Rutile (β-)MnO2 surfaces and vacancy formation for high electrochemical and catalytic performance.
MnO2 is a technologically important material for energy storage and catalysis. Recent investigations have demonstrated the success of nanostructuring for improving the performance of rutile MnO2 in Li-ion batteries and supercapacitors and as a catalyst. Motivated by this we have investigated the stability and electronic structure of rutile (β-)MnO2 surfaces using density functional theory. A Wulff construction from relaxed surface energies indicates a rod-like equilibrium morphology that is elongated along the c-axis, and is consistent with the large number of nanowire-type structures that are obtainable experimentally. The (110) surface dominates the crystallite surface area. Moreover, higher index surfaces than considered in previous work, for instance the (211) and (311) surfaces, are also expressed to cap the rod-like morphology. Broken coordinations at the surface result in enhanced magnetic moments at Mn sites that may play a role in catalytic activity. The calculated formation energies of oxygen vacancy defects and Mn reduction at key surfaces indicate facile formation at surfaces expressed in the equilibrium morphology. The formation energies are considerably lower than for comparable structures such as rutile TiO2 and are likely to be important to the high catalytic activity of rutile MnO2.


Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies.
Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-G's pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies that can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-Å structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1, that recognize distinct epitopes. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. Targeted mutations can similarly stabilize RABV-G in the pre-fusion conformation, a key step toward structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and this will facilitate the development of improved vaccines and prophylactic antibodies.


Mitochondrial Function in Gilles de la Tourette Syndrome Patients With and Without Intragenic IMMP2L Deletions.
Background: Gilles de la Tourette syndrome (GTS) is a neurodevelopmental condition characterized by motor and vocal tics. The underlying etiology remains largely unknown, and GTS is considered as a complex multifactorial disorder associated with effects of several genes in combination with environmental factors. The inner mitochondrial membrane peptidase, subunit 2 (IMMP2L) has been suggested as one of the susceptibility genes for GTS, and IMMP2L-deficient mouse and human cells show increased levels of mitochondrial oxidative stress and altered cell fate programming. Hence, a potential involvement of IMMP2L-induced mitochondrial dysfunction in GTS pathology is yet to be elucidated. To address this, we investigated mitochondrial function in a group of GTS patients with intragenic IMMP2L deletions and compared with GTS without IMMP2L deletions and healthy controls. Methods: Mitochondrial function in fibroblasts from GTS patients and non-GTS parents (with and without IMMP2L deletions) compared to healthy controls were evaluated by measuring mitochondrial superoxide production, mitochondrial membrane potential, mitochondrial mass, and mitochondrial respiration. In addition, we evaluated apoptosis and senescence. Results: None of the mitochondrial parameters assessed in this study were significantly distinctive when comparing GTS patients with and without IMMP2L deletions against healthy controls or parents with or without IMMP2L deletions, and we did not observe altered cell programming. Conclusion: This study suggests that IMMP2L deletions do not lead to a substantial general mitochondrial dysfunction in GTS fibroblasts. Assessing a large cohort of controls and patients of similar age and gender would possibly reveal small differences in mitochondrial function. However, it is possible that IMMP2L variants affect mitochondrial function during specific instances of stress stimuli or in brain regions suggested to be affected in GTS.


[Safety of gastroenterologist-directed propofol administration for endoscopic procedures: 10-year experience in a private clinic in Lima, Peru].
To evaluate safety of propofol combined with Meperidine and Midazolam in colonoscopies, upper endoscopies (EGD) and Endoscopic Ultrasound (EUS) administered by a nurse supervised by a trained gastroenterologist. To compare the required doses of propofol among older and younger than 75 years old. Retrospective descriptive study including patients 18 years of age and older who received propofol for EGD, colonoscopy (or EGD + colonoscopy) and EUS. The patients were given a baseline dose of Meperidine (25 mg) and Midazolam (1-3 mg) intravenously (IV). After 2-3 minutes, they received an IV bolus of propofol between 10-30 mg. Repeat boluses of 10-20 mg were administered at intervals no lesser than 60 seconds during the procedure, as needed according to patient`s tolerance to the procedure. Between September 2006 and September 2016, 9,704 procedures were performed, of which 1,598 were EGD, 3,065 colonoscopies, 2,492 EGD + colonoscopies and 57 EUS. There were 3,912 women (59.1%), and the average age was 57.1 ± 14.6 years. Eight hundred eighty (12.5%) were older than 75 years. The average dose of propofol for all the procedures was 83.2 ± 48.1 mg, for EGD and colonoscopy was 59.7 ± 36.2 mg and 77.2 ± 41 mg respectively. The average dose used in patients >75 years for EGD was 47.5 ± 37.8 mg, for colonoscopies 58.3 ± 33.4 mg and for EGD + colonoscopies was 78.7 ± 42.7 mg compared to patients <75 years in whom the average dose for EGD was 61.1 ± 35.8 mg (p<0.05), in colonoscopies was 80.5 ± 41.3 mg (p<0.05) and in EGD + colonoscopies 105.9 ± 50.2 mg (p<0.05). There were no sedation-related complications. Propofol combined with meperidine and midazolam in endoscopic procedures directed by a trained gastroenterologist is safe. Elderly patients (>75 years old) required significantly less doses of propofol for EGD, colonoscopy, EGD/colonoscopy and EUS.


Role of Bordetella pertussis RseA in the cell envelope stress response and adenylate cyclase toxin release.
Bordetella pertussis is the bacterial agent of the human disease such as whooping cough. In many bacteria, the extracellular function sigma factor σE is central to the response to envelope stress, and its activity is negatively controlled by the RseA anti-sigma factor. In this study, the role of RseA in B. pertussis envelope stress responses was investigated. Compared with the wild-type strain, an rseA mutant showed elevated resistance to envelope stress and enhanced growth at 25 °C. rpoH and other predicted σE target genes demonstrated increased transcription in the rseA mutant compared with the wild-type parent. Transcription of those genes was also increased in wild-type B. pertussis and Escherichia coli under envelope stress, whereas no stress-induced increase in transcription was observed in the rseA mutant. rseA inactivation was also associated with altered levels of certain proteins in culture supernatant fluids, which showed increased adenylate cyclase toxin (CyaA) levels. The increased CyaA in the mutant was correlated with an apparent increased stability of the extracellular toxin and increased production of CyaA-containing outer membrane vesicles. Consistent with this, compared with the wild-type strain, rseA mutant cells produced increased numbers of large surface-associated vesicles.


Using magnetic resonance imaging and spectroscopy in cancer diagnostics and monitoring: preclinical and clinical approaches.
Nuclear Magnetic Resonance (MR) based imaging has become an integrated domain in today's oncology research and clinical management of cancer patients. MR is a unique imaging modality among numerous other imaging modalities by providing access to anatomical, physiological, biochemical and molecular details of tumour with excellent spatial and temporal resolutions. In this review we will cover established and investigational MR imaging (MRI) and MR spectroscopy (MRS) techniques used for cancer imaging and demonstrate wealth of information on tumour biology and clinical applications MR techniques offer for oncology research both in preclinical and clinical settings. Emphasis is given not only to the variety of information which may be obtained but also the complementary nature of the techniques. This ability to determine tumour type, grade, invasiveness, degree of hypoxia, microvacular characteristics, and metabolite phenotype, has already profoundly transformed oncology research and patient management. It is evident from the data reviewed that MR techniques will play a key role in uncovering molecular fingerprints of cancer, developing targeted treatment strategies and assessing responsiveness to treatment for personalized patient management, thereby allowing rapid translation of imaging research conclusions into the benefit of clinical oncology.


Pulmonary imaging and function in the common cold.
The common cold is generally considered to be an upper respiratory tract infection. We studied the lower respiratory tract in 76 otherwise healthy young adults with the common cold. Viral infection was diagnosed in 56 (74%) of the 76 subjects. Rhinovirus was detected in 42 (55%) subjects. Chest radiography (CR) and high-resolution computerized tomography (HRCT) were carried out in 40 subjects on day 7, and pulmonary function testing with bronchodilator challenge was carried out in 36 patients on days 7 and 21 of the study. Clinical examinations were carried out on days 1, 7 and 21. The subjects recorded their symptoms on a diary card for 20 d. The mean duration of cough was 8.4 (SD 6.5) d and that of sputum production 5.9 (SD 6.4) d. No abnormal findings were detected in the lungs on auscultation. CR and HRCT showed no pulmonary changes associated with the common cold. No clinically remarkable increases were seen in peak expiratory flow, forced expiration volume in 1 s or forced vital capacity after bronchodilator challenge on either days 7 or 21. All patients made a clinical recovery without antimicrobial therapy within 21 d. We conclude that the common cold in young otherwise healthy adults is an upper respiratory tract infection and that clinically important abnormalities in the lower respiratory tract are rare.


Microvascular burden and Alzheimer-type lesions across the age spectrum.
The occurrence of microvascular and small macrovascular lesions and Alzheimer's disease (AD)-related pathology in the aging human brain is a well-described phenomenon. Although there is a wide consensus about the relationship between macroscopic vascular lesions and incident dementia, the cognitive consequences of the progressive accumulation of these small vascular lesions in the human brain are still a matter of debate. Among the vast group of small vessel-related forms of ischemic brain injuries, the present review discusses the cognitive impact of cortical microinfarcts, subcortical gray matter and deep white matter lacunes, periventricular and diffuse white matter demyelinations, and focal or diffuse gliosis in old age. A special focus will be on the sub-types of microvascular lesions not detected by currently available neuroimaging studies in routine clinical settings. After providing a critical overview of in vivo data on white matter demyelinations and lacunes, we summarize the clinicopathological studies performed by our center in large cohorts of individuals with microvascular lesions and concomitant AD-related pathology across two age ranges (the younger old, 65-85 years old, versus the oldest old, nonagenarians and centenarians). In conjunction with other autopsy datasets, these observations fully support the idea that cortical microinfarcts are the only consistent determinant of cognitive decline across the entire spectrum from pure vascular cases to cases with combined vascular and AD lesion burden.


