[Indications and pregnancy outcomes of intrapartum cesarean section after the new partogram applied].
To study the changes of intrapartum cesarean rate, cesarean indications and pregnancy outcomes after the new partogram applied. Totally 3 290 pregnant women trying to vaginal delivery which were managed according to the new partogram in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from August to October in 2014(new partogram group)were involved; 2 987 pregnancy women trying to vaginal delivery from May to July in 2014 which were managed according to the old partogram(old partogram group)were involved as control. The intrapartum cesarean rate, cesarean indications and the pregnancy outcomes between the two groups were analyzed. The rate of intrapartum cesarean delivery was 8.50%(254/2 987)in old partogram group, and was significantly higher than that in new partogram group(6.2%, 204/3 290; P<0.01). Cesarean indications in old partogram group included 18 labor protraction(7.1%, 18/254), 82 labor arrest(32.3%, 82/254), 44 relative cephalopelvic disproportion(17.3%, 44/254), 80 fetal distress(31.5%, 80/254), 23 intrauterine infection(9.1%, 23/254)and 7 cesarean delivery on maternal request(CDMR; 2.8%, 7/254). Cesarean indications in new partogram group included 33 labor arrest(16.2%, 33/204), 71 relative cephalopelvic disproportion(34.8%, 71/204), 73 fetal distress(35.8%, 73/204)and 22 intrauterine infection(10.8%, 22/204), 5 CDMR(2.5%, 5/204). There were no significant differences in incidence of asphyxia neonatorum and puerperal morbidity(P> 0.05), but the incidence of postpartum hemorrhage in new partogram group was higher than the old partogram group[6.9%(14/204)versus 1.6%(4/254), P<0.05]. After the new partogram applied, the rate of intrapartum cesarean delivery is significantly decreased, but the incidence of postpartum hemorrhage is increased.


A retrospective study of human cystic echinococcosis in Jordan.
Some 676 human cases of cystic echinococcosis (CE) were recorded from 18 major hospitals in Jordan from January 1985 to October 1993. The number and origins of the cases indicate that CE is an endemic and widespread disease in Jordan. Operations for the extraction of hydatid cysts represented 0.1% of all surgical operations carried out in the surveyed hospitals during the study period (excluding Caesarean sections). The mean annual surgical incidence of CE was estimated to be 0.5-8.2 per 100,000 population, depending on the governorate studied, with an overall mean of 2.9 per 100,000. Incidence was higher in the more rural eastern and south-western governorates than elsewhere, and more cases fell in the 21-30-year age group than in any other. Many more of the cases were female than male (443 v. 233; P < 0.001). The liver was the most common organ infected (54.5% of cases), followed by the lungs (12.1%), and multiple hydatidosis usually involved the liver.


The G protein-coupled receptor N-terminus and receptor signalling: N-tering a new era.
G protein-coupled receptors (GPCRs) are a vast family of membrane-traversing proteins, essential to the ability of eukaryotic life to detect, and mount an intracellular response to, a diverse range of extracellular stimuli. GPCRs have evolved with archetypal features including an extracellular N-terminus and intracellular C-terminus that flank a transmembrane structure of seven sequential helices joined by intracellular and extracellular loops. These structural domains contribute to the ability of a GPCR to be correctly synthesised and inserted into the cell membrane, to interact with its cognate ligand(s) and to couple with signal-transducing heterotrimeric G proteins, allowing the activated receptor to selectively modulate a number of signalling cascades. Whilst well known for its importance in receptor translation and trafficking, the GPCR N-terminus is underexplored as a participant in receptor signalling. This review aims to discuss and integrate recent advances in knowledge of the vital roles of the GPCR N-terminus in receptor signalling.


Analysis of amino-terminal variants of amyloid-β peptides by capillary isoelectric focusing immunoassay.
Here we present a novel assay for the separation and detection of amino-terminal amyloid-β (Aβ) peptide variants by capillary isoelectric focusing (CIEF) immunoassay. Specific amino-terminally truncated Aβ peptides appear to be generated by β-secretase (BACE1)-independent mechanisms and have previously been observed in cerebrospinal fluid (CSF) after BACE1 inhibitor treatment in an animal model. CIEF immunoassay sensitivity is sufficient to detect total Aβ in CSF without preconcentration. To analyze low-abundance amino-terminally truncated Aβ peptides from cell culture supernatants, we developed a CIEF-compatible immunoprecipitation protocol, allowing for selective elution of Aβ peptides with very low background. CIEF immunoassay and immunoprecipitation mass spectrometry analysis identified peptides starting at residue Arg(5) as the main amino-terminal Aβ variants produced in the presence of tripartite BACE1 inhibitor in our cell culture model. The CIEF immunoassay allows for robust relative quantification of Aβ peptide patterns in biological samples. To assess the future possibility of absolute quantification, we have prepared the Aβ peptides Aβ(x-10), Aβ(x-16), and Aβ(5-38(D23S)) by using solid phase peptide synthesis as internal standards for the CIEF immunoassay.


Arm control recovery enhanced by error augmentation.
Here we present results where nineteen stroke survivors with chronic hemiparesis simultaneously employed the trio of patient, therapist, and machine. Massed practice combined with error augmentation, where haptic (robotic forces) and graphic (visual display) distortions are used to enhance the feedback of error, was compared to massed practice alone. The 6-week randomized crossover design involved approximately 60 minutes of daily treatment three times per week for two weeks, followed by one week of rest, and then repeated using the alternate treatment protocol. A therapist provided a visual target using a tracking device that moved a cursor in front of the patient, who was instructed to maintain the cursor on the target. The patient, therapist, technician-operator, and rater were blinded to treatment type. Several clinical measures gauged outcomes at the beginning and end of each 2-week period and one week post training. Results showed incremental benefit across most but not all days, abrupt gains in performance, and a benefit to error augmentation training in final evaluations. This application of interactive technology may be a compelling new method for enhancing a therapist's productivity in stroke-rehabilitation.


Parenteral nutrition for marrow transplant recipients: evaluation of an increased nitrogen dose.
The use of total parenteral nutrition in bone marrow transplant (BMT) recipients is well recognized. These patients as a result of treatment with chemotherapy and immunosuppressive agents undergo catabolic stress. The metabolic effect of an increased nitrogen dose during total parenteral nutrition (TPN) was studied in 28 BMT patients. Patients were given TPN formulas providing a nitrogen intake of either 267 +/- 44 mg of N/kg/d or 330 +/- 60 mg of N/kg/d. Total calories, nonprotein and protein, were held constant at 40 kcal/kg/d for all patients. Data was collected for three periods posttransplant beginning at 3 days posttransplant through day 16. Both study TPN formulas improved patient weight and TIBC values over baseline. Nitrogen balance (NB) values were not significantly different at any study period. However, an overall group effect favored the H-N formula (p less than 0.01). BMT patients undergo catabolic stress which was reflected by average values of 24-hour urine urea nitrogen increasing from 8.1 +/- 4 g/d at baseline to 19.8 +/- 7.2 g/d at period 3 (p less than 0.01). The H-N formula did not differentially increase blood urea nitrogen or serum creatinine levels. Metabolic cart measures also showed no increase in metabolic rate, oxygen consumption, carbon dioxide production, or percent contribution of protein to total metabolic expenditure. Providing a caloric intake of 40 kcal/kg/d was excessive, where 30 to 35 kcal/kg/d would meet metabolic demands. Pertinent clinical outcomes including length of stay, relapse rate, and survival were monitored, but no conclusions could be drawn in this study. The H-N formula was more effective in reducing loss of lean body mass without causing detrimental metabolic effects in BMT patients.


Application of recombinant DNA technology in epitope mapping and targeting. Development and characterization of a panel of monoclonal antibodies against the 7B2 neuroendocrine protein.
Three mouse monoclonal antibodies (Moabs) have been obtained with specificity for the 7B2 protein, a proposed member of the granin family of neuroendocrine proteins. Bacterially produced hybrid proteins of 7B2 were used as immunogens. The Moabs were designated MON-100, MON-101, and MON-102. Furthermore, we report the construction of 35 deletion mutants of the glutathione S-transferase-7B2 (GST-7B2) fusion-gene using recombinant DNA technology. The hybrid proteins encoded by eleven of these mutants were used in epitope mapping experiments and the results of these studies strongly suggested that recognition of 7B2 by all three Moabs involved the same 16 amino acid region of 7B2 (from amino acid residue 128-135). This was further substantiated by the observation that MON-101 and MON-102 specifically recognized a conjugate between bovine serum albumin and the synthetic peptide Phe-Glu-Pro-Glu-His-Asp-Tyr-Pro-Gly-Leu-Gly-Lys based upon the deduced amino acid sequence of the predicted epitope region in 7B2. In an approach to generate a series of 7B2-specific Moabs targeted against another epitope region in the 7B2 protein, the hybrid protein encoded by deletion mutant pPV32 was used as the immunogen. This protein lacked the epitope region recognized by the first series of Moabs. A second series of three Moabs, designated MON-142, MON-143, and MON-144, was obtained and, in all three cases, the region of 7B2 from amino acid residue 64-94 appeared to be involved in specific recognition by the Moabs. The whole panel of six anti-7B2 antibodies appeared to be useful in immunoprecipitation and Western blot analysis of the 7B2 protein and specifically stained neuroendocrine cells in immunohistochemical experiments. Using a double determinant sandwich enzyme immunoassay, 7B2 protein levels in rat pituitary were determined as 20 ng/mg tissue.


