Acetylsalicylic Acid Exerts Potent Antitumor and Antiangiogenic Effects in Cutaneous and Uveal Melanoma Cell Lines.
Acetylsalicylic acid (ASA) has been investigated for a potential anticancer role in several cancers, such as colorectal, ovarian, and endometrial cancer. Moreover, ASA has been shown to abrogate various processes that contribute to tumor growth and progression. The aim of this study was to evaluate the effects of ASA on cutaneous melanoma (CM) and uveal melanoma (UM). Human CM and UM cells were treated with 5 mM ASA and assessed for changes in cellular functions. Antiangiogenic effects of ASA were determined using an ELISA-based assay for 10 proangiogenic cytokines, and then validated by Western blot. Finally, proteomic analysis of ASA-treated cells was performed to elucidate the changes that may be responsible for ASA-mediated effects in melanoma cells. Treatment with ASA significantly inhibited the proliferation, invasion, and migration capabilities, and caused a significant decrease in angiogenin and PIGF secretion in both CM and UM. Mass spectrometry revealed 179 protein changes associated with ASA in the CM and UM cell lines. These results suggest that ASA may be effective as an adjuvant therapy in metastatic CM and UM. Future studies are needed to determine the regulating targets that are responsible for the antitumor effects of ASA.


Diversity in olfactory receptor repertoires is associated with dietary specialization in a genus of frugivorous bat.
Mammalian olfactory receptor genes (ORs) are a diverse family of genes encoding proteins that directly interact with environmental chemical cues. ORs evolve via gene duplication in a birth-death fashion, neofunctionalizing and pseudogenizing over time. Olfaction is a primary sense used for food detection in plant-visiting bats, but the relationship between dietary specialization and OR repertoire diversity is unclear. Within neotropical Leaf-nosed bats (Phyllostomidae), many lineages are plant specialists, and some have a distinct OR repertoire compared to insectivorous species. Yet, whether specialization on particular plant genera is associated with the evolution of specialized, less diverse OR repertoires has never been tested. Using targeted sequence capture, we sequenced the OR repertoires of three sympatric species of short-tailed fruit bats (Carollia), which vary in their degree of specialization on the fruits of Piper plants. We characterized orthologous vs duplicated receptors among Carollia species, and explored the diversity and redundancy of the receptor gene repertoire. At the species level, the most dedicated Piper specialist, Carollia castanea, had lower OR diversity compared to the two generalists (C. sowelli and C. perspicillata), but we discovered a few unique sets of ORs within C. castanea with high redundancy of similar gene duplicates. These unique receptors potentially enable C. castanea to detect Piper fruit odorants better than its two congeners. Carollia perspicillata, the species with the most generalist diet, had a higher diversity of intact receptors, suggesting the ability to detect a wider range of odorant molecules. Variation among ORs may be a factor in the coexistence of these sympatric species, facilitating the exploitation of different plant resources. Our study sheds light on how gene duplication and changes in OR diversity may play a role in dietary adaptations and underlie ecological interactions between bats and plants.


Once Daily Accelerated Partial Breast Irradiation: Preliminary Results with Helical Tomotherapy®.
Accelerated partial breast irradiation (APBI) is becoming an option for patients with low-risk breast cancer. The current practice is 38.5 Gy in 10 fractions b.i.d. over 5 days. This fractionation has a higher bioequivalent dose compared to the standard schedule. We report on preliminary results of once-daily APBI in patients treated with TomoTherapy®. Patients with unifocal-breast disease who underwent breast-conserving surgery were enrolled in the study. Treatment was administered with TomoTherapy, by contouring in accordance with the NSABP B-39/RTOG 0413 APBI protocol. Treatment schedule was 38.5 Gy in 10 once-daily fractions. EORTC Cosmetic Rating System was adopted for cosmetic outcome. From 2010 to 2013, 111 patients were treated. With a median follow-up of 34 months, no ipsilateral breast recurrence was observed. Very few patients (1-4%) assessed their cosmetic outcome as fair or poor during follow-up. Once-daily APBI with TomoTherapy yielded good cosmetic results without compromising local control efficacy.


Do Disparities in Wait Times to Operative Fixation for Pathologic Fractures of the Long Bones and 30-day Complications Exist Between Black and White Patients? A Study Using the NSQIP Database.
Racial disparities in outcomes after orthopaedic surgery have been well-documented in the fields of arthroplasty, trauma, and spine surgery; however, little research has assessed differences in outcomes after surgery for oncologic musculoskeletal disease. If racial disparities exist in the treatment of patients with pathologic long bone fractures, then they should be identified and addressed to promote equity in patient care. (1) How do wait times between hospital admission and operative fixation for pathologic fractures of long bones differ between Black and non-Hispanic white patients, after controlling for confounding variables using propensity score matching? (2) How does the proportion of patients with 30-day postoperative complication differ between these groups after controlling for confounding variables using propensity score matching? Using the National Surgical Quality Improvement Program database, we analyzed 828 patients who underwent fixation for pathologic fractures from 2012 to 2018. This database not only provides a large enough sample of pathologic long bone fracture patients to conduct the present study, but also it contains variables such as time from hospitalization to surgery that other national databases do not. After excluding patients with incomplete data (4% of the initial cohort), 775 patients were grouped by self-reported race as Black (12% [94]) or white (88% [681]). Propensity score matching using a 1:1 nearest-neighbor match was then used to match 94 Black patients with 94 white patients according to age, gender, BMI, American Society of Anesthesiologists physical status classification, anemia, endstage renal disease, independence in performing activities of daily living, congestive heart failure, and pulmonary disease. The primary outcome of interest was the number of days between hospital admission and operative fixation, which we assessed using a Poisson regression and report as an incidence risk ratio. The secondary outcomes were the occurrences of major 30-day postoperative adverse events (failure to wean off mechanical ventilation, cerebrovascular events, renal failure, cardiovascular events, reoperation, death), minor 30-day adverse events (reintubation, wound complications, pneumonia, and thromboembolic events), and any 30-day adverse events (defined as the pooling of all adverse events, including readmissions). These outcomes were analyzed using a bivariate analysis and logistic regression with robust estimates of variance and are reported as odds ratios. Because any results on disparities rely on rigorous control of other baseline demographics, we performed this multivariable approach to ensure we were controlling for confounding variables as much as possible. After controlling for potentially confounding variables such as age and gender, we found that Black patients had a longer mean wait time (incidence risk ratio 1.5 [95% CI 1.1 to 2.1]; p = 0.01) than white patients. After controlling for confounding variables, Black patients also had greater odds of having any postoperative adverse event (OR 2.1 [95% CI 1.1 to 3.8]; p = 0.02), including readmission (OR 3.3 [95% CI 1.5 to 7.6]; p = 0.004). The racial disparities in pathologic long bone fracture care found in our study may be attributed to fundamental racial biases, as well as systemic socioeconomic disparities in the US healthcare system. Identifying and eliminating the racial, socioeconomic, and sociocultural biases that drive these disparities would improve care for patients with orthopaedic oncologic conditions. One possible way to reduce these disparities would be to implement standardized surgical care pathways for pathological long bone fractures across different institutions to minimize variation in important aspects of care, such as time to surgical fixation. Further insight is needed on the types of standardized care pathways and the implementation mechanisms that are most effective. Level III, therapeutic study.


Exploring Digital Health Use and Opinions of University Students: Field Survey Study.
During university, students face some potentially serious health risks, and their lifestyle can have a direct effect on health and health behaviors later in life. Concurrently, university students are digital natives having easy access to the internet and new technologies. Digital health interventions offer promising new opportunities for health promotion, disease prevention, and care in this specific population. The description of the current use of and opinions on digital health among university students can inform future digital health strategies and interventions within university settings. The aim of this exploratory study was to report on university students' use and opinions regarding information and communication technologies for health and well-being, taking into account sociodemographic and self-rated general and mental health correlates. This field survey was conducted from March to April 2017. An informed consent form and a paper questionnaire were given to students aged 18 to 24 years in 4 university campuses in Bordeaux, France. The survey was formulated in 3 sections: (1) sociodemographic characteristics and self-rated general and mental health, (2) information about the use of digital health, and (3) opinions about digital health. Data were analyzed using descriptive statistics and tests of independence. A total of 59.8% (303/507 females) students completed the questionnaire. Concerning digital health use, 34.9% (174/498) had at least 1 health app mostly for physical activity (49.4%, 86/174) and general health monitoring (41.4%, 72/174,), but only 3.9% (20/507) of students had a wearable device. Almost all (94.8%, 450/476) had searched for Web-based health-related information at least once in the last 12 months. The most sought health-related topics were nutrition (68.1%, 324/476); pain and illnesses (64.5%, 307/476); and stress, anxiety, or depression (51.1%, 243/476). Although Wikipedia (79.7%, 357/448) and general health websites (349/448, 77.9%) were the most consulted sources, students considered institutional or official websites as the most credible sources (309/335, 92.2%). There were significant differences in digital health use by gender, field, and year of study. No statistically significant association was found between digital health use and self-rated general and mental health status. Concerning opinions on digital health, although 94.1% (475/505) of students estimated that today's digital health cannot replace traditional health services and medical consultations, 44.6% (207/464) of students declared that this could be possible in the future, provided that digital health interventions are promoted by institutional or official entities. University students are largely using the internet for health information seeking, but using less mobile health apps and very few wearable devices. Our data suggest that digital health has the potential for improving health and well-being at the university, especially if digital health interventions take into account students' profiles, interests, and needs.


Comparative Study of Automated Algorithms for Brain Arteriovenous Malformation Nidus Extent Identification Using 3DRA.
When performing a brain arteriovenous malformation (bAVMs) intervention, computer-assisted analysis of bAVMs can aid clinicians in planning precise therapeutic alternatives. Therefore, we aim to assess currently available methods for bAVMs nidus extent identification over 3DRA. To this end, we establish a unified framework to contrast them over the same dataset, fully automatising the workflows. We retrospectively collected contrast-enhanced 3DRA scans of patients with bAVMs. A segmentation network was used to automatically acquire the brain vessels segmentation for each case. We applied the nidus extent identification algorithms over each of the segmentations, computing overlap measurements against manual nidus delineations. We evaluated the methods over a private dataset with 22 3DRA scans of individuals with bAVMs. The best-performing alternatives resulted in [Formula: see text] and [Formula: see text] dice coefficient values. The mathematical morphology-based approach showed higher robustness through inter-case variability. The skeleton-based approach leverages the skeleton topomorphology characteristics, while being highly sensitive to anatomical variations and the skeletonisation method employed. Overall, nidus extent identification algorithms are also limited by the quality of the raw volume, as the consequent imprecise vessel segmentation will hinder their results. Performance of the available alternatives remains subpar. This analysis allows for a better understanding of the current limitations.


