Protective effects of household-based TB interventions are robust to neighbourhood-level variation in exposure risk in Lima, Peru: a model-based analysis.
Untargeted active screening and treatment programmes for tuberculosis (TB) have not been shown to be more effective than passive screening and isoniazid preventive therapy (IPT) for reducing TB incidence. In this manuscript, we compare the efficacy of targeting screening and IPT on high-risk household contacts of diagnosed TB cases, with less-targeted active screening approaches in Lima, Peru. We conducted a population-based prospective cohort study within households of TB cases in Lima. We identified all adults diagnosed with incident pulmonary TB from 2009 through 2012 at 106 participating public health centres (HC) within our catchment area of ∼3.3 million inhabitants. We estimated combined effects of community and household exposure on the risk of latent TB infection (LTBI) and incident TB disease. We used simulation modelling to assess the efficacy of TB screening programmes for reducing the risk of incident TB in these contacts. Individuals with household exposure to TB are more likely to present with LTBI and TB disease than those without this exposure, despite wide variation in community exposure. Simulations suggest that more cases are prevented by 1000 administrations of IPT to tuberculin skin test (TST)-positive household contacts of identified TB cases (30, 95% CI = 16,47) than from blanket screening and treatment in the community (7, 95% CI = 2,17). Household exposure remains a major driver of incident TB risk among household contacts of identified TB cases. Targeting interventions on these individuals is likely to prevent more cases of TB than blanket screening of individuals in the community.


Panenteric capsule endoscopy versus ileocolonoscopy plus magnetic resonance enterography in Crohn's disease: a multicentre, prospective study.
Crohn's disease diagnosis and monitoring remains a great clinical challenge and often requires multiple testing modalities. Assessing Crohn's disease activity in the entire gastrointestinal (GI) tract using a panenteric capsule endoscopy (CE) system could be used as an alternative to colonoscopy and cross-sectional imaging. This study assessed the accuracy and safety of panenteric CE in Crohn's disease as compared with ileocolonoscopy (IC) and/or magnetic resonance enterography (MRE). A prospective, multicentre study was performed in subjects with established Crohn's disease. Individuals with proven small bowel patency underwent a standardised bowel preparation, followed by CE ingestion and IC either the same or following day. MRE, IC, and CE interpretations were performed by blinded central readers using validated scoring systems. The primary endpoint was the overall sensitivity of CE vs MRE and/or IC in Crohn's disease subjects. Study enrolment included 158 subjects from 21 sites in the USA, Austria, and Israel. Of those, 99 were included in the analysis. Imaging modality scores indicated none to mild inflammation in the proximal small bowel and colon, but discrepant levels of inflammation in the terminal ileum. Overall sensitivity for active enteric inflammation (CE vs MRE and/or IC) was 94% vs 100% (p=0.125) and specificity was 74% vs 22% (p=0.001). Sensitivity of CE was superior to MRE for enteric inflammation in the proximal small bowel (97% vs 71%, p=0.021), and similar to MRE and/or IC in the terminal ileum and colon (p=0.500-0.625). There were seven serious adverse advents of which three were related to the CE device. Panenteric CE is a reliable tool for assessing Crohn's disease mucosal activity and extent compared with more invasive methods. This study demonstrates high performance of the panenteric CE as compared to MRE and/or IC without the need for multiple tests in non-stricturing Crohn's disease. ClinicalTrials.gov NCT03241368.


Using Laser-Assisted Indocyanine Green Angiography to Assess the Nipple-Areolar Complex Survival During Reduction Mammoplasty.
In reduction mammoplasty, preserving an appropriate skin flap is crucial to achieve a favorable postoperative appearance and prevent blood supply disorders in the nipple-areolar complex (NAC). Previous studies have indicated that a thinner or narrower flap is more favorable for breast shaping, but it also increases the risk of blood supply disorders. Accessing the blood perfusion of the NAC and determining the critical threshold for NAC viability are essential aspects of reduction mammoplasty. This study aims to utilize indocyanine green (ICG) angiography to assess the NAC perfusion during reduction mammoplasty. It also seeks to identify critical thresholds of various indicators affecting NAC survival and provide guidance for skin flap trimming. Thirty-eight patients who underwent reduction mammoplasty were included. Each patient received ICG angiography before and after skin flap trimming. Data on NAC perfusion, skin flap length, width, thickness, and other relevant indicators were collected. Among the patients, 5 experienced NAC blood supply disorders. Multiple linear regression analysis demonstrated the NAC blood supply had a significant correlation with the tissue thickness at the pedicle base (P < 0.001) and length-to-width ratio across the nipple (P < 0.05). The cut-off points of the thickness at the pedicle base and length-to-width ratio across the nipple are 1.15 cm and 1.71 for NAC survival and favorable breast shaping. ICG angiography can effectively assess NAC blood supply and postoperative survival. Authors can predict the survival of NAC and guide the flap trimming during the operation based on the cut-off points.


[Effect of ionol on the stomach lesion in rats during immobilization stress].
Intragastric administration of the antioxidant ionol (50 mg/kg/a day) for 7 days did not prevent the formation of ulcers or massive hemorrhages to the gastric mucosa in immobilized animals, increased the number of petechiae and lowered that of erosions. In this case the parietal pH increased in the stomach and dropped in the remaining divisions of the alimentary tract. The combined action of stress and ionol brought about marked hypocoagulation. Ionol exerted a protective action on the stress-induced activation of lipid peroxidation in the stomach but did not produce any such effect on the liver.


On the genesis of granulosa-cell ovarian tumors. Experimental data.
The ovaries and ovarian tumors induced in albino virgin mice of lines A and CC-57 by intravaginal treatment with different blastomogenic substances, such as polyurethan; 7,12-dimethylbenz-(alpha)anthracene; 8-hydroxyquinoline and synestrol, were studied histologically. 330 cases were under study, including 78 as control. The granulosa elements of ovarian follicles were found to be involved in the processes of epithelial transformation and tumorogenesis. Pretumor changes are reported to be under study in 56 cases, granulosa-cell tumors or proliferates morphologically identical to them -- in 26 cases. The data presented show close relations of the peculiarities of differentiation as well as proliferative processes in the epithelium of the women genitals and the ovarian granulosa tissue.


Step baroreflex response in awake patients undergoing carotid surgery: time- and frequency-domain analysis.
Step baroreceptor stimulation can provide an insight into the baroreflex control mechanism, yet this has never been done in humans. During carotid surgery under regional anesthesia, a step increase in baroreceptor stimulation occurs at carotid declamping immediately after removal of the intra-arterial atheromatous plaque. In 10 patients, the R-R interval and systolic and diastolic blood pressures (BP) were continuously recorded, and signals obtained within the time window from 10 min before until 10 min after carotid declamping were analyzed. Mean +/- SD time signals, power spectra, and transfer and coherence functions before and after declamping were calculated. Immediately after carotid declamping, both heart rate (HR) and BP declined in an exponential-like manner lasting 10.3 +/- 5.9 min, and their power spectra increased in the entire frequency range. Transfer function magnitude and coherence functions between BP and HR increased predominantly in the midfrequency region (approximately 0.1 Hz), with no change in phase function. Thus, in carotid endarterectomy patients, step increase in baroreceptor gain elicits a prolonged decline in HR and BP. Frequency analyses support the notion that the baroreflex control mechanism generates the midfrequency HR and BP variability, although other frequency regions are also affected.


Fractionated follow-up chemotherapy delays the onset of resistance in bone metastatic prostate cancer.
Prostate cancer to bone metastases are almost always lethal. This results from the ability of metastatic prostate cancer cells to co-opt bone remodeling leading to what is known as the vicious cycle. Understanding how tumor cells can disrupt bone homeostasis through their interactions with the stroma and how metastatic tumors respond to treatment is key to the development of new treatments for what remains an incurable disease. Here we describe an evolutionary game theoretical model of both the homeostatic bone remodeling and its co-option by prostate cancer metastases. This model extends past the evolutionary aspects typically considered in game theoretical models by also including ecological factors such as the physical microenvironment of the bone. Our model recapitulates the current paradigm of the "vicious cycle" driving tumor growth and sheds light on the interactions of heterogeneous tumor cells with the bone microenvironment and treatment response. Our results show that resistant populations naturally become dominant in the metastases under conventional cytotoxic treatment and that novel schedules could be used to better control the tumor and the associated bone disease compared to the current standard of care. Specifically, we introduce fractionated follow up therapy - chemotherapy where dosage is administered initially in one solid block followed by alternating smaller doeses and holidays - and argue that it is better than either a continuous application or a periodic one. Furthermore, we also show that different regimens of chemotherapy can lead to different amounts of pathological bone that are known to correlate with poor quality of life for bone metastatic prostate cancer patients.


Association of Multiorgan Computed Tomographic Phenomap With Adverse Cardiovascular Health Outcomes: The Framingham Heart Study.
Increased ability to quantify anatomical phenotypes across multiple organs provides the opportunity to assess their cumulative ability to identify individuals at greatest susceptibility for adverse outcomes. To apply unsupervised machine learning to define the distribution and prognostic importance of computed tomography-based multiorgan phenotypes associated with adverse health outcomes. This asymptomatic community-based cohort study included 2924 Framingham Heart Study participants between July 2002 and April 2005 undergoing computed tomographic imaging of the chest and abdomen. Participants are from the offspring and third-generation cohorts. Eleven computed tomography-based measures of valvular/vascular calcification, adiposity, and muscle attenuation. All-cause mortality and cardiovascular disease (myocardial infarction, stroke, or cardiovascular death). The median age of the participants was 50 years (interquartile range, 43-60 years), and 1422 (48.6%) were men. Principal component analysis identified 3 major anatomic axes: (1) global calcification (defined by aortic, thoracic, coronary, and valvular calcification); (2) adiposity (defined by pericardial, visceral, hepatic, and intrathoracic fat); and (3) muscle attenuation that explained 65.7% of the population variation. Principal components showed different evolution with age (continuous increase in global calcification, decrease in muscle attenuation, and U-shaped association with adiposity) but similar patterns in men and women. Using unsupervised clustering approaches in the offspring cohort (n = 1150), we identified a cohort (n = 232; 20.2%) with an unfavorable multiorgan phenotype across all 3 anatomic axes as compared with a favorable multiorgan phenotype. Membership in the unfavorable phenotypic cluster was associated with a greater prevalence of cardiovascular disease risk factors and with increased all-cause mortality (hazard ratio, 2.61; 95% CI, 1.74-3.92; P < .001), independent of coronary artery calcium score, visceral adipose tissue, and 10-year global cardiovascular disease Framingham risk, and it provided improvement in metrics of discrimination and reclassification. This proof-of-concept analysis demonstrates that unsupervised machine learning, in an asymptomatic community cohort, identifies an unfavorable multiorgan phenotype associated with adverse health outcomes, especially in elderly American adults. Future investigations in larger populations are required not only to validate the present results, but also to harness clinical, biochemical, imaging, and genetic markers to increase our understanding of healthy cardiovascular aging.


