Dietary carotenoids and risk of breast cancer in Chinese women.
There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, the protective effect of carotenoids on breast cancer has been inconclusive. To investigate whether intake of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin is inversely associated with breast cancer risk, a case-control study was conducted in China during 2004-2005. The cases were 122 female patients aged 24-87 years with histopathologically confirmed breast cancer. 632 healthy women age-matched were randomly recruited from outpatient clinics. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable food frequency questionnaire. The USDA nutrient composition database was used to calculate intake of the specific carotenoids. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), accounting for age, locality, education, body mass index, smoking, passive smoking, physical activity, number of children breastfed, menopausal status, oral contraceptive use, biopsy-confirmed benign breast diseases, family history of breast cancer, and total energy intake. Compared with the highest versus lowest quartile of intake, the adjusted ORs were 0.26 (95% CI 0.14-0.46) for lycopene, 0.38 (95% CI 0.21-0.71) for beta-carotene, 0.43 (95% CI 0.23-0.82) for beta-cryptoxanthin, and 0.37 (95% CI 0.20-0.68) for total carotenoids, with statistically significant tests for trend. There was no association with breast cancer for alpha-carotene and lutein/zeaxanthin. It is concluded that higher intake of lycopene, beta-carotene and beta-cryptoxanthin is associated to a lower risk of breast cancer among Chinese women. More research to examine the relationship between carotenoids and breast cancer risk is warranted.


Morphing and vectoring impacting droplets by means of wettability-engineered surfaces.
Driven by its importance in nature and technology, droplet impact on solid surfaces has been studied for decades. To date, research on control of droplet impact outcome has focused on optimizing pre-impact parameters, e.g., droplet size and velocity. Here we follow a different, post-impact, surface engineering approach yielding controlled vectoring and morphing of droplets during and after impact. Surfaces with patterned domains of extreme wettability (high or low) are fabricated and implemented for controlling the impact process during and even after rebound--a previously neglected aspect of impact studies on non-wetting surfaces. For non-rebound cases, droplets can be morphed from spheres to complex shapes--without unwanted loss of liquid. The procedure relies on competition between surface tension and fluid inertial forces, and harnesses the naturally occurring contact-line pinning mechanisms at sharp wettability changes to create viable dry regions in the spread liquid volume. Utilizing the same forces central to morphing, we demonstrate the ability to rebound orthogonally-impacting droplets with an additional non-orthogonal velocity component. We theoretically analyze this capability and derive a We(-.25) dependence of the lateral restitution coefficient. This study offers wettability-engineered surfaces as a new approach to manipulate impacting droplet microvolumes, with ramifications for surface microfluidics and fluid-assisted templating applications.


Dipole source analysis of laser-evoked subdural potentials recorded from parasylvian cortex in humans.
The location of the human nociceptive area(s) near the Sylvian fissure is still controversial in spite of evidence from imaging and evoked potential studies that noxious heat stimuli activate somatosensory areas in that region. Some studies have suggested the secondary somatosensory cortex (SII) on the upper bank of the Sylvian fissure posterior to the central sulcus, others the anterior insula or parietal area 7b. In this study, we applied dipole source analysis techniques to laser-evoked potentials (LEPs) that were recorded from subdural grid electrodes in three patients. As a functional marker, auditory-evoked potentials (AEPs) with a generator on the opposite bank of the Sylvian fissure were recorded from the same electrodes. The LEP global field power (GFP), a measure of spatial variance, showed a first peak at about 150 ms latency, corresponding to the latency of the N1 recorded from the scalp. In contrast to scalp recordings, the amplitude of the first GFP peak recorded from the grid was larger than the second peak (P2). This finding suggests that the generator of N1, but not that of later LEP components, was close to the subdural grids. When a regional source was fitted to the first GFP peak, its location was within the frontoparietal operculum in all patients. On average, the LEP source was 13 mm anterior, 6 mm superior, and 2 mm medial of the AEP source. This relative location also suggests a source within the frontoparietal operculum overlying the insula. At the latency of the first GFP peak, source orientation pointed inward, suggesting a generator within the inner vertical surface of the operculum. Somatotopy was assessed in one patient and was consistent with that of the projection area of the presumed nociceptive thalamic nucleus posterior part of the ventromedial nucleus, but differed from that of SII. These findings suggest that the nociceptive area in human parasylvian cortex that is activated most rapidly by noxious heat pulses may be separate from the tactile SII area.


Isolation and characterization of a mutant of Saccharomyces cerevisiae with pleiotropic deficiencies in transcriptional activation and repression.
The isolation of the dep1 mutant of Saccharomyces cerevisiae is reported. The mutant was identified by its disability to regulate expression of structural genes involved in phospholipid biosynthesis, INO1, CHO1 and OPI3, in response to supplementation with soluble lipid precursors. Expression of the INO1, CHO1 and OPI3 genes was not fully derepressed in the absence of soluble lipid precursors, inositol and choline in the dep1 mutant, as compared to wild type. The mutant also exhibited incomplete repression of these same genes in the presence of inositol and choline. Repression by phosphate of the PHO5 gene was reduced in the mutant, as was derepression of this gene in the absence of phosphate. In addition, we show that expression of INO1 and OPI3 structural genes is strongly dependent on the growth phase both in wild-type and dep1 mutant strains. However, in the mutant, elevated basal steady-state mRNA levels were reached in the late stationary growth phase, independent of supplementation conditions. The dep1 mutation represents a new complementation group with respect to phospholipid synthesis and was mapped to a position of about 12 cM distal from the centromere on the left arm of chromosome I. Deficiencies in transcription activation and repression of metabolically unrelated genes, as well as reduced mating efficiency and lack of sporulation of homozygous diploid dep1/dep1 mutants indicate a pleiotropic regulatory function of the DEP1 gene product. Thus, Dep1p appears to be a new member of a class of transcriptional modulators, including Rpd1p/Sin3p/Ume4p/Sdi1p/Gam3p, Rpd3p, Spt10p and Spt21p.


Integrated training for aphasia: an application of part-whole learning to treat lexical retrieval, sentence production, and discourse-level communications in three cases of nonfluent aphasia.
The purpose of this study was to evaluate integrated training for aphasia (ITA), a multicomponent language-production treatment based on part-whole learning that systematically trains lexical retrieval, sentence production, and discourse-level communications. Specific research objectives were to evaluate acquisition of target structures, statistical parameters associated with learning variables, treatment generalization, and the efficacy of individual treatment components. ITA was administered to 3 individuals with nonfluent aphasia following a multiple-baseline, across-behaviors design. Effect size and correlational coefficients were computed to assess acquisition, generalization, and maintenance of target structures. Standardized tests and a treatment efficacy questionnaire were also completed. A significant treatment effect was found in 2 of the 3 participants. In addition, as is seen in normal skill acquisition, practice time and error rate were significantly correlated. All participants demonstrated evidence of generalization on standardized language measures. Only 1 participant improved, however, on the communication measures. Results of the treatment component analysis revealed significant differences in the perceived efficacy of individual therapy tasks. Findings add to the evidence supporting multicomponent aphasia treatments, provide preliminary support for ITA and the application of a part-whole learning approach, and suggest that specific treatment components may contribute differentially to outcomes and generalization effects.


Coping and resilience among ethnoracial individuals experiencing homelessness and mental illness.
The multiple challenges that ethnoracial homeless individuals experiencing mental illness face are well documented. However, little is known about how this homeless subpopulation copes with the compounding stressors of racial discrimination, homelessness and mental illness. This study is an in-depth investigation of the personal perceived strengths, attitudes and coping behaviors of homeless adults of diverse ethnoracial backgrounds experiencing homelessness and mental illness in Toronto, Canada. Using qualitative methods, 36 in-depth semi-structured interviews were conducted to capture the perspectives of ethnoracial homeless participants with mental illness on coping and resilience. Transcripts were analyzed using thematic analysis. Similar to prior findings in the general homeless population, study participants recognized personal strengths and attitudes as great sources of coping and resilience, describing hope and optimism, self-esteem and confidence, insight into their challenges and spirituality as instrumental to overcoming current challenges. In addition, participants described several coping strategies, including seeking support from family, friends and professionals; socializing with peers; engaging in meaningful activities; distancing from overwhelming challenges; and finding an anchor. Findings suggest that homeless adults with mental illness from ethnoracial groups use similar coping strategies and sources of resilience with the general homeless population and highlight the need for existing services to foster hope, recognize and support individual coping strategies and sources of resilience of homeless individuals experiencing complex challenges.


Therapeutic and Protective Potency of Bee Pollen Against Neurotoxic Effects Induced by Prenatal Exposure of Rats to Methyl Mercury.
MeHg is a widely distributed environmental toxicant with harmful effects on the developing and adult nervous system. This study aimed to evaluate the therapeutic and protective efficacy of pollen grain in improving the toxic effects of MeHg, through the measurement of selected biochemical parameters linked to oxidative stress, energy metabolism, and neurotransmission in brain homogenates of male pups' neonates. Forty healthy pregnant female rats were randomly divided into five groups, and after delivery, each group was consisting of 10 male neonates: (1) neonates delivered by control mothers, (2) neonates delivered by bee pollen treated mothers who received bee pollen at the dose of 200-mg/kg body weight from postnatal day 0 for 4 weeks, (3) neonates delivered by MeHg-treated mothers who received MeHg at the dose of 0.5 mg/kg/day via drinking water from gestational day 7 till postnatal day 7 of delivery, (4) therapeutic group: neonates delivered by MeHg-treated mothers followed by bee pollen treatment who received bee pollen at the dose of 200-mg/kg body weight from postnatal day 0 for 4 weeks, and (5) protective group: neonates delivered by MeHg and bee pollen-treated mothers. Mothers continued receiving the bee pollen at the same dose until day 21. Biochemical parameters linked to oxidative stress and energy metabolism and neurotransmission were investigated in brain homogenates of neonates from all the five groups. MeHg treatment showed an increase in oxidative stress markers like lipid peroxidation and catalase activity coupled with a non-significant decrease in glutathione level. Impaired energy metabolism was ascertained via the inhibition of creatine kinase and lactate dehydrogenase activities. Dramatic decrease of Mg2+ and K+ concentrations confirmed the neurotransmission defect. Interestingly, the bee pollen treatment was highly effective in restoring the catalase, lactate dehydrogenase, and creatine kinase activities in addition to normalizing the levels of Mg2+, K+, lipid peroxidation, and glutathione. Overall, the exposure to MeHg during the developing brain stages was highly effective to show signs and symptoms of neuronal toxicity. Furthermore, it has been concluded that bee pollen can be used safely to ameliorate oxidative stress, poor detoxification as well as metal ion defects, and neuronal death as a critical mechanisms involved in the etiology of numerous neurological disorders.


