Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 18-49 years of age, naive to 23-valent pneumococcal polysaccharide vaccine.
Based on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60-64 years of age have been published. The same study also included a cohort of adults aged 18-49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18-49 years of age compared with adults 60-64 years of age for whom PCV13 is approved. Adults naive to PPSV23 were grouped by age into 2 cohorts: 18-49 years (n=899; further stratified by age into 3 subgroups 18-29, 30-39, and 40-49 years) and 60-64 years (n=417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated. In adults aged 18-49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60-64 years. Immune responses were highest in the youngest age subgroup (18-29 years). Local reactions and systemic events were more common in adults 18-49 years compared with 60-64 years and were self-limited. Immune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections.


Increased iodine uptake in thyroid carcinoma after treatment with sodium butyrate and decitabine (5-Aza-dC).
To determine if epigenetic-modifying drugs can increase iodine uptake in thyroid carcinoma cell lines. Human thyroid carcinoma cell lines were tested for iodine uptake before and after treatment with epigenetic-modifying agents. Thyroid carcinoma cell lines DRO and 2-7 had high levels of DNA methylation (74% and 80%) compared with normal thyroid tissue (6%) (P < 0.05). This finding correlated with low levels of sodium iodide symporter (NIS) expression in the untreated thyroid carcinoma cell line. Combination treatment with the epigenetic-modifying agents 5-aza-2'-deoxycytidine and sodium butyrate resulted in increases in NIS messenger RNA levels, global histone acetylation, and 9- and 8-fold increases in I(125) uptake for the DRO and 2-7 cells, respectively. Epigenetic-modifier drugs represent a novel adjuvant treatment for those patients with radioablation-resistant thyroid cancer. Epigenetic-modifying agents show potential for treatment of radioablation-resistant thyroid cancer.


Resistance pattern and maternal knowledge, attitude and practices of suspected Diarrheagenic Escherichia coli among children under 5 years of age in Addis Ababa, Ethiopia: cross sectional study.
Diarrheal illness remains one of the leading causes of morbidity and mortality among children under 5 years of age worldwide, especially in developing countries. Diarrheagenic Escherichia coli (DEC) is the major cause of gastroenteritis in children in the developing world and is associated with high resistance levels to antibiotics. The aims of this study were to isolate and determine susceptibility patterns of DEC among children under 5 years of age with acute diarrhea and to assess maternal knowledge, attitude and practice towards childhood diarrhea. A cross sectional study was conducted from August-December 2015 at 3 selected health institutions. Stool samples were cultured and isolated E. coli species were run for antimicrobial susceptibility testing using disk diffusion method. In addition, children's caretakers were interviewed using structured questionnaires including a Knowledge, Attitude and Practice (KAPs) survey. Bivariate and multivariate logistic regression analysis was used to quantify the effect of different risk factors on bacterial related diarrhea. A total of 253 children, 115 males and 138 females with acute diarrhea were enrolled. E. coli was identified in a total of sixty-one children (24.1%), followed by Shigella (9.1%) and Salmonella (3.95%). Additionally, eighty-six children (34.0%) had parasites identified in stool samples. E. coli isolates showed 83.6% resistance to ampicillin and augmentin followed by, trimethoprim-sulfamethoxazole (62.3%). Multiple resistances were observed in 72.1% of isolates; however, more than 90% of the strains were sensitive to ciprofloxacin and ceftriaxone. Caretakers identified the following as causes of infection: contaminated food and water (83.4%), microorganisms (55.3%), inadequate breast milk (54.1%), teething (45.1%), house flies (43.1%) and evil eye (15.8%). No hand washing before meals and low levels of knowledge had a significant association with E. coli infection (p < 0.05). In children with suspected diarrheagenic E. coli, we observed a high frequency of multidrug resistant E. coli. Furthermore, study subjects with low awareness about source, cause and symptoms of the disease were more likely to acquire suspected diarrheagenic E. coli infections. Thus, there is a need for more education in addition to continuous surveillance of the prevalence and antibiotic susceptibility pattern of diarrheal bacterial isolates in hospitals and in the community.


Sexually differentiated flight responses of the Mexican bean beetle to larval and adult nutrition.
Flight of male and female Mexican bean beetle adults was examined in laboratory tests. The experimental design made it possible to examine flight behavior not only with respect to different types of hosts (young vs senescent common bean foliage) but also with respect to effects due to their utilization during particular stages of beetle development. The median flight time of males was significantly affected by the adult host, but not by the juvenile host; whereas, the median flight time of females tended to be more affected by the juvenile than by the adult host. These different effects of hosts on the flight times of males and females resulted in sexual dimorphism in flight when the sexes were fed senescent foliage as adults. Although age significantly affected the flight time of both males and females, the reproductive status of females did not affect their flight times. The significance of these results are discussed with respect to the influence of the nutritional complexity of habitats on life history strategies and population dynamics.


Spatial attention in hypothetically psychosis-prone college students.
This study tested the hypothesis that psychosis-prone individuals show patterns of visual search that suggest a lateralized cerebral hemispheric abnormality, similar to one hypothesized by Venables (1980) to underlie cognitive dysfunction in schizophrenia. Self-report measures of psychiatric vulnerability were completed by 881 college students. Experimental subjects (n = 73) were those with high scores on one of four psychosis-proneness scales. Control subjects (n = 33) scored within 0.5 SD of the mean on all scales. Subjects were tested using verbal and nonverbal visual search tasks designed to detect abnormalities in the spatial distribution of attention. When searching random arrays of nonverbal stimuli, 53% of the experimental subjects used an erratic search strategy similar to that typically observed in right-brain-damaged patients, compared with 23% of controls. The most deviant search patterns were shown by subjects who scored high on Physical Anhedonia and Perceptual Aberration-Magical Ideation. The results suggest that early development of schizophrenic disorder might be associated with dysfunction of right-hemispheric mechanisms of attentional control.


Respiratory diseases and allergies in two polluted areas in East Germany.
This cross-sectional epidemiological study collected health data for 2,470 school children between 5 and 14 years of age (89% of eligible children) who had lived most of their lives in either one of two counties strongly impacted by industrial pollution (Bitterfeld and Hettstedt) or in a neighboring county without any sources of industrial pollution (Zerbst). The objective of the study was to examine whether regional differences--with respect to the occurrence of childhood respiratory diseases and symptoms or allergies--exist and, if such differences are found, whether they persist when we adjust for the effects of known risk factors such as medical and sociodemographic factors or factors related to the indoor environment. Controlling for medical, sociodemographic, and indoor factors, according to parental reports, children residing in Hettstedt have about a 50% increased lifetime prevalence for physician-diagnosed allergies, eczema, and bronchitis compared to children from Zerbst and about twice the number of respiratory symptoms such as wheeze, shortness of breath, and cough without cold. Sensitization to common aeroallergens according to skin prick tests [odds ratio (OR) = 1.38; 95% confidence interval (CI), 1.02-1.86] and specific IgE levels (OR = 1.75; CI, 1.31-2.33) was more common for children from Hettstedt than children from the nonpolluted county. Bitterfeld children, on the other hand, more often received a diagnosis of asthma and eczema than children residing in Zerbst and also showed slightly increased sensitization rates. In conclusion, industrial pollution related to mining and smelting operations in the county of Hettstedt were associated with a higher lifetime prevalence of respiratory disorders and an increased rate of allergic sensitization in children between the ages of 5 and 14 years. Further studies are needed to determine what role the high dust content of heavy metals plays in Hettstedt.


Correlation of follicular diameter with oocyte recovery and maturity at the time of transvaginal follicular aspiration.
Forty-four consecutive patients undergoing transvaginal follicular aspiration for in vitro fertilization underwent ultrasonic measurement of follicular diameter at the time of oocyte retrieval to determine the correlation of follicular size with recovery rates and oocyte maturity. Based on the results of 412 follicles aspirated, the data were grouped by size (less than or equal to 11, 12-14, 15-17, 18-20, and greater than or equal to 21 mm) and oocyte maturity. Recovery rates were significantly higher in 18- to 20-mm follicles (P less than 0.01) and lower in those less than or equal to 11 mm (P less than 0.001). The probability of retrieving a metaphase I or II oocyte was significantly lower in follicles less than or equal to 11 mm (P less than 0.001), somewhat higher in 12- to 14-mm follicles (P less than 0.01), and equally high among the other groups. There were no differences in the incidence of fractured zonas. We conclude that follicles greater than or equal to 15 mm provide the highest probability of retrieving mature oocytes and the low recovery rates of mature oocytes from follicles less than or equal to 11 mm suggest that, in selected circumstances, the operating surgeon may choose not to aspirate them.


High prevalence of asymptomatic CMV shedding in healthy children attending the minnesota state fair.
Young children in the household are a known risk factor for maternal CMV infection and consequently, congenital infection in infants. However, little is known about viral shedding in pre-school aged children. To estimate the prevalence of CMV DNA shedding and CMV antibodies among healthy children and their mothers. A study of children ages 0 through 5 years was undertaken at the 2019 Minnesota State Fair. Children and their mothers were assessed for CMV shedding by procurement of a saliva swab for CMV PCR testing. An optional finger-stick for capillary blood was used to assess CMV antibodies. A total of 109 children and 85 mothers were enrolled. The prevalence of CMV saliva shedding among children (mean age 3.1 years, SE=0.16) and their mothers was 12/109 (11.0%) and 1/85 (1.2%), respectively. The prevalence of CMV DNA among children peaked at 3 years of age (26%) while the mean viral load was greatest at one year of age (236,693 IU/mL). CMV IgG antibodies among those who agreed to a finger-stick were detected in 16/35 mothers (45.7%) and 0/7 children (0%). Mothers of children aged 5 years or greater had the highest seroprevalence (61.5%). The prevalence of CMV salivary shedding in this unselected sample of young children was approximately 11.0%. The overall maternal seroprevalence in our sample was <50%, suggesting these women are at risk for acquisition of a primary CMV infection in subsequent pregnancies.