A cell-permeable Stat3 SH2 domain mimetic inhibits Stat3 activation and induces antitumor cell effects in vitro.
Given the role of constitutively active Signal Transducer and Activator of Transcription (Stat) 3 in human tumors, Stat3 inhibitors would be useful as novel therapeutics and as tools for probing Stat3-mediated tumor processes. We herein report that a 28-mer peptide, SPI, derived from the Stat3 SH2 domain, replicates Stat3 biochemical properties. Studies show SPI and Stat3 (or Stat3 SH2 domain) bind with similar affinities to known Stat3-binding phosphotyrosine (pY) peptide motifs, including those of the epidermal growth factor receptor (EGFR) and the high-affinity, IL-6R/gp130-derived pY-peptide, GpYLPQTV-NH(2). Consequently, SPI functions as a potent and selective inhibitor of Stat3 SH2 domain:pTyr interactions and disrupts the binding of Stat3 to the IL-6R/gp130 peptide, GpYLPQTV-NH(2). Fluorescence imaging and immunofluorescence staining/laser-scanning confocal microscopy show SPI is cell membrane-permeable, associates with the cytoplasmic tail of EGFR in NIH3T3/hEGFR, and is present in the cytoplasm, but strongly localized at the plasma membrane and in the nucleus in malignant cells harboring persistently active Stat3. Moreover, SPI specifically blocks constitutive Stat3 phosphorylation, DNA binding activity, and transcriptional function in malignant cells, with little or no effect on the induction of Stat1, Stat5, and Erk1/2(MAPK) pathways, or on general pTyr profile at the concentrations that inhibit Stat3 activity. Significantly, treatment with SPI of human breast, pancreatic, prostate, and non-small cell lung cancer cells harboring constitutively active Stat3 induced extensive morphology changes, associated with viability loss and apoptosis. Our study identifies SPI as a novel molecular probe for interrogating Stat3 signaling and that functions as a selective inhibitor of Stat3 activation with antitumor cell effects.


Fusobacterium necrophorum and Bacteroides melaninogenicus as etiologic agents of foot rot in cattle.
Fusobacterium necrophorum (Sphaerophorus necrophorus) and Bacteroides melaninogenicus were the predominant bacteria isolated from biopsy specimens of lesions in cattle affected with foot rot. Mixed inoculums of the 2 bacteria, applied to the scarified interdigital skin or inoculated intradermally into the interdigital skin of test cattle, induced typical lesions of foot rot. Both bacteria were reisolated in large numbers from the induced lesions.


Continuous anastomotic technique in microsurgery.
Patency rates and histologic findings were evaluated in a pilot study in which continuous and interrupted anastomotic techniques were applied to blood vessels less than 1 mm in external diameter. The results of the continuous suture technique were encouraging and we feel that the advantages gained in time and ease of performance may recommend this technique to those who need to perform large numbers of microvascular anastomoses in animals.


IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment.
The prolongation of progression-free survival (PFS) in patients with advanced ovarian cancer by antiangiogenic therapy has been shown in several clinical trials. However, although an anti-VEGF antibody (bevacizumab) is the only option currently available, its efficacy is limited and it is not cost effective for use in all patients. Therefore, the development of a novel antiangiogenic drug, especially composed of small-molecule compounds, could be a powerful armament for ovarian cancer treatment. As NF-κB signaling has the potential to regulate VEGF expression, we determined to identify whether VEGF expression is associated with NF-κB activation and to investigate the possibility of a novel IKKβ inhibitor, IMD-0354 (IMMD Inc.), as an antiangiogenic drug. Tissue microarrays from 94 ovarian cancer tissues were constructed and immunohistochemical analyses performed. We revealed that IKK phosphorylation is an independent prognostic factor (PFS: 26.1 vs. 49.8 months, P = 0.011), and is positively correlated with high VEGF expression. In in vitro analyses, IMD-0354 robustly inhibited adhesive and invasive activities of ovarian cancer cells without impairing cell viabilities. IMD-0354 significantly suppressed VEGF production from cancer cells, which led to the inhibition of angiogenesis. In a xenograft model, the treatment of IMD-0354 significantly inhibited peritoneal dissemination with a marked reduction of intratumoral blood vessel formation followed by the inhibition of VEGF expression from cancer cells. IMD-0354 is a stable small-molecule drug and has already been administered safely to humans in other trials. Antiangiogenic therapy targeting IKKβ is a potential future option to treat ovarian cancer.


Post-mortem whole-body magnetic resonance imaging of human fetuses: a comparison of 3-T vs. 1.5-T MR imaging with classical autopsy.
To prospectively compare diagnostic accuracy of fetal post-mortem whole-body MRI at 3-T vs. 1.5-T. Between 2012 and 2015, post-mortem MRI at 1.5-T and 3-T was performed in fetuses after miscarriage/stillbirth or termination. Clinical MRI diagnoses were assessed using a confidence diagnostic score and compared with classical autopsy to derive a diagnostic error score. The relation of diagnostic error for each organ group with gestational age was calculated and 1.5-T with 3-T was compared with accuracy analysis. 135 fetuses at 12-41 weeks underwent post-mortem MRI (followed by conventional autopsy in 92 fetuses). For all organ groups except the brain, and for both modalities, the diagnostic error decreased with gestation (P < 0.0001). 3-T MRI diagnostic error was significantly lower than that of 1.5-T for all anatomic structures and organ groups, except the orbits and brain. This difference was maintained for fetuses <20 weeks gestation. Moreover, 3-T was associated with fewer non-diagnostic scans and greater concordance with classical autopsy than 1.5-T MRI, especially for the thorax, heart and abdomen in fetuses <20 weeks. Post-mortem fetal 3-T MRI improves confidence scores and overall accuracy compared with 1.5-T, mainly for the thorax, heart and abdomen of fetuses <20 weeks of gestation. • In PM-MRI, diagnostic error using 3-T is lower than that with 1.5-T. • In PM-MRI, diagnostic scan rate is higher using 3-T than 1.5-T. • In PM-MRI, concordance with classical autopsy increases with 3-T. • PM-MRI using 3-T is particularly interesting for thoracic and abdominal organs. • PM-MRI using 3-T is particularly interesting for fetuses < 20 weeks' gestation.


Evaluation of clinical and paraclinical effects of intraosseous vs intravenous administration of propofol on general anesthesia in rabbits.
This prospective study aimed to compare the intraosseous (IO) and intravenous (IV) effects of propofol on selected blood parameters and physiological variables during general anesthesia in rabbits. Thirty New Zealand White rabbits were studied. Six rabbits received IV propofol (group 1) and another 6 rabbits, were injected propofol intraosseously (Group 2) for 30 minutes (experimental groups). Rabbits of the third and fourth groups received IV and IO normal saline at the same volume given to the experimental groups, respectively. In the fifth group IO cannulation was performed but neither propofol nor normal saline were administered. Blood profiles were assayed before induction and after recovery of anesthesia. Heart and respiratory rates, rectal temperature, saturation of peripheral oxygen and mean arterial blood pressure were recorded. Heart rate increased significantly 1 to 5 minutes after induction of anesthesia in experimental groups (P < 0.05). Although mean arterial blood pressure decreased significantly from baseline, values remained above 60 mm Hg (P < 0.05). Respiratory rate decreased significantly in experimental groups, but remained higher in group 2 (P < 0.05). The lymphocyte count decreased significantly in group 1 (P < 0.05). The concentration of alkaline phosphatase in all rabbits, aspartate aminotransferase and gamma-glutamyl transferase in the first group and gamma-glutamyl transferase in the third group increased significantly (P < 0.05). Total bilirubin decreased significantly in group 2 (P < 0.05). All measured values remained within normal limits. Based on the least significant physiological, hematological and biochemical effects, the IO injection of propofol appears to be safe and suitable method of anesthesia in rabbits with limited vascular access.


Research Priorities in Psychiatric Mental Health Nursing: Funding Availability, Recently Published Work, and Future Directions for Advancing Our Science.
Identifying and sharing psychiatric mental health (PMH) research priorities can help identify gaps in the literature, determine training needs for nurses, and assist investigators in locating funding. The aims for this project included: (1) identify PMH nursing specialty research priorities from large, public funding entities; (2) compare the identified research priorities and scholarly articles published in 2020; and (3) outline future directions for advancing the science of PMH nursing. Strategic plans of funding entities for PMH research were reviewed for research priorities. Summarized priorities were then compared with publications from peer-reviewed PMH nursing journals. Work conducted in the United States was extracted and categorized as original research, evidence-based practice (EBP), or quality improvement (QI), then design and population. Priorities from 13 funding entities comprised three domains (education, research, and practice), with nine areas, 30 topics, and subtopics. Eight journals produced 432 articles with 99 (23%) conducted in the United States. Among these journals, publications fitting research priorities ranged from 1 to 33 articles. Of the 99 articles, 85% were original research and 15% were either EBP or QI. Descriptive articles comprised 64% and 23% tested interventions. Populations studied included workforce; adults; infants, children, and adolescents; and parents. All published articles by the U.S. PMH nurses matched the funding priorities, but not all funding priorities were addressed by 2020 publications. The majority of work was conducted outside of the United States and most published from the United States was descriptive, contrary to many United States funders' priorities for interventional research.