Generation of correlated photon pairs in micro/nano-fibers.
We study the generation of correlated photon pairs via spontaneous four-wave mixing (SFWM) in a 15 cm long micro/nano-fiber (MNF). The MNF is properly fabricated to satisfy the phase-matching condition for generating the signal and idler photon pairs at wavelengths of about 1310 and 851 nm, respectively. Photon-counting measurements yield a coincidence-to-accidental ratio of 530 for a photon production rate of about 0.002 (0.0005) per pulse in the signal (idler) band. We also analyze the spectral information of the signal photons originating from SFWM and Raman scattering (RS). In addition to discovering some unique features of RS, we find the bandwidth of the individual signal photons is much greater than the calculated value for the MNF with homogeneous structure. Our investigations indicate the MNF is a promising candidate for developing the sources of nonclassical light and the spectral property of photon pairs can be used to noninvasively test the diameter and homogeneity of the MNF.


Signature patterns of DNA restriction fragments of Helicobacter pylori before and after treatment.
The genomic DNA of Helicobacter pylori was studied by electrophoretic analysis of restriction endonuclease fragments. Twenty seven isolates from eight patients in the United Kingdom, obtained before and after treatment with nitrofurantoin, and two reference strains from Australia and Peru were investigated. Digestion of DNA with HaeIII, which gave the clearest band pattern of the 20 enzymes tested, showed that each set of isolates from a single patient had a unique band pattern. The DNA signature band patterns of strains from different patients were less than or equal to 62% similar (average 43%); similarities of patterns from the same patient were generally greater than or equal to 86%. Some minor but reproducible polymorphisms (less than or equal to five bands) in the signature region were detected in most consecutive isolates. Plasmid DNA was detected in isolates from five patients, but major pattern differences were attributed to genomic variation. It is concluded that the HaeIII DNA digest signature fingerprints provide a reproducible and sensitive method of discriminating between isolates of H pylori.


Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial.
Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction. To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam. Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal. Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs 92%; P < .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P = .18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P = .48). In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion. clinicaltrials.gov Identifier: NCT00095251.


High-speed surface display through hybrid processing.
We propose a high-speed surface reconstruction from three-dimensional data through optical-digital hybrid processing.Surface images are currently reconstructed through digital processing, which takes a long time mainly because of the rotation and interpolation of the volume data. In the proposed system, slice images of threedimensional volume data are optically rotated and interpolated. In principle, one surface image can be obtained in the video rate when we use the same number of sets of optical processors as slices to be processed. Furthermore, this system could lead to a hybrid three-dimensional simulator; most operations such as rotation, cutting, digging holes, and peeling skins are interactively achieved at the video speed. Fundamental experiments are described that confirm the effectiveness of this method.


Alternative medicine, worker health, and absenteeism in the United States.
Health related absenteeism costs an estimated $153 billion annually in the United States (Witters and Agrawal, 2011).1 Chronic conditions (major contributors to absenteeism) are often successfully managed by Complementary and Alternative Medicine (CAM). As CAM becomes an increasingly visible component of healthcare, firms may wish to consider whether CAM therapies can help reduce illness-related absenteeism. This paper aims to extend the literature on healthcare utilization and absenteeism by exploring whether CAM treatment is associated with fewer workdays missed due to illness. Using the 2007 National Health Interview Survey (NHIS) and propensity score matching (PSM), this study estimates the relationship between visits to CAM practitioners, health, and illness-related absenteeism. In a sample of 8820 workers, the average annual number of workdays lost due to illness is 3.69. Visiting an acupuncturist correlates with lower absenteeism among men (1.182 fewer workdays missed, p<0.05), whereas visiting a naturopathic doctor correlates with 2.359 and 2.521 fewer workdays missed for women and men, respectively (both p<0.001). Active mind-body practices, massage, chiropractic and acupuncture treatments are all significantly associated with improved health. Estimates suggest that some CAM modalities correlate with lower absenteeism, and many correlate with improved health. Two limitations of this study are worth noting. First, a small proportion of the sample uses CAM, limiting the generalizability of results. Second, if health conscious individuals are more likely to use CAM, then health attitudes may be contributing to lower absenteeism among the treated. Further research is needed to identify a causal relationship between CAM treatment, health, and absenteeism.


Adult liver transplantation and steroid-azathioprine withdrawal in cyclosporine (Sandimmun)-based immunosuppression - 5 year results of a prospective study.
New immunosuppressants are said to be superior to cyclosporine due to their higher incidence of steroid sparing and to the reduced incidence of side-effects. From May 1992 to February 1995, 79 adults underwent primary liver transplantation using cyclosporine A (Sandimmun)-based triple drug immunosuppression. Nine patients who died early after liver transplantation due to reasons unrelated to immunological problems were excluded from this analysis. The long-term outcome of the remaining 70 patients was prospectively studied in relation to steroid and azathioprine withdrawal. They were re-evaluated 6-monthly in relation to liver and kidney function; cholesterolemia, infection, de novo diabetes mellitus and arterial hypertension, malignancy, ophthalmological and osteomuscular diseases. In case of rejection occurring during or after steroid tapering, patients were switched, by protocol, to tacrolimus therapy. Median follow-up was 81 months (range 60-96). Forty-four patients (62.8 %) were biopsied 5 years after transplant; 20 patients (28.6 %) were biopsied at a median follow-up of 32 months (range 7.8-47). Six patients (8.6 %) who refused biopsies more than 1 year after liver transplantation had normal liver values throughout the whole follow-up period. Five-year actual patient and graft survivals were 75 % and 65.8 %, respectively, for the whole group (n = 79) and 85.7 % and 74.3 % for the studied group (n = 70). Steroids could be withdrawn in all but two patients (97.1 %) at a median time of 7 months (range 3-42). Steroids were restarted in six patients (8.6 %) for extrahepatic reasons. Freedom from steroids was thus observed in 62 patients (88.6 %). Seven patients (10 %) had rejection after steroid tapering; six were switched to tacrolimus. Two patients (2.9 %) needed retransplantation because of acute and chronic rejection whilst still being on full immunosuppression. In total, three patients (4.3 %) had histological signs of chronic rejection during follow-up. At 5 years post-transplant, 66.6 % and 13.3 % of the 60 patients at risk were on cyclosporine and tacrolimus monotherapy, respectively; 93.3 % were steroid-free. Mean creatinine and cholesterol levels were 1.56 +/- 1.3 mg/dl and 193.5 +/- 56.6 mg/dl; incidences of de novo arterial hypertension, insulin dependent diabetes mellitus were 26.6 % and 13.3 %. Two patients (2.8 %) developed post-transplant lymphoproliferative disease, two (2.8 %) had skin cancer. Cyclosporine-based immunosuppression allows safe steroid withdrawal in most patients and cyclosporine monotherapy can be achieved in two-thirds without compromising graft and patient survival. Results of new immunosuppressive strategies should be approached with caution, especially when considering steroid sparing and the incidence of side-effects.


The role of mRNA and protein stability in the function of coupled positive and negative feedback systems in eukaryotic cells.
Oscillators and switches are important elements of regulation in biological systems. These are composed of coupling negative feedback loops, which cause oscillations when delayed, and positive feedback loops, which lead to memory formation. Here, we examine the behavior of a coupled feedback system, the Negative Autoregulated Frustrated bistability motif (NAF). This motif is a combination of two previously explored motifs, the frustrated bistability motif (FBM) and the negative auto regulation motif (NAR), which both can produce oscillations. The NAF motif was previously suggested to govern long term memory formation in animals, and was used as a synthetic oscillator in bacteria. We build a mathematical model to analyze the dynamics of the NAF motif. We show analytically that the NAF motif requires an asymmetry in the strengths of activation and repression links in order to produce oscillations. We show that the effect of time delays in eukaryotic cells, originating from mRNA export and protein import, are negligible in this system. Based on the reported protein and mRNA half-lives in eukaryotic cells, we find that even though the NAF motif possesses the ability for oscillations, it mostly promotes constant protein expression at the biologically relevant parameter regimes.


