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For university students, who are often under significant stress to perform well, sleep is particularly important, playing roles in learning and academic performance. Research demonstrates a relationship between hope and sleep quality. However, most work concerns Western samples, and the hope construct has been criticized for a Western bias. No research investigates sleep quality’s relationship to “negotiable fate,” a construct more relevant to Asian cultures. Whereas hope involves the individualistic expectancy that goals are achievable through personal action, negotiable fate involves the more collectivist-informed belief that control can be exercised over goals within limits of fate (family, community, society, other external factors). We investigated the relationship of hope and negotiable fate with sleep quality in 160 university students in Hong Kong, administering measures of hope, negotiable fate, sleep quality, depression, anxiety, stress, and life satisfaction. Lower hope was associated with poorer self-reported sleep quality. In addition, consistent with past research, mental health variables (particularly stress) accounted for significant variance in this relationship. Negotiable fate, however, did not relate to sleep quality.

While prominent measures of hope are largely cognitive in nature, many scholars and laypeople view hope primarily as an emotion. Although Snyder’s Elaborated Hope Theory attempts to theoretically balance these two perspectives, no measure yet exists of hope as a purely emotional process, only as a cognitive process. Overlooking the emotional features of hope limits our ability to more fully and precisely understand this construct. As such, across three studies (N = 2,900), we develop and validate the Trait Emotion Hope Scale (TEHS). In Study 1, we report on item development and piloting of the TEHS, examining internal consistency as well as convergent and discriminant validity. Study 2 includes an exploratory factor analysis (EFA) and further examines internal consistency and construct validity. Finally, in Study 3 we report a confirmatory factor analysis (CFA) to cross-validate the factor structure identified in Study 2 in a large, international sample. Importantly, we find that the TEHS accounts for significant unique variance beyond cognitive hope, indicating that the two constructs are distinct and not redundant. Taken together, these three studies demonstrate that the TEHS is psychometrically sound and provides a valid measure for those interested in examining hope as an emotion in their research.

In this study, Hsu et al. show that inhibition of CDK7/12/13 attenuates maladaptive transcriptional activation in cultured cardiomyocytes and a mouse model of heart failure, suggesting that targeting the transcription machinery might be a therapeutic approach to treat heart failure with reduced ejection fraction.

We present a case where Hyphopichia burtonii, a yeast, speciated from peritoneal fluid in a cirrhotic patient with secondary peritonitis. The patient, a man in his 60s with decompensated cirrhosis, was admitted for an upper gastrointestinal (GI) bleed. On admission, he was treated empirically for spontaneous bacterial peritonitis (SBP) but failed to improve with antibiotics. Serial paracenteses revealed polymicrobial peritonitis and rising peritoneal polymorphonuclear leukocytes (PMNs). These findings raised concerns for secondary peritonitis, prompting an abdominal computed tomography (CT) scan which revealed ischemic bowel. Among the peritoneal microbiota isolated, Hyphopichia burtonii predominated. Hyphopichia burtonii has only recently been reported as a human pathogen, previously it had only reported as a pathogen in bats[1,2].

Purpose: To report long-term evolution of unilateral focal choroidal excavation in a patient with ABCA4-related retinopathy. Observations: A 51-year-old female with ABCA4-related retinopathy developed a small juxtafoveal defect in Bruch's membrane in a region of macular atrophy in her left eye. In follow-up, the defect widened and subsequently developed into a focal choroidal excavation. Over the next 8 years, serial optical coherence tomography imaging illustrated the conversion of the focal choroidal excavation from conforming subtype into non-conforming subtype with eventual macular hole formation. Conclusions and importance: The long-term follow-up of a patient with serial imaging highlights the potential dynamic nature of focal choroidal excavation in ABCA4-related retinopathy. Progressive retinal degeneration may influence focal choroidal excavation morphology and may promote macular hole formation.

Objective Determine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).Methods We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach.Results Twenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults.Conclusions We report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes.Trial registration number NCT04358302.