Morphometric and biochemical characteristics of ventricular hypertrophy in male rainbow trout (Oncorhynchus mykiss).
We examined the morphometric and biochemical effects of ventricular hypertrophy in male rainbow trout (Oncorhynchus mykiss) during sexual maturation. Our investigation focused on characterizing the growth of ventricular layers, on cardiomyocyte dimensions (length, cross-sectional area and cell volume) and on the activities of enzymes involved in intermediary metabolism. Relative ventricle mass (100 x ventricle mass/body mass) increased by as much as 2.4-fold during sexual maturation [as defined by an increasing gonadosomatic index (100 x gonad mass/body mass)], and this resulted in an increased proportion of epicardium relative to endocardium. Ventricular enlargement was associated with increased length (+31 %) and transverse cross-sectional area (+83 %) of cardiomyocytes, which resulted in an expansion of up to 2.2-fold in mean myocyte volume (from 1233 to 2751 micron3). These results indicate that sexual maturation induces ventricular enlargement through myocyte hypertrophy. Cell length and cross-sectional area were similar in both myocardial layers, and myocytes were elliptical rather than circular in transverse cross section. Ventricular hypertrophy did not alter transverse cell shape, perhaps reflecting the maintenance of short diffusion distances for small molecules as cells hypertrophy. Myocyte hypertrophy could not account entirely for the sevenfold range of ventricle masses from different-sized fish, indicating that myocyte hyperplasia contributes substantially to ventricular growth as trout grow. Measurements of the maximal activities of metabolic enzymes demonstrated that ventricular hypertrophy was associated with (1) higher epicardial but not endocardial activities of citrate synthase (by 23 %) and beta-hydroxyacyl-CoA dehydrogenase (by 20 %); (2) lower activities of hexokinase (by 50 %) in both layers, and (3) no change in lactate dehydrogenase or pyruvate kinase activities, which were also similar between layers. These results suggest that the energetic needs of the hypertrophied trout ventricle may be met through increased reliance on fatty acid oxidation, particularly by the endocardium, but decreased reliance on glucose as a metabolic fuel in both layers.


Unnecessary work tasks and mental health: a prospective analysis of Danish human service workers.
According to the "stress-as-offense-to-self" perspective, work tasks that are considered unnecessary or unreasonable - so-called "illegitimate work tasks" - are likely to elicit stress-reactions. Previous studies, mostly cross-sectional, have shown that illegitimate tasks are associated with increased self-reported stress, cortisol, and counterproductive work behavior. In this article, we examine the prospective association between unnecessary work tasks, one type of illegitimate work tasks, and mental health among Danish human service workers. Further, we explore whether this association is modified by sex, age, occupational position, and baseline mental health status. The data were obtained from self-administered questionnaires from 1351 Danish human service workers in three waves of data-collection during 1999-2005. We measured unnecessary work tasks by a single item, and assessed mental health using the 5-item mental health inventory from the Short form 36 questionnaire. We analyzed data using multi-level modeling, adjusting for potential confounding by sex, age, cohabitation, occupational position, and baseline mental health. Unnecessary work tasks were prospectively associated with a decreased level of mental health. This association was stronger for employees with poor baseline mental health and tended to be more pronounced among older employees. Among participants with poor baseline mental health, the association was explained by neither psychological demands nor decision latitude. Our findings suggest that the prevention of unnecessary work tasks may benefit employee mental health, particularly among employees with pre-existing mental health problems.


Short-term complications associated with surgery for high-grade spondylolisthesis in adults and pediatric patients: a report from the scoliosis research society morbidity and mortality database.
Although it is generally agreed upon that surgery for high-grade spondylolisthesis (HGS) is associated with more complications than low-grade spondylolisthesis, its description is primarily based on case reports and relatively small case series. To assess short-term complication rates associated with the surgical treatment of HGS in pediatric and adult patients and to identify factors associated with increased complication rates. All cases of HGS from the Scoliosis Research Society Morbidity and Mortality database for the year 2007 were reviewed. Patients were classified as pediatric (≤18 years) or adult (>18 years). Complications were tabulated, and the rates were compared between the patient groups and based on clinical and surgical factors. 165 cases of HGS were reported (88 pediatric, 77 adult). There were 49 complications (29.7%) in 41 patients (24.8%), with no difference in the proportions of pediatric vs adult patients with a complication (P = .86). Occurrence of new neurological deficit after surgery was the most common complication, seen in 19 (11.5%) patients. Performance of an osteotomy was associated with a higher incidence of new neurological deficits in both adult and pediatric groups (P = .02 and P = .012, respectively). Although most of the new neurological deficits improved over follow-up, 10% had no improvement. This study provides short-term complication rates associated with surgical treatment for HGS in adult and pediatric patients and may prove valuable for patient counseling, surgical planning, and in efforts to improve the safety of patient care.


A method of improving the spatial resolution of treatments that involve a multileaf collimator.
In this paper we present a novel method of reducing the dosimetric effects of the finite leaf width of a multileaf collimator (MLC) in conformal and intensity modulated radiotherapy (IMRT). This is achieved by decomposing the required high-resolution fluence distribution into two orthogonal components, which are delivered with two leaf sweeps with head-twists differing by 90 degrees. Before the decomposition stage, a filter is applied to the required beam to force it to have a constant gradient in the two delivery directions. The component deliveries were found to be very spiky in nature, resulting in very inefficient delivery with the scanning leaves of our MLC. This method was evaluated using film dosimetry of four idealized beams: a 45 degree edge, a circle, a hemispherical intensity modulated beam (IMB) and a sine-like IMB. The measurements showed that this method had significantly reduced the effects of the 1 cm leaf width of our MLC at the 50% isodose level, but there was significant overdosage at the edge of the field and immediately inside the held edge. This method shows promise but further work is required before it may find clinical utility.


Factors Associated With Workplace and Interpersonal Trust in the Supervisory System of a Community Health Worker Programme in a Rural South African District.
Key to effective supportive supervision, and ultimately performance of community health workers (CHWs), is the nature of relationships in the formal health system at the coal face of programmes. The central character and defining feature of effective relationships, in turn, is the ability to engender trust. This study describes factors associated with workplace and interpersonal trust, the relationship between the two sets of trust factors and how this shaped perceived performance of CHWs in ward-based outreach teams (WBOTs) in a rural South African district. In the context of a wider study of supportive supervision of CHWs, factors recognised to be associated with trust in the literature were studied qualitatively in Ngaka Modiri Molema district, North West Province. Focus group discussions (FGDs) and individual interviews were conducted by the first author with CHWs (23), team leaders (12), facility managers (10) and middle managers (5). Interviews were recorded, translated and transcribed. Perceptions of trust factors associated with workplace and interpersonal trust were analysed thematically. The interviews revealed a climate of considerable workplace mistrust due to the perceived abandonment of the WBOTs programme by managers at all levels, and this affected support and supervision of WBOTs. However, there was a degree of variability and discretion in expressions of interpersonal trust at the coal face, leading to different perceptions of the competence and functionality of the WBOTs. Mistrust in the workplace and poor interpersonal relationships translated into low confidence in the ability of CHWs, which in turn compromised the performance of these teams. The study contributes empirical evidence on how workplace trust factors impact on interpersonal trust factors and the possible implications of both sets of trust factors on perceived performance of CHWs. Wider trust in the health system have a significant bearing on interpersonal trust between CHWs and other players in the primary healthcare (PHC) system.


Understanding the Postpartum Cesarean Pain Experience Among Individuals With Publicly Funded Insurance: A Qualitative Investigation.
Pain is the most common postpartum concern and has been associated with adverse outcomes, such as difficulty with neonatal bonding, postpartum depression, and persistent pain. Furthermore, racial and ethnic disparities in the management of postpartum pain are well described. Despite this, less is known regarding patients' lived experiences regrading postpartum pain. The purpose of this study was to assess patient experiences related to postpartum pain management after cesarean birth. This is a prospective qualitative study of patients' experiences with postpartum pain management after cesarean birth at a single large tertiary care center. Individuals were eligible if they had publicly funded prenatal care, were English or Spanish speaking, and underwent a cesarean birth. Purposive sampling was used to ensure a racially and ethnically diverse cohort. Participants underwent in-depth interviews using a semistructured interview guide at 2 time points: postpartum day 2 to 3 and 2 to 4 weeks after discharge. Interviews addressed perceptions and experiences of postpartum pain management and recovery. Data were analyzed using the constant comparative method. Of 49 participants, 40.8% identified as non-Hispanic Black and 40.8% as Hispanic. The majority (59.2%) had experienced a cesarean birth with a prior pregnancy. Thematic analysis yielded 2 overarching domains: (1) experience of pain after cesarean birth and (2) pain management and opioid use after cesarean birth. Themes related to the experience of pain included pain as a meaningful experience, pain not aligned with expectations, and limitations caused by pain. All participants discussed limitations caused by their pain, voicing frustration with pursuing activities of daily living, caring for home and family, caring for neonate, and impact on mood. Themes related to pain management and opioid use addressed a desire for nonpharmacologic pain management, positive and negative experiences using opioids, and hesitancy and perceived judgement regarding opioid use. Several participants described experiences of judgement regarding the request for opioids and needing stronger pain medications, such as oxycodone. Understanding experiences regarding postpartum cesarean pain management and recovery is essential to improving patient-centered care. The experiences identified by this analysis highlight the need for individualized postpartum pain management, improved expectation counseling, and the expansion of multimodal pain management options.