Analysis of the Recomposition of Norms and Representations in the Field of Psychiatry and Mental Health in the Age of Electronic Mental Health: Qualitative Study.
For the World Health Organization, electronic health (eHealth) is seen as an effective way to improve therapeutic practices and disease prevention in health. Digital tools lead to major changes in the field of mental medicine, but specific analyses are required to understand and accompany these changes. Our objective was to highlight the positions of the different stakeholders of the mental health care system on eHealth services and tools, as well as to establish professional and user group profiles of these positions and the uses of these services. In order to acquire the opinions and expectations of different categories of people, we carried out a qualitative study based on 10 focus groups (n=70, from 3-12 people per group) composed of: general practitioners, psychiatrists, psychologists, social workers, occupational therapists, nurses, caregivers, mental health services users, user representatives, and the general public. The analyses of focus group discussions were performed independently by four investigators through a common analysis grid. The constant comparative method was adopted within this framework. The interviewees expressed different problems that new technologies engender in the field of mental health. What was previously strictly under the jurisdiction of physicians now tends to be fragmented and distributed over different groups and locations. New technologies reposition care in the field of domestic, rather than therapeutic, activities, and thus the conception of care as an autonomous activity in the subject's life is questioned. The ideal of social autonomy through technology is part of the new logic of health democracy and empowerment, which is linked to a strong, contemporary aspiration to perform. Participants emphasized that there was the potential risk of a decrease in autonomy for the digitally engaged patient, while personal empowerment could become a set of obligations. This qualitative research highlights the heterogeneity of opinions among the groups and within each group. It suggests that opinions on electronic mental health devices are still far from being stabilized, and that a change management process should be set up to both regulate the development and facilitate the use of these tools.


Prescribing of potentially inappropriate medications to elderly people.
To estimate the prevalence and predictors of medications deemed potentially inappropriate for the elderly among family physicians' patients aged 65 and older (seniors) taking multiple prescribed medications. Forty-eight randomly selected family practices in 16 towns and cities in Southern Ontario, Canada and 889 of their senior patients were recruited into a randomized trial. We conducted a cross-sectional analysis of prescription insurance data from the provincial universal prescription insurance database over 12 months, from the 777 seniors who completed the trial and agreed to have their data released. The prevalence and patient and physician predictors of use of a potentially inappropriate medication (PIM), as defined by published widely accepted criteria, were examined. The median number of prescriptions filled was 24. Nearly one-fifth (16.3%) of the seniors received at least one prescription for a PIM, with short-acting benzodiazepine prescriptions for longer than 30 days (6.4%) and oxybutynin (3.7%) being the types prescribed most frequently. In univariate and multiple variable analyses, women were found to be statistically significantly more likely to be prescribed a PIM (adjusted OR = 1.6; 95% confidence interval = 1.0-2.4). Age, education, self-rated health, number of health conditions, and number of prescriptions were not associated with PIM use. Physician gender, family medicine certification status, and time since graduation were not significantly associated with PIM prescribing. Prescribing of PIMs, especially of short-acting benzodiazepines was common in seniors taking multiple medications. Interventions to reduce use of PIM, especially long-term benzodiazepines, are important in primary care.


Membrane-type matrix metalloproteinases: Their functions and regulations.
Membrane-type matrix metalloproteinases (MT-MMPs) form a subgroup of the matrix metalloproteinase (MMP) family, and there are 6 MT-MMPs in humans. MT-MMPs are further sub-classified into type I transmembrane-type (MT1, -MT2-, MT3- and MT5-MMPs) and glycosylphosphatidylinositol (GPI)-anchored type (MT4- and MT6-MMPs). In either case MT-MMPs are tethered to the plasma membrane, and this cell surface expression provides those enzymes with unique functionalities affecting various cellular behaviours. Among the 6 MT-MMPs, MT1-MMP is the most investigated enzyme and many of its roles and regulations have been revealed to date, but the potential roles and regulatory mechanisms of other MT-MMPs are gradually getting clearer as well. Further investigations of MT-MMPs are likely to reveal novel pathophysiological mechanisms and potential therapeutic strategies for different diseases in the future.


Uterine and placental expression of HPGD in cows during pregnancy and release of fetal membranes.
15-Hydroxyprostaglandin dehydrogenase (HPGD) plays a key role in prostaglandins (PGs) catabolism. Its expression and activity appear to be regulated by progesterone (P4). We investigated the HPGD mRNA-expression and protein localization in placentomes and interplacental uterine sites throughout gestation (Study I), and after fetal membranes retention (RFM) compared with normally delivered fetal membranes (DFM) (Study II). Furthermore, we analyzed the influence of aglepristone (AP), dexamethasone (GC) or cloprostenol (CP), on HPGD expression in bovine placentomes (Study III). Tissues from late gestation (D272) and at normal term (NT) served as controls. HPGD was highest in all sites at the beginning of pregnancy and at (NT). Following induced parturition HPGD was lower after (AP) and (GC) compared with (NT), and was similar in RFM and DFM. Placentomes stained primarily in fetal compartments; interplacentomal signals were observed in endometrial glandular and luminal epithelium. Results indicate that HPGD may play a role during establishment and termination of gestation.


Absence of an Association between Macular Degeneration and Young-Onset Dementia.
A few population-based studies have reported an association between prior age-related macular degeneration and senile dementia. No study has explored a possible link between prior macular degeneration and young-onset dementia (YOD). This case-control study aimed to evaluate the association of YOD with prior macular degeneration diagnosed in the 5-year period before their index date. Data for this retrospective observational study were retrieved from Taiwan's National Health Insurance (NHI) dataset. A total of 36,577 patients with newly diagnosed YOD from January 2010 to December 2017 were identified as the study cohort, assigning their diagnosis date as their index date. Comparison patients were identified by propensity score-matching (three per case, n = 109,731 controls) from the remaining NHI beneficiaries of the period, their index date being the date of their first ambulatory care claim in the year of diagnosis of their matched YOD case. Chi-square test revealed no significant difference in the prevalence of prior macular degeneration between cases and controls (1.1% vs. 1.0%, p = 0.111). Conditional logistic regression analysis also showed an unadjusted odds ratio (OR) for prior macular degeneration of 1.098 among cases relative to controls (95% CI: 0.9797-1.232). Adjusted analysis confirmed that YOD was not associated with prior macular degeneration, adjusted odds ratio 1.098 (95% CI = 0.979-1.232). We conclude that patients with macular degeneration are not at increased risk for YOD.


Using ergonomics to enhance safe production at a surface coal mine--a case study with powder crews.
Job tasks that involve exposure to work-related musculoskeletal disorder (WMSD) risk factors may impact both the risk of injury and production downtime. Common WMSD risks factors associated with mining tasks include forceful exertions, awkward postures, repetitive motion, jolting and jarring, forceful gripping, contact stress, and whole body and segmental vibration. Mining environments that expose workers to temperature/humidity extremes, windy conditions, and slippery and uneven walking surfaces also contribute to injury risk. National Institute for Occupational Safety and Health (NIOSH) researchers worked with powder crew members from the Bridger Coal Company to identify and rank routine work tasks based on perceived exposure to WMSD risk factors. This article presents the process followed to identify tasks that workers believed involved the greatest exposure to risk factors and discusses risk reduction strategies. Specifically, the proposed prill truck design changes addressed cab ingress/egress, loading blast holes, and access to the upper deck of the prill truck.


In vivo changes in central and peripheral insulin sensitivity in a large animal model of obesity.
Obesity disrupts homeostatic energy balance circuits leading to insulin resistance. Here we examined in vivo peripheral and central insulin sensitivity, and whether central insensitivity in terms of the voluntary food intake (VFI) response occurs within the hypothalamus or at blood-brain transfer level, during obesity and after subsequent weight loss. Sheep with intracerebroventricular (i.c.v.) cannulae were fed complete diet for 40 wk ad libitum (obese group) or at control level (controls). Thereafter, obese sheep were food restricted (slimmers) and controls fed ad libitum (fatteners) for 16 wk. Dual-energy x-ray absorptiometry (DEXA) measured total body fat, insulin analyses in blood and cerebrospinal fluid (CSF) assessed blood-brain transfer, i.v. glucose tolerance test (GTT) and insulin tolerance test (ITT) measured peripheral insulin sensitivity, and VFI responses to icv insulin assessed intrahypothalamic sensitivity. Insulinemia was higher in obese than controls; plasma insulin correlated with DEXA body fat and CSF insulin. Insulinemia was higher in fatteners than slimmers but ratio of CSF to plasma insulin correlated only in fatteners. Plasma glucose baseline and area under the curve were higher during GTT and ITT in obese than controls and during ITT in fatteners than slimmers. GTT and ITT glucose area under the curve correlated with DEXA body fat. VFI decreased after i.c.v. insulin, with response magnitude correlating negatively with DEXA body fat. Overall, insulin resistance developed first in the periphery and then within the brain, thereafter correlating with adiposity; central resistance in terms of VFI response resulted from intrahypothalamic insensitivity rather than impaired blood-brain transfer; modest weight loss improved peripheral but not central insulin sensitivity and induced central hypoinsulinemia.


Consensus Recommendations for Combined Aesthetic Interventions in the Face Using Botulinum Toxin, Fillers, and Energy-Based Devices.
The aging process is a complex interplay of intrinsic and extrinsic factors across multiple layers of the face. Accordingly, combining aesthetic interventions targeting different manifestations of aging often leads to better results than single modalities alone. However, no guidelines for a pan-facial approach using multiple interventions have been published to date. To develop consensus recommendations for the optimal combination and ideal sequence of botulinum toxin (BoNT), hyaluronic acid, calcium hydroxylapatite, and microfocused ultrasound with visualization (MFU-V) in persons of all Fitzpatrick skin types. Fifteen specialists convened under the guidance of a certified moderator. Consensus was defined as approval from 75% to 94% of all participants, whereas agreement of ≥95% denoted a strong consensus. Optimal aesthetic treatment of the face begins with a thorough patient assessment and an individualized treatment plan. Spacing consecutive treatments 1 to 2 weeks apart allows for resolution of side effects and/or to assess results. For same-day treatments, BoNT and fillers may be performed together in either sequence, whereas MFU-V is recommended before injectable agents. Expert consensus supports a combination approach using multiple modalities in specific sequence for the safe and effective treatment of the aging face.


