Traditional treatment of mental disorders in rural Ethiopia.
Mental disorders are known to be as prevalent in Ethiopia as in other countries. Only 26 psychiatrists are working in the country with close to 80 million inhabitants. To this should be added clinics run by psychiatric nurses in most of the general hospitals. This means that still most of the mentally ill in the country are trected and cared for in a traditional way. This paper presents the situation regarding traditional treatment of mental illness in a rural area in central Ethiopia, Butajira, with a population of about 350,000 persons, predominantly Muslim. All traditional healers in Butajira area were mapped by asking key informants. Twenty-four healers were so identified and interviewed about their perception of mental illness and the treatment they offer. Clients from the healers and patients from the local health centre were interviewed about their opinions on the service given. A majority of both clients and patients were satisfied with the consultation, but the clients of the healers were more satisfied than the patients in health centres. As most persons with mental disorders are treated by traditional healers in rural Ethiopia and in most other developing countries it is important to do more comprehensive studies on the traditional treatment and to find ways of collaboration between traditional practice and modern medicine.


Smoking cessation among African Americans: what we know and do not know about interventions and self-quitting.
Many studies on cessation interventions and self-quitting have been conducted, but few have focused on African Americans. The purpose of this review was to critically evaluate the available studies and make recommendations for future research. Articles published from 1988 to 1998 were collected using Medline and other data bases, as well as personal communication. Studies were divided into two categories: evaluations of specific cessation interventions and examinations of self-quit behaviors and related factors. Studies were tabulated using author/year, study design/sample size, variables/results, and comments. In the intervention studies, church-based programs may provide an effective location for cessation interventions, but the studies to date did not demonstrate unequivocal effectiveness. In clinic programs, there do not appear to be any interventions that are particularly effective. In community-based interventions, there were no differences for African and Caucasian Americans. With regard to self-quitting, sociodemographic variables were similarly related to cessation as in the general population, as were smoking history variables. All other categories did not contain enough information for firm conclusions to be drawn. There are some interventions that appear to be useful, but little information is available on self-quitting. More research is needed on the natural history of quitting, on the social norms for smoking among African American groups, and on the conceptual dimensions of race in the context of this research.


Gold nanoparticles in biology: beyond toxicity to cellular imaging.
Gold, enigmatically represented by the target-like design of its ancient alchemical symbol, has been considered a mystical material of great value for centuries. Nanoscale particles of gold now command a great deal of attention for biomedical applications. Depending on their size, shape, degree of aggregation, and local environment, gold nanoparticles can appear red, blue, or other colors. These visible colors reflect the underlying coherent oscillations of conduction-band electrons ("plasmons") upon irradiation with light of appropriate wavelengths. These plasmons underlie the intense absorption and elastic scattering of light, which in turn forms the basis for many biological sensing and imaging applications of gold nanoparticles. The brilliant elastic light-scattering properties of gold nanoparticles are sufficient to detect individual nanoparticles in a visible light microscope with approximately 10(2) nm spatial resolution. Despite the great excitement about the potential uses of gold nanoparticles for medical diagnostics, as tracers, and for other biological applications, researchers are increasingly aware that potential nanoparticle toxicity must be investigated before any in vivo applications of gold nanoparticles can move forward. In this Account, we illustrate the importance of surface chemistry and cell type for interpretation of nanoparticle cytotoxicity studies. We also describe a relatively unusual live cell application with gold nanorods. The light-scattering properties of gold nanoparticles, as imaged in dark-field optical microscopy, can be used to infer their positions in a living cell construct. Using this positional information, we can quantitatively measure the deformational mechanical fields associated with living cells as they push and pull on their local environment. The local mechanical environment experienced by cells is part of a complex feedback loop that influences cell metabolism, gene expression, and migration.


Validation of a soy questionnaire with repeated dietary recalls and urinary isoflavone assessments over one year.
This study assessed the validity and reliability of a 12-item soy questionnaire designed for use in cancer prevention research. The questionnaire measures soy intake over the past year. Subjects were 199 healthy 35- to 46-yr-old premenopausal women participating in an ongoing soy intervention study. Soy questionnaire estimates of isoflavone intake over 1 yr were compared with individual and combined estimates from two reference measures covering the same period: three or four repeated 24-h recalls and one or two repeated urine analyses. The sensitivity and specificity of the soy questionnaire in classifying high vs. low exposure (high exposure = soy intervention group membership) were comparable with 24-h recalls and were superior to urine analyses (sensitivity = 94.8%, 97.9%, and 71.1%; specificity = 95.1%, 97.1%, and 90.3% for the soy questionnaire, 24-h recalls, and urine analyses, respectively). Soy questionnaire isoflavone estimates were highly correlated with the combination of the two reference measures for the entire study population. Its brevity, ease of administration, and good measurement properties over a 1-yr period make the soy questionnaire well suited to the needs of researchers who wish to identify high and low consumers of soy foods, especially in populations who consume traditional Asian soy foods.


Novel TRPS1 frameshift variant in tricho-rhino-phalangeal syndrome type I accompanied by zinc deficiency.
Tricho-rhino-phalangeal syndrome type I (TRPS1), caused by pathogenic variants in the transcriptional repressor GATA-binding 1 gene (TRPS1), is characterized by ectodermal and skeletal anomalies including short stature and sparse scalp hair during infancy. TRPS1 encodes a zinc finger protein transcription factor that contributes to bone homeostasis by regulating perichondral mineralization, chondrocyte proliferation, and apoptosis. Here, a male infant aged 14 months presented with sparse scalp hair, deformed nails, fused teeth, and postnatal growth retardation without neurodevelopmental disorder. As endocrinological measurements revealed low serum zinc levels, he was treated with zinc acetate hydrate, which improved his growth velocity and scalp hair. Whole-exome sequencing revealed that this patient harbored a novel pathogenic de novo heterozygous TRPS1 frameshift variant, c.2819_2822del, p.(His940Argfs*6). Zinc deficiency induces zinc finger protein dysfunction via effects on protein folding and assembly, affecting target gene transcription and apoptosis. The symptoms of TRPS1 are similar to those caused by inadequate levels of zinc, an essential trace element with important roles in tissue growth and repair. Accompanying zinc deficiency may have affected the function of important zinc finger proteins, resulting in phenotypic deterioration. Analysis of zinc metabolism in patients harboring TRPS1 variants will enhance understanding the variety of phenotypes of TRPS1.


50 shades of lockdown: sex workers' hidden world during COVID pandemic.
The COVID-19 pandemic had a huge impact on psychological health and socioeconomic structures. The consequences of COVID-19 on the physical, psychological, and social spheres have been extensively studied, except for aspects concerning sexuality and sex workers, in terms of physical, social and economic impact, but also as a possible cause for viral transmission. With the intention of counteracting the lack of research, from September 2020 to August 2022, we distributed an anonymous questionnaire to Sex Workers' associations aimed at investigating the impact of the pandemics on sex workers. In the period examined we received and reviewed 147 questionnaires from women, men, and transsexuals. The prevention of the viral transmission during a pandemic is of utmost importance but should not be exclusively promoted at the expense of other important prevention initiatives. Safeguarding psycho-physical health of the general population, including effective health educational communications emphasizing the importance of sexual activity in mental and physical health should be part of ongoing health objectives. These approaches need to include sex workers of all genders-particularly racialized and marginalized sex workers-in public health planning and messaging alongside structural interventions. Full decriminalization of sex work and access to workplace protections are key to protecting both sex workers' and clients' health. Sex workers of all genders have often been among the first hit by epidemics and the last to be protected-it is long past time to change that.


Regulation of endothelial nitric oxide synthase and postnatal angiogenesis by Rac1.
Diminished bioavailability of nitric oxide is a hallmark of endothelial dysfunction and is associated with a broad spectrum of vascular disorders such as impaired angiogenesis. Because Rac1, a Rho family member, mediates cellular motility and generation of reactive oxygen species, it could be involved in the regulation of endothelial nitric oxide production. However, the pathophysiological consequences of postnatal endothelial Rac1 deletion on endothelial function have not been determined. We generated endothelial-specific Rac1 haploinsufficient mice (EC-Rac1(+/-)) using Cre-loxP technology. The EC-Rac1(+/-) mice have decreased expression and activity of endothelial nitric oxide synthase (eNOS), impaired endothelium-dependent vasorelaxation, and mild hypertension compared with control (Rac1(+/flox)) mice. Hind limb ischemia model and aortic capillary sprouting assay showed that eNOS activity and angiogenesis was impaired in EC-Rac1(+/-) mice. Indeed, Rac1 promotes eNOS gene transcription through p21-activated kinase but not NADPH oxidase, increases eNOS mRNA stability, and enhances eNOS activity by promoting endothelial uptake of l-arginine. These findings indicate that endothelial Rac1 is essential for endothelium-dependent vasomotor response and ischemia-induced angiogenesis. These effects of Rac1 on endothelial function are largely due to the upregulation of eNOS through multiple mechanisms that are mediated, in part, by p21-activated kinase. Therapeutic strategies to enhance Rac1 function, therefore, may be important for preventing endothelial dysfunction.


Germacrone inhibits early stages of influenza virus infection.
Highly pathogenic influenza viruses pose a serious public health threat to humans. Although vaccines are available, antivirals are needed to efficiently control disease progression and virus transmission due to the emergence of drug-resistant viral strains. In this study, germacrone, which is a major component of the essential oils extracted from Rhizoma Curcuma, was found to inhibit influenza virus replication. Germacrone showed antiviral activity against the H1N1 and H3N2 influenza A viruses and the influenza B virus in a dose-dependent manner. The viral protein expression, RNA synthesis and the production of infectious progeny viruses were decreased both in MDCK and A549 cells treated with germacrone. In a time-of-addition study, germacrone was found to exhibit an inhibitory effect on both the attachment/entry step and the early stages of the viral replication cycle. Germacrone also exhibited an effective protection of mice from lethal infection and reduced the virus titres in the lung. Furthermore, the combination of germacrone and oseltamivir exhibited an additive effect on the inhibition of influenza virus infection, both in vitro and in vivo. Our results suggest that germacrone may have the potential to be developed as a therapeutic agent alone or in combination with other agents for the treatment of influenza virus infection.


