation of ocular minitablets prepared with different bioadhesive Carbopol-starch components.
The purpose of this study was to evaluate different bioadhesive ocular formulations based on drum dried waxy maize starch (DDWM), Amioca starch and Carbopol 974P. The concentrations of Carbopol 974P in the mixtures varied between 5 and 25% (w/w). The rheological properties of the non-sterilized and gamma-irradiated physical blends of Carbopol 974P with either DDWM or Amioca were compared to those of the corresponding co-spray dried Amioca starch/Carbopol powders. Higher viscosity or consistency values were measured for sterilized co-spray dried powder mixtures containing an amount of Carbopol 974P equal or above 15% (w/w) compared to the physical blends. Sustained release minitablets (2 mm, 6 mg), consisting of sodium fluorescein as model drug and the bioadhesive powders, were manufactured at a compression force of 1.25 kN. Afterwards, the tablets were sterilized with gamma-irradiation. The amount of Carbopol in the co-spray dried powder mixtures on the one hand and gamma-irradiation on the other hand had no significant influence on the crushing strength and friability of the minitablets evaluated. However, these two factors affected the in vitro release properties of the minitablets. The slowest release was obtained with tablets containing 25% Carbopol 974P, which unfortunately possess mucosal irritating properties. By using co-spray dried Amioca with 15% (w/w) Carbopol 974P, a slower release can be achieved compared to the physical mixtures of DDWM or Amioca starch with Carbopol 974P. Moreover, this ocular formulation is very promising and is preferred, as it did not cause any mucosal irritation and released the model drug for at least 12 h, after application in the fornix.


A procedure for the determination of lead in green vegetables at concentrations down to 1 microgram/kg.
An accurate and highly sensitive dry ashing/graphite furnace atomic absorption spectrometry (GFAAS) procedure has been developed for the measurement of lead in green vegetables. The accuracy of the method was established by analysis of standard reference materials and confirmed by isotope dilution using an inductively coupled plasma-mass spectrometer (ICP-MS). The limit of detection (wet weight) of the technique is 1-3 micrograms/kg with relative standard deviations ranging from 6% for a sample of kale containing 500 micrograms/kg to 20% for cabbage containing 3.0 micrograms/kg.


Exercise training improves microvascular function in patients with Chagas heart disease: Data from the PEACH study.
Chagas heart disease (CHD) impairs the systemic microvascular function. We investigated the effects of exercise training on cutaneous microvascular function among patients with CHD. Patients from the PEACH study were randomly assigned to a supervised exercise training 3 times/week for 6 months (Trained; n = 10) or a control group (Untrained; n = 8). Both groups underwent evaluation of microvascular function before, and at 3- and 6-months of follow-up. Cutaneous vascular conductance (CVC) was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh), sodium nitroprusside (SNP) and during post-occlusive reactive hyperemia (PORH). At 3-months of follow-up, no difference was detected between groups in CVC responses to ACh (p = 0.50), SNP (p = 0.26) and HRPO (p = 0.65). However, at 6-months of follow-up, trained vs. untrained patients improved CVC induced by SNP-iontophoresis (0.19 ± 0.10 vs. 0.14 ± 0.15 APU.mmHg-1; p = 0.05) and PORH (0.63 ± 0.15 vs. 0.48 ± 0.18 APU.mmHg-1; p = 0.05). CVC response to ACh-iontophoresis was similar between groups (0.19 ± 0.11 vs. 0.22 ± 0.17 APU.mmHg-1; p = 0.38). Exercise training performed during 6 months improved the cutaneous microvascular function of CHD patients. Further studies evaluating the mechanism involved in this response are warranted.


Cognitive control, intentions, and problem solving in skill learning.
We investigate flexibility and problem solving in skilled action. We conducted a field study of mountain bike riding that required a learner rider to cope with major changes in technique and equipment. Our results indicate that relatively inexperienced individuals can be capable of fairly complex 'on-the-fly' problem solving which allows them to cope with new conditions. This problem solving is hard to explain for classical theories of skill because the adjustments are too large to be achieved by automatic mechanisms and too complex and rapid to be achieved by cognitive processes as they are usually understood. A recent theory, Mesh, can explain these results because it posits that skill-specific cognitive abilities develop during skill learning and that control typically involves an interplay between cognitive and automatic mechanisms. Here we develop Mesh further, providing a detailed explanation for these problem solving abilities. We argue that causal representation, metacognitive awareness and other forms of performance awareness combine in the formulation and control of action strategies. We also argue that the structure of control present in this case is inconsistent with Bratman's model of intentions, and that, in the face of high uncertainty and risk, intentions can be much more labile than Bratman recognises. In addition, we found limitations and flaws in problem solving which illuminate the representations involved. Finally, we highlight the crucial role of social and cultural learning in the development of complex skills.


[Establishment of Multidimensional Structured Training Curriculum in Surgery].
In Germany, medical education is defined and controlled by the medical association; however hospitals are responsible for its implementation. Surgical trainees do not only need to acquire theoretical knowledge, but also practical skills. For years, young surgeons were trained primarily in the operating theatre. Nowadays, ethical concerns as well as time and budget limitations and legislated restrictions on surgeons' working hours argue for modern training concepts. Therefore, we have developed a training curriculum to ensure a structured surgical education. A standardised surgical education leading to well-trained surgeons can improve the satisfaction of young surgical trainees, increase the safety of patients and optimise clinical efficacy. The acceptance of standardised surgical education and its implementation within the surgeons' working hours is an important task for the future.


[Clinical aspect of herpes zoster and the pathogenesis of symptomatic cranial nerve zosters].
The prognosis of shingles is generally good, however if cranial nerves are affected, the course of disease may be very serious. It is still doubtful if latent virus-in the sense of a trigger mechanism-may be activated by dental surgical interventions and cause a symptomatic herpes zoster of cranial nerves. Serious loss of teeth as an oral manifestation of shingles, with panostitis and retarded healing show the seriousness of the tissue changes. The virus can invade the plexus between the facial and trigeminal nerves and can thus travel within the same epineural sheath from one nerve to the other. It follows that in each case of a herpes zoster of cranial nerves, irrespective of location, no dental surgery should be undertaken, even in the initial stage, because - it may increase the extension of the disease along the nerves - it may cause a viraemia - it may initiate uncalled for intraoperative and postoperative complications. Therapy with high doses of antibiotics is indicated.