Management of iron deficiency anemia: a survey of pediatric hematology/oncology specialists.
Iron deficiency anemia (IDA) is the most common hematologic condition in children and adolescents in the United States (US). No prior reports have described the management of IDA by a large cohort of pediatric hematology/oncology specialists. A 20-question electronic survey that solicited responses to two hypothetical cases of IDA was sent to active members of the American Society of Pediatric Hematology/Oncology (ASPHO) in the US. Of 1,217 recipients, 398 (32.7%) reported regularly treating IDA and completed the survey. In a toddler with nutritional IDA, 15% (N = 61) of respondents reported ordering no diagnostic test beyond a complete blood count. Otherwise, wide variability in laboratory testing was reported. For treatment, most respondents would prescribe ferrous sulfate (N = 335, 84%) dosed at 6 mg/kg/day (N = 248, 62%) divided twice daily (N = 272, 68%). The recommended duration of iron treatment after resolution of anemia and normalized serum ferritin varied widely from 0 to 3 months. For an adolescent with heavy menstrual bleeding and IDA, most respondents recommended ferrous sulfate (N = 327, 83%), with dosing based on the number of tablets daily. For IDA refractory to oral treatment, intravenous iron therapy was recommended most frequently, 48% (N = 188) using iron sucrose, 17% (N = 68) ferric gluconate, and 15% (N = 60) low molecular weight iron dextran. The approach to diagnosis and treatment of IDA in childhood was widely variable among responding ASPHO members. Given the lack of an evidence base to guide clinical decision making, further research investigating IDA management is needed.


Analysis of Red Blood Cell Parameters in Dogs with Various Stages of Degenerative Mitral Valve Disease.
Although peripheral blood analysis has become increasingly automated, microscopy is the only available method for the diagnosis of anisocytosis and poikilocytosis. The aims of the study were to compare RBC volume data obtained with two different analysers and by manual assessment of smears and to compare this data between dogs in various stages of heart failure secondary to degenerative mitral valvular (DMV) disease. The impact of diuretic administration on RBC morphology was also assessed. Sixty-eight dogs, 56 in different stages of DMV disease and 12 as healthy controls, were studied. Impedance and flow cytometry haematological analyses were performed for each animal. Additionally, two smears were prepared for manual analysis. RBC structure, staining, and size differences were recorded. There were no significant differences between the blood morphological parameters assessed using haematological analysers nor between dogs receiving diuretic treatment and those not treated. Based on the manual smear, significantly higher erythrocyte anisocytosis was observed in the dogs with symptomatic DMV disease than in the control group. Haematological analysers based on impedance and flow cytometry provide reliable and comparable morphological results in dogs with heart failure. However, microscopic assessment of blood smears is a more reliable tool to detect erythrocyte anisocytosis.


Influences of encapsulated polyphosphate incorporation on oxidative stability and quality characteristics of ready to eat beef Döner kebab during storage.
The effect of different polyphosphates (sodium tripolyphosphate, STP; sodium hexametaphosphate, HMP; sodium pyrophosphate, SPP) and ratios of unencapsulated (u) and encapsulated (e) forms of these polyphosphates (PP, 0.5%) on lipid oxidation inhibition and quality characteristics of ground beef döner kebab were evaluated. STP usage provided lower cooking loss (CL) than HMP or SPP (P < .05). Döners containing STP had higher pH than those with HMP or SPP (P < .05). Regardless of ePP ratio in the total added PP (0.5%), added ePP created the same effect on CL and pH as 0.5% uPP in döner samples. The highest orthophosphate (OP) was obtained with STP, followed by SPP, HMP and control (no PP; P < .05). OP values generally decreased with increasing ePP ratio up to 0.4% in the total added PP (P < .05). Thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide (LPO) in döners containing PP were lower than control (P < .05). The lowest TBARS and LPO were determined in döners containing STP or SPP (P < .05). In general, increasing ePP ratio (up to 0.2% for STP and SPP, and 0.4% for HMP) in the total added PP provided further reduction in TBARS and LPO (P < .05). TBARS and LPO results suggested that ePP incorporation may be strategic implementation for meat industry to control lipid oxidation in ready to eat döner kebab.


EXAFS investigations of temperature-dependent structure in cobalt-59 molecular NMR thermometers.
Cobalt-59 nuclei are known for extremely thermally sensitive chemical shifts (δ), which in the long term could yield novel magnetic resonance thermometers for bioimaging applications. In this manuscript, we apply extended X-ray absorption fine structure (EXAFS) spectroscopy for the first time to probe the exact variations in physical structure that produce the exceptional thermal sensitivity of the 59Co NMR chemical shift. We apply this spectroscopic technique to five Co(iii) complexes: [Co(NH3)6]Cl3 (1), [Co(en)3]Cl3 (2) (en = ethylenediamine), [Co(tn)3]Cl3 (3) (tn = trimethylenediamine), [Co(tame)2]Cl3 (4) (tame = 1,1,1-tris(aminomethyl)ethane), and [Co(diNOsar)]Cl3 (5) (diNOsar = dinitrosarcophagine). The solution-phase EXAFS data reveal increasing Co-N bond distances for these aqueous complexes over a ∼50 °C temperature window, expanding by Δr(Co-N) = 0.0256(6) Å, 0.0020(5) Å, 0.0084(5) Å, 0.0006(5) Å, and 0.0075(6) Å for 1-5, respectively. Computational analyses of the structural changes reveal that increased connectivity between the donor atoms encourages complex structural variations. These results imply that rich temperature-dependent structural variations define 59Co NMR thermometry in macrocyclic complexes.


Head and Neck Hemangiopericytoma: A Rare Case Report and Literature Review.
Hemangiopericytomas (HPCs) are rare vascular tumors, and head and neck hemangiopericytoma (HNHPC) accounts for 11% to 16% of all HPCs, possibly occurring at any age. However, according to a recent study, HNHPC was most frequently observed in middle-aged adults and had a slight predominance of female patients. In the present case, we report the successful treatment of HNHPC.


[Effects of aroma therapy and music intervention on pain and anxious for breast cancer patients in the perioperative period].
To investigate the effect of the aroma therapy and music intervention on anxious and pain for the breast cancer patients in the perioperative period and the potential mechanisms. Methods: A total of 100 breast cancer patients who received surgical treatment in the comprehensive hospitals of Hunan province were recruited for this study. Patients were assigned randomly into a control group, an aroma therapy group, a music intervention group, and a joint-therapy group (n=25 per group). The patients in the control group received regular post-surgical nursery, while the patients from other groups received aroma therapy, music intervention, or both in addition to the regular nursery. The scale of anxiety and pain were measured. The measurements were carried at three time points, namely 30 min before the surgery (T1), 30 min after the recovery period of anesthesia (T2), and 4 hours after the removal of anesthesia tubing (T3). Repeated ANOVA was used to perform statistic analysis. Results: The scale of pain was significantly increased at the post-operation (T2, T3) compared to pre-surgery (T1). The therapeutic group showed significant decrease in pain at post-operation (T3) comparing with the control group (P<0.05). The scale of anxiety was the highest at pre-surgery (T1). During anaesthesia recovery, the anxiety of patients at post-operation T2 and T3 in the therapeutic groups significantly decreased compared with the control group (P<0.05). Conclusion: Both the aroma therapy and the music therapy can decrease the stress-responsive anxiety and pain for the breast cancer patients in the perioperative period.


Altered Regulation of the Glucose Transporter GLUT3 in PRDX1 Null Cells Caused Hypersensitivity to Arsenite.
Targeting tumour metabolism through glucose transporters is an attractive approach. However, the role these transporters play through interaction with other signalling proteins is not yet defined. The glucose transporter SLC2A3 (GLUT3) is a member of the solute carrier transporter proteins. GLUT3 has a high affinity for D-glucose and regulates glucose uptake in the neurons, as well as other tissues. Herein, we show that GLUT3 is involved in the uptake of arsenite, and its level is regulated by peroxiredoxin 1 (PRDX1). In the absence of PRDX1, GLUT3 mRNA and protein expression levels are low, but they are increased upon arsenite treatment, correlating with an increased uptake of glucose. The downregulation of GLUT3 by siRNA or deletion of the gene by CRISPR cas-9 confers resistance to arsenite. Additionally, the overexpression of GLUT3 sensitises the cells to arsenite. We further show that GLUT3 interacts with PRDX1, and it forms nuclear foci, which are redistributed upon arsenite exposure, as revealed by immunofluorescence analysis. We propose that GLUT3 plays a role in mediating the uptake of arsenite into cells, and its homeostatic and redox states are tightly regulated by PRDX1. As such, GLUT3 and PRDX1 are likely to be novel targets for arsenite-based cancer therapy.


Acceptability of telepsychiatry in American Indians.
Telepsychiatry differs from in-person treatment in terms of its delivery mechanism, and this dissimilarity may increase cultural differences between the provider and the patient. Because cultural competence and identification can impact patient satisfaction ratings, we wanted to explore whether cultural differences in our study population influenced telepsychiatric and in-person interviews. Here, we compared the acceptability of conducting psychiatric assessments with rural American Indian veterans by real-time videoconferencing versus inperson administration. The Structured Clinical Interview for DSM-IIIR (SCID) was given to participants both in person and by telehealth. A process measure was created to assess participants' responses to the interview type concerning the usability of the technology, the perceptions of the interviewee/interviewer interaction, the cultural competence of the interview, and satisfaction with the interview and the interview process. The process measure was administered to 53 American Indian Vietnam veterans both in-person and by real-time interactive videoconferencing. Mean responses were compared for each participant. Interviewers were also asked several of the same questions as the participants; answers were compared to the corresponding participant responses. Overall, telepsychiatry was well received and comparable in level of patient comfort, satisfaction, and cultural acceptance to in-person interviews. We also found evidence to suggest that interviewers sometimes interpreted participant satisfaction as significantly less favorable than the participants actually responded. Despite the potential of videoconferencing to increase cultural differences, we found that it is an acceptable means for psychiatric assessment of American Indian veterans and presents an opportunity to provide mental health services to a population that might otherwise not have access.


Chromatography with supercritical fluids.
In supercritical fluid chromatography (SFC) the mobile phase is neither a gas nor a liquid, but is a supercritical fluid. As a result of the unique properties of supercritical fluids, SFC is rapidly becoming a prominent separation technique for the analysis of reactive, thermally labile, and nonvolatile compounds. This article reviews the history, instrumentation, and practice of the technique. Particular emphasis is placed on the different programming methods that allow elution to be selectively controlled in ways that are unique to SFC.


