Hypogammaglobulinemia in lung transplant recipients.
Infectious complications continue to represent a significant source of morbidity and mortality in lung transplant recipients. Identifying specific, remediable immune defects is of potential value. After one lung transplant patient with recurrent infections was noted to be severely hypogammaglobulinemic, a screening program for humoral immune defects was instituted. The objectives were to define the prevalence of hypogammaglobulinemia in lung transplant recipients, assess levels of antibody to specific pathogens, and correlate infectious disease outcomes and survival with immunoglobulin levels. All lung transplant recipients followed at a single center between October 1996 and June 1999 underwent a posttransplant humoral immune status survey as part of routine posttransplant follow-up. This survey consists of total immunoglobulin levels (IgG, IgM, IgA), IgG subclasses (IgG1-4), and antibody titers to Pneumococcus, diphtheria, and tetanus. Since February 1997, this survey has been incorporated into the pretransplant evaluation as well. Humoral survey results for October 1996 through July 1999 were recorded, and clinical information on major infectious disease outcomes was obtained from chart reviews, discharge summaries, the Cleveland Clinic Unified Transplant Database, and review of all microbiological studies and pathology results for each patient. Of 67 patients with humoral immune surveys drawn posttransplant, 47 (70%) had IgG levels less than 600 mg/dl (normal 717-1410 mg/dl), of which 25 (37%) had IgG levels less than 400 mg/dl ("lowest IgG group") and 22 (33%) had IgG levels between 400 and 600 mg/dl ("moderately low IgG group"). A total of 20 patients (30%) had IgG levels of more than 600 mg/dl ("normal IgG group"). Infections that were significantly more common in the lowest IgG group, and more common in the moderately low IgG group than the normal IgG group, included: number of pneumonias (P=0.0006), bacteremias (P=0.02), total bacterial infections (P=0.002), tissue-invasive cytomegalovirus (P=0.01), invasive aspergillosis (P=0.001), total fungal infections (P=0.001), and total infections (P=0.006). Median hospital days per posttransplant year was significantly different in the three groups (11.0 vs. 7.4 vs. 2.8 days, P=0.0003.) Invasive aspergillosis occurred in 44% of the lowest IgG group, 9% of the moderately low IgG group, and 0% of the normal IgG group (P<0.001). Survival was poorest in the lowest IgG group and intermediate in the moderately low IgG group. IgG subclass deficiencies occurred in a variety of patterns. Hypogammaglobulinemic patients lacked protective responses to Pneumococcus in 14/47 (30%), diphtheria in 15%, and tetanus in 19%. In a group of 48 patients screened pretransplant, 90% had normal immunoglobulin levels. Hypogammaglobulinemia in lung transplant recipients is more common than has been previously recognized. An IgG level of less than 400 mg/dl identifies a group at extremely high risk of bacterial and fungal infections, tissue-invasive cytomegalovirus, and poorer survival. Immunoglobulin monitoring may offer an opportunity for intensive surveillance, tapering of immunosuppression, and preemptive therapy for infection.


Assessing distress in the community: psychometric properties and crosswalk comparison of eight measures of psychological distress.
Many measures are available for measuring psychological distress in the community. Limited research has compared these scales to identify the best performing tools. A common metric for distress measures would enable researchers and clinicians to equate scores across different measures. The current study evaluated eight psychological distress scales and developed crosswalks (tables/figures presenting multiple scales on a common metric) to enable scores on these scales to be equated. An Australian online adult sample (N = 3620, 80% female) was administered eight psychological distress measures: Patient Health Questionnaire-4, Kessler-10/Kessler-6, Distress Questionnaire-5 (DQ5), Mental Health Inventory-5, Hopkins Symptom Checklist-25 (HSCL-25), Self-Report Questionnaire-20 (SRQ-20) and Distress Thermometer. The performance of each measure in identifying DSM-5 criteria for a range of mental disorders was tested. Scale fit to a unidimensional latent construct was assessed using Confirmatory Factor Analysis (CFA). Finally, crosswalks were developed using Item Response Theory. The DQ5 had optimal performance in identifying individuals meeting DSM-5 criteria, with adequate fit to a unidimensional construct. The HSCL-25 and SRQ-20 also had adequate fit but poorer specificity and/or sensitivity than the DQ5 in identifying caseness. The unidimensional CFA of the combined item bank for the eight scales showed acceptable fit, enabling the creation of crosswalk tables. The DQ5 had optimal performance in identifying risk of mental health problems. The crosswalk tables developed in this study will enable rapid conversion between distress measures, providing more efficient means of data aggregation and a resource to facilitate interpretation of scores from multiple distress scales.


Efficacy of wearable vibration dressings on full-thickness wound healing in a hyperglycemic rat model.
Local low-frequency vibration promotes blood flow and wound healing in hard-to-heal diabetic foot ulcers (DFUs). However, vibration treatment is challenging in patients with DFUs due to wound management difficulties and low adherence. Consequently, developing wearable self-care devices becomes imperative for effective wound healing. This study introduces a wearable vibration dressing and assesses its impact on wound healing in hyperglycemic rats. Low-frequency vibration at 52 Hz was applied to the wound for 40 min/day in awake rats. Relative wound areas on post-wounding days (PWDs) 4-7 were significantly smaller and the wound closure rate was significantly higher in the vibration group than in the control group (p < 0.05, respectively). The total haemoglobin at baseline and after vibration on post-wounding day 7 was significantly larger in the vibration group than in the control group (p < 0.05). On PWD 7, the thickness of the granulation tissue was significantly higher in the vibration group than in the control group (p < 0.05). Moreover, the number of blood vessels at the wound site and vascular endothelial growth factor A protein expression were significantly higher in the vibration group than in the control group (p < 0.05, respectively). The ratio of (CD68+ /iNOS+ )/(CD163+ ) macrophages in the vibration group was significantly lower than that in the control group (p < 0.05). These results indicate the potential of wearable vibration dressings as new self-care devices that can promote angiogenesis and blood flow, improve inflammation, and enhance wound healing in DFUs.


Characteristic forms of the upper part of the oral cavity in newborns with isolated cleft palate.
To determine the functional and morphological compensation of the lack of integrity in the upper part of the oral cavity in newborns with isolated cleft palate. Integrity of the upper part of the oral cavity is required for the effective pumping of amniotic fluid, the essential mode of nutrition in intrauterine life. The adaptation could be seen immediately after birth. Plaster casts of the upper part of the oral cavity in 60 newborns with isolated cleft palate of various extent and plaster casts of the upper part of the oral cavity in 27 newborns without cleft were used. A number of surface points were identified and used for a trigonometric morphological analysis. The parameters of the upper part of the oral cavity in four groups of newborns with various extent of isolated cleft palate were compared with newborns without cleft palate. The results indicate a shift of the functional oral cavity into the nasal cavity and the pharynx, depending on the extent of the cleft. The pumping activity of the tongue forms the upper part of the oral cavity and consequently the tongue moves into the nasal cavity and pharynx, depending on the extent of the cleft. In this way, effective pumping of amniotic fluid is possible despite the cleft. This is of vital importance for the fetus during intrauterine life. A poorly passable or even unpassable respiratory way is only of secondary importance during that time.


[Roentgenoendovascular occlusion in patients with cancer of the kidneys].
Roentgenendovascular occlusion of the renal artery was used in 116 patients with renal carcinoma, in 70 of them the embolization was performed as a preoperative measure 3-12 days (7 days at an average) before nephrectomy. Embolization was also performed in 46 patients with spreaded renal carcinoma with metastases or with somatic diseases preventing surgical interventions. The roentgenendovascular occlusion reduced the time of operation and blood loss in nephrectomy, especially in patients with great hypervascularized tumors. In patients with inoperable renal carcinoma embolization was followed by arrest of hematuria, relief of pain and prevented progress of the disease.


Exploration of Benefits and Potential Harmful Effects of an Online Forum for Visitors to the Suicide Prevention Platform in The Netherlands.
Background: Online forums that enable peer-to-peer interaction are widespread and readily available. Aim: This study aimed to identify the reach, benefits, and potential harmful effects for visitors to an online forum embedded in a suicide prevention platform in The Netherlands. Method: The study collected web-based questionnaires from online forum users and moderated posts. Descriptive quantitative and qualitative analyses were performed. Results: The online forum had 330 members in 2017, of whom 130 were active users (posting at least one message). Respondents (n = 106) experienced from a high severity of suicidal ideation (78%). A minority (12%) visited the forum to find suicide methods and 3% to find a suicide partner. Among respondents who had visited the forum more than once (n = 49), 53% reported no changes in feelings directly after forum use, 35% felt better and 12% felt worse. Peer support and anonymity were the most mentioned benefits, whereas no personal contacts and few reactions to postings were perceived as limitations. Suicide threats and the search for methods were the main reasons for moderating posts. Limitations: Usage habits and user experiences were available from a relatively small group that visited the forum more than once. Conclusion: In its current form, the forum has a low reach with few benefits and a potential for harm for its users. With a questionable benefit-to-risk ratio, the added value of the online forum appears to be small.


Photocatalytic degradation of methyl-red by immobilised nanoparticles of TiO2 and ZnO.
In this work, we report on the degradation of methyl-red (2-(4-Dimethylamino-phenylazo)-benzoic acid--C.I. 13020) under UV irradiation in the presence of nanosized ZnO and TiO2. Oxide nanocrystals with controlled size were synthesised by using non-hydrolytic approaches and tested for the photocatalysed degradation. The performances of the immobilised nanoparticles were compared with their commercial counterparts after immobilization onto a solid support. The influence of some experimental conditions, namely pH and dye concentration, were investigated by monitoring the dye decoloration spectrophotometrically. Several intermediate by-products were identified by HPLC-MS, showing that two different mechanisms were operative during the photocatalytic oxidation.