The article identifies three principles of classification of initial and mixed abbreviations relating to the vocabulary of the nuclear industry: according to their lexical and grammatical category (appellatives, nomens, onyms), their pronunciation (alphabetism and acronyms) and their origin (proper and borrowed abbreviations). The types and characteristics of abbreviations are studied by means of the descriptive, contextual, pragmatic and structural methods in order to identify their specific features which are likely to denote the abbreviations of the professional discourse. The sample language material includes the vocabulary of the nuclear industry. The outcomes of the research make it possible to draw the following conclusions about the general and specific characteristics of abbreviations in professional discourse: 1) according to the communicative-discursive approach, the abbreviation process ensures the success of a communicative act providing the idea to be short and clear; 2) the use of abbreviations outside the professional discourse can lead to communicative failure due to the existing discursive antinomy friend or foe that defines professional language users and people irrelevant to the professional discourse; 3) the abbreviations-appellatives are likely to predominate due to long-word terms as a characteristic of a developing industry and a young terminological system; 4) the numerical or alphabetic part of abbreviations is seen as their specific features that can make sense for professionals and absolutely vague for the rest of native speakers; 5) abbreviations-onyms, including ergonyms and chrematonyms, follow the general linguistic trends; 6) alphabetisms come over acronyms that is non-typical for Modern Russian and is caused by a great number of long-word terms, often including abbreviations with hard-to-pronounce sound combinations, as well as preserving the informational significance of components or provoking homonymous repulsion processes.

Lipofuscin of retinal pigment epithelium (RPE) cells is a complex heterogeneous system of chromophores which accumulates as granules during the cell’s lifespan. Lipofuscin serves as a source of various cytotoxic effects linked with oxidative stress. Several age-related eye diseases such as macular degeneration of the retina, as well as some severe inherited eye pathologies, are accompanied by a significant increase in lipofuscin granule concentration. The accumulation of carotenoids in the RPE could provide an effective antioxidant protection against lipofuscin cytotoxic manifestations. Given the highly lipophilic nature of carotenoids, their targeted delivery to the vulnerable tissues can potentially be assisted by special proteins. In this study, we demonstrate how protein-mediated delivery of zeaxanthin using water-soluble Bombyx mori carotenoid-binding protein (BmCBP-ZEA) suppresses the photoinducible oxidative stress in RPE cells caused by irradiation of lipofuscin with intense white light. We implemented fluorescence lifetime imaging of the RPE cell culture ARPE-19 fed with lipofuscin granules and then irradiated by white light with and without the addition of BmCBP-ZEA. We demonstrate that after irradiation the mean fluorescence lifetime of lipofuscin significantly increases, while the presence of BmCBP-ZEA at 200 nM concentration suppresses the increase in the average lifetime of lipofuscin fluorescence, indicating an approx. 35% inhibition of the oxidative stress. This phenomenon serves as indirect yet important evidence of the efficiency of the protein-mediated carotenoid delivery into pigment epithelium cells.

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

The article focuses on studying chrematonyms in nuclear and space industry professional discourse. The analysis of 734 Russian, English, Italian, French, German, Polish and Japanese lexemes nominating spacecraft, spaceships, nuclear reactors and nuclear research facilities resulted in discovering three common ways in the process of generating and functioning of chrematonyms in the professional discourse, including a lexico-semantic nomination (formed by means of onimization of appellatives, transonymization of personal and precedent names, toponyms, chrematonyms and cosmonims, deonimization); the word-formation considers the sound, syllabic and mixed abbreviation, as well as the formation of compound words; the syntactic method involves the formation of simple and complex substantive combinations of words. The authors conclude that chrematonyms as a class of onims have a specific linguistic meaning, affecting the semantic generation of the proper name in an inanimate object of material culture and emphasizing the unique and differential feature of the object and point to their specifically professional linguistic feature: motivation, derivative character, terminological unity, and frequency of usage. The research demonstrates the following special aspects of functioning of chrematonyms in the professional discourse: play on words, allusions and metaphors, ameliorative and deteriorative connotative meanings, which reflect non-typical processes for professional lexis and perform a peace-maintaining function of the language.