Microwave-assisted tissue processing for same-day EM-diagnosis of potential bioterrorism and clinical samples.
The purpose of this study was to explore the turnaround times, section and image quality of a number of more "difficult" specimens destined for rapid diagnostic electron microscopy (EM) after microwave-assisted processing. The results were assessed and compared with those of conventionally processed samples. A variety of infectious agents, some with a potential for bioterrorism, and liver biopsies serving as an example for routine histopathology samples were studied. The samples represented virus-producing cell cultures (such as SARS-coronavirus, West Nile virus, Orthopox virus), bacteria suspensions (cultures of Escherichia coli and genetically knockout apathogenic Bacillus anthracis), suspensions of parasites (malaria Plasmodium falciparum, Leishmania major, Microsporidia cuniculi, Caenorhabditis elegans), and whole Drosophila melanogaster flies infected with microsporidia. Fresh liver samples and infected flies were fixed in Karnovsky-fixative by microwaving (20 min), all other samples were fixed in buffered glutaraldehyde or Karnovsky-fixative overnight or longer. Subsequently, all samples were divided to evaluate alternative processing protocols: one part of the sample was OsO4-postfixed, ethanol-dehydrated, Epon-infiltrated (overnight) in an automated tissue processor (LYNX, Leica), and polymerized at 60 degrees C for 48 h; in parallel the other part was microwave-assisted processed in the bench microwave device (REM, Milestone), including post-osmication and the resin block polymerization. The microwave-assisted processing protocol required at minimum 3 h 20 min: the respective epon resin blocks were uniformly polymerized allowing an easy sectioning of semi- and ultrathin sections. Sections collected on non-coated 200 mesh grids were stable in the electron beam and showed an excellent preservation of the ultrastructure and high contrast, thus allowing an easy, unequivocal and rapid assessment of specimens. Compared with conventional routine methods, microwave technology facilitates a significant reduction in sample processing time from days to hours without any loss in ultrastructural details. Microwave-assisted processing could, therefore, be a substantial benefit for the routine electron microscopic diagnostic workload. Due to its speed and robust performance it could be applied wherever a rapid electron microscopy diagnosis is required, e.g., if bioterrorism or emerging agents are suspected. Combining microwave technology with digital image acquisition, the 1-day diagnosis based on ultrathin section electron microscopy will become possible, with crucial or interesting findings being consulted or shared worldwide with experts using modern telemicroscopy tools via Internet.


Longitudinal associations of away-from-home eating, snacking, screen time, and physical activity behaviors with cardiometabolic risk factors among Chinese children and their parents.
Background: Little is known about intergenerational differences in associations of urbanization-related lifestyle behaviors with cardiometabolic risk factors in children and their parents in rapidly urbanizing China.Objective: We tested the intergenerational differences in longitudinal associations of away-from-home eating, snacking, screen time, and leisure-time sports with high waist-to-height ratio (WHtR), elevated blood pressure (BP), elevated glycated hemoglobin (HbA1c), and elevated C-reactive protein (CRP) among Chinese children and their parents.Design: We studied children enrolled in the longitudinal China Health and Nutrition Survey (1991-2009, 7 surveys) aged 7-17 y in ≥2 surveys (average follow-up: 2.3 surveys out of a possible 4 surveys with the age restriction; n = 3875, including 1175 siblings) and their parents (2947 mothers, 2632 fathers) living in the same household. We used 3 consecutive interviewer-administered 24-h dietary recalls to derive a 3-d average for away-from-home eating (nonconsumer, >0 and <1 meal/d, or ≥1 meals/d) and consumption of fruit or vegetable snacks (any or none) and other snacks (any or none) and a self-reported 7-d physical activity recall for screen time (≤1, >1 and ≤2, or >2 h/d) and leisure-time sports (any or none). Random-effects logistic regression was used to examine the associations of lagged (average: 3 y) behaviors with cardiometabolic risk factors (WHtR, BP, HbA1c, and CRP).Results: We detected intergenerational differences in associations between lagged behaviors and risk factors (P-interaction < 0.1). Generation-specific models showed that lagged away-from-home eating of ≥1 meal/d (compared with none) was negatively associated with parents' high WHtR (OR: 0.68; 95% CI: 0.53, 0.88) but positively associated with children's high WHtR (OR: 1.46; 95% CI: 1.01, 2.12). Lagged fruit and vegetable snack consumption was negatively related to parents' (OR: 0.76; 95% CI: 0.59, 0.97) and children's (OR: 0.58; 95% CI: 0.33, 1.00) high WHtR. Lagged screen time (>2 compared with ≤1 h/d) was positively associated with parents' (OR: 2.58; 95% CI: 1.56, 4.28) and children's high WHtR (OR: 2.26; 95% CI: 1.06, 4.83).Conclusion: Parent-offspring differences in associations between lifestyle behaviors and cardiometabolic risk factors provide insight into intergenerational differences in cardiometabolic risk with urbanization.


The repeatability of adaptive radiation during long-term experimental evolution of Escherichia coli in a multiple nutrient environment.
Adaptive radiations occur when a species diversifies into different ecological specialists due to competition for resources and trade-offs associated with the specialization. The evolutionary outcome of an instance of adaptive radiation cannot generally be predicted because chance (stochastic events) and necessity (deterministic events) contribute to the evolution of diversity. With increasing contributions of chance, the degree of parallelism among different instances of adaptive radiations and the predictability of an outcome will decrease. To assess the relative contributions of chance and necessity during adaptive radiation, we performed a selection experiment by evolving twelve independent microcosms of Escherichia coli for 1000 generations in an environment that contained two distinct resources. Specialization to either of these resources involves strong trade-offs in the ability to use the other resource. After selection, we measured three phenotypic traits: 1) fitness, 2) mean colony size, and 3) colony size diversity. We used fitness relative to the ancestor as a measure of adaptation to the selective environment; changes in colony size as a measure of the evolution of new resource specialists because colony size has been shown to correlate with resource specialization; and colony size diversity as a measure of the evolved ecological diversity. Resource competition led to the rapid evolution of phenotypic diversity within microcosms. Measurements of fitness, colony size, and colony size diversity within and among microcosms showed that the repeatability of adaptive radiation was high, despite the evolution of genetic variation within microcosms. Consistent with the observation of parallel evolution, we show that the relative contributions of chance are far smaller and less important than effects due to adaptation for the traits investigated. The two-resource environment imposed similar selection pressures in independent populations and promoted parallel phenotypic adaptive radiations in all independently evolved microcosms.


The Treatment of Bone Marrow Lesions Associated with Advanced Knee Osteoarthritis: Comparing Intraosseous and Intraarticular Injections with Bone Marrow Concentrate and Platelet Products.
Bone marrow lesions are a radiographic indication of bony pathology closely associated with advanced osteoarthritis of the adjacent joint. Injection of autologous orthobiologic products, including bone marrow concentrate and platelet-rich plasma, have demonstrated safety and efficacy in treating both advanced osteoarthritis (via intraarticular injection) and associated bone marrow lesions (via intraosseous injection). The relative efficacy of intraarticular versus intraosseous injection of orthobiologics has not been evaluated at the present time. The objective was to evaluate differences in orthobiologic bone marrow lesions treatment, either as a collateral result of intraarticular injection with bone marrow concentrate and platelet products alone, or intraosseous plus intraarticular injection as measured by patient reported outcomes. This study employed a prospective case-matched cohort design. This study took place at a single outpatient interventional orthopedic pain clinic. Using data from a prospective orthobiologic treatment registry of knee patients, a population of knee osteoarthritis with bone marrow lesions patients who had undergone only intraarticular knee injections of bone marrow concentrate and platelets (for symptomatic advanced osteoarthritis) were age, gender, and disease severity case-matched to a series of advanced osteoarthritis and bone marrow lesions patients who underwent intraosseous plus intraarticular injections. Self-reported patient outcomes for Numeric Pain Scale, International Knee Documentation Committee, lower extremity functional scale, and a modified single assessment numeric evaluation were compared between the 2 treatment groups. Eighty patients were included, 40 in each group. Although pain and functional outcome scores were significantly improved in both treatment groups, there was no statistically significant differences in patient reported outcomes based on the type of treatment. There are several limitations to this study, including multiple providers performing the injections, varying onset of symptoms to treatment, and additional injections after their initial treatment, that were not controlled. In addition, increasing the sample size may be beneficial as well, particularly with the large bone marrow lesions group, which did suggest possible improvement with intraosseous plus intraarticular over the intraarticular, although was not statistically significant in our sample. Limited data availability for this cohort as well as some missing data are other limitations to consider. Treating knee bone marrow lesions with intraosseous bone marrow concentrate and platelet products did not affect patient reported outcomes.


Observations on the rare association between portal and pulmonary hypertension.
Pulmonary arterial hypertension with severe pulmonary vascular disease is a rare association of portal hypertension in man, be it the result of cirrhosis of the liver or obstruction of the portal vein. We induced portal hypertension in 23 rats by partially ligating the portal vein or by totally occluding it in two stages. The rats were killed between one and 15 months after operation. A collateral circulation of varicose, anastomotic vessels was established, and in six animals well-marked oesophageal varices developed. Despite this evidence of sustained portal hypertension, hypertrophy did not develop in the right ventricle or in the media of the pulmonary trunk or muscular pulmonary arteries in any of the animals. This suggests that mechanical obstruction of the portal vein per se is not responsible for the development of pulmonary hypertension. Other factors, perhaps of a humoral nature, appear to be required to induce this rare association of portal hypertension but we have been unable to identify these. In particular, blood levels of oestrogen were not raised after ligation of the portal vein.


Weekly moxifloxacin and rifapentine is more active than the denver regimen in murine tuberculosis.
Treatment of tuberculosis with an efficacious once-weekly regimen would be a significant achievement in improving patient adherence. Currently, the only recommended once-weekly continuation phase regimen of isoniazid plus rifapentine (10 mg/kg) is inferior to standard twice-weekly therapy with isoniazid plus rifampin and is, therefore, restricted to non-high-risk patients. The substitution of moxifloxacin, a new 8-methoxyfluoroquinolone, for isoniazid and an increase in the dose of rifapentine could augment the activity of once-weekly regimens. To test this hypothesis we evaluated the sterilizing activity of improved once-weekly rifapentine-based continuation phase regimens in a murine model that mimics the treatment of high-risk patients with tuberculosis. The bactericidal activity of standard daily therapy and standard intermittent therapy ("Denver" regimen) was also assessed to evaluate the effect of intermittent drug administration during the initial phase of therapy. After 2 mo of treatment, lung colony-forming unit counts were 1 log(10) lower in mice treated with standard daily therapy than with the Denver regimen. During the continuation phase, the sterilizing activity of once-weekly moxifloxacin plus rifapentine (15 mg/kg) was significantly greater than that of the predominantly twice-weekly Denver regimen of isoniazid plus rifampin. No significant difference in sterilizing activity was detected between once-weekly isoniazid plus rifapentine (15 mg/kg) and the Denver regimen. These results suggest that the efficacy of the once-weekly isoniazid plus rifapentine continuation phase regimen can be increased by substituting moxifloxacin for isoniazid and by increasing the dose of rifapentine to a clinically acceptable level of 15 mg/kg.