DNA-dependent protein kinase: Epigenetic alterations and the role in genomic stability of cancer.
DNA-dependent protein kinase (DNA-PK), a member of phosphatidylinositol-kinase family, is a key protein in mammalian DNA double-strand break (DSB) repair that helps to maintain genomic integrity. DNA-PK also plays a central role in immune cell development and protects telomerase during cellular aging. Epigenetic deregulation due to endogenous and exogenous factors may affect the normal function of DNA-PK, which in turn could impair DNA repair and contribute to genomic instability. Recent studies implicate a role for epigenetics in the regulation of DNA-PK expression in normal and cancer cells, which may impact cancer progression and metastasis as well as provide opportunities for treatment and use of DNA-PK as a novel cancer biomarker. In addition, several small molecules and biological agents have been recently identified that can inhibit DNA-PK function or expression, and thus hold promise for cancer treatments. This review discusses the impact of epigenetic alterations and the expression of DNA-PK in relation to the DNA repair mechanisms with a focus on its differential levels in normal and cancer cells.


CLP290 promotes the sedative effects of midazolam in neonatal rats in a KCC2-dependent manner: A laboratory study in rats.
Immature neurons dominantly express the Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) rather than the K+-Cl- cotransporter isoform 2 (KCC2). The intracellular chloride ion concentration ([Cl-]i) is higher in immature neurons than in mature neurons; therefore, γ-aminobutyric acid type A (GABAA) receptor activation in immature neurons does not cause chloride ion influx and subsequent hyperpolarization. In our previous work, we found that midazolam, benzodiazepine receptor agonist, causes less sedation in neonatal rats compared to adult rats and that NKCC1 blockade by bumetanide enhances the midazolam-induced sedation in neonatal, but not in adult, rats. These results suggest that GABA receptor activation requires the predominance of KCC2 over NKCC1 to exert sedative effects. In this study, we focused on CLP290, a novel KCC2-selective activator, and found that midazolam administration at 20 mg/kg after oral CLP290 intake significantly prolonged the righting reflex latency even in neonatal rats at postnatal day 7. By contrast, CLP290 alone did not exert sedative effects. Immunohistochemistry showed that midazolam combined with CLP290 decreased the number of phosphorylated cAMP response element-binding protein-positive cells in the cerebral cortex, suggesting that CLP290 reverted the inhibitory effect of midazolam. Moreover, the sedative effect of combined CLP290 and midazolam treatment was inhibited by the administration of the KCC2-selective inhibitor VU0463271, suggesting indirectly that the sedation-promoting effect of CLP290 was mediated by KCC2 activation. To our knowledge, this study is the first report showing the sedation-promoting effect of CLP290 in neonates and providing behavioral and histological evidence that CLP290 reverted the sedative effect of GABAergic drugs through the activation of KCC2. Our data suggest that the clinical application of CLP290 may provide a breakthrough in terms of midazolam-resistant sedation.


Induction of apoptosis by lupeol and mango extract in mouse prostate and LNCaP cells.
Prostate cancer (PCA) is one of the most invasive malignancy and second leading cause of cancer related deaths in United States and some other countries. Long latency period makes PCA an ideal disease for pharmacologic or nutritional chemoprevention. Lupeol, a triterpene present in mango and other fruits, has shown to possess anticancer properties in in vivo and in vitro assays. Here, we recorded the apoptogenic activity in mouse prostate by lupeol and mango pulp extract (MPE). Testosterone was injected subcutaneously (5 mg/kg body weight) for 14 consecutive days to male Swiss albino mice. Lupeol/MPE supplementation resulted in arrest of prostate enlargement in testosterone-treated animals. In mouse prostate tissue, lupeol and MPE supplementation resulted in a significantly high percentage of apoptotic cells in the hypodiploid region. The induction of apoptosis in mouse prostate cells was preceded by the loss of mitochondrial transmembrane potential and DNA laddering. In testosterone-induced mouse prostate, upregulation of antiapoptotic B-cell non-Hodgkin lymphoma-2 and downregulation of proapoptotic Bcl-2-associated X protein and caspase-3 were also recorded. We further observed apoptogenic activities of lupeol in an in vitro model using human prostate cancer cells [lymph node carcinoma of the prostate (LNCaP)]. The apoptogenic response of lupeol-induced changes in LNCaP cells can be summarized as early increase of reactive oxygen species followed by induction of mitochondrial pathway leading to cell death. Thus, the results of this study demonstrate that lupeol/MPE is effective in combating testosterone-induced changes in mouse prostate as well as causing apoptosis by modulating cell-growth regulators.


The Effectiveness of the Transtheoretical Model to Improve Physical Activity in Healthy Adults: A Systematic Review.
Despite the known risks of physical inactivity, only 50% of adults meet the recommended guidelines for physical activity (PA). Therefore, numerous interventions have been designed to increase PA across a lifespan. The purpose of this systematic review was to determine the effectiveness of interventions based on the transtheoretical model to improve PA in healthy adults. Electronic databases (CINAHL, MEDLINE, Psychology & Behavioral Sciences Collection, PsycINFO, Sociological Collection, and SPORTDiscus) were systematically searched from January 2001 to May 2020. A total of 11 randomized pretest-posttest studies were included in this review. Ten studies utilized a subjective measurement of PA, and 3 studies included an objective measure. Five studies demonstrated significant improvements in PA for the transtheoretical model-based intervention groups compared with control/comparison groups; however, 6 studies demonstrated no differences between groups. The findings suggest that there is inconsistent evidence to support the use of interventions based on the transtheoretical model to improve PA in adult populations. Interventions were more successful when materials were delivered via in-person counseling and when study participants were in the precontemplation or contemplation phases at baseline.


Effect of cardiopulmonary bypass on thiol/disulfide homeostasis in congenital heart surgery.
This study aims to investigate whether thiol/disulfide homeostasis parameters measurements could be used as a new biomarker to predict the pre- and post-cardiopulmonary bypass oxidative status of pediatric patients undergoing congenital heart surgery. A total of 40 children with congenital heart disease (17 males, 23 females; mean age: 39.6±40.0 months; range, 2 to 216 months) who underwent open-heart surgery were included. The control group consisted of 40 age- and sex-matched healthy children (18 males, 22 females; mean age: 42.8±46.6 months; range, 12 to 156 months). The patients with congenital heart disease were divided into two groups as cyanotic patients (n=18) and acyanotic patients (n=22). Thiol/disulfide parameters were compared among the cyanotic, acyanotic congenital heart disease patients, and control group preoperatively (pre-CPB). The effects of cardiopulmonary bypass on thiol/disulfide parameters, pre-CBP, immediately after cardiopulmonary bypass (post-CPB0), and 24 h after cardiopulmonary bypass (post-CPB24) were investigated. The mean native and total thiol levels in the cyanotic patients were significantly lower than those in the acyanotic patients and control group (p<0.0001). The cyanotic group exhibited higher disulfide levels than the acyanotic group (p<0.01). The mean native thiol and total thiol levels significantly decreased in the post-CPB0 (p<0.0001). The mean disulfide levels significantly increased in the post-CPB0 than the pre-CPB values (p<0.001). Post-CPB24 native and total thiol levels were elevated compared to post-CPB0 (p<0.0001). The mean disulfide levels significantly increased in the post-CPB24 period than the post-CPB0 values (p<0.001). The survivor patients responded better to oxidative stress than non-survivor patients. Thiol/disulfide measurement is a promising biomarker in determining the pre- and post-cardiopulmonary bypass oxidative status of pediatric patients undergoing congenital heart surgery. The interpretation of thiol/disulfide levels, pre- and postoperatively, may be used in predicting mortality and outcomes of these patients earlier.


Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina.
The recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in nonmodel organisms. Host-pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungus Melampsora larici-populina when it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection. Using an array of genome scan methods based on different features of nucleotide diversity, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype-phenotype statistical association, and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although our samples are nearly contemporary to the selective sweep, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus, which can be explained by a soft selective sweep (where selection acts on standing variation) and by the impact of recombination in mitigating the impact of selection. Therefore, it seems that properties of the life cycle of M. larici-populina, which entails both high genetic diversity and outbreeding, has facilitated its adaptation.


Molecular basis for the methylation specificity of ATXR5 for histone H3.
In plants, the histone H3.1 lysine 27 (H3K27) mono-methyltransferases ARABIDOPSIS TRITHORAX RELATED PROTEIN 5 and 6 (ATXR5/6) regulate heterochromatic DNA replication and genome stability. Our initial studies showed that ATXR5/6 discriminate between histone H3 variants and preferentially methylate K27 on H3.1. In this study, we report three regulatory mechanisms contributing to the specificity of ATXR5/6. First, we show that ATXR5 preferentially methylates the R/F-K*-S/C-G/A-P/C motif with striking preference for hydrophobic and aromatic residues in positions flanking this core of five amino acids. Second, we demonstrate that post-transcriptional modifications of residues neighboring K27 that are typically associated with actively transcribed chromatin are detrimental to ATXR5 activity. Third, we show that ATXR5 PHD domain employs a narrow binding pocket to selectively recognize unmethylated K4 of histone H3. Finally, we demonstrate that deletion or mutation of the PHD domain reduces the catalytic efficiency (kcat/Km of AdoMet) of ATXR5 up to 58-fold, highlighting the multifunctional nature of ATXR5 PHD domain. Overall, our results suggest that several molecular determinants regulate ATXR5/6 methyltransferase activity and epigenetic inheritance of H3.1 K27me1 mark in plants.


Prediction of compliance with outpatient referral in patients with schizophrenia and psychoactive substance use disorders.
Most patients with concurrent schizophrenia and psychoactive substance use disorders may be adequately treated as outpatients. However, many do not comply with outpatient referrals and are therefore at heightened risk for rehospitalization. Drawing on standardized interview data collected during an index hospitalization, we developed a logistic regression model to predict compliance with outpatient treatment. The model was tested on a confirmatory sample, and its sensitivity and specificity were further evaluated in a cross-validation study of 1000 random samples. In a reference sample, the logistic function distinguished compliant from noncompliant patients in 37 (76%) of 49 cases. In a confirmatory sample, compliance status was predicted for 11 (78%) of 14 patients with a sensitivity of 1.00 and a specificity of 0.67. Women and patients with negative syndrome schizophrenia were compliant with outpatient referral, whereas those with mixed syndromes were most likely to be noncompliant. Cross-validation supports the stability of the model. While most persons with schizophrenia and concurrent substance abuse comply with integrated outpatient treatment, most who cannot may be predicted in advance.