Phenolic glycosides from Lindera obtusiloba and their anti-allergic inflammatory activities.
Eight phenolic glycosides, tachioside (1), isotachioside (2), koaburaside (3), 2,6-dimethoxy-4-hydroxyphenyl-1-O-beta-D-glucopyranoside (4), 4,6-dihydroxy-2-methoxyphenyl-1-O-beta-D-glucopyranoside (5), a mixture of erigeside C (6a) and salidroside (6b), and 6-hydroxyphenyl)-1-O-beta-D-glucopyranoside (7) were isolated from the stems of Lindera obtusiloba Blume. The structures of the isolates were determined by 1H-, 13C-NMR, COSY, HMQC, and HMBC spectroscopy. To evaluate their anti-allergic inflammatory activities, the inhibitory effects of isolates (1-7) on histamine release and on the gene expressions of tumor necrosis factor (TNF)-a and interleukin (IL)-6 were examined using human mast cells; previous studies have reported that TNF-alpha and IL-6 release from mast cells is positively related to the severity of allergic symptoms. Of the tested compounds, koaburaside (3), 2,6-dimethoxy-4-hydroxyphenyl-1-O-beta-D-glucopyranoside (4), and (6-hydroxyphenyl)-1-O-beta-D-glucopyranoside (7) suppressed histamine release from mast cells as compared with gallic acid (positive control). In particular, 6-hydroxyphenyl)-1-O-beta-D-glucopyranoside (7) attenuated the gene expressions of the proinflammatory cytokines TNF-alpha and IL-6 in human mast cells. Our results support the notion that phenolic glycosides isolated from L. obtusiloba inhibit mast-cell-derived allergic inflammation, histamine, and proinflammatory cytokines.


Isolation and characterization of influenza C virus inhibitor in rat serum.
Two hemagglutination inhibitors for influenza C virus were isolated from pooled sera of normal rats by sequential chromatography on Blue Sepharose CL 6B, Ultrogel AcA 22, and DEAE-cellulose. The two inhibitors were identified as alpha 1-macroglobulin and murinoglobulin by comparison with the authentic samples. These inhibitors abolished the hemagglutination by influenza C virus strains but did not affect the hemagglutination by influenza A and B virus strains. Hemagglutination inhibition activity of both inhibitors was completely destroyed by incubation with influenza C virus at 37 degrees C but not with the other types of influenza virus, indicating that the inhibitors are specific for influenza C virus. The inhibitory activity was also destroyed by incubation with neuraminidase from Arthrobacter ureafaciens. By contrast, no activity was lost after treatment with neuraminidase from Vibrio cholerae. These results suggest that the sialic acid residue(s) which is cleavable by the former neuraminidase but not by the latter is essential for the hemagglutination inhibition. The two inhibitors were inactivated by treating with sodium hydroxide and methylamine but not with sodium metaperiodate.


Validation of the Proxy Version of Symptom Screening in Pediatrics Tool in Children Receiving Cancer Treatments.
Primary objectives were to evaluate the interrater reliability and validity of proxy-report Symptom Screening in Pediatrics Tool (SSPedi) in children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients. Secondary objective was to describe the interrater reliability of each SSPedi item. Respondents were children aged eight to 18 years with cancer or HSCT recipients, and their parents or guardians. We enrolled two pediatric respondent groups. The more symptomatic group was receiving active treatment for cancer, admitted to hospital, and expected to be in a hospital three days later. The less symptomatic group either was in maintenance therapy for acute lymphoblastic leukemia or had completed cancer treatments. Convergent validity was evaluated by comparing proxy-reported mucositis, nausea and vomiting, pain, and total SSPedi scores, with child self-reported validated scales, and we hypothesized fair correlations. Discriminant validity was evaluated by comparing proxy-reported total SSPedi scores between groups. Interrater reliability of each SSPedi item was evaluated. Four hundred thirty-nine child and parent or guardian pairs were recruited. Mean difference in proxy-reported SSPedi scores between the more and less symptomatic groups was 8.2, 95% CI 6.6-9.8. All hypothesized relationships among measures were observed. Intraclass correlation coefficients for SSPedi items ranged from 0.34 (problems with thinking) to 0.80 (diarrhea). Proxy-report SSPedi is reliable and valid in children aged 8 years to 18 years with cancer and HSCT recipients. Future work should support proxy-reported symptom assessment in clinical settings where children are not able to self-report or communicate bothersome symptoms.


Pemetrexed in second line and beyond small cell lung cancer: a Hoosier Oncology Group phase II study.
: Small cell lung cancer (SCLC) is initially a chemotherapy-sensitive disease. Nevertheless, drug-resistance results in disease recurrence in most patients. Many drugs, including antimetabolites, are active, but only minimal progress has been made in improving survival times for those with advanced disease. Based on the need to discover better systemic therapies, we conducted a phase II study of pemetrexed in patients with relapsed SCLC. : Eligible patients had SCLC or poorly differentiated neuroendocrine cancers of the lung, Eastern Cooperative Oncology Group performance status of 0 to 2, and had received less than or equal to two prior chemotherapy regimens (additional targeted agents were allowed). Both chemotherapy-sensitive (relapse >/=90 days from completion of first line therapy) and chemotherapy-resistant (progressive disease during or within 90 days from completion of first line treatment) patients were eligible and analyzed separately. Pemetrexed was administered at 500 mg/m intravenously every 21 days for up to six cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. The primary objective of the trial was to estimate the clinical benefit rate (complete plus partial response plus stable disease) in each group. : From January 2005 to September 2005, 20 patients were enrolled in the chemotherapy-sensitive arm and 23 patients in the chemotherapy-resistant arm. The majority of patients were men, the median age of the two groups were 62.5 and 65, respectively; 75% had a performance status of 0 or 1, and more than 50% had received more than one prior regimen. Grade 3/4 toxicities were as expected for pemetrexed. Progressive disease was the best response in 16 patients (80%) in the chemo-sensitive group and 19 patients (83%) in the chemo-refractory group. One patient had a partial response and three had stable disease in each group. : Pemetrexed has minimal single agent activity in relapsed SCLC.


Pre- and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States.
A higher folate intake is associated with a decreased colorectal cancer risk in observational studies, but recent evidence suggests that excessive folate supplementation may increase colorectal cancer risk in some individuals. Therefore, mandatory folic acid fortification of grain products in the United States may have unintended negative consequences. We examined the association between folate intake and colorectal cancer risk, including 8.5 y of postfortification follow-up. We examined the association between folate intake and colorectal cancer in the NIH-AARP Diet and Health Study-a US cohort study of 525,488 individuals aged 50-71 y initiated in 1995-1996. Dietary, supplemental, and total folate intakes were calculated for the pre- and postfortification periods (before and after 1 July 1997) based on a baseline food-frequency questionnaire. HRs and 95% CIs were calculated by using multivariable Cox proportional hazards regression models. During follow-up through 31 December 2006 (mean follow-up: 9.1 y), 7212 incident colorectal cancer cases were identified. In the postfortification analysis (6484 cases), a higher total folate intake was associated with a decreased colorectal cancer risk (HR for ≥900 compared with <200 μg/d: 0.70; 95% CI: 0.58, 0.84). The highest intakes specifically from supplements (HR: 0.82; 95% CI: 0.72, 0.92) or from diet (HR: 0.81; 95% CI: 0.67, 0.97) were also protective. The pattern of associations was similar for the prefortification period, and no significant differences between time periods were observed. In this large prospective cohort study that included 8.5 y of postfortification follow-up, folate intake was associated with a decreased colorectal cancer risk. Given that the adenoma-carcinoma sequence may take ≥10 y, additional follow-up time is needed to fully examine the effect of folic acid fortification.


Simultaneous determination of volatile organic compounds with a wide range of polarities in urine by headspace solid-phase microextraction coupled to gas chromatography/mass spectrometry.
Volatile organic compounds (VOCs) are ubiquitous environmental pollutants that have a high vapor pressure at room temperature. Some VOCs have been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC), because they can bind to DNA and cause cell mutations. Therefore, monitoring of VOCs in human urine is very important to evaluate the correlation between exposure to VOCs and human disease. We have developed an improved analytical method for the simultaneous determination of VOCs with a wide range of polarities in human urine samples by headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography/mass spectrometry (GC/MS). In the improved method, a bi-polar carboxen-polydimethylsiloxane (CAR/PDMS) fiber was used for the optimized extraction of 15 VOCs with a wide range of polarities, including benzene, toluene, ethylbenzene, xylenes (BTEX), alkylbenzenes, cresols, and naphthalene, in human urine samples. Extracted VOCs from the human urine were effectively separated by GC using a mid-polarity column (DB-35, 35% phenylmethylpolysiloxane) and monitored by MS using extracted ion monitoring (EIM) mode. Under the optimized method, the linearity of the calibration curves was greater than 0.993. The limits of detection (LODs) at a signal-to-noise (S/N) ratio of 3 were 0.3-0.6 ng/mL. The coefficients of variation were in the range of 0.1-9.7% for within-day variation and 0.2-14.2% for day-to-day variation. The method was shown to be rapid and simple for the simultaneous determination of VOCs with a wide range of polarities in human urine and it could be applied to monitoring and to biomedical investigations to check exposure to VOCs. Copyright © 2017 John Wiley & Sons, Ltd.


Effects of calmodulin antagonists on the active Ca2+ uptake by rat liver mitochondria.
The mechanism of Ca2+ transport by rat liver mitochondria was investigated with respect to the possible involvement of calmodulin in this process. We studied the action of exogenous calmodulin isolated from brain tissue on the Ca2+-transport system, as well as the effect of two types of calmodulin antagonists; the phenothiazine drugs trifluoperazine and chlorpromazine and the more specific substance compound 48/80. Our results show that Ca2+ transport by mitochondria and mitochondrial ATPase activity are insensitive to exogenous calmodulin, although they can be inhibited by the phenothiazines. Since no effect of compound 48/80 was observed, we believe that the phenothiazines act through a mechanism that does not involve calmodulin. This is in accord with our inability to locate significant quantities of calmodulin in mitochondria by radioimmunoassay analysis. Our results further show that trifluoperazine and chlorpromazine also inhibit the electron-carrier system of the respiratory chain, and this effect may mediate their inhibitory action on Ca2+ transport when it is energized by respiration instead of ATP hydrolysis.