Summary: In this study low-input RNA-sequencing was used to annotate the molecular identity of endothelial cells isolated and immunopurified with CD144 microbeads. Using this technique, comparative gene expression profiling from healthy subjects and patients with type 2 diabetes mellitus identified both known and novel pathways linked with EC dysfunction. Modeling of diabetes by treating cultured ECs with high glucose identified shared changes in gene expression in diabetic cells. Overall, the data demonstrate how purified ECs from patients can be used to generate new hypotheses about mechanisms of human vascular disease. Key Words: endothelial cells, gene expression, diabetes mellitus, endothelial cell dysfunction

Abstract Background Primary spontaneous pneumothorax is a common disorder occurring in young adults without underlying lung disease. Although tobacco smoking is a well-documented risk factor for spontaneous pneumothorax, an association between electronic cigarette use (that is, vaping) and spontaneous pneumothorax has not been noted. We report a case of spontaneous pneumothoraces correlated with vaping. Case presentation An 18-year-old Caucasian man presented twice with recurrent right-sided spontaneous pneumothoraces within 2 weeks. He reported a history of vaping just prior to both episodes. Diagnostic testing was notable for a right-sided spontaneous pneumothorax on chest X-ray and computed tomography scan. His symptoms improved following insertion of a chest tube and drainage of air on each occasion. In the 2-week follow-up visit for the recurrent episode, he was asymptomatic and reported that he was no longer using electronic cigarettes. Conclusions Providers and patients should be aware of the potential risk of spontaneous pneumothorax associated with electronic cigarettes.

OBJECTIVES:. To establish the feasibility of empirically testing crisis standards of care guidelines. DESIGN:. Retrospective single-center study. SETTING:. ICUs at a large academic medical center in the United States. SUBJECTS:. Adult, critically ill patients admitted to ICU, with 27 patients admitted for acute respiratory failure due to coronavirus disease 2019 and 37 patients admitted for diagnoses other than coronavirus disease 2019. INTERVENTIONS:. Review of electronic health record. MEASUREMENTS AND MAIN RESULTS:. Many U.S. states released crisis standards of care guidelines with algorithms to allocate scarce healthcare resources during the coronavirus disease 2019 pandemic. We compared state guidelines that represent different approaches to incorporating disease severity and comorbidities: New York, Maryland, Pennsylvania, and Colorado. Following each algorithm, we calculated priority scores at the time of ICU admission for a cohort of patients with primary diagnoses of coronavirus disease 2019 and diseases other than coronavirus disease 2019 (n = 64). We assessed discrimination of 28-day mortality by area under the receiver operating characteristic curve. We simulated real-time decision-making by applying the triage algorithms to groups of two, five, or 10 patients. For prediction of 28-day mortality by priority scores, area under the receiver operating characteristic curve was 0.56, 0.49, 0.53, 0.66, and 0.69 for New York, Maryland, Pennsylvania, Colorado, and raw Sequential Organ Failure Assessment score algorithms, respectively. For groups of five patients, the percentage of decisions made without deferring to a lottery were 1%, 57%, 80%, 88%, and 95% for New York, Maryland, Pennsylvania, Colorado, and raw Sequential Organ Failure Assessment score algorithms, respectively. The percentage of decisions made without lottery was higher in the subcohort without coronavirus disease 2019, compared with the subcohort with coronavirus disease 2019. CONCLUSIONS:. Inclusion of comorbidities does not consistently improve an algorithm’s performance in predicting 28-day mortality. Crisis standards of care algorithms result in a substantial percentage of tied priority scores. Crisis standards of care algorithms operate differently in cohorts with and without coronavirus disease 2019. This proof-of-principle study demonstrates the feasibility and importance of empirical testing of crisis standards of care guidelines to understand whether they meet their goals.

Introduction Direct-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.Methods Several design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and dissemination Direct-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration number ClinicalTrials.gov Registry (NCT04358302).

The sex-bias of disease susceptibility has remained a puzzling aspect of several autoimmune conditions, including post-infection viral autoimmunity. In the last half of the twentieth century, the incidence rate of female-biased autoimmunity has steadily increased independent of medical advances. This has suggested a role for environmental factors, such as endocrine disrupting chemicals, which have been described to interfere with endocrine signaling. Endocrine involvement in the proper function of innate and adaptive immunity has also been defined, however, these two areas have rarely been reviewed in correlation. In addition, studies addressing the effects of endocrine disruptors have reported findings resulting from a broad range of exposure doses, schedules and models. This experimental heterogeneity adds confusion and may mislead the translation of findings to human health. Our work will normalize results across experiments and provide a necessary summary relevant to human exposure. Through a novel approach, we describe how different categories of ubiquitously used environmental endocrine disruptors interfere with immune relevant endocrine signaling and contribute to autoimmunity. We hope this review will guide identification of mechanisms and concentration-dependent EDC effects important not only for the sex-bias of autoimmunity, but also for other conditions of immune dysfunction, including post-infection autoreactivity such as may arise following severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, Herpes Simplex virus.

