Sustainable synthesis of uridine-5'-monophosphate analogues by immobilized uracil phosphoribosyltransferase from Thermus thermophilus.
Nowadays enzymatic synthesis of nucleic acid derivatives is gaining momentum over traditional chemical synthetic processes. Biotransformations catalyzed by whole cells or enzymes offer an ecofriendly and efficient alternative to the traditional multistep chemical methods, avoiding the use of chemical reagents and organic solvents that are expensive and environmentally harmful. Herein we report for the first time the covalent immobilization a uracil phosphoribosyltransferase (UPRT). In this sense, UPRT from Thermus thermophilus HB8 was immobilized onto glutaraldehyde-activated MagReSyn®Amine magnetic iron oxide porous microparticles (MTtUPRT). According to the catalyst load experiments, MTtUPRT3 was selected as optimal biocatalyst for further studies. MTtUPRT3 was active and stable in a broad range of temperature (70-100 °C) and in the pH interval 6-8, displaying maximum activity at 100 °C and pH 7 (activity 968 IU/gsupport, retained activity 100%). In addition, MTtUPRT3 could be reused up to 8 times in the synthesis of uridine-5'-monophosphate (UMP). Finally, MTtUPRT3 was successfully applied in the sustainable synthesis of different 5-modified uridine-5'-monophosphates at short times. Taking into account these results, MTtUPRT3 would emerge as a valuable biocatalyst for the synthesis of nucleoside monophosphates through an efficient and environmentally friendly methodology.


Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway.
Wound healing is a complex dynamic process involving a large number of biological events. Excessive oxidative stress is a key factor delaying wound healing. Hydrogen is an antioxidant, anti-inflammatory, and antiapoptotic medical gas with safety, effectiveness, and penetrability. However, the effects of local treatment of hydrogen on wound healing and its potential mechanisms remain unclear. In this study, Kunming (KM) mice were used to set up a wound model. All the mice were randomly divided into the control, the local treatment with saline group, the local treatment with the hydrogen-rich saline group, and the intraperitoneal injection of the hydrogen-rich saline group. To evaluate the impact of hydrogen-rich saline on wound healing, we assessed the wound healing rate, wound closure time, histomorphology, oxidative stress indicators, inflammatory cytokines, the apoptosis index, and the expression of the nuclear factor-erythroid-related factor 2(Nrf-2). Furthermore, the immortalized nontumorigenic human epidermal (HaCaT) cells were chosen to investigate the therapeutic effects of hydrogen-rich medium on oxidative stress and its underlying mechanisms. The results showed that local treatment of hydrogen-rich saline shortened wound closure time and reduced the level of proinflammatory cytokines and lipid peroxidation. Meanwhile, it decreased the cell apoptosis index and increased the Nrf-2 expression. Besides, hydrogen-rich medium relieved the oxidative stress via the activation of the Nrf-2/heme oxygenase-1 (HO-1) pathway. In conclusion, local treatment of hydrogen-rich saline exhibits the healing-promoting function through antioxidant, anti-inflammatory, and antiapoptotic effects. Hydrogen relieves the oxidative stress in the wound microenvironment via Nrf-2/HO-1 signaling pathway. This study may offer a new strategy to promote wound healing and a new perspective to illustrate the mechanism of wound healing.


Patient-Reported Barriers and Enablers to Deprescribing Recommendations During a Clinical Trial (Shed-MEDS).
Effective deprescribing requires shared decision making between a patient and their clinician, and should be used when implementing evidence-based deprescribing conversations. As part of the Shed-MEDS clinical trial, this study assessed barriers and enablers that influence patient decision making in deprescribing to inform future implementation efforts and adaptations. Shed-MEDS, a randomized controlled deprescribing trial, included hospitalized older adults discharging to post-acute care facilities. A trained clinician reviewed each participant's medical history and medication list to identify medications with potential for deprescribing. The study clinician then conducted a semistructured patient-centered deprescribing interview to determine patient (or surrogate) concerns about medications and willingness to deprescribe. Reeve et al.'s (2013) framework was used to categorize barriers and enablers to deprescribing from the patient's perspective, including "appropriateness of cessation," "fear," "dislike of a medication," "influences," and "process of cessation." Overall, participants/surrogates (N = 177) agreed with 63% (883 total medications) of the study clinician's deprescribing recommendations. Thematic analysis revealed that "appropriateness" of a medication was the most common barrier (88.2%) and enabler (67.3%) to deprescribing. Other deprescribing enablers were in the following domains: "influences" (22.7%), "process" (22.5%), "pragmatic" (19.4%), and "dislike" (5.3%). Use of a semistructured deprescribing interview conversation tool allowed study clinicians to elicit individual barriers and enablers to deprescribing from the patient's perspective. Participants in this study expressed more agreement than disagreement with study clinicians' deprescribing recommendations. These results should inform future implementation efforts that incorporate a patient-centered framework during deprescribing conversations. NCT02979353.


Increase of beta 1-6-branched oligosaccharides in human esophageal carcinomas invasive against surrounding tissue in vivo and in vitro.
The -GlcNAc beta 1-6Man- (beta 1-6) branched N-glycosidic oligosaccharides expressed on tumor cells have been found to contribute to malignant and metastatic potential in experimental tumor models. Phaseolus vulgaris leukoagglutinin (L-PHA) requires the beta 1-6-linked lactosamine antenna for high-affinity binding and was used histochemically to characterize the distribution of these sugar structures in human esophageal squamous cell carcinomas from 42 patients. Leukoagglutinin-reactive carcinoma cells in the invasive tumors were distributed predominantly on the outer surface of the tumor adjacent to the surrounding tissue. Furthermore, when TE 1 cells, a human esophageal squamous cell carcinoma line, were cultured in a collagen gel matrix to obtain colonies in a three-dimensional form, these colonies exhibited high affinity for L-PHA binding only in the outer cell layer facing the collagen matrix, unrelated to the cell growth cycle. These findings suggest that the increase in beta 1-6-branched oligosaccharides in esophageal carcinomas is an important trait of the tumor in the invasion into the surrounding tissue.


Higher Derived Time in Range With IDegLira Versus Insulin Glargine U100 in People With Type 2 Diabetes.
Derived time in range (dTIR), calculated from self-monitored blood glucose (SMBG-dTIR) profiles, has demonstrated correlation with risk of cardiovascular and microvascular complications. This post hoc analysis of the DUAL V and DUAL VIII trials aimed to compare dTIR with an insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus insulin glargine 100 units/mL (glargine U100) in people with type 2 diabetes (T2D). Nine-point SMBG profiles were taken more than 24 hours at baseline and end of trial (EOT: 26 weeks [DUAL V] and 104 weeks [DUAL VIII]) and used to derive the percentage of readings within target range (70-180 mg/dL). Estimated treatment differences (ETDs, IDegLira-glargine U100) were analyzed using analysis of covariance, with treatment as fixed effects and baseline response as a covariate. ETDs for change from baseline to EOT in dTIR were significantly greater with IDegLira versus glargine U100 in DUAL V (4.18%, P = .027) and DUAL VIII (5.17%, P = .001). The proportions of people achieving ≥70% dTIR at EOT with IDegLira and glargine U100, respectively, were 62% and 60% in DUAL V (P = .7541), and 50% and 26% in DUAL VIII (P < .0001). The proportion achieving a ≥5% increase in dTIR from baseline to EOT with IDegLira and glargine U100 was 63% in both groups in DUAL V (P = .9043), and 44% and 25%, respectively, in DUAL VIII (P < .0001). IDegLira was associated with significantly greater increases in dTIR versus basal insulin alone in people with T2D. ClinicalTrials.gov, NCT01952145 (DUAL V); ClinicalTrials.gov, NCT02501161 (DUAL VIII).


Six point mutations that cause factor XI deficiency.
We have identified six novel types of mutation that cause factor XI deficiency, an inherited bleeding disorder. Two are point mutations that interfere with the normal splicing of exons in the mRNA and four are point mutations that result in amino acid substitutions. One of these amino acid substitutions (Asp 16-->His) is near the amino terminal end of the protein. The other three amino acid substitutions (Leu 302-->Pro, Thr 304-->Ile, and Glu 323-->Lys) are in the fourth apple domain, a region that mediates dimerization of identical subunits of factor XI. All four amino acid substitutions cause a reduction in the amount of factor XI secreted from cells grown in vitro.


Intestinal Perforation due to Deep Infiltrating Endometriosis during Pregnancy: Case Report.
We report the case of a 33 year-old woman who complained of severe dysmenorrhea since menarche. From 2003 to 2009, she underwent 4 laparoscopies for the treatment of pain associated with endometriosis. After all four interventions, the pain recurred despite the use of gonadotropin-releasing hormone (GnRH) analogues and the insertion of a levonorgestrel intrauterine system (LNG-IUS). Finally, a colonoscopy performed in 2010 revealed rectosigmoid stenosis probably due to extrinsic compression. The patient was advised to get pregnant before treating the intestinal lesion. Spontaneous pregnancy occurred soon after LNG-IUS removal in 2011. In the 33rd week of pregnancy, the patient started to feel severe abdominal pain. No fever or sings of pelviperitonitis were present, but as the pain worsened, a cesarean section was performed, with the delivery of a premature healthy male, and an intestinal rupture was identified. Severe peritoneal infection and sepsis ensued. A colostomy was performed, and the patient recovered after eight days in intensive care. Three months later, the colostomy was closed, and a new LNG-IUS was inserted. The patient then came to be treated by our multidisciplinary endometriosis team. The diagnostic evaluation revealed the presence of intestinal lesions with extrinsic compression of the rectum. She then underwent a laparoscopic excision of the endometriotic lesions, including an ovarian endometrioma, adhesiolysis and segmental colectomy in 2014. She is now fully recovered and planning a new pregnancy. A transvaginal ultrasound (TVUS) performed six months after surgery showed signs of pelvic adhesions, but no endometriotic lesions.