[Current management of venous malformations].
Venous malformations represent 2/3rds of all vascular malformations and are frequently much more complex than they appear to be. Patients with large venous malformations require a deep analytical and radiological study, as well as specific treatment to control any possible localised intravascular coagulation. If the lesions are extensive, especially in the lower member, a study should be made to detect the presence of an underlying osteoporosis with the idea of preventing pathological fractures. Equally, a check must be made for arthropathy, and an early prophylactic synovectomy must be considered when the radiological extension makes this advisable, with the idea of avoiding irreversible damage to the joints with the passage of time. Currently, microfoam scleropathy is favoured as the treatment of choice for low-flow vascular malformations. In the not too distant future, the use of selective antiangiogenic medicines, besides low-molecular-weight heparins, will serve to control and treat malformations.


Iatrogenic Ureteral Obstruction During Transvaginal Oocyte Retrieval.
Transvaginal oocyte retrieval is a crucial step in assisted reproductive technology. Various complications may arise during this procedure. Ureteral injury is a rare, but a serious complication in gynecological practice. During oocyte retrieval, ureteral injuries, detachment and obstruction can be seen, though rare. In this study, we will present ureteral obstruction that develops secondary to small hematoma, which mimics ovarian cyst torsion or ruptured ovarian cyst.


Curcumin inhibits the growth of AGS human gastric carcinoma cells in vitro and shows synergism with 5-fluorouracil.
The inhibitory effect of curcumin and its synergism with 5-fluorouracil (5-FU) on the growth of the AGS human gastric carcinoma cell line was examined. Cell cycle analysis was used to elucidate the mechanisms for the inhibition by curcumin. Curcumin significantly inhibited the growth of AGS cells in a dose- and time-dependent manner (P <.05). Curcumin caused a 34% decrease in AGS proliferation at 5 micromol/L, 51% at 10 micromol/L, and 92% at 25 micromol/L after 4 days of treatment. When curcumin (10 micromol/L) was removed after a 24-hour exposure, the growth pattern of curcumin-treated AGS cells was similar to that of control cells, suggesting reversibility of curcumin on the growth of AGS cells. Combining curcumin with 5-FU significantly increased growth inhibition of AGS cells compared with either curcumin or 5-FU alone (P <.05), suggesting synergistic actions of the two drugs. After 4 days of treatment with 10 micromol/L of curcumin, the G2/M phase fraction of cells was 60.5% compared with 22.0% of the control group, suggesting a G2/M block by curcumin treatment. Because the curcumin concentrations (5 micromol/L) used in our study were similar to steady-state concentrations (1.77 +/- 1.87 micromol/L) in human serum of subjects receiving chronic administration of a commonly recommended dose (8 g/day), curcumin may be useful for the treatment of gastric carcinoma, especially in conjunction with 5-FU.


Amplification of nuclear deformation of breast cancer cells by seeding on micropatterned surfaces to better distinguish their malignancies.
Information about the mechanical properties of cancer cells leads to new insights about their malignancy levels. The more flexible the cancer cells and their nuclei are, the more aggressive and invasive they are. Flexibility is a result of composition and properties of molecular constituents of cells and its extent is expressed by deformation. Differences in the mechanical properties could be modulated by topography and chemistry of the substrate. In this study, the main hypothesis is that the difference in the mechanical properties of malignant and benign breast cancer cells could be used as a discriminator of these cells and reflected by the extent of nuclear deformation on micropatterned substrates. We compared benign (MCF10A), malignantnoninvasive (MCF7), and malignant highly invasive (MDAMB231) breast cancer cell lines using their nuclear deformability on micropatterned surfaces designed with square prism-shaped micropillars of poly(methyl methacrylate) (PMMA) (8 μm high, 4 × 4 μm2 area, 4 μm gap). Several shape descriptors (circularity, solidity, roundness, aspect ratio) were used to analyze nuclear deformation. We were able to discriminate the three cells when the descriptor circularity and hydrophobic micropatterned surfaces were used. The cells showed nuclear deformability in the order following the extent of their malignancies. The most aggressive cell, MDAMB231, had the lowest circularity value, 0.37, whereas the noninvasive malignant, MCF7, and benign, MCF10A, cells had higher values 0.47 and 0.77, respectively. Mechanism of the deformation was shown at the molecular level that the expression of Lamin A/C and Nesprin-2 genes decreased with increased nuclear deformation. In summary, biomechanical properties of cells can provide useful information about their cancer state and they can be reflected in the biological markers.


Blood pressure in dementia, mild cognitive impairment, and subjective cognitive decline related to time of death.
It is unknown whether systolic blood pressure (SBP) drop is part of the normal aging process or due to the onset of dementia for some people. SBP drop is referring to the decrease in blood pressure often seen before death. Thus, the aim of this study was to examine whether SBP at time of diagnosis of dementia, mild cognitive impairment, or subjective cognitive decline was associated with years prior to death, and whether these associations were modified by diagnoses, age, and sex. Participants were 2,236 patients from the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog), who died during follow-up (2009-2017) for whom we had valid blood pressure measurements. Mean age at diagnosis was 77.5 years (SD 8.3), and patients were followed for an average of 3.9 years (SD 2.2, maximum 10.5 years). The patients had subjective cognitive decline (95), mild cognitive impairment (573), dementia (1,401), or no diagnoses related to cognitive deficits (167). SBP as dependent variable was regressed against years prior to death. In men, SBP was 1.8 mmHg lower per year closer to death (p < .01), and this trend was linear without any acceleration. This association between years prior to death and SBP in men was not modified by age, year of diagnosis, or diagnosis. There was no such association in women. SBP was significantly lower for those diagnosed close to death in men, but not in women. This association was not modified by either age or onset of diagnosis. Thus, the lowering of SBP is more related to closeness to death and sex than to dementia or age. The downward trend was linear all 10 years prior to death, with no acceleration closer to death.


Genetic variance and covariance patterns for body weight and energy balance characters in an advanced intercross population of mice.
We estimated heritabilities and genetic correlations for a suite of 15 characters in five functional groups in an advanced intercross population of over 2000 mice derived from a cross of inbred lines selected for high and low heat loss. Heritabilities averaged 0.56 for three body weights, 0.23 for two energy balance characters, 0.48 for three bone characters, 0.35 for four measures of adiposity, and 0.27 for three organ weights, all of which were generally consistent in magnitude with estimates derived in previous studies. Genetic correlations varied from -0.65 to +0.98, and were higher within these functional groups than between groups. These correlations generally conformed to a priori expectations, being positive in sign for energy expenditure and consumption (+0.24) and negative in sign for energy expenditure and adiposity (-0.17). The genetic correlations of adiposity with body weight at 3, 6, and 12 weeks of age (-0.29, -0.22, -0.26) all were negative in sign but not statistically significant. The independence of body weight and adiposity suggests that this advanced intercross population is ideal for a comprehensive discovery of genes controlling regulation of mammalian adiposity that are distinct from those for body weight.


The phosphoinositide 3-kinase pathway.
Phosphorylated lipids are produced at cellular membranes during signaling events and contribute to the recruitment and activation of various signaling components. The role of phosphoinositide 3-kinase (PI3K), which catalyzes the production of phosphatidylinositol-3,4,5-trisphosphate, in cell survival pathways; the regulation of gene expression and cell metabolism; and cytoskeletal rearrangements are highlighted. The PI3K pathway is implicated in human diseases including diabetes and cancer, and understanding the intricacies of this pathway may provide new avenues for therapuetic intervention.


Roles of reactive oxygen species-degrading enzymes of Francisella tularensis SCHU S4.
Francisella tularensis is a facultative intracellular bacterium utilizing macrophages as its primary intracellular habitat and is therefore highly capable of resisting the effects of reactive oxygen species (ROS), potent mediators of the bactericidal activity of macrophages. We investigated the roles of enzymes presumed to be important for protection against ROS. Four mutants of the highly virulent SCHU S4 strain with deletions of the genes encoding catalase (katG), glutathione peroxidase (gpx), a DyP-type peroxidase (FTT0086), or double deletion of FTT0086 and katG showed much increased susceptibility to hydrogen peroxide (H2O2) and slightly increased susceptibility to paraquat but not to peroxynitrite (ONOO(-)) and displayed intact intramacrophage replication. Nevertheless, mice infected with the double deletion mutant showed significantly longer survival than SCHU S4-infected mice. Unlike the aforementioned mutants, deletion of the gene coding for alkyl-hydroperoxide reductase subunit C (ahpC) generated a mutant much more susceptible to paraquat and ONOO(-) but not to H2O2. It showed intact replication in J774 cells but impaired replication in bone marrow-derived macrophages and in internal organs of mice. The live vaccine strain, LVS, is more susceptible than virulent strains to ROS-mediated killing and possesses a truncated form of FTT0086. Expression of the SCHU S4 FTT0086 gene rendered LVS more resistant to H2O2, which demonstrates that the SCHU S4 strain possesses additional detoxifying mechanisms. Collectively, the results demonstrate that SCHU S4 ROS-detoxifying enzymes have overlapping functions, and therefore, deletion of one or the other does not critically impair the intracellular replication or virulence, although AhpC appears to have a unique function.