Oxysterol 7 alpha-hydroxylase activity by cholesterol 7 alpha-hydroxylase (CYP7A).
A 7 alpha-hydroxylation is necessary for conversion of both cholesterol and 27-hydroxycholesterol into bile acids. According to current theories, cholesterol 7 alpha-hydroxylase (CYP7A) is responsible for the former and oxysterol 7 alpha-hydroxylase (CYP7B) for the latter reaction. CYP7A is believed to have a very high substrate specificity whereas CYP7B is active toward oxysterols, dehydroepiandrosterone, and pregnenolone. In the present study, 7 alpha-hydroxylation of various oxysterols in liver and kidney was investigated. Surprisingly, human cholesterol 7 alpha-hydroxylase, CYP7A, expressed as a recombinant in Escherichia coli and COS cells, was active toward 20(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol. This enzyme has previously been thought to be specific for cholesterol and cholestanol. A partially purified and reconstituted cholesterol 7 alpha-hydroxylase enzyme fraction from pig liver showed 7 alpha-hydroxylase activity toward the same oxysterols as metabolized by expressed recombinant human and rat CYP7A. The 7 alpha-hydroxylase activity toward 20(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol in rat liver was significantly increased by treatment with cholestyramine, an inducer of CYP7A. From the present results it may be concluded that CYP7A is able to function as an oxysterol 7 alpha-hydroxylase, in addition to the previously known human oxysterol 7 alpha-hydroxylase, CYP7B. These findings may have implications for oxysterol-mediated regulation of gene expression and for pathways of bile acid biosynthesis. A possible use of 20(S)-hydroxycholesterol as a marker substrate for CYP7A is proposed.


Analysis of enamel structure and mineral density after different bleaching protocols using micro-computed tomography.
This study aims to investigate the effect of three different bleaching applications on structural integrity, mineral volume (MV) and density of the enamel by using micro-computed tomography (Micro-CT) and evaluate the colour effectiveness using CIEDE2000. Twenty-four maxillary premolar teeth were divided into three groups (n = 8) (group 1: 40% HP gel with erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser activation; group 2: 40% HP gel with diode laser activation; group 3: 16% CP gel). Bleaching protocols were applied and colour alteration was obtained. Data were calculated with CIEDE2000 before and after bleaching. A Micro-CT was used to scan the specimens before and after the bleaching application. Statistical analysis was performed by ANOVA. No significant difference was observed between the groups for colour changes (p > .05). Micro-CT analysis showed significant differences in structural thickness, structural separation, mineral density and MV for the different ROIs before and after bleaching for all groups (p<.05). All of the bleaching methods represented similar efficiency. However, bleaching with Er,Cr:YSGG laser was less harmful to enamel in comparison with other bleaching methods. The present results may be useful for establishing a numerical standard for the change in bleaching with laser systems in dental hard tissues.


Glufosinate-tolerant tobacco plants directed by the promoter of adenylate kinase gene of rice.
A DNA clone containing the 5' part of the adenylate kinase (AK) gene was isolated from a rice genomic library, and its nucleotide sequence was determined. This clone consists of 5' upstream, five exons and four introns of the AK gene. All of the determined donor and receptor sites contained 'GT' and 'AG' consensus splice sequences. Transgenic tobacco plants harbouring a chimeric gene consisting of the 5' upstream sequence of the AK gene fused with the gene encoding phosphinothricin acetyl transferase were generated. They showed tolerance to glufosinate to a level four times higher than its commercial dose.


Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants.
Vulnerability of specific brain regions and neuronal populations is a characteristic feature of Alzheimer disease and Down syndrome. Cholinergic neurons of the basal forebrain degenerate in both disorders. The basis for neuronal degeneration is unknown. Mouse trisomy 16 (Ts 16) is an animal model of Down syndrome. We sought an experimental system in which the survival and development of Ts 16 basal forebrain cholinergic neurons could be examined beyond the fetal period. As Ts 16 mice do not survive birth, we transplanted fetal Ts 16 and control basal forebrain into the hippocampus of young adult mice. Transplanted neurons survived and grew neurites in all grafts. Over time, we observed selective atrophy of cholinergic neurons in Ts 16 grafts. Denervation of the hippocampus produced a significant increase in the size of Ts 16 cholinergic neurons. This suggests that hippocampal-derived neurotrophic factors acted to prevent degeneration. beta/A4-amyloid-containing plaques were not seen. Ts 16 provides a model of spontaneous, genetically determined neurodegeneration that may be used to understand better the molecular pathogenesis of neuronal dysfunction in Alzheimer disease and Down syndrome.


The response to TLR ligation of human CD16⁺CD14⁻ monocytes is weakly modulated as a consequence of persistent infection with the hepatitis C virus.
Little is known about the frequency and function of CD16(+)CD14(-) monocytes from chronic HCV patients. We observed that the absolute numbers and ratio of CD16(+)CD14(-) to CD14(+)CD16(-) monocytes were similar between chronic HCV patients and healthy individuals. Functionally, we found that CD16(+)CD14(-) monocytes are more responsive to TLR8-ligation and only weakly responsive to LPS stimulation in producing TNF as compared to CD14(+)CD16(-) monocytes. We found no overt impairment of the function of CD16(+)CD14(-) monocytes from patients, except for an augmented induction of MIP-1β-producing CD16(+)CD14(-) monocytes upon TLR4-ligation. However, the increased frequency of MIP-1β-producing CD16(+)CD14(-) monocytes was not associated with viral load, ALT or fibrosis level. Our findings indicate that, different from other infectious diseases, the frequency and function of CD16(+)CD14(-) monocytes are only minimally altered as a consequence of the persistent state of HCV infections, and our findings therefore do not suggest a role for CD16(+)CD14(-) monocytes in HCV pathogenesis.


Pharmacokinetics of anticancer drugs in children.
Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of distribution, hepatic (doxorubicin, cyclophosphamide), and renal (bleomycin, methotrexate) clearances. These differences in pharmacokinetics as a function of age alter systemic exposure to chemotherapy, and may alter the efficacy and toxicity profile for standard doses of antineoplastic drugs. The relationship of systemic exposure to toxicity has been most clearly defined for methotrexate. Clinical monitoring of methotrexate serum concentrations, and adjustment of folinic acid dosages and duration of rescue based on methotrexate disposition is now routine. More recently, pharmacodynamic data have been published for high-dose methotrexate, epipodophyllotoxins, cisplatin, and cytarabine (cytosine arabinoside), indicating a relation between drug disposition and toxicity or efficacy. Collectively, these data suggest that the pharmacokinetics of many anticancer drugs in children is different from adults, and that variability in drug disposition may have an important influence on toxicity or efficacy.


Different types of tea products attenuate inflammation induced in Trypanosoma brucei infected mice.
An in vivo study was carried out to determine the effect of different types of Kenyan tea extracts on male Swiss albino mice infected with Trypanosoma brucei brucei isolate KETRI 2710. The isolate produced a similar clinical picture after a pre-patent period of 5 days post-infection (DPI). Parasitemia levels in the untreated mice and those given different teas developed exponentially at similar rates reaching similar densities at the peak of parasitemia 8 DPI. Between 9 and 13 DPI parasitemia decreased more rapidly in tea treated compared to the untreated mice which indicated that tea lowered parasitemia level. Anaemia indicated by a fall in erythrocyte packed cell volume (PCV) occurred within 4 DPI and remained below the normal levels until the terminal stages of the disease. A significant difference (P<0.05) was observed 11 DPI between the tea treated and the untreated mice indicating that tea enhanced resistance to erythrocyte destruction. Mice treated with tea exhibited significantly (P<0.01) reduced parasite-induced hypoalbuminemia as compared to the untreated. Since albumin is a negative acute phase protein, it shows a decrease during inflammatory conditions and therefore its elevation in the mice given tea in this study clearly demonstrated that tea ameliorated inflammation induced by T. b. brucei. Although green and white teas were superior in most of these characteristics, black tea, which is the principle tea product from Kenya, displayed remarkable properties some even comparable to those of green tea. Interestingly, tea was more efficacious than dexamethasone an established anti-inflammatory drug, demonstrating its therapeutic potential.


Interaction of rice (Oryza sativa) lectin with N-acetylglucosaminides. Fluorescence studies.
The interaction of lectin isolated from rice (Oryza sativa) embryos with N-acetylglucosaminides was studied by equilibrium dialysis and fluorescence. Equilibrium dialysis with 4-methylumbelliferyl-(GlcNac)2 showed that rice lectin (Mr 38000) contains four equivalent saccharide-binding sites. Addition of the N-acetylglucosaminides GlcNac, (GlcNac)2 and (GlcNac)3 enhanced the intrinsic fluorescence of rice lectin and this was accompanied by a 10nm blue-shift of its maximum fluorescence with (GlcNac)2 and (GlcNac)3. These changes in intensity allowed determination of the association constants, which increased with the number of saccharide units: at 20 degrees C, Ka = (1.3 +/- 0.1) X 10(3), (5.1 +/- 0.4) X 10(4) and (2.6 +/- 0.1) X 10(5) M-1 for GlcNac, (GlcNac)2 and (GlcNac)3 respectively. The binding enthalpy, delta H0, for the three glucosaminides were very low and ranged from -12.1 to -20.6 kJ X mol-1. The results are compared with those obtained with wheat-germ agglutinin, another GlcNac-specific gramineaous lectin.


[Experience of garasone use in surgical practice].
The efficiency of garasone (Schering-Plau) in preoperative and postoperative treatment was evaluated in 50 patients. Controls (48 pts) were treated by combinations of antibiotics (0.25% levomycetin and 20% sodium sulfacyl solutions) and antiinflammatory drugs (0.1% dexamethasone and maxidex). The postoperative inflammatory reaction ceased much sooner in the patients treated with garasone than in the controls. Conjunctival edema, corneal edema, and descemetitis completely disappeared on days 4-5 after the operation in the study group and only on day 6 in the control. Higher efficiency of garasone can be attributed to the advantages of its components: wide-spectrum gentamicin and its high bioavailability for the eyeball tissues and an effective steroid betamethasone. One more advantage of garasone is that it is convenient to use (a single flask, no need in repeated instillations). The results recommend garasone for wide use for prevention and treatment of postoperative inflammatory diseases of the eyes.