Effect of lignin-blocking agent on enzyme hydrolysis of acid pretreated hemp waste.
Hemp wastes (stems and branches), fractionated after hemp flower extraction for the production of cannabidiol oil, were utilized as a potentially renewable resource for the sugar flatform process. Hydrolysis of cellulose from the acid pretreated hemp biomass using a commercial enzyme was tested and evaluated for its chemical composition, morphological change, and sugar recovery. Acid pretreated hemp stems and branches, containing 1% glucan (w/v) solids, were hydrolyzed for 72 h using 25 mg enzyme protein per g glucan. A 54% glucose conversion was achieved from the treated branches versus a 71% yield from the treated stems. Raw branches and stems yielded 35% and 38% glucose, respectively. Further tests with a lignin-blocking additive (e.g. bovine serum albumin) resulted in a 72% glucose yield increase for stem hydrolysis using 10 mg enzyme protein per g glucan. While pretreatment promotes amorphous hemicellulose decrease and cellulose decomposition, it causes enzyme inhibition/deactivation due to potential inhibitors (phenols and lignin-derived compounds). This study confirms the addition of non-catalytic proteins enhances the cellulose conversion by avoiding non-productive binding of enzymes to the lignin and lignin-derived molecules, with lignin content determining the degree of inhibition and conversion efficiency.


Are the clinical benefits of oral prenalterol in ischaemic heart failure due to beta blockade? A six month randomised double blind comparison with placebo.
The clinical effects of the oral beta 1 partial agonist, prenalterol, were investigated in 37 patients (29 male, eight female; mean age 57 years) with chronic ischaemic left ventricular failure using a placebo controlled randomised double blind protocol over six months. All patients were limited by dyspnoea (New York Heart Association class III) despite treatment with digoxin and diuretics. Twenty eight patients completed the protocol. Moderate clinical improvement was seen in the prenalterol group, whereas there was little change in the placebo group. Bicycle exercise capacity increased over six months in the prenalterol and placebo groups but only achieved statistical significance for prenalterol when compared with baseline values. Maximum exercise heart rate was significantly reduced in the prenalterol group compared with placebo. Radionuclide left ventricular ejection fraction at rest and during exercise and cardiothoracic ratio showed no significant improvement in either group over six months. Prenalterol was well tolerated and produced no increase in frequency of angina or ventricular arrhythmias. Prenalterol produced clinical benefits and improved exercise tolerance while reducing exercise heart rate. A moderate placebo response was noted. The apparent beta blocking effect of prenalterol may be as important as the beta 1 agonist effect in producing these benefits. Prenalterol has, however, been withdrawn because of side effects in animals.


Detection systems for antibody responses against herpes B virus.
Herpes B virus (BV) infection is highly prevalent among adult Asian macaques and rarely causes severe disease in infected animals. In contrast, BV infection of humans can induce fatal encephalitis in the absence of treatment. Therefore, the development of diagnostic tests for specific and sensitive detection of antibodies against BV is an important task. The cross-reactivity of antibodies against BV with related simplex viruses of other primates may afford an opportunity to obtain sensitive detection systems without the need to work with the highly pathogenic BV. Moreover, it has been proposed that use of recombinant viral glycoproteins may allow for a detection of antibody responses against BV with high specificity. However, limited data are available for both approaches to BV diagnostic. Here, we report that simian agent 8 (SA8; infects African green monkeys)- and herpesvirus papio 2 (HVP-2; infects baboons)-infected cells allow for a more sensitive detection of antibody responses against BV in macaques than lysates of herpes simplex virus type 1 and 2 (HSV-1/2; infect humans)-infected cells and a commercial HSV ELISA (Enzygnost® Anti-HSV/IgG). In addition, we show that sera from BV-infected macaques frequently contain antibodies against the recombinant BV glycoprotein gD (BV gD) that has been previously proposed as a diagnostic target for discriminating BV- and HSV-induced antibodies. However, we found that antibodies of some HSV-infected human patients also reacted with BV gD. In contrast, only sera of HSV-1- and HSV-2-infected humans, but not sera from BV-infected macaques, reacted with HSV-1/2 gG. Collectively, these results suggest that both SA8 and HVP-2 allow for sensitive and comparable detection of BV-directed antibody responses in macaques and that the combination of BV gD and HSV-1/2 gG needs to be complemented by a least one additional viral glycoprotein for reliable discrimination between antibody responses against BV and HSV-1/2 in humans.


Efficacy of pegylated interferon and ribavirin for retreatment of chronic HCV infection in HIV co-infected patients failing a previous standard interferon-based regimen.
Combination of pegylated interferon (Peg-IFN) and ribavirin is the standard treatment for HCV infection in HIV co-infected patients. However, data available on the efficacy of this therapy in co-infected patients who failed a former interferon-based regimen are limited. We analysed the efficacy and safety of the Peg-IFN alfa-2a or alfa-2b plus ribavirin combination in a multicentre observational cohort study including 54 HCV/HIV co-infected patients who had failed to respond to or relapsed on interferon-based treatment. The primary efficacy endpoint was the proportion of patients who achieved a sustained virological response (SVR), defined as HCV RNA <50 IU/mL 24 weeks after completion of therapy. By intention-to-treat analysis, 30% of the patients achieved an SVR. Viral eradication by genotype was 18.9% (7/37) genotype 1; 57.1% (8/14) genotype 3 and 33.3% (1/3) genotype 4. The only independent predictor of SVR was genotype 3 (odds ratio: 5.3; 95% confidence interval: 1.4-19.8). Fourteen (38%) patients with genotype 1 had undetectable viral load at week 48 of treatment. Nevertheless, 50% of them relapsed during the follow-up period. Severe adverse events or progression of HIV infection did not occur during the study; however, 39% of the patients required Peg-IFN dose reduction because of intolerance or haematological toxicity. Combined Peg-IFN and ribavirin achieved a substantial rate of SVR in HCV/HIV co-infected patients who failed a prior standard interferon-based regimen. The decision to retreat any co-infected patient should be individual-based. More aggressive strategies may be necessary to avoid the high relapse rate observed among patients with genotype 1.


Prevalence and Predictors of Obstructive Sleep Apnea in Patients with Chronic Obstructive Pulmonary Disease Undergoing Inpatient Pulmonary Rehabilitation.
The aim of our study was to evaluate the prevalence and predictors of obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD) undergoing inpatient pulmonary rehabilitation programs (PRPs). A retrospective data review of consecutive stable patients with a known diagnosis of COPD, admitted for PRP between January 2007 and December 2013. Full overnight polysomnography (PSG) and Epworth Sleepiness Scale (ESS) were assessed in all patients. Out of 422 evaluated patients, 190 (45%) showed an Apnea Hypopnea Index (AHI) ≥ 15 events/hour and underwent OSA treatment. Patients with OSA were significantly younger and had a less severe airway obstruction as compared to patients without OSA. There were no significant differences in cardiac comorbidities nor in arterial blood gases. As expected, patients with OSA showed significantly more severe diurnal symptoms, as assessed by the ESS and higher body mass index (BMI). However, only 69 out of 190 patients with OSA (36.3%) showed an ESS >10, whereas 25% of them had BMI ≤25 and 41% of them had a BMI <30. In all, 68% of patients with OSA were discharged with continuous positive airway pressure (CPAP), 15% with Bilevel ventilation, and 17% without any ventilatory treatment. In conclusion, in the population studied, the combination of OSA and COPD was frequent. BMI and ESS values commonly considered cutoff values for the prediction of OSA in the general population may not be accurate in a subgroup of patients with COPD.


Toward a clearer understanding of causal concepts in epidemiology.
In this manuscript, I share insights into causal concepts that emerged from creating and refining a simple example originally designed for teaching causal epidemiologic concepts. The insights that emerged are primarily related to the difference between how a causal effect occurs in an individual and what our methods assume about how a causal effect occurs when we estimate its effect in a population. In an individual, the causal effect of exposure on disease occurrence results from the interaction of several causal factors in that individual, not from a single factor in isolation. The result of this interaction within an individual determines an individual's causal type (e.g., doomed, exposure causative, exposure preventive, immune) with respect to a particular exposure contrast and target (etiologic) time period. In a population, the causal effect of exposure on disease frequency depends on the distribution of causal types of individuals in that population, not necessarily on the population distribution of covariates. Yet in epidemiology, when we attempt to estimate the effect of a potential cause of interest, we (through the methods we use) usually do not account for this within individual causal interaction. This failure to account for within-individual causal interactions has interesting implications for causal inference, as I illustrate here: (1) an effect estimate can be simultaneously confounded and unconfounded, (2) there can be confounding even if no variables satisfy the traditional criteria for being considered a confounder, (3) there can be no confounding even if there are variables that do satisfy the traditional confounder criteria, (4) the magnitude of confounding caused by a variable need not depend on the strength of the exposure-variable association, (5) a directed acyclic graph does not always correctly identify the presence of confounding, (6) the common-cause confounder criterion is imperfect, and (7) a time-varying confounder does not necessarily lead to time-varying confounding. Our example illustrates that confounding is a "team sport": single variables do not confound by themselves; confounding depends on how variables interact in individuals, not just on how variables are distributed within and across populations. Because confounding depends on how variables interact in individuals, methods that ignore causal interactions in individuals are not guaranteed to be confounding identification methods.


Cocaine Use and Incarceration: A Rare Cause of Bowel Ischemia, Perforation, and Gastrointestinal Hemorrhage.
Cocaine use is rising in persons ≥50 years old and in black and socioeconomically disadvantaged communities. Cocaine-induced bowel ischemia and gastrointestinal injury are deadly findings that have been previously described in the literature. In this report, we present a case of small bowel ischemia, perforation, and upper gastrointestinal hemorrhage co-occurring in a 62-year-old incarcerated male with a 15-year history of cocaine use. The patient presented from jail, peritonitic in septic shock, and was promptly taken for emergent surgical exploration. He was found to have massive fecal peritonitis secondary to full-thickness ischemia and perforation of the jejunum and ileum. Immediately postoperatively, the patient developed a large volume of hemorrhage from multiple gastric and duodenal ulcers refractory to endoscopic intervention, ultimately requiring emergent embolization of the gastroduodenal artery. His course was further complicated by severe septic shock with a blunted response to catecholamine vasopressors. Early recognition and aggressive treatment of the gastrointestinal complications and the unique critical care challenges associated with cocaine use facilitated this patient's eventual full recovery.