Enhanced Valley Polarization in WS2 /LaMnO3 Heterostructure.
Monolayer transition metal dichalcogenides have attracted great attention for potential applications in valleytronics. However, the valley polarization degree is usually not high because of the intervalley scattering. Here, a largely enhanced valley polarization up to 80% in monolayer WS2 under nonresonant excitation at 4.2 K is demonstrated using WS2 /LaMnO3 thin film heterostructure, which is much higher than that for monolayer WS2 on SiO2 /Si substrate with a valley polarization of 15%. Furthermore, the greatly enhanced valley polarization can be maintained to a high temperature of about 160 K with a valley polarization of 53%. The temperature dependence of valley polarization is strongly correlated with the thermomagnetic curve of LaMnO3 , indicating an exciton-magnon coupling between WS2 and LaMnO3 . A simple model is introduced to illustrate the underlying mechanisms. The coupling of WS2 and LaMnO3 is further confirmed with an observation of two interlayer excitons with opposite valley polarizations in the heterostructure, resulting from the spin-orbit coupling induced splitting of the conduction bands in monolayer transition metal dichalcogenides. The results provide a pathway to control the valleytronic properties of transition metal dichalcogenides by means of ferromagnetic van der Waals engineering, paving a way to practical valleytronic applications.


Evaluation of validity of midwifery special courses in Isfahan University of Medical Sciences.
The aim of training midwifery student is to increase scientific and practical abilities in trainees in order to present caring health services. Then, the evaluation tools of these abilities have great importance. This study tried to evaluate the content validity, criterion validity and base validity of academic exams. This cross-sectional research was an evaluated type that has been done on 18 special theoretical courses of midwifery in 2 semesters in 2007-2008. The data gathered by checklists. The data about questionnaire and the result of analyzing exam questions (final and midterm) were compiled by 2 educating experts of medical education and 2 experts for each course. The data analyzed by SPSS software. For determining the base validity, spearman correlation test and for presenting descriptive results, distribution tables were applied. The evaluation of 1013 questions showed that in 18 courses, in 61.18% of exams, more than 90% of questions had content validity and in 28.27% of exams, in more than 90% of questions, criterion validity had been considered. The results showed that in 92.38% of questions, content validity and in 80.45% of questions, criterion validity was considered. 11 courses out of 18 courses had base validity. This survey showed that content validity of the exam questions in midwifery special theoretical courses was in favorable levels. But, the criterion validity of exam questions was far away from the ideal level. Then, education in each session can help the teachers achieve their exam purposes.


Analysis of very-high surface area 3D-printed media in a moving bed biofilm reactor for wastewater treatment.
Moving Bed Biofilm Reactors (MBBRs) can efficiently treat wastewater by incorporating suspended biocarriers that provide attachment surfaces for active microorganisms. The performance of MBBRs for wastewater treatment is, among other factors, contingent upon the characteristics of the surface area of the biocarriers. Thus, novel biocarrier topology designs can potentially increase MBBR performance in a significant manner. The goal of this work is to assess the performance of 3-D-printed biofilter media biocarriers with varying surface area designs for use in nitrifying MBBRs for wastewater treatment. Mathematical models, rendering, and 3D printing were used to design and fabricate gyroid-shaped biocarriers with a high degree of complexity at three different levels of specific surface area (SSA), generally providing greater specific surface areas than currently available commercial designs. The biocarriers were inoculated with a nitrifying bacteria community, and tested in a series of batch reactors for ammonia conversion to nitrate, in three different experimental configurations: constant fill ratio, constant total surface area, and constant biocarrier media count. Results showed that large and medium SSA gyroid biocarriers delivered the best ammonia conversion performance of all designs, and significantly better than that of a standard commercial design. The percentage of ammonia nitrogen conversion at 8 hours for the best performing biocarrier design was: 99.33% (large SSA gyroid, constant fill ratio), 94.74% (medium SSA gyroid, constant total surface area), and 92.73% (large SSA gyroid, constant biocarrier media count). Additionally, it is shown that the ammonia conversion performance was correlated to the specific surface area of the biocarrier, with the greatest rates of ammonia conversion (99.33%) and nitrate production (2.7 mg/L) for manufactured gyroid biocarriers with a specific surface area greater than 1980.5 m2/m3. The results suggest that the performance of commercial MBBRs for wastewater treatment can be greatly improved by manipulation of media design through topology optimization.


Plastidial and cytosolic thiol reductases participate in the control of stomatal functioning.
Stomatal movements via the control of gas exchanges determine plant growth in relation to environmental stimuli through a complex signalling network involving reactive oxygen species that lead to post-translational modifications of Cys and Met residues, and alter protein activity and/or conformation. Thiol-reductases (TRs), which include thioredoxins, glutaredoxins (GRXs) and peroxiredoxins (PRXs), participate in signalling pathways through the control of Cys redox status in client proteins. Their involvement in stomatal functioning remains poorly characterized. By performing a mass spectrometry-based proteomic analysis, we show that numerous thiol reductases, like PRXs, are highly abundant in guard cells. When investigating various Arabidopsis mutants impaired in the expression of TR genes, no change in stomatal density and index was noticed. In optimal growth conditions, a line deficient in cytosolic NADPH-thioredoxin reductases displayed higher stomatal conductance and lower leaf temperature evaluated by thermal infrared imaging. In contrast, lines deficient in plastidial 2-CysPRXs or type-II GRXs exhibited compared to WT reduced conductance and warmer leaves in optimal conditions, and enhanced stomatal closure in epidermal peels treated with abscisic acid or hydrogen peroxide. Altogether, these data strongly support the contribution of thiol redox switches within the signalling network regulating guard cell movements and stomatal functioning.


Whole blood collected on filter paper provides a minimally invasive method for assessing human transferrin receptor level.
Iron deficiency is the most common micronutrient deficiency worldwide, and transferrin receptor (TfR) level has been identified as an important measure of iron status that is not confounded by inflammation. However, logistical constraints associated with sample collection and processing have limited efforts to measure TfR, particularly at the community level. Standardized filter paper provides a relatively convenient and minimally invasive means for collecting and transporting samples of whole blood from simple finger pricks, and we present results of our validation of an improved method for quantifying TfR in dried blood spots. The method is based on commercially available reagents and uses capillary blood that is applied directly from the finger to filter paper, eliminating the need for premeasurement at the collection site. The blood spot TfR assay is precise and reliable, agrees well with plasma TfR, and can be performed at any facility with a microplate reader and basic laboratory equipment. Concentrations of TfR remain stable for at least 4 wk when blood spots are stored at room temperature, but begin to deteriorate after 3 d of exposure to higher temperatures. The advantages and disadvantages of the blood spot TfR method are discussed, as well as its potential contribution to future field-based studies of iron deficiency.


Compact optical true time delay beamformer for a 2D phased array antenna using tunable dispersive elements.
A hardware-compressive optical true time delay architecture for 2D beam steering in a planar phased array antenna is proposed using fiber-Bragg-grating-based tunable dispersive elements (TDEs). For an M×N array, the proposed system utilizes N TDEs and M wavelength-fixed optical carriers to control the time delays. Both azimuth and elevation beam steering are realized by programming the settings of the TDEs. An experiment is carried out to demonstrate the delay controlling in a 2×2 array, which is fed by a wideband pulsed signal. Radiation patterns calculated from the experimentally measured waveforms at the four antennas match well with the theoretical results.


Electrical properties of lead-free 0.98(Na0.5K0.5)NbO3-0.02Ba(Zr0.52Ti0.48)O3 piezoelectric ceramics by optimizing sintering temperature.
Lead-free 0.98(Na0.5K0.5)NbO3-0.02Ba(Zr0.52Ti0.48)O3 [0.98NKN-0.02BZT] ceramics were fabricated by the conventional mixed oxide method with sintering temperature at 1,080°C to 1,120°C. The results indicate that the sintering temperature obviously influences the structural and electrical properties of the sample. For the 0.98NKN-0.02BZT ceramics sintered at 1,080°C to 1,120°C, the bulk density increased with increasing sintering temperature and showed a maximum value at a sintering temperature of 1,090°C. The dielectric constant, piezoelectric constant [d33], electromechanical coupling coefficient [kp], and remnant polarization [Pr] increased with increasing sintering temperature, which might be related to the increase in the relative density. However, the samples would be deteriorated when they are sintered above the optimum temperature. High piezoelectric properties of d33 = 217 pC/N, kp = 41%, dielectric constant = 1,951, and ferroelectric properties of Pr = 10.3 μC/cm2 were obtained for the 0.98NKN-0.02BZT ceramics sintered at 1,090°C for 4 h.


The risk groups for coronary heart disease in Koreans. Assessment by distribution of serum lipid concentrations.
Coronary heart disease is the most severe form of disease caused by atherosclerosis; and there is a strong relationship between serum lipid concentrations and atherosclerosis. By decade of life, means, standard deviations and selected percentiles were calculated according to sex for serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride in 69,563 Koreans. The prevalence of dyslipoproteinemias which were related to high risk of coronary heart disease were assessed. The mean concentrations of serum total cholesterol and LDL-C in the Korean population were 5.02 mmol/l and 3.00 mmol/l. The 75th and 90th percentile concentrations of total cholesterol were 5.59 mmol/l and 6.24 mmol/l. The mean concentrations of serum triglyceride and HDL-C were 1.58 mmol/l and 1.30 mmol/l. The hyperlipoproteinemia type IV (4.8%) was the most frequent, followed by Type IIa (4.6%), hypoalphalipoproteinemia (3.3%), and type IIb (0.2%). According to the National Cholesterol Education Program Adult Treatment Panel II, 4.1% of Korean adults needed the initial drug therapy and 10.8% the initial dietary therapy for hypercholesterolemia. The age and sex-specific treatment guidelines for hypercholesterolemia would make it possible that early intervention could be applied to atherosclerosis in Korean adults.


Antischistosome IgG4 and IgE responses are affected differentially by chemotherapy in children versus adults.
Specific IgG4 and IgE responses and polyclonal cytokine profiles were studied in 110 Schistosoma haematobium-infected persons before and 5 weeks after chemotherapy. Pretreatment IgG4 responses to soluble egg antigen (SEA) correlated with intensity of infection. After chemotherapy, a significant decrease in egg output and circulating anodic antigen was associated with a substantial drop in the IgG4 response to SEA (IgG4-SEA) in adults and children, suggesting that egg laying is a major stimulus for IgG4-SEA. After chemotherapy, IgG4 and IgE to adult worm antigen and IgE to SEA increased in children but remained unchanged in adults. This indicates that the immunoregulatory mechanisms operative in S. haematobium-infected adults differ from those in infected children. The effect of treatment on cytokine profiles was determined following stimulation of whole blood with anti-CD3 antibodies. A significant decrease in interleukin-4 production after treatment indicated that reduction in helminth load may lead to a reduced number of Th2-type cells.