[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study].
Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) μmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) μmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) μmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.


TTaPP: Together Take a Pause and Ponder: A Critical Thinking Tool for Exploring the Public/Private Lives of Patients.
The broad use of social networking and user-generated content has increased the online footprint of many individuals. A generation of healthcare professionals have grown up with online search activities as part of their everyday lives. Sites like Facebook, Twitter, and Instagram have given the public new ways to share intimate details about their public and private lives and the lives of their friends and families. As a result, careproviders have the ability to find out more about their patients with just the tap of a key or the click of a mouse. This type of online searching for patient information is known as patient-targeted googling or PTG. This article provides an overview of the emergence of PTG, identifies the potential benefits and possible pitfalls of engaging in PTG, and explores current ethical frameworks that guide decisions about PTG. The article describes the development of a critical thinking tool developed by the Behavioral Health Ethics Committee at CHI Health, that can serve as a best-practice model for other hospitals and health systems. Called TTaPP (Together Take a Pause and Ponder), this tool is designed to help healthcare professionals across settings practice collaborative critical thinking skills as they consider the ethical questions of whether or not to engage in PTG. Finally, this article suggests areas for further study, including ways to prompt collaboration and appropriate documentation by maximizing electronic medical records systems, exploring the effectiveness of the TTaPP tool as a way to promote a culture of collaborative critical thinking practices, and the attitudes of patients and the public regarding PTG.


Mouse complement receptor-related gene y/p65-neutralized tumor vaccine induces antitumor activity in vivo.
Two mouse tumor cell lines, Meth A (BALB/c mouse-derived fibrosarcoma) and MM46 (C3H/He mouse-derived mammary tumor), were shown to express high levels of complement receptor-related gene y/p65 (Crry/p65), a membrane-bound complement-regulatory protein. Inhibiting the complement-regulatory activity of Crry/p65 with mAb 5D5 induced high levels of C3 deposition on in vivo tumor-derived Meth A and MM46 cells. To determine the effect of Crry/p65 blockade and increased C3 deposition on in vivo tumor growth, Meth A and MM46 cells were treated with 5D5 mAb and injected into BALB/c and C3H/He mice, respectively. Pretreating MM46 cells with 5D5 mAb significantly suppressed their tumorigenicity when injected s.c. Pretreatment with 5D5 mAb had a modest effect on Meth A s.c. tumor growth. Because complement is involved in the induction of an immune response, we investigated the effect of Crry/p65 blockade and increased C3 deposition on the immunogenicity of the tumor cells in a vaccination protocol. Vaccination of mice with irradiated Meth A cells pretreated with 5D5 mAb protected mice from subsequent challenge. In contrast, vaccination with irradiated Meth A cells without pretreatment was not protective. Survival was correlated with a high titer IgM response and specific CTL activity. These data demonstrate that the functional inhibition of Crry/p65 on tumor cells affects tumor growth and immunogenicity, and that the complement deposition resulting from this inhibition can act in concert with antitumor effector mechanisms to elicit potent antitumor immunity in vivo.


The action of selection on codon bias in the human genome is related to frequency, complexity, and chronology of amino acids.
The question of whether synonymous codon choice is affected by cellular tRNA abundance has been positively answered in many organisms. In some recent works, concerning the human genome, this relation has been studied, but no conclusive answers have been found. In the human genome, the variation in base composition and the absence of cellular tRNA count data makes the study of the question more complicated. In this work we study the relation between codon choice and tRNA abundance in the human genome by correcting relative codon usage for background base composition and using a measure based on tRNA-gene copy numbers as a rough estimate of tRNA abundance. We term major codons to be those codons with a relatively large tRNA-gene copy number for their corresponding amino acid. We use two measures of expression: breadth of expression (the number of tissues in which a gene was expressed) and maximum expression level among tissues (the highest value of expression of a gene among tissues). We show that for half the amino acids in the study (8 of 16) the relative major codon usage rises with breadth of expression. We show that these amino acids are significantly more frequent, are smaller and simpler, and are more ancient than the rest of the amino acids. Similar, although weaker, results were obtained for maximum expression level. There is evidence that codon bias in the human genome is related to selection, although the selection forces acting on codon bias may not be straightforward and may be different for different amino acids. We suggest that, in the first group of amino acids, selection acts to enhance translation efficiency in highly expressed genes by preferring major codons, and acts to reduce translation rate in lowly expressed genes by preferring non-major ones. In the second group of amino acids other selection forces, such as reducing misincorporation rate of expensive amino acids, in terms of their size/complexity, may be in action. The fact that codon usage is more strongly related to breadth of expression than to maximum expression level supports the notion, presented in a recent study, that codon choice may be related to the tRNA abundance in the tissue in which a gene is expressed.


The leading global health challenges in the artificial intelligence era.
Millions of people's health is at risk because of several factors and multiple overlapping crises, all of which hit the vulnerable the most. These challenges are dynamic and evolve in response to emerging health challenges and concerns, which need effective collaboration among countries working toward achieving Sustainable Development Goals (SDGs) and securing global health. Mental Health, the Impact of climate change, cardiovascular diseases (CVDs), diabetes, Infectious diseases, health system, and population aging are examples of challenges known to pose a vast burden worldwide. We are at a point known as the "digital revolution," characterized by the expansion of artificial intelligence (AI) and a fusion of technology types. AI has emerged as a powerful tool for addressing various health challenges, and the last ten years have been influential due to the rapid expansion in the production and accessibility of health-related data. The computational models and algorithms can understand complicated health and medical data to perform various functions and deep-learning strategies. This narrative mini-review summarizes the most current AI applications to address the leading global health challenges. Harnessing its capabilities can ultimately mitigate the Impact of these challenges and revolutionize the field. It has the ability to strengthen global health through personalized health care and improved preparedness and response to future challenges. However, ethical and legal concerns about individual or community privacy and autonomy must be addressed for effective implementation.


[Variation of neurotrophic factors expression in spinal cord and muscle after root avulsion of brachial plexus].
To investigate the variation of neurotrophic factors expression in spinal cord and muscle after root avulsion of brachial plexus. Forty-eight Wistar rats were involved in this study and according to the observing time in 1st day, 1st week, 4th week, 8th week, and 12th week after avulsion, and the control, were divided into 6 groups. By immunohistochemical and hybridization in situ assays, the expression of nerve growth factor (NGF) on muscle, basic fibroblast growth factor(bFGF) and its mRNA on the neurons of corresponding spinal cord was detected. Computer image analysis system was used to calculate the result. After the root avulsion of brachial plexus occurred, expression of NGF increased and reached to the peak at the 1st day. It subsided subsequently but was still higher than normal control until the 12th week. While expression of bFGF and its mRNA increased in the neurons of spinal cord and reached to the peak at the 1st week. Then it dropped down and at the 12th week it turned lower than normal control. After root avulsion of brachial plexus, neurotrophic factors expression increase on target muscle and neurons of corresponding spinal cord. It maybe the autoregulation and may protect neuron and improve nerve regeneration.


Is acupuncture effective in the treatment of fibromyalgia?
We conducted this study to assess the effectiveness of acupuncture in the treatment of fibromyalgia syndrome (FMS), report any adverse effects, and generate hypotheses for future investigation. We searched MEDLINE, EMBASE, Manual Therapy Information System, the Cochrane registry, the University of Maryland Complementary and Alternative Medicine in Pain, the Centralized Information Service for Complementary Medicine, and the National Institutes of Health Office of Alternative Medicine databases for the key words "acupuncture" and "fibromyalgia." Conference abstracts, citation lists, and letters supplemented the search. We selected all randomized or quasi-randomized controlled trials, or cohort studies of patients with FMS who were treated with acupuncture. Methodologic quality, sample characteristics, type of acupuncture treatment, and outcomes were extracted. Statistical pooling was not performed because of the differences in control groups. Seven studies (3 randomized controlled trials and 4 cohort studies) were included; only one was of high methodologic quality. The high-quality study suggests that real acupuncture is more effective than sham acupuncture for relieving pain, increasing pain thresholds, improving global ratings, and reducing morning stiffness of FMS, but the duration of benefit following the acupuncture treatment series is not known. Some patients report no benefit, and a few report an exacerbation of FMS-related pain. Lower-quality studies were consistent with these findings. Booster doses of acupuncture to maintain benefit once regular treatments have stopped have been described anecdotally but not investigated in controlled trials. The limited amount of high-quality evidence suggests that real acupuncture is more effective than sham acupuncture for improving symptoms of patients with FMS. However, because this conclusion is based on a single high-quality study, further high-quality randomized trials are needed to provide more robust data on effectiveness.