A Lower-Back Exoskeleton With a Four-Bar Linkage Structure for Providing Extensor Moment and Lumbar Traction Force.
Lower back pain and related injuries are prevalent and serious problems in various industries, and high compression force to the lumbosacral (L5/S1) region has been known as one of the key factors. Previous research on passive lower back exoskeletons focused on reducing lumbar muscle activation by providing an extensor moment. Additionally, lumbar traction forces can reduce the compression force, and is a common treatment method for lower back pain in clinics. In this paper, we propose a novel passive lower back exoskeleton that provides both extensor moment and lumbar traction force. The working principle of the exoskeleton, extending the coil springs during lumbar flexion, and its design criteria regarding the amount of each force element were provided. The kinematic model explained its operation, and the dynamic simulation estimated its performance and validated its satisfaction with the design criteria. The biomechanical model provided a brief insight into the expected exoskeleton's effect on the reduced lower back compression force. Ten subjects performed static holding and dynamic lifting tasks, and the generated force elements in two directions, parallel and perpendicular to the trunk, were evaluated using a force sensor and electromyography sensors, respectively. The experiment demonstrated a pulling force opposite to the direction of intradiscal pressure and reduced erector spinae activation. This implies the effect of wearing the exoskeleton to decrease the intervertebral pressure during static back bending or heavy lifting tasks.


Advanced oxidation and disinfection processes for onsite net-zero greywater reuse: A review.
Net-zero greywater (NZGW) reuse, or nearly closed-loop recycle of greywater for all original uses, can recover both water and its attendant hot-water thermal energy, while avoiding the installation and maintenance of a separate greywater sewer in residential areas. Such a system, if portable, could also provide wash water for remote emergency health care units. However, such greywater reuse engenders human contact with the recycled water, and hence superior treatment. The purpose of this paper is to review processes applicable to the mineralization of organics, including control of oxidative byproducts such as bromate, and maintenance of disinfection consistent with potable reuse guidelines, in NZGW systems. Specifically, TiO2-UV, UV-hydrogen peroxide, hydrogen peroxide-ozone, ozone-UV advanced oxidation processes, and UV, ozone, hydrogen peroxide, filtration, and chlorine disinfection processes were reviewed for performance, energy demand, environmental impact, and operational simplicity. Based on the literature reviewed, peroxone is the most energy-efficient process for organics mineralization. However, in portable applications where delivery of chemicals to the site is a concern, the UV-ozone process appears promising, at higher energy demand. In either case, reverse osmosis, nanofiltration, or ED may be useful in controlling the bromide precursor in make-up water, and a minor side-stream of ozone may be used to prevent microbial regrowth in the treated water. Where energy is not paramount, UV-hydrogen peroxide and UV-TiO2 can be used to mineralize organics while avoiding bromate formation, but may require a secondary process to prevent microbial regrowth. Chlorine and ozone may be useful for maintenance of disinfection residual.


Bevacizumab for the treatment of pediatric retinal and choroidal diseases.
To determine the efficacy of off-label intravitreal bevacizumab (IVB) for the treatment of pediatric retinal and choroidal vascular diseases. Retrospective, non-comparative, open-label, interventional, consecutive case series of all patients younger than 18 years treated with off-label IVB at a single center from January 1, 2005, to January 1, 2008. Primary outcome measures with best-corrected visual acuity by age-appropriate testing and central macular thickness by time-domain optical coherence tomography. Thirty-five eyes of 33 patients were treated with IVB alone or in combination with other treatments for choroidal neovascularization, Coats' disease, familial exudative vitreoretinopathy, and various other indications. IVB was used in 24 eyes to reduce excess retinal fluid and exudation. Mean Snellen visual acuity improved from 20/170 at baseline to 20/100 at 1 month (P = .006), 20/80 at 3 months (P = .006), and 20/50 at 6 months (P = .023). Central macular thickness improved from 356 μm at baseline to 287 μm at 6 months (P = .028). IVB was used in 11 eyes to control peripheral retinal neovascularization and iris rubeosis. Although IVB reduced vascular engorgement, it did not prevent the progression of preretinal tractional forces. Mean visual acuity was maintained at each time point. No systemic or ocular adverse events were directly attributable to IVB in any patient. IVB reduced vascular leakage and temporarily regressed pathologic neovascularization of the choroid, retina, and iris in this series of pediatric patients. Further prospective studies are warranted.


Adult Brainstem Gliomas: Retrospective Analysis of 51 Patients.
Brainstem gliomas (BSG) constitute less than 2% of brain tumors in adults. Therapeutic options are limited and BSG are associated with a high morbidity and mortality. We reviewed the records of 51 patients with BSG treated at the Institute of Neurosurgery, Clinical Center of Serbia in Belgrade between 1998 and 2012. We recorded demographic and clinical variables as well as radiological findings and survival. Of the 51 patients, 62.7% were male and 37.3% were female. The mean age was 30.6±19.3 years. High grade glioma (Astrocytoma grade III and IV) was most common at the age of 38.2±17.9 years (t=.481, p=0.017) while low grade glioma (Astrocytoma grade I and II) was common in younger age as 25.4±17.4 years (X2=4.013; p=0.045), with localization in the pons (X2=5.299; p=0.021) and exophytic presentation (X2=3.862; p=0.049). Ataxia, as initial symptom, was a predictor of poor outcome (HR:5.546, p=0.012). Due to its specific localization, BSG present a major challenge for neurosurgery, because of the necessity of safe approach for radical resection. Histological verification of BSG determines the need for additional therapeutic procedures such as radiotherapy and chemotherapy. Benefit from correct diagnosis is reflected in the avoidance of potentially adverse effects of treatment.


Decreased signal transducers and activators of transcription (STAT) protein expression in lymphatic organs during EAE development in mice.
Experimental autoimmune encephalomyelitis (EAE) is mediated by myelin-specific CD4+ T cells secreting Th1 and/or Th17 cytokines. Signal transducer and activator of transcription (STAT) family proteins have essential roles in transmitting Th1 and/or Th17 cytokine-mediated signals. However, most studies demonstrating the importance of the STAT signaling system in EAE have focused on distinct members of this family, often looking at their role specifically in the central nervous system, or in vitro. There is limited information available regarding the temporal and spatial expression patterns of each STAT protein and interplay between STAT proteins over the course of EAE development in critical lymphatic organs in vivo. In the present study, we demonstrate dramatic and progressive decrease of all six STAT family members (STAT1, STAT2, STAT3, STAT4, STAT5, STAT6) in the spleen and lymph nodes through the course of EAE development in SJL/J mice, in contrast with almost steady expression of thymic STAT proteins. Decreased splenic and lymphatic STAT expression was accompanied by significant enlargement of the spleen and lymph nodes, and histological proliferation of T cell areas with remodeling of the splenic microstructure in EAE mice. All STAT family members except STAT2 were mainly confined in T cell areas in spleen, whereas they were distributed in a protein specific manner in thymus. We present here a comprehensive analysis of all six members of the STAT family in spleen, lymph nodes and thymus through the development phase of EAE. Results suggest that EAE induced inflammatory T cells may develop distinct biological features different from normal splenic T cells due to altered STAT signaling.


Acetaminophen Responsive miR-19b Modulates SIRT1/Nrf2 Signaling Pathway in Drug-Induced Hepatotoxicity.
Previous studies suggest that activation of SIRT1 protects liver from acetaminophen (APAP)-induced injury; however, the detailed mechanism of SIRT1 modulation in this process is still incomplete. Therefore, this study was to investigate the pathophysiological role of SIRT1 in APAP-mediated hepatotoxicity. We found that SIRT1 mRNA and protein were markedly upregulated in human LO2 cells and mouse liver upon APAP exposure. In vitro, the specific knockdown of SIRT1 expression ultimately aggravated APAP-evoked cellular antioxidant defense in LO2 cells. Moreover, lentivirus-mediated knockdown of hepatic SIRT1 expression exacerbated APAP-induced oxidative stress and liver injury, especially reduction of Nrf2 and subsequent downregulation of several antioxidant genes. Intriguingly, 30 mg/kg SRT1720, the specific SIRT1 activator, which greatly enhanced Nrf2 expression and antioxidant defense, and then eventually reversed APAP-induced hepatic liver injury in mice. Furthermore, APAP responsive miR-19b played an important role in regulating SIRT1 expression, whereas overexpression miR-19b largely abolished the induction of SIRT1 by APAP in vitro and in vivo. Specific SIRT1 3'-UTR mutation, which disrupted the interaction of miRNA-3'UTR, and successfully abrogated the modulation by miR-19b. Notably, hepatic miR-19b overexpression worsened the APAP-induced hepatotoxicity. In general, our results support the notion that the strong elevation of SIRT1 by APAP responsive miR-19b may represent a compensatory mechanism to protect liver against the drug-induced damage, at least in part by enhancing Nrf2-mediated antioxidant capacity in the liver.


Risk Factors for Nondiagnostic Imaging in a Real-World Deployment of Artificial Intelligence Diabetic Retinal Examinations in an Integrated Health care System: Maximizing Workflow Efficiency Through Predictive Dilation.
In the pivotal clinical trial that led to Food and Drug Administration De Novo "approval" of the first fully autonomous artificial intelligence (AI) diabetic retinal disease diagnostic system, a reflexive dilation protocol was used. Using real-world deployment data before implementation of reflexive dilation, we identified factors associated with nondiagnostic results. These factors allow a novel predictive dilation workflow, where patients most likely to benefit from pharmacologic dilation are dilated a priori to maximize efficiency and patient satisfaction. Retrospective review of patients who were assessed with autonomous AI at Johns Hopkins Medicine (8/2020 to 5/2021). We constructed a multivariable logistic regression model for nondiagnostic results to compare characteristics of patients with and without diagnostic results, using adjusted odds ratio (aOR). P < .05 was considered statistically significant. Of 241 patients (59% female; median age = 59), 123 (51%) had nondiagnostic results. In multivariable analysis, type 1 diabetes (T1D, aOR = 5.82, 95% confidence interval [CI]: 1.45-23.40, P = .01), smoking (aOR = 2.86, 95% CI: 1.36-5.99, P = .005), and age (every 10-year increase, aOR = 2.12, 95% CI: 1.62-2.77, P < .001) were associated with nondiagnostic results. Following feature elimination, a predictive model was created using T1D, smoking, age, race, sex, and hypertension as inputs. The model showed an area under the receiver-operator characteristics curve of 0.76 in five-fold cross-validation. We used factors associated with nondiagnostic results to design a novel, predictive dilation workflow, where patients most likely to benefit from pharmacologic dilation are dilated a priori. This new workflow has the potential to be more efficient than reflexive dilation, thus maximizing the number of at-risk patients receiving their diabetic retinal examinations.