5-hydroxytryptamine: its facilitative action on [3H]dopamine release from the retina.
5-Hydroxytryptamine (5-HT) at 5 X 10(-4) M caused a two-fold increase in [3H]dopamine (DA) release from retinal particulate fractions of the carp (Cyprinus carpio). The 5-HT action was dose- and Ca2+-dependent. The three 5-HT agonists examined (5-methoxytryptamine, 5-methoxy-N,N-dimethyltryptamine and tryptamine) were more effective than 5-HT on [3H]DA release. 5,6-Dihydroxytryptamine was the strongest competitor among drugs tested for [3H ]DA uptake, but did not evoke any significant release of [3H]DA. Noradrenaline (or DA) at 5 X 10(-4) M produced a large increase in [3H]DA release from the particulate fractions, but its action was Ca2+-independent. The 5-HT-induced DA release could be seen in the frog retina but not in the rat retina, which does not contain indoleamine-accumulating cells. The results obtained strongly suggest that 5-HT stimulates [3H ]DA release through a receptor mechanism on DAergic terminals and modifies the DA-cell's function in the retina.


Arthroscopic Repair of a High-Grade Partial Articular-Sided Subscapularis Tendon Tear Without Bursal-Sided Tendon Overtension.
The subscapularis tendon is one of the shoulder's primary anterior stabilizers along with capsulolabral tissues to prevent anterior dislocation and attaches to the lesser tuberosity. Subscapularis tendon ruptures can cause anterior shoulder pain and weakness of internal rotation. Patients with partial-thickness tears of subscapularis tendons who do not respond to conservative treatment may be candidates for surgical repair. The transtendon repair of a partial articular-sided subscapularis tendon tear, like the transtendon repair of a PASTA (partial articular supraspinatus tendon avulsion), can result in overtension and bunching of the bursal-sided subscapularis tendon. We propose an all-inside arthroscopic transtendon repair technique of a high-grade partial articular-sided subscapularis tendon tear without bursal-sided tendon overtension or bunching.


An explorative study comparing levels of soluble mediators in control and osteoarthritic synovial fluid.
Soluble mediators in synovial fluid (SF) are acknowledged as key players in the pathophysiology of osteoarthritis (OA). However, a wide-spectrum screening of such mediators in SF is currently lacking. In this study, the levels of 47 mediators in the SF of control donors and osteoarthritic (OA) patients were compared. SF was collected from control donors (n = 16) and end-stage knee OA patients (n = 18) and analysed for 47 cytokines, chemokines and growth factors using several multiplex enzyme-linked immunosorbent assays (ELISAs). A Mann-Whitney U test was used to determine differences between OA and control controls. A principal component analysis (PCA) was performed to cluster the 47 mediators. The majority of the mediators could be detected in both control and OA SF. Interleukin (IL)-6, interferon inducible protein (IP)-10, macrophage derived chemokine (MDC), platelet derived growth factor (PDGF)-AA and regulated on activation normal T cell expressed and secreted (RANTES) levels were found to be higher in OA compared to control SF (P < 0.001). Leptin, IL-13, macrophage inflammatory protein (MIP)-1β, soluble CD40 (sCD40L) levels were higher and eotaxin and granulocyte colony-stimulating factor (G-CSF) levels were lower in OA SF than in control SF, albeit borderline significant (P < 0.05). The PCA enabled identification of six clusters of mediators, which explained 76% of the variance. The current study provides the first extensive profile of cytokines, chemokines and growth factors present in control and OA SF. Increased levels of mediators such as MDC and IL-6 imply involvement of inflammatory processes and might be associated with the influx of inflammatory cells in OA synovial tissue. Moreover, the performed cluster analysis indicated multiple clusters, which could indicate different pathophysiological pathways in the joint.


Does IBD Portend Worse Outcomes in Patients with Rectal Cancer? A Case-Matched Analysis.
Patients with IBD are at increased risk for developing colorectal cancer. However, overall survival and disease-free survival for rectal cancer alone in patients with IBD has not been reported. This study aimed to determine overall survival and disease-free survival for patients with rectal cancer in IBD versus non-IBD cohorts. This is a retrospective cohort study. This study was conducted at an IBD referral center. All consecutive adult patients with IBD diagnosed with rectal cancer and at least 1 year of postsurgery follow-up were included and matched in a 1:2 fashion (age, sex, preoperative stage) with patients with rectal cancer who did not have IBD. Five-year overall survival and disease-free survival, 30-day postoperative complication, readmission, reoperation, and mortality rates were measured. Survival rates were calculated using Kaplan-Meier estimates. The association of risk factors and long-term outcomes was assessed using Cox proportion hazard models. A total of 107 study patients with IBD who had rectal cancer were matched to 215 control patients; preoperative stages were as follows: 31% with stage I, 19% with stage II, 40% with stage III, and 10% with stage IV. Differences were observed (IBD vs non-IBD) in neoadjuvant chemotherapy (33.6% vs 52.6%, p = 0.001) and preoperative radiotherapy (35.5% vs 53.5%, p = 0.003). Postoperative complication rates were similar. On surgical pathology, patients with IBD had more lymphovascular invasion (12.9% vs 5.6%, p = 0.04) and positive circumferential resection margins (5.4% vs 0.9%, p = 0.03). On multivariable analysis, the diagnosis of IBD did not significantly impact long-term mortality (HR, 0.91; 95% CI, 0.53-1.57; p = 0.73) or disease-free survival (HR, 1.36; 95% CI, 0.84-2.21; p = 0.22). This study was limited by its retrospective design and the use of single-center data. Patients have rectal cancer with IBD and without IBD have similar long-term and disease-free survival, despite lower rates of neoadjuvant treatment and higher margin positivity in patients with IBD. See Video Abstract at http://links.lww.com/DCR/B271. ¿LA ENFERMEDAD INFLAMATORIA INTESTINAL ACARREA PEORES RESULTADOS EN PACIENTES CON CÁNCER RECTAL? UN ANÁLISIS DE CASOS-COINCIDENTES: Los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de desarrollar cáncer colorrectal. Sin embargo, no se ha informado la supervivencia general y la supervivencia libre de enfermedad para el cáncer rectal solo en pacientes con EII.Determinar la supervivencia general y la supervivencia libre de enfermedad para pacientes con cáncer rectal en cohortes con EII versus sin EII.Estudio de cohorte retrospectivo.Centro de referencia para enfermedad inflamatoria intestinal.todos los pacientes adultos con EII diagnosticados con cáncer rectal, consecutives, y al menos un año de seguimiento postoperatorio se incluyeron y se emparejaron de manera 1: 2 (edad, sexo, etapa preoperatoria) con pacientes con cáncer rectal sin EII.Se midieron la supervivencia general a cinco años y la supervivencia libre de enfermedad, complicaciones postoperatorias a los 30 días, reingreso, reoperación y tasas de mortalidad.Las tasas de supervivencia se calcularon utilizando estimaciones de Kaplan-Meier. La asociación de factores de riesgo y resultados a largo plazo se evaluó mediante modelos de riesgo de proporción de Cox.Un total de 107 pacientes con EII y cáncer rectal se compararon con 215 pacientes de control; las etapas preoperatorias fueron las siguientes: 31% de Etapa I, 19% de Etapa II, 40% de Etapa III y 10% de Etapa IV. Se observaron diferencias (EII versus no EII) en quimioterapia neoadyuvante (33.6% frente a 52.6%, p = 0.001) y radioterapia preoperatoria (35.5% frente a 53.5%, p = 0.003). Las tasas de complicaciones postoperatorias fueron similares. En la patología quirúrgica, los pacientes con EII tuvieron más invasión linfovascular (12.9% frente a 5.6%, p = 0.04) y márgenes de resección circunferencial positivos (5.4% frente a 0.9%, p = 0.03). En el análisis multivariable, el diagnóstico de EII no tuvo un impacto significativo en la mortalidad a largo plazo (HR 0.91; IC del 95%: 0.53-1.57, p = 0.73) o la supervivencia libre de enfermedad (HR 1.36; IC del 95%: 0.84-2.21, p = 0.22)Diseño retrospectivo, centro único de datos.Los pacientes con EII y sin EII con cáncer rectal tienen una supervivencia similar a largo plazo y libre de enfermedad, a pesar de las tasas más bajas de tratamiento sneoadyuvante y un mayor margen positivo en pacientes con EII. Consulte Video Resumen en http://links.lww.com/DCR/B271.


Expression of Fos immunoreactivity in rat brain during dehydration: effect of duration and timing of water deprivation.
Water deprivation induces expression of the immediate early gene c-fos in specific brain regions, most likely as a result of the activation of cells that are responsive to changes in osmolality and/or blood volume. We hypothesized that the magnitude of c-fos expression would be a function of both the duration of water deprivation and the time of day at which the deprivation started. This study was designed to examine the pattern of Fos-like immunoreactivity (FLI) following water deprivation in rats under normal light/dark conditions (nLD) and reverse light/dark conditions (rLD). Rats were deprived of water but not food either for 0, 5, 16, 24 or 48 h. As expected, hematocrit ratio (HCT), osmolality (OSM), plasma renin activity (PRA) and weight loss increased as a function of duration of water deprivation. In non-deprived rats (0 h), very little FLI was observed in most brain regions. The number of cells showing FLI increased with duration of water deprivation in the supraoptic nucleus (SON), paraventricular nucleus (PVN), organum vasculosum laminae terminalis (OVLT), median preoptic nucleus (MnPO) and subfornical organ (SFO) in both nLD and rLD conditions. However, the pattern of FLI differed between nLD and rLD conditions. Compared to corresponding nLD groups after 5 or 24-h water deprivation, rLD groups had significantly more FLI in SON and PVN, and higher PRA and HCT. Also, weight loss and FLI in the MnPO were greater after 5 h, and FLI in the SFO was greater after 24 h under rLD compared to nLD conditions. Our findings indicate that the magnitude of c-fos expression, and change in weight and plasma parameters were a function of both the duration of water deprivation and the time of day at which the deprivation started. This may result from ingestion of food early in the deprivation periods during the rLD tests, thus producing greater change in osmolality and blood volume.