A Minimally Interventional Approach to Oesophageal Atresia Repair With Early Enteral Feeding is Safe, Optimises Neonatal Outcomes, and Reduces Resource use.
Recent series of newborn Oesophageal Atresia (OA) repair continue to report widespread use of chest drains, gastrostomy, routine contrast studies and parenteral nutrition (PN) despite evidence suggesting these are superfluous. We report outcomes using a minimally interventional approach to post-operative recovery. Ethically approved (15/WA/0153), single-centre, retrospective case-note review of consecutive infants with OA 2000-2022. Infants with OA and distal trache-oesophageal fistula undergoing primary oesophageal anastomosis at initial surgery were included (including those with comorbidities such as duodenal atresia, anorectal malformation and cardiac lesions). Our practice includes routine use of a trans-anastomotic tube (TAT), no routine chest drain nor gastrostomy, early enteral and oral feeding, no routine PN and no routine contrast study. Data are median (IQR). Of total 186 cases of OA treated during the time period, 157 met the inclusion criteria of which 2 were excluded as casenotes unavailable. TAT was used in 150 infants. A chest drain was required in 13 (8%) and two infants had a neonatal gastrostomy. Enteral feeds were started on postoperative day 2 (2-3), full enteral feeds established by day 4 (4-6) and oral feeds started on day 5 (4-8). PN was required in 15%. Median postoperative length of stay was 10 days (8-17). Progress was quicker in term infants than preterm. One infant died of cardiac disease prior to neonatal discharge. Two planned post-operative contrast studies were performed (surgeon preference) and a further 7 due to clinical suspicion of anastomotic leak. Contrast study was therefore avoided in 94%. There were 2 anastomotic leaks; both presented clinically at day 4 and day 8 after oral feeds had been started. Our minimally interventional approach is safe. It facilitates prompt recovery with lower resource use, reduced demand on nursing staff, reduced radiation burden, and early discharge home compared to published series without adversely affecting outcomes. Level 4.


Oxidative balance score and risk of prostate cancer: results from a case-cohort study.
Prostate cancer is a disease with a complex etiology. Oxidative stress has been implicated in its pathogenesis; however, few prospective studies have investigated the association between an oxidative stress/balance score and risk of prostate cancer. We investigated associations between an oxidative balance score, calculated as the summation of individual scores obtained from five pro-oxidative and eight anti-oxidative exposures, as well as each individual constituent of the score and risks of prostate cancer overall, and by clinical characteristics, in a case-cohort study (661 cases and 1864 subcohort) nested within the Canadian Study of Diet, Lifestyle, and Health cohort. Men in the lowest quintiles of each pro-oxidant exposure received a score of four (the highest score), while those in the highest quintile received a score of zero (the lowest score). In contrast, scoring for all anti-oxidants was performed in the opposite way. Total oxidative balance score was calculated by summating all individual scores of pro- and anti-oxidative variables, with higher values indicating a higher antioxidant status. The average oxidative balance score was similar between prostate cancer cases and men in the subcohort: 25.2 and 25.3, respectively. There was no association between oxidative balance score and overall risk of prostate cancer with hazard ratios (HRs) of 1.00, 1.02, 1.03, 0.97 and 1.01 for increasing quintiles of the score (p-trend=0.71). There were also no associations for non-advanced or advanced disease, or when analysis was restricted to incident cases that arose after two years of follow-up (n=508). In general constituents of the score were not associated with prostate cancer, except for red meat intake (HR=1.44; 95%CI 1.06-1.95 comparing Q5 vs. Q1) and lycopene (HRs of 0.7-0.8 for increasing quintiles). Our findings do not support an association between oxidative balance score and risks of overall prostate cancer or advanced disease.


Combination of Melatonin and Zoledronic Acid Suppressed the Giant Cell Tumor of Bone in vitro and in vivo.
Melatonin (Mlt) confers potential antitumor effects in various types of cancer. However, to the best of our knowledge, the role of Mlt in the giant cell tumor of bone (GCTB) remains unknown. Moreover, further research is required to assess whether Mlt can enhance the therapeutic effect of zoledronic acid (Zol), a commonly used anti-GCTB drug. In this research, we investigated the effects of Mlt, Zol, and the combination of these two drugs on GCTB cells' characteristics, including cell proliferation, apoptosis, osteogenic differentiation, migration, and invasion. The cell counting kit-8 (CCK-8) assay, colony formation assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL), alkaline phosphatase (ALP) staining, alizarin red staining (ARS), scratch wound healing assay, and transwell experiment were performed, respectively. Our results showed that Mlt could effectively inhibit the proliferation, migration, and invasion of GCTB cells, as well as promote the apoptosis and osteogenic differentiation of tumor cells. Of note, a stronger antitumor effect was observed when Mlt was combined with Zol treatment. This therapeutic effect might be achieved by inhibiting the activation of both the Hippo and NF-κB pathways. In conclusion, our study suggests that Mlt can be a new treatment for GCTB, which could further enhance the antitumor effect of Zol.


Confocal laser microscopic observation of glycocalyx production by Staphylococcus aureus in vitro.
We used a scanning confocal laser microscope to study the effects of various agents on sugar production by Staphylococcus aureus in vitro. S. aureus cells attached to coverslips in Pl-TSB (plasma:tryptic soy broth=1:1) were stained with fluorescein isothiocyanate-conjugated concanavalin A (FITC-conA) and were more strongly stained over time. We considered that the materials that stained positive for FITC-conA consistent with S. aureus cells were sugars, probably glycocalyx, produced by the S. aureus cells. Since the cells in the stationary growth phase alone were strongly stained with FITC-conA, all S. aureus cells attached to the coverslips in Pl-TSB were considered to be in this phase (low growth rate). The positive staining for FITC-conA was markedly reduced when fibrin was not formed in Pl-TSB with plasmin and sucrose, and was also markedly reduced when the fibrin in Pl-TSB was destroyed with plasmin. In conclusion, the results of the present study indicate that the existence of fibrin is essential for glycocalyx production and biofilm formation of S. aureus cells to aid in the attachment of S. aureus cells in vitro, because S. aureus cells attached on coverslips and fibrin alone produce glycocalyx. Of the antimicrobial agents tested, sulfadiazine silver most strongly inhibited the production of FITC-conA-positive materials by S. aureus cells at a sub-MIC concentration. Plasmin, sucrose, and sulfadiazine silver may be useful topical applications for use on clinical dermatology for the prevention and the treatment of staphylococcal biofilms. We consider that this simple method is very useful for the detection of S. aureus glycocalyx on dermatology field.


Effect of Acellular Amniotic Membrane Matrix Patch on Healing of Cut Surface After Sleeve Gastrectomy in Rats.
Background: The aim of this study was to evaluate the effect of acellular amniotic membrane matrix patch on healing cut surface after sleeve gastrectomy in rats. Methods: Thirty male Wistar albino rats were divided into three groups: control (n = 10), Experiment-1 (n = 10), and Experiment-2 (n = 10) groups. Control group rats underwent only sleeve gastrectomy with primary gastrorrhaphy. Experiment-1 group rats underwent sleeve gastrectomy, primary gastrorrhaphy and covered with acellular amniotic membrane matrix patch. Experiment-2 group rats underwent sleeve gastrectomy, incomplete primary gastrorrhaphy and covered with acellular amniotic membrane matrix patch. All rats were sacrificed on the fifth postoperative day. Macroscopic findings and histopathologic alterations were evaluated and compared. Results: There was a statistically significant difference between levels of PMNs, granulation formation and vascularization, distributions of edema, type of mucosal epithelium, and fibroblastic proliferation according to groups (p < 0.05). The PMNs level in the Experiment-1 group was significantly lower than the control group (p < 0.05). In experiment groups, the level of granulation tissue, vascularization and fibroblastic proliferation was significantly higher than the control group (p < 0.05). The levels of edema and type of mucosal epithelium of the experiment groups were significantly lower than the control group (p < 0.05). Conclusion: Covering sleeve gastrectomy cut surface area with acellular amniotic membrane matrix results better healing. Moreover, acellular amniotic membrane matrix provides safe healing even in incomplete sutured area.


Cruciferous vegetables reduce morphological markers of colon cancer risk in dimethylhydrazine-treated rats.
Consumption of cruciferous vegetables has been associated with reduced colon cancer risk in human populations. However, little experimental evidence exists to support this association. Here, we report the effects of diets containing cruciferous vegetables on colon cancer risk. In Expt. 1, rats were fed a vegetable-free (basal) diet or diets containing different lyophilized cruciferous vegetables in concentrations between 4 and 10%. In Expt. 2, rats were fed the basal diet or diets containing 10-22.6% fresh cruciferous vegetables. Diets were fed for 2 wk (Expt. 1) or 3 wk (Expt. 2) before and 7 wk (Expt. 1) or 12 wk (Expt. 2) after administration of the colon carcinogen 1,2-dimethylhydrazine. Rats fed fresh vegetables were also injected with a low dose of carcinogen 18-24 h prior to termination. Groups fed lyophilized vegetables did not differ in aberrant crypt foci (ACF), sialomucin-producing foci, or mucin-depleted foci (MDF) numbers. However, all fresh vegetable diets significantly decreased ACF (approximately 40%) and MDF numbers. Activities of the hepatic phase I enzyme CYP2E1 did not differ among groups in either experiment. Hepatic glutathione S-transferase (GST) and quinone reductase activities did not differ among groups fed fresh vegetables, whereas the lyophilized cabbage diets decreased GST activity compared with the basal diet. Groups did not differ in apoptosis and cell proliferation labeling indices in colonic mucosa. This study indicates that fresh but not lyophilized cruciferous vegetables reduce colon cancer risk in rats. These results do not support changes in hepatic carcinogen metabolism or colonic crypt cytokinetics as a mechanism.