Structure of a symmetric photosynthetic reaction center-photosystem.
Reaction centers are pigment-protein complexes that drive photosynthesis by converting light into chemical energy. It is believed that they arose once from a homodimeric protein. The symmetry of a homodimer is broken in heterodimeric reaction-center structures, such as those reported previously. The 2.2-angstrom resolution x-ray structure of the homodimeric reaction center-photosystem from the phototroph Heliobacterium modesticaldum exhibits perfect C2 symmetry. The core polypeptide dimer and two small subunits coordinate 54 bacteriochlorophylls and 2 carotenoids that capture and transfer energy to the electron transfer chain at the center, which performs charge separation and consists of 6 (bacterio)chlorophylls and an iron-sulfur cluster; unlike other reaction centers, it lacks a bound quinone. This structure preserves characteristics of the ancestral reaction center, providing insight into the evolution of photosynthesis.


Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation.
The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.


Investigation of level density parameter effects on (p,n) and (p,2n) reaction cross-sections for the fusion structural materials 48Ti, 63Cu and 90Zr.
The materials used in fusion reactor must be resistance to the harmful effects of radiation in the manner of material itself. Selection of the appropriate materials used in nuclear reactor has a crucial importance to achieve the maximum efficiency and security. Ti, Cu and Zr are known to be employed as first wall materials in fusion reactors. In this study, level density parameter effects on (p,n) and (p,2n) reaction cross-section calculations have been investigated by employing different level density models within TALYS 1.8 computer code for 48Ti, 63Cu and 90Zr selected as target materials. Also, for these isotopes (p,n) and (p,2n) reaction cross-section calculations have been done by using two different level density models of EMPIRE 3.2 code. For calculations; Constant Temperature Fermi Gas Model, Back Shifted Fermi Gas Model, Generalised Super Fluid Model and Microscopic level densities (temperature dependent Hartree Fock Bogolyubov, Gogny Force) from Hilaire's combinatorial tables have been used from TALYS 1.8. In addition, Generalised Superfluid Model and Hartree Fock Bogolyubov Model have been selected for calculations from EMPIRE 3.2 code. To appoint the best level density model, the relative variance analyses have been done. The cross-section calculations have been repeated via TALYS 1.8 level density models by changing the a parameter replacing with the obtained one from the best level density model result and value taken from the literature for each isotope. To analyze and comment about the outcomes of the study, a comparison of the results have been done with each other and the experimental data taken from the literature.


Maternal exposure to trichloroethylene in drinking water and birth-weight outcomes.
An ecological epidemiological study was conducted with data obtained from an environmental dose-reconstruction study and the Arizona Birth Information Tapes. Before 1981, a portion of the city of Tucson water-distribution system was contaminated with trichloroethylene (i.e., < 5 micrograms per liter of water to 107 micrograms per liter of water). Target and comparison populations were selected with a Geographic Information System. Logistical-regression analysis revealed an association between maternal exposure to trichloroethylene via drinking water and very-low-birth-weight babies (i.e., < 1,501 grams) (odds ratio = 3.3; 95% confidence interval = 0.5, 20.6; and Wald chi-square p value = 0.2). No association was found between maternal exposure to trichloroethylene via drinking water and low birth weight or full-term low-birth-weight infants (gestational period > 35 wk and < 46 wk).


Comparison of Gingival Recession of Mandibular Incisors of Class III Patients Immediately after Compensatory or Surgical Orthodontic Treatment.
This study aimed to compare gingival recession in mandibular anterior teeth in patients with Class III malocclusion, immediately after compensatory or surgical orthodontic treatment. The sample consisted of 40 patients with Class III malocclusion, divided into two groups: Group 1 (compensatory), 20 patients treated with compensatory orthodontics, with a mean initial age of 20.26 years (standard deviation [SD] . = 7.44), mean final age of 23.07 years (SD = 7.32), and mean treatment time of 2.81 years (SD =0.84). Group 2 (surgical), who undergone orthodontic-surgical treatment, with a mean initial age of 23.08 years (SD =5.48), mean final age of 25.43 years (SD =5.12), and mean treatment time of 2.35 years (SD =1.56). Intraoral photographs taken before and after removal of the fixed orthodontic appliance were used to measure the gingival recession, from the cervical of the mandibular incisors from the most cervical point of the gingival margin to the cementoenamel junction. In the initial and final cephalograms, the position of the mandibular incisors was measured. The intergroup comparison was performed using the independent t-test. The results showed that there was no statistically significant difference in the gingival recession at the beginning, at the end, and of changes with treatment between the compensatory and surgical groups. It was concluded that the compensatory and surgical orthodontic treatments for Class III malocclusion showed similar results regarding the gingival recession of the mandibular incisors.


Baseline hemodynamic state and response to hemodilution in patients with acute cerebral ischemia.
Hemodynamic data were obtained in 9 patients (mean age 65 yrs) with carotid territory cerebral infarct within the preceding 24 hours (mean 14 +/- 8) as part of a pilot study testing the feasibility and safety of hypervolemic hemodilution. Pulmonary arterial catheters (PACs) were placed without complication in all patients, and after baseline measurements were obtained, up to 1500 cc of 6% hetastarch in 0.9% sodium chloride was administered the first day and up to 1000 cc per day the second and third days. Pulmonary wedge pressure (PWP) rose from 6.3 +/- 3.5 to 14.4 +/- 3.4 mm Hg (p less than 0.001) without development of congestive heart failure in any patient. This was accompanied by a drop in hematocrit (Hct) from 40.3 +/- 3.4 to 32.9 +/- 2.0 (p less than 0.001) and rise in cardiac output (CO) from 4.3 +/- 1.0 to 5.3 +/- 0.6 (p less than 0.05). Phlebotomy of 250 cc was performed in 2 patients and 500 cc in one in order to reduce Hct to desired levels. The volume of fluid needed to raise PWP to 15 was unpredictable (2361 +/- 1106 cc) and therefore PACs were necessary to monitor the rate and volume of fluid administration. The data show that PWP is sufficiently low and Hct sufficiently high following stroke in most patients that hemodilution by volume expansion with phlebotomy added if necessary can be undertaken safely with appropriate monitoring of hemodynamic function, and that this therapy results in optimal reduction of Hct and increased CO without risk of hypotension.


Genetic engineering of yellow betalain pigments beyond the species barrier.
Betalains are one of the major plant pigment groups found in some higher plants and higher fungi. They are not produced naturally in any plant species outside of the order Caryophyllales, nor are they produced by anthocyanin-accumulating Caryophyllales. Here, we attempted to reconstruct the betalain biosynthetic pathway as a self-contained system in an anthocyanin-producing plant species. The combined expressions of a tyrosinase gene from shiitake mushroom and a DOPA 4,5-dioxygenase gene from the four-o'clock plant resulted in successful betalain production in cultured cells of tobacco BY2 and Arabidopsis T87. Transgenic tobacco BY2 cells were bright yellow because of the accumulation of betaxanthins. LC-TOF-MS analyses showed that proline-betaxanthin (Pro-Bx) accumulated as the major betaxanthin in these transgenic BY2 cells. Transgenic Arabidopsis T87 cells also produced betaxanthins, but produced lower levels than transgenic BY2 cells. These results illustrate the success of a novel genetic engineering strategy for betalain biosynthesis.


The Next Generation of Clinical Decision Making Tools: Development of a Real-Time Prediction Tool for Outcome of Prostate Biopsy in Response to a Continuously Evolving Prostate Cancer Landscape.
We evaluate whether annual updating of the PCPT Risk Calculator would improve institutional validation compared to static use of the PCPT Risk Calculator alone. Data from 5 international cohorts including SABOR, Cleveland Clinic, ProtecT, Tyrol and Durham VA, comprising 18,400 biopsies, were used to evaluate an institution specific annual recalibration of the PCPT Risk Calculator. Using all prior years as a training set and the current year as the test set, annual recalibrations of the PCPT Risk Calculator were compared to static use of the PCPT Risk Calculator in terms of AUC and the Hosmer-Lemeshow goodness of fit statistic. For predicting high grade disease the median AUC (higher is better) of the recalibrated PCPT Risk Calculator (static PCPT Risk Calculator) across all test years for the 5 cohorts was 67.3 (67.5), 65.0 (60.4), 73.4 (73.4), 73.9 (74.1) and 69.6 (67.2), respectively, and median Hosmer-Lemeshow goodness of fit statistics indicated better fit for recalibration compared to the static PCPT Risk Calculator for Cleveland Clinic, ProtecT and the Durham VA but not for SABOR and Tyrol. For predicting overall cancer median AUC was 63.5 (62.7), 61.0 (57.3), 62.1 (62.5), 66.9 (67.3) and 68.5 (65.5), respectively, and median Hosmer-Lemeshow goodness of fit statistics indicated a better fit for recalibration in all cohorts except for Tyrol. A simple method has been provided to tailor the PCPT Risk Calculator to individual hospitals to optimize its accuracy for the patient population at hand.


Factors influencing dental students to attend for eye examination.
This investigation sought to determine those factors influencing dental students to attend for eye examination together with the frequency of such tests and level of eyesight correction. A questionnaire was constructed and circulated to all clinical dental students attending lectures and practical classes in Dundee over a 1-week period. This ascertained the age and sex of the respondents and gathered information on what had prompted each individual to attend for eye examination. The knowledge of any visual problems and their correction was also ascertained. All 114 questionnaires that were distributed were completed. The mean elapsed time interval since the last eye examinations was 1.81 (standard deviation = 1.19) years. The frequency of attendance was not affected by gender. Those who had had their eyesight corrected were significantly (P < 0.01) more likely to attend for examination every 2 years than those without correction. Good eyesight is important for the practice of dentistry and, although this is well recognized, it is apparent that the need for regular testing has not been understood by all. Strenuous efforts should be made to ensure that this message is impressed upon dental undergraduates from an early stage in their careers so that they may undergo screening every 2 years throughout their professional careers.