The Prevalence of Diabetes in Autistic Persons: A Systematic Review.
It has been proposed that autistic individuals are at an increased risk of type 1 and type 2 diabetes. Improved understanding of diabetes prevalence in autistic persons will help inform resource allocation for diabetes-related public health measures for this patient group. To conduct a systematic review of published literature pertaining to type 1 and type 2 diabetes prevalence in autistic individuals, including comparison with their non-autistic peers. Eligibility criteria included studies investigating the prevalence of diabetes in autistic individuals, as well as having been published in the English language. A systematic search of online databases (MEDLINE, PsycINFO, CINAHL, EMBASE and PubMed) was conducted on 4th April 2020. Additional approaches included the ancestry method, grey literature searches and expert consultation. Studies were qualitatively analysed with reporting quality appraised. 19 eligible studies were identified, 7 of which provided type-specific diabetes prevalence data. Of 15 studies that included a non-autistic control group, 9 reported a higher diabetes prevalence among autistic persons, with a statistically significant difference in 4 studies. Studies demonstrating a higher diabetes prevalence in autistic groups had higher average study population sizes and reporting quality ratings. It is uncertain whether diabetes is significantly more prevalent in autistic persons relative to their non-autistic peers, though larger studies suggest a trend in this direction. Nevertheless, diabetes is a significant public health issue for the autistic community, which may require a tailored approach for identification and management. Prospero database registration number: CRD42019122176.


M1 Macrophages Are More Susceptible to Necroptosis.
Macrophages play a crucial role in host innate immune defense against infection and tissue injury. Although macrophage activation and polarization has been well studied, we know less regarding the role of macrophage activation/polarization in inflammation-associated necrotic cell death. By using bone marrow-derived macrophages, we have recently demonstrated that M1 macrophages are much more susceptible than M0 and M2 subtypes of macrophages to necrotic cell death. Moreover, we showed that the enhanced necroptosis in M1 macrophages is dependent on the kinase activity of receptor-interacting protein kinase-3 (RIPK3) and may involve the upregulation of key necroptosis signaling molecules including RIPK3, mixed lineage kinase domain-like protein, and Z-DNA/ RNA binding protein 1. Our findings provide novel insights into the mechanisms of M1 macrophage engagement in inflammation and tissue injury.


Changes in regional cerebral blood flow abnormalities in late-life depression following response to electroconvulsive therapy.
The impact of electroconvulsive therapy (ECT) on the regional cerebral blood flow (rCBF) abnormalities in late-life depression is still unknown and the clinical significance of these findings in late-life depression has not been fully discussed. Using single photon emission computed tomography (SPECT) with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO), we examined the changes of rCBF patterns in nine late-life patients with major depressive episodes before and following response to ECT compared with nine age- and sex-matched healthy volunteers. Statistical comparisons were made on both region-of-interest (ROI) and voxel-by-voxel bases. In ROI-based analyses, a mean rCBF was significantly decreased in the patients before ECT compared with the control, significantly increased (normalized) in the patients 2 weeks after ECT compared with that before ECT, and still increased in the patients 12 weeks after ECT compared with that before ECT. In voxel-by-voxel analyses, a significant rCBF reduction was found in the bilateral pre- and subcallosal anterior cingulate cortex, the bilateral caudal orbitofrontal cortex, the right insular cortex and the right posterior middle frontal gyrus in patients before ECT compared with the control, and similar rCBF patterns were shown at 2 weeks and 12 weeks after ECT. We propose the hypothesis that a mean rCBF reduction may have a state-related property while persistent anterior paralimbic hypoperfusion may have a trait-like property, which relates to the relapse vulnerability as well as a tendency toward medication failure and illness chronicity in late-life depression.


The availability of the primer activation signal (PAS) affects the efficiency of HIV-1 reverse transcription initiation.
Initiation of reverse transcription of a retroviral RNA genome is strictly regulated. The tRNA primer binds to the primer binding site (PBS), and subsequent priming is triggered by the primer activation signal (PAS) that also pairs with the tRNA. We observed that in vitro reverse transcription initiation of the HIV-1 leader RNA varies in efficiency among 3'-end truncated transcripts, despite the presence of both PBS and PAS motifs. As the HIV-1 leader RNA can adopt two different foldings, we investigated if the conformational state of the transcripts did influence the efficiency of reverse transcription initiation. However, mutant transcripts that exclusively fold one or the other structure were similarly active, thereby excluding the possibility of regulation of reverse transcription initiation by the structure riboswitch. We next set out to determine the availability of the PAS element. This sequence motif enhances the efficiency of reverse transcription initiation, but its activity is regulated because the PAS motif is initially base paired within the wild-type template. We measured that the initiation efficiency on different templates correlates directly with accessibility of the PAS motif. Furthermore, changes in PAS are critical to facilitate a primer-switch to a new tRNA species, demonstrating the importance of this enhancer element.


Old But Good: Modified-Release Prednisone in Rheumatoid Arthritis.
Since more than 50 years glucocorticoids represent the milestone in the treatment of inflammatory diseases, including rheumatoid arthritis (RA). However, many patients with RA present a circadian rhythm in symptoms severity with a significant worsening in the morning, that correlates with cyclic changes in circulating hormones and cytokines. Classical steroid therapy given in the morning fails to intercept this pathophysiological phenomenon. In the last years, a novel formulation of prednisone has been developed in order to better fit these variations, improve efficacy and minimize adverse events (chronotherapy). This modified-release (MR) prednisone is administered in the evening at 10.00 p.m. and absorbed after about 4 hours. In this article, we reviewed the recent clinical trials evaluating the efficacy of MR prednisone in RA patients, including two randomized controlled double-blind clinical trials Circadian Administration of Prednisone in Rheumatoid Arthritis - 1 (CAPRA-1) and CAPRA-2 and other nonrandomized observational studies. According to the available evidence, MR prednisone seems effective in ameliorating morning stiffness in RA patients. In conclusion, the use of MR prednisone in the treatment regimen could be a costeffective choice in a significant proportion of RA patients, particularly in those with a clinical phenotype characterized by morning stiffness or morning recrudescence of pain. With regards to the safety, MR prednisone adverse events profile does not differ from that of IR glucocorticoids.


[Understanding the world as experienced by HIV-positive pregnant women].
This study aims at understanding how a HIV-infected pregnant woman perceives her corporeality in being-in-the-world bearing another being corroborating with the concepts of body and corporeality. It is a qualitative study with a phenomenological approach. HIV-positive pregnant women under pre-natal follow-up took part in the study. Semi-structured interview was carried out to collect the information. The hermeneutic approach was chosen to interpret the collected information. The discourses gave rise to two themes: being in the world while infected with the virus and the concepts of body in the world of HIV-positive pregnant women's concepts of body-in-the-world.


Effects of etiology on inpatient rehabilitation outcomes in 65- to 74-year-old patients with incomplete paraplegia from a nontraumatic spinal cord injury.
To examine differences in rehabilitation outcomes for older patients with a nontraumatic spinal cord injury (NT-SCI) for 5 etiologic diagnoses: degenerative spinal disease (DSD), malignant spinal tumor, benign spinal tumor, vascular ischemia, and spinal abscess. Retrospective cohort study that used Medicare claims and assessment data. A total of 479 inpatient rehabilitation hospitals and units. A total of 1780 Medicare beneficiaries (65-74 years old) with incomplete paraplegia attributable to NT-SCI who were discharged from inpatient rehabilitation facilities from 2002 through 2005. Not applicable. Length of stay, discharge Functional Independence Measure (FIM) instrument motor item and subscale scores, and discharge destination. Demographic characteristics varied by etiology group. Mean +/- SD rehabilitation stays ranged from 13.3 +/- 7.7 days for DSD to 26.4 +/- 13.4 days for vascular ischemia. Adjusted data showed stays differed (P < .001) across etiology groups. Adjusted discharge mean self-care and mobility subscores revealed that patients with DSD and benign tumor were more independent (P < .001) than patients with a malignant tumor or spinal abscess. Patients with vascular ischemia were more dependent (P < .01) in mobility than the DSD and benign tumor groups. Etiologic differences (P < .01) in independence in discharge FIM modifiers for walking (FIM > or = 4), bladder (FIM > or = 6) and bowel management (FIM > or = 6) and bowel accidents/continence (FIM > or = 6), but not bladder accidents (FIM > or = 6), were present. The percent of patients discharged to a community residence ranged from 59.3% to 92.6%. Adjusted data showed that significantly larger percentages (P < .01) of patients in the DSD and malignant tumor groups than in the spinal abscess group were discharged to a community residence (versus nursing home). There are etiologic differences in demographics, rehabilitation length of stay, functional outcomes, and discharge destination in elderly patients with NT-SCI.


Identification and elimination of the competing N-acetyldiaminopentane pathway for improved production of diaminopentane by Corynebacterium glutamicum.
The present work describes the development of a superior strain of Corynebacterium glutamicum for diaminopentane (cadaverine) production aimed at the identification and deletion of the underlying unknown N-acetyldiaminopentane pathway. This acetylated product variant, recently discovered, is a highly undesired by-product with respect to carbon yield and product purity. Initial studies with C. glutamicum DAP-3c, a previously derived tailor-made diaminopentane producer, showed that up to 20% of the product occurs in the unfavorable acetylated form. The strain revealed enzymatic activity for diaminopentane acetylation, requiring acetyl-coenzyme A (CoA) as a donor. Comparative transcriptome analysis of DAP-3c and its parent strain did not reveal significant differences in the expression levels of 17 potential candidates annotated as N-acetyltransferases. Targeted single deletion of several of the candidate genes showed NCgl1469 to be the responsible enzyme. NCgl1469 was functionally assigned as diaminopentane acetyltransferase. The deletion strain, designated C. glutamicum DAP-4, exhibited a complete lack of N-acetyldiaminopentane accumulation in medium. Hereby, the yield for diaminopentane increased by 11%. The mutant strain allowed the production of diaminopentane as the sole product. The deletion did not cause any negative growth effects, since the specific growth rate and glucose uptake rate remained unchanged. The identification and elimination of the responsible acetyltransferase gene, as presented here, display key contributions of a superior C. glutamicum strain producing diaminopentane as a future building block for bio-based polyamides.