ABSTRACT Invasive fungal infections constitute a lethal threat, with patient mortality as high as 90%. The incidence of invasive fungal infections is increasing, especially in the setting of patients receiving immunomodulatory agents, chemotherapy, or immunosuppressive medications following solid-organ or bone marrow transplantation. In addition, inhibitors of spleen tyrosine kinase (Syk) have been recently developed for the treatment of patients with refractory autoimmune and hematologic indications. Neutrophils are the initial innate cellular responders to many types of pathogens, including invasive fungi. A central process governing neutrophil recognition of fungi is through lectin binding receptors, many of which rely on Syk for cellular activation. We previously demonstrated that Syk activation is essential for cellular activation, phagosomal maturation, and elimination of phagocytosed fungal pathogens in macrophages. Here, we used combined genetic and chemical inhibitor approaches to evaluate the importance of Syk in the response of neutrophils to Candida species. We took advantage of a Cas9-expressing neutrophil progenitor cell line to generate isogenic wild-type and Syk-deficient neutrophils. Syk-deficient neutrophils are unable to control the human pathogens Candida albicans, Candida glabrata, and Candida auris. Neutrophil responses to Candida species, including the production of reactive oxygen species and of cytokines such as tumor necrosis factor alpha (TNF-α), the formation of neutrophil extracellular traps (NETs), phagocytosis, and neutrophil swarming, appear to be critically dependent on Syk. These results demonstrate an essential role for Syk in neutrophil responses to Candida species and raise concern for increased fungal infections with the development of Syk-modulating therapeutics. IMPORTANCE Neutrophils are recognized to represent significant immune cell mediators for the clearance and elimination of the human-pathogenic fungal pathogen Candida. The sensing of fungi by innate cells is performed, in part, through lectin receptor recognition of cell wall components and downstream cellular activation by signaling components, including spleen tyrosine kinase (Syk). While the essential role of Syk in macrophages and dendritic cells is clear, there remains uncertainty with respect to its contribution in neutrophils. In this study, we demonstrated that Syk is critical for multiple cellular functions in neutrophils responding to major human-pathogenic Candida species. These data not only demonstrate the vital nature of Syk with respect to the control of fungi by neutrophils but also warn of the potential infectious complications arising from the recent clinical development of novel Syk inhibitors for hematologic and autoimmune disorders.

Candida spp. are the fourth leading cause of nosocomial blood stream infections in North America. Candida glabrata is the second most frequently isolated species, and rapid development of antifungal resistance has made treatment a challenge. In this study, we investigate the therapeutic potential of metformin, a biguanide with well-established action for diabetes, as an antifungal agent against C. glabrata. Both wild type and antifungal-resistant isolates of C. glabrata were subjected to biguanide and biguanide-antifungal combination treatment. Metformin, as well as other members of the biguanide family, were found to have antifungal activity against C. glabrata, with MIC50 of 9.34 ± 0.16 mg/mL, 2.09 ± 0.04 mg/mL and 1.87 ± 0.05 mg/mL for metformin, phenformin and buformin, respectively. We demonstrate that biguanides enhance the activity of several antifungal drugs, including voriconazole, fluconazole, and amphotericin, but not micafungin. The biguanide-antifungal combinations allowed for additional antifungal effects, with fraction inhibition concentration indexes ranging from 0.5 to 1. Furthermore, metformin was able to lower antifungal MIC50 in voriconazole and fluconazole-resistant clinical isolates of C. glabrata. We also observed growth reduction of C. glabrata with rapamycin and an FIC of 0.84 ± 0.09 when combined with metformin, suggesting biguanide action in C. glabrata may be related to inhibition of the mTOR complex. We conclude that the biguanide class has direct antifungal therapeutic potential and enhances the activity of select antifungals in the treatment of resistant C. glabrata isolates. These data support the further investigation of biguanides in the combination treatment of serious fungal infections.