[Paraneoplastic retinopathy simulating cone dystrophy with achromatopsia].
A 72-year-old woman developed recurrent blindness on exposure to bright light (sunlight). Examination revealed total achromatopsia; bilateral central scotomas, predominant suppression of the cone response by electroretinography, and narrowing of the retinal arteries on ophthalmoscopy. The general examination revealed a pelvic tumor that later proved to be a pleomorphic carcinoma of presumed uterine origin. The patient died of metastatic disease 9 months after the ocular symptoms developed. Histopathologic examination of the eyes revealed loss of the photoreceptors, most extensive in the macular regions, and selective loss of the cones from the rest of the retinas. No ocular metastases of inflammation were found. The changes described are interpreted as paraneoplastic retinopathy of autoimmune origin.


Comparative distribution of the alpha 1(IV), alpha 5(IV), and alpha 6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients.
We have shown previously that the 5' ends of the genes for the alpha 5(IV) and alpha 6(IV) collagen chains lie head-to-head on Xq22 and are deleted in patients with Alport syndrome (AS)-associated diffuse leiomyomatosis. In this study, we raised a rabbit anti-human alpha 6(IV)chain antibody, demonstrated its specificity by the analysis of recombinant NC1 domains af all six type IV chains, and studied the distribution of the alpha 6(IV) chain in relation to the alpha 1(IV) and alpha 5(IV) chains in human adult and fetal tissues involved in AS and diffuse leiomyomatosis. The alpha 6(IV) chain colocalizes with the alpha 5(IV) chain in basement membranes (BMs) of many tissues, but not in glomerular BM. These data exclude the alpha 6(IV) chain as a site for AS mutations. The head-to-head genomic pairing of the alpha 5(IV) and alpha 6 (IV) genes implies coordinate transcription of the two genes. Differential localization of the alpha 5(IV) and alpha 6(IV) chains shows that the two chains are not always coordinately regulated. The alpha 6(IV) chain, together with the alpha 3(IV)-alpha 5(IV) chains, was absent from all renal BMs in eight patients with X-linked AS while the alpha 1(IV) and alpha 2(IV) chains were increased. The data support the existence of two independent collagen networks, one for the alpha 3(IV)-alpha 6(IV) chains and one for the alpha 1(IV) and alpha 2(IV) chains.


Impairment of airway mucociliary transport by Pseudomonas aeruginosa products. Role of oxygen radicals.
We previously showed that the supernatant of a Pseudomonas aeruginosa (PA) culture and its constituents pyocyanin and 1-hydroxyphenazine inhibit ciliary activity of dispersed tracheal epithelial cells in vitro via the generation of oxygen radicals by phagocytes. In the present study, we wished to determine if tracheal mucus velocity (TMV) is also impaired by PA supernatant and if oxygen radicals have a mediating role. In conscious sheep, TMV (measured with a radiographic method) was determined before and serially following aerosol challenge with the cell-free supernatant of a PA culture or unconditioned culture medium (control). TMV decreased from a mean (+/- SEM) baseline of 6.7 +/- 1.1 mm/min (n = 6) by 29, 35, and 25% at 0.5, 3, and 24 h after challenge, respectively (p < 0.05), and returned to baseline 1 wk later (-6%, p = NS). Control medium had no effect on TMV (maximum decrease by 15% at 0.5 h). Aerosolized catalase blunted the effect of PA supernatant on TMV. To determine if the impairment of TMV involved ciliary inhibition, tissues were mounted in a chamber and ciliary beat frequency (CBF) and surface liquid velocity (SLV) were measured with a microscopic method. PA supernatant decreased both CBF (maximum mean decrease 12%; n = 5, p < 0.05) and SLV (maximum mean decrease 78%; n = 5, p < 0.05) in a dose-dependent fashion, with a correlation between the two parameters; these effects were blocked by catalase.(ABSTRACT TRUNCATED AT 250 WORDS)


Online Ratings of Neurosurgeons: An Examination of Web Data and its Implications.
Patient satisfaction ratings are increasingly used for hospital rankings, referral base and physician reimbursement. As such, online physician rating websites (PRWs) are quickly becoming a topic of interest. To analyze the distribution of neurosurgeons' ratings on the 3 most widely used PRWs, and examine factors associated with positive and negative ratings. We used a key term search to identify board-certified neurosurgeons on 3 widely used PRWs: RateMD.com, Healthgrades.com, and Vitals.com. Data were collected on average rating and number of ratings. Demographic, training-related and practice-related data, as well as location of practice, and place of training were also collected. Data was non-normally distributed (P < .001 for all 3). Having fewer reviews was associated with higher variance in ratings between PRWs for a given surgeon (odds ratio 0.99, P = .001). All surgeons below the 25th percentile with respect to the number of reviews that had been written about them were eliminated. Of the remaining surgeons (n = 3054), the median composite score was 4.11 out of 5, interquartile range (3.69, 4.44). Surgeons had higher median modified composite scores if they were fellowship-trained (P = .0001) or graduated from a top 25 medical school (P = .0117), but not if they graduated from a top 25 residency (P = .1056). Surgeons located in major cities had higher median composite scores (P = .0025). Online ratings for neurosurgeons must be evaluated in context. Median ratings are generally high, but variable between websites. Median scores also vary among regions and practice settings. Higher scores were associated with ranking of medical school, recent graduation, and fellowship training completion.


Direct cytotoxicity against chicken erythrocytes in mice. III. Degrees of radiosensitivity and cross-reactivity of cytotoxicity, delayed hypersensitivity and antibody production.
Exposure to 600 rad of X-irradiation 3 h after primary immunization with chicken erythrocytes (CRBC) abolished the production of antibodies and the generation of killer T cells, but scarcely affected the induction of delayed footpad reactions. Exposure to irradiation 3 h after secondary immunization reduced only slightly the generation of killer T cells and reduced slightly or substantially the production of antibodies. Delayed reactions persisted for long periods after elicitation in irradiated, boosted mice. Cross-reactivity between CRBC and quail erythrocytes (QRBC) was very weak with respect to the cytotoxicity, antibody and delayed reaction raised after primary immunization. Those raised after secondary immunization with the homologous antigen showed some degrees of cross-reactivity to another antigen. The booster with QRBC in CRBC-primed mice augmented the response to CRBC with respsect to the induction of cytotoxicity and delayed footpad reaction, but only weakly affected the response with respect to the production of antibody. Therefore, effector cells of cytotoxicity and delayed footpad reaction showed greater degrees of cross-reactivity than antibody-producing cells during an anamnestic response. The cross-reactive response raised after secondary immunization was radioresistant with respect to cytotoxicity and delayed footpad reaction but radiosensitive with respect to antibody production. Cytoxicity to immunizing antigen was inhibited by the unlabelled homologous antigen. Cytotoxicity to a cross-reacting antigen was inhibited by the same cross-reacting antigen and also by an immunizing antigen. There may exist heterogeneous populations of cytotoxic lymphocytes with different abilities to recognize antigens.


Copper(ii) complexes with tridentate halogen-substituted Schiff base ligands: synthesis, crystal structures and investigating the effect of halogenation, leaving groups and ligand flexibility on antiproliferative activities.
To investigate the effect of different halogen substituents and leaving groups and the flexibility of ligands on the anticancer activity of copper complexes, sixteen copper(ii) complexes with eight different tridentate Schiff-base ligands containing pyridine and 3,5-halogen-substituted phenol moieties were synthesized and characterized by spectroscopic methods. Four of these complexes were also characterized by X-ray crystallography. The cytotoxicity of the complexes was determined in three different tumor cell lines (i.e. the A2780 ovarian, HCT116 colorectal and MCF7 breast cancer cell line) and in a normal primary fibroblast cell line. Complexes were demonstrated to induce a higher loss of cell viability in the ovarian carcinoma cell line (A2780) with respect to the other two tumor cell lines, and therefore the biological mechanisms underlying this loss of viability were further investigated. Complexes with ligand L1 (containing a 2-pycolylamine-type motif) were more cytotoxic than complexes with L2 (containing a 2-(2-pyridyl)ethylamine-type motif). The loss of cell viability in A2780 tumor cells was observed in the order Cu(Cl2-L1)NO3 > Cu(Cl2-L1)Cl > Cu(Br2-L1)Cl > Cu(BrCl-L1)Cl. All complexes were able to induce reactive oxygen species (ROS) that could be related to the loss of cell viability. Complexes Cu(BrCl-L1)Cl and Cu(Cl2-L1)NO3 were able to promote A2780 cell apoptosis and autophagy and for complex Cu(BrCl-L1)Cl the increase in apoptosis was due to the intrinsic pathway. Cu(Cl2-L1)Cl and Cu(Br2-L1)Cl complexes lead to cellular detachment allowing to correlate with the results of loss of cell viability. Despite the ability of the Cu(BrCl-L1)Cl complex to induce programmed cell death in A2780 cells, its therapeutic window turned out to be low making the Cu(Cl2-L1)NO3 complex the most promising candidate for additional biological applications.


Principle mechanisms underlying venous thromboembolism: epidemiology, risk factors, pathophysiology and pathogenesis.
Deep vein thrombosis (DVT) and pulmonary embolism (PE) are distinct but related aspects of the same dynamic disease process known as venous thromboembolism (VTE). An estimated 200,000 new cases occur in the United States every year, including 94,000 with PE, resulting in an incidence of 23 per 100,000 patients per year-cases. Without treatment, pulmonary embolism is associated with a mortality rate of approximately 30%, causing nearly 50,000 deaths per year. Moreover, based on post-mortem studies, two-thirds of the patients with pulmonary emboli remain undiagnosed. Clinically, PE may present as (1) isolated dyspnea, (2) pleuritic pain and/or hemoptysis, and (3) circulatory collapse. However, clinical history and examination can be notoriously misleading in reaching a diagnosis. A number of acquired etiologic risk factors (predispositions) are associated with a tendency to develop VTE. These include increasing age, immobilization, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, as well as certain types of oral contraception and hormone replacement therapy. In addition, a variety of genetic risk factors, such as factor V Leiden, protein S or C deficiency have also been identified. However, in at least half of the instances, no predisposing factors can be identified (idiopathic PE). In the majority of cases thromboemboli originate in the deep veins of the calf or pelvis. The pathogenic conditions for VTE comprise a triad of factors and include (1) venous stasis, (2) hypercoagulable states, and (3) vascular endothelium injury. Occlusion of pulmonary arteries has variable and transient clinical and pathophysiologic consequences, involving both mechanical and reflex effects of vascular occlusion with a consecutive perfusion defect as well as the release of vasoactive and other inflammatory mediators. The objectives of this article are to present an overview of the etiologic and pathogenic factors promoting VTE as well as the pathophysiologic and inflammatory processes following PE.