Melatonin Inhibits Testosterone Synthesis in Rooster Leydig Cells by Targeting CXCL14 through miR-7481-3p.
Melatonin has been proved to be involved in testosterone synthesis, but whether melatonin participates in testosterone synthesis by regulating miRNA in Leydig cells is still unclear. The purpose of this study is to clarify the mechanism of melatonin on Leydig cells testosterone synthesis from the perspective of miRNA. Our results showed that melatonin could significantly inhibit testosterone synthesis in rooster Leydig cells. miR-7481-3p and CXCL14 were selected as the target of melatonin based on RNA-seq and miRNA sequencing. The results of dual-luciferase reporter assays showed that miR-7481-3p targeted the 3'-UTR of CXCL14. The overexpression of miR-7481-3p significantly inhibited the expression of CXCL14 and restored the inhibitory role of melatonin testosterone synthesis and the expression of StAR, CYP11A1, and 3β-HSD in rooster Leydig cells. Similarly, interference with CXCL14 could reverse the inhibitory effect of melatonin on the level of testosterone synthesis and the expression of StAR, CYP11A1, and 3β-HSD in rooster Leydig cells. The RNA-seq results showed that melatonin could activate the PI3K/AKT signal pathway. Interference with CXCL14 significantly inhibited the phosphorylation level of PI3K and AKT, and the inhibited PI3K/AKT signal pathway could reverse the inhibitory effect of CXCL14 on testosterone synthesis and the expression of StAR, CYP11A1 and 3β-HSD in rooster Leydig cells. Our results indicated that melatonin inhibits testosterone synthesis by targeting miR-7481-3p/CXCL14 and inhibiting the PI3K/AKT pathway.


The fidelity of replication of the three-base-pair set adenine/thymine, hypoxanthine/cytosine and 6-thiopurine/5-methyl-2-pyrimidinone with T7 DNA polymerase.
With the goal of constructing a genetic alphabet consisting of a set of three base pairs, the fidelity of replication of the three base pairs T(H) (5-methyl-2-pyrimidinone)/H(S) (6-thiopurine; thiohypoxanthine), C/H (hypoxanthine) and T/A was evaluated using T7 DNA polymerase, a polymerase with a strong 3'-->5' exonuclease activity. An evaluation of the suitability of a new base pair for replication should include both the contribution of the fidelity of a polymerase activity and the contribution of proofreading by a 3'-->5' exonuclease activity. Using a steady-state kinetics method that included the contribution of the 3'-->5' exonuclease activity, the fidelity of replication was determined. The method determined the ratio of the apparent rate constant for the addition of a deoxynucleotide to the primer across from a template base by the polymerase activity and the rate constant for removal of the added deoxynucleotide from the primer by the 3'-->5' exonuclease activity. This ratio was designated the eni (efficiency of net incorporation). The eni of the base pair C/H was equal to or greater than the eni of T/A. The eni of the base pair T(H)/H(S) was 0.1 times that of A/T for T(H) in the template and 0.01 times that of A/T for H(S) in the template. The ratio of the eni of a mismatched deoxynucleotide to the eni of a matched deoxynucleotide was a measure of the error frequency. The error frequencies were as follows: thymine or T(H) opposite a template hypoxanthine, 2x10(-6); H(S) opposite a template cytosine, <3x10(-4). The remaining 24 mismatched combinations of bases gave no detectable net incorporation. Two mismatches, hypoxanthine opposite a template thymine or a template T(H), showed trace incorporation in the presence of a standard dNTP complementary to the next template base. T7 DNA polymerase extended the primer beyond each of the matched base pairs of the set. The level of fidelity of replication of the three base pairs with T7 DNA polymerase suggests that they are adequate for a three-base-pair alphabet for DNA replication.


Inelastic neutron scattering study of a nonmagnetic collapsed tetragonal phase in nonsuperconducting CaFe2As2: evidence of the impact of spin fluctuations on superconductivity in the iron-arsenide compounds.
The relationship between antiferromagnetic spin fluctuations and superconductivity has become a central topic of research in studies of superconductivity in the iron pnictides. We present unambiguous evidence of the absence of magnetic fluctuations in the nonsuperconducting collapsed tetragonal phase of CaFe2As2 via inelastic neutron scattering time-of-flight data, which is consistent with the view that spin fluctuations are a necessary ingredient for unconventional superconductivity in the iron pnictides. We demonstrate that the collapsed tetragonal phase of CaFe2As2 is nonmagnetic, and discuss this result in light of recent reports of high-temperature superconductivity in the collapsed tetragonal phase of closely related compounds.


Perception of Acceptable Range of Smiles by Specialists, General Dentists and Lay Persons and Evaluation of Different Aesthetic Paradigms.
One of the most important goals of restorative dentistry is to restore the patient's aesthetic. Smile analysis is subjective and it differs from person to person. An aesthetic smile involves a harmonious relationship between various parameters including the hard and soft tissues. The aim of the study was to identify the acceptable range of several smiles (alone and in conjunction with the face) by specialists, general dentists as well as lay persons; and to identify the values of different criteria i.e., the Golden Proportion (GP), the Recurrent Esthetic Dental proportion (RED), Width to Height ratio (W/H ratio), the Apparent Contact Dimension (ACD), and lateral incisor position in a smile. Hundred photographs of 50 subjects were taken, 50 of the smile alone and 50 of the individual's frontal view of face. The photographs of the smiles and the faces were assessed for the aesthetic acceptability by 30 evaluators including 10 specialists with advanced training, 10 general dentists and 10 lay persons. Irreversible hydrocolloid impressions were made of the dentitions of all the individuals using stock trays and were poured in dental stone. Measurements were made on the facial surface of the teeth on the models and were recorded in millimeters using a sharp tipped digital vernier calliper. Data was analyzed to evaluate the presence of different parameters assessed in the smiles. Mean and standard deviation values for the percentage of only the agreeable smiles were calculated in both individual smile analysis and in conjunction with the face. The non agreeable smiles were excluded from further statistical analysis. Pearson Correlation Coefficient was calculated to compare the values obtained in all the three groups. More number of smiles were considered agreeable by the general dentists when compared to the specialists and the number even increased in case of evaluation by lay persons. Greater number of smiles was found to be agreeable when they were evaluated in conjunction with the face. Rather than assessment of individual numeric parameter that defines an ideal aesthetic smile, a smile to be aesthetic should harmonize with the composition of the face.


Molecular and genetic analysis of multiple changes in the levels of production of virulence factors in a subcultured variant of Streptococcus mutans.
We previously isolated a variant strain, Xc100L, which shows decreased production of a surface protein antigen with a molecular mass of 190 kDa (PAc), after repeated subculturing of Streptococcus mutans strain Xc [Koga, T. et al. (1989) J.Gen. Microbiol. 135, 3199-3202]. In the present study, the levels of expression of the gtfB, gtfC, gtfD and ftf genes coding for polysaccharide-synthesizing enzymes in strain Xc100L were compared with those in strain Xc. Western blot analysis revealed multiple differences in the levels of production of these enzymes between these two strains. The amounts of the gtfB and gtfC gene products responsible for water-insoluble glucan synthesis in strain Xc100L were lower than those in strain Xc, whereas the amounts of the gtfD and ftf gene products responsible for water soluble glucan synthesis and fructan synthesis, respectively, in strain Xc100L were higher than those in strain Xc. Northern blot analysis revealed that the amounts of the four enzymes and PAc produced by strain Xc100L reflected the relative amounts of mRNAs from the genes. The chloramphenicol acetyltransferase gene was fused with each of these five genes, and the transcriptional activity of each gene in strain Xc100L was quantitatively compared with that in strain Xc. The chloramphenicol acetyltransferase assay also indicated that the phenotypic differences between strain Xc and strain Xc100L were due to differences in the transcriptional activities of the virulence genes. No differences in the nucleotide sequences of the promoter regions of the gtfB, gtfC, gtfD, ftf and pac genes were found between strain Xc and strain Xc100L. It is possible that a factor(s) affecting the levels of transcription of the multiple virulence genes exists in S. mutans.


Sane and safe: Forced social distancing to prevent human-to-human transmission of COVID-19.
The current outbreak of COVID-19, originating from the city of Wuhan in China and ultimately involving over 200 countries, is now a global concern. Evidence indicates that COVID-19 spread to humans from wild animals, causing severe respiratory tract infections in humans; the typical symptoms of COVID include cough, high-grade fever, sore throat, and difficulty in breathing. The infection spreads from human to human via droplets. Therefore, social or physical distancing can reduce spread within communities. Asymptomatic spread can also occur during family gatherings or in the workplace; thus, we must enforce physical distancing as much as possible to reduce the spread of cases.


No Interactive Effects of Sex and Persistent Cytomegalovirus on Immune Phenotypes in Young Children: The Generation R Study.
Persistent infections with cytomegalovirus (CMV) differentially affect the host immune phenotype in middle-aged males and females. Because CMV already impacts on T-cell memory at a young age, we studied whether these effects were modified by sex in 1,079 children with an average age of 6 years. Sex and CMV independently impacted on multiple B-cell and T-cell subsets. However, there was no significant effect of their interaction. Importantly, the effects of sex and CMV were in part explained by age and infection with other herpesviruses. Thus, immune aging is likely to be more complex, with involvement of hormonal changes with age, socioeconomic status, birth characteristics, and pathogen exposure.


Estimating the broad-sense heritability of early growth of cowpea.
Cowpea is an important tropical crop. It provides a large proportion of the food resource for the African human population and their livestock. The yield and quality of cowpea have been dramatically improved through traditional breeding strategies for the past few decades. However, reports of heritability estimates for early growth of cowpea are rare. We designed a simple experiment to estimate the broad-sense heritability of early growth. We randomly selected 15 cowpea varieties among a total of 5000 cowpea accessions maintained in the cowpea breeding facility at the University of California, Riverside to examine the genetic determination of early growth of cowpea (measured as the height at day five after seeding). The estimated broad-sense heritability on the individual plant basis is 0.2190. However, the corresponding estimate on the plant mean basis (average of four plants) is 0.5198, which is very high for a quantitative trait. The high heritability may explain why traditional breeding for cowpea growth is so effective. Since the design of experiment and method of data analysis are novel, this report can serve as an educational note for students in the area of quantitative genetics and plant breeding.