Five-year follow-up in patients after therapy stratification based on intracoronary pressure measurement.
Invasive coronary angiography (ICA) alone fails to accurately select patients with intermediate stenoses who should be treated by percutaneous coronary intervention (PCI). Previous studies have demonstrated the usefulness of fractional flow reserve (FFR) for identifying patients in whom deferring an intended PCI would be more beneficial than performing the planned procedure. The long-term safety of FFR-based therapy stratification, however, remains unknown. Therefore, the aim of this study was to retrospectively evaluate the long-term safety of an FFR-based therapy stratification in patients with intermediate coronary lesions detected by ICA. We included 56 patients presenting with a 50% to 75% angiographic stenosis by visual assessment on ICA, with negative, inconclusive, or no stress test, and in whom the intended PCI was deferred based on the result of the FFR measurement (ie, FFR > or = 0.75). The occurrence of major adverse cardiac events during a 5-year follow-up period was recorded. A complete 5-year follow-up was available in all patients. Mean follow-up was 1868 +/- 380 days. During follow-up, 16 events (1 cardiac death, 4 noncardiac deaths, 11 revascularization procedures) occurred. The combined rate of cardiac death and nonfatal myocardial infarction was 1.8% over 5 years. Nine PCI procedures (5 target vessel, 4 nontarget vessel) were performed during follow-up based on objective signs of ischemia. The angina status was not different between inclusion and the 5-year follow-up. Deferring PCI in patients without critical reduction in FFR may be a safe option during long-term follow-up.


Parental HIV disclosure in Burkina Faso: experiences and challenges in the era of HAART.
Increasingly parents living with HIV will have to confront the dilemmas of concealing their lifelong treatment or disclosing to their children exposed to their daily treatment practices. However, limited data are available regarding parental HIV disclosure to children in Burkina Faso. Do parents on antiretroviral therapy disclose their HIV status to their children? What drives them? How do they proceed and how do children respond? We conducted in-depth interviews with 63 parents of children aged seven and above where the parents had been in treatment for more than 3 years in two major cities of Burkina Faso. Interviews addressed parental disclosure and the children's role in their parents' treatment. The rate of parental HIV status disclosure is as high as that of non-disclosure. Factors associated with parental disclosure include female sex, parent's older age, parent's marital history and number of children. After adjustment, it appears that the only factor remaining associated with parental disclosure was the female gender of the parent. In most of the cases, children suspected, and among non-disclosers many believed their children already knew without formal disclosure. Age of the children and history of divorce or widowhood were associated with parental disclosure. Most parents believed children do not have the necessary emotional skills to understand or that they cannot keep a secret. However, parents who disclosed to their children did not experience blame nor was their secret revealed. Rather, children became treatment supporters. Challenges to parental HIV disclosure to children are neither essential nor specific since disclosure to adults is already difficult because of perceived risk of public disclosure and subsequent stigma. However, whether aware or not of their parents' HIV-positive status, children contribute positively to the care of parents living with HIV. Perceptions about children's vulnerability and will to protect them against stigma lead parents to delay disclosure and not to overwhelm them with their experience of living with HIV. Finally, without institutional counselling support, disclosure to children remains a challenge for both parents and children, which suggests a need for rethinking of current counselling practices.


Divided visual attention as a predictor of bumping while walking: the Salisbury Eye Evaluation.
The purpose of this study was to determine the association between bumping while walking and divided visual attention, as measured by the useful field of view (UFOV). The Salisbury Eye Evaluation is a population-based study of community-dwelling adults, aged 72 to 92 at the third round of data collection. Participants walked a circuitous 32.8-m course, seeded with obstacles, and the number of bumps made while traversing the course was counted. UFOV divided attention score was based on processing speed: the time taken to identify a central target, and the location of a peripheral target simultaneously. Association between number of bumps and UFOV score was assessed in a generalized linear model, with adjustment for vision and attention measures that might explain the UFOV score. Of the 1504 participants in this study, 10.1% did not attempt the mobility course. In a model adjusting for demographic, physical, cognitive and attention, and vision measures, a decrease of 50 ms in processing speed for the divided-attention task was associated with a 4.9% increase (P = 0.004) in number of bumps made over the course. Receiver operating characteristic curves were created for the UFOV and visual field tests, to determine accuracy in detecting those with a high number of bumps. The visual field test had slightly higher area under the curve, but positive predictive value for both tests was low. The UFOV test of divided attention, as measured by processing speed, independently predicted bumping while walking. These data suggest that poor visual attention is a significant risk factor for bumping while walking.


[The use of computers in hematologic cytologic studies].
The review is concerned with the use of computers in studies of hematopoietic cells. It includes a wide range of methods and instruments from a simple reading of measurements in automatic cell analyzers to the design of expert systems and mathematical simulation of cellular physiology. Some examples illustrate a clinical use of data of karyotype, cell kinetics studies, computer morphometry, cytophotometric and morphometric evaluation of cytochemical reactions for diagnosis and prognosis.


Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations.
The (embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1) is a newly discovered protein associated with cerebral ischemic/reperfusion (I/R) injury. However, little is known of ELAVL1 in ischemic stroke patients. To investigate the clinical significance of collateral circulation and serum ELAVL1 in patients with carotid atherosclerosis (CAS) and ischemic stroke. The present prospective cohort investigation included 317 ischemic stroke patients and 300 CAS patients admitted between March 2020 and March 2022. Collateral circulation was measured using digital subtraction angiography (DSA) and graded using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading system. Enzyme-linked immunosorbent assays (ELISAs) were used to measure serum ELAVL1, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The serum levels of total cholesterol (TC), triglyceride (TG), high-density leptin cholesterol (HDL-C), and low-density leptin cholesterol (LDL-C) were also measured. The serum levels of ELAVL1, CRP, IL-6, TNF-α, and LDL-C were all markedly higher, while HDL-C was significantly lower in ischemic stroke patients compared to the CAS patients. Serum ELAVL1 was markedly higher in ASITN/SIR grade 0-1 patients compared to grade 2-4 patients. Also, ELAVL1 correlated positively with serum CRP, IL-6, TNF-α, TC, and LDL-C, and negatively with HDL-C. Receiver operating characteristic (ROC) curves showed that ELAVL1 and collateral circulation have the potential to be used as biomarkers for the diagnosis of ischemic stroke. Meanwhile, CRP, IL-6, TNF-α, HDL-C, ASITN/SIR grading, and ELAVL1 were independent risk factors for ischemic stroke. We found that serum ELAVL1 was associated with clinical outcomes of ischemic stroke patients, while the combination of ELAVL1 and collateral circulation could be used as a potential biomarker for ischemic stroke diagnosis.


Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author's Perspective.
The utility of platelet-rich plasma (PRP) has spanned various fields of dermatology from chronic ulcer management to trichology and aesthetics, due to its role in wound healing. Though PRP is being used over a long time, there is still confusion over proper terminology to define, classify and describe the different variations of platelet concentrates. There is also a wide variation in the reported protocols for standardization and preparation of PRP, in addition to lack of accurate characterization of the tested products in most articles on the topic. Additionally, the high cost of commercially available PRP kits, precludes its use over a larger population. In this article, we review the principles and preparation methods of PRP based on available literature and place our perspective in standardizing a safe, simple protocol that can be followed to obtain an optimal consistent platelet yield.


Significance of Glycemic Variability in Diabetes Mellitus.
The goal of diabetes treatment is to maintain good glycemic control, prevent the development and progression of diabetic complications, and ensure the same quality of life and life expectancy as healthy people. Hemoglobin A1c (HbA1c) is used as an index of glycemic control, but strict glycemic control using HbA1c as an index may lead to severe hypoglycemia and cardiovascular death. Glycemic variability (GV), such as excessive hyperglycemia and hypoglycemia, is associated with diabetic vascular complications and has been recognized as an important index of glycemic control. Here, we reviewed the definition and evaluated the clinical usefulness of GV, and its relationship with diabetic complications and therapeutic strategies to reduce GV.


Regression of mature lymphatic vessels in the cornea by photodynamic therapy.
Corneal (lymph) angiogenesis is a predominant risk-factor for immune rejection after transplantation. Techniques to regress pre-existing pathological corneal lymphatic vessels prior to transplantation are missing so far. Therefore we analysed the possibility to regress corneal lymphatic vessels by photodynamic therapy (PDT), after intrastromal verteporfin injection. Combined hemangiogenesis and lymphangiogenesis was induced in female BALB/c mice using the murine model of suture-induced inflammatory neovascularisation. Thereafter, the treatment group received an intrastromal injection of verteporfin (controls: phosphate buffered saline (PBS)) followed by PDT. Corneas were excised at different time points (1 day, 5 days and 10 days) after PDT and corneal whole mounts were stained with CD31 and LYVE-1 to quantify hemangiogenesis and lymphangiogenesis. Whereas blood vessels showed no significant reduction after PDT, lymphatic vessels could significantly be reduced with PDT after intrastromal verteporfin injection: 1 day after PDT, lymphatic vessels were reduced by 62% (p=0.20). After 5 days and 10 days, lymphatic vessels were reduced by 51% and 48% (p<0.001), respectively. This study for the first time shows that PDT after corneal intrastromal verteporfin injection can selectively regress lymphatic vessels. This may become a new 'preconditioning strategy' to reduce pre-existing corneal lymphatic vessels prior to transplantation and thereby reduce allograft rejection in high-risk patients.


Stroke and bleeding risk in atrial fibrillation.
Non-valvular atrial fibrillation (AF) is the most common cardiac arrhythmia in the clinical setting. AF increases both the risk and severity of strokes, and is associated with substantial morbidity and mortality. Despite the clear net clinical benefit of oral anticoagulants (OACs) in patients with AF at risk for stroke, major bleeding events, especially intracranial bleeds, may be devastating. In the last decade, four new OACs have been approved for stroke prevention in patients with AF and are at least as effective as warfarin with better bleeding profiles. These new agents have changed and simplified our approach to stroke prevention because the threshold for initiation of OACs is lowered. An important clinical practice shift is the initial identification of "low-risk" patients who do not need antithrombotic therapy, with low-risk comprising CHA2DS2-VASc {Congestive heart failure, Hypertension, Age ≥75 years (double), Diabetes mellitus, previous Stroke/transient ischemic attack/thromboembolism (double), Vascular disease, Age 65-74 years, and female gender (score of 0 for males and 1 for female)}. Subsequent to this step, effective stroke prevention consisting of OACs can be offered to patients with one or more stroke risk factors. Apart from stroke risk, another consideration is bleeding risk assessment, with a focus on the use of the validated HAS-BLED {Hypertension, Abnormal renal/liver function, Stroke, Bleeding history, Labile international normalized ratio (INR), Elderly (age >65 years), drugs or alcohol concomitantly} score. A high HAS-BLED score can flag patients potentially at risk for bleeding, and alert clinicians to the need for careful review and follow up, and the need to consider potentially correctable bleeding risk factors that include uncontrolled hypertension, labile INRs, concomitant aspirin use, and alcohol excess.