The present research has been conducted within the scope of such relevant direction of linguistics as functional lexicology, and is associated with the identification of semantic modifications of the word, which are conditioned by contextual features of its use. The adjectives atomic and nuclear became the object of the analysis: we give their characteristics in the lexical system of the Russian language, present the frequency of their use in different types of discourse, study more than 300 contexts of their use with nouns in the modern political discourse. The adjectives are studied in their direct and figurative meanings in neutral texts, as well as in pejorative (negative) and ameliotory (positive) contexts. It has been established that the Russian political discourse is characterized by prevailing use of adjectives atomic and nuclear in direct meaning. It has been revealed that the basis of metaphorization as the main way of creating figurative meanings of the adjectives in the political discourse is represented with such features as powerful release of energy, concentration, innovativeness, progress. We show the mechanism of leveling the pejorative axiological component of the phrase atomic bomb arising from its use in direct meaning and the appearance of ameliotory connotative meanings in the neutral phrase nuclear reactor. It has been found that the units under study are not recorded by lexicographic sources in figurative meanings, since they express an occasional sense in the political discourse.

Background. Vaginal cancer is a rare disease with poor clinical outcomes and limited therapeutic options. In the United States (US), minority women and older women are disproportionately diagnosed with late-stage vaginal cancer. Sociodemographic characteristics, risk behaviors, and cooccurring conditions are linked to vaginal intraepithelial neoplasia (VaIN). The diagnosis of VaIN is more prevalent among older women and women living with HIV (WLWH). The Caribbean basin has one of the highest rates of anogenital cancers in the Western Hemisphere. In the US, vaginal infections are more prevalent among Caribbean women, and these infections contribute to higher rates of Human Papilloma Virus (HPV). Given the high rate of anogenital cancers in the Caribbean and the high rates of HPV among Caribbean women in the US, we sought to describe the occurrence of VaIN in a cohort of Black non-Hispanic WLWH. The cohort was followed by an interdisciplinary team of providers with the University of Miami, Miller School of Medicine. Results. Caribbean Americans were living with HIV longer and more were uninsured; more African Americans endorsed cigarette and illicit substance use. Caribbean Americans trended towards the highest grades of VaIN (VaIN 2+) at baseline, but more African Americans progressed to VaIN 2+ in subsequent biopsies. Conclusion. In this cohort of Caribbean American and African American women living with HIV diagnosed with VaIN, Caribbean Americans had the highest grade of VaIN at baseline, but more African Americans progressed to more advanced stages of the disease.

Macrophages play a critical role in the elimination of fungal pathogens. They are sensed via cell surface pattern-recognition receptors and are phagocytosed into newly formed organelles called phagosomes. Phagosomes mature through the recruitment of proteins and lysosomes, resulting in addition of proteolytic enzymes and acidification of the microenvironment. Our earlier studies demonstrated an essential role of Dectin-1-dependent activation of spleen tyrosine kinase (Syk) in the maturation of fungal containing phagosomes. The absence of Syk activity interrupted phago-lysosomal fusion resulting in arrest at an early phagosome stage. In this study, we sought to define the contribution of Syk to the control of phagocytosed live Candida glabrata in primary macrophages. To accurately measure intracellular yeast division, we designed a carboxyfluorescein succinimidyl ester (CFSE) yeast division assay in which bright fluorescent parent cells give rise to dim daughter cells. The CFSE-labeling of C. glabrata did not affect the growth rate of the yeast. Following incubation with macrophages, internalized CFSE-labeled C. glabrata were retrieved by cellular lysis, tagged using ConA-647, and the amount of residual CFSE fluorescence was assessed by flow cytometry. C. glabrata remained undivided (CFSE bright) for up to 18 h in co-culture with primary macrophages. Treatment of macrophages with R406, a specific Syk inhibitor, resulted in loss of intracellular control of C. glabrata with initiation of division within 4 h. Delayed Syk inhibition after 8 h was less effective indicating that Syk is critically required at early stages of macrophage–fungal interaction. In conclusion, we demonstrate a new method of tracking division of C. glabrata using CFSE labeling. Our results suggest that early Syk activation is essential for macrophage control of phagocytosed C. glabrata.