United States Normative Attitudes for Pursuing Parenthood as a Function of Gender, Sexual Orientation, and Age.
Decisions about whether or not to become a parent are significant parts of normative human development. Many studies have shown that married different-sex couples are expected to become parents, and that many social pressures enforce this norm. For same-sex couples, however, much less is known about social norms surrounding parenthood within marriage. This study examined injunctive norms and descriptive norms for the pursuit of parenthood as a function of age, gender, and sexual orientation. Participants in an internet survey included 1020 (522 heterosexual, 498 lesbian/gay) cisgender people from across the United States Findings showed that norms, especially descriptive norms, for the pursuit of parenthood for heterosexual people were much stronger than those for lesbian women and gay men, and that norms for lesbian women were stronger than those for gay men. These differences were more pronounced for older, heterosexual, and male participants. However, lesbian and gay participants, especially gay men, reported that lesbian and gay people ought to become parents to the same extent as heterosexual people. Overall, the results indicated that, regardless of sexual orientation, adults report that lesbian and gay married people ought to become parents, but that they expect only a minority of these couples will pursue parenthood. This research provided a glimpse into how Americans are envisioning family formation among same-sex couples today.


Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions.
Filopodia are actin-rich membrane protrusions essential for cell morphogenesis, motility, and cancer invasion. How cells control filopodium initiation on the plasma membrane remains elusive. We performed experiments in cellulo, in vitro, and in silico to unravel the mechanism of filopodium initiation driven by the membrane curvature sensor IRSp53 (insulin receptor substrate protein of 53 kDa). We showed that full-length IRSp53 self-assembles into clusters on membranes depending on PIP2. Using well-controlled in vitro reconstitution systems, we demonstrated that IRSp53 clusters recruit the actin polymerase VASP (vasodilator-stimulated phosphoprotein) to assemble actin filaments locally on membranes, leading to the generation of actin-filled membrane protrusions reminiscent of filopodia. By pulling membrane nanotubes from live cells, we observed that IRSp53 can only be enriched and trigger actin assembly in nanotubes at highly dynamic membrane regions. Our work supports a regulation mechanism of IRSp53 in its attributes of curvature sensation and partner recruitment to ensure a precise spatial-temporal control of filopodium initiation.


Nucleotide sequence of the xanthine guanine phosphoribosyl transferase gene of E. coli.
The nucleotide sequence of the gpt coding for the enzyme xanthine guanine phosphoribosyl transferase has been determined. The gene codes for a protein of molecular weight 16,950. The construction of deletions in the gpt gene which can be used for the genetic analysis of mutations in the gpt gene, is described.


Phylogenetic evidence for a major reversal of life-history evolution in plethodontid salamanders.
The transition from aquatic to terrestrial eggs is a key evolutionary change that has allowed vertebrates to successfully colonize and exploit the land. Although most amphibians retain the primitive biphasic life cycle (eggs deposited in water that hatch into free-living aquatic larvae), direct development of terrestrial eggs has evolved repeatedly and may have been critical to the evolutionary success of several amphibian groups. We provide the first conclusive evidence for evolutionary reversal of direct development in vertebrates. The family Plethodontidae (lungless salamanders) contains the majority of salamander species, including major radiations of direct developers. We reconstruct the higher level phylogenetic relationships of plethodontid salamanders using molecular and morphological data and use this phylogeny to examine the evolution of direct development. We show that the predominantly biphasic desmognathines, previously considered the sister group of other plethodontids, are nested inside a group of direct-developing species (Plethodontini) and have re-evolved the aquatic larval stage. Rather than being an evolutionary dead end, the reversal from direct developing to biphasic life history may have helped communities in eastern North America to achieve the highest local diversity of salamander species in the world.


Stand-alone laboratory information systems versus laboratory modules incorporated in the electronic health record.
The increasing availability of laboratory information management modules within enterprise electronic health record solutions has resulted in some institutional administrators deciding which laboratory information system will be used to manage workflow within the laboratory, often with minimal input from the pathologists. This article aims to educate pathologists on many of the issues and implications this change may have on laboratory operations, positioning them to better evaluate and represent the needs of the laboratory during this decision-making process. The experiences of the authors, many of their colleagues, and published observations relevant to this debate are summarized. There are multiple dimensions of the interdependency between the pathology laboratory and its information system that must be factored into the decision. Functionality is important, but management authority and gap-ownership are also significant elements to consider. Thus, the pathologist must maintain an active role in the decision-making process to ensure the success of the laboratory.


[Beta-endorphin and stress hormones in patients affected by osteoarthritis undergoing thermal mud therapy].
Thermal mud is a therapeutic agent widely used in the treatment of painful arthritic processes. The mechanism by which mud therapy works is still not well known. Its effect continues for months after completion of treatment. In order to verify whether thermal mud treatment brings about changes in the production of hormone peptides from proopiomelanocortin, the levels of plasma beta-endorphin and some hormones of the pituitary-adrenal glands (ACTH and cortisol) were determined in patients affected by osteoarthritis undergoing thermal mud therapy. The levels of plasma beta-endorphin and some hormones of the pituitary-adrenal glands (ACTH and cortisol) were assessed by radiometric methods in seventeen males affected by osteoarthritis. The patients underwent a cycle of twelve sessions of thermal mud therapy. The tests were carried out immediately before thermal treatment, immediately after the first session, twelve days after the start of treatment, and again one month after completion of the treatment. beta-endorphin levels decreased significantly twelve days after the start of treatment. The level was still lower, although not significantly, even thirty days after completion of the treatment. Plasma ACTH also decreased during treatment. The decrease of this hormone was progressive and persisted after completion of treatment. Significant variations compared to baseline were found only thirty days after completion of treatment. Plasma cortisol decreased significantly after only one session of mud therapy. This hormone did not decrease any further during treatment, however, after twelve days it was still significantly lower than baseline. After completion of treatment, cortisol slightly increased, but thirty days later it was still lower, although not significantly, than baseline. It may be suggested that thermal treatment, by reducing inflammation, reduced pain and therefore diminished the cause of stress.


Isolation of biofunctional bovine immunoglobulin G from milk- and colostral whey with mixed-mode chromatography at lab and pilot scale.
The aim of the present work was to develop a new scalable and cost-efficient process to isolate bovine immunoglobulin G from colostral whey with high purity and minimal loss of activity. The mixed mode material Mercapto-Ethyl-Pyridine-Hypercel™ was identified appropriate for direct capture of immunoglobulin G. The binding mechanism is primarily based on hydrophobic interactions at physiological conditions. As compared to immunoglobulin G, all other low molecular whey proteins such as α-Lactalbumin or β-Lactoglobulin, except lactoperoxidase, are more hydrophilic and were therefore found in the flow-through fraction. In order to remove lactoperoxidase as an impurity the column was combined in series with a second mixed mode material (Capto™- with N-benzoyl-homocysteine as ligand) using the same binding conditions. At pH 7.5 the carboxyl group of this ligand is negatively charged and can hence bind the positively charged lactoperoxidase, whose isoelectric point is at pH 9.6. After sample application, the columns were eluted separately. By combining the two columns it was possible to obtain immunoglobulin G with a purity of >96.1% and yield of 65-80%. The process development was carried out using 1 mL columns and upscaling was performed in three steps up to a column volume of 8800 mL for the Hypercel™ column and 3000 mL for the Capto™- column. At this scale it is possible to obtain 130-150 g pure immunoglobulin G from 3 L colostrum within five hours, including the regeneration of both columns. Additionally, the impact of freeze-drying on the isolated immunoglobulin G was studied. The nativity of the freeze dried immunoglobulin was above 95%, which was proven by reversed phase liquid chromatography and validated by differential scanning calorimetry. The activity of immunoglobulin G was preserved over the isolation process and during drying as measured by enzyme-linked immunosorbent assay. In conclusion, by applying the proposed isolation process, it becomes feasible to obtain pure, active and stable imunnunoglobulin G at large scale.


Surface coatings that promote rapid release of peptide-based AgrC inhibitors for attenuation of quorum sensing in Staphylococcus aureus.
Staphylococcus aureus is a major human pathogen responsible for a variety of life-threatening infections. The pathogenicity of this organism is attributed to its ability to produce a range of virulence factors and toxins, including the superantigen toxic shock syndrome toxin-1 (TSST-1). While many S. aureus infections can be treated using conventional antibiotics, strains resistant to these bactericidal agents have emerged. Approaches that suppress pathogenicity through mechanisms that are nonbactericidal (i.e., antivirulence approaches) could provide new options for treating infections, including those caused by resistant strains. Here, we report a nonbactericidal approach to suppressing pathogenicity based on the release of macrocyclic peptides (1 and 2) that inhibit the agr quorum sensing (QS) circuit in group-III S. aureus. It is demonstrated that these peptides can be immobilized on planar and complex objects (on glass slides, nonwoven meshes, or within absorbent tampons) using the rapidly dissolving polymer carboxymethylcellulose (CMC). Peptide-loaded CMC films released peptide rapidly (<5 min) and promoted strong (>95%) inhibition of the agr QS circuit without inducing cell death when incubated in the presence of a group-III S. aureus gfp-reporter strain. Peptide 1 is among the most potent inhibitors of QS in S. aureus reported to date, and the group-III QS circuit regulates production of TSST-1, the primary cause of toxic shock syndrome (TSS). These results thus suggest approaches to treat the outer covers of tampons, wound dressings, or other objects to suppress toxin production and reduce the severity of TSS in clinical and personal care contexts. Because peptide 1 also inhibits QS in S. aureus groups-I, -II, and -IV, this approach could also provide a pathway for attenuation of QS and associated virulence phenotypes in a broader range of contexts.


The kinetic mechanism of the major form of ox kidney aldehyde reductase with D-glucuronic acid.
The steady-state kinetics of the major form of ox kidney aldehyde reductase with d-glucuronic acid have been determined at pH7. Initial rate and product inhibition studies performed in both directions are consistent with a Di-Iso Ordered Bi Bi mechanism. The mechanism of inhibition by sodium valproate and benzoic acid is shown to involve flux through an alternative pathway.