Onset of dementia is associated with apolipoprotein E epsilon4 in Down's syndrome.
We examined the influence of apolipoprotein E (apoE) genotype on risk of dementia in 82 adults with Down's syndrome (DS). Compared with those with an apoE 3/3 genotype, the group of adults with DS with apoE 2/4, 3/4, and 4/4 genotypes were 5 times more likely to become demented (RR = 4.7; 95% CI = 1.2, 17.9). We hypothesize that the increased risk of dementia may be mediated by exacerbation of beta-amyloid deposition.


Effect of low pH on the hepatitis A virus maturation cleavage.
Cleavage of VP0 to VP2 via intramolecular scission is known as the viral maturation cleavage, as VP0 is found in immature particles, whilst VP2 is found in mature particles. The effect of low pH on the kinetics of hepatitis A virus (HAV) capsid protein VP0 cleavage in provirions was examined by Western blot analysis. VP0 scission was found to be dramatically enhanced under acidic conditions, similar to those encountered on entry of virus particles into the cell via endocytosis. The cleavage of VP0 to VP2 led to an increase in the specific infectivity of viral particles, indicating that mature virions are more infectious than immature provirions. The data are consistent with a model where conformational changes induced by low pH aid scission of VP0, and the increase in kinetics of VP0 cleavage may have relevance for viral uncoating, as only mature HAV particles are thought capable of uncoating within the host cell.


Parent experiences of inpatient pediatric care in relation to health care delivery and sociodemographic characteristics: results of a Norwegian national survey.
The national survey of parent experiences with inpatient pediatric care contribute to the Norwegian system of health care quality indicators. This article reports on the statistical association between parent experiences of inpatient pediatric care and aspects of health care delivery, child health status and health outcome as assessed by the parents, and the parents' sociodemographic characteristics. 6,160 parents of children who were inpatients at one of Norway's 20 pediatric departments in 2005 were contacted to take part in a survey that included the Parent Experience of Pediatric Care questionnaire. It includes 25 items that form six scales measuring parent experiences: doctor services, hospital facilities, information discharge, information about examinations and tests, nursing services and organization. The six scales were analyzed using OLS-regression. 3,308 (53.8%) responded. Mean scores ranged from 62.81 (organization) to 72.80 (hospital facilities) on a 0-100 scale where 100 is the best possible experience. Disappointment with staff, unexpected waiting, information regarding new medication, whether the staff were successful in easing the child's pain, incorrect treatment and number of previous admissions had a statistically significant association with at least five of the PEPC scale scores. Disappointment with staff had the strongest association. Most sociodemographic characteristics had weak or no associations with parent experiences. The complete relief of the child's pain, reducing unexpected waiting and disappointment with staff, and providing good information about new medication are aspects of health care that should be considered in initiatives designed to improve parent experiences. In the Norwegian context parent experiences vary little by parents' sociodemographic characteristics.


SRC drives growth of antiestrogen resistant breast cancer cell lines and is a marker for reduced benefit of tamoxifen treatment.
The underlying mechanisms leading to antiestrogen resistance in estrogen-receptor α (ER)-positive breast cancer is still poorly understood. The aim of this study was therefore to identify biomarkers and novel treatments for antiestrogen resistant breast cancer. We performed a kinase inhibitor screen on antiestrogen responsive T47D breast cancer cells and T47D-derived tamoxifen and fulvestrant resistant cell lines. We found that dasatinib, a broad-spectrum kinase inhibitor, inhibited growth of the antiestrogen resistant cells compared to parental T47D cells. Furthermore western blot analysis showed increased expression and phosphorylation of Src in the resistant cells and that dasatinib inhibited phosphorylation of Src and also signaling via Akt and Erk in all cell lines. Immunoprecipitation revealed Src: ER complexes only in the parental T47D cells. In fulvestrant resistant cells, Src formed complexes with the Human Epidermal growth factor Receptor (HER)1 and HER2. Neither HER receptors nor ER were co-precipitated with Src in the tamoxifen resistant cell lines. Compared to treatment with dasatinib alone, combined treatment with dasatinib and fulvestrant had a stronger inhibitory effect on tamoxifen resistant cell growth, whereas dasatinib in combination with tamoxifen had no additive inhibitory effect on fulvestrant resistant growth. When performing immunohistochemical staining on 268 primary tumors from breast cancer patients who had received tamoxifen as first line endocrine treatment, we found that membrane expression of Src in the tumor cells was significant associated with reduced disease-free and overall survival. In conclusion, Src was identified as target for treatment of antiestrogen resistant T47D breast cancer cells. For tamoxifen resistant T47D cells, combined treatment with dasatinib and fulvestrant was superior to treatment with dasatinib alone. Src located at the membrane has potential as a new biomarker for reduced benefit of tamoxifen.


Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity.
Carbon dioxide absorbents degrade sevoflurane, particularly at low gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A). Compound A causes renal proximal tubular injury in rats but has had no effect on blood urea nitrogen (BUN) or creatinine concentrations in patients. This investigation compared the effects of low-flow sevoflurane and isoflurane on renal tubular function in surgical patients using conventional (BUN and creatinine) and finer indices of renal injury, specifically those biomarkers sensitive for compound A toxicity in rats (glucosuria, proteinuria, and enzymuria [N-acetyl-beta-D-glucosaminidase (NAG) and alpha-glutathione-S-transferase (alpha GST)]). Consenting patients with normal preoperative renal function at two institutions were randomized to receive sevoflurane (n = 36) or isoflurane (n = 37) in oxygen and air. Total gas flow was 1 l/min, opioid doses were minimized, and barium hydroxide lime was used to maximize anesthetic degradation. Inspiratory and expiratory compound A concentrations were quantified every 30-60 min. Blood and urine were obtained before and 24-72 h after anesthesia for laboratory evaluation. Sevoflurane and isoflurane groups were similar with respect to age, weight, sex, American Society of Anesthesiologists status, anesthetic duration (3.7 or 3.9 h), and anesthetic exposure (3.6 or 3 minimum alveolar concentration [MAC]-hour). Maximum inspired compound A concentration (mean +/- standard deviation) was 27 +/- 13 ppm (range, 10-67 ppm). Areas under the inspired and expired compound A concentration versus time curves (AUC) were 79 +/- 54-ppm-h (range, 10-223 ppm-h) and 53 +/- 40 ppm-h (range, 6-159 ppm-h), respectively. There was no significant difference between anesthetic groups in postoperative serum creatinine or BUN, or urinary excretion of protein, glucose, NAG, proximal tubular alpha GST, or distal tubular pi GST. There was no significant correlation between compound A exposure (AUC) and protein, glucose, NAG, alpha GST, or pi GST excretion. Postoperative alanine and aspartate aminotransferase concentrations were not different between the anesthetic groups, and there were no significant correlations between compound A exposure and alanine or aspartate aminotransferase concentrations. The renal tubular and hepatic effects of low-flow sevoflurane and isoflurane were similar as assessed using both conventional measures of hepatic and renal function and more sensitive biochemical markers of renal tubular cell necrosis. Moderate duration low-flow sevoflurane anesthesia, during which compound A formation occurs, appears to be as safe as low-flow isoflurane anesthesia.


Spent hops extract (Humulus Lupulus L.) attenuates inflammation and angiogenesis of the retina via the nuclear factor-kappaB and protein kinase B/extracellular signal-regulated kinase pathways.
Spent hops extract (SHE) is a plant extract containing compounds with proven anti-inflammatory and anti-angiogenic activities. However, extract may exert synergic effects compared to its individual polyphenol components. Inflammatory diseases of the retina may lead to visual impairment, a reduction of the comfort of life, and even blindness due to the formation of new pathological blood vessels. More effective therapeutic options are being sought. The goal of the present study was to investigate the anti-inflammatory and anti-angiogenic potentials of SHE on human retinal pigment epithelial cells (ARPE-19) stimulated by lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-α). The SHE (250 μg/mL) was found to downregulate the gene expression of interleukin 6 (IL-6) to 33% in LPS-triggered cells; it also reduced both matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) mRNA expression to 13% and 43% respectively, and their activity to 82% (MMP-2) and 57% (MMP-9), compared to TNF-α-stimulated cells. Also, SHE modulated the TNF-α-induced expression of vascular endothelial growth factor (VEGF) and endothelial growth factor receptor 2 (VEGFR2). It is possible that SHE inhibited retinal inflammation and angiogenesis by suppressing the nuclear factor kappa B (NF-κB), protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways. Our results demonstrate that SHE has anti-inflammatory and anti-angiogenic potential against retinal diseases. This is the first such study to report on the efficacy of SHE on retinal inflammatory diseases.


Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP).
To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV. We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.


COVID-19 and pandemic planning in the context of rural and remote homelessness.
Addressing the vulnerability and unique needs of homeless populations during pandemics has been a major component of the Canadian federal response to the COVID-19 crisis. Rural and remote communities, however, have received little to no funding to aid in their care of homeless people during the pandemic. Similarly, there has been little to no research on rural communities' pandemic preparedness in the context of homelessness. There are large numbers of homeless individuals in rural and remote Canada, including Indigenous peoples who are over-represented in homeless populations. Rural communities, including rural and remote Indigenous communities, are often isolated and more limited than urban areas in their capacity to respond to pandemics. They are particularly vulnerable due to fewer healthcare and social service resources-the lack of which has been particularly evident during the COVID-19 pandemic. In this commentary, we suggest that policy-makers need to take seriously the situation of rural homelessness in Canada, its implications for individual and community health, and consequences in the context of pandemics. Policy- and decision-makers can address these concerns through increased homelessness funding and support for rural and remote communities, policy change to recognize the unique challenges associated with rural pandemic planning and homelessness, and more research that can be translated into policy, programs, and supports for rural homelessness and pandemic planning response.