Conservation of promoter sequence but not complex intron splicing pattern in human and hamster genes for 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Regulation of the expression of 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase is a critical step in controlling cholesterol synthesis. Previous studies in cultured Chinese hamster ovary cells have shown that HMG-CoA reductase is transcribed from a cholesterol-regulated promoter to yield a heterogeneous collection of mRNAs with 5' untranslated regions of 68 to 670 nucleotides in length. Synthesis of these molecules is initiated at multiple sites, and multiple donor sites are used to excise an intron in the 5' untranslated region. In the current paper, I report that human HMG-CoA reductase gene resembles the Chinese hamster gene in having multiple sites of transcription initiation that are subject to suppression by cholesterol. The human gene differs from the hamster gene in that a single donor splice site is used to excise the intron in the 5' untranslated region. All of the resulting RNAs have short 5' untranslated regions of 68 to 100 nucleotides. This difference in the splicing pattern of the first intron is species specific and not a peculiarity of cultured cells in that HMG-CoA reductase mRNAs from Syrian hamster livers resemble those of the cultured Chinese hamster ovary cells. Comparison of the DNA sequences of the HMG-CoA reductase promoters from three different species--humans, Syrian hamsters, and Chinese hamsters--shows a highly conserved region of 179 nucleotides that extends from 220 to 42 nucleotides upstream of the transcription initiation sites. This region is 88% identical between the human and Chinese hamster promoter. When fused to the coding region of the Escherichia coli chloramphenicol acetyltransferase gene, this highly conserved region of the reductase gene directs the cholesterol-regulated expression of chloramphenicol acetyltransferase in transfected hamster cells, further indicating the interspecies conservation of the regulatory elements.


Interventions for women who report domestic violence during and after pregnancy in low- and middle-income countries: a systematic literature review.
Domestic violence is a leading cause of social morbidity and may increase during and after pregnancy. In high-income countries screening, referral and management interventions are available as part of standard maternity care. Such practice is not routine in low- and middle-income countries (LMIC) where the burden of social morbidity is high. We systematically reviewed available evidence describing the types of interventions, and/or the effectiveness of such interventions for women who report domestic violence during and/or after pregnancy, living in LMIC. Published and grey literature describing interventions for, and/or effectiveness of such interventions for women who report domestic violence during and/or after pregnancy, living in LMIC was reviewed. Outcomes assessed were (i) reduction in the frequency and/or severity of domestic violence, and/or (ii) improved physical, psychological and/or social health. Narrative analysis was conducted. After screening 4818 articles, six studies were identified for inclusion. All included studies assessed women (n = 894) during pregnancy. Five studies reported on supportive counselling; one study implemented an intervention consisting of routine screening for domestic violence and supported referrals for women who required this. Two studies evaluated the effectiveness of the interventions on domestic violence with statistically significant decreases in the occurrence of domestic violence following counselling interventions (488 women included). There was a statistically significant increase in family support following counselling in one study (72 women included). There was some evidence of improvement in quality of life, increased use of safety behaviours, improved family and social support, increased access to community resources, increased use of referral services and reduced maternal depression. Overall evidence was of low to moderate quality. Screening, referral and supportive counselling is likely to benefit women living in LMIC who experience domestic violence. Larger-scale, high-quality research is, however, required to provide further evidence for the effectiveness of interventions. Improved availability with evaluation of interventions that are likely to be effective is necessary to inform policy, programme decisions and resource allocation for maternal healthcare in LMIC. Systematic review registration number: PROSPERO CRD42018087713.


Mental health nurse prescribing: A qualitative, systematic review.
The aim of the present qualitative, systematic review was to identify and summarize qualitative research that focussed on mental health nurse prescribing, synthesize findings, and outline key themes discerned. In November 2016, a systematic search was conducted for primary studies of the electronic databases PubMed, Excerpta Medica, (Embase), Cumulative Index to Nursing and Allied Health Literature, Scopus, and PsycINFO. Of the 101 papers identified through the search strategy, 12 qualitative studies met the review inclusion criteria. These studies included perspectives from nurses, doctors, and patients/clients regarding their attitudes about, and experiences of, nurse prescribing. Three themes emerged from the review: (i) patient-centred care; (ii) professional role; and (iii) professional support. Nurse prescribers embrace a patient-centred approach, providing timely and effective medication management. Adequate education and continuing professional development inclusive of clinical supervision enable competency development in nurse prescribing, supportive professional relationships, and patient safety. Further research is necessary to establish safety and demonstrate enhanced clinical outcomes from mental health nurse prescribing.


Kinetics of immune responses in deer mice experimentally infected with Sin Nombre virus.
Deer mice are the principal reservoir hosts of Sin Nombre virus, the etiologic agent of most hantavirus cardiopulmonary syndrome cases in North America. Infection of deer mice results in persistence without conspicuous pathology, and most, if not all, infected mice remain infected for life, with periods of viral shedding. The kinetics of viral load, histopathology, virus distribution, and immune gene expression in deer mice were examined. Viral antigen was detected as early as 5 days postinfection and peaked on day 15 in the lungs, hearts, kidneys, and livers. Viral RNA levels varied substantially but peaked on day 15 in the lungs and heart, and antinucleocapsid IgG antibodies appeared in some animals on day 10, but a strong neutralizing antibody response failed to develop during the 20-day experiment. No clinical signs of disease were observed in any of the infected deer mice. Most genes were repressed on day 2, suggesting a typical early downregulation of gene expression often observed in viral infections. Several chemokine and cytokine genes were elevated, and markers of a T cell response occurred but then declined days later. Splenic transforming growth factor beta (TGF-β) expression was elevated early in infection, declined, and then was elevated again late in infection. Together, these data suggest that a subtle immune response that fails to clear the virus occurs in deer mice.


Major histocompatibility complex class II-transfected tumor cells present endogenous antigen and are potent inducers of tumor-specific immunity.
We have developed an immunotherapy in which tumor cells transfected with syngeneic major histocompatibility complex (MHC) class II genes are cell-based vaccines for the treatment of established tumor and metastatic disease. If this strategy is to be used clinically, convenient methods for generating class II+ tumor cells are necessary. Interferon-gamma treatment or transduction of the class II transactivator (CIITA) gene induces class II expression but also up-regulates the class II-associated accessory molecules, invariant chain (Ii) and DM. To determine if interferon-gamma treatment and CIITA transduction are potential immunotherapies, we assessed the tumorigenicity of sarcoma cells expressing combinations of class II, Ii, and DM. Since we hypothesized that class II-transfected tumor cells not coexpressing Ii and DM present endogenously encoded tumor peptides, we have assessed the transfectants for antigen presentation activity to MHC class II-restricted antigen-specific CD4(+) T cells. Tumor challenge studies demonstrate that tumor cells expressing class II without coexpression of Ii or Ii plus DM are highly immunogenic and preferentially present endogenous antigens, while tumors coexpressing class II with Ii or Ii plus DM are not effective immunogens. Because tumor rejection correlates with expression of class II without coexpression of Ii and DM, the most efficacious vaccines will express MHC class II without coexpression of Ii and DM and will preferentially present endogenous antigen.


Alcohol use and cognition at mid-life: the importance of adjusting for baseline cognitive ability and educational attainment.
The nature of the relationship between cognition and alcohol consumption remains controversial. Studies have reported negative, positive, and nonsignificant effects of alcohol consumption on cognition. Problematic throughout the literature is that baseline cognitive ability has not been adequately controlled in previous studies, and even educational attainment is only sometimes controlled. Because such variables may be associated with both alcohol intake and later-life cognition, we hypothesize that the observed relationship between alcohol intake and cognition may change when these variables or other conditions in early life have been controlled. We examined the relationship of alcohol intake and cognition at age 53 using the Wisconsin Longitudinal Study, which has followed Wisconsin high school graduates from 1957 to 1992. Our measures include cognitive ability test scores from the freshman and junior years of high school, educational attainment, an abstract reasoning test score at age 53, alcohol intake at age 53, and other measures. When no controls were used, both men and women with low levels of alcohol consumption at 53 (i.e., 0-1 drink per day) had better scores on the abstract reasoning subtest of the Wechsler Adult Intelligence Scale (WAIS-R) at age 53 than subjects who never drank or currently did not drink. However, after adjusting for adolescent-measured cognitive ability and educational attainment, men with low levels of consumption no longer had higher abstract reasoning scores than nondrinking men, but they still did have higher abstract reasoning scores than men who drank more than one drink per day. For women, adjusting for cognitive ability and educational attainment eliminated all significant effects of alcohol on cognition, and reversed the nonsignificant result that women with higher consumption had the highest cognition scores. These results demonstrate the importance of adjusting for baseline cognitive ability when attempting to study the effect of long-term alcohol use patterns on cognition, and that educational attainment cannot be considered a valid substitute for baseline cognition scores. Much of the apparent benefit of moderate alcohol intake on cognition in our society may well be explained by differential rates of alcohol consumption among subjects with differing baseline cognitive ability scores. Neither is there evidence that moderate alcohol intake reduces cognitive functioning.


Physico-chemical and toxicological characterization of iron-containing albumin nanoparticles as platforms for medical imaging.
Iron oxide-containing magnetic nanoparticles (MNPs) have certain advantages over currently used contrast agents for tumor imaging by magnetic resonance imaging (MRI) as they offer the possibility of functionalization with ligands and tracers. Functionalized MNPs also may be used for targeted tumor therapy. In the current study nanoparticles (NPs) consisting of recombinant human serum albumin (rHSA) with incorporated hydrophilic (NH4)2Ce(IV)(NO3)6-γ-Fe2O3 particles (CAN maghemite particles) for medical imaging were produced and characterized. For this purpose CAN maghemite particles were incorporated into an rHSA matrix to yield rHSA-NPs. The resulting NPs were analyzed by transmission electron microscopy, photon correlation spectroscopy, and atomic absorption. The sizes of the manufactured NP were 170 ± 10 nm, and the zeta-potential was -50 ± 3 mV. The NPs remained stable when stored after lyophilization with sucrose 3% [w/v] as a cryoprotector. They showed pro-inflammatory properties without cell and animal toxicity in vivo and were highly contrasting in MRI. In conclusion, this report introduces novel rHSA NP with favorable properties containing iron oxide for detection by MRI.