Breast feeding and mental and motor development at 12 months in a low-income population in northeast Brazil.
The aim of this prospective study was to investigate the association between breast feeding and mental and motor development at age 12 months, controlling for comprehensive measures of the child's socio-economic, maternal and environmental background, and nutritional status. A cohort of 205 infants born during May-August 2001 in a poor area in the interior of the State of Pernambuco was enrolled, of whom 191 were tested at age 12 months with the Bayley Scales of Infant Development II, and in whom breast-feeding status was measured at days 1, 10, 30, 60, 90, 120, 150, 180, 270 and 360. After adjusting for potential confounders, full breast feeding (i.e. exclusive or predominant) at 1 month was associated with a small but significant benefit in mental development (+3.0 points, P = 0.02) compared with partial or no breast feeding. No additional advantage in mental development was found with longer durations of full breast feeding. Full breast feeding at 1 month was associated with improved behaviour for two of 10 ratings tested: initiative with tasks (P = 0.003) and attention (P = 0.02). No association between breast feeding and motor development was found.


Application of Individualized Speed Zones to Quantify External Training Load in Professional Soccer.
This study aimed to examine the interchangeability of two external training load (ETL) monitoring methods: arbitrary vs. individualized speed zones. Thirteen male outfield players from a professional soccer team were monitored during training sessions using 10-Hz GPS units over an 8-week competitive period (n = 302 observations). Low-speed activities (LSA), moderate-speed running (MSR), high-speed running (HSR) and sprinting were defined using arbitrary speed zones as <14.4, 14.4-19.8, 19.8-25.1 and ≥25.2 km·h-1, and using individualized speed zones based on a combination of maximal aerobic speed (MAS, derived from the Yo-yo Intermittent recovery test level 1), maximal sprinting speed (MSS, derived from the maximal speed reached during training) and anaerobic speed reserve (ASR) as <80% MAS, 80-100% MAS, 100% MAS or 29% ASR and ≥30% ASR. Distance covered in both arbitrary and individualized methods was almost certainly correlated in all speed zones (p < 0.01; r = 0.67-0.78). However, significant differences between methods were observed in all speed zones (p < 0.01). LSA was almost certainly higher when using the arbitrary method than when using the individualized method (p < 0.01; ES = 5.47 [5.18; 5.76], respectively). Conversely, MSR, HSR and sprinting speed were higher in the individualized method than in the arbitrary method (p < 0.01; ES = 5.10 [4.82; 5.37], 0.86 [0.72; 1.00] and 1.22 [1.08; 1.37], respectively). Arbitrary and individualized methods for ETL quantification based on speed zones showed similar sensitivity in depicting player locomotor demands. However, since these methods significantly differ at absolute level (based on measurement bias), arbitrary and individualized speed zones should not be used interchangeably.


Cost-Effectiveness of Dementia Prevention Interventions.
Assessment of cost-effectiveness of interventions to address modifiable risk factors associated with dementia requires estimates of long-term impacts of these interventions which are rarely directly available and must be estimated using a range of assumptions. To test the cost-effectiveness of dementia prevention measures using a methodology which transparently addresses the many assumptions required to use data from short-term studies, and which readily incorporates sensitivity analyses. We explore an approach to estimating cost-effective prices which uses aggregate data including estimated lifetime costs of dementia, both financial and quality of life, and incorporates a range of assumptions regarding sustainability of short- term gains and other parameters. The approach is addressed in the context of the theoretical reduction in a range of risk factors, and in the context of a specific small-scale trial of an internet-based intervention augmented with diet and physical activity consultations. The principal outcomes were prices per unit of interventions at which interventions were cost-effective or cost-saving. Taking a societal perspective, a notional intervention reducing a range of dementia risk-factors by 5% was cost-effective at $A460 per person with higher risk groups at $2,148 per person. The on-line program costing $825 per person was cost-effective at $1,850 per person even if program effect diminished by 75% over time. Interventions to address risk factors for dementia are likely to be cost-effective if appropriately designed, but confirmation of this conclusion requires longer term follow-up of trials to measure the impact and sustainability of short-term gains.


Patient self-injection of methotrexate for inflammatory arthritis: a study evaluating the introduction of a new type of syringe and exploring patients' sense of empowerment.
To evaluate the introduction of a new type of syringe for patients on a self-injection of methotrexate (MTX) programme and explore patients' sense of empowerment relating to the self-injection of MTX. Data were collected using a postal questionnaire, which yielded quantitative and qualitative data. The questionnaire was sent to all eligible patients in the primary care setting who self-injected MTX (n=24). The response rate was 88% (n=21). Patients' responses illustrated numerous disadvantages of using the syringe, particularly difficulties with the syringe stopper, syringe handling and leakage potential of the mildly cytotoxic drug MTX. The advantages included the ease of syringe storage and longer use by date. Difficulties in using the syringe, and the amount of support and training from hospital staff were among the factors affecting patients' sense of empowerment. Although a small study, this work indicates that there may be benefits in a collaboration between hospital staff and the syringe manufacturer, to modify the new syringe to address the problems noted. The potential of cytotoxic MTX spillage being minimized is recognized, making the new syringe more suitable for use by patients with inflammatory arthritis. Patient training may help to alleviate difficulties in using a new syringe, which, in turn, may also increase patients' sense of empowerment.


Isospora ashmoonensis sp. nov. from blackcap warbler, Sylvia atricapilla in Egypt.
Microscopic examination of faecal samples collected from naturally infected blackcap warbler, Sylvia atricapilla revealed the presence of a new Isospora species; I. ashmoonensis. Oocysts were subspherical to oval, measuring 24.0 (21.0-25.0) microns in length and 20.0 (19.0-20.5) microns in width. A micropyle and an oocyst residuum were absent whereas one polar granule was seen. Ellipsoidal sporocysts contained a stieda body and measured 17.0 (16.0-18.5) x 9.2 (9.0-10.0) microns. Sporulation took place within 50 hrs. at room temperature. Developmental stages of the parasite in epithelial cells of the posterior third of the ileum were also described.


Involvement of maternal grandmother and teenage mother in intervention to reduce pacifier use: a randomized clinical trial.
To assess the impact of an intervention for teenage mothers with the involvement of maternal grandmothers on the prevalence of pacifier use in the first six months of life. This randomized clinical trial involved 323 teenage mothers, allocated to four groups: intervention with teenagers only, intervention with teenagers and their mothers, and respective controls. Six breastfeeding counseling sessions, including the recommendation to avoid the use of a pacifier, were delivered at the maternity ward and subsequently at the teenagers' homes, at seven, 15, 30, 60, and 120 days postpartum. Data on infant feeding and pacifier use were collected monthly by interviewers blinded to group allocation. The impact of the intervention was measured by comparing survival curves for pacifier use in the first six months of life and mean time to pacifier introduction. The intervention had a significant impact on reducing pacifier use only in the group in which grandmothers were involved. In this group, the intervention delayed by 64 days the introduction of a pacifier (21-85 days), compared to 25 days in the group without the participation of grandmothers (65-90 days). The intervention reduced pacifier use in the first six months of life and delayed its introduction until beyond the first month when grandmothers were involved. The intervention did not have a significant impact when only teenage mothers were involved.


Allosteric Competition and Inhibition in AMPA Receptors.
Excitatory neurotransmission is principally mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). Dysregulation of AMPARs is the cause of many neurological disorders and how therapeutic candidates such as negative allosteric modulators inhibit AMPARs is unclear. Here, we show that non-competitive inhibition desensitizes AMPARs to activation and prevents positive allosteric modulation. We dissected the noncompetitive inhibition mechanism of action by capturing AMPARs bound to glutamate and the prototypical negative allosteric modulator, GYKI-52466, with cryo-electron microscopy. Noncompetitive inhibition by GYKI-52466, which binds in the transmembrane collar region surrounding the ion channel, negatively modulates AMPARs by decoupling glutamate binding in the ligand binding domain from the ion channel. Furthermore, during allosteric competition between negative and positive modulators, negative allosteric modulation by GKYI-52466 outcompetes positive allosteric modulators to control AMPAR function. Our data provide a new framework for understanding allostery of AMPARs and foundations for rational design of therapeutics targeting AMPARs in neurological diseases.


Estimation of serum C-reactive protein activity in periodontal health and disease and response to treatment: a clinico-biochemical study.
Periodontitis is a chronic infectious disease affecting periodontium having multifactorial etiology, can cause significant systemic challengein addition to localized inflammation, tissue damage, and bone resorption. A serological marker of systemic inflammation known as C-reactive protein has been linked to an increased risk for a number of pathological conditions, including cardiovascular diseases. To estimate levels of serum C-reactive protein in healthy individuals and subjects with periodontal diseases and to compare serum C-reactive protein levels in subjects having periodontal disease pre-operatively & post-operatively. The study was conducted on 60 subjects age ranging from 35 to 60 years. 30 individuals with healthy periodontium were in group 1 (control group) and the remaining 30 were diagnosed as adult periodontitis were in group 2 (experimental group). Periodontal examination done using gingival index, plaque index, periodontal pocket depth, and Russel's index. CRP levels were examined between group 1 and group 2 and in group 2 between baseline visit before treatment and 2 months after treatment. The findings of this study show a significant connection between periodontal disease and the inflammatory marker CRP in the body, as well as a tendency for a significant decrease in serumCRP levels following periodontitis therapy. At baseline, there was a positive correlation among C-reactive protein, probing pocket depth, and Russell's index. As CRP is a key mediator for cardiovascular disease, an increase in C- reactive protein levels in periodontal diseases suggests a significant connection between periodontitis and cardiovascular diseases. Early periodontal treatment might decrease the severity of cardiovascular disease that already exists. This suggests that periodontal examination should be part of routine practicealong with cardiovascular examination.