A genome-wide functional assay of signal transduction in living mammalian cells.
We describe a genome-wide functional assay for rapid isolation of cell clones and genetic elements responsive to specific stimuli. A promoterless beta-lactamase reporter gene was transfected into a human T-cell line to generate a living library of reporter-tagged clones. When loaded with a cell-permeable fluorogenic substrate, the cell library simultaneously reports the expression of a large number of endogenous genes. Flow cytometry was used to recover individual clones whose reporter-tagged genes were either induced or repressed following T-cell activation. Responsive clones were expanded and analyzed pharmacologically to identify patterns of regulation associated with specific genes. Although demonstrated using T cells, the genomic assay could be applied to map downstream transcriptional consequences for any propagating cell line in response to any stimulus of interest.


Stress-induced glucocorticoid receptor activation determines functional recovery following ischemic stroke.
A major consequence of stroke is permanent motor disturbance, such as postural imbalance and loss of skilled movement. The degree of neuronal and functional loss and subsequent recovery after stroke is influenced by hypothalamic-pituitary-adrenal axis activation and the response to glucocorticoid hormones. This study investigated if recovery after stroke is related to glucocorticoid receptor (GR) activation in a rat model of stroke. Adult male rats were pre-trained and tested in a skilled reaching task and received a focal ischemic motor cortex lesion. One group of animals received daily restraint stress starting one week pre-lesion up to three weeks post-lesion. Immuno-histochemical analysis of GR expression was performed to determine receptor activation. Stress reduced reaching success in naïve animals and diminished recovery of limb use. Exaggerated functional loss in stressed rats was related to increased GR activation in the lesion hemisphere as indicated by nuclear GR location. These findings provide a mechanistic link between stress-induced motor disability and GR activation in a rat model of stroke. The elevated receptor activation proposes synergistic effects of stress and stroke to modulate the impact of glucocorticoids on motor system function at the genomic level. The modulation of GR biosynthesis may alter responsiveness to stroke treatment and compromise recovery.


Reasons for the adoption of celibacy among older men and women living with HIV/AIDS.
The reasons for becoming celibate following diagnosis with HIV/AIDS were examined using focused interviews with 63 infected older adults (ages 50-68). Forty-eight percent reported they were currently celibate or had been celibate following diagnosis with HIV/AIDS. Women reported celibacy (78%) more than men (36%). Although men and women reported some similar reasons for celibacy, most notably fear of infecting others and fear of reinfection, we also found gender differences in the reasons for celibacy. Additional reasons offered by women included loss of interest in sex, anger and distrust of men, and desire to focus on themselves rather than men. Other reasons offered by men included fear of rejection or stigmatization, difficulty with sexual performance, and negative body image. The prevalence of celibacy and the finding that many reasons for celibacy are related to fear, anger, and distrust suggests that older adults may have difficulty resuming healthy sexual relationships following diagnosis with HIV/AIDS.


Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations.
The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5'-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development.


Computer-aided socket design for trans-femoral amputees.
Computer-aided socket design (CASD) is a technique for the design of prosthetic sockets using the advantageous features of computer graphics and calculation. This paper describes a computer-aided technique used to design sockets for patients with trans-tibial lower limb amputations.


Establishing a definitive airway in the trauma patient by novice intubators: A randomised crossover simulation study.
Establishing a definitive airway, defined as a tube placed in the trachea with cuff inflated below the vocal cords, is standard of care in pre-hospital airway management of the trauma patient. However, in this setting, and using manual in-line stabilisation of the neck, success rate of intubation by inexperience providers is suboptimal. The use of supraglottic airway devices that allow blind tracheal intubation has been suggested as an alternative method by the Advanced Trauma Life Support (ATLS) programme of the American College of Surgeons. We aimed to compare intubation with the standard intubation technique (direct laryngoscopy [DL]) with blind intubation through an intubating-laryngeal mask airway (I-LMA) during manual in-line stabilisation of the neck. A randomised, crossover manikin study was performed with 29 emergency medical technicians undergoing training for paramedic status. Outcome measures were success rate in one intubation attempt, duration of intubation, and assessment of ease-of-use. Study subjects had a higher success rate of tracheal intubation with I-LMA than with DL (27/29 vs. 18/29, p<0.025), and I-LMA was assessed as easier to use (4 vs. 3, p<0.0001). Longer duration of intubation was found with I-LMA compared to DL (54.2 vs. 42.8s, p<0.002). Success rate of correct placement of I-LMA within the airway was 28/29 (96.5%). Time to achieve correct placement of I-LMA within the airway was shorter than duration of tracheal intubation with DL (26.9 vs. 42.8s, p<0.0001). Novice intubators had a higher success rate of intubation with I-LMA than with DL, but duration of intubation was longer with I-LMA. Time to achieve correct placement of I-LMA within the airway was shorter than duration of tracheal intubation with DL. Findings of this simulation study suggest that in the presence of manual in-line stabilisation of the neck, I-LMA-guided intubation is the preferred technique for novice intubators.


Multi-omic, Single-Cell, and Biochemical Profiles of Astronauts Guide Pharmacological Strategies for Returning to Gravity.
The National Aeronautics and Space Administration (NASA) Twins Study created an integrative molecular profile of an astronaut during NASA's first 1-year mission on the International Space Station (ISS) and included comparisons to an identical Earth-bound twin. The unique biochemical profiles observed when landing on Earth after such a long mission (e.g., spikes in interleukin-1 [IL-1]/6/10, c-reactive protein [CRP], C-C motif chemokine ligand 2 [CCL2], IL-1 receptor antagonist [IL-1ra], and tumor necrosis factor alpha [TNF-α]) opened new questions about the human body's response to gravity and how to plan for future astronauts, particularly around initiation or resolution of inflammation. Here, single-cell, multi-omic (100-plex epitope profile and gene expression) profiling of peripheral blood mononuclear cells (PBMCs) showed changes to blood cell composition and gene expression post-flight, specifically for monocytes and dendritic cell precursors. These were consistent with flight-induced cytokine and immune system stress, followed by skeletal muscle regeneration in response to gravity. Finally, we examined these profiles relative to 6-month missions in 28 other astronauts and detail potential pharmacological interventions for returning to gravity in future missions.


Galantamine-induced improvements in cognitive function are not related to alterations in alpha(4)beta (2) nicotinic receptors in early Alzheimer's disease as measured in vivo by 2-[18F]fluoro-A-85380 PET.
The nicotinic acetylcholine receptor (nAChR) system plays a regulatory role in a number of cognitive processes. Cholinesterase inhibitors (i.e., galantamine) that potentiate cholinergic neurotransmission improve cognitive function in Alzheimer's disease (AD); however, the relationship between these effects and associated changes in nAChRs are yet to be established in vivo. 2-[18F]Fluoro-A-85380 (2-FA) binds to nAChRs and with positron emission tomography (PET) imaging provides a composite measure of receptor density and ligand affinity. This study aimed to: (1) quantify nAChRs in vivo in 15 drug-naïve patients with mild AD before and after chronic treatment with galantamine, using 2-FA and PET, and (2) examine the relationship between treatment-induced changes in nAChRs and improvements in cognitive function. Participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of approximately 200 MBq of 2-FA on two occasions (before and after 12 weeks, galantamine treatment). A 3-day washout period preceded the second scan. Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). Performance on global measures of cognition significantly improved following galantamine treatment (p < 0.05). This improvement extended to specific cognitive measures of language and verbal learning. No significant differences in nAChR DV(S) before and after galantamine treatment were found. The treatment-induced improvement in cognition was not correlated with regional or global nAChR DV(S), suggesting that changes in nAChRs may not be responsible for the improvements in cognition following galantamine in patients with mild AD.


A scientometric study of publications on delirium from 2001 to 2020.
This study aims to evaluate the publications on delirium by using bibliometric analysis. The Scopus database was evaluated for publications on delirium, during the period of 2001-20. The search results were analyzed for the origin of country, origin of institution, authorship, collaborations, type of article, source of funding, and number of citations. The searches of Scopus database yielded 22,941 publications, originating from 139 countries. Compared to the decade of 2001-2010, the number of publications on delirium doubled in the decade of 2011-2020. The majority of the papers were research articles (58.26%), and the papers were cited for mean number of 20.53 times. Only a small proportion of the papers were based on funding (13.14%). Maximum number of papers emerged from United States of America. In terms of institutional affiliations, among the authors from top 20 institutes, 15 were from United States, 2 from Netherlands and 1 each from Canada, Germany and United Kingdom. In terms of authors, the research productivity of the top 20 most productive authors varied from 172 to 612 publications with 12 authors belonging to United States, 2 from Italy and 1 each from Canada, Greece, India, Ireland, Netherland and the United Kingdom. The maximum number of papers were published in Journal of the American Geriatric Society and based on the number of citations the New England Journal of Medicine was the most impactful journal. Over the years number of publications on delirium have increased, majority of the publications have emerged from United States.


Examining the Role of Complement in Predicting, Preventing, and Treating Hemolytic Transfusion Reactions.
Red blood cell (RBC) transfusion is a critical component of optimal management for a broad range of conditions. Regardless of the indication, pretransfusion testing is required to appropriately match RBC donors and recipients to provide immunologically compatible blood. Although this approach is effective in the vast majority of situations, occasionally, patients will inadvertently receive an incompatible RBC transfusion, which can result in a hemolytic transfusion reaction (HTR). In addition, patients with life-threatening anemia and a complex alloantibody profile, which precludes rapid procurement of compatible RBCs, may also receive incompatible RBCs, placing them at risk for an HTR. Despite the rarity of these clinical situations, when incompatible blood transfusion results in an HTR, the consequences can be devastating. In this review, we will explore the challenges associated with actively preventing and treating acute HTRs following incompatible RBC transfusion. In doing so, we will focus primarily on the role of complement, not only as a key player in HTRs, but also as a potential target for the prevention and treatment of HTRs.


Correction and removal of expression of concern: Natural steroid-based cationic copolymers cholesterol/diosgenin-r-PDMAEMAs and their pDNA nanoplexes: impact of steroid structures and hydrophobic/hydrophilic ratios on pDNA delivery.
[This corrects the article DOI: 10.1039/D1RA00223F.].