Transformation of Aspergillus nidulans with the hygromycin-resistance gene, hph.
Aspergillus nidulans strain G191 was transformed to hygromycin resistance using plasmid pDH25, which contains the bacterial hygromycin B phosphotransferase gene (hph) fused to promoter elements of the A. nidulans trpC gene. Southern hybridizations of transformants revealed multiple, integrated copies of the vector. A pleiotropic effect conferring increased hygromycin B sensitivity was found to be associated with the A. nidulans pyrG89 allele. Plasmid pDH25 features a ClaI site immediately preceding the hph start codon thus permitting convenient replacement of the trpC sequences with other eukaryotic promoters.


Pharmacokinetics of oral meloxicam in ruminant and preruminant calves.
The pharmacokinetics of oral meloxicam has been studied in ruminant, but not preruminant calves. Oral meloxicam was administered at 0.5 mg/kg to six ruminant calves via gavage (RG); to six preruminant calves via gavage (PRG); and to six preruminant calves via suckling in milk replacer (PRF). Plasma drug concentrations, determined over 120-h postadministration, were analyzed by compartmental and noncompartmental methods. The rate of drug absorption was faster (P<0.01) in PRF (0.237±0.0478/h) than RG calves (0.0815±0.0188/h), while absorption in PRG calves (0.153±0.128/h) was not different from other groups. C(max) was lower (P=0.03) in PRF (1.27±0.430 μg/mL) than in PRG calves (2.20±0.467 μg/mL), while C(max) of RG calves (1.95±0.955 μg/mL) was not different from other groups. V/F was higher in PRF calves (365±57 mL/kg) than either PRG (177±63 mL/kg, P<0.01) or RG (232±83 mL/kg, P=0.01) calves. These observations were likely due to differences in bioavailability, physiological maturity, and timing of the drug delivery into different compartments of the ruminant gastrointestinal tract. Results suggest that an adjustment in meloxicam dose may be necessary when administered with milk replacer.


Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet.
Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.


Optic Nerve Head Morphology in Nonarteritic Anterior Ischemic Optic Neuropathy Compared to Open-Angle Glaucoma.
To compare optic nerve head (ONH) morphology of optic nerve atrophy between eyes with primary open-angle glaucoma (POAG) and eyes with a history of nonarteritic anterior ischemic optic atrophy (NAION) using enhanced depth imaging (EDI) with spectral-domain optical coherence tomography (SD-OCT). In this cross-sectional study, 121 eyes of 91 patients consisted of moderate to severe POAG (n = 32 eyes), visual field mean deviation-matched NAION (n = 30 eyes) and their fellow eyes (n = 30 eyes), and healthy controls (n = 29). The optic discs were scanned using SD-OCT and measurements were obtained using HEYEX software 6.0. Lamina cribrosa (LC) thickness and anterior lamina cribrosa depth (ALD) at three scans (midsuperior, central, and midinferior) were determined and compared. In addition, prelaminar tissue thickness was measured at three points of a single central scan. There was no significant difference in the visual field mean deviation (MD) between the NAION and POAG groups (P > 0.99), but both groups had a significantly worse MD than the healthy group (P < 0.001). The NAION and POAG groups had similar peripapillary retinal nerve fiber layer (pRNFL) thickness (P < 0.99). Eyes with POAG had greater ALD and thinner LC than control eyes and NAION eyes in all regions of the ONH (P < 0.001 for both). There was a marked prelaminar tissue thinning in POAG eyes compared to control and NAION eyes (P < 0.001). Lamina cribrosa thickness and ALD of NAION eyes were not different from their fellow eyes and control eyes. Although prelaminar thickness was thinner in NAION eyes compared to their fellow eyes (P = 0.005), it was thicker than in control eyes (P < 0.001). Despite profound thinning and posterior displacement of LC in POAG, the thickness and position of LC in NAION eyes are similar to those seen in healthy control and their fellow eyes.


Effects of different heat-moisture treatments on the physicochemical properties of brown rice flour.
We evaluated the effect of heat-moisture treatment (HMT) on the main chemical components, physical properties, and enzyme activities of two types of brown rice flour: high-amylose Koshinokaori and normal-quality Koshiibuki. Five different HMTs using brown rice (moisture content was 12.0%) were assessed: 0.1 MPa/120 °C for 5 or 10 min, 0.2 MPa/134 °C for 5 or 10 min and 0.3 MPa/144 °C for 10 min. HMT, decreased the α-amylase and lipase activities, and fat acidity, and slightly increased the dietary fiber and resistant starch levels. After 2 months' storage at 35 °C, rice samples that were treated with 0.2 MPa/134 °C or 0.3 MPa/144 °C for 10 min had a lower fat acidity than untreated samples, which would be useful for long-term storage and export of rice flour. And HMT exhibited inhibition of retrogradation in the pasting and physical properties, which is profitable to promote the qualities of the rice products.


Enabling older people with mental health needs to engage with community social care: A scoping review to inform a theory of change.
Despite apparent need, many older people with cognitive impairment and/or mental health needs do not fully engage with social care. This can manifest in different ways, including passive or aggressive attempts to avoid or repel care workers. However, little is known about how to support such individuals in their own homes and deliver effective care. Against this background, we undertook a scoping review with a view to developing a preliminary theory of change suggesting how care might be modified to engage this client group. The most recent search was conducted on 21/04/21. Papers were included if they (i) focused on older people (65+) living at home with social care needs and (ii) described difficulties/problems with the provision/receipt of social care associated with individuals' mental health needs. Twenty-six citations were identified through electronic database searches and reference screening, and the results were charted according to key theory of change concepts (long-term outcomes, preconditions, interventions, rationale and assumptions). All the included papers were related to people with dementia. Four subgroups of papers were identified. The first highlights those external conditions that make it more likely an intervention will be successful; the second describes specific interventions to engage older people who by virtue of their mental health needs have not engaged with social care; the third explores what services can be done to increase service uptake by older people with mental health needs and their caregivers more generally; and the fourth details theoretical approaches to explaining the behaviour of people with dementia. Each provides information that could be used to inform care delivery and the development of interventions to improve engagement with health and social care for these individuals. The study concludes that different framing of engagement difficulties, such as that offered through positioning theory, may assist in future service design.


Dampening of diurnal intraocular pressure fluctuation by combined trabeculotomy and sinusotomy in eyes with open-angle glaucoma.
Large diurnal intraocular pressure (IOP) fluctuation ([INCREMENT]IOP) is believed to be one of the causes of progression in glaucomatous changes. Some fully medicated glaucoma patients whose IOPs are controlled during the regular office hours (10:00 to 16:00 h) still have progression in glaucomatous changes and IOP elevation during off-office hours. The purpose of this study was to determine whether [INCREMENT]IOP is dampened after combined trabeculotomy and sinusotomy (LOT+SIN) in glaucoma patients with low IOPs during the regular office hours. Fourteen eyes of 8 open-angle glaucoma patients who had large [INCREMENT]IOP despite low IOPs during the office hours were studied. The IOP was measured every 3 hours for 24 hours before and >3 months after the operation. The IOPs were measured in the sitting position with a Goldmann applanation tonometer. All patients underwent LOT+SIN. All patients had IOP elevations >20 mm Hg between 0:00 and 3:00 hours before the operation, and none had an IOP peak after the operation. The postoperative mean IOP (16.5±1.7 to 13.9±2.0 mm Hg, P=0.00064), the maximum IOP (21.9±2.4 to 16.1±2.5 mm Hg, P=0.0020), and [INCREMENT]IOP (8.9±2.7 to 4.3±1.2 mm Hg, P=0.0032) were significantly lower than the preoperative values. However, the minimum IOP was not reduced significantly (13.0±1.9 to 11.7±1.7 mm Hg). The diurnal [INCREMENT]IOPs are dampened by LOT+SIN in glaucoma patients with controlled IOPs during regular office hours. These results indicate that these surgical procedures can be used for the treatment of open-angle glaucoma patients.


Bone marrow-derived and synovium-derived mesenchymal cells promote Th17 cell expansion and activation through caspase 1 activation: contribution to the chronicity of rheumatoid arthritis.
Th17 cells have been implicated in rheumatoid arthritis (RA). We hypothesized that the interaction of T cells with bone marrow-derived mesenchymal stem cells (BM-MSCs) or with fibroblast- like synoviocytes (FLS) might, with the help of T cell-secreted inflammatory cytokines (i.e., interleukin-17A [IL-17A], tumor necrosis factor α [TNFα], and/or interferon-γ [IFNγ]), promote Th17 cell expansion and activation. Peripheral blood mononuclear cells (PBMCs) from healthy blood donors were cocultured with BM-MSCs or FLS from RA patients or osteoarthritis (OA) patients. Cocultures were exposed to phytohemagglutinin with or without IL-17A, TNFα, or IFNγ. Quantitative reverse transcription-polymerase chain reaction analysis, enzyme-linked immunosorbent assay, and cytofluorometry were used to measure IL-17A production. Interaction of PBMCs with BM-MSCs inhibited Th1 and Th2 responses, but promoted Th17 cell expansion, as early as 24 hours, as demonstrated by increases in retinoic acid receptor-related orphan nuclear receptor γ or IL-17A messenger RNA (mRNA) levels, IL-17A secretion levels, and IL-17A-secreting cell frequency, as well as by T cell switching to the Th17 pathway after 2 rounds of stimulation with MSCs. IL-17A production was also increased in PBMCs stimulated with anti-CD3 plus anti-CD28 or in isolated CD3+ or CD45RO+ T cells, thus demonstrating the role of T cell activation. Levels of mRNA for IL-6, IL-8, and IL-1β were further amplified when T cell-secreted inflammatory cytokines were added. Interestingly, OA FLS or RA FLS also enhanced IL-17A and IL-6 production, but only RA FLS enhanced IFNγ and IL-1β production. We further demonstrated that MSC-mediated Th17 promotion requires caspase 1 activation by using an inhibitory peptide and measuring its activity. We found that the interaction of MSCs or FLS with T cells promotes the activation and expansion of Th17 cells through caspase 1 activation. Since proinflammatory and T cell-secreted inflammatory cytokines are also amplified, this mechanism may participate in the chronicity of RA.