Morphological evidence of basal keratinocyte migration during the re-epithelialization process.
The regeneration of wounded stratified epithelium is accomplished via the migration of keratinocytes from the margins of the wound. However, the process of keratinocyte migration on the wound surface and the role of epithelial stem cells during re-epithelialization remain to be elucidated. Therefore, we administered BrdU to embryonic mice and generated epithelial defects on the buccal mucosa of these mice at two weeks after birth, using CO(2) laser irradiation, with which we removed the entire thickness of the epithelium. In the unwounded epithelium, cytokeratin 14, p63, and BrdU were localized within the basal layer of the epithelium, but the majority of cells within the regenerated epithelium were immunopositive for these proteins. PCNA-negative and BrdU-positive basal keratinocytes, which evidence a slow cell cycle, were localized solely within the basal layer of the unwound epithelium facing the tips of dermal papillae. After laser irradiation, these basal keratinocytes facing the tips of the papillae evidenced positive immunoreactivity for PCNA, in addition to BrdU. These results indicate that epithelial stem cells of oral mucosa may be localized in the basal layer of the epithelium facing the tips of dermal papillae, and may migrate laterally with other basal keratinocytes in response to external stimuli.


[Identification of the actual experiencing of pain. Methodological basis for an evaluation].
The doctors don't have reliable instruments in order to detect the painful experience in a patient with intention of deceiving. The objective of this investigation is the development of an instrument that helps the doctors on that task. The investigation is based on that the pain is not possible to evoke. A patient that doesn't feel pain, really, will introduce the modifications characteristic of all memory when requests you that he/she describe the pain that says feel. The will of deceit will also distort their description. A discriminant analysis will detect the difference between the description of a pain that is not present and another that yes it are, and between the sincere descriptions of the deceiving one. The descriptions of the pain carried out by two different samples of nursing students have been studied with a list of pair of antonym adjectives (Osgood's semantic differential). A subgroup of the first sample described a pain that they suffered in the same moment of description, and the other subgroup described a suffering pain some days before. In the other sample, a subgroup made a sincere description of their pain and other subgroup described the pain with will of deceiving the interviewer. The investigation has provided two discriminant models. A discriminant model differentiates between a present and another remembered pain (sensibility: 0.75; specificity: 0.85; kappa reliability: 0.60; p < 0.000000001; probability of success p: 89%). The other discriminant model differentiates between a description of a pain with will of deceiving and another pain described sincerely (sensibility: 0.94; specificity: 0.95; kappa reliability: 0.89; p < 0.000000001; probability of success p: 97%). The results of this investigation seem to demonstrate that it is possible to discriminate between the descriptions of real pains and the suspicious pains of not being real, and that also one is able to discriminate between pains described with will of deceit and pains described sincerely. These discriminant models allows to classify the description of the subjects in four groups: "liars", "sincere", "magnifiers", and "psychogenic". However, it is necessary still carry out more effort of investigation so that these results could be replied in patients that suffer pain.


Expression and functional role of ALDH1 in cervical carcinoma cells.
Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1- positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.


Comparison of retinoblastoma reduction for chemotherapy vs external beam radiotherapy.
To determine the time course and extent of tumor reduction associated with systemic chemotherapy or external beam radiotherapy (EBRT) in the treatment of advanced intraocular retinoblastoma. Retrospective review of children with Reese-Ellsworth stages IV and V retinoblastoma undergoing primary globe-conserving therapy with either systemic chemoreduction or EBRT. Study variables were recorded at baseline, at monthly intervals for the first 6 months, and at 12 months after the initiation of treatment. Tumor volumes were calculated using basal area and height values determined by ultrasonography, physical examination, and fundus photographic review. Outcome measures included tumor volume, tumor reduction, regression pattern, treatment-related complications, metastases, and survival. Twenty-six eyes of 26 patients were evaluated for tumor response; 18 patients were treated with systemic chemotherapy and 8 patients were treated with EBRT. Median follow-up was 36 months. A mean 68% reduction in tumor volume occurred after 1 cycle of chemotherapy compared with a 12% reduction at a similar time point (1 month) after initiation of EBRT (P<.004). There was no statistically significant difference in tumor volume reduction between treatment modalities at the 12-month follow-up visit. Both systemic chemoreduction and EBRT achieved 100% globe conservation and 100% patient survival in this series. Retinoblastoma reduction exhibits a differential time course based on the applied primary treatment. Systemic chemotherapy is associated with earlier tumor reduction than EBRT.


Thyroid Disease in Pregnancy: A Clinical Survey among Endocrinologists, Gynecologists, and Obstetricians in Israel.
To study the current practices in the management of subclinical hypothyroidism (SCH) and thyroid nodules during pregnancy of obstetricians/gynecologists (OB/GYNs) and endocrinologists in Israel. An electronic questionnaire was sent by email to all members of the Israeli Endocrine Society and the Israel Society of Obstetrics and Gynecology. Questionnaires included demographic data and clinical scenarios with questions regarding the screening and management of pregnant women with SCH, hypothyroxinemia, and a palpable thyroid nodule. The questionnaire for OB/GYNs was slightly modified. We received 90 responses from endocrinologists and 42 responses from OB/GYNs. Among endocrinologists, 39% would repeat a thyroid-stimulating hormone (TSH) test of 2.9 mU/L with normal free thyroxine and treat with thyroxine if the second result was above 2.5 mU/L. Among OB/GYNs, 73% would manage a woman with SCH at the beginning of her pregnancy by themselves and only 22% would start thyroxine after a first TSH result above 2.5 mU/L. Concerning screening, 57% endocrinologists and 71% OB/GYNs recommended screening for thyroid dysfunction in every woman at the beginning of her pregnancy. Among endocrinologists, 54% would order an ultrasound for a palpable thyroid nodule and perform a fine needle aspiration only for suspicious lesions. The medical approach to thyroid disease in pregnant women remains a matter of controversy. Our results support the need for larger and prospective clinical studies.


Basilar-type migraine: clinical, epidemiologic, and genetic features.
It remains uncertain whether basilar-type migraine (BM) is a subtype of migraine with typical aura (MTA) or a distinct phenotype or genotype. To analyze the symptomatology, familial distribution, and genotype of BM. The authors recruited 105 families comprising 362 patients with MTA or BM (International Classification of Headache Disorders-1 criteria). Among these patients, 38 patients from 29 families had BM. In 12 of the families with BM with an apparently dominant inheritance the authors sequenced all exons of the CACNA1A (chromosome 19) and ATP1A2 (chromosome 1) genes responsible for most cases of the autosomal dominantly inherited familial hemiplegic migraine and performed a linkage analysis of chromosome 1 and 19 with a nonparametric or autosomal dominant parametric model using an affected only analysis. BM occurred in 10% (38/362) of patients with MTA. The basilar-type aura had a median duration of 60 minutes and comprised vertigo 61%, dysarthria 53%, tinnitus 45%, diplopia 45%, bilateral visual symptoms 40%, bilateral paresthesias 24%, decreased level of consciousness 21%, hypacusia 21%, and ataxia 5%. The relative frequency of the individual basilar-type symptoms was not different from patients with hemiplegic migraine from a previous study. The patients with BM were equally distributed among the 105 families with MTA (p = 0.37). The attacks of MTA were identical in families with or without BM. No causative mutations and no linkage was identified. Basilar-type aura seemingly may occur at times in any patient with migraine with typical aura. There is no firm clinical, epidemiologic, or genetic evidence that BM is an independent disease entity different from MTA.


The strange case of less C-sections: Hospital ownership, market concentration, and DRG-tariff regulation.
We evaluate the relationship between hospital ownership and responses to a policy providing large financial incentives for vaginal deliveries and financial disincentives for C-sections. We compare for-profit, nonprofit, and public hospitals operating in a public health care system organized according to the quasi-market model. We first theoretically show that hospital ownership matters insofar different hospitals are characterized by different ethical preferences. We also show that competition makes ownership less important. We then consider the case study of Lombardy in Italy. We exploit spatial variation in hospital ownership and in market concentration at the local level to evaluate the relationship between ownership and the probability of C-section. According to theory, empirical results strongly suggest that competitive pressures from alternative providers tend to homogenize behaviors. However, in local monopolies, in presence of a strong monetary incentive toward vaginal deliveries, we do observe less C-section from private for-profit hospitals than from public and private nonprofit hospitals, especially when C-sections are medically appropriate.


University Isotope Separator at Oak Ridge: The UNISOR Consortium.
The UNISOR cooperative project, envisioned more than 3 years ago, is now successfully working. Research problems that involve a full range of experiments on nuclei far from beta stability are being investigated jointly by groups of scientists from several institutions. Some of the first work reported (16) included the identification, half-lives, and decay schemes of three new isotopes, (186)T1, (188)T1, and (116)I; the first or new decay schemes of (189)T1, (190)T1, (117)Xe, and (117)I; and the results of the perturbed gamma-gamma directional correlation work in (126)Xe. UNISOR is already stimulating international interest. A report (1) on the new research being planned with an isotope separator on-line to ORIC was presented at a Soviet Academy of Sciences meeting on nuclear structure in 1971. At an international nuclear physics conference in Munich in August 1973, Academician G. N. Flerov, director of the heavy-ion laboratory in Dubna, said the UNISOR project had inspired his laboratory to secure funds for a new, much improved isotope separator which is now installed on-line to their heavy-ion cyclotron to be used for detailed studies of nuclei far from stability. The UNISOR model for research has inspired a second such project, the Atomic Physics Consortium at Oak Ridge (APCOR). After an exploratory conference at Oak Ridge, scientists from ten institutions met in November 1973 to form an organizing committee for APCOR. As with UNISOR, the universities and the AEC will each provide a significant portion of the capital and operating costs. Heavy ions have opened up much new research in atomic physics, but such accelerator-based research represents a real "shift from traditional approaches concerning how, where, and on what time scale atomic physics experiments should be done" (17).