Correlation and significance of COX-2, Ki67, VEGF and other immune indexes with the growth of malignant pulmonary nodules.
This study intends to explore the factors affecting the growth of pulmonary nodules in the natural process by immunohistochemical method. 40 cases of pulmonary nodules followed up for more than 3 years were divided into growth group (n = 20) and stable group (n = 20). The expressions of cyclooxygenase-2 (COX-2), Ki67, vascular endothelial growth factor (VEGF), CD44V6, epidermal growth factor receptor (EGFR), double microsome 2 (MDM2) and transforming growth factor (TGF)-β1 in pulmonary nodules were detected by immunohistochemical method so as to explore the relationship between it and the growth of pulmonary nodules. Compared with stable pulmonary nodules, the positive rates of COX-2, Ki67 and VEGF in the growth group were 85%, 80% and 55%, respectively. There was significant difference between the stable group and the growth group (P < 0.05). The correlation between other indexes and the growth of pulmonary nodules was not statistically significant (Pcd44v6 = 0.104;PEGFR = 0.337; PMDM2 = 0.49; PTGF-β1 = 0.141). In the subgroup of patients with non-invasive lung cancer, there was a correlation between VEGF and the growth of pulmonary nodules (P < 0.05). The high expression of COX-2, Ki67 and VEGF proteins may be significantly related to the growth of pulmonary nodules, and VEGF may be an important factor affecting the growth of malignant pulmonary nodules. This study intends to provide a research direction for further searching for the essential causes of the growth of pulmonary nodules.


Characterization of Cellular Viability Using Label-Free Brightfield Live-Cell Imaging.
In recent years, the assembly and annotation of chemogenomic libraries have gained interest by the phenotypic screening community. Apart from basic annotations of the compound potency and selectivity, these compound libraries benefit in particular from annotation regarding the effect of the inhibitors on cellular viability to distinguish between on-target effects of a compound and unspecific cytotoxicity. Here, we provide a protocol to determine viability as a first determinant in compound quality control, using the Incucyte live-cell imaging system. The compounds are classified according to their calculated growth rate to determine a cytotoxic, cytostatic, or healthy outcome. All compounds affecting the growth rate can be further evaluated regarding their specific effects on cell health in a high-content live-cell multiplex assay, described in Chapter 5 .


Studies on the central pressor activity of dibutyryl cyclic AMP.
The effects of the central administration (i.c.v.) of dibutyryl cyclic AMP (DBcAMP) on arterial blood pressure and heart rate were studied in the rat. The cyclic nucleotide produced a dose-dependent rise in blood pressure and an accompanying tachycardia. Maximal pressor effect of a single dose of DBcAMP (350 micrograms) was observed 25 min post injection and the duration of the response was 60 min. Chemical degeneration of central catecholaminergic neurons with 6-hydroxydopamine treatment abolished the pressor response to DBcAMP. Partial chemical degeneration of central serotonin pathways with 5,6-dihydroxytryptamine did not significantly alter the effect. The pressor activity of the cyclic nucleotide was attenuated by central administration of phentolamine. Spinal cord section at the C6-C7 level or peripheral chemical degeneration of catecholaminergic neurons combined with bilateral adrenalectomy abolished the pressor response to DBcAMP. It was concluded that the pressor response to i.c.v. administration of DBcAMP is mediated by central catecholaminergic pathways and is the result of an increase in efferent sympathetic outflow and release of catecholamines from the adrenal medulla.


A Bayesian machine learning approach for drug target identification using diverse data types.
Drug target identification is a crucial step in development, yet is also among the most complex. To address this, we develop BANDIT, a Bayesian machine-learning approach that integrates multiple data types to predict drug binding targets. Integrating public data, BANDIT benchmarked a ~90% accuracy on 2000+ small molecules. Applied to 14,000+ compounds without known targets, BANDIT generated ~4,000 previously unknown molecule-target predictions. From this set we validate 14 novel microtubule inhibitors, including 3 with activity on resistant cancer cells. We applied BANDIT to ONC201-an anti-cancer compound in clinical development whose target had remained elusive. We identified and validated DRD2 as ONC201's target, and this information is now being used for precise clinical trial design. Finally, BANDIT identifies connections between different drug classes, elucidating previously unexplained clinical observations and suggesting new drug repositioning opportunities. Overall, BANDIT represents an efficient and accurate platform to accelerate drug discovery and direct clinical application.


Functionalization of biodegradable magnesium alloy implants with alkylphosphonate self-assembled films.
Mg and Mg-alloys are promising materials for biodegradable implants. In order to slowdown the Mg-alloy (AZ91D) degradation and enhance its biocompatibility, the alloy surface was modified with alkylphosphonate self-assembling films. The binding configuration and the structural organization of alkylphosphonate monolayers on the Mg-alloy surface were investigated using contact angle measurements, FTIR, and XPS. Combination of FTIR and XPS data indicated the presence of several different bonding modes (mono-, di-, and tri dentate) of phosphonate head groups with the alloy surface. The existence of well organized and ordered self-assembled alkylphosphonate monolayers with good barrier protecting properties in a physiological solution is a key step in the development of biocompatible Mg-alloy implants.


A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients.
We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day -6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p = 0.001) whilst citrulline was lower (p = 0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32+/-4 versus 37+/-3, p = 0.001) whilst CRP was higher (74+/-48 versus 34+/-38, p = 0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications.


A systematic review of cost-effective treatment of postoperative rotator cuff repairs.
The Bundled Payments for Care Improvement initiative combines payment of multiple services for episodes of care into 1 bundle. Rotator cuff repair is a likely candidate for future inclusion. The objective of this study was to determine cost-effective, high-quality postoperative rehabilitation dosing and cryotherapy for patients undergoing rotator cuff repair based on systematic review of the literature. Systematic review of level I and level II articles was performed in PubMed, Cochrane Databases, and PEDro. Conference references and bibliographies were also reviewed. For postoperative therapy, keywords included rotator cuff, rotator cuff repair, exercise therapy, exercise, unsupervised, self-care, postoperative period, physical therapy, and physiotherapy; for cryotherapy, keywords included rotator cuff repair, shoulder, cryotherapy, and ice. Five studies compared postoperative outcomes in participants assigned to supervised therapy vs. unsupervised therapy. Three found no difference between groups. One found improved outcomes in supervised therapy. Limitations included that therapies were not consistently defined and significant methodologic issues were present, decreasing the applicability and validity of the results. Five articles examined cryotherapy outcomes in the postoperative shoulder. Two studies showed improved patient outcomes with cryotherapy vs. no cryotherapy; 2 studies showed no decrease in joint space temperatures at 90 minutes but decrease in temperature at 4 to 23 hours postoperatively. One study indicated that an ice bag and Ace bandage might be as effective as continuous, compressive cryotherapy units using patient-reported outcomes. Further studies are needed to determine effective dosing of physical therapy after rotator cuff repair. Cryotherapy is favorable and cost-effective using simple methods for delivery.


Effects of multiple exemplar training on the emergence of derived relations in preschool children learning a second language.
We evaluated the facilitative effects of multiple exemplar training (MET) on the establishment of derived tact relations in typically developing children. A multiple-probe design across stimulus sets was implemented to introduce MET. Participants were first taught to conditionally relate dictated names in English to their corresponding objects (listener behavior; A-B relations), followed by tests for derived tacts (B-A relations). If participants failed these tests, MET was implemented whereby tact relations were explicitly taught with novel stimulus sets, followed by test probes with the original training set. MET continued with novel stimuli until participants met criterion for the emergence of derived tact relations or after exposure to three MET sets. Results indicated failed tests for tact relations following direct training in listener relations, and marked improvements in derived tact relations following MET across all participants.


Sex differences in mental health among older adults: investigating time trends and possible risk groups with regard to age, educational level and ethnicity.
Older women report lower mental health compared to men, yet little is known about the nature of this sex difference. Therefore, this study investigates time trends and possible risk groups. Data from the Doetinchem Cohort Study (DCS) and the Longitudinal Aging Study Amsterdam (LASA) were used. General mental health was assessed every 5 years, from 1995 to 1998 onwards (DCS, n = 1412, 20-year follow-up, baseline age 55-64 years). Depressive and anxiety symptoms were assessed for two birth cohorts, from 1992/1993 onwards (LASA cohort 1, n = 967, 24-year follow-up, age 55-65 years,) and 2002/2003 onwards (LASA cohort 2, n = 1002, 12-year follow-up, age 55-65 years) with follow-up measurements every 3-4 years. Mixed model analyses showed that older women had a worse general mental health (-6.95; -8.36 to 5.53; range 0-100, ∼10% lower), more depressive symptoms (2.09; 1.53-2.63; range 0-60, ∼30% more) and more anxiety symptoms (0.86; 0.54-1.18; range 0-11, ∼30% more) compared to men. These sex differences remained stable until the age of 75 years, where after they decreased due to an accelerated decline in mental health for men compared to women. Sex differences and their course by age were consistent over successive birth cohorts, educational levels and ethnic groups (Caucasian vs. Turkish/Moroccan). There is a consistent female disadvantage in mental health across different sociodemographic groups and over decennia (1992 vs. 2002) with no specific risk groups.


A novel digestion method based on a choline chloride-oxalic acid deep eutectic solvent for determining Cu, Fe, and Zn in fish samples.
A novel and efficient digestion method based on choline chloride-oxalic acid (ChCl-Ox) deep eutectic solvent (DES) was developed for flame atomic absorption spectrometry (FAAS) determination of Cu, Zn, and Fe in biological fish samples. Key parameters that influence analyte recovery were investigated and optimized, using the fish protein certified reference material (CRM, DORM-3) throughout the procedure. In this method, 100 mg of the sample was dissolved in ChCl-Ox (1:2, molar ratio) at 100°C for 45 min. Then, 5.0 mL HNO(3) (1.0 M) was added. After centrifugation, the supernatant solution was filtered, diluted to a known volume, and analyzed by FAAS. Under optimized conditions, an excellent agreement between the obtained results and the certified values was observed, using Student's t-test (P=0.05); the extraction recovery of the all elements was greater than 95.3%. The proposed method was successfully applied to the determination of analytes in different tissues (muscle, liver, and gills) having a broad concentration range in a marine fish sample. The reproducibility of the method was validated by analyzing all samples by our method in a different laboratory, using inductively coupled plasma optical emission spectrometry (ICP-OES). For comparison, a conventional acid digestion (CAD) method was also used for the determination of analytes in all studied samples. The simplicity of the proposed experimental procedure, high extraction efficiency, short analysis time, lack of concentrated acids and oxidizing agents, and the use of safe and inexpensive components demonstrate the high potential of ChCl-Ox (1:2) for routine trace metal analysis in biological samples.