Improvements to leaf photosynthetic rates of crops can be achieved by targeted manipulation of individual component processes, such as the activity and properties of RuBisCO or photoprotection. This study shows that simple forward genetic screens of mutant populations can also be used to rapidly generate photosynthesis variants that are useful for breeding. Increasing leaf vein density (concentration of vascular tissue per unit leaf area) has important implications for plant hydraulic properties and assimilate transport. It was an important step to improving photosynthetic rates in the evolution of both C3 and C4 species and is a foundation or prerequisite trait for C4 engineering in crops like rice (Oryza sativa). A previous high throughput screen identified five mutant rice lines (cv. IR64) with increased vein densities and associated narrower leaf widths (Feldman et al., 2014). Here, these high vein density rice variants were analyzed for properties related to photosynthesis. Two lines were identified as having significantly reduced mesophyll to bundle sheath cell number ratios. All five lines had 20% higher light saturated photosynthetic capacity per unit leaf area, higher maximum carboxylation rates, dark respiration rates and electron transport capacities. This was associated with no significant differences in leaf thickness, stomatal conductance or CO2 compensation point between mutants and the wild-type. The enhanced photosynthetic rate in these lines may be a result of increased RuBisCO and electron transport component amount and/or activity and/or enhanced transport of photoassimilates. We conclude that high vein density (associated with altered mesophyll cell length and number) is a trait that may confer increased photosynthetic efficiency without increased transpiration.

We retrospectively analyzed a series of 151 cases of cutaneous leishmaniasis treated between 1967 and 1982. One-hundred-and-thirty-nine (92%) patients presented with active lesions and were treated with daily doses of meglumine antimoniate: 81 adults received a 5-ml vial IM and 58 children received 1 to 5ml. Forty-five (32.4%) patients underwent continuous treatment with meglumine antimoniate for 25 to 116 days without rest intervals, and 94 (67.6%) intermittent treatment with 2 to 5 series of meglumine antimoniate. Intermittent series could include schedules of daily IM applications for 10 to 25 days each and intervals varying from 10 to 60 days. Antimony dose was calculated for 66 (47.5%) patients and ranged from 3.9 to 28.7 Sb5+/kg/day. Of these, 35 patients received >10mg and 31 patients

A high leaf vein density is both an essential feature of C4 photosynthesis and a foundation trait to C4 evolution, ensuring the optimal proportion and proximity of mesophyll and bundle sheath cells for permitting the rapid exchange of photosynthates. Two rice mutant populations, a deletion mutant library with a cv. IR64 background (12,470 lines) and a T-DNA insertion mutant library with a cv. Tainung 67 background (10,830 lines), were screened for increases in vein density. A high throughput method with handheld microscopes was developed and its accuracy was supported by more rigorous microscopy analysis. Eight lines with significantly increased leaf vein densities were identified to be used as genetic stock for the global C4 Rice Consortium. The candidate population was shown to include both shared and independent mutations and so more than one gene controlled the high vein density phenotype. The high vein density trait was found to be linked to a narrow leaf width trait but the linkage was incomplete. The more genetically robust narrow leaf width trait was proposed to be used as a reliable phenotypic marker for finding high vein density variants in rice in future screens.

INTRODUÇÃO: A doença meningocócica (DM) continua merecendo avaliações quanto a sua multicausalidade endêmica e epidêmica e seu comportamento evolutivo, nos diferentes locais. MATERIAL E MÉTODOS: Partindo da padronização da investigação epidemiológica da DM no Município do Rio de Janeiro a partir da epidemia da década de 70, foram analisados 4.155 casos notificados de 1976 a 1994, através de estudo retrospectivo, descritivo e analítico, com base nas fichas de investigação epidemiológica da Secretaria Municipal de Saúde. Os testes utilizados para análise estatística foram: o chi², o de Wilcoxon-Mann-Whitney e de Kruskal-Wallis. RESULTADOS: O estudo resultou na definição de três períodos, classificados como pós-epidêmico (1976/79), endêmico (1980/86) e epidêmico (1987/94), diferenciados pelas taxas de incidência e pelo sorogrupo do meningococo predominante. As taxas de incidência médias por período no município foram, respectivamente, de 3,51; 1,67 e 6,53 casos/100.000 habitantes. Os sorogrupos A e C predominaram no período pós-epidêmico, o B e o A no endêmico e o B no epidêmico. A letalidade média praticamente não se modificou no decorrer do tempo, mas variou segundo o hospital de internação, tendo sido sempre menor no hospital estadual de referência em relação aos demais públicos e privados. CONCLUSÃO: As maiores taxas de incidência e letalidade corresponderam aos menores de um ano e o risco de adoecer foi maior no sexo masculino. Os maiores coeficientes de incidência tenderam a ocorrer nas mesmas áreas do município, nos três períodos epidemiológicos, e a população que reside em favelas teve um risco de adoecimento duas vezes maior.