Protection of NAD(P)H:quinone oxidoreductase 1 against renal ischemia/reperfusion injury in mice.
Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage. quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. The purpose of this study was to investigate whether NQO1 modulates the renal I/R injury (IRI) associated with NADPH oxidase (NOX)-derived ROS production in an animal model. We analyzed renal function, oxidative stress, and tubular apoptosis after IRI. NQO1(-/-) mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1(-/-) mice, the cellular NADPH/NADP(+) ratio was significantly higher and NOX activity was markedly higher than in those of NQO1(+/+) mice. The activation of NQO1 by β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I/R. Moreover, the βL treatment significantly lowered the cellular NADPH/NADP(+) ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I/R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADP(+) modulation. These results provide convincing evidence that NQO1 activation might be beneficial for ameliorating renal injury induced by I/R.


Verrucous carcinoma in association with oral submucous fibrosis.
Oral verrucous carcinoma is a form of well differentiated squamous cell carcinoma characterized by exophytic over growth. It is slow growing and locally invasive tumor occurring in 6 th and 7 th decade of life. Smoking and chewing tobacco is found to be the most common etiological factor of verrucous carcinoma although oral leukoplakia may act as a predisposing factor. This is a rare case of oral verrucous carcinoma seen in association with oral submucous fibrosis in a younger patient with long standing history of chewing tobacco.


Effects of subject velocity on ground reaction force measurements and stance times in clinically normal horses at the walk and trot.
The objective of the study reported here was to evaluate the effects of changing velocity on stance time and ground reaction force (GRF) measurements in horses at the walk and trot. Force plate gait analysis was used to evaluate clinically normal horses at variable velocities. Ground reaction force measurements and stance times were recorded and compared. 12 adult horses. Data were obtained from 192 valid trials at the walk and 162 valid trials at the trot. Vertical, braking, and propulsive peak forces and impulses were measured. Pearson's correlation coefficients were determined for velocity and stance time and all measured forces and impulses in the forelimbs and hind limbs. Trials were divided into distinct velocity ranges. Trials obtained at velocities within the established ranges were analyzed to evaluate changes in vertical, braking, and propulsive peak forces and impulses at differing speeds within the walk and trot gaits. At the walk and trot, a significant negative correlation was found between velocity and forelimb and hind limb stance times. Velocity and stance time were significantly correlated with many of the GRF and impulse measurements. Velocity was significantly correlated with vertical and braking forces in the hind limbs at the walk, with vertical force in the forelimbs at the trot, and with braking force in the forelimbs and hind limbs at the trot. Velocity and stance time correlated significantly with forelimb and hind limb vertical impulses. Forelimb and hind limb stance times decreased significantly as velocity increased. Hind limb braking force increased and forelimb and hind limb vertical impulses decreased significantly as walk velocity increased. Forelimb braking force increased significantly between velocity ranges at the trot. Results of this study confirm that a significant negative linear correlation exists between subject velocity and stance times in clinically normal horses at the walk and trot. Significant correlations were also identified between velocity and many GRF measurements, indicating that subject velocity does influence the generation of GRF measurements in horses. Variation in subject velocity should be minimized when performing force-plate analysis in horses.


[A seroconversion study of the measles component of the MMR vaccine in adolescents of the town of Sabrosa].
The Portuguese national programme of vaccination has instituted a two-dose MMR vaccine schedule. The second dose of MMR (measles-mumps-rubella combined vaccine) is given at 11-13 years of age, for both sexes. This study was conducted to evaluate the duration of immunity of the monovalent measles vaccine, and the efficacy of a second dose given as MMR. MMR (Triviraten Berna with the strain Edmonston-Zagreb) was given to the 38 participants. Blood samples were collected before and after vaccination. Thirty-six participants had been vaccinated with measles monovalent vaccine during childhood. To measure anti-measles IgG (mIgG), an enzyme immunoassay was used. Participants were classified as "susceptible" or "immune", using 200 mIU/ml (milli international units per millilitre) as the threshold for "immune". Geometric mean concentration (GMC) of mIgG was 1401 mIU/ml in prevaccination sera (n = 38). Thirty-five (92%) of the adolescents were "immune". Only the two unvaccinated had a positive measles history. GMC in the sera of the 36 vaccinated participants was 1301 mIU/ml. Neither the time since measles vaccination nor age at vaccination were correlated with the levels of mIgG. After receiving MMR, all adolescents became "immune". GMC of mIgG was 2879 mIU/ml in postvaccination sera (n = 38). In 28 (74%) participants, mIgG levels increased after receiving MMR. Mean concentration increase was 1082 mIU/ml. For measles, results support the use of a two-dose MMR vaccine schedule in Portugal.


The Vi antigen of Salmonella typhi: molecular analysis of the viaB locus.
Strains of Salmonella typhi isolated from the blood of patients with typhoid fever invariably express a capsular polysaccharide, termed the Vi antigen. Vi antigen expression is controlled by two separate chromosomal loci, viaA and viaB. The viaA locus is commonly found in enteric bacteria. In contrast, the viaB locus appears to be specific to Vi-expressing strains of Salmonella and Citrobacter. Here the cloning, expression and analysis of viaB determinants from S. typhi Ty2 is described. Whole-cell DNA from strain Ty2 was size-fractionated and cloned into the pLA2917 cosmid vector. A recombinant cosmid, pVT1, conferring a Vi-positive phenotype upon Escherichia coli and upon the Vi-non-expressing strain Ty21a of S. typhi, was characterized and used for further studies. Transposon Tn5 insertion mutagenesis demonstrated that the Vi-antigen-encoding region on pVT1 consisted of a 15 kb fragment. A subclone, designated pVT3, which contained an 18 kb insert, was sufficient to confer Vi antigen expression upon E. coli and S. typhi Ty21a. Results of recombination experiments indicated that this DNA sequence was the viaB locus of S. typhi Ty2. In E. coli SE5000 maxicells, the viaB determinants encoded at least eight polypeptides, with molecular masses of 80, 65, 59, 48, 44, 39, 35 and 28 kDa. Functional characterization of viaB mutations in S. typhi Ty2 suggested that the 80 and 65 kDa proteins were required for cell-surface localization of the Vi antigen.


Comparison of nitrogen mustard, cytarabine and dacarbazine as pleural sclerosing agents in rabbits.
We have previously shown that the intrapleural injection of mitozantrone but not bleomycin resulted in pleural fibrosis. Mechlorethamine hydrochloride (nitrogen mustard) was used extensively in the past to control malignant effusions, with relatively good success. The objective of this study was to determine if the intrapleural injection of nitrogen mustard would produce pleural sclerosis in our experimental model in rabbits. We therefore evaluated sclerosing capabilities of nitrogen mustard as well as those of cytarabine and dacarbazine. Nitrogen mustard (0.4 and 0.8 mg x kg(-1)), cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were instilled intrapleurally into anaesthetized rabbits. Twenty eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.8 mg x kg(-1) nitrogen mustard was effective in creating pleural fibrosis, either grossly or microscopically. The mean degree (scale 0-4) of gross pleurodesis in the rabbits that received 0.8 mg x kg(-1) nitrogen mustard was 3.2+/-1.0 and the mean degree of microscopic pleural fibrosis was 3.5+/-0.8. The intrapleural injection of 0.4 mg x kg(-1) nitrogen mustard and the different doses of cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were ineffective in producing pleurodesis. From this study, we conclude that the intrapleural injection of 0.8 mg x kg(-1) of nitrogen mustard produces clinically significant pleurodesis in rabbits. Consideration should be given to future clinical studies utilizing 0.6-0.8 mg x kg(-1) nitrogen mustard intrapleurally for the treatment of malignant pleural effusion.


Detection of visual-field deterioration by Glaucoma Progression Analysis and Threshold Noiseless Trend programs.
To compare the ability of Glaucoma Progression Analysis (GPA) and Threshold Noiseless Trend (TNT) programs to detect visual-field deterioration. Patients with open-angle glaucoma followed for a minimum of 2 years and a minimum of seven reliable visual fields were included. Progression was assessed subjectively by four masked glaucoma experts, and compared with GPA and TNT results. Each case was judged to be stable, deteriorated or suspicious of deterioration A total of 56 eyes of 42 patients were followed with a mean of 7.8 (SD 1.0) tests over an average of 5.5 (1.04) years. Interobserver agreement to detect progression was good (mean kappa = 0.57). Progression was detected in 10-19 eyes by the experts, in six by GPA and in 24 by TNT. Using the consensus expert opinion as the gold standard (four clinicians detected progression), the GPA sensitivity and specificity were 75% and 83%, respectively, while the TNT sensitivity and specificity was 100% and 77%, respectively. TNT showed greater concordance with the experts than GPA in the detection of visual-field deterioration. GPA showed a high specificity but lower sensitivity, mainly detecting cases of high focality and pronounced mean defect slopes.


Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation.
Menaquinone-7 (MK-7), a member of the vitamin K2 family, performs several functions, all related to its recognised effect on post-translational carboxylation of certain protein-bound glutamate residues. Due to its lipophilic structure MK-7 is soluble in olive oil, so the aim of the present study was to test whether extra-virgin (EV) olive oil enriched with MK-7 significantly increases MK-7 plasma levels and has an effect on osteocalcin and its carboxylation status. Healthy young volunteers (n 12) were administered 20 ml EV olive oil per d for 2 weeks, followed by 2 weeks of the same amount of olive oil enriched with 45 μg and then 90 μg MK-7, with an appropriate washout time in between. Blood was collected and plasma separated in each phase of the study. We found that integration of the diet with EV olive oil alone did not produce any significant variation of MK-7 plasma levels compared with baseline. Supplementation with MK-7-enriched olive oil resulted in a significant and dose-dependent increase in plasma levels. The high dose also significantly increased carboxylated osteocalcin (cOC) and decreased undercarboxylated osteocalcin (ucOC) plasma levels, resulting in a significant increase in the cOC:ucOC ratio. A significant correlation was also found between percentage variation of plasma cOCA:ucOC ratio and increase in plasma MK-7 levels. We conclude that regular consumption of MK-7-enriched olive oil may constitute a valid approach in order to preserve some key biochemical mechanisms controlling bone mineralisation.