Evaluating the environmental and economic impact of mining for post-mined land restoration and land-use: A review.
Mining has been a long-standing key player in economic development, employment, infrastructure, and supply of essential raw materials for society. It has served as a viable route to economic transformation in resource-rich countries like Australia, Canada, the United States, and parts of Africa. In this review, the impact of mining has been conceptualized into economic, environmental, and social impacts. While it is clear that mining has transformed many economies, it has also impacted negatively on the environment and, to some extent, society. Some of the negative impacts of mining are loss of vegetation cover, mass destruction of water bodies, loss of biodiversity, land-use changes and food insecurity, increased social vices and conflicts, high cost of living, and air pollution. However, reclamation has been a viable way of reducing the negative impacts of abandoned mine lands and ensure productive and efficient utilization of mine wastelands. Compaction, low or high pH, low water holding capacity, gullies, bulk density, deficiency of micro, and macronutrients are the major factors limiting the productivity of mine wastelands. A combination of physical, chemical, and biological restoration practices is ideal for restoring the mine soil productivity. While the physical method deals with earth-battering, thus putting the land back to shape, the chemical and biological methods include various amendments such as biochar, compost, synthetic fertilizers, synthetic chelates, shrubs, and grasses, and nanoparticles. A combination of these three restoration methods restores soil fertility, stimulates microbial growth, and facilitates early ecological succession. However, before embarking on reclamation, the particular post-mined land use should be clearly stated, such as conservations, forestry, agriculture, construction, intensive recreation, non-intensive recreation, and lake or pool through land suitability and selection analyses. This review has guiding significance and recommendations for mining and post-mined rehabilitation.


Bimetallic co-doping engineering over nickel-based oxy-hydroxide enables high-performance electrocatalytic oxygen evolution.
Enhancing the electrocatalytic oxygen evolution reaction (OER) performance is essential to realize practical energy-saving water electrolysis and CO2 electroreduction. Herein, we report a bimetallic co-doping engineering to design and fabricate nickel-cobalt-iron collaborative oxy-hydroxide on nickel foam that labeled as NiCoFeOxHy-NF. As expected, NiCoFeOxHy-NF exhibits an outstanding OER activity with current density of 10 mA cm-2 at 194 mV, Tafel slope of 53 mV dec-1, along with the robust long-term stability, which is significantly better than bimetallic NiCo and NiFe combinations. Comprehensive computational simulations and characterizations jointly unveil that the twisted ligand environment induced by heteroatoms ensures the balance strength between the metal-oxygen hybrid orbital states and the oxidized intermediates adsorption, thus lowering the oxygen cycling energy barriers for overcoming the sluggish OER kinetics. Moreover, a novel phase transition behavior is monitored by in-situ Raman spectra under OER operating conditions, which facilitates electron-mass transfer as well as boosts the exposure of activity sites. For practical applications, Ni2P-NF || NiCoFeOxHy-NF and Cu || NiCoFeOxHy-NF couples were constructed to realize high-efficiency water electrolysis and CO2 electrochemical reduction for the production of valuable H2 and C2H4, respectively. This work elucidates a novel mechanism by which bimetallic co-doping improves the electrocatalytic OER activity of nickel-based hydroxides.


The control of jaw-opener motoneurons during active sleep.
Brainstem and spinal cord motoneurons that innervate somatic musculature serving antigravity functions are postsynaptically inhibited during active sleep. However, it has been reported that hypoglossal motoneurons (which do not innervate antigravity muscles) are not postsynaptically inhibited during active sleep, but are disfacilitated. In the present report we describe changes, during active sleep, in the excitability and membrane potential of digastric and synergistic motoneurons of the trigeminal motor pool; these neurons do not perform antigravity functions. The experiments described in the present report were performed in chronic cats that were prepared for intracellular recording. The motoneurons hyperpolarized an average of 11 mV (S.D. +/- 1.29, n = 8, P < 0.005) during active sleep compared to quiet sleep. Hyperpolarization was accompanied by a reduction in the excitability of the somadendritic regions of the neurons, as indicated by an increase in the delay of propagation of antidromic spikes from the initial segment to the somadendritic portion of the cell. High gain membrane potential recordings from these motoneurons revealed the occurrence of a remarkably large number of hyperpolarizing potentials during active sleep. When K-chloride-filled microelectrodes were utilized and chloride ions were injected intracellularly, the polarity of these potentials was reversed. During phasic episodes of active sleep, there was a clear increase in hyperpolarizing potential activity, a blockade of somadendritic spikes and phasic reductions in the amplitude of the initial segment spikes. Hyperpolarizing potentials occurred in conjunction with ponto-geniculo-occipital waves.(ABSTRACT TRUNCATED AT 250 WORDS)


The impact of therapeutic doses of paracetamol on serum total antioxidant capacity.
A link between regular paracetamol intake and asthma in adults has recently been postulated. Detoxification of paracetamol may deplete stores of glutathione, which is one of the major antioxidants present in the lung. A reduced source of glutathione in the lung may lead to increased oxidative damage to the epithelium and hence increased frequency and severity of asthma attacks in susceptible individuals. This study aimed to determine whether regular intake of maximum therapeutic doses of paracetamol reduced serum antioxidant capacity in healthy volunteers. Fifteen young healthy volunteers (nine men, six women, mean age 21.3 years, range 19-32) took maximum therapeutic doses of paracetamol (1 g four times a day) for 14 days. On days 0 and 14 blood samples were taken at baseline and hourly for a period of 4 h following ingestion of 1 g paracetamol. Single venous blood samples were collected 1 h after ingestion of 1 g paracetamol on days 4, 7 and 10. Blood samples were analysed for serum paracetamol concentration and total antioxidant capacity. Mean total antioxidant capacity was significantly reduced over the 3-h post-dosing on both days 0 and 14 (P < 0.01). The results from days 4, 7 and 10 showed a trend towards reduced antioxidant activity over time. On day 14 values were consistently lower compared with the corresponding times on day 0 (P < 0.01 at 0, 1, 3 and 4 h, P < 0.05 at 2 h). Chronic ingestion of maximum therapeutic doses of paracetamol depletes serum antioxidant capacity in healthy volunteers in as few as 14 days, possibly by a reduction in glutathione. This may have implications for analgesic use in asthmatic individuals. Further studies are now required to assess the impact of paracetamol on antioxidant defences in the lung.


Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: survival outcomes and patient selection.
Chemotherapy hyperthermic intraperitoneal chemotherapy (HIPEC) is playing an ever increasing role in the management of colorectal cancer (CRC) with peritoneal metastases (PM) as results approach those of surgical resection of liver metastases. Selection criteria for treatment type, sequence and timing of currently available therapies remain ill-defined. We review the current published literature analyzing outcomes by treatments with surgery, systemic chemotherapy, cytoreductive surgery (CRS) and HIPEC, and ongoing clinical trials. A clinical pathway that incorporates all currently available therapies, determining the timing and sequence of such therapies was constructed. Most of the literature on outcome data comes from studies reporting the results of CRS and HIPEC with large series showing a median survival of 32-47 months. Meanwhile, the vast majority of patients, over 90% in the United States, are being treated with palliative systemic therapies following the NCCN guidelines. Cooperation between medical and surgical oncologists represents an unmet need in oncology when it comes to patients with CRC with PM. The presented clinical pathway constitutes a feasible and much needed first step to start this cooperation.


Masseter spasm after succinylcholine administration.
We report the case of a 20-year-old woman who developed masseter spasm after receiving succinylcholine for rapid sequence intubation. Sometimes referred to as "jaws of steel," masseter spasm secondary to anesthetic administration may progress to malignant hyperthermia. Although succinylcholine-induced masseter spasm is uncommon, it is important to be prepared to deal with this entity when administering succinylcholine.


Ex vivo-In vivo correlation of retinol stratum corneum penetration studies by confocal Raman microspectroscopy and tape stripping.
Skin penetration studies of topically applied drugs are a challenging topic in the development of semisolid formulations. The most commonly used methods can be differentiated by their character into ex vivo/in vivo, invasive/non-invasive and offline/in-line measurements. In this study, we compare ex vivo tape stripping, an invasive technique, which is often used, to confocal Raman microspectroscopy (CRM), ex and in vivo, to establish a correlation between those methods. Retinol was used as a model drug, applied in an oil-in-water emulsion, to compare the skin penetration profiles obtained by the different methods.


Comparison of label-free and label-based strategies for proteome analysis of hepatoma cell lines.
Within the past decade numerous methods for quantitative proteome analysis have been developed of which all exhibit particular advantages and disadvantages. Here, we present the results of a study aiming for a comprehensive comparison of ion-intensity based label-free proteomics and two label-based approaches using isobaric tags incorporated at the peptide and protein levels, respectively. As model system for our quantitative analysis we used the three hepatoma cell lines HepG2, Hep3B and SK-Hep-1. Four biological replicates of each cell line were quantitatively analyzed using an RPLC-MS/MS setup. Each quantification experiment was performed twice to determine technical variances of the different quantification techniques. We were able to show that the label-free approach by far outperforms both TMT methods regarding proteome coverage, as up to threefold more proteins were reproducibly identified in replicate measurements. Furthermore, we could demonstrate that all three methods show comparable reproducibility concerning protein quantification, but slightly differ in terms of accuracy. Here, label-free was found to be less accurate than both TMT approaches. It was also observed that the introduction of TMT labels at the protein level reduces the effect of underestimation of protein ratios, which is commonly monitored in case of TMT peptide labeling. Previously reported differences in protein expression between the particular cell lines were furthermore reproduced, which confirms the applicability of each investigated quantification method to study proteomic differences in such biological systems. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.