Temporally resolved neural dynamics underlying handwriting.
How do the temporal dynamics of neural activity encode highly coordinated visual-motor behaviour? To capture the millisecond-resolved neural activations associated with fine visual-motor skills, we devised a co-registration system to simultaneously record electroencephalogram and handwriting kinematics while participants were performing four handwriting tasks (writing in Chinese/English scripts with their dominant/non-dominant hand). The neural activation associated with each stroke was clearly identified with a well-structured and reliable pattern. The functional significance of this pattern was validated by its significant associations with language, hand and the cognitive stages and kinematics of handwriting. Furthermore, the handwriting rhythmicity was found to be synchronised to the brain's ongoing theta oscillation, and the synchronisation was associated with the factor of language and hand. These major findings imply an implication between motor skill formation and the interplay between the rhythms in the brain and the peripheral systems.


Long-term tacrine (Cognex) treatment: effects on nursing home placement and mortality, Tacrine Study Group.
To assess the possible association between tacrine (Cognex, manufactured by Parke-Davis, Morris Plains, NJ) dose and likelihood of nursing home placement (NHP) or death in patients with AD. A 30-week, randomized, double-blind, placebo-controlled, parallel-group multicenter clinical trial involving 663 patients, after which patients were treated openly and followed up a minimum of 2 years later. At baseline, outpatients were at least 50 years of age, met criteria for probable AD, with baseline Mini-Mental State Examination scores between 10 and 26 (inclusive), were otherwise healthy, and had a caregiver who could provide assessments and ensure medication compliance. mandomized assignment to placebo or one of three ascending dosage regimens of tacrine over 30 weeks, followed by open label treatment for all patients who began the double-blind trial. NHP and death were examined using logistic regression. PATIENTS who remained on tacrine and were receiving doses > 80 mg/d or > 120 mg/d were less likely to have entered a nursing home than patients on lower doses (odds ratios > 2.7,2.8, respectively.) There was a trend for lower mortality for patients receiving > 120 mg/d (p = 0.063). Treatment with tacrine at doses > 80 mg/d was associated with a reduced likelihood of NHP. These data demonstrate that tacrine's 30-week effects on cognitive function and clinicians' global ratings may generalize to effects on a major milestone of AD. Future studies should attempt to replicate these findings prospectively.


Physical size of the donor locus and transmission of Haemophilus influenzae ampicillin resistance genes by deoxyribonucleic acid-mediated transformation.
The properties of donor deoxyribonucleic acid (DNA) from three clinical isolates and its ability to mediate the transformation of competent Rd strains to ampicillin resistance were examined. A quantitative technique for determining the resistance of individual Haemophilus influenzae cells to ampicillin was developed. When this technique was used, sensitive cells failed to tolerate levels of ampicillin greater than 0.1 to 0.2 mug/ml, whereas three resistant type b beta-lactamase-producing strains could form from the colonies in 1- to 3-mug/ml levels of the antibiotic. DNA extracted from the resistant strains elicited transformation of the auxotrophic genes in a multiply auxotrophic Rd strain. For two of the donors, transformation to ampicillin resistance occurred after the uptake of a single DNA molecule approximately 104-fold less frequently than transformation of auxotrophic loci and was not observed to occur at all with the third. The frequency of transformation to ampicillin resistance was two- to fivefold higher in strain BC200 (Okinaka and Barnhart, 1974), which was cured of a defective prophage. All three clinical ampicillin-resistant strains were poor recipients, but the presence of the ampicillin resistant genes in strain BC200 did not reduce its competence. Sucrose gradients of DNA from ampicillin-resistant transformants of BC200 and from the original ampicillin-resistant strains showed that: (i) all the DNA preparations had high molecular weights; (ii) donor activity for ampicillin resistance sedimented heterogeneously and in parallel with genome DNA up to the highest molecular weights observed (100 x 106 to 200 x 106); and (iii) genetic transformation of ampicillin resistance from strain BC200-amp90383 required the physical integrity of a linearly integrated segment of DNA having a molecular weight of about 25 x 106 to 30 x 106.


A planar unimorph-based actuator with large vertical displacement capability. II. Theory.
A piezoelectric actuator utilizing a planar trellis-like arrangement of multiple unimorph elements is described which produces displacements perpendicular to the plane of the actuator. The unimorph elements are connected in series mechanically so that the vertical displacement of each unimorph element in the structure adds to the vertical displacements of the other elements, resulting in a large overall vertical displacement at the output of the actuator. A simple electromechanical model of the actuator is developed. The model consists of a voltage-actuated force source, which is the result of the piezoelectric properties of the unimorph bars that make up the actuator, in parallel mechanically with a stiff spring that models the elastic response, both bending and twisting, of the unimorph elements. The long moment arms inherent in the geometry of the actuator make a substantial contribution to the overall compliance of the actuator. The addition of stiffeners to the actuator can significantly reduce the effect of these moment arms, and thus substantially increase the stiffness of the actuator. As a result, the force generation capability of the actuator is significantly increased without affecting its displacement capability.


Bone blood flow in the rat determined by the uptake of radioactive particles.
1. Two different suspensions of radioactive particles, 99Tcm-labelled microspheres and 59Fe-labelled resin particles, were injected into the rat central circulation in order to study the distribution of blood flow to the skeleton. 2. Measurements of particle uptake showed that the mean proportion of cardiac output flowing to the skeleton was 3-1%, a figure much lower than the valve of 27% found by Brookes (1970) in a similar experiment. 3. The blood flow per unit mass to individual bones covered a wide range.


Suicide Prevention Training - Improving the Attitudes and Confidence of Rural Australian Health and Human Service Professionals.
Suicide rates are higher in rural and remote areas of Australia compared with major cities. To evaluate the impact of a brief, community-based suicide prevention educational intervention on the attitudes and confidence of rural South Australian health and human service professionals. Participants attended a 1-day suicide prevention education program, and completed a survey at four time points: baseline (T1), immediately pretraining (T2), immediately posttraining (T3), and 4-month follow-up (T4). Main outcome measures were self-reported attitudes and confidence when working with people vulnerable to suicide. A total of 248 people attended the training, with 213 participants completing the survey at T1, 236 at T2, 215 at T3, and 172 at T4. There were significant improvements in 11 of the 14 attitude items between T2 and T3 (immediate change), and between T1 and T4 (maintained change). Further, there were significant improvements in all four confidence items between T2 and T3, and T1 and T4. Despite the repeated-measures design, findings are limited by the lack of a control group. Findings extend the international evidence by indicating the value of brief suicide prevention education for improving health and human service professionals' attitudes and confidence in rural Australia.


Penetration of Escherichia coli O157:H7 into lettuce tissues as affected by inoculum size and temperature and the effect of chlorine treatment on cell viability.
Penetration of Escherichia coli O157:H7 into iceberg lettuce tissues and the effect of chlorine treatment on cell viability were evaluated. Attachment of different inoculum levels (10(9), 10(8), and 10(7) CFU/ml) was examined by determining the number of cells at the surface and the cut edge of lettuce leaves (2 by 2 cm). E. coli O157:H7 attached preferentially to cut edges at all inoculum levels, with greater attachment per cm2 of lettuce at higher inoculum levels. A longer attachment time allowed more cells to attach at both sites. Immunostaining with a fluorescein isothiocyanate-labeled antibody revealed that cells penetrated into lettuce leaves from cut edges. Cells showed greater penetration when lettuce was held at 4 degrees C compared with 7, 25, or 37 degrees C and were detected at an average of 73.5 +/- 16.0 microm below the surfaces of cut tissues. Penetrating cells were mostly found at the junction of lettuce cells. The viability of attached cells after treatment with 200 mg/liter (200 ppm) of free chlorine for 5 min was examined by plating on tryptic soy agar and by a nalidixic acid elongation method. Although chlorine treatment caused significant reduction in attachment (0.7- and 1.0-log reduction at surfaces and cut edges, respectively), cells remained attached at high numbers (7.9 and 8.1 log CFU/cm2 at surfaces and cut edges, respectively). Elongated cells were observed in stomata and within the tissues of the lettuce, indicating they were protected from contact with chlorine.


Psychoneuroimmunology and preterm birth. A holistic model for obstetrical nursing practice and research.
This article presents a framework through which nurses can conceptualize premature labor and birth for both practice and research. Use of the psychoneuroimmunology (PNI) model may guide the study of the problem of preterm birth in a more holistic manner, discovering relationships between the body and the mind that may affect how nurses can intervene to prevent premature birth. Nursing assessment of risk needs to include those situations that may lead to increased stress or anxiety, as is supported by research based on the PNI model. Reduction of stressors that lead to physiological changes related to the stress response can affect the incidence of preterm labor. Interventions to decrease stress and poor coping behaviors need to be tested and integrated into practice.


[LOGNORMAL-NLSQ-technique. Evaluation of a new mathematical method for determining blood volume].
This paper describes the investigation of a new mathematical method of calculating blood volume. The new method determines the blood volume by calculating the product of the mean circulation transit time. The mean transit time is calculated from the body transport function. To examine the accuracy of the LOGNORMAL-NLSQ technique, 45 concentration time curves were measured in an in vitro recirculation model with variable clearance. The calculated volume was 4% smaller than the actual volume. This may be attributed to the functional dead space within the model, and is tolerable for clinical situations. The LOGNORMAL-NLSQ technique might acquire considerable importance in future, especially since it provides accurate results very quickly.


Fundamentals of impedance cardiography.
The most widely used impedance method for cardiac stroke volume and cardiac output measurements is described. It uses band electrodes around the ends of the thorax and forward extrapolation of the systolic portion of the impedance waveform. Studies performed to determine the physiological origin of the impedance change and the apparently conflicting results are summarized. Comparative studies with other methods are briefly discussed. It is concluded that for the present technique to be placed on a sound scientific base, it is necessary to determine what regions or organs contribute to the impedance change recorded from the thoracic surface, but that it shows remarkably good correlation with other cardiac output measurement systems if applied to a select relatively healthy population, given all the assumptions involved.


Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis.
Objective Periostin is an extracellular matrix protein that is elevated in the sinonasal tissues of patients with chronic rhinosinusitis (CRS). The purpose of this study was to determine whether serum periostin could serve as a molecular biomarker of nasal polyp burden in sinonasal disease. Study Design Prospective cohort study. Setting Academic medical center. Subjects and Methods Serum periostin levels were measured by ELISA on blood samples collected from patients undergoing sinus surgery for CRS (n = 71), further stratified by phenotype as defined by nasal polyps and asthma. Results were compared with assays performed on control subjects (n = 62). Results Mean serum periostin levels were markedly elevated in patients with CRS versus controls (66.1 ng/mL [95% CI, 51.6-80.6] vs 38.7 ng/mL [95% CI, 34.4-42.9], respectively, P = .004). In addition, mean periostin levels were significantly higher in CRS patients with nasal polyps as compared with those without polyps (94.8 ng/mL [95% CI, 67.3-122.4] vs 41.1 ng/mL [95% CI, 35.2-47.0], respectively, P < .001). Periostin levels did not correlate with sex ( P = .473), smoking history ( P = .748), aspirin-exacerbated respiratory disease status ( P = .136), oral steroid use within 1 month of surgery ( P = .281), use of topical steroid nasal spray ( P = .864), or number of prior sinus operations ( P = .973). Conclusion Serum periostin appears to be a novel molecular biomarker for the presence of nasal polyps and may serve as an indicator of CRS endotypes.


Development and initial testing of functional task exercise on older adults with cognitive impairment at risk of Alzheimer's disease--FcTSim programme--a feasibility study.
The purpose of this study was to illustrate the development of a new functional task-based exercise programme and initially test its feasibility as well as effectiveness for older adults with mild cognitive impairment (MCI). This study used a single-group repeated-measures design. A total of 11 patients (mean age 71.8 years) were recruited to participate in a structured functional task exercise programme for 10 weeks. All outcome measures were undertaken at baseline, post-intervention and post-3-month follow-up using the Neurobehavioral Cognitive Status Examination (NCSE), Verbal Fluency Test (VFT), Chinese Version Verbal Learning Test (CVVLT), Lawton Instrumental Activities of Daily Living Scale (Lawton IADL) and Problems in Everyday Living test (PEDL). Data were analysed using a repeated-measures analysis of variance. Cohen's d effect size was used to assess the practical significant effects. The participants showed significant improvement in NCSE composite score, VFT, CVVLT total free recall, CVVLT 10-minute delayed free recall, Lawton IADL and PEDL. Results of this study demonstrate that the newly designed functional task exercise programme, which uses simulated tasks, is feasible and beneficial to cognitive functions and functional status of older persons with MCI. The findings of the current study further reinforce occupational therapy practitioners' understanding that "occupation" is a "means" and an "end". Further study with a larger population is needed to draw more definitive conclusions.


Bicuculline administration into ventromedial hypothalamus: effects on fear and regional brain monoamines and GABA concentrations in rats.
The effects of bicuculline methiodide administration into ventromedial hypothalamus (15 ng per site, bilaterally) on fear behavior and monoamines (NA, DA, 5-HT) and GABA in structures of the brain defensive system (hypothalamus, midbrain gray matter, amygdala, hippocampus and frontal cortex) were studied. Fear behavior was examined in the modified version of light-dark transition test. The time out from the illuminated compartment of chamber, the time spent there and number of returns to the illuminated compartment was measured. Additionally motor activity, i.e., number of crossings and rearings in dark as well as in the illuminated part of compartment, was registered. Blockade of GABAA receptors in the ventromedial hypothalamus resulted in increased fear behavior, i.e. decrease of time out from illuminated compartment and decrease of the time spent there. Motor behavior remained unchanged. HPLC analysis showed reduction of GABA concentration in all investigated brain structures. An increase of NA concentration in all examined structures with exception of the hypothalamus without effect on MHPG/NA was observed as well. Dopamine level remained unchanged, but DOPAC/DA ratio increased in all structures, except frontal cortex. Also HVA/DA ratio increased in the hypothalamus and midbrain. 5-HT concentration increased only in midbrain, 5-HIAA increased in midbrain and in frontal cortex, and 5-HIAA/5-HT ratio increased only in frontal cortex. These results indicate that GABA-ergic and monoaminergic systems remain in functional interactions and that these interactions may play an important role in the neurochemical regulation of fear behavior. The possible mechanism of GABA--monoaminergic interactions is discussed.


Characterization of the pars tuberalis and hypothalamus transcriptome in female sheep under different reproductive stages.
For understanding the molecular events underlying the follicular (F) and luteal (L) phases of estrous cycle, and anestrous (A) phase, the pars tuberalis (PT), and hypothalamus (HT) transcriptomes of 21 ewes were studied. In HT, 72 and 3 differential expression genes (DEGs) were found when comparing F vs. A and L vs. A, respectively. In PT, 6 and 4 DEGs were found in F vs. A and L vs. A comparisons, respectively. Enrichment analysis for DEGs between the F and A phases in the HT revealed significant clusters, mainly associated with actin-binding, and cytoskeleton, that are related to neural plasticity modulated by gonadal steroid hormones, as well as with oxytocin signaling. We found that DEGs in PT had higher differences in expression levels than those found in HT. In this sense, the ITLN was highly upregulated in the F and L vs. A phases, being MRPL57 and IRX4 highly downregulated in L vs. A comparison. The DDC gene in PT, related to LH regulation, was upregulated in the F phase. The gene set enrichment analysis (GSEA) revealed multiple pathways related to neurotransmission and neuronal plasticity. Our study reveals new candidate genes involved in the reproductive stages' transitions in seasonal sheep.


Mortality and Risk Stratification of HIV Infected Individuals.
For the first decade and a half after the Human Immunodeficiency Virus (HIV) was first identified, the prognosis for most people infected with HIV was quite poor. Life insurance companies responded accordingly and insurance laboratories developed new means to test for the infection. However, it is now clear that people with HIV infection are living longer and that the majority of deaths occurring among those on treatment are now no longer due to AIDS-defining illnesses. This review examines the results of selected studies which analyzed mortality outcomes in those with HIV infection, the many factors which influence those outcomes, and the limitations in the data and in their applicability to an insurance population.


History of hypertension and eplerenone in patients with acute myocardial infarction complicated by heart failure.
In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (n=6632), eplerenone-associated reduction in all-cause mortality was significantly greater in those with a history of hypertension (Hx-HTN). There were 4007 patients with Hx-HTN (eplerenone: n=1983) and 2625 patients without Hx-HTN (eplerenone: n=1336). Propensity scores for eplerenone use, separately calculated for patients with and without Hx-HTN, were used to assemble matched cohorts of 1838 and 1176 pairs of patients. In patients with Hx-HTN, all-cause mortality occurred in 18% of patients treated with placebo (rate, 1430/10 000 person-years) and 14% of patients treated with eplerenone (rate, 1058/10 000 person-years) during 2350 and 2457 years of follow-up, respectively (hazard ratio [HR]: 0.71; 95% CI: 0.59 to 0.85; P<0.0001). Composite end point of cardiovascular hospitalization or cardiovascular mortality occurred in 33% of placebo-treated patients (3029/10 000 person-years) and 28% of eplerenone-treated patients (2438/10 000 person-years) with Hx-HTN (HR: 0.82; 95% CI: 0.72 to 0.94; P=0.003). In patients without Hx-HTN, eplerenone reduced heart failure hospitalization (HR: 73; 95% CI: 0.55 to 0.97; P=0.028) but had no effect on mortality (HR: 0.91; 95% CI: 0.72 to 1.15; P=0.435) or on the composite end point (HR: 0.91; 95% CI: 0.76 to 1.10; P=0.331). Eplerenone should, therefore, be prescribed to all of the post-acute myocardial infarction patients with reduced left ventricular ejection fraction and heart failure regardless of Hx-HTN.


Symplastic continuity between companion cells and the translocation stream: long-distance transport is controlled by retention and retrieval mechanisms in the phloem.
Substantial symplastic continuity appears to exist between companion cells (CCs) and sieve elements of the phloem, which suggests that small solutes within the CC are subject to indiscriminate long-distance transport via the translocation stream. To test this hypothesis, the distributions of exotic and endogenous solutes synthesized in the CCs of minor veins were studied. Octopine, a charged molecule derived from arginine and pyruvate, was efficiently transported through the phloem but was also transferred in substantial amounts to the apoplast, and presumably other non-phloem compartments. The disaccharide galactinol also accumulated in non-phloem compartments, but long-distance transport was limited. Conversely, sucrose, raffinose, and especially stachyose demonstrated reduced accumulation and efficient transport out of the leaf. We conclude that small metabolites in the cytosol of CCs do enter the translocation stream indiscriminately but are also subject to distributive forces, such as nonselective and carrier-mediated membrane transport and symplastic dispersal, that may effectively clear a compound from the phloem or retain it for long-distance transport. A model is proposed in which the transport of oligosaccharides is an adaptive strategy to improve photoassimilate retention, and consequently translocation efficiency, in the phloem.


National Early Warning Score 2 (NEWS2) better predicts critical Coronavirus Disease 2019 (COVID-19) illness than COVID-GRAM, a multi-centre study.
Clinical scores to rapidly assess the severity illness of Coronavirus Disease 2019 (COVID-19) could be considered of help for clinicians. Recently, a specific score (named COVID-GRAM) for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, based on a nationwide Chinese cohort, has been proposed. We routinely applied the National Early Warning Score 2 (NEWS2) to predict critical COVID-19. Aim of this study is to compare NEWS2 and COVID-GRAM score. We retrospectively analysed data of 121 COVID-19 patients admitted in two Clinics of Infectious Diseases in the Umbria region, Italy. The primary outcome was critical COVID-19 illness defined as admission to the intensive care unit, invasive ventilation, or death. Accuracy of the scores was evaluated with the area under the receiver-operating characteristic curve (AUROC). Differences between scores were confirmed used Hanley-McNeil test. The NEWS2 AUROC curve measured 0.87 (standard error, SE 0.03; 95% CI 0.80-0.93; p < 0.0001). The COVID-GRAM score AUROC curve measured 0.77 (SE 0.04; 95% CI 0.68-0.85; p < 0.0001). Hanley-McNeil test showed that NEWS2 better predicted severe COVID-19 (Z = 2.03). The NEWS2 showed superior accuracy to COVID-GRAM score for prediction of critical COVID-19 illness.