Pleural fluid cytokines correlate with tissue inflammatory expression in tuberculosis.
A tertiary care research centre in São Paolo, Brazil. To quantify interleukin (IL) 8, tumour necrosis factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF) and transforming growth factor beta(1) (TGF-beta(1)) in pleural fluid from tuberculous patients, correlating its values with the histopathological patterns in pleural biopsies. Cytokines were quantified in patients with transudates secondary to congestive heart failure (n = 8) and exudates secondary to tuberculosis (TB; n = 39). In parietal pleural biopsies from TB patients, the histological patterns of the inflammatory response were quantified by morphometric analysis (stereological point-counting method). IL-8, TNF-alpha, VEGF and TGF-beta(1) levels were higher in TB than in transudates. A positive correlation existed between components of the fibrinoid exudative phase with pleural fluid IL-8 (R = 0.52, P = 0.004) and VEGF (R = 0.42, P = 0.0021) levels. A negative correlation existed between pleural fluid IL-8 (R = -0.37, P = 0.048) and VEGF (R = -0.44, P = 0.0015) levels with tissue components of fibroproliferation. The high pleural levels of TNF-alpha, IL-8, VEGF and TGF-beta(1) suggest the involvement of these cytokines in the TB immunological response. The positive correlation between pleural fluid IL-8 and VEGF with the components of the acute exudative phase and the negative correlation between these cytokines with the fibroproliferative components suggest a temporary inflammatory response in the pleural space.


Plasma membrane proton ATPase from human kidney.
Distal urinary acidification is thought to be mediated by a proton ATPase (H+-ATPase). We isolated a plasma membrane fraction from human kidney cortex and medulla which contained H+-ATPase activity. In both the cortex and medulla the plasma membrane fraction was enriched in alkaline phosphatase, maltase, Na+,K+-ATPase and devoid of mitochondrial and lysosomal contamination. In the presence of oligomycin (to inhibit mitochondrial ATPase) in the presence of ouabain (to inhibit Na+,K+-ATPase) and in the absence of Ca (to inhibit Ca2+-ATPase) this plasma membrane fraction showed ATPase activity which was sensitive to dicyclohexylcarbodiimide and N-ethylmaleimide. This ATPase activity was also inhibited by vanadate, 4,4'-diisothiocyano-2,2'-disulfonic stilbene and ZnSO4. In the presence of ATP, but not GTP or UTP, the plasma membrane fraction of both cortex and medulla was capable of quenching of acridine orange fluorescence, which could be dissipated by nigericin indicating acidification of the interior of the vesicles. The acidification was not affected by presence of oligomycin or ouabain indicating that it was not due to mitochondrial ATPase or Na+,K+-ATPase, respectively. Dicyclohexylcarbodiimide and N-ethylmaleimide completely abolished the acidification by this plasma membrane fraction. In the presence of valinomycin and an outward-directed K gradient, there was increased quenching of acridine orange, indicating that the H+-ATPase is electrogenic. Acidification was not altered by replacement of Na by K, but was critically dependent on the presence of chloride. In summary, the plasma membrane fraction of the human kidney cortex and medulla contains a H+-ATPase, which is similar to the H+-ATPase described in other species, and we postulate that this H+-ATPase may be involved in urinary acidification.


Effects of activated protein C on ventilator-induced lung injury in rats.
Mechanical ventilation with a high tidal volume (VT) increases lung and systemic plasminogen activator inhibitor (PAI)-1 levels and alveolar fibrin deposition. Activated protein C (APC) may decrease PAI activity in endothelial cell-conditioned medium and thus enhance fibrinolysis. The aims of this study were to test the hypothesis that APC can neutralize PAI-1 activity and improve lung function in an animal model of ventilator-induced lung injury. Rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP; HVZP) protocol by a volume-cycled ventilator for 2 h at a VT of 30 ml/kg, a respiratory rate of 25 breaths/min, and an FiO(2) of 0.21. Fifteen minutes before ventilation, the rats received intravenous APC (250 microg/kg, HVZP+APC group) or normal saline (vehicle; HVZP group). Another group that received no ventilation served as the control group. Levels of arterial blood gas tension were comparable between the two ventilation groups throughout the study period. Rats treated with the HVZP protocol exhibited significantly higher total protein and macrophage inflammatory protein-2 concentrations in bronchoalveolar lavage fluid (BALF) and higher lung PAI-1 mRNA expression and plasma active PAI-1 levels than did the control group. Administration of APC tended to reduce the BALF protein content and systemic PAI-1 activity but did not improve the lung histology in the HVZP+APC group. Plasma levels of D-dimers were comparable among the three study groups. These results suggest that APC administered at a higher dosage might improve lung function by reducing alveolar protein leakage and systemic coagulation.


Facial Diplegia-Complication or Manifestation of SARS-CoV-2 Infection? A Case Report and Systemic Literature Review.
Since the outbreak of the new coronavirus, healthcare systems around the world have witnessed not only COVID-19 symptoms but also long-term complications of the aforementioned, including neurological problems. We report a clinical case of an adult patient with bilateral facial nerve palsy and progressive ascending paresis of the limbs after contracting the novel coronavirus (COVID-19). Additionally, the systematic review aimed to identify and summarize specific clinical features, outcomes and complications of the studies focusing on bilateral facial diplegia as a sequela of COVID-19 infection. The total number of analyzed patients was 15. Only one patient was diagnosed with isolated bilateral palsy; the rest had Guillain-Barré Syndrome (GBS). With one exception, all the presented cases had favorable outcomes, with facial palsy recovery from slight to almost complete. In patients with a confirmed COVID-19 diagnosis, bilateral facial palsy may be an isolated symptom as well as a variant of GBS. Symptoms of cranial nerve damage during a COVID-19 infection may explain the appearance of facial nerve damage. In order to clarify the spectrum of neurological manifestations and a causal relation between SARS-CoV-2, COVID-19 vaccination and neurological symptoms, direct attention towards the study of this virus is crucial. It seems reasonable to recognize human coronavirus as another potential GBS trigger.


Capillary array high-performance liquid chromatography of nucleic acids and proteins.
An array of monolithic poly(styrene/divinylbenzene) capillaries with individual column thermostats was constructed to demonstrate its utility for the separation of nucleic acids, proteins, and tryptic digests in combination with UV absorbance detection. Because of polymerization-related variation in surface area of monolithic columns, the concentration of acetonitrile required for elution of DNA fragments in denaturing HPLC may vary sufficiently to affect the degree of denaturation. Modulation of column temperature offers a convenient way to harmonize elution profiles among columns. Individual regulation of column temperature also provides the means to determine rapidly in a single parallel run the optimum temperature for resolution of biomolecules. Given the high reproducibility of separations among columns and the ease with which poly(styrene/divinylbenzene)-based stationary phases can be modified to accommodate different modes of chromatography, such arrays will find broad applicability in proteogenomics.


Predictions of episodic memory following moderate to severe traumatic brain injury during inpatient rehabilitation.
We examined memory self-awareness and memory self-monitoring abilities during inpatient rehabilitation in participants with moderate to severe traumatic brain injury (TBI). A total of 29 participants with moderate to severe TBI and 29 controls matched on age, gender, and education completed a performance prediction paradigm. To assess memory self-awareness, participants predicted the amount of information they would remember before completing list-learning tasks and visual-spatial memory tasks. Memory self-monitoring was assessed by participants' ability to increase accuracy of their predictions after experience with the tests. Although the TBI participants performed more poorly than controls on both episodic memory tasks, no significant group differences emerged in memory self-awareness or memory self-monitoring. The TBI participants predicted that their memory performances would be poorer than that of controls, accurately adjusted their predictions in accordance with the demands of the tasks, and successfully modified their predictions following experience with the tasks. The results indicate that moderate to severe TBI individuals in the early stages of recovery can competently assess the demands of externally driven metamemorial situations and utilize experience with task to accurately update their knowledge of memory abilities.


Single-base substitution in P1B-ATPase gene is associated with a major QTL for seed cadmium concentration in soybean.
Cadmium (Cd) is a pollutant metal present in soils and toxic to biologic organisms. Previous studies using recombinant inbred lines derived from a cross between soybean (Glycine max [L.] Merr.) cultivars Harosoy and Fukuyutaka revealed a major quantitative trait loci for seed Cd concentration (cd1) in chromosome 9. The genome sequence of Williams 82 suggested that a P(1B)-ATPase gene involved in the transport of metals was located in the vicinity of cd1. cDNA sequencing suggested existence of two types of transcripts: one (GmHMA1a) consisting of 9 exons and 8 introns and the other (GmHMA1b) consisting of 8 exons and 7 introns. The putative polypeptide, GmHMA1a, consisted of 885 amino acids, whereas premature termination of translation of GmHMA1b generated a putative polypeptide with 559 amino acids. GmHMA1a had a 49.8% similarity with AtHMA3, a P(1B)-ATPase of Arabidopsis. GmHMA1a of Fukuyutaka differed from that of Harosoy by a single-base substitution that led to an amino acid substitution from E to G at amino acid position 608. A derived cleaved amplified polymorphic sequence (dCAPS) marker was developed to detect the base substitution, and this dCAPS marker was successfully associated with seed Cd concentration. Transgenic experiments may be necessary to verify that GmHMA1 actually corresponds to cd1.