Microbial oxidation of dispersed graphite by nitrifying bacteria 2011.2.
A facile and green microbial method to produce graphite oxide nanosheets and nanoparticles is described. The obtained graphite oxide nanosheets have few layers with 0.7-1.5 nm height and 50-300 nm size. The carbon nanoparticles possess the size of 20-60 nm and the height of 2-4 nm.


The Burden of Gastroesophageal Reflux Disease on Patients' Daily Lives: A Cross-Sectional Study Conducted in a Primary Care Setting in Serbia.
Recent data from the studies conducted in the Western countries have proved that patients with gastroesophageal reflux disease have significantly impaired health-related quality of life compared to general population. The study is aimed at evaluating the burden of reflux symptoms on patients'health-related quality of life. The study involved 1,593 patients with diagnosed gastroesophageal reflux disease.The Serbian version of a generic self-administered Centers for Disease Control and Prevention questionnaire was used. Statistical analyses included descriptive statistics, Pearson chi-square test and a multiple regression model. Among all participants, 43.9% reported fair or poor health. Mean value of unhealthy days during the past 30 days was 10.4 days, physically unhealthy days 6.4 days, mentally unhealthy days 5.3 days and activity limitation days 4.3 days. Furthermore, 24.8% participants reported having ≥ 14 unhealthy days, 14.9% had 14 physically unhealthy days, 11.8% reported 14 mentally unhealthy days, and 9.4% had ≥ 14 activity limitation days. This study addressed complex relationships between reflux symptoms and patients'impaired everyday lives.


A group I intron riboswitch.
Riboswitches are mRNA-based elements that regulate gene expression via binding of a specific ligand. Breaker and coworkers have now discovered a novel type of regulatory RNA motif that acts by c-di-GMP-dependent control of a self-splicing group I intron ribozyme (Lee et al., 2010).


Nocturnal hypoxemia and long-term oxygen therapy in COPD patients with daytime PaO2 60-70 mmHg.
Six European treatment centers contributed to a controlled trial to study nocturnal hypoxemia in COPD patients having daytime PaO2 of 60-70 mmHg. The trial is composed of two parts: first, patients inclusion, taking men aged under 70 years, excluding sleep apnea syndrome and all other concomitant pathologies leading to nocturnal desaturation. We described this population and determined the frequency and degree of nocturnal desaturation. Correlations between different daytime and sleep parameters have also been established. The second part concerns the study of the two sub-populations of nocturnal desaturators and nondesaturators. This is followed by random allocation of the desaturators to oxygen or no oxygen treatment. We defined significant nocturnal desaturation as cumulated unsaturation period, exceeding 30% of total time, in bed spent under SaO2 lower than 90%. Twenty out of 46 patients were desaturators (43%). Only the first part is dealt with in this article.


N16 suppresses RANKL-mediated osteoclatogenesis by down-regulating RANK expression.
N16 is an active protein existing in Pinctada martensi. Our previous studies have demonstrated that N16 inhibited osteoclast differentiation in vitro. To better understand how N16 regulates osteoclast differentiation, RAW264.7 cells, a murine monocytic cell line and murine bone marrow-derived macrophages (BMMs) were adopted. Treatment of RAW264.7 cells with RANKL activated osteoclastogenesis and N16 inhibited the formation of multinucleated osteoclasts and TRAP activity. The suppression occurred at the early stage of osteoclastogenesis. Moreover, we found that N16 inhibited PU.1 and MITF expressions, mirroring the inhibition of RANK expressions, indicating that N16 inhibited RANK expression by down-regulating the expressions of MITF and PU.1, thus preventing osteoclastogenesis.


The people behind the papers - Roman Szabo and Thomas Bugge.
Dysregulated activity of cell surface proteolytic enzymes has a wide range of developmental and pathological consequences, but the underlying mechanisms are often poorly understood. A new Development paper uses mice to model a severe inherited form of enteropathy and the role of the serine protease matriptase in the disease's progression. We caught up with first author Roman Szabo and his supervisor Thomas Bugge, Senior Investigator at the NIH National Institute of Dental and Craniofacial Research in Bethesda, Maryland, to find out more about the story.


Simulation vs. Understanding: A Tension, in Quantum Chemistry and Beyond. Part B. The March of Simulation, for Better or Worse.
In the second part of this Essay, we leave philosophy, and begin by describing Roald's being trashed by simulation. This leads us to a general sketch of artificial intelligence (AI), Searle's Chinese room, and Strevens' account of what a go-playing program knows. Back to our terrain-we ask "Quantum Chemistry, † ca. 2020?" Then we move to examples of Big Data, machine learning and neural networks in action, first in chemistry and then affecting social matters, trivial to scary. We argue that moral decisions are hardly to be left to a computer. And that posited causes, even if recognized as provisional, represent a much deeper level of understanding than correlations. At this point, we try to pull the reader up, giving voice to the opposing view of an optimistic, limitless future. But we don't do justice to that view-how could we, older mammals on the way to extinction that we are? We try. But then we return to fuss, questioning the ascetic dimension of scientists, their romance with black boxes. And argue for a science of many tongues.


Immunocytochemical localization of substance P, methionine-enkephalin and somatostatin in the cat intestinal wall.
The localization of substance P-(SP-), methionine-enkephalin (met-Enk-) and somatostatin (SOM-)like immunoreactivity was studied in the cat pyloric sphincter, ileum, ileocecal sphincter and proximal colon. The enteric plexuses in all regions examined contained SP-, met-Enk- and SOM-like immunoreactive varicose nerve fibres. A large number of especially SP- and met-Enk-containing varicosities were often seen to encircle the nerve cell bodies and processes in the two ganglionic plexuses. The SOM-like immunoreactive perikarya were the only peptide-containing nerve cells, preferentially located in the submucous ganglia. The predominant localization of the SOM-like immunoreactive neurons in the two enteric plexuses of the ileum was the most pronounced regional difference in the distribution pattern of the peptides. Among the layers of the cat intestinal wall the circular muscle contained the most peptide-immunoreactive fibres in contrast to the longitudinal muscle. Evidence was obtained for the occurrence of single peptide-immunoreactive varicose nerve fibres in muscularis mucosae as well as around the glands and the blood vessels. Immunoreactive endocrine cells occurred mainly in the ileum mucosa.


Stapedectomy--fistula repair.
Perilymphatic fistulae have been proposed to occur most frequently on the short side of the graft in stapedectomized patients. The usual recommendation in fistula cases has been replacement of the entire prosthesis by a piston and tissue graft complex. In this case the stapedectomy had been performed, using a polyethylene Shea strut, 15 years previously. The air-bone gap had been closed during this entire period. A fistula was suspected after sudden hearing loss developed after barotrauma. At the time of exploratory tympanotomy, a fistula was noted on the long side of the oval window graft. It was elected to leave the polyethylene tube prosthesis in place because of its solid fixation, both laterally and medially. The fistula was closed by subcutaneous tissue graft.


[Geneva's "pharmacy from the heart": towards a better access to drugs for uninsured patients].
For more than ten years in Geneva, a partnership between community pharmacies and health care workers in the public sector guarantees a better access to medications for people living in poverty and without health insurance. After a carefully selection, unused medicines are distributed to selected groups of persons in need. This partnership is fully integrated in the local public/private network of institutions active in the fight against inequalities towards access to care.


Tight clustering for large datasets with an application to gene expression data.
This article proposes a practical and scalable version of the tight clustering algorithm. The tight clustering algorithm provides tight and stable relevant clusters as output while leaving a set of points as noise or scattered points, that would not go into any cluster. However, the computational limitation to achieve this precise target of tight clusters prohibits it from being used for large microarray gene expression data or any other large data set, which are common nowadays. We propose a pragmatic and scalable version of the tight clustering method that is applicable to data sets of very large size and deduce the properties of the proposed algorithm. We validate our algorithm with extensive simulation study and multiple real data analyses including analysis of real data on gene expression.


Excess of (236)U in the northwest Mediterranean Sea.
In this work, we present first (236)U results in the northwestern Mediterranean. (236)U is studied in a seawater column sampled at DYFAMED (Dynamics of Atmospheric Fluxes in the Mediterranean Sea) station (Ligurian Sea, 43°25'N, 07°52'E). The obtained (236)U/(238)U atom ratios in the dissolved phase, ranging from about 2×10(-9) at 100m depth to about 1.5×10(-9) at 2350m depth, indicate that anthropogenic (236)U dominates the whole seawater column. The corresponding deep-water column inventory (12.6ng/m(2) or 32.1×10(12) atoms/m(2)) exceeds by a factor of 2.5 the expected one for global fallout at similar latitudes (5ng/m(2) or 13×10(12) atoms/m(2)), evidencing the influence of local or regional (236)U sources in the western Mediterranean basin. On the other hand, the input of (236)U associated to Saharan dust outbreaks is evaluated. An additional (236)U annual deposition of about 0.2pg/m(2) based on the study of atmospheric particles collected in Monaco during different Saharan dust intrusions is estimated. The obtained results in the corresponding suspended solids collected at DYFAMED station indicate that about 64% of that (236)U stays in solution in seawater. Overall, this source accounts for about 0.1% of the (236)U inventory excess observed at DYFAMED station. The influence of the so-called Chernobyl fallout and the radioactive effluents produced by the different nuclear installations allocated to the Mediterranean basin, might explain the inventory gap, however, further studies are necessary to come to a conclusion about its origin.


Quercetin potentiates TNF-induced antiviral activity.
Tumor necrosis factor (TNF) produces a dose-dependent inhibition of vesicular stomatitis virus (VSV), encephalomyocarditis virus (EMCV), and herpes simplex virus type 1 (HSV-1) replication in WISH cells. The antiviral activity of TNF against VSV and EMCV is greatly enhanced by combination with quercetin. Induction of 2',5'-oligo-adenylate (2-5A) synthetase by TNF is also enhanced by quercetin. Addition of polyclonal antibodies to human interferon (IFN)-beta completely blocked both enhancement of antiviral activity and 2-5A synthetase induction.