An immunodominant 90-kilodalton Aspergillus fumigatus antigen is the subunit of a catalase.
We have identified, purified, and characterized structurally and functionally a 90-kDa immunodominant antigen associated with the water-soluble fraction of Aspergillus fumigatus. This antigen is recognized by 90.3% of serum samples from patients with aspergilloma and should be considered either by itself or better in combination with other purified antigens as a candidate for developing a standardized immunoassay for the detection of aspergilloma. p90 is a glycoprotein containing at least two two N-linked sugar chains of 2 and 5 kDa, respectively, which are not necessary for its reactivity with aspergilloma serum samples. Using specific anti-p90 rabbit serum, we have demonstrated that under native conditions, p90 exists in oligomeric form and has associated catalase activity. This activity is resistant to extreme temperatures (> 60 degrees C), reducing agents (40 mM dithiothreitol), high concentrations of denaturing agents such as 8 M urea and 8% sodium dodecyl sulfate, and treatments with ethanol-chloroform-water (5:3:10 [vol/vol]) mixtures.


A single administration of 'microbial' D-alanine to healthy volunteers augments reaction to negative emotions: A comparison with D-serine.
Activation of the glutamate N-methyl-D-aspartate receptor with its co-agonist D-serine has been shown to improve subjective mood in healthy volunteers. D-alanine is another potent N-methyl-D-aspartate receptor co-agonist which arises from the natural breakdown of host gut microbes, and is predominantly sequestered in the pituitary. This may suggest that D-alanine influences the neuroendocrine stress response which may then impact on emotion. The current study explored the effects of D-serine and D-alanine on emotional processing, cognition and the levels of the stress hormone cortisol in healthy volunteers. In a double-blind, placebo-controlled randomised study, participants (n=63) received a single oral dose of either D-serine, D-alanine (60 mg/kg) or placebo and then performed the Emotional Test Battery and N-back task (two hours post-administration) and provided saliva samples at fixed intervals. Subjects administered with D-alanine were faster at identifying facial expressions of fear, surprise and anger, and at categorising negative self-referential words. Participants on D-alanine also showed a trend to recall more words than placebo in a memory task. D-serine did not have any meaningful effects in any of the tasks. Neither amino acid had a significant effect on salivary cortisol or working memory. This study is the first to suggest that D-alanine can modulate emotional cognitive processing after a single dose. The lack of findings for D-serine nevertheless contrasts a previous study, emphasising a need for further investigation to clarify discrepancies. A better understanding of the physiological actions of D-amino acids would be beneficial in evaluating their therapeutic potential.


A systematic review of the effectiveness of primary health education or intervention programs in improving rural women's knowledge of heart disease risk factors and changing lifestyle behaviours.
Cardiovascular disease is the leading cause of death and disability for women in Australia. Women living in rural areas are at greater risk of heart disease, because of limited access and availability of healthcare in rural areas. Lifestyle is a major determinant to the risk of heart disease. Risk factors such as smoking, hypertension, diet, physical activity and alcohol intake can be controlled or modified by lifestyle changes. As heart disease develops over many years, women need to be following healthy lifestyle practices and reduce their chance of a first or recurrent heart attack. To determine the effectiveness of primary health education or intervention programs for cardiac risk reduction in healthy women living in rural areas. Types of participants. Women aged 16-65 years, living in rural areas, who participated in primary healthcare education programs. Types of interventions. Primary health education or intervention programs aimed at improving rural women's knowledge of their risk of heart disease, for example group work, videos, telephone, workshops, educational material and counselling. Types of outcomes. Primary outcomes included: • Knowledge level of heart disease risk factors. • Lifestyle modification, for example dietary improvements such as reduced daily salt intake, increased intake of fruit and vegetables and decreased intake of fat, increased frequency of exercise, decreased levels of smoking, alcohol intake within national guidelines. • Health assessment measures, for example blood pressure, body weight, cholesterol levels. Types of studies. Any randomised controlled trials, other experimental studies, as well as cohort, case-control and cross-sectional studies were considered for inclusion. Search strategy. A search for published and unpublished studies in the English language was undertaken. Each study was appraised independently by two reviewers using the standard Joanna Briggs Institute instruments. Information was extracted from studies meeting quality criteria using the standard Joanna Briggs Institute tools. Although similar outcomes are explored in many of the studies, the variable outcome measures precluded the use of meta-analysis. Data are therefore summarised in tables or by using narrative analysis. Nine trials were included in the review. Three trials compared the effects of interventions on physical activity, one on smoking and five on multiple risk factors. Studies following interventions targeting physical activity reported that women's physical activity can be increased and that these increases can be sustained at 12 months. While there were decreases in blood pressure at 6 months, studies with a 5-year follow up found no decreases for both systolic and diastolic blood pressure. Overall results of studies into dietary modification programs also did not sustain an effect over a longer period of time. The results of this review suggest that in rural areas, lifestyle interventions delivered by primary care providers in primary care settings to patients at low risk appeared to be of marginal benefit. Resources and time in primary care might be better spent on patients at higher risk of cardiovascular disease, such as those with diabetes or existing heart disease.


APOBEC deaminases as cellular antiviral factors: a novel natural host defense mechanism.
The APOBEC (acronym for apolipoprotein B editing catalytic polypeptide) family of cytidine deaminases are widely distributed in the biological world and play a central role in diverse enzymatic pathways. Members of this family (APOBEC3G and APOBEC3F) have been recently shown to be able to restrict HIV-1 replication in physiologically relevant target cells (macrophages, lymphocytes), presumably by triggering extensive deamination of the viral RNA/DNA replication intermediates. This natural antiretroviral host defense mechanism is counteracted by the HIV-1 protein Vif, which is able to target APOBECs to degrade. The so-called "Vif/APOBEC3G paradigm" has been confirmed by a growing literature. However, evidence arising from recent studies has expanded this view, showing that the replication of other viruses is also restricted by APOBEC family members and suggesting antiviral mechanism(s) of action unrelated to the catalytic activity of these proteins. Furthermore, evolutionary investigations on primates have shown that APOBEC3 gene expansion might be related to an ancient adaptive selection to prevent endogenous genetic instability, indicating an additional ancient protective role of APOBECs. This article is aimed at broadening the current knowledge about the antiviral activity of the APOBEC members and to highlight the notion that their role(s) might be more general than previously anticipated.


Na+ electrochemical gradient and Na+-Ca2+ exchange in rat proximal tubule.
The basolateral cell membrane of the rat proximal tubule contains a Na+-Ca2+ exchanger that may participate in the regulation of cytosolic calcium (Cai) and Ca2+ transport. In this work, the activity and orientation of the Na+-Ca2+ exchanger was studied in rat proximal tubules. The experiments were based on the thermodynamic notion that the exchanger is driven by the prevalence of either of two electrochemical gradients, that for Na+ (delta mu Na+) or for Ca2+ (delta mu Ca2+). Reductions in delta mu Na+, achieved by lowering extracellular Na+ (Nao) from 150 to 15 mM, increased Cai, decreased 45Ca efflux, and increased 45Ca influx. These changes occurred concurrently. When delta mu Na+ was reduced by increasing intracellular Na+ (Nai) with 10(-3) M oubain, Cai also increased. The effect of ouabain was probably dependent on Nai accumulation because the surge in Cai was prevented by exposure of the tubules to 5 mM Nao before ouabain exposure. On the other hand, when delta mu Na+ was lowered mM Nao and then by reducing Nao to 15 mM, Cai rose in two additive stages. We conclude from these data that in the rat proximal tubule the basal state of the Na+-Ca2+ exchanger is in forward mode, Nao-Cai. Moreover, the function of the Na+-Ca2+ exchanger is in accord with predictions derived from a thermodynamic analysis of its function.


Histone modifications in senescence-associated resistance to apoptosis by oxidative stress.
Aging and age-related diseases are associated with cellular senescence that results in variable apoptosis susceptibility to oxidative stress. Although fibroblast senescence has been associated with apoptosis resistance, mechanisms for this have not been well defined. In this report, we studied epigenetic mechanisms involving histone modifications that confer apoptosis resistance to senescent human diploid fibroblasts (HDFs). HDFs that undergo replicative senescence display typical morphological features, express senescence-associated β-galactosidase, and increased levels of the tumor suppressor genes, p16, p21, and caveolin-1. Senescent HDFs are more resistant to oxidative stress (exogenous H2O2)-induced apoptosis in comparison to non-senescent (control) HDFs; this is associated with constitutively high levels of the anti-apoptotic gene, Bcl-2, and low expression of the pro-apoptotic gene, Bax. Cellular senescence is characterized by global increases in H4K20 trimethylation and decreases in H4K16 acetylation in association with increased activity of Suv420h2 histone methyltransferase (which targets H4K20), decreased activity of the histone acetyltransferase, Mof (which targets H4K16), as well as decreased total histone acetyltransferase activity. In contrast to Bax gene, chromatin immunoprecipitation studies demonstrate marked enrichment of the Bcl-2 gene with H4K16Ac, and depletion with H4K20Me3, predicting active transcription of this gene in senescent HDFs. These data indicate that both global and locus-specific histone modifications of chromatin regulate altered Bcl-2:Bax gene expression in senescent fibroblasts, contributing to its apoptosis-resistant phenotype.


Anticancer effects of fraction isolated from fruiting bodies of Chaga medicinal mushroom, Inonotus obliquus (Pers.:Fr.) Pilát (Aphyllophoromycetideae): in vitro studies.
The medicinal mushroom Chaga, Inonotus obliquus (Pers.:Fr.) Pilát (Hymenochaetaceae), has been used in folk medicine in Russia, Poland, and most of the Baltic countries, as a cleansing and disinfecting measure, and as decoctions for stomach diseases, intestinal worms, liver and heart ailments, and cancer treatment. Many reports have been published concerning the health promoting functions of this mushroom, including antibacterial, hepatoprotective, anti-inflammatory, antitumor, and antioxidant activities. The purpose of the present study was evaluation of in vitro anticancer activity of fraction IO4 isolated from I. obliquus. The effect on cell proliferation, motility and viability was assessed in a range of cancer and normal cells. Chaga fraction prepared from dried fruiting bodies was subjected to anticancer evaluation in human lung carcinoma (A549), colon adenocarcinoma (HT-29), and rat glioma (C6) cell cultures. Human skin fibroblasts (HSF), bovine aorta endothelial cells (BAEC), models of rat oligodendrocytes (OLN-93), hepatocytes (Fao), rat astroglia, and mouse neurons (P19) were applied to test toxicity in normal cells. The following methods were applied: tumor cell proliferation (MTT assay and BrdU assay), cytotoxicity (LDH assay), tumor cell motility (wound assay), tumor cell morphology (May-Grünwald-Giemsa staining), and death detection (ELISA). Chaga fraction elicited anticancer effects which were attributed to decreased tumor cell proliferation, motility and morphological changes induction. Of note is the fact that it produced no or low toxicity in tested normal cells. The data presented could open interesting paths for further investigations of fraction IO4 as a potential anticancer agent.