[Blepharoplasty after tumor ("cancer eye") removal from the eyes of cattle].
A literature review of surgical techniques used for resection of periocular tumors with conservation of the eyelid is accompanied by a report of the author's personal experience with blepharoplasty in cattle. Included are 13 cases of Fleckvieh cows with squamous cell carcinoma. Five animals were without tumor recurrence after an average time of 10.7 months, while seven animals with recurrence of the neoplasm had mean survival time of 10.6 months. Those five cows had been slaughtered for unrelated problems, the others because of recurrence of the ocular tumor. One patient was slaughtered five days after surgery because of complications of wound healing.


Photocatalytic redox-neutral hydroxyalkylation of N-heteroaromatics with aldehydes.
Hydroxyalkylation of N-heteroaromatics with aldehydes was achieved using a binary hybrid catalyst system comprising an acridinium photoredox catalyst and a thiophosphoric acid organocatalyst. The reaction proceeded through the following sequence: (1) photoredox-catalyzed single-electron oxidation of a thiophosphoric acid catalyst to generate a thiyl radical, (2) cleavage of the formyl C-H bond of the aldehyde substrates by a thiyl radical acting as a hydrogen atom transfer catalyst to generate acyl radicals, (3) Minisci-type addition of the resulting acyl radicals to N-heteroaromatics, and (4) a spin-center shift, photoredox-catalyzed single-electron reduction, and protonation to produce secondary alcohol products. This metal-free hybrid catalysis proceeded under mild conditions for a wide range of substrates, including isoquinolines, quinolines, and pyridines as N-heteroaromatics, as well as both aromatic and aliphatic aldehydes, and tolerated various functional groups. The reaction was applicable to late-stage derivatization of drugs and their leads.


Acquired carbapenemases in Gram-negative bacterial pathogens: detection and surveillance issues.
Acquired carbapenemases are emerging resistance determinants in Gram-negative pathogens, including Enterobacteriaceae, Pseudomonas aeruginosa and other Gram-negative non-fermenters. A consistent number of acquired carbapenemases have been identified during the past few years, belonging to either molecular class B (metallo-beta-lactamases) or molecular classes A and D (serine carbapenemases), and genes encoding these enzymes are associated with mobile genetic elements that allow their rapid dissemination in the clinical setting. Therefore, detection and surveillance of carbapenemase-producing organisms have become matters of major importance for the selection of appropriate therapeutic schemes and the implementation of infection control measures. As carbapenemase production cannot be simply inferred from the resistance profile, criteria must be established for which isolates should be suspected and screened for carbapenemase production, and for which tests (phenotypic and/or genotypic) should be adopted for confirmation of the resistance mechanism. Moreover, strategies should be devised for surveillance of carbapenemase producers in order to enable the implementation of effective surveillance programmes. The above issues are addressed in this article, as a follow-up to an expert meeting on acquired carbapenemases that was recently organized by the ESCMID Study Group for Antibiotic Resistance Surveillance.


Transgender women's experiences and beliefs about hormone therapy through and beyond mid-age: An exploratory UK study.
Background: Little is known about transgender women's beliefs and experiences of hormone therapy (HT), as part of their transition process, and particularly as they grow older. Aims: This study aimed to investigate: (i) transgender women's experiences and attitudes to HT, and (ii) expectations of what might occur and/or what occurred after they reached "menopausal age." Methods: Participants were recruited through invitations to an online survey sent to 138 Lesbian, gay, bisexual, transgender plus (LGBT+) support groups across the UK. Sixty-seven transgender women consented and completed the questionnaire; responses were analyzed using a mixed-methods approach. The beliefs about medicines questionnaire (BMQ) was used to assess beliefs about HT, while an inductive thematic qualitative approach was used to explore participants' personal expectations and experiences of HT and their views about the menopause. Results: Participants were aged on average 49 years ranging from 20 to 79 years old. Most (96%) were taking HT. BMQ scores revealed strong beliefs about the necessity of HT and some concerns. Positive views about HT were expressed, with themes including treatment importance, personal and mental health benefits, but concerns about long-term effects, side effects, and maintaining access to the treatment were also mentioned. Views about menopause included uncertainty and questioning of its relevance; some mentioned changes to HT dosage, but most expected to use HT indefinitely. Discussion: This study provides exploratory qualitative and quantitative information about transgender women's views about HT and menopause. Practical implications include improving access to HT and provision of evidence-based information about long-term use.


Biomedicine, public health, and citizenship in the advent of antiretrovirals in Botswana.
Often celebrated as a model of development in Africa, Botswana nonetheless endured a severe HIV epidemic. This article describes the singularity of the Botswana experience in facing AIDS and creating the widest possible access to antiretroviral medications for its citizens. Through exploration of different sets of actors and the construction of their ethics of treatment, it is possible to examine how free and universal access was created within the national antiretroviral program. This article underscores the importance of the site and the local dynamics in the advent of an ethics of access to treatment for Botswana citizens. At the intersection of national citizenship, pharmaceutical philanthropy, and biomedical collaborations, Botswana is an exemplary case (one of the first and unique in its kind) of global health programs for access to drugs in which patients' rights are tied to science and pharmaceutical development. As such it also bears some limitations and concerns over its sustainability.


Interactive Effects of CO2 Concentration and Water Regime on Stable Isotope Signatures, Nitrogen Assimilation and Growth in Sweet Pepper.
Sweet pepper is among the most widely cultivated horticultural crops in the Mediterranean basin, being frequently grown hydroponically under cover in combination with CO2 fertilization and water conditions ranging from optimal to suboptimal. The aim of this study is to develop a simple model, based on the analysis of plant stable isotopes in their natural abundance, gas exchange traits and N concentration, to assess sweet pepper growth. Plants were grown in a growth chamber for near 6 weeks. Two [CO2] (400 and 800 μmol mol-1), three water regimes (control and mild and moderate water stress) and four genotypes were assayed. For each combination of genotype, [CO2] and water regime five plants were evaluated. Water stress applied caused significant decreases in water potential, net assimilation, stomatal conductance, intercellular to atmospheric [CO2], and significant increases in water use efficiency, leaf chlorophyll content and carbon isotope composition, while the relative water content, the osmotic potential and the content of anthocyanins did change not under stress compared to control conditions support this statement. Nevertheless, water regime affects plant growth via nitrogen assimilation, which is associated with the transpiration stream, particularly at high [CO2], while the lower N concentration caused by rising [CO2] is not associated with stomatal closure. The stable isotope composition of carbon, oxygen, and nitrogen (δ13C, δ18O, and δ15N) in plant matter are affected not only by water regime but also by rising [CO2]. Thus, δ18O increased probably as response to decreases in transpiration, while the increase in δ15N may reflect not only a lower stomatal conductance but a higher nitrogen demand in leaves or shifts in nitrogen metabolism associated with decreases in photorespiration. The way that δ13C explains differences in plant growth across water regimes within a given [CO2], seems to be mediated through its direct relationship with N accumulation in leaves. The changes in the profile and amount of amino acids caused by water stress and high [CO2] support this conclusion. However, the results do not support the use of δ18O as an indicator of the effect of water regime on plant growth.


IDEA: Interactive Display for Evolutionary Analyses.
The availability of complete genomic sequences for hundreds of organisms promises to make obtaining genome-wide estimates of substitution rates, selective constraints and other molecular evolution variables of interest an increasingly important approach to addressing broad evolutionary questions. Two of the programs most widely used for this purpose are codeml and baseml, parts of the PAML (Phylogenetic Analysis by Maximum Likelihood) suite. A significant drawback of these programs is their lack of a graphical user interface, which can limit their user base and considerably reduce their efficiency. We have developed IDEA (Interactive Display for Evolutionary Analyses), an intuitive graphical input and output interface which interacts with PHYLIP for phylogeny reconstruction and with codeml and baseml for molecular evolution analyses. IDEA's graphical input and visualization interfaces eliminate the need to edit and parse text input and output files, reducing the likelihood of errors and improving processing time. Further, its interactive output display gives the user immediate access to results. Finally, IDEA can process data in parallel on a local machine or computing grid, allowing genome-wide analyses to be completed quickly. IDEA provides a graphical user interface that allows the user to follow a codeml or baseml analysis from parameter input through to the exploration of results. Novel options streamline the analysis process, and post-analysis visualization of phylogenies, evolutionary rates and selective constraint along protein sequences simplifies the interpretation of results. The integration of these functions into a single tool eliminates the need for lengthy data handling and parsing, significantly expediting access to global patterns in the data.


Extended breast cancer treatment with an aromatase inhibitor (Letrozole) after tamoxifen: why, who and how long?
Breast cancer remains a leading cause of cancer death in women worldwide, and the risk for disease recurrence continues despite improvements in screening and treatment and the use of prophylactic estrogen-inhibiting therapies such as tamoxifen. A number of long-term studies now indicate a significant risk for breast cancer recurrence among patients who have undergone the currently recommended five years of tamoxifen adjuvant therapy following successful treatment of their initial disease. This ongoing recurrence risk extends even to patients commonly considered at low risk for relapse, that is, those with low-grade, small tumors, and/or node-negative disease. Treatment with tamoxifen for more than five years appears detrimental rather than beneficial and, therefore, tamoxifen is not indicated for use beyond the initial five years. Endometrial cancer and thromboembolism are among the serious adverse events that have been observed with long-term tamoxifen treatment. The aromatase inhibitors are able to reduce overall estrogen levels and appear to be better tolerated over a long term. Letrozole is the most potent aromatase inhibitor and has been available in Europe since 1996 and in the United States since 1997. Letrozole has been approved for first-line treatment of postmenopausal women with hormone-receptor-positive or hormone-receptor-unknown, advanced or metastatic breast cancer in the United States and Europe, as well as for neoadjuvant treatment (primary systemic therapy) of early breast cancer prior to surgery in many countries. The results of the pivotal MA-17 trial demonstrate that letrozole is unique in its ability to improve disease-free survival in breast cancer patients who have undergone tamoxifen therapy for five years. The MA-17 results indicate that extended adjuvant therapy with letrozole reduces risk of recurrence in this setting by 42%, reduces risk of distant recurrence (metastasis), and may improve patient survival in the node-positive patient population. The results also show letrozole to be well tolerated and safe over the length of follow-up. The trial outcomes have led to the approval of letrozole for the extended adjuvant indication in more than 40 countries worldwide. Re-randomization of letrozole-treated patients from this pivotal trial is underway to investigate if ten years of extended adjuvant endocrine therapy leads to further improvement, and the results of this extension study should aid in resolving several open questions regarding extended adjuvant therapy, including who should be treated and for how long.