The prevalence of self-reported peptic ulcer in the United States.
The purpose of this study was to draw a current picture of the sociodemographic characteristics of peptic ulcer in the United States. During the National Health Interview Survey of 1989, a special questionnaire on digestive diseases was administered to 41,457 randomly selected individuals. Data were retrieved from public use tapes provided by the National Center for Health Statistics. Odds ratios were calculated by logistic regression after adjustment for sample weights in the survey. Of adult US residents, 10% reported having physician-diagnosed ulcer disease, and one third of these individuals reported having an ulcer in the past year. Old age, short education, low family income, being a veteran, and smoking acted as significant and independent risk factors. Gastric and duodenal ulcer occurred in both sexes equally often. Duodenal ulcer was more common in Whites than non-Whites, while gastric ulcer was more common in non-Whites. The age-related rise and socioeconomic gradients of peptic ulcer represent the historic scars of previous infection rates with Helicobacter pylori. The racial variations reflect different ages at the time of first infection; younger and older age at the acquisition of H. pylori appear to be associated with gastric and duodenal ulcer, respectively.


Ethnic and Adipose Depot Specific Associations Between DNA Methylation and Metabolic Risk.
Metabolic risk varies according to body mass index (BMI), body fat distribution and ethnicity. In recent years, epigenetics, which reflect gene-environment interactions have attracted considerable interest as mechanisms that may mediate differences in metabolic risk. The aim of this study was to investigate DNA methylation differences in abdominal and gluteal subcutaneous adipose tissues of normal-weight and obese black and white South African women. Body composition was assessed using dual-energy x-ray absorptiometry and computerized tomography, and insulin sensitivity was measured using a frequently sampled intravenous glucose tolerance test in 54 normal-weight (BMI 18-25 kg/m2) and obese (BMI ≥ 30 kg/m2) women. Global and insulin receptor (INSR) DNA methylation was quantified in abdominal (ASAT) and gluteal (GSAT) subcutaneous adipose depots, using the Imprint methylation enzyme-linked immunosorbent assay and pyrosequencing. INSR gene expression was measured using quantitative real-time PCR. Global DNA methylation in GSAT varied according to BMI and ethnicity, with higher levels observed in normal-weight white compared to normal-weight black (p = 0.030) and obese white (p = 0.012) women. Pyrosequencing of 14 CpG sites within the INSR promoter also showed BMI, adipose depot and ethnic differences, although inter-individual variability prevented attainment of statistical significance. Both global and INSR methylation were correlated with body fat distribution, insulin resistance and systemic inflammation, which were dependent on ethnicity and the adipose depot. Adipose depot and ethnic differences in INSR gene expression were observed. We show small, but significant global and INSR promoter DNA methylation differences in GSAT and ASAT of normal-weight and obese black and white South African women. DNA methylation in ASAT was associated with centralization of body fat in white women, whereas in black women DNA methylation in GSAT was associated with insulin resistance and systemic inflammation. Our findings suggest that GSAT rather than ASAT may be a determinant of metabolic risk in black women and provide novel evidence that altered DNA methylation within adipose depots may contribute to ethnic differences in body fat distribution and cardiometabolic risk.


Myeloid and histiocytic sarcomas in subantarctic fur seals Arctocephalus tropicalis, Brazil.
Histopathological and immunohistochemical methods were used to diagnose round cell tumors in 2 subantarctic fur seals Arctocephalus tropicalis with marked anemia. Although wild-born, both individuals were placed under human care while juveniles in a Brazilian aquarium. Both pinnipeds were PCR tested for herpesvirus, and 1 was infected with otariid gammaherpesvirus 5 (OtHV-5), previously described in a subantarctic fur seal stranded in Brazil. Although some gammaherpesviruses can cause sarcomas and other neoplasms, it was not possible to definitively associate OtHV-5 with the neoplasm. To our knowledge, these are the first neoplasm records in subantarctic fur seals.


Comparison of the laminar distribution of input from areas 17 and 18 of the visual cortex to the lateral geniculate nucleus of the cat.
The feedback from area 18 of the cat visual cortex to the lateral geniculate nucleus has been investigated by labeling and reconstructing seventeen axons of known receptive field position and eye preference. The distribution of boutons from each axon was quantified with respect to the compartments of the geniculate complex, and the results were compared with an equivalent analysis of fourteen area 17 axons. Area 18 axons form large, sparse arborizations that extend up to 1.9 mm laterally (1170 +/- 85 microm; mean +/- SEM), with a core of relatively dense innervation spanning on average 600 +/- 70 microm (mean +/- SEM). Thus, they have the potential to influence the transmission of visual information from well beyond their own classical receptive fields. In this respect, they are surprisingly similar to the axons from area 17, despite the fact that the two cortical areas have very different retinotopy. However, there are important differences between the pathways. Area 18 axons project more heavily to the C layers and medial interlaminar nucleus. Whereas the input from both areas to the A layers is biased toward the layer appropriate to the eye preference of each axon, the area 18 input to magnocellular layer C is not. The distribution of area 18 boutons favors the bottom of their preferred A layer, and the area 17 boutons favor the top. These differences mirror those seen in the afferent pathways, suggesting that each cortical area preferentially targets the cells from which it receives input. Finally, their greater diameter suggests that area 18 axons provide the earliest feedback signal in the corticogeniculate loop.


Health Education for Women and Children: A Community-Engaged Mutual Learning Curriculum for Health Trainees.
Intimate partner violence (IPV) affects the physical and psychological health of survivors and their children; however, to our knowledge, no comprehensive health curriculum exists for this population. As a partnership between a transitional housing program (THP) and an academic medical center, we developed a health education curriculum for female IPV survivors using the principles of community-based participatory research (CBPR). After partnering with a community-based organization, and recruiting participants (IPV survivors), the curriculum is then taught by health trainees. The materials needed to facilitate the 10 workshops are provided and include: a facilitator's guide; workshop materials, including PowerPoint slides and handouts; a training guide for a community partner to teach facilitators about IPV; a sample focus group guide for curricular evaluation that aligns with CBPR methodologies; a sample time line for curricular implementation; and CBPR resources. The curriculum was implemented for two 9-month periods between September 2014 and June 2016. During the first session, 80% of women attended at least one workshop and during the second session, 65% of women did the same. Participants and staff at the THP found the curriculum engaging and requested that it be implemented yearly. The community-academic partnership offered prehealth and health trainees the opportunity to learn effective methods of delivering health education and to understand some of the challenges associated with surviving IPV. Such education can be provided to trainees at any stage and across multiple specialties (e.g., medical, nursing, public health, or social work). There is potential to replicate this mutual learning curriculum in a wide variety of other settings serving mothers and children.


Surveyors finding problems with medication standards.
* Nearly half (43%) of surveyed hospitals in the first half of 2007 were not compliant with the standard requiring medications be properly and safely stored. * One of the top issues The Joint Commission sees is facilities not ensuring medications are stored acceptably for product stability. * Review occurrence reports with risk managers and ask frontline staff what procedures they find difficult.


Pre-tibial myopericytoma: a case report.
Myopericytoma (MPC) is a rare, benign tumour often presenting as a cutaneous growth commonly in the lower extremities. It is distinguished by its concentric layering of spindle shaped myoid appearing cells perivascularly. These cells diagnostically stain positive to alpha smooth-muscle actin and rarely positive to desmin stain. This case study reviews the presentation of a 56-year-old male with a slow-growing, pre-tibial lesion developing over a 7-8 year period. This lesion was asymptomatic and demonstrated vascular involvement on ultrasound scan. This lesion measured 19 × 15 × 9 mm histologically and contained bland spindle cells surrounding vessels that interestingly stained positive to both alpha smooth-muscle actin and desmin. The histological findings in correlation to clinical presentation and imaging led to a diagnosis of MPC.


Efficacy of Acetylcholinesterase Inhibitors on Cognitive Function in Alzheimer's Disease. Review of Reviews.
Alzheimer's disease (AD) is the most common form of dementia over the age of 65. It is estimated that 115.4 million people will be affected by AD by 2050. Acetylcholinesterase inhibitors (AChEI) are the only available and approved treatment for AD. The aim of the present study was to analyse the evidence on the efficacy of the AChEI in the treatment of cognitive symptoms of Alzheimer's disease. For that purpose, a review of review of the systematic reviews (SRs) on this topic was carried out by Web of Science, PubMed, and The Cochrane Library, among others, were searched until 24 September 2021. Thirteen of the 1773 articles evaluated the efficacy of AChEI on cognitive function and/or general condition and/or behavioural disturbances of patients with mild to moderate AD. Methodological quality and risk of bias were rated using the ROBIS scale. The quality of the identified studies was high for nine of them, unclear for two, and finally only in two of the 13 studies did we detect low quality. Overall, AChEI showed very low efficacy in improving cognition in patients with mild to moderate AD. Better results were obtained in improving global state, with donepezil being the most effective treatment. No improvements in behavioural disturbances were found. Few high-quality reviews provide clear evidence of the effects of AChEI on cognition, global change, behaviour, and mortality. The data suggest that AChEI stabilize or slow cognitive deterioration, improving global status. In addition, data indicate that the use of AChEI decreases mortality in patients with mild to moderate AD. However, there is no evidence that they improve patient behaviour. Donepezil is the best therapeutic alternative at a dose of 10 mg/day.