Foraging sequence, energy intake and torpor: an individual-based field study of energy balancing in desert golden spiny mice.
We studied the relationship between sequence of foraging, energy acquired and use of torpor as an energy-balancing strategy in diurnally active desert golden spiny mice. We hypothesised that individuals that arrive earlier to forage will get higher returns and consequently spend less time torpid. If that is the case, then early foragers can be viewed as more successful; if the same individuals arrive repeatedly early, they are likely to have higher fitness under conditions of resource limitation. For the first time, we show a relationship between foraging sequence and amount of resources removed, with individuals that arrive later to a foraging patch tending to receive lower energetic returns and to spend more time torpid. Torpor bears not only benefits but also significant costs, so these individuals pay a price both in lower energy intake and in extended periods of torpor, in what may well be a positive feedback loop.


OX40 ligand and OX40 are increased in atopic dermatitis lesions but do not correlate with clinical severity.
The interaction between the OX40 ligand (OX40L) and OX40 has been suggested to have pathogenetic significance in atopic dermatitis (AD). The purpose of this study was to investigate the expression and relevance of OX40L and OX40 in AD skin. OX40L and OX40 were stained immunohistochemically on the cryosections of the lesional and non-lesional skin of 17 subjects with moderate-to-severe AD and of 10 patients with psoriasis vulgaris. Phorbol myristate acetate (PMA) stimulated keratinocytes and cell membrane preparations from PMA-stimulated keratinocytes or LAD-2 mast cells were incubated with peripheral blood mononuclear cells (PBMC) in the presence or absence of blocking monoclonal antibodies to OX40L, CD30L or ICAM-1. We show for the first time that the staining intensity of OX40L and the number of OX40(+) cells are significantly greater in the lesional dermis than in the healthy-looking dermis in AD (P < 0.001 in both comparisons) and also in psoriasis (P = 0.01 and P < 0.001 respectively), but neither molecule correlate significantly with the clinical severity of AD. Living keratinocytes and cell membranes from LAD-2 mast cells and keratinocytes increased the PBMC proliferation response. Anti-OX40L antibody inhibited, in a similar fashion as anti-ICAM-1 and anti-CD30L, PBMC proliferation induced by LAD-2 membranes, but stimulated that induced by keratinocytes. Our findings provide evidence for the involvement of OX40 and OX40L in the pathogenesis of AD though they are not specific to AD and in vitro results suggest complex interaction.


Idiopathic scoliosis in identical (monozygotic) twins.
The exact nature of the primary predisposing cause of idiopathic scoliosis is unknown. Hereditary and/or environmental factors may be responsible. Two sets of identical twins presenting in adolescence with concordant scoliotic curves were studied and lend support for a hereditary predisposition favoring a multifactorial inheritance.


[The action of a pulsed magnetic field on the electrical resistance of the skin].
The skin of 32 rabbits and 10 patients (7 males and 3 females aged 32-48) was exposed to impulse magnetic field (IMF) with intensity of 1.0-1.5 T and frequency of 45 paired impulses a minute. The 5-minute exposure resulted in a 50% decrease in the skin electrical resistance both in patients and animals. On aftertreatment minute 2 the resistance started recovering and returned to the baseline on minute 6 in animals and 4 in patients. Changes in electrical resistance of the skin are attributed to emergence of IMF-related electrical induction.


Top-down influences of written text on perceived clarity of degraded speech.
An unresolved question is how the reported clarity of degraded speech is enhanced when listeners have prior knowledge of speech content. One account of this phenomenon proposes top-down modulation of early acoustic processing by higher-level linguistic knowledge. Alternative, strictly bottom-up accounts argue that acoustic information and higher-level knowledge are combined at a late decision stage without modulating early acoustic processing. Here we tested top-down and bottom-up accounts using written text to manipulate listeners' knowledge of speech content. The effect of written text on the reported clarity of noise-vocoded speech was most pronounced when text was presented before (rather than after) speech (Experiment 1). Fine-grained manipulation of the onset asynchrony between text and speech revealed that this effect declined when text was presented more than 120 ms after speech onset (Experiment 2). Finally, the influence of written text was found to arise from phonological (rather than lexical) correspondence between text and speech (Experiment 3). These results suggest that prior knowledge effects are time-limited by the duration of auditory echoic memory for degraded speech, consistent with top-down modulation of early acoustic processing by linguistic knowledge.


Receptor-mediated uptake and transport of macromolecules in the human placenta.
The human placenta is required to be the anchor, the conduit and the controller during pregnancy. The survival of the baby and its associated placenta is dependent upon the placenta shielding the embryo/fetus from harm, e.g., autoimmune disease - thrombophilia, antiphospholipid syndrome or infections, while simultaneously providing for the passage of critical nutrients (e.g., amino acids, vitamins) and beneficial immunoglobulins. In a number of instances, the movements of macromolecules into and through the placenta can result in the passage of the intact molecules into the fetal circulation or in the case of proteins - catabolism to amino acids which are utilized by the placenta and the fetus for continued growth and development. The transfer of two such macromolecules, immunoglobulin G (IgG) and vitamin B12 (cyanocobalamin or B12), are examined as to the unique receptor-mediated transfer capability of the human placenta, its transfer specificity as related to specific receptors and the role of endogeneous placental proteins (trancobalamins) in facilitating the recognition and transport of specifically B12. Brief comparisons will be made to other animal species and the differences in specific organ transfer capabilities.


Extradural extension of primitive neuroectodermal tumor--case report.
A 13-year-old boy presented with a primitive neuroectodermal tumor (PNET) with unusual extracranial extension. Precontrast computed tomography showed the tumor as a ring-shaped high-density area which was enhanced postcontrast, with a low-density center. Magnetic resonance imaging showed the tumor as a low-intensity area on the T1-weighted images with marked enhancement by gadolinium-diethylenetriaminepentaacetic acid, and high intensity on the T2-weighted images. The central area appeared as high intensity on both images, suggesting free methemoglobin. The tumor was subtotally removed. Histological examination demonstrated PNET. Despite irradiation (20 Gy) to the surgical site, and further tumor removal, he died 6 months later. This case showed PNET can extend extracranially. Diagnosis and treatment of such a tumor located extracranially and intracranially require careful consideration.


Deep brain photoreceptors control light-seeking behavior in zebrafish larvae.
Most vertebrates process visual information using elaborately structured photosensory tissues, including the eyes and pineal. However, there is strong evidence that other tissues can detect and respond to photic stimuli. Many reports suggest that photosensitive elements exist within the brain itself and influence physiology and behavior; however, a long-standing puzzle has been the identity of the neurons and photoreceptor molecules involved. We tested whether light cues influence behavior in zebrafish larvae through deep brain photosensors. We found that larvae lacking eyes and pineal perform a simple light-seeking behavior triggered by loss of illumination ("dark photokinesis"). Neuroanatomical considerations prompted us to test orthopedia (otpa)-deficient fish, which show a profound reduction in dark photokinesis. Using targeted genetic ablations, we narrowed the photosensitive region to neurons in the preoptic area. Neurons in this region express several photoreceptive molecules, but expression of the melanopsin opn4a is selectively lost in otpa mutants, suggesting that opn4a mediates dark photokinesis. Our findings shed light on the identity and function of deep brain photoreceptors and suggest that otpa specifies an ancient population of sensory neurons that mediate behavioral responses to light.


Interactions between cyclic nucleotides and common cations: an ab initio molecular dynamics study.
We present the first, to the best of our knowledge, ab initio molecular dynamics (AIMD) investigation on three aqueous solutions where an abasic cyclic nucleotide model is solvated in the presence of distinct cations (i.e., Na+, K+ and Mg2+). We elucidate the typical modalities of interaction between those ionic species and the nucleotide moiety by first-principles numerical simulations, starting from an inner-shell binding configuration on a time scale of 100 ps (total simulation time of ∼600 ps). Whereas the strong "structure-maker" Mg2+ is permanently bound to one of the two oxygen atoms of the phosphate group of the nucleotide model, Na+ and K+ show binding times τb of 65 ps and 10-15 ps, respectively, thus reflecting their chemical nature in aqueous solutions. Furthermore, we qualitatively relate these findings to approximate free-energy barriers of the cations' unbinding obtained by means of exploratory well-tempered metadynamics. With the aim of shedding light on the features of commonly employed force-fields (FFs), classical MD simulations (almost 200 trajectories with a total simulation time of ∼18 μs) using the biomolecular AMBER FF are also reported. By choosing several combinations of the parametrization for the water environment (i.e., TIP3P, SPC/E and OPC) and cations (i.e., Joung-Cheatham, Li-Merz 12-6 and Li-Merz 12-6-4), we found significant differences in the radial distribution functions and residence times compared to the ab initio results. The Na+ and K+ ions wrongly show quasi-identical radial distribution functions and the Li & Merz 12-6-4 Lennard-Jones parameters for Mg2+ were found to be essential in quickly reaching the binding state consistent with AIMD.