Permissive and non-permissive reactive astrocytes: immunofluorescence study with antibodies to the glial hyaluronate-binding protein.
Two distinct types of reactive astrocytes were studied in rat CNS. Reactive astrocytes secondary to penetrating trauma (anisomorphic gliosis) were induced by stab wounds to the brain. Reactive astrocytes secondary to Wallerian degeneration (isomorphic gliosis) were induced in spinal cord dorsal columns by dorsal rhizotomy proximal to dorsal root ganglia. Anisomorphic glial scars did not stain with antibodies to the glial hyaluronate-binding protein (GHAP), a structural glycoprotein of white matter extracellular matrix. Conversely, isomorphic glial scars were still GHAP-positive 3 months after dorsal root transection. Only after 5 months did GHAP immunoreactivity start to disappear from the isomorphic glial scar. Extensive dorsal rhizotomy was performed at the lumbar level to produce Wallerian degeneration of spinal cord dorsal columns. One month later, the rats were reoperated and two thoracic dorsal roots were implanted in the degenerated dorsal columns. The rats were examined 1 month after grafting. As expected, there was a dense anisomorphic glial scar at the site of surgery, while the dorsal columns above the graft showed isomorphic gliosis. Extensive axonal growth was observed in the dense glial scar surrounding the graft. Conversely, no axonal growth was observed in the degenerated dorsal columns undergoing isomorphic gliosis above the implant. The findings suggested that GHAP-negative astrocytes responding to traumatic injury are permissive for axonal growth and that GHAP-positive astrocytes responding to Wallerian degeneration are not permissive.


Rates of insulin secretion in INS-1 cells are enhanced by coupling to anaplerosis and Kreb's cycle flux independent of ATP synthesis.
Mechanistic models of glucose stimulated insulin secretion (GSIS) established in minimal media in vitro, may not accurately describe the complexity of coupling metabolism with insulin secretion that occurs in vivo. As a first approximation, we have evaluated metabolic pathways in a typical growth media, DMEM as a surrogate in vivo medium, for comparison to metabolic fluxes observed under the typical experimental conditions using the simple salt-buffer of KRB. Changes in metabolism in response to glucose and amino acids and coupling to insulin secretion were measured in INS-1 832/13 cells. Media effects on mitochondrial function and the coupling efficiency of oxidative phosphorylation were determined by fluorometrically measured oxygen consumption rates (OCRs) combined with (31)P NMR measured rates of ATP synthesis. Substrate preferences and pathways into the TCA cycle, and the synthesis of mitochondrial 2nd messengers by anaplerosis were determined by (13)C NMR isotopomer analysis of the fate of [U-(13)C] glucose metabolism. Despite similar incremental increases in insulin secretion, the changes of OCR in response to increasing glucose from 2.5 to 15mM were blunted in DMEM relative to KRB. Basal and stimulated rates of insulin secretion rates were consistently higher in DMEM, while ATP synthesis rates were identical in both DMEM and KRB, suggesting greater mitochondrial uncoupling in DMEM. The relative rates of anaplerosis, and hence synthesis and export of 2nd messengers from the mitochondria were found to be similar in DMEM to those in KRB. And, the correlation of total PC flux with insulin secretion rates in DMEM was found to be congruous with the correlation in KRB. Together, these results suggest that signaling mechanisms associated with both TCA cycle flux and with anaplerotic flux, but not ATP production, may be responsible for the enhanced rates of insulin secretion in more complex, and physiologically-relevant media.


The effect of honey on the intestinal anastomotic wound healing in rats with obstructive jaundice.
Jaundice has been associated with an increased incidence of postoperative hernias, decreased wound and anastomotic bursting pressure, and reduced tissue collagen synthesis. This study is aimed to examine the possible effects of honey supplementation on anastomotic wound healing in obstructive jaundice (OJ) model. Eighty wistar-albino rats were divided into four groups as control, OJ, O plus artificial honey and OJ plus honey. Rats were fed with standard rat chow (SRC) in group-I&II, SRC plus 10 mg/kg/day honey in group-4 and SRC plus artificial honey including the same caloric amount with honey in group-3. Colon anastomoses were performed in all groups. Also, common bile duct ligation was performed in group-1, group-2 and group-3. On the postoperative 3rd and 7th days, anastomotic healing was evaluated. The hydroxyproline level was significantly lower in the jaundiced animals compared with the controls and those given honey or artificial honey (p<0.05). The anastomotic bursting pressure results showed a correlation with the hydroxyproline results, and the use of honey significantly increased the bursting pressure compared with that of the bile duct ligated group (p<0.05). The oral administration of honey can be considered when attempts at conventional internal drainage fail in obstructive jaundice (Tab. 2, Fig. 6, Ref. 20). Full Text (Free, PDF) www.bmj.sk.


Genetical and molecular studies on gerM, a new developmental locus of Bacillus subtilis.
A transposon Tn917 insertion between gerE and ilvB has identified a new developmental locus, gerM, in Bacillus subtilis. gerM96::Tn917 affects both sporulation and germination. DNA on either side of the transposon has been cloned and includes the previously cloned sdhC and gerE loci. gerE terminates 2.1 kb from the end of the transposon. The gerM96::Tn917 mutant is oligosporogenous, yielding approximately 1% of the number of wild-type heat resistant spores in liquid medium and 10% on solid medium. Six hours after the onset of sporulation alkaline phosphatase and glucose dehydrogenase levels were 90% and 7%, respectively, of those of the wild-type. At this time 50% of the mutant cells were still dividing. The occurrence of multiple polar septa and 'pygmy' cells suggested a block at stage II of sporulation. Following addition of germinants, mutant spores prepared on nutrient agar lost heat resistance normally but released slightly less dipicolinic acid than wild-type spores. They also showed only partial loss of optical density, associated with a phase-grey appearance and striations in the cortex suggesting partial degradation. Expression of the gerM gene was monitored by production of beta-galactosidase encoded by a promotorless lacZ gene fused to the gerM96::Tn917 insertion. It occurred 1.5-4 h after commencement of sporulation. Transcription was directed from a promoter on the gerE side of gerM and was unaffected by a mutation in the gerE gene.


[Morphological characteristics of the lymphoid tissues in the newborn children].
Quantitative and qualitative analysis and statistical processing of thymus, trachea, duodenum ileum, coecum and appendix in newborns demonstrated that by the moment of birth peripheral immunogenesis organs were not equally formed due to peculiarities of their function in postnatal ontogenesis. Lymphoid nodules were absent in tracheal mucosa and adjacent lymph nodes showed loss of lymphoid noules aswell. However intensive formation of lymphoid structures took place in the walls of the gut, especially large intestine. The appendix, lymphoid tissue of which was not, in fact, developed at all, made an exception.


Molecular control of endothelial cell behaviour during blood vessel morphogenesis.
The vertebrate vasculature forms an extensive branched network of blood vessels that supplies tissues with nutrients and oxygen. During vascular development, coordinated control of endothelial cell behaviour at the levels of cell migration, proliferation, polarity, differentiation and cell-cell communication is critical for functional blood vessel morphogenesis. Recent data uncover elaborate transcriptional, post-transcriptional and post-translational mechanisms that fine-tune key signalling pathways (such as the vascular endothelial growth factor and Notch pathways) to control endothelial cell behaviour during blood vessel sprouting (angiogenesis). These emerging frameworks controlling angiogenesis provide unique insights into fundamental biological processes common to other systems, such as tissue branching morphogenesis, mechanotransduction and tubulogenesis.


Biological control of foodborne pathogens by lactic acid bacteria: A focus on juice processing industries.
The use of lactic acid bacteria (LAB) in foods as biocontrol agents against foodborne pathogens has become increasingly known. Under the premise that controlling the adhesion of microorganisms to food contact surfaces is an essential step for meeting the goals of food processing, the aim of this work was to investigate the inhibitory and anti-biofilm effectiveness of Lactobacillus rhamnosus GG (ATCC 53103) and Lactobacillus casei (ATCC 393) against Escherichia coli O157:H7, Salmonella enterica and Listeria monocytogenes. Lactobacillus strains (108CFU/ml) and pathogens (104CFU/ml) were evaluated to monitor LAB anti-adhesive and antibiofilm effect, in two main scenarios: (i) co-adhesion and (ii) pathogen incorporation to stainless steel surfaces with a protective biofilm of Lactobacillus cells. In (i) the predominant effect was observed in L. rhamnosus against S. enterica and L. monocytogenes, whereas in (ii) both LAB significantly reduced the number of pathogenic adherent cells. The effect of pre-established LAB biofilms was more successful in displacing the three pathogens than when they were evaluated under co-adhesion. These findings show that both LAB can be considered good candidates to prevent or inhibit the adhesion and colonization of L. monocytogenes, S. enterica and E. coli O157:H7 on surfaces and conditions of relevance for juice processing industries, offering alternatives for improving the safety and quality of fruit-based products.