Collaborative care clinician perceptions of computerized cognitive behavioral therapy for depression in primary care.
In Veterans Health Administration's (VA) Primary Care-Mental Health Integration (PC-MHI) models, primary care providers, care managers, and mental health clinicians collaboratively provide depression care. Primary care patients, however, still lack timely, sufficient access to psychotherapy treatment. Adapting PC-MHI collaborative care to improve uptake of evidence-based computerized cognitive behavioral therapy (cCBT) may be a potential solution. Understanding primary care-based mental health clinician perspectives is crucial for facilitating adoption of cCBT as part of collaborative depression care. We examined PC-MHI mental health clinicians' perspectives on adapting collaborative care models to support cCBT for VA primary care patients. We conducted 16 semi-structured interviews with PC-MHI nurse care managers, licensed social workers, psychologists, and psychiatrists in one VA health-care system. Interviews were audio-recorded, transcribed, coded using the constant comparative method, and analyzed for overarching themes. Although cCBT awareness and knowledge were not widespread, participants were highly accepting of enhancing PC-MHI models with cCBT for depression treatment. Participants supported cCBT delivery by a PC-MHI care manager or clinician and saw it as an additional tool to engage patients, particularly younger Veterans, in mental health treatment. They commented that current VA PC-MHI models did not facilitate, and had barriers to, use of online and mobile treatments. If effectively implemented, however, respondents thought it had potential to increase the number of patients they could treat. There is widespread interest in modernizing health systems. VA PC-MHI mental health clinicians appear open to adapting collaborative care to increase uptake of cCBT to improve psychotherapy access.


Design of wide-angle solar-selective absorbers using aperiodic metal-dielectric stacks.
Spectral control of the emissivity of surfaces is essential in applications such as solar thermal and thermophotovoltaic energy conversion in order to achieve the highest conversion efficiencies possible. We investigated the spectral performance of planar aperiodic metal-dielectric multilayer coatings for these applications. The response of the coatings was optimized for a target operational temperature using needle-optimization based on a transfer matrix approach. Excellent spectral selectivity was achieved over a wide angular range. These aperiodic metal-dielectric stacks have the potential to significantly increase the efficiency of thermophotovoltaic and solar thermal conversion systems. Optimal coatings for concentrated solar thermal conversion were modeled to have a thermal emissivity <7% at 720K while absorbing >94% of the incident light. In addition, optimized coatings for solar thermophotovoltaic applications were modeled to have thermal emissivity <16% at 1750K while absorbing >85% of the concentrated solar radiation.


Sesquiterpene variability in the gorgonian genus Plexaurella.
Gorgonian corals have proven to be a prolific source of a variety of biologically active terpenes. Corals of the genus Plexaurella are known to be the source of a diverse array of sesquiterpenes, and past reports have indicated variability in terpene content. This study involved an examination of the terpene chemistry of 109 individuals of five of the six known species of this genus in an attempt to identify links between sesquiterpene chemistry and species, location and depth. The data indicated a high level of variability of sesquiterpene content and essentially no correlation between species and sesquiterpene chemistry. There was also no correlation between location or depth and sesquiterpene content. We therefore conclude that Plexaurella spp. are chemically indistinguishable species with respect to terpene chemistry.


Protein phosphatase 2A in Saccharomyces cerevisiae: effects on cell growth and bud morphogenesis.
We have cloned three genes for protein phosphatases in the yeast Saccharomyces cerevisiae. Two of the genes, PPH21 and PPH22, encode highly similar proteins that are homologs of the mammalian protein phosphatase 2A (PP2A), while the third gene, PPH3, encodes a new PP2A-related protein. Disruptions of either PPH21 or PPH22 had no effects, but spores disrupted for both genes produced very small colonies with few surviving cells. We conclude that PP2A performs an important function in yeast cells. A disruption of the third gene, PPH3, did not in itself affect growth, but it completely prevented growth of spores disrupted for both PPH21 and PPH22. Thus, PPH3 provides some PP2A-complementing activity which allows for a limited growth of PP2A-deficient cells. Strains were constructed in which we could study the phenotypes caused by either excess PP2A or total PP2A depletion. We found that the level of PP2A activity has dramatic effects on cell shape. PP2A-depleted cells develop an abnormal pear-shaped morphology which is particularly pronounced in the growing bud. In contrast, overexpression of PP2A produces more elongated cells, and high-level overexpression causes a balloonlike phenotype with huge swollen cells filled by large vacuoles.


A role for rheumatoid factor enhancement of Plasmodium falciparum schizont inhibition in vitro.
Studies were undertaken to determine whether rheumatoid factor (RF) was present in immune human and Aotus trivirgatus monkey sera which inhibited Plasmodium falciparum schizonts in vitro and to determine whether RF could be responsible for or contribute to merozoite agglutination in the parasite inhibition test. Additional studies were conducted to determine the effect of exogenous RF on schizont inhibition when used alone or in conjunction with immune or normal sera. RF was not detected in any of the 11 immune monkey sera or the 3 immune human sera which were tested. However, when RF was added to immune human or Aotus sera, levels of schizont inhibition increased significantly over levels obtained with immune serum alone. When RF was used alone or in conjunction with normal sera, levels of schizont inhibition were comparable to those obtained with normal serum. Furthermore, adsorption of the RF with immunoglobulin G-coated erythrocytes removed the enhancing activity. The results of this study indicate that RF, which is sometimes produced during acute or chronic malarial infection, may contribute nonspecifically to the enhanced clearance of plasmodia in vivo.


Predicting and assessing rupture in protein gels under oscillatory shear.
Soft materials may break irreversibly upon applying sufficiently large shear oscillations, a process whose physical mechanism remains largely elusive. In this work, the rupture of protein gels made of sodium caseinate under an oscillatory stress is shown to occur in an abrupt, brittle-like manner. Upon increasing the stress amplitude, the build-up of harmonic modes in the strain response can be rescaled for all gel concentrations. This rescaling yields an empirical criterion to predict the rupture point way before the samples are significantly damaged. "Fatigue" experiments under stress oscillations of constant amplitude can be mapped onto the former results, which indicates that rupture is independent of the temporal pathway in which strain and damage accumulate. Finally, using ultrasonic imaging, we measure the local mechanical properties of the gels before, during and after breakdown, showing that the strain field remains perfectly homogeneous up to rupture but suddenly gives way to a solid-fluid phase separation upon breakdown.


Dual-field imaging polarimeter using liquid crystal variable retarders.
An imaging Stokes-vector polarimeter using liquid crystal variable retarders (LCVRs) has been built and calibrated. Operating in five bands from 450 to 700 nm, the polarimeter can be changed quickly between narrow (12 degrees ) and wide (approximately 160 degrees) fields of view. The instrument is designed for studying the effects of differing sky polarization upon the measured polarization of ground-based objects. LCVRs exhibit variations in retardance with ray incidence angle and ray position in the aperture. Therefore LCVR-based Stokes polarimeters exhibit unique calibration challenges not found in other systems. Careful design and calibration of the instrument has achieved errors within +/-1.5%. Clear-sky measurements agree well with previously published data and cloudy data provide opportunities to explore spatial and spectral variations in sky polarization.


DNA-gadolinium-gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells.
The unambiguous imaging of transplanted cells remains a major challenge to understand their biological function and therapeutic efficacy. In vivo imaging of implanted cells is reliant on tagging these to differentiate them from host tissue, such as the brain. We here characterize a gold nanoparticle conjugate that is functionalized with modified deoxythymidine oligonucleotides bearing Gd(III) chelates and a red fluorescent Cy3 moiety to visualize in vivo transplanted human neural stem cells. This DNA-Gd@Au nanoparticle (DNA-Gd@AuNP) exhibits an improved T1 relaxivity and excellent cell uptake. No significant effects of cell uptake have been found on essential cell functions. Although T1 relaxivity is attenuated within cells, it is sufficiently preserved to afford the in vivo detection of transplanted cells using an optimized voxel size. In vivo MR images were corroborated by a post-mortem histological verification of DNA-Gd@AuNPs in transplanted cells. With 70% of cells being correctly identified using the DNA-Gd-AuNPs indicates an overall reliable detection. Less than 1% of cells were false positive for DNA-Gd@AuNPs, but a significant number of 30% false negatives reveals a dramatic underestimation of transplanted cells using this approach. DNA-Gd@AuNPs therefore offer new opportunities to visualize transplanted cells unequivocally using T1 contrast and use cellular MRI as a tool to derive biologically relevant information that allows us to understand how the survival and location of implanted cells determines therapeutic efficacy.


Seawater strontium isotopic variations from 2.5 million years ago to the present.
Measurements of marine carbonate samples indicate that during the past 2.5 million years the (87)Sr/(86)Sr ratio of seawater has increased by 14 x 10(-5). The high average rate of increase of (87)Sr/(86)Sr indicates that continental weathering rates were exceptionally high. Nonuniformity in the rate of increase suggests that weathering rates fluctuated by as much as +/-30 percent of present-day values. Some of the observed shifts in weathering rates are contemporaneous with climatic changes inferred from records of oxygen isotopes and carbonate preservation in deep sea sediments.


Benefits of mindfulness meditation in reducing blood pressure and stress in patients with arterial hypertension.
The objective of this randomized controlled trial is to evaluate the benefits of mindfulness meditation in controlling ambulatory blood pressure (BP) and the impact of the intervention on anxiety, stress and depression levels in a Mediterranean population. Twenty-four and 18 patients [n = 42; mean age 56.5 (7.7) years; similar men and women proportions] with high-normal BP or grade I hypertension were enrolled to an intervention and a control group, respectively. For 2 h/week over 8 weeks, the intervention group received mindfulness training and the control group attended health education talks. The patients attended pre-intervention, week 4, week 8 and week 20 follow-up visits. 61.9% of the patients had anxiety, 21.4% depression, 19.0% were smokers and 14.2% were diabetic (no significant differences between the 2 groups). At baseline, the intervention group had non-significant higher clinically measured BP values, whereas both groups had similar ambulatory BP monitoring (ABPM) values. At week 8, the intervention group had statistically significant lower ABPM scores than the control group (124/77 mmHg vs 126/80 mmHg (p < 0.05) and 108/65 mmHg vs 114/69 mmHg (p < 0.05) for 24-h and night-time systolic BP (SBP), respectively) and also had lower clinically measured SBP values (130 mmHg vs 133 mmHg; p = 0.02). At week 20 (follow-up), means were lower in the intervention group (although not statistically significant). Improvements were observed in the intervention group in terms of being less judgemental, more accepting and less depressed. In conclusion, by week 8 the mindfulness group had lower clinically measured SBP, 24-h SBP, at-rest SBP and diastolic BP values.