The therapeutic prospects of N-acetylgalactosamine-siRNA conjugates.
RNA interference has become increasingly used for genetic therapy following the rapid development of oligonucleotide drugs. Significant progress has been made in its delivery system and implementation in the treatment of target organs. After a brief introduction of RNA interference technology and siRNA, the efficiency and stability of GalNAc-siRNA conjugates are highlighted since several oligonucleotide drugs of GalNAc have been approved for clinical use in recent years. The structure and features of GalNAc-siRNA conjugates are studied and the clinical efficiency and limitations of oligonucleotide-based drugs are summarized and investigated. Furthermore, another delivery system, lipid nanoparticles, that confer many advantages, is concluded, includ-ing stability and mass production, compared with GalNAc-siRNA conjugates. Importantly, developing new approaches for the use of oligonucleotide drugs brings hope to genetic therapy.


Refractory constrictive pericarditis caused by an immune checkpoint inhibitor properly managed with infliximab: a case report.
Immune checkpoint inhibitors (ICIs) can cause cardiac immune-related adverse events (irAEs), including pericarditis. Cardiovascular events related to pericardial irAE are less frequent, but fulminant forms can be fatal. However, the diagnosis and treatment strategies for pericardial irAE have not established. A 58-year-old man was diagnosed with advanced non-small-cell lung cancer and nivolumab was administered as 5th-line therapy. Eighteen months after the initiation of nivolumab, the patient developed limb oedema and increased body weight. Although a favourable response of the cancer was observed, pericardial thickening and effusion were newly detected. He was diagnosed with irAE pericarditis after excluding other causes of pericarditis. Nivolumab was suspended and a high-dose corticosteroid was initiated. However, right heart failure (RHF) symptoms were exacerbated during the tapering of corticosteroid because acute pericarditis developed to steroid-refractory constrictive pericarditis. To suppress sustained inflammation of the pericardium, infliximab, a tumour necrosis factor-alfa inhibitor, was initiated. After the initiation of infliximab, the corticosteroid dose was tapered without deterioration of RHF. Exacerbation of lung cancer by irAE treatment including infliximab was not observed. IrAE should be considered when pericarditis develops after the administration of ICI even after a long period from its initiation. Infliximab rescue therapy may be considered as a 2nd-line therapy for steroid-refractory irAE pericarditis even with constrictive physiology.


Quantitative imaging and statistical analysis of fluorescence in situ hybridization (FISH) of Aureobasidium pullulans.
Image and multifactorial statistical analyses were used to evaluate the intensity of fluorescence signal from cells of three strains of A. pullulans and one strain of Rhodosporidium toruloides, as an outgroup, hybridized with either a universal or an A. pullulans 18S rRNA oligonucleotide probe in direct or indirect FISH reactions. In general, type of fixation (paraformaldehyde or methanol-acetic acid) had no apparent effect on cell integrity and minimal impact on fluorescence. Permeabilization by enzyme treatment for various times, though needed to admit high Mw detection reagents (avidin-FITC) in indirect FISH, tended to nonspecifically degrade cells and lower the signal. Digestion was unnecessary and undesirable for the directly labelled probes. Multilabelled (five fluorescein molecules) probes enhanced fluorescence about fourfold over unilabelled probes. Overall, direct FISH was preferable to indirect FISH and is recommended especially for studies of microbes on natural substrata.


I(8)Sb(10)Ge(36).
Single crystals of the title compound, octa-iodide deca-anti-monate hexa-tria-conta-germanide, were grown by chemical transport reactions. The structure is isotypic with the analogous clathrates-I. In this structure, the (Ge,Sb)(46) framework consists of statistically occupied Ge and Sb sites that atoms form bonds in a distorted tetra-hedral arrangement. They form polyhedra that are covalently bonded to each other by shared faces. There are two polyhedra of different sizes, viz. a (Ge,Sb)(20) dodeca-hedron and a (Ge,Sb)(24) tetra-cosa-hedron in a 1:3 ratio. The guest atom (iodine) resides inside these polyhedra with symmetry m3 (Wyckoff position 2a) and 2m (Wyckoff position 2d), respectively.


The High School Competencies Scale (H-Comp Scale): A First Validation Study.
Researchers widely explored non-intellective study factors because they play a central role in academic performance and are potentially more modifiable than intellective ones. The scientific literature suggests that the non-intellective factors can be classified into three main areas: self-concept, which refers to self-esteem and efficacy, motivation and emotional reactions; the area of study, related to study dedication and operative skills; and the area of relationships, comprising those with family, fellow students and teachers. Basing on these findings, the C-Comp Scale has been developed and tested in the past, addressed to college students. This study aimed to adapt and test a new version of this questionnaire on high school students. A pilot study was conducted on 364 Italian high school students to adapt and test the new version of the questionnaire, called the H-Comp Scale. The following study, conducted on 792 Italian high school students, provided further evidence of its reliability, structural validity, and concurrent validity with general self-efficacy, academic self-efficacy, social self-efficacy, and academic performance. The H-Comp Scale showed to possess excellent reliability and structural and concurrent validity. The final version is composed of twelve subscales, aggregated in three areas, with just 48 items: Study (Intrinsic Motivation, Extrinsic Motivation, Time Management, Study Dedication), Self (Learning Assessment, General Self-Esteem, Self-Efficacy, Reaction to Failures, Emotional Control), and Relationships (Family Relationships, Fellow Student Relationships, Teacher Relationships). The H-Comp Scale would be a useful and easy-to-use instrument to support school counselors, tutors, teachers, and researchers in exploring different types of non-intellective variables, to better project educational intervention aimed to improve high school students' academic performance and satisfaction.


Involvement of Abnormal Gut Microbiota Composition and Function in Doxorubicin-Induced Cardiotoxicity.
Doxorubicin (Dox), a chemotherapeutic anthracycline agent for the treatment of a variety of malignancies, has a limitation in clinical application for dose-dependent cardiotoxicity. The purpose of this study was to explore the relationship between the composition/function of the gut microbiota and Dox-induced cardiotoxicity (DIC). C57BL/6J mice were injected intraperitoneally with 15 mg/kg of Dox, with or without antibiotics (Abs) administration. The M-mode echocardiograms were performed to assess cardiac function. The histopathological analysis was conducted by H&E staining and TUNEL kit assay. The serum levels of creatine kinase (CK), CK-MB (CK-MB), lactic dehydrogenase (LDH), and cardiac troponin T (cTnT) were analyzed by an automatic biochemical analyzer. 16S rRNA gene and metagenomic sequencing of fecal samples were used to explore the gut microbiota composition and function. Dox caused left ventricular (LV) dilation and reduced LV contractility. The levels of cardiomyocyte apoptosis and myocardial enzymes were elevated in Dox-treated mice compared with the control (Con) group. 16S rRNA gene sequencing results revealed significant differences in microbial composition between the two groups. In the Dox group, the relative abundances of Allobaculum, Muribaculum, and Lachnoclostridium were significantly decreased, whereas Faecalibaculum, Dubosiella, and Lachnospiraceae were significantly increased compared with the Con group at the genus level. Functional enrichment with Cluster of orthologous groups of proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the Dox mice displayed different clusters of cellular processes and metabolism from the Con mice. The different species and their functions between the two groups were associated with the clinical factors of cardiac enzymes. Moreover, depletion of the gut microbiota could alleviate Dox-induced myocardial injury and cardiomyocyte apoptosis. The study here shows that composition imbalance and functional changes of the gut microbiota can be one of the etiological mechanisms underlying DIC. The gut microbiota may serve as new targets for the treatment of cardiotoxicity and cardiovascular diseases.


Overexpression of ornithine decarboxylase decreases ventricular systolic function during induction of cardiac hypertrophy.
Ornithine decarboxylase (ODC), the first enzyme of polyamine metabolism, is rapidly upregulated in response to agents that induce a pathological cardiac hypertrophy. Transgenic mice overexpressing ODC in the heart (MHC-ODC mice) experience a much more dramatic left ventricular hypertrophy in response to β-adrenergic stimulation with isoproterenol (ISO) compared to wild-type (WT) controls. ISO also induced arginase activity in transgenic hearts but not in controls. The current work studies the cooperation between the cardiac polyamines and L-arginine (L-Arg) availability in MHC-ODC mice. Although ISO-induced hypertrophy is well-compensated, MHC-ODC mice administered L-Arg along with ISO showed a rapid onset of systolic dysfunction and died within 48 h. Myocytes isolated from MHC-ODC mice administered L-Arg/ISO exhibited reduced contractility and altered calcium transients, suggesting an alteration in [Ca(2+)] homeostasis, and abbreviated action potential duration, which may contribute to arrhythmogenesis. The already elevated levels of spermidine and spermine were not further altered in MHC-ODC hearts by L-Arg/ISO treatment, suggesting alternative L-Arg utilization pathways lead to dysregulation of intracellular calcium. MHC-ODC mice administered an arginase inhibitor (Nor-NOHA) along with ISO died almost as rapidly as L-Arg/ISO-treated mice, while the iNOS inhibitor S-methyl-isothiourea (SMT) was strongly protective against L-Arg/ISO. These results point to the induction of arginase as a protective response to β-adrenergic stimulation in the setting of high polyamines. Further, NO generated by exogenously supplied L-Arg may contribute to the lethal consequences of L-Arg/ISO treatment. Since considerable variations in human cardiac polyamine and L-Arg content are likely, it is possible that alterations in these factors may influence myocyte contractility.