Turgor Pressure Regulation in Valonia utricularis: Effect of Cell Wall Elasticity and Auxin.
The electrical membrane resistance rho(0) of the marine alga Valonia utricularis shows a marked maximum in dependence on the turgor pressure. The critical pressure, P(c), at which the maximum occurs, as well as its absolute value, rho(0) (max), are strongly volume-dependent. Both P(c) and rho(0) (max), increase with decreasing cell volume. It seems likely, that these relationships reflect the elastic properties of the cell wall, because the volumetric elastic modulus, epsilon, is also volume-dependent, increasing hyperbolically with cell volume. Both P(c) and rho(0) (max) can be affected by external application of indole-3-acetic acid at concentrations of 2.10(-7)m to 2 .10(-5)m. The critical pressure is shifted by 1.2 to 6 bars toward higher pressures and the maximum membrane resistance increased up to 5.6-fold. During the course of the experiments (up to 4 hours), however, IAA had no effect on the volumetric elastic modulus, epsilon.The maximum in membrane resistance is discussed in terms of a pressure-dependent change of potassium fluxes. The volume dependence of P(c) and rho(0) (max) suggests that not only turgor pressure but also epsilon must be considered as a regulating parameter during turgor pressure regulation. On this basis a hypothesis is presented for the transformation of both, a pressure signal and of changes in the elastic properties of the cell wall into alterations of ion fluxes. It is assumed that the combined effects of tension and compression of the membranes as well as the interaction between membrane and cell wall opposingly change the number of transport sites for K(+) providing a turgor-sensing mechanism that regulates ion fluxes. The IAA effects demonstrated are consistent with this view, suggesting that the basic mechanisms for turgor pressure regulation and growth regulation are similar.Any relation connecting growth rate with turgor pressure should be governed by two parameters, i.e. by a yielding pressure, at which cell growth starts, and by the critical pressure, at which it ceases again.


Cytotoxicity, Colour Stability and Dimensional Accuracy of 3D Printing Resin with Three Different Photoinitiators.
Biocompatibility is important for the 3D printing of resins used in medical devices and can be affected by photoinitiators, one of the key additives used in the 3D printing process. The choice of ingredients must be considered, as the toxicity varies depending on the photoinitiator, and unreacted photoinitiator may leach out of the polymerized resin. In this study, the use of ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPO-L) as a photoinitiator for the 3D printing of resin was considered for application in medical device production, where the cytotoxicity, colour stability, dimensional accuracy, degree of conversion, and mechanical/physical properties were evaluated. Along with TPO-L, two conventional photoinitiators, phenylbis (2,4,6-trimethylbenzoyl) phosphine oxide (BAPO) and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO), were considered. A total of 0.1 mol% of each photoinitiator was mixed with the resin matrix to prepare a resin mixture for 3D printing. The specimens were printed using a direct light processing (DLP) type 3D printer. The 3D-printed specimens were postprocessed and evaluated for cytotoxicity, colour stability, dimensional accuracy, degree of conversion, and mechanical properties in accordance with international standards and the methods described in previous studies. The TPO-L photoinitiator showed excellent biocompatibility and colour stability and possessed with an acceptable dimensional accuracy for use in the 3D printing of resins. Therefore, the TPO-L photoinitiator can be sufficiently used as a photoinitiator for dental 3D-printed resin.


The gene encoding the stem cell antigen, CD34, is conserved in mouse and expressed in haemopoietic progenitor cell lines, brain, and embryonic fibroblasts.
The human haemopoietic cell surface antigen, CD34, is a 105 - 120 kd cell surface glycoprotein whose stage-specific expression by stem cells and lineage-specific progenitor cells suggests a role in regulating early events in blood cell differentiation. A murine gene and cDNA encoding a closely homologous protein have been isolated. The gene is organized in eight exons in 22 kb of DNA. The first exon lies in a GC- and CpG-rich island. The sequence of the gene and the cDNA predict a 382 amino acid-long protein containing an N-terminal signal peptide and one transmembrane region 73 amino acids from the C-terminus. The extracellular part of the protein contains: a 140 amino acid-long-N-terminal region, 40% of whose residues are serine or threonine potential attachment sites for O-linked carbohydrate, as well as five potential attachment sites for N-linked carbohydrate. Proximal to the extracellular membrane there is a 79 amino acid-long cysteine-rich region. The homology with the human sequence is highest in the intracellular domain (90% amino acid identity) and lowest in the N-terminal region (43% amino acid identity). The protein is not homologous with any other proteins currently in the databases. The expression of the murine gene by a number of haemopoietic progenitor cell lines suggests that the CD34 function in haemopoiesis may be conserved between man and mouse. The high level of expression in a number of embryonic fibroblast cell lines and in brain imply a function outside of haemopoiesis.


General pharmacology of the anxiolytic compound metaclazepam in comparison to other benzodiazepines.
7-Bromo-5-(2-chlorophenyl)-2,3-dihydro-2-(methoxymethyl)-1H-1,4- benzodiazepine X HCl (metaclazepam, KC-2547, Ka-2547, Talis) is a novel 1,4-benzodiazepine characterized by a high selectivity of its anxiolytic effects. The present experiments were performed to contribute to its general pharmacological profile and to evaluate possible risks especially on the cardiovascular field in comparison to standard benzodiazepines. The experiments were performed in guinea pig isolated ileal and papillary muscle preparations, anesthetized cats and dogs, conscious renal hypertensive (RHR) and pithed rats. At intravenous, intraduodenal and repeated oral administration of metaclazepam in anesthetized cats and dogs and RHR arterial hypotension, if any, occurred only at rather high dosages. Tilting experiments in dogs did not show any risk for postural hypotension due to metaclazepam. In guinea pig papillary muscles and in anesthetized dogs (i.v.), metaclazepam had a moderate negative inotropic effect. A diminution of stroke volume was seen only at high i.v. doses whereas cardiac output was maintained nearly constant by an increase in heart rate. In guinea pig papillary muscles metaclazepam, like diazepam, had only a tendency to prolong the refractory period. Unlike diazepam, i.v. metaclazepam had no relevant depressant effect on respiration in anesthetized cats. No specific interaction of metaclazepam with alpha- or beta-adrenoceptors was found in pithed rats and anesthetized cats. The papaverine-like, unspecific spasmolytic profile in the guinea pig isolated ileum suggests that metaclazepam has no relevant antimuscarinic properties. In anesthetized cats neither metaclazepam nor diazepam showed an effect on neuromuscular transmission; metaclazepam caused a markedly weaker inhibition of the polysynaptic linguomandibular reflex than diazepam and did not influence the monosynaptic patellar reflex. In conclusion, the results with metaclazepam did not indicate side effects limiting its therapeutic use as an anxiolytic. Its potential in producing untoward side effects on the cardiovascular and respiratory systems and its central muscle relaxant properties appear to be considerably weaker than with diazepam or bromazepam. Substantial overdosage may result in hypotension and/or impairment of cardiac contractility.


Mechanoactivation of Wnt/β-catenin pathways in health and disease.
Mechanical forces play an important role in regulating tissue development and homeostasis in multiple cell types including bone, joint, epithelial and vascular cells, and are also implicated in the development of diseases, e.g. osteoporosis, cardiovascular disease and osteoarthritis. Defining the mechanisms by which cells sense and respond to mechanical forces therefore has important implications for our understanding of tissue function in health and disease and may lead to the identification of targets for therapeutic intervention. Mechanoactivation of the Wnt signalling pathway was first identified in osteoblasts with a key role for β-catenin demonstrated in loading-induced osteogenesis. Since then, mechanoregulation of the Wnt pathway has also been observed in stem cells, epithelium, chondrocytes and vascular and lymphatic endothelium. Wnt can signal through both canonical and non-canonical pathways, and evidence suggests that both can mediate responses to mechanical strain, stretch and shear stress. This review will discuss our current understanding of the activation of the Wnt pathway in response to mechanical forces.


[Analysis of risk factors of patients with chronic liver failure complicated invasive fungal infections].
To evaluate the risk factors of chronic liver failure (CLF) complicated invasive fungal infections (IFI) and prevention and treatment. The clinical data and risk factors of 52 patients with CLF complicated IFI were analyzed retrospectively and were compared with those not complicated IFI. Risk factors were analyzed by chi-square test and Logistic regression test and Ridit test. In 52 patients with CLF complicated IFI, there were 69 fungal infections in different tissue and organs, the most were in oral cavity, but other tissue and organs especially bellows infections were rising. Candida albicans infections were the most, but cryptococcus neoformans infections and aspergillus infections were rising. The risk factors included species of bacteria infections, serum total bilirubin, hospital days, times of antibiotics using, number of invasive operation, species of antibiotics and degrees of ascites. The mortality of patients with CLF complicated IFI were much higher than those not complicated IFI. Patients with CLF complicated IFI have poor progress and prognosis. The effective prevent methods are treating primary disease actively, reducing hospital days, detecting patients' body fluids closely, identifying source of infection as early as possible, using antibiotics correctly, reducing or avoiding invasive operation, using immunoactivators and disinfecting air regularly.


ECIDS: standardizing the data for Birth to 3 programs.
There is a compelling need for standardized coding schemes to represent data collected for children receiving services through Milwaukee County early intervention (Birth to 3) programs. We are standardizing Birth to 3 data in our ongoing development of the Early Childhood Integrated Database System. Our efforts balance the need for individualized service plans with the need for aggregate analysis.


Clinical social work practice and technology: personal, practical, regulatory, and ethical considerations for the twenty-first century.
The world that social work exists in is no longer defined by traditional physical settings and boundaries, such as schools, agencies, or even offices. With the advent of the Internet and digital communications, social work now exists in a far more complex reality, with clients and social workers engaging across multiple platforms, and sometimes even unintentionally and without one another's awareness. The implications of this can be ethical, practical, regulatory, and personal. This article explores these areas of concern and suggests strategies professionals can use to navigate these complex issues related to technology and clinical practice.


[Ophthalmic aspects in Celsus' work De medicina libri octo].
The article presents Aulus Cornelius Celsus (living in Roman Empire 15 BC - 50 AD) and his famous work "De medicina libri octo", one of the main sources of knowledge on the ancient medicine. It briefly goes through the content of the medical treaties. A wider discussion of the following ophthalmic aspects, included in Book VI and Book VII, is provided: the anatomy of the eye, the description of ophthalmic diseases, methods of its preventive treatment and surgery. It is also mentioned that the work contains the first description of cataract surgery (couching method) in the medical literature. The article underlines the popularity enjoyed by Celsus' work in medieval Europe.