Biphasic effect of short-term pregnancy hormone treatment on N-methyl-N-nitrosourea-induced mammary carcinogenesis in young and old rats.
This study examined the development of N-methyl-N-nitrosourea (MNU)-induced mammary carcinomas in young and old female Lewis rats following short-term treatment with estrogen and progesterone to mimic pregnancy. Rats exposed at 4 weeks of age to MNU were treated at 6 weeks of age (early MNU/young E/P treatment) or at 24 weeks of age (early MNU/old E/P treatment) with a 21-day slow-release pellet containing 0.5 mg 17β-estradiol and 32.5 mg progesterone (E/P). Other rats were exposed to MNU at 22 and again at 23 weeks of age, and were treated with E/P at 24 weeks of age (late MNU/old E/P treatment). All experimental groups were compared with respective MNU-exposed age-matched E/P-untreated rats. Overt mammary carcinomas (≥1 cm in diameter) that were positive for hormone receptors were reduced in young E/P-treated rats, while hormone receptor-negative overt mammary carcinomas increased in old E/P-treated rats. The rate of development of small-sized mammary carcinoma (<1 cm in diameter) was similar in early MNU/young E/P-treated and late MNU/old E/P-treated groups, but higher in early MNU/old E/P-treated rats compared with respective E/P-untreated rats. At the termination of the experiment, normal mammary gland architecture had not been influenced by E/P treatment, although E/P treatment of older rats caused an increase in proliferating cell nuclear antigen (PCNA) labeling of the mammary tissue. Thus, the impact of short-term E/P treatment on MNU-induced rat mammary carcinogenesis is age-dependent and shows biphasic effects; the development of hormone-dependent overt mammary carcinomas was reduced in young rats but the development of hormone-independent overt mammary carcinomas increased in older rats. The enhanced outgrowth of hormone-independent overt mammary carcinomas by E/P treatment in old age is due to accelerated cell proliferation at the promotion/progression phase of mammary carcinogenesis. Age at short-term E/P treatment is crucial for breast cancer control.


Estimation of N-terminal telopeptides of type I collagen in periodontal health, disease and after nonsurgical periodontal therapy in gingival crevicular fluid: A clinico-biochemical study.
This study explored gingival crevicular fluid (GCF) N-terminal telopeptides of type I collagen (NTx) levels in periodontal health, disease and after nonsurgical periodontal therapy along with its association with the clinical parameters. Study comprised of three groups of 10 subjects each: Healthy (Group I), gingivitis (Group II), and periodontitis (Group III), while Group III patients after scaling and root planning (SRP) constituted Group IV. Gingival index (GI), probing pocket depth (PPD), clinical attachment loss (CAL), and radiological parameters were recorded. GCF samples were analyzed by competitive-enzyme-linked immunosorbent assay. Samples in Group III and Group IV tested positive for NTx whereas in Group I and Group II, NTx was not detected. Mean NTx levels were higher in Group III (6.79 ± 0.94 nanomole bone collagen equivalents per liter [nm BCE/L]) compared to Group IV (5.73 ± 0.95 nm BCE/L) which was statistically significant. Positive correlation was seen between the clinical parameters and the NTx levels in Group III and IV. As NTx is specific bone turnover marker, it is detected only in periodontitis Group and the values decline after SRP. Failure to detect NTx in Group I and II, relates to the minimum or no resorption at the sample sites.


Determination of naphthazarin derivatives in endemic Turkish Alkanna species by reversed phase high performance liquid chromatography.
The quantification of free and total alkannins in 13 endemic Anatolian Alkanna species is described for the first time. Extraction of the samples was performed by sonication with hexane, followed by hydrolysis in 1 N NaOH. For analysis, a new HPLC method, utilizing reversed phase material (Synergi Max RP), was developed and successfully validated. The obtained data confirmed that the assay is sensitive (LOD of 13 ng on-column for alkannin), accurate (the recovery rate was 92.3%) and precise (RSD<or=6.8% for intra-day precision; RSD<or=4.8% for inter-day precision). LC-MS experiments were performed to assure peak identity and purity. Quantitative results revealed that roots of Alkanna tubulosa showed the highest amount of total alkannins (0.84%), while Alkanna mughlae contained the highest percentage of free alkannins (0.04%). Compared to the commonly used A. TINCTORIA (total alkannins: 0.11 to 0.54%; free alkannins: 0.002 to 0.01%) these two species could therefore serve as alternative sources for medicinally important alkannin derivatives.


[New species of mites of the genus Ptilonyssus (Gamasina: Rhinonyssidae) isolated from Passeriformes (Aves: Passeriformes) from Russia and neighboring countries].
Eight new species of the genus Ptilonyssus (Berl. et Troues.) (Gamasina: Rhinonyssidae) from nasal cavities of the passeriformes from territory of the former USSR are described: P. ammomani sp. n. from Ammomanus deserti (Alaudidae) collected in Turkmenistan; P. spini sp. n. from Spinus spinus (Fringillidae) of Kaliningrad district (Russia); P. ripariae sp. n. from Riparia riparia (Hirundinidae) and P. acanthopneustes sp. n. from Phylloscopus borealis (Sylviidae) collected in Tjumen district (Russia); P. pyrrhulinus sp. n. from Pyrrhula pyrrhula (Fringillidae) and P. anthi sp. n. from Anthus trivialis (Motacillidae) of Rjazan district; P. sylviicola sp. n. from Sylviae communis (Sylviidae) collected in Tatarstan; P. cyanosylviae sp. n. from Cyanosylvia svecica (Turdidae) collected from Novosibirsk district.


Developing an alternative alcohol advertising complaint review system: lessons from a world-first public health advocacy initiative.
Young people in Australia are frequently exposed to alcohol marketing. Leading health organisations recommend legislative controls on alcohol advertising as part of a comprehensive approach to reduce alcohol-related harm. However, Australia relies largely on industry self-regulation. This paper describes the development and implementation of the Alcohol Advertising Review Board (AARB), a world-first public health advocacy initiative that encourages independent regulation of alcohol advertising. The AARB reviews complaints about alcohol advertising, and uses strategies such as media advocacy, community engagement and communicating with policy makers to highlight the need for effective regulation. In 4 years of operation, the AARB has received more complaints than the self-regulatory system across a similar period. There has been encouraging movement towards stronger regulation of alcohol advertising. Key lessons include the importance of a strong code, credible review processes, gathering support from reputable organisations, and consideration of legal risks and sustainability. The AARB provides a unique model that could be replicated elsewhere.


Female reproductive signaling, and male mating behavior, in the olive baboon.
Baboon sexual swellings are among the largest and most colorful signals displayed by any mammal, and many baboon studies have shown an association between sexual swellings and both female and male sexual behavior. However, the extent to which female behavior and sexual swellings combine to signal the timing of ovulation and the fertile period to males, and the extent to which males use these and other signals when determining patterns of mating behavior, remain key topics of research. Here we assess the social and sexual behavior of both female and male olive baboons with respect to detailed measures of swelling size made from digital photographs, measures of fecal progestogen and estrogen levels, and estimates of the timing of ovulation and the fertile period based on those levels. Female aggression and grooming behavior were unrelated to fecal progestogen and estrogen levels, but there were some significant relationships between these hormonal measures and presenting behaviors. Measures of female behavior collected during the study did not appear to reveal the timing of ovulation or the fertile period. Male consortship behavior was closely tied to fine-scale changes in sexual swelling size, but copulation behavior was not. Copulation behavior of consorting males was, however, linked to the timing of both ovulation and the fertile period, suggesting that males did have knowledge about these timings. Together these results suggest that males used fine-scale swelling size changes when deciding when to consort, but that consorting males did not use fine-scale swelling size changes in deciding when to copulate. We propose that swelling size may advertise the period during which males should consort with females, with other signals available only from closer inspection then used by consorting males to assess the timing of the fertile period more accurately. An important implication of this interpretation is that different males may have access to different signals of ovulation at any one time. Such a system would allow females to offer different males different information simultaneously, perhaps offering a solution to the 'female dilemma' of how females can simultaneously assure and confuse paternity in multi-male societies.


Proton-Assisted Recoupling (PAR) in Peptides and Proteins.
Proton-assisted recoupling (PAR) is examined by exploring optimal experimental conditions and magnetization transfer rates in a variety of biologically relevant nuclear spin-systems, including simple amino acids, model peptides, and two proteins-nanocrystalline protein G (GB1), and importantly amyloid beta 1-42 (M0Aβ1-42) fibrils. A selective PAR protocol, SUBPAR (setting up better proton assisted recoupling), is described to observe magnetization transfer in one-dimensional spectra, which minimizes experiment time (in comparison to two-dimensional experiments) and thereby enables an efficient assessment of optimal PAR conditions for a desired magnetization transfer. In the case of the peptide spin systems, experimental and simulated PAR data sets are compared on a semiquantitative level, thereby elucidating the interactions influencing PAR magnetization transfer and their manifestations in different spin transfer networks. Using the optimum Rabi frequencies determined by SUBPAR, PAR magnetization transfer trajectories (or buildup curves) were recorded and compared to simulated results for short peptides. PAR buildup curves were also recorded for M0Aβ1-42 and examined conjointly with a recent structural model. The majority of salient cross-peak intensities observed in the M0Aβ1-42 PAR spectra are well-modeled with a simple biexponential equation, although the fitting parameters do not show any strong correlation to internuclear distances. Nevertheless, these parameters provide a wealth of invaluable semiquantitative structural constraints for the M0Aβ1-42. The results presented here offer a complete protocol for recording PAR 13C-13C correlation spectra with high-efficiency and using the resulting information in protein structural studies.


Characterizing Reimbursements for Medicare Patients Receiving Endovascular Abdominal Aortic Aneurysm Repair at Vascular Quality Initiative Centers.
Endovascular aortic aneurysm repair (EVR) has a major financial impact on health care systems. We characterized reimbursement for index EVR hospitalizations among Medicare beneficiaries having surgery at Vascular Quality Initiative (VQI) centers. We linked Medicare claims to VQI clinical registry data for patients undergoing EVR from 2003 to 2015. Analysis was limited to patients fully covered by fee-for-service Medicare parts A and B in the year of their operation and assigned a corresponding diagnosis-related group for EVR. The primary outcome was Medicare's reimbursement for inpatient hospital and professional services, adjusted to 2015 dollars. We performed descriptive analysis of reimbursement over time and univariate analysis to evaluate patient demographics, clinical characteristics, procedural variables, and postoperative events associated with reimbursement. This informed a multilevel regression model used to identify factors independently associated with EVR reimbursement and quantify VQI center-level variation in reimbursement. We studied 9,403 Medicare patients who underwent EVR at VQI centers during the study period. Reimbursements declined from $37,450 ± $9,350 (mean ± standard deviation) in 2003 to $27,723 ± $10,613 in 2015 (test for trend, P < 0.001). For patients experiencing a complication (n = 773; 8.2%), mean reimbursement for EVR was $44,858 ± $23,825 versus $28,857 ± $9,258 for those without complications (P < 0.001). Intestinal ischemia, new dialysis requirement, and respiratory compromise each doubled Medicare's average reimbursement for EVR. After adjusting for diagnosis-related group, several patient-level factors were independently associated with higher Medicare reimbursement; these included ruptured abdominal aortic aneurysm (+$2,372), additional day in length of stay (+$1,275), and being unfit for open repair (+$501). Controlling for patient-level factors, 4-fold variation in average reimbursement was seen across VQI centers. Reimbursement for EVR declined between 2003 and 2015. We identified preoperative clinical factors independently associated with reimbursement and quantified the impact of different postoperative complications on reimbursement. More work is needed to better understand the substantial variation observed in reimbursement at the center level.