In vivo cell-cycle profiling in xenograft tumors by quantitative intravital microscopy.
Quantification of cell-cycle state at a single-cell level is essential to understand fundamental three-dimensional (3D) biological processes such as tissue development and cancer. Analysis of 3D in vivo images, however, is very challenging. Today's best practice, manual annotation of select image events, generates arbitrarily sampled data distributions, which are unsuitable for reliable mechanistic inferences. Here, we present an integrated workflow for quantitative in vivo cell-cycle profiling. It combines image analysis and machine learning methods for automated 3D segmentation and cell-cycle state identification of individual cell-nuclei with widely varying morphologies embedded in complex tumor environments. We applied our workflow to quantify cell-cycle effects of three antimitotic cancer drugs over 8 d in HT-1080 fibrosarcoma xenografts in living mice using a data set of 38,000 cells and compared the induced phenotypes. In contrast to results with 2D culture, observed mitotic arrest was relatively low, suggesting involvement of additional mechanisms in their antitumor effect in vivo.


Sex Differences in the Association Between Stress, Loneliness, and COVID-19 Burden Among People with HIV in the United States.
Little is known about the psychological implications of the coronavirus disease 2019 (COVID-19) pandemic on people with HIV. The purpose of this study was to assess the impact of COVID-19 among men and women with HIV in Miami, Florida. We hypothesized that the burden of the COVID-19 pandemic will be higher for women, and psychological factors will increase COVID-19 burden among them. People with (n = 231) and without HIV (n = 42) residing in Miami, Florida completed a survey assessing psychological outcomes such as loneliness, depression, and stress, as well as the burden of COVID-19, on their daily lives. t-Tests and chi-square analyses were used to assess sex differences in study variables. Logistic regression was used to compare the interaction effects predicting stress and loneliness by COVID-19 burden and sex. A total of 273 completed the survey; the outcomes of the study, loneliness, and stress did not differ by HIV status (p = .458 and p = .922). Overall, men and women reported similar prevalence of COVID-19 burden. However, a greater proportion of women reported losing childcare than men (18% vs. 9%, p = .029, respectively), as well as losing mental health care (15% vs. 7%, p = .049, respectively). There was a significant interaction between COVID-19 burden and sex for loneliness and stress such that the association between COVID-19 burden and loneliness was greater for women (p < .001) than for men (p = .353) and the association between COVID-19 burden and stress was greater for women (p = .013) than men (p = .628). Both men and women with HIV are impacted by the COVID-19 pandemic, but women may experience higher levels of stress and loneliness than men. Sex differences may require tailored interventions to more effectively mitigate the impact of the pandemic on mental health.


Wettability Alteration of Calcite by Nonionic Surfactants.
The process of selecting an effective surfactant for wettability alteration is dependent on a number of factors, including mineral type, temperature, salinity, and nature of adsorbed oil and ultimately how the molecular structure of the surfactant interacts with all of these. Here, we present an experimental study of the effectiveness of nonionic surfactants with different hydrophobic groups and different lengths of hydrophilic ethylene oxide oligomers. The surfactants selected alter the wettability of the rock primarily by acting on the water-rock and oil-rock interfaces. The dynamics of wettability alteration is measured by the evolution of contact angles of oil drops on initially oil-wet surfaces at three different temperatures. Wettability alteration is found to be enhanced by surfactants with shorter hydrophilic units and increased temperatures. Experimental observations are efficiently summarized by a few thermodynamic and kinetic parameters. Qualitative experiments are performed to study surfactant-induced dewetting of oil films. Finally, a model involving "coating" and "sweeping" mechanisms is proposed to explain the mechanism of surfactant action.


Alcohol-Based Handrub Utilization Practice for COVID-19 Prevention Among Pharmacy Professionals in Ethiopian Public Hospitals: A Cross-Sectional Study.
Rubbing the hands with alcohol-based handrub (ABHR) is globally recommended as the preferred approach to prevent healthcare-associated infections in most routine encounters with patients, except in cases handwashing with soap and water is advised. Inappropriate utilization of ABHR could have detrimental effects, most importantly during the coronavirus disease (COVID-19) pandemic, which include exposure of healthcare professionals to healthcare-associated infections and the development of resistant microorganisms. In a hospital setting, the utilization of ABHR among frontline healthcare workers including pharmacy professionals is low. Therefore, the purpose of this study was to explore the current practice of hand rubbing among pharmacy professionals in public hospitals of Addis Ababa during the pandemic of COVID-19. The study was a cross-sectional study using a self-reported questionnaire conducted among pharmacy professionals in public hospitals found in Addis Ababa from 10th May to 9th June, 2020 to recognize ABHR utilization rate. Data were collected on a sample of 384 pharmacy professional by a self-administered questionnaire. Data analysis was done using software for the statistical package for social science version 25.0. To identify the significant predictors of ABHR utilization practice bivariable and multivariable logistic regressions were carried out. Crude odds ratio and adjusted odds ratio with 95% confidence interval were calculated to determine the predictors. Out of 384 participants, three hundred and four participants were included in the final analyses after the exclusion of incomplete responses. Female participants represented 41.4% of the study participants. More than half (58.9%) of the pharmacy professionals had sufficient knowledge on ABHR utilization for COVID-19 prevention. Similarly, 56.6% of pharmacy professionals had positive attitude towards ABHR for COVID-19 prevention. But only 35.9% of the study participants had good ABHR utilization practice. Despite the modest level of knowledge and attitude towards ABHR, pharmacy professionals' utilization practice of ABHR for COVID-19 prevention was found to be suboptimal. Provision of ABHR solutions through hospitals and increasing the awareness of pharmacy professionals on ABHR needs to be encouraged.


Cost-effectiveness of bariatric surgery in adolescents with severe obesity in the UK.
Evidence shows that surgery for severe obesity in adults improves health and psychological functioning, and is cost-effective. Data on bariatric surgery for adolescents with severe obesity are extremely limited, with no evidence on cost-effectiveness. We evaluated the lifetime cost-effectiveness of bariatric surgery compared with no surgery in adolescents with severe obesity from the UK's National Health Service perspective. Eighteen adolescents with body mass index ≥40 kg m-2 who underwent bariatric surgery (laparoscopic Roux en Y Gastric Bypass [RYGB] [N = 9], and laparoscopic Sleeve Gastrectomy [SG] [N = 9]) at University College London Hospitals between January 2008 and December 2013 were included. We used a Markov cohort model to compare the lifetime expected costs and quality-adjusted life years (QALYs) between bariatric surgery and no surgery. Mean cost of RYGB and SG procedures were £7100 and £7312, respectively. For RYGB vs. no surgery, the incremental cost/QALY was £2018 (95% CI £1942 - £2042) for males and £2005 (95% CI £1974 - £2031) for females. For SG vs. no surgery, the incremental cost/QALY was £1978 (95% CI £1954 - £2002) for males and £1941 (95% CI £1915 - £1969) for females. Bariatric surgery in adolescents with severe obesity is cost-effective; it is more costly than no surgery however it markedly improved quality of life.


Correlation of affective temperament and psychiatric symptoms in palliative care cancer patients.
Psychiatric symptoms are common in terminally ill patients. Studies linking temperamental traits and psychiatric disorders in patients suffering from advanced disease are rare. This study investigated the influence of temperament on depression and anxiety in palliative care cancer patients. A total of 53 patients at the palliative care unit (PCU) of the Medical University of Vienna were enrolled in the study. Patients filled out the TEMPS-M and the brief PHQ-9 questionnaires to examine associations between temperament, psychiatric symptoms and sociodemographic parameters. Pain (67%), anorexia (58%), constipation (42%) and nausea/vomiting (40%) were the most prevalent self-reported symptoms. Self-reported symptoms of depression were less commonly reported (21.8%) than unveiled by the structured assessment by the PHQ-9 questionnaire: 26.4% (n = 14) showed mild symptoms of depression and 64.1% (n = 34) had a major depressive disorder (MDD) according to PHQ-9. The depressive and cyclothymic temperaments showed significant associations with depressive (both: p < 0.001) as well as symptoms of anxiety (p = 0.002; p = 0.036). Furthermore, the anxious temperament was significantly associated with symptoms of depression (p = 0.027). Mood disorders are common in palliative care patients, as the majority of the patients were suffering from MDD. The depressive, cyclothymic and anxious temperaments were found to be correlated with depressive and anxious symptoms. A sensitization in this field might bring further improvements for the quality of life of palliative care patients and help to appropriately address psychiatric symptoms in palliative care.


The N Terminus of Autographa californica Multiple Nucleopolyhedrovirus DNA Polymerase Is Required for Efficient Viral DNA Replication and Virus and Occlusion Body Production.
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) DNA polymerase (DNApol) plays a crucial role in viral DNA synthesis, and the N terminus (residues 1 to 186) is highly conserved in the baculovirus DNApol family. However, the functional role of the N terminus of DNApol has not yet been characterized. Here we report a functional analysis of the AcMNPV DNApol N terminus. We truncated the DNApol N terminus to construct truncation mutants Bac-GFP-PolΔ64, Bac-GFP-PolΔ110, and Bac-GFP-PolΔ186, which lack 64, 110, and 186 N-terminal residues, respectively. Although the truncation mutants rescued viral DNA synthesis and infectious virus production, the level of DNA replication decreased, and Bac-GFP-PolΔ64, Bac-GFP-PolΔ110, and Bac-GFP-PolΔ186 showed 10-fold, 89-fold, and 891-fold reductions in infectious viral yield compared to that of the wild-type repair virus, respectively. Production of occlusion bodies was compromised for all truncation mutants. Further bioinformatic analysis showed that the first 64 amino acids (aa) at the extreme N terminus contains a conserved α(-helix)-β(-sheet)-β-β secondary-structure region, and further downstream sequence from aa 67 to 186 is comprised of four conserved sequence motifs. Multiple alanine point substitutions in the α-β-β-β structure region or the four sequence motifs in the N terminus impaired viral DNA replication and resulted in reduction of virus yield and occlusion body production. Together, our results suggested that the secondary structure and four conserved motifs within the N terminus of AcMNPV DNApol are important for viral DNA synthesis, infectious virus yield, and production of occlusion bodies.IMPORTANCE DNA polymerase (DNApol) is highly conserved in all baculoviruses and is required for viral DNA replication. The N terminus is one of the highly conserved regions of baculovirus DNApols. Our results showed that the N terminus of baculovirus DNA polymerase plays an important role in efficient viral DNA synthesis and infectious virus yield and production of occlusion bodies. We identified five features, including a highly conserved secondary structure and four conserved amino acid motifs, in the AcMNPV DNApol N terminus, all of which are important for efficient viral DNA synthesis, infectious virus yield, and production of occlusion bodies.