Refractory postsurgical pyoderma gangrenosum in a patient with Beckwith Wiedemann syndrome: response to multimodal therapy.
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that may be difficult to diagnose and treat. We presented a 41-year-old woman who required skin grafting following third-degree burns to her left breast. She suffered recurrent graft dehiscence and infections over many years, prompting elective bilateral reduction mammoplasty. She subsequently developed suture margin ulcerations unresponsive to topical therapies and antibiotics. Skin biopsies were non-specific, and a clinical diagnosis of PG was established. Although initially responsive to corticosteroids, wounds promptly recurred following steroid taper. She was treated unsuccessfully with various immunomodulatory agents and underwent elective bilateral mastectomy. Following a mastectomy, she developed progressive deep chest wall ulcerations. She failed numerous immunomodulatory treatments, surgical wound closure and negative pressure wound therapy. Ultimately, treatment with adalimumab, mycophenolate mofetil and prednisone, in addition to hyperbaric oxygen therapy facilitated progressive healing. Our case highlights the role of collaborative multimodal therapy for the treatment of refractory PG.


Molecular characterization of mutants of the acetate regulatory gene facB of Aspergillus nidulans.
The facB gene of Aspergillus nidulans encodes a DNA binding transcriptional activator required for growth on acetate as a sole carbon source. FacB contains N-terminal GAL4-like Zn(II)2Cys6 (or C6 zinc) binuclear cluster DNA binding and leucine zipper-like heptad repeat motifs and central and C-terminal acidic alpha-helical regions. facB recessive loss of function mutants are deficient in acetate induction of acetyl-CoA synthase, isocitrate lyase, malate synthase, acetamidase, and NADP-isocitrate dehydrogenase. Characterization of lesions in facB mutant alleles has localized important functional regions of the FacB protein. Two extreme mutants are shown to lack the C-terminal region of the protein. Two temperature sensitive mutants contain amino acid substitutions in the DNA binding domain and are shown to affect acetate induction of amdS-lacZ expression and confer temperature sensitive in vitro DNA binding. Two temperature sensitive facB mutations result in thermolability of acetyl-CoA synthase, isocitrate lyase, and malate synthase but not acetamidase or NADP-isocitrate dehydrogenase in crude extracts. This suggests that FacB may have a structural role in acetate metabolism in addition to its regulatory function.


The role of novel antipsychotics in bipolar disorders.
Patients with bipolar disorder frequently receive antipsychotic agents during both the acute and maintenance phases of treatment. Conventional antipsychotics are effective against mania, but they may induce depressive symptoms and expose patients with bipolar disorder to increased risks of tardive dyskinesia. Recent studies have shown risperidone to be effective for acute mania, both as monotherapy and in combination with mood stabilizers; this agent has also shown efficacy as add-on maintenance therapy in open-label studies as it exhibited both antimanic and antidepressant effects. Olanzapine, another novel antipsychotic, is also effective against both manic and depressive symptoms and in the maintenance treatment as indicated by an open-label study. Data on other novel agents are more limited.


Glutamine Synthetases of Higher Plants : Evidence for a Specific Isoform Content Related to Their Possible Physiological Role and Their Compartmentation within the Leaf.
The chromatographic properties of glutamine synthetase isoforms have been investigated in a wide range of higher plant leaves and shoots using ion exchange chromatography. Different patterns of glutamine synthetase isoform content were observed. Among higher plants, four patterns or groups could be recognized. The first group is characterized by having only cytosolic glutamine synthetase, whereas the second group is distinguished by having only chloroplastic glutamine synthetase. The third group is characterized by cytosolic glutamine synthetase being a minor component of the total leaf glutamine synthetase activity. The fourth group is distinct from the other groups in having high cytosolic and chloroplast glutamine synthetase activity. Immunological studies have been undertaken on a few species from each group to identify unambiguously both cytosolic and chloroplastic glutamine synthetases.


Immunotherapy in atopic dermatitis.
In the past decade, the emergence of biologics targeting human cytokine networks has advanced a new era in atopic dermatitis therapy. Dupilumab, in particular, the most widely studied and used IL-4/IL-13 inhibitor, has been considered a milestone in the treatment of patients with moderate-to-severe atopic dermatitis. In addition to the IL-4 and IL-13 pathways, many other cytokines and receptors have been newly targeted as therapeutic options. In this review, the authors provide an overview of the approved and tested biologics and JAK inhibitors for the treatment of atopic dermatitis, including their advantages and limitations.


Test day and lactation yield predictions in Italian simmental cows by ARMA methods.
Autoregressive Moving Average (ARMA) models, originally developed in the contest of time series analysis, were used to predict Test Day (TD) yields of milk production traits in dairy cows. ARMA models areable to take into account both the average lactation curve of homogeneous groups of animals and the residual individual variability that may be explained in terms of probability models, such as Autoregressive (AR) and Moving Average (MA) processes. Milk, fat, and protein yields of 6000 Italian Simmental cows with 8 TD records per lactation were analyzed. Data were grouped according to parity (1st, 2nd, and 3rd calving) and fitted to a Box-Jenkins ARMA model in order to predict TD yields in five situations of incomplete lactations. Reasonable accuracies have been obtained for a limited horizon of prediction: average correlations among actual and predicted data were 0.85, 0.72, and 0.80 for milk, fat and protein yields when the first predicted TD was one step ahead (on average 42d) of the last actual record available. Cumulative 305-d yields were calculated using all actual (actual yields) or actual plus forecasted (estimated yields) daily yields. Accuracy of lactation predictions was remarkable even when only a few actual TD records were available, with values of 0.88 for milk and protein and 0.84 for fat for the correlations between actual and estimated yields when 6 out of 8 TD records were predicted. Accuracy rapidly increases with the number of actual TD available: correlations were about 0.96 for milk and protein and 0.93 for fat when 4 out of 8 TD records were predicted. In comparison with other prediction methods, ARMA modelsare very simple and can be easily implemented in data recording software, even at the farm level.


Sarcophilia, cremation and Sir Henry Thompson (1820-1904).
Sarcophilia, a neologism for an attachment to human remains, is set in a review of the history of the disposal of the dead. The ancient practice of cremation was relaunched late in the 19th century by the urological surgeon cum social reformer Sir Henry Thompson. He was stimulated by Edwin Chadwick and Charles Dickens, and by Charles Darwin's observations on the earthworm. Sarcophilia is the reason for the controversial Human Tissue Act of 2004.


The Medical Management of Cerebral Edema: Past, Present, and Future Therapies.
Cerebral edema is commonly associated with cerebral pathology, and the clinical manifestation is largely related to the underlying lesioned tissue. Brain edema usually amplifies the dysfunction of the lesioned tissue and the burden of cerebral edema correlates with increased morbidity and mortality across diseases. Our modern-day approach to the medical management of cerebral edema has largely revolved around, an increasingly artificial distinction between cytotoxic and vasogenic cerebral edema. These nontargeted interventions such as hyperosmolar agents and sedation have been the mainstay in clinical practice and offer noneloquent solutions to a dire problem. Our current understanding of the underlying molecular mechanisms driving cerebral edema is becoming much more advanced, with differences being identified across diseases and populations. As our understanding of the underlying molecular mechanisms in neuronal injury continues to expand, so too is the list of targeted therapies in the pipeline. Here we present a brief review of the molecular mechanisms driving cerebral edema and a current overview of our understanding of the molecular targets being investigated.


Small cell carcinoma of the cervix: a clinicopathologic and immunohistochemical study of 23 cases.
Twenty-three patients with primary small cell carcinoma of the uterine cervix are presented. Their ages ranged between 23 and 63 years (average, 43 years). Blood spotting or vaginal bleeding was the most common clinical presentation. Histologically, the tumors were densely cellular and showed trabecular nesting or a sheet-like pattern. The neoplastic cells had scant cytoplasm, round nuclei, absence of nucleoli, and finely dispersed chromatin. Nuclear molding, single cell necrosis, and high mitotic activity were found in all tumors. There was a minor component of large cell neuroendocrine carcinoma in three cases, while foci of adenocarcinoma were identified in two cases. Immunohistochemical studies were performed in all 23 tumors which showed immunoreactivity for cytokeratin. Ten small cell carcinomas were immunoreactive for chromogranin, 13 for synaptophysin, and 10 expressed p53 protein. Treatment modalities included hysterectomy alone or combined with chemotherapy and/or radiation therapy. A few patients received chemotherapy and/or radiation alone. Follow-up information was obtained in 22 cases; 15 patients died of tumor between 6 and 43 months, while seven patients have remained alive 12 to 273 months. One patient was lost to follow-up. Small cell carcinoma of the cervix is a highly aggressive neoplasm. However, early diagnosis and combined therapeutic modalities may lead to longer survival in some patients. Although the use of immunohistochemistry may be helpful in the diagnosis, small cell carcinoma still remains a morphologic diagnosis.


[Epidemiological, social and public health aspects of tuberculosis in Ferrara in the 19th century].
Our first study of tuberculosis in Ferrara during the nineteenth century, whose results have been recently published, focused on disease treatment. Here we present the descriptive analysis of mortality, with the following results being attained: two behavioural patterns are detected with regard to the onset of disease, before and after 1850; TB is a specific disease that affects all parts of the body in all age groups: childhood, and active and passive populations; there are no significant differences with regard to gender; as regards the occupations performed by the deceased, those related to industry and agriculture and to various other activities and services are those with the highest mortality; tuberculosis has a seasonal pattern; summer and autumn are the periods of greatest prevalence (hot weather and humidity are factors that affect the respiratory system); among the forms of tuberculosis it can be observed that up to the year 1850 people died in Ferrara either of pulmonary tuberculosis or TB localised in other areas; from 1851 onward there appears to have been a dramatic change, with a decrease in unspecific diagnosis but the appearance of disease manifestations in its various clinical forms.