Local adaptation and migratory habits balance spatial-genetic structure between continental and insular chestnut tiger butterflies in East Asia.
Geographic and climatic differences between islands and continents may affect the evolution of their biota, and promote divergent selection in species distributed in both landscapes. To assess spatial-genetic structure, we genotyped 18 expressed sequence tag-simple sequence repeat (EST-SSR) loci and sequenced two mtDNA markers (ND5 and COI) and one nuclear marker (EF1α) in two subspecies of the butterfly Parantica sita. Compared with nuclear markers, mtDNA had a stronger signal of population structure. Approximate Bayesian computation (ABC) suggested that a continuous-gene-flow model best described the data. According to this model, the two subspecies diverged approximately 23.1 kya, with 10 times more introgression from the continental (ssp. sita) to the insular subspecies (ssp. niphonica) than vice versa. Ecological niche modelling was performed to predict the paleo- and current potential distributions and elucidate the geohistorical process, which revealed a northeastern, insular origin. Winter precipitation and annual temperature range were the main determinants of the subspecies distributions. Maximum-likelihood population-effects models showed that the population differentiation of the insular and continental subspecies was primarily affected by environmental resistance and local climate. Sex-biased migration capacity and long-term precipitation-driven divergence between the continental and insular lineages shaped the current genetic structure of P. sita. Evidence from the nuclear markers confirmed intersubspecific gene flow despite adaptive divergence between the subspecies. These results imply that the continental subspecies is still capable of returning to the island and introgressing with the insular subspecies.


Trends in Periprosthetic Knee Infection and Associated Costs: A Population-Based Study Using National Data.
Given increasing demand for primary knee arthroplasties, revision surgery is also expected to increase, with periprosthetic joint infection (PJI) a main driver of costs. Recent data on national trends is lacking. We aimed to assess trends in PJI in total knee arthroplasty revisions and hospitalization costs. From the National Inpatient Sample (2003-2016), we extracted data on total knee arthroplasty revisions (n = 782,449). We assessed trends in PJI prevalence and (inflation-adjusted) hospitalization costs (total as well as per-day costs) for all revisions and stratified by hospital teaching status (rural/urban by teaching status), hospital bed size (≤299, 300-499, and ≥500 beds), and hospital region (Northeast, Midwest, South, and West). The Cochran-Armitage trend test (PJI prevalence) and linear regression determined significance of trends. PJI prevalence overall was 25.5% (n = 199,818) with a minor increasing trend: 25.3% (n = 7,828) in 2003 to 28.9% (n = 19,275) in 2016; p < 0.0001. Median total hospitalization costs for PJI decreased slightly ($23,247 in 2003-$20,273 in 2016; p < 0.0001) while median per-day costs slightly increased ($3,452 in 2003-$3,727 in 2016; p < 0.0001), likely as a function of decreasing length of stay. With small differences between hospitals, the lowest and highest PJI prevalences were seen in small (≤299 beds; 22.9%) and urban teaching hospitals (27.3%), respectively. In stratification analyses, an increasing trend in PJI prevalence was particularly seen in larger (≥500 beds) hospitals (24.4% in 2003-30.7% in 2016; p < 0.0001), while a decreasing trend was seen in small-sized hospitals. Overall, PJI in knee arthroplasty revisions appears to be slightly increasing. Moreover, increasing trends in large hospitals and decreasing trends in small-sized hospitals suggest a shift in patients from small to large volume hospitals. Decreasing trends in total costs, alongside increasing trends in per-day costs, suggest a strong impact of length of stay trends and a more efficient approach to PJI over the years (in terms of shorter length of stay).


Modeling intraindividual variation in unsafe driving in a naturalistic commuting environment.
Commuting to work by car is a frequently occurring activity that poses a salient risk to worker safety. Although general stress perceptions have been linked to indicators of unsafe commuting in cross-sectional studies, little is known about whether and how day-to-day variability in stressor exposure and subjective and affective strain reactions covary with intraindividual variability in unsafe driving while commuting over time. A major contributor to this knowledge gap is the lack of a validated methodology to link subjective self-report variables to objective driving performance criteria in a naturalistic commuting environment. Data were collected from university staff employees (N = 50) over a 2-week sample of daily experiences and objective recordings of unsafe driving behaviors. We applied a multilevel methodology to evaluate a model in which exposure to daily hindering and challenging components of work stress, end-of-workday psychological distress, and end-of-workday negative affect influence objectively monitored unsafe driving behaviors in a naturalistic commuting environment. Results indicated that employees were less likely to drive unsafely during their postwork commute on days in which they encountered more challenge stressors at work (odds ratio = .63). However, employees who experienced heightened negative affective spillover were more likely to drive unsafely during their postwork commute (odds ratio = 1.96). We discuss the theoretical, practical, and methodological implications of our findings for research on employee commuting safety. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Dominant transcript expression profiles of human protein-coding genes interrogated with GTEx dataset.
The discovery and quantification of mRNA transcripts using short-read next-generation sequencing (NGS) data is a complicated task. There are far more alternative mRNA transcripts expressed by human genes than can be identified from NGS transcriptome data and various bioinformatic pipelines, while the numbers of annotated human protein-coding genes has gradually declined in recent years. It is essential to learn more about the thorough tissue expression profiles of alternative transcripts in order to obtain their molecular modulations and actual functional significance. In this report, we present a bioinformatic database for interrogating the representative tissue of human protein-coding transcripts. The database allows researchers to visually explore the top-ranked transcript expression profiles in particular tissue types. Most transcripts of protein-coding genes were found to have certain tissue expression patterns. This observation demonstrated that many alternative transcripts were particularly modulated in different cell types. This user-friendly tool visually represents transcript expression profiles in a tissue-specific manner. Identification of tissue specific protein-coding genes and transcripts is a substantial advance towards interpreting their biological functions and further functional genomics studies.


On the role of granule yield strength for the compactibility of granular solids.
The objective of this article was to explore the relationship between mechanical properties of single granules and the evolution in tensile strength and tablet micro-structure. Granules of different expected deformation behavior were used as model materials. It is suggested that the role of plasticity in this context is twofold: firstly, to affect the rate of compactibility and thus the pressure range needed to reach the maximal attained tablet strength and, secondly, to affect the mode of deformation of the granules and thus the maximal attained tablet strength. A decrease in yield pressure of single granules increased the tablet tensile strength at a given compaction pressure. The yield pressure can be controlled by the granule composition and porosity.


Nonapeptide Receptor Distributions in Promising Avian Models for the Neuroecology of Flocking.
Collective behaviors, including flocking and group vocalizing, are readily observable across a diversity of free-living avian populations, yet we know little about how neural and ecological factors interactively regulate these behaviors. Because of their involvement in mediating a variety of social behaviors, including avian flocking, nonapeptides are likely mediators of collective behaviors. To advance the neuroecological study of collective behaviors in birds, we sought to map the neuroanatomical distributions of nonapeptide receptors in three promising avian models that are found across a diversity of environments and widely ranging ecological conditions: European starlings, house sparrows, and rock doves. We performed receptor autoradiography using the commercially available nonapeptide receptor radioligands, 125I-ornithine vasotocin analog and 125I-linear vasopressin antagonist, on brain tissue sections from wild-caught individuals from each species. Because there is known pharmacological cross-reactivity between nonapeptide receptor subtypes, we also performed a novel, competitive-binding experiment to examine the composition of receptor populations. We detected binding in numerous regions throughout the brains of each species, with several similarities and differences worth noting. Specifically, we report that all three species exhibit binding in the lateral septum, a key brain area known to regulate avian flocking. In addition, sparrows and starlings show dense binding in the dorsal arcopallium, an area that has received scant attention in the study of social grouping. Furthermore, our competitive binding results suggest that receptor populations in sparrows and starlings differ in the lateral septum versus the dorsal arcopallium. By providing the first comprehensive maps of nonapeptide receptors in European starlings, house sparrows, and rock doves, our work supports the future use of these species as avian models for neuroecological studies of collective behaviors in wild birds.


Local adaptation: Mechanical fit between floral ecotypes of Nerine humilis (Amaryllidaceae) and pollinator communities.
Geographic variation in floral morphology is often assumed to reflect geographic variation in pollinator communities and associated divergence in selective pressures. We studied populations of Nerine humilis (Amaryllidaceae) to assess whether geographic variation in floral form is the result of local adaptation to different pollinator communities. We first tested for associations between floral traits and visitor communities, and found that populations with similar floral morphologies were visited by similar insect communities. Mean style length in each population was also closely associated with the mean body length of the local visitor community. A reciprocal translocation experiment demonstrated that native phenotypes set more seed than translocated phenotypes. Single visitation experiments showed that native flowers received more pollen, and set more seed per visit, than introduced phenotypes in both populations. This suggests that the effectiveness of pollinator visits is determined by the degree of mechanical fit between flowers and visitors. We provide strong evidence that the observed among-population variation in floral traits is an adaptive response to geographic variation in the pollinator community.


Emerging Trends in Financing of Adult Heart Transplantation in the United States.
This study examined longitudinal trends in types of payers for adult heart transplantations in the United States. In the last decade, volume of heart transplantations in the United States has substantially increased, a trend that has coincided with Medicaid expansion and greater insurance coverage in the general U.S. Limited data are available characterizing the changes in payer mix supporting these recent increases in heart transplantation activity. De-identified data were obtained from the Organ Procurement and Transplantation Network for heart transplantation recipients 18 to 64 years of age in the United States between 1997 and 2017. Primary sources of insurance payment were determined at the time of transplantation in aggregate and stratified by sex and race. Changes in volume and payer mix of patients added to the candidate waitlist between 1997 and 2017 were also examined. A total of 36,340 adults from 18 to 64 years of age underwent heart transplantations between 1997 and 2017. Support by public payer insurance increased from 28.2% (in 1997) to a peak of 48.8% (in 2016). Medicaid coverage increased from 9.4% in 1997 to 15.5% in 2007 and remained stable to 2017 (14.7%; β-coefficient: +0.23% [0.04]; p < 0.001 for trend). Medicare beneficiaries accounted for 18.2% of recipients in 1997, 22% in 2007, and 30.3% in 2016 (β-coefficient: +0.60% [0.06]; p < 0.001 for trend). The proportion of transplantation candidates receiving Medicare coverage increased over time across all races and both sexes. Similar aggregate patterns were observed in waitlist trends for adult heart transplantation candidates. Public payer insurance has emerged as an increasingly dominant source of funding for adult heart transplantations in the United States, supporting nearly half of all transplants in 2017.


Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase, detected by mass spectrometry in human plasma following deliberate overdose.
The goal of this study was to develop a method to detect pesticide adducts in tryptic digests of butyrylcholinesterase in human plasma from patients poisoned by pesticides. Adducts to butyrylcholinesterase in human serum may serve as biomarkers of pesticide exposure because organophosphorus and carbamate pesticides make a covalent bond with the active site serine of butyrylcholinesterase. Serum samples from five attempted suicides (with dichlorvos, Aldicarb, Baygon and an unknown pesticide) and from one patient who accidentally inhaled dichlorvos were analyzed. Butyrylcholinesterase was purified from 2 ml serum by ion exchange chromatography at pH 4, followed by procainamide affinity chromatography at pH 7. The purified butyrylcholinesterase was denatured, digested with trypsin and the modified peptide isolated by HPLC. The purified peptide was analyzed by multiple reaction monitoring in a QTRAP 4000 mass spectrometer. This method successfully identified the pesticide-adducted butyrylcholinesterase peptide in four patients whose butyrylcholinesterase was inhibited 60-84%, but not in two patients whose inhibition levels were 8 and 22%. It is expected that low inhibition levels will require analysis of larger serum plasma volumes. In conclusion, a mass spectrometry method for identification of exposure to live toxic pesticides has been developed, based on identification of pesticide adducts on the active site serine of human butyrylcholinesterase.


[Long-term application of warfarin or acenocumarol in patients with fibrillating arrhythmia: the effects compared].
Thromboembolic complications (cerebral infarction and system embolism) are the most threatening ones in patients with ciliary arrhythmia without valvular lesions. Transoesofhageal echocardiography is the method of choice in detection of left atrial auricle thrombosis, which is the main source of thromboembolism in this category of patients. Primary and secondary prevention of thromboembolic complications in patients with ciliary arrhythmia is a topical problem, still remaining unsolved. Administration of indirect anticoagulants, which are the preparations of choice, demands strict doctor's supervision and continuous laboratory monitoring. The study presents authors' own data, based upon the observation of patients treated with either warfarin or acenocumarol. The paper demonstrates equal efficiency of both cumarine anticoagulants. The frequency of haemorrhagic complications after 12-month therapy with either warfarin or acenocumorol in patients with ciliary arrhythmia without valvular lesions was comparable. Warfarin provided more stable level of anticoagulation and thus long-term warfarin therapy was characterized by lower risk of complication.


Early-adult correlates of maltreatment in girls with attention-deficit/hyperactivity disorder: Increased risk for internalizing symptoms and suicidality.
We examined whether maltreatment experienced in childhood and/or adolescence prospectively predicts young adult functioning in a diverse and well-characterized sample of females with childhood-diagnosed attention-deficit/hyperactivity disorder (N = 140). Participants were part of a longitudinal study and carefully evaluated in childhood, adolescence, and young adulthood (M age = 9.6, 14.3, and 19.7 years, respectively), with high retention rates across time. A thorough review of multisource data reliably established maltreatment status for each participant (M κ = 0.78). Thirty-two (22.9%) participants experienced at least one maltreatment type (physical abuse, sexual abuse, or neglect). Criterion variables included a broad array of young adult measures of functioning gleaned from multiple-source, multiple-informant instruments. With stringent statistical control of demographic, prenatal, and family status characteristics as well as baseline levels of the criterion variable in question, maltreated participants were significantly more impaired than nonmaltreated participants with respect to self-harm (suicide attempts), internalizing symptomatology (anxiety and depression), eating disorder symptomatology, and well-being (lower overall self-worth). Effect sizes were medium. Comprising the first longitudinal evidence linking maltreatment with key young adult life impairments among a carefully diagnosed and followed sample of females with attention-deficit/hyperactivity disorder, these findings underscore the clinical importance of trauma experiences within this population.


High dietary calcium attenuates the enhanced vasoconstrictor effects of serum from salt-loaded rats.
The effect of calcium supplementation and salt loading on blood pressure, serum electrolytes, and vasoconstrictor response to serum and vascular prostaglandin synthesis were studied in Sprague Dawley rats. The mean arterial pressure of salt-loaded rats was higher (P < 0.05) than the mean arterial pressure of normal rats, salt-loaded-calcium-fed rats, or calcium-fed rats. Serum from salt-loaded rats had lower serum potassium (4.47 +/- 0.39 Meq/L) and salt-loaded-calcium-fed rats (5.14 +/- 0.47 Meq/L). The vasoactivity of serum from the salt-loaded rats (1116.67 +/- 160.13 mg) was higher than the contraction produced by sera from normal rats (643.80 +/- 37.50 mg) or from salt-loaded-calcium fed rats (562.47 +/- 37.50 mg). Indomethacin did not alter the contractile response of aortae from normal rats and salt-loaded rats to noradrenaline, but it significantly enhanced the contractile response of aortae from salt-loaded-calcium-fed and calcium-fed rats. The results suggest that dietary calcium may lower blood pressure by reducing the circulating levels of some plasma vasoactive factors induced by salt loading and by enhancing the synthesis of vasodilator prostaglandins.


Causes of abnormal vaginal bleeding in a Family Practice Center.
Abnormal vaginal bleeding had an incidence of 20.0 per 1,000 woman-years in patients of the Kanawha Valley Family Practice Center. Contraception-related bleeding was the most common cause, accounting for 28 percent of the cases. Anovulatory and dysfunctional uterine bleeding were the next most common causes, accounting for 15 percent and 13 percent, respectively. All three causes were uncommon in women aged 41 to 55 years, and absent in women older than 55 years. Perimenopausal bleeding, the dominant cause of abnormal vaginal bleeding in the 41-to-55-year group, was also absent in women older than 55 years of age. In women 56 years of age or older, endometrial carcinoma caused 28.6 percent of the bleeding; it did not occur in any other group.


Cross-Modal Associations between Sounds and Drink Tastes/Textures: A Study with Spontaneous Production of Sound-Symbolic Words.
Many languages have a word class whose speech sounds are linked to sensory experiences. Several recent studies have demonstrated cross-modal associations (or correspondences) between sounds and gustatory sensations by asking participants to match predefined sound-symbolic words (e.g., "maluma/takete") with the taste/texture of foods. Here, we further explore cross-modal associations using the spontaneous production of words and semantic ratings of sensations. In the experiment, after drinking liquids, participants were asked to express their taste/texture using Japanese sound-symbolic words, and at the same time, to evaluate it in terms of criteria expressed by adjectives. Because the Japanese language has a large vocabulary of sound-symbolic words, and Japanese people frequently use them to describe taste/texture, analyzing a variety of Japanese sound-symbolic words spontaneously produced to express taste/textures might enable us to explore the mechanism of taste/texture categorization. A hierarchical cluster analysis based on the relationship between linguistic sounds and taste/texture evaluations revealed the structure of sensation categories. The results indicate that an emotional evaluation like pleasant/unpleasant is the primary cluster in gustation.


Opening a band gap without breaking lattice symmetry: a new route toward robust graphene-based nanoelectronics.
Developing graphene-based nanoelectronics hinges on opening a band gap in the electronic structure of graphene, which is commonly achieved by breaking the inversion symmetry of the graphene lattice via an electric field (gate bias) or asymmetric doping of graphene layers. Here we introduce a new design strategy that places a bilayer graphene sheet sandwiched between two cladding layers of materials that possess strong spin-orbit coupling (e.g., Bi2Te3). Our ab initio and tight-binding calculations show that a proximity enhanced spin-orbit coupling effect opens a large (44 meV) band gap in bilayer graphene without breaking its lattice symmetry, and the band gap can be effectively tuned by an interlayer stacking pattern and significantly enhanced by interlayer compression. The feasibility of this quantum-well structure is demonstrated by recent experimental realization of high-quality heterojunctions between graphene and Bi2Te3, and this design also conforms to existing fabrication techniques in the semiconductor industry. The proposed quantum-well structure is expected to be especially robust since it does not require an external power supply to open and maintain a band gap, and the cladding layers provide protection against environmental degradation of the graphene layer in its device applications.


Waveguide lenses with multimode interference for low-loss slab propagation.
It is shown that a nearly ideal two-dimensional focusing Gaussian beam can be synthesized by use of a linear combination of the two lowest-order even modes of an optical waveguide. This property can be used to couple laterally guided modes across slab waveguide regions with low loss. The technique is illustrated by use of a conventional multimode interference (MMI) geometry, in which the MMI coupler transforms the fundamental mode of an initial waveguide into a focusing Gaussian beam, which is then fed to a slab region. Two-dimensional beam propagation simulations show that the beam does not initially diverge in the slab region, but rather comes to a focus. A second MMI coupler then transforms the diverging beam back to the initial mode. A structure is designed that can couple the fundamental mode of a 9-microm-wide waveguide across an 88-microm-long slab region with only a 0.036-dB loss. This technique can be applied to improve the performance of small-angle waveguide crossings and integrated turning mirrors.


Overcoming Challenges to Make Bacteriophage Therapy Standard Clinical Treatment Practice for Cystic Fibrosis.
Individuals with cystic fibrosis (CF) are given antimicrobials as prophylaxis against bacterial lung infection, which contributes to the growing emergence of multidrug resistant (MDR) pathogens isolated. Pathogens such as Pseudomonas aeruginosa that are commonly isolated from individuals with CF are armed with an arsenal of protective and virulence mechanisms, complicating eradication and treatment strategies. While translation of phage therapy into standard care for CF has been explored, challenges such as the lack of an appropriate animal model demonstrating safety in vivo exist. In this review, we have discussed and provided some insights in the use of primary airway epithelial cells to represent the mucoenvironment of the CF lungs to demonstrate safety and efficacy of phage therapy. The combination of phage therapy and antimicrobials is gaining attention and has the potential to delay the onset of MDR infections. It is evident that efforts to translate phage therapy into standard clinical practice have gained traction in the past 5 years. Ultimately, collaboration, transparency in data publications and standardized policies are needed for clinical translation.