Nonreciprocal packaging of human immunodeficiency virus type 1 and type 2 RNA: a possible role for the p2 domain of Gag in RNA encapsidation.
The ability of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) to cross-package each other's RNA was investigated by cotransfecting helper virus constructs with vectors derived from both viruses from which the gag and pol sequences had been removed. HIV-1 was able to package both HIV-1 and HIV-2 vector RNA. The unspliced HIV-1 vector RNA was packaged preferentially over spliced RNA; however, unspliced and spliced HIV-2 vector RNA were packaged in proportion to their cytoplasmic concentrations. The HIV-2 helper virus was unable to package the HIV-1 vector RNA, indicating a nonreciprocal RNA packaging relationship between these two lentiviruses. Chimeric proviruses based on HIV-2 were constructed to identify the regions of the HIV-1 Gag protein conferring RNA-packaging specificity for the HIV-1 packaging signal. Two chimeric viruses were constructed in which domains within the HIV-2 gag gene were replaced by the corresponding domains in HIV-1, and the ability of the chimeric proviruses to encapsidate an HIV-1-based vector was studied. Wild-type HIV-2 was unable to package the HIV-1-based vector; however, replacement of the HIV-2 nucleocapsid by that of HIV-1 generated a virus with normal protein processing which could package the HIV-1-based vector. The chimeric viruses retained the ability to package HIV-2 genomic RNA, providing further evidence for a lack of reciprocity in RNA-packaging ability between the HIV-1 and HIV-2 nucleocapsid proteins. Inclusion of the p2 domain of HIV-1 Gag in the chimera significantly enhanced packaging.


Hospital computing and the costs and quality of care: a national study.
Many believe that computerization will improve health care quality, reduce costs, and increase administrative efficiency. However, no previous studies have examined computerization's cost and quality impacts at a diverse national sample of hospitals. We linked data from an annual survey of computerization at approximately 4000 hospitals for the period from 2003 to 2007 with administrative cost data from Medicare Cost Reports and cost and quality data from the 2008 Dartmouth Health Atlas. We calculated an overall computerization score and 3 subscores based on 24 individual computer applications, including the use of computerized practitioner order entry and electronic medical records. We analyzed whether more computerized hospitals had lower costs of care or administration, or better quality. We also compared hospitals included on a list of the "100 Most Wired" with others. More computerized hospitals had higher total costs in bivariate analyses (r=0.06, P=.001) but not multivariate analyses (P=.69). Neither overall computerization scores nor subscores were consistently related to administrative costs, but hospitals that increased computerization faster had more rapid administrative cost increases (P=.0001). Higher overall computerization scores correlated weakly with better quality scores for acute myocardial infarction (r=0.07, P=.003), but not for heart failure, pneumonia, or the 3 conditions combined. In multivariate analyses, more computerized hospitals had slightly better quality. Hospitals on the "Most Wired" list performed no better than others on quality, costs, or administrative costs. As currently implemented, hospital computing might modestly improve process measures of quality but does not reduce administrative or overall costs.


[Results of the effectiveness of long-term treatment of patients with benign prostatic hyperplasia].
A long-term proskar (finasterid, MSD) treatment was given to 428 patients with benign prostatic hyperplasia (BPH). The response was achieved in 93.8-95.8% patients. The duration of the course should be at least 12 months. Side effects were rare: libido, erection, ejaculate volume diminished in 5.1, 5.6 and 4.2% patients, respectively. 20 patients were operated on after proskar therapy. Such pretreatment reduced glandular prostatic tissue.


Prdm1a directly activates foxd3 and tfap2a during zebrafish neural crest specification.
The neural crest comprises multipotent precursor cells that are induced at the neural plate border by a series of complex signaling and genetic interactions. Several transcription factors, termed neural crest specifiers, are necessary for early neural crest development; however, the nature of their interactions and regulation is not well understood. Here, we have established that the PR/SET domain-containing transcription factor Prdm1a is co-expressed with two essential neural crest specifiers, foxd3 and tfap2a, at the neural plate border. Through rescue experiments, chromatin immunoprecipitation and reporter assays, we have determined that Prdm1a directly binds to and transcriptionally activates enhancers for foxd3 and tfap2a and that they are functional, direct targets of Prdm1a at the neural plate border. Additionally, analysis of dominant activator and dominant repressor Prdm1a constructs suggests that Prdm1a is required both as a transcriptional activator and transcriptional repressor for neural crest development in zebrafish embryos.


Laparotomic vs. laparoscopic rectopexy in complete rectal prolapse.
The aim of this study was to compare the functional and clinical results of laparotomic and laparoscopic rectopexy in 2 homogeneous groups of patients with complete rectal prolapse and fecal incontinence. Between January 1989 and December 1997, twenty-three patients underwent abdominal rectopexy. Thirteen patients (group A, 12 females and 1 male, mean age 57.3, range 22-76 years), and 10 patients (group B, 10 females, mean age 52.3, range 26-70 years) were submitted respectively to either Wells laparotomic or laparoscopic rectopexy by the same surgical team using the same surgical technique and materials. Before the operation a detailed clinical history was collected, and the patients were studied by inspection and digital examination of the anorectum, proctosigmoidoscopy, pancolonic transit time, dynamic defecography, anorectal manometry and anal electromyography. After the operation all patients underwent perineal physiotherapy, external electric stimulation, and perineal biofeedback. Mean follow-up was 37.1 (range 6-90) months in group A and 25.7 (range 6-49) months in group B. Values were compared by chi(2), Mann-Whitney U, and Wilcoxon tests as appropriate. Differences were considered significant at p < 0.05. In both groups dyschezia and fecal incontinence improved significantly (p < 0.05) after the operation. The basal pressure of the anal sphincter, squeezing pressure and rectoanal reflex improved without significance, and anal-perineal pain was not significantly reduced. In group B the postoperative hospital stay was lower than in group A, with a reduction in costs. Laparoscopic Wells rectopexy has the same clinical and functional results as laparotomic rectopexy, but with a shorter postoperative hospital stay and lower costs.


Delaying time to first nocturnal void may have beneficial effects on reducing blood glucose levels.
Experimental studies disrupting sleep and epidemiologic studies of short sleep durations indicate the importance of deeper and longer sleep for cardiometabolic health. We examined the potential beneficial effects of lengthening the first uninterrupted sleep period (FUSP) on blood glucose. Long-term data (≥3 months of treatment) were derived from three clinical trials, testing low-dose (10-100 µg) melt formulations of desmopressin in 841 male and female nocturia patients (90 % of which had nocturnal polyuria). We performed post hoc multiple regression with non-fasting blood glucose as dependent variable and the following potential covariates/factors: time-averaged change of FUSP since baseline, age, gender, race, ethnicity, baseline glucose, baseline weight, change in weight, patient metabolic status (normal, metabolic syndrome, type II diabetes), dose, follow-up interval, and time of random glucose sampling. Increases in FUSP resulted in statistically significant reductions in blood glucose (p = 0.0131), even after controlling for all remaining covariates. Per hour increase in time to first void was associated with glucose decreases of 1.6 mg/dL. This association was more pronounced in patients with increased baseline glucose levels (test of baseline glucose by FUSP change interaction: p < 0.0001). Next to FUSP change, other statistically significant confounding factors/covariates also associated with glucose changes were gender, ethnicity, metabolic subgroup, and baseline glucose. These analyses indicate that delaying time to first void may have beneficial effects on reducing blood glucose in nocturia patients. These data are among the first to suggest that improving sleep may have salutary effects on a cardiometabolic measure.


Fatigue Risk Management: The Impact of Anesthesiology Residents' Work Schedules on Job Performance and a Review of Potential Countermeasures.
Long duty periods and overnight call shifts impair physicians' performance on measures of vigilance, psychomotor functioning, alertness, and mood. Anesthesiology residents typically work between 64 and 70 hours per week and are often required to work 24 hours or overnight shifts, sometimes taking call every third night. Mitigating the effects of sleep loss, circadian misalignment, and sleep inertia requires an understanding of the relationship among work schedules, fatigue, and job performance. This article reviews the current Accreditation Council for Graduate Medical Education guidelines for resident duty hours, examines how anesthesiologists' work schedules can affect job performance, and discusses the ramifications of overnight and prolonged duty hours on patient safety and resident well-being. We then propose countermeasures that have been implemented to mitigate the effects of fatigue and describe how training programs or practice groups who must work overnight can adapt these strategies for use in a hospital setting. Countermeasures include the use of scheduling interventions, strategic naps, microbreaks, caffeine use during overnight and extended shifts, and the use of bright lights in the clinical setting when possible or personal blue light devices when the room lights must be turned off. Although this review focuses primarily on anesthesiology residents in training, many of the mitigation strategies described here can be used effectively by physicians in practice.


Selecting speed-dependent pathways for a programmable nanoscale texture by wet interfaces.
The realization of well-defined and ordered structures on the nanoscale is a main issue in nanoscience and nanotechnology, biotechnology and other related fields like plastic or organic electronics. Among the bottom-up approaches, to date, self-assembly (equilibrium aggregates) received a major attention. In spite of this, far from equilibrium conditions allow for the generation of a wider landscape of organized systems depending on the set of control parameters employed. Under an adaptation vision of the structures, here we report some case studies showing how it is possible to programme and control the nanoscale features of ordered super- or supra-aggregates at wet interfaces by modulating the dynamic parameters. In particular, speed is foreseen as a threshold factor for changing the aggregation mechanism along with the shape and degree of order of the structures as well as, within a specific aggregation path, their size and defectivity.