What re-enactment earns us.
Evidence from both behavioural and brain studies suggests that perception of actions and their outcomes may induce (overt or covert) production of related actions in perceivers. Three views of the proper function of such re-enactment have been suggested: imitation, identification, and anticipation. Here I propose that the proper function of re-enactment is to subserve anticipation of upcoming action. Re-enactment exploits the motor system's inbuilt capacity to anticipate the consequences of action and extends it from the planning of own action to the perception of foreign action.


The distribution of naloxone to heroin users.
Overdose deaths are a major contributor to excess mortality among heroin users. It has been proposed that opioid overdose morbidity and mortality could be reduced substantially by distributing the opioid antagonist naloxone to heroin users. The ethical issues raised by this proposal are evaluated from a utilitarian perspective. The potential advantages of naloxone distribution include the increased chance of comatose opioid users being quickly resuscitated by others present at the time of an overdose, naloxone's safety and its lack of abuse potential. The main problems raised by the proposal are: the medico-legal complications of medical practitioners prescribing a drug that is most likely to be administered to and by people other than the one for whom it is prescribed; the economic costs of distributing naloxone sufficiently widely to have an impact on overdose morbidity and mortality; and the potentially greater cost-effectiveness of simpler educational interventions. Given the possible benefits of naloxone distribution, it may be worthwhile considering a controlled trial of naloxone distribution to high-risk heroin users.


Injury Prevention Programs for Throwing Injuries in Softball Players: A Systematic Review.
Throwing-related injuries occur commonly in softball players. Preventative programs can be implemented to assist in identifying and correcting risk factors that could potentially lead to injury and therefore time missed from both practice and games. The purpose of this study was to determine if position-specific injury prevention programs have been developed to decrease the risk of throwing-related injuries in softball players. A systematic review was performed using the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) guidelines. PubMed, PMC, and EBSCO were searched for articles on injury prevention programs using the following key terms: softball, injury prevention, throwing injuries, pitcher, and shoulder. Studies that involved fast-pitch softball and included female participants as well as rehabilitation programs were included. Articles that highlighted slow-pitch softball or did not include female participants were excluded. Level 1. The initial search identified 1605 articles. After implementing a filter, 131 articles remained. Thirteen articles were screened out as duplicates. After screening for inclusion criteria, 7 articles remained and were included in the systematic review. Decreased range of motion (ROM) in both the upper and the lower extremities, unbalanced muscular strength, and fatigue were identified as risk factors for throwing injuries in softball players. Within the upper extremity, strength and ROM of the rotator cuff muscles, biceps, and extensors of the forearm were emphasized. The main focus of the lower extremity was the strength of the gluteal muscles and ROM of the lumbopelvic-hip complex. Only 1 study detailed an injury prevention program for softball players. The prevention program outlined was generalized for all softball players and was not position specific. There is a paucity of information about injury prevention programs for softball players. Of the evidence analyzed, balanced strengthening of the upper and lower extremities while maintaining dynamic range of motion was frequently utilized in developing an injury prevention program.


Costimulation-induced rounding in Tetrahymena thermophila: early cell shape transformation induced by sexual cell-to-cell collisions between complementary mating types.
Mixing of starved cells of complementary mating types of Tetrahymena thermophila induces shortening of their longitudinal length within 10 min of mixing. This early morphogenetic transformation in preconjugant sexual interaction (costimulation period) was named "costimulation-induced rounding" (CIR). CIR is the earliest morphological change that has ever been found in the costimulation period and differs from "synchronous rounding" in the vegetative cell cycle, because CIR cells are still able to form food vacuoles, while cells in synchronous rounding do not have this ability. When sexual cell-to-cell collisions between two mating types were hampered by unidirectional stirring for 20 min after mixing of the two mating types, both CIR and conjugation were delayed by 20 min. When secreted materials needed for the onset of costimulation were removed by washing the cells with 10 mM Tris-HCl, pH 7.4, before mixing the two mating types, both CIR and conjugation were delayed by about 30 min. CIR-like rounding was not induced by cell-free medium either from the opposite mating type or from mixed costimulated cells. These results indicated that CIR is induced when cells are activated to form conjugating pairs by cell-to-cell collisions between complementary mating types in the presence of secreted molecules.


Interactions between Global Health Initiatives and country health systems: the case of a neglected tropical diseases control program in Mali.
Recently, a number of Global Health Initiatives (GHI) have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD) Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali's health system where it was first implemented in 2007. Campaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each). Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts burdening local health systems. The campaign budget barely financed institutional strengthening. Finally, though the initiative rested at least partially on national structures, pressures to absorb donated drugs and reach short-term coverage results contributed to distract energies away from other priorities, including overall health systems strengthening. Our study indicates that positive synergies between disease specific interventions and nontargeted health services are more likely to occur in robust health services and systems. Disease-specific interventions implemented as parallel activities in fragile health services may further weaken their responsiveness to community needs, especially when several GHIs operate simultaneously. Health system strengthening will not result from the sum of selective global interventions but requires a comprehensive approach.


Antibodies against active-site peptides common to glucosyltransferases of mutans streptococci.
Polyclonal antibodies were raised against peptides derived from an active-site sequence common to the family of mutans streptococcal glucosyltransferases (GTFs). The sequence contains an aspartic acid residue that functions in formation of the enzyme transition state in catalysis. Two GTFs were targeted with similar but not identical sequences in this region: one that synthesizes an alpha-1,3-linked water-insoluble glucan and a homologous GTF that synthesizes an alpha-1,6-linked water-soluble glucan. For each enzyme, an 8-mer and 22-mer peptide were prepared. The two peptide lengths were chosen in order to increase the likelihood of the peptides folding in a conformation similar to that of the native enzyme. Each peptide immunogen produced high titers of antibody in rabbits, and all antisera cross-reacted with all peptides, albeit to various degrees. Native enzyme showed weak interaction with antisera, which, on the basis of enzyme denaturation experiments, likely reflects binding to a small but finite population of denatured enzyme in the sample. GTF was assayed for inhibition in the presence of protein A-purified immunoglobulin G from each antiserum. Given the mass of the antibody and catalytic importance of the peptide, any enzyme-antibody complex formation would result in enzyme inhibition. No significant inhibition was observed, which demonstrates that either polyclonal antibodies raised against each of the four peptides cannot access this active-site region, or antibodies do not recognize the native enzyme conformation. The advantages and challenges of generating antibodies against enzyme active-site peptides are discussed in the context of the crystal structure of Aspergillus oryzae alpha-amylase, which has a homologous peptide segment which serves the same catalytic function.


Effects of tamoxifen on steroid hormone receptors and hormone concentration and the results of DNA analysis by flow cytometry in endometrial carcinoma.
Tamoxifen is a nonsteroidal triphenylethylene derivate with a predominant antiestrogen activity, used in the endocrine treatment of breast and endometrial cancer. It is not known which endometrial carcinomas will respond favorably to tamoxifen and which ones will not. The aim of this study was to find out whether tamoxifen has an effect on hormone steroid receptors, hormone concentration, DNA content, and proliferative activity in endometrial cancer and to correlate the tamoxifen-induced changes with pathologic parameters such as clinical stage, tumor differentiation, depth of invasion, and histologic type. Thirty postmenopausal women with endometrial carcinoma were treated with 30 mg of tamoxifen daily for 7-10 days after curettage. Steroid hormone receptors (estrogen and progesterone receptors), levels of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, progesterone, testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and DNA ploidy and proliferative activity were determined before and after therapy. The patients were also divided into favorable and unfavorable prognosis groups according to classical histological parameters. The patients in the favorable group consisted of patients with stage I disease, well and moderately differentiated tumors, favorable histologic type, and a depth of myometrial invasion of less than (1/3). The patients with only one of the unfavorable parameters (clinical stage II or III, poorly differentiated tumors, unfavorable histologic types, and deeper invasion of myometrium) were included in the unfavorable prognosis group. After the treatment, there was a net increase in the progesterone receptors and sex hormone binding globulin and a significant decrease in the estrogen receptors. The increase in progesterone receptors and decrease in estrogen receptors occurred in the patient group with favorable prognosis regarding histologic type, degree of differentiation, and clinical stage, but also in the unfavorable prognosis group regarding the depth of myometrial invasion. Statistically significant decrease in the follicle-stimulating hormone concentration was observed in the groups with favorable prognosis regarding histologic type, depth of myometrial invasion, and grade of differentiation. Concentration of sex hormone binding globulin was significantly increased in groups with favorable prognosis if histologic type and grade of differentiation were taken into account. On the other hand, there was a significant decrease in the concentration of luteinizing hormone in the group with unfavorable histologic type and also a decrease in progesterone concentration in patients with unfavorable prognosis regarding the grade of differentiation. There was no statistical significance either in the concentrations of other hormones measured or in the DNA analysis by flow cytometry. Our results revealed that tamoxifen can increase progesterone receptors and decrease estrogen receptors in endometrial cancer. The effect was most pronounced in tumors with favorable clinicopathologic parameters. We conclude that tamoxifen therapy can induce progesterone receptor synthesis even in tumors with low initial progesterone receptor levels, making such tumors potentially responsive to additional hormonal therapy with progesterone.


An efficient, overall [4+1] cycloaddition of 1,3-dienes and nitrene precursors.
Intermolecular cycloadditions of conjugated dienes and nitrene precursors usually produce aziridines. A generally useful method was lacking to directly provide the [4+1] cycloadducts, 3-pyrrolines. We have realized this transformation by using an uniquely active catalyst, copper(II) 1,1,1,5,5,5-hexafluoroacetylacetonate ([Cu(hfacac)(2)]). The method is applicable to a wide array of dienes with good yields. When 1,4-disubstituted dienes are used as substrates, good-to-excellent cis or trans selectivity can be obtained. Interestingly, the cis or trans preference depends on the nature of the substituents, rather than diene geometry. Mechanistic studies reveal that the [4+1] cycloaddition proceeds through diene aziridination and subsequent ring expansion. Among common copper catalysts, only [Cu(hfacac)(2)] can efficiently catalyze both steps, which explains the unique efficiency of the catalyst.