Moving From Static to Dynamic Models of the Onset of Mental Disorder: A Review.
In recent years, there has been increased focus on subthreshold stages of mental disorders, with attempts to model and predict which individuals will progress to full-threshold disorder. Given this research attention and the clinical significance of the issue, this article analyzes the assumptions of the theoretical models in the field. Psychiatric research into predicting the onset of mental disorder has shown an overreliance on one-off sampling of cross-sectional data (ie, a snapshot of clinical state and other risk markers) and may benefit from taking dynamic changes into account in predictive modeling. Cross-disciplinary approaches to complex system structures and changes, such as dynamical systems theory, network theory, instability mechanisms, chaos theory, and catastrophe theory, offer potent models that can be applied to the emergence (or decline) of psychopathology, including psychosis prediction, as well as to transdiagnostic emergence of symptoms. Psychiatric research may benefit from approaching psychopathology as a system rather than as a category, identifying dynamics of system change (eg, abrupt vs gradual psychosis onset), and determining the factors to which these systems are most sensitive (eg, interpersonal dynamics and neurochemical change) and the individual variability in system architecture and change. These goals can be advanced by testing hypotheses that emerge from cross-disciplinary models of complex systems. Future studies require repeated longitudinal assessment of relevant variables through either (or a combination of) micro-level (momentary and day-to-day) and macro-level (month and year) assessments. Ecological momentary assessment is a data collection technique appropriate for micro-level assessment. Relevant statistical approaches are joint modeling and time series analysis, including metric-based and model-based methods that draw on the mathematical principles of dynamical systems. This next generation of prediction studies may more accurately model the dynamic nature of psychopathology and system change as well as have treatment implications, such as introducing a means of identifying critical periods of risk for mental state deterioration.


Effects of desflurane on spinal somatosensory-evoked potentials and conductive spinal cord evoked potential.
Spinal somatosensory-evoked potential (interspinous-space-recorded evoked potentials after peripheral nerve or dermatomal stimulation) and conductive spinal cord evoked potential (interspinous-space-recorded evoked potentials after spinal cord stimulation) were analyzed in rats under different concentrations of the anesthetic desflurane. To investigate and compare the effects of a new volatile anesthetic, desflurane, on the common intraoperative neuromonitoring models. Intraoperative evoked potentials are sensitive to most anesthetics. Interpretation of the data becomes complicated because of a suppression effect caused by the anesthesia. Desflurane has become a valuable anesthetic in neurosurgery because of its pharmacokinetic advantages. Fifteen rats were placed under general anesthesia, and vital signs were closely monitored. Needle recording electrodes were placed stereotactically into the thoracolumbar interspinous ligament; dermatomal somatosensory-evoked potential by L5 dermatome, mixed-nerve somatosensory-evoked potential by sciatic nerve stimulation, and spinal cord evoked potential of the same recording electrodes elicited by C2-C3 interspinous stimulation were obtained. The effects of desflurane were examined at end-tidal concentrations of 6% (1.05 minimal alveolar concentration), 9% (1.57 minimal alveolar concentration), and 12% (2.10 minimal alveolar concentration). Amplitude decreased and latency was delayed in all three kinds of potentials, and the more so with higher concentrations. Comparing 9% with 6% desflurane, the amplitude in dermatomal somatosensory-evoked potential, mixed-nerve somatosensory-evoked potential, and spinal cord evoked potential decreased to 84.3%, 88.9%, and 70.8%, respectively, values with no statistically significant difference. However, at 12%, again compared with 6%, the amplitude decreased further to 64.4%, 70.3%, 41.8%, respectively; mixed-nerve somatosensory-evoked potential and dermatomal somatosensory-evoked potential were significantly more preserved than spinal cord evoked potential (P = 0.04). The concentration of desflurane alters the amplitude of somatosensory-evoked potential and spinal cord evoked potential, and, to a lesser degree, delays the latency; spinal cord evoked potential is more liable to be suppressed than somatosensory-evoked potential. The dose-dependent suppression effect on amplitude should be considered when interpreting changes during surgery. Furthermore, the potential benefit of somatosensory-evoked potential elicited by direct major nerve stimulation should be considered because of its large amplitude and higher resistance, even with a greater concentration of volatile anesthetics.


The potential of Synechococcus elongatus UTEX 2973 for sugar feedstock production.
It is important to obtain abundant sugar feedstocks economically and sustainably for bio-fermentation industry, especially for producing cheap biofuels and biochemicals. Besides plant biomass, photosynthetic cyanobacteria have also been considered to be potential microbe candidates for sustainable production of carbohydrate feedstocks. As the fastest growing cyanobacterium reported so far, Synechococcus elongatus UTEX 2973 (Syn2973) might have huge potential for bioproduction. In this study, we explored the potentials of this strain as photo-bioreactors for sucrose and glycogen production. Under nitrogen-replete condition, Syn2973 could accumulate glycogen with a rate of 0.75 g L(-1) day(-1) at the exponential phase and reach a glycogen content as high as 51 % of the dry cell weight (DCW) at the stationary phase. By introducing a sucrose transporter CscB, Syn2973 was endowed with an ability to secrete over 94 % sucrose out of cells under salt stress condition. The highest extracellular sucrose productivity reached 35.5 mg L(-1) h(-1) for the Syn2973 strain expressing cscB, which contained the similar amounts of intracellular glycogen with the wild type. Potassium chloride was firstly proved to induce sucrose accumulation as well as sodium chloride in Syn2973. By semi-continuous culturing, 8.7 g L(-1) sucrose was produced by the cscB-expressing strain of Syn2973 in 21 days. These results support that Syn2973 is a promising candidate with great potential for production of sugars.


Novel Therapies in Platinum-refractory Metastatic Germ Cell Tumor: A Case Report with a Focus on a PD-1 Inhibitor.
Testicular germ cell tumor (GCT) is the most common malignancy in young males between the ages of 15 to 35 years. Although the overall cure rate of GCTs approaches 95%, almost 25% of patients with distant metastases die from the cancer. Active investigations on novel treatment options for platinum-refractory GCTs include immunotherapies such as program-death 1 (PD-1)/program death-ligand 1 (PD-L1) inhibitors. In this case, we report a patient with metastatic GCTs who was treated with pembrolizumab, a PD-L1 inhibitor, in a phase II study after failing several lines of chemotherapy. We highlighted the rationale for the use of PD-L1 inhibitor in this population.


Large Vessel Occlusion Prediction in the Emergency Department with National Institutes of Health Stroke Scale Components: A Machine Learning Approach.
To determine the feasibility of using a machine learning algorithm to screen for large vessel occlusions (LVO) in the Emergency Department (ED). A retrospective cohort of consecutive ED stroke alerts at a large comprehensive stroke center was analyzed. The primary outcome was diagnosis of LVO at discharge. Components of the National Institutes of Health Stroke Scale (NIHSS) were used in various clinical methods and machine learning algorithms to predict LVO, and the results were compared with the baseline method (aggregate NIHSS score with threshold of 6). The Area-Under-Curve (AUC) was used to measure the overall performance of the models. Bootstrapping (n = 1000) was applied for the statistical analysis. Of 1133 total patients, 67 were diagnosed with LVO. A Gaussian Process (GP) algorithm significantly outperformed other methods including the baseline methods. AUC score for the GP algorithm was 0.874 ± 0.025, compared with the simple aggregate NIHSS score, which had an AUC score of 0.819 ± 0.024. A dual-stage GP algorithm is proposed, which offers flexible threshold settings for different patient populations, and achieved an overall sensitivity of 0.903 and specificity of 0.626, in which sensitivity of 0.99 was achieved for high-risk patients (defined as initial NIHSS score > 6). Machine learning using a Gaussian Process algorithm outperformed a clinical cutoff using the aggregate NIHSS score for LVO diagnosis. Future studies would be beneficial in exploring prospective interventions developed using machine learning in screening for LVOs in the emergent setting.


RESEARCH ON EXTRACTION TECHNOLOGY, ANTIBACTERIAL AND ANTIOXIDANT ACTIVITY OF ETHANOL EXTRACT FROM LEAVES OF ABUTILON THEOPHRASTI MEDIC.
This paper described the extraction procedure and determination method for the total flavonoids in ethanol extract from the leaves of Abutilon theophrasti Medic., and evaluated antibacterial and antioxidant activity. Maximum extraction yield was achieved using 60% ethanol, 1 : 30 (g/mL) of a ratio of material to solvent, 20 min of extraction time, 40 kHz of ultrasonic frequency, 100 W of ultrasonic power, 600C of extraction temperature and two extraction cycles. Total flavonoids content was 16.79 RE mg/g medicinal materials. The extracts had effective antibacterial activity against 24 test strains from S. aureus and E. coli, MICs ranged from 2.18 to 8.7 mg/mL; it was also revealed that the extracts demonstrated high flavonids content and potent antioxidant activity, achieved by hydroxyl radical, DPPH radical and ABTS radical scavenging. These results indicated thathe extract may be a promising plant demonstrating antibacterial and antioxidant activities.


Summary of data reported to CDC's national automated biosurveillance system, 2008.
BioSense is the US national automated biosurveillance system. Data regarding chief complaints and diagnoses are automatically pre-processed into 11 broader syndromes (e.g., respiratory) and 78 narrower sub-syndromes (e.g., asthma). The objectives of this report are to present the types of illness and injury that can be studied using these data and the frequency of visits for the syndromes and sub-syndromes in the various data types; this information will facilitate use of the system and comparison with other systems. For each major data source, we summarized information on the facilities, timeliness, patient demographics, and rates of visits for each syndrome and sub-syndrome. In 2008, the primary data sources were the 333 US Department of Defense, 770 US Veterans Affairs, and 532 civilian hospital emergency department facilities. Median times from patient visit to record receipt at CDC were 2.2 days, 2.0 days, and 4 hours for these sources respectively. Among sub-syndromes, we summarize mean 2008 visit rates in 45 infectious disease categories, 11 injury categories, 7 chronic disease categories, and 15 other categories. We present a systematic summary of data that is automatically available to public health departments for monitoring and responding to emergencies.