Do physicians underrecognize obesity?
A physician's advice is among the strongest predictors of efforts toward weight management made by obese patients, yet only a minority receives such advice. One contributor could be the physician's failure to recognize true obesity. The objectives of this study were to assess physicians' ability to recognize obesity and to identify factors associated with recognition and documentation of obesity. Internal medicine residents and attending physicians at three academic urban primary care clinics and their adult patients participated in a study using recognition and documentation of patient obesity as the main measures. A total of 52 physicians completed weight assessments for 400 patients. The mean patient age was 51 years, 56% were women, 77% were Hispanic, and 67% had one or more obesity-related comorbidity. There were 192 (48%) patients, of whom 66% were correctly identified by physicians as being obese, 86% of those with a body mass index (BMI) ≥ 35, but only 49% of those with a BMI of 30 to 34.9 (P < 0.0001). Fewer obese Hispanic patients were identified than were non-Hispanic patients (62% vs 76%; P = 0.03). No physician characteristics were significantly associated with recognition of obesity. Physicians documented obesity as a problem for 51% of patients. Attending physicians documented obesity more frequently than did residents (64% vs 43%, odds ratio 2.5, 95% confidence interval 1.3-4.6) and normal-weight physicians documented obesity more frequently than overweight physicians (58% vs 41%, odds ratio 2.0, 95% confidence interval 1.0-4.0). Documentation was more common for patients with a BMI ≥ 35 and for non-Hispanics. Documentation was not more common for patients with obesity-related comorbidities. Physicians have difficulty recognizing obesity unless patients' BMI is ≥ 35. Training physicians to recognize true obesity may increase rates of documentation, a first step toward treatment.


[Western blot, ELISA and indirect immunofluorescence test evaluation of Leishmania (Leishmania) infantum-infected dogs].
Evaluating canine visceral leishmaniasis diagnostic test performance in Colombia and adapting the Western blot test in naturally and experimentally infected dogs. Sera were obtained from 10 experimentally L. Infantum-infected dogs, 5 naturally infected dogs, 16 healthy dogs, 26 Babesia canis, Erhlichia canis, Dirofilaria immitis, Trypanosoma cruzi and Leishmania (Viannia) spp infected dogs, 40 dogs from non-endemic areas and 150 from endemic areas. Sera were tested for L. infantum infection using immunofluorescent antibody (IFAT), ELISA and Western blot (WB) tests. Positives results were obtained for 73 % of known infected dogs by the IFAT test and false positives were obtained for 2.5 % of non-infected dogs using WB. ELISA was not efficient for diagnosis. 24 antigenic fractions were recognised in tested sera using WB; however, 29, 34, 50, 69, 75, 86, 99 and 123 kDa bands were recognised in sera from dogs from non-endemic areas, healthy dogs and Trypanosoma cruzi, Erhlichia canis, Dirofilaria immitis and Babesia canis infected dogs. The 13 kDa fraction proved potentially useful for diagnosing canine visceral leishmaniasis. The separate use of parasitological and serological test could lead to misdiagnosis of Leishmania infection; using both kinds of technique simultaneously is thus highly recommended.


Motor unit recruitment and proprioceptive feedback decrease the common drive.
It has been documented that concurrently active motor units fire under the control of a common drive. That is, the firing rates show high correlation with near-zero time lag. This degree of correlation has been found to vary among muscles and among contractions performed at different force levels in the same muscle. This study provides an explanation indicating that motor units recruited during a contraction cause an increase in the variation (SD) and a decrease in the degree (amplitude) of the correlation of the firing rates. The degree of correlation is lower in muscles having greater spindle density. This effect appears to be mediated by the proprioceptive feedback from the spindles and possibly the Golgi tendon organs. Muscle spindles in particular respond to the mechanical excitation of the nonfused muscle fibers and provide a discordant excitation to the homonymous motoneurons, resulting in a decrease in the correlation of the firing rates of motor units. The implication of this work is that the decreased correlation of the firing rates in some muscles is not necessarily an indication of a decreased common drive from the CNS, but rather an inhibitory influence of the proprioceptive feedback from the peripheral nervous system. This explanation is useful for understanding various manifestations of the common drive reported in the literature.


Exhaled nitric oxide in asthmatic children exposed to relevant allergens: effect of flunisolide.
Inhaled corticosteroids are capable of reducing the level of exhaled nitric oxide (expiratory nitric oxide fraction (FE,NO)) in asthmatic patients in a dose-dependent fashion. The aim of this study was to evaluate whether or not treatment with an inhaled steroid can prevent changes in FE,NO after the exposure to relevant allergens, following avoidance, in asthmatic children allergic to house dust mite. Thirty-two house dust mite-allergy asthmatic children were randomly allocated to treatment with inhaled flunisolide (500 microg b.i.d) or placebo and evaluated before and 2 weeks after a period of natural exposure to mite antigens. Lung function and FE,NO were evaluated. FE,NO was increased in the placebo-treated group after antigen exposure. Treatment with inhaled flunisolide prevented such increase in FE,NO (p<0.001). No change was observed in lung function parameters. Inhaled flunisolide is effective in preventing the increase in airway inflammation observed in allergic asthmatic children re-exposed to allergens.


Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen.
A number of diabetogenic stimuli interact to influence insulin promoter activity, making it an attractive target for both mechanistic studies and therapeutic interventions. High-throughput screening (HTS) for insulin promoter modulators has the potential to reveal novel inputs into the control of that central element of the pancreatic beta-cell. A cell line from human islets in which the expression of insulin and other beta-cell-restricted genes are modulated by an inducible form of the bHLH transcription factor E47 was developed. This cell line, T6PNE, was adapted for HTS by transduction with a vector expressing green fluorescent protein under the control of the human insulin promoter. The resulting cell line was screened against a library of known drugs for those that increase insulin promoter activity. Members of the phenothiazine class of neuroleptics increased insulin gene expression upon short-term exposure. Chronic treatment, however, resulted in suppression of insulin promoter activity, consistent with the effect of phenothiazines observed clinically to induce diabetes in chronically treated patients. In addition to providing insights into previously unrecognized targets and mechanisms of action of phenothiazines, the novel cell line described here provides a broadly applicable platform for mining new molecular drug targets and central regulators of beta-cell differentiated function.


Astragaloside IV ameliorates motor deficits and dopaminergic neuron degeneration via inhibiting neuroinflammation and oxidative stress in a Parkinson's disease mouse model.
Oxidative stress and neuroinflammation are the key and early events during the pathological process of Parkinson's disease (PD). Thus, therapeutic intervention to regulate oxidative stress and neuroinflammation would be an effective strategy to alleviate the progression of PD. Astragaloside IV, the main active component isolated from Astragalus membranaceus, has been shown to possess anti-inflammatory and anti-oxidant properties in neurodegeneration diseases, however, the molecular mechanisms of Astragaloside IV in the pathology of PD are still unclear. In this study, we explored the mechanisms of Astragaloside IV of PD on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model and lipopolysaccharide (LPS)-induced BV2 microglia cells. Our results showed Astragaloside IV significantly alleviated behavioral impairments and dopaminergic neuron degeneration induced by MPTP. Also, Astragaloside IV inhibited microglia activation and reduced the oxidative stress of MPTP mouse model. In addition, Astragaloside IV significantly inhibited NFκB mediated NLRP3 inflammasome activation and activated Nrf2 both in vivo and in vitro. Furthermore, Astragaloside IV lessened reactive oxygen species (ROS) generation in LPS-induced BV2 microglia cells remarkably. These findings demonstrate that Astragaloside IV protects dopaminergic neuron from neuroinflammation and oxidative stress which are largely dependent upon activation of the Nrf2 pathways and suppression of NFκB/NLRP3 inflammasome signaling pathway. Therefore, Astragaloside IV is a promising neuroprotective agent that should be further developed for neurodegeneration diseases.


A signature of attractor dynamics in the CA3 region of the hippocampus.
The notion of attractor networks is the leading hypothesis for how associative memories are stored and recalled. A defining anatomical feature of such networks is excitatory recurrent connections. These "attract" the firing pattern of the network to a stored pattern, even when the external input is incomplete (pattern completion). The CA3 region of the hippocampus has been postulated to be such an attractor network; however, the experimental evidence has been ambiguous, leading to the suggestion that CA3 is not an attractor network. In order to resolve this controversy and to better understand how CA3 functions, we simulated CA3 and its input structures. In our simulation, we could reproduce critical experimental results and establish the criteria for identifying attractor properties. Notably, under conditions in which there is continuous input, the output should be "attracted" to a stored pattern. However, contrary to previous expectations, as a pattern is gradually "morphed" from one stored pattern to another, a sharp transition between output patterns is not expected. The observed firing patterns of CA3 meet these criteria and can be quantitatively accounted for by our model. Notably, as morphing proceeds, the activity pattern in the dentate gyrus changes; in contrast, the activity pattern in the downstream CA3 network is attracted to a stored pattern and thus undergoes little change. We furthermore show that other aspects of the observed firing patterns can be explained by learning that occurs during behavioral testing. The CA3 thus displays both the learning and recall signatures of an attractor network. These observations, taken together with existing anatomical and behavioral evidence, make the strong case that CA3 constructs associative memories based on attractor dynamics.


Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with a topically acting antiglaucoma sulfonamide.
The X-ray crystal structure for the adduct of human carbonic anhydrase (hCA) II with a topically acting antiglaucoma sulfonamide (the 2-N,N-diethylaminoethylamide of 5-(4-carboxybenzenesulfonamido-1,3,4-thiadiazole-2-sulfonamide), has been resolved at a resolution of 1.6A. This compound is a very potent inhibitor of the physiologically most relevant isozyme hCA II for the secretion of aqueous humor within the eye K(I) of 1.4 nM), and in animal models of glaucoma showed very effective intraocular pressure (IOP) lowering after topical administration. Surprisingly, the inhibitor bound within the enzyme active site is in the sulfonylimido-4H- delta(2)-1,3,4-thiadiazoline tautomeric form. The inhibitor is directly bound to the Zn(II) ion of the enzyme through the deprotonated primary sulfonamide moiety, participating to the classical hydrogen bond network involving residues of the zinc-binding function and Thr 199 and Glu 106. The 1,3,4-thiadiazoline fragment of the inhibitor makes two hydrogen bonds with the active site residue Thr 200, the secondary sulfonamide moiety makes two hydrogen bonds involving a water molecule and the residue Gln 92, whereas the phenyl ring of the inhibitor participates to an edge-to-face interaction with the phenyl ring of Phe 131, the two cycles being almost perfectly perpendicular to each other. The tertiary amine fragment of the carboxamido tail and the carboxamido moiety itself make hydrogen bonds with water molecules present at the rim of the active site entrance and van der Waals contacts with His 4, Trp 5, and Phe 20. All these multiple interactions never evidenced previously in CA-sulfonamide complexes, explain the very high affinity of this inhibitor for the hCA II active site and may allow further optimization of this class of inhibitors.


[A Swedish example of integrated perinatal mental health care].
Mental disorders are common during the perinatal period and expose mother and child to major risks. Almost all women in Sweden attend maternal and child health care centers regularly before and after birth. This constitutes a unique opportunity to detect women with early signs of mental disorder or at risk of recurrence of prior illness. Identified women need fast access to diagnostic and treatment providers with specialized knowledge on perinatal mental disorders. As perinatal mental disorders can have severe consequences for mothers and their children a tight cooperation between caregivers is often needed.


Preference for autogenous song by auditory neurons in a song system nucleus of the white-crowned sparrow.
Neuronal activity in the hyperstriatum ventrale, pars caudale (HVc) is associated with and necessary for the production of song by songbirds. HVc neurons also respond to acoustic stimuli. The present investigation assessed the auditory response properties of neurons in HVc by testing with the individual bird's own (autogenous) song and the songs of conspecific birds. Throughout HVc, multiunit clusters preferentially responded to autogenous song. Selectivity for autogenous song was apparent even when compared to similar intradialect songs, and neuronal clusters preferred autogenous song over the (tutor) song model that birds heard during the impressionable phase early in life. The responses to autogenous song were stable in the adult. HVc neurons were sensitive to the acoustic parameters of autogenous song and consistently exhibited a diminished response to modified song. In contrast, field L neurons, which are presumed to be a source of auditory input to HVc, did not exhibit selectivity for autogenous song and showed no special sensitivity to the acoustic parameters of autogenous song. These observations implicate song (motor) learning in shaping the response properties of HVc, but not field L, auditory neurons. It is proposed that HVc auditory neurons may contribute to a bird's ability to discriminate among conspecific songs by acting as an "autogenous reference" during perception of those songs.


Prostate Cancer Can Be Detected Even in Patients with Decreased PSA Less than 2.5 ng/ml after Treatment of Chronic Prostatitis.
We evaluated men with documented chronic prostatitis and elevated serum prostate-specific antigen (PSA) to determine whether treatment with antibiotics and anti-inflammatory drugs can lower serum PSA and the cancer detection rate in patients with post-treatment PSA <4 ng/ml. Eighty-six men who presented with serum PSA greater than 4 ng/ml and who were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions were included in this prospective study. Patients meeting these criteria underwent treatment with a 4-week course of antibiotics and nonsteroidal anti-inflammatory agents. Follow-up PSA and transrectal ultrasonography-guided prostate biopsy were performed within 2 months of treatment for all patients. Mean patient age was 56.2 years (range, 37-72 years). Mean PSA (ng/ml) decreased by 33.8%, from 8.12 (range, 4.02-24.8) to 5.37 (range, 1.35-12.94), after treatment (p=0.001). Pathological studies revealed prostate cancer in 18 cases (20.9%), chronic inflammation in 64 (74.4%), and benign prostatic hypertrophy in 4 (4.7%). The prostate cancer detection rate according to the follow-up PSA level, below 2.5, from 2.5 to 4.0, and above 4.0, was 13.3% (2/15), 13.6% (3/22), and 26.5% (13/49), respectively. When chronic prostatitis with elevated PSA is identified, antibiotic and anti-inflammatory treatment can lower these PSA levels. However, the possibility of prostate cancer remains in patients whose PSA level decreases to less than 4 ng/ml, even in those with a PSA level less than 2.5 ng/ml.


Phloem differentiation: induced stimulation by gibberellic Acid.
Gibberellic acid solutions supplied through micropipettes to explants from dormant branches of white pine (Pinus strobus L.) stimulate changes in the cambial zone. Immature sieve cells expand radially and exhibit cytological changes usually associated with spring maturation. Diflerentiation of sieve cells continues in response to treatment and is recognized by the birefringence of secondary walls when examined with the polarizing microscope.


Stereoscopic images in confocal (tandem scanning) microscopy.
Stereoscopic pair images with parallel projection geometry are obtained by through-focusing along two inclined axes while recording two (summed and stacked) images with a microscope with a very shallow depth of field. The two stack images sample the same depth slice of translucent or reflective specimens. The method will work most conveniently with a tandem scanning microscope (a direct-view, confocal scanning optical microscope). This is a direct method for recording stereo images that can be used to the limit of resolution in optical microscopy. It demonstrates a previously unrealized advantage of confocal optical microscopy.


Knowledge-based temporal abstraction in diabetes therapy.
We suggest a general framework for solving the task of creating abstract, interval-based concepts from time-stamped clinical data. We refer to this problem-solving framework as the knowledge-based temporal-abstraction (KBTA) method. The KBTA method emphasizes explicit representation, acquisition, maintenance, reuse, and the sharing of knowledge required for abstraction of time-oriented clinical data. We describe the subtasks into which the KBTA method decomposes its task, the problem-solving mechanisms that solve these subtasks, and the knowledge necessary for instantiating these mechanisms in a particular clinical domain. We have implemented the KBTA method in the RESUME system and have applied it to the task of monitoring the care of insulin-dependent diabetics.


Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association.
Background Recently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS. Methods and Results Data were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with <4 months symptom duration, evident ongoing inflammatory disease, suspected volume depletion, or declined consent were excluded. All patients had typical POTS symptoms; some, however, had additional nonorthostatic complaints not usually associated with POTS. The latter patients underwent additional testing for known MCA biochemical mediators including prostaglandins, histamine, methylhistamine, and plasma tryptase. The study comprised 69 patients who met POTS diagnostic criteria. In 44 patients (44/69, 64%) additional nonorthostatic symptoms included migraine, allergic complaints, skin rash, or gastrointestinal symptoms. Of these 44 patients, 29 (66%) exhibited at least 1 laboratory abnormality suggesting MCA disorder, and 11/29 patients had 2 or more such abnormalities. Elevated prostaglandins (n=16) or plasma histamine markers (n=23) were the most frequent findings. Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder. Conclusions Laboratory findings suggesting MCA disorder were relatively common in patients diagnosed with POTS and who present with additional nonorthostatic gastrointestinal, cutaneous, and allergic symptoms. While solitary abnormal laboratory findings are not definitive, they favor MCA disorder being considered in such cases.


Effect of vitamin D supplementation on blood pressure in blacks.
Blacks have significantly higher rates of hypertension than whites, and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on blood pressure in blacks. During 2 winters from 2008 to 2010, 283 blacks (median age, 51 years) were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 international units of cholecalciferol per day. At baseline, 3 months, and 6 months, systolic and diastolic pressure and 25-hydroxyvitamin D were measured. The 3-month follow-up was completed in 250 (88%) participants. The difference in systolic pressure between baseline and 3 months was +1.7 mm Hg for those receiving placebo, -0.66 mm Hg for 1000 U/d, -3.4 mm Hg for 2000 U/d, and -4.0 mm Hg for 4000 U/d of cholecalciferol (-1.4 mm Hg for each additional 1000 U/d of cholecalciferol; P=0.04). For each 1-ng/mL increase in plasma 25-hydroxyvitamin D, there was a significant 0.2-mm Hg reduction in systolic pressure (P=0.02). There was no effect of cholecalciferol supplementation on diastolic pressure (P=0.37). Within an unselected population of blacks, 3 months of oral vitamin D3 supplementation significantly, yet modestly, lowered systolic pressure. Future trials of vitamin D supplementation on blood pressure are needed to confirm these promising results, particularly among blacks, a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension.


A first insight into the genomic diversity of Leptospira strains isolated from patients in Cuba.
Leptospirosis is a neglected disease causing severe infections in humans and animals. Due in part to misdiagnosis, this infectious disease results in nearly 60,000 deaths per year around the globe. This study represents the first effort to describe the diversity of pathogenic Leptospira in Cuba based on whole-genome sequencing. We have collected nineteen whole-blood samples from patients that were diagnosed as having leptospirosis between 2008 and 2012 in Cuba. In addition, we have enhanced our sample set by three historical strains that were used for the development of a human vaccine in 1990s. The Leptospira strains were grown and serotyped by the microscopic agglutination test, and the draft genomes were generated by NGS (Illumina). Subsequently, the core genomes were analyzed and compared to the genetic data available from other Caribbean islands and countries in Central America. Core genome Multi-locus Sequence Typing (cgMLST) revealed four different core genome clonal groups (cgCGs), with the highest number of samples belonging to L. interrogans, followed by L. borgpetersenii and L. kirschneri. All cgCGs that were found in Cuba have been also identified from multiple origins across the globe, except in neighbor countries and Central America. Serotyping divided the samples into the serogroups Canicola, Ballum and Pomona. The most frequent cgCGs, cgCG28, associated with serogroup Canicola, and cgCG15, associated with serogroup Ballum, have also been identified from samples isolated from dogs, rodents, and pigs; suggesting that these hosts represent the major source of human infection in Cuba. The vaccine strains did not significantly differ from the recent patient isolates. However, the increasing prevalence of samples belonging to the serogroup Ballum combined with the fact that the available vaccine in Cuba represents inactivated Leptospira belonging to serogroups other than Ballum, should be a valuable information for the National and Regional Leptospirosis Control Programs.