Large-scale genomics projects are identifying biomarkers to detect human disease. B. pseudomallei and B. mallei are two closely related select agents that cause melioidosis and glanders. Accurate characterization of metagenomic samples is dependent on accurate measurements of genetic variation between isolates with resolution down to strain level. Often single biomarker sensitivity is augmented by use of multiple or panels of biomarkers. In parallel with single biomarker validation, advances in DNA sequencing enable analysis of entire genomes in a single run: population-sequencing. Potentially, direct sequencing could be used to analyze an entire genome to serve as the biomarker for genome identification. However, genome variation and population diversity complicate use of direct sequencing, as well as differences caused by sample preparation protocols including sequencing artifacts and mistakes. As part of a Department of Homeland Security program in bacterial forensics, we examined how to implement whole genome sequencing (WGS) analysis as a judicially defensible forensic method for attributing microbial sample relatedness; and also to determine the strengths and limitations of whole genome sequence analysis in a forensics context. Herein, we demonstrate use of sequencing to provide genetic characterization of populations: direct sequencing of populations.

We describe methods for rapid sequencing of the entire human mitochondrial genome (mtgenome), which involve long-range PCR for specific amplification of the mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify sequence variants and heteroplasmy, as well as de novo sequence assembly. These methods have been used to study 40 publicly available HapMap samples of European (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate

The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) measured the effectiveness of the drug cholestyramine for lowering cholesterol levels. The patients in the study were measured for compliance (the proportion of the intended dose actually taken) and for cholesterol decrease. The compliance-response regression for the Treatment group shows a smooth increasing effect of the drug in cholesterol level with increasing compliance. However, a similar, though less dramatic, compliance-response regression is seen in the Control group. This article investigates the recovery of the true dose-response curve from the Treatment and Control compliance-response curves. A simple model is proposed, analyzed, and applied to the LRC-CPPT data. Under this model, part but not all of the true dose-response curve can be estimated., 1. INTRODUCTION Figure 1 shows results from the Stanford portion of the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). This was a placebo-controlled double-blind randomized clinical trial concerning the [...]

We examined effects on intestinal absorption of cholesterol and triglycerides and intestinal lipoprotein formation by feeding rats diets in which saturated fatty acids (palmitic plus stearic) comprised 78%, 68%, 48%, or 38% of triglyceride fatty acids. Absorption into lymph of radiolabeled cholesterol was proportional to triglyceride absorption. The rates of absorption of these lipids were related inversely to the % saturated fatty acids fed. The distribution of newly absorbed cholesterol and triglyceride into intestinal lipoproteins differed. With increasing cholesterol absorption more was recovered in very low density lipoproteins in contrast to the appearance preferentially in chylomicrons of larger quantities of fatty acid. Lymph lipid content did not reflect a consistent pattern in relation to the experimental diet fed. The fatty acid composition of triglyceride-rich lymph lipoproteins resembled the diet closely. One-quarter of the intestinal lymph particles from rats fed the highly saturated diets was flattened and polygonal as judged by electron microscopy if cooled to room temperature; whereas with the same diets, particles collected and isolated at 37 degrees C were round. Proportions of A-I and C apolipoproteins in triglyceride-rich intestinal particles varied inversely; apoA-I increased as fat/cholesterol absorption was greater. Diet-induced alterations in plasma lipoproteins and increased circulating triglycerides in this study in rats were unrelated to the variations in intestinal absorption or lymph lipoprotein formation.