Similarity among the Drosophila (6-4)photolyase, a human photolyase homolog, and the DNA photolyase-blue-light photoreceptor family.
Ultraviolet light (UV)-induced DNA damage can be repaired by DNA photolyase in a light-dependent manner. Two types of photolyase are known, one specific for cyclobutane pyrimidine dimers (CPD photolyase) and another specific for pyrimidine (6-4) pyrimidone photoproducts[(6-4)photolyase]. In contrast to the CPD photolyase, which has been detected in a wide variety of organisms, the (6-4)photolyase has been found only in Drosophila melanogaster. In the present study a gene encoding the Drosophila(6-4)photolyase ws cloned, and the deduced amino acid sequence of the product was found to be similar to the CPD photolyase and to the blue-light photoreceptor of plants. A homolog of the Drosophila (6-4)photolyase gene was also cloned from human cells.


Voice Function in Gender-Diverse People Assigned Female at Birth: Results From a Participant-Centered Mixed-Methods Study and Implications for Clinical Practice.
Purpose The purpose of this study was to investigate whether there were indications of restrictions to voice function in our group of gender-diverse people assigned female at birth (GD peopleAFAB) and whether the participants would benefit from professional voice support. Method We conducted a descriptive, cross-sectional, mixed-methods study combining qualitative content analyses of semistructured interviews, phoniatric examinations, and acoustical voice analyses. Fourteen German-speaking GD peopleAFAB participated. The data were examined for indications of restrictions to voice function according to the results of participant self-evaluation, auditory-perceptual analyses, laryngostroboscopic examinations, and acoustical measurements. Results All participants presented with indications of restrictions to voice function, with vocal power, voice quality, singing voice, laryngeal function, pitch range/variability, and vocal control having found to be most frequently affected (in over 60% of participants). Sixty-four percent of participants expressed an interest in professional voice support, with clinicians and researchers recommending professional voice support for 67% and 71%, respectively. Conclusions GD peopleAFAB may experience restrictions to a range of domains of voice function and request or be recommended to participate in professional voice support. Research into this area needs to be intensified so that a more in-depth understanding of the potential voice problems GD peopleAFAB might experience can be produced and members of this group can be provided with more comprehensive, evidence-based, and high-quality professional support if and when they need it.


HIV and tuberculosis co-infection in East Asia and the Pacific from 1990 to 2017: results from the Global Burden of Disease Study 2017.
Periodic surveillance is crucial to provide information for resource allocation to control HIV/AIDS, tuberculosis (TB), and their co-infection, especially in areas with high morbidity and mortality like East Asia and the Pacific. Therefore, we examined the morbidity and mortality of HIV/AIDS and TB co-infection in this region from 1990 to 2017. Utilizing the Global Burden of Disease (GBD) Study 2017, we obtained incidence, prevalence, and mortality numbers and rates of HIV/AIDS and TB co-infection, including HIV and drug-susceptible TB (DS-TB), multidrug-resistant TB without extensive drug resistance (MDR-TB without XDR), and extensive drug-resistant TB (XDR-TB). The trends in incidence, prevalence, and mortality from 1990 to 2017 for each co-infection type were analyzed using join-point regression modelling. In 2017, there were 238,372, 4,294, and 392 new cases of HIV-infected DS-TB, HIV-infected MDR-TB without XDR, and HIV-infected XDR-TB, respectively. The number of prevalent cases and deaths were 383,809 and 12,197 of HIV-infected DS-TB, 7,811 and 1,168 of HIV-infected MDR-TB without XDR, and 713 and 282 of HIV-infected XDR-TB. From 1990 to 2017, the age-standardized incidence rate and prevalence rate of HIV-infected DS-TB, and the prevalence rate of HIV-infected XDR-TB continuously increased; the incidence rate of HIV-infected XDR-TB increased from 1990 to 2005 before stabilizing. However, the incidence and prevalence rates of HIV-infected MDR-TB without XDR-as well as the mortality rates of all co-infection types-have decreased in the last 5 years. Even though the mortality rates of all HIV and TB co-infection types have decreased recently, the overall trends in both incidence and prevalence rates of HIV-infected DS-TB and XDR-TB have been increasing since 1990. Efforts to control co-infection across drug resistance types should be continued and further strengthened.


Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: exploiting Randle's cycle.
Right ventricular hypertrophy (RVH) and RV failure are major determinants of prognosis in pulmonary hypertension and congenital heart disease. In RVH, there is a metabolic shift from glucose oxidation (GO) to glycolysis. Directly increasing GO improves RV function, demonstrating the susceptibility of RVH to metabolic intervention. However, the effects of RVH on fatty acid oxidation (FAO), the main energy source in adult myocardium, are unknown. We hypothesized that partial inhibitors of FAO (pFOXi) would indirectly increase GO and improve RV function by exploiting the reciprocal relationship between FAO and GO (Randle's cycle). RVH was induced in adult Sprague-Dawley rats by pulmonary artery banding (PAB). pFOXi were administered orally to prevent (trimetazidine, 0.7 g/L for 8 weeks) or regress (ranolazine 20 mg/day or trimetazidine for 1 week, beginning 3 weeks post-PAB) RVH. Metabolic, hemodynamic, molecular, electrophysiologic, and functional comparisons with sham rats were performed 4 or 8 weeks post-PAB. Metabolism was quantified in RV working hearts, using a dual-isotope technique, and in isolated RV myocytes, using a Seahorse Analyzer. PAB-induced RVH did not cause death but reduced cardiac output and treadmill walking distance and elevated plasma epinephrine levels. Increased RV FAO in PAB was accompanied by increased carnitine palmitoyltransferase expression; conversely, GO and pyruvate dehydrogenase (PDH) activity were decreased. pFOXi decreased FAO and restored PDH activity and GO in PAB, thereby increasing ATP levels. pFOXi reduced the elevated RV glycogen levels in RVH. Trimetazidine and ranolazine increased cardiac output and exercise capacity and attenuated exertional lactic acidemia in PAB. RV monophasic action potential duration and QTc interval prolongation in RVH normalized with trimetazidine. pFOXi also decreased the mild RV fibrosis seen in PAB. Maladaptive increases in FAO reduce RV function in PAB-induced RVH. pFOXi inhibit FAO, which increases GO and enhances RV function. Trimetazidine and ranolazine have therapeutic potential in RVH.


Total lymphocyte count as a possible surrogate of CD4 cell count to prioritize eligibility for antiretroviral therapy among HIV-infected individuals in resource-limited settings.
To characterize the value of total lymphocyte counts in predicting risk of death among patients initiating triple combination antiretroviral therapy. Study subjects included antiretroviral-naive persons aged 18 years or older who initiated treatment with triple combination therapy between August 1 1996 and September 30 1999 in a population-based observational cohort of HIV-infected individuals. Total lymphocyte counts as well as CD4 count and plasma viral load were assessed at baseline. Separate Cox proportional hazards models were devised to evaluate the effect on survival of total lymphocyte count in lieu of or with CD4 count after adjustment for other prognostic factors including plasma viral load. A total of 733 antiretroviral-naive persons initiated triple drug combination antiretroviral therapy over the study period with a median follow-up of 29.5 months. In the first analysis, only baseline CD4 cell counts of 50-199 cells/microl or less than 50 microl were associated with an increased risk of mortality [adjusted relative risk (ARR) 2.90; 95% CI: 1.40, 5.98] and (ARR 6.30; 95% CI: 2.93, 13.54), respectively. When CD4 counts were excluded from the analysis as if unavailable, total lymphocyte count of between 0.8 and 1.4 G/I, and less than 0.8 G/I were both significantly associated with an increased risk of mortality (ARR 2.36; 95% CI: 1.16, 4.78) and (ARR 6.17; 95% CI: 2.93, 13.01), respectively. Total lymphocyte count may provide a simple and cost-effective alternative for prioritizing therapy initiation in resource-limited settings. Our results suggest that, if appropriately validated, judicious application of total lymphocyte counts could overcome one of the practical obstacles to more widespread provision of antiretroviral therapy in resource-poor settings.


[Hemianopsias in cortical and subcortical lesions of the visual system: what is the difference?].
The neuronal correlate of perception in the visual area remains unimpaired in lesions of the optic tracts or the radiatio optica. Hemianopsias due to lesions of these pathways are perceived immediately. On the contrary, hemianopsias due to a lesion of the visual cortex are not perceived or are only indirectly realized. It has not been established if a lesion of the primary visual area alone is sufficient to make the patient unaware of a hemianopsia or if additional impairments of the peristriate visual areas are required. Data processing within the cortical visual projection chain makes it likely, however, that a lesion of the striate cortex is enough. Under physiological conditions an uniformly illuminated field is represented in the neuronal activity by the borders of the field. Neurons within the field are not activated. The higher visual cortical areas can so not discriminate if an input missing from V1 is a result of the physiological processing or of a lesion. Scotomas are therefore not perceived. By analogy this argument should also hold for a hemianopic "scotoma".