Assessment of silent embolism from carotid endarterectomy by use of diffusion-weighted imaging: work in progress.
Transcranial Doppler studies have suggested that microemboli are released into the arterial circulation during the majority of carotid endarterectomy (CEA) procedures. This, together with the observation that neuropsychological performance may decline postoperatively, has led to concern that cerebral infarction may occur unrecognized during CEA. Our objective was to examine this risk with diffusion-weighted imaging, a technique that is highly sensitive to acute cerebral infarction. Eighteen participants (median age, 68 years; age range, 56-87 years) were assessed with diffusion-weighted imaging and the National Institutes of Health Stroke Scale before and after CEA. Imaging was performed using single-shot echo-planar imaging with a maximum diffusion sensitivity of b = 1000 s/mm(2) applied to three orthogonal planes. Preoperative imaging was performed a median of 2.5 hours before surgery (range, 0.5-12.5 hours) and 15 hours after surgery (range, 1.5-58.5 hours). Two neuroradiologists independently interpreted the diffusion-weighted images, blinded to operative status and clinical findings. There was no diffusion-weighted imaging evidence of silent embolism in this series of 18 participants (95% confidence interval limits, 0 to 10%). Clinical complications were confined to one case of confusion occurring after CEA; the diffusion-weighted imaging results were normal in this case. There is no evidence from our series that silent cerebral infarction is a common occurrence during CEA. These data provide further support for the safety of CEA.


[Use of oral contraceptives and increased risk of cervical cancer].
A recently published meta-analysis and a large cohort study showed independently that use of oral contraceptives (OC) leads to an increased relative risk (RR) of cervical cancer. This RR increased with the duration of OC use and was 1.90 after 5 years or more (95% CI: 1.69-2.13). The increased RR decreased after cessation of OC use and was normal again Io years later. Longstanding OC use enhances human papillomavirus (HPV) transcription and decreases HPV clearance, resulting in more frequent persistence of HPV, an increase of cervical intraepithelial neoplasia, and an increased RR of cervical cancer. The increase in cervical cancer by OC is, however, associated with a fully compensatory decrease in the incidence of other malignancies, in particular ovarian cancer and endometrial cancer. Based on these findings, there are no reasons to discourage the use of OC by women in the Netherlands.


Protocadherin 7 is overexpressed in castration resistant prostate cancer and promotes aberrant MEK and AKT signaling.
Castrate resistant prostate cancer (CRPC) accounts for almost all prostate cancer (PCa) deaths. Aberrant activation of ERK/MEK and PI3K/AKT signaling pathways plays an important role in subsets of patients with CRPC. The role of protocadherin 7 (PCDH7) in modulating these signaling pathways is investigated for the first time in PCa in the present investigation. PCDH7 expression was analyzed in CRPC/neuroendocrine prostate cancer (NEPC) dataset. Protein expression was assessed by Western blotting and immunohistochemistry, and messenger RNA (mRNA) by quantitative real-time polymerase chain reaction. Small hairpin ribonucleic acid was used to knockdown PCDH7. Colony formation, cell migration, and invasion studies were done using standard protocols. PCDH7 amplification/mRNA upregulation was observed in 41% of patients in CRPC/NEPC dataset. PCDH7 was also overexpressed in CRPC cells. Increased PCDH protein expression was observed during tumor progression in PCa tissues and in TRAMP mice. Epidermal growth factor treatment resulted in aberrant activation of ERK/AKT. Knockdown of PCDH7 decreased ERK, AKT, and RB phosphorylation and reduced colony formation, decreased cell invasion, and cell migration. These data show for the first time that PCDH7 is overexpressed in a large number of patients with CRPC and suggest that PCDH7 may be an attractive target in subsets of patients with CRPC for whom there is no cure to-date.


Effect of Fusarium virguliforme phytotoxin on soybean gene expression suggests a role in multidimensional defence.
Sudden death syndrome (SDS), caused by Fusarium virguliforme, is an important yield-limiting disease of soybean. This soil-borne fungus colonizes soybean roots causing root rot, and also releases a phytotoxin that is translocated to leaves causing interveinal chlorosis and necrosis leading to defoliation and early maturation. The objective of our study was to compare gene expression profiles during the early response of soybean leaves exposed to sterile culture filtrates of F. virguliforme in soybean genotypes with different levels of resistance to SDS. The analysis identified SDS-related defence genes that were induced in the most resistant genotype, but not in the other genotypes. Further functional annotations based on sequence homology suggested that some of the induced genes probably encode proteins involved in cell wall modification, detoxification, defence responses, primary metabolism and membrane transport. Quantitative real-time reverse-transcribed polymerase chain reaction confirmed the differential transcript accumulation of a subset of these genes. In addition, in silico mapping of differentially expressed genes to SDS-resistant quantitative trait loci allowed for the identification of new potential defence genes that could be genetically mapped to the soybean genome, and could be used further in a marker-assisted selection programme. A comparison of the response of soybean to F. virguliforme phytotoxin (Fv toxin) relative to other biotic and abiotic stresses revealed that the resistance response to Fv toxin is quite similar to the response to inoculation with an incompatible Pseudomonas syringae pv. glycinea strain, suggesting that Fv toxin might induce hypersensitive response pathways in soybean leaf tissues in the absence of pathogen in these tissues.


Ligand binding to transiently accessible sites: mechanisms for varying apparent binding rates.
Many biological processes are characterized by models where ligand has continuous access to binding sites. Use-dependent processes such as ion channel blockade appear to represent a class of processes where binding site access is transient and is dependent on channel conformation (state). (Alternatively, the existence of a proper conformation for binding might be transient.) We assume binding takes place only with a site that is accessible or in a bindable conformation. For ion channels, channel conformation responds to local chemical or electrical stimulation. The stimulus amplitude determines the mixture of channels with accessible and inaccessible sites. When conformation equilibrium is achieved rapidly in relation to ligand binding, then ligand binding can be considered the result of an apparent binding rate determined by the true binding rate as modified by the fraction of accessible sites. With repetitive stimulation, the continuous access model can be extended to a setting where apparent binding rates repetitively switch in response to the stimulus induced variation in mixture of site states. The resulting theoretical description provides a means for relating equilibrium binding parameters with those obtained under conditions of repetitive stimulation. In particular: (1) binding is piecewise exponential; (2) the envelope of binding measured at each pulse in a train varies exponentially with an apparent rate linearly dependent on the mixture specific rates; and (3) the steady state degree of binding site saturation is linearly dependent on the mixture specific equilibria.


6 Paths of ERK5 signaling pathway regulate hepatocyte proliferation in rat liver regeneration.
Generally, extra-cellular-signal-regulated kinase 5 (ERK5) signaling pathway regulates many physiological activities, such as cell proliferation and cell differentiation. However, little is known about how ERKS signaling pathway composed of 15 paths participates in regulating hepatocyte proliferation during liver regeneration (LR). In this study, to explore the influence ERK5 signaling pathway upon hepatocytes at gene transcription level, rat genome 230 2.0 array was used to detect expression changes of 75 related genes in isolated hepatocytes from rat regenerating liver. Bioinformatics and systems biology methods were applied to analyze the precise role of ERK5 signaling pathway in regulating hepatocyte proliferation during LR. Results showed that 62 genes were contained in the array and 22 genes were significantly changed. It was found that 6 paths were related to hepatocyte proliferation during rat LR. Among them, paths 3, 6 and 13 of ERK5 signaling pathway modulated cell cycle progression by decreasing the negative influence on ERK5 and paths 3, 4, 8 and 9 by reinforcing the positive influence on ERK5. In summary, the study shows that 22 genes and 6 paths of ERK5 signaling pathway participate in regulating proliferation of hepatocytes in rat LR.


[Clinical management of oral disorders in breastfeeding].
To address aspects associated with the early detection and clinical management of oral disorders in breastfeeding. Review of bibliographic sources (research articles, technical books, dissertations and national and international publications) focused on the clinical management of oral disorders in breastfed babies. Suction disorders may lead to inadequate actions that can compromise the mother/baby relation during breastfeeding. Healthcare professionals may have an important role in these cases, as they can detect such disorders early. For that end, they must be able to assess breastfeeding and be prepared to manage oral disorders clinically. In the clinical management of babies with breastfeeding difficulties significant aspects of the oral physiology and breastfeeding observation should be considered. We stress the importance of an interdisciplinary team work and the need for oral training and specialized care in most complex cases. The baby's oral disorders in breastfeeding can be corrected if they were early detected. Healthcare professionals may help mothers and babies to overcome these problems if they have knowledge that enable them to perform right clinical procedures.


Evaluation of Quality of Life and Care Needs of Turkish Patients Undergoing Hematopoietic Stem Cell Transplantation.
This descriptive study explored the quality of life and care needs of Turkish patients who underwent hematopoietic stem cell transplantation. The study sample consisted of 100 hematopoietic stem cell transplant patients. Their quality of life was assessed using Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale. The mean patient age was 44.99 ± 13.92 years. Changes in sexual functions, loss of hair, loss of taste, loss of appetite, and sleep disturbances were the most common symptoms. The quality of life of transplant patients was moderately affected; the functional well-being and social/family well-being subscales were the most adversely and least negatively affected (12.13 ± 6.88) dimensions, respectively. Being female, being between 50 and 59 years of age, being single, having a chronic disease, and having a history of hospitalization were associated with lower quality of life scores. Interventions to improve functional status, physical well-being, and emotional status of patients during the transplantation process may help patients cope with treatment-related impairments more effectively. Frequent screening and management of patient symptoms in order to help patients adapt to life following allogeneic hematopoietic stem cell transplantation are crucial for meeting care needs and developing strategies to improve their quality of life.


Association between dietary patterns during pregnancy and birth size measures in a diverse population in Southern US.
Despite increased interest in promoting nutrition during pregnancy, the association between maternal dietary patterns and birth outcomes has been equivocal. We examined maternal dietary patterns during pregnancy as a determinant of offspring's birth weight-for-length (WLZ), weight-for-age (WAZ), length-for-age (LAZ), and head circumference (HCZ) Z-scores in Southern United States (n=1151). Maternal diet during pregnancy was assessed by seven dietary patterns. Multivariable linear regression models described the association of WLZ, WAZ, LAZ, and HCZ with diet patterns controlling for other maternal and child characteristics. In bivariate analyses, WAZ and HCZ were significantly lower for processed and processed-Southern compared to healthy dietary patterns, whereas LAZ was significantly higher for these patterns. In the multivariate models, mothers who consumed a healthy-processed dietary pattern had children with significantly higher HCZ compared to the ones who consumed a healthy dietary pattern (HCZ β: 0.36; p=0.019). No other dietary pattern was significantly associated with any of the birth outcomes. Instead, the major outcome determinants were: African American race, pre-pregnancy BMI, and gestational weight gain. These findings justify further investigation about socio-environmental and genetic factors related to race and birth outcomes in this population.