Qualitative and quantitative research into the development and feasibility of a video-tailored physical activity intervention.
Continued low adherence to physical activity recommendations illustrates the need to refine intervention strategies and increase their effectiveness. The purpose of this study was to conduct formative research related to the development of a next generation of computer-tailored interventions that use online tailored video-messages to increase physical activity. Five focus groups (n = 30), aimed at males and females, aged between 35 and 60 years, that do not meet the physical activity recommendation, were conducted to allow in-depth discussion of various elements related to the development of an online video-tailored intervention. In addition, a series of questions were delivered to a random sample (n = 1261) of Australians, using CATI survey technology, to gain more information and add a quantitative assessment of feasibility related to the development of the intervention. Focus group data was transcribed, and summarised using Nvivo software. Descriptive and frequency data of the survey was obtained using SPSS 18.0. Nearly all of the focus group participants supported the concept of a video-tailored intervention and 35.8% of survey participants indicated that they would prefer a video-based over a text-based intervention. Participants with a slow internet-connection displayed a lower preference for video-based advice (31.9%); however less than 20% of the survey sample indicated that downloading videos would be slow. The majority of focus group and survey participants did not support the idea of using mobile phones to receive this kind of intervention and indicated that video-tailored messages should be shorter than 5 minutes. Video-delivery of content is very rich in information, which increases the challenge to appropriately tailor content to participant characteristics; focus-group outcomes indicated a large diversity in participant preferences. 52.4% of survey participants indicated that the videos should be convincing and motivating. These results provide valuable information to develop an innovative video-tailored physical activity intervention. The results support the feasibility of such intervention, both in terms of users being ready to participate in it, as well as from a point of view whereby current internet infrastructure is able to cope with the demands of downloading videos. Though promising, a number of specific challenges in the development of these interventions were identified (e.g. the videos need to be short, made professionally, and tailor to a larger number of variables) and will need to be overcome in the development and evaluation of this new type of physical activity intervention.


Use of administrative data to identify health plan members with unrecognized bipolar disorder: a retrospective cohort study.
This retrospective cohort study used an algorithmic case-finding system on claims data from nationwide commercial health plans to validate previously identified predictors of unrecognized bipolar disorder among adults. Retrospective cohort design. Using logistic regression, 2 claims data sets were evaluated to explore potential predictors; the first included claims for all healthcare encounters (all-encounters data set); the second excluded mental health provider claims (carve-out data set). A total of 280,244 members aged 18 to 64 years were included from 2 commercial health plans. Claims related to attention deficit-hyperactivity disorder, depression, depression treated with antipsychotics, use of 3 (of 5) classes of psychotherapeutic drugs, younger age, and sex were all significant predictors of a subsequent diagnosis of bipolar disorder. In the all-encounters data set, a predicted value of 5% or greater yielded a sensitivity of 9.8% and a specificity of 99.9%; a predicted threshold of 3% increased sensitivity to 20.7%; area under the receiver operating characteristic curve (AUC) was 0.82. Performance of the model was acceptable in the carve-out data set, with AUC 0.69. The case-finding system described here, which compares favorably with other screening tests used in primary care, may have significant value in helping physicians to identify patients with unrecognized bipolar disorder.


The Effect of Personality Traits of Managers/Supervisor on Job Satisfaction of Medical Sciences University Staffs.
Todays people are spending most of their time life in their workplace therefore investigation for job satisfaction related factors is necessities of researches. The purpose of this research was to analyze the effect of manager's personality traits on employee job satisfaction. The present study is a descriptive and causative-comparative one utilized on a statistical sample of 44 managers and 119 employees. It was examined and analyzed through descriptive and inferential statistics of Student's t-test (independent T), one-way ANOVA, and Kolmogorov-Smirnov test. Findings showed that the managers and supervisors with personality traits of extraversion, eagerness to new experiences, adaptability, and dutifulness had higher subordinate employee job satisfaction. However, in the neurotic trait, the result was different. The results showed that job satisfaction was low in the aspect of neurosis. Based on this, it is suggested that, before any selection in managerial and supervisory positions, candidates receive a personality test and in case an individual has a neurotic trait, appropriate interference takes place both in this group and the employees' one.


Clinical and histologic features of striated muscle hamartoma: possible relationship to Delleman's syndrome.
We describe 5 new cases of striated muscle hamartoma (SMH) and review the 7 cases previously described in the literature. Eleven of the 12 patients had single lesions centrally located on the chin (4), near the ala of the nose (3), on the upper chest (3), and on the upper lip (1). Histologically all of the lesions were characterized by a central core containing bundles and individual fibers of skeletal muscle as well as other mesenchymal elements. The muscle fibers penetrated the dermis among numerous folliculo-sebaceous structures. Of the 12 cases of SMH, 3 had other associated congenital anomalies including a cleft lip in 1 patient and a thyroglossal duct sinus in another with single lesions, and preauricular sinuses, low-set ears and bilateral sclerocorneas in the case of multiple SMH. The relationship of SMH with oculocerebrocutaneous syndrome is discussed, and we conclude that at least some of the skin appendages associated with that syndrome are SMH.


Isolation and identification of phenolic antioxidants in black rice bran.
Black rice bran contains phenolic compounds of a high antioxidant activity. In this study, the 40% acetone extract of black rice bran was sequentially fractionated to obtain 5 fractions. Out of the 5 fractions, ethyl acetate fraction was subfractionated using the Sephadex LH-20 chromatography. The antioxidant activity of phenolic compounds in the extracts was investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, 2,2-azino-bis-(3-ethylenebenzothiozoline-6-sulfonic acid) (ABTS) radical cation assay, reducing power. The subfraction 2 from ethyl acetate fraction had the highest total phenolic contents (TPC) (816.0 μg/mg) and the lowest EC50 values (47.8 μg/mL for DPPH radical assay, 112.8 μg/mL for ABTS radical cation assay, and 49.2 μg/mL for reducing power). These results were 3.1, 1.3, and 2.6 times lower than those of butylated hydroxytoluene (BHT), respectively. At a concentration of 100 μg/mL, the antioxidant activity and TPC of various extracts was closely correlated, with correlation coefficients (R(2) ) higher than 0.86. The major phenolic acid in subfraction 2 was identified as ferulic acid (178.3 μg/mg) by HPLC and LC-ESI/MS/MS analyses. Our finding identified ferulic acid as a major phenolic compound in black rice bran, and supports the potential use of black rice bran as a natural source of antioxidant.


Benefits of Multifaceted Chemopreventives in the Suppression of the Oral Squamous Cell Carcinoma (OSCC) Tumorigenic Phenotype.
Over one third of patients who have undergone oral squamous cell carcinoma (OSCC) surgical resections develop life-threatening and often untreatable recurrences. A variety of drugs, intended for management of recurrent or disseminated cancers, were designed to exploit cancer cells' reliance upon overexpressed receptors and gratuitous signaling. Despite their conceptual promise, clinical trials showed these agents lacked efficacy and were often toxic. These findings are consistent with evasion of pathway-targeted treatments via extensive signaling redundancies and compensatory mechanisms common to cancers. Optimal secondary OSCC chemoprevention requires long-term efficacy with multifaceted, nontoxic agents. Accordingly, this study evaluated the abilities of three complementary chemopreventives, that is, the vitamin A derivative fenretinide (4-HPR, induces apoptosis and differentiation, inhibits signaling proteins, and invasion), the estrogen metabolite 2-methoxyestradiol (2-ME, apoptosis-inducing, antiangiogenic), and the humanized mAb to the IL6R receptor tocilizumab (TOC, reduces IL6 signaling) to suppress OSCC gratuitous signaling and tumorigenesis. Modeling studies demonstrated 4-HPR's high-affinity binding at STAT3's dimerization site and c-Abl and c-Src ATP-binding kinase sites. Although individual agents suppressed cancer-promoting pathways including STAT3 phosphorylation, STAT3-DNA binding, and production of the trans-signaling enabling sIL6R, maximal chemopreventive effects were observed with agent combinations. OSCC tumor xenograft studies showed that locally delivered TOC, TOC+4-HPR, and TOC+4-HPR+2-ME treatments all prevented significant tumor growth. Notably, the TOC+4-HPR+2-ME treatment resulted in the smallest overall increase in tumor volume. The selected agents use diverse mechanisms to disrupt tumorigenesis at multiple venues, that is, intracellular, tumor cell-ECM, and tumor microenvironment; beneficial qualities for secondary chemopreventives. Cancer Prev Res; 10(1); 76-88. ©2016 AACR.


Associations between employee and manager gender: impacts on gender-specific risk of acute occupational injury in metal manufacturing.
Prior research has shown increased risk of injury for female employees compared to male employees after controlling for job and tasks, but have not explored whether this increased risk might be moderated by manager gender. The gender of one's manager could in theory affect injury rates among male and female employees through their managers' response to an employee's psychosocial stress or through how employees differentially report injuries. Other explanations for the gender disparity in injury experience, such as ergonomic factors or differential training, are unlikely to be impacted by supervisor gender. This study seeks to explore whether an employee's manager's gender modifies the effect of employee gender with regards to risk of acute injury. A cohort of employees and managers were identified using human resources and injury management data between January 1, 2002 and December 31, 2007 for six facilities of a large US aluminum manufacturing company. Cox proportional hazards models were employed to examine the interaction between employee gender and whether the employee had female only manager(s), male only manager(s), or both male and female managers on injury risk. Manager gender category was included as a time varying covariate and reassessed for each employee at the midpoint of each year. The percentage of departments with both female and male managers increased dramatically during the study period due to corporate efforts to increase female representation in management. After adjustment for fixed effects at the facility level and shared frailty by department, manager gender category does not appear to moderate the effect of employee gender (p = 0.717). Manager category was not a significant predictor (p = 0.093) of time to first acute injury. Similarly, having at least one female manager did not modify the hazard of injury for female employees compared to males (p = 0.899) and was not a significant predictor of time to first acute injury (p = 0.601). Prior findings suggest that female manufacturing employees are at higher risk for acute injury compared to males; this analysis suggests that this relationship is not affected by the gender of the employee's manager(s).


The effect of cigarette branding and plain packaging on female youth in the United Kingdom.
Cigarette packaging is the most prominent form of tobacco marketing remaining in countries such as the United Kingdom. The current study examined perceptions of cigarette packaging among female youth and the potential impact of "plain" cigarette packaging regulations. A national sample of 947 16- to 19-year-old female subjects in the United Kingdom completed an online survey. Participants were randomized to view 10 cigarette packs designed according to one of four experimental conditions: fully branded female packs, the same packs without descriptor words, the same packs without brand imagery or descriptors ("plain" packs), and branded non-female brands. Participants rated packs on measures of appeal and health risk, positive smoker image, and completed a behavioral pack selection task. Plain packs were rated as the least appealing and worse tasting compared with all other conditions. Plain packs were also associated with fewer false beliefs about health risks compared with branded packs. Removing brand descriptors from packs significantly reduced measures of appeal and taste, particularly for brands with flavor descriptors, such as cherry and vanilla. Plain packs were significantly less likely to be associated with positive images, such as glamour, sophistication, and slimness. Most importantly, respondents were significantly less likely to accept a pack of cigarettes when offered only plain versus branded packs (p = .026). Marketing in the form of pack branding remains a potent tool for increasing the appeal of tobacco products to young women. The findings provide empirical support for plain cigarette packaging regulations in Australia to be implemented in 2012.