Gas chromatographic-mass spectrometric analysis of plasma oxybutynin using a deuterated internal standard.
A gas chromatographic-mass spectrometric method is described for the quantitative analysis of plasma oxybutynin. Deuterated oxybutynin served as the internal standard and its synthesis is described. Chromatographic separation on a methylsilicone capillary column avoided the thermal decomposition observed using a packed column. Electron-impact ionization and selected-ion monitoring of the alpha-cleavage fragments of drug and internal standard permitted quantitation of oxybutynin down to 0.25 ng/ml of plasma. At the 2 ng/ml level the accuracy and precision are 4 and 10%, respectively, and improved at higher drug concentrations. Application of the method to the pharmacokinetics of oral oxybutynin in man demonstrated rapid absorption and elimination of the drug.


Age-related decrease in muscle satellite cells is accompanied with diminished expression of early growth response 3 in mice.
Skeletal muscle regeneration is mostly dependent on muscle satellite cells. Proper muscle regeneration requires enough number of satellite cells. Recent studies have suggested that the number of satellite cells in skeletal muscle declines as we age, leading to the impairment of muscle regeneration in older population. Our earlier study demonstrated that zinc finger transcription factor early growth response 3 (Egr3) plays an important role for maintaining the number of myoblasts, suggesting that age-related decrease in muscle satellite cell should be associated with the expression levels of Egr3. The aim of this study was to investigate whether aging would alter the Egr3 expression in satellite cells. A couple groups of male C57BL/6J mice were examined in this study: young (3 Mo) and old (17 Mo). Immunohistochemical staining showed that the satellite cell number decreased in normal and injured muscles of old mice. In fluorescence-activated cell sorting-isolated muscle satellite cells from normal and injured muscles, the mRNA expression of Egr3 was significantly decreased with age regardless of injury. In harmony with these results, Pax7 mRNA levels also decreased in the satellite cells from old mice. Alternatively, inhibition of Egr3 expression by shRNA decreased Pax7 protein expression in cultured myoblasts. These results suggest that Egr3 is associated with the age-related decline of muscle satellite cells in older population. Also, Egr3 might be implicated in the regulation of Pax7. Therefore, the loss of Egr3 expression may elucidate attenuated MSCs function and muscle regeneration in older age.


Dissociation of plasminogen activator from the transformed phenotype in a 5-bromodeoxyuridine dependent mutant of Syrian hamster melanoma cells.
The relationship between plasminogen activator levels and the expression of the transformed phenotype was studied in a 5-bromodeoxyuridine (BrdUrd) dependent mutant of Syrian hamster melanoma cells. In terms of cell morphology and cellular interactions, the BrdUrd dependent cells resemble transformed cells when grown in the presence of BrdUrd but resemble untransformed cells when grown in the absence of BrdUrd. It was found that the BrdUrd dependent cells release significant levels of plasminogen activator only when cultured in the absence of BrdUrd. In the presence of BrdUrd, the release of plasminogen activator by the dependent cells is suppressed, and the decreased level of plasminogen activator released in the presence of BrdUrd seems to be due to the decreased production of active enzyme. Growth tests revealed that the BrdUrd dependent cells, when attached to a substrate, required BrdUrd in order to attain high densities. Furthermore, the cells are able to grow well in soft agar only in the presence of BrdUrd. These results suggest that the production and release of high levels of plasminogen activator are not related (either as cause or effect) to the expression of the transformed phenotype in the BrdUrd dependent cells. The effect of dog serum (as a plasminogen source) on the BrdUrd dependent cells also was tested. It was found that cells cultured in medium containing dog serum exhibit a morphological alteration, but only in the absence of brdUrd. The morphological response of the cells to dog serum resembles that previously observed with virus-transformed cells. In the BrdUrd dependent cells, the morphological response to dog serum appears correlated with the release of plasminogen activator but separated from other transformed characteristics.


Density-dependent mortality in Pinus sylvestris caused by the snow blight pathogen Phacidium infestans.
Relationships between disease incidence and the density of host plant populations were investigated in the Pinus sylvestris-Phacidium infestans host-fungal pathogen association, in which the season of death of plants killed up to 3 years previously could be accurately determined. Significant (P<0.05), positive density-dependent relationships between the proportion of plants dying in the winters of 1987-1988, 1988-1989 or 1989-1990 and the original stand density were detected in 12 of 26 comparisons. Of the remaining comparisons, all but three had positive regression coefficients for the same association. Plants killed up to 2 years previously contributed to inoculum production. The use of "standing dead" as a predictor in the analyses showed that the proportion of plants dying in the winters of 1988-1989 or 1989-1990 was generally better correlated with standing dead in the previous summer than with the density of the original population. Significant (P<0.05), positive density-dependent associations were also found between the proportion of living plants in 1990 infected with P. infestans and the number of standing dead plants in all nine comparisons. In contrast, only four of the nine associations between these proportions of infected plants and population density were significant. The strength of the density-dependent relationships varied substantially within and between sites. Much of this variation appears to be due to differences in the stage of development of the epidemics occurring at different sites.


Comparison of the primary structures, cytotoxicities, and affinities to phospholipids of five kinds of cytotoxins from the venom of Indian cobra, Naja naja.
The molecular mechanism underlying the hemolytic and cytolytic processes of cobra cytotoxins (CTXs) is not yet fully elucidated. To examine this, we analyzed the amino acid sequences, hemolytic and cytotoxic activities, and affinities to phospholipids of the five major CTXs purified from the venom of Indian cobra, Naja naja. CTX2, CTX7, and CTX8 belonged to S-type, and CTX9 and CTX10 to P-type. Comparisons of CTX7 with CTX8 and CTX9 with CTX10 revealed similar primary structures and hemolytic and cytolytic activities. CTX2, whose primary structure was rather different from the others, showed several times weaker hemolytic and cytolytic biological activities than the others. The comparison of CTX2 with CTX7 suggested the importance of Lys30 in loop II for the strong hemolytic and cytolytic activities of S-type CTXs. Cloning of 12 CTX cDNAs from the Naja naja venom cDNA library revealed that 18 out of 23 substitutions found in CTX cDNAs were nonsynonymous. This clearly indicated the accelerated evolution of CTX genes. Multiple sequence alignment of 51 kinds of CTX cDNAs and calculations of nonsynonymous and synonymous substitutions indicated that the codons coding the three loops' regions, which may interact with the hydrophobic tails of phospholipids, have undergone an accelerated evolution. In contrast, the codons coding for amino acid residues considered to participate in the recognition and binding of the hydrophilic head groups of phospholipids, eight Cys residues, and those likely stabilizing β core structure, were all conserved.


Buckyball-, carbon nanotube-, graphite-, and graphene-enhanced dehydrogenation of lithium aluminum hydride.
Compared to C60, carbon nanotubes, and graphite, graphene more effectively lowers the dehydrogenation temperature and improves the dehydrogenation kinetics of LiAlH4. With 15 wt% graphene incorporation, the initial hydrogen release temperature is ~80 °C (60 °C lower than that of pristine LiAlH4).


Nutritional interaction in an alga-barnacle association.
Nitrogen is the major growth-limiting nutrient for marine algae. One potential source of nitrogen for marine algae is ammonium released by invertebrates. Many mid-intertidal reefs in northeastern New Zealand are dominated by a close association between the honeycomb barnacle Chamaesipho columna and an encusting brown alga Pseudolithoderma sp. Growth of Pseudolithoderma was enhanced in the presence of live C. columna, which released ammonium at a greater rate than the maximum rate of ammonium uptake by Pseudolithoderma. Algal tissue on barnacle tests had a lower C:N ratio than tissue located more than 2 cm from the nearest barnacle, suggesting the barnacle is an important source of nitrogen for the alga. The role of nutrient exchange in determining ecological patterns of species in marine communities is discussed.


Food intake, eating-related complaints, and smell and taste sensations in patients with cancer of the lung, ovary and breast undergoing chemotherapy.
Nutritional status and energy and protein intake were studied in 52 patients with cancer of the breast, ovary or lung before, after 1, and after 3 cycles of aggressive chemotherapy. Pre-treatment intakes were somewhat lower than recommended and did not change after 3 cycles of chemotherapy, neither did nutritional status. Many patients had eating-related complaints, but these complaints did not increase significantly with chemotherapeutic treatment. In 31 patients electrical taste detection thresholds and chemical smell detection thresholds were measured before and after 3 cycles of chemotherapy. Changes in thresholds had no relation to changes in energy and protein intake. Perceived taste and smell changes were not reflected in chemosensory threshold values.


A short form of the metacognitions questionnaire: properties of the MCQ-30.
The metacognitions questionnaire (MCQ) measures individual differences in a selection of metacognitive beliefs, judgments and monitoring tendencies considered important in the metacognitive model of psychological disorders. The development and properties of a shortened 30-item version of the MCQ, the MCQ-30, are reported. Construct validity was evaluated by confirmatory and exploratory factor analysis. Overall, the fit indices suggested an acceptable fit to a five-factor model consistent with the original MCQ. Exploratory factor analysis supported a five-factor structure, which was almost identical to the original solution obtained in previous studies with the full MCQ. The five factors are cognitive confidence, positive beliefs about worry, cognitive self-consciousness, negative beliefs about uncontrollability of thoughts and danger, and beliefs about need to control thoughts. The MCQ-30 showed good internal consistency and convergent validity, and acceptable to good test-retest reliability. Positive relationships between metacognitions and measures of worry and obsessive-compulsive symptoms provided further support for the validity of the measure and the metacognitive theory of intrusive thoughts. The psychometric properties of MCQ-30 suggest that the instrument is a valuable addition to the assessment of metacognitions that has the advantage of being more economical to use compared with the original MCQ.