Lipophagy-derived fatty acids undergo extracellular efflux via lysosomal exocytosis.
The autophagic degradation of lipid droplets (LDs), termed lipophagy, is a major mechanism that contributes to lipid turnover in numerous cell types. While numerous factors, including nutrient deprivation or overexpression of PNPLA2/ATGL (patatin-like phospholipase domain containing 2) drive lipophagy, the trafficking of fatty acids (FAs) produced from this pathway is largely unknown. Herein, we show that PNPLA2 and nutrient deprivation promoted the extracellular efflux of FAs. Inhibition of autophagy or lysosomal lipid degradation attenuated FA efflux highlighting a critical role for lipophagy in this process. Rather than direct transport of FAs across the lysosomal membrane, lipophagy-derived FA efflux requires lysosomal fusion to the plasma membrane. The lysosomal Ca2+ channel protein MCOLN1/TRPML1 (mucolipin 1) regulates lysosomal-plasma membrane fusion and its overexpression increased, while inhibition blocked FA efflux. In addition, inhibition of autophagy/lipophagy or MCOLN1, or sequestration of extracellular FAs with BSA attenuated the oxidation and re-esterification of lipophagy-derived FAs. Overall, these studies show that the well-established pathway of lysosomal fusion to the plasma membrane is the primary route for the disposal of FAs derived from lipophagy. Moreover, the efflux of FAs and their reuptake or subsequent extracellular trafficking to adjacent cells may play an important role in cell-to-cell lipid exchange and signaling.Abbreviations: ACTB: beta actin; ADRA1A: adrenergic receptor alpha, 1a; ALB: albumin; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A1; BECN1: beclin 1; BHBA: beta-hydroxybutyrate; BSA: bovine serum albumin; CDH1: e-cadherin; CQ: chloroquine; CTSB: cathepsin B; DGAT: diacylglycerol O-acyltransferase; FA: fatty acid; HFD: high-fat diet; LAMP1: lysosomal-associated membrane protein 1; LD: lipid droplet; LIPA/LAL: lysosomal acid lipase A; LLME: Leu-Leu methyl ester hydrobromide; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MCOLN1/TRPML1: mucolipin 1; MEF: mouse embryo fibroblast; PBS: phosphate-buffered saline; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PLIN: perilipin; PNPLA2/ATGL patatin-like phospholipase domain containing 2; RUBCN (rubicon autophagy regulator); SM: sphingomyelin; TAG: triacylglycerol; TMEM192: transmembrane protein 192; VLDL: very low density lipoprotein.


Amplification of Escherichia coli in a Continuous-Flow-PCR Microfluidic Chip and Its Detection with a Capillary Electrophoresis System.
Polymerase chain reaction (PCR) is a traditional method employed for the amplification of a target gene that has played an important role in biomolecular diagnostics. However, traditional PCR is very time-consuming because of the low-temperature variation efficiency. This work proposes a continuous-flow-PCR (CF-PCR) system based on a microfluidic chip. The amplification time can be greatly reduced by running the PCR solution into a microchannel placed on heaters set at different temperatures. Moreover, as capillary electrophoresis (CE) is an ideal way to differentiate positive and false-positive PCR products, a CE system was built to achieve efficient separation of the DNA fragments. This paper describes the process of amplification of Escherichia coli (E. coli) by the CF-PCR system built in-house and the detection of the PCR products by CE. The results demonstrate that the target gene of E. coli was successfully amplified within 10 min, indicating that these two systems can be used for the rapid amplification and detection of nucleic acids.


GRP78: a chaperone with diverse roles beyond the endoplasmic reticulum.
Glucose-regulated protein 78 (GRP78) is a well-characterized molecular chaperone that is ubiquitously expressed in mammalian cells. GRP78 is best known for binding to hydrophobic patches on nascent polypeptides within the endoplasmic reticulum (ER) and for its role in signaling the unfolded protein response. Structurally, GRP78 is highly conserved across species. The presence of GRP78 or a homologue in nearly every organism from bacteria to man, reflects the central roles it plays in cell survival. While the principal role of GRP78 as a molecular chaperone is a matter of continuing study, independent work demonstrates that like many other proteins with ancient origins, GRP78 plays more roles than originally appreciated. Studies have shown that GRP78 is expressed on the cell surface in many tissue types both in vitro and in vivo. Cell surface GRP78 is involved in transducing signals from ligands as disparate as activated alpha2-macroglobulin and antibodies. Plasmalemmar GRP78 also plays a role in viral entry of Coxsackie B, and Dengue Fever viruses. GRP78 disregulation is also implicated in atherosclerotic, thrombotic, and auto-immune disease. It is challenging to posit a hypothesis as to why an ER molecular chaperone, such as GRP78, plays such a variety of roles in cellular processes. An ancient and highly conserved protein such as GRP78, whose primary function is to bind to misfolded polypeptides, could be uniquely suited to bind a wide variety of ligands and thus, over time, could assume the wide variety of roles it now plays.


Functional layered materials with heavy metal lone pair cations, Pb2+, Bi3+, and Te4.
Owing to their various important structure-driven properties, functional layered materials have been of great interest. In this feature article, a series of recently discovered novel layered materials with heavy metal lone pair cations containing Pb2+, Bi3+, and Te4+ are introduced. The layered materials include (1) the first Pb2+-Kemp's triacid coordination complex showing selective CO2 adsorption and an intercalative ligand addition reaction, Pb3[C6(CH3)3(CO2)3H6]2[DMF]3, (2) a tailor-made polar lead borate chloride with a very strong second-harmonic generation (SHG) response, Pb2BO3Cl, (3) a white light emitting single component Pb+-based coordination polymer exhibiting high quantum efficiency and thermal stability, Pb[NC5H3(CO2)2], (4) noncentrosymmetric (NCS) n = 3 Dion-Jacobson layered perovskites with a variety of NCS characteristics, polar RbBi2Ti2NbO10 and nonpolar CsBi2Ti2TaO10, (5) layered bismuth oxyfluoride nitrates revealing photocatalytic properties and large SHG, Bi2OF3(NO3) and Bi6O6F5(NO3), (6) a layered bismuth tellurium nitrate hydroxide with multiple NCS chromophores, Bi2Te2O6(NO3)2(OH)2(H2O), (7) a mixed-valent layered tellurite-tellurate with robust ion-exchange behavior, Na2Te2O6·1.5H2O, and (8) a metastable lithium molybdenum tellurite undergoing Li+-exchange-driven facile structural transformation reactions, Li2Mo3TeO12. The syntheses, structures, representative properties, and structure-property relationships for the layered materials are presented.


Calcium-sensing receptors and parathyroid hormone-related protein in the caudal neurosecretory system of the flounder (Platichthys flesus).
The caudal neurosecretory system of the flounder (Platichthys flesus) has been examined by immunocytochemistry and in situ hybridization for the expression of parathyroid hormone-related protein (PTHrP) and calcium-sensing receptors (CaSR). The N-terminus nucleotide and deduced amino acid sequences of flounder PTHrP were determined and used to prepare oligonucleotide probes and homologous antiserum. The Dahlgren cells of the posterior spinal cord and their axons contained PTHrP protein which was also detected around the capillaries of the urophysis. PTHrP gene expression was abundant in the Dahlgren perikarya and axons in the spinal cord, but it was absent from nerve endings in the urophysis. Calcium-sensing receptor protein was present in the Dahlgren perikarya and axons, also with abundant gene expression, but there was neither protein nor mRNA in the urophysis. There were no apparent differences between freshwater- and seawater-adapted fish in either CaSR or PTHrP expression in the caudal neurosecretory system. These observations suggest that Dahlgren cells produce PTHrP which may be released from axons abutting capillaries in the urophysis. However, the sensing of ionic calcium appears to be confined to the perikarya of the Dahlgren cells in the spinal cord neuropil, suggesting that they are responsive to calcium in the central nervous system rather than the general circulation.


Combining distributed regression and propensity scores: a doubly privacy-protecting analytic method for multicenter research.
Sharing of detailed individual-level data continues to pose challenges in multi-center studies. This issue can be addressed in part by using analytic methods that require only summary-level information to perform the desired multivariable-adjusted analysis. We examined the feasibility and empirical validity of 1) conducting multivariable-adjusted distributed linear regression and 2) combining distributed linear regression with propensity scores, in a large distributed data network. We compared percent total weight loss 1-year postsurgery between Roux-en-Y gastric bypass and sleeve gastrectomy procedure among 43,110 patients from 36 health systems in the National Patient-Centered Clinical Research Network. We adjusted for baseline demographic and clinical variables as individual covariates, deciles of propensity scores, or both, in three separate outcome regression models. We used distributed linear regression, a method that requires only summary-level information (specifically, sums of squares and cross products matrix) from sites, to fit the three ordinary least squares linear regression models. A comparison set of analyses that used pooled deidentified individual-level data from sites served as the reference. Distributed linear regression produced results identical to those from the corresponding pooled individual-level data analysis for all variables in all three models. The maximum numerical difference in the parameter estimate or standard error for all the variables was 3×10-11 across three models. Distributed linear regression analysis is a feasible and valid analytic method in multicenter studies for one-time continuous outcomes. Combining distributed regression with propensity scores via modeling offers more privacy protection and analytic flexibility.


A real-time measurement system for long-life flood monitoring and warning applications.
A flood warning system incorporates telemetered rainfall and flow/water level data measured at various locations in the catchment area. Real-time accurate data collection is required for this use, and sensor networks improve the system capabilities. However, existing sensor nodes struggle to satisfy the hydrological requirements in terms of autonomy, sensor hardware compatibility, reliability and long-range communication. We describe the design and development of a real-time measurement system for flood monitoring, and its deployment in a flash-flood prone 650 km(2) semiarid watershed in Southern Spain. A developed low-power and long-range communication device, so-called DatalogV1, provides automatic data gathering and reliable transmission. DatalogV1 incorporates self-monitoring for adapting measurement schedules for consumption management and to capture events of interest. Two tests are used to assess the success of the development. The results show an autonomous and robust monitoring system for long-term collection of water level data in many sparse locations during flood events.