Arsenic Exposure and Immunotoxicity: a Review Including the Possible Influence of Age and Sex.
Increasing evidence suggests that inorganic arsenic, a major environmental pollutant, exerts immunosuppressive effects in epidemiological, in vitro, and animal models. The mechanisms, however, remain unclear, and little is known about variation in susceptibilities due to age and sex. We performed a review of the experimental and epidemiologic evidence on the association of arsenic exposure and immune diseases. The majority of the studies described arsenic as a potent immunosuppressive compound, though others have reported an increase in allergy and autoimmune diseases, suggesting that arsenic may also act as an immune system stimulator, depending on the dose or timing of exposure. Limited information, due to either the high concentrations of arsenic used in in vitro studies or the use of non-human data for predicting human risks, is available from experimental studies. Moreover, although there is emerging evidence that health effects of arsenic manifest differently between men and women, we found limited information on sex differences on the immunotoxic effects of arsenic. In conclusion, preliminary data show that chronic early-life exposure to arsenic might impair immune responses, potentially leading to increased risk of infections and inflammatory-like diseases during childhood and in adulthood. Further investigation to evaluate effects of arsenic exposure on the developing immune system of both sexes, particularly in human cells and using concentrations relevant to human exposure, should be a research priority.


Down-regulation of vesicular stomatitis virus transcription by the matrix protein of influenza virus.
The matrix (M1) protein isolated from influenza A/WSN/33 virus, when reconstituted with ribonucleoprotein (RNP) cores of vesicular stomatitis virus (VSV), resulted in inhibition of VSV transcription in vitro. The presence of endogenous wild-type (wt) or mutant (tsO23) VSV matrix (M) protein on RNP cores did not prevent down-regulation of VSV transcription by reconstituted influenza virus M1 protein. In fact, endogenous VSV wt M protein augmented transcription inhibition by M1 protein reconstituted with RNP/M protein cores, whereas mutant tsO23 M protein endogenous to RNP cores had no effect on down-regulation of VSV transcription by M1 protein. These data suggest that VSV M protein and influenza virus M1 protein recognize two different sites on RNP cores responsible for down-regulation of VSV transcription. Monoclonal antibodies (MAbs) directed to epitope 2 of M1 protein had been previously shown to reverse transcription inhibition by M1 protein on influenza virus RNP cores, but the same epitope 2-specific MAb had little effect on transcription inhibition by M1 protein reconstituted with VSV RNP cores. VSV M protein bears a striking resemblance biologically and genetically to the M1 protein, including, as shown here, their capacity to bind viral RNA. However, the VSV wt M protein exhibited no capacity to down-regulate transcription by influenza virus RNP cores. The significance of these studies is the identification on VSV RNP templates of at least two separate sites for recognition of protein factors that repress VSV transcription.


Pesticide tolerance in amphibians: induced tolerance in susceptible populations, constitutive tolerance in tolerant populations.
The role of plasticity in shaping adaptations is important to understanding the expression of traits within individuals and the evolution of populations. With increasing human impacts on the environment, one challenge is to consider how plasticity shapes responses to anthropogenic stressors such as contaminants. To our knowledge, only one study (using mosquitoes) has considered the possibility of induced insecticide tolerance. Using populations of wood frogs (Lithobates sylvaticus) located close to and far from agricultural fields, we discovered that exposing some populations of embryos and hatchlings to sublethal concentrations of the insecticide carbaryl induced higher tolerance to a subsequent lethal concentration later in life. Interestingly, the inducible populations were located >800 m from agricultural areas and were the most susceptible to the insecticide. In contrast, the noninducible populations were located close to agricultural areas and were the least susceptible. We also found that sublethal concentrations of carbaryl induced higher tadpole AChE concentrations in several cases. This is the first study to demonstrate inducible tolerance in a vertebrate species and the pattern of inducible and constitutive tolerance among populations suggests the process of genetic assimilation.


Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson's disease.
Power spectra from local field potentials (LFPs) recorded post-operatively from the deep brain stimulation (DBS) macroelectrode show prominence of the beta rhythm (11-30 Hz) in untreated Parkinson's disease (PD). Dopaminergic medication and movement attenuate this beta band in PD. In this pilot study of six sides in four patients, we recorded LFPs from the DBS electrode in untreated PD patients in the operating room. In all cases, there was a peak in the time-frequency spectrogram in the beta frequency range when the patients were at rest, which was associated with attenuation in the same range with movement. The actual frequency range and the strength of the beta peak varied among cases. In two patients, intra-operative constraints permitted recording of LFPs at rest, before and immediately after subthalamic nucleus (STN) DBS. In both patients we documented that STN DBS caused a significant attenuation in power in the beta band at rest that persisted for 15-25 s after DBS had been turned off (P < 0.01). From one case, our data suggest that the beta rhythm attenuation was most prominent within the STN itself. This study shows for the first time that STN DBS attenuates the power in the prominent beta band recorded in the STN of patients with PD. These pilot findings raise the interesting possibility of using this biomarker for closed loop DBS or neuromodulation.


Non-interacting surface solvation and dynamics in protein-protein interactions.
Protein-protein interactions control a plethora of cellular processes, including cell proliferation, differentiation, apoptosis, and signal transduction. Understanding how and why proteins interact will inevitably lead to novel structure-based drug design methods, as well as design of de novo binders with preferred interaction properties. At a structural and molecular level, interface and rim regions are not enough to fully account for the energetics of protein-protein binding, even for simple lock-and-key rigid binders. As we have recently shown, properties of the global surface might also play a role in protein-protein interactions. Here, we report on molecular dynamics simulations performed to understand solvent effects on protein-protein surfaces. We compare properties of the interface, rim, and non-interacting surface regions for five different complexes and their free components. Interface and rim residues become, as expected, less mobile upon complexation. However, non-interacting surface appears more flexible in the complex. Fluctuations of polar residues are always lower compared with charged ones, independent of the protein state. Further, stable water molecules are often observed around polar residues, in contrast to charged ones. Our analysis reveals that (a) upon complexation, the non-interacting surface can have a direct entropic compensation for the lower interface and rim entropy and (b) the mobility of the first hydration layer, which is linked to the stability of the protein-protein complex, is influenced by the local chemical properties of the surface. These findings corroborate previous hypotheses on the role of the hydration layer in shielding protein-protein complexes from unintended protein-protein interactions.


Systemic short-chain fatty acids rapidly alter gastrointestinal structure, function, and expression of early response genes.
Luminal and systemic short chain fatty acids (SCFA) stimulate mucosal proliferation but the mechanism(s) is unclear. This study examined acute effects of systemic SCFAs on gastrointestinal structure and function and signals potentially mediating SCFA-induced mucosal proliferation. Male Sprague-Dawley rats (246+/-2 g) received nutrients as either standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous formulation containing SCFAs (TPN + SCFA). Animals were randomized to one of five treatments: standard TPN for 72 hr, TPN + SCFA for 72 hr, or standard TPN followed by TPN + SCFA for the final 6, 12, and 24 hr. SCFAs reduced (P < 0.003) ileal protein within 6 hr. Jejunal GLUT2 expression was increased (P=0.0001) in all SCFA groups and ileal GLUT2 protein in the 6-, 12-, and 24-hr SCFA groups (P < 0.05). SCFAs increased (P < 0.003) ileal proglucagon abundance following 6, 12, and 24 hr, and plasma GLP-2 concentration following 12 hr (P < 0.03). Jejunal c-myc expression was increased (P < 0.001) following 6, 12, and 24 hr of SCFAs. SCFAs increased ileal c-myc, c-jun, and c-fos expression following 24 hr (P < 0.02), 12 hr (P < 0.05) and 6, 12, and 24 hr (P=0.0001), respectively. In conclusion, systemic SCFAs increase plasma GLP-2 and ileal proglucagon mRNA, GLUT2 expression and protein, and c-myc, c-jun, and c-fos expression.


Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization.
Early embryo miscarriage is linked to inadequate endometrial decidualization, a cellular transformation process that enables deep blastocyst invasion into the maternal compartment. Although much of the cellular events that underpin endometrial stromal cell (ESC) decidualization are well recognized, the individual gene(s) and molecular pathways that drive the initiation and progression of this process remain elusive. Using a genetic mouse model and a primary human ESC culture model, we demonstrate that steroid receptor coactivator-2 (SRC-2) is indispensable for rapid steroid hormone-dependent proliferation of ESCs, a critical cell-division step which precedes ESC terminal differentiation into decidual cells. We reveal that SRC-2 is required for increasing the glycolytic flux in human ESCs, which enables rapid proliferation to occur during the early stages of the decidualization program. Specifically, SRC-2 increases the glycolytic flux through induction of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3), a major rate-limiting glycolytic enzyme. Similarly, acute treatment of mice with a small molecule inhibitor of PFKFB3 significantly suppressed the ability of these animals to exhibit an endometrial decidual response. Together, these data strongly support a conserved mechanism of action by which SRC-2 accelerates the glycolytic flux through PFKFB3 induction to provide the necessary bioenergy and biomass to meet the demands of a high proliferation rate observed in ESCs prior to their differentiation into decidual cells. Because deregulation of endometrial SRC-2 expression has been associated with common gynecological disorders of reproductive-age women, this signaling pathway, involving SRC-2 and PFKFB3, promises to offer new clinical approaches in the diagnosis and/or treatment of a non-receptive uterus in patients presenting idiopathic infertility, recurrent early pregnancy loss, or increased time to pregnancy.