A Meta-Analysis of Traditional Radial Access and Distal Radial Access in Transradial Access for Percutaneous Coronary Procedures.
Radial approaches are classified into traditional radial access (TRA) and more contemporary distal radial access (DRA), with recently published comparative studies reporting inconsistent outcomes. As there have been several recent randomized control trials (RCT), we assessed the totality of evidence in an updated meta-analysis to compare outcomes of DRA and TRA. We searched PubMed, CENTRAL, Web of Science, EMBASE, and Cochrane Database of Systematic Reviews from inception to August 2022 for studies comparing DRA and TRA for coronary angiography. Primary outcomes were the rate of radial artery occlusion (RAO) and access failure. Secondary outcomes included hematomas and puncture site bleeding. The pooled risk ratio (RR) with 95 % confidence interval (95 % CI) was calculated for each outcome. A total of 14,071 patients undergoing coronary angiography from 23 studies, including 5488 patients from 10 RCTs. The mean age of the study population was 59.8 ± 5.9 years with 66.2 % men. Outcomes for a total of 6796 (48.3 %) patients undergoing DRA and 7166 (50.9 %) patients undergoing TRA were compared. DRA was associated with a lower rate of RAO (RR = 0.36, 95CI [0.27, 0.48], I2 = 0 %) but an increased risk of vascular access failure (RR = 2.38, 95CI [1.46, 3.87], I2 = 82.7 %). There was no significant difference in the rate of bleeding or hematoma formation. In an updated metanalysis, DRA is associated with lower rates of RAO but with higher rates of access failure.


Development of the Cantonese Hearing In Noise Test (CHINT).
To develop a Cantonese version of the Hearing In Noise Test (CHINT) with the same features as the English Hearing In Noise Test (HINT) (Nilsson, Soli, & Sullivan, 1994). The CHINT was developed in five separate studies: (1) evaluation of initial materials; (2) creation of sentence materials; (3) equalization of sentence difficulty; (4) creation of sentence lists; and (5) evaluation of response variability, inter-list reliability, and establishment of norms. Using the CHINT material, reception thresholds for sentences were measured under four headphone test conditions: Quiet, and in noise with noise simulated as originating from 0 degrees (noise front), 90 degrees (noise right), and 270 degrees (noise left). The speech source was located at 0 degrees in all conditions. The locations of the speech and noise sources were simulated using virtual audio processing, as with the English HINT. The noise conditions consisted of listening with noise fixed at 65 dBA with the level of speech varied in an adaptive procedure. A total of 142 subjects with normal hearing thresholds participated in the five studies. Two versions of the test materials, twenty-four 10-sentence lists and twelve 20-sentence lists, were created from a single set of 240 sentences containing 10 syllables per sentence. Using the twenty-four 10-sentence lists, mean thresholds under earphones in quiet were measured at 19.4 dBA and reception thresholds for sentences of -3.9 dB for noise front, -10.6 dB for noise right, and -10.5 dB for noise left. Similar results were obtained using the 20-sentence lists (19.4, -4.0, -10.9, and -11.0 dB, respectively, for quiet, noise front, noise right, and noise left conditions). There was low response variability within each list. High inter-list reliability suggests that consistent results could be obtained using any list. Confidence intervals are reported. The CHINT norms for listening in quiet and noise conditions were comparable to those for the English HINT. The CHINT is the first standardized Cantonese sentence speech intelligibility test. The CHINT was developed using the same rationale as the English HINT, allowing norm reference results from the two tests to be compared directly across languages. Results showed the CHINT is a reliable test. The CHINT would benefit from further evaluation of validity.


[Effect of electromagnetic field of extremely low frequency on ATPase activity of actomyosin].
The Mg2+/Ca2+ and K(+)-ATPase actomyosin activity of rabbit skeletal muscle was evaluated by the Fiske-Subbarow method during a five-hour exposition of protein solutions in electromagnetic field of extremely low frequency of 8 Hz and 25 microT induction. The results of the study of the ATPase activity of actomyosin upon electromagnetic exposure have shown statistically significant changes that are characterized by a rather complex time dynamics. After 1, 2 and 4 hours of exposure of protein solutions the effect of ELF EMF exposure inhibits the ATPase activity compared to control samples, which are not exposed to the magnetic field. By the third and fifth hours of exposure to the electromagnetic field, there is a significant increase in the ATPase activity of actomyosin. It should be noted that a similar pattern of change in enzyme activity was universal, both for the environment by Mg2+ and Ca2+, and in the absence of these ions in the buffer. This can evidence for Ca(2+)-independent ways of the infuence of electromagnetic field (EMP) on biologic objects. In our opinion, the above effects are explained by EMP influence on the dynamic properties of actomyosin solutions, which are based on the processes of spontaneous dynamic formation of structure.


Macromolecular crowding and its consequences.
Incompatible pairs of polymers separate into two phases in aqueous solution above a few percentage points total concentration. Protein pairs can also produce phase separation, but at somewhat higher concentrations. In this chapter, we explore the effect of high background concentrations of macromolecules on phase separation of pairs of species which would not be at sufficiently high concentration to separate in the absence of the uninvolved species. Effects produced by such high background concentrations are known as macromolecular crowding. Dramatic enhancements in various association reactions due to crowding have been predicted and observed but its effects on phase separation in biological mixtures typical of the cytoplasm have not been examined. Here, we describe a calculation based on the Flory-Huggins treatment of concentrated polymer solutions that sheds some light on this issue. We find that a background of 20 wt % of a high molecular weight species greatly reduces the concentrations needed to produce phase separation in a mixture of two incompatible macromolecules if one is more hydrophobic than the other. Given the high total concentration of macromolecules in cytoplasm, it is perhaps surprising that phases have not been observed. This issue is discussed and some explanations offered.


Radiotoxicity of thallium-201 in mouse testes: inadequacy of conventional dosimetry.
When TI-201 is concentrated in mouse testes, the low-energy Auger electrons following its electron-capture decay are found to be much more effective in causing loss of testicular weight and reduction of sperm heads than the energetic beta particles from similarly distributed TI-204. These results are contrary to expectations based on conventional dosimetry of tissue-incorporated radionuclides, and point to possible underestimation of risks by the currently adopted dosimetric procedures, especially in the case of radionuclides decaying by electron capture and internal conversion.


Quality of life domains among non-Hodgkin lymphoma survivors: an integrative literature review.
Survival rates of individuals with non-Hodgkin lymphoma (NHL) have increased in the past several years, as has the prevalence of older adults who are managing late and long-term effects of the disease and its treatment. In this integrative review, the state of the science for determining the quality of life (QOL) among NHL survivors is outlined. An online search of Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and the Cochrane Library databases was conducted using the following Keywords: non-Hodgkin lymphoma, health-related quality of life, quality of life, and impact of cancer. Eighteen studies published between 2000 and 2010 are reviewed. Of these, 17 were descriptive, cross-sectional designs, and one was a systematic review. The studies included participants of varying ages and years post-diagnosis as reported in several countries. Importantly, many used one or more QOL measures as outcome variables. Future research is needed on older and minority cancer populations and should include longitudinal and interventional studies.


ATP-dependent transport of aflatoxin B1 and its glutathione conjugates by the product of the multidrug resistance protein (MRP) gene.
Glutathione-S-transferase-catalyzed conjugation of glutathione (GSH) to aflatoxin B1-8,9-epoxide plays an important role in preventing binding of this ultimate carcinogen to target macromolecules. Once formed, the aflatoxin B1-epoxide-GSH conjugates are actively extruded from the cell by an unidentified ATP-dependent export pump or pumps. Two possible candidates for this GSH conjugate pump are the 190-kDa multidrug resistance protein (MRP) and the 170-kDa P-glycoprotein. Both proteins belong to the ATP-binding cassette superfamily of transmembrane transport proteins and confer resistance to a similar spectrum of natural-product drugs. Using membrane vesicles from MRP-transfected cells, we found that MRP transports GSH conjugates of both the endo-isomers and exo-isomers of aflatoxin B1-8,9-epoxide in an ATP-dependent, osmotically sensitive manner (V(max) = 180 pmol/mg/min, K(m) = 189 nM). Membrane vesicles from P-glycoprotein-overexpressing cells showed very low levels of transport. MRP-mediated transport was inhibited by an MRP-specific monoclonal antibody and by a variety of GSH derivatives and cholestatic steroid glucuronides. ATP-dependent transport of unmodified aflatoxin B1 by MRP-enriched membrane vesicles was low but markedly enhanced in the presence of 5 mM GSH, even though GSH conjugates of aflatoxin B1 were not formed by the vesicles. These data demonstrate that MRP is capable of energy-dependent transport of aflatoxin B1 and its GSH conjugates and suggest a potential protective role for MRP in mammalian chemical carcinogenesis.


The ventricular gradient and repolarization.
The ventricular gradient concept of Wilson was an important insight into the physiology of ventricular repolarization and its electrocardiographic expression. For many years the validity of the concept was questioned because QRST deflection area was not independent of ventricular activation sequence but it is now evident that electrotonic effects on repolarization account for that behavior. There is solid theoretic and experimental evidence that QRST deflection area depends on disparity of repolarization. The established relation of disparate repolarization to arrhythmia vulnerability provides an important clinical objective for measurement of the QRST area and promising evidence for the prediction of arrhythmias has been obtained. Finally, there is evidence that the sufficiently sampled map of QRST deflection areas provides useful information concerning the distribution of repolarization properties as well as their disparity.