Pulsed laser-induced liquid jet for skull base tumor removal with vascular preservation through the transsphenoidal approach: a clinical investigation.
The transsphenoidal approach has recently been used to treat complex lesions beyond the sella turcica, but the difficulties of dealing with small vessels, deep and narrow space, and working angle may limit the procedures. To overcome these problems, we have developed a pulsed laser-induced liquid jet (LILJ) system to dissect tumor tissue with preservation of fine blood vessels within deep and narrow working spaces and evaluated its utility and safety. The LILJ system was applied to 14 consecutive patients with uncharacteristically complex skull base tumor treated through the extended transsphenoidal approach. This system consists of a bayonet-shaped catheter incorporating a jet generator formed of stainless tube (external diameter 1.10 mm, internal diameter 0.78 mm), which was surrounded by a coaxial polytetrafluoroethylene 14-G equivalent suction tube to be able to incorporate into the confined working spaces. Minor modifications could be fitted for the catheter (15 to 18 cm length, straight or side flexion tip), and total weight was around 7 g. Precise dissection and mass reduction of the tumor were obtained in all cases except one recurrent case of chordoma with significant fibrosis due to radiation. Both small arteries and veins were preserved, allowing subsequent microsurgical devascularization. Intraoperative blood loss was minimal, and tumor removal rate was satisfactory after the introduction of the system. No complication was related to use of the LILJ system. Although comparison between conventional surgical instruments is mandatory in the future, the present study suggests that the LILJ system can achieve safe and optimum removal of complex skull base tumor. Potential application for minimally invasive endoscopic system, as well as potentials for changing the design of the catheter in according to preference of surgeon with low cost, may give advantages over conventional surgical instruments.


Hepatitis C virus-associated membranoproliferative glomerulonephritis in renal allografts.
In renal transplantation, chronic allograft nephropathy is the leading cause of long-term graft losses, transplant glomerulopathy being its glomerular form. Differential diagnosis from recurrent or de novo membranoproliferative glomerulonephritis should be established. Whether hepatitis C virus is associated with cryoglobulinemia and glomerular damage in renal allograft recipients, as in native kidneys, is not known. We identified six hepatitis C virus-infected renal allograft recipients with proteinuria higher than 1.5 g/day, microhematuria, and membranoproliferative glomerulonephritis. Virologic and immunologic studies were conducted. Low serum levels of circulating immune complexes and cryoglobulins were observed, which were type II immunoglobulin G polyclonal-immunoglobulin Mk monoclonal in all six patients. Classical serum complement pathway activation and at least one type of autoantibodies were present in all of them. Hepatitis C virus RNA was found in higher concentrations in cryoprecipitate than in serum (percentage of enrichment ranged from 341 to 18,200%). Hepatitis C virus genotype was 1b in 4 of 6 patients, 1a in 1 of 6 patients, and 2a in 1 of 6 patients. In renal histology prominent parietal diffuse deposition of immunoglobulin M was the rule. Glomerular subendothelial electron-dense deposits with fibrillar appearance were observed in the two patients in which electron microscopy provided information about glomeruli. In renal allograft recipients hepatitis C virus infection may be associated with type II cryoglobulinemia which may lead to membranoproliferative glomerulonephritis. Immunologic and virologic studies may help to differentiate hepatitis C virus-associated membranoproliferative glomerulonephritis from transplant glomerulopathy.


Epidemiology, Outcomes and Tolerability of Protracted Treatment of Nontuberculous Mycobacterial Infections at a Community Teaching Hospital in the Southeastern United States.
Nontuberculous mycobacterial (NTM) infections present a treatment challenge for clinicians and patients. There are limited data about current susceptibility patterns and treatment outcomes in U.S. adults. This was a 10-year, single-center, retrospective, observational cohort study of adults with a positive NTM culture and clinical suspicion of infection between 1 January 2010 and 30 June 2020. The primary objective was to identify predictors for favorable treatment outcomes. Key secondary objectives were characterization of NTM epidemiology, susceptibility profiles, and safety and tolerability of treatment, including the proportion of subjects with an antimicrobial change and the reasons for the change. Of 250 subjects diagnosed with NTM infection, the most prevalent NTM isolates were Mycobacterium avium intracellulare complex (66.8%) followed by Mycobacterium abscessus (17.6%). Antimicrobial susceptibility data were available for 52.4% of the cohort (45.8% slow growers; 54.2% rapid growers). Only 88 (35%) subjects received treatment with evaluable clinical outcomes. The proportion of subjects with a favorable outcome was 61.4%. More subjects in the unfavorable outcome group experienced a change in antimicrobial therapy (73.5% vs. 51.9%, p = 0.043). The most common reason for antimicrobial change was adverse drug events (n = 36, 67.9%). In the regression model, private insurance was associated with a favorable outcome, whereas having multiple antimicrobial changes was associated with an unfavorable outcome. The complexity of NTM treatment and high incidence of medication-related issues suggest the necessity of interdisciplinary collaboration to improve overall treatment outcomes in NTM infections.


Hypothalamic GABA receptor functional regulation and liver cell proliferation.
GABAergic alterations in hypothalamus during compensatory hyperplasia after partial hepatectomy (PH), lead nitrate (LN) induced direct hyperplasia and N-nitrosodiethylamine (NDEA) induced neoplasia in liver were investigated. Serum GABA levels were increased in all 3 experimental groups compared with the control. GABA content decreased in hypothalamus of PH and NDEA treated rats, while it increased in LN treated rats. GABA(A) receptor number and affinity in hypothalamic membrane preparations of rats showed a significant decrease in PH and NDEA treated rats, while in LN treated rats the affinity increased without any change in the receptor number. The GABA(B) receptor number increased in PH and NDEA treated rats, while it decreased in LN treated rats. The affinity of the receptor also increased in NDEA treated rats. Plasma NE levels showed significant increase in PH and NDEA rats compared with the control while it decreased in LN treated rats. The results of the present study suggests that liver cell proliferation is influencing the hypothalamic GABAergic neurotransmission and these changes regulate the hepatic proliferation through the sympathetic stimulation.


The development of a model of psychological first aid for non-mental health trained public health personnel: the Johns Hopkins RAPID-PFA.
The Johns Hopkins Center for Public Health Preparedness, which houses the Centers for Disease Control and Prevention-funded Preparedness and Emergency Response Learning Center, has been addressing the challenge of disaster-caused behavioral health surge by conducting training programs in psychological first aid (PFA) for public health professionals. This report describes our approach, named RAPID-PFA, and summarizes training evaluation data to determine if relevant knowledge, skills, and attitudes are imparted to trainees to support effective PFA delivery. In the wake of disasters, there is an increase in psychological distress and dysfunction among survivors and first responders. To meet the challenges posed by this surge, a professional workforce trained in PFA is imperative. More than 1500 participants received a 1-day RAPID-PFA training. Pre-/postassessments were conducted to measure (a) required knowledge to apply PFA; (b) perceived self-efficacy, that is, belief in one's own ability, to apply PFA techniques; and (c) confidence in one's own resilience in a crisis context. Statistical techniques were used to validate the extent to which the survey successfully measured individual PFA constructs, that is, unidimensionality, and to quantify the reliability of the assessment tool. Statistically significant pre-/postimprovements were observed in (a) knowledge items supportive of PFA delivery, (b) perceived self-efficacy to apply PFA interventions, and (c) confidence about being a resilient PFA provider. Cronbach alpha coefficients ranging from 0.87 to 0.90 suggested that the self-reported measures possessed sufficient internal consistency. Findings were consistent with our pilot work, and with our complementary research initiatives validating a variant of RAPID-PFA with faith communities. The RAPID-PFA model promises to be a broadly applicable approach to extending community behavioral health surge capacity. Relevant next steps include evaluating the effectiveness of trained providers in real crisis situations, and determining if PFA training may have potential beyond the disaster context.


Long-term results of the application of solvent-dehydrated bone xenograft and duramater xenograft for the healing of oroantral osseous defects: a pilot experimental study.
The aim of this study was to investigate the long-term effects of the use of human cadaveric solvent-dehydrated bone graft and duramater as a barrier membrane for the treatment of oroantral communication. Standard oroantral osseous defects were created in five minipigs. Subjects received cancellous bone graft in the form of block or microchips, duramater or a combination of bone and membrane. Uneventful healing was achieved in all of the subjects, clinically including the control site which did not receive any material. The operated bone segments were evaluated both by radiological and histological examinations after 6 months. Radiological evaluation was carried out using bone density analysis software and histological evaluation made by light microscopy. Radiological and histological results revealed that bone grafting of oroantral osseous defects improved the bone quality. However, application of duramater did not change this activity, both alone or combined with bone grafts. Within the limits of this experimental study, although solvent-dehydrated bone grafts were found superior and could be applied for the healing of osseous oroantral defects, resorbable membranes did not contribute to this process.


Optical nanoantennas with tunable radiation patterns.
We address new optical nanoantenna systems with tunable highly directional radiation patterns. The antenna comprises a regular linear array of metal nanoparticles in the proximity of an interface with high dielectric contrast. We show that the radiation pattern of the system can be controlled by changing parameters of the excitation, such as the polarization and/or incidence angles. In the case of excitation under the total reflection condition, the system operates as a nanoscopic source of radiation, converting the macroscopic incident plane wavefront into a narrow beam of light with adjustable characteristics. We derive also simple analytical formulas which give an excellent description of the radiation pattern and provide a useful tool for analysis and antenna design.


[Dry eye: etiopathogenesis and treatment].
Dry eye is a multifactorial disease of tears and ocular surface that causes discomfort, visual disturbance and tear film instability. It is a common disorder that affects specially adults and women and can cause quality of life impairment comparable to migraine, shortness of breath and chronic renal insufficiency, depending on its symptoms or complications. New concepts regarding physiopathology, classification and treatment have been presented and should be known by ophthalmologists because of their relevance on day-by-day application. There are about 100 different medications currently in use for dry eye besides other methods of treatment, so it is necessary to establish what is really safe and effective for dry eye. This paper presents a review about Dry Eye Syndrome etiopathogenesis and treatment.


Sodium polyanethol sulfonate sensitivity of anaerobic cocci.
Growth of Peptostreptococcus anaerobius was shown to be totally inhibited by sodium polyanethol sulfonate (SPS). Other anaerobic cocci grew in the presence of SPS although some strains of Peptococcus prevotii and Peptococcus magnus showed delayed growth. A SPS disk assay for the presumptive identification of P. anaerobius is described.