High affinity binding of anti-oestrogen to the chick liver nuclear oestrogen receptor.
Tamoxifen is a potent inhibitor of specific oestrogen-induced yolk protein synthesis by chicken liver. The oestradiol receptor in salt extracts of liver nuclei from oestrogen-treated chicks has a K(d) for oestradiol of 0.7+/-0.2nm. Tamoxifen and its metabolite, monohydroxytamoxifen, compete for binding to the salt-soluble nuclear receptor with K(i) values of 2.6 and 0.1nm respectively. The anti-oestrogens show much less inhibition of [(3)H]oestradiol binding when assays are carried out using intact nuclei. The competition by unlabelled oestradiol for [(3)H]oestradiol binding to receptor is identical in both salt extracts and intact nuclei. This suggests that intact nuclei contain components which bind anti-oestrogens, but not oestradiol. While tamoxifen and desmethyltamoxifen will readily dissociate from the salt-soluble nuclear oestrogen receptor, monohydroxytamoxifen does not dissociate under the conditions generally used for exchange assays. A modified assay was developed in which 60-70% of monohydroxytamoxifen-bound sites were shown to be exchangeable for [(3)H]oestradiol. Soluble receptor preparations were first incubated in a 1.7% charcoal suspension at 37 degrees C for 15min before assay of specific oestradiol binding. This technique was used in examining the effects of tamoxifen and monohydroxytamoxifen given in vivo on the nuclear oestrogen receptor concentration. Despite their 30-fold difference in binding affinity for the receptor, both anti-oestrogens increase nuclear receptor levels to about the same degree. When given with oestradiol, both compounds have the same apparent partial inhibitory effect on the oestrogen-induced increase in nuclear receptor. These data are consistent with the metabolic hydroxylation of tamoxifen before binding to the hepatic oestrogen receptor.


Large-aperture high-resolution x-ray collimator for the Solar Maximum Mission.
A description is presented of a flight-qualified large-aperture 12 x 12-sec of arc angular resolution multigrid x-ray collimator developed for the Solar Maximum Mission (SMM) flat crystal spectrometer. This collimator, designed for the 1.4-22.4-A wavelength range, utilizes an optical bench/metering structure to align and support prealigned grid subassemblies. One advantage of this scheme is to provide ready access to the grid subassemblies for inspection and/or servicing. The optical bench is a lightweight, rigid, and stable aluminum honeycomb structure. Aluminum is a viable material choice in this application because of the good thermal control expected in the SMM instrument package. The grids are of a compound and bimetallic design, having 63.5-microm square holes on an 88.9-microm spacing in 8-microm thick gold, which is in turn supported by a 76-microm thick Invar grid having 600-microm square holes on a 739-microm spacing. The small apertures in the gold provide the 12-sec of arc collimation with the Invar grids providing wide angle off-axis blocking out to an ~35-min of arc view angle. The collimator has seven individual channels, four of a 5.1- x 10-cm area and three of a 1.3- x 10-cm area. Laboratory measurements gave an average angular resolution of 12.5-sec of arc FWHM with 0.259 transmission for the large area channels and 12.0 sec of arc and 0.200 transmission for the small area channels. A hypothetical perfectly aligned collimator would have 12.5-sec of arc resolution and 0.300 transmission. A thermal filter composed of two layers of ~1000-A thick aluminum prevents solar heating of the front collimator grids by absorbing longer wavelength radiation while passing most of the x radiation in the band of interest. The filter was flight qualified by passing a protoflight acoustic test environment of 147-dB total sound level, 20-microN/M(2) reference, for 1-min duration.


Malleability of Alcohol Consumption: Evidence from Migrants.
How malleable is alcohol consumption? Specifically, how much is alcohol consumption driven by the current environment versus individual characteristics? To answer this question, we analyze changes in alcohol purchases when consumers move from one state to another in the United States. We find that if a household moves to a state with a higher (lower) average alcohol purchases than the origin state, the household is likely to increase (decrease) its alcohol purchases right after the move. The current environment explains about two-thirds of the differences in alcohol purchases. The adjustment takes place both on the extensive and intensive margins.


Effect of calcium membrane blockers on in vivo vasoconstrictor properties of norepinephrine, angiotensin II and vasopressin.
In the present study the in vivo role of transcellular calcium influx in humorally-mediated vasoconstriction was examined in conscious rats using two chemically dissimilar inhibitors of cellular calcium uptake, namely verapamil (Ver, 50 micrograms/kg/min) and nifedipine (Nif, 7.5 micrograms/kg/min). The pressor effect of arginine vasopressin (AVP, 10 mU/kg/min), angiotensin II (AII, 0.3 micrograms/kg/min) and norepinephrine (NE, 4 micrograms/kg/min) was virtually abolished by Ver and Nif. None of the pressors when infused alone increased mean arterial pressure (MAP) by increasing cardiac index (CI). During the administration of the calcium antagonists and AII or NE, CI was slightly but not significantly higher than with AII or NE alone. A modest fall in CI occurred with AVP and Ver but not with AVP and Nif. Thus, the effect of calcium antagonists to block the pressor responses of AVP, NE and AII was primarily by preventing the increase in peripheral vascular resistance rather than depressing CI. In summary, transcellular calcium influx appears to constitute the common in vivo pathway for constriction of peripheral blood vessels by AVP, NE and AII. These findings have substantial pathogenetic and therapeutic implications in hypo- and hypertensive states.


3D hand motion trajectory prediction from EEG mu and beta bandpower.
A motion trajectory prediction (MTP) - based brain-computer interface (BCI) aims to reconstruct the three-dimensional (3D) trajectory of upper limb movement using electroencephalography (EEG). The most common MTP BCI employs a time series of bandpass-filtered EEG potentials (referred to here as the potential time-series, PTS, model) for reconstructing the trajectory of a 3D limb movement using multiple linear regression. These studies report the best accuracy when a 0.5-2Hz bandpass filter is applied to the EEG. In the present study, we show that spatiotemporal power distribution of theta (4-8Hz), mu (8-12Hz), and beta (12-28Hz) bands are more robust for movement trajectory decoding when the standard PTS approach is replaced with time-varying bandpower values of a specified EEG band, ie, with a bandpower time-series (BTS) model. A comprehensive analysis comprising of three subjects performing pointing movements with the dominant right arm toward six targets is presented. Our results show that the BTS model produces significantly higher MTP accuracy (R~0.45) compared to the standard PTS model (R~0.2). In the case of the BTS model, the highest accuracy was achieved across the three subjects typically in the mu (8-12Hz) and low-beta (12-18Hz) bands. Additionally, we highlight a limitation of the commonly used PTS model and illustrate how this model may be suboptimal for decoding motion trajectory relevant information. Although our results, showing that the mu and beta bands are prominent for MTP, are not in line with other MTP studies, they are consistent with the extensive literature on classical multiclass sensorimotor rhythm-based BCI studies (classification of limbs as opposed to motion trajectory prediction), which report the best accuracy of imagined limb movement classification using power values of mu and beta frequency bands. The methods proposed here provide a positive step toward noninvasive decoding of imagined 3D hand movements for movement-free BCIs.


Family medicine: Perception and attitudes among Indian medical students.
Currently, family medicine is not taught as a part of the undergraduate medical curriculum in India. In this context, the perceptions and attitudes of Indian medical students regarding family medicine as a career choice were studied. This study aims to study the perceptions and attitudes prevalent among Indian medical students regarding family medicine as a career choice and discuss its future implications. Cross-sectional survey study design. We conducted a cross-sectional survey of undergraduate medical (MBBS) students attending the 2016 medical student conference DEMEDCON at Sri Devaraj Urs Medical College in Kolar, Karnataka, India. Besides demographics, the survey included questions pertaining to awareness, exposure, and interest in family medicine in India. We also asked an open-ended question regarding the respondent's perception of the future of family medicine in India. Simple statistics such as mean and frequency (%) were calculated. Given the small sample size, no formal tests for statistical significance were performed. Responses were collected from 45 students between the ages of 18-24 from 6 medical colleges across Karnataka and Puducherry. The majority (64%) of respondents were in their 3rd or 4th year of medical college. 98% of respondents expressed a desire to learn more about family medicine as a specialty, and 82% expressed a need to introduce it as a subject in medical college. However, only 58% were aware of the Medical Council of India accredited status of family medicine in India. There exists a significant lack of awareness and inadequate exposure among Indian medical students toward family medicine. Nonetheless, there is widespread optimism and a desire to learn more about the subject. Increased awareness and avenues for exposure to family medicine in the formal undergraduate medical curriculum is the need of the hour.


Effects of different diets on voluntary consumption of ethanol in UChA and UChB rats.
Based on the decrease of voluntary consumption of ethanol observed in rats of UChA (low ethanol consumer) and UChB (high ethanol consumer) strains, coincident to the use of a new issue of a commercial diet, the effects of two new diets devoid of animal food were studied. One of these diets (Diet 3) induced an increase of the voluntary consumption of ethanol in a proportion of UChA rats, in such a way that its frequency distribution curve resulted in a bimodal one because of the presence of individuals which drank as much alcohol as UChB rats. This diet is a useful tool for the study of eventual nutrimental factors which decrease ethanol intake.


Lipid-like material as the source of the uncharacterized organic carbon in the ocean?
The composition and formation mechanisms of the uncharacterized fraction of oceanic particulate organic carbon (POC) are not well understood. We isolated biologically important compound classes and the acid-insoluble fraction, a proxy of the uncharacterized fraction, from sinking POC in the deep Northeast Pacific and measured carbon isotope ratios to constrain the source(s) of the uncharacterized fraction. Stable carbon and radiocarbon isotope signatures of the acid-insoluble fraction were similar to those of the lipid fraction, implying that the acid-insoluble fraction might be composed of selectively accumulated lipid-like macromolecules.


Opioid control of luteinizing hormone secretion in humans.
The observation that heroin-addicted subjects are amenorrheic and/or hypogonadic suggested a possible role of endogenous opioid peptides (EOP) in the regulation of the hypothalamus-pituitary-gonodal axis. Because EOP are localized all through the axis, they may influence the reproductive function acting at various levels. The injection of morphine decreases plasma LH levels, abolishing the pulsatile pattern of secretion. The evidence that naloxone, an opiate receptor blockade, increases LH levels suggests a tonic inhibitory action of EOP. The naloxone-induced LH increase is not observed before pubertal maturation, in both sexes, and is absent in children with delayed or precocious puberty and in those with Klinefelter's or Turner's syndrome, suggesting a role of gonadal function on the opioid control of LH secretion. In adult women this LH response to naloxone is present during the periovulatory and the luteal phase of the menstrual cycle, suggesting a permissive role of estradiol and mainly of progesterone on the action of EOP on the LH secretion. Indeed, in amenorrheic subjects naloxone lacks to stimulate plasma LH levels and the treatment for the induction of ovulation restores this activity. An increased inhibitory action of EOP on GnRH release may explain the inefficacy of naloxone to stimulate LH secretion in hypogonadotropinic patients, while a decreased action has been hypothesized in postmenopausal women. The clinical implications of EOP in reproductive medicine appear to be promising.