Generation of influenza virus from avian cells infected by Salmonella carrying the viral genome.
Domestic poultry serve as intermediates for transmission of influenza A virus from the wild aquatic bird reservoir to humans, resulting in influenza outbreaks in poultry and potential epidemics/pandemics among human beings. To combat emerging avian influenza virus, an inexpensive, heat-stable, and orally administered influenza vaccine would be useful to vaccinate large commercial poultry flocks and even migratory birds. Our hypothesized vaccine is a recombinant attenuated bacterial strain able to mediate production of attenuated influenza virus in vivo to induce protective immunity against influenza. Here we report the feasibility and technical limitations toward such an ideal vaccine based on our exploratory study. Five 8-unit plasmids carrying a chloramphenicol resistance gene or free of an antibiotic resistance marker were constructed. Influenza virus was successfully generated in avian cells transfected by each of the plasmids. The Salmonella carrier was engineered to allow stable maintenance and conditional release of the 8-unit plasmid into the avian cells for recovery of influenza virus. Influenza A virus up to 10⁷ 50% tissue culture infective doses (TCID50)/ml were recovered from 11 out of 26 co-cultures of chicken embryonic fibroblasts (CEF) and Madin-Darby canine kidney (MDCK) cells upon infection by the recombinant Salmonella carrying the 8-unit plasmid. Our data prove that a bacterial carrier can mediate generation of influenza virus by delivering its DNA cargoes into permissive host cells. Although we have made progress in developing this Salmonella influenza virus vaccine delivery system, further improvements are necessary to achieve efficient virus production, especially in vivo.


Genes responsible for nisin synthesis, regulation and immunity form a regulon of two operons and are induced by nisin in Lactoccocus lactis N8.
Nisin is a small post-translationally modified lanthionine-containing peptide (lantibiotic) produced by certain Lactococcus lactis strains which has a high antimicrobial activity against several pathogenic Gram-positive bacteria. Northern blots and RT/PCR analysis of the nisin-producing strain N8 revealed that the nisZBTCIPRKFEG gene cluster, responsible for nisin biosynthesis, immunity and regulation, consists of two operons, nisZBTCIPRK and nisFEG. The promoter of the nisFEB operon was mapped. The -35 to -1 region upstream of the transcription start of the nisFEG promoter showed 73% identity with the corresponding region upstream of the nisA and nisZ gene. In contrast to earlier reports, nisin was found to be secreted during the early stages of growth was well as later in the growth cycle. The secreted nisin was adsorbed on the surface of the cells and was released to the medium during mid-exponential growth, when the pH in the medium fell below 5.5. In nisZB antisense and nisT deletion mutant strains constructed in this study the transcription of the nisin operons, nisin production and immunity were lost. Provision of external nisin restored the transcription of both operons in the mutant strains, showing that the operons are coordinately regulated by mature nisin. Nisin induction of the mutant strains also resulted in an increased amount of the NisI protein and an increase in the level of immunity. Induction using higher concentrations of nisin yielded a higher level of immunity. These results showed that the nisin promoters are under positive control in an autoregulatory manner and that antimicrobial peptides can also function as signal molecules.


The historiographical approach taken in the nineteenth and twentieth centuries to the work of Jesuit doctors and apothecaries in the a Plata region in the eighteenth century.
The positions of Pedro Arata, Moisés Santiago Bertoni, Carlos Leonhardt and Guillermo Furlong in the debate about the role of the Society of Jesus in the introduction and development of science in the La Plata region are investigated. Written between 1890 and the late 1950s, these authors' works not only analyze the medical, pharmaceutical and botanical knowledge of the Jesuit missionaries in the 1600s and 1700s, but also evaluate their contribution to scientific thinking in the countries colonized by Spain and Portugal. Their positions foretaste the historiographical debate about the reactionary nature of the Jesuit order and reflections about the contribution made by indigenous knowledge of American pharmacopeia to the knowledge the missionaries took to the continents where they were active.


Neural activity associated with metaphor comprehension: spatial analysis.
Though neuropsychological data indicate that the right hemisphere (RH) plays a major role in metaphor processing, other studies suggest that, at least during some phases of this processing, a RH advantage may not exist. The present study explores, through a temporally agile neural signal--the event-related potentials (ERPs)--, and through source-localization algorithms applied to ERP recordings, whether the crucial phase of metaphor comprehension presents or not a RH advantage. Participants (n=24) were submitted to a S1-S2 experimental paradigm. S1 consisted of visually presented metaphoric sentences (e.g., "Green lung of the city"), followed by S2, which consisted of words that could (i.e., "Park") or could not (i.e., "Semaphore") be defined by S1. ERPs elicited by S2 were analyzed using temporal principal component analysis (tPCA) and source-localization algorithms. These analyses revealed that metaphorically related S2 words showed significantly higher N400 amplitudes than non-related S2 words. Source-localization algorithms showed differential activity between the two S2 conditions in the right middle/superior temporal areas. These results support the existence of an important RH contribution to (at least) one phase of metaphor processing and, furthermore, implicate the temporal cortex with respect to that contribution.


Antepartum diagnosis of the "terminal" fetal state by cardiotocography.
Since 1969 it has been the policy of this department to perform regular cardiotocograms on all patients admitted during the antenatal period for severe hypertension, with or without proteinuria, and on those in whom poor intrauterine fetal growth was suspected. In five such patients where the fetus died in utero, beat-to-beat variation was reduced and late decelerations were observed. In a further twelve patients similar changes made delivery by elective Caesarean section appear advisable. Half of the infants so delivered had severe metabolic acidosis at birth.


Palm boards are not action measures: an alternative to the two-systems theory of geographical slant perception.
Whereas most reports of the perception of outdoor hills demonstrate dramatic overestimation, estimates made by adjusting a palm board are much closer to the true hill orientation. We test the dominant hypothesis that palm board accuracy is related to the need for motor action to be accurately guided and conclude instead that the perceptual experience of palm-board orientation is biased and variable due to poorly calibrated proprioception of wrist flexion. Experiments 1 and 3 show that wrist-flexion palm boards grossly underestimate the orientations of near, reachable surfaces whereas gesturing with a free hand is fairly accurate. Experiment 2 shows that palm board estimates are much lower than free hand estimates for an outdoor hill as well. Experiments 4 shows that wrist flexion is biased and noisy compared to elbow flexion, while Experiment 5 shows that small changes in palm board height produce large changes in palm board estimates. Together, these studies suggest that palm boards are biased and insensitive measures. The existing literature arguing that there are two systems in the perception of geographical slant is re-evaluated, and a new theoretical framework is proposed in which a single exaggerated representation of ground-surface orientation guides both action and perception.


Effects of nicotine infusion on the metabolism of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in rats.
The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a lung carcinogen in the rat and believed to be a causative agent for lung cancer in smokers. To exert its carcinogenic potential NNK is metabolically activated by cytochrome P450-catalyzed alpha-hydroxylation. Nicotine and NNK share metabolic pathways. The purpose of this study was to determine whether nicotine alters the fraction of NNK undergoing activation to carcinogenic metabolites. Rats received acute (36 h) or chronic (2 week) s.c. infusions of nicotine at rates producing serum nicotine concentrations 2-3 times the usual venous nicotine concentrations measured in smokers. A single dose of [5-3H]-NNK was administered i.p. 24 h prior to the end of each infusion. Urine was collected for 24 h thereafter and NNK metabolites quantified by radioflow HPLC. Neither acute nor chronic nicotine infusion had any effect on the extent of NNK metabolism by alpha-hydroxylation. These data suggest that nicotine infusion, at rates simulating the higher doses of nicotine replacement therapy now being studied for smoking cessation, neither induces nor inhibits NNK metabolism appreciably and therefore should not alter the formation of carcinogenic NNK metabolites.


Advances in information technology. Implications for medical education.
Few kinds of technology have had as broad an impact on the recent affairs of humanity as have information technologies. The appearance and rapid spread in the past several years of innovations such as the Internet's World Wide Web and the emergence of computer networks connecting tens to hundreds of millions of people worldwide have occurred with startling rapidity. These global events portend substantial changes in the delivery of health care, the conduct of biomedical research, and the undergraduate, graduate, and continuing education of health professionals. This report will attempt to succinctly review the following: (1) the characteristics of modern information technologies and recent trends that are most relevant to medical education and to the world in which future practitioners, researchers, and educators will live and work; (2) the implications of these technologies for the development of educational goals (in other words, the specific information technology skills that future health professionals will need); (3) the issues associated with the use of these technologies in the process of education; and (4) implications for near-term action by University of California medical schools and academic medical centers.


Respiratory interactions of soil bacteria with (semi)conductive iron-oxide minerals.
Pure-culture studies have shown that dissimilatory metal-reducing bacteria are able to utilize iron-oxide nanoparticles as electron conduits for reducing distant terminal acceptors; however, the ecological relevance of such energy metabolism is poorly understood. Here, soil microbial communities were grown in electrochemical cells with acetate as the electron donor and electrodes (poised at 0.2 V versus Ag/AgCl) as the electron acceptors in the presence and absence of iron-oxide nanoparticles, and respiratory current generation and community structures were analysed. Irrespective of the iron-oxide species (hematite, magnetite or ferrihydrite), the supplementation with iron-oxide minerals resulted in large increases (over 30-fold) in current, while only a moderate increase (∼10-fold) was observed in the presence of soluble ferric/ferrous irons. During the current generation, insulative ferrihydrite was transformed into semiconductive goethite. Clone-library analyses of 16S rRNA gene fragments PCR-amplified from the soil microbial communities revealed that iron-oxide supplementation facilitated the occurrence of Geobacter species affiliated with subsurface clades 1 and 2. We suggest that subsurface-clade Geobacter species preferentially thrive in soil by utilizing (semi)conductive iron oxides for their respiration.