Rapid antigenic-type replacement and DNA sequence evolution of canine parvovirus.
Analysis of canine parvovirus (CPV) isolates with a panel of monoclonal antibodies showed that after 1986, most viruses isolated from dogs in many parts of the United States differed antigenically from the viruses isolated prior to that date. The new antigenic type (designated CPV type 2b) has largely replaced the previous antigenic type (CPV type 2a) among virus isolates from the United States. This represents the second occurrence of a new antigenic type of this DNA virus since its emergence in 1978, as the original CPV type (CPV type 2) had previously been replaced between 1979 and 1981 by the CPV type 2a strain. DNA sequence comparisons showed that CPV types 2b and 2a differed by as few as two nonsynonymous (amino acid-changing) nucleotide substitutions in the VP-1 and VP-2 capsid protein genes. One mutation, resulting in an Asn-Asp difference at residue 426 in the VP-2 sequence, was shown by comparison with a neutralization-escape mutant selected with a non-CPV type 2b-reactive monoclonal antibody to determine the antigenic change. The mutation selected by that monoclonal antibody, a His-Tyr difference in VP-2 amino acid 222, was immediately adjacent to residue 426 in the three-dimensional structure of the CPV capsid. The CPV type 2b isolates are phylogenetically closely related to the CPV type 2a isolates and are probably derived from a common ancestor. Phylogenetic analysis showed a progressive evolution away from the original CPV type. This pattern of viral evolution appears most similar to that seen in some influenza A viruses.


Basic characteristics of Sporolactobacillus inulinus BCRC 14647 for potential probiotic properties.
The basic characteristics of the spore-forming lactic acid bacterium, Sporolactobacillus inulinus BCRC 14647, was evaluated in vitro for its potential probiotic properties. Assessments including acid and bile salt tolerance, adhesiveness, and antagonistic effects on pathogenic Salmonella enteritidis BCRC 10744, as well as inhibition factors of spent culture supernatant (SCS) and an invasion assay, were conducted using Lactobacillus acidophilus BCRC 10695 and two bifidobacteria (Bifidobacterium bifidum BCRC 14615 and B. longum BCRC 11847) as a reference. In the results, S. inulinus spores presented significantly higher survival rates than the vegetative cell form in acidic conditions as well as the reference bifidobacteria. However, L. acidophilus showed the highest viability among all tested strains. Similar results were found in the bile tolerance test. Compared with the reference strains, the vegetative cell form of S. inulinus possessed a proper adhesive characteristic (71.7 bacteria/field for S. inulinus and 91.3 and 45.7 bacteria/field for B. bifidum and B. longum, respectively). In the adhesion assay, both the spore form of S. inulinus (17.1 bacteria/field) and the negative control, L. bulgaricus BCRC 14009 (5.9 bacteria/field), displayed nonadhesive traits. The vegetative cells of S. inulinus and its SCS both dramatically decrease the adhesion of S. enteritidis to Caco-2 cells; meanwhile, the SCS of S. inulinus vegetative cells inhibited the growth of S. enteritidis in the inhibition zone test. The existing inhibition factor could be assumed to be lactic acid in the SCS. From the results of the invasion assay, S. inulinus showed high safety properties. In conclusion, based on these in vitro evaluations, results suggest that S. inulinus presents probiotic features of great potential in the vegetative cell form.


A new subtype-specific monoclonal antibody for IAP-survivin identifies high-risk patients with diffuse large B-cell lymphoma and improves the prognostic value of bcl-2.
Anti-apoptotic factors including IAP-survivin and bcl-2 are involved in carcinogenesis and predict for disease outcome for patients with cancer. We used RT-PCR and specific primers to generate two recombinant IAP-survivin proteins; one encoding for the full-length protein and the second comprising the survivin sequence incorporating amino acids 98 to 142. Both proteins were used to immunize mice and as capture antigens to screen NS1/immune splenocyte hybridoma supernatants for anti-survivin antibody in ELISA assays. The antibody designated F2-9C3 was most effective and reacted with both recombinant proteins and with the native protein present in lysates of A549 (lung carcinoma) and Jurkat cells in Western blots, immunoprecipitation and formalin-fixed tissue sections. Immunohistochemical staining of normal and neoplastic tissues showed association of the F2-9C3 antibody with the mitotic spindles. Expression of survivin was not detected elsewhere in sections of normal tissue while all neoplastic tissues examined, including those from patients with diffuse large B-cell lymphoma (DLBCL), showed significant expression of survivin. The intensity and localization of staining in these tumours varied and was observed in cytoplasm and/or nuclei. High nuclear expression of survivin predicted the disease outcome in patients with DLBCL. This association was evident when relating intensity to patient survival (p=0.0321) and strengthened when a score was calculated based on both staining intensity and the proportion of the reactive tumour cells (p=0.0128; reduction in the mean survival times: 35% and 46%, respectively). Elevated expression of bcl-2 protein also identified the high-risk patients (p=0.0095; reduction in mean survival time: 37%). Over-expression of both factors was a more powerful indicator of poor prognosis than either marker alone (p=0.0054, 70% reduction in mean survival time). In conclusion, our novel F2-9C3 monoclonal antibody is effective in determination of expression of IAP-survivin in neoplastic tissue. Nuclear overexpression of IAP-survivin using this antibody predicts the disease outcome in patients with DLBCL and significantly improves the predictive power of bcl-2 in these patients.


Early femoral loosening of the titanium 3M capital cemented hip: A lesson relearned.
A 4-year follow-up study is presented comparing 3M Capital cemented hip replacements with Charnley low friction arthroplasty controls. The mean radiological follow-up in the Capital and Charnley groups was 47 months (25 to 61) and 47 months (23 to 66) respectively. All cases were performed by the same surgical team over the same period (April 1991-October 1993). The operative technique including femoral preparation and cementing technique was identical in each group. Charnley broaches were used for femoral preparation in both groups and Charnley cups were used in all cases. In all of the 3m Capital cases cobalt-chrome femoral heads were used. There was no case selection for either group. Six of the 21 Capital femoral components were deemed to be loose on radiological criteria. None of the Charnley hips was loose. This represents an unacceptably high incidence of radiological femoral stem loosening in the Capital hip replacement. A previous uncontrolled study has attributed early failures to deficient femoral preparation and/or cementing technique. We suggest that early femoral stem loosening in the Capital hip occurs despite satisfactory operative technique in contrast with the results using the Charnley total hip replacement. (Hip International 2002; 1: 17-22).


Early assisted discharge with generic community nursing for chronic obstructive pulmonary disease exacerbations: results of a randomised controlled trial.
To determine the effectiveness of early assisted discharge for chronic obstructive pulmonary disease (COPD) exacerbations, with home care provided by generic community nurses, compared with usual hospital care. Prospective, randomised controlled and multicentre trial with 3-month follow-up. Five hospitals and three home care organisations in the Netherlands. Patients admitted to the hospital with an exacerbation of COPD. Patients with no or limited improvement of respiratory symptoms and patients with severe unstable comorbidities, social problems or those unable to visit the toilet independently were excluded. Early discharge from hospital after 3 days inpatient treatment. Home visits by generic community nurses. Primary outcome measure was change in health status measured by the Clinical COPD Questionnaire (CCQ). Treatment failures, readmissions, mortality and change in generic health-related quality of life (HRQL) were secondary outcome measures. 139 patients were randomised. No difference between groups was found in change in CCQ score at day 7 (difference in mean change 0.29 (95% CI -0.03 to 0.61)) or at 3 months (difference in mean change 0.04 (95% CI -0.40 to 0.49)). No difference was found in secondary outcomes. At day 7 there was a significant difference in change in generic HRQL, favouring usual hospital care. While patients' disease-specific health status after 7-day treatment tended to be somewhat better in the usual hospital care group, the difference was small and not clinically relevant or statistically significant. After 3 months, the difference had disappeared. A significant difference in generic HRQL at the end of the treatment had disappeared after 3 months and there was no difference in treatment failures, readmissions or mortality. Early assisted discharge with community nursing is feasible and an alternative to usual hospital care for selected patients with an acute COPD exacerbation. NetherlandsTrialRegister NTR 1129.


Unexpected effects of prey dimensions and morphologies on the size selective feeding by two bacterivorous flagellates (Ochromonas sp. and Spumella sp.).
Current models on protistan size-selective feeding assume that contact probability is the factor that largely explains observed food preferences. Contact probability is generally expected to be positively correlated with prey size and therefore to explain observed food selection for larger prey items. We critically tested these basic assumptions on size-selective feeding using the interception-feeding chrysomonad nanoflagellates Ochromonas sp. and Spumella sp. Mechanisms of differential feeding were studied during distinct stages of the selection process (i.e. contact probability, capture efficiency, ingestion efficiency, and differential digestion) by means of high-resolution video microscopy. Food selection was investigated using a mixture of microspheres ranging from 0.3-2.2 microm in diam., as well as a mixed bacterial community. In contrast to current model assumptions, the contact probability was highest for microspheres of intermediate size (0.9-1.2 microm), but was not generally positively correlated with prey size over the whole prey size range. Capture and ingestion also proved to be involved in size selection: these patterns were also independent of the food concentration (p = 0.968 for Ochromonas, p = 0.971 for Spumella). Even though the capture rate was significantly higher for attached flagellates than for swimming flagellates (p < 0.001), size selectivity was not affected (p > 0.05). Our results indicate that: (i) size selection is not actively regulated by these flagellates, but is a passive process; (ii) contact probability is not generally positively correlated with prey size, but shows a maximum for intermediate-sized prey in the prey size spectrum of 0.3-2.2 microm; and (iii) selection steps other than contact probability are crucial for size selection and should be integrated in models on size selection.