Methamphetamine use is associated with childhood sexual abuse and HIV sexual risk behaviors among patrons of alcohol-serving venues in Cape Town, South Africa.
South Africa's Western Cape has experienced a dramatic increase in methamphetamine ("meth") use over the past decade. There is concern that meth may further fuel the HIV epidemic in this country because of its association with risky sexual behaviors. This study describes the prevalence of meth use and its relation to HIV sexual risk behaviors among patrons of alcohol-serving venues. Participants (N=3328) were surveyed in 12 venues in a mixed race township. Logistic regression models were used to examine the relations between meth use and sexual risk behaviors, and structural equation models were used to test whether meth use mediates the relationship between childhood sexual abuse and current sexual risk. Meth use in the past 4 months was more common among Coloured than Black persons (10.5% vs. 3.5%). Meth users were more likely than non users to use marijuana, inhalants, and injection drugs, have a history of childhood sexual and/or physical abuse, and experience and/or perpetrate intimate partner violence. Among both men and women, meth use was associated with greater odds of engaging in sexual risk behaviors, and meth use partially mediated the relationships between childhood sexual abuse and all sexual risk behaviors. Meth users in this setting are at increased risk for HIV due to their greater likelihood of engaging in sexual risk behaviors and being in violent relationships. There is an urgent need to provide targeted HIV prevention and substance abuse treatment to meth users living in townships in Cape Town.


Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs.
Ataxia-telangiectasia (A-T) is characterized by a markedly increased sensitivity to ionizing radiation, increased incidence of cancer, and neurodegeneration, especially of the cerebellar Purkinje cells. Ionizing radiation oxidizes macromolecules and causes tissue damage through the generation of reactive oxygen species (ROS). We therefore hypothesized that A-T is due to oxidative damage resulting from loss of function of the A-T gene product. To assess this hypothesis, we employed an animal model of A-T, the mouse with a disrupted Atm gene. We show that organs which develop pathologic changes in the Atm-deficient mice are targets of oxidative damage, and that cerebellar Purkinje cells are particularly affected. These observations provide a mechanistic basis for the A-T phenotype and lay a rational foundation for therapeutic intervention.


Hypersensitivity reactions to the Sabin vaccine in children with cow's milk allergy.
The Sabin vaccine is used world-wide, and most children with food allergies receive it without incident. However, in the 2009 vaccination campaign conducted in Argentina, four children experienced immediate-type hypersensitivity reactions following vaccination. We aimed to review the medical history of the affected children, study their allergic condition after the episodes and analyse the presence of allergenic vaccine components. Patients were selected based on their immediate allergic reactions following vaccination. They were assessed for allergies to cow's milk and hen's egg. The presence of cow's milk proteins in the vaccine was tested by various immunoassays involving cow's milk- or α-lactalbumin-specific polyclonal rabbit antiserum and patient sera. All of the patients had a history of milk allergy, and no history or current evidence of egg hypersensitivity was found. Levels of cow's milk- and Sabin vaccine-specific IgE were increased, and the result of a skin prick test with cow's milk proteins or the Sabin vaccine was positive in each patient. In addition, an ELISA using specific rabbit antiserum detected α-lactalbumin in the Sabin vaccine. When α-lactalbumin was employed as a soluble inhibitor in a competitive ELISA, binding to vaccine-coated plates by cow's milk- or α-lactalbumin-specific rabbit antiserum or by patient serum containing IgE was inhibited. We have demonstrated that these patients were allergic to cow's milk, and had circulating and mast cell-bound IgE antibodies specific to cow's milk proteins. We found that the Sabin vaccine contained α-lactalbumin, which may have been responsible for the reactions elicited following vaccination with the Sabin and dual viral vaccines in combination.


Shock syndrome in primary dengue infections.
During 1974, 114 patients with dengue hemorrhagic fever were studied at the Bankok Children's Hospital. Over 40% of the patients had dengue shock syndrome. Five fatal cases were included in the study. Primary dengue infections were identified by absent or low titered antibodies in acute sera and the sequential development of IgM antibodies followed by IgG antibodies during convalescence. Three patients, aged 4,8, and 12 years, had primary dengue infections with shock. Although no convalescent sera could be tested two other patients, aged 7 to 12 years, with fatal disease also appeared to have primary infections. At the time of shock patients with primary infections had subnormal concentrations of complement factor 3. The data show that in older children dengue shock syndrome associated with complement depression can occur during primary as well as secondary infections.


Ketorolac tromethamine absorption, distribution, metabolism, excretion, and pharmacokinetics in animals and humans.
Ketorolac tromethamine (KT), a potent non-narcotic analgesic, with cyclooxygenase inhibitory activity, was administered (14C-labeled and unlabeled) intravenously (iv), orally (po), and intramuscularly (im) in solution to humans, cynomolgus monkeys, rabbits, rats, and mice. KT was absorbed rapidly (Tmax less than 1.0 hr) and efficiently (greater than 87%) following po and im doses in all species. The plasma half-life of ketorolac (K) ranged from 1.1 hr (rabbits) to 6.0 hr (humans). The protein binding of K ranged from 72.0% (mouse) to 99.2% (humans). Linear pharmacokinetics of K was observed in the mouse after single oral doses of KT ranging from 0.25 to 16 mg/kg. Radioactivity was excreted predominantly into urine, ranging from 78.9% (mouse) to 102% (monkey) following iv doses. The dose was excreted into urine primarily as K conjugates, K, and p-hydroxy-K in humans. The monkey was similar to humans with respect to kinetics, but did not form the p-hydroxy metabolite. The rabbit was unusual in that it exhibited substantial presystemic metabolism (50%). The rat excreted a much higher percentage of radioactivity into the feces and formed an additional unidentified metabolite. The most comparable species with respect to humans metabolically was the mouse. The metabolism and excretion of K was similar following iv, po, and im doses within each species studied.


Characterization of a new virulent phage (MLC-A) of Lactobacillus paracasei.
A new virulent bacteriophage (MLC-A) was recently isolated in Argentina from a probiotic dairy product containing a strain of Lactobacillus paracasei. Observation of the lysate with an electron microscope revealed bacteriophage particles with an icosahedral capsid of 57 +/- 2 nm; with a collar and a noncontractile tail of 156 +/- 3 nm terminating with a baseplate to which a tail fiber was attached. Therefore, phage MLC-A belongs to the Siphoviridae family. This phage was able to survive the pasteurization process and was resistant to alcohols and sodium hypochlorite (400 mg/kg). Only peracetic acid could inactivate high-titer suspensions of phages in a short time. The maximum rates of phage adsorption to its host cells were obtained at 30 degrees C with a pH between 5 and 7, and in the presence of calcium or magnesium ions. The host range of phage MLC-A encompassed L. paracasei and Lactobacillus casei strains, but it was not able to infect Lactobacillus rhamnosus or Lactobacillus gasseri strains. One-step growth kinetics of its lytic development revealed latent and burst periods of 30 and 135 min, respectively, with a burst size of about 69 +/- 4 plaque-forming units per infected cell. Phage MLC-A had a distinctive restriction profile when compared with the 2 well-studied Lactobacillus phages, PL-1 and J-1. The genome size of the MLC-A phage was estimated to be approximately 37 kb. This study presents the description of the first phage specific for L. paracasei isolated in Argentina. The isolation of phage MLC-A indicates that, beside lactic acid bacteria starters, probiotic cultures can also be sensitive to virulent phages in industrial processes.


Toward functional glycomics by localization of tissue lectins: immunohistochemical galectin fingerprinting during diethylstilbestrol-induced kidney tumorigenesis in male Syrian hamster.
The current study focused on galectins (-1, -3, -4, -7, and -8) and deliberately performed immunohistochemical fingerprinting to explore their complexity in a context of experimental renal carcinogenesis. The diethylstilbestrol (DES)-induced renal tumors in male Syrian hamster kidney (SHKT) represent a unique animal model for the study of estrogen-dependent renal malignancies. Kidney sections of DES-treated hamsters (3 days to 11 months of DES exposure) were analyzed by immunohistochemistry using a panel of non-crossreactive antibodies raised against galectins-1, -3, -4, -7, and -8. Levels of expression were quantitatively determined by using computer-assisted microscopy on immunostained tissue sections. Except for galectin-4, all above mentioned galectins were expressed in kidney tumors. Small clusters of galectin-1-positive, most likely preneoplastic cells at the corticomedullary junction were already evident 1 week after DES administration. Galectin-1 and -3 expression was apparently associated with the first steps of the neoplastic transformation, because small tumorous buds were found to be positive after 1 month of treatment. In contrast, galectins-7 and -8 were detected in large tumors and medium-sized tumors, respectively, thereby indicating an involvement in later stages of DES-induced SHKT. Galectins-1, -3, -7, and -8 were also detected by immunofluorescence staining in the HKT-1097 cell line established from SHKT, thus illustrating the stability of galectin expression in tumor cells. Our data document the presence and differential regulation of galectins in the course of renal tumorigenesis in the model of DES-induced SHKT.


Mediating role of post-traumatic growth in the relationship between inadequate disaster recovery and mental health outcomes: long-term evidence from the Wenchuan earthquake.
Background: The mental health outcomes from disasters have aroused great concern worldwide, yet few studies incorporate a long-term disaster recovery perspective. Evidence has also emerged about the importance of the social determinants of mental health, but aspects of recovery including disruptions to livelihoods and social networks remain relatively understudied. Objective: This study utilizes cognitive adaptation theory to examine the long-term relationship between inadequate disaster recovery and mental health outcomes while considering domains of post-traumatic growth (PTG) as mediators. Methods: A cross-sectional study was conducted among 1369 adult survivors of the 2008 Wenchuan earthquake. Correlation analyses and multivariable regression analyses examined the association between inadequate disaster recovery and mental health outcomes, while parallel multiple mediator models and structural equation model explored the mediating role of PTG among these relationships. Results: 52.2% and 8.1% of the respondents reported inadequate recovery on livelihood and social ties, respectively. Inadequate disaster recovery was associated with higher levels of PTSD and depressive symptoms, and this association was partially mediated by PTG. Lower reported PTG on the interpersonal relationship and new possibilities domains mediated the association between inadequate livelihood recovery on PTSD and depressive symptom severity, and enhanced personal strength mediated the association between inadequate social ties recovery on these symptoms. Conclusion: Enhancing disaster recovery is essential for mental health protection, and PTG may be a valuable starting point in cognitive therapy to protect against stress responses after trauma.