The pathogenesis of cingulate atrophy in behavioral variant frontotemporal dementia and Alzheimer's disease.
Early atrophy of the cingulate cortex is a feature of both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), with degeneration of the anterior cingulate region increasingly recognized as a strong predictor of bvFTD. The total number of neurons in this region, rather than the density of neurons, is associated with mood disturbance in other dementias, although there are no data on the extent and magnitude of neuronal loss in patients with bvFTD. While the density of small populations of neurons in this region has been assessed, it is unlikely that the degree of atrophy of the cingulate cortex seen in bvFTD can be explained by the loss of these subpopulations. This suggests that there is more generalized degeneration of neurons in this region in bvFTD.The present study assesses total neuronal number, as well as characteristic pathologies, in the anterior and posterior cingulate cortices of pathologically confirmed bvFTD (N = 11) and AD (N = 9) patients compared with age-matched controls (N = 14). The bvFTD cohort comprised 5 cases with tau pathology (Pick's disease), and 6 with TDP-43 pathology. At postmortem, atrophy was detected in the anterior and posterior cingulate cortices of bvFTD cases, but only in the posterior cingulate cortex of AD cases. As predicted, there was a significant reduction in both the density and total number of neurons in the anterior but not the posterior cingulate cortex of bvFTD cases with the opposite observed for the AD cases. Importantly, neuronal loss in the anterior cingulate cortex was only observed in cases with tau pathology. This study confirms significant neuronal loss in the posterior but not anterior cingulate cortex in AD, and demonstrates that significant neuron loss in bvFTD occurs only in the anterior cingulate cortex but only in cases with tau pathology compared with cases with TDP pathology. We propose that significant neurodegeneration in the anterior cingulate cortex may be useful in differentiating the pathological subtypes in vivo.


The inflammatory cytokine interleukin-23 is elevated in lung cancer, particularly small cell type.
Interleukin (IL)-17 and IL-23 play roles in inflammation and autoimmunity. The function of the IL-17/IL-23 pathway has not been completely evaluated in cancer patients. We aimed to investigate serum IL-17 and IL-23 levels and their relationship with clinicopathological and biochemical parameters in lung cancer patients. Forty-five lung cancer patients and 46 healthy volunteers were included in the study. IL-17 and IL-23 measurements were made with the ELISA method. The ages of patients (53-84 years) and healthy subjects (42-82 years) were similar. Serum IL-23 levels were higher in lung cancer patients than in healthy subjects (491.27 ±1263.38 pg/ml vs. 240.51 ±233.18 pg/ml; p = 0.032). IL-23 values were higher in small cell lung cancer (SCLC) patients than in non-small cell lung cancer (NSCLC) patients (1325.30 ±2478.06 pg/ml vs. 229.15 ±103.22 pg/ml; p = 0.043). Serum IL-17 levels were lower in the patients, but the difference was not statistically significant (135.94 ±52.36 pg/ml vs. 171.33 ±133.51 pg/ml; p = 0.124). Presence of comorbid disease (diabetes mellitus, hypertension or chronic obstructive lung disease) did not have any effect on the levels of IL-17 or IL-23. Erythrocyte sedimentation rate values were positively correlated with cytokine levels, but serum albumin levels were negatively correlated. Serum IL-23 levels are elevated in lung cancer patients, particularly those with SCLC. IL-17 and IL-23 values are correlated with inflammatory markers in the patients.


Advancing evidence-based digital health through an innovative research environment: an academic-industry collaboration case report.
The proliferation of technology enthuses clinicians, researchers, and entrepreneurs to revolutionize health care and care delivery. Intersecting in the field of digital health, academic-industry collaboration (AIC) play a critical role in advancing evidence-based innovations into real world application. AIC models vary, but historically have not included the strong emphasis on rapid research and discovery that the digital health field demands. Due to the voluminous availability of real time patient and client data, academic health centers offer a rich interdisciplinary environment to develop, pilot and evaluate innovations in pragmatic settings. Despite the opportunity between academic health centers and industry to advance digital health innovation through rapid research, limited evidence exists of such collaboration. The purpose of this case report is to examine an AIC facilitating research of new health technologies within an academic health center. This paper presents a case report involving collaboration between diverse technology industry partners and an academic health center that encompasses a university health system (UCHealth), a university technology transfer office (CU Innovations), an innovation center (CARE Innovation Center), and research collaborators (mHealth Impact Laboratory). Case assertions discuss the lessons learned and recommendations when implementing such collaboration in practice. The principal finding is that academic health centers offer an innovative environment for AIC in digital health. Collaborations between academia and industry provide much promise in ensuring health innovations are scientifically sound while meeting the needs of a rapidly evolving technical climate.


Apoptosis in human hepatoma cell lines by chemotherapeutic drugs via Fas-dependent and Fas-independent pathways.
Many chemotherapeutic drugs have been found to exert their mode of action via induction of apoptosis in cancer cells. The mechanisms involved in this process are not clear. Recent studies have shown that the Fas/Fas ligand (FasL) system is a key factor controlling apoptotic cell death. In the present study, the involvement of Fas in chemotherapeutic drug-induced apoptosis in hepatoma cell lines was investigated. Five different human hepatoma cell lines, Hep G2, Hep G2.2.15, Hep 3B, SK-Hep-1, and PLC/PRF/5, were used. It was found that they expressed different levels of Fas. However, all five cell lines were susceptible to apoptosis when treated with chemotherapeutic drugs such as 5-fluorouracil (5-FU) or cisplatin. In Hep G2 that constitutively expressed Fas, 5-FU or cisplatin treatment caused an increase in the expression of Fas before the formation of oligonucleosomal DNA fragments, a typical feature of apoptosis. However, in Hep 3B, where Fas is undetectable, apoptosis could also be induced by 5-FU or cisplatin without induction of Fas. The agonistic anti-Fas antibody (CH-11) was capable of inducing apoptosis by itself and promoted drug-induced apoptosis in Hep G2 but not in Hep 3B. The antagonistic anti-Fas antibody (ZB4) inhibited drug-induced apoptosis in Hep G2. Our results suggest that apoptosis can be induced in hepatoma cell lines via both Fas-dependent and Fas-independent pathways.


Potassium-argon ages of lunar rocks from mare tranquillitatis and oceanus procellarum.
Crystalline rocks from Mare Tranquillitatis have yielded potassium-argon dates as old as 3.8 x 10(9) years. Crystalline rocks from Oceanus Procellarum give potassium-argon ages as old as 2.8 x 10(9) years. Evidently the maria are ancient features of the moon and were not formed contemporaneously, a conclusion that also has been verified by other methods. The potassium-argon ages of rocks from Oceanus Procellarum show much more loss of argon than the rocks from Mare Tranquillitatis, an indication that the rocks at Oceanus Procellarum have experienced more severe shock effects or longer cooling rates.


Collagen fibril diameter distributions in rabbit anterior cruciate and medial collateral ligaments: changes with maturation.
This study presents morphometric analyses of the collagen fibril diameters of rabbit anterior cruciate and medial collateral knee ligaments of New Zealand White rabbits (young, age two months and adult, age thirty-six to forty months). Measurements were made from transmission electron micrographs of transverse ligament sections of approximately 50,000x magnification. Statistically significant differences in the mean fibril diameters were found between the anterior cruciate and medial collateral ligaments of the thirty-six to forty month old animals (.069 +/- .005, .092 +/- .016 mm, p < .1); however, no statistical significance was found for differences between these ligaments in two month old animals (.077 +/- .006, .082 +/- .009, p > .1). These data support the idea that known differences in fibril distributions of adult rabbit anterior cruciate and medial collateral ligaments develop with maturation, and may reflect both the cellular environment in which the fibrocytes of these ligaments are subject to, as well as the developmental genetic program of these cell populations.


Long-term risk of aneurysmal subarachnoid hemorrhage after a negative aneurysm screen.
The objective was to assess the risk of aneurysmal subarachnoid hemorrhage (aSAH) in the initial 15 years after negative aneurysm screening in persons with one first-degree relative with aSAH. From a cohort of first-degree relatives of patients with aSAH who underwent screening between 1995 and 1997 (n = 626), we included those with a negative screening (n = 601). We retrieved all causes of death and sent a questionnaire to screenees who were still alive. If aSAH was reported, we reviewed all medical data. We assessed the incidence of aSAH in this cohort with survival analysis and calculated an incidence ratio by dividing the observed incidence with the age- and sex-adjusted incidence in the general population. Of the 601 screenees, 3 had aSAH during 8,938 follow-up patient-years (mean 14.9 years). After 15 years, the cumulative incidence was 0.50% (95% confidence interval: 0.00%-1.06%) with an incidence rate of 33.6 per 100,000 person-years; the incidence rate ratio was 1.7 (95% confidence interval: 0.3-5.7). In the first 15 years after a negative screening, the risk of aSAH in persons with one first-degree relative with aSAH is not nil, but in the range of that in the general population, or even higher. Whether this finding justifies serial aneurysm screening in this population requires further study.


Limited spatial response to direct predation risk by African herbivores following predator reintroduction.
Predators affect ecosystems not only through direct mortality of prey, but also through risk effects on prey behavior, which can exert strong influences on ecosystem function and prey fitness. However, how functionally different prey species respond to predation risk and how prey strategies vary across ecosystems and in response to predator reintroduction are poorly understood. We investigated the spatial distributions of six African herbivores varying in foraging strategy and body size in response to environmental factors and direct predation risk by recently reintroduced lions in the thicket biome of the Addo Elephant National Park, South Africa, using camera trap surveys, GPS telemetry, kill site locations and Light Detection and Ranging. Spatial distributions of all species, apart from buffalo, were driven primarily by environmental factors, with limited responses to direct predation risk. Responses to predation risk were instead indirect, with species distributions driven by environmental factors, and diel patterns being particularly pronounced. Grazers were more responsive to the measured variables than browsers, with more observations in open areas. Terrain ruggedness was a stronger predictor of browser distributions than was vegetation density. Buffalo was the only species to respond to predator encounter risk, avoiding areas with higher lion utilization. Buffalo therefore behaved in similar ways to when lions were absent from the study area. Our results suggest that direct predation risk effects are relatively weak when predator densities are low and the time since reintroduction is short and emphasize the need for robust, long-term monitoring of predator reintroductions to place such events in the broader context of predation risk effects.