Early methylphenidate administration to young rats causes a persistent reduction in the density of striatal dopamine transporters.
Methylphenidate is widely and effectively used for the treatment of attention deficit hyperactivity disorder during early childhood and adolescence, but until now possible effects of this treatment on brain development and the maturation of monoaminergic systems have not been investigated systematically. This experimental animal study describes the effects of methylphenidate administration (2 mg/kg/day) for 2 weeks to very young (prepubertal) and somewhat older (postpubertal) rats on the densities of dopamine, serotonin, and norepinephrine transporters in the striatum and in the midbrain. As shown by ligand-binding-assays, the K(D) values of all three transporters were unaffected by this treatment. No alterations were found for the Bmax values of [3H]-paroxetine and [3H]-nisoxetine binding, but the density of dopamine transporters (Bmax values of [3H]-GBR binding) in the striatum (but not in the midbrain) was significantly reduced after early methylphenidate administration (by 25% at day 45), and this decline reached almost 50% at adulthood (day 70), that is, long after termination of the treatment. This is the first empirical demonstration of long-lasting changes in the development of the central dopaminergic system caused by the administration of methylphenidate during early juvenile life.


Four Weeks of Probiotic Supplementation Alters the Metabolic Perturbations Induced by Marathon Running: Insight from Metabolomics.
Few data are available that describe how probiotics influence systemic metabolism during endurance exercise. Metabolomic profiling of endurance athletes will elucidate mechanisms by which probiotics may confer benefits to the athlete. In this study, twenty-four runners (20 male, 4 female) were block randomised into two groups using a double-blind matched-pairs design according to their most recent Marathon performance. Runners were assigned to 28-days of supplementation with a multi-strain probiotic (PRO) or a placebo (PLB). Following 28-days of supplementation, runners performed a competitive track Marathon race. Venous blood samples and muscle biopsies (vastus lateralis) were collected on the morning of the race and immediately post-race. Samples were subsequently analysed by untargeted 1H-NMR metabolomics. Principal component analysis (PCA) identified a greater difference in the post-Marathon serum metabolome in the PLB group vs. PRO. Univariate tests identified 17 non-overlapped metabolites in PLB, whereas only seven were identified in PRO. By building a PLS-DA model of two components, we revealed combinations of metabolites able to discriminate between PLB and PRO post-Marathon. PCA of muscle biopsies demonstrated no discernible difference post-Marathon between treatment groups. In conclusion, 28-days of probiotic supplementation alters the metabolic perturbations induced by a Marathon. Such findings may be related to maintaining the integrity of the gut during endurance exercise.


Dietary fatty acid composition alters magnesium metabolism, distribution, and marginal deficiency response in rats.
Based on dietary intake recommendations, magnesium deficiency commonly occurs throughout the world. However, widespread pathological conditions induced by dietary magnesium deficiency have not been identified. This discrepancy may be caused by other dietary factors ameliorating or exacerbating the response to a marginal magnesium deficiency and/or the length of the deficiency. Thus, a study was performed to determine whether the n-6/n-3 fatty acid composition of the diet affects the response to marginal magnesium deprivation, and whether the effect was dependent upon the length of deprivation. Weanling female rats were fed diets containing 250 mg/kg magnesium in a factorial arrangement with dietary variables of supplemental magnesium at 0 or 250 mg/kg (total of 250 or 500 mg/kg) and fat sources of 75 g/kg corn oil or 65 g/kg fish (menhaden) oil plus 10 g/kg linoleic acid. After 8 and 12 weeks on their respective diets, each rat was placed in a metabolic cage for a 16-hour collection of urine. After 13 weeks, the rats were anesthetized with ether for the collection of plasma and organs. Marginal magnesium deficiency was confirmed by decreased urinary excretion and femur, tibia and vertebrae concentrations of magnesium. Dietary oil influenced the effect of marginal magnesium deficiency on magnesium metabolism, distribution and oxidative stress indicators. Fish oil, but not corn oil, significantly decreased urinary magnesium excretion and increased kidney magnesium concentration. Femur magnesium was significantly decreased by marginal magnesium deficiency in rats fed fish oil but not in rats fed corn oil, and liver magnesium concentration was decreased by fish oil. Marginal magnesium deficiency increased plasma extracellular superoxide dismutase and cysteine (component of glutathione) in rats fed corn oil but not in rats fed fish oil. Urinary prostaglandin E₂ excretion was significantly decreased by marginal magnesium deficiency at 8 weeks, but not at 12 weeks; an increase between weeks 8 and 12 in marginally magnesium-deficient rats fed fish oil caused this change in significance. The findings show that the dietary fatty acid composition affects the response of rats to marginal magnesium deprivation. The findings also indicate that dietary or physiological factors affecting oxidative stress could affect the response to marginal magnesium deficiency, and that a response to a dietary change that takes time to develop, such as an increase in dietary n-3 fatty acids, may result in signs of marginal deficiency being different over time.


Using deep convolutional neural networks to identify and classify tumor-associated stroma in diagnostic breast biopsies.
The breast stromal microenvironment is a pivotal factor in breast cancer development, growth and metastases. Although pathologists often detect morphologic changes in stroma by light microscopy, visual classification of such changes is subjective and non-quantitative, limiting its diagnostic utility. To gain insights into stromal changes associated with breast cancer, we applied automated machine learning techniques to digital images of 2387 hematoxylin and eosin stained tissue sections of benign and malignant image-guided breast biopsies performed to investigate mammographic abnormalities among 882 patients, ages 40-65 years, that were enrolled in the Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project. Using deep convolutional neural networks, we trained an algorithm to discriminate between stroma surrounding invasive cancer and stroma from benign biopsies. In test sets (928 whole-slide images from 330 patients), this algorithm could distinguish biopsies diagnosed as invasive cancer from benign biopsies solely based on the stromal characteristics (area under the receiver operator characteristics curve = 0.962). Furthermore, without being trained specifically using ductal carcinoma in situ as an outcome, the algorithm detected tumor-associated stroma in greater amounts and at larger distances from grade 3 versus grade 1 ductal carcinoma in situ. Collectively, these results suggest that algorithms based on deep convolutional neural networks that evaluate only stroma may prove useful to classify breast biopsies and aid in understanding and evaluating the biology of breast lesions.


Intracavity adaptive optics. 2: Tilt correction performance.
This paper continues the discussion of the detailed experimental study conducted on adaptive optical control methodologies inside a laser resonator.(1) In this paper we discuss the experimental results for the correction of tilt within a laser resonator utilizing a multidither zonal COAT system. The tilt aberration was introduced in three different ways: (1) static tilt was introduced while the COAT system was open loop and then the control loop closed, (2) static tilt was incrementally introduced while the COAT system control loop was closed loop (denoted as continuously closed loop), and (3) dynamic tilt was applied while the COAT system's control loop was closed. Experimental data are presented on the correction capability of the COAT system for each method of introduction of tilt over a large range of tilt angles and control loop configurations (open/ closed and continuously closed). Limitations of the system are discussed, and design recommendations and conclusions are provided.


Vps1, a recycling factor for the traffic from early endosome to the late Golgi.
Recycling of cellular membranes and their constituents plays a role for cell survival and growth. In the budding yeast, there are recycling traffics from early and late endosomal compartments to the late Golgi. Here, we examined a possible role for Vps1, a large GTPase, in the recycling traffic of GFP-Snc1 from early endosomes to the late Golgi. In the absence of Vps1 we observed an aberrant accumulation of GFP-Snc1 puncta in the cytoplasm that we identified as early endosomes. The N-terminal GTPase and the C-terminal GED domains of Vps1 are essential for Vps1's function in Snc1 recycling. Our finding of genetic interactions of VPS1 with genes involved in early endosome-to-Golgi traffic further suggests Vps1 functions as a recycling factor in the membrane traffic. Finally, we provide evidence that the severe accumulation of GFP-Snc1 cytoplasmic puncta in vps1Δ cells is attributed to a mild defect in the retention of the GARP component Vps51 at the late Golgi, as well as a severe disruption of actin cables.


Overexpression of Pax5 is not sufficient for neoplastic transformation of mouse neuroectoderm.
The developmental control genes of the Pax family are essential for brain development. Several Pax genes are also involved in chromosomal translocations causing malignancies in humans, and Pax5 expression is deregulated in medulloblastomas. We have investigated whether Pax5 can induce tumors in the developing mouse brain. Primary mouse embryonic neuroectodermal cells were retrovirally transduced with mouse Pax5 and transplanted into the brain of syngeneic host mice. No tumors developed in 36 transplants after one year, and there were no alterations in the differentiation pattern of the neural transplants. We then generated transgenic mice expressing human Pax5 under control of the Engrailed-2 promoter, which is expressed in the cerebellar external granule cell layer and in medulloblastomas. Sustained expression was achieved in the cerebellum of transgenic animals throughout lifetime. Expression levels were similar to those observed in human medulloblastomas. Again, cerebellar morphogenesis was undisturbed, and no tumors arose. These results strongly argue against a dominant transforming activity of PAX5 in NEC and in cerebellar granule cell precursors of mice, and underline the restricted tissue-specificity of PAX5 related oncogenesis.


Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird.
Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a 'time bomb' that reduces longevity in the absence of any obvious phenotypic consequences early in life.