Reassessment of the function of somatolactin alpha in lipid metabolism using medaka mutant and transgenic strains.
Somatolactin alpha (SLa) is a fish-specific peptide hormone secreted from the pituitary. In medaka, SLa functions to darken the skin color and lack of SLa makes it pale. Transcription of SLa is enhanced or suppressed when fish are kept in dark or bright conditions, respectively, indicating SLa's important role in background acclimation of the skin color. Bizarrely, however, the lack of SLa seems to cause the additional defect of increased triglycerides in organs, which could not be rescued (decreased) by its overexpression. To assess this enigmatic result, we investigated genetic (the SLa, Slc45a2, r, and Y genes) and nongenetic (age, fasting, water temperature, and background color) effects on hepatic triglycerides. These experiments found that percent hepatic triglycerides quickly change in response to external/internal environments. Effects of SLa seemed to be much less obvious, although it may increase the proportion of hepatic triglycerides at least during certain breeding conditions or under certain genetic backgrounds. The present results do not exclude the possibility that SLa takes part in lipid metabolism or other physiological processes. However, we suggest that skin-color regulation is the only definite role of SLa so far demonstrated in this species.


Trends in Colposcopy Volume: Where Do We Go From Here?
To describe the change in colposcopy volume in light of recent guideline shifts, which target higher-risk women while limiting unnecessary procedures in low-risk women. After institutional review board approval, colposcopy clinic visits at a large-volume referral center from January 2010 to December 2015 were reviewed. All women diagnosed with abnormal cervical cytology who were referred and subsequently underwent colposcopic evaluation were included. Mean monthly and annual clinic volumes were calculated. Return visit proportions were compared using chi-square test. Negative binomial regression analysis was used to examine trends. There were a total of 8722 colposcopy clinic visits between January 2010 and December 2015. Approximately 7395 visits (85%) were new patient visits, and 1327 visits (15%) were return visits. The percentage of return visits declined dramatically during the study period from 22.9% (2011) of total visits to 9.0% in 2015 (P < 0.001). Annual clinic volume ranged from 903 to 1884 with a mean monthly volume of 121.13 visits (SD, 42.1). Annual volume was highest in 2011 (n = 1884) and has since demonstrated a steady decline. In 2015, average monthly volume (75.3 visits) dropped to nearly one third of its peak 218 visits per month in July 2010. In a large referral clinic that adheres to guideline-based screening and management recommendations, monthly colposcopy volume has declined dramatically with a reduction by two thirds compared with peak volume in 2010.


Finding a most parsimonious or likely tree in a network with respect to an alignment.
Phylogenetic networks are often constructed by merging multiple conflicting phylogenetic signals into a directed acyclic graph. It is interesting to explore whether a network constructed in this way induces biologically-relevant phylogenetic signals that were not present in the input. Here we show that, given a multiple alignment A for a set of taxa X and a rooted phylogenetic network N whose leaves are labelled by X, it is NP-hard to locate a most parsimonious phylogenetic tree displayed by N (with respect to A) even when the level of N-the maximum number of reticulation nodes within a biconnected component-is 1 and A contains only 2 distinct states. (If, additionally, gaps are allowed the problem becomes APX-hard.) We also show that under the same conditions, and assuming a simple binary symmetric model of character evolution, finding a most likely tree displayed by the network is NP-hard. These negative results contrast with earlier work on parsimony in which it is shown that if A consists of a single column the problem is fixed parameter tractable in the level. We conclude with a discussion of why, despite the NP-hardness, both the parsimony and likelihood problem can likely be well-solved in practice.


[Physiopathology and biomechanics of hip osteoarthritis]
Several factors seem to play a relevant role in the pathogenesis of hip osteoarthritis. Among these, an altered biomechanic and neuromuscular integrity of the hip joint should be considered. This is a review of the recent international literature concerning the role of loads and strengths acting on the hip joint, in order to better understand the pathogenesis and the physiopathology of the hip osteoarthritis. The study of these factors might be important to prevent the development of the osteoarthritis and might suggest the conservative treatment. In particular, the role of the balance among the muscles working in maintaining the equilibrium of the acting strengths is matter of discussion. The articular and neuromuscular dysfunction might induce an altered load distribution in the hip, particularly on the articular cartilage surface, and seems to favour the development of hip osteoarthritis.


Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer's Disease Development in Mexico City Young Females.
Given the epidemiological trends of increasing Alzheimer's disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre- and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins. Exposures are associated with early brain gene imbalance in oxidative stress, inflammation, innate and adaptive immune responses, along with epigenetic changes, accumulation of misfolded proteins, cognitive deficits, and brain structural and metabolic changes. The Apolipoprotein E (APOE) 4 allele, the most prevalent genetic risk for AD, plays a key role in the response to air pollution in young girls. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5-2 SD from average IQ). This review focused on the relationships between gender, BMI, systemic and neural inflammation, insulin resistance, hyperleptinemia, dyslipidemia, vascular risk factors, and central nervous system involvement in APOE4 urbanites exposed to PM2.5 and magnetite combustion-derived iron-rich nanoparticles that can reach the brain. APOE4 young female heterozygous carriers constitute a high-risk group for a fatal disease: AD. Multidisciplinary intervention strategies could be critical for prevention or amelioration of cognitive deficits and long-term AD progression in young individuals at high risk.


microRNAs in heart disease: putative novel therapeutic targets?
microRNAs (miRs) are short, approximately 22-nucleotide-long non-coding RNAs involved in the control of gene expression. They guide ribonucleoprotein complexes that effect translational repression or messenger RNA degradation to targeted messenger RNAs. miRs were initially thought to be peculiar to the developmental regulation of the nematode worm, in which they were first described in 1993. Since then, hundreds of different miRs have been reported in diverse organisms, and many have been implicated in the regulation of physiological processes of adult animals. Of importance, misexpression of miRs has been uncovered as a pathogenic mechanism in several diseases. Here, we first outline the biogenesis and mechanism of action of miRs, and then discuss their relevance to heart biology, pathology, and medicine.


The CRE luc bioluminescence transgenic mouse model for detecting ligand activation of GPCRs.
Numerous assays have been developed to investigate the interactions between G-protein-coupled receptors (GPCRs) and their ligands since GPCRs are key therapeutic targets. Reporter-based assays using the cAMP response element (CRE) coupled with bioluminescence from a luciferase reporter have been used extensively in vitro with high-throughput screens (HTS) of large chemical compound libraries. We have generated a transgenic mouse model (CRE luc) with a luciferase reporter under the control of a synthetic promoter that contains several CREs, which supports real-time bioimaging of GPCR ligand activity in whole animals, tissues, or primary cells. In the CRE luc model, GPCR signaling through the cAMP pathway can be detected from the target GPCR that is in a native cellular environment with a full complement of associated receptors and membrane constituents. Multiple independent lines have been produced by random integration of the transgene, resulting in tissue expression profiles covering the major organs. The goal of the CRE luc model is to accelerate the transition from HTS to profiling of GPCR small-molecule leads in preclinical animal disease models, as well as define the mechanism of action of GPCR drugs in three experimental formats: primary cells, tissue homogenates, and whole animals.


The use of barbed sutures in obstetrics and gynecology.
Despite the multitude of different procedures performed with a host of different wound closure biomaterials, no study or surgeon has yet identified the perfect suture for all situations. In recent years, a new class of suture material-barbed suture-has been introduced into the surgeon's armamentarium. This review focuses on barbed suture to better understand the role of this newer material in obstetrics and gynecology.


Is tissue cross-talk important in cancer cachexia?
Recent work suggests molecular cross-talk between adipose tissue and muscle that occurs through adipokines and myokines. These molecules act in an endocrine fashion to play an intricate role in regulating body composition in both health and disease. Studies in exercise physiology have focused on the molecular cross-talk between adipose tissue and muscle that occurs through adipokines and myokines and on the role these molecules may play in chronic diseases. Similarly, integrative physiology in obesity and diabetes has long emphasised the importance of chronic inflammation, increased adipocyte lipolysis, and increased levels of circulating free fatty acids in the adipose-muscle cross-talk that contributes to lipotoxicity and insulin resistance in muscle. Cachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, quality of life, and duration of survival. Although cachexia in patients with cancer is characterized by systemic inflammation, increased lipolysis, insulin resistance, and reduced physical activity, there has been little effort to manipulate the integrative physiology of adipose tissue and muscle tissue for therapeutic gain.


Determinants of technology adoption and continued use among cognitively impaired older adults: a qualitative study.
Technology offers opportunities to support older adults with mild cognitive impairments to remain independent and socially connected, but is often not used. Although determinants of technology use among older adults in general are well studied, much less is known about how these factors impact technology use behaviour in cognitively impaired older adults. This study aimed to bridge this gap in research by examining the factors underlying technology use in community-dwelling older adults with mild cognitive impairments. We applied a generic qualitative design and used 16 semi-structured interviews to collect data from Belgian (Flemish) community-dwelling older adults diagnosed with Mild Cognitive Impairment or dementia and informal caregivers. To get data from different perspectives, a focus group with professional caregivers was added. We used thematic analysis with an inductive approach to identify and select themes from the data. We identified two themes: introduction of technology and determinants of technology adoption and continued use. Successful technology adoption in cognitively impaired older adults is need-driven and subject to individual, technological and contextual characteristics. Specific for older adults with cognitive impairments are the importance of disease awareness and cognitive ability for adoption and continued use, respectively. Although social support can be a valuable alternative to technology, it is an important facilitator of continued technology use in these older adults. Similarly, integration of technologies in daily routines can buffer discontinuation of technologies. Future research is encouraged to validate our findings in a postpandemic era and to further develop a novel theoretical framework for technology acceptance among older adults with cognitive impairments. Moreover, identification of crucial determinants as well as strategies to remove use barriers are also important future research tasks. Clinical practice should focus on improving disease awareness to facilitate technology adoption and policies should invest in training and support of professional caregivers and in reimbursement strategies to facilitate implementation of technology in practice.


Modes of experience and psychiatric education.
This paper describes two modes that an effective psychiatrist uses in understanding his patients. One mode is termed the rational-active, and the other sensuous-receptive. These modes present special problems in psychiatric education. The best teaching occurs when the superviser works in both modes and consistently and sensitively communicates these modes of experience to a resident.