Anxiety and depression in women and men from early pregnancy to 3-months postpartum.
To investigate high-anxiety and depression in women and men from early pregnancy to 3-months postpartum, 260 Portuguese couples (N = 520) filled in the State-Anxiety Inventory (STAI-S) and the Edinburgh Post-Natal Depression Scale (EPDS) at the first, second, and third pregnancy trimesters, childbirth, and 3-months postpartum. Rates for high-anxiety (STAI-S ≥ 45) in women (13.1%; 12.2%; 18.2%; 18.6%; 4.7%) and men (10.1%; 8.0%, 7.8%; 8.5%; 4.4%) and for depression (EPDS ≥ 10) in women (20.0%, 19.6%, 17.4%, 17.6%; 11.1%) and men (11.3%; 6.6%; 5.5%; 7.5%; 7.2%) were high. Rates for depression were higher than rates for high-anxiety only in women during early pregnancy and the postpartum, but not at the third pregnancy trimester and childbirth. Rates for high-anxiety and depression were higher in women than in men during pregnancy/childbirth, but not at 3-months postpartum. Rates for high-anxiety but not rates for depression were higher during pregnancy/childbirth compared to 3-months postpartum and only in women. Considering that 15.9% of the parents-to-be were highly anxious and/or depressed during pregnancy-comparing to 9.3% at 3-months postpartum-particular attention should be drawn to both women's and men's mental health early in pregnancy.


Estimating the range of incremental cost-effectiveness thresholds for healthcare based on willingness to pay and GDP per capita: A systematic review.
Decision-making in healthcare policy involves assessing both costs and benefits. In determining the cost-effectiveness (CE) threshold, willingness to pay (WTP) per quality-adjusted life year (QALY), GDP per capita, and other factors are important. However, the relationship between WTP/QALY or GDP per capita and the CE threshold is unclear. It is important to clarify the relationship between WTP/QALY and GDP to provide a clear basis for setting the CE threshold. The purpose of this study was to compare WTP/QALY and GDP per capita, and to develop a new CE threshold range based on WTP using GDP per capita. The relationship between WTP/QALY and healthy life expectancy (HALE) was also investigated. We searched MEDLINE, EMBASE and Web of Science from 1980/01/01 to 2020/12/31 using the following selection criteria (latest search: Dec 2021):1, studies that estimated WTP/QALY; 2, the general population was surveyed; 3, the article was in English. From the collected articles, we obtained average values of WTP/QALY for various countries and compared WTP/QALY with GDP per capita. The correlation between WTP/QALY and HALE was also examined. We identified 20 papers from 17 countries. Comparison of mean WTP/QALY values with GDP per capita showed that most WTP/QALY values were in the range of 0.5-1.5 times GDP per capita, though the median values were less than 0.5 times. Comparison of WTP/QALY with HALE showed a statistically significant positive correlation when Taiwan was excluded as an outlier. Our results suggest a CE threshold range of 0.5-1.5 times GDP per capita is appropriate but lower than the WHO-recommended range of 1-3 times. The correlation between WTP/QALY and HALE suggests that investment in healthcare is reflected in an increased healthy life expectancy. Since WTP is based on consumer preferences, this range could be used to set a generally acceptable criterion.


A systematic review and meta-analysis of randomized trials and prospective studies comparing covered and bare self-expandable metal stents for the treatment of malignant obstruction in the digestive tract.
Self-expandable metal stents (SEMS) are widely used for the palliative treatment of malignant gastrointestinal obstruction. Our aim was to evaluate the evidence comparing covered and bare SEMS in the digestive tract using meta-analytical techniques. A literature search was performed using PubMed, Cochrane Library, and Embase databases for comparative studies assessing the two types of stents. The primary outcomes of interest were stent patency and patient survival; second outcomes included technical success, clinical success, tumor ingrowth, tumor overgrowth, and stent migration. A random-effects model was conducted. Pooled analysis was done separately based on the different segments of the digestive tract. Eleven studies (8 randomized controlled trials and 3 prospective cohort studies) including a total of 1376 patients were identified. Covered SEMS were equivalent to bare SEMS in terms of technical success, clinical success, stent patency (gastroduodenal obstruction: HR =0.87, 95% CI 0.53-1.42; colorectal obstruction: HR =0.89, 95% CI 0.18-4.45; biliary obstruction: HR =0.73, 95% CI 0.41-1.32) and survival rates (esophageal obstruction: HR =1.80, 95% CI 0.73-4.44; gastroduodenal obstruction: HR =0.83, 95% CI 0.55-1.26; biliary obstruction: HR =0.99, 95% CI 0.77-1.28), although bare stents were more prone to tumor ingrowth (esophageal obstruction: RR =0.10, 95% CI 0.01-0.77; gastroduodenal obstruction: RR =0.12, 95% CI 0.03-0.55; colorectal obstruction: RR =0.21, 95% CI 0.06-0.70; biliary obstruction: RR =0.21, 95% CI 0.06-0.69), whereas covered stents had the higher risk of stent migration (gastroduodenal obstruction: RR =5.01, 95% CI 1.53-16.43; colorectal obstruction: RR =11.70, 95% CI 2.84-48.27; biliary obstruction: RR =8.11, 95% CI 1.47-44.76) and tumor overgrowth (biliary obstruction: RR =2.03, 95% CI 1.08-3.78). Both covered and bare SEMS are comparable in efficacy for the palliative treatment of malignant obstruction in the digestive tract. Each type of the stents has its own merit and demerit relatively.


Human heat shock protein 70 peptide complexes specifically activate antimelanoma T cells.
Members of the heat shock protein 70 (HSP70) family display a broad cellular localization and thus bind a repertoire of chaperoned peptides potentially derived from proteins of different cellular compartments. In this report, we show that HSP70 purified from human melanoma can activate T cells recognizing melanoma differentiation antigens in an antigen- and HLA class I-dependent fashion. HLA class I-restricted anti-melanoma T cells were susceptible to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 complexed peptides were able to gain access to the class I HLA presentation pathway. In addition, MHC matching between the melanoma cells used as a source of HSP and the responding T cells were not required, indicating that HSP70 activation may occur across MHC barriers. Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed peptides or HSP70 purified from antigen-negative cells was also able to induce IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism. In this case, however, higher doses of HSP70 were required. The capacity to activate class I-restricted, antitumor T cells as well as antigen-presenting cells, together with the finding that the HSP70 chaperoned peptide repertoire includes melanoma-shared epitopes, holds promise for a HSP70-based cancer vaccine.


Mothers and their pregnancies: a comparison of three population-based cohorts in Southern Brazil.
Mothers from the 1982, 1993 and 2004 Pelotas birth cohorts were compared across biological, socioeconomic, demographic and reproductive characteristics. Women in the 2004 cohort had higher levels of education, gained more weight during pregnancy, and were heavier at the beginning and end of their pregnancy than mothers who gave birth in 1993 and 1982. There was an important increase in obesity rates (body mass index > 30kg/m(2)) over the 22 years of the study. Mean parity decreased from 1.3 in 1982 to 1.1 in 2004, with a growing proportion of primiparas and a decline in the proportion of women with > or = 4 children. The mean birth interval increased from 33.5 months in 1982 to 65.7 in 2004. Smoking during pregnancy decreased from 35.6% in 1982 to 25.1% in 2004. As with other characteristics, the change in smoking status differed according to income, with higher reductions among the wealthiest (from 24.9% to 8.7%) than among the poorest mothers (from 43.7% to 33.6%). In general terms, between 1993 and 2004 there was a decrease in the prevalence of maternal risk factors for unfavorable perinatal outcomes.


Use of anesthetic agents in neonates and young children.
Some drugs used for sedation and anesthesia produce histopathologic central nervous system changes in juvenile animal models. These observations have raised concerns regarding the use of these drugs in pediatric patients. We summarized the findings in developing animals and describe the steps that the Food and Drug Administration (FDA) and others are taking to assess potential risks in pediatric patients. The FDA views this communication as opening a dialog with the anesthesia community to address this issue. We reviewed the available animal studies literature examining the potential neurotoxic effects of commonly used anesthetic drugs on the developing brain. The search strategy involved crossing the keywords neurotoxic and neuroapoptosis with the following general and specific terms: anesthetic, N-methyl-d-aspartate (NMDA), ketamine, midazolam, lorazepam, fentanyl, methadone, morphine, meperidine, isoflurane, nitrous oxide, sevoflurane, halothane, enflurane, desflurane, propofol, etomidate, barbiturate, methoxyflurane, and chloral hydrate. We summarized several studies sponsored by the FDA in rats and monkeys, initially examining the potential for ketamine, as a prototypical agent, to induce neurodegeneration in the developing brain. Numerous animal studies in rodents indicate that NMDA receptor antagonists, including ketamine, induce neurodegeneration in the developing brain. The effects of ketamine are dose dependent. The data suggest that limiting exposure limits the potential for neurodegeneration. There is also evidence that other general anesthetics, such as isoflurane, can induce neurodegeneration in rodent models, which may be exacerbated by concurrent administration of midazolam or nitrous oxide. There are very few studies that have examined the potential functional consequences of the neurodegeneration noted in the animal models. However, the studies that have been reported suggest subtle, but prolonged, behavioral changes in rodents. Although the doses and durations of ketamine exposure that resulted in neurodegeneration were slightly larger than those used in the clinical setting, those associated with isoflurane were not. There are insufficient human data to either support or refute the clinical applicability of these findings. Animal studies suggest that neurodegeneration, with possible cognitive sequelae, is a potential long-term risk of anesthetics in neonatal and young pediatric patients. The existing nonclinical data implicate not only NMDA-receptor antagonists, but also drugs that potentiate gamma-aminobutyric acid signal transduction, as potentially neurotoxic to the developing brain. The potential for the combination of drugs that have activity at both receptor systems or that can induce more or less neurotoxicity is not clear; however, recent nonclinical data suggest that some combinations may be more neurotoxic than the individual components. The lack of information to date precludes the ability to designate any one anesthetic agent or regimen as safer than any other. Ongoing studies in juvenile animals should provide additional information regarding the risks. The FDA anticipates working with the anesthesia community and pharmaceutical industry to develop strategies for further assessing the safety of anesthetics in neonates and young children, and for providing data to guide clinicians in making the most informed decisions possible when choosing anesthetic regimens for their pediatric patients.