Diversity of hepatotoxic cyanobacteria in the Nile Delta, Egypt.
Optimized denaturing gradient gel electrophoresis (DGGE) fingerprinting and real-time PCR were performed to identify and quantify the potential hepatotoxic microcystin- and nodularin-producing cyanobacteria present in freshwater samples collected during different seasons at three different sites from the Nile River Delta. The combined use of molecular gene markers (targeting the aminotransferase domain of the hepatotoxin synthetase modules and the 16S rRNA gene) and light microscopy demonstrated the dominance of different freshwater Microcystis phylotypes, including the potential hepatotoxin producers M. wesenbergii and M. aeruginosa, several Synechococcus and Cyanobium phylotypes, as well as the presence of Nodularia spumigena and Cylindrospermopsis raciborskii in the samples "collected during summer 2006 and winter 2007". Certain seasonal changes (summer and winter) in Microcystis microdiversity were detected. Real-time PCR revealed no difference in the quantities of potential hepatotoxin-producing cyanobacterial communities between summer and winter, but did show differences between the three sampling sites investigated. The expression of the aminotransferase domain analyzed by DGGE fingerprinting demonstrated that all Microcystis phylotypes present in the samples might have been active at the time of the sampling. Statistical analysis showed a significant effect of TP, and not TN, on the relative abundance of the potentially hepatotoxic cyanobacterial community.


Access to risk-appropriate hospital care and disparities in neonatal outcomes in racial/ethnic groups and rural-urban populations.
Variations in infant and neonatal mortality continue to persist in the United States and in other countries based on both socio-demographic characteristics, such as race and ethnicity, and geographic location. One potential driver of these differences is variations in access to risk-appropriate delivery care. The purpose of this article is to present the importance of delivery hospitals on neonatal outcomes, discuss variation in access to these hospitals for high-risk infants and their mothers, and to provide insight into drivers for differences in access to high-quality perinatal care using the available literature. This review also illustrates the lack of information on a number of topics that are crucial to the development of evidence-based interventions to improve access to appropriate delivery hospital services and thus optimize the outcomes of high-risk mothers and their newborns.


Distinct Protein Expression Profiles of Solid-Pseudopapillary Neoplasms of the Pancreas.
Solid-pseudopapillary neoplasm (SPN) is an uncommon pancreatic tumor with mutation in CTNNB1 and distinct clinical and pathological features. We compared the proteomic profiles of SPN to mRNA expression. Pooled SPNs and pooled non-neoplastic pancreatic tissues were examined with high-resolution mass spectrometry. We identified 329 (150 up-regulated and 179 down-regulated) differentially expressed proteins in SPN. We identified 191 proteins (58.1% of the 329 dysregulated proteins) with the same expression tendencies in SPN based on mRNA data. Many overexpressed proteins were related to signaling pathways known to be activated in SPNs. We found that several proteins involved in Wnt signaling, including DKK4 and β-catenin, and proteins that bind β-catenin, such as FUS and NONO, were up-regulated in SPNs. Molecules involved in glycolysis, including PKM2, ENO2, and HK1, were overexpressed in accordance to their mRNA levels. In summary, SPN showed (1) distinct protein expression changes that correlated with mRNA expression, (2) overexpression of Wnt signaling proteins and proteins that bind directly to β-catenin, and (3) overexpression of proteins involved in metabolism. These findings may help develop early diagnostic biomarkers and molecular targets.


Scandinavian clinical practice guideline on choice of fluid in resuscitation of critically ill patients with acute circulatory failure.
The task force on Acute Circulatory Failure of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine produced this guideline with recommendations concerning the use of crystalloid vs. colloid solutions in adult critically ill patients with acute circulatory failure. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to grade the quality of evidence and to determine the strengths of the recommendations. As efficacy and harm may vary in different subpopulations of patients with acute circulatory failure, we produced recommendations for general intensive care unit (ICU) patients and those with sepsis, trauma and burn injury. For general ICU patients and those with sepsis, we recommend using crystalloids for resuscitation rather than hydroxyethyl starch and we suggest using crystalloids rather than gelatin and albumin. For patients with trauma we recommend to use crystalloids for resuscitation rather than colloid solutions. For patients with burn injury we provide no recommendations as there are very limited data from randomised trials on fluid resuscitation in this patient population. We recommend using crystalloid solutions rather than colloid solutions for resuscitation in the majority of critically ill patients with acute circulatory failure.


Alpha-lipoic acid effectively attenuates ionizing radiation-mediated testicular dysfunction in rats: Crosstalk of NF-ĸB, TGF-β, and PPAR-ϒ pathways.
Radiotherapy is one of the principal approaches employed in the treatment of pelvic cancers. Nevertheless, testicular dysfunction and infertility are among the most common adverse effects in young adult cancer survivors. Clinically, alpha-lipoic acid (LA) has been applied to improve the quality of sperm with a satisfactory effect. Therefore, the present study investigated the underlying mechanisms of the radioprotective effects of LA against testicular damage. Male Sprague-Dawley rats were exposed to 10 Gy of whole-body ϒ-radiation and LA (50 mg/kg, P.O.) was administered one week before and three days post-irradiation. LA showed remarkable capacity in preserving testicular tissue against radiation damage by improving histological and ultrastructural changes of disorganized seminiferous tubules, besides enhancing its diameter, germinal epithelial thickness, and Johnsen's score. Radiation instigated a significant decrease in sperm quality and quantity associated with depletion of serum testosterone levels, while the LA administration maintained spermatogenesis. Strikingly, LA exhibited antioxidant properties by restoring reduced glutathione levels and antioxidant enzyme activities such as catalase and glutathione-s-transferase, besides diminishing malondialdehyde levels in the testis of irradiated group. Furthermore, LA alleviated testicular inflammation through downregulation of nuclear factor-ĸB (NF-ĸB) expression with a subsequent reduction in interleukin (IL)-6 and cyclooxygenase-2 expression, accompanied by the augmented expression of the anti-inflammatory cytokine IL-10. Additionally, testicular fibrosis markers including Masson's trichrome and transforming growth factor (TGF)-β expression were noticeably declined in LA-treated irradiated rats, together with the upregulation of peroxisome proliferator-activated receptor-ϒ expression. Collectively, LA ameliorates radiation-mediated spermatogenesis-defects and testicular-damage via suppression of oxidative stress/NF-ĸB/TGF-β signaling.


Predation shapes sperm performance surfaces in guppies.
Sperm velocity is a key determinant of competitive fertilization success in many species. Selection is therefore expected to favour the evolution of faster sperm when the level of sperm competition is high. However, several aspects can determine the direction and strength of selection acting on this key performance trait, including ecological factors that influence both sperm competition and the strength of selection acting on correlated traits that may constrain evolutionary responses in sperm velocity. Here, we determine how a key ecological variable, the level of predation, shapes sperm swimming speed across 18 Trinidadian populations of guppies ( Poecilia reticulata). We use performance analysis, a statistical tool akin to the familiar methods of multivariate selection analyses, to determine how the level of predation influences sperm velocity (modelled as a performance trait) when accounting for correlated pre- and postcopulatory traits that are also impacted by predation. We show that predation affects the combination of pre- and postcopulatory traits that ultimately predict sperm performance. Overall, we report evidence for disruptive relationships between sperm performance and combinations of ornaments and sperm morphology, but the specific combinations of traits that predict sperm velocity depended on the level of predation. These analyses underscore the complex nonlinear interrelationships among pre- and postcopulatory traits and the importance of considering ecological factors that may ultimately change the way in which multiple traits interact to determine a trait's performance value. As such, our results are likely to be broadly applicable across systems where selection is influenced by ecological conditions.


Quantitative analysis of cell shape and the cytoskeleton in developmental biology.
Computational approaches that enable quantification of microscopy data have revolutionized the field of developmental biology. Due to its inherent complexity, elucidating mechanisms of development requires sophisticated analysis of the structure, shape, and kinetics of cellular processes. This need has prompted the creation of numerous techniques to visualize, quantify, and merge microscopy data. These approaches have defined the order and structure of developmental events, thus, providing insight into the mechanisms that drive them. This review describes current computational approaches that are being used to answer developmental questions related to morphogenesis and describe how these approaches have impacted the field. Our intent is not to comprehensively review techniques, but to highlight examples of how different approaches have impacted our understanding of development. Specifically, we focus on methods to quantify cell shape and cytoskeleton structure and dynamics in developing tissues. Finally, we speculate on where the future of computational analysis in developmental biology might be headed. This article is categorized under: Technologies > Analysis of Cell, Tissue, and Animal Phenotypes Early Embryonic Development > Gastrulation and Neurulation Early Embryonic Development > Development to the Basic Body Plan.


The Ebbinghaus retention curve: training does not increase the ability to apply pressure immobilisation in simulated snake bite--implications for snake bite first aid in the developing world.
Pressure immobilisation (PIM) has been recommended for field management of bites by some venomous snakes. A narrow range of pressures under the encompassing wrap is necessary for PIM to limit venom spread. This study sought to evaluate the effect of focused training on volunteers' ability to apply PIM and to retain such skill over time. Forty volunteers were randomly divided into two groups: Group 1 (N=20; controls) received standard written instructions in PIM application; and Group 2 (N=20) received focused instruction during a 4-h training session (including hands-on practice and real-time feedback regarding pressures achieved). After voicing confidence with the technique, volunteers were tested at 1h, 1 day, 3 days and 3 months post training. One-hour post training, no volunteers in the control group were successful in applying PIM with the correct pressure. Twelve volunteers (60%) in Group 2 achieved target pressures 1h after training. However, there was rapid loss of ability to apply PIM correctly by Group 2, falling to just 25% success at 3 days, with little further deterioration at 3 months. Neither written instructions nor intense training with feedback adequately prepares individuals to apply PIM with correct pressures under the wrap.