They Are Just Light Bulbs, Right? The Personality Antecedents of Household Energy-Saving Behavioral Intentions among Young Millennials and Gen Z.
Small individual behaviors such as household energy-saving behaviors may have major environmental impacts. Individuals may combat global warming by replacing traditional light bulbs with more energy-efficient light bulbs such as LED bulbs, which save electricity and reduce greenhouse gas emissions. Guided by the integrative model of behavioral prediction, the current study explored the effects of five individual personality differences (i.e., consideration of future consequences, environmental value orientation, individualism and collectivism, regulatory focus, and self-monitoring) on young Millennials' and Gen Z's attitudes, perceived norms, perceived control, and intention to switch light bulbs. The results of a survey indicated that environmental value orientation, individualism and collectivism, regulatory focus, and self-monitoring all significantly predicted attitudes, perceived norms, and perceived control, which predicted behavioral intention. The findings suggested the complex psychological nuance of environmental protection behaviors, even among the "greenest" generations. Implications and directions for future studies were discussed.


Factors Associated with Engaging in Evidence-Based Psychotherapy During the First Year of Posttraumatic Stress Disorder Treatment Between 2017 and 2019.
To address the burden of posttraumatic stress disorder (PTSD), the Veterans Health Administration (VHA) implemented evidence-based psychotherapies (EBPs) for PTSD at all VHA medical centers. Prior investigations show EBP utilization has increased following the initial nationwide implementation. However, most patients still do not engage in EBPs and those who do often have substantial delays between diagnosis and treatment which is associated with poorer treatment outcomes. The goal of the current study is to identify patient and clinical factors associated with initiating EBP and completing a minimally adequate dose of treatment within the first year of a new PTSD diagnosis. Overall, 263,018 patients started PTSD treatment between 2017 and 2019 and 11.6% (n = 30,462) initiated EBP during their first year of treatment. Of those who initiated EBP, 32.9% (n = 10,030) received a minimally adequate dose. Older patients were less likely to initiate EBP, but more likely to receive an adequate dose when they did initiate. Black, Hispanic/Latino/a, and Pacific Islander patients' likelihood of initiating EBP was not significantly different than White patients, but these patients were less likely to receive an adequate dose. Patients with comorbid depressive disorders, bipolar disorder, psychotic disorders, or substance use disorders were less likely to initiate EBP, while patients reporting MST were more likely to initiate EBP. This study identifies several patient-level disparities that could be prioritized to increase EBP utilization. In our evaluation, most patients did not engage in EBP during their first year of PTSD treatment, which is consistent with previous evaluations of EBP utilization. Future research should focus on understanding the flow of patients from PTSD diagnosis to treatment to support effective PTSD care delivery.


2'-5' oligoadenylate synthetase‑like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability.
Endothelial nitric oxide synthase (eNOS) decreases following inflammatory stimulation. As a master regulator of endothelial homeostasis, maintaining optimal eNOS levels is important during cardiovascular events. However, little is known regarding the mechanism of eNOS protection. In this study, we demonstrate a regulatory role for endothelial expression of 2'-5' oligoadenylate synthetase-like 1 (OASL1) in maintaining eNOS mRNA stability during athero-prone conditions and consider its clinical implications. A lack of endothelial Oasl1 accelerated plaque progression, which was preceded by endothelial dysfunction, elevated vascular inflammation, and decreased NO bioavailability following impaired eNOS expression. Mechanistically, knockdown of PI3K/Akt signaling-dependent OASL expression increased Erk1/2 and NF-κB activation and decreased NOS3 (gene name for eNOS) mRNA expression through upregulation of the negative regulatory, miR-584, whereas a miR-584 inhibitor rescued the effects of OASL knockdown. These results suggest that OASL1/OASL regulates endothelial biology by protecting NOS3 mRNA and targeting miR-584 represents a rational therapeutic strategy for eNOS maintenance in vascular disease.


JavaCyte, a novel open-source tool for automated quantification of key hallmarks of cardiac structural remodeling.
Many cardiac pathologies involve changes in tissue structure. Conventional analysis of structural features is extremely time-consuming and subject to observer bias. The possibility to determine spatial interrelations between these features is often not fully exploited. We developed a staining protocol and an ImageJ-based tool (JavaCyte) for automated histological analysis of cardiac structure, including quantification of cardiomyocyte size, overall and endomysial fibrosis, spatial patterns of endomysial fibrosis, fibroblast density, capillary density and capillary size. This automated analysis was compared to manual quantification in several well-characterized goat models of atrial fibrillation (AF). In addition, we tested inter-observer variability in atrial biopsies from the CATCH-ME consortium atrial tissue bank, with patients stratified by their cardiovascular risk profile for structural remodeling. We were able to reproduce previous manually derived histological findings in goat models for AF and AV block (AVB) using JavaCyte. Furthermore, strong correlation was found between manual and automated observations for myocyte count (r = 0.94, p < 0.001), myocyte diameter (r = 0.97, p < 0.001), endomysial fibrosis (r = 0.98, p < 0.001) and capillary count (r = 0.95, p < 0.001) in human biopsies. No significant variation between observers was observed (ICC = 0.89, p < 0.001). We developed and validated an open-source tool for high-throughput, automated histological analysis of cardiac tissue properties. JavaCyte was as accurate as manual measurements, with less inter-observer variability and faster throughput.


Spectral domain - Optical coherence tomography (SD-OCT) as a monitoring tool for alterations in mouse lenses.
The eye lens displays a variety of phenotypes in the wake of genetic modifications or environmental influences. Therefore, a high-resolution in vivo imaging method for the lens is desirable. Optical coherence tomography (OCT) has become a powerful imaging tool in ophthalmology, especially for retinal imaging in small animal models such as mice. Here, we demonstrate an optimized approach specifically for anterior eye segment imaging with spectral domain OCT (SD-OCT) on several known murine lens cataract mutants. Scheimpflug and histological section images on the same eye were used in parallel to assess the observed pathologies. With SD-OCT images, we obtained detailed information about the different alterations from the anterior to the posterior pole of the lens. This capability makes OCT a valuable high-resolution imaging modality for the anterior eye segment in mouse.


Bias in 238U decay chain members measured by γ-ray spectrometry due to 222Rn leakage.
In this work we investigate and quantify how effectively the noble gas 222Rn is trapped inside measurement beakers used in high-resolution gamma-ray spectrometry. We test six types of different beakers commonly utilized in γ spectrometry, including one novel construction, the γBeaker. We assessed 222Rn leakage by injecting 222Rn rich air into the examined beakers and investigated the abnormal decrease in 222Rn daughters - 214Pb and 214Bi. The measured decay times were used to estimate the 222Rn leakage. In addition, we investigated the influence of an additional beaker sealed with tape. However, the additional beaker sealing only slightly reduced the 222Rn escape and was not reproducible. Almost every tested beaker exhibited heavy 222Rn leakage. This may lead to an underestimation and radioactivity over-dispersion of 238U decay chain members when they are measured via their 222Rn daughter products.


Preoperative geriatric nutritional risk index is an independent prognostic factor for postoperative survival after gallbladder cancer radical surgery.
Currently, the surgical outcomes of gallbladder cancer (GBC) are not always satisfactory. The geriatric nutritional risk index (GNRI) can effectively assess nutritional status. This study intends to investigate whether the preoperative GNRI can predict the prognosis of GBC. 202 consecutive GBC patients who underwent treatment from 2010 to 2017 were selected and analyzed retrospectively. By using the univariate and multivariate Cox regression analyses on overall survival (OS) and recurrence-free survival (RFS), the preoperative GNRI of GBC patients was evaluated. Among the 202 patients, the GNRI of the 86 patients (42.6%) was less than 98. The patients with low preoperative GNRI had the median OS of 26 months, which was less than the median OS of 39 months among those patients who had higher preoperative GNRI (P < 0.001). Univariate analysis showed that low GNRI was related to short survival time (HR 3.656, 95% CI 2.308-5.790, P < 0.001). In addition, the results of multivariate analysis revealed that, the patients with low GNRI showed a lower OS (HR 2.207, 95% CI 1.131-4.308, P = 0.020) and RFS (HR 2.964, 95% CI 1.577-5.571, P = 0.001) than those patients with higher GNRI. GNRI is an independent indicator of poor prognosis in GBC patients after GBC radical surgery.


Electronic excitation energies of Zn(i)O(i) clusters.
Time-dependent density-functional theory (TDDFT) is used to study the excitation energies of the global minima of small Zn(i)O(i) clusters, i = 1-15. The relativistic compact effective core potentials and shared-exponent basis set of Stevens, Krauss, Basch, and Jasien (SKBJ), systematically enlarged with extra functions, were used throughout this work. In general, the calculated excitations occur from the nonbonding p orbitals of oxygen. These orbitals are perpendicular to the molecular plane in the case of the rings and normal to the spheroid surface for 3D clusters. The calculated excitation energies are larger for ringlike clusters as compared to 3D clusters, with the excitation energies of the latter structures lying close to the visible spectrum. The difference between Kohn-Sham eigenvalues of the orbitals involved in the electronic excitations studied have also been compared to the TDDFT results of the corresponding excitations for two approximate density functionals, that is, MPW1PW91 and B3LYP, the latter being more accurate. Moreover, they approach the TDDFT value as the cluster size increases. Therefore, this might be a practical method for estimating excitation energies of large Zn(i)O(i) clusters.


Absorbable synthetic mesh (polyglactin 910) for the formation of a pelvic "lid" after radical pelvic resection.
Isolation of the abdominal contents from the denuded, potentially infected pelvis after radical pelvic surgery has been advocated. Of the many materials evaluated, omentum is usually chosen. In six patients in whom omentum was unsuitable, we have substituted polyglactin 910 (Vicryl, Ethicon, Sommerville, New Jersey) mesh to form a pelvic "lid." In these patients, omentum was either densely adherent in the upper abdomen because of prior surgery or was removed as part of surgical treatment for recurrent cancer. Vicryl mesh formed a "lid" across the true pelvis. No gastrointestinal complications occurred in these patients. Four patients developed pelvic infections that resolved after surgical drainage and antibiotic therapy. No patients developed peritonitis above the pelvis. No chronic infections have been found in more than 12 to 48 months of follow-up. In this preliminary experience, Vicryl mesh appears to be useful for the formation of a pelvic "lid" after exenterative pelvic surgery when